Katie Connolly, Melanie Ostrekher and EliAa Rennert-May, chapter editors Doreen Ezeife and Nigel Tan, associate editors Steven Wong, EBM editor Dr. Ramesh Prasad, Dr. Martin Sc:hreiber and Dr. Gemini Tanna, staff editors
Basic Anatomy Review ................... 2 Anatomy of the Kidney Renal Structure and Function Renal Hemodynamics Differential Diagnoses of Common Presentations . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Azotemia Proteinuria Hematuria Assessment of Renal Function ............. 6 Measurement of Renal Function Urinalysis Urine Microscopy Urine Electrolytes Electrolyte Disorders. . . . . . . . . . . . . . . . . . . . . 9 Sodium Homeostasis Hyponatremia Hypernatremia Potassium Homeostasis Hypokalemia Hyperkalemia Acid-Base Disorders .................... 16 Metabolic Acidosis Metabolic Alkalosis Renal Failure .......................... 19 Presentation of Renal Failure Acute Kidney Injury (AKI) ................ 20 Approach to AKI Chronic Kidney Disease (CKD) ••••••••••.• 21 Management of Chronic Kidney Disease Renal Replacement Therapy ............. 22 Dialysis Renal Transplantation Glomerular Disease .................... 23 Terminology of Glomerular Changes Presentation of Glomerular Disease Investigations for Glomerular Disease Secondary Causes of Glomerular Disease Infections and Glomerular Disease Tubulointerstitial Disease ............... 27 Tubulointerstitial Nephritis (TIN) Acute Tubular Necrosis (ATN) Analgesic Nephropathies Vascular Diseases of the Kidney .......... 30 Large Vessel Disease Small Vessel Disease Systemic Diseases and the Kidney ........ 32 Hypertension (HTN) Hypertensive Nephrosclerosis Renovascular Hypertension Renal Parenchymal Hypertension Multiple Myeloma Malignancy Diabetes and the Kidney ................ 34 Cystic Diseases of the Kidney ............ 36 Adult Polycystic Kidney Disease Medullary Sponge Kidney Autosomal Recessive Polycystic Kidney Disease Common Medications ••••••.••••••.•••• 38 Landmark Nephrology Trials •.••••••.•••• 39 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

Toronto Notes 2011

Nephrology NPI

NPl Nephrology



Basic Anatomy Review
Anatomy of the Kidney

Renal Structure and Function
The Nephron • basic structural and functional unit ofthe kidney, approximately I million per kidney • 2 main components: glomerulus and attached renal tubule (Figure I) • direction of blood flow: afferent arteriole -+ glomerular capillaries -+ efferent artuiale -+ vasa recta (the capil.laries surrounding the tubules) -+renal venules


Osmatic diuratics liEzide diu191ics K+ Sparing diantics
o.-.lingII!Dolloop ·.

( ) L.oapdiul'ltics




! :z:

i ·;a


N1+-K- 2CI-

H,D -





0 [



1. N1p1Jnm Compa1ants
Tlble 1. MaJor Fu1dons of the Kidneys
1. Willa EKrltiGn

Ghmarular fi1nl1ion
Tubailr secretion Tub.-r calllxllism Tubailr tllaCI and Wllllr rubsGiptilll Tubaar Kseaetion Tub.-r HaecratiCII HCO, synlheais ..:1 rBaa!ption Tubular Ca, Mg. P04 lnllspart
Elytlqail!lil pracb:lian lcorttxl Vitamin Ddvation [25[0H)D 1,25(0HJDI Ranil praductian (JG applfiiUi)

(urea, Cl)

Eiu:mian of nitragnJUs prDib:ls of pratailrnelllbalism

Excretion af organic (!Ne) and Dfllllnic bases (Cr) llnllkdawn end ucratian af drugs {..tDalicl, diul'llicll) end peplida hlmlanes (mast pituillry harmCIIIIS, ilsUin.
Clllllds vduma s1a1us and osmolar balance Clllllds pllillssium cai!CI!nlnllian Al:id-basa balance Al:id-basa balance .Min Ca. Ma-1'04 harnaastasis Calcium hiDII!IISialis

Red lilad eel proU;Iian

Allin VIICUI.-ra&i&Wlcellllaldastlmle sacratian Allin ECF Allin VIICUiar rnista1ce
Glucose !llp!iY lllllintailed in prnlanged staiYIIIion

....aod ............... Na IIKL18tian Ranil praductian
Gluconeogereis tfmm lacbde, py!\MII8 end smila acids)

'IbroDlo Nota 2011

Buic Anatomy Review

Nephrology NP3

The Glomerulus • site where blood constituents are filtered through to the kidney tubules fur excretion or reabsorption • consistB of following cell types 1. capillary endotbelial cells and podocytes • support the glomerular basement membrane (GBM) and furm the plasma filtration apparatus 2.mesangialcells • have contractile properties and produce substances to help control blood flow 3. parietal epithelium • covers the interior of Bowman's capsule • filtration occurs aaoss the GBM Into Bowman's space (Figure 2) • filtration barrier: conaists ofcapillary endothelium, GBM. podocyte filtration alit& • particles are selectively filtered by size (<60 kDa) and charge (negatlve charge repelled)

I!J---Aifanllnt artariola

I. Bowman's Cllpde 4. M111111111ium


z. Bawmln'SipiiCI

(pari81111 &pilhtllium) 5. Mlllllllllill calla

6. CIIPiiiiY 7. EndGihalilll cell

8. Glomerular BM

Figure 2. The Glamerjjus The Renal Tubules • reabsorption and seaetion occur between the renal tubules and vasa recta untll tubular fluid is transfurmed Into urine for excretion • each anatDmic segment of the nephron has unique characteristics and specialized functions that enable selective transport of solutes and water • proximal tubule • responsible for reabsorbing -60% offiltered NaCl and water, as well as -90% offiltered bicarbonate and most critical nutrients !II1Cb. as glucose and amino acids •loop ofHenle • consists of three major segments by cellular morphology and location: descending thin limb, ascending thin l.!.mb. and ascending thick limb •important role in urinary concentrating ability by contributing to the generation ofa hypertonic medullary interstitium • contributes to reabsorption ofcalcium and magnesium ions • distal comrol.uted tubule • reabsorbs -596 of the filtered NaCl • composed of a tight epithelium with llttl.e water permeab:llity • regulates pH by absorbing bicarbonate and secreting H • reabsorbs caldum In response to parathyroid hormone • collecting duct • regulates the final composition of the urine • important fur hormonal regulation of salt and water balance (water reabsorption governed by antidiuretic hormone) • reabsorption ofsodium and secretion of potassium at cortical collecting duct regulated by aldosterone

Renal Hemodynamics
• Renal Blood Flow (RBF) of Renal Plasma Flow (RPF): 2096 ofcardiac output= 1000 mlJmin • Glomerular Filtration Rate (GFR) • the rate of fl.uJ.d transfer between glomerular capillaries and Bowman's space • 120 ml/min in healthy adult= 173 IJday, of which 99% is reabsorbed, giving a daily urine
output ofl.0-1.5 L
GIDmrulu fillmiDn 11m!

• highest in early adulthood, decreasing thereafter

GFR - K, 1M' - Alii r, = ultnlillndion caallicilnt AP = hylhstJdic pnmnn All = DlmotiC PIIIISUIII
Nit ouMwd pr811Uf8

-111111 ARF/Iaxi11 • llanaiii1Bry obllruclian A/C • • Chronic IUUainlllrBiiiB nephritis C • Pyalal'lllplriis • llanBI vain Dllslructian AIC !thrombosis. .IJt • llmal/l. 5. a..AldOSielone -4--· kidney · .. normal = 0. - I ro · · Lungs •• • 0 --o f). Cr and other compounds in the blood 1 Azcaml• . tumau.1.II ar!Briala 2.. ) -. nrllnlian illha · .ECV aapsis) • Hapat011111lll synlhme 1 llrlnaiM! + l'osklnrllt/C lllllllructia•l • Anattlmic (1hirt. Kidn8'f complliitian .Hr • • I . Gl. E. entire GU net e.aryJ • NC {llPAlUS. campn181ian YIICUilil. polllbda tr. BPH) • • lilaniiii.· Angiulenlin II Adnml cortax Stinullllian of Na 6\ . slllnBI. 1' bie1nbo11118 Differential Diagnoses of Common Presentations Azotemia Definition • higher urea and Cr are usually caused by inability of the kidney to excrete urea. · .g. rise ln perfusion pressure causes afferent arteriolar coll8trlctl. . I . lrilll • ..iutre!J.on..1.•. VuoCGIIIbictian 2.. ACE I. 1' lldoataruna AngiDIInlill .NP4 Nephrology Buic Anatomy Rniew/Differentlal Dlagnoses of Common PruentalioDI 1'oroDio 2011 • renal autoregulation maJntains a constant GFR over a range of mean arterial pressures (70 to 180 m. leading to a decrease in GFR • tubuloglomerular feedback: changes in [Na] delivery to macula densa lead to afferent arteriolar tone (increased delivery Cllll8e8 afferent constriction) • Filtration Fraction (FF) • percentage of RPF filtered across the glomeruli • expressed as a ratio: FF = GFRJRPF.ssificltian af AzatBIIH . DIC. JG eel belllsym!lllhBtic narva IIM!u!Eon B·_ . . . 2 mechanisms of autoregulatl.. aartic dissactian.·r .. 1' vasc1*nmoo1h mulda IJliWih 3.2 or 20% • angiotensin II (An) causes constrktion of renal efferent arterioles which increases FF thereby malnta!DingGFR • renin is released from Juxtaglomerular apparatus in response to decreased RPF Livlr Vesoeanstrir:tion 1.. embcilc.g.._.. 3.IJt Rlnll • Al:uiiii!Djar nKilllil .Jmt. n:.-. z•m lml crisis) F"11111r1 4.mHg). ar._. \ Hillin _ .-tl'leAII • Acutllllllergiej inlllrllitill neplriil A A-ICIIIIIAI!ing C-dnnic181ting 12" . 1' Nl reablorplion 4.A + llfrpovallnlil) • IUd lou8l (hamorrhaae.-.. lkin.on: • myogenic mechanism: release of vasoactive factors in response to alterations in perfusion pressure.

.. fever.Giom.73m2/daywith hypoalbuminemia (<35 giL) .glom1111lonephri1is wti. amyloidosis. Classification of Proteinuria Table 2. mild glomerular disease can lead to a mild dagrae of proteinuria. edema is partly secondary to salt and Wlll8r l'lltllntion 2. GN Post-strap. gold. prolifllllltive lasioos may also be associlllad with scrne degree of proteinuria Up to 2000 mg pll' day Possible tubular disease because of failure to reabsorb filtered proteins Investigations • urine R&M.-r • No111111lly. abdominal!pelvic ultrasound • serology: ANA.. Waldensbllm'a macroglobulinemia • t Tulluloiraratitill • Nonndy low molacular waight {LMWI proteins i <60 kD) pus through glomerular filtnltion blrriar and ana raabsolbad in proximaltmule • Proximal1ubule dysfunction causes impan. Cr • further workup (if degree of proteinuria >0. p-ANCA. Thus. RF. hypertansiva nephrosclerosis • Figure 5. GN lgA nephropBihy • LMW -low molecular GN . HIY..8 mglmmol is the earliest sign of diabetic nephropathy • composition of normal total urine protein • 60% filtered plasma protein: 50% albumin. {Ovarprocklction of LMW protainsl • e. 25% other • 40% Tamm-Horsfall mucoprotein secreted from tubular cells tm . Hep C. glucose. Daily Excretion of Protein Daily Elu:nrtion <150 mg tollll protein (and < 30 mg albumil) 30-300 mg albumin >3500 mg total protein Variable llllount of proteinuria Nanna! MiCIDIIIbwninuria Nephrotic range proteinuria 3.lymphomal • Lymphom1. Second1ry • SystEmic disease • Sl.d l'labsorplion and incraased exJ:relion af LMW proteins • Albumin {>60 kDI is NOT affected• Thus. . monoclon•l gammopathy of undanninad significiii'ICII C111 be seen with glornerulll' clsease.e. Thus. albtnin is NOT filtarud through a nonmlll giDIJIIIIIIuS • Damage to any component of tha QIDIIIIIIIIar filtration barriar mulls in loss of albumin and other high MW proteins..5 g/1.11vartlaw • production of LMW proteins which axceeds the reabsorptive capacity of the proximal 1ub\Q • Plasma cllll dyscmiu: produce light chain lg myeloma.. casts and/or hematuria) • CBC. sickle cell. Hap Band C.g. Fabry's. c-ANCA. 15% Ig.ldanstrom'a macroglobulinemia. bllctarial endocarditis • Hlllditary/Jnelllbolic • Alport's. solid tumour • Others • Cryoglobulinemia. i. NP34) • an elevated ACR or 2.E. C&S. diabetes. edema is secondary to hypoalbuminemia {low oncDtic but also due to enhanced renal tubular reabsorption af filtered sodium and water (mechanism uncer111inl Primary • • • • • • Minimal Change GN Membranous GN Focal segmental glomeruloaclerosis {FSGSI Membrano-prolif. Hep B. electrolytes. CHF} PATHOLOGIC PIQ11:1NUIIA + 1 + htllaiDail: 1 Tubulaintamitial {impairud resorption! • <2 gfday • e. ASOT • indications for nephrology referral • ACR >30-1000 mglmmol • nephrotic syndrome: marked proteinuria >3. the 111ntion barrier is selectively penneable to SIZE {<60 kDI and CHARGE {repels nagativa particles). urea.5 glday.r•r • I o. heavy melllls • Cancer {carcinoma.g. Fanconi"s IJY!ldrome • I Doss of large protains (albuminII I Glan. polycystic kidney disease • Medications • NSAIOs. vasculitis • Infectious disease • HIV. W. multiple myeloma. 24-hr urine protein and Cr • urine and serum immunoelectrophoresis.Toronto Notes 2011 Differential Diagnosis of Common Presentationa Nephrology NPS Proteinuria Definition • 24-hour urine protein: gold standard to assess degree of proteinuria (see Table 2) • urine albumin-to-creatinine ratio (ACR): used to screen for diabetic nephropathy • Microalbwninuria • defined as ACR mglmmol (female) or mg/mmol (male) • marker of vascular endothelial function • an important prognostic marker for kidney disease in diabetes and hypertension (see Diabetes and Kidney. I Proteinuria I Physiologic • Orthostlllic • Absence of protainuria overnight • Usually resolves spontaneously • (exercise.

ICrJ.if +ve for heme: myoglobinuria or hemoglobinuria .ANA. Goodpastura's. >2-3 RBCs/HPF on microscopy -ve dipstick. cerebral aneurysm (PCKD). 24-hr urine volume and urine [ Cr] • GFR= (urine [Cr] xurinevolumeinmL)/(plasma [Cr] xdurationofurine collection in minutes) • two major errors limiting the accuracy of CrCl • increasing Cr secretion can overestimate true GFR. irritative and obstructive urinary symptoms (UTI) • urine R&M.ic patients • incomplete urine collection can underestimate true GFR. 1rauma. Urologic • Nephrolithiasis. food dyes (e. no RBCI • Myoglobin (rhabdomyolysis) Prilllllry • • • • • • .ASOT).if -ve for heme: pseudohematuria.NP6 Nephrology DUferential Diagnosea of Common Preaentatiom/. C3. . x urjne !low r11!: [Cr)- Measurement of Renal Function • • • • • • • Glomerular Filtration Rate (GFR) = rate of filtration of plasma by the glomeruli most renal functions decline in parallel with a decrease in GFR GFR is often estimated using serum creatinine concentrations [ Cr] creatinine (Cr) is a metabolite of creatine (intermediate in muscle energy metabolism) Cr is freely filtered at the glomerulus with no tubular reabsorption and minimal secretion (10%) rate of production determined by muscle mass Cr excreted= Cr filtered (at steady state) .. SLE. rifampin). HSP • Infection • Pyelonephritis • Heneditary • AIport's.. Cr • 24-hr urine stone workup: calcium.. over-collection of urine overestimates it . urea.. no RBCI • Pseudohematurill • Food (basts). Calculate creatinine clearance (CrCl) • calculation provides reasonable estimate of GFR • measure plasma [Cr]. magnesium. sickle cell " I s [1rue hematuria) • Hemoglobin (hemolysis) • I . serology (. p-ANC. 24-hr urine protein and Cr.g. madicati011 (rifampin) • H1111aluria +ve dipsticll. er-=cr_ [Cr). porphyria) • microscopic hematuria: normal coloured urine.. uric acid. diet. cysteine • further workup (if casts and/or proteinuria): CBC.. .g. GN Post-51rap.. the urine should be centrifuged • it is hematuria only if the sediment is red... Ct. +ve dipllick. oxalate.. GN Rapidly-progressive GN nephritis (ICuta and chronic) Papillary necrosis lgA naphroplllhy • Comective tissue diseases (CTDJ • Waganar's... beets) or metabolites (e.t. bladder) of stre1111 " Second1ry . recent URTI. test for heme with a dipstick ...m. particularly in azotem. c-. There is an inverse relati011ship between sarum Cr concentration and CrCI at steady state. x GFR = [CrJ. x urin flow ms(ml/min) GFR . hearing loss (Alpert's).Jrg-Stnluss.. polycystic kidnsy disaasa (PCKD) Figura 6. electrolytes. An Approach to Hamll'lllria Investigations for Hematuria • Hx and Px: family history of nephrolithiasis. C4. pro. or tea-coloured urine • in gross hematuria.. cystoscopy ± urology consult Assessment of Renal Function . RF. C&S. citrate. abdo/pelvic ultrasound. dyes.A..tatitis. Consider medications (e.+ve RBCs Hematological • Coaguloplllhy..Aneasment of Renal Function Toronto Notes 2011 Hematuria Definition • presence ofblood or RBCs in urine • gross hematuria: pink. no casts • Blood at beginning (lni!Yitis) or end [prostate. urethritis • Dysuria or flank pain common • Isomorphic RBCs.. Ways to Estimate GFR I..g.ANCA. tumour. red.t----------------. If the supernatant is red.

NP34) • sulfosalicylic acid detects all protein in urine by precipitation • gold standard: 24-hr urine collection for total protein . GI bleed) causes urea level to rise • ECF volume depletion causes a rise in urea independent of GFR or plasma [CrI • in addition to filtration. specific gravity of 1. errors in Cr measurement • very high bilirubin level causes [Cr] to be falsely low • acetoacetate (a ketone body) and certain drugs (cefoxitin) create falsely high [Cr] Measurement of Urea Concentration • urea is the m. proximal tubule dysfunction (e. . gender.030 • values <1.. IWripra. a significant amount of urea is reabsorbed along the tubule • reabsorption is increased in sodium-avid states such as ECF volume depletion • typical ratio of urea to [Cr] in serum is 1:12 in Canadian units (using mmol/L for urea and !llllol!L for Cr)..5 ml/s) 3. ·}----------------.010 reflect dilute urine.. Specific Gravity • ratio of the mass of equal volumes of urine/H 20 • normal range is 1. Bence-Janes. but may be colourtess (dillllellls insipidus.. Function incruH in Urwa Volume depletion (prarenalezotemial Gl hemonllage High protlin diet Sepsis Celllbolic lllrt8 with tilsuu bnlakdown Cortic:osteroid or cytotoldc agents In lira Low protein diet Livar disalsa Urinalysis • use dipstick in freshly voided urine specimen to assess the following: 1.020 = 600m0sm ... excess Wlt8r intalal]. bright yallow (due to ribofiiMn ingestion or vitamin . Z4 hour Urinll Callectian 1.001 to 1. Collect second morning CIIJIIy: Cloudilass may indicate infection Colour: usually pllla yallow or lllllbar. and 14:1 in US units (urea expressed as BUN in mgldl and Cr in mgldL) . MDRD (Modification of Diet in Renal Disease) formula • most common way in which GFR is estimated • complex formula incorporating age..010 in end stage renal disease (isosthenuria) 2. consider: • renal tubular acidosis • UTI with urease-producing bacteria (e.6 mUmin 4. Cockcroft-Gault formula • serum Cr used along with age. Mrican descent • GFR is reported as ml/min/L73m2 body surface area Limitations of Using Serum Cr Measurements I.Toronto Notes 2011 Assessment of Renal Function Nephrology NP7 2..g. values >1.13 mgldL) in both of these patients • 20 year-old man who weighs 100 kg. gender and weight (kg) to estimate GFR (see sidebar) • nonnal range is >90 ml/min (> 1.. C&nical Settings in which Urw. pregnancy) 3.d lndaptlmlont llf Rn.g. . GFR = 144 mUmin • 80 year-old woman who weighs 50 kg. if persistently alkaline. elderly.. but it takes time for Cr to accumulate and then re-establish steady state 2.020 reflect concentrated urine • value usually 1. GFR = 30.aj or end product of protein metabolism • plasma urea concentration is a measurement of renal function but should not be use alone as it is modified by a variety of factors • urea production reflects dietary intake of protein and catabolic rate. or dlllt yaUow (conciiTII'IDd urina in inlnMiscu!er volume depletion] 3..g. CrCI (mVmin] = I11!H!!fll X wt (kg) X 12 I X 0.g.plasma [CrI is influenced by the rate of Cr production • lower production with smaller muscle mass (ie.85 in W0111111] (Crl.. Glucose • freely filtered at glomerulus and reabsorbed in proximal tubule • causes of glucosuria include 1. lliscllld first morning $JI&Cim&n 2. pH • urine pH is normally between 4.. bltwnn voids 4. GFR must fall substantially before plasma [CrI rises above normal laboratory range • with progressive renal failure. lg. must be in steady state • constant GFR and rate of production of Cr from muscles • sudden injury may reduce GFR substantially.g.bllllll).ity Lut 2 digits of lila specific g111Yity x 30 = urine osmolality approximatEly e.0.. increased protein intake or catabolism (sepsis.... low weight) • e. Eslinwting Urillll DIIIIDI. consider plasma [Crl oflOO f!InOl!L (1.. Collect all subsequent urina for lila next24 hi"$ 3. . other proteins (e. trimethoprim) interfere with Cr secretion 5.. remaining nephrons compensate with hyperfiltration • GFR is relatively preserved despite significant structural damage 3. serum Cr. contribution of tubular secretion to Cr excretion is increased when GFR is low • CrCl overestimates GFR • certain drugs (cimetidine. Tamm-Horsfall) may be missed • microalbuminuria (defined as 30-300 mglday) is not detected by standard dipstick (see Diabetes and the Kidney. Proteus) . trauma. Lenl Ia MfKt. . Fanconi's syndrome) 4. hyperglycemia >9-11 mmol/L (>160-200 mg!dl) leads to filtration that exceeds tubular resorption capacity 2. increased GFR (e.5-7. Protein • dipstick only detects albumin..g. female. (umol!ll Cockcroft-Gault Fonnlll . ·}-----------------.

g. ethylene glycol poisoning sulfur .NP8 Nephrology Assessment of Renal Function Toronto Notes 2011 5o Leukocyte Esterase • enzyme found in WBC and detected by dipstick • presence ofWBCs indicates infection (e.51fday] Pigmented gnmlar casts (heme grarular casls.. fasting T•nninolagy B.clllll pdhclogy Reduced lblhocllaf sii. CELLS Erythrocytes • normal range = 2-3 RBCs per high power field (HPF) • hematuria = greater than 2-3 RBCs/HPF • dysmorphic RBCs and/ or RBC casts suggest glomerular bleeding (e. myoglobinuria (rhabdomyolysis) and true hematuria (RBCs seen on microscopy) o Urine Microscopy • centrifuge urine specimen for 3-5 minutes. consider: chronic urethritis. exercise] Glomerulll' bleedilg (glomerulonephritis. viral infections Eosinophils • detected using Wright's or Hansel's stain (not affected by urine pH) • consider allergic interstitial nephritis. Hlltf IIQI8Itive pdhclogy.alkaline urine calcium oxalate . proliferative glomerulonephritis) • isomorphic RBCs.. low sensitivity for UTI • +ve dipstick for leukocyte esterase and nitrites is 94% specific for diagnosing a UTI 6. UTI) or inflammation (e. lllllwilfl •inoopr o o <21111 eels per <4v.sulfa-containing antibiotics . interslitial nelllritis Heavy proteiruria (>3.g. resuspend sediment and plate on slide • shaking tube vigorously may disrupt casts 0 0 oSmll•li• >211dcellslll afCI'/Iflll powarfilll o Smahmollltcl tiiPf) hcleria >4vAilecells perhpf elliS . vasculitis} lnfeclian (pyelaneplritis] lnllanmrtion (interstitial nephritis} Acute tubulll" necrosis Glomerulonephritis.. atheroembolic disease Oval Fat Bodies • renal tubular cells filled with lipid droplets • seen in heavy proteinuria (e. Interpretation of Casts Hyaline casls Red blood cell casts White blood call casls Physiologic (concenlnrted urile. AIN) • nitrates in urine are converted by bacteria to nitrites • high specificity.JIIi:n ILtnotrmediU 1. discard supernatant. Hemoglobin Red 1)111 calls WlitiCIIcasts QllllljwQt o •nil Aly 111 or ltplne • .consider hyperoxaluria. gout) calcium phosphate . no casts suggest extraglomerular bleeding (e. negative culture)..g. . interstitial nephritis. CRYSTALS • • • • uric acid.g.liit8CIIs • positive in hemoglobinuria (hemolysis). calculi. muddy brown] Fatty casts 3.. o 7. papillary necrosis. CASTS • cylindrical structures formed by intratubular precipitation of Tamm-Horsfall mucoprotein.e. bladder Ca) Leukocytes • • • • normal range = up to 3 WBCs/HPF pyuria = greater than 3 WBCs/HPF indicates inflammation or infection if persistent sterile pyuria present (i.g. cells may be trapped within the matrix of protein Table 3. prolonged starvation. Ketones • positive in alcoholic/diabetic ketoacidosis.. nephrotic syndrome) 2.._.. .g. renal TB.consider acid urine. hyperuricosuria (e. prostatitis. Nitrites . fever.

Toronto Notes 2011 . each of which urine and plasma concentmian (e.5 mmoVL Chloride (CI) 95-105 mmoVL Bicarbonall (HC01) I 8-23 mmoVL llypaMIIamic Increased Nonnal to increased SJ lnspira!DfY Clllcldes NonnaVincreased Present Variable Increased DecntaSed lntnwuc:ular JVP BloDd prassura Ausculllltioo CJf hBBrt Allsculllltioo CJf lungs lntenlitial Skin tull!Dr Edema (dependent) Tachyt:arlia Nonnal Decreased Absent Decreased Decreased Increased Dlh• Urine output Body weight Hct.l.l. . electrolyte excretion depends on intake and current physiological state therefore results must be interpreted in the context of a patient's current state. e.ular fluid relative to Na • both can be associated with normal. ECF volume depletion: expect low urine [Na] (kidneys should be retaining Na) • a high urine [Na] in this setting suggests a renal problem or the action of a diuretic • urine [Na] <10 mmolJL suggests the patient is pre-renal 2. or urea) that cannot freely traverse the plasma membrane contribute to effective osmolality and induce transcellular shifts of water • water moves out of cells in response to increased ECF osmolality • water moves into cells in response to decreased ECF osmolality • physiologically..X 1DO Many fonnuills uud in nephrology 11111 derived from 1he division of two frllctiDRI.g. K. U... daily urinary potassium excretion rate should be decreased (<20 mmolJd) in the setting of hypokalemia • if higher than 20 mmolJd. osmolality and pH no 'normal' values. Cl.. Co.g. = .. + Wl'2l· In 1he cqe of it is UNJPNo + UcJPc. INal"'. 1. tubular disease (e.S. pre-renal • high urine Na (>40 mmolJL) in the setting of hyponatremia: generally from causes such as diuretics. not Na concentration • Na deficiency leads to ECF volume contraction • Na excess leads to ECF volume expansion • clinical signs and symptoms of hyponatremia and hypernatremia are secondary to cells (especially in the brain) shrinking (hypematremia) or swelling (hyponatremia) Tabla 4. Examples of Common Urine Electrolyte Abnormalities • high urine Na (>20 mmolJL) in the setting of acute renal failure: indicates renal disease vs. X ICrl. urine pH is useful to grossly assess renal acidification • "low" pH (<5.g.ular fluid relative to Na • hypernatremia is too little water in the extracel.... decreased or increased total body Na • solutes (such as Na.5) in the presence oflow serum pH is an appropriate renal response • a high pH in this setting might indicate a renal acidification defect (e. . SIADH • additionally.IP. RTA) Electrolyte Disorders Sodium Homeostasis Introduction • hyponatremia and hypernatremia are disorders of water balance • hyponatremia suggests too much water in the extracel.. ECF volume is determined by Na content. suggests renal etiology • osmolality is useful to estimate the kidney's concentrating ability • refers to the fractional excretion ofNa • FENa =Urine [Na] xPlasma [Cr]/ (Plasma [Na] xUrine [Cr]) • <1% suggests the pathology is prerenal • • • • .g. Sodium [Na) 135·145 mmaVL (K) 3. serum pruteil .x [Crlurilo Fractional Excrwlion of Sodium FEti. which 1hln givls the above equation. Bartter's syndrome).. glucose. Clinical Assessment of ECF Volume (Total Body Na) Fllid Campartmall: Hypovolllllic Decreased Orlho6tatic «op .Assetl8lllent of Renal Function/Electrolyte Disorders Nephrology NP9 Urine Electrolytes can use to evaluate the source of an electrolyte abnormality or grossly assess tubular function commonly measure: Na..

urine.g. ADH is acting when it should not be • may be physiological (due to volume stimulus) or pathological (other reasons) • volume mediated ADH release can be due to true or effective volume depletion • causes of true volume depletion: losses from skin.. neurological disease.g.g.. somnolence.. anorexia. blood or 3rd spacing • effective volume depletion: CHF and cirrhosis • pathological ADH release: SIADH and endocrine deficiency • SIADH . see Table 5 • adrenal insufficiency (decreased volume and co-secretion ofADH and CRH) • hypothyroidism (decreased cardiac output. ectopic production. schizophrenia) • ability to excrete water is compromised in people with low solute excretion (particularly urea) • e. muscle cramps. surgery). 3.. normal or decreased (most common) serum osmolality Mechanisms of Hyponatremia 1. decreased level of consciousness (LOC) .. Hypo-Osmol• (dilutionall • Most common cause of hyponatremia • Excess water in relidion to sodium stores which can be decreased. Hyponatremia with no (or minimal) urine • advanced renal failure with oliguria may be associated with hyponatremia if the patient ingests even a moderate amount of dilute fluids If 1111 urin8 osmolality is unknown.. decreased GFR) .w watEr out of cells diluting the Na in ECF • Usually glucose (nanaly hypertonic mannitol) • Evary I 0 mmoVL incraua in blood glucose results in 3 mmoVL dacraaS8 in Na • y ltyp!lrwlemic: u. CRF TrNtmlllt • Treatment golll is Naloss with ralatively mora water loss • Treat with sahnd water restriction and sometimes diurelics Figure 1.NP10 Nephrology mectrotyte Disorders Toronto Notes 2011 Hyponatremia • hyponatremia: serum [Na] <136 mmol!L • can be associated with increased. 11111nnitoll • Pseudohyponatramia -lab artnct seen with severe hyperlipidemia or panaprotainamia (e. nausea.J • Altalal insufficiency • Hypothyroidism U_<10D • "-Ychogenic polydipsia Traat1111nt • Tnaat with water restriction • Tnaat with salt and wlllllr (i. BUUIII81he urine is hypoolill101ar/dilu1e. lung disease. low urea excretion 2. Hyponatremia despite dilute urine (U0 .g multiple myelomaI • HypaP. elderly women with "tea and toast" diet low protein intake..-----------------. .<100) • expect urine to be dilute with hyponatremia (ADH should be suppressed) • due to excessive water intake that overwhelms the kidneys' normal water excretion capacity • psychogenic polydipsia in psychiatric patients (e.>20 • lliurelics • Salt-wasting nephropathy U. stress (pain.. malaise.. bum1) Treat11111nt • Treatment goal is to replenish lost Na AND water • Treat with nonmal or {rarely) hypertonic saline • For faster treatment usa nonmiiiiRIIine + furo&emide u >2D . Hyponatremia with concentated urine (Uoam>200) • if urine remains concentrated.. . nausea.<2Q/anuric • CHF • Cirrhosis and ascites • Pregnancy y Euvulemic u_>1DD • SIADH [normlll U.g. • ARF. velocity of progression from onset • acute hyponatremia (<24-48 hours) more likely to be symptomatic • chronic hyponatremia (>24-48 hours) less likely to be symptomatic due to adaptation • adaptation: normalization of brain volume through loss of cellular electrolytes (within hours) and organic osmolytes (within days) • adaptation is responsible for the risks associated with overly rapid correction • neurologic symptoms predominate (secondary to cerebral edema) -headache. nonmal salina) y Hypovulemic U. GI. nonnal or increased • Categorized by volume 5brtus as datannined by clinical assessment • I Hyponatremia I10-011111olu • RIJIIIntion in ECF of larae volumes of isotonic fluids that do not contain 10dium (e. disorientation..a... weakness. personality changes.OIIIIIolar (transloc:ati-11 • Extra osmol us in ECF <h.<10 • Diarrhea • Excessive sweating • Third spacing (e. pancnaatitis. depressed reflexes. An Approach to Hyponatremia Signa and Symptoms • depend on degree of hyponatremia and more importantly. lethargy.many causes including medications..

.e.g..g.Na in 0. avoid if cirrhosis or congestive heart failure as nephrotoxic in these settings) • extra osmoles. Frequent moniiDring at 5e111111 Na and urine output il essential. central pontine myelinolysis: cranial nerve palsies. Impact of IV Solution on Plasma Na • funnula to estimate the change in serum Na caused by retention of 1 L of any infusate [TBW = (for men) 0.. refractory • furosemide and IV NS • demeclocyline 300-600 mg PO bid (antagonizes effect of ADH on collecting duct. augments excretion of electrolyte-free Hp) • consider NaCl tablet or Oxocubes• as a source ofNa 3. treat as symptomatic B. NeCI = 513 mmaVL Na in 5% NeCI .5 x wt (kg) women 2. if severe symptoms (seizures or decreased LOC) • must partially correct acutely • aim for increase ofNa by 1-2 mmol/L/hr for 4-6 hrs • limit total rise to 8 mmol/L in 24 hrs • IV 3% NaCl at 1-2 cc/kg/hr • may need furosemide 2.. not exteed BmmoVI/24 hrs Ldess . urine osmolality urine Na <10-20 mmolJL suggests volume depletion as the cause of hyponatremia assess for causes of SIADH (see Table 5) TSH. Cr serum osmolality. and therefore rapid rise in serum Nalevel) • patient with psychogenic polydipsia.Bxwt (kg) man. Chronic or Unknown 1. quadriplegia.. HzO Dlllcit 1nd TBW Eqllllti1.45% NaCI = 77 mmoi/L Na in O. <24-48 hrs dumion. ' .Toronto Notes 2011 mectrolyte Disorders Nephrology NP11 Complications • seizures.uaUy thefi!$1: sign of dangerously rapid C01111Ction of serum &Odium . respiratory arrest.K NaCI = 154 mmoi/L Na in 3'11. the ADH level falls suddenly causing sudden brisk water diuresis.. . Definitely Arote (known to have developed over <24-48 hours) • commonly occurs in hospital (dilute IV fluid+ reason for ADH excess e. free T4.serum !Nal TBW+lL • this formula assumes there are no losses of water or electrolytes . ea-ntratlon of Na in Common lnfuut...-----------------.g.. post-operative) • less risk from rapid correction since adaptation has not fully occurred • if symptomatic • correct rapidly with 3% NaCll-2 cc/kglh up to serum Na=125-130 mmolJL • may need furosemide to address volume overload • if asymptomatic. which may be irreversible (e. patient with hypol18ln!mil dua to SIADH from nausea • G ravofll' givan for lllliaf of hypo1111nmia induced nausaa • ADH quickly turned off in tha lbunC8 of 01111181. and lhe serum [Na+] rises rapidly • Plltill'lt at risk of osmotic d1111'(11inlllion • High output dilute urine (> 100 cc. glucose.__________________ . TBW = 0. pennanent brain damage.give oral urea (increases loss ofwater without Na. Options jf overly rapid correction occurs • give water (i. H10 deficit = TBW x ([Na]plllsma140)/140 . treatment depends on severity • if marked fall in plasma [Na]. coma. Conection of Na in hyponab8mia should dlfinitlly known to t. (for women) 0. deprived of water Investigations • ECF volume status assessment • • • • • • • serum electrolytes. 30-60 g/day) • slow rate of IV 3% NaCI (e. < 1DD mOsmiL) in lha sstting of hyponalr8mia is u.6 x wt(kg).lhr. switch to IV D5W) • give ADH to stop water diuresis (DDAVP 1-2 IV) .. 1111 kidnl'fS rapidly excrete the excess free water.. and cortisol levels consider CT chest if suspect pulmonary cause of SIADH consider CT head if suspect CNS cause Treatment of Hyponatremia • general measures for all patients • water restrict (1 Uday) • treat underlying cause • monitor serum Na frequently to ensure correction is not occurring too rapidly • monitor urine output frequently: high output of dilute urine is the first sign of dangerously rapid correction of hyponatremia A. '. of Rlpld Conallan of ll'fponlllntnU • lnadvart8nt rapid c011'8ction of hyponatremia can eiiSily occur • e.. decreased LOC) Risk Fac:tors for Osmotic Demyelination • rise in serum [Na] with correction >8 mmolJL/d if chronic hyponatremia • associated hypokalemia and/or malnutrition • if patient with hyponatremia and hypovolemia is given large volume of isotonic fluid (ADH is stimulated by hypovolemia. when hypovolemia is corrected. death • risk of brain cell shrinkage with rapid correction of hyponatremia • can develop osmotic demyelination of pontine and extrapontine neurons. brainstem herniation.. . 10 cclhr = 120 mmol/day of sodium which will increase serum [Na] by about 3 mmol/Uday) 'a..1BW = O.9% normal saline (NS) + furosemide (reduces urine osmolality.855 mmaVL Na in Ringer's = 130 mmolll Na inD5W = 0 C. if asymptomatic • water restrict to< 1 Uday fluid intake • consider IV 0.5 x wt(kg)] change in serum Na = infusate [Nal ..g.

I Is patient putting out a small volume [500 mlJd) of miXimaly [ > 8DD mOsnv\u) Ll'ina? + I .. high urine sodium (>20-40 mmol/L) 3... rarely due to hypertonic Na gain results from problems with water intake (access.. diuretics. seizures. malabsorption) • Remota renal loss I . focal neurologic deficits. urine that is inappropriately concentrated for the serum osmolality 2.NP12 Nephrology mectrotyte Disorders Toronto Notes 2011 Syndrome of Inappropriate Antidiuretic Hormone Secretion (SlADH} 1. No Positive renlll re.. D1 . coma.onse to DDAVP 511% increasa in urina osmolality? • I I v.. An Approach ta Hyparnatramia Signs and Symptoms • with acute hypc:matrcmia no time for adaptation. always a hyperosmolar state usually due to net water loss. Disorders Associated with SIADH Tumaur Small ceiiCa Bronchog111ic Ca AdenoCa of panCI'I!IIS disease Pulm11111ry Pneumonia Lung abscess CNS Mass lesion Encephalitis Subaraclnlid hemorrhage Acute psychosis Acute intermittent poqilyria Drugs MiiCIIIueaus Thymoma TB Acute respiratory failure S1roke Positive pressure ventiation Head trauma Antidepressants TCAs SSRis V"ncristine Cyclophosphamide sllrte Pain Severe nausea HIV Dill• DDAVP Oxytocin Nicotine Cllb1111BZ8pi'le Barbiturates Chlorpropamide Hypernatremia • • • • hypernatremia: serum [Na] >145 mmol/L too little water relative to total body Na. HypiMIIImic (raN) • IIII'O!renic [hypertonic salina or NaHCO. thirst..) • Cushing's syndrorna • Hyparald01111ronism • Traat wi1h salt restriction.. thirst) and/or site of increased water loss (renal or extrarenal) • less common than hyponatremia because patients are protected against hypernatremia by thirst and release of ADH I Hypemmamia I .. weakness. neuromuscular irritability. wmer replacement • Dialysis if ranal failure Nan-llypemlamlc .. 01 I Figura I. skin • Gl [dianhaa) • Osmotic (lactulosa... signs ofhypovolcmia Complications • increased risk of vascular rupture resulting in intracranial hemorrhage • rapid correction may lead to cerebral edema due to ongoing brain hyperosmolarity . therefore more likely to be symptomatic • adaptive response: cells import and generate new osmotically active particles to normalize size • due to brain cell shrinkage: altered mental status. • Diuretics [loop) • Osmotic diurasis • Hyparglycamia • Endoganous[uraa with axcass NG protein faads) • \W • Insensible water loss • Respinrtory. death • ± polyuria....highFENa Table 5. No Is urine osmole excretion rme > 750 mOsm/d 1 .

45% NS approximately equals 500 mL free water • use formula (see Hyponatremia. vascular events. fall in urine volume • treat with DDAVP • nephrogenic Dl: exogenous ADH fails to concentrate urine as kidneys do not respond • treat with water (IV D5W or PO water).5-5.. 0.0 mEq/L • in response to K load. thiazides may help as well (reduced ECF volume stimulates proximal tubular reabsorption of sodium and water. granulomatous diseases. . rapid removal from ECF is necessary to prevent life-threatening hyperkalemia • insulin. or elevated (nephrogenic) • dehydration test: HzO deprivation until loss of 3% of body weight or until urine osmolarity rises above plasma osmolarity. most likely Dl • administer DDAVP (exogenous ADH) (10 fig intranasally or 2 fig SC): • central Dl: diagnosed ifthere is rise in urine osmolality. must first correct volume depletion with NS bolus • loss of water is often accompanied by loss of Na but a proportionately larger water loss • in patients with presumed normal total body Na content.6 x wt(kg) for men.. and malignancy • nephrogenic DI: lithium (most common).5 mmol/Uhour or 12 mmol/Uday Treatment of Hyparvolemic Hyparnatramia • general measures as above • hypervolemic hypematremia: remove excess total body Na with diuresis or dialysis (if renal failure present). use formula to calculate water deficit: H20 deficit= TBW x (serum rNa! . if fails to concentrate urine. leading to less delivery of glomerular filtrate to ADH sensitive parts of renal tubule. correct H2 0 deficit with hypotonic IV solution • lL DSW approximately equals 1 L free water • 11 0. as oral route is preferred for fluid administration • if unable to replace PO or NG. causing Na reabsorption and K excretion • metabolic alkalosis • hypomagnesemia • increased non-reabsorbablc: anions in tubule: lumen: HC03. hypercalcemia. catecholaminc:s and acid-base status influence K movement into cells • aldosterone has a minor effect • potassium excretion is regulated at the distal nephron • K excretion = urine flow rate x urine [K] Factors which Increase Renal K Loss • hyperkalemia • increased distal tubular urine flow rate and Na delivery (thiazides and loop diuretics) • increased aldosterone activates epithelial sodium channel (eNa C) in cortical collecting duct. NP 11) to estimate expected change in serum Na with 1 Linfusate • aim to to lower [Na] by no more than 12 mmolJL in 24 hours (0. and congenital Diagnosis • urine osmolality inappropriately low in patient with hypematremia (UDIIn <300 mOsm!kg) • serum vasopressin concentration may be absent or low (central). penicillin. "free water" is water without sodium • encourage patient to drink pure water..Toronto Notes 2011 Treatment of Hypovolemic Hypernatremia mectrolyte Disorders Nephrology NP13 • general measures for all patients • give free water (oral or IV) • treat underlying cause • monitor serum Na frequently to ensure correction is not occurring too rapidly • if evidence of hemodynamic instability.5 mmol/L/hr) • must also provide maintenance fluids and replace ongoing losses • rule of thumb: give 2 cc/kglhour of free water to correct serum [Na] by about 0.140) [TBW = 0. salicylate . hypokalemia. • collecting tubule is impermeable to water due to absence of ADH or impaired response to ADH • central defect in release of ADH (central DI) or renal response to ADH (nephrogenic DI) Etiology • central Dl: neurosurgery. and therefore lower urine volume: results) Potassium Homeostasis • approximately 98% of total body K stores are intracellular • normal serum K ranges from 3. then replace water deficit using D5W DIABETES INSIPIDUS (DI} . COIT8Ction of 181\1111 INal in hypernalremia snould not exceed 12 mmoVl/241n..5 x wt(kg) for women] 140 • replace free water deficit. trauma.

TTKG =transtubular potassium gradient =(UJJPJ/(Uoom/PomJ 6. and rarely paralysis with eventual respiratory impairment • arrhythmias occur at variable levels of K. begin treatment immediately 2. hypomagnesemia.. emergency measures: obtain ECG.. if potentially life threatening.aldoslllrnne mineralocorticoid [Cushing's.0-3. + llyparllln•i¥11 • 1" hyperakloslllrnnism {e. and constipation • if severe: arrhythmias.Bartter's {loop of Henle dyafunction: furosemide-lib effect) .-ldlou {1rue hemll1llria) • Hemoglobin {hemolyiil) + U.lle • DKA • RTA Variable • HypoMg • Vomiting/NG TTl(G = Trant-Tubolllr KGraclent Figura 9.g Conn's syndrome) • 2° (renovascular disease. rule out transcellular shifts ofK as cause ofhypokalemia 3. serum [Mg] Hypokalemia DICQIIsedlnhlq • Limited diatary in!Bb • Cll. more likely if digoxin use. may also assess plasma renin and aldosterone levels. Ji1-egonills {v. ECG Changes in Hypokalemia .lls Mlllllbolic alkalosis {IQH axchanqa across call mambrana) I111LJin {llimulatus NII/I( AlPBse) Catacholaminas.. generalized weakness. >30 mEq/day TTKG >7 IIBnallaaaa CheckBP + into C.. An Approach to Hypaklllamia Signs and Symptoms • usually asymptomatic. increases risk of digitalis toxicity Figura 10.. myalgia. fatigue. thaophylline (stimulllle Na/K All'ase} Tocolytic agents Uptake into newly forming cells -Vitamin 811 injections i1 pernicious anemia Colony stimulating factors 'I' WBC production + I I • . or CAD • ECG changes are more predictive of clinical picture than serum [K] • U waves most important (low amplitude wave following aT wave) • flattened or inverted T waves • depressed ST segment • prolongation of Q-T interval • with severe hypokalemia: P-R prolongation.5 mmol/L) • nausea. 24-hr K excretion or spot urine K 5.5 mEq/L Approach to Hypokalemia 1. hydrnchloruthilllide) ranall01111 duatll hyparaldoslllrnnism and mlllllbolic alkalosis) • Inherited renal tubular lesions . vomiting. muscle cramps.Gitelman's (disbl convoluted tlb. wide QRS.NP14 Nephrology mectrotyte Disorders Toronto Notes 2011 Hypokalemia • serum [K] <3. check BP and acid-base status 7. I I Hypo.. Aclclamlc • . Alhlemic • Diurulics (furosemide.martives • Vilous adenoma • u. muscle necrosis. exogenous) + .or -mota•ivl Check acid bll$8 sbdus .. assess contribution of dietary K intake 4. <25 mEq/day TTKG <3 + ® KG I • • • • • • 1 Gllo-• • Diarrhea • L.ntolin )..y ingll&lion + lnc. reni1 tumour} • Non. arrhytlmtias. if renal K loss. particularly when mild (3.

ad lntaq Cellular Releue Intravascular hemolysis Rhabdomyolysis Insulin deficiency Hyperosmolar states (e. hypaaldosteranism o Associated with DM2. KClliquid solutions • IV . NSAIDs.g. HIV Adrenal insufficiency ol any cause (e. correct with extreme caution • risk of hyperkalemia with potassium replacement especially high in elderly. rule out factitious hyperkalemia. AIDS.usually KCl in saline solutions. low aldollerone) Decrusad Aldllltlrona Praductian (nonnal aldolterone) ldecraued tubular raspo••l K-sparing diuretics o Spironolactone • Amiloride • Tri1111terene Hyporeninemic.. amiloride) can prevent renal Kloss • restore Mg if necessary Hyperkalemia • serum [K] >5.. palpitations.Toronto Notes 2011 mectrolyte Disorders Nephrology NP15 Treatment • treat underlying cause • if urine output and renal function are impaired. max.0 mEq!L Approach to Hyperkalemia 1. Causes of Hyperkalemia hctitious lnc. paresthesias. 40 mmol/L via peripheral vein. and any K retaining medications 4. metastatic can car) • ACE inhibitors o AngiotEnsin II receptor blockers • Heparin • Congenital adranal hyperplasia with 21-bydroxylase deficiency o Other K-splling drugs • Pantamidi'la • Trimethaprim o Cyclasparine. emergency measures: obtain ECG. muscle stiffness. and hypoventilation • impaired renal ammoniagenesis and metabolic acidosis • ECG changes and cardiotoxidty (do not correlate well with serum [K]) • peaked and narrow T waves • decreased amplitude and eventual loss of P waves • prolonged PR interval . infusion 20 mmo!Jhr o K-sparing diuretics (triamterene. diabetics. spironolactone. potassium repletion (decrease in serum [K] of 1 mEq is very roughly 100-200 mEq of total body loss) • oral sources. especially if transcellular shift caused hypokalemia • if true K deficit. calculate TTKG = (Uk/PJ<)/(U0 om/P01111) • TTKG <7 = decreased effective aldosterone function • TTKG >7 = normal aldosterone function Table 6. hyperglycemia) Matabolic acidosis (axcaptfor katD-and lactic acidosis) Tumour lysis syndrome Drugs o Beta-blockers • Digitalis avardase (blocks NII/XATPase) • Succinylcholine Decreased GFR o RIJ1al failure • Law effectiw circulating volume • NSAIDs in renal insufficiency Nonnal GFR but hypoaldasteronism (saaTable7) Sample hemolysis* Sample taken from vein whera IV KCI is ruming Prolonged use af tourniquet Leukocytosis (eldreme) ThrombocytDsis (extreme) Diet IVKCI KCitabs substitute 'Most camman Tabla 7. Addison's diseasa. estimate GFR (calculate CrCl using Cockcroft-Gault) 6. if life threatening begin treatment inunediately 2. hold exogenous K. Causes of Hyperkalemia with normal GFR Dacrusad Aldostarona Sti11U. if normal GFR. chronic interstitial tablets (K-Dur-). 60 mmolJL via central vein. repeat blood test 3. (low renin. and patients with decreased renal function • beware of excessive potassium repletion. ascending paralysis. assess potential causes of transcellular shift 5. areflexia.. tacrolimus o Pseudohypoaldosteronism (rare inherited tubular disardnl Signs and Symptoms • usually asymptomatic but may develop nausea.g. avoid dextrose solutions (may exacerbate hypokalemia via insulin release) • max. muscle weakness.

add Ca gluconate to above Tnilllllenl of Hypllllcelemll SEE BIG KDROP SEE . Protect the Heart • Ca gluconate 1-2 amps (10 mL of10% solution} IV • antagonizes cardiac toxicity of hyperkalemia. lasts 1-2 h • monitor capillary blood glucose q lh because of risk of hypoglycemia • can n:peat every 4-6 hours • NaHC03 1-3 amps (given as 3 amps of7. inadequate compensation means there is also respiratory acidosis..NP16 Nephrology mectrolyte Disorders/Add-Base Disorders • widening of QRS and eventual merging with T wave (sine-wave pattern) • AVblock • ventricular fibrillation. asystole Toronto Notes 2011 .5 mg IV • onset of action 30-90 min.5 and 7.. life threatening hyperkalemia unn:sponsive to therapy) Acid-Base Disorders • acid-base homeostasis influences protein function and can critically affect tissue and organ function with consequences to cardiovascular. .Ka. no ECG changes: add insulin to above n:gimen • [K] >7.main benefit may be the diarrhea it causes) plus sorbitol PO to avoid constipation (must ensure that patient has a bowel movement after resin is administen:d ) • Kayexalate• enemas with tap water (not sorbitol enemas as they can cause colonic necrosis) • dialysis (renal failun:. in metabolic acidosis. Dialysis 1.5% or 8. and controversial how much K is actually n:moved .xaim11 DIOP.0 and/or ECG changes: first priority is to protect the heart. Shift K into Cells • regular insulin (Insulin R) 10-20 units IV. drives K into cells in exchange for H • (Ventolin•) in nebulized form (dose= 2 cc or 10 mg inhaled) or 0.Calcium gluconata BIG. overcompensation means there is also respiratory alkalosis ... 1 2 3 4 5 In patients with dilbetes and increued [K+] and hypervfycamia.. or if patient is symptomatic • tailor therapy to severity ofincrease in [K] and ECG changes • [K] <6. Normal T W11W Peaking T W11W Paaksd 1 g Figura 11. increase the loss ofK via urine and/or GI tract (see below) • [K] between 6.. protects cardiac conduction system.g. with 1-2 amp DSOW (give DSOWbefon:insulin) • onset of action 15-30 min. often jUI! giving insulin to mtore euglycamia is sufficient to correct the hyperkalemia. transient effect. n:spiratory. metabolic and CNS function • see Respirolo!O" R5 for mon: information on respiratory acidosis/alkalosis • normal concentration ofHC03 = 24 mEq!L • normal pC02 = 40 mmHg • each add base disorder has an appropriate compensation • inadequate compensation or overcompensation indicates the presence of a second acid-base disorder • e. lasts 30-60 minutes 2. Bicllb. Glucosa I. Enhance K Removal from Body • via urine (prefern:d approach) • furosemide mg IV). Insulin.0.5 and normal ECG • tn:at underlying cause.4% NaHC03 in lL D5W) • onset of action 15-30 min. may need IV NS to avoid hypovolemia • fludrocortisone (synthetic mineralocorticoid} if suspect aldosterone deficiency • via gastrointestinal tract • cation-exchange n:sins: calcium resonium or Kayexalate• (increasingly falling out of favor as they bind Na in exchange for K. stop K intake.Diuretics.B·IIQDnist. ECG Changes in Hyperkalemia Treatment • acute therapy is warranted ifECG changes are present. . stimulates Na/K ATPase • caution if patient has heart disease as tachycardia may result from this high dose ofbeta2 agonist 3. no effect on serum [K] • onset within minutes.

Olmoillr Gap = mea&ured OIITiolality . OR another cause of acidosis plus ethanol ingestion UHful EqudDn• 1. Calculate plasma anion gap (PAG) • PAG = Na. thiamine deficiency. Ketoacidosis • diabetic • starvation • alcoholic (decreased carbohydrate intake and vomiting) 3.Type B: failure to metabolize normally produced lactic acid in the liver due to severe liver disease.Toronto Notes 2011 Acid-Due Disorders Nephrology NP17 Reepiratury acido•i• Acute: 1' 10 PCO.piratury alludosi• Acute: ".metabolized to formic acid • ethylene glycol (toxic to brain and kidneys). range 10-14 • PAG can be altered by plasma albumin level: for each 10 giL fall in albumin. then: 1.. lower baseline PAG by 3 (e.g. = ". requires carbohydrate malabsorption (e. a.Glycol Lactic Acidosis . = ". excessive alcohol intake.5 HCO. " + 2. = 1' 3 HCO.. lncreaJed PAG Metabolk Acidosis (4 types) 1.metabolized to oxalic acid (envelope shaped crystals in urine) • salicylate 4. short bowel syndrome)..glycol Salicylstes or ASA ICARMEL Ketoacidosis lllnal Failur.g. Toxins • methanol (toxic to brain and retina.2 HCO. PAG = [Na] .Type A: due to tissue hypoperfusion (any cause of shock). Lactic acidosis (2 types) • L-lactic acid . Evaluate compensation (Figure 12) . Metlllnol Ethyl. consider: methanol poisoning. there is a coexisting non-AG metabolic acidosis • if increase in PAG > decrease HC03.10 PCO.calculated osmolality • calculated osmolality= (2 x Na) + urea+ glucose (all units are in mmolJL) • normal osmolar gap < 10 • if gap> 10. = 1' 1 HCO. Figure 12. or metfonnin accumulation (metformin interferes with electron transport chain) • D-lactic add: rare syndrome characterized by episodes of encephalopathy and metabolic acidosis. An Approach to Acid-Baaa Disordars Metabolic Acidosis Identify Main Disturbanc). ischemic bowel.[HC01-l (nonnal range = 10·141 2.mlllolic Aeidoli• MUDPILES Metlllnol Uremia Dillbetic/alcoholic/llarvation katuacidosis PII'Bidehyde lsopropylalcohoV11011 Lactic scidosis Ethyl. diminished colonic motility and impaired D-lactate metabolism 2. expect PAG = 6) 3. If PAG elevated. Advanced renal failure (i.[CI] . Qlranic: ".calculided osmolality (normal < 1Dl 3. and renal disease leads to impaired bicarbonate production) Ill:' C. Chronic: 1' 10 PCO. is plasma [albumin]= 20 giL.(HC03 + Cl) baseline= 12. .10 PCO. Calculated Osmolality = 2[Na] IUreal + (Glucose] Etiology and Pathophysiology 1.e..a very low GFR causes anion retention. there is a coexisting metabolic alkalosis 4. a carbohydrate load.. compare increase in PAG with decrease in HC03 • if increase in PAG < decrease in HC03. ethylene glycol poisoning. serum Cr increased at least Sx above baseline . Calculate osmolar gap • osmolar gap = measured osmolality.•n of lncrnMd Anian Glp M. can cause blindness and brain death). profound hypoxemia . colonic bacteria that produce D-lactic acid..

. 1' HCD. lll<CI'IItion. oxalate.of Non-Anian Glp Mmba6c Allillosil HARDUP Acetamlamide It' RTA* Diarrhea* Urehlroenteric fi5tulll Pancreaticoduodenal fistulil increased *Most Common 2. NH 4) in urine • if <0.llkalosisl • Cirrhosis • ASA overdcn. + II + Salina resislllnt ICheck blood Hyperten. therefore increased [HC03 ] • post-hypercapnia: renal compensation for respiratory acidosis is HC03 retention.g. Salina 1111ponsiva + + I I I .e. NaHCO.I I I I . suggests problem is lack ofNlf. suggests adequate Nlf. poorly tolerated transition from overly aggressive alkali loading. N•llllllllnllin • Exogenous alkali • S8\111'8 hypokalemia • Bartter's..t in urine (likely nonrenal cause: diarrhea) • if >0. Normal PAG Metabolic Acidosis (Hyperc. drag• Na -+ 1' Nil exctlltion Figure 13.g.ic Acidosis) • diarrhea (HC03 loss from GI tract) • RTA (renal tubular acidosis) • type I RTA (distal): inability to fully excrete H load as Nl4 therefore accumulates • type II RTA (proximal): impaired HCO. decreased ECF volume.. sulphate) • note: lactate and ketoacid anions can be metabolized to HC03 • risks of sodium bicarbonate therapy • hypokalemia: causes K to shift into cells (correct K deficit first) • ECF volume overload: Na load given with NaHC03 . . U0 <20 mEq/1. milk alkali syndrome • diuretics (contraction alkalosis): decreased excretion ofHC03.t in urine (e... . especially with very low pH (<7) • no metabolizable anion (e. An Approach to Metabolic Alkalosis . salicylate.----------------.g...g..e • Sepsia Metabolic Alkalosis Pathophysiology • requires initiating event and maintenance factors • initiating event • GI (vomiting. rapid correction of respiratory disorder results in transient excess of HC03 • maintenance factors • volume depletion: increased proximal reabsorption ofNaHC03 and increased aldosterone • hyperaldosteronism (1 o or 2°): distal Na reabsorption in exchange forK and H excretion leads to HC03 generation. distal RTA) . .Cl • calculation establishes the presence or absence of unmeasured +ve ions (e..g. reabsorption • type IV RTA: defective ammoniagenesis due to decreased aldosterone... NG tube) or renal loss ofH • exogenous alkali (oral or parenteral administration). Gilelm1111's Nate: cannot use tD assess volume st11t11s i1 presenoe of alkalemia: 1' HCO. incraesad PAG metabolic acidosis + resp. can exacerbate pulmonary edema • overshoot alkalosis: abrupt. use Urine Anion Gap= (Na + K) .ivll • 1• hyperaldosteronism • 2° hyperaldosteronism • Cushing's syndrome + + I I . <8 mmol/L.NP18 Nephrology Add-Due Disorders Toronto Notes 2011 c . stimulus for ammoniagenesis and HC03 generation I Metabolic alkalolis (1' pH. hyporesponsiveness or hyperkalemia • to help distinguish renal causes from non-renal causes.hlorem. aldosterone also promotes hypokalemia • hypokalemia: transcellular K/H exchange. NP15) • consider treatment with exogenous alkali (e....) if: • severe reduction in [HC03 ] e. Pilar dlulllllcl 11 Post-hypercapnia • Volume depleted I I Volume depleted I I Normal ECF vohne I + + I Diundic .a Mi1111d Dilar*rwlth NRr Narmal pH (i. formate. partial conversion of accumulated organic anions to HC03 and persisting hyperventilation 3 Clinical Sc-rlosdml'roll. Treatment of Metabolic Acidosis • treat underlying caus • insulin for DKA • restore tissue perfusion for 'l}rpe A lactic acidosis • ethanol + dialysis for methanol or ethylene glycol poisoning • alkaline diuresis ± dialysis ifASA overdose • correct coexisting disorders ofK (see Hyperkalemia. U >20 mElJIL 0 IAssess volume atatus + I + Gil•• Vomiting • NGtube II ...

increased tissue breakdown) • Ca (rare. straining. atherosclerosis GI: peptic ulcer disease. Volume Overload • due to increase in total body Na content • signs: weight gain. and possibly K-sparing diuretic • saline sensitive metabolic alkalosis (most common) • treabnent: volume repletion • ±carbonic anhydrase inhibitor (e. acetazolamide) to facilitate loss ofHC03 in urine • saline resistant metabolic alkalosis • ECF volume normal or high • usually aldosterone or glucocorticoid excess • remove source of aldosterone or glucocorticoid ± spironolactone Renal Failure Presentation of Renal Failure • signs and symptoms depend on acuity of onset.breathing cannot be stopped. happens during recovery phase after rhabdomyolysis-induced acute kidney injury or in settings where hypercalcemia contributes to renal failure. pericarditis. such as in multiple myeloma or sarcoidosis) • uricacid • low • Na (failure to excrete excessive water intake) • Ca (decreased Vit D activation. somnolence. pleuritic chest pain. decreased taste GU: irritative and/or obstructive urinary tract symptoms (e. decreased libido • MSK: nocturnal muscle cramps. hypoalbuminemia) • HC03 (especially with sepsis or severe heart failure) 3. muscle weakness • skin: pruritus. severity of insult. hyporeflexia PNS: "glove and stocking" type sensory neuropathy. hematuria. estrogen. stupor. Electrolyte Abnormalities ·high • K (decreased renal excretion. replenish K and Mg deficits. treatment of reversible disease process 1. increased insulin resistance • dermatologic: pruritus. ecchymosis. pericardia! friction rub GI: anorexia. bleeding tendency (platelet dysfunction).g. yellow discolouration Complications CNS: decreased LOC. LH • metabolic: • renal osteodystrophy: secondary increased PTH due to decreased Ca. see Figure 12) Treatment • treat underlying cause • correct underlying disease. seizure CVS: cardiomyopathy. gastroduodenitis. CHF. nausea and vomiting. frequency. causing the manifestations of uremic syndrome Signs and Symptoms of Renal Failure • • • • • CNS: headache. progesterone • increased FSH. high P04 and low active vitamin D • osteitis fibrosa cystica • hypertriglyceridemia. wrist or foot drop CVS: shortness of breath.g. infections endocrine: • decreased testosterone. accelerated atherogenesis • decreased insulin requirements. amenorrhea. pulmonary or peripheml edema 2. adaptation to nephron loss/ dysfunction. Uremic Syndrome • retention of urea and other metabolites as well as deficiencies of hormones. AVM hematologic: anemia. asterixis. increased tissue breakdown) • P04 (decreased renal excretion. palpable bladder (if bladder problem has contributed to renal failure) • endocrine: weight loss. confusion. hyperphosphatemia. hematoma. nocturia). arrhythmia.Toronto Notes 2011 Add-Base Disorders/Renal Failure Nephrology NP19 Evaluate compensation (identify co-existing respiratory acid-base disorders) • hypoventilation (an upper limit to compensation exists. urgency. H1N. lethargy. pallor. calciphylaxis (vascular Ca deposition) • • • • • .

.. crystals • urinary indices • Foley catheterization (rule out bladder outlet obstruction) • fluid challenge (ie. . An Appro1ch tD Acute Kidney Injury llri1l (NI] <2ll >40 <I >40 IIi¢ <2ll <350rnllslrwt8H..ATN • WBC-AIN • RBC-GN Cl11111 to PDit-B-1 EtiDIIIIIt' • Known solitary kidney • Olderman • Rucunt retroperito1181111 surgury • Anuria •Palpablubladder • Ultrasound shows hydronephrosis .r • Vasculitis • Malignant HTN • Thrombotic microangiopatily • Cholastarolamboli • Large vessel disease . incrtuad HR. . Cr. • NSAID5 1 "•••nil + 1 . hydronephr06is.P >I\ Approach to AKI Investigations -------------------------------------------- llrileiCTWAI FeNa llrileOSIIIIIIIily >500 • blood: CBC. Definition Thu 2 mOll: common CIIUIIIII of acute kidney injury in hospilllized patients 1111 prerenal1120hlmia and acubl tubular IIICrosis. urea (think prerenal if increase in urea is relatively greater than increase in Cr). Pra-rnll fro11 Ani Figure 14. preliminary measures • pre-renal • correct prerenal factors: optimize volume status and cardiac performance.. Ca. hold ACEI/ARB • renal • exclude reversible renal causes: die nephrotoxic drugs. C&S. strictures) vs. stenting 2. fluid bolus to rule out most pre-renal causes) • imaging: abdo U/S (assess kidney size. • Urina ollllllllllli1y >500 mOsmfkv • Fractional uxcrvtion af Na <1'lr. electrolytes..)-----------------.. treat complications • fluid overload • NaCl restriction • high dose loop diuretics • hyperkalemia (refer to Treatment of Hyperkalemia... lllypavolemill I PDit·rlllll [aspac:ly if solitary kidney) I I I Neurogenic I Diaordared Autoregulation • ACEVARBs • Calcinuurin ilhibitors [cydosporina. treat infection. polyuria) . CI111111D Pn_.. Cr) • abnormal urine volume (anuria. definitive therapy depends on etiology • note: renal transplant is not a therapy for AKI . • abrupt decline in renal function leading to increased nitrogenous waste products • formerly known as Acute Renal Failure (ARF) Clinical Features • azotemia (increased BUN. casts.. Cllllll to Rlnal Etiology • Appropriate dinical contaxt • Urinalysis positive for casts: • Pigmented g111nular. P04 • urine volume. post-nmal obstruction) • indications for renal biopsy • diagnosis is not certain • prerenal azotemia or ATN is unlikely • oliguria persists >4 weeks Treatment 1.. Absalubl • Humorrlulgu • Glloss • Skin loss • Ranalloss + . Dllfwentl.NP20 Nephrology Acute Kidney Injury (AKI) Toronto Notes 2011 Acute Kidney Injury (AKI) ·)-----------------. pigmenlld gnnullrCIIII 'lllacull. .. R&M: sediment.lllll Elialllgy • Clinical: Dlc111uad BP. Effective • Low cardiac output • • Sapsis •3rdspacing + Allltomic • Uratar • Bladder • U1'8111111 . IGiom••ll.. oliguria. functional (neuropathy) • treat with Foley catheter. nephrostomy.. lllrn. lrld orthostatic HR and BP chlngas • I11C11181ad [u11a] > > lncraaad [Cr] • Urine [Na] <10-20 mmoVI.. NP16) • adjust dosages of medications cleared by kidney 3. indwelling bladder catheter. tacrolimus) • Hypen:lllcemill . I'N-nlll «rN Normal RBC. and optimize electrolytes • post-renal • consider obstruction: structural (stones.mber that p111rt1nal fliiUrtl Cllrll&ad to ATN.r lllnt1111titial I I Tu•ular I • GN • AIN • ATN ..

diselle.4% lncidenc1 llf Etlalagilla llf Chronic Kidney Dii-ICm) Diabetes HypartBIIIion Interstitial nephriti&' Cystir/HirediiB!y/Congenital SecondllfY GNI\Iasculitis GlomenJonephrilis OtharJ\!nknown 9.Toronto Notes 2011 . liAS blacbdl raOOcad IIIII rilk al hllllllai1111 in peliellts with diablli: Pllilnls with no!Miilbelic CKD. Cltill!lchlnnal bbclan 11111 ot111r ll'llillyparllllsNe-bllld thenvfl theavt illhe slid\'._ . l'llillllwith a.Dl(. . target Hct 33-36% • DDAVP for prolonged bleeding time if patient has clinical bleeding or invasive procedures • ACEI for hypertension (target 130/80 or less).dy .e. antacids) • medical • treatment of secondary hyperparathyroidism • calcium supplements (e. . 42. llllldti:Twanty-!Mirilll{N = 457!iiiWIIII incblld....._: RAS blocbde llduced CV aull:omes in dilbatic nepllropllhv • Will u no!Miilbelic em ..Acute Kidney Injury/Chronic Kidney Disease (CKD) Nephrology NP21 Prognosis • high morbidity and mortality in patients with sustained AKI and multi-organ failure Chronic Kidney Disease (CKD) Definition • abnormal markers (Cr.1% 2. 3._: To Multi th1 roll alllrin IIQiallnlin s....lm Management of Chronic Kidney Disease • diet • protein restriction with adequate caloric intake limits endogenous protein catabolism • K restriction (40 mmol/day) • Na and water restriction • P04 restriction (1 gld) • avoid extra-dietary Mg (i... urea) • GFR <60 ml/min for >3 months or • kidney pathology seen on biopsy or • decreased renal size on U/S (kidneys <9 em) • clinical features of chronic kidney disease • volume overload and hypertension • electrolyte and acid-base balance disorders (e. l'lllbilllil: A sa...NIJihrotoxins: IMiid IIIPhnrtaxic drugs [ASA. C..7% 4. . ijdnly IIIII_.Dstaodystrophy: giva il. .Electrolytes: monitDr K P.!1% 26. .. liAS bloc:bde dectelsed CV oulcGme CGirj1llld ID llllllfnll111npy.Low-nitrogen diet E . .4% Table 8.Hypertansion NEPHION II . decreasing PTH) • sodium bicarbonate for metabolic acidosis • erythropoietin injections (Hct <30%) for anemia.. . metabolic acidosis) • uremia .g. llril. Clnli-•o.. 2002) Definition Stqe1 GFR <!:90 Ncrmal or increased Gm Mild decrease in Gm Modaral9 decrease in GFR Moderate decrease in GFR S8\111'8 decr88SB in GFR S1qe2 60-89 45-59 30-44 S1qa31 Stqe3b Manqlllllld llf Complicllti. 155:791-1!5 .-..25-dibydroxy-vitamin D) if hypocalcemic • sevelamer (phosphate binder) if both hypercalcemic and hyperphosphatemic • vitamin D analogues are being introduced in the near future • cinacalcet for hyperparathyroidism (sensitizes parathyroid to Ca. TUMS•) treats hypocalcemia when given between meals and binds phosphate when given with meals • consider calcitriol (1..llf em Slqe4 Stqe5 15-29 End &!age renal di&ea&e < 15 (or dialy&i&l N . peritoneal dialysis) • renal transplantation between meals Ito increased Cal and with mills (1D bind and decreased POJ N . loop diuretics when GFR <25 rnUmin • statins for dyslipidemia • adjust dosages for renally excreted medications (avoid nephrotoxic medications) • dialysis (hemodialysis...pH: mebbolil: acidosis H . gentamicin) end adjust doses of renally excreted medications AmllettrJZ118.. Stages of Chronic Kidney Disease IKIDOQI. .. .!1% 7. Can1llrld ID plabo.: Rlndomillld I:GIIbGied lrilll111d llllly!ld CV CIUII:omll il pDIIII Mdl cllanic ijctluy diMIIIICXIIVprgOOJril lllllad with RAS inhibillnl blockll$i.llerin lfiQiallnlil IIWiflm bb:kldt-buld 1hlllpyMil pllceba lllllllllllfnll (bell-lllocklr.i: lliUir ma.g..RBCs: m1111111ge anemia with arythropoiatin D .ys1lm (liAS] bDcUde in ClnliJvuaHr cv IIUb:llrlll in pllilnbi with c:lmlnil. ...

.Jpia Ordara !MUST BE INDIVIDUAUZED) . three times per week).0 mg!d.Z5 • HC!la 40 3. hypotensian. if not acandidll:e far diaysis.5 Indications for Dialysis in Chronic Renal Failure • absolute indications • volume overload unresponsive to medication • hyperkalemia unresponsive to medication • severe metabolic acidosis unresponsive to medication • neurologic signs or symptoms of uremia (encephalopathy. pericarditis. Peritoneal Dialysis VI. .S.. 2L or to target dry weightI • Na 140 lean budjusted by stilling II: 155 and "rampilg" down to Serum K Dilllysllhl 4-6 1.5 minimize cmnpingl • K (based an serum (KJI 3. the serum Cr level quoted as >350 IUDoliL (>4.. 4h 3 1irnaflwk or 2h daly) • Q Blood Flow (Max 4011 cc/min) • Ultnlfitration (e...5 • Ca I.g.g. four exchanges per day) or cyclic (CCPD.NP22 Nephrology Renal Replacem.L) or BUN >36 mmol/L (100 mg/dL. Wh•ta lnitiltll DIALYSIS or full [1 DOD Ulh]) • IV fluid to support BP {e. continuous {CVVHD) or sustained low efficiency (SLED) • peritoneal dialysis: peritoneum acts as a semipermeable membrane similar to hemodialysis filter • advantages: independence. no renal function Success depends on presence of residual renal function Residual renal function not as important Ftom: Nlllionll . . or within 1 year of an anticipated need • refer patients with chronic renal disease to a nephrologist early on to facilitate treatment and plan in advance for RRT Tabla 9.4 Z.oclllian Slow Fa8t Hospital (usually) Horne OsmDiic IJI!SSUre via dextrose dialysate Concentration gradient and convection Peritoneum Indwelling catheter il peritoneal cavity lnfactian at cathatur sita Bacterial peritonitis Melabolic effects of glucose Difficult to achieva ade!J!ata clearance il patients with large body mass CrCI <ZO ml/rnin • Educat8 patient regarding dialysis. collapse) Bactenmia Bleeding due to hepain Hemodynamic rtrass of axtracorporaal circuit Disequi!ibrilm syndrome (headache. ce111bral adama.. co-morbidities. better rehabilitation rates • available as continuous ambulatory (CAPD.L).. Type (e. • Haw tD Wfb Di. in order to avoid dialysis kidney func:tion Young. residual renal functian Bed-bound. FBDI un111 >35-50mM • length le. nausea. ligh functioning.g.lopaltly. . clinical picture also important) • relative indications • anorexia • decreased cognitive functioning • profound fatigue and weakness • severe anemia unresponsive to erythropoietin • persistent severe pruritus • restless leg syndrome • hemodialysis: blood is filtered across a semipermeable membrane removing accumulated toxic waste products.q. Hemodialysis • Heparin [none. IWSI Rate l. muscle cramps rellll!d to soluWwaterflux over short time) NOTE • Cockcroft-Gault equation (or Modification of Diet in Renal Disaequatianl should ba used to measure • Monitor far ul"llllic complications • Significant benefits in qllllity of Iife can occur if dialysis started before CrCI <15 mVmin • It is unclaar whether patients who s111rt dialysis early hive inc1111sed survival • A praamptive transplant can ba c0111idarad patient is ttabla.ent Therapy Toronto Notes 2011 Renal Replacement Therapy Dialysis lndlc:llliDna fvr Dilllyaia Hypl!blemia lrafractoryl Acidosis lrulnctoryl VoiU11111 OVIIrkllld 1111fractory) Elevated urea (>35-50 mM) Pericarditis Encephalopathy Edema!pulm01111ryl or Acidosis (rulnctory) Eleclrolylll imbalance lrefractoryl Intoxication (e.. fewer stringent dietary restrictions. solutes.-----------------. neuropathy.g.-----------------. excess fluid (ultrafiltration).g.. makllamngamiiiD far AV fillula CrCI <15 ml/min • Waigh risk lll1d banafill for initialing dialysis CrCI < 1Dml/rnin • Dialysis should be initiated Ultnfillndian Solule Remcml Hythlstatic pressure Concentration gradient llld convection Semi-permeable artificial membrane Line from vessel to artificial kidney Membrane Mlthod Complications Vasculll" accll88 (c!DII.. tight [500 Ullil ... methanol I Overtoad (rulnctory volume ovarkllld) • Pulm-rv edema lhmia • Encephl.5 <3.. and restoring buffering agents to the bloodstream • available as intermittent (e. machine carries out exchanges overnight) • patients with chronic kidney disease should be referred for surgery to attempt construction of a primary AV fistula when their eGFR is <20 mL/min. seizures) • uremic pericarditis • refractory accelerated hypertension • clinically significant bleeding diathesis • persistent severe nausea and vomiting • plasma Cr >1060 IUDOl!L (12 mg!d.

Cancbin: lflllu mlllty1D DlX. lit is iriaricr1D llX. NP32) • chronic allograft nephropathy • early allograft damage caused by episodes of acute rejection and acute peritransplant injuries • immunologic and nonimmunologic factors (HTN... .-----------------. pdenls 46.. l'lliiiD c.n • .511MilllllllfliRe in hllll1l ratialor D1X Vlnlll NHD ralnlce.dergoing LlX venus NHD. . age of donor... Nephrology NP23 CD1111110Diy IJud lmmunDSupprauin Drup Calcinelllin inllillilors • Cyclosporine • Tacrolimus Antiprvlifwmivlt 11111dic.t 5331ive damr lllXJ 1rlnsplad patieals m IIDCbJnll homa dialysis {NHDj l1:3:3111iol or d-.Toronto Notes 2011 Renal Replacement Therapy/Glomerular Diseue ..5 g/1. transplant renal artery anastomosed to external iliac artery of recipient • 1 year renal allograft survival rates . . rise in Cr. Significlri survinl blllefitlor pllierQ _. Kaposi's sarcoma. Signliclnt rnonalty hmnllllia l'llll:tian willlllX 10. Renal Transplantation • • • • • • preferred modality of RRT..tio• • Mycophenolate Mofetil • Azathioprine Other qlllts • Sirolimus • Pnldnisone Complications • leading causes oflate allograft loss: chronic rejection and death with functioning graft • #1 cause of mortality in transplanted patients is cardiovascular disease • immunosuppressant drug therapy: side effects include infections. wu• CIUII mlllbllty Presentation of Glomerular Disease Important Points To Remember • each glomerulopathy presents as one of 4 major glomerular syndromes • acute nephritic • nephrotic • rapidly progressive glomerulonephritis • asymptomatic urinary abnormalities • each glomerulopathy can be caused by a primary disease OR can occur secondary to a systemic disease • some glomerulopathy can present as more than one syndrome at different times 1. best way to reverse uremic signs and symptoms provides maximum replacement of GFR only therapy shown to improve survival in patients with ESRD native kidneys usually left in situ 2 types: deceased donor.73 m 2 /day) • abrupt onset hematuria (microscopic or macroscopic) • azotemia (increased Cr and urea) . llllldlld cola! with Yll'l MIIQII fulluw 141 .ed donor1lllll!ilrt !Maam: l'lirBy aull:anw Noctmll homecliysisverulille Glomerular Disease Terminology of Glomerular Changes • terms applying to a population of glomeruli in the kidney • diffuse: majority ofglomeruli abnormal (>50%) • focal: some glomeruli affected • terms applying to an indMdual glomerulus • global: entire glomerulus abnormal • segmental: only part of the glomerulus abnormal Types of Changes • proliferation: hyperplasia of one ofthe glomerular cell types (mesangial.. ACUTE NEPHRITIC SYNDROME Clinical/Lab Features • proteinuria (but <3. ± fever • de novo glomerulonephritis (usually membranous) • new-onset diabetes mellitus (often due to prednisone use) • cyclosporine or tacrolimus nephropathy (refer to Small Vessel Disease. endothelial.... with or without inflammatory cell infiltration • membranous changes: capillary wall thickening due to immune deposits or alterations in basement membrane • crescent formation: parietal epithelial cell proliferation and mononuclear cell infiltration from crescent-shape in Bowman's space bltdll: No sigricanl dillerence il uvivll • hmrd NHD 11111 DlX. parietal epithelial).lnnlt*nt Nacfllnll " -.. . living donor (related or unrelated) kidney transplanted into iliac fossa. oliguria. new onset diabetes) • CMV (cytomegalovirus) infection and other opportunistic infections usually occur between 1 and 6 months post-transplant • BK virus (polyoma virus) nephropathy can result from over-immunosuppresion and lead to graft loss Anti-lymphocyt• antiiiiDdi• • Thymoglabulin • Ntplru/IJill Tlllfl/llt 20f». hyperlipidemia.. 24:2915-2918 S1udy: illlrolplctiw. post-transplant lymphoproliferative disorder) • acute rejection: graft site tenderness. . quality of graft.n. .. malignancy (skin. 6ftwhile Iwere llllll:l!ed tD 533 dlcnlld daacr lrlnlpiMt (D1X) patilllll . ' ..

.-nlll Mambranoprolifaratiwe Glomeeulosderosis Glomeeulonephrilil Nodular Diabetes mellitus. dipyridamole Treat undBriying controversial cause Steroids The Nephritic-Nephrotic Spectrum • glomerular pathology can present with a clinical picture anywhere on a spectrum with pure nephritic and pure nephrotic syndromes at the extremes (see Figure 15) Naphratic lntarmadiate Naphritic Hamatu.{iBM disaasa PolyariErilis nodosa Wegener's granulomatosis Henoch. malaria. inlecl8d &hunt Gold. protein Cand pnrtein S lost in urineI Change Membranous Glomeruloplllly HBV. Gil Focal S. Protein C and ProteinS urinary losses) • patient may report frothy urine • glomerular pathology on renal biopsy: • minimal change disease (or minimal lesion disease or nil disease) . Edama 4. ACB. &teroids Steroids._• -' Ntphrilie Syndrume PHAROH It' • puffyeyes • smoky urine Proteinuria Hematuria Azutemil RBC euts Oliguria Hypertension Etiology • etiology can be divided into low and normal complement levels (Table 10) • frequently immune-mediated. Oval fat bodies (microscopy( 6.tive GN Crescentic GN • HBV.5 g/1.. .NP24 Nephrology Glomerular Disease • RBC casts and/or dysmorphic RBCs in urine • oliguria • HTN (due to salt and water retention) Toronto Notes 2011 F.e. solid breast. lipiduria 5. with Ig and C3 deposits found in GBM • outcome dependent on etiology Table 10.ria. penicillamine Heroin Recllce BP.. glomeruli appear normal on light microscopy • membranous glomerulopathy • focal segmental glomerulosclerosis (FSGS) • membranoproliferative glomerulonephritis • nodular glomerulosclerosis • each can be idiopathic or secondary to a systemic disease or drug (sirolimus can cause proteinuria without obvious glomerular pathology) Tabla 11.----------------. amyloidosis Secondary CIUSIS DI\IIICIIUIIS Th... Sevn proteinuria (>3. 2.. leukemia. HBV. Etiology of Nephritic Syndrome Low Complement Laval Postinfectious GN Mambranoprolifarativa GN Secondary Cues Nonnll Camplamant Lartl lgA nephropathy Anti. lymphoma. HIV. Hypereoag!Jahle stile (antithrombin Ill. Hypollbumilemia 3.E • Cryoglobulinamia Figura 15. SLE.5 Qfdl 2. . Hyperlipidemia. Tha Spectrum of Glomerular Pathology . SLE. Naphrotic Syndroma Minimal Prwentation -' Nepllratie Syndnlme 1. HCV •SL..i.lipiduria (fatty casts and oval fat bodies on microscopy) • hypercoagulable state (due to antithrombin III.. NEPHROTIC SYNDROME Clinical/Lab Features • heavy proteinuria (> Hodgkin's lymphoma NSAIDs Reflux ne(h'opathy..Schonlein pLrpura Goodpasue's synrtome Slf Endocarditis Abscess or shunt neplritis Cryoglobulinemia . ACEI. obe&ity HCV.73m2/d) • hypoalbuminemia • edema • hyperlipidemia (elevated LDL cholesterol). ACEVARB fur proiBinuria Aspirin. "- [ Protainara FSGS Membranous gtomarulopathy Minimal change Membranoproliferative GN Focal proliferative GN • lgA nephropllhy • ldioplllhic membranoprolifenrtive GN Diffuse prolifen..

amyloid. ASYMPTOMATIC URINARY ABNORMALITIES Clinical/Lab Features • isolated proteinuria (usually <2 glday) and/or isolated microscopic or macroscopic hematuria • isolated proteinuria • can be postural • occasionally can signal beginning of more serious GN (e. mv • urinalysis: RBCs. FSGS. ANA. a diagnosis of exclusion after other possibilities are ruled out Investigations for Glomerular Disease • blood work • first presentation: electrolytes. C3. piuci-immune) 60'J(. p-ANCA..• 15% of cases lmmuno.g. 4.ftuorncence Linear pattern due to lgG 111d SUing Pattem C3 deposition along capillary loops Antibodies against type IV collagen in GBM Primuyc. C4. SLE.GBM m iltld . without proteinuria. benign • benign recurrent hematuria: hematuria associated with febrile illness. proteinuria <2 glday • thin basement membrane disease: usually autosomal dominant.. urea. casts. albumin. VDRL.. depends on underlying cause Tabla 12.. pleural effusion) • renal ultrasound • renal biopsy (percutaneous or open) ifheavyproteinuria or renal insufficiency. WBCs. corticosteroids + cyclophosphamide or other cytotoxic agent + plasmapheresis in select cases • prognosis: 50% recovery with early treatment. RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS (RPGN) Clinical/Lab Features • a subset of nephritic syndrome in which renal failure progresses in weeks to months • crescent formation usually seen on renal biopsy • RBC casts and/or dysmorphic RBCs in urine • classified by immunofluorescence staining (see Table 12) • treatment: underlying cause for postinfectious. IgA nephropathy. %111RPGNC. Cr. Henoch-Sclxlnleil pLrpura s-nduvc. ESR.Toronto Notes 2011 Glomerular Disease Nephrology NP25 3. usually presents after viral URTI • hereditary nephritis (Alport's disease): X-linked nephritis often associated with sensorineural hearing loss. exercise or immunization.. CHF.. cryoglobulins. serum immunoelectrophoresis. RPGN Type II: Immune Complex m•iltlll 24% of cases Granular pattern due to subendlllhelial or subepithelial deposits DllgG and C3 Most often di&sa&e RPGN Type Ill: Non-immUDI lllldillld (i. and cause not obviously diabetic nephropathy • urine immunoelectrophoresis • for Bence-Jones protein if proteinuria present . ASOT (anti-streptolysin titres).. diabetic nephropathy) • hematuria with or without proteinuria • IgA nephropathy (Berger's disease): most common type of primary glomerular disease worldwide.e. fasting lipids • determining etiology: CBC.{lBM disease Goodpasture's disease lgA nephropathy Post-infectious GN. protein • 24-hr urine for protein and CrCl • radiology • CXR (infiltrates. Cryoglobulinemia. RPGN Classification RPGNTpl: AJrti. of cases No immune stailing Vasculitis of glomerular capillaries Idiopathic Wegener's {c-ANCA +vel Microscopic polyangiitis (p-ANCA +vel Cilurv-Stn!uss (ANCA -vel z• to systemic Idiopathic anti. HBV and HCV serology. c-ANCA.

progressive renal insufficiency • prognosis: kidney failure within one year without treatment • therapy: short-term.... Advanced sclerotic lupus nephritis llll.... I month! lhUd Mb Clllsl fallllwing 11111iaian .HIV-assodated nephropathy • histology: focal and segmental glomerular collapse with mesangial sclerosis. nat oocammon IIIII fiiJill Minimal meungilll lupus nephritis dillale: lialrsilllld Rl!llllmlltion in Slf 11M niles far ior9-111nn plliert ll1d !lllft·uvMI complllb1l Mll1boee obleMd in IIIJIHjiabetc 11011-SI. cyclophosphamide.. tenofovir._.. 10% progress to CRF Goodpasture's Disease • • • • • antibodies against type IV collagen present in lungs and GBM more common in 3rd and 6th decades of life. International Society of Nephrology/Renal Pathology Society Classification of Lupus Nephritis 2003 HIV-Assoc:iated Renal Disease 1...IIId -b1dionnybM i11lependent plldic!Nit lbiilyfur cliic:ll M:GmB in 1lllrlpy al nllpllilis 1111 nlld 10 ba inlllplltld in cunjundiln. I + I Cl111111 + CIIIIIV Mesangial proliferative lupus nephritis Focal lupus nephritis Diffuse lupus nephritis lllln... gkJcacolticuids in cumbinltian with IAinQIImllliclcy Ia blln dlmlll'lllrltld on¥ fur c.tmlld ESRil Planning Figure 16.. senrn C3111M only imit8d lbity 10 llflldictllle 1t1P01111i ID IJealmentllld ny be Ullid . onlr • Mllillnll: 1181111 urila !llftilllriB....IIIOCillld with considlrlbil iiurmltion.llll Amyloidosis • nodular deposits of amyloid in mesangium. self-limiting course. 67:1115-B .... . heavy proteinuria.tnt Trelllmtnt Lowest possible Steroids dose of steroids 1111d obsei'VIIIion cytotoxic drugs (consider dialysis or renal 1ransplant with severe disease! • l • + + ClassY Membranous lupus nephritis Steroids (corrtrovarsiall • • l l • • ClllsVI + . HAART Henoch-Schonlein Purpura (HSP) • seen more commonly in children • purpura on buttocks and legs. ACEI.ln short· 1111 medium-term It Ieist lillilll emcy llllll'fll!d wi1h pulse cyclgpholpluidullld • um 1axicny pofile: faiUitu NSpond b.. abdominal pain. prednisone or sulfa may prevent recurrence .. Mil Rlspmtltionl*ng thl melhod al choict. TB. rheumatoid arthritis. "collapsing FSGS" • tubular cystic dilation and tubule-reticular inclusions • clinical features: predominant in black men... .. usually related to amyloid light chain (AL) • presents as nephrotic range proteinuria with progressive renal insufficiency • can be primary or secondary • secondary causes: multiple myeloma. arthralgia and fever • glomeruli show varying degrees of mesangial hypercellularity • IgA and C3 staining of mesangiwn • usually benign._.NP26 Nephrology Glomerular Disease Toronto Notes 2011 Secondary Causes of Glomerular Disease !flyalic (Sill AmlillluD Oir 2008... high dose steroids. men slightly more affected than females present with RPGN type I and hemoptysis/dyspnea pulmonary hemorrhage more common in smokers and males treat with plasma exchange...tich 11'8 h .:In pltienlsMII pralflnM 1up.. indinavir) and other drugs used to treat HIV-assodated infections 2..g..ll neplrii1.ydaphosphm!Haied reQimllll.. v.. Class I and II do nat need lriiBtmant direcllld Ill renal lesions • • • l • • • Cllllll . Ch1191 in imiTM1ilgicl111111 (lllli-dsDNA. advene l.. antiretroviral drugs (e. prednisone Wegener's Granulomatosis • 80% of patients have renal involvement • focal segmental necrotizing RPGN with no immune staining • majority of patients with renal disease are c-ANCA positive • may be indolent or fulminant in progression • vasculitis and granulomas rarely seen on renal biopsy • treating with cyclophosphamide.E patients.h:ts. direct nephrotoxic effect ofHIV infection. malignancy Systemic Lupus Erythematosus (Figure 16) • lupus nephritis can present as any of the glomerular syndromes • nephrotic syndrome with an active sediment is most common presentation • glomerulonephritis caused by immune complex deposition in capillary loops and mesangium with resulting renal injury • serum complement levels are usually low during periods of active renal disease • children and males with SLE are more likely to develop nephritis SLE Claaificatian I ..

fever.g. collecting duct (e. analgesics. plasmapheresis • overall prognosis: 75% renal recovery Infections and Glomerular Disease Shunt Nephritis • immune-complex mediated nephritis associated with chronically infected ventriculoatrial shunts inserted for treatment of hydrocephalus • presents as acute nephritic syndrome with decreased serum complement • nephrotic range proteinuria in 25% of patients Infective Endocarditis • manifests as mild form of acute nephritic syndrome with decreased serum complement • S. sickle cell anemia. heavy metals) • Fanconi syndrome: decreased reabsorption in proximal tubule causing glycosuria. polyarteritis nodosa. hypouricemia • proximal RTA (decreased bicarbonate absorption): Type II RTA 2. membranoproliferative GN Hepatitis C • membranoproliferative GN. aureus is most common infecting agent • treatment with appropriate antibiotics usually resolves GN Hepatitis B • membranous GN. PCKD) • urine concentrating defect • polyuria (nephrogenic DI) 1. proximal tubule (e. multiple myeloma. ACUTE TUBULOINTERSTlTIAL NEPHRITIS Definition • rapid (days to weeks) decline in renal function • 10-20% of all acute kidney injury . Raynaud's phenomenon and arthralgias • at least 50% of patients have hepatitis C • renal disease seen in 40% of patients (isolated proteinuria/hematuria progressing to nephritic syndrome) • most patients have decreased serum complement (C4 initially) • treat hepatitis C.Toronto Notes 2011 Glomerular Diaeaae/Tubulointerstitial Diaease Nephrology NP27 Cryoglobulinemia • cryoglobulin&: monoclonal IgM and polyclonal IgG • presents as purpura.g. phosphaturia. type N RTA 3.g. aminoaciduria. cryoglobulinemia Syphilis • membranous GN Malaria • variable glomerular involvement Tubulointerstitial Disease Tubulointerstitial Nephritis (TIN) Definition • cellular infiltrates affecting primarily the renal interstitium and tubular cells • functional tubule defects are disproportionately greater than the decrease in GFR • classified as acute or chronic Signs and Symptoms • manifestation of disease depends on site of tubule affected 1. distal tubule (e. obstruction) • distal RTA (Type I RTA) • Na-wasting nephropathy • ± hyperkalemia. amyloidosis.

Sjogren's. hyperkalemia. furosemide • infections • bacterial pyelonephritis.mixedessentialcryoglobulinemia • idiopathic Pathophysiology • acute inflammatory cell infiltrates into renal interstitium Signs and Symptoms • • • • • acute renal failure if hypersensitivity reaction: may see fever. cephalosporins 2. uric acid nephropathy • vascular disease: ischemic nephrosclerosis. arthralgia. CMY. hypokalemia. quinolones. tacrolimus • heavy metals (lead. toxoplasmosis. cadmium. Wegener's granulomatosis • immune: SLE. moderate proteinuria and signs of abnormal tubule function Etiology • persistence or progression of acute TIN • urinary tract obstruction: most important cause of chronic TIN • chronic pyelonephritis: due to vesicoureteral reflux or UTI with obstruction • nephrotoxins • exogenous • analgesics: NSAIDs (common). hyponatremia • gallium scan shows intense signal due to inflammatory infiltrate • renal biopsy definitive Treatment • treat underlying cause (e. antibiotics: beta-lactams. renal graft rejection • hereditary: cystic diseases of the kidney. antibiotics if pyelonephritis) • corticosteroids (may be indicated in allergic or immune disease) Prognosis • recovery within 2 weeks if underlying insult can be eliminated 2. allopurinol. brucellosis. acetaminophen • cisplatin. mercury. Legionella. mild proteinuria. CHRONIC TUBULOINTERSTrTIAL NEPHRITIS Definition • characterized by slowly progressive renal failure. cyclosporine. lithium.Sjogren'ssyndrome. Goodpasture's. other: NSAIDs.sarcoidosis. acute allograft rejection. copper). WBC casts.g. leptospirosis • immune • SLE. rifampin. sulfonamides.NP28 Nephrology 'IUbulointerstitial Diseaae Toronto Notes 2011 Etiology • hypersensitivity I. Balkan (endemic) nephropathy . sickle cell disease • others: radiation. skin rash. sarcoidosis. atheroembolic disease • malignancies: multiple myeloma • granulomatous: TB. amyloidosis. Streptococcus. arsenic • radiation • chinese herbs • endogenous • hypercalcemia. stop offending medications. lithium. cryoglobulinemia. EBV. oxalate. hematuria • eosinophils if allergic interstitial nephritis • blood • increased Cr and urea • eosinophilia if drug reaction • normal PAG metabolic acidosis (renal tubular acidosis) • hypophosphatemia. serum sickness-like syndrome if pyelonephritis: flank pain and costo-vertebral angle (CVA) tenderness other signs and symptoms based on underlying etiology hypertension and edema are uncommon Investigations • urine • sterile pyuria.

ToxiM I Endogenous • Endotoxins (bacterial) • Myoglobin • Hemoglobin .Aminoglycosides . decreased Ca.Amphotericin B • Antiviral {cidofovir) • Antinaoplastics . post surgical Skin l011es Gllosses Ranalloues EffvctNII c•culating Valuma Haart failure Uver failure Sepsis Anaphylaxis .Methotrexate • Conti'IISt madill • Haavymlltals • Other . Ca. or administration of nephrotoxic drug • urine: high FEN.g.Fluorinated anaesthstic .. Cr. Etiology of ATN . increased P04> hypoalbuminemia Investigations • blood: CBC. P04> blood gases • urine: R&M. P04) and anemia Findings which Suggest Chronic Tubulointerstitial Nephritis • normal PAG metabolic acidosis • hyperkalemia (out of proportion to degree of renal insufficiency) • polyuria.E1ilylena glvcol YIIMI Dcclulion • large or smal renal artery involvement Figure 17. rhabdomyolysis. electrolyte disturbances) • progressive renal failure with azotemia and uremia • dependent on underlying etiology Treatment • stop offending agent or treat underlying disease • supportive measures: correct metabolic disorders (Ca. nocturia • partial or complete Fanconi's syndrome • urine: mild proteinuria. I • • • • • • • • .. urea. electrolytes.. osmolality • ECG • abdominal ultrasound [ Acute Tubular Nacrosis [ Exogenous • Antibiotics .Caphalosporins .Toronto Notes 2011 Tubulointeratitial DiAease Nephrology NP29 Pathophysiology • fibrosis of interstitium with atrophy of tubules. sepsis. pigmented-granular casts Complications • hyperkalemia: can occur rapidly and cause serious arrhythmia • metabolic acidosis. eletrolytes. acidosis. few RBCs and WBCs. no RBC casts • ultrasound: shrunken kidneys with irregular contours Acute Tubular Necrosis (ATN) -------------------------- Definition • abrupt and sustained decline in GFR within minutes to days after lschemidnephrotoxic insult • GFR shuts down to avoid life-threatening loss of electrolytes from non-functioning tubules Etiology • see Figure 17 Clinical Presentation • typically presents as an abrupt rise in urea and Cr after a hypotensive episode..Cisplatin . lechemia I Clrculldlng Valuma Hemorrhage ilcl. mononuclear cell inflammation Signs and Symptoms • tubular dysfunction (e... I .

cyclosporine on morning of procedure if possible ..dnltion dlnr. Acute Interstitial Nephritis (AIN) • majority due to fenoprofen (60%).ra... psychiatric symptoms and Gl disturbance • papillary necrosis • gross hematuria... ar ll'lll1liiDl on nephropattlf. Acute Tubular Necrosis (ATN) • • • • • incidence of renal dysfunction is related to the severity of acetaminophen ingestion vascular endothelial damage can also occur both direct toxicity and ischemia contribute to the tubular damage renal function spontaneously returns to baseline within 1-4 weeks dialysis may be required during the acute episode of ingestion 5. RENAL ARTERY OCCLUSION • important. vasculitis.xygenase enzyme. potentially reversible cause of renal failure Etiology • abdominal trauma.. dialysis rarely needed 2. may require interval dialysis • short term high dose steroids ( 1 mglkg/day of prednisone) may hasten recovery 3.antagonistic effect of prostaglandins} Vascular Diseases of the Kidney Large Vessel Disease 1.. il para Prevention • correct fluid balance before surgical procedures • for patients with chronic renal disease requiring radiographic contrast: giveN-acetylcysteine 600-1200 mg PO bid day before and day of procedure • use renal-adjusted doses of nephrotoxic drugs in patients with renal insufficiency • isotonic NaHC03 at 3 mlJkg over lh before procedure and 1 ml/kglh for 6h post-procedure if not contraindicated • avoid giving diuretics..62 IOA4·o. embolism. underlying renal disease. naproxen • may be associated with minimal change glomerulopathy and nephrotic range proteinuria • resolves eventually with discontinuation ofNSAID. hypovolemia (diuretics. rudomillld. cirrhosis. Ca:llaon: foi.. extrarenal compression.48-716]). DlhlriiJIIIIIdilnat lflect risk • nep/lruplthy. iiDJIIII.. conlnlllad • largely supportive once underlying problem is corrected • loop diuretics may help manage volume overload and reduce tubular metabolic requirements to allow for recovery (controversial) • consider early dialysis in severe/rapidly progressing cases to prevent uremic syndrome 1lills tl1lt used these igdillllait:lllllrQ!.Nlplnfllhy feaoklopam dopmill.:ln111141 (RR = 0. Vasomotor Acute Kidney Injury (AKI) • normally prostaglandins vasodilate renal arterioles to maintain blood flow • NSAIDs act by blocking cycloo...B8]) llld Thllop1¥i111 (RR = 0.IC8lytcyslain8 il mGI9 IH!Ir. HTN (2° to hyporeninemic hypoaldosteronism) • excess water retention (due to elimination of ADH.. hypercoaguable state. Chronic Interstitial Nephritis • due to excessive consumption of antipyretics (phenacetin or acetaminophen} in combination withNSAIDs • associated with emotional stress.. ACE inhibitors.llnutridl.NP30 Nephrology . CHF.23-1. aortic dissection • kidney transplant more vulnerable .:Todlnna1beelftctive11811al .. Furoserride increesed the risk (RR = lZ1 (1. 11.06]) !Wad thl risk llliiPhroplthy more thin saline IIane. Other Effects of NSAIDs • sodium retention (2° to reduced GFR} • hyperkalemia.49 (0. c... SIUy 0. 11111ii. surgery. Analgesic Nephropathies 1. flank pain. nephrotic syndrome) • clinically: develop prerenal azotemia within a few days of starting NSAID • treatment: discontinue NSAID... thereby preventing prostaglandin synthesis and causing renal ischemia • more common in elderly..148:214-84 .... Tubulointerstitial DiaeaseNuc:ular Diseases of the Kidney Therapy Toronto Notes 2011 AmlnlrriiMid2011. declining renal function • calyceal filling defect seen with IVP .."ring sign" • increased risk of transitional cell carcinoma of renal pelvis • good prognosis if discontinue analgesics 4..... ibuprofen....

or solitary functioning kidney) Investigations • renal arteriography (more reliable but risk of contrast-mediated ATN. kidney is already shrunken. time 111111 C'l Mil. thrombolysis. elevated plasma LDH. nausea. ISCHEMIC RENAL DISEASE (RENAL ARTERY STENOSIS) • chronic renal impairment secondary to hemodynamically significant renal artery stenosis or microvascular disease • significant cause ofESRD: 15% in patients over 50 years old (higher prevalence if significant vascular disease) • usually associated with large vessel disease elsewhere • causes 1. duplex Doppler U/S Treatment • anticoagulation with heparin then warfarin (1 yr or indefinitely. atheroembolic renal disease) • contrast-enhanced CT or magnetic resonance angiography. lrDwntion: I'IR:ullnlaus JMialllrilltion &IIID!gl with 11111i:ll1hiiiiP'f [l.chqll in mel fln:tion af ClllltiJine c:oncermtion _. RENAL VEIN THROMBOSIS Etiology • hypercoagulable states (e. However.g. nd 55 patients 120') BlqE!irmc:ed I pasl-pmcedlllll thenivfalne Risk Factors • >50 years old • • • • • • smoking other atherosclerotic disease severe/refractory HTN and/or hypertensive crises asymmetrical renal size increasing Cr with ACEUARB flash pulmonary edema with normal LV function must establish presence of renal vessel stenosis and prove it is responsible for renal dysfunction duplex Doppler U/S (kidney size. timel. sickle cell • clinical presentation determined by rapidity of occlusion and formation of collateral circulation • acute: nausea/vomiting. significant trauma. IIIII natally. sudden rise in proteinuria • chronic: increasing proteinuria and/or tubule dysfunction Investigations • renal venography (gold standard). age 30-50 NE/Af21J09. percutaneous angioplasty + stent.lllllils. atherosclerosis . :flank pain • leukocytosis. elevated AST.eooplatalat. LDH. surgical thrombectomy llruculn6n-llllllll:ll n. ti11111Dfim mil ewnt.more common in females.n. hematuria. ECF volume depletion. BP Clllb'GQ versus mml lkiiDamu: Prny CIIJbDTIII. vomiting. captopril renal scan) renal arteriography (gold standard) ts• Investigations • • • • • Cancbin: llenllftly lt'I'IKIArizlti carries 5ignificlnt ri5b Mhoullll'( beneil Ill nnl fln:tian oriiCOIIdlly11111:c1n1 cam!Bid1D lllldUifliiiPI' Treatment • medical therapy.g. blood flow): good screening test (operator dependent) CT or MR angiography (effective noninvasive tests to establish presence of stenosis) ACE inhibitor renography (ie. nephrotic syndrome. 31 pltiea111911 llplria:ld 1 plriplac:ldullli:IIJ1IIclllion. extrinsic compression of renal vein. 361:1953-62 S1udy: WIH:arUt 111-bildllll RCT. flank pain. surgical revascularization • little or no benefit if therapy is late Le. fibromuscular dysplasia .Toronto Notes 2011 Vascular Diseasea of the Kidney Nephrology NP31 Signs and Symptoms {depend on presence of collateral circulation} • fever. CI' or MR angiography. especially membranous). !4)af34mantlls l'lliiiii:DpltiiiiiiSinuiiQIJOiwilll l1hllusdllulic Ulosis in lllaut onellflllllllely llld benefit af -ulndion. therapy can be considered to save the opposite kidney if normal 3. percutaneous angioplasty or clot extraction. ALP • acute onset hypertension (activation ofRAAS) or sudden worsening oflong-standing hypertension • renal dysfunction (if bilateral. malignancy (e.a.Iftldilll falaw. Sewndery IUI:1111111 inc:lJde liP. blulll: No •PCIIII dil\lrence il ci1119 af -1 fln:tian inllrwntion lll1d rnedicll1hnpv t:anlral No &igniicant diflaranc:n in IllY HCalldll'( were fOIIId bltweln l'l'mCUirizltio llld medical1hellpy cDIII!ul. RCC).more common in elderly 2. ± rise in Cr. depending on risk factors) .rtar llaoArllly S11101il 2. duplex Doppler studies (operator dependent) Treatment • prompt localization of occlusion and restoration of blood flow • anticoagulation.

TTP.less frequent now due to lower doses of calcineurin inhibitors hifl181t OJIIIIIrUiillie mctiullllas.. ol . largely irreversible nephrotoxicity major cause of kidney failure in other solid organ transplant (e.. ATHEROEMBOLIC RENAL DISEASE • progressive renal insufficiency due to embolic obstruction of small and medium-sized renal vessels by atheromatous emboli • spontaneous or after renal artery manipulation (surgery.. angiography.llft-Gd GfR 12 mollllulllrbnplllllllion... 51.NP32 Nephrology Vascular Diseasea of the Kidney/Systemic Diseases and the Kidney Toronto Notes 2011 Small Vessel Disease 1. wllo did 11111 hm ranll crilil.. Cllcllliln: llwdosB 11croiinls IIIII using ildldion 1llmpNi: in!IJIIO!Uppllllion iiiiiJII111111Jl11111 Systemic Diseases and the Kidney Hypertension (HTN) • • • • HTN occurs in about 20% of population etiology classified as primary ("essential». post-partum renal failure renal involvement more common in HUS than TTP renal involvement characterized by fibrin thrombi in glomerular capillary loops ± arterioles treatment • depends on cause • supportive therapy • TTP: plasma exchange. percutaneous angioplasty) • anticoagulants and thrombolytics interfere with ulcerated plaque healing and can worsen disease • presentation: acute or chronic.. HTN encephalopathy • renal involvement usually occurs early in the course of illness • treatment BP control with ACEI slows progression of renal disease Eslinalld Coc:tr.. microangiopathy. dBIIII occ:uned in 31% ollhB plllilds. HYPERTENSIVE NEPHROSCLEROSIS • see Hypertension..1 IIIII sericu lllvene MID.. l'llilnla: 1645 p!lients scheduled ta receilt 1 ...OOI iqJITiild dole cydolporile Md *oirus. progressive renal dysfunction.1. patiarG wllo inibllv dilllysi5 3'II I Bmon1hs 1111r... CALCINEURIN INHIBITOR NEPHROPATHY • • • • cyclosporine and tacrolimus causes both acute reversible and chronic. II M111 (p<O. reduce dose of cyclosporine or switch to another immunosuppressive drug • chronic: result of obliterative arteriolopathy causing interstitial nephritis and CRF (striped :fibrosis). 1:11111 . visual cohort-wMII follow " of 5-I 0years. DIC. 56... 2. 251:2562-75 s...idl dBcianb iniLoction.Jailn: llllnllcrisis Cll1 M1111111Q11dwhn llypWnliol contraiiiiiMIII ACE illlibibn 2.g. Pllilnll: 145 paliiJU w iducilnxllnnlllllll crisis w11a inl6im111d li&2paaMh IICiari*w.7for IIIIlS I. SCLERODERMA • 50% scleroderma patients have renal involvement (mild proteinuria. llc!Girooslln sbliliclnllv ••Ill r.: Six!y-0111 J*CII1I ol ptltilutlwitl-1 crilil good outx:ons (55 hid 110 diltflis 111d 3418C8ivld 11mPQIIIY dilllvsist onlv 4 rl 1bese pllierQ chronic rellll fliUe 111d ..l) lillndl'd dose cyct)IJIQ!ila. . corticosteroids (splenectomy and rituximab if refractory) • avoid platelet transfusions and ASA .4 mVmin VI. c. .. avoid angiographic and surgical procedures in patients with diffuse atherosclerosis 3. 51.t.. llld dea!iaed ..dJ. heart) acute: due to afferent and efferent glomerular capillary constriction leading to decreased GFR (tubular vacuolization) • pre-renal azotemia • treatment calcium channel blockers or prostaglandin analogs. Farrt.. lie TIICIIhlsn llso I'-d dlclllllld IIIII riiCID 11jel:tion Ill 6 n. ._.. NP32 .q)._!lin IIQiinlt 11 olher 1rms.. 3) lowdou--. "onion skin• hypertrophy of small renal arteries.. THROMBOTIC MICROANGIOPATHY • • • • a spectrum which includes HUS._.. 4 reepeciMiy.4. makes up 90% of cases) or secondary diseases of renal parenchyma or renal vasculature can cause secondary hypertension conversely... HTN) • histology: media thickened. dlcianb iniLoction.dls ll1d 12111111111svs.Mid2lXXl..-m-t dilllysil. 17. hypertension due to other factors can cause renal disease (hypertensive nephrosclerosis) or worsen pre-existing renal disease . labile hypertension. . rftorrimd controlled iill will IZIIIOIIIIfolcJw. ARF. 4) low doll illlhls Mil 4. Thn110 iiiRicl in Mill pllilnt lllrviwl.W*'ilm...: NJrcoplalollfe COrticollaroidiiMd ailher.SidrM hlllhB higlat incidaiiCI of dlll. P". .:1111 TICIGiilllllllm llllowllllignific:lndv hifi!BJ IGI'R It 12IIU!Ihl COIIfllld 111111 111111' M111 (65. need fordBy$is IIIII Ill\' dalllllllllllg paliiJU Mil nlllli crilil . Gllltlrlllln 50' IIIII regimes hild 1lle liMist ill:idea ol dill1helllut . NEJM mrl.. high Cr. fibrinoid necrosis of afferent arterioles and glomeruli • 10-15% scleroderma patients have a "scleroderma renal crisis": malignant liTN (usually within the first few years). volume overload. 5. extrarenal atheroembolic disease support diagnosis (livedo reticularis is a classic sign) • pathology: needle-shaped cholesterol clefts (due to tissue-processing artifacts) with surrounding tissue reaction in small/medium-sized vessels • no effective treatment.nt dilytisw .-onlllllililllls...

tion of vascular intralobular and all&rent arterioles endothelium Clinil:<ll Pll:lure African American. frequent follow-up Can progress to renal fllilure despite patient adherence Lower dBP tu 1Q0. chronic hypertensive disease Uri111lpia Mid pnrtainuria. usually males >55 years. normal urine sedinant Acute aiBVillion in BP (dBP > 120 rrrnHg) HTN encephalopathy Protainuria and hematuria (RBC casts) Therapy Blood pr8S$U18 control. GFR is dependent on A11-induced efferent arteriolar constriction which raises filtration fraction (GFR/RBF) Investigations renal U/S and Dopplers digital subtraction angiography (risk of contrast nephropathy) renal scan before and after ACEI (accentuates difference in GFR) MR angiography (avoid gadolinium contrast if eGFR <30 ml/min because of risk of systemic dermal fibrosis) • gold standard is arterial angiography • • • • Treatment • BP lowering medications (ACEI is drug of choice if unilateral renal artery disease but contraindicated ifbilateral renal artery disease) • angioplasty ± stent • angioplasty for simple fibromuscular dysplasia lesion in young patients • occasionally surgical bypass Renal Parenchymal Hypertension • HTN caused secondary to GN. smokers • fibromuscular hyperplasia: dista12/3 renal artery or segmental branches. diabetic nephropathy. or any other chronic renal disease • mechanism of HTN not fully understood but may include • excess renin-angiotensin-aldosterone system activation due to inflammation and fibrosis in multiple small intra-renal vessels • production of unknown vasopressors. disn. release of aldosterone increases Na and water retention • elevated blood pressure can in turn lead to further damage of kidneys and worsening HTN • 2 types of renovascular HTN (RAS) • atherosclerotic plaques: proximall/3 renal artery. undllllyilg chronic kidllll'f disease. most common cause of secondary hypertension • suspect if • negative family history of HTN • sudden onset or exacerbation of HTN • difficult to control with antihypertensive therapy • epigastric or flank bruit • spontaneous hypokalemia (renin activation from underperfused kidney) • history of diffuse atherosclerosis Etiology and Classification • decreased renal perfusion of one or both kidneys leads to increased renin release and subsequent angiotensin production • increased angiotensin raises blood pressure in 2 ways 1. lack of production of unknown vasodilators. causes generalized arteriolar constriction 2.Toronto Notes 2011 Systemic Diseases and the Kidney Nephrology NP33 Hypertensive Nephrosclerosis Tabla 13. usually young females • patients with bilateral renal artery stenosis are at risk of ARF with ACEI or NSAIDs • when there is decreased renal blood flow (RBF).1 10mmHg within &-24 hour& More aggressive treatment can cause ischemic event Identify and treat underlying cause of HTN Lower survival renal insufficiency develops Prognlllil Renovascular Hypertension ----------------------------- • HTN caused by renovascular disease • 1-2% of all hypertensive patients. AIN. Slow vascular sclerosis with ischemic changes affacting Fibrinoid namsis of arterioles. or lack of clearance of endogenous vasopressor • ineffective sodium excretion with fluid overload .. Chronic vs. Malignant Nephrosclerosis Mlllipnt Nephl"llld_.

. . Diabetes and the Kidney • diabetic nephropathy: presence of microalbuminuria or overt nephropathy in patients with DM who lack indicators of other renal diseases • most common cause of end-stage renal failure in North America • 35-50% ofType 1 will develop nephropathy... .----------------. can progress rapidly to kidney failure oMIDD • deposits of monoclonal Ig in kidney. . liver.NP34 Nephrology Systemic Diseasea and the Kidney/Diabetea and the Kidney Investigations Toronto Notes 2011 • as well as investigations for renovascular HTN. renal function declines.. dialysis with end-stage disease • ACE inhibitor and/or ARB may provide added benefit (monitor K and Cr) Multiple Myeloma futuiW of Mulliplll .cemia • light chain cast nephropathy (LCCN) or "myeloma kidney" • hyperuricemia • infection • secondary amyloidosis • monoclonal Ig deposition disease {MIDD) • diffuse tubular obstruction • LCCN • large tubular casts in urine sediment (light chains+ Tamm-Horsfall protein) • proteinuria and renal insufficiency. heart and other organs • mostly light chains (85-90%) • causes nodular glomerulosclerosis (similar to diabetic nephropathy) • lab features: increased BUN. 50% patients reach ESRD within 7-10 years OM i& 11118 of the caulilli of ESRD that doas not resuk in smaUkidneys at of ESRD. . urine protein immunoelectrophoresis positive for Bence-Jones protein (not detected on urine dipstick) • poor candidates for kidney transplantation Malignancy • cancer can have many different nephrological manifestations • kidney transplantation cannot be performed unless malignancy is cured • solid tumours: mild proteinuria or membranous GN • lymphoma: minimal change GN {Hodgkin's) or membranous GN {non-Hodgkin's) • renal cell carcinoma • tumour lysis syndrome: hyperuricemia. PCKD and multipl1 rn'(llollll... ... diffuse tubular obstruction • chemotherapy (especially cisplatin): ATN or chronic TIN • pelvic tumours/mets: post-renal failure secondary to obstruction • 2• amyloidosis • radiotherapy (radiation nephritis) . radionuclide scan) • serology for collagen-vascular disease • renal biopsy Treatment • most chronic renal disease is irreversible. unknown percentage ofType2 • at diagnosis up to 30% of Type 2 have albuminuria (75% mkroalbuminuria. CT.0 m!Vmmol in males > Z. CARU Calcium (elevated) Anemia llanlll Failure Lytic Bon l. increased Cr. Abnonnll Urine ACR Values from 20D8 Canadian Diabetes Association CPG > 2. The othen._. HIV nephropathy...----------------. . 1118 amyloidosia. but treatment of HTN can slow the progression of renal insufficiency • control ECF volume: Na restriction (88 mmol/day intake).B m!Vmmol in f811111es . diuretic. 25% overt nephropathy) • microalbuminuria is a risk factor for progression to overt nephropathy and cardiovascular disease • once proteinuria is established.. additional tests may include • 24-hour urinary estimations of Cr clearance and protein excretion • imaging {U/S.Hions Infections • malignant proliferation of plasma cells in the bone marrow with the production of immunoglobulins • patients may present with severe bone disease and renal failure • light chains are filtered at the glomerulus and appear as Bence-Jones proteins in the urine (monoclonal light chains) • kidney damage can occur by several mechanisms: • hypen:al...

Will limilrwith 1llrrillf1an (189) IIIII 11milcil (174. N=85421• a t:ai!Dalltian of both Mluyo.00. llultl: Thllllllllllr of aull:llmiiMIIIIIIimi'-lar111miartln ranipril (1150. rule out nondiabetic renal disease • avoid unnecessary potential nephrotoxins (NSAIDs. Autonomic Neuropathy • affects bladder leading to functional obstruction and urinary retention • residual urine promotes infection • obstructive nephropathy 111111 o. ndiclabl. ACR in men >20 mglmmol.01. !llllbniz8d oontnJied bill.OIM)IIIII carnbinllian lhnpr (p=0. daublt-llild.t-wD TthUtln. HR 1. a 0. llda PRltliNiria11 • Qflllll ax11nt U. +ve urine dipstick • normalGFR • very expanded mesangial matrix • stage4 • increased proteinuria (>500 mgl24hr) • decreased GFR • <20% glomerular filtration surface area present • sclerosed glomeruli .Toronto Notes 2011 Diabetes and the Kidney Nephrology NP35 • associated with liTN and diabetic retinopathy (especially Type 1 diabetes) and/or neuropathy (especially Type 2 diabetes) • indication of possible nondiabetic renal disease in diabetic patients • rising Cr with little/no proteinuria • lack of retinopathy or neuropathy (microvascular complications) • persistent hematuria (microscopic or macroscopic) • signs or symptoms of systemic disease • inappropriate time course. PCKD.tud Gfll dlcliwd lent with 11nq.rillllllqlllred Mil 1elmitlllln or 2008. 2. especially if patient hu DM 111d renal in&Ufficiency.. Accelerated Atherosclerosis • common finding • decreased GFR • may increase Angiotensin II production resulting in increased BP • increased risk of ATN secondary to contrast media 3. . ldl il . Pri:iplll: 25. ACEI c. Therefore. but -IIIOCiltld willl JXIGIIIr malaull:llll"ll.1JDWn (80 ll9'd. Cancbin: Renll oulcomes IWit simillr in both IIIINsatllli 111d CombinlliDn u. aminoglycosides.0-20 mg/mmol in men (18-180 mgld). dye studies) S1udy: l'rDip8ctiw.inCIIIIIIdMII coriinltionthenlpv(1233.34111'111 men fllqUBrtwilll canminllion 111arapy 1212.g..01). HR 1. 372:547-553 llilwy albumin IIXCratian -lea willllllnillr1ln (p=O.51. . GFR and Urine Protein ovar Time in Diabetes 1..ll It Hijl Yucllil' IIIII (tlfTAII6ET S1udy) 4. llllrllnllll: fllilllll NCM eh rmnipril (10 mw'd.1111 n. The need lor dilt.Clll1iWia..09. 1. cloubq II Clllllinine IMland d11t1.BS-1. short duration ofDM • family history of nondiabetic renal disease (e.18. N=85761.10.C011. Alpert's) DIABETIC RENAL COMPLICATIONS (Urine Prolllin) "' 0 --- fE Time Figure 18. using MDRD equation) • Type 1 DM: annually in adults after 5 years with diagnosis • Type 2 DM: at diagnosis then annually • must have at least 2/3 abnormal ACRs to diagnose nephropathy • with DM and CKD: urine ACR and serum Cr (for eGFR) every 6 months • delay screening if transient cause of albuminuria or low eGFR • evaluate for other causes of proteinuria.-: alalyU. p=D. catJse hyperkalemia.001l coriinltion1lillllll\'(p<O. Ea.037).12·1.'sis or of .ap.01-1.. nadllarapy. rapidly rising Cr.038). 1. Progressive Glomerulosclerosis • classic diabetic glomerular lesion: Kimmelstiel-WII. ACR is >28 mg/mmol (>250 mg/d) • clinically detectable proteinuria.01-1. O. (> 180 mg/d). 2.Z4.son nodular glomerulosclerosis (15-20%) • more common lesion is diffuse glomerulosclerosis with a uniform increase in mesangial matrix • stage 1 • increased GFR (120-150%) -compensatory hyperfiltration of remaining nephrons • ± slightly increased mesangial matrix • stage2 • detectable mlcroalbuminuria (between 0-300 mg/24 hours) • Albumin-Creatinine ratio (ACR) 2... 1111.g. IIR 1. Papillary Necrosis • Type 1 DM susceptible to ischemic necrosis of medullary papillae • sloughed papillae may obstruct ureter • can present as renal colic or with obstructive features ± hydronephrosis 2008 Canadian Diabetics Association Clinical Practice Guidelines on Chronic Kidney Disease in Diabetes • screen for microalbuminuria with a random urine test for albumin to Cr ratio (ACR) and eGFR with a serum creatinine (e. be ISUre to wmch serum K.8-28 mglmmol in women (25-250 mg/d) • increased mesangial matrix • stage 3 • macroalbuminuria (>300 mgl24h). in women.620 pllilllls will! median b'low141 of 5& moadts.

.. progressive kidney function loss.g. 345:881-869 .. IIIII was Qllllllll'{ WIII1Diarat8d.iJp o/3. Priorities in the Management of Patients with DM 1. lllllli-attmil:ily) with NIB1111d napbrvpl1hy [llillry lllurii:Cr lid senl11 Cr .similr..em'li cl.. multiple cysts throughout renal parenchyma...CrCl <60 mL/min: ARB • 2 line agents: nondihydropyridine calcium channel blockers (diltiazem. glycemic control. HTN.. spleen. diverticulitis) • HTN (increased renin due to focal compression ofintrarenal arteries by cysts) (60-75%) • ± palpable kidneys Common Complications • urinary tract and cyst infections. Rilldornillld. pllcaho. cerebral aneurysm (10%). medullary cystic kidney..lllian: LDIIflln carllfTid rnl benelils in patients will!. lipid control 2. . 011 dillllicl.llln 50 mg 1'0 OO(t:Ud Ill doubled lflll4 Mlks) VI. BUN. a. most common. urine R&M (to assess for hematuria) . monitor for significant worsening of renal function or h!ferkalemia • if >30% rise in serum Cr or hyperkalemia. seminal vesicles. lhllrndlln: t. . ClrmlyiiCtirG IIQIIIISI. usually stabilizes after 2-4 weeks.000). medullary sponge kidney.yfmm CW CIUIBS. antiplatelet therapy (as indicated) • BP control.. at least 3 genes: PKD1 (chr 16p). optimization ofBP in patients who are hypertensive • treat according to hypertension guidelines accomplished by renal U/S (enlarged kidneys.illl !CCII. PKD2 (chr 4q). 01 dllth.. multiple asymptomatic hepatic cysts (33%). increased cortical thickness.. thyroid. flank and chronic back pain Clinical Course • polycystic changes are always bilateral and can present at any age • clinical manifestations rare before age 20-25 • kidneys are normal at birth but may enlarge to 10 times normal size • variable progression to renal functional impairment (ESRD in up to 50% by age 60) Investigations • radiographic diagnosis. cortrolld trill Ylitll m1111 fulliJw. . iblbiHfm. and aorta llllierU willl Type I cilbetes no eftect on Gill was IMQd il the bN·rmin diet group. (4):Cil002181 _ . discontinue medication and consider 2 line agent • consider holding ACEI. vascular protection for all patients with diabetes • ACEI. 12 lluciii-IIVi-. 2dilllleles 1111 118pi'Riplllly..NP36 Nephrology Diabetes and the Kidney/Cystic Diseases ofthe Kidney Toronto Notes 2011 O...t lllll'llullbil b BP cliqn abiL Slcoadlly 11'111 poi'dl. gross) • nocturia (urinary concentrating defect) • rarely extra-renal presentation (e. pilcebf.llti!Ju$jtltllsv 2007.:tial: Rlld01nised carmlled 1rial (IItTs) IIIII behn ad lfla' SUiits of thlllllcts rl mlriclld prollin diet on renll flllction in Uljecls will! cilbltll. nephrolithiasis (5-15%). ARB and/or diuretic with acute illness and in women before becoming pregnant • consider referral to nephrologist if ACR >60 mg/mmol.lllhlllqlllt8 of hDijlitlilltion for hllrtfliU. verapamil) • ACEI and ARB can be safely used together if needed for control of significant proteinuria (monitor for hyperkalemia and acute rise in creatinine) • check serum Cr and K levels within 1 week of initiating ACEI or ARB and at time of acute illness • serum Cr can safely be allowed to rise up to 30% with initiation of ACEI or ARB.Candlly lllldpoinll ilcbled IIIJIIIidily llld lllllltllj. Signa and Symptoms • often asymptomatic. PKD2 (1:1. occasionally reveals more cystic involvement) • gene linkage analysis for PKD1 for asymptomatic carriers • Cr. ovary.ill'llilawilb'l'yJIIIZDIIIId Naplnp6f NEJM 2Dl1. Codltn l.: To review rlllay Adult Polycystic Kidney Disease • PKD1 (1:400)..: The riskrlend·sll. CRF. IIUy sn. Harllit IICIIIdllllt. polycystic kidney disease (autosomal dominant and recessive) and acquired cystic kidney disease (in chronic hemodialysis patients) . *' c:. S.. renal protection for DM patients with nephropathy (even in absence ofliTN) • Type 1 DM: ACEI • 2 DM: CrCl >60 mL/min: ACEI or ARB.01 delllll was luwlr in pitieD on III'A'jJIOIBil da Cystic Diseases of the Kidney • characterized by epithelium-lined cavities filled with fluid or semisolid debris within the kidneys • includes: simple cysts (present in SO% of population over SO).. PKD3 (location not yet determined) • polycystin protein from PKD1 responsible for cell-cell and cell-matrix interaction • defect can lead to abnormal cell growth and cyst formation • extrarenal manifestations. diverticulosis and mitral valve prolapse (25%) • polycystic liver disease rarely causes liver failure • less common: cysts in pancreas.. splaying of renal calyces) • cr abdo with contrast (for equivocal cases. WIS tignificlnttv lowarv. on111e progqanoftilbllic Dlpi'Riplllly. unable to achieve BP targets or unable to stay on ACEI or ARB l'nllliiiiiAII:tiDn llr llllllli: 111111 D-. . accounts for about 10% of cases of renal failure • autosomal dominant... eGFR <30 mUmin....4 Yll'l· l'llilnll: 1513 Jllllients!1111111age60. lifestyle modification.: incillnct rl doublng rl swn Cr {IUIZS\IIIId ESRD !RR but hid 110 1111 rilkof dlllll. m 1111ie.: l'rinlly endpoilts ilcUied iblbli'G rl swn Ct ESRil. discovered incidentally on imaging or by screening those with FHx • acute abdominal flank pain/dull lumbar back pain • hematuria (microscopic frequently initial sign. ruptured berry aneurysm.

HTN. "swiss cheese" appearance on morphology • treat UTis and stone formation as indicated • does not result in renal failure Autosomal Recessive Polycystic Kidney Disease • • • • • 1:20. characteristic radial pattern ("bouquet of flowers"). chronic kidney disease treated with kidney and/or liver transplant . hematuria and recurrent UTis are common features an estimated 10% of patients who present with renal stones have medullary sponge kidney nephrocalcinosis on abdominal x-ray in 50% patients. ciprofloxacin: able to penetrate cyst walls. its manifestations and inheritance pattern • genetic counselling: transmission rate 50% from affected parent • prevention and early treatment of urinary tract and cyst infections (avoid instrumentation of GUtract) • TMP /SMX.Toronto Notes 2011 Cystic Diseues of the Kidney Nephrology NP37 Treatment • goal: to preserve renal function by prevention and treatment of complications • educate patient and family about disease.000 incidence prenatal diagnosis by enlarged kidneys perinatal death from respiratory failure patients who survive perinatal period develop CHF. often detect asymptomatic patients incidentally • diagnosis: contrast filled medullary cysts on IVP. usually diagnosed in 4th-5th decades multiple cystic dilatations in the collecting ducts of the medulla renal stones. achieve therapeutic levels • adequate hydration to prevent stone formation • avoid contact sports due to greater risk of injury to enlarged kidneys • screen for cerebral aneurysms if family history of aneurysmal hemorrhages • monitor blood pressure and treat hypertension with ACEI • dialysis or transplant for ESRD (disease does not recur in transplanted kidney) • may require nephrectomy to create room for renal transplant Medullary Sponge Kidney • • • • • common. autosomal dominant.

-runaciiJ aliskimn (llasitaze] Vascular smoolh mllll:kl.irilibits reabsorption DfWIIIrand 1' adam!lllus stale$ urinary IIXI:IIIion Df1Dxic matarials II wsoconlllricting lfTN net CardioprDiecliVII ellicta I• wsodilation -> BP RllnoprotactiVIIIfflcts l'revel1ts II mediated aldolllrtlnl nlll1111 fnlm adrlnal cor11x n action on praximal Rillll111bules 1' Na and H0 exallion -> BP 1 Redul:es fibrosis and athenlgenesis VIISCUill' &moolh muscilll manritDI: oJ. praximalllJJulls II AICiplor: II CardioprullcliVII ellicta (111 action on vasculrr Renopratective etfecta smoolh ITIJida BP l'revel1ts anlliDiensin II mediated aldolllrtlnlllllllla fnlm adrlnal corllx and action on proximal Rilllll111bules 1' Na ..IICitea [iipironra:tuna). 1:1" Tliazide Diurllica hydrochloruthiazida (HCTZ) chlaruthillzide (Dilliltj (Lozule. valsarttll(Diovan") !Wnisartan (ro.Table 14.d H0 exallion 1 llract lfTN: lllllllll12&-100 PO 00 cnesartan 8-32 PO oo irt:Jesartan 150-300 PO OD wlsarbln DO telni$8111n 2HO PO OD 400-800 PO DD 26-40 mg PO OD Hyperkalemia CIU!ion .jistiC elfecl 1hiazide Conan• lrfpokalemia drug with 1hiazidatallduc1 CollbiaaliP All* Dyazida• tlriamterene + HClZ) Aldlctllid8 8 (spironDIIClona + HClZ) Mloduratic•(amilmida + HClZ) Vasntic8 (nlapril + HClZ) Zlisllntic• Pisinopril + HCTZ) O.. lrfpok*ni11. Lozideltj matDiaz!llla (Zir=lyn.induced (ITIIX 600 mlfd) until dsii!ld rtllipon118 lrfpocalcemi11..2.I'IIIil:l ltiC8TDI UAII Ran II tubules (proximal n duct) To ".. lllnemidl (Dernadat') Nl!ii(I2CI1Tinsport ± renal and VIISDdilltary lllhlc1s (Kloss. ada11111.. . oJ. hyponatnmia.400 mlfday Oil/bid amilorida: &-10 DO Hypok*nia I11C1181ed serum lillie levels PracipitDs gooty idtacks.Dapdilntia8 Eumpln Sita Dl Acciol llick Df Loop Df Han Ia Mecllanism If AICial (Secondary Bllc1j IIIIICIIian Doli!a Advana EfllcCs QO bumllllnida (Bumaellluinaxe) ethlcrynlbl (Edecrin. 1' H Ca uaation) 1st lila fur eaantillllfTN Treatment Df edema Idiopathic hypert:alciuriaand stonea [ia...5-20 PO DD/Did c.1D PO OD mg tnnlolapril: HTN-1-4 OD t . cinliDtic ascites.5-25 PO DO (m11X 50 rngld) 2&-200 mlfday Oil/bid dosing lfTN: 50-200 mlfday Oil/bid doling Hyparaldosteronism. fu1111amida: Allarw in sLMB-1111siiMI individuals naplrrutic synd111ma.zo. cystic fibrosis (amiIoride vilco&ity of secretions) Combina ACE-irilibitar fDr syrJIIII.intnacrenial or jllii'IOcQjillr prassu111 NOIHillbsorilabla solutn incriiiSil osmDtic prassUrl Df filtratl MobilizllliDnDIIIKCISSfllid . BP (less affiCtiv8 due tD Valuma deplltion with matabolic abiosis lfTN . hypemllciLI'ia (with i1llne furmation) lrfponatremia). chlorthalidona (fWvton8) spi!IIRolllctona(AidiC!Dne•] triamtlnlna([)yrlnium•) amiloride (MUnorS) Disbll convolutlld tuoole In Nt/CIIIInsportar (K lost.20-80 rngld PO 00/hid nrtaction) Pracipitmas ldtacks ..Diii:O. 1' fnle Wltar claarance in SIAIJIJ.q. hypacllllcenia EIMtdlipids Gklc011eintuiiJiliiCI Hyperkalemia (elUtion with ACE irilibi!Dr) TriamiiAinl can ba naphru!Dxic (rn) Neplrlllijhia Gyna1111111ia (IIS!rDgllic efltct Df spironollclonl) Patnaillt-spalilg Cortical duct Na llabsorption) antagonist Clo111 apiclll Na chann• SMni IVJIM/PD q&-Sh Elactrolytl abniiiTTIIIIitia.m!Wca dOII8 in hapatic impeirmant Acute kidney injny Rlllin Altlpisa antagonist Inhibits mnin plllductiDn and activity Cardioprotactivl and renoprutactive IMIIuatsd HTN llliskimn 15!l-JOD PO DD Hyperkalemia • a ./1' IQ i 8 ACB rurnipril [Allee.f e.60 min Transiant110luma axpansion Elactrolytl abnormlllitias [ i Na. f .tcardisiiJ eprusartan (TMten.. 1' Hsacretion..25-100 00 lfTN -12.10[1.3[1.bataslnsipidus RII!Wcas K caused by other loss fllamB/hyparvDIInia HCTZ: ede11111. adrenal inhiMor at1he qiotnin lfTN cortax. caplopril (CapDtanltj Tissuas dillull81r Pr-m 11mipril: HTN. Astllna Hyperkalamia A!pnulocyiDsis (captapril) Acute kidney injny us1. ARB IOII8rtln (Comare) candasartan (AtiCind<tj irbesrrtan [Avap111. Drugs In Nephrology Clauificllian I.25-2 w\IIIV. enlllapril lisinoprii(Prinivir') tnmdolapril [MII'ik. 1' Casxmdion) lA ad111111 secandllry tD CHF. ICP: 0. olmasartan [0......

18:1889-1898 SYMPHONY NEJMZ001. 347:2010-19 IDNT IRMA ONTARGET REIN RENAAL RENAL NEJM2001. 361:1627-38 ROAD JASN2001. steroids and low-dose tacrolifllls effectively maintail stable renal function following renal transplantation. 354:359-64 NEJM2001. ACEI were renoprotective iJ patients with nonnephrotic range proteinuria Losartan conferred significant renal benefits in patients with type 2 diabetes and napiJapathy and was ganeraly well-tolerated High intensity continuous renal-replacement therapy in acute kidney iljury does not inprove survival or outcomes compared to low intensity treatment. 351:1952-61 ELITE NEJM 2007. 345:870-8 lMicet 2008. 372:547-33 iimctJt 1999.6SIRAL NEJM2009. 345:861-9 NEJM2009. BP. 329:1456-62 Captapril protscts against deterioration in ranal function in insulin-dependent diabetic nephropathy and is more effecti\le than blood-pressure control alone Treatment with ACEitrandolapril alone or trandolapril combined with Vlllllp8mil d11C1811sed the incidence of microalbuminuria in patients with type Zdiabetes and hypertension with nonnoalbumiooria Renal artery revascularization compared to medical therapy does not improve 11!11111 function. 257:2562-75 HEMO NEJM2002. 361:1953-62 DETAIL NEJMZ004. rnainll!nance of ranallunction. renal or cardiovascular events. or mortality and carries significant operative risks The ARB telrniser1lln and the ACEI enalaprilare etJllllly effective in slowing ranal function delarioralion in type 2 diabatas with mild to moderate hyp811Bnsion and aar1y naptropathy S1lnlard irrmunosuppresion therapy in ranal tnn.plant patients low dosetacrolimus is superior to cyclosporina and sirolifllls in reduction of acute rejection. MMF. and is essociated with higher rates of hypophosphatemia Uptitration of either ACEI Benazepril or ARB Losartan to optinal antiproteinuria doses conferred benefit on renal outcome in patients without diabetes and had proteinuria and ranal ilsulliciency Daclizumab induction. 351:1941-1951 . Possible benefit in cardiac-related outcomes with high flux membranes Treetment with irbesartan reduced the risk of developing end-stage renal disaase and worsening renal function lrbes811Bn is ranoprotective independently of its blood-fJII!SSure lowering effect in patients with type 2 diabetes and microalbuminuria Telmisartan and ramipril monotherapy reduced proteillria and rise in creatinina in patients with high vascular risk In non-diabetic nephropathy. without the nagativa Blfacts on renal function commonly reported for standard CNI regimens BENEDICT NEJM2004. 357:2562-75 . 345:851-&D NEJM 2001. 111d allograft survival Use of high dose dialysis or high flux memblllll!s versus standard dose or low flux in thrice-weekly dialysis does not improve survival or outcomes.Toronto Notes 2011 Landmark Nephrology Triala Nephrology NP39 Landmark Nephrology Trials Trill ACEI and Diabetic Rlftnlce NEJM 1993.

Caopar ME. NEJM. Hliperin Ml. (1998].lfwww.Limus M (1995]. Gold ate in MB. John lUll CA.Iilllcka PG.(19981. Primer on Kidney liseues. G. Mcfarllna P. Vol.NP40 Nephrology References Toronto Notes 2011 References Adler SG. Val 42: 3!5-418. (19!181. 2001. et II. alactmlyla.hmt DJ. 2l111111n 8. 1581-1589.tigi!Dn. Hakim R. Smith.w. New Ywk: Cland1ill.l'llscual M. dDGVtdo!lilloc. Fischer R. Renal Diseese: AConcl!plual ApJiroach. Pucket Melil. 351(1t.NEJM. 1-21). GDidatain MB. Mosby: Naw Yort. MIIIIDr SJ. Napllapalhy: Canadi1n Dilllllll Allocillian clinical prlctica tuidalinll axpart commit!IL Mtp//lw. Effac:tJ of IDArlln anlilnll Crial'lscul• in l'ltiants with Type 21ilbatas111d Nephropathy. 346{5t3DS. 3rd ed.diabltll. Churchill DN. 1547-59. 131S. prulli11ria. l!llin RP. SundUimoorthy M. Nei111111 EG. Gnllled E. Grerierg.(2ll02). CMAJ. alilllrruril. llll (198111. Kinsey. Lau J.: New Yort. TDII*lira EB. (1999].IIau1iir P. 33[51: 1004-1010. llcnoyln._ JAm Soc NlplrGI. Kaine WF. Rll\'iiW ai!IQQ !IRIII fliU. Hudson BG. Halperin M. 358. A J mar Killis. Madici111141h ld.JIIsad IPJIRIICh. Vol. Vol. Andreoli TE at Cecil Essentials of Medicine. lrd ad. Jerwll J. Gabow PA. Samnara lor 3 clinical clsrkllan medicine: hyponatremia and hypamatramia. Mllias NE. DanadioJII. NIW 1hl m111111g1m11nt of diab111s: aphysicilll's tuida. (19991 CiMca1 pnctic8 tuillllilas lor initiatian al dialysis. KatsayR. Vol. NEJM.w. Vol. HarcourtBlaca & Co. (1 9931. Ftahally J. Mechllilms of Disease: Alport's Synd!ame. Johnson RJ.. NEJM. 6111 ad.(2ll031. 10 S231H1. 348: 2543-2556. Hunsicbl LG. CiMca1 pmcb clnrie di&eue in adults: Pill l Gbmarul• fittmion rata. Slbltina M. Cor.(2ll021. NEJM.Lang SM.llonwntra.13Z8. Blli. Protairama.(2003I. (2ll081 T*isnn. rist USIISII!IInt. A. (19991. Andi'D!Iue HJ. Hns SB. L8vey AS. San llego: Academic Pless. S.. Ma1111gement of ife threlterirG acid-base disorders pill I. ONTARGET m. GrandeJP. Llwis EJ. An au1tn8 aiSAIIItiiiiDpiCi in gtlmarullr 111d lr8llrrrmt for naphrology1Rina&L Amaril:ln Jaulllli of Killll'f Comprallnivl clinical naphrology. Mitch WE.html. ud stRtlication: 2ll00 wcutive updale. Sat al. or bath in patients 111igh risk lomsculu IMII1li.ring CormiUII for thllilvision Dfthl Ham ph ill RR at II. Bain SC. Schiftl H. elimination (I'ARA!lE): 1 pOiition pepar altha Nltio1llll Kidney Famdltion.libition on liabatic NIJRapethy. WM. 2nd ad. Vol. Daily Hamodialysis and 1hl Outcome of Aaa Renal FaiU. Vol 342(201: 1483-1499. LippincllttWillau.fnzyme Wilition in Type 2Diabe11s and Naplnap11hy.1'atJssirm. Hams S. Saundlr Publisq Philllllllphia. Andi'D!Iua HJ. 100001 clinicallfiCiice Quidelnes lor clllanic disease: evalurlion. Rohda Tha Elllcts of AngiJtlnsii-Corrnrting Enl'l"la . Bramar BM. HypoMtremia.h J. & Wlins. Artlv.and scid·blsa pllysiDiogy: I problam. St. 2ll02. 861-861. Klrllerv B. dBIIctian. Aullllomal domin1nt di. AJ9o1nin-lleceplor Blockllde VIISU5 Converting.http.. Levin A. Baltimora: Wililma & 21)01.ct/ Mallzar. Val 338(21: 107-11. American Familyl'hysicillls. NEJM. da Zaluw D.Jil (1 9961. Dclallar 29. Trwii\Uon K. .embblfcl)lllicr/Jflrf.{2001l.l/lw. Mlliu NM. Schreiber M. 345(121. kuteranal fliU. Myn. Madsllld S. 347:738-748. CllajQr 4.(2ll041. 1987. 334(221:1448·1460.1D.1952-61. Kimel K. NEJM. 338 !11: 2&-33.(2Wll. Vol. http.1niliBiion DfDi. NEJM. lalla S. Canadian Society of Nephrabgy. 1lndl All. (1 999]. Jindal KK. Vol.htm Kalina WF. Goodpaslire's Syndrome. clmification. Houldan R. NEJM. Fluid.(2ll031. JAm SGc Nephrol. Medi:al J1119111: lgAnephropathy.ivingstone. Andi'D!JU8 HJ.(2ll041.. NEJM. Mallllgamant of ill thraatarirQ acid-bela disordara pill II.ina: Tba Ganaralllolpital Handbook of hlamal Madicina. The Lancet. 329(51:332-342. Mllias NM. Vol352: 13HO. Vol. Vol.. lAd Type NCollagen. Clinicall'rlctice Guidalinll fol tha Managamant of Dilllllll in Canida. Thldhani R. Vol. ud ather rrartn. Vol&.

... ........ .......••••••.. associate editors Steven Wong.................... ........ . ... 44 Stroke . Tara Rutin and Courtney Scott.... 42 Overview of Sleep Disturbances of Alertness and Sleep CNS Infections .. 36 Approach to Pain Syndromes Neuropathic Pain Tic Douloureux Postherpetic Neuralgia (PHN) Complex Regional Pain Syndromes (CRPS) Thalamic Pain (Dejerine Roussy Syndrome) Headache . EBM editor Dr.. .... ... ......... ............ 29 Amyotrophic Lateral Sclerosis (ALS) Other Motor Neuron Diseases Toronto Notes 2011 Peripheral Neuropathies . ... ..... ......... ...... ... 34 Clinical Approach Polymyositis/Dermatomyositis Myotonic Dystrophy Duchenne and Becker Muscular Dystrophy Cerebellar Disorders . ... 44 Terminology Approach to Stroke Stroke Syndromes Ischemic Stroke Hemorrhagic Stroke Hypertensive Stroke Global Cerebral Ischemia Treatment of Stroke Primary and Secondary Prevention Stroke Rehabilitation Multiple Sclerosis (MS) ••••••... staff editor The Neurological Exam . . .....................N Neurology Mina Atia. .. .... ...... 4 Lumbar Puncture ....... 22 Disorders of Lateral Gaze Internuclear Ophthalmoplegia (I NO) Diplopia Nystagmus Abnormalities of Pupils •••.. . .. 21 Abnormalities of Eye Movements .. 52 Neurology Nl . .. ........ . ........... ... 2 General Exam and Mental Status Cranial Nerves Exam Motor Exam Sensory Exam Coordination Exam and Gait Basic Anatomy Review . .. ... ........ .. .. ....•••• 49 Common Medications ... . .... ............• 23 Relative Afferent Pupillary Defect (RAPD) Horner's Syndrome Anisocoria Movement Disorders ..... ... ..... . .... ..... 32 Paraneoplastic Syndrome Tumours of the Nervous System Neuromuscular Junction Diseases ..... ......... .. .. ... .. ..... ...•••••••••••... 35 Wernicke-Korsakoff Syndrome Cerebellar Ataxias Vertigo .............. . 17 NEURO-OPHTHALMOLOGY Abnormalities of Vision ••••. 32 Clinical Approach Myasthenia Gravis (MG) Lambert-Eaton Myasthenic Syndrome (LEMS) Myopathies..... ............ ..... ....... .•••••••••••. . . .. 36 Pain Syndromes .. . .... .. ......... . ................... .. ..... ... ... 30 Neuro-oncology . .... . ........ 7 Seizure Disorders and Epilepsy ... 8 Seizure Status Epilepticus Behavioural Neurology ..... ....... 39 Clinical Approach to Headaches Migraine Headaches Episodic Tension-Type Headache Chronic Tension-Type Headache Cluster Headache Sleep Disorders ....... . .... .... ... ... ... 51 Landmark Neurology Trials........ 36 Galt Disturbances ... .. 10 Acute Confusional State/Delirium Dementia Alzheimer's Disease (AD) lewy Body Disease (LBD) Frontotemporal Dementia (FTD) Creutzfeldt-Jakob Disease (CJD) Normal Pressure Hydrocephalus (NPH) Aphasia Apraxia Agnosia Cranial Nerve Deficits ....... chapter editors Doreen Ezeife and Nigel Tan...... ... .. .. ... ..• 20 Acute Visual Loss Optic Neuritis Anterior Ischemic Optic Neuropathy Amaurosis Fugax Central Retinal Vein Occlusion (CRVO) Optic Disc Edema Optic Disc Atrophy Abnormalities of Visual Field . . .. ........ ... David Chan. .. ........ 52 References .. ........ ......... .. 44 Spinal Cord Syndromes ...... 25 Overview of Movement Disorders Function of the Basal Ganglia Approach to Movements Disorders Parkinson's Disease (PD) Other Parkinsonian Disorders Huntington's Disease Dystonia Tic Disorders Tourette's Syndrome Motor Neuron Disease .

ands. strength If patient has not brought their glasses. fasdculations. Mini-Mentll Status Exam (MMSEI D111111in Orillllltian Regiltration Score Task /5 Time: Ye. Sensory: Vl-V3. head injury/bruises (battle sign. swallowing • Accessory (CNXI): trapezius and sternocleidomastoid • Hypoglossal (CNXII): tongue muscle bulk..Think compressive lesions. Month. clock drawing. VISual Acuity: test each eye individually using best corrected vision b.age /5 /3 /5 /3 /2 /1 /3 /1 Place: Counlly. Day. Rinne. nrreriorrectus. hemorrhages • Extra Ocular Movements (EOM) a. VISceral motor: salivary and lacrimal glands • Vestibulocochlear (CNVIII) a. Glasgow Coma Scale) • cognition: Folstcin Mini-Mental Status Exam (MMSE).N2 Neurology The Neurological Exam Toronto Notes 2011 The Neurological Exam General Exam and Mental Status • vitals: pulse (especially rhythm). corneal reflex (efferent) b. Floor lmmediilte Recall: 3 wnlated items Spell 'WORLD' backwards or do Sarial7s Delayed recall af previous 3 items Naming: Pen. havalhem look through a pinhole for ----(_. superior rectus. Cochlear: test each ear masking the other with white noise. VISceral sensory: taste of anterior 2/3 oftongue c. vocal cord function. tongue biting • CVS: carotid bruits.. masseter. Date Attlnlian and CanCIDiration Recall Lan. BP.. CNIII with pupil1paring -Think vascular caus1s likl diabetic ophthalmoplagia CNIII with pupil involvement.nrrerioroblique b. VISual Fields: test all4 quadrants for each eye individually c. Caloric!WielQis cows Cold Oppositll WIII"TI1 Same . Trochlear (CNlV): superior oblique c. Weber • Glossopharyngeal (CNIX) and Vagus (CNX): palatal elevation. caloric reflexes b. corneal reflex (afferent) b.. . or buts' 3-Step Command: "take this paper in your left hand. Motor: temporalis. Building. and place it on the floor with your right hand. optic disc pallor. optic disc edema. Vestibular: nystagmus (described based on fast phase). Season. raccoon eyes). City. and set the hands to 'ten after eleven'. Sensorimotor: muscles offacial expression. Province. swinging flashlight test (for RAPD) d. Pupil: direct and consensual pupillary reaction (afferent limb). temperature • H&N: meningismus. fuld it in half. medial rectus. hyperacussis (stapedius). T1ble 1. Abducens (CNVI):lateralrectus • Trigeminal (CNV) a. best CDITBCIIId vision. put in all the numbers. Watch Repetition: 'No ifs. Cranial Nerves Exam • Olfactory (CNI): test each nostril separately to identify common odours • Optic (CNII) a." Read and obey: 'CLOSE YOUR EYES' Writing: Write afull sentence Copy: /1 DI'IWing TOTAL /1 /30 Pentagons (1 0 Zbisecting! Cognitive impaiment if <24/30 . Fundoscopy. gag reflex. heart murmurs Neurological • mental status: WC (AVPU scale. Oculomotor (CNIII): levator palpebrae superioris. accommodation. jaw jerk reflex • Facial (CNVII) a. venous pulsations.. frontal lobe testing (for perserveration) • clock drawing: give patient a blank piece of paper and tell them to draw the face of a clock.-. pterygoids.


Romberg Stable with eyes open and closed = normal Stable with eyes open. Edinger-westphal nuclei 7. IV ventricle Midbrain 1. Fasciculus gracilis 11. Corticospinal tract and corticonuclear fibres 4. Pontine nucleus 2. Occulomotor (Ill) nucleus complex (motor) B. Decussation of medial lemniscus 4. Medial lemniscus 5. festination. hemiplegic. extinction. heel-to-shin. Substantia nigra 5.N4 Neurology The Neurological Exam/Basic Anatomy Review Toronto Notes 2011 Sensory Exam • primary sensation • spinothalamic tract: pain and temperature • dorsal column: proprioception and vibration • cortical sensation • graphesthesia. Arcuate fibres Pons 1. suggesting loss of joint position sense Falls with eyes open and closed = cerebellar or vestibular syndromes Coordination Exam and Gait • coordination exam • finger-to-nose. apraxic. Medial lemniscus 9. Nucleus cuneatus B. ataxic. Brainstem = Cerebrocerebellum Spinocerebellum _ Vestibulocerebellum Vermis Saggital section through brainstem and cerebellum Flocculus Tonsils Nodulus Anterior view Figure 2. Nucleus of spinal tract of trigeminal (V) nerve (descending) 6. Lateral vestibular nucleus 11. Spinal tract of trigeminal (V) nerve 7. Nucleus gracilis 1D. Trigeminal (V) nerve fibres B. Cerebellum . Cerebral peduncle 4. stereognosis. broad-based • tandem gait • heel-to-toe walking • Romberg • pull test for retropulsion See Functional Neuroanatomy software Basic Anatomy Review • see also Neurosurgery. Corticospinal tract 2. Superior colliculus §' @ Figure 1. Red nucleus 6. Fasciculus cuneatus 9. Occulomotor (1111 nerve fibres 3. Nucleus of abducens (VI) nerve 9. rapid alternating movement • stance and gait • gait: antalgic. Central canal 12. Central canal 11. foot drop. falls with eyes closed = +ve Romberg. Middle cerebellar peduncle 12. Spinothalamic tract 1D. Lateral spinothalamic tract and spinotectal fibres 3. Reticular fonnation 5. Nucleus of facial (VII) nerve (motor) 6. Nucleus of spinal tract of trigeminal (V) nerve 1D. NS24 for Dermatome/Myotome information Medulla 1. Interpeduncular fossa 2. Facial (VII) nerve fibres 7. Abducens nerve fibres 3. 2 point discrimination 119.

Chillf Figun 5. Spi1Dihlllmic Tnct Triguminal ganglion . IJj \!1 Alcill m111cl88 • I Figun 7. from fac:e • . ]f0/-\ l Thelanu \ ...s 0 e. CalticaiiJinal Malar Patlway . Discriminatin Touch Pltlway ! o j T of thupinal nM:t: trigeminaloocleus Spinal triguminalrM:Iu• .. . 1\' lntamel ''\ capaule · ' \ [ ·.: Column) fra111 Face Figun li..'IbroDlo Nota 2011 Buic Anatomy Review Neurology NS il matar cariJDI: 1 Alcill \1 } oJ Axial muld" I Figun 3.\ It V'·. Axial muld" l . Spinlllllllamic Pain Pltlway fra111 Face Uppar mlllllr mu111111 in mamr car!IIX . '\.. Discriminatin Touch Patlway Column) fra111 BadJ 4..__ I J face I SENGryi:Gitsx rsgian '\ 1 Mediallemniscus ttrigeminllllemniscus) I 'f. .__. .

N6 Neurology





Flg1re 1. Sympathellc Md Par•ympatludlc Pathway

Toronto Notes 2011

Lumbar Puncture

Neurology N7

Lumbar Puncture
Indications • diagnostic: CNS infection (meningitis, encephalitis), inflammatory disorder (MS, Guillain-Barre, vasculitis), subarachnoid hemorrhage (CT negative), CNS neoplasm (neoplastic meningitis) • therapeutic: to administer anesthesia, chemotherapy, contrast media; to decrease intracranial pressure (pseudotwnour cerebri, nonnal pressure hydrocephalus) Contraindication& • increased intracranial pressure (ICP) - could lead to cerebral herniation • CT first if immunocompromised, possible CNS disease, new-onset seizures, papilledema, altered LOC, focal neurologic findings, >60 years old • infection over lumbar puncture (LP) site • uncooperative patient Complications • tonsillar herniation • post-LP headache (5-40%) -clear pattern: worse when upright, better supine; generally onset within 24 hrs • prevention: smaller gauge (ie. 22) needle, reinsert stylet prior to needle removal, blunt ended



The needle for a lumbar punclin is insertBcl into one of L3·4, L4-5, or L5.S1

The volume of CSF removed during a lurnb11r puncture i& ruplsni&hed within
one hour.



• symptomatic treatment: caffeine and sodium benzoate injection • corrective treatment: blood patch • spinal epidural hematoma • infection What to send LP for • Tube #I: Cell Count and Differential: RBCs and WBCs and differential • xanthochromia [yellow bilirubin pigmentation) implies recent bleed into cerebrospinal fluid (CSF)I • Tube #2: Chemistry: Glucose (compare to serum glucose) and protein • Tube #3: Microbiology: Gram stain and C&S • specific tests depending on clinical situation/suspicion • viral: PCR for herpes simplex virus (HSV) • bacterial: polysaccharide antigens of H. injluenzae, N. meningitidis, S. pneumococcus • fungal: Cryptococcal antigen, India ink stain (cryptococcus), culture • TB: Acid-Fast stain, TB culture, TB PCR • Tube #4: Cytology (for evidence of malignant cells) • Tube #5: RBCs: compare RBC cell count to that of tube #l
Tabla 5. Lumbar Puncture lntarpral:ltion (Normal vs. Various Infectious Causes)

Do nat delay antibiotics while waiting

fer alumb11r puncture if suspicion of

RBC in tuba #1 > >#5 -1r8umatic tap RBC in tube #1




<0.45 gil

60% of serum glc >3.0mmoL'l Normal

Cells O..SWBC, DRBC 0 neutrophills <100Dx1D'/l. Lymphocytes mostly, somePMNs >11XX!x1o'/l. PMNs

Cle.- or opaiBSCent

Normal or slightly increased <0.45-IIJI\. > 11Ji\.


Opalescent yellow, may clot Clear or opaiBSCent

Decreased ( < 25% serum glc or <2.0 mmoi/L) llecraasad (usually <2.0-4.0 mmoi/L)

Granulomatoullnlection fun;jal)

ncraased but usually <51Jil

<11XXlx1o'!L Lymphocyllls

N8 Neurology

Seizure Disorders and Epilepsy

Toronto Notes 2011

Seizure Disorders and Epilepsy

Mldlcll EmetgiiiCyl S1atus Epilepticus can cause irmtanible brain damage without traatmant

• seizure - transient neurological dysfunction caused by excessive activity of cortical neurons, resulting in paroxysmal alteration of behaviour and/or EEG changes • epilepsy - chronic condition characterized by two or more unprovoked seizures • ictal- during seizure • post-ictal- period following a seizure when there may be a state of confusion/somnolence • inter-ictal- period between seizures during which epileptic discharges may be seen on EEG • status epUepticus- seizure lasting >30 minutes without spontaneous cessation or recurrent seizures without full return to consciousness inter-ictally






+'. Panial- Simpla

can secondarily become - - - - - - - - - - - - - - - - - •Generahzad






Abet nee

Motor Sensory








Fevar Metabolic Trauma


Figura 1D. Classification of Saizuras
Stroke is the most common cause of late-onset (>50 'f8lll' of age) seizures,
accounting for 53-BO'K. of c__


+ +



+ ...


• idiopathic • identifiable etiology: vascular, congenital, neurodegenerative or other neurologic disorders, neoplasm, trauma, childhood epilepsy syndromes, infection, metabolic, toxins, genetic • cryptogenic

Signs and Symptoms • generalized seizures
• tonic-clonic (grand mal): • prodrome of unease or irritability hours to days before the attack • tonic ictal phase: tonic muscle contractions, arm flexion and adduction, leg • extension, 'cry' as respiratory muscle spasm and air is expelled; lasts 10-30 seconds • clonic ictal phase: clonus involving violent jerking of face and limbs, tongue biting, incontinence; <90 seconds • post-ictal: decreased WC, flaccid limb and jaw, extensor plantar reflexes, loss of corneal reflexes lasting hours, headache, confusion, aching muscles, sore tongue, amnesia, elevated serum CK lasting hours • absence (petit mal): usually only seen in children, unresponsive for 5-10 seconds with arrest of activity, staring, blinking or eye-rolling, no post-ictal confusion; 3Hz spike and slow wave activity on EEG • tonic: decreased LOC with muscle contraction in flexion or extension ± drop attack, arrest of respiration causing cyanosis • clonic: decreased LOC with repetitive clonic jerks • myoclonic: brief contractions localized to muscle groups of one or more extremities or more generalized • atonic: loss of postural tone leading to drop attack

• partial seizures
• simple (no change in level of consciousness): • motor: rhythmic jerking or sustained spasm oflocalized muscles± forceful turning of eyes and head to side contralateral to focal discharge (adversive seizure); may start in one location and spread to another (Jacksonian March); possible post-ictal hemiparesis (Todd's paralysis) • sensory: numbness/tingling/"electric" sensation of affected parts that may spread to other locations; other forms include visual, auditory, olfactory, gustatory, vertiginous • autonomic: epigastric discomfort. pallor, sweating, flushing, piloerection, papillary dilatation • psychiatric: symptoms rarely occur without impairment of consciousness and are more commonly complex partial

topinsmate. MRI (if suggestion of focal deficit. EEG Nota thllt frontal saiZIDI (raral can look. . nasal 0 2. . . movement disorder. progression or >25 years of age) Treatment • anticonvulsant& • psychosocial issues: stigma of seizures.. calcium. lamolrigina. . perception) • forms: dJ5phasic. illusions.. educate patient and family. running. visceral. Timing Day or Night May occur May occur Spontaneous Dftan intsr-iclill di&chqas Increased Day.. forced eye closure. Consider switching medicatio111.•1 Dllfwentill DiltP*il of Connlslons Syncope.tic: lima af Onset Pasitian Onlllt Seizure Day or niltrt Any Sudden or brief Possibla spscific aura Normal or cyanotic Uncommon outside of ictus Srii:OPB Day Upright. taste. lib a puudasG!n WilD odd mo1Dr activity that may occur.. S181'8Dlypic. urea. thiamine 100 mg IY. rigidity. Aura Colaur Duration lncoll:inanca Dizzy. fumbling. blurring. . magnesium glucose. CBC. automatisms May be prolonged Opisthotonos. anticonvulsant levels • focused history • general physical exam (once seizures controlled): LOC. complex partial and secondarily u-ndized 118izur•l: clllbarnllz8pine. Frontoparietal cortex seizures are auggested by contndllhnl facal118nsory or motor plwnam•111. cognitive (disorientation of time sense). ph1111ytuin. Tabla 7. scenes. HEENT (tongue biting. lip-smacking.•.. pelvic thrust crying Motllr ActMty l'ng•ncy I MUll TIIBIIIQIInicity of anticonwlunts due 1D increased risk of open neural tuba dafvct. electrolytes. urinary incontinence. Advisa patient pregnancy 1D take 5 mgfday of folic acid. CBC. Classic Factors Differentiating Seizure versa Pseudosaizures (Conversion Disorder) . swallowing. PfliUIIbelin. pseudoll8izurv. alcoholic blackouts.. motor exam . narcolepsy (r.. cardiac murmurs or arrhythmias. Tempo111llobe eplepsy is suggestad by an 1110 of fvar. "* out teillm IIIli YM:0111110111D present with boll!I Investigations . vital signs.l------------------. anger). diaphoresis Brief Possible but rare Rare Occasionel brief jerks Rare unless from fall None No111111l "-\. dysmnesic (deja vu). magnesium. phanob. vigabatrin Abnncasaizurn (a type of gan8111lizad seizure): ethosuximide Status Epilepticus • initial measures: ABCs. liver function tests. mig111inn !confusional.alapi8X'fl Briuf or prolonged Common Occurs in tonic-clonic or co1J111ex partial Common Common. hypoglycemia. papilledema).lavelinlcebrm. smells). scratching.l------------------. glucose 50 ml IY. creatinine. toxicology screen and alcohol level. other people present Rare Rare Suggestion ::!: stinulus Nonnal Nonnal PhpiCIIInjury lncoll:inanca llepraduction af Attac:k . gabapenlin. affective (fear.Toronto Notes 2011 Seizure Diaorders and Epilepllf Neurology N9 • complex (alteration of mood. structure hallucinations (music. laco11mide. ESR... Classic Factors Differentiating Seizure versa Syncope "-{•. irragular axtnmity moVIITI8nts. EEG. 11A. hyperv8ntilatian. panic disordlr. memory. shakilg heed. not recuntent Gradual hellucinationt. signs of neurocutaneous disorders. IV with NS. olfactury or gumtory Chomu:llri. FBG. pregnancy issues • surgical treatment if focal Narrow spectrum {simple partial. advise of dangerous activities including driving. primidone. aphasia. epigastric fullness • automatism (chewing. neck stiffness.. Complex partial s!ll1us can resemble ll:hizophnmia or pl'jl:hotic daprvuion. nlfinamida. or d6jl w sen1lllions. . tiagabine. disrobing. Antic--Ill Mlldi:ltiBraad spectrum (germalized from onsll and partial onset seizures): felb.. Trigg en Duration Uncommon Emotionel disturbance Brief or prolonged Synchronous. complete neurologic exam.. lighth88dad Pallor Common.tlillll.EEG • bloodwork: electrolytes. tongue biting Common i1 absence or conlJiex partial Normal or Abnonnal Past-ictal Motllr ActMty Injury Autumatilllll "-\. . zonisamide ' • evaluation of new onset seizures: history and physical.mate. continuation of actions prior to decreased LOC) followed by distant staring unresponsiveness Table &. Patients will hiM license suspended Llltil seizure free for EEG Prolldil 'l'wloleiBJres do IIIII &month&. ECG. calcium. verlebrabesilarl. vitals. MinistJy of T111nsportation must be conllcted by law far Ill patients who have had auizurl. oxcarblmpine. Wl)roate. decreased breath sounds.

1-2 (or Diazepam 10 mg IV over 2 mini Lumbar Punc:ture with Gram stain and Treat pl'llllmptivllly with anliliotics .LP negative CT (non-contrast) Vacular Subarachnoid hemormage marbd variability.l-----------------. Smtus Epilapticus Behavioural Neurology . IC8v' Clilicel Fallllnls Thunderclap headache Increased ICP Meningisrrus Focal neurological signs Fever. Laboratory investigations • • • .. polyspika discharges. subdural hematoma lP LP.. poor attention. headache.ICU 2. actiw joinhi 1-'igllions CT (non-contrast) lP Angiogra(tly CT.MRI CT wilh contrast (often ring enhancing lesion) CT (non-contrast) MRI ANA.•.Jr-----------------._..NIO Neurolo8Y Seizure Disorders and EpUepayJBehavioural Neurology Toronto Notes 2011 it•.. Kfvwr or meningismus spib. mood disorder.. . nausea. NB No organic signs or svn. and marbd psychomotor Stroke/IIA w. headache. RF MRI Angiography CT (non-contrast) MRI j'\. Glucose 50 mliV 5...rtoms Deficiencies in vitamins Endocrinopatllias Acute vascular insults Toxins HIIV'( millis Saizunl PriiiiiiiY Psychilbic EEG No specific tests .. hemorrhage. Convulsive Seizure Tf11111:115 Stllbll Epileptic•• . IIIXiaty disorder Increased ICP Focal neurological signs Papiladema See Seizure Disorders andEpilepsy. lor'IIZapam 0. Burst suppression (on EEGI Figura 11. 2.ctiDUI Menilgitis Encephalitis Abscess TI'IUIIIIIic Difluse axonal shear. .ABCs EEG findings sugg•IM of Epilepsy: lbnonnalspikas. seizure Status epilepticus Todd's phenornanon Psychotic disorder. Reflex asymmeby or unilatel'll Babinski aign may bs indicativa of afuc:all85ion. Selected Intracranial Causes of Acute Confusion Etialllgy . pholophobia Meningisrrus Focal neurological signs Fever. Continuous infusion of MidiiZIJIIIriV' propuloVpun1Dbarbitlll 3. epidural hematoma. 59-92% of epilepsy is picked wilh repeated EEGs. • Dulirium is characterized by awte onut.&l. • see Psychiatry..M Delirium is a medical emergency CBrT'finU significant risk of morbidity and mortality. . PS17 Acute Confusional State/Delirium Table 8. 4. fluctuating level of consciousness. :t seizure Increased ICP Focal neurological signs Trauma Hx Increased ICP Focal n1111rological signs Skin r. l. . Fosphanytoin 1OOG-1500 mg IV at 150 m!Vmin or Phanytoill OOG-1500 mg IV at a max of 50 mG"min Another 10 mWkg of F08phanytoin or Phunytoin Phalobarbital 1OOG-1500 mg IV tlowly 1·2h (Tihctay SE) l.M Visual hallucilations more indicate organic diseas1.... Etiology of Delirium I WATCH DEATH lnfuctious Withdrawal from drugs Acute matabolic: dilllnlar Trauma CNS pdlology Hypoxia Autoimmune Acuta CNS Vll&culiti& Neapllltic Mass eh:t/edema. Vrtlllsigns 3. 20-59% of first EEG are positive in epilepsy. ANCA. ..wave compiiXIS. changes.

e. antipsychotics. normal pressure hydrocephalus (NPH). 10-20% vascular dementia • <5% reversible: hypothyroid. antipsychotics Dementia • see Psychiatry. leaving stove on.l. heavy metals • issues to consider • failure to cope • fitness to drive • caregiver education and stress • respite services and day programs • power of attorney Villlmin 112 Deficiency Symp1D1111 • Mllcroqlic llnemia • Confusion or change in men1111 sta1111 {if lldwnced) • Dlcreaud vibnrtion • Oistal numbnllill and parlllllmia • Weakness with UMN findings • Dianhea. orientation. glucose.General Measures • • • • • • • see Psychiatr:y. anorexia. subdural hematoma • must rule out delirium History • geriatric giants • incontinence/falls/polypharmacy • memory and safety (wandering. lipids. hepatic or renal failure. calendars) avoid restraints or catheters stop all unnecessary medications treat underlying cause. similarities. HIY. renal • alcohol. but not level of consciousness Epidemiology • 15% ofthose >65 years of age have dementia • common etiologies: 60-SO% Alzheimer's Disease (AD). nutritional deficiencies. psychosis. proverb) • + Baycrest Neurocognitive Assessment Investigations • depends on suspected etiologies (see Tables 9 and 10) • CBC (note MCV for evidence of alcohol use). leaving doors unlocked. ceruloplasmin. medications (sedative hypnotics.. heavy metals. depression (pseudodementia). ANA. ANCA. B12 deficiency. cortisol. anticholinergics). language. copper. PSIS Definition • an acquired. losing objects) • behavioural (mood. smoking • OTCs. B12o RBC folate • electrolytes. history of head trauma • collateral history is usually very helpful ADLI "DEATH" Dressing IADU "SHAFT" Shopping Houubaping Eating Ambulating Toileting Hygiene Acc:ountilg Food preparation Transportlltion Physical Examination • • • • • blood pressure hearing and vision neurological exam as directed depending on risk factors and history MMSE or MOCA • + clock drawing • +frontal lobe testing (go/no-go. abstraction.. LFTs. anxiety. neoplastic. antidepressants. renal function. brain tumour. thyroid dysfunction. generalized and (usually) progressive impairment of cognitive function (i. depression and infection Etiology • see Table 9 for common causes of dementia • see Table 10 for acquired causes of dementia • reversible causes: Wernicke-Korsakoft medication (benzodiazepines. anti-dsDNA. pallor. 1'/.glucose. PSIS well-lit room hearing aids and glasses orienting stimuli (clocks. suicidal ideation.) • affects content. accessibility • history of vascular disease. compliance. 1'/-. beta-blockers.Toronto Notes 2011 Behavioural Neurology Neurology Nil Management of Acute Confusion . serum calcium • CThead • MRI as indicated • as clinically indicated. etc.J.VDRL. NPH. personality changes. herbal remedies. word lists. SOB • Ftltigue • wills • advanced directives (DNR) . aggression) • ADLs and IADLs • cardiovascular. recall. Wilson's Disease. cortisol. memory. anticholinergics). toxicology. TSH. endocrine.

N12 Neurolo8Y Behavioural Neurolo8Y Toronto Notes 2011 Teble 9. 1029 Rapidly progressive.Jacob disease Syphilis FIMII". nausea Localizing neum Chronic Chronic abscess HIV Creutzfelt. &Ubdural hematoma SlE Mass effect/edema.MRI CT contrast lnvestiptialll Infectious Chronic meningitis LP + investigetions HIV serology EEG LP WRL CT (non-contrast) Traumatic: Diffuse axonal shear. RH9 lncreaed ICP Localizing neum signs Systemic S&S of cancer LP. papilledema Localizing naum signs See Rheumatoloov.failure to recognize or identify objects despite intact sensory function d. apraxia. CJDJ VQCUIIIr dumunlia) Endocrine (hypathyruid) Space occupying lesion (chronic Huntington's disease Multi-infarct d11111Bntia Molecular testing MRI. d11111Bntia (e.impaired ability to learn new information 2. parsiMIIiltion Decreased social Progressive non-fluent aphasia Memory relatively spared Chorea Abrupt onset StEpwise de!Eiionrtion Dysexecutive syndrome Focal neurological findings Systemic S&S Dl vasculitis CT or MRI. ANCA.SPECT Huntington's. one of the following cognitive disturbance a. Apraxia .Hu antibodies Neaplutic Alzheimer's Disease (AD) • see P&ycbiatcy.planning. anterograde amnesia . Disturbance in executive function . myoclonus Trauma llx Increased ICP. sequencing. PSIS Definition • progressive cognitive decline interfering with social and occupational functioning characterized by the following 1.impaired ability to carry out motor activities despite intact motor function c. autosomal dominant • 3 major genes for autosomal dominant AD have been identified: • amyloid precursor protein (chromosome 21) • presenilin 1 (chromosome 14) • presenilin 2 (chromosome 1) • the E4 polymorphism of apolipoprotein E is a susceptibility genotype (E2 is protective) 4 A"lllllf IIIII D If AD Anterograde amnesia Aphasia ApiiiXil Agnosia Disturbance in uecutiva function . RF MRI AngiJgraphy Teble 10. m:ganizing. Aphasia -language disturbance b. Common Ceuses of Dementi• It' Dtmentill DDx Etiology Primuy llegananrliVB Key Cli1icll Fellures Allheiner's disease Lewy body disease VITAMIN D VEST V"rtamin deficiency (812. headache. agnosia Hallucinations Parkinsonism Fluctuating Disinhibition. Agnosia . abstracting Pathophysiology • genetic factors • a minority (<7%) ofAD cases are familial. SPECT CT or MRI. epidural hematoma. Pick's disease) MRI. folatll. hemorrhage.g. HIV) Nonnll pressure hydrocephalus Duganendive (Aizhuirne(s.SPECT hematoma) Toxic (alcohol) eNS vasculitis ANA. seillft Paraneoplastic MRI. anli-dsllNA CT contrast MRI Ani). myoclonus Ataxia. thiamine) lntnlcranilll tumour TIBUITIII Memory impairment Aphasia. headache Increased ICP Localizing nauro signs See Dil!!§!ll. ANA. Acquired Causes of Dementia Etiology Key Clinical Features Fever. SPECT (hulld injury) Anoxia Metabolic (diabetes) fnflclion (pollti11C8p/llllitis.

memory loss may or may not be an early feature • one {possible LBD) or two {probable LBD) of the following: • fluctuating cognition with pronounced variation in attention and alertness • recurrent visual hallucinations • parkinsonism . galantamine (Reminyl•) • relative contraindications: bradycardia. CAD. abstract reasoning. asthma. or increased risk of ulcers and GI bleeding • galantamine is contraindicated in patients with hepatic/renal impairment • memantine (Ebixa•) is an NMDA-receptor antagonist that has some benefits in later stage AD • other .Toronto Notes 2011 Behavioural Neurology Neurology N13 • pathology (although not necessarily specific for AD) • gross pathology • diffuse cortical atrophy. CHF. COPD. especially frontal. parietal. Ievell evidence) • symptomatic management • low dose neuroleptic • trazodone for sleep disturbance • antidepressants Prognosis • progressive • mean duration of disease 10 years Lewy Body Disease (LBD) Definition • progressive cognitive decline interfering with social or occupational function. and executive function • psychiatric manifestations • major depressive disorder {5-896) • psychosis (20%) • motor manifestations {late) • parkinsonism (consider Lewy body disease) Investigations • • • • perform investigations to rule out other causes of dementia as necessary EEG: generalized slowing (nonspecific) MRI: dilatation oflateral ventricles. and temporal lobes • microscopic pathology • senile plaques (extracellular deposits of amyloid in the gray matter of the brain) • neurofibrillary tangles (intracytoplasmic paired helical filaments with beta-amyloid and hyperphosphorylated Tau protein) • biochemical pathology • 50-90% reduction in action of choline acetyltransferase Epidemiology • 1/12 of population 65-75 years of age • l/3 of population >85 years of age • accounts for 60-80% of all dementias Risk Factors • family history of AD • head injury • low education level • smoking • aluminum (controversial) • Down's syndrome Signs and Symptoms • cognitiveimpairment • memory impairment for newly acquired information (early) • deficits in language. arrhythmia.although efficacy not proven • ginkgo biloba • Vit E (caution: >400 IU/day associated with excess mortality. ulcers. widening of cortical sulci SPECT: hypometabolism in temporal and parietal lobes Treatment • acetylcholinesterase inhibitors have been shown to improve cognitive function • donepezil rivastigmine (Exelon•).

Nl4 Neurolo8Y Behavioural Neurolo8Y Toronto Notes 2011 Etiology and Pathogenesis • Lewy bodies (eosinophilic cytoplasmic inclusions) found in both cortical and subcortical structures Epidemiology • 15-25% of all dementias Signs and Symptoms • :O.g. glabellar) • parkinsonism Investigations • MRI/SPECT . peak incidence between 50-70 years old . donepezil) Prognosis • typical survival3-6 years Frontotemporal Dementia (FTD) Definition • progressive dementia characterized by core symptoms of either disinhibition and emotional lability or of apathy and detachment Etiology and Pathogenesis • gross pathology • atrophy of frontal and temporal poles • microscopic pathology • Pick bodies (intraneuronal inclusions containing abnormal Tau proteins) Epidemiology • 10% of all dementias Signs and Symptoms • core features • behavioural disorder • impairment of personal conduct and of regulation of social interactions • decline in personal hygiene and grooming • mental rigidity/inflexibility • perseverative and stereotyped behaviour • speech and language • altered speech output (economy or pressure of speech) • echolalialperseveration • physical signs • primitive reflexes (ie. pout. extrapyramidal symptoms) • REM sleep disorder Treatment • acetylcholinesterase inhibitors (e. astrocytosis and neuronal loss Epidemiology • rare (1 in a million). neuroleptic malignant syndrome. grasp. palmomental.uctuation in cognition with progressive decline • visual hallucinations • parkinsonism • repeated falls • sensitivity to neuroleptic medications (develop rigidity.frontotemporal atrophy/hypometabolism Creutzfeldt-Jakob Disease (CJD) Definition • rare degenerative fatal brain disorder Pathophysiology • prion proteins causing alterations in the brain such as spongiform changes.

. more psychiatric symptoms.. progresses over years Histopathology • sponglform changes. EEG.Y.ntftw • an acquired disturbance of language characterized by errom in speech production. writing 6. spontaneous speech •fluency • paraphasia&: semantic ("cbm for "tablej. NS7 NPH Prog-bl llf Cl-11: Triad AID A11DciWA!nxil af Damantia h:DIIIilmce Aphasia Definition ----------------------------------------------- \•. toothbrush. Longer duration. electrodes • variant: earlier onset. Mad Cow disease) • kuru: historically due to cannabalism in Papua New Guinea laadilll tD nUGnll loa.culus association bundle connects Wernicke's and Broca's areas • >9996 of right-banded people have left hemisphere language representation • 7096 ofleft-handed people have left hemisphere language representation. 1596 have right hemisphere representation.Toronto Nota 2011 Neurology NlS Clinical Presentation • sparadk CJD: rapidly progressive demenling illness causing death within months. InJections (human growth hormone products). no risk facmrs • hereditary CJD: family history or tests positive fur genetic mutation (5-10%) • acquired CJD: transmitted via exporure to prion in nervous system tissue (<1%) • Iatrogenic CJD transmitted In organ transplants.. . comprehension (auditory and reading) 5. sdsllors) • education level • native language • learning difficulties • assessment for aphasia 1. Th&laft: han.. comprehension. or reading IIIIICJUIIII in Iimas! Ill riF!-Mnded people and 70% of lllfi-Mnded PIIOP'-- Neuroanatomy of Aphasia • Broca's area (posterior inferior frontal lobe) involved in speech production (expressive) • Wemick. neologism& W. associated with myoclonus • cerebellar ataxia • cxtrapyramidsl signs • aldnelk mutism and cortical bUndness sometimes occur •fatalwlthinlyear • EEG: triphasic compleus Diagnosis • rule out treatable dementia. The inflctio1111orm iJ aln:nmally fDided and leads tD abnormal fDidina af no11111l prian pra1Ji111. .. ab&ence of triphasic . and 15% have bilateral representation Assessment of Language • asseaament ofcontext • handedness (writing. writing.e's area (posterior superior temporal. . astrocytosls and neuronal. Broca's and Wemlcb's Ar. neurologic exam. loss • occur sporadically Treatment • no known treatment Normal Pressure Hydrocephalus • see NeuJ'OS11IFI'. ia domir-. drawing.y to confirm diagnosis is brain biopsy/autopsy 1\fpes • sparadk CJD: most common form (8596).. Prion prollins have 11 normll fonn and 111 irnc:lioua form. repetition 3.micb's area: poetllrior apect af 1" tampan! IJYIUII Figure 12. Thae aln:lrmally fDided prgtein•IIVIII'8glllll compleus on EEG (Le.namlng 4. • panencephalopathic form: primarily seen in Japan. or phonemic ('"clable" for "table") 2. MRI • only wsr. lobe) used for annprehension oflanguage (receptive) • angular gyrus is responsible fur relaying written visual stimuli to Wernicke's area fur reading comprehension • the arcuate fascl.

but may continue for >1 year • with recovery.ryoutthe lelmed .aryTCA• Relatively Spared POor Relatively Spared Poor Posterior superior len1Jmllobe Arcuate fasciculus 1. combing one's hair Preparilg and mailing an envalope Copying afigure Dressing specilil:llyla the inllbily Ia c. • M11yskilll uida from plllliln naedad to canyiMthesaiiSb. impaired comprehension. Table 11. Temporoparietal watershed between MCA and PCA taritories Numerous possible locations Alomic Fluent Good Good lt:A=T11llS4:Grlic:IIIPhasil II"B typicllly ISIOCilted Mil carablllllllllllil (a..u Apbasilllocalizes 111e lesion to the dominant cerabral bemllpbare. drMing. \1\otita matter lesions deep to (1) Combined sensory and motor tllnscortical Posterior infaior frontal lobe AND posterior superior temporal lobe MixadTCA• No.nuent MaturTCA• 1. cRw. Fronlllllobe watershed between MCA and ACA territories 2.ftuent Fluent Fluent Fluent Poor Poor Poor Good Poor Good Poor Poor Poor Good Poor Global Wernicke"• Canduc:tion Scn. ataxia.. CO poilonif'G....Nl6 Neurolo8Y Behavioural Neurolo8Y Toronto Notes 2011 -t•. hypabrllliln) Prognosis • most recovery from stroke-related aphasia occurs in first three months.-nts iMJiwd in conslnrjjon. or inattention Clin icopathologic:al Correlations Table 12. •dresl. post-MI..oclizllian I'Dsterior irmor frontal lobe Broca"• No.. Agnosia Definition • disorder in the recognition of the significance of sensory stimuli in the presence of intact sensation and naming .g. the type of aphasia may evolve • poor prognosis: global aphasia Apraxia Definition • inability to perform skilled voluntary motor sequences that cannot be accounted for by weakness. Subcortical temporopilistal 2. Ideomotor ldelliOIIII Canlbuctianal• Dressing• Inability to parforrn skilled laamed motor sequencas Inability to sequence actions Inability to draw or consbuct Inability to dress Blowing out a mall:h.. Apraxia Tests Hemi1pheres Lalt Right and left Right and left Right !Ill merely tile illlbiily Ia canstruct. Approach to Aphasias Fluency lllpalitian Good Good Poor Good Naning POor POor Llsian l. . sensory loss.nuent No..ftuent No.

. chronic meningeal inflammation. intm"eron treatment of hepatitis C virus. .. atrophic rhinitis (leprosy) • c:entral: lesion of olfactory pathway • Kallman syndrome.. L. .lllmanrflsyndrorne ila conganitll dilordrr of .. resting eye position is •down s. SO 0 Shiny H. m... Lai Zllll& CN Ill: Oculomotor Nerve Clinic:al Features E. Nearology/Craaial Nerve Defi.. __ _ _ 1/1 C31llid .lci!Macle • ptosis..... . Dilgnastic PasitiDns Df GilD 1D lsola1B Primary Ac:tio• uf Common Lealona • • • • midbrain: bilateral with contralateral pyramidal signs ± mydrlasls posterior commwlicating artery aneurysm: early mydrlasis then CNm palsy cavernous sinus (internal carotid aneurysm.r agnDBia..tions Tillie 13.®/' 10 \ JR Mit ii' •LR .. temporal arteritis... SAH.ilm. . Canrnaus SEa .. msta. and lsft-right llsarianbdiDR. Pnllaplg1DIII lnalility Ill ranun abjact prann18d vi&ualy 2"to disCIIIIBct batws111 viul CDitax 111d III!PgB li8IIS Viul JIIIC8pliorr is inlllct 111 dllmoiiiba18d by viul matching lnaiJiity to ra:ognize firnililrrfaces iJ the pesen:e of Biatenrl accpjal!lqJonrlanm or r9i iiaior inllct vi.nlll ·*"""---v. V1 and V2 as Wflllas pain and proptosis. Ill.eeions iRVGivilg tha C'8V8111DU8 liar1 111M pallliea of Ill. Fi•gar Aplasia lnaiJiily to idediy objects by touch lnaiJiily to racagniza... 1\f.. lnaiJiily to pan:aive cHI' Alllnlt_. and cartical 1111n111ry lOIS. meningioma. herpes simplex.. considrr rnailglring. and hypoganiiiiDinlpil: hypogan. If 1111111mill il nlll: UlociiiiBd wi1h loa af \. Aa•Diils Apen:apiM VIIUII Aplla Aaacillila \'111111 Apllil lnaiJiity to l1lllle or demanslrale 1he use mill object jJ'BIIIIIIad vilully zt to dilllarled visual pan:aptian Recognilian by tiU:h 181011ils intllc:l Lisian BIBIBal cartex . slnua thrombosis) ischemia ofCNIII (DM.tary r----lnt. ' .. Parkinson's diaease ''...rbinitts. IBid 1o i 0 Figun 14. Pariml '-ii!M Lssians of1he dominant Pllrietalloba n chnctlrizBd by Gamnlll!"a Syndro1111: acak:ulia. HTN. '. . head injury. agraphia.cting canlnl of CIIUIII pupilllry . lf.c .. and pailt to Dial filga!s llaminant hemisphara Cranial Nerve Deficits CN 1: Anosmia Cllnlc:al Features • absence ofsense ofsmell associated with a lo98 of taste • usually not recognized by patient ifit is uni1atera1 Classification • D8l8l: odours do not reach olfactory receptors because of physical obstrudion • heavy smoking. N20 SR LJt IR .l pen:eptian and inllct auditory IIICO(Jitian tampa10-accipitll ragian Anlaillr pll'ietal llbe in 1he llmsphere app01ita tha lffactad hind CabJr .eliOM of1ha pwillll IDIIe are clwBI:IIrized by 11111111et. sinusltis • olfadory neuroepithelial: destruction of receptors or their axon filaments • intluenza. CN II: Optic Nerve • see Neuro-Ophthalmology.•.. meningioma..nd abducted). 11111111. '.D81Jt1naaia.• to mydriQia while infan:lion (mr. atherosclerosis): pupil sparing ["\. aneuryam. pupil dilated (mydriasis) Figun 13. Pup•ry cOMiril:blrfibiVII&re on lha par1ohalllllllpiCI: af CNIII au cornprlllion of the neml.dh Neurology Nl7 Clinicopethologic:•l Correl.. l.. albinism.'IbroDlo Nota 2011 Bebaivoaral.. Jlii/fi----111 :mwr-----IV • . cranial surgery.nd out'" (depressed s.•.. chronl..

CN IV is the only mnill nerve that exits pcmaio!ly 111d cro111111 thu midlinu.. congenital • other: cavernous sinus lesion..)-----------------. syringobulbia.. meningioma) . . sarcoidosis. DM mononeuropathy. V 2 • normal sensory exam • etiologies: idiopathic. trauma. mating a1&111 localizing sign. multiple sclerosis (5%) • pain lasts seconds/minutes over days/weeks. or temporal arteritis • congenital. orbital fissure (tumour. CN V: Trigeminal Nerve Lesions • trigeminal neuralgia. ipsilateral brainstem lesion. hyperacusis. usually middle-aged and elderly • medical treatment carbamazepine. narcotics do not help • if medical treatment fails (order increasingly invasive): gamma knife. parotid gland disease Forehlllld i15p11recl in a UMN CN VII lasion due to bilateral innervation from cerabral hemispheres. granuloma) deficit. . contralateral parietal lesion Trigeminal Neuralgia (Tic Douloureux) • excruciating unilateral paroxysmal shooting "electricn pains in trigeminal root territory • usually in V3 distribution ± V 1. metastatic infiltration of nerve. Ramsay-Hunt (HSV). multiple sclerosis or vascular lesion with MRI H•1111• later of Tri111111inal Nem: typi:lllly illVIIMs Vl (opthalmic division]. shaving.. CN VI: Abducens Nerve Clinical Features • inability to abduct the eye on the affected side • patient complains ofhorizontal diplopia. orbital fissure. Hutcbi•on·s Sign: tip of no.may be secondary to DM. invasive percutaneous denervation (radiofrequency/glycerol). CN VII: Facial Nerve Clinical Features • ipsilateral facial weakness (involuntary and voluntary) • impaired lacrimation. idiopathic. compression by tortuous blood vessel (SCA). A CN IV lesion may cause a con1nllateral CN IV: Trochlear Nerve Clinical Features • diplopia (with downward and inward gaze). cavernous sinus.•. demyelination) . hemorrhage.false localizing sign ofincreased ICP • cavernous sinus (carotid aneurysm.. microvascular decompression • rule out structural lesion.. HTN. pr8dicts comul involvement. taste d)15function of anterior 2/3 oftongue Investigations • brainstem (LMN) versus cortical (UMN) symptoms and signs help localize lesion Differential Diagnosis • idiopathic= Bell's Palsy. applying make-up • F > M.. eating.associated with facial weakness and contralateral pyramidal signs • tentorial orifice (compression. cerebellopontine angle tumours. numbness behind auricle. cerebellopontine angle tumour (5%). talking.Duane's syndrome it''has 1h1 longast in1rllcrsnial couru CN VI lDid is wlnerable to increased ICP. minimized with head tilt to opposite side • patient may complain of difficulty going down stairs or reading Lesions • common: ischemic (DM. .Nl8 Neurolo8Y Cranial Nerve Deficits Toronto Notes 2011 -"{.. remits for weeks/months • triggers: touching face. CN IV is at ri&k of 1rlluma during neurosurgical procedures ilvalving the midbrain becausu of it$ long in1rllc11111illl CDUfM. worse on ipsilateral lateral gaze Common Lesions • pons (infarction. herpes zoster. demyelination. thrombosis) • vascular. . decreased salivation.e involvllllllll. HTN). trauma (TBI or surgical). cold wind. otitis media/mastoiditis. EBV.. percutaneous balloon microcompression. 80-90% of cases (see OT23) • other: temporal bone fracture. . .

.• ri. UMN VL llt'IN fllcill N8M1 Palsy CN VIII: Vestibulocochlear Nerve rt•. CN IX: Glossopharyngeal Nerve Clinical Features • sharp paroxy8l1l8l pain of posterior pha.ralllla. and XII.. S. indistinct speech Plrlicul. IIIIBDrrrj!llilil. triggered by swallowing • taste dysfunction in posterior 113 oftongue • absent gag re:flex (dysphagia) wt. poliomyelilit.MG) Myapathv (a.IICI'IIIIi!g for th8 Prlll8nce D1 and .g. tumour11 Talala 14. demy11inlltion. c:up a.. in prtlxi'nily to the l'llpillloly l:lllntnl.s1111ss Canballllr disease Canballar outflow tnlct diSIIIII Connection& il the nucl. SWIIowing diiPBnda on liferent inlarmllion vii CN V..Df the tralrtulsolm. X..rynx radlating to ear. NDITIIII is inilillhld when lh• IDIIfJI 1h1'8W1a bolus blt:lt Slured.JOI) CN X: Vagus Nerve Clinical Features • dysphagia (palatal and pharyngeal weakness) • dysarthria (laryngeal weakness): inability to produce understandable speech due to impajred phonation (laryngeal sound production) and/or resonance (the alteration of sounds in the cavity between the larynx and the lips/nares) secondary to impaired motor control over peripheral speech organs llllrlll:nniiVIIUIIIMe: mngioma. . IX.difticully Mill villltory "R" Dilliculty consiiiBlt& purilcad by tlllgus a1d l_.llll8g. and X and mo1or action via CN v. Al.. .y by CN XII. the cornet tilt il1o DIIIIMI tha plltillll Ginldng WIQr !rum a. IYrinaotutil.nd IDDting for coughing._CniUI llarw dafi5b (CN IX. Treatment • carbamazepine or surgical ablation of CN IX D. Tha bolus slimuiiiiBs tha 10ft palal8 to slsva18 llld the bolu• is dlllldlld into 1ha Of1IPiwynx. tt.. u.... Cllluilbtion af Dyar1fuill Qusili:alial ----t•. DMfMI into the pa.. X. or "wtlness" Df vaice. I'IIIUrD!Inmll.ius i1 the meciiAI.c1: the phlryngalll conslric1Dn cunnct.S) f'a1Dnl niiVI (a. llliDn (Balra 1118krl Cranial Nerve Defidb B.11.U•claar llliDn Neurology Nl9 Figure 15. tha Slow 111d manu!GKius Slllliled or Straka TIDID. Swallowing 111d n coordinllecl1o prevent IIIJinllion.. meningitis lniaiiMI: strDU..l • the swallcrwi'lg centra. choking.i n g rillk fill' IIPildian. GBSI NIUUIII&CUIIr junction (8..JO.lsbil8ldlwlly-tongue mowm111111ra innarwbld udllli. rhythm lmprap..1111 (e. tha p181811CB rJ I gllg raftM ia illlll'icillnt llltlur..g.ill CIIIIOIIIID pnub:sd by lips Mo1Dr ne1. Ftlcill n. llllroeytuma Nadc trau11111. miiBibllll.'IbroDlo Nota 2011 A.g.urgary. Demyelination DlgenaretiCII '-Ynx Ha1111 Lawpilched llld the weal conls clo11. VIL IX.

N21. .ptched Monotonous DealiSCendo volume Hyperkinetic Parkinson's disease Other causes of parkinsonism (see Movement Disonlets) llmtington's disease ChD1'8iform • Prolonged senlllnce segments intermixed with silences • Variable. PM-polymyositis CN XI: Accessory Nerve Clinical Features • ipsilateral shoulder drop.. compression by space occupying lesion (e. OP24 . Classification of Dysarthria (continued) Extrapyramidal Hypokinetic Low. OP37 and Stroke section. optic tract/chiasm lesion. retinal detachment • optic nerve: optic neuritis. Multiple Sclerosis. IJ. Anterior Ischemic Optic Neuropathy • • • • --------------- If you ill'll8Cl the diagnolis of qiant cen arteritis do not wait for biopsy rasLJts. anterior ischemic optic neuropathy (arteritic. MG -llftllllhril gmis. aneurysm) • vascular: TWamaurosis fugax.. RH17) Amaurosis Fugax • see Qphthalmology. N44 Central Retinal Vein Occlusion (CRVO) • see Qphthalmology.l-dlnni!Dmyasitis.. non-arteritic).g. weakness on turning head to contralateral side CN XII: Hypoglossal Nerve Clinical Features • tongue deviation toward side oflesion • chronic LMN lesion: ipsilateral tongue atrophy and fasciculations NEURO-OPHTHALMOLOGY Abnormalities of Vision Acute Visual Loss • ophthalmologic: acute angle closure glaucoma.N20 Neurolo8Y Cranial Nerve Defu:its/Neuro-Ophthalmolo8f Toronto Notes 2011 Table 14. Beqin treatment immediatelyl see also Optic Disc Edema. improper stn!ss Dystonia muscuiCIUm deformans Other hyperkinetic extrapynrnidal disarders (see MavemenrDisonfets) • Bursting quality Dystonic • Slow speaking rate • Prolonged individual phonemes "Abbmiatians: ALS. vitreous hemorrhage. migraine • infectioD}inflammation: endophthalmitis Optic Neuritis • see optic Disc Edema.. central retinal artery or vein occlusion.. N 49 .'lllroma. N21 clinical presentation: painless vision loss over hours to days non-arterltic: (NAION): vision loss due to atherosclerosis arteritic (AION): normally due to giant cell arteritis (see RheumatoloGY.amyrAJopliic lltllllscllrolis. carotid-cavernous sinus fistula • CNS: stroke. GBS -Guillain-Bami l'.

the more porterior the lesion • check all hemiplegic patients fur ipsilateral homonymous hemianopsia (e. Leber's hereditary optic neuropathy.taritic. compressive tumour. optic neuritis. . jaw deucicetion If GCA: headache. AION. . congenital • praartatioa: disc pallor.l8duce mrnids I arteritic lOP. decreaeed colour vision • treatment: none (irreversible). left hemisphere -+right visual field defect) i Q Figun 1&. Cherlll:telistic Vis•l Field Dlfecbi with 1.'IbroDlo Nota 2011 Neuro-Opbl:halmoloBf Neurology N21 Optic Disc Edema Tillie 15. optimim risk factors. glaucoma. vial IV(ratcnl) lnCI1!BSI!d ICP one Tf8Bimusa Calsidar ASA I non. retiMI hemanhages hlllllllhllge Ghlll cell arteritis Associated with vascUopathy Etlalaal• Tralnlam MS. low visual acuity.J. no VIllOUS jQsatians taldam•. Swollen diac.I fii!IM RAPD !liC if llllerior RAPD No RAI'Il Pale llll!rnenllll diiC ad111111. :t laser Optic Disc Atrophy • etlologln. V8IIDUJ relilal Ct.. peripheral vision defect. Commo1 Causes of Opac Disc Edell• Optic Nlllllll Age Plplllllml AIDN CIIVO <50 llld cohu vision Pail (esp with eye movanent} Alrr 'mion SynpiMs Rapid Pf'OW888iv8 cemal le 'liullou visimllaa with .J. flml 11191f98111R.g. aim to prevent Abnormalities of Visual Field Definitions • monocalar • scotoma: an area ofabsent or diminished vision within an otherwise Intact visual field • binoc:alar • hemianopsia: loss ofhalfof the visual field • homonymoWI: loss of either the right or left half of the visual field in both eyes • bitemporal: loss of both temporal visual fields (lesion ofclrlasm) • quadr.mtanopsJa: loss ofone quarter of the visual :field BrTEMPORAL HEMIANOPSIA • chiasmallesion • in clilldren: craniopharyngioma • In middle aged: pituitary mass • in elderly: meningioma HOMONYMOUS HEMIANOPSIA • retrochiasmallesion • the more congruent. . acuity >50 Unillleralecuta field datact M1h .81iaas Alal!g the Viull Plthvny . foil( hx:al neurologicll deficits NoRAPD DiiC retiwl hemanllage. cokuvision >50 IWIIteral Vllilllle vision lou CardiDvascular risk !aetas Heaclschl!.

see Multiple Sclerosis. tumour. . Diplopia worse at end of the day suggests myasthenia gravis {e. N32) •other • orbital trauma. 2) full excursion of contralateral eye in abduction but with monocular abduction nystagmus • cannot be overcome by caloric testing • accommodation reflex intact • may be bilateral • upbeating nystagmus on upward gaze often present Left {abnormal} Diplopia Monocular • mostly due to relatively benign optical problems (refractive error.N22 Neurology Neuro-Ophthalmology Toronto Notes 2011 Abnormalities of Eye Movements Disorders of Lateral Gaze Etiology • brainstem infarcts • multiple sclerosis • tumours Pathophysiology • voluntary eye movements are triggered in the frontal eye fields. Internuclear Ophthalmopliegia 11•. bilaterally in the frontal lobes • each frontal eye field controls voluntary saccades to the contralateral side via connections to the contralateral paramedian pontine reticular formation (PPRF) • a unilateral lesion in one frontal eye field: prevents voluntary saccades to the opposite side.trauma • CN VI (abducens) • DM. N49) • brain stem infarction • neoplasm • AV malformations • Wernicke's encephalopathy Pathophysiology • results from a lesion in medial longitudinal fasciculus (MLF) which disrupts coordination between CN VI nucleus in pons and the contralateral CNIII nucleus in midbrain -+ disrupts conjugate horizontal gaze R Standard {normal} - Right {normal} Clinical Features • on gaze away from the side of the lesion: • I) adduction ofipsilateral eye is impaired. and to look towards the lesion. trauma • isolated CN III palsy with pupil sparing usually due to DM and most will resolve spontaneously in several months • isolated CN III palsy with pupil involved usually indicates compressive lesion (especially posterior communicating artery aneurysm) • CN IV (trochlear) • DM. eyes deviate away from the lesion • cannot be overcome with doll's eye maneuver • seizure involving a frontal eye field: cause eye deviation towards the opposite side . eyes deviate toward the side of the lesion • can be overcome with doll's eye maneuver • a unilateral lesion in the PPRF in the pons: prevents voluntary saccades to the ipsilateral side. N17) • CN III (oculomotor) • DM. A lesion in the brainstem causes the eyes to "look toward" the side of the hemiplegia..g. aneurysm. If only diplopia on extremes of gaze. ... cover each eye in isolation during extremes of gaze. The covered eye that makes the outermost image disappear is the one with pathology. Internuclear Ophthalmoplegia (INO) Etiology • MS (most common. functional) Binocular • cranial nerve palsy (see Cranial Nerves. located anterior to the precentral gyrus. and to look away from the lesion. tumour • Wernicke's encephalopathy • Miller-Fischer variant of GBS • leptomeningial disease Vergence {normal} © Shelley Wall 2003 Figure 17. raised ICP (false localizing sign) • muscle • Graves' ophthalmopathy • neuromuscular junction • myasthenia gravis (MG) (see Myasthenia Gravis. cataract. tumour.. fatiguable}. trauma. A lesion in a cerebral hemisphere causes eyes to "look away" from the hemiplegia.

. small amplitude movements ofthe eyes that are rhythmic in nlrtnre • direction of nystagmus is defined by the rapid component of the eye movement • can be categorized by movement type (pendular... involuntary.H-----"?'\ Edingar-Was1phll Namll . RAPD ...Toronto Nota 2011 Neuro-Ophthalmology Neurology N23 Nystagmus • definition: rapid. Dii'IICt raspons1 CGn18IIIIUII reapo!118 ry.. advanced glaucoma PreC8atal nucleus ( 1 1 1 ... jerking.... central retinal artery/vein occlusion. large retinal detachment. both pupils constrict • when damaged side is Illuminated.. and better to accommodation • differential diagnosis • optic neuritis is the most common cause of RAPD • other causes: optic nerve compression.. coarse) or as normal vs.-+-. rotatory.. both pupils paradoxically dilate because the damaged eye perceives less light relative to normal eye • pupil reacts poorly to light. CGn81riction of lllmulltad f10J8 ® ---- COIIItriction of IDIIimulllllld f10J8 Figu. OP33 Definition • a fallure ofdirect pupillary responses to light. both pupils should constrict initially • when normal side is illuminated. pathological Abnormalities of Pupils Relative Afferent Pupillary Defect (RAPD) (Marcus-Gunn Pupil) • see also Ol!hthalmolop. 18._. caused by a defect In the visual afferent pathway anterior to the optic chiasm • clinical testing • swinging llgbt test • swing light from one eye ID the other.

post-ganglionic • paredrine (hydraxyamphetamlne. medulla (brainstem stroke). cavernous sinus IIlllli8. D E 0 F"IJirl 19. paravertebral mass. trauma (lncluding surgical) • clinical confirmation with cocaine test cocaine does not dilate a miotic Homer's pupiL Cocaine blocks the reuptake of nora.. anhydrosis (lack of sweating). MS.. carotid artery dissection • 3rd-order neuron (postganglionic): cluster headache.olOBY 1'oroDio 2011 Horner's Syndrome Definition . but will dilate ifthere is a pre-ganglionic or central lesion • no test to di1ferentiate central from pre-ganglionic lesion Short ciery llllirth*niclnnch ohigaminalg111glion c. pre-ganglionic vs.. intracranial tumoUIS. syringomyelia • 2nd-order neuron (preganglionic): apical lung cancer (Pancoast's tumour).dtenaline. Sympatflatic of Pupilary Dlatian Anisocoria • clefiDltion: unequal size of the pupJls • see Qphtha1moloo OP31 . spinal tumcnu. and apparent enophthalmos • lesions occur anywhere along the sympathetic pathway on the affected side • 1st-order neuron (central): hypothalamus...N24 Neurology Neuro-Ophtbalm. stimulates noradrenaline release) will not dilate in a case of post-ganglionic lesion. ' H-'• Sylllnne •PIDIIil • lliollis • Anhydrasis • a sympathetic defect • clinical features: partial ptosis (drooping eyelid). miosis (conrtricted pupil).rvical u-I'Giion . which dJlates a normal pupil • central vs.

especially distally Slow ami/or small alflllilude movements Rapid jerky movarnentthat looks semi·puposeful Excessive movements associated with neuroleptics Co-corrtnlction of and antagonists causing sustained twisting movements Episodes of halted mCJIDr action. . PATltWAY DIRECT ---.e.Toronto Notes 2011 Movement Disorders Neurology N25 Movement Disorders Overview of Movement Disorders Tabla . .. . most movements sean in movarnent disordersl [i. 6. which then activate two pathways: direct and indirect • indirect cortex striatum GPe STN GPi/SNr thalamus motor cortex • activation ofthis pathway causes inhibition of the thalamus and ultimately prevents movement • direct: cortex striatum -+ GPi/SNr -+ thalamus -+ motor cortex • activation of this pathway removes the inhibitory effect of the GPi on the thalamus.dng D•llllblngM-. It receives input from the cortex and thalamus to inhibit the globus pallidus pars interns (GPi) and substantia nigra reticularis (SNr). They project fibres to the cortical motor areas via the ventral thalamus (thalamocortical) to prevent excess movement using tonic inhibition (in particular the GPi) • the cerebral cortex initiates movement via excitatory (glutamatergic) projections to the striatum.--. vi11UIIl1hreat.g. or Function of the Basal Ganglia • the striatum (caudate and putamen) is the input of the basal ganglia.nt IIVPerldnul•: BXCess of movement (i.' Tl'llllllr Soma myoclonus is rtim!Ws sensitive and can be induced by noise.e. squinnilgl Loss of rruscle contraction (negative myodonusl Slow writhing movements. thereby allowing movement pinprick. can be suppressed Rhythmic alternating movements .. aspacially cllrilg walking Unilateral violent flingir¥4 movement Briel muscle group contraction 1hat is either focal.. Neural Connections Df the Basal Ganglia .--• Figure 20. light.. Bridyldn•iill Charea Dpldnllil Dysblnil Free. movement.. segmental.-.GABA ----.. bradykinesia and freezingl HvPokilllllia: reduction in movarnent H1111iballism Myoclonus Myukimil Tachykin•i• TICS . or generalized Muscle quivering Acceleration of movements Stereotyped actions due to inner urge.·: Excitatory connections connections . promoting movement • the GPi and SNr are the output of the basal ganglia.. Muvamant Disorder Definitions Aladhisia Altlrilil A1hltolis Subjective restlessness relieved by stereotypic movements (e.

Syndenham's chorea. Describe the movements. Association with OCD and ADHD . writer's cramp) b. cerebellar. heavy metal poisoning. Figure 21. Consider the differential diagnoses for the movements named 11•. Wilson's disease c. CO. anticonvulsants. Differential Diagnoses 1. Wilson's disease. blepharospasm. cerebrovascular disease.)-------------------. Wilson's disease. anticonvulsants. adult onset or senile b. stroke. hyperglycemic Propranolol. Secondary dystonia: thalamotomy. demyelination. and CT/MRI (cerebellar disease) as indicated by type of tremor. myoclonus-dystonia c. MS Treat underlying cause Physiologic.. drugs. Parkinsonism. benign essential. drug toxicity. APLA syndrome. ' >90% of essential tremor does not need treatment. Mn. anxiety. head trauma. Horizontal Section of Basal Ganglia Approach to Movements Disorders 1. ' In a young patient ( <45) must do TSH (thyroid disease). sedatives. Wilson's disease. Dystonia-plus syndromes: dopa-responsive dystonia. especially in the upper extremities b. cyanide. alcohol. Postural: physiologic. mental retardation syndromes c.. Primary tic disorders: transient tic disorder. CNS tumour. CJD. SLE. Syndenham's chorea. mercury poisoning Table 17. Approach to Tremors Resting Body Part Characteristics Worse with Associated Sx DDx Distal UE 3-7Hz pill rolling Rest while concentrating "TRAP" IPD. Alcohol dampens essential tremor. Wilson's disease Sinemet. Heterodegenerative dystonias: Parkinsonian disorders. senile chorea. PNS injury.Dystonia a. Treabnent 2. Wilson's disease • benign essential tremor is a common autosomal dominant trait that presents as a bilateral postural tremor of the vertical axis. Huntington's disease 4. Gilles de la Tourette. thyrotoxicosis.Chorea: Huntington's disease. neuroacanthocytosis.l-------------------. Name the movements (see Table 16) 3. Resting: Parkinsonism.N26 Neurology Movement Disorders Toronto Notes 2011 Splenium of corpus callosum © Lucy Zhang 2011 '. primidone 11•. Primary dystonia: familial. chronic tic disorder. methanol) d. alcohol.Tics a. anticonwlsants. Wilson's disease. drugs/toxins (L-dopa. Secondary tic disorders: encephalitis. Most common cause of chorea is drug therapy for Parkinson's disease.. carbon monoxide poisoning. sporadic (torticollis. Intention: brainstem lesion. surgery. anticholinergics. Alcohol potentiates intention tremor. Tremor: a. tardive dyskinesia. sedative/alcohol withdrawal. Classify each as hyperkinesias or hypokinesias 2. pregnancy chorea 3. cerebellar lesion. drugs. hyperthyroid. ceruloplasmin (Wilson's disease). neuroleptics. DBS Postural Uf/head/voice 6·12Hz fine tremor Sustained posture (outstretched arms} ± Autosomal dominant FHX Intention Anywhere <5Hz coarse tremor Finger to nose Cerebellar findings Cerebellar disorders. '. benign essential tremor.

subthalamic). dysarthia and dysphagia • corticobasal degeneration: tauopathy with varied presentations but classically presents with unilateral parkinsonism. thus reduced dopamine in striatum leading to disinhibition of the indirect pathway and decreased activation of the direct pathway causing increased inhibition of cortical motor areas • a-synucleinopathy: a-synuclein accumulates in Lewy bodies and causes neuritis in substantia nigra Signs and Symptoms • positive motor • rest tremor: asymmetric 4-5Hz "pill-rolling" tremor.'bmdykin81ia Postuml instability . anxiety ley Puki•onim F•tur•• TW lllJIIIor Rigidity Aki1181ii-. as is postural instability • Lewy Body disease (see Behavioural Neurology. micrographia.MPTP (neurotoxin) Pathophysiology • loss of dopaminergic neurons in pars compacta of substantia nigra. dystonia/myoclonus. sexual dysfunction Treatment • pharmacologic (levodopa/carbidopa). pesticides). "wearing-offu). especially hands • rigidity: lead-pipe hypertonus. anticholinergics (especially ifprominent tremors). amantadine. Both are associated with early autonomic dysfunction (previously Shy-Drager syndrome) • vascular parkinsonism: multi-infarct presentation with lower body parkinsonism Huntington's Disease Etiology and Pathogenesis • genetics: autosomal dominant CAG repeat disorder with anticipation of Huntington gene on chromosome 4leading to accumulation of defective protein in neurons • pathology: global cerebral atrophy.g. pallidotomy. shuffling gait with acceleration and flexed body • cognition: bradyphrenia (slow to think/respond). especially affects the striatum. autosomal recessive Parkin gene or DJ-1 gene mutation Ouvenile onset) • . tlliVII histDry • autonomic: later findings of constipation. pallidal. embryonic dopaminergic stem cell transplantation • levodopa related fluctuation: delayed onset of response (affected by mealtime). random oscillations of on-off symptoms • major complication oflevodopa therapy is dyskinesias • psychiatric (see Ps_ychiatr:y) Other Parkinsonian Disorders • parkinsonism: akinesia (bradykinesia and low amplitude) often accompanied by rigidity.. MAOI • adjuncts: DA agonists. Nl3) • progressive supranuclear palsy: tauopathy with limited vertical gaze (classically downgaze). apraxia ± "alien limbs" phenomenon • multiple syatem atrophy: synucleinopathy presenting as either cerebellar predominant (previously olivo-ponto cerebellar atrophy or OPCA) or parkinsonism predominant (previously striato-nigral degeneration). aprosody (monotonous speech). genetics • famllial (10%): autosomal dominant a-synuclein mutations. lasts seconds • postural instability: late finding of falls. MAOI.e.. late finding of dementia • behavioural: personality change. deep brain stimulation (thalamic. early falls. depression. leading to increased activity of the direct pathway and decreased activity of the indirect pathway . Levodopa is a dopamine precursor. COMT inhibitors • surgical: thalamotomy.U. cogwheeling due to superimposed tremor • negative motor • bradykinesia: slow small amplitude movements. dysarthria. • mainstay of treatment carbidopa decreases peripheral conversion to dopamine • treatment of early PD: DA agonists. . decreased spontaneous speech.m • Poor ruponu to L·dopa • Abrupt onset of symptmns • Rapid progression • Earlylalls • Early autonomic dysfunction • Symmllric symptoms It onut • Early age of onset (<50) • Early cognitive impairment • FHx of psydliabic/demenling disonln • Re1:ent diagnosis af psychiabic dillllsa • History of encephalitis • UnUSUII toxin axpDSUI'B • ExUnsiv. hypophonia.Toronto Notes 2011 Movement Disorders Neurology N27 Parkinson's Disease (PD) ----------------------------------- Etiology • sporadic: combination of oxidative stress to dopaminergic neurons. difficulty initiating movement • related findings: masked facies. shuffling gait with decreased arm swing • freezing: occurs with walking triggered by initiating stride or barriers/destinations. environmental toxins (e.. urinary retention. end-of-dose deterioration (i. sleep disturbances.. Conlldw an Alterllldve Dilgnasis If Atypical Parlcirwo. accelerated aging. axial rigidity and akinesia. Tremor is an optional feature.

touching • vocal tics • simple: blowing. atrophy of cerebral cortex and caudate nucleus • genetic testing Treatment • • • • no disease altering treatment psychiatric symptoms: antidepressants and antipsychotics chorea: neuroleptics and benzodiazepines dystonia: botulinum toxin Dystonia --------------------------------------------------- Epidemiology • most common movement disorder encountered in movement disorder clinics after parkinsonism Features • worse with fatigue. shrugging of shoulders. coughing. echopraxia (imitate gestures).g. abdominal tension. bouts of violence • psychosis • juvenile onset (Westphal variant): begins in adolesence with bradykinesia and rigidty with a severe progressive course spanning 5 to 10 years Investigations • MRI: enlarged ventricles. place hand on face for cervical dystonia) • more likely to be progressive and generalize ifyounger onset or if leg dystonia Treatment Batulirun toxin {BOTOXI acts by preventing ACh the neuromuscular junction. anhedonia. muscle relaxants (Baclofen). neuroleptics). grinding teeth. throat clearing • complex: coprolalia (shout obscenities). dopamine for dopa-responsive dystonia • surgical: surgical denervation of affected muscle. • local medical: botulinum toxin • systemic medical: anticholinergics. stereotaxic thalamotomy (unilateral dystonia). head jerking • dystonic: bruxism. psychosis and chorea • chorea: begins as movement of eyebrows and forehead. depression. fidgetiness. throwing. relieved by sleep or specific tactile/proprioceptive stimuli ('geste antagoniste: e. sustained mouth opening • complex: copropraxia (obscene gestures). palilalia (repeat own phrases) Treatment • dopamine blocker . stress. impulsive. posteroventral pallidotomy Tic Disorders Clinical Classification • motortics • simple: blinking. benzodiazepines. antidopaminergics (reserpine. irritability progressing over 15 years to frank dementia. and parakinesia (pseudopurposeful movement to mask involuntary limb jerking) • progresses to dance-like or ballism. echolalia (repeat others' phrases). but varies with degree of anticipation from 5-70 Signs and Symptoms • typical progression: insidious onset with clumsiness. grunting. and in late stage is replaced by dystonia and rigidity • dementia: progressive memory impairment and loss of intellectual capacity • mood changes: irritability.N28 Neurolo8Y Epidemiology Movement Disorders Toronto Notes 2011 • North American prevalence 4-8/100. emotions.000 • mean age of onset 35-44 years.

. predomirnnt p11in. reinnervation.g. denervation). tongue atrophy and fasciculations • pseudobulbar affect or emotional lability • sparing of ocular muscles and of sphincters Investigations • EMG: denervation (3limbs + paraspinal). M>F Signs and Symptoms • tics: wide variety that wax and wane in type and severity • can be voluntarily suppressed for some time but are preceded by unpleasant sensation that is relieved once tic is carried out • psychiatric: compulsive behaviours (associated with OCD and ADHD). '. lhlrp wavas. fibre-type grouping • rule out cord disease/compression with CT or MR. cranial nerve nuclei. Multiple tics a day nearly everyday or intermittently throughout 1 year with no tic-free periods greater than 3 months 3. anticholinergics (e. 'rageS: sleep-wake disturbances. dysphagia. Presence of motor and vocal tic at some point during illness. rehabilitation (PT.g. death due to respiratory failure il'' inconllittlnt with ALS IW FilaSen110ry ax. fasciculations • muscle biopsy: small angulated fibres (ie. Onset prior to 18 years of age 4. early nutritional support. autoimmune paraneoplastic. hyperactive behaviour. viral. psychosocial support Prognosis • median survival3 years (longer ifventilatory support). Not due to effect of a substance or general medical condition Epidemiology • prevalence among adolescents 3-5/100. often improves in adolescence and 50% are tic-free by 18 years Motor Neuron Disease Amyotrophic Lateral Sclerosis (ALS) (aka Lou Gehrig's Disease) Definition • progressive degeneration of motor neurons causing UMN and LMN symptoms Etiology • genetic (5-10% familial. complax repllilive disc:tlarges. BiPAP).000. not necessarily concurrently 2. SSRI • non-pharmacologic: ventilatory support (e. SLP).I Management • disease specific: riluzole • muscle stiffness/spasticity: baclofen.g. bowel or bladder incontinence. glutamate toxicity.Toronto Notes 2011 Movement Disorders/Motor Neuron Disease Neurology N29 Tourette's Syndrome (aka Gilles de Ia Tourette's Syndrome) Definition according to DSM IV 1. idiopathic Pathology • degeneration and loss of motor neurons with astrocytic gliosis • bunina bodies (eosinophilic hyaline intracytoplasmic inclusions) in 7096 • disorder of anterior horn cells of spinal cord. amitriptyline).000 with onset between 40-60 (earlier if familial) Signs and Symptoms • limb motor symptoms: segmental and asymmetrical UMN and LMN symptoms of limbs • bulbar findings: dysarthria. especially SOD1 mutation). cognitive mllld& wallkm!H. and corticospinal tract Epidemiology • 5/100. TCA. clonazepam Prognosis • Begins at 5 years progressively increasing until I 0 years. learning disabilities Treatment • clonidine. Denuvation on EMG Fibrillations. raimarvation11111pliluda and duration of mlllllr units. OT. tizanidine • sialorrhea: TCA (e. scopolamine patch) • pseudobulbar affect: dextromethorphan/quinidine.

CIDP. worse at night • signs: Tinel's sign. alcohol.N30 Neurolo8Y Motor Neuron Diseue/Perlpheral Neuropathies Toronto Notes 2011 Other Motor Neuron Diseases • prograsive muscular atrophy (progras. mv. . impotence.. toxins. stocking-glove distribution}. uremia • chronic inflammatory demyelinating polyneuropathy (CIDP} • chronic relapsing sensorimotor polyneuropathy with increase protein in CSF and demyelination (shown on EMG/NCS) • course is fluctuating compared to acute onset of GBS • treatment firstline is prednisone: alternatives are plasmapheresis.e.Iymphoma. tumour infiltration. posterior tibial (tarsal canal) • mononeuropatby multiplex: deficit affecting multiple discrete nerves (asymmetric) • most commonly due to diabetes • polyneuropathy: symmetrical distal stocking-glove pattern • presentation: symmetrical distal sensorimotor deficit affecting longest fibres first (i. and asathioprine • critical illness polyneuropathy • associated with sepsis and multisystem organ failure. Sensory neuropattw of feet pr8Y8nt them from adequately compeiiSiting for lass of vestibular function.. infarction (i. ----t•. RH9 see HIV serology Laprosy serology Nerve biopsy Lyme serology LP (1' protsin.1ing polynauropllhy (ClOP). HIV. OM. not futal with variable disability. radiation.g. Axonal (most common): pain> mDior 2._'. DDx of M-neuropltllr Mljlipllll Vasculitis (e.diMUI... hypotonia. or are hereditary • other important etiologies: SLE. chronic inflammatory demyeli111. progression of dysesthesia early.. bowel and blldd1r dysfunction 3. dlll'll'(llinlling neuroplllhin hiiVI dlc11111Sed velocity on NCS.. cervical rib) • lumbosacral plexopathy (rare.. later onset than ALS..r. prassura paiiJY predisposition.. Dlabellc Neara. renal disease:. thenar muscle wasting. substances. median (at pronator teres). Axonal neuropatllies hiiVI decr. thoracic outlet syndrome (i._. diabetes). idiopathic neuritis.. ± anti-GM1 Ab. onhcmatic hypotension. sensory deficit • EMG and NCS: slowing at wrist (both motor and sensory) • Bell's Palsy (most common cranial neuropathy): see OtolaeyngolQg}'> OT23 • other less common mononeuropathies due to entrapment/compression: ulnar (compression at elbow}. .lumbosacral roots) • plempatby: deficit matching distribution of a nerve plexus • brachial plexopathy • upper (C5-C7}: LMN sx of shoulder and upper ann muscles (Erb's palsy) •lower (C8-Tl): LMN sx and sensory sx of forearm and hand (Klumpke's palsy) • DDx: trauma. peroneal (due to crossing legs or surgical positioning). ± radiation to elbow. atrophy • multifocal motor neuropathy: conduction block on NCS. Diffarential Diagnosis of Symmetric Polyneuropathy• Etiology+ V. Cranial niURipelhy: CNIII (pupil sparing) > IV > VI infarct or compression ._. weakness later • most polyneuropathies are due: to medical conditions like diabetes. treatable with IVIg .Cul• . 5-10% of patients in ALS centres • primary lateral sclerosis (progressive pseudobulbar palsy): UMN symptoms. DDx of o. ea. compression • mononeuropatby: single nerve deficit • carpal tunnel syndrome (most common): compression of median nerve at wrist • symptoms: wrist pain. pr8SIIn palsy predisposition (herediWy).ased amplitude on NCS. 5-10% of patients in ALS centres • spinal muscular atrophy: pediatric disease with symmetric LMN symptoms • polll:-polio syndrome: residual asymmetric muscle weakness.llnllting Ntluropllthy GBS. B12 deficiency.dlles 1. no 1' cells) LP (1' protein) HIV Leprosy Lyme Immune GBS CIDP Ctronic SAY! . PAN). storage disaue. paresthesia first 3 digits. Mononeuropllthy multiplex: ll8MI 4. multifocal motor neuropathy (pun motor). leprosy..g. Ischemic Ischemic Ischemic AxonaVdemyelination lnfillrative AxonaVdemyalination Demyelination Demyelination Clrunic Clrunic Ctronic Clrunic Clrunic Clrunic Acute Madlliliel lmllltiptisee PAN SlE RA SAY! SAY! SAY! S/A S/A M M RH17 RH& sae BtlllliTIIIIIllagy. aminoglycosides) should not be given to diabetic&. paraneoplaslic. later onset.e. dipthlria. Lvm.. .. IVIg. Peripheral Neuropathies • monoradiculopatby: dennatomal deficit due to single nerve root lesion • due to disc herniation or root compression causing radicular pain • polyradic:ulopathy: multiple dermatome deficits due to multiple nerve root lesions • most common cauda equina syndrome (ie. ureoidosis..ivt: bulbar pahy): only LMN symptoms with asymmetric weakness. Ototoxic drugs (e. gaslroplnsis. paraprotBinemia. especially unilateral) • DDx: idiopathic neuritis. severe sensorimotor axonal neuropathy Table 18. obturator (from childbirth). Saturday night palsy (radial nerve entrapment at spiral groove of humerus). asymmetric LMN symptoms..e. leprosy. amiodarone. Autonomic: anhydrosis.

Toronto Notes 2011

Peripheral Neuropathies

Neurology N31

Table 18. Differential Diagnosis of Symmetric Polyneuropathy" (continued)

AxonaVdamyalination AxonaVdemyelination AxonaVdemyelination Axonal Demyelination Axonal Axonal Axonal lschemio'axanal Axonal Axonal Axonal Axonal Axonal

Chronic Chronic Chronic Chronic Chronic


lnvesligllions G811111ic testing Anti-Hu SPEP Skelellll bone survey SPEP




Myaloma Lymphoma Monoclonal gammapa1hy Taxin

Bone manow biopsy


SPEP Bone manow biopsy GGT Urile heavy metals

Heavy metals Medications

sw-acute sw-acute sw-acuta
Chronic Chronic Chronic

Drug levels


Hypothyroidism Ranal hlikuu

Fasting glucose, HbA1C, 2hr OGTT
TSH, T4 Lytes, Cr, BUN V'rtamin 812 Urile parphyrins biopsy


Brz deficiency


Porphyria Amyloid

Sw-acute sw-acute sw-acuta


GBS-Qilllin-Bant -polyuteritisnodosa; SLI-systemic ._ RA-me...r.tuid lllhritis; Cll' -IDmic nlmnltory polyrldiciD!aJruplthy; HMSN-hllldllry IRIIIIrsansary nauro]ll1hy; SPB' -sarum pnlblin allclrophDnllis; S- senscny; M- matDr; A-IUI!mnic +Mostcanvn!1VII'p)l1lrltatiologiasil illicstype

Guillain-Barre Syndrome (GBS) • definition: acute rapidly evolving polyneuropathy • risk factors and etiology • pathophysiology suspected to be focal inflammation • viral/bacterial infections and vaccinations, have been shown to predispose to GBS • signs and symptolll8 • sensory: distal and symmetric paresthesias, loss ofproprioception and vibration sense, pain • motor: weakness starting distally in legs, areflexia • autonomic: blood pressure dysregulation, arrhythmias, bladder dysfunction
• investigationa • CSF: albuminocytological dissociation (high protein, normal WBC) • EMG/NCS: conduction block, differential or focal (motor>sensory) slowing, decreased

GBS is a neurological emergency due to risk of imminent raspinrtory failtn.



F-wave • subtypes 1. Acute inflammatory demyelinating polyneuropathy (AIDP) 2. Acute motor-sensory axonal neuropathy (AMSAN) 3. Acute motor axonal neuropathy (AMAN) • treatment • disease specific: IVIg or plasmapheresis • nonpharmacologic: admit and monitor vital signs and vital capacity due to risk of respiratory failure, manage dysautonomia, manage pain • prognosis • nadir of symptoms at 2-3 weeks, with resolution at 4-6 weeks • 5% mortality (higher ifiCU), 7-15% permanent substantial deficits Diagnostic Approach to Peripheral Neuropathies 1. Differentiate: motor vs. sensory vs. autonomic l. Pattern of Deficit: symmetry, focal vs. diffuse, upper vs. lower limb, cranial nerve involment 3. Tempo: acute to chronic, relapsing remitting vs. constant 4. Good History: PMH, detailed family tree, exposures (e.g. insects, toxins, sex. travel), systemic symptoms 5. Detailed Peripheral Neuro Bum: LMN findings, differentiate between root and peripheral nerves, check cranial nerves, check respiratory status

Miller-RICIH!r Y11rimt af GBS - Triild 1. Ophthalmoploqill

2. Ataxia 3. Arvllexil



Mg and pi1Ui111apilemillalld tD morv rapid improvement, less intensive care

and less ventillllion, but do not change
mortality or ralaps1 ram.

N32 Neurolo8Y

Neuro-oncology/Neurom115Cular Junction Diseaaa

Toronto Notes 2011

Paraneoplastic Syndromes
• uncommon complication of cancer; often is the presenting complaint

• likely an autoimmune attack on the nervous sym:em by tumour antigens

Associated Neoplasms • small cell lung cancer: cerebellar degeneration, encephalitis, opsoclonus-myoclonus,
retinopathy, neuropathy, Lambert-Eaton syndrome • breast: cerebellar degeneration, encephalomyelitis, opsoclonus-myoclonus • thymoma: myasthenia gravis • other syndromes: necrotizing myelopathy, motor neuron syndrome, neuropathies, mononeuritis multiplex, polymyositis and dermatomyositis, encephalitis

• antibodies commonly ordered include anti-Hu, anti-Ri and anti-Yo

• unsatisfactory and often palliative. Options to consider are steroids, IVIg, plasmapheresis and treatment of malignancy

Tumours of the Nervous System
• see NS9

Neuromuscular Junction Diseases
Clinical Approach to Disorders of the Neuromuscular Junction
Tabla 19. Common Disorders of the Neuromuscular Junction

OculluAiulblr pamis

+ +



', ..



Post-exen:ile enhlncement Reflexes
ANS anti:hulin. .ic Sx

+ + + +

+ +

Dis1un of 1h1 niUilllllllscular junction typically feature prominent fatiguability.



Associated conditions
Rapatilivll EMG stimulatilll


Small cell carcinoma


1' (rapid sti'I'IJiation)
-.1- (slow

1' (rapid stimulation)
>lr (slow stimulation)

Myasthenia Gravis (MG)
Etiology and Pathophysiology
• damage and blockade of post-synaptic acetylcholine receptors by specific antibodies • 15% of patients with myasthenia gravis have associated thymic neoplasia, 85% have thymic

• autoimmune disorder

• bimodal age of onset - 20's (mostly women) and 60's (mostly men)

Toronto Notes 2011 Signs and Symptoms

Neuromusc:ula.r Junction Diseasea

Neurology N33

• see also Table 19 • fatiguability and weakness of skeletal muscles without reflex, sensory, or coordination abnormalities • typically ocular (diplopia/ptosis) -+bulbar (dysarthria/dysphagia) -+ necldlexors/extensors -+ proximal limbs • respiratory muscle weakness may lead to respiratory failure

Myasthenia Gravis is a neurological emergency due to 1he risk of imminent rnpillllory failure I


,, ,,

• edrophonium (Tensilon•) test -can result in respiratory difficulty so have crash cart nearby • assess for improvement over 2 minutes following edrophonium injection ·EMG • repetitive stimulation -+ decremental response • single fibre electromyography shows increased jitter (80-10096 sensitivity) • anti-acetylcholine receptor antibody assay (70-80% sensitivity) • MUSK antibody may be used if seronegative for AChR antibody • CT/MRI to screen for thymoma/thymic hyperplasia
Tensilon• is a drug 1hat inhibit$ acltylcholinestlrllsl. It improvM mJscll function immadilltaly in my811henia

gravis, but not in cholinergic crisis.


• thymectomy • 8596 of patients show improvement or remission • symptomatic relief • acetylcholinesterase inhibitors (e.g. pyridostigmine) • does not affect primary pathologic process -+ rarely result in control of disease when used alone • immunosuppression • steroids are mainstay oftreatment - 70-80% remission rate • azathioprine, cyclophosphamide and mycophenolate as adjuncts to steroids or as steroid sparing therapy • short-term immunomodulation (for crises) • IVIg and plasmapheresis

zClinical Forms rrf Mpltllenil GriVis 1. Ocular [15"'} 2. Gene1111ized (85%1

• 3096 eventual spontaneous remission

Lambert-Eaton Myasthenic Syndrome (LEMS)
Etiology and Pathophysiology
• downregulation of presynaptic voltage-gated Calcium channels 2° to specific channel binding antibody causing decreased amounts of ACb released into the synaptic cleft • 50-6696 are ultimately associated with small cell carcinoma of the lung

Signs and Symptoms
• • • • weakness of skeletal muscles without sensory or coordination abnormalities reflexes are diminished or absent, but increase after active muscle contraction bulbar and ocular muscles affected in 25% prominent anticholinergic autonomic symptoms (dry mouth >impotence> constipation > blurred vision)



Lambert-Eaton myas1hanic syndrome can be differentiated from myasthenia Qlllvis, by 1ha phenomenon of postexercise facilitlltion.

• • • • edrophonium test (see Myasthenia Gravis) -+ no response EMG: rapid (> 10Hz) repetitive stimulation -+ incremental response screen for malignancy, especially small cell lung cancer post-exercise facilitation- an incremental response to repetitive stimulation due to presynaptic calcium accumulation

Treatment • tumour removal
• acetylcholine modulation • increased acetylcholine release (3-4 diaminopyridine) • decreased acetylcholine degradation (pyridostigmine) • immunomodulation • steroids, plasmapheresis, IVIg

nt lnfanution to Reganllnf Myapllthilll • Weakness: proximal > distal • Pain: myalgias. MELAS. and myoglobumimria Episodic W8ilkness between attacks Parasitic.mitochondrial encepllllomyopathy. bifacial weakness.. and Polymyositis/Dermatomyositis • see RH13 Myotonic Dystrophy Etiology and Pathophysiology • unstable trinucleotide repeat in DMK gene (protein kinase} at 19ql3. . calcium panel Toxicology Biopsy: selective loss of thick Myosin filaments ..N34 Neurolo8Y Myopathiea Toronto Notes 2011 Myopathies Clinical Approach to Muscle Diseases Table 20... stand from sit • Anna: n111ch above Alina Proximal wen-s • Legs: climbing slllirl.. '. conmon Proximal > distal myopathy Exercise intolerance Rhabdomyolysis •Abbreviltion5: MBliiF -ITilochoncnl encephlllomyoplllhy slrulie-like episodes rauged llld fibe11. serum cortisol.&les Can be paraneoplastic Ksr lnvatigations 1' CK Biopsy: endomesial Necrosis 1' CK Biopsy: parifasciculll' atrophy .. triangular face giving a drooping/dull appearance . '. rnsen. but no impaired • MyotDnil [difficulty with relaxldioo) Sarcoido8is Inclusion body myositis ACE IIMII Biopsy: IJliiUIOIIllls Weak quads and deep finger flexors See Endocrinology 1' CK Biopsy: ilclusion bodias TSH.. wash hair Becksr Myotonic dystrophy . bactErial. cramping. Endoc:rin1 Thyroid (1' or -1-) Cushing's syndrome Parathyroid (1' or -1-) Medication Critical illness myopathy Myoplllllisl1118 chlllle1llrizad by prominent symmetric proximal Medication or toxin history weakness end lbsant SIIIIIO!'f chlngal. mrtins and IIIT!mnmrBis 1' lactate 1' serurnturinary myoglobil Pllst-sxen:ise 1'cr-I-K Increased lactate Biopsy: ragged red fibres Heredililry Periodic Parllylil Heredililry Periodic paralysis MERRF MELAS ICI!ImsSayre Mitochandriil Ptosis.. lactic I!Cifbis.tion Dermatomyositis lmporu. Hereditary Dystrophy ICU patient Hx steroid& and nondepolarizing palltfzing agents Faiure to ween from ventilation Mya[gies Inflammatory myopathy onset {Duchenne and Becker) Prograssiw proxi11111l muscle -knass pseudohypertrophy Distal myopathy Myotonia Genetic anticipation Exercise-related rnyalgias.. frontal baldness {including women).. '.... or vinll Duchenne 1' ITI'fl9obin Biopsy: abnormal dyttrophin Staining Genetic testing Good Cll.ti. Hereditary Mltlbolic McArdle's Common Mellicalio1111bat Cauu Mpptllhy Steroids. '.3 • number of repeats correlates with severity of symptoms. autosomal dominant Epidemiology • most common adult muscular dystrophy • prevalence 3-5/100 000 Signs and Symptoms • appearance: ptosis. Myopathies Etiology lnlllmmiiDry Polymyositis Mya[gies Pharyngeal involvement Mya[gias Similar to polymyositi& Characteri&tic r...

impaired proprioception and vibration • death in 10-20 years from cardiomyopathy or kyphoscoliotic pulmonary restriction • autosomal dominant: spinocerebellar ataxias (SCA. dysdiadochokinesis. vitamin E deficiency • Friedreich's ataxia: prevalence 2/100 000. uncoordinated. Dandy-Walker cysts) Hereditary Ataxias • autosomal recesaive: includes Friedreich's ataxia. retinal degeneration. confusion. The ataxia can be due to cerebellar atrophy or alcohol polyneuropathy Cerebellar Ataxias Congenital Ataxias • early onset nonprogressive ataxias associated with various syndromes as well as development abnormalities (e. look for difficult tandem gait and broad based gait • intention tremor: elicit on finger-to-nose testing.s) of which 30 exist. dysarthria. decreased intraocular pressure • EMG: subclinical myotonia -long runs with declining frequency and amplitude Treatment • no cure • management of myotonia: phenytoin Duchenne and Becker Muscular Dystrophy • see Pediatrics.g. P46 Cerebellar Disorders Clinico-Anatomic Correlations • vermis: trunk/gait ataxia • cerebellar lobe (i.elicit scanning/telegraphic/slurred speech on spontaneous speech (see Dysarthria. lurching gait • dysmmetria: irregular placement ofvoluntary limb or ocular movement • dysdiadochokinesis: unable to perform rapid alternating movements (e. Arnold-Chiari malformation. onset between 8 and 15 years • signs: gait and limb ataxia. and increases as target is approached • hypotonia: decreased resistance to passive muscular extension. ataxia telangiectasia. rebound phenomenon. most are CAG repeats . pronationsupination task) • postural instability: look for truncal ataxia on sitting (titubation =rhythmic rocking of trunk and head). extensor plantar reflex. Nl9) • ataxia: broad-based. atrial arrhythmias) • respiratory: hypoventilation 2° to muscle: weakness • ocular: subcapsular cataracts. lateral): tremor.typically orthogonal to intended movement. decreased EOM. nystagamus Symptoms and Signs of Cerebellar Dysfunction • nystagmus: observe on extra-ocular movement testing (most common is gaze-evoked nystagmus) • dysarthria (ataxic dysarthria): abnormal modulation of speech velocity and volume.Toronto Notes 2011 Myopathies/Cerebellar Disorders Neurology N35 • physical exam • distribution ofweakness: distal greater than proximal (in contrast to other myopathic disorders) • myotonia: delayed relaxation of musclc:s after exertion (elicit by tapping on thenar muscles with hammer) • cardiac: 90% have conduction defects ( 1° heart block.occurs immediately after injury to lateral cerebellum • pendular patellar reflex: knee reflex causes pendular motion ofleg occurs after injury to cerebellar hemispheres • rebound phenomenon: overcorrection after displacement of a limb (with both arms extended --+ pushing both will cause one to rebound up if there is lesion on that side) Wernicke-Korsakoff Syndrome • deficiency of thiamine due to alcohol abuse • acute: apathy.g. weakness. areflexia. ataxia (truncal and gait) • without treatment progresses to encephalopathy and ultimately death • treatment: thiamine 100 mg • Korsakoff's syndrome: progressive decline ofboth anterograde and retrograde memory • note that alcohol can also cause a cerebellar ataxia separate from thiamine deficiency.e.

OT12 Gait Disturbances Approach to Gait Disturbances I. Extrapyramidal: bani ganglia inhibita BJa:llll mCMimanb. If movement is elaborate and inconsistent. If normal width. Miller-Fischer (GBS) • children: tumours. thiamine deficiency • toxins: carbon monoxide.ataxia • if high stepping and positive Romberg. tingling) • Dysesthesiae: spontaneous or evoked pain with inappropriate quality or excessive quantity • Allodynia: a dysesthetic response to a nonnoxious stimulus • Hyperalgesia: an exaggerated pain response to a noxious stimulus . Wilson's.magnetic/apraxic gait • frontal lobe pathology due to normal pressure hydrocephalus or cerebrovascular disease 4. hypothyroidism. basilar migraine • autoimmune: MS.. heavy metals..spastic gait • bilateral circumduction due to spastic paraparesis from cerebral palsy.look at posture • if stooped with no armswing. multiple system atrophy) • systemic: alcohol..g. lithium.cerebellar ataxia • veers to side of the lesion • if scissoring of legs or toe walking.bilateral foot drop • if feet barely leave ground or disjointed movement .g. Clrlblllum: afflcts coordination of 2.antalgic gait._. If no high stepping. look for height of step • if high stepping bilaterally. celiac sprue. Pyramidal: main ouUiow from cor1ex to spinal cord 2. phenytonin.Marche a petit pas • due to diffuse infarction of both cerebral hemispheres (lacunar) r-t•. CENTRAL MOTOR SYSTEMS 3 compn•nb tu til• cantrol af pit 1. 3. bypassing nociceptive pathways • Spontaneous pain: unprovoked burning. Length of stride • if small paces . solvents • vascular: infarct. look at width between feet • if wide-based. or lancinating pain • Paresthesiae: spontaneous or evoked abnormal nonpainful sensations (e. deformity or hemiparetic gait • antalgic gait is due to pain from an MSK problem • hemiparetic gait involves a foot drop and circumduction of spastic leg due to UMN lesion 6. If normal stride length. post-viral Vertigo • see Otolaryngology.sensory ataxia • loss of joint position sense (+ve Romberg) • if wide based without high stepping . multiple sclerosis or cord compression 3. conaicler functional pit • rule out an odd gait due to chorea from Huntington's disease Pain Syndromes Approach to Pain Syndromes .Parkinsonian gait • look for other signs of extrapyramidal disorders • if upright with exaggerated armswing . If no waddling. lookfor stabllity of pelvis • if rotation of pelvis . look at symmetry • if asymmetric . bleed. especially when being observed.N36 Neurolo8Y Cerebellar Disorden/Vertigo/Gait Diaturbances/Pain Syndromes Toronto Notes 2011 Acquired Ataxias • neurodegeneration (e. • Pinprick CIIUUI sharpnns rnldimd byJIIJfibani • Pain to damage is mediated by Cfibres Definitions • Nociceptive pain: pain arising from normal activation of peripheral nociceptors • Neuropathic pain: pain arising from direct injury to neural tissue..waddling gait • proximal muscle weakness due to congenital deformity or myopathy 5. shooting.

thyroid disease.cognitive behavioural theraphy. N18 Postherpetic Neuralgia (PHN) Definition • pain persisting beyond 3 months in the region of a cutaneous outbreak ofherpes zoster Etiology and Pathogenesis • destruction of the sensory ganglion neurons (e.Toronto Notes 2011 Pain Syndromes Neurology N37 Medical Pain Control • primary analgesics: OTCs. meditation. facet joint denervation • deep brain stimulation (DBS) or dorsal column stimulation Neuropathic Pain Definition • pain resulting from a disturbance of the central or peripheral nervous system Symptoms and Signs • hyperalgesia/allodynia • subjectively described as -burning. DBS (thalamus) • other therapies: • neuropsychiatry .post surgical. carbamazepine). sympatholytics (phenoxybenzamine). cervical and lumbar radiculopathies. numbness (Le. SSRis).physiotherapy • CAM . long acting opiate. stocking/sock distribution) • can be spontaneous or stimulus evoked • distribution may not fall along classical neuro-anatomicallines Associated Issues • sleep difficulty • anxiety/stress/mood alteration • sexual dysfunction Causes of Neuropathic: Pain • peripheral neuropathy • systemic disease . post-stroke. anticonvulsants (gabapentin. pernicious anemia. chemotherapy • infectious . Botox. opiates • adjuvants: antidepressants (TCAs. psychotherapy • rehabilitation . Nl8). anticonvulsant. dorsal root. capsaicin cream. trigeminal. TCM Tic Douloureux (Trigeminal Neuralgia) • see Trigeminal Nerve. heat/cold.acupuncture. tic douloureux (see Trigeminal Nerve.g. SNRI. renal disease. nerve injury • nerve root: post-herpetic neuralgia. nerve block • surgical therapies: dorsal column neurostimulator. intrathecal opioid or clonidine. pricking. electric shock. spinal cord injury • Complex Regional Pain Syndromes (see N38) •malignancy Treatment • pharmacotherapy: TCA.alcoholism.HN • trauma . phantom limb. or geniculate ganglia) secondary to reactivation of herpes zoster infection Epidemiology • 10-15% of all patients with cutaneous herpes zoster • >80% of herpes zoster infected patients >80 years old . rheumatoid arthritis • nutritional/toxicity. massage therapy. baclofen.diabetes. topical lidocaine. plexopathies • central: MS. pregabalin) Surgical Pain Control • direct delivery: implantable morphine pump • central ablation: stereotactic thalamotomy. a2-adrenergic agonists (clonidine. spinal tractotomy or dorsal root entry lesion • peripheral ablation: nerve blocks. perception of swelling.

presence of an initiating noxious event 2. thickened fascia with contractures. evidence during the course of symptoms of edema. gabapentin. dorsal root entry zone lesion Complex Regional Pain Syndromes (CRPS) Definitions • CRPS is a pain syndrome characterized by the following 1. longer-acting famciclovir and valaciclovir more effective) may prevent PHN in patients over 50 years • PHN • medical: TCA. opiate. continuing pain. changes in skin blood flow. allodyrua.-Definition • hypersensitivity to pain as a result of damage to the thalamus Etiology and Pathogenesis • injury to ventral posterolateral (VPL) and ventral posteromedial (VPM) nuclei of the thalamus • ischemic stroke • hypertensive vascular hemorrhage Signs and Symptoms • begins with hemianesthesia • then persistent spontaneous burning contralateral to lesion • altered response to light cutaneous and deep painful stimuli Treatment • medical: amitriptyline. or abnormal vasomotor activity 4. or hyperalgesia with pain disproportionate to inciting event 3. intermittent spontaneous lancinating/jabbing pain. lidocaine patch. anti-convulsants • surgical: stereotactic thalamic stimulation (may increase sensory deficit) . cracked/brittle nails • stage III (atrophic) • pain: paroxysmal spread • autonomic: thin. intrathecal methylprednisolone • surgical: spinal tractotomy. allodynia • distribution: thoracic > trigeminal > cervical > lumbar > sacral Treatment • acute herpes zoster • early treatment with antiviral agents (acyclovir. hair loss. shiny skin. bony demineralization Investigations • diagnosis is clinical • trial of differential neural blockade may be helpful Treatment • medical: phenoxybenzamine (sympatholytic) • surgical: paravertebral sympathetic ganglion blockade Thalamic Pain (Dejerina Roussy Syndrome) . absence of conditions that would otherwise account for degree of pain and dysfunction Classification • CRPS type I (reflex sympathetic dystrophy): minor injuries of limb or lesions in remote body areas precede onset of symptoms • CRPS type II (causalgia): injury of peripheral nerves precedes the onset of symptoms Signs and Symptoms • stage I (acute) • pain: burning or aching disproportionate to initial injury • autonomic: edema and temperature inequality • stage II (dystrophic) • pain: constant and increased by stimulus to affected part • autonomic: osteoporosis. pregabalin.N38 Neurolo8Y Pain Syndromes Toronto Notes 2011 Signs and Symptoms • types of pain: constant deep ache or burning. cool hyperhydrotic skin.

.. Pllysicll Signs MIRII!IIdllnt neurolovic deficibi.• • Nllll JWA 2006. P(Utling '*" u- a .. gait • indications for a • new-onset headache. . 110 clinical flllfln was found lo hlllllful inlllivJ imcrlrill pethoQ in a 1118111iniiUMYHawM!..tiilllldlclw Mil wmiling 3..Toronto Notes 2011 Headache Neurology N39 a.Llls . rhinorrhea Eyaid !hop Acute Rx • Oz • Sumatriptan (IIIISII or injection) Prophylaxis • Verapamil • Lithium • Methylsergide • Pnmisolone Six Dl Seria• Halldac......llil Pllilnt wilb 11Hdde . nocturnal Constant... worse in PM Tlrobbing Modarata-severa Noise Light Strainilg Coujing Activity Rest Nausi!I1/VDmiting Photo/phonophobia Aura Muscle tension in scall)'neck Tandar scalp artaias AcuteRx •MA • NSAIDS • Triptans • Ergotamine Prophylaxis • l'ropnllolol • TCA • Anticonvulsents + Retroorbilll 10mh-2... heat.. massage) Phannacological • Simple analgesics • Tricyclic antidepressants Walking around ARoc:iltad Sx Red watery eve Nasal congestion or rhinoi'Thea Unilateral Homer's Red watery eye. constant Mild-modarata Depression Anxiety 12% 10-30 F>M Aga of Ollllt SexBia Family HistaiY M>F +++ Uniateral>bilateral Fronto-tenwal Haurs-days Gradual.Primary TCIIIioa-Typa Prevalence Migrma .32-0.7 {21-52) 5... meningismus..4inl1ion of 4-72 UnilideriiiOCIIion cr N .5-3181.... stiff neck Variable Meningitis: oours-days SAH: thunderclap onset Variable S8\111'8 Snfty . papilledema... stabbing S8\111'8 (waklls from sleep) Light abnonnlllraJroiDQicll1111111 111ddneli-typl hlldlch1 Duality Severity Pravoldng 10...3 {2. ThaiR far dafiW or polllil1i n-i11111inl dill!jlllllii VlrillwM!I U... perform a lumbar puncture N.for dilgnosing nipile i$ . {0.1lh dlronic helldldle 1he plellllence is l. uizul"ls.Serious Meningllllrrilatilll Incidence Age of Onset SP:Bils Locetion Duration Onset/Coull8 Quilty . 2. months. meningismus. or 3. thunderclap headache. The most of. -a indivi!UI c1inicll IIU. AccomplfTYing impaired mental sbllus. worse in AM Unlike any previaus headache Severe Te11poral Arteritis <<1% >60 No bias Ten'flOIBI Variable Variable Tt.ns Will luund 1o 1xt ]IIICictive of lignili:lnt petholoQr. pupils (symmetry). Table ZZ....d by 11-.0-7.3-9.61 EtOH Noise Hunger Slaap deprivation Pallating Rest No vomiting No photophobia Muscle tension i'1 Non1)harmacological • Psychological counseling • Physical modalities (e. can be severe <1% Any age No bias Generalized. 3.521 TllpiC1ivltf. inlhose prasal1ing wi1h new lllldlclw the prMiince is 32'Jo • in 1hose jiiUidiiQ Ylilll t!UIIIarcllp hlllldlchl the prMimct is 43\ {211-611\)..8 {11·2. retinal hemorrhages).. aching.4-UI 1..61 2. 24 {1.... Headaches.ln Ylll niglint-typl lllldlclw the prMiince is Howavll.g. c:QI8r-tp haadache Daily headache for weeks... focal neurologic deficits.77-1.11\). fundi (papilledema.2111111 0.lllmblr rlfiiUM pr8I8IE Mdl 3111d feiW U. The lUdden onset Ill a savm headache..lllliaal cmc.l'J..5 {1. . New headaches beginning after age 50.urrrrm..4-12) 3.creased lllraa'anill Pressure <1% Any age No bias Any location Chronic Gradual..Disllblingint!llsily Table 21. IIIII Clustar <1% 20-40 70% 15-40 F>M Nona Bilateral frontal MinLIII!s-days lndual.. headache with worrisome symptoms (fever.3 {1. worse in PM Band-like.11 IQUIMbld lllldlclwv. nnmanic: p- Dnltlil!lllillllwilb .8 {2... morning headache) • if CT is negative but suspicion of SAH or meningitis..ocatiCII Dul'llion Onset/CGune The prawlence rl ii'Uicllnill pllllology {!111111 problliiitylwrias lnlll011 v. 2!1&:1 274-83 Headache Clinical Approach to Headaches Investigations • good history and physical to rule out serious causes of headache • important aspects of neurologic exam: LOC and MSE._ lnaluda: 1. Headaches. haurs l. deep tendon reflexes and Babinski..6·6.-obbing Variable.. Dnlllil . pronator drift.J Eumilllllign: O. altered LOC. or focal fl-. .2 {1. Ill th8le dilllrant popullbs..Nlu• or-womiling D. a.. trauma.41 {0.. worst headache of life. h.

Etialagy Photophobia Focal deficits (e. Migraina •ra• can mimic olhar causas • neurovascular theory of migraines (controversial) • baseline state of neuron hyper-excitability • during migraine: wave of neuronal excitation followed by wave of depression • associated with vasoconstriction and dilation • initiating event may occur in brainstem • trigger: stress. incompressible • Tender Stluctur• lnvalftd in Nacicllptian of H. malignant HTN or pseudotumour cerebri). malignllll hypertension (GCA) SAH . oftnnsient neurological dsficit8 (e. post lumbar puncture.zigzags. • Larve in1rlcranial vessels • CNV • Dura Pretlisone See also Rheumatology. drugs (estrogen.. venous sinus thrombosis Secondary causes of headaches • SAH. NSS Polymyalgia rheumatica Jaw/tongue claucication Visual loss artery change&: • Finn.g.. nodular.g.. exertional Headaches with serious risk to life or function • subarachnoid hemorrhage (SAH). postdrome • aura • fully reversible symptom of focal cerebral dysfunction lasting <60 minutes • examples: • homonymous visual disturbance (fortification spectra . nitroglycerin).Seriouslcontinuedl Meeinglll lniltion lnci'IIISid Lying down Valsalva H81ldlow Exertion Standing/sitting Pressure Tempol'll Arllrilis PrCMIIcing Head movement Pllllilting Associltld Sx Rest and Neck stiffness . migraine. moderate-severe (interfers with daily activity). chocolate. altered mood. drugs/toxins (in particular analgesia-induced/medication overuse) Migraine Headaches Definition (common migraine) • <?:5 attacks fulfilling each of the following criteria • 4-72 h duration • 2 of the following: unilateral. aggravated by routine phy5ical activity • 1 of the following: nausea/vomiting. sinusitis. RH17 Meningitis. Epidemiology • 18% females. IH . hormonal changes. '. tyramines (e. nitrites (e.d migraine due to risk of stroke.UCU. herniation (from space-occupying lesion). visual symptoms due to wave through occipital cortex) Signs and Symptoms • stages of uncomplicated migraine i.N40 Neurolo8Y Headache Toronto Notes 2011 Table 22. intracranial hemorrhage. liAs and seizuras). pulsating.111blrachnaid hernarrlllge. frequency decreases with age {especially at menopause) Etiology and Pathophysiology ..giant cellarllritis Primary Headache disorders • tension-type. GCA. ice pick. scintillating scotomata spots) • unilateral paresthesiae and numbness or weakness • aphasia • prodrome/postdrome: appetite change. Headaches .g. red wine).. cluster.idiopathic iltrlcnlill hyperllnsiun. prodrome (hours to days before headache onset) ii aura iii. stroke. temporal arteritis. CN pelsi111) Kemig's sign Brudzinski's sign Nausel/vomiling Focal neuro Sx DecriiiiSad lewl of consciousness Focal neuro Sx Pupilledeme CTJMRI and treat appropriatl!ly See also Neurosuroerv.. photophobia/phonophobia/osmophobia 1hB 01111 contracapliva pill il con1rlindicmd with complicat. caffeine withdrawal.. headache (see Table 21 for description oftypical headache) iv. trauma. IIH. processed meats) • auras are felt to be due to a wave of excitation/depression leading to the symptoms experienced in an aura (e. meningitis/encephalitis. autonomic symptoms. 6% males. psychomotor agitation/retardation . temporal arteritis.g. meningitis.. '.g. increased intracranial pressure (space-occupying lesion. sleep excess/deprivation. SAH Twnour..

Mlin lids.Toronto Notes 2011 Headache Neurology N41 Phi!R:IIIGgiell'h. no vomiting b. For prilllll pain 1111111211.. Mhlla ID¥Mt NNT for 0111 madi:atian beilg 3. DHE). SHT antagonists (methylsergide).5 mg.hemiplegiclhemisensory migraine . ergots (dihydroergotamine. The l:iwestlf« for 0111 madi:atian -2. pressing/tightening (nonpulsating) quality b... pilctillctanrollld IItTs of piwn'abgc 1nltment of lade mignrine rl1111de!ati. at least 2 of the following pain characteristics a. miosis or ptosis.. no photophobia or phonophobia Cencl•ian: !Mrl' most lrellllnenl$ were . both of the following (or only one is present): a.. Tylenol• #3 • migraine prophylaxis: anticonvulsant& (divalproex.basilar-type migraine (occipital headache with diplopia. at least five attacks fulfilling criteria 2 to 4 below 2. TCA (amitryptiline.llld IUbcullnlous FGr IIA 11lilf d 211.6 far UilripiM IIJl mg.. For susllined 11!111.. There W8l'll no drug-11Hirug complrilanl.ed . eyelid edema. number of days with such headaches: less than 180 days per year 2. calcium channel blocker (verapamil) Episodic Tension-Type Headache Diagnostic Criteria 1. M:omes inc:bled heldac:l!e . supraorbital and/or temporal pain lasting 15 to 180 minutes (untreated) 3. average headache frequency of more than 15 days per month for more than 6 months fulfilling the following criteria 2. iiDiirG .022 pllilla in 1111111.. at least two of the following pain characteristics: a.. • classification of migraines • common migraine: no aura • classic migraine: with aura (headache follows reversible aura in 60min) • complicated migraine: with severe/persistent sensorimotor deficits • examples: .llld lflm1l llffildJ will*l24 baurs.. Dill Will Millila for I Dill medicDns.. nonpulsatile (tightening) b. or phonophobia 4. restlessness/agitation 4.. Evidance-1111811 for m9lina llllllllchl 55:754-63 Chronic Tension-Type Headache ----------------------- Diagnostic Criteria 1. headache lasting from 30 minutes to 7 days 3.. dutdl of lludy IIIII liming or \ypll rlresc:ue medication. 2ilbanml melbtions. wi111NNTIIII1gi11Qfrom2.C.. both of the following a.. facial sweating. no more than one of the following: nausea. headache associated with ipsilateral (to pain): conjunctival injection or lacrimation... A prophylactic agll'll is 111Commlllldad Dilly if mignline attacks are severe enough ID C4US8 impairment af I patient's quality of life or Ha patient hat >3 mignill8f/month lhlrt have not responded 1natment. IJiflilld fllilffor 24 botn..1111111 llllctivt.. topiramate). naproxen • moderate to severe migraine treatment • triptans (most effective). mild-moderate intensity c. photophobia. dll!lbii-IJind. mild or moderate intensity (may inhibit but does not prohibit activities) c....Wat 111111 2holn.ophthalmoplegic migraine • acephalgic migraine (aka migraine equivalent): aura without headache Management • avoid triggers • mild to moderate migraine treatment • 1st line treatment: NSAIDS . Su:a: SlivBrlllin SO at •l. 111 intelwrmans wm ellectiw u:ept CftgG!4'. vertigo.24b NNT r111ged fTom U ellec:ts cauld 1111 be 1111¥md IVSflntilaly. Nartqy 200). Dllllllhdilll: Nunarrl patients.1 far RizlllriptJn 10 mg. no nausea or vomiting b. bilateral location d no aggravation from climbing stairs or similar routine physical activity 3.0for lll1lltripiM 6mg s. severe unilateral. secondary headache types not suggested or confirmed Cluster Headache Diagnostic Criteria 1.! to IIMII i1llnily {21.ASA..11ar IUI'I1atriplln 6 mg I. llffilctivt. nasal congestion or rhinorrhea. !'lin 2002. not attributed to another disorder . Subcutnauslll11llriptln IIIII IIIII 1riptn. propranolol.. ttw lilwllt NNT 2.. at least 10 previous headache episodes fulfilling criteria 2 through 4.41arnmiptM2. ataxia. nortriptyline).eto 5. and altered level of consciousness) . bilateral d not aggravated by normal routine 4.l'llc:tice p11111181ar: {1111 evidence t... ITeedorn frgm plin II 2 tan. 91:241-51 lludr..

..examples: dementia. antidepressants. beta waves (> 13 Hz). receives afferents from the retina and possibly from the lateral geniculate body. Huntington's disease. 1. decrease in BP/HR/CO/RR • Rapid Eye Movement (REM) sleep: mixed frequencies on EEG with low voltage and sawtooth waves. increased GH release.treatment: benzodiazepine receptor agonists or heterocyclic antidepressants • sleep apnea .DDx: heart failure. Alcohol shorten& llaap latency and promotes drowsiness.-. nicotine. and periaquaductal gray Sleep Stages • Stage 1: 50% of alpha waves get replaced by theta waves (4-7 Hz). dreaming 2...obstructive sleep apnea: refer to Respirology. lnlrinsic sleep disorders 2. but I&ads to poor sleep mainteniiiCe duma second half olllnp.. restless leg syndrome.. rule out depression or disordered breathing • non-restorative sleep • differential diagnosis • primary insomnia • psychophysiologic hyperarousal from efforts to fall asleep .treatment: improve sleep hygiene • sleep state misperception: normal sleep demonstrated despite complaint of poor sleep • idiopathic insomnia . mercury • fatal familial insomnia: rare degenerative prion disease of increasing sleep . . neuropathy.. dopamine agonist l-2h prior to bed • secondary insomnia • poor sleep hygiene • transient situation: associated with major life change or stressful event . non-restorative • categoriea • sleep onset: diffi. glucocorticoids.oition: subjective complaint of poor sleep quality. sweating • others: environmental. copper.. Slaap debt of ·somnogens· {possibly adanosina) Iiiii wi1h tina spent awaka Disturbances of Alertness and Sleep . radiculopathy. rule out disordered breathing. . muscle paralysis.N42 Neurolo8Y Sleep Disorders Toronto Notes 2011 Sleep Disorders .. Circadian rhythm: suprachiumalic nucleus i1 hypolllalamus Overview of Sleep Definition • sleep is a reversible state of unresponsiveness and lack of perceptual awareness of the environment Anatomy of Sleep • the suprachiasmatic nucleus (SCN).onset insomnia leading to death within 7 to 13 months . lead. Circadian llllllllld disordn Coma • see NS35 ... Exbinsic aeap disorde. Insomnia • defi. altitude (lower FI02 ) .central sleep apnea: no effort to breath over 10 seconds ... iron deficiency . 90% of RLS . 3. amphetamines. rule out intrinsic sleep disorder with sleep study • sleep offset: early morning awakening... it projects not only to other hypothalamic nuclei. slow rolling eye movements. brainstem dysfunction • restless leg syndrome (RLS) and periodic limb movement disorder (PLMD) . still eye movements.depression has been shown to be associated with short REM latency • secondary to neurologic disorders . low muscle tone. thalamus.resolves on its own • secondary to psychiatric disorders (80% ofpsychiatric patients) . . rapid eye movements..RLS: unpleasant sensations creeping along leg leads to need to move legs leading to problems with sleep initiation . alcohol.culty falling asleep..PLMD: repetitive leg movements in sleep.DDx: spasticity.. and anxiety • maintenance: waking up. excess salivation.located in the anterior hypothalamus.. atlantoaxial subluxation. alcohol.. . arsenic. 3 Cablgur!R of DyaDIIIJiilla 1. high muscle tone • Stage 2: vertex K complexes.associated symptoms: fever. lateral medullary syndrome.treatment: iron supplement.. high muscle tone • Stage 3 and 4 (Delta sleep): slow wave (<2 Hz) but high voltage activity on EEG.. but also to the basal forebrain.examples: caffeine. hemiballism. sedative (withdrawal of night). pregnancy. eye movement is still. myotonic dystrophy • secondary to drugs/toxins . Parkinson's disease. and high voltage (positive and negative) discharges with spindles on EEG.. cholinergic brain state. R32 . cocaine. syringobulbia.

agitation. automatisms. sleep deprivation. '. medications Circadian Abnormalities • familial advanced sleep phase syndrome • autosomal dominant condition of early morning awakening (i. walkinglrunning. and appearance of being awake • aggravated by napping in narcolepsy. sits up in bed and screams. . urinary retention. htllophyW!agy • treatment • lifestyle modification ("cat naps·) can occassionally be effective management on their own. .. no epileptic activity • rule out psychiatric or other sleep disorders Nlln. driving) • modafinal (non-amphetamine stimulant) • amphetamines avoided because of their propensity for habituation • selegilene (metabolized in part to amphetamine). is a stimulant that also reduces cataplexy symptoms.olep-v.e. completion of complex tasks. '.. sleep paralysis (unable to move upon wakening for 2-3 minutes).. . hypothalamic tumours.. polysomnograph shows: • excess chin tone on EMG and/or excess chin or limb twitching on EMG • 1 of: excess limb/body jerking. sleep deprivation.. "morning larksu) • pathophysiology: codon mutation of Per gene leads to a 4 hours advance of sleep. night terror • predominantly in children • somnambulism: sleep walking (ranges from sitting up in bed to violent sleep behaviour) • 1-15% of population. and clomipramine are also effective Parasomnias Associated with Slow Wave Sleep: Arousals • occur in first 113 of sleep during stage 3 and 4 • arousals associated with confusion/disorientation. night terrors can occur at any time of the night • associated with fever. choreiform movements. Cltlplexy: brief episodes of muscle p111111y$is in 181PDfll8 IXJ exceA emotion (l. eyes open. hypnogogic/hypnopompic hallucinations (vivid dreams or hallucinations at sleep onset or at awakening) • 10% of patients suffer all four symptoms («narcolepsy/cataplexy tetrad•) • epidemiology: M>F. external noise. • others: moxindol. REM sleep aroUSBI is IISSIICimd wilh rapid awekanilg 111d vivid draam recan. stress/anxiety. seen on 2/4 naps during a multiple sleep latency test . rarely familial • diagnosis: based on clinical history+ EEG findings of REM in <15 min of sleep onset. lllll!lhDrl. enuresis • different from other slow wave sleep arousals. sympathetic activity. . temperature and melatonin rhythms • shift work deep disorder: due to sleeping at times different than normal circadian rhythm • delayed sleep phase syndrome: body's circadian rhythm is delayed compared to time displayed on clock • time zone change syndrome Qet lag) REM Sleep Behaviour Disorder • pathophysiology: loss of spinal inhibition that normally occurs in REM sleep leading to hyperpolarization of ventrolateral reticulospinal tract motor neurons of spinal cord • diagnostic criteria (American Sleep Disorder Association): diagnosis requires at least #2 and 3 are fulfilled 1. child is not consolable. injurious behaviour during sleep 2. sleep apnea. movement associated with dreaming state 3._---------------. vocalizations.. • night terror: abrupt awakening associated with fear and autonomic stimulation • in children (ages 2 to 4). certain activities are restricted (e. Slow WBVe sleep arousal is 11$50Cillted with confusion and amiiBiia. onset in adolescence/early adult • symptoms can become less troublesome with age but it is a life-long disorder • etiology: post head injury.g. diazepam • confusional drunkneas: partial arousal from slow wave sleep associated with confusion and startling... prevalence 1:2000. resolves by adolescence • clinical presentation: child awakes suddenly. multiple sclerosis. '. bladder distention. fever. verbalization. difficult to arouse • associated with fever.. excess exercise. injurious behaviours. at least 1 of: • potentially harmful behaviours in sleep • acting out dreams • disruption of sleep due to activities 4. with greatest frequency in childhood • clinical presentation: agitation.palienl$ have d11C1811$ed levels of hypacretin in CSF. but not in children. dilated pupils. resistance to being consoled. increased muscle tone. medications • increases the risk of psychoneurosis in adults.. enuresis. amnesia • treatment: self-limiting.Toronto Notes 2011 Sleep Disorders Neurology N43 Narcolepsy • irresistible desire to sleep in inappropriate circumstances and places • clinical features: cataplexy.g. ± open eyes.. pemoline.

systemic infection. hypoglycemia. verbalization. especially during non-REM sleep • triggers: sleep deprivation • treatment of sleep disorders decreases seizures. endocrine. arthritis • mood disorders • alcohol abuse • cerebral degenerative disorders • trauma • dementia: insomnia associated with wandering. metabolic. wheezing and SOB can interrupt sleep • GERD • fibromyalgia: associated with pain. ID6 Spinal Cord Syndromes • see Neurosu. fatigue. conversion disorder .meos NS28 Stroke Terminology • Stroke: sudden onset neurological deficits of a vascular basis lasting longer than 24 hours • Transient Ischemic Attack (TIA): sudden onset neurological deficits of a vascular basis that resolve after a brief period (usually <30 min) • Revenible Ischemic Neurological Deficit (RIND or minor stroh): sudden onset neurological deficits of a vascular basis lasting >24 hours that resolve completely or near completely within days • Stroke in evolution or progressing stroke: stroke that is actively progressing due to propagation of underlying vascular etiology to include further vascular territory over hours Sb'Oke I Thrombotic Embolic lntnlcnbral Subarachnoid Subdural/Epidural Figura 22. nonrefreshing sleep. tumours. pregnancy. aggression. Is the patient a candidate for tPA? • Onset: time when last known to be awake and symptoms free • Mimics to rule out: post-ictal. Has the patient had a stroke? 2. muscle tenderness and trigger points CNS Infections • see Infectious Diseases. exercise. Classification of Stroke Approach to Stroke • Initial AslleiSDleDt Goals 1. and treatment of epilepsy improves sleep • astluna/COPD: lower airway obstruction.N44 Neurolo8Y Sleep Disorden/CNS Infections/Spinal Cord Syndroma/Stroh Toronto Notes 2011 Medical Disorder Affecting Sleep • nocturnal leg cramps: DM. delirium during early evening ("sundowning") • Parkinsonism: sleep onset and sleep maintenance insomnia • sleep related epilepsy: brain synchronization is increased during sleep leading to an increased frequency of seizures during sleep. Parkinson's disease. coughing.

leg. lentiform. MCA 1. . no warning TIA. and face • pure sensory loss: hemisensory loss (usually thalamic) • ataxic hemiparesis: ipsilateral ataxia and leg paresis • dysarthria-clumsy hand syndrome: dysarthria. look for arrhythmias likl atrial fibrillation. mitral valve prolapse. multifocal if cardiac origin. . than llansition to Wllfllm. leukocytosis. . hiccup • Lacunar Infarcts (basal ganglia. If possibility of cardioembolic source. heroin).es11 items that evalullbJ: 11 1. CN III palsy.8val of consciousness 21 V"11ual syR&m 31 Motor systam 41 Sensory system 5ll. arrhythmia. internal capsule. preceded by TIAs • embolus: abrupt onset. Wernicke's (receptive) aphasia (if in dominant hemisphere) • Internal carotid: premonitory TIA or transient monocular blindness (amaurosis fugax)._. impaired horizontal EOM impairment. rheumatic heart disease. . lacunar infarcts (due to chronic HTN) • cardiac disorders: mural thrombus. posterior limb internal capsule) • pure motor hemiparesis: contralateral arm. locked-in syndrome • distal (usually embolic) occlusion (aka Top of the Basilar Sydrome): decreased LOC.l------------------. reactive myosis. Ischemic Stroke Etiology • thrombosis: stepwise deficits. midbrain findings (vertical gaze palsy.. thalamus. contralateral agraphesthesia and astereognosis. ipsilateral facial sensory thrombosis should be considered in the differential diagnosis of stroke and headache. but can also have seizures. . SLE. 2. ER38 for more tPA details) . nystagmus. prosthetic heart valves • hematologic disorders: thrombocytosis. maximal at onset. NN. MRI with gadolinium is the bast diagnostic t11st. The National lnstitul of Health Stnlb Scale (NIHISI is a standardized clinicalaxaminatian that dlllllrmines the severity of an acute stroke. 4.._________________ . dysphagia. It is an uncommon cause of either. coma. endocarditis. or cranial narva plllsies. It can 11160 be Uied to monitor respolllill to treatment over time. seizure more likely Conditions Associated with Increased Risk of Cerebral Ischemia • 'VUcular disorders: atherosclerosis. 3.. mass effect decreases sulci) • hypodensity of parenchyma • insular ribbon sign • hyperdense MCA sign • ASPECT score: where 10/10 is normal and <4/10 signifies high risk of bleed with tPA • subtract 1 point for each of following structures if abnormal within the ischemic hemisphere: caudate. asymptomatic or similar to MCA occlusion • PCA: contralateral homonymous hemianopsia (especially superiorly). 5. drug abuse (cocaine.._. alexia without agraphia. anosognosia.see sidebar) • applies mainly to MCA territory • CT signs of acute stroke • loss of cortical white-grey differentiation • sulcal effacement (i. ipsilateral Homer's. The scale u. vertical nystagmus. loss of bladder control (hypertonic detrusor) • MCA: proximal occlusion involves all of the below findings • superior division: contralateral face and arm paresis and sensory loss. vertigo.. dysarthria. mild hand weakness and clumsiness . Stroke Syndromes Stroke Syndromes According to Vascular Territory • ACA: contralateral paresis and sensory loss. tPA may be offered to the patient within the appropriate time limits (see Emergency Medicine. Cerebralnno•s. migraines. insula...Toronto Notes 2011 Stroke Neurology N45 Assessment • NIH Stroke Scale (NIHSS. amphetamines. vasculitis. contralateral limb impairment of pain and temperature. 6 Treatment • if no hemorrhage on cr and there is a clinical indication. facial weakness. hypercoagulable states ._________________. Patients often present with headache alone.. .or quadriplegia. Broca's (expressive) aphasia (if in dominant hemisphere) • inferior division: contralateral homonymous hemianopsia (esp. INO). occipital findings (anomia. carotid or vertebral dissection...e. but iSIIUOCiK!Bd with high morbidity and morllllity.. AIDS. dysphagia. contralateral neglect.. focal neurological deficits. inferiorly). Treatment is typically anticoagulation with heparin initially. hemi. decerebrate or decorticate posturing • PICA (Lateral Medullary or Wallenburg Syndrome): ipsilateral ataxia.angUIIge abiities Scoring (l!/421: O=no stroke H=mild stroke 5-15=moderate stroklil 15·20=moderate to 111verutroke 21-42=18111118 stroke tPA should be considered if scoru 6 or greater. venous or sinus thrombosis.. visual agnosia) • ifbilateral: cortical blindness or prosopagnosia • Basilar artery • proximal (usually thrombosis) occlusion: CN VI palsy. syphilis. polycythemia. sickle cell disease. CN III palsy.

.4% of patients had a symptomatic intracerebral hemorrhage (0.1111'=110. chronic HTN. plliam. •t-----------------. Practical Guidelines • general • ABC's.. cerebellum. ECG • diagnosis • make the correct etiological diagnosis so you have a rational approach for secondary prevention of stroke • consider transfer to stroke centre for neuroprotective or thrombolytic therapy if the patient is seen in first few hours (have been proven effective in clinical tests) Thrombolysis • rt-PA (recombinant tissue plasminogen activator) within 3 hours of acute ischemic stroke onset (NINDS trial) • treated patients were 30% more likely to have minimal or no disability at 3 months • 6.nm carrman in 1111 (p<O. carubllll amyloid angiopathy. Mlllndm: Whea IHSieSied It 12 months flumtile lima rJ . corticosteroids for vasogenic edema Global Cerebral Ischemia • etiology: inadequate blood flow to brain to meet metabolic demands (e. .. SBP=1B5. ACUTE STROKE MANAGEMENT Goals • ensure medical stability • limit or prevent neuronal death linD.. lntm:nblll hiii"IIIIIIIIQI. This process affects mainly smaller penetrating arteries (<200 mm in diameter) leading to lacunar infarcts of the basal ganglia and thalamus • acute HTN can cause hypertensive encephalopathy with dBP > 130 or sBP>200 assoc with findings on fundoscopy.t-----------------. . racant Gl or GU lllmorrhage. 1rauma. and llllrnlllial: IVt.. . or other cause • epidural/subdural hematoma c. . VDRL. Hypertensive Stroke Etiology • BP above upper limit of autoregulation of cerebral blood flow (normal is 150-200 mmHg). headaches.. inthll3. and pons . urgent CT to rule out hemorrhage and assess infarct • other labs and tests: CBC.OOII. INR. Investigations • • • • • • • bloodwork: CBC.rilli anlll rl Treatment of Stroke A. drug HUH. man.. AVM. visual disturbances and change in WC due to microinfarctions and petechial hemorrhages • pathology: hemorrhages occur from rupture of damaged blood vessels. •t-----------------.fA P41 Mill milnl or na dillebiily 38%.. likely at the site of Charcot-Bouchard aneurysms • most common sites: putamen. Hemorrhagic Stroke Etiology • intraurebral (ICH): hypertensive. NN. The classic sits of hypar111nsiva hamorrhagn is 1h1 bual ganglia. lliBifl v.. cholesterol and lipids ECG Cf± MRI lumbar puncture (rule out subarachnoid hemorrhage) intrarterial angiography or MRA (anterior circulation TIAs or dissection) carotid doppler or transcranial doppler echocardiography SullaiiVian StNI Syndro11111 Vartabrobasilar insufficiency dua stenosis associated with left arm 1118 causing vertigo. left arm daudication. check glucose. ESR. MCA and PCA 1-I'A in AMI Slniii-IINDS Tlilll NULf 1995. pabocunbaled lrill(3 month Pllilllt: &24 plli8llls (llllllllag& 76 y. hemorrhaoe in cmlnl irfin:ll.tiltl Mill iscllenic: slrolce rl reced onset.fA given Mhi13 hours of onset rl ICUll ilchlnic llrOiai lllll:tionllaub:oml 1113li'IJIIIIIL The riskrliml:nlnl il ilcrNied. the areas of the brain most severdy affected are the watershed areas between ACA.. PTT.. morll8y or rail rJ 11am111 strolrl 'IEJIJ 1 999.6% in placebo group) • treatment did not affect mortality compared to placebo but patients with severe strokes were more likely to have favourable outcomes if treated with rt-PA. All rnri1l.g. benefits of rt-PA were sustained at 12 months na dillebiily. a. Clllllbia1: Nt.031.. serum glucose.N46 Neurolo8Y Stroke Toronto Notes 2011 . 58'JI. 333:1581-7 Study: lllndanilld. cardiac arrest) • when hypotension is less severe.fA (OJlllAI arpllcabaMhin Mlin outcomll: NuW:Igic dllfili 1124 iiDin INI!SS sc*land functiansl oull:ome 1131111111hs (CIIII'flllilllllllllj. or other cause • subarachnoid (SAH): aneurysm. DISAH. focal neural Sx. 65\ v. willlll!llignifil:ant difln1ce in 340:1781-71... lhelt were more !lllieniJ il the t.. d!IIHI-illnd. Treatment • surgical: decompression to prevent herniation if cerebellar hematoma or superficial hemorrhage of cerebral white matter • medical (controversial): antihypertensive to lower dBP to -100 mmHg (typically nitroglycerin or furosemide used cautiously). amyloid angiopathy. p=0.. •. lumoUili. acute HTN • chronic HTN stimulates cerebral blood vessels causing adaptive changes like hyalinization and lipidosis to preserve the blood-brain barrier..-llfiCH ffTN. AVM. Theru wu no ll9ifart dillaiiiiC8 in morllily.ulll: l1wl wn na significlnt cltflnace 1124 hOUII.. IIIII IIIIINidlncB rl inlnlmllilll bllllliiiiNga an Cl Excmians inckllld hx rl racant linD or racant 11J'Q81r. anticoagulation. . coagulopathias. thalamus.

.. NS21 Asymptomatic Carotid Bruit • suggests the presence of atherosclerotic stenosis and signifies increased risk for both cerebral and myocardial infarction • modify risk factors... recent Gl or urinaty hamonhaga. .ll31.tion.500 Rl bidL IIJid hd. in hlllllllllllgic lllab il t!ae M.Toronto Notes 2011 Anti-Platelet Therapy Stroke Neurology N47 • give ASA at presentation • give antiplatelet agents if ASA not suitable or if already taking ASA • clopidogrel (75 mg daily) • ASA + dipyridamole (Aggrenox•) . see Neurosw:w:y. lnl!rvenlion: Hlll111e patients..aggressiveRx to d8CI'88Sa BP. C11J1111rilh'lith 6munlll .. Also aptian of intra-erterial tPA for specific dinical silliBtians Rlllti¥11 contrlindicltion• to tPA Early signs of I111Q8 cnbral inflllrc. 1M pllilnls wn lllllomly ID riCIM apirin. PMH ICH.MCtlt 1997. uizln at &troks annt. Treatment Condition Antiplatelet Anticoagulation Thrombolytic Endwrectomy ± Carotid Stanalis TIA Cardiac Carotid or + ± + ± ± noncamprauibla silll.110 lll'iill. p=D. renal failure.IIOI:IIed ldraclianlllcl hl.. recant LP or arterial punctu11111t + ± + (carotidl StralaHHvalulion Strob • Antiplltelet: o o Cardiac Carotid or vertibmbasilar dipyramole. o Carotid Endartereclllmy: 50-99% stenosis with law risk of periapellltive death or disabling strDks Blood Pressure Control • do not lower the blood pressure unless the hypertension is severe • antihypertensive therapy is withheld for at least 5 days after thromboembolic stroke unless there is acute MI. sBP >185. '.. Sinllllrill I. Afflr llljlltmeol fw prudielld ]RQIIIIIil. ± antiplatelet therapy • if stenosis >60%. • avoid hyperglycemia which will increase the infarct size B. 341:15i._. hemorrhage or mns an CT. pregnant. carotid endarterectomy reduces the risk of stroke by 1% per year (but 5% risk of complications) Hypertension • primary prevention '-dllge. 111cent ITllljar &llfllllry or tnluma. Sx of SAIVparicllldiliili/'MI. risk of stroke is 2% per year. lher8 WISIIO 'aniiCIIt diffniCI in d8l1h Ill ZwnQ. dBP >110.S1 lludy: llllndDniled. halh. 110 heparin and aspiril vs... Alllollllll Cantraindicltio• to tPA Improving Sx.-lllaCitBd baplrin. BP llllllt be lowered to sBP < 185 and dBP < 11 0 before IPA is given. . + + (carotidl '.1hrombacytopenia.m 15000 ar 12._ IUipiiCtld ICUIII isclaric llnlial rl racaat onset • prevent complications • NPO if swallowing difficulty • DVT prophylaxis iflimb weakness • initiate rehabilitation • therapy (see also Primary and Secondary Prevention below) • determine the vascular territory and etiology. . Cllllllilllar.. o. hlplrin. Hx AVM or ansury&m. blalll: FGr ba1ll hepllil vs. sBP above 220 mmHg. or dNth «dlpendlncy 116 manllll. uncontroUad serum glucose.. 111 CGIIIIU!dicdons ID. high INR or aPTT. .lrin.111d 110 clair ildicllions lor. Similllly. heparin 111 aspiin.. . and is less beneficial for those with symptomatic moderate stenosis (50-69%). . • antihypertensives reduce the risk of ischemic stroke in elderly patient with isolated systolic hypertension (SHEP trial) • ramiprillO mg OD is effective in patients at high risk for cardiovascular disease (HOPEStroke trial) • ACEI reduce the risk of stroke beyond their antihypertensive effect • secondary prevention • ACEI and thiazide diuretics are useful in patients with a Hx of stroke/TIA (PROGRESS trial) . >85.. . + Anticaagulllio1: Heparin IV to ll!liii'DPriate lllrget level then warfarin to INR 2-3 lbrombalrti:: 1h IV infusion of ll!Cambnmt tissue plasminogen activator (rt. minor Sx. aortic dissection. dopidagrel + ± Mthin IMYMb. tidopidine. liltJ 8ipirin gnllp I decrelled list of delllll 01 depellllence d 6111rils 1141* 1000 18wir.. Table 23. Bath aspirin and bupuiHIIaCitBd pllilabi hid raaDII ilchumic lfnlbl \'lithil 14 days. .. ud dlltll ar deplndiiiC:y It 6manllll. OTHER MANAGEMENT ISSUES . NIHSS >22. hill wn llloCIIBd :m mg daily. or dBP above 120 mmHg • acutely elevated BP is necessary to maintain brain perfusion • most patients with an acute cerebral infarct are initially hypertensive and their BP will fall spontaneously within 1-2 days • IV labetalol is usually first line ifneeded Blood Sugar . aflsll byalimila'-lilld i. then treat accordingly • lower temperature if febrile Primary and Secondary Prevention Carotid Territory Event ----------------- • carotid endarterectomy benefits those with symptomatic severe stenosis (70-99%)..PAI for ischemic stroke within 3h of stroke onset Get 24h CT to 1\10 ICH. resistant HlN. Canlbin: TheiST IUIIQIIIJ thlt 11piin slaJid be lllftad inrnednly llftaollle onset rl ilch8mic 1Jm1111n 48 hL willl110 ll'idlnCI!i illnmnill llnlb..

..&8. venous thrombosis RRR (MC!J CVmomity Al-c:IUIIII rn!ltlly 100 fC!] S1roka 32\ (1 61u 441 67(431u 1451 ML slnlb.RtiiiF Hurt t.. dissection. . IIIUII: Stroke Rehabilitation • individualized based on severity and nature of impairment._ .N48 Neurolo8Y Stroke Toronto Notes 2011 Anti-Platelet Therapy • primary prevention • current evidence has not finnly established a protective role for antiplatelet agents for low-risk patients without a prior stroke/TIA • secondary prevention • generally ASA is chosen as the initial antiplatelet of choice for stroke prevention • other agents (ASA + dipyridamole. Eldlsions ilcludld clmc lwr rA lllnornl lim 111 flllction. 75\ l1lllll willl nomtlilg 111111 \'olio were CDIIIidenid 1D be IIIUbPnlillS. may require inpatient program and continuation through home care or outpatient services • multidisciplinary approach includes • dysphagia assessment and dietary modifications • communication rehabilitation • cognitive and psychological assessments including screen for depression • therapeutic exercise programs • assessment of ambulation and evaluation of need for as&istive devices. 20 538 plllienls aged 40 tl80 ¥1811 (28\ rA 1Q8. 1. diUIIII-illild. 11d slnlb.J dDsl rA 40 llrJ lirrwu11tii dUy... 11ft 0. dilbetJs. llllj01 CDIDI1IIY events.IIId lklusa Tnlltlly ill pelilnts llliPICUII5 yaw risk rJ CUftlllllryhelrtdi-e. clopidogrel) are reserved for those who suffer cerebrovascular symptoms while on ASA • warfarin is generally reserved for specific indications in stroke prevention.. RRR (MC!J NNT !CII S1roka M(151u34l 73(511D131I Major C11M111Y Z7\ (21 1D 331 33 (261u 461 13\ (61u 19) 58 (371D 128) Al-c:ue rn!ltlly CllldlliD1: SimWSIIIin llf8ly Nduced 1118 Iiiii: rA ltiGII. Hypercholesterolemia • primary prevention • statins reduce the risk of stroke in patients with CAD or at high risk for cardiovascular events... splints or bracing • vocational rehabilitation . falicJw.I1lljorC011111ryMIIIS. even with normal cholesterol (CARE study) • secondary prevention • more evidence is needed for high-risk patients with symptomatic cerebrovascular disease.llld oO!ers. as wd II oii•'411W• MID and 01'81111 mor111ty. ..-. 380:7-22 S1ully: llltldani1ld. rill: rJ d81111 frlln CD101111Y MlllciualbecUirA dilllll. 4. Mlil Ou1amll: lnclJded lkuallld vacull Tnlltlly.. ar Z2\(141D3Ill Z6{191D431 16\ (5tu 251 56 {321u 1SSI evm. cardiac!atrial rA 5Ylll'..d kraw t:erebravlscullt diseue. IK rJ pdlllll 1-. TNIImaotwMh llllliprillWdUCid the rill: of IIIW (3A piiRII'IIvs. the risk of stroke decreases to baseline within 2-5 years Physical Activity • regular physical activity is an important lifestyle measure in stroke prevention and this effect has a dose-response in terms ofboth intensity and duration of activity S1llill il 511111 . Clldlsla1: 1n lilts atliah rilkfor ClldwasaW mri1ri reU:ed !be risk rA slroke. but statins are generally used in these patients as well Atrial Fibrillation • primary and secondary prevention • warfarin is the first-line agent Smoking • primary prevention • smoking increases risk of stroke in a dose-dependent manner • secondary prevention • after smoking cessation.. 111 trOd hv1ftnllion. pllllllbocanballd trill Mil .. 1I'IISCie disuse.1 piii'CIIII.. .-: RurHn1lllllm8nt 4wll8b rA piiCibo fallowld bv 4-6 Mlb rJ I ro.af21)02. . Pl&ra were111eri !lllbnimd 1D lm-tllin 40 II1IVd 01 pllcabo.

and necrosis • Acute Disseminated Encephalomyelitis (ADEM): monophasic demyelinating disorder with multifocal neurologic symptoms seen mainly in children often following infection or vaccination Figure 23. bladder dysfunction. [1 juxtacorticallesion]. [1 infratentoriallesion]. intention tremor) • symptoms not commonly found in MS: visual field defects. ::J Progressive r Pragrenive Prograsaiva Relapsing MSVariants • Devic's =Neuromyelitis optica (NMO): severe optic neuritis and extensive transverse myelitis extending >3 vertebral segments • Benign MS: RR without major disability by 10 yau-s • CJinically Isolated Syndrome (CIS): single MS-like episode • CJinically Absent MS: MRI disease only • 'I\unefactive MS: solitary lesion >2 em mimicking neoplasms on MRI • Fulminant MS (Marburg): rapidly progressive and fatal MS associated with severe axonal damage. progressive hemiparesis . inflammation. juxta cortical region. and dorslateral spinal cord • Dawson's fingers: periventricular lesions extending superiorly into corpus callosum • CSF: oligoclonal bands in 90%. spasticity. 3F:1M. Investigations • MRI: demyelinating plaques appear as hyperintense lesions on T2 weighted MRI. [3 periventricular lesions] Features • symptoms in order of frequency: fatigue.Toronto Notes 2011 Multiple Scleroais (MS) Neurology N49 Multiple Sclerosis (MS) Definition • Multiple Sclerosis: a chronic inflammatory disease of the CNS characterized by relapsing remitting. depression. corpus callosum. brainstem. except PPMS occurs in an older population with 1F:1M Diagnosis • Dissemination in Space and in Time as based on the revised McDonald criteria • Dissemination in Time: 2 or more attacks. . numbness. with active lesions showing enhancement with gadolinium • typical locations: periventricular. 30% concordance for monozygotic twins. neurologic symptoms due to demyelination and early relative sparing ofaxons Relapsing Remitting Clinical Patterns of MS (Figure 23) • relapsing remitting (RRMS) 85%... secondary progressive (SPMS) • RRMS can become SPMS l! i "" c I .. cerebellar peduncles. impaired gait. aphasia. Mort aymptoms in MS n duiiD cont brainsbm and optic nerve lesions. primary progressive (PPMS) 10%. visual disturbance. new gadolinium enhancing lesion 3 months later. 2-4% risk in offspring of affected mother or father • environmental • MS is more common in region with less sun exposure and thus lower stores of vitamin D • MS has also been linked to certain viruses. weakness. progressive relapsing (PRMS) 5%. or new T2lesions > 1 month after first attack • Dissemination in Space: clinical evidence of 2 or more lesions.. or progressive.. Clinical Patterns of MS Etiology • genetic • polygenetic: the HLA-DR2 gene has been demonstrated to be a genetically susceptible area. pain • Lhermitte's sign: flexion of neck causes electric shock sensation down back into limbs indicating cervical cord lesion • Uhthoff's phenomenon: worsening of symptoms (classically optic neuritis) in heat • SPMS: classically weakness oflegs in pyramidal distribution paired with cerebellar findings of arm (ie. or three of [1 gadolinium enhancing or 9 T2lesions].. apraxia. cognitive disturbance. increased IgG concetration • evoked potentials (visua1Jauditory/somatosensory): delayed but well-preserved wave forms . in particular an association with EBV has been found Epidemiology • onset 17-35.

presenting with optic neuritis. RRMS.tvene lfllcts.. plabo. 2:Cil005218..«1·0. CS). Coclme rjSllmltic !Miw..lllial: Aaltllllt. p<D.ftct 1160 pilieals with fiest ridarnywlrm wilh lnin MRI (cliicllly ilolllled syndromes. D.. glatiramer acetate (Copaxone•) and natalizumab (Tysabri•) • CIS: early treatment with Avonex may delay potential second attack • RRMS: DMT reduces rate of relapse by 30%. 2 RtT and qulli. D.N50 Neurolo8Y Multiple Sclerosis (MS) Toronto Notes 2011 ..53 [(5\ Cl 0. methylphenidate • education and coUD8eling: MS society. young. attacks shorter and less severe • SPMS: interferon-beta may slow progression • PPMS: immusuppressant therapy (e.. modafinil... .. gabapentin • fatigue: amantidine.. RebW).71l. and ..71.. SlUr... Tbara 1llllmlntCIIdlliy prog181si011 Treatment • acute treatment: methylprednisolone 500-1000 mg IV daily X 3-7 days ± taper • diseue modifying therapy (DMT): interferon-beta (Betaseron•. poor response to therapy 1D lilicdv delnile t. . 11116: Apooled odds 111iD (OR) rl 0. low burden of disease on initial MRI.-lllblliplllc:ln* Codnle Brtllllse Sytt Rer 2008.. psychosocial issues Prognosis • good prognostic indicators: female. Methotrexate•) • symptomatic treabnent • spasticity: baclofen... dantrolene.g..llll.a... (No IIIJpraprilll glllinrnlr ICitllllrilll W8llllaurJ)...... higher rates of disability.tS • pllienls Mil em in • _.limlfllml. carbamazepine. support groups. benzodiazepine • bladder dysfunction: oxybutynin • pain: TCA. low rate of relapse early in disease • PPMS: poor prognosis.IS... Avonex•.Wll)forpatilllts an fNV811US It one M'O odds ndiowu 0.. COIM!rtiag 1D liliclly deliile t..... c-.ian llflbllftl E.52 (95\.

abdominal cramps. hiSIOry of melanoma or undiagnosed skin lesions Hypotension.Tabla 24. dry mouth. or known sensitivity to tricyclic compounds such as Hypersensitivity to dunepezil or 1o piperidine derivatives Pregnancy. senurtion of hlllll. increased salivation. hypersensitivity to the drug. uncontroled hypertension. orthostlllic hypotension. transient myocardial ischemia.partial :!: 2" generalillltion. hypersensitivity to Cllybutinin Headache. SMre hepatic disease Hemiplegiclbasilar migraine. megacolon. fillip.5 mglspray. cardiac anest. dyt. constiplllion. dry mouth. hlllklcillllions. insomnia.kinesias in last 14 days. vtntricular tachyclldia. and anorexia Injection II!ICiions. obstructive uroplllhy. headache. ischemic heart disease. dianhea. higiKiose ASA therapy. increased akinesia. drowsiness Coronary artery vasospasm. maximum Migraine Anticonvulsn carbamazepile Tegrr!Die [Carbatrol. Makness. headache. fascicullllions. severe rnylsthenia pis. hypotension. increase by 200 mgld up to 800-1200 mlfd (individual doses) needed n Epilepsy. May caue significant rebound headache CNS disturbances (drowsiness.. . use of MAO inhibHors in last 14 days Hisllly d bone llllllllW depression. C) a·• f MAOBimibitor selegiline EldepryP SmgPObid Partanson's Disease MAOBimibitor pyridostigmine Mestinon111 600 mlfd PO divided in 5-6 doses Range 6().5 mgld q2-4wks. coronary artery vasospasm. muscle weakness Dizziness. headache. ganeralizlld tonic-i:lonic Mild to moderatll Alzheimer's Oisease.. use of triptans in last 24 hours. uncontrolled hypertension..1500 mlfd Myastlllllia Gravis Gl or GU obstruction Triptlm surnatriptan 2ft. dizziness. ischemic heert disease. daytime sedation. increased periistalsis. ischemic heart use of MAO inhibitor in last 14 days. hypotonia. dizziness!. muscle cRimps. diarrllea. dizziness. use of MAO inhibitor Side Ellecll Nausea. pain. fatip. MS) I ll:l I 5mg PO OD. vantricU&r fibrilllllion. hepatic disease. halklcinations Headache. hallucinlllions. maximum 200 mlfd Mi!Jlline Ergot dihydroergotamine Mig ran' Hemiplegiclbasilar migraine. peripheral vascular disease.. diarrllea. variable for intrathecal route derivatives Antispasmodic Anticholingergic oxybutynin clbide Ditropen111 SmgPObid neurogeric bladder or reftex neurogenic bladder Glaucoma.1DO mg PO pm. nasal congestion. nausea. Gl obstruction.. hypersensitivity to nllllnl or recombinant interferon beta Hypersensitivity 1o baclofen (Spinal Cord lnjlry) Nasal spray 0. unsteadiness. myalgia) tend to decrease overtime Transient drowsiness. use of in past 24 hours. injection site necrosis. vomHing. may increase to 10mg PO OD altar 4-6 Meks Betaseron111 0. Lewy Body Disease Relapsing. b Muscle RelaxantAnti spastic baclolen Lioresall Up to 20 mg PO qid. . hyposalivation. urinllrV retention. diarrhea. diaphoresis. cnl!rovascdar disease. increased bronchial seavtions.&mitting and Secondary Progressive Mulitple Sclerosis Spasticity (i. convulsions. miosis. risk of hypertensive crisis with tyramine-containing foods Nausea. myocardial infarction. dizziness l .25 mg PO bid. Caution with renal or hepatic diseil5e Concomitant use of meperidine or tricyclic IIIJiid8pniiiSanl8 I J . 1111usea. chwsiness. increase by 2. peripheral vascular disease. IIIMII8 hepatic or ranal dysfmction.e. confusion. nausea. insomnia. disease. hypersensitivity to donepszil or to piperidine Dupwine ptVCUr&llr Dop511ine agonist bromucriptine P!lrlodeP 1. constiplllion.. dyspepsia. EpitolinUSAI Cholinesterue lnhibHor donepszil Start at 106-200 mg PO 0[). 1111usea/vomiting. abdominal cramps. peripheral vascular disease. vomiting. muscle cRimps. dizziness. uncontrolled hypertension.25 mg (8 MU) SC every other day lmmunomodulator interferon bet&-. flu-like symptoms (fever. chills. nausea. hypertllnsiva aisis. Common Madications Medlanilm af Al:tioWCI•• Gclllric Name kll'odupa + carbidupa TriiiBNU18 IIDiiiiJI Carbidopa 25 ml)'levodopa 100 mg PO 1id Maxinum 200 mg carbidopa and 2000 mg levodupa per day lllllcdons Partanson's Disease Canlrlildicatiuns N51UW-Ingle glaucoma. up to 10-30 mg PO tid Partanson's Disease Concomitant use of potent inhibitors of CYP3A4. anamia Nausea. skin rash.

16th ldition. IMitul E.9!1% benefited more from carotid endartarectomy 1han bast medical therapy NASCET NINDSt-PA tPA reduces mortality llld long-tenn disability when ministered within 3 hours of aculll straka tPA improved clinical ouii:Qmas wla1 adminislllrad within 3to 4. TGIOI11D: Mcllllw-llill Campania. TGIOI11D: McGtaw-Hill pp.Ids 12005). 118(7):825-36.Uiipluclerosis: lllialagy. Ann Naurol 2005 Dac. Kappas I. Hamilton: BC Declalr. Cacil Essentials ci rnlliciie. Losc:alill J. pp. Weilshe!U BG. 171-782.ils-cllllificatian. Harlq HP. pp. pp.. CMAJ. Benjanin.368:283-92. eds 120011. 5th edition.. Kaaper II. Fnmllnl W. 203·mi. UppincDI W. 2nd Mabsy Inc. 211-13. I513): 69&-711. pp. FeTri FF 12001 1'rlelical to lila c1111 medical plllient St Ur. MISSicl'llletles: Blactwel Publisliing. Blidayasiri R. Hamilton: BC Declalr. Slri1h WT. £dan ll. Garcia A.I. 162&-30. 333:1581-7 NEJM 2008. 5th edition. 359:1317-29 NEJM 2008. S1llb lildsay K. Garcil A. Feslil SK.Reviaw. lDrQo DL. MacKnight C. Saundi!S EI18Vill pp 1120-41. 2004. Diagnosis and 1relllmelll ol dementia: 1.N52 Neurolo8Y Landmark Neurology Trials/References Toronto Notes 2011 Landmark Neurology Trials Trill Refei'IIICI NEJM 1991. Waters MF.lltiC Nualgia: An CIINII rilk llcl1n ullfll il ciical 'ractil:l? CD811 PG. Cluchii. Lllldlllm-Gr&llll Mlit al. MT 12001). Statuupllplicus. p.on1111illll Blidayasiri R. Griggs RC Cecil EsSIIIIials of Mldicine7th Edition Andraall CaTpenr. Harrison's rl internal medil:ine. 654-656. Chow t Berrie M. Bane L. 1625.ilptic• lcMtanstlii Dll Ailrldgl BK. Drganimd Qatiellllstroke 111i1j care lor stroke (Stroke Unnrialis11' Colllbora1ian).. Lancet2001. Gila CC 12005).cPain Cllvnic Pain. 97U. p. 617-9. Gri!IIIS RC. 36·40. Bkins JS. 359:1238-51 NEJM 2006.l/wMY.. Silver J. Sc:utt F. Bamrlllin Allll al. New Jersev: Humana Prea Inc. t. The Washington Mlnualci Madi:al Tharspllllics. Philldllphia: Hlriay and Beluslnc. M1111clllletles: Blactwel Publisliing. 1ilardars Motor Syslam Marshlll FJ. Risk assessment and primary prevention ci Alzhllimardil8u8.338114):970-6. 2008 Mardi 25. Chi]J!er 24 Nuak9:11sarders Yamada KA.. M1m11s.. 7:445-53 NEJM 1995. Sadolmick AD. HIUSel' Sl. Harrison's inlllmll medicioa. NFJM 2001. ads (2001). Griggs..71·2. hnvald E.. Spinal CGrd . stroke risk llftar EpiiiPIJ lrMsienl ischlemic lllllck. ··Sc-- Claaificatian Subcammitlee rl the 24IS11:9-160. RIIIIIMII PM. 111-28.Ur R. Barjllrjn.Uiiple sclerosis. Robilard A. 2008 Fab 26. The 1nllmatimal Claaificatian rl Headadle Disoolen. Johnston SC. NEJM 2000. Slmh WT. ltlinglil SC. Viii! Saundln Co. eds DHice ]IIICiice of niiiiUIDgy. t. 2003 Neu10bgy and 1Jstr1ted. Azer-Benlsilnov MT 120011. Headadle Society. Willal'sDIII•• Aminal! MJ... Dlllllllil Patler1011 C. Cecil Essentials ci metile. 345:311-8 Results Patienl1 with sy111:1tama1ic cellllid stenosis of 71}. Viii! Saunders Ca.. Cecil Essentials ol Medicine 7111 &ltianAndreoli. llnna111 Praa.5 hours of aculll ischemic strokB ECASS 3 PROFESS SPARCL Tempcnllobe epilepsy + surgery ASA + dypiridamole and clopidop showed similar banslits in secondary strokB prevention The observed benefit of sllltins in patienl1 with a recent stroke or TIA disease is also axlllnded to Surgery is superior to prolonged medical therapy in !Brqlorallobe epilepsy References Bnil Dlllh Wjdicu EF. N. MN. Rlllidilnts manull of medicine. Dlak MJ. Neurological dillarill dillgllOiis: a prioritized IPIIfDlCh. Jamalltlll JL. Jamelltlll JL. Gri!IIIS RC. pp. 3111 Edition. Enlll'g Med Cfric North Arraica1897. The Coclme Da!Bbne ci Systematic Reviews2001. 355:549-59 NEJM 2001. 16th edition. NEJM 1998. Residents manull of medicine. ea. and l'rMIIilll. 131. Slllllllls MA._ W. 2nd dian. 254-56. Graenb1111 1:\\ Simon RP. Plillldei!Da: Else\lier Sc:iell:e. H8ldlchl Amblti BK. Waters MF. HM1181 Sl. 244. .. 12-13. Palmln CH. Salrlders BseWer pp 1090-100. 344116): 1215-21. C1111111an Prasanting !'. 222·23. pp. Carpen!Br CCJ. pp. Fu:i AS. et al and 1relllmelll rl dementia: 2. Feighlner JW.. Gila CC 12005).. Rodri!Ja M. Ferri FF 1200n 1'rlelical !ollie care lithe medical plllient St Ur. Carpenter. lUi AS. w. Jarjodll A. Filippi M.58t6l:840-6. Tha Br11in Dallth. hnvald E. Feldman Hll Jacava C. Validlliln IIIII raiDrnant of scarasto p!lldict vary 111rt. http. IIIII. GY. Parsistant V8ga1ativa State II.. IBie 3. TGIOI11D: McGtaw-Hill pp.. pp.178151:548-S&. (20021 Eslllnlills of Physical Mliiciia and lllhebililllian. Inc. CMAJ.rt.APrimary Guile to l'nlctical Mlnag. Review. llizlnlallld Efilaply Amblti Mobiy Inc. Carpenter rnl WAins J1P 531·534. 57. Gills MF. dilgnasis. pp. Naurulogie Spill! t:Qid l'j!JIIllllllll. Griggs. D. eds 12005). AMdlllll S. Nlw JllrWf. Dilgnasli: critmia far multiple sclllr111is: 2005 ravilianstothe "Mcllanlld Crilaril". Losc:alill J. ad (2005). LDrQo DL. and newtrt811Nnt 111111gits. NOKWOrlllv Jlll!Jcdinetli C. 343l131: 938-52. Diagnosis. Neurological dillarill dillgllOiis: a prioritized ljlpiOICh. 95U4. pp.Ningstone p.ai9: Clnical 61h lditian.

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