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17 - Toronto Notes 2011 - Nephrology

17 - Toronto Notes 2011 - Nephrology

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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 YllSoad:i.ve 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

E.II ar!Briala 2. BPH) • • lilaniiii. ... lkin.iutre!J. I .. entire GU net e. Gl. a... . aartic dissactian. 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. 1' Nl reablorplion 4.g. Kidn8'f complliitian . nrllnlian illha · . z•m lml crisis) F"11111r1 4.-tl'leAII • Acutllllllergiej inlllrllitill neplriil A A-ICIIIIIAI!ing C-dnnic181ting 12" .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. DIC.· Angiulenlin II Adnml cortax Stinullllian of Na 6\ . - I ro · · Lungs •• • 0 --o f).1. \ Hillin _ . normal = 0.•. 1' bie1nbo11118 Differential Diagnoses of Common Presentations Azotemia Definition • higher urea and Cr are usually caused by inability of the kidney to excrete urea. lrilll • .·r . · .on: • myogenic mechanism: release of vasoactive factors in response to alterations in perfusion pressure.AldOSielone -4--· kidney · ..g. . ar.-111111 ARF/Iaxi11 • llanaiii1Bry obllruclian A/C • • Chronic IUUainlllrBiiiB nephritis C • Pyalal'lllplriis • llanBI vain Dllslructian AIC !thrombosis._. JG eel belllsym!lllhBtic narva IIM!u!Eon B·_ . 5.. slllnBI. campn181ian YIICUilil.Hr • • I . rise ln perfusion pressure causes afferent arteriolar coll8trlctl.ssificltian af AzatBIIH . Cr and other compounds in the blood 1 Azcaml• . 2 mechanisms of autoregulatl. 3.mHg). 1' vasc1*nmoo1h mulda IJliWih 3.on.1. polllbda tr. tumau. VuoCGIIIbictian 2._.. 1' lldoataruna AngiDIInlill . n:..Jmt.. . embcilc.-.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.IJt • llmal/l.A + llfrpovallnlil) • IUd lou8l (hamorrhaae.aryJ • NC {llPAlUS. ) -.ECV aapsis) • Hapat011111lll synlhme 1 llrlnaiM! + l'osklnrllt/C lllllllructia•l • Anattlmic (1hirt..-. ACE I.IJt Rlnll • Al:uiiii!Djar nKilllil ..

15% Ig.E... mild glomerular disease can lead to a mild dagrae of proteinuria. casts and/or hematuria) • CBC.e.g. 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. ASOT • indications for nephrology referral • ACR >30-1000 mglmmol • nephrotic syndrome: marked proteinuria >3. 25% other • 40% Tamm-Horsfall mucoprotein secreted from tubular cells tm . Hap Band C. vasculitis • Infectious disease • HIV.r•r • I o.8 mglmmol is the earliest sign of diabetic nephropathy • composition of normal total urine protein • 60% filtered plasma protein: 50% albumin.-r • No111111lly. W. {Ovarprocklction of LMW protainsl • e.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. Thus. HIY. 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.5 g/1. RF.ldanstrom'a macroglobulinemia. 24-hr urine protein and Cr • urine and serum immunoelectrophoresis. Cr • further workup (if degree of proteinuria >0. the 111ntion barrier is selectively penneable to SIZE {<60 kDI and CHARGE {repels nagativa particles). Classification of Proteinuria Table 2. solid tumour • Others • Cryoglobulinemia. edema is partly secondary to salt and Wlll8r l'lltllntion 2. Fabry's.11vartlaw • production of LMW proteins which axceeds the reabsorptive capacity of the proximal 1ub\Q • Plasma cllll dyscmiu: produce light chain lg myeloma..Giom. bllctarial endocarditis • Hlllditary/Jnelllbolic • Alport's.lymphomal • Lymphom1. p-ANCA.. Thus. Hep B. I Proteinuria I Physiologic • Orthostlllic • Absence of protainuria overnight • Usually resolves spontaneously • (exercise. heavy melllls • Cancer {carcinoma. multiple myeloma. fever. urea. Hep C. gold. diabetes. amyloidosis. CHF} PATHOLOGIC PIQ11:1NUIIA + 1 + htllaiDail: 1 Tubulaintamitial {impairud resorption! • <2 gfday • e. glucose. Fanconi"s IJY!ldrome • I Doss of large protains (albuminII I Glan. polycystic kidney disease • Medications • NSAIOs.. monoclon•l gammopathy of undanninad significiii'ICII C111 be seen with glornerulll' clsease. C&S. i. GN lgA nephropBihy • LMW -low molecular GN . c-ANCA. 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.. sickle cell. electrolytes. Second1ry • SystEmic disease • Sl.glom1111lonephri1is wti. hypertansiva nephrosclerosis • Figure 5. .d l'labsorplion and incraased exJ:relion af LMW proteins • Albumin {>60 kDI is NOT affected• Thus.5 glday. abdominal!pelvic ultrasound • serology: ANA.73m2/daywith hypoalbuminemia (<35 giL) .g. NP34) • an elevated ACR or 2. 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. GN Post-strap. 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.

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

. 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). 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. Z4 hour Urinll Callectian 1.ity Lut 2 digits of lila specific g111Yity x 30 = urine osmolality approximatEly e. serum Cr. Specific Gravity • ratio of the mass of equal volumes of urine/H 20 • normal range is 1.13 mgldL) in both of these patients • 20 year-old man who weighs 100 kg.. 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. Eslinwting Urillll DIIIIDI.d lndaptlmlont llf Rn.g.bllllll). Glucose • freely filtered at glomerulus and reabsorbed in proximal tubule • causes of glucosuria include 1. Collect all subsequent urina for lila next24 hi"$ 3.....010 in end stage renal disease (isosthenuria) 2. IWripra. consider: • renal tubular acidosis • UTI with urease-producing bacteria (e. other proteins (e. .plasma [CrI is influenced by the rate of Cr production • lower production with smaller muscle mass (ie.. ·}-----------------. specific gravity of 1.010 reflect dilute urine. GFR = 144 mUmin • 80 year-old woman who weighs 50 kg. NP34) • sulfosalicylic acid detects all protein in urine by precipitation • gold standard: 24-hr urine collection for total protein . bright yallow (due to ribofiiMn ingestion or vitamin .. but it takes time for Cr to accumulate and then re-establish steady state 2. Lenl Ia MfKt. consider plasma [Crl oflOO f!InOl!L (1. female.. but may be colourtess (dillllellls insipidus. C&nical Settings in which Urw. lg. elderly.5-7. GFR must fall substantially before plasma [CrI rises above normal laboratory range • with progressive renal failure. Tamm-Horsfall) may be missed • microalbuminuria (defined as 30-300 mglday) is not detected by standard dipstick (see Diabetes and the Kidney. Bence-Janes.5 ml/s) 3. . lliscllld first morning $JI&Cim&n 2. pregnancy) 3.Toronto Notes 2011 Assessment of Renal Function Nephrology NP7 2. trauma. proximal tubule dysfunction (e. pH • urine pH is normally between 4. hyperglycemia >9-11 mmol/L (>160-200 mg!dl) leads to filtration that exceeds tubular resorption capacity 2. Proteus) . contribution of tubular secretion to Cr excretion is increased when GFR is low • CrCl overestimates GFR • certain drugs (cimetidine.. or dlllt yaUow (conciiTII'IDd urina in inlnMiscu!er volume depletion] 3.. gender and weight (kg) to estimate GFR (see sidebar) • nonnal range is >90 ml/min (> 1.g... (umol!ll Cockcroft-Gault Fonnlll . Collect second morning CIIJIIy: Cloudilass may indicate infection Colour: usually pllla yallow or lllllbar. .0..030 • values <1.g. trimethoprim) interfere with Cr secretion 5. 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.85 in W0111111] (Crl.g.g. low weight) • e. excess Wlt8r intalal]. CrCI (mVmin] = I11!H!!fll X wt (kg) X 12 I X 0..020 reflect concentrated urine • value usually 1. increased protein intake or catabolism (sepsis. values >1... gender. and 14:1 in US units (urea expressed as BUN in mgldl and Cr in mgldL) . remaining nephrons compensate with hyperfiltration • GFR is relatively preserved despite significant structural damage 3.. Cockcroft-Gault formula • serum Cr used along with age. 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. Mrican descent • GFR is reported as ml/min/L73m2 body surface area Limitations of Using Serum Cr Measurements I. increased GFR (e.020 = 600m0sm .. MDRD (Modification of Diet in Renal Disease) formula • most common way in which GFR is estimated • complex formula incorporating age.001 to 1..g. Fanconi's syndrome) 4. Protein • dipstick only detects albumin.6 mUmin 4. if persistently alkaline. must be in steady state • constant GFR and rate of production of Cr from muscles • sudden injury may reduce GFR substantially. bltwnn voids 4..

vasculitis} lnfeclian (pyelaneplritis] lnllanmrtion (interstitial nephritis} Acute tubulll" necrosis Glomerulonephritis. Hlltf IIQI8Itive pdhclogy. 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.consider hyperoxaluria. nephrotic syndrome) 2. fever. no casts suggest extraglomerular bleeding (e.. viral infections Eosinophils • detected using Wright's or Hansel's stain (not affected by urine pH) • consider allergic interstitial nephritis.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. Nitrites . .sulfa-containing antibiotics . myoglobinuria (rhabdomyolysis) and true hematuria (RBCs seen on microscopy) o Urine Microscopy • centrifuge urine specimen for 3-5 minutes. ethylene glycol poisoning sulfur .e.alkaline urine calcium oxalate . calculi. discard supernatant.. lllllwilfl •inoopr o o <21111 eels per <4v. CASTS • cylindrical structures formed by intratubular precipitation of Tamm-Horsfall mucoprotein. Interpretation of Casts Hyaline casls Red blood cell casts White blood call casls Physiologic (concenlnrted urile. low sensitivity for UTI • +ve dipstick for leukocyte esterase and nitrites is 94% specific for diagnosing a UTI 6.g.. consider: chronic urethritis. prolonged starvation.g. UTI) or inflammation (e.consider acid urine. atheroembolic disease Oval Fat Bodies • renal tubular cells filled with lipid droplets • seen in heavy proteinuria (e.g.g. prostatitis. 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 . papillary necrosis.. fasting T•nninolagy B.. interslitial nelllritis Heavy proteiruria (>3. renal TB. exercise] Glomerulll' bleedilg (glomerulonephritis.JIIi:n ILtnotrmediU 1. interstitial nephritis. muddy brown] Fatty casts 3. CRYSTALS • • • • uric acid. gout) calcium phosphate .g.51fday] Pigmented gnmlar casts (heme grarular casls. proliferative glomerulonephritis) • isomorphic RBCs. 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. . Hemoglobin Red 1)111 calls WlitiCIIcasts QllllljwQt o •nil Aly 111 or ltplne • . cells may be trapped within the matrix of protein Table 3. Ketones • positive in alcoholic/diabetic ketoacidosis. AIN) • nitrates in urine are converted by bacteria to nitrites • high specificity.clllll pdhclogy Reduced lblhocllaf sii. negative culture).g.liit8CIIs • positive in hemoglobinuria (hemolysis). hyperuricosuria (e.._. o 7...

g.g. serum pruteil . tubular disease (e. = . each of which urine and plasma concentmian (e. U.. daily urinary potassium excretion rate should be decreased (<20 mmolJd) in the setting of hypokalemia • if higher than 20 mmolJd.. INal"'. 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 • • • • .X 1DO Many fonnuills uud in nephrology 11111 derived from 1he division of two frllctiDRI.ular fluid relative to Na • both can be associated with normal. 1.. Sodium [Na) 135·145 mmaVL (K) 3. SIADH • additionally... urine pH is useful to grossly assess renal acidification • "low" pH (<5.. osmolality and pH no 'normal' values. K.. 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.l. which 1hln givls the above equation.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.ular fluid relative to Na • hypernatremia is too little water in the extracel.Toronto Notes 2011 . 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.g. X ICrl.. pre-renal • high urine Na (>40 mmolJL) in the setting of hyponatremia: generally from causes such as diuretics. glucose.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.IP. ECF volume is determined by Na content.g..x [Crlurilo Fractional Excrwlion of Sodium FEti.. e. Bartter's syndrome)..S. . electrolyte excretion depends on intake and current physiological state therefore results must be interpreted in the context of a patient's current state.l. + Wl'2l· In 1he cqe of it is UNJPNo + UcJPc. . Examples of Common Urine Electrolyte Abnormalities • high urine Na (>20 mmolJL) in the setting of acute renal failure: indicates renal disease vs.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. Clinical Assessment of ECF Volume (Total Body Na) Fllid Campartmall: Hypovolllllic Decreased Orlho6tatic «op . Co. RTA) Electrolyte Disorders Sodium Homeostasis Introduction • hyponatremia and hypernatremia are disorders of water balance • hyponatremia suggests too much water in the extracel. 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. Cl. decreased or increased total body Na • solutes (such as Na.

. malaise.g multiple myelomaI • HypaP. decreased level of consciousness (LOC) . . decreased GFR) .<10 • Diarrhea • Excessive sweating • Third spacing (e.g. see Table 5 • adrenal insufficiency (decreased volume and co-secretion ofADH and CRH) • hypothyroidism (decreased cardiac output. Hyponatremia despite dilute urine (U0 . low urea excretion 2. 11111nnitoll • Pseudohyponatramia -lab artnct seen with severe hyperlipidemia or panaprotainamia (e. nonmal salina) y Hypovulemic U. blood or 3rd spacing • effective volume depletion: CHF and cirrhosis • pathological ADH release: SIADH and endocrine deficiency • SIADH .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. ectopic production. elderly women with "tea and toast" diet low protein intake.NP10 Nephrology mectrotyte Disorders Toronto Notes 2011 Hyponatremia • hyponatremia: serum [Na] <136 mmol!L • can be associated with increased.. anorexia.. • ARF.g.many causes including medications. GI.J • Altalal insufficiency • Hypothyroidism U_<10D • "-Ychogenic polydipsia Traat1111nt • Tnaat with water restriction • Tnaat with salt and wlllllr (i.<2Q/anuric • CHF • Cirrhosis and ascites • Pregnancy y Euvulemic u_>1DD • SIADH [normlll U. stress (pain.a. neurological disease. 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.. muscle cramps.OIIIIIolar (transloc:ati-11 • Extra osmol us in ECF <h... . An Approach to Hyponatremia Signa and Symptoms • depend on degree of hyponatremia and more importantly. Hypo-Osmol• (dilutionall • Most common cause of hyponatremia • Excess water in relidion to sodium stores which can be decreased. lethargy.. weakness. 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... CRF TrNtmlllt • Treatment golll is Naloss with ralatively mora water loss • Treat with sahnd water restriction and sometimes diurelics Figure 1.<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. pancnaatitis. depressed reflexes.. nausea. 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 .-----------------. lung disease.>20 • lliurelics • Salt-wasting nephropathy U... BUUIII81he urine is hypoolill101ar/dilu1e. somnolence. nausea.g.g.. schizophrenia) • ability to excrete water is compromised in people with low solute excretion (particularly urea) • e. normal or decreased (most common) serum osmolality Mechanisms of Hyponatremia 1. Hyponatremia with concentated urine (Uoam>200) • if urine remains concentrated. surgery). disorientation. 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.. urine. personality changes. 3. 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.

avoid if cirrhosis or congestive heart failure as nephrotoxic in these settings) • extra osmoles.serum !Nal TBW+lL • this formula assumes there are no losses of water or electrolytes . 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. pennanent brain damage. the ADH level falls suddenly causing sudden brisk water diuresis. 1111 kidnl'fS rapidly excrete the excess free water.. 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. 10 cclhr = 120 mmol/day of sodium which will increase serum [Na] by about 3 mmol/Uday) 'a.9% normal saline (NS) + furosemide (reduces urine osmolality.. < 1DD mOsmiL) in lha sstting of hyponalr8mia is u. death • risk of brain cell shrinkage with rapid correction of hyponatremia • can develop osmotic demyelination of pontine and extrapontine neurons. Frequent moniiDring at 5e111111 Na and urine output il essential.. of Rlpld Conallan of ll'fponlllntnU • lnadvart8nt rapid c011'8ction of hyponatremia can eiiSily occur • e. <24-48 hrs dumion. central pontine myelinolysis: cranial nerve palsies.__________________ . free T4.. and lhe serum [Na+] rises rapidly • Plltill'lt at risk of osmotic d1111'(11inlllion • High output dilute urine (> 100 cc.. Chronic or Unknown 1.45% NaCI = 77 mmoi/L Na in O..give oral urea (increases loss ofwater without Na.g. brainstem herniation. 30-60 g/day) • slow rate of IV 3% NaCI (e.. 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. '.K NaCI = 154 mmoi/L Na in 3'11. (for women) 0. ea-ntratlon of Na in Common lnfuut. Definitely Arote (known to have developed over <24-48 hours) • commonly occurs in hospital (dilute IV fluid+ reason for ADH excess e.Bxwt (kg) man. refractory • furosemide and IV NS • demeclocyline 300-600 mg PO bid (antagonizes effect of ADH on collecting duct. 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. and therefore rapid rise in serum Nalevel) • patient with psychogenic polydipsia.. 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. respiratory arrest. Cr serum osmolality. coma.Toronto Notes 2011 mectrolyte Disorders Nephrology NP11 Complications • seizures. .e.lhr. HzO Dlllcit 1nd TBW Eqllllti1..g. when hypovolemia is corrected.g.855 mmaVL Na in Ringer's = 130 mmolll Na inD5W = 0 C. switch to IV D5W) • give ADH to stop water diuresis (DDAVP 1-2 IV) ... ' . Options jf overly rapid correction occurs • give water (i..5 x wt(kg)] change in serum Na = infusate [Nal . glucose. 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.Na in 0.. Conection of Na in hyponab8mia should dlfinitlly known to t. if asymptomatic • water restrict to< 1 Uday fluid intake • consider IV 0. TBW = 0.uaUy thefi!$1: sign of dangerously rapid C01111Ction of serum &Odium . augments excretion of electrolyte-free Hp) • consider NaCl tablet or Oxocubes• as a source ofNa 3.1BW = O. quadriplegia. urine osmolality urine Na <10-20 mmolJL suggests volume depletion as the cause of hyponatremia assess for causes of SIADH (see Table 5) TSH. . treatment depends on severity • if marked fall in plasma [Na]. treat as symptomatic B. which may be irreversible (e.g. deprived of water Investigations • ECF volume status assessment • • • • • • • serum electrolytes.6 x wt(kg). H10 deficit = TBW x ([Na]plllsma140)/140 . not exteed BmmoVI/24 hrs Ldess .-----------------..5 x wt (kg) women 2.. NeCI = 513 mmaVL Na in 5% NeCI .

. HypiMIIImic (raN) • IIII'O!renic [hypertonic salina or NaHCO. urine that is inappropriately concentrated for the serum osmolality 2.... always a hyperosmolar state usually due to net water loss. neuromuscular irritability. D1 . No Positive renlll re.. 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..) • Cushing's syndrorna • Hyparald01111ronism • Traat wi1h salt restriction. skin • Gl [dianhaa) • Osmotic (lactulosa. 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. focal neurologic deficits. 01 I Figura I.NP12 Nephrology mectrotyte Disorders Toronto Notes 2011 Syndrome of Inappropriate Antidiuretic Hormone Secretion (SlADH} 1.. • Diuretics [loop) • Osmotic diurasis • Hyparglycamia • Endoganous[uraa with axcass NG protein faads) • \W • Insensible water loss • Respinrtory. death • ± polyuria.... thirst... malabsorption) • Remota renal loss I . 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.highFENa Table 5... coma. An Approach ta Hyparnatramia Signs and Symptoms • with acute hypc:matrcmia no time for adaptation. signs ofhypovolcmia Complications • increased risk of vascular rupture resulting in intracranial hemorrhage • rapid correction may lead to cerebral edema due to ongoing brain hyperosmolarity .. wmer replacement • Dialysis if ranal failure Nan-llypemlamlc . diuretics.onse to DDAVP 511% increasa in urina osmolality? • I I v. seizures. rarely due to hypertonic Na gain results from problems with water intake (access. No Is urine osmole excretion rme > 750 mOsm/d 1 . 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.

and therefore lower urine volume: results) Potassium Homeostasis • approximately 98% of total body K stores are intracellular • normal serum K ranges from 3.5 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. vascular events. granulomatous diseases. hypokalemia. 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.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. leading to less delivery of glomerular filtrate to ADH sensitive parts of renal tubule. salicylate . penicillin.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). and malignancy • nephrogenic DI: lithium (most common). rapid removal from ECF is necessary to prevent life-threatening hyperkalemia • insulin. and congenital Diagnosis • urine osmolality inappropriately low in patient with hypematremia (UDIIn <300 mOsm!kg) • serum vasopressin concentration may be absent or low (central). 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. trauma.45% NS approximately equals 500 mL free water • use formula (see Hyponatremia.140) [TBW = 0. as oral route is preferred for fluid administration • if unable to replace PO or NG. if fails to concentrate urine. most likely Dl • administer DDAVP (exogenous ADH) (10 fig intranasally or 2 fig SC): • central Dl: diagnosed ifthere is rise in urine osmolality. correct H2 0 deficit with hypotonic IV solution • lL DSW approximately equals 1 L free water • 11 0.0 mEq/L • in response to K load. use formula to calculate water deficit: H20 deficit= TBW x (serum rNa! . then replace water deficit using D5W DIABETES INSIPIDUS (DI} . thiazides may help as well (reduced ECF volume stimulates proximal tubular reabsorption of sodium and water... "free water" is water without sodium • encourage patient to drink pure water.. hypercalcemia. • 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.6 x wt(kg) for men. 0.5-5..5 x wt(kg) for women] 140 • replace free water deficit. . COIT8Ction of 181\1111 INal in hypernalremia snould not exceed 12 mmoVl/241n. or elevated (nephrogenic) • dehydration test: HzO deprivation until loss of 3% of body weight or until urine osmolarity rises above plasma osmolarity. causing Na reabsorption and K excretion • metabolic alkalosis • hypomagnesemia • increased non-reabsorbablc: anions in tubule: lumen: HC03. 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). 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.

y ingll&lion + lnc.0-3.g Conn's syndrome) • 2° (renovascular disease.. muscle cramps. rule out transcellular shifts ofK as cause ofhypokalemia 3. if renal K loss. hypomagnesemia.. if potentially life threatening.. <25 mEq/day TTKG <3 + ® KG I • • • • • • 1 Gllo-• • Diarrhea • L. fatigue.5 mEq/L Approach to Hypokalemia 1. may also assess plasma renin and aldosterone levels. 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.lls Mlllllbolic alkalosis {IQH axchanqa across call mambrana) I111LJin {llimulatus NII/I( AlPBse) Catacholaminas. Aclclamlc • . muscle necrosis. vomiting.Bartter's {loop of Henle dyafunction: furosemide-lib effect) . wide QRS. myalgia. check BP and acid-base status 7...or -mota•ivl Check acid bll$8 sbdus .ntolin ). arrhytlmtias. 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 • . TTKG =transtubular potassium gradient =(UJJPJ/(Uoom/PomJ 6. I I Hypo. Ji1-egonills {v.-ldlou {1rue hemll1llria) • Hemoglobin {hemolyiil) + U. serum [Mg] Hypokalemia DICQIIsedlnhlq • Limited diatary in!Bb • Cll.NP14 Nephrology mectrotyte Disorders Toronto Notes 2011 Hypokalemia • serum [K] <3. An Approach to Hypaklllamia Signs and Symptoms • usually asymptomatic. increases risk of digitalis toxicity Figura 10. Alhlemic • Diurulics (furosemide. more likely if digoxin use. hydrnchloruthilllide) ranall01111 duatll hyparaldoslllrnnism and mlllllbolic alkalosis) • Inherited renal tubular lesions . and constipation • if severe: arrhythmias.aldoslllrnne mineralocorticoid [Cushing's. reni1 tumour} • Non. + llyparllln•i¥11 • 1" hyperakloslllrnnism {e. assess contribution of dietary K intake 4. exogenous) + . begin treatment immediately 2.Gitelman's (disbl convoluted tlb.lle • DKA • RTA Variable • HypoMg • Vomiting/NG TTl(G = Trant-Tubolllr KGraclent Figura 9. 24-hr K excretion or spot urine K 5.5 mmol/L) • nausea.. emergency measures: obtain ECG. >30 mEq/day TTKG >7 IIBnallaaaa CheckBP + into C. generalized weakness..martives • Vilous adenoma • u. and rarely paralysis with eventual respiratory impairment • arrhythmias occur at variable levels of K. ECG Changes in Hypokalemia . particularly when mild (3..

60 mmolJL via central vein. max. 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 . areflexia. 40 mmol/L via peripheral vein. emergency measures: obtain ECG. KClliquid solutions • IV .g. repeat blood test 3. hold exogenous K. (low renin. spironolactone. correct with extreme caution • risk of hyperkalemia with potassium replacement especially high in elderly. palpitations.usually KCl in saline solutions. paresthesias. tablets (K-Dur-). 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. especially if transcellular shift caused hypokalemia • if true K deficit. amiloride) can prevent renal Kloss • restore Mg if necessary Hyperkalemia • serum [K] >5. HIV Adrenal insufficiency ol any cause (e.ad lntaq Cellular Releue Intravascular hemolysis Rhabdomyolysis Insulin deficiency Hyperosmolar states (e. muscle weakness. assess potential causes of transcellular shift 5.g. hypaaldosteranism o Associated with DM2. rule out factitious hyperkalemia. 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. tacrolimus o Pseudohypoaldosteronism (rare inherited tubular disardnl Signs and Symptoms • usually asymptomatic but may develop nausea. estimate GFR (calculate CrCl using Cockcroft-Gault) 6. avoid dextrose solutions (may exacerbate hypokalemia via insulin release) • max.food. low aldollerone) Decrusad Aldllltlrona Praductian (nonnal aldolterone) ldecraued tubular raspo••l K-sparing diuretics o Spironolactone • Amiloride • Tri1111terene Hyporeninemic. AIDS. Causes of Hyperkalemia hctitious lnc.0 mEq!L Approach to Hyperkalemia 1. Causes of Hyperkalemia with normal GFR Dacrusad Aldostarona Sti11U.. NSAIDs. potassium repletion (decrease in serum [K] of 1 mEq is very roughly 100-200 mEq of total body loss) • oral sources... if normal GFR. infusion 20 mmo!Jhr o K-sparing diuretics (triamterene. ascending paralysis. Addison's diseasa. and any K retaining medications 4. if life threatening begin treatment inunediately 2.Toronto Notes 2011 mectrolyte Disorders Nephrology NP15 Treatment • treat underlying cause • if urine output and renal function are impaired. diabetics. and patients with decreased renal function • beware of excessive potassium repletion. muscle stiffness. calculate TTKG = (Uk/PJ<)/(U0 om/P01111) • TTKG <7 = decreased effective aldosterone function • TTKG >7 = normal aldosterone function Table 6. chronic interstitial nephritis.

add Ca gluconate to above Tnilllllenl of Hypllllcelemll SEE BIG KDROP SEE .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:. n:spiratory.Ka.. Protect the Heart • Ca gluconate 1-2 amps (10 mL of10% solution} IV • antagonizes cardiac toxicity of hyperkalemia. 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. ECG Changes in Hyperkalemia Treatment • acute therapy is warranted ifECG changes are present.B·IIQDnist.0 and/or ECG changes: first priority is to protect the heart. or if patient is symptomatic • tailor therapy to severity ofincrease in [K] and ECG changes • [K] <6.5 mg IV • onset of action 30-90 min. increase the loss ofK via urine and/or GI tract (see below) • [K] between 6. Glucosa I. in metabolic acidosis. Insulin. often jUI! giving insulin to mtore euglycamia is sufficient to correct the hyperkalemia.. transient effect.5 and normal ECG • tn:at underlying cause.5% or 8. 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.g. asystole Toronto Notes 2011 . Normal T W11W Peaking T W11W Paaksd 1 g Figura 11. no ECG changes: add insulin to above n:gimen • [K] >7. no effect on serum [K] • onset within minutes. inadequate compensation means there is also respiratory acidosis. Bicllb.0.xaim11 DIOP.. 1 2 3 4 5 In patients with dilbetes and increued [K+] and hypervfycamia. Dialysis 1. drives K into cells in exchange for H • (Ventolin•) in nebulized form (dose= 2 cc or 10 mg inhaled) or 0. with 1-2 amp DSOW (give DSOWbefon:insulin) • onset of action 15-30 min. lasts 30-60 minutes 2.. . and controversial how much K is actually n:moved .5 and 7. overcompensation means there is also respiratory alkalosis .NP16 Nephrology mectrolyte Disorders/Add-Base Disorders • widening of QRS and eventual merging with T wave (sine-wave pattern) • AVblock • ventricular fibrillation.. stimulates Na/K ATPase • caution if patient has heart disease as tachycardia may result from this high dose ofbeta2 agonist 3. 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. Shift K into Cells • regular insulin (Insulin R) 10-20 units IV. Enhance K Removal from Body • via urine (prefern:d approach) • furosemide mg IV)..4% NaHC03 in lL D5W) • onset of action 15-30 min. stop K intake. .Diuretics. 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.Calcium gluconata BIG. protects cardiac conduction system.

requires carbohydrate malabsorption (e. then: 1. = ".Glycol Lactic Acidosis . = 1' 1 HCO. Figure 12. ischemic bowel. a carbohydrate load.Type B: failure to metabolize normally produced lactic acid in the liver due to severe liver disease. ethylene glycol poisoning. there is a coexisting non-AG metabolic acidosis • if increase in PAG > decrease HC03.piratury alludosi• Acute: ". can cause blindness and brain death). Olmoillr Gap = mea&ured OIITiolality . colonic bacteria that produce D-lactic acid.g. excessive alcohol intake. lncreaJed PAG Metabolk Acidosis (4 types) 1. short bowel syndrome). thiamine deficiency.Type A: due to tissue hypoperfusion (any cause of shock). or metfonnin accumulation (metformin interferes with electron transport chain) • D-lactic add: rare syndrome characterized by episodes of encephalopathy and metabolic acidosis.2 HCO. Calculated Osmolality = 2[Na] IUreal + (Glucose] Etiology and Pathophysiology 1. compare increase in PAG with decrease in HC03 • if increase in PAG < decrease in HC03.. diminished colonic motility and impaired D-lactate metabolism 2. there is a coexisting metabolic alkalosis 4..[CI] . expect PAG = 6) 3. OR another cause of acidosis plus ethanol ingestion UHful EqudDn• 1. Evaluate compensation (Figure 12) . a. Calculate osmolar gap • osmolar gap = measured osmolality.mlllolic Aeidoli• MUDPILES Metlllnol Uremia Dillbetic/alcoholic/llarvation katuacidosis PII'Bidehyde lsopropylalcohoV11011 Lactic scidosis Ethyl. and renal disease leads to impaired bicarbonate production) Ill:' C.Toronto Notes 2011 Acid-Due Disorders Nephrology NP17 Reepiratury acido•i• Acute: 1' 10 PCO. profound hypoxemia . is plasma [albumin]= 20 giL. Chronic: 1' 10 PCO.. PAG = [Na] . Calculate plasma anion gap (PAG) • PAG = Na.. lower baseline PAG by 3 (e.[HC01-l (nonnal range = 10·141 2. consider: methanol poisoning. .e. " + 2. Toxins • methanol (toxic to brain and retina.a very low GFR causes anion retention.10 PCO.5 HCO. serum Cr increased at least Sx above baseline . Lactic acidosis (2 types) • L-lactic acid . = 1' 3 HCO. If PAG elevated. Advanced renal failure (i. Ketoacidosis • diabetic • starvation • alcoholic (decreased carbohydrate intake and vomiting) 3.glycol Salicylstes or ASA ICARMEL Ketoacidosis lllnal Failur.metabolized to formic acid • ethylene glycol (toxic to brain and kidneys).g.calculided osmolality (normal < 1Dl 3.metabolized to oxalic acid (envelope shaped crystals in urine) • salicylate 4.calculated osmolality • calculated osmolality= (2 x Na) + urea+ glucose (all units are in mmolJL) • normal osmolar gap < 10 • if gap> 10.10 PCO. Qlranic: "...•n of lncrnMd Anian Glp M.(HC03 + Cl) baseline= 12. = ". An Approach to Acid-Baaa Disordars Metabolic Acidosis Identify Main Disturbanc). range 10-14 • PAG can be altered by plasma albumin level: for each 10 giL fall in albumin. Metlllnol Ethyl.

distal RTA) . lll<CI'IItion. incraesad PAG metabolic acidosis + resp.. hyporesponsiveness or hyperkalemia • to help distinguish renal causes from non-renal causes. U0 <20 mEq/1..e. + II + Salina resislllnt ICheck blood Hyperten. An Approach to Metabolic Alkalosis . Pilar dlulllllcl 11 Post-hypercapnia • Volume depleted I I Volume depleted I I Normal ECF vohne I + + I Diundic . Normal PAG Metabolic Acidosis (Hyperc. reabsorption • type IV RTA: defective ammoniagenesis due to decreased aldosterone.g. formate..g.of Non-Anian Glp Mmba6c Allillosil HARDUP Acetamlamide It' RTA* Diarrhea* Urehlroenteric fi5tulll Pancreaticoduodenal fistulil increased *Most Common 2.ivll • 1• hyperaldosteronism • 2° hyperaldosteronism • Cushing's syndrome + + I I . use Urine Anion Gap= (Na + K) . aldosterone also promotes hypokalemia • hypokalemia: transcellular K/H exchange. U >20 mElJIL 0 IAssess volume atatus + I + Gil•• Vomiting • NGtube II . 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 . 1' HCD. NP15) • consider treatment with exogenous alkali (e..... Salina 1111ponsiva + + I I I . Gilelm1111's Nate: cannot use tD assess volume st11t11s i1 presenoe of alkalemia: 1' HCO.. milk alkali syndrome • diuretics (contraction alkalosis): decreased excretion ofHC03.a Mi1111d Dilar*rwlth NRr Narmal pH (i.) if: • severe reduction in [HC03 ] e.llkalosisl • Cirrhosis • ASA overdcn.t in urine (likely nonrenal cause: diarrhea) • if >0.g. 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.NP18 Nephrology Add-Due Disorders Toronto Notes 2011 c . therefore increased [HC03 ] • post-hypercapnia: renal compensation for respiratory acidosis is HC03 retention. . suggests problem is lack ofNlf. . NH 4) in urine • if <0. stimulus for ammoniagenesis and HC03 generation I Metabolic alkalolis (1' pH..e • Sepsia Metabolic Alkalosis Pathophysiology • requires initiating event and maintenance factors • initiating event • GI (vomiting. suggests adequate Nlf. can exacerbate pulmonary edema • overshoot alkalosis: abrupt.g. NG tube) or renal loss ofH • exogenous alkali (oral or parenteral administration). 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.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. oxalate... N•llllllllnllin • Exogenous alkali • S8\111'8 hypokalemia • Bartter's..g.. decreased ECF volume.----------------. NaHCO. salicylate. especially with very low pH (<7) • no metabolizable anion (e. <8 mmol/L. . poorly tolerated transition from overly aggressive alkali loading.Cl • calculation establishes the presence or absence of unmeasured +ve ions (e. drag• Na -+ 1' Nil exctlltion Figure 13.. partial conversion of accumulated organic anions to HC03 and persisting hyperventilation 3 Clinical Sc-rlosdml'roll.I I I I ...hlorem.t in urine (e.

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

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

TUMS•) treats hypocalcemia when given between meals and binds phosphate when given with meals • consider calcitriol (1. 42.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... gentamicin) end adjust doses of renally excreted medications AmllettrJZ118.Toronto Notes 2011 . 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).. loop diuretics when GFR <25 rnUmin • statins for dyslipidemia • adjust dosages for renally excreted medications (avoid nephrotoxic medications) • dialysis (hemodialysis... l'lllbilllil: A sa.Electrolytes: monitDr K P. Clnli-•o..... liAS blacbdl raOOcad IIIII rilk al hllllllai1111 in peliellts with diablli: Pllilnls with no!Miilbelic CKD..in il. . .!1% 26. antacids) • medical • treatment of secondary hyperparathyroidism • calcium supplements (e. llril.. diselle._: To Multi th1 roll alllrin IIQiallnlin s.dy .Dl(._: RAS blocbde llduced CV aull:omes in dilbatic nepllropllhv • Will u no!Miilbelic em ..e.. llllldti:Twanty-!Mirilll{N = 457!iiiWIIII incblld. Stages of Chronic Kidney Disease IKIDOQI.. 3.Dstaodystrophy: giva calci..NIJihrotoxins: IMiid IIIPhnrtaxic drugs [ASA..pH: mebbolil: acidosis H . Can1llrld ID plabo. .Low-nitrogen diet E .. 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. liAS bloc:bde dectelsed CV oulcGme CGirj1llld ID llllllfnll111npy.Hypertansion NEPHION II ..4% lncidenc1 llf Etlalagilla llf Chronic Kidney Dii-ICm) Diabetes HypartBIIIion Interstitial nephriti&' Cystir/HirediiB!y/Congenital SecondllfY GNI\Iasculitis GlomenJonephrilis OtharJ\!nknown 9..llf em Slqe4 Stqe5 15-29 End &!age renal di&ea&e < 15 (or dialy&i&l N . .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. l'llillllwith a. ..g..!1% 7..-..: Rlndomillld I:GIIbGied lrilll111d llllly!ld CV CIUII:omll il pDIIII Mdl cllanic ijctluy diMIIIICXIIVprgOOJril lllllad with RAS inhibillnl blockll$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.llerin lfiQiallnlil IIWiflm bb:kldt-buld 1hlllpyMil pllceba lllllllllllfnll (bell-lllocklr. Cltill!lchlnnal bbclan 11111 ot111r ll'llillyparllllsNe-bllld thenvfl theavt illhe slid\'. . .RBCs: m1111111ge anemia with arythropoiatin D .ys1lm (liAS] bDcUde in ClnliJvuaHr cv IIUb:llrlll in pllilnbi with c:lmlnil.g. . . 155:791-1!5 .7% 4. C. . ijdnly IIIII_.i: lliUir ma..4% Table 8.._ . peritoneal dialysis) • renal transplantation between meals Ito increased Cal and with mills (1D bind and decreased POJ N .1% 2.. metabolic acidosis) • uremia . decreasing PTH) • sodium bicarbonate for metabolic acidosis • erythropoietin injections (Hct <30%) for anemia.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.

nausea. IWSI Rate l. co-morbidities. ce111bral adama. if not acandidll:e far diaysis.. ligh functioning. neuropathy.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. Hemodialysis • Heparin [none. . Wh•ta lnitiltll DIALYSIS or full [1 DOD Ulh]) • IV fluid to support BP {e.g.0 mg!d. 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.lopaltly.5 • Ca I.S.. methanol I Overtoad (rulnctory volume ovarkllld) • Pulm-rv edema lhmia • Encephl. residual renal functian Bed-bound..q. fewer stringent dietary restrictions.. . four exchanges per day) or cyclic (CCPD.4 Z. no renal function Success depends on presence of residual renal function Residual renal function not as important Ftom: Nlllionll .5 <3.g.Z5 • HC!la 40 3. 4h 3 1irnaflwk or 2h daly) • Q Blood Flow (Max 4011 cc/min) • Ultnlfitration (e.. tight [500 Ullil .NP22 Nephrology Renal Replacem... 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. 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. in order to avoid dialysis kidney func:tion Young.g. • Haw tD Wfb Di.Jpia Ordara !MUST BE INDIVIDUAUZED) . seizures) • uremic pericarditis • refractory accelerated hypertension • clinically significant bleeding diathesis • persistent severe nausea and vomiting • plasma Cr >1060 IUDOl!L (12 mg!d. 2L or to target dry weightI • Na 140 lean budjusted by stilling II: 155 and "rampilg" down to Serum K Dilllysllhl 4-6 1. Peritoneal Dialysis VI. hypotensian. 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.L). excess fluid (ultrafiltration). three times per week). the serum Cr level quoted as >350 IUDoliL (>4.g. continuous {CVVHD) or sustained low efficiency (SLED) • peritoneal dialysis: peritoneum acts as a semipermeable membrane similar to hemodialysis filter • advantages: independence.g.5 minimize cmnpingl • K (based an serum (KJI 3.. collapse) Bactenmia Bleeding due to hepain Hemodynamic rtrass of axtracorporaal circuit Disequi!ibrilm syndrome (headache. better rehabilitation rates • available as continuous ambulatory (CAPD. Type (e. pericarditis.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.L) or BUN >36 mmol/L (100 mg/dL.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. solutes.. . FBDI un111 >35-50mM • length le.. ... and restoring buffering agents to the bloodstream • available as intermittent (e.-----------------.-----------------. 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.

n • .n. living donor (related or unrelated) kidney transplanted into iliac fossa..73 m 2 /day) • abrupt onset hematuria (microscopic or macroscopic) • azotemia (increased Cr and urea) . transplant renal artery anastomosed to external iliac artery of recipient • 1 year renal allograft survival rates . 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».. . 24:2915-2918 S1udy: illlrolplctiw. 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. llllldlld cola! with Yll'l MIIQII fulluw 141 . age of donor.. l'lliiiD c. parietal epithelial). 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. rise in Cr. ' . ... ± fever • de novo glomerulonephritis (usually membranous) • new-onset diabetes mellitus (often due to prednisone use) • cyclosporine or tacrolimus nephropathy (refer to Small Vessel Disease.-----------------. 6ftwhile Iwere llllll:l!ed tD 533 dlcnlld daacr lrlnlpiMt (D1X) patilllll .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.dergoing LlX venus NHD. endothelial. malignancy (skin. 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. post-transplant lymphoproliferative disorder) • acute rejection: graft site tenderness..lnnlt*nt Nacfllnll " -.5 g/1.. hyperlipidemia.. NP32) • chronic allograft nephropathy • early allograft damage caused by episodes of acute rejection and acute peritransplant injuries • immunologic and nonimmunologic factors (HTN. ACUTE NEPHRITIC SYNDROME Clinical/Lab Features • proteinuria (but <3. pdenls 46. .. .Toronto Notes 2011 Renal Replacement Therapy/Glomerular Diseue .. quality of graft. Cancbin: lflllu mlllty1D DlX.511MilllllllfliRe in hllll1l ratialor D1X Vlnlll NHD ralnlce.. oliguria.. Signliclnt rnonalty hmnllllia l'llll:tian willlllX 10. . Kaposi's sarcoma. Significlri survinl blllefitlor pllierQ _.t 5331ive damr lllXJ 1rlnsplad patieals m IIDCbJnll homa dialysis {NHDj l1:3:3111iol or d-. Renal Transplantation • • • • • • preferred modality of RRT. lit is iriaricr1D llX.. .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.. Nephrology NP23 CD1111110Diy IJud lmmunDSupprauin Drup Calcinelllin inllillilors • Cyclosporine • Tacrolimus Antiprvlifwmivlt 11111dic..

penicillamine Heroin Recllce BP. Edama 4.lipiduria (fatty casts and oval fat bodies on microscopy) • hypercoagulable state (due to antithrombin III. Oval fat bodies (microscopy( 6. with Ig and C3 deposits found in GBM • outcome dependent on etiology Table 10. Etiology of Nephritic Syndrome Low Complement Laval Postinfectious GN Mambranoprolifarativa GN Secondary Cues Nonnll Camplamant Lartl lgA nephropathy Anti. "- [ Protainara FSGS Membranous gtomarulopathy Minimal change Membranoproliferative GN Focal proliferative GN • lgA nephropllhy • ldioplllhic membranoprolifenrtive GN Diffuse prolifen.----------------. malaria.. .. inlecl8d &hunt Gold. 2. Hyperlipidemia. SLE. HBV. SLE. lymphoma. Naphrotic Syndroma Minimal Prwentation -' Nepllratie Syndnlme 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. NEPHROTIC SYNDROME Clinical/Lab Features • heavy proteinuria (>3.. amyloidosis Secondary CIUSIS DI\IIICIIUIIS Th. .-nlll Mambranoprolifaratiwe Glomeeulosderosis Glomeeulonephrilil Nodular Diabetes mellitus.Schonlein pLrpura Goodpasue's synrtome Slf Endocarditis Abscess or shunt neplritis Cryoglobulinemia . &teroids Steroids. Hypollbumilemia 3. ACEVARB fur proiBinuria Aspirin.tive GN Crescentic GN • HBV.e. ACEI.5 g/1. HCV •SL.73m2/d) • hypoalbuminemia • edema • hyperlipidemia (elevated LDL cholesterol). HIV.i.5 Qfdl 2. lipiduria 5. . solid breast. 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. Sevn proteinuria (>3. Hypereoag!Jahle stile (antithrombin Ill. protein Cand pnrtein S lost in urineI Change Membranous Glomeruloplllly HBV._• -' 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. 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) .ria.. 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..py Hodgkin's lymphoma NSAIDs Reflux ne(h'opathy.. leukemia. ACB. obe&ity HCV. Gil Focal S.{iBM disaasa PolyariErilis nodosa Wegener's granulomatosis Henoch.E • Cryoglobulinamia Figura 15. Tha Spectrum of Glomerular Pathology .

e. ANA. ESR. and cause not obviously diabetic nephropathy • urine immunoelectrophoresis • for Bence-Jones protein if proteinuria present .. a diagnosis of exclusion after other possibilities are ruled out Investigations for Glomerular Disease • blood work • first presentation: electrolytes. serum immunoelectrophoresis. cryoglobulins. p-ANCA.Toronto Notes 2011 Glomerular Disease Nephrology NP25 3. fasting lipids • determining etiology: CBC..GBM m iltld . C4. ASOT (anti-streptolysin titres). urea. mv • urinalysis: RBCs. Cr. depends on underlying cause Tabla 12. SLE. 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. c-ANCA. CHF.g. IgA nephropathy. C3.• 15% of cases lmmuno. piuci-immune) 60'J(.ftuorncence Linear pattern due to lgG 111d SUing Pattem C3 deposition along capillary loops Antibodies against type IV collagen in GBM Primuyc. 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. 4.. casts. without proteinuria. WBCs. corticosteroids + cyclophosphamide or other cytotoxic agent + plasmapheresis in select cases • prognosis: 50% recovery with early treatment. 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. VDRL.. albumin. diabetic nephropathy) • hematuria with or without proteinuria • IgA nephropathy (Berger's disease): most common type of primary glomerular disease worldwide. RPGN Classification RPGNTpl: AJrti. usually presents after viral URTI • hereditary nephritis (Alport's disease): X-linked nephritis often associated with sensorineural hearing loss.{lBM disease Goodpasture's disease lgA nephropathy Post-infectious GN. Henoch-Sclxlnleil pLrpura s-nduvc.. protein • 24-hr urine for protein and CrCl • radiology • CXR (infiltrates. Cryoglobulinemia. 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.. proteinuria <2 glday • thin basement membrane disease: usually autosomal dominant. amyloid. benign • benign recurrent hematuria: hematuria associated with febrile illness. %111RPGNC.. pleural effusion) • renal ultrasound • renal biopsy (percutaneous or open) ifheavyproteinuria or renal insufficiency. FSGS. exercise or immunization. HBV and HCV serology.

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. 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 . ACEI. I + I Cl111111 + CIIIIIV Mesangial proliferative lupus nephritis Focal lupus nephritis Diffuse lupus nephritis lllln. I month! lhUd Mb Clllsl fallllwing 11111iaian . tenofovir. . Class I and II do nat need lriiBtmant direcllld Ill renal lesions • • • l • • • Cllllll .. International Society of Nephrology/Renal Pathology Society Classification of Lupus Nephritis 2003 HIV-Assoc:iated Renal Disease 1......tich 11'8 h ..HIV-assodated nephropathy • histology: focal and segmental glomerular collapse with mesangial sclerosis.. HAART Henoch-Schonlein Purpura (HSP) • seen more commonly in children • purpura on buttocks and legs. 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. 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. gkJcacolticuids in cumbinltian with IAinQIImllliclcy Ia blln dlmlll'lllrltld on¥ fur c.. high dose steroids. ...IIIOCillld with considlrlbil iiurmltion.. Ch1191 in imiTM1ilgicl111111 (lllli-dsDNA.. Advanced sclerotic lupus nephritis llll. 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.NP26 Nephrology Glomerular Disease Toronto Notes 2011 Secondary Causes of Glomerular Disease !flyalic (Sill AmlillluD Oir 2008. heavy proteinuria.g..... antiretroviral drugs (e..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 + .... progressive renal insufficiency • prognosis: kidney failure within one year without treatment • therapy: short-term..ln short· 1111 medium-term It Ieist lillilll emcy llllll'fll!d wi1h pulse cyclgpholpluidullld • um 1axicny pofile: faiUitu NSpond b.:In pltienlsMII pralflnM 1up. cyclophosphamide.tmlld ESRil Planning Figure 16. 67:1115-B ... prednisone or sulfa may prevent recurrence ._. TB....llll Amyloidosis • nodular deposits of amyloid in mesangium.ll neplrii1. 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. onlr • Mllillnll: 1181111 urila !llftilllriB. abdominal pain. indinavir) and other drugs used to treat HIV-assodated infections 2.. v. rheumatoid arthritis.ydaphosphm!Haied reQimllll... self-limiting course.E patients.. "collapsing FSGS" • tubular cystic dilation and tubule-reticular inclusions • clinical features: predominant in black men. Mil Rlspmtltionl*ng thl melhod al choict.. advene l._. direct nephrotoxic effect ofHIV infection.. senrn C3111M only imit8d lbity 10 llflldictllle 1t1P01111i ID IJealmentllld ny be Ullid .IIId -b1dionnybM i11lependent plldic!Nit lbiilyfur cliic:ll M:GmB in 1lllrlpy al nllpllilis 1111 nlld 10 ba inlllplltld in cunjundiln.h:ts.

g. aureus is most common infecting agent • treatment with appropriate antibiotics usually resolves GN Hepatitis B • membranous GN. distal tubule (e. phosphaturia.g.Toronto Notes 2011 Glomerular Diaeaae/Tubulointerstitial Diaease Nephrology NP27 Cryoglobulinemia • cryoglobulin&: monoclonal IgM and polyclonal IgG • presents as purpura. amyloidosis. polyarteritis nodosa. aminoaciduria. collecting duct (e. PCKD) • urine concentrating defect • polyuria (nephrogenic DI) 1. ACUTE TUBULOINTERSTlTIAL NEPHRITIS Definition • rapid (days to weeks) decline in renal function • 10-20% of all acute kidney injury . 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. proximal tubule (e. type N RTA 3. multiple myeloma. membranoproliferative GN Hepatitis C • membranoproliferative GN. 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. fever. 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.g. heavy metals) • Fanconi syndrome: decreased reabsorption in proximal tubule causing glycosuria. analgesics. obstruction) • distal RTA (Type I RTA) • Na-wasting nephropathy • ± hyperkalemia. hypouricemia • proximal RTA (decreased bicarbonate absorption): Type II RTA 2. sickle cell anemia.

Balkan (endemic) nephropathy .mixedessentialcryoglobulinemia • idiopathic Pathophysiology • acute inflammatory cell infiltrates into renal interstitium Signs and Symptoms • • • • • acute renal failure if hypersensitivity reaction: may see fever. mild proteinuria. cephalosporins 2. cyclosporine. antibiotics: beta-lactams. atheroembolic disease • malignancies: multiple myeloma • granulomatous: TB. lithium. mercury. hyponatremia • gallium scan shows intense signal due to inflammatory infiltrate • renal biopsy definitive Treatment • treat underlying cause (e. arthralgia. oxalate. allopurinol. Goodpasture's. sickle cell disease • others: radiation. amyloidosis.sarcoidosis. stop offending medications. leptospirosis • immune • SLE. lithium. renal graft rejection • hereditary: cystic diseases of the kidney. Sjogren's. tacrolimus • heavy metals (lead. acute allograft rejection. WBC casts. toxoplasmosis. hypokalemia. rifampin.NP28 Nephrology 'IUbulointerstitial Diseaae Toronto Notes 2011 Etiology • hypersensitivity I. brucellosis. skin rash. sarcoidosis. uric acid nephropathy • vascular disease: ischemic nephrosclerosis. copper). hyperkalemia. cadmium.g. acetaminophen • cisplatin. sulfonamides. 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). hematuria • eosinophils if allergic interstitial nephritis • blood • increased Cr and urea • eosinophilia if drug reaction • normal PAG metabolic acidosis (renal tubular acidosis) • hypophosphatemia. furosemide • infections • bacterial pyelonephritis. quinolones. Legionella. CHRONIC TUBULOINTERSTrTIAL NEPHRITIS Definition • characterized by slowly progressive renal failure. other: NSAIDs. CMY. arsenic • radiation • chinese herbs • endogenous • hypercalcemia. 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. Wegener's granulomatosis • immune: SLE. antibiotics if pyelonephritis) • corticosteroids (may be indicated in allergic or immune disease) Prognosis • recovery within 2 weeks if underlying insult can be eliminated 2. Streptococcus. EBV.Sjogren'ssyndrome. cryoglobulinemia.

few RBCs and WBCs.Toronto Notes 2011 Tubulointeratitial DiAease Nephrology NP29 Pathophysiology • fibrosis of interstitium with atrophy of tubules. Etiology of ATN . acidosis. pigmented-granular casts Complications • hyperkalemia: can occur rapidly and cause serious arrhythmia • metabolic acidosis.E1ilylena glvcol YIIMI Dcclulion • large or smal renal artery involvement Figure 17.. lechemia I Clrculldlng Valuma Hemorrhage ilcl. electrolytes... Ca. P04> blood gases • urine: R&M.Fluorinated anaesthstic .Amphotericin B • Antiviral {cidofovir) • Antinaoplastics . post surgical Skin l011es Gllosses Ranalloues EffvctNII c•culating Valuma Haart failure Uver failure Sepsis Anaphylaxis .. eletrolytes. osmolality • ECG • abdominal ultrasound [ Acute Tubular Nacrosis [ Exogenous • Antibiotics .g. 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. or administration of nephrotoxic drug • urine: high FEN.Caphalosporins . increased P04> hypoalbuminemia Investigations • blood: CBC. 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. P04) and anemia Findings which Suggest Chronic Tubulointerstitial Nephritis • normal PAG metabolic acidosis • hyperkalemia (out of proportion to degree of renal insufficiency) • polyuria.. urea. rhabdomyolysis.. sepsis. nocturia • partial or complete Fanconi's syndrome • urine: mild proteinuria.Aminoglycosides .Cisplatin . Cr. decreased Ca. I • • • • • • • • .Methotrexate • Conti'IISt madill • Haavymlltals • Other . I . mononuclear cell inflammation Signs and Symptoms • tubular dysfunction (e. ToxiM I Endogenous • Endotoxins (bacterial) • Myoglobin • Hemoglobin .

underlying renal disease. DlhlriiJIIIIIdilnat lflect risk • nep/lruplthy..Nlplnfllhy feaoklopam dopmill. c.48-716]). aortic dissection • kidney transplant more vulnerable . naproxen • may be associated with minimal change glomerulopathy and nephrotic range proteinuria • resolves eventually with discontinuation ofNSAID. Acute Interstitial Nephritis (AIN) • majority due to fenoprofen (60%). surgery.23-1. ACE inhibitors.IC8lytcyslain8 il mGI9 IH!Ir. 11."ring sign" • increased risk of transitional cell carcinoma of renal pelvis • good prognosis if discontinue analgesics 4. iiDJIIII.. Tubulointerstitial DiaeaseNuc:ular Diseases of the Kidney Therapy Toronto Notes 2011 AmlnlrriiMid2011.. embolism..dnltion dlnr... thereby preventing prostaglandin synthesis and causing renal ischemia • more common in elderly.. extrarenal compression. Other Effects of NSAIDs • sodium retention (2° to reduced GFR} • hyperkalemia... 11111ii. nephrotic syndrome) • clinically: develop prerenal azotemia within a few days of starting NSAID • treatment: discontinue NSAID.. Furoserride increesed the risk (RR = lZ1 (1. CHF.49 (0. SIUy 0.. flank pain. hypercoaguable state.. cirrhosis... cyclosporine on morning of procedure if possible .llnutridl. 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... psychiatric symptoms and Gl disturbance • papillary necrosis • gross hematuria. Chronic Interstitial Nephritis • due to excessive consumption of antipyretics (phenacetin or acetaminophen} in combination withNSAIDs • associated with emotional stress. vasculitis..B8]) llld Thllop1¥i111 (RR = 0.ra. Analgesic Nephropathies 1. 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. may require interval dialysis • short term high dose steroids ( 1 mglkg/day of prednisone) may hasten recovery 3...... ibuprofen. RENAL ARTERY OCCLUSION • important. dialysis rarely needed 2. 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!.:Todlnna1beelftctive11811al .NP30 Nephrology .. declining renal function • calyceal filling defect seen with IVP .... Ca:llaon: foi.. ar ll'lll1liiDl on nephropattlf...:ln111141 (RR = 0.06]) !Wad thl risk llliiPhroplthy more thin saline IIane.62 IOA4·o.148:214-84 .. potentially reversible cause of renal failure Etiology • abdominal trauma. Vasomotor Acute Kidney Injury (AKI) • normally prostaglandins vasodilate renal arterioles to maintain blood flow • NSAIDs act by blocking cycloo. hypovolemia (diuretics. HTN (2° to hyporeninemic hypoaldosteronism) • excess water retention (due to elimination of ADH.antagonistic effect of prostaglandins} Vascular Diseases of the Kidney Large Vessel Disease 1.xygenase enzyme.. rudomillld.

lrDwntion: I'IR:ullnlaus JMialllrilltion &IIID!gl with 11111i:ll1hiiiiP'f [l.more common in elderly 2. 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. malignancy (e. !4)af34mantlls l'lliiiii:DpltiiiiiiSinuiiQIJOiwilll l1hllusdllulic Ulosis in lllaut onellflllllllely llld benefit af -ulndion. duplex Doppler U/S Treatment • anticoagulation with heparin then warfarin (1 yr or indefinitely.a. age 30-50 NE/Af21J09. 361:1953-62 S1udy: WIH:arUt 111-bildllll RCT.lllllils. nausea. atheroembolic renal disease) • contrast-enhanced CT or magnetic resonance angiography. IIIII natally. 31 pltiea111911 llplria:ld 1 plriplac:ldullli:IIJ1IIclllion. RCC). therapy can be considered to save the opposite kidney if normal 3. CI' or MR angiography. 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. blood flow): good screening test (operator dependent) CT or MR angiography (effective noninvasive tests to establish presence of stenosis) ACE inhibitor renography (ie. 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.eooplatalat. depending on risk factors) . 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. time 111111 C'l Mil. ti11111Dfim mil ewnt. atherosclerosis . surgical revascularization • little or no benefit if therapy is late Le. vomiting. duplex Doppler studies (operator dependent) Treatment • prompt localization of occlusion and restoration of blood flow • anticoagulation. elevated plasma LDH.n. especially membranous). extrinsic compression of renal vein. LDH. kidney is already shrunken. RENAL VEIN THROMBOSIS Etiology • hypercoagulable states (e. elevated AST. nephrotic syndrome.g. fibromuscular dysplasia . BP Clllb'GQ versus mml lkiiDamu: Prny CIIJbDTIII.g.chqll in mel fln:tion af ClllltiJine c:oncermtion _. ALP • acute onset hypertension (activation ofRAAS) or sudden worsening oflong-standing hypertension • renal dysfunction (if bilateral. However. ± rise in Cr. significant trauma. ECF volume depletion. sickle cell • clinical presentation determined by rapidity of occlusion and formation of collateral circulation • acute: nausea/vomiting. timel. hematuria. :flank pain • leukocytosis.Toronto Notes 2011 Vascular Diseasea of the Kidney Nephrology NP31 Signs and Symptoms {depend on presence of collateral circulation} • fever. percutaneous angioplasty or clot extraction.more common in females. sudden rise in proteinuria • chronic: increasing proteinuria and/or tubule dysfunction Investigations • renal venography (gold standard). flank pain. Sewndery IUI:1111111 inc:lJde liP. thrombolysis. surgical thrombectomy llruculn6n-llllllll:ll n. percutaneous angioplasty + stent. or solitary functioning kidney) Investigations • renal arteriography (more reliable but risk of contrast-mediated ATN.Iftldilll falaw.rtar llaoArllly S11101il 2.

idl dBcianb iniLoction.. 1:11111 . SCLERODERMA • 50% scleroderma patients have renal involvement (mild proteinuria. 5.. 3) lowdou--. 2. TTP.ad-. need fordBy$is IIIII Ill\' dalllllllllllg paliiJU Mil nlllli crilil . 4 reepeciMiy.W*'ilm. 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». reduce dose of cyclosporine or switch to another immunosuppressive drug • chronic: result of obliterative arteriolopathy causing interstitial nephritis and CRF (striped :fibrosis)...: 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 .. c.OOI iqJITiild dole cydolporile Md *oirus. HTN) • histology: media thickened.g. 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. llc!Girooslln sbliliclnllv ••Ill r. ... II M111 (p<O. DIC. Pllilnll: 145 paliiJU w iducilnxllnnlllllll crisis w11a inl6im111d li&2paaMh IICiari*w. "onion skin• hypertrophy of small renal arteries.dJ..NP32 Nephrology Vascular Diseasea of the Kidney/Systemic Diseases and the Kidney Toronto Notes 2011 Small Vessel Disease 1.Jailn: llllnllcrisis Cll1 M1111111Q11dwhn llypWnliol contraiiiiiMIII ACE illlibibn 2.dls ll1d 12111111111svs.133:600-3 cohort-wMII follow " of 5-I 0years.l) lillndl'd dose cyct)IJIQ!ila.. P"... NP32 . HYPERTENSIVE NEPHROSCLEROSIS • see Hypertension. rftorrimd controlled iill will IZIIIOIIIIfolcJw.t.-m-t dilllysil. labile hypertension. lie TIICIIhlsn llso I'-d dlclllllld IIIII riiCID 11jel:tion Ill 6 n. 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... avoid angiographic and surgical procedures in patients with diffuse atherosclerosis 3. l'llilnla: 1645 p!lients scheduled ta receilt 1 ._!lin IIQiinlt 11 olher 1rms. 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. .nt dilytisw .4.Mid2lXXl.. microangiopathy. . IIIII regimes hild 1lle liMist ill:idea ol dill1helllut .llft-Gd GfR 12 mollllulllrbnplllllllion. .sv.. CALCINEURIN INHIBITOR NEPHROPATHY • • • • cyclosporine and tacrolimus causes both acute reversible and chronic.. largely irreversible nephrotoxicity major cause of kidney failure in other solid organ transplant (e.SidrM hlllhB higlat incidaiiCI of dlll.1 IIIII sericu lllvene MID.: NJrcoplalollfe COrticollaroidiiMd ailher.:1111 TICIGiilllllllm llllowllllignific:lndv hifi!BJ IGI'R It 12IIU!Ihl COIIfllld 111111 111111' M111 (65. volume overload. wllo did 11111 hm ranll crilil. hypertension due to other factors can cause renal disease (hypertensive nephrosclerosis) or worsen pre-existing renal disease ... visual changes...4 mVmin VI..... 17. 51.q). dlcianb iniLoction. Thn110 iiiRicl in Mill pllilnt lllrviwl.-onlllllililllls. . THROMBOTIC MICROANGIOPATHY • • • • a spectrum which includes HUS._.. makes up 90% of cases) or secondary diseases of renal parenchyma or renal vasculature can cause secondary hypertension conversely. 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.. 4) low doll illlhls Mil 4. corticosteroids (splenectomy and rituximab if refractory) • avoid platelet transfusions and ASA . NEJM mrl.1.. 51. patiarG wllo inibllv dilllysi5 3'II I Bmon1hs 1111r.. 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.. dBIIII occ:uned in 31% ollhB plllilds.. high Cr. Gllltlrlllln 50'1.. angiography. ARF....7for IIIIlS I. llld dea!iaed . 251:2562-75 s. progressive renal dysfunction._. percutaneous angioplasty) • anticoagulants and thrombolytics interfere with ulcerated plaque healing and can worsen disease • presentation: acute or chronic.. Farrt.. fibrinoid necrosis of afferent arterioles and glomeruli • 10-15% scleroderma patients have a "scleroderma renal crisis": malignant liTN (usually within the first few years). ol .less frequent now due to lower doses of calcineurin inhibitors hifl181t OJIIIIIrUiillie mctiullllas.. 56.

smokers • fibromuscular hyperplasia: dista12/3 renal artery or segmental branches.Toronto Notes 2011 Systemic Diseases and the Kidney Nephrology NP33 Hypertensive Nephrosclerosis Tabla 13.tion of vascular intralobular and all&rent arterioles endothelium Clinil:<ll Pll:lure African American. Chronic vs. 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. 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). lack of production of unknown vasodilators.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. or lack of clearance of endogenous vasopressor • ineffective sodium excretion with fluid overload . disn. Slow vascular sclerosis with ischemic changes affacting Fibrinoid namsis of arterioles. chronic hypertensive disease Uri111lpia Mid pnrtainuria. undllllyilg chronic kidllll'f disease. normal urine sedinant Acute aiBVillion in BP (dBP > 120 rrrnHg) HTN encephalopathy Protainuria and hematuria (RBC casts) Therapy Blood pr8S$U18 control. usually males >55 years. frequent follow-up Can progress to renal fllilure despite patient adherence Lower dBP tu 1Q0. Malignant Nephrosclerosis Mlllipnt Nephl"llld_.. 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. 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. causes generalized arteriolar constriction 2. AIN. 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.

. . but treatment of HTN can slow the progression of renal insufficiency • control ECF volume: Na restriction (88 mmol/day intake). additional tests may include • 24-hour urinary estimations of Cr clearance and protein excretion • imaging {U/S.. can progress rapidly to kidney failure oMIDD • deposits of monoclonal Ig in kidney.. heart and other organs • mostly light chains (85-90%) • causes nodular glomerulosclerosis (similar to diabetic nephropathy) • lab features: increased BUN. . HIV nephropathy.. 1118 amyloidosia..B m!Vmmol in f811111es .0 m!Vmmol in males > Z. dialysis with end-stage disease • ACE inhibitor and/or ARB may provide added benefit (monitor K and Cr) Multiple Myeloma futuiW of Mulliplll .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..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.. PCKD and multipl1 rn'(llollll. increased Cr. 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. radionuclide scan) • serology for collagen-vascular disease • renal biopsy Treatment • most chronic renal disease is irreversible.----------------. CARU Calcium (elevated) Anemia llanlll Failure Lytic Bon l.. diffuse tubular obstruction • chemotherapy (especially cisplatin): ATN or chronic TIN • pelvic tumours/mets: post-renal failure secondary to obstruction • 2• amyloidosis • radiotherapy (radiation nephritis) . renal function declines. . 25% overt nephropathy) • microalbuminuria is a risk factor for progression to overt nephropathy and cardiovascular disease • once proteinuria is established. Abnonnll Urine ACR Values from 20D8 Canadian Diabetes Association CPG > 2..NP34 Nephrology Systemic Diseasea and the Kidney/Diabetea and the Kidney Investigations Toronto Notes 2011 • as well as investigations for renovascular HTN.. . diuretic. liver. unknown percentage ofType2 • at diagnosis up to 30% of Type 2 have albuminuria (75% mkroalbuminuria.. .. The othen. 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.----------------._... CT. 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.

llda PRltliNiria11 • Qflllll ax11nt U. GFR and Urine Protein ovar Time in Diabetes 1. Therefore. . ldl il . p=D.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.1JDWn (80 ll9'd. Ea.09.. 1.. Autonomic Neuropathy • affects bladder leading to functional obstruction and urinary retention • residual urine promotes infection • obstructive nephropathy 111111 o.12·1. IIR 1. 2. in women. daublt-llild. PCKD. 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. 372:547-553 llilwy albumin IIXCratian -lea willllllnillr1ln (p=O.620 pllilllls will! median b'low141 of 5& moadts. ACR is >28 mg/mmol (>250 mg/d) • clinically detectable proteinuria. HR 1.BS-1. +ve urine dipstick • normalGFR • very expanded mesangial matrix • stage4 • increased proteinuria (>500 mgl24hr) • decreased GFR • <20% glomerular filtration surface area present • sclerosed glomeruli .1111 n.OIM)IIIII carnbinllian lhnpr (p=0. ndiclabl.ll It Hijl Yucllil' IIIII (tlfTAII6ET S1udy) 4. rule out nondiabetic renal disease • avoid unnecessary potential nephrotoxins (NSAIDs.inCIIIIIIdMII coriinltionthenlpv(1233. be ISUre to wmch serum K. O. Progressive Glomerulosclerosis • classic diabetic glomerular lesion: Kimmelstiel-WII..t-wD TthUtln. nadllarapy.8-28 mglmmol in women (25-250 mg/d) • increased mesangial matrix • stage 3 • macroalbuminuria (>300 mgl24h). a 0.038).Z4. (> 180 mg/d).ap. rapidly rising Cr. . especially if patient hu DM 111d renal in&Ufficiency. ACEI c. Will limilrwith 1llrrillf1an (189) IIIII 11milcil (174. Pri:iplll: 25.001l coriinltion1lillllll\'(p<O. Alpert's) DIABETIC RENAL COMPLICATIONS (Urine Prolllin) "' 0 --- fE Time Figure 18. ACR in men >20 mglmmol. 1.01. cloubq II Clllllinine IMland d11t1. llllrllnllll: fllilllll NCM eh rmnipril (10 mw'd. dye studies) S1udy: l'rDip8ctiw. 2. N=85761..0-20 mg/mmol in men (18-180 mgld).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.-: alalyU.Clll1iWia. HR 1. catJse hyperkalemia.C011.34111'111 men fllqUBrtwilll canminllion 111arapy 1212.18. Accelerated Atherosclerosis • common finding • decreased GFR • may increase Angiotensin II production resulting in increased BP • increased risk of ATN secondary to contrast media 3. but -IIIOCiltld willl JXIGIIIr malaull:llll"ll.01).01-1. 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.'sis or of .037).51.g. The need lor dilt. 1111. N=85421• a t:ai!Dalltian of both Mluyo.in Cancbin: Renll oulcomes IWit simillr in both IIIINsatllli 111d CombinlliDn u...g.10.00. aminoglycosides.rillllllqlllred Mil 1elmitlllln or 2008. p=0. llultl: Thllllllllllr of aull:llmiiMIIIIIIimi'-lar111miartln ranipril (1150.01-1.. !llllbniz8d oontnJied bill.tud Gfll dlcliwd lent with 11nq. short duration ofDM • family history of nondiabetic renal disease (e.

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

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. 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. "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. often detect asymptomatic patients incidentally • diagnosis: contrast filled medullary cysts on IVP.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. 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. HTN. ciprofloxacin: able to penetrate cyst walls. chronic kidney disease treated with kidney and/or liver transplant . autosomal dominant. usually diagnosed in 4th-5th decades multiple cystic dilatations in the collecting ducts of the medulla renal stones. characteristic radial pattern ("bouquet of flowers").000 incidence prenatal diagnosis by enlarged kidneys perinatal death from respiratory failure patients who survive perinatal period develop CHF.

ICP: 0..zo.f e. cinliDtic ascites.3[1.induced (ITIIX 600 mlfd) until dsii!ld rtllipon118 lrfpocalcemi11.. hypemllciLI'ia (with i1llne furmation) lrfponatremia).d H0 exallion 1 llract lfTN: lllllllll12&-100 PO 00 cnesartan 8-32 PO oo irt:Jesartan 150-300 PO OD wlsarbln DO telni$8111n 2HO PO OD 400-800 PO DD 26-40 mg PO OD Hyperkalemia CIU!ion .. olmasartan [0.irilibits reabsorption DfWIIIrand 1' adam!lllus stale$ 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. hyponatnmia.. 1' fnle Wltar claarance in SIAIJIJ.. lrfpok*ni11.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.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 .400 mlfday Oil/bid amilorida: &-10 DO Hypok*nia I11C1181ed serum lillie levels PracipitDs gooty idtacks.bataslnsipidus RII!Wcas K caused by other loss fllamB/hyparvDIInia HCTZ: ede11111.20-80 rngld PO 00/hid nrtaction) Pracipitmas ldtacks . 1:1" Tliazide Diurllica hydrochloruthiazida (HCTZ) chlaruthillzide (Dilliltj (Lozule..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.2. adrenal inhiMor at1he qiotnin lfTN cortax. BP (less affiCtiv8 due tD Valuma deplltion with matabolic abiosis lfTN ..5-20 PO DD/Did c. Drugs In Nephrology Clauificllian I.Table 14.tcardisiiJ eprusartan (TMten. enlllapril lisinoprii(Prinivir') tnmdolapril [MII'ik.q. Astllna Hyperkalamia A!pnulocyiDsis (captapril) Acute kidney injny us1... Lozideltj matDiaz!llla (Zir=lyn.10[1. 1' H Ca uaation) 1st lila fur eaantillllfTN Treatment Df edema Idiopathic hypert:alciuriaand stonea [ia. f . ada11111. cystic fibrosis (amiIoride vilco&ity of secretions) Combina ACE-irilibitar fDr syrJIIII. chlorthalidona (fWvton8) spi!IIRolllctona(AidiC!Dne•] triamtlnlna([)yrlnium•) amiloride (MUnorS) Disbll convolutlld tuoole In Nt/CIIIInsportar (K lost.I'IIIil:l ltiC8TDI UAII Ran II tubules (proximal n duct) To ".-runaciiJ aliskimn (llasitaze] Vascular smoolh mllll:kl.intnacrenial or jllii'IOcQjillr prassu111 NOIHillbsorilabla solutn incriiiSil osmDtic prassUrl Df filtratl MobilizllliDnDIIIKCISSfllid . . fu1111amida: Allarw in sLMB-1111siiMI individuals naplrrutic synd111ma. oJ. 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 CHF.IICitea [iipironra:tuna).. 1' Hsacretion. ARB IOII8rtln (Comare) candasartan (AtiCind<tj irbesrrtan [Avap111.60 min Transiant110luma axpansion Elactrolytl abnormlllitias [ i Na. lllnemidl (Dernadat') Nl!ii(I2CI1Tinsport ± renal and VIISDdilltary lllhlc1s (Kloss. 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 ..1D PO OD mg tnnlolapril: HTN-1-4 OD t ..../1' IQ i 8 ACB rurnipril [Allee.5-25 PO DO (m11X 50 rngld) 2&-200 mlfday Oil/bid dosing lfTN: 50-200 mlfday Oil/bid doling Hyparaldosteronism.. caplopril (CapDtanltj Tissuas dillull81r Pr-m 11mipril: HTN.25-100 00 lfTN -12.25-2 w\IIIV. valsarttll(Diovan") !Wnisartan (ro. 1' Casxmdion) lA ad111111 secandllry tD CHF.Diii:O.ao IVJIM/PD q&-Sh Elactrolytl abniiiTTIIIIitia.

345:851-&D NEJM 2001. 361:1627-38 ROAD JASN2001. 354:359-64 NEJM2001. 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. without the nagativa Blfacts on renal function commonly reported for standard CNI regimens BENEDICT NEJM2004. MMF. BP. renal or cardiovascular events. 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. 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.plant patients low dosetacrolimus is superior to cyclosporina and sirolifllls in reduction of acute rejection. steroids and low-dose tacrolifllls effectively maintail stable renal function following renal transplantation. 257:2562-75 HEMO NEJM2002. 18:1889-1898 SYMPHONY NEJMZ001. 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.6SIRAL NEJM2009. 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. rnainll!nance of ranallunction. 357:2562-75 . 347:2010-19 IDNT IRMA ONTARGET REIN RENAAL RENAL NEJM2001.Toronto Notes 2011 Landmark Nephrology Triala Nephrology NP39 Landmark Nephrology Trials Trill ACEI and Diabetic Rlftnlce NEJM 1993. 372:547-33 iimctJt 1999. 351:1952-61 ELITE NEJM 2007. 351:1941-1951 . 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. 345:870-8 lMicet 2008. 361:1953-62 DETAIL NEJMZ004. 345:861-9 NEJM2009.

Clinicall'rlctice Guidalinll fol tha Managamant of Dilllllll in Canida. Ftahally J. Kinsey. lalla S. Gold ate in MB.(2Wll.(2003I. Saundlr Publisq Philllllllphia. lrd ad. Andi'D!Iue HJ.. KatsayR. http. Mllias NM. (1 9931. Primer on Kidney liseues. Llwis EJ. Vol. HarcourtBlaca & Co. St. Mechllilms of Disease: Alport's Synd!ame. NEJM.1niliBiion DfDi. Klrllerv B. HypoMtremia. Artlv. American Familyl'hysicillls. Madici111141h ld. (2ll081 T*isnn. NEJM. GDidatain MB. Jindal KK.html. CMAJ. Vol352: 13HO. 1-21). Mallllgamant of ill thraatarirQ acid-bela disordara pill II. 131S. Vol. 1547-59. Andreoli TE at Cecil Essentials of Medicine. Houldan R. 33[51: 1004-1010.hmt DJ. Vol&. Val 338(21: 107-11. or bath in patients 111igh risk lomsculu IMII1li. Trwii\Uon K. 2nd ad. Lau J. A J mar Killis. WM. 100001 clinicallfiCiice Quidelnes lor clllanic disease: evalurlion. LippincllttWillau.NP40 Nephrology References Toronto Notes 2011 References Adler SG.13Z8. Grerierg. Rll\'iiW ai!IQQ !IRIII fliU.diabltll.1D. GrandeJP. 6111 ad.1'atJssirm. 3rd ed. (1 999]. Schiftl H. rist USIISII!IInt. 348: 2543-2556. Schreiber M.ring CormiUII for thllilvision Dfthl Ham ph ill RR at II. Napllapalhy: Canadi1n Dilllllll Allocillian clinical prlctica tuidalinll axpart commit!IL Mtp//lw. Hunsicbl LG. NEJM. Fluid.w. 347:738-748. Fischer R. 1987. 358. Effac:tJ of IDArlln anlilnll Crial'lscul• in l'ltiants with Type 21ilbatas111d Nephropathy. (19991 CiMca1 pnctic8 tuillllilas lor initiatian al dialysis. New Ywk: Cland1ill. CllajQr 4. Blli. Mcfarllna P. Levin A. The Lancet.Limus M (1995]. Slbltina M.ina: Tba Ganaralllolpital Handbook of hlamal Madicina. (1999].ivingstone. Canadian Society of Nephrabgy. Rohda Tha Elllcts of AngiJtlnsii-Corrnrting Enl'l"la . Mosby: Naw Yort. 2l111111n 8.Iilllcka PG.{2001l. elimination (I'ARA!lE): 1 pOiition pepar altha Nltio1llll Kidney Famdltion. Vol. Goodpaslire's Syndrome. Pucket Melil. dBIIctian. ud ather rrartn.l'llscual M. Jerwll J. Hns SB. alilllrruril.Lang SM. l!llin RP. Churchill DN.: New Yort. Vol. Aullllomal domin1nt di. clmification.. Hakim R. Andi'D!Iua HJ. 2001. 345(121. alactmlyla. 10 S231H1. Bain SC. 338 !11: 2&-33.and scid·blsa pllysiDiogy: I problam.JIIsad IPJIRIICh. da Zaluw D. Johnson RJ.fnzyme Wilition in Type 2Diabe11s and Naplnap11hy. & Wlins. Nei111111 EG. Thldhani R.(2ll031. 2ll02. Kimel K.IIau1iir P. Protairama. Mitch WE. Mllias NE. llll (198111. Hudson BG. ud stRtlication: 2ll00 wcutive updale. Renal Diseese: AConcl!plual ApJiroach._ JAm Soc NlplrGI. dDGVtdo!lilloc. Sat al. Hams S.llonwntra. Vol. llcnoyln.tigi!Dn.lfwww. (1998]. 861-861. Gnllled E. NEJM. .(2ll041.libition on liabatic NIJRapethy. A.w.. Ma1111gement of ife threlterirG acid-base disorders pill I. G. NEJM. NEJM.Jil (1 9961. prulli11ria. Halperin M. ONTARGET m.h J.. Kaine WF. et II. TDII*lira EB. Vol. Vol. Mlliu NM.(19981.(2ll031. L8vey AS. Cor. Smith. Vol. An au1tn8 aiSAIIItiiiiDpiCi in gtlmarullr 111d lr8llrrrmt for naphrology1Rina&L Amaril:ln Jaulllli of Killll'f lise-.(2ll02). Samnara lor 3 clinical clsrkllan medicine: hyponatremia and hypamatramia.http. DanadioJII. 1lndl All. Hliperin Ml. San llego: Academic Pless. kuteranal fliU. NIW 1hl m111111g1m11nt of diab111s: aphysicilll's tuida. 329(51:332-342. Dclallar 29. CiMca1 pmcb clnrie di&eue in adults: Pill l Gbmarul• fittmion rata.NEJM. Madsllld S.l/lw. Andi'D!JU8 HJ.embblfcl)lllicr/Jflrf. Medi:al J1119111: lgAnephropathy. Myn.. NEJM. John lUll CA. MIIIIDr SJ. lAd Type NCollagen. Caopar ME. NEJM. Vol. S. 351(1t.1952-61. Vol 342(201: 1483-1499. 334(221:1448·1460. 1581-1589. Vol. SundUimoorthy M. (19991.lds Comprallnivl clinical naphrology. 346{5t3DS. AJ9o1nin-lleceplor Blockllde VIISU5 Converting. Gabow PA. Daily Hamodialysis and 1hl Outcome of Aaa Renal FaiU. JAm SGc Nephrol. NEJM. Bramar BM.(2ll021.(2ll041. (19!181.htm Kalina WF. Baltimora: Wililma & 21)01. Val 42: 3!5-418.ct/ Mallzar. Vol.

..... .... ....•••• 49 Common Medications .• 23 Relative Afferent Pupillary Defect (RAPD) Horner's Syndrome Anisocoria Movement Disorders ......... . . ... ... 36 Galt Disturbances .. ....... ..... .. ...... 34 Clinical Approach Polymyositis/Dermatomyositis Myotonic Dystrophy Duchenne and Becker Muscular Dystrophy Cerebellar Disorders .. .....• 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 . ... ... ............ . ... ... ... .... 36 Pain Syndromes .. 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 . . ......... 44 Spinal Cord Syndromes . 42 Overview of Sleep Disturbances of Alertness and Sleep CNS Infections ... 44 Stroke ........ ...... ..... ......... ........................ ....... .... . ..... 22 Disorders of Lateral Gaze Internuclear Ophthalmoplegia (I NO) Diplopia Nystagmus Abnormalities of Pupils •••.. .... ............... .. .. chapter editors Doreen Ezeife and Nigel Tan... .. . ....... associate editors Steven Wong... staff editor The Neurological Exam ... .. ...••••••.... ... 52 Neurology Nl ..... ... . .•••••••••••.. 32 Paraneoplastic Syndrome Tumours of the Nervous System Neuromuscular Junction Diseases .... .... ........ 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) ••••••....... ...... 52 References ... 17 NEURO-OPHTHALMOLOGY Abnormalities of Vision ••••... .. David Chan.. ...... ....... 39 Clinical Approach to Headaches Migraine Headaches Episodic Tension-Type Headache Chronic Tension-Type Headache Cluster Headache Sleep Disorders . ... .. .... ... .. .. ... .. 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 ..... ... Tara Rutin and Courtney Scott. .. ........... .. . .................... ...... .... 32 Clinical Approach Myasthenia Gravis (MG) Lambert-Eaton Myasthenic Syndrome (LEMS) Myopathies.. 21 Abnormalities of Eye Movements ...... ... ... .. .•••••••••••. .. .. . .... 8 Seizure Status Epilepticus Behavioural Neurology ....... 29 Amyotrophic Lateral Sclerosis (ALS) Other Motor Neuron Diseases Toronto Notes 2011 Peripheral Neuropathies ...... ... 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. .... ... ....... .......... ................. .......... 35 Wernicke-Korsakoff Syndrome Cerebellar Ataxias Vertigo . .... 4 Lumbar Puncture ... 51 Landmark Neurology Trials. 7 Seizure Disorders and Epilepsy ................ ..........N Neurology Mina Atia... 30 Neuro-oncology . .. ...... ..... . .... . .. ... .. 2 General Exam and Mental Status Cranial Nerves Exam Motor Exam Sensory Exam Coordination Exam and Gait Basic Anatomy Review .... ..

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


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

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

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

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

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

etc. NPH. nutritional deficiencies. abstraction.glucose.General Measures • • • • • • • see Psychiatr:y. 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. copper. 10-20% vascular dementia • <5% reversible: hypothyroid. 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. antipsychotics. heavy metals. ANCA.) • affects content. TSH. subdural hematoma • must rule out delirium History • geriatric giants • incontinence/falls/polypharmacy • memory and safety (wandering. neoplastic. 1'/. orientation. compliance. medications (sedative hypnotics. Wilson's Disease. ceruloplasmin. PSIS well-lit room hearing aids and glasses orienting stimuli (clocks. memory. accessibility • history of vascular disease. herbal remedies.. thyroid dysfunction. antipsychotics Dementia • see Psychiatry.VDRL. leaving doors unlocked. glucose. anti-dsDNA. SOB • Ftltigue • wills • advanced directives (DNR) . brain tumour. ANA. anticholinergics). renal function. lipids. toxicology. renal • alcohol. endocrine.e. generalized and (usually) progressive impairment of cognitive function (i.J. beta-blockers. word lists. HIY. hepatic or renal failure. LFTs. cortisol. smoking • OTCs. serum calcium • CThead • MRI as indicated • as clinically indicated. pallor. leaving stove on.Toronto Notes 2011 Behavioural Neurology Neurology Nil Management of Acute Confusion . 1'/-. depression (pseudodementia). normal pressure hydrocephalus (NPH). similarities.l. anticholinergics). calendars) avoid restraints or catheters stop all unnecessary medications treat underlying cause. losing objects) • behavioural (mood. suicidal ideation. B12 deficiency.. cortisol. anxiety. PSIS Definition • an acquired. language. but not level of consciousness Epidemiology • 15% ofthose >65 years of age have dementia • common etiologies: 60-SO% Alzheimer's Disease (AD). 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. proverb) • + Baycrest Neurocognitive Assessment Investigations • depends on suspected etiologies (see Tables 9 and 10) • CBC (note MCV for evidence of alcohol use). anorexia. antidepressants. psychosis. recall. B12o RBC folate • electrolytes. personality changes. aggression) • ADLs and IADLs • cardiovascular.

Apraxia .impaired ability to carry out motor activities despite intact motor function c. CJDJ VQCUIIIr dumunlia) Endocrine (hypathyruid) Space occupying lesion (chronic Huntington's disease Multi-infarct d11111Bntia Molecular testing MRI. PSIS Definition • progressive cognitive decline interfering with social and occupational functioning characterized by the following 1. nausea Localizing neum Chronic Chronic abscess HIV Creutzfelt. 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 . Disturbance in executive function . Agnosia . &Ubdural hematoma SlE Mass effect/edema.impaired ability to learn new information 2. agnosia Hallucinations Parkinsonism Fluctuating Disinhibition. headache. one of the following cognitive disturbance a. thiamine) lntnlcranilll tumour TIBUITIII Memory impairment Aphasia. apraxia. 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. ANCA.SPECT hematoma) Toxic (alcohol) eNS vasculitis ANA. SPECT CT or MRI. Pick's disease) MRI. papilledema Localizing naum signs See Rheumatoloov. RF MRI AngiJgraphy Teble 10. anli-dsllNA CT contrast MRI Ani). 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. RH9 lncreaed ICP Localizing neum signs Systemic S&S of cancer LP. Acquired Causes of Dementia Etiology Key Clinical Features Fever. d11111Bntia (e.Jacob disease Syphilis FIMII". abstracting Pathophysiology • genetic factors • a minority (<7%) ofAD cases are familial.failure to recognize or identify objects despite intact sensory function d.MRI CT contrast lnvestiptialll Infectious Chronic meningitis LP + investigetions HIV serology EEG LP WRL CT (non-contrast) Traumatic: Diffuse axonal shear.SPECT Huntington's. HIV) Nonnll pressure hydrocephalus Duganendive (Aizhuirne(s. sequencing. seillft Paraneoplastic MRI. Aphasia -language disturbance b. folatll. epidural hematoma. myoclonus Trauma llx Increased ICP. myoclonus Ataxia.N12 Neurolo8Y Behavioural Neurolo8Y Toronto Notes 2011 Teble 9.Hu antibodies Neaplutic Alzheimer's Disease (AD) • see P&ycbiatcy. ANA. anterograde amnesia . SPECT (hulld injury) Anoxia Metabolic (diabetes) fnflclion (pollti11C8p/llllitis. headache Increased ICP Localizing nauro signs See Dil!!§!ll. m:ganizing. hemorrhage.g.planning. 1029 Rapidly progressive.

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 . galantamine (Reminyl•) • relative contraindications: bradycardia. abstract reasoning. widening of cortical sulci SPECT: hypometabolism in temporal and parietal lobes Treatment • acetylcholinesterase inhibitors have been shown to improve cognitive function • donepezil rivastigmine (Exelon•). parietal. CAD. 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. 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. 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 . 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. asthma. CHF.although efficacy not proven • ginkgo biloba • Vit E (caution: >400 IU/day associated with excess mortality. arrhythmia. ulcers. COPD. especially frontal.Toronto Notes 2011 Behavioural Neurology Neurology N13 • pathology (although not necessarily specific for AD) • gross pathology • diffuse cortical atrophy.

uctuation in cognition with progressive decline • visual hallucinations • parkinsonism • repeated falls • sensitivity to neuroleptic medications (develop rigidity. extrapyramidal symptoms) • REM sleep disorder Treatment • acetylcholinesterase inhibitors (e.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. peak incidence between 50-70 years old . palmomental. glabellar) • parkinsonism Investigations • MRI/SPECT . grasp.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. astrocytosis and neuronal loss Epidemiology • rare (1 in a million). pout. neuroleptic malignant syndrome. 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.g.

namlng 4. 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. repetition 3. progresses over years Histopathology • sponglform changes.Y.Toronto Nota 2011 Neurology NlS Clinical Presentation • sparadk CJD: rapidly progressive demenling illness causing death within months. toothbrush. comprehension.. Thae aln:lrmally fDided prgtein•IIVIII'8glllll compleus on EEG (Le. MRI • only wsr. more psychiatric symptoms.. The inflctio1111orm iJ aln:nmally fDided and leads tD abnormal fDidina af no11111l prian pra1Ji111. Th&laft: han. writing. associated with myoclonus • cerebellar ataxia • cxtrapyramidsl signs • aldnelk mutism and cortical bUndness sometimes occur •fatalwlthinlyear • EEG: triphasic compleus Diagnosis • rule out treatable dementia. neologism& W.y to confirm diagnosis is brain biopsy/autopsy 1\fpes • sparadk CJD: most common form (8596).. EEG. neurologic exam.ntftw • an acquired disturbance of language characterized by errom in speech production. 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.e's area (posterior superior temporal. loss • occur sporadically Treatment • no known treatment Normal Pressure Hydrocephalus • see NeuJ'OS11IFI'. spontaneous speech •fluency • paraphasia&: semantic ("cbm for "tablej. . comprehension (auditory and reading) 5. writing 6. InJections (human growth hormone products). Broca's and Wemlcb's Ar. . • panencephalopathic form: primarily seen in Japan. Mad Cow disease) • kuru: historically due to cannabalism in Papua New Guinea laadilll tD nUGnll loa. Longer duration.micb's area: poetllrior apect af 1" tampan! IJYIUII Figure 12. electrodes • variant: earlier onset. or phonemic ('"clable" for "table") 2.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. astrocytosls and neuronal. sdsllors) • education level • native language • learning difficulties • assessment for aphasia 1. Prion prollins have 11 normll fonn and 111 irnc:lioua form.. drawing. ab&ence of triphasic . 1596 have right hemisphere representation. and 15% have bilateral representation Assessment of Language • asseaament ofcontext • handedness (writing. NS7 NPH Prog-bl llf Cl-11: Triad AID A11DciWA!nxil af Damantia h:DIIIilmce Aphasia Definition ----------------------------------------------- \•... ia domir-. . 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.

nuent No.. 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.. post-MI. Agnosia Definition • disorder in the recognition of the significance of sensory stimuli in the presence of intact sensation and naming . Apraxia Tests Hemi1pheres Lalt Right and left Right and left Right !Ill merely tile illlbiily Ia canstruct. \1\otita matter lesions deep to (1) Combined sensory and motor tllnscortical Posterior infaior frontal lobe AND posterior superior temporal lobe MixadTCA• No. CO poilonif'G. but may continue for >1 year • with recovery. 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. Fronlllllobe watershed between MCA and ACA territories 2.nuent MaturTCA• 1..ryoutthe lelmed . combing one's hair Preparilg and mailing an envalope Copying afigure Dressing specilil:llyla the inllbily Ia c.ftuent No. 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. •dresl.. Approach to Aphasias Fluency lllpalitian Good Good Poor Good Naning POor POor Llsian l. Table 11...ftuent Fluent Fluent Fluent Poor Poor Poor Good Poor Good Poor Poor Poor Good Poor Global Wernicke"• Canduc:tion Scn. cRw. impaired comprehension.g.Nl6 Neurolo8Y Behavioural Neurolo8Y Toronto Notes 2011 -t•. hypabrllliln) Prognosis • most recovery from stroke-related aphasia occurs in first three months. . ataxia. sensory loss.u Apbasilllocalizes 111e lesion to the dominant cerabral bemllpbare.-nts iMJiwd in conslnrjjon...aryTCA• Relatively Spared POor Relatively Spared Poor Posterior superior len1Jmllobe Arcuate fasciculus 1. or inattention Clin icopathologic:al Correlations Table 12.. drMing. Subcortical temporopilistal 2.oclizllian I'Dsterior irmor frontal lobe Broca"• No. • M11yskilll uida from plllliln naedad to canyiMthesaiiSb.

.. chronl. Parkinson's diaease ''..cting canlnl of CIIUIII pupilllry ..lci!Macle • ptosis. msta....l pen:eptian and inllct auditory IIICO(Jitian tampa10-accipitll ragian Anlaillr pll'ietal llbe in 1he llmsphere app01ita tha lffactad hind CabJr . atherosclerosis): pupil sparing ["\. 1\f. V1 and V2 as Wflllas pain and proptosis. considrr rnailglring.eeions iRVGivilg tha C'8V8111DU8 liar1 111M pallliea of Ill. SO 0 Shiny H. Ill.tions Tillie 13. '. albinism. L.'IbroDlo Nota 2011 Bebaivoaral. Jlii/fi----111 :mwr-----IV • . Pariml '-ii!M Lssians of1he dominant Pllrietalloba n chnctlrizBd by Gamnlll!"a Syndro1111: acak:ulia... and hypoganiiiiDinlpil: hypogan. pupil dilated (mydriasis) Figun 13. chronic meningeal inflammation.dh Neurology Nl7 Clinicopethologic:•l Correl. sinusltis • olfadory neuroepithelial: destruction of receptors or their axon filaments • intluenza. ' . aneuryam.nd abducted). l.nd out'" (depressed s.... Fi•gar Aplasia lnaiJiily to idediy objects by touch lnaiJiily to racagniza.. IBid 1o i 0 Figun 14. 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. meningioma.. 11111111.. If 1111111mill il nlll: UlociiiiBd wi1h loa af \. .c . . slnua thrombosis) ischemia ofCNIII (DM... .. and cartical 1111n111ry lOIS.D81Jt1naaia. resting eye position is •down s. Canrnaus SEa . meningioma.tary r----lnt. atrophic rhinitis (leprosy) • c:entral: lesion of olfactory pathway • Kallman syndrome. herpes simplex.®/' 10 \ JR Mit ii' •LR . Lai Zllll& CN Ill: Oculomotor Nerve Clinic:al Features E. temporal arteritis. and lsft-right llsarianbdiDR. SAH. N20 SR LJt IR . ...rbinitts.. 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...•.lllmanrflsyndrorne ila conganitll dilordrr of . HTN.ilm. CN II: Optic Nerve • see Neuro-Ophthalmology... cranial surgery. ..eliOM of1ha pwillll IDIIe are clwBI:IIrized by 11111111et. m.. intm"eron treatment of hepatitis C virus.•.r agnDBia. . '. lf.. __ _ _ 1/1 C31llid . Pup•ry cOMiril:blrfibiVII&re on lha par1ohalllllllpiCI: af CNIII au cornprlllion of the neml.. 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 .• to mydriQia while infan:lion (mr.. Nearology/Craaial Nerve Defi. lnaiJiily to pan:aive cHI' Alllnlt_. head injury. 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. agraphia.nlll ·*"""---v.

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

u..ius i1 the meciiAI. IIIIBDrrrj!llilil.MG) Myapathv (a.. Demyelination DlgenaretiCII '-Ynx Ha1111 Lawpilched llld the weal conls clo11..Df the tralrtulsolm. Ftlcill n. llliDn (Balra 1118krl Cranial Nerve Defidb B. indistinct speech Plrlicul.ill CIIIIOIIIID pnub:sd by lips Mo1Dr ne1... in prtlxi'nily to the l'llpillloly l:lllntnl. demy11inlltion.. IYrinaotutil. tt. or "wtlness" Df vaice. X.i n g rillk fill' IIPildian. miiBibllll.llll8g.11.1111 (e. triggered by swallowing • taste dysfunction in posterior 113 oftongue • absent gag re:flex (dysphagia) wt.. meningitis lniaiiMI: strDU. Treatment • carbamazepine or surgical ablation of CN IX D.g. NDITIIII is inilillhld when lh• IDIIfJI 1h1'8W1a bolus blt:lt Slured.rynx radlating to ear. CN IX: Glossopharyngeal Nerve Clinical Features • sharp paroxy8l1l8l pain of posterior pha._CniUI llarw dafi5b (CN IX.g.nd IDDting for coughing.s1111ss Canballllr disease Canballar outflow tnlct diSIIIII Connection& il the nucl.. and X and mo1or action via CN v. poliomyelilit. SWIIowing diiPBnda on liferent inlarmllion vii CN V. S.. tumour11 Talala 14. I'IIIUrD!Inmll. .y by CN XII.• ri. tha p181811CB rJ I gllg raftM ia illlll'icillnt llltlur. Cllluilbtion af Dyar1fuill Qusili:alial ----t•.'IbroDlo Nota 2011 A.S) f'a1Dnl niiVI (a. DMfMI into the pa..ralllla.. X. c:up a. rhythm lmprap.. ... Tha bolus slimuiiiiBs tha 10ft palal8 to slsva18 llld the bolu• is dlllldlld into 1ha Of1IPiwynx. llllroeytuma Nadc trau11111. GBSI NIUUIII&CUIIr junction (8. tha Slow 111d manu!GKius Slllliled or Straka TIDID.JO.l • the swallcrwi'lg centra.difticully Mill villltory "R" Dilliculty consiiiBlt& purilcad by tlllgus a1d l_..c1: the phlryngalll conslric1Dn cunnct..IICI'IIIIi!g for th8 Prlll8nce D1 and .g. and XII. IX. Swallowing 111d n coordinllecl1o prevent IIIJinllion.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. UMN VL llt'IN fllcill N8M1 Palsy CN VIII: Vestibulocochlear Nerve rt•.lsbil8ldlwlly-tongue mowm111111ra innarwbld udllli. choking.urgary.U•claar llliDn Neurology Nl9 Figure 15. the cornet tilt il1o DIIIIMI tha plltillll Ginldng WIQr !rum a. VIL IX. Al.

N20 Neurolo8Y Cranial Nerve Defu:its/Neuro-Ophthalmolo8f Toronto Notes 2011 Table 14. N 49 . . central retinal artery or vein occlusion. vitreous hemorrhage. OP24 . non-arteritic). Multiple Sclerosis. optic tract/chiasm lesion. GBS -Guillain-Bami l'..amyrAJopliic lltllllscllrolis. PM-polymyositis CN XI: Accessory Nerve Clinical Features • ipsilateral shoulder drop.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.g. Anterior Ischemic Optic Neuropathy • • • • --------------- If you ill'll8Cl the diagnolis of qiant cen arteritis do not wait for biopsy rasLJts. IJ. aneurysm) • vascular: TWamaurosis fugax.. compression by space occupying lesion (e.'lllroma. improper stn!ss Dystonia muscuiCIUm deformans Other hyperkinetic extrapynrnidal disarders (see MavemenrDisonfets) • Bursting quality Dystonic • Slow speaking rate • Prolonged individual phonemes "Abbmiatians: ALS. retinal detachment • optic nerve: optic neuritis. carotid-cavernous sinus fistula • CNS: stroke. Classification of Dysarthria (continued) Extrapyramidal Hypokinetic Low. RH17) Amaurosis Fugax • see Qphthalmology.l-dlnni!Dmyasitis. 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. Beqin treatment immediatelyl see also Optic Disc Edema. N21. MG -llftllllhril gmis. 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. N44 Central Retinal Vein Occlusion (CRVO) • see Qphthalmology. OP37 and Stroke section. migraine • infectioD}inflammation: endophthalmitis Optic Neuritis • see optic Disc Edema. anterior ischemic optic neuropathy (arteritic....

glaucoma. :t laser Optic Disc Atrophy • etlologln. .l8duce mrnids I arteritic lOP.'IbroDlo Nota 2011 Neuro-Opbl:halmoloBf Neurology N21 Optic Disc Edema Tillie 15.81iaas Alal!g the Viull Plthvny . Swollen diac. AION. retiMI hemanhages hlllllllhllge Ghlll cell arteritis Associated with vascUopathy Etlalaal• Tralnlam MS. .g. optimim risk factors. peripheral vision defect. 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. .. V8IIDUJ relilal Ct. vial IV(ratcnl) lnCI1!BSI!d ICP one Tf8Bimusa Calsidar ASA I non. flml 11191f98111R.J.I fii!IM RAPD !liC if llllerior RAPD No RAI'Il Pale llll!rnenllll diiC ad111111. optic neuritis.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. decreaeed colour vision • treatment: none (irreversible). Cherlll:telistic Vis•l Field Dlfecbi with 1. Leber's hereditary optic neuropathy. foil( hx:al neurologicll deficits NoRAPD DiiC retiwl hemanllage. the more porterior the lesion • check all hemiplegic patients fur ipsilateral homonymous hemianopsia (e. acuity >50 Unillleralecuta field datact M1h . left hemisphere -+right visual field defect) i Q Figun 1&. 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 . low visual acuity. compressive tumour. no VIllOUS jQsatians taldam•. congenital • praartatioa: disc pallor.taritic.J. cokuvision >50 IWIIteral Vllilllle vision lou CardiDvascular risk !aetas Heaclschl!. jaw deucicetion If GCA: headache.

g. 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... cataract. . 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. A lesion in a cerebral hemisphere causes eyes to "look away" from the hemiplegia.trauma • CN VI (abducens) • DM. aneurysm. trauma. Internuclear Ophthalmopliegia 11•. tumour. N17) • CN III (oculomotor) • DM. raised ICP (false localizing sign) • muscle • Graves' ophthalmopathy • neuromuscular junction • myasthenia gravis (MG) (see Myasthenia Gravis. and to look away from the lesion. see Multiple Sclerosis.. fatiguable}. cover each eye in isolation during extremes of gaze. and to look towards the lesion.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. tumour • Wernicke's encephalopathy • Miller-Fischer variant of GBS • leptomeningial disease Vergence {normal} © Shelley Wall 2003 Figure 17. located anterior to the precentral gyrus. N32) •other • orbital trauma.. tumour. 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. If only diplopia on extremes of gaze. Internuclear Ophthalmoplegia (INO) Etiology • MS (most common. A lesion in the brainstem causes the eyes to "look toward" the side of the hemiplegia. 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. The covered eye that makes the outermost image disappear is the one with pathology. functional) Binocular • cranial nerve palsy (see Cranial Nerves. 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. 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 . . Diplopia worse at end of the day suggests myasthenia gravis {e.

.H-----"?'\ Edingar-Was1phll Namll . large retinal detachment.. pathological Abnormalities of Pupils Relative Afferent Pupillary Defect (RAPD) (Marcus-Gunn Pupil) • see also Ol!hthalmolop. jerking. RAPD ..... CGn81riction of lllmulltad f10J8 ® ---- COIIItriction of IDIIimulllllld f10J8 Figu. central retinal artery/vein occlusion... OP33 Definition • a fallure ofdirect pupillary responses to light.. 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. coarse) or as normal vs.Toronto Nota 2011 Neuro-Ophthalmology Neurology N23 Nystagmus • definition: rapid. involuntary. both pupils should constrict initially • when normal side is illuminated... rotatory. 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. Dii'IICt raspons1 CGn18IIIIUII reapo!118 ry.. both pupils paradoxically dilate because the damaged eye perceives less light relative to normal eye • pupil reacts poorly to light. 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. advanced glaucoma PreC8atal nucleus ( 1 1 1 .._.-+-. 18..

paravertebral mass. intracranial tumoUIS. pre-ganglionic vs. ' H-'• Sylllnne •PIDIIil • lliollis • Anhydrasis • a sympathetic defect • clinical features: partial ptosis (drooping eyelid). 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. D E 0 F"IJirl 19.. anhydrosis (lack of sweating). miosis (conrtricted pupil).. which dJlates a normal pupil • central vs.rvical u-I'Giion . carotid artery dissection • 3rd-order neuron (postganglionic): cluster headache. MS. spinal tumcnu. post-ganglionic • paredrine (hydraxyamphetamlne.. and apparent enophthalmos • lesions occur anywhere along the sympathetic pathway on the affected side • 1st-order neuron (central): hypothalamus.N24 Neurology Neuro-Ophtbalm. medulla (brainstem stroke). trauma (lncluding surgical) • clinical confirmation with cocaine test cocaine does not dilate a miotic Homer's pupiL Cocaine blocks the reuptake of nora. cavernous sinus IIlllli8.olOBY 1'oroDio 2011 Horner's Syndrome Definition .dtenaline... syringomyelia • 2nd-order neuron (preganglionic): apical lung cancer (Pancoast's tumour). stimulates noradrenaline release) will not dilate in a case of post-ganglionic lesion. Sympatflatic of Pupilary Dlatian Anisocoria • clefiDltion: unequal size of the pupJls • see Qphtha1moloo OP31 .

vi11UIIl1hreat. promoting movement • the GPi and SNr are the output of the basal ganglia. 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..GABA ----.. bradykinesia and freezingl HvPokilllllia: reduction in movarnent H1111iballism Myoclonus Myukimil Tachykin•i• TICS . most movements sean in movarnent disordersl [i.e.--. Muvamant Disorder Definitions Aladhisia Altlrilil A1hltolis Subjective restlessness relieved by stereotypic movements (e..' Tl'llllllr Soma myoclonus is rtim!Ws sensitive and can be induced by noise.nt IIVPerldnul•: BXCess of movement (i. Bridyldn•iill Charea Dpldnllil Dysblnil Free. light. thereby allowing movement pinprick. or generalized Muscle quivering Acceleration of movements Stereotyped actions due to inner urge. can be suppressed Rhythmic alternating movements . It receives input from the cortex and thalamus to inhibit the globus pallidus pars interns (GPi) and substantia nigra reticularis (SNr).--• Figure 20. 6.g.e. 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. . segmental.. . 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. PATltWAY DIRECT ---.·: Excitatory connections connections ..dng D•llllblngM-. movement. . Neural Connections Df the Basal Ganglia . or Function of the Basal Ganglia • the striatum (caudate and putamen) is the input of the basal ganglia.. aspacially cllrilg walking Unilateral violent flingir¥4 movement Briel muscle group contraction 1hat is either focal.-. squinnilgl Loss of rruscle contraction (negative myodonusl Slow writhing movements..Toronto Notes 2011 Movement Disorders Neurology N25 Movement Disorders Overview of Movement Disorders Tabla .

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

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.. dysarthria.U.'bmdykin81ia Postuml instability . anticholinergics (especially ifprominent tremors). dysarthia and dysphagia • corticobasal degeneration: tauopathy with varied presentations but classically presents with unilateral parkinsonism. pesticides). urinary retention. Conlldw an Alterllldve Dilgnasis If Atypical Parlcirwo. especially hands • rigidity: lead-pipe hypertonus. pallidal. decreased spontaneous speech. sleep disturbances.MPTP (neurotoxin) Pathophysiology • loss of dopaminergic neurons in pars compacta of substantia nigra. environmental toxins (e. pallidotomy. as is postural instability • Lewy Body disease (see Behavioural Neurology. lasts seconds • postural instability: late finding of falls. anxiety ley Puki•onim F•tur•• TW lllJIIIor Rigidity Aki1181ii-. leading to increased activity of the direct pathway and decreased activity of the indirect pathway . MAOI. genetics • famllial (10%): autosomal dominant a-synuclein mutations. "wearing-offu). 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. late finding of dementia • behavioural: personality change. tlliVII histDry • autonomic: later findings of constipation. axial rigidity and akinesia. end-of-dose deterioration (i. dystonia/myoclonus. 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). hypophonia. • mainstay of treatment carbidopa decreases peripheral conversion to dopamine • treatment of early PD: DA agonists. shuffling gait with acceleration and flexed body • cognition: bradyphrenia (slow to think/respond). autosomal recessive Parkin gene or DJ-1 gene mutation Ouvenile onset) • .g. sexual dysfunction Treatment • pharmacologic (levodopa/carbidopa).. depression. early falls. MAOI • adjuncts: DA agonists. accelerated aging. micrographia. Levodopa is a dopamine precursor. shuffling gait with decreased arm swing • freezing: occurs with walking triggered by initiating stride or barriers/destinations. Tremor is an optional feature. COMT inhibitors • surgical: thalamotomy. 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. . subthalamic). amantadine. especially affects the striatum. deep brain stimulation (thalamic. cogwheeling due to superimposed tremor • negative motor • bradykinesia: slow small amplitude movements.e. embryonic dopaminergic stem cell transplantation • levodopa related fluctuation: delayed onset of response (affected by mealtime). Nl3) • progressive supranuclear palsy: tauopathy with limited vertical gaze (classically downgaze). aprosody (monotonous speech). 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.. difficulty initiating movement • related findings: masked facies..Toronto Notes 2011 Movement Disorders Neurology N27 Parkinson's Disease (PD) ----------------------------------- Etiology • sporadic: combination of oxidative stress to dopaminergic neurons.

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.000 • mean age of onset 35-44 years. 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. and parakinesia (pseudopurposeful movement to mask involuntary limb jerking) • progresses to dance-like or ballism. fidgetiness. echolalia (repeat others' phrases). irritability progressing over 15 years to frank dementia. stereotaxic thalamotomy (unilateral dystonia). benzodiazepines. touching • vocal tics • simple: blowing. anhedonia. shrugging of shoulders. and in late stage is replaced by dystonia and rigidity • dementia: progressive memory impairment and loss of intellectual capacity • mood changes: irritability. abdominal tension. antidopaminergics (reserpine. • local medical: botulinum toxin • systemic medical: anticholinergics. grunting.g.N28 Neurolo8Y Epidemiology Movement Disorders Toronto Notes 2011 • North American prevalence 4-8/100. emotions. throwing. depression. neuroleptics). throat clearing • complex: coprolalia (shout obscenities). head jerking • dystonic: bruxism. coughing. relieved by sleep or specific tactile/proprioceptive stimuli ('geste antagoniste: e. stress. psychosis and chorea • chorea: begins as movement of eyebrows and forehead. posteroventral pallidotomy Tic Disorders Clinical Classification • motortics • simple: blinking. impulsive. echopraxia (imitate gestures). grinding teeth. muscle relaxants (Baclofen). but varies with degree of anticipation from 5-70 Signs and Symptoms • typical progression: insidious onset with clumsiness. sustained mouth opening • complex: copropraxia (obscene gestures). palilalia (repeat own phrases) Treatment • dopamine blocker . 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. dopamine for dopa-responsive dystonia • surgical: surgical denervation of affected muscle.

not necessarily concurrently 2. viral.g. OT. fibre-type grouping • rule out cord disease/compression with CT or MR. autoimmune paraneoplastic. rehabilitation (PT. 'rageS: sleep-wake disturbances. complax repllilive disc:tlarges. lhlrp wavas. BiPAP). death due to respiratory failure il'' inconllittlnt with ALS IW FilaSen110ry ax.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. tongue atrophy and fasciculations • pseudobulbar affect or emotional lability • sparing of ocular muscles and of sphincters Investigations • EMG: denervation (3limbs + paraspinal). bowel or bladder incontinence. psychosocial support Prognosis • median survival3 years (longer ifventilatory support). 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). anticholinergics (e. scopolamine patch) • pseudobulbar affect: dextromethorphan/quinidine. Multiple tics a day nearly everyday or intermittently throughout 1 year with no tic-free periods greater than 3 months 3. cognitive mllld& wallkm!H. glutamate toxicity. and corticospinal tract Epidemiology • 5/100. SSRI • non-pharmacologic: ventilatory support (e. tizanidine • sialorrhea: TCA (e. dysphagia.I Management • disease specific: riluzole • muscle stiffness/spasticity: baclofen. Denuvation on EMG Fibrillations. cranial nerve nuclei. Presence of motor and vocal tic at some point during illness. amitriptyline). raimarvation11111pliluda and duration of mlllllr units.000. 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. especially SOD1 mutation).g. hyperactive behaviour.g. TCA. denervation). reinnervation. Not due to effect of a substance or general medical condition Epidemiology • prevalence among adolescents 3-5/100. . Onset prior to 18 years of age 4. SLP). 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. learning disabilities Treatment • clonidine.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. '. clonazepam Prognosis • Begins at 5 years progressively increasing until I 0 years. predomirnnt p11in. fasciculations • muscle biopsy: small angulated fibres (ie. early nutritional support.

llnllting Ntluropllthy GBS.ivt: bulbar pahy): only LMN symptoms with asymmetric weakness. chronic inflammatory demyeli111. RH9 see HIV serology Laprosy serology Nerve biopsy Lyme serology LP (1' protsin. treatable with IVIg . prassura paiiJY predisposition. hypotonia. 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. Diffarential Diagnosis of Symmetric Polyneuropathy• Etiology+ V. diabetes).g. Autonomic: anhydrosis.g. IVIg. 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. . toxins. stocking-glove distribution}. alcohol. severe sensorimotor axonal neuropathy Table 18.. storage disaue. thenar muscle wasting..N30 Neurolo8Y Motor Neuron Diseue/Perlpheral Neuropathies Toronto Notes 2011 Other Motor Neuron Diseases • prograsive muscular atrophy (progras. . aminoglycosides) should not be given to diabetic&. ± anti-GM1 Ab._'. radiation. thoracic outlet syndrome (i. impotence. paraprotBinemia..e. later onset than ALS. leprosy. leprosy. peroneal (due to crossing legs or surgical positioning).ased amplitude on NCS. . pr8SIIn palsy predisposition (herediWy). PAN). asymmetric LMN symptoms....e. paresthesia first 3 digits.r. weakness later • most polyneuropathies are due: to medical conditions like diabetes. 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. Ototoxic drugs (e. Sensory neuropattw of feet pr8Y8nt them from adequately compeiiSiting for lass of vestibular function. gaslroplnsis. especially unilateral) • DDx: idiopathic neuritis. Dlabellc Neara. ureoidosis.dlles 1. tumour infiltration. DDx of M-neuropltllr Mljlipllll Vasculitis (e. Cranial niURipelhy: CNIII (pupil sparing) > IV > VI infarct or compression . 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}. 5-10% of patients in ALS centres • spinal muscular atrophy: pediatric disease with symmetric LMN symptoms • polll:-polio syndrome: residual asymmetric muscle weakness. infarction (i. dipthlria. worse at night • signs: Tinel's sign. B12 deficiency. DDx of o... multifocal motor neuropathy (pun motor). amiodarone. not futal with variable disability. median (at pronator teres)..Iymphoma. substances.... onhcmatic hypotension. renal disease:.e.Cul• . ± radiation to elbow. Saturday night palsy (radial nerve entrapment at spiral groove of humerus). and asathioprine • critical illness polyneuropathy • associated with sepsis and multisystem organ failure.. Mononeuropllthy multiplex: ll8MI 4. cervical rib) • lumbosacral plexopathy (rare. dlll'll'(llinlling neuroplllhin hiiVI dlc11111Sed velocity on NCS. CIDP. or are hereditary • other important etiologies: SLE. paraneoplaslic.1ing polynauropllhy (ClOP). Axonal neuropatllies hiiVI decr.. 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. no 1' cells) LP (1' protein) HIV Leprosy Lyme Immune GBS CIDP Ctronic SAY! .. bowel and blldd1r dysfunction 3. Axonal (most common): pain> mDior 2. HIV._. Lvm. 5-10% of patients in ALS centres • primary lateral sclerosis (progressive pseudobulbar palsy): UMN symptoms. ea. later onset._. obturator (from childbirth).diMUI. ----t•.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. mv. compression • mononeuropatby: single nerve deficit • carpal tunnel syndrome (most common): compression of median nerve at wrist • symptoms: wrist pain. atrophy • multifocal motor neuropathy: conduction block on NCS. idiopathic neuritis. OM. progression of dysesthesia early.

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

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. bifacial weakness. . Myopathies Etiology lnlllmmiiDry Polymyositis Mya[gies Pharyngeal involvement Mya[gias Similar to polymyositi& Characteri&tic r. or vinll Duchenne 1' ITI'fl9obin Biopsy: abnormal dyttrophin Staining Genetic testing Good Cll.. wash hair Becksr Myotonic dystrophy ..... Hereditary Mltlbolic McArdle's Common Mellicalio1111bat Cauu Mpptllhy Steroids... frontal baldness {including women).. '. '. MELAS. calcium panel Toxicology Biopsy: selective loss of thick Myosin filaments ..nt lnfanution to Reganllnf Myapllthilll • Weakness: proximal > distal • Pain: myalgias. bactErial. stand from sit • Anna: n111ch above hlllld.3 • number of repeats correlates with severity of symptoms. serum cortisol. cramping.&les Can be paraneoplastic Ksr lnvatigations 1' CK Biopsy: endomesial Necrosis 1' CK Biopsy: parifasciculll' atrophy .to Alina Proximal wen-s • Legs: climbing slllirl. '. autosomal dominant Epidemiology • most common adult muscular dystrophy • prevalence 3-5/100 000 Signs and Symptoms • appearance: ptosis. and Polymyositis/Dermatomyositis • see RH13 Myotonic Dystrophy Etiology and Pathophysiology • unstable trinucleotide repeat in DMK gene (protein kinase} at 19ql3.. and myoglobumimria Episodic W8ilkness between attacks Parasitic. 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. 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. '. triangular face giving a drooping/dull appearance .N34 Neurolo8Y Myopathiea Toronto Notes 2011 Myopathies Clinical Approach to Muscle Diseases Table 20.. 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..ti.. conmon Proximal > distal myopathy Exercise intolerance Rhabdomyolysis •Abbreviltion5: MBliiF -ITilochoncnl encephlllomyoplllhy slrulie-like episodes rauged llld fibe11.mitochondrial encepllllomyopathy..tion Dermatomyositis lmporu. rnsen... lactic I!Cifbis.

extensor plantar reflex. decreased EOM. ataxia telangiectasia. and increases as target is approached • hypotonia: decreased resistance to passive muscular extension.g. areflexia. retinal degeneration. impaired proprioception and vibration • death in 10-20 years from cardiomyopathy or kyphoscoliotic pulmonary restriction • autosomal dominant: spinocerebellar ataxias (SCA. Arnold-Chiari malformation.g. P46 Cerebellar Disorders Clinico-Anatomic Correlations • vermis: trunk/gait ataxia • cerebellar lobe (i.typically orthogonal to intended movement. uncoordinated. rebound phenomenon. weakness. onset between 8 and 15 years • signs: gait and limb ataxia. atrial arrhythmias) • respiratory: hypoventilation 2° to muscle: weakness • ocular: subcapsular cataracts. 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. lateral): tremor. 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. pronationsupination task) • postural instability: look for truncal ataxia on sitting (titubation =rhythmic rocking of trunk and head). lurching gait • dysmmetria: irregular placement ofvoluntary limb or ocular movement • dysdiadochokinesis: unable to perform rapid alternating movements (e.s) of which 30 exist. Nl9) • ataxia: broad-based. vitamin E deficiency • Friedreich's ataxia: prevalence 2/100 000. look for difficult tandem gait and broad based gait • intention tremor: elicit on finger-to-nose testing. most are CAG repeats .elicit scanning/telegraphic/slurred speech on spontaneous speech (see Dysarthria.e. 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. dysarthria. dysdiadochokinesis. Dandy-Walker cysts) Hereditary Ataxias • autosomal recesaive: includes Friedreich's ataxia. confusion.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. 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.

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

thyroid disease.HN • trauma . baclofen. 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 . 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 . carbamazepine). heat/cold. a2-adrenergic agonists (clonidine.physiotherapy • CAM . massage therapy. long acting opiate. nerve block • surgical therapies: dorsal column neurostimulator.acupuncture. anticonvulsants (gabapentin. spinal cord injury • Complex Regional Pain Syndromes (see N38) •malignancy Treatment • pharmacotherapy: TCA. intrathecal opioid or clonidine. anticonvulsant.diabetes. 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. electric shock. plexopathies • central: MS. SNRI. opiates • adjuvants: antidepressants (TCAs.g. capsaicin cream. post-stroke. renal disease. DBS (thalamus) • other therapies: • neuropsychiatry .cognitive behavioural theraphy. dorsal root.post surgical. SSRis). pricking. pernicious anemia. spinal tractotomy or dorsal root entry lesion • peripheral ablation: nerve blocks. perception of swelling. rheumatoid arthritis • nutritional/toxicity. 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. numbness (Le. nerve injury • nerve root: post-herpetic neuralgia.alcoholism. chemotherapy • infectious . tic douloureux (see Trigeminal Nerve. Nl8). sympatholytics (phenoxybenzamine).Toronto Notes 2011 Pain Syndromes Neurology N37 Medical Pain Control • primary analgesics: OTCs. psychotherapy • rehabilitation . Botox. TCM Tic Douloureux (Trigeminal Neuralgia) • see Trigeminal Nerve. cervical and lumbar radiculopathies. trigeminal. meditation. pregabalin) Surgical Pain Control • direct delivery: implantable morphine pump • central ablation: stereotactic thalamotomy. phantom limb. topical lidocaine.

N38 Neurolo8Y Pain Syndromes Toronto Notes 2011 Signs and Symptoms • types of pain: constant deep ache or burning. longer-acting famciclovir and valaciclovir more effective) may prevent PHN in patients over 50 years • PHN • medical: TCA. dorsal root entry zone lesion Complex Regional Pain Syndromes (CRPS) Definitions • CRPS is a pain syndrome characterized by the following 1.-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. anti-convulsants • surgical: stereotactic thalamic stimulation (may increase sensory deficit) . intermittent spontaneous lancinating/jabbing pain. opiate. shiny skin. cracked/brittle nails • stage III (atrophic) • pain: paroxysmal spread • autonomic: thin. changes in skin blood flow. 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. or hyperalgesia with pain disproportionate to inciting event 3. 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) . allodynia • distribution: thoracic > trigeminal > cervical > lumbar > sacral Treatment • acute herpes zoster • early treatment with antiviral agents (acyclovir. intrathecal methylprednisolone • surgical: spinal tractotomy. allodyrua. thickened fascia with contractures. or abnormal vasomotor activity 4. cool hyperhydrotic skin. lidocaine patch. gabapentin. hair loss. continuing pain. evidence during the course of symptoms of edema. presence of an initiating noxious event 2.

perform a lumbar puncture N. New headaches beginning after age 50.1lh dlronic helldldle 1he plellllence is l...3 {2. {0. meningismus.... 2.11\). months. can be severe <1% Any age No bias Generalized..5 {1.. haurs l..Disllblingint!llsily Table 21. 3. or focal fl-. 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.lllliaal cmc. AccomplfTYing impaired mental sbllus.. . rhinorrhea Eyaid !hop Acute Rx • Oz • Sumatriptan (IIIISII or injection) Prophylaxis • Verapamil • Lithium • Methylsergide • Pnmisolone Six Dl Seria• Halldac.Primary TCIIIioa-Typa Prevalence Migrma .5-3181. Headaches..creased lllraa'anill Pressure <1% Any age No bias Any location Chronic Gradual.Nlu• or-womiling D.. meningismus. deep tendon reflexes and Babinski. worse in PM Band-like. inlhose prasal1ing wi1h new lllldlclw the prMiince is 32'Jo • in 1hose jiiUidiiQ Ylilll t!UIIIarcllp hlllldlchl the prMimct is 43\ {211-611\).lllmblr rlfiiUM pr8I8IE Mdl 3111d feiW U. nnmanic: p- Dnltlil!lllillllwilb ...J Eumilllllign: O. headache with worrisome symptoms (fever.d by 11-.3 {1.. The most of.4-12) 3. fundi (papilledema... h. trauma..g. focal neurologic deficits. heat.. a... nocturnal Constant.4inl1ion of 4-72 UnilideriiiOCIIion cr N . Dnlllil ...Llls .ocatiCII Dul'llion Onset/CGune The prawlence rl ii'Uicllnill pllllology {!111111 problliiitylwrias lnlll011 v. Table ZZ...6·6. pupils (symmetry). c:QI8r-tp haadache Daily headache for weeks. 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. thunderclap headache.... Headaches.Serious Meningllllrrilatilll Incidence Age of Onset SP:Bils Locetion Duration Onset/Coull8 Quilty .2 {1.. pronator drift.urrrrm....0-7.• • Nllll JWA 2006.61 EtOH Noise Hunger Slaap deprivation Pallating Rest No vomiting No photophobia Muscle tension i'1 Non1)harmacological • Psychological counseling • Physical modalities (e. 110 clinical flllfln was found lo hlllllful inlllivJ imcrlrill pethoQ in a 1118111iniiUMYHawM!. altered LOC.._ lnaluda: 1.-obbing Variable. Ill th8le dilllrant popullbs..... morning headache) • if CT is negative but suspicion of SAH or meningitis.11 IQUIMbld lllldlclwv.8 {2.. IIIII Clustar <1% 20-40 70% 15-40 F>M Nona Bilateral frontal MinLIII!s-days lndual. stiff neck Variable Meningitis: oours-days SAH: thunderclap onset Variable S8\111'8 Snfty . . 24 {1.Toronto Notes 2011 Headache Neurology N39 a... ThaiR far dafiW or polllil1i n-i11111inl dill!jlllllii VlrillwM!I U.. aching.4-UI 1.l'J.521 TllpiC1ivltf. retinal hemorrhages).. P(Utling '*" u- a .77-1. 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. gait • indications for a • new-onset headache.61 2. stabbing S8\111'8 (waklls from sleep) Light abnonnlllraJroiDQicll1111111 111ddneli-typl hlldlch1 Duality Severity Pravoldng 10....41 {0. uizul"ls.32-0.2111111 0... The lUdden onset Ill a savm headache. or 3...ns Will luund 1o 1xt ]IIICictive of lignili:lnt petholoQr. papilledema. worse in AM Unlike any previaus headache Severe Te11poral Arteritis <<1% >60 No bias Ten'flOIBI Variable Variable Tt. Pllysicll Signs MIRII!IIdllnt neurolovic deficibi..3-9..for dilgnosing nipile i$ . worst headache of life.8 {11·2. -a indivi!UI c1inicll IIU. ..llil Pllilnt wilb 11Hdde .tiilllldlclw Mil wmiling 3.7 {21-52) 5. 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.ln Ylll niglint-typl lllldlclw the prMiince is Howavll.

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. venous sinus thrombosis Secondary causes of headaches • SAH. NSS Polymyalgia rheumatica Jaw/tongue claucication Visual loss artery change&: • Finn. IH .. psychomotor agitation/retardation . • Larve in1rlcranial vessels • CNV • Dura Pretlisone See also Rheumatology. Epidemiology • 18% females.. 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.g. intracranial hemorrhage. scintillating scotomata spots) • unilateral paresthesiae and numbness or weakness • aphasia • prodrome/postdrome: appetite change. temporal arteritis. migraine.. photophobia/phonophobia/osmophobia 1hB 01111 contracapliva pill il con1rlindicmd with complicat. postdrome • aura • fully reversible symptom of focal cerebral dysfunction lasting <60 minutes • examples: • homonymous visual disturbance (fortification spectra . visual symptoms due to wave through occipital cortex) Signs and Symptoms • stages of uncomplicated migraine i. increased intracranial pressure (space-occupying lesion. meningitis/encephalitis.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 .d migraine due to risk of stroke. tyramines (e. cluster. aggravated by routine phy5ical activity • 1 of the following: nausea/vomiting. '...UCU.. post lumbar puncture. liAs and seizuras). autonomic symptoms. malignllll hypertension (GCA) SAH . sinusitis.g. IIH. moderate-severe (interfers with daily activity). prodrome (hours to days before headache onset) ii aura iii. meningitis. trauma. hormonal changes. red wine). ice pick. 6% males. Etialagy Photophobia Focal deficits (e. herniation (from space-occupying lesion). caffeine withdrawal. exertional Headaches with serious risk to life or function • subarachnoid hemorrhage (SAH)..g. '. pulsating. Headaches . nitrites (e.idiopathic iltrlcnlill hyperllnsiun. GCA.zigzags. incompressible • Tender Stluctur• lnvalftd in Nacicllptian of H. RH17 Meningitis.g. processed meats) • auras are felt to be due to a wave of excitation/depression leading to the symptoms experienced in an aura (e. headache (see Table 21 for description oftypical headache) iv. chocolate..N40 Neurolo8Y Headache Toronto Notes 2011 Table 22. nodular. malignant HTN or pseudotumour cerebri).111blrachnaid hernarrlllge. oftnnsient neurological dsficit8 (e. frequency decreases with age {especially at menopause) Etiology and Pathophysiology . sleep excess/deprivation. SAH Twnour. 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. stroke. temporal arteritis. nitroglycerin). drugs (estrogen.giant cellarllritis Primary Headache disorders • tension-type.g.. altered mood.

ASA.gm.. pilctillctanrollld IItTs of piwn'abgc 1nltment of lade mignrine rl1111de!ati. both of the following (or only one is present): a.ed . SHT antagonists (methylsergide). supraorbital and/or temporal pain lasting 15 to 180 minutes (untreated) 3. Subcutnauslll11llriptln IIIII IIIII 1riptn...... at least two of the following pain characteristics: a. nortriptyline)..basilar-type migraine (occipital headache with diplopia. dutdl of lludy IIIII liming or \ypll rlresc:ue medication. facial sweating. at least 10 previous headache episodes fulfilling criteria 2 through 4.24b NNT r111ged fTom U ellec:ts cauld 1111 be 1111¥md IVSflntilaly. vertigo.l'llc:tice p11111181ar: {1111 evidence t. propranolol... mild-moderate intensity c. Mlin lids. at least 2 of the following pain characteristics a. Evidance-1111811 for m9lina llllllllchl 55:754-63 Chronic Tension-Type Headache ----------------------- Diagnostic Criteria 1. naproxen • moderate to severe migraine treatment • triptans (most effective). 111 intelwrmans wm ellectiw u:ept CftgG!4'.. dll!lbii-IJind.6 far UilripiM IIJl mg. mild or moderate intensity (may inhibit but does not prohibit activities) c. no photophobia or phonophobia Cencl•ian: !Mrl' most lrellllnenl$ were .1111111 llllctivt.Toronto Notes 2011 Headache Neurology N41 Phi!R:IIIGgiell'h. There W8l'll no drug-11Hirug complrilanl.41arnmiptM2.11ar IUI'I1atriplln 6 mg I... headache associated with ipsilateral (to pain): conjunctival injection or lacrimation. 2ilbanml melbtions. both of the following a..! to IIMII i1llnily {21. 91:241-51 lludr.. !'lin 2002. bilateral location d no aggravation from climbing stairs or similar routine physical activity 3..0for lll1lltripiM 6mg s. • 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: . restlessness/agitation 4. For prilllll pain 1111111211. topiramate).. wi111NNTIIII1gi11Qfrom2. bilateral d not aggravated by normal routine 4. The l:iwestlf« for 0111 madi:atian -2..llld IUbcullnlous FGr IIA 11lilf d 211. ttw lilwllt NNT 2. average headache frequency of more than 15 days per month for more than 6 months fulfilling the following criteria 2. For susllined 11!111. ergots (dihydroergotamine.. IJiflilld fllilffor 24 botn. iiDiirG .. photophobia.. no vomiting b. M:omes inc:bled heldac:l!e ...5 mg.llld lflm1l llffildJ will*l24 baurs. Mhlla ID¥Mt NNT for 0111 madi:atian beilg 3.C.Wat 111111 2holn.. TCA (amitryptiline. Tylenol• #3 • migraine prophylaxis: anticonvulsant& (divalproex. ITeedorn frgm plin II 2 tan. llffilctivt. Dllllllhdilll: Nunarrl patients.eto 5. not attributed to another disorder . nonpulsatile (tightening) b. calcium channel blocker (verapamil) Episodic Tension-Type Headache Diagnostic Criteria 1. at least five attacks fulfilling criteria 2 to 4 below 2. Dill Will Millila for I Dill medicDns. severe unilateral. DHE)..hemiplegiclhemisensory migraine .. Nartqy 200). 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. number of days with such headaches: less than 180 days per year 2. ibuprofen. no more than one of the following: nausea.1 far RizlllriptJn 10 mg.. or phonophobia 4.. headache lasting from 30 minutes to 7 days 3. eyelid edema. secondary headache types not suggested or confirmed Cluster Headache Diagnostic Criteria 1. no nausea or vomiting b. Su:a: SlivBrlllin SO at •l... miosis or ptosis. pressing/tightening (nonpulsating) quality b. nasal congestion or rhinorrhea. ataxia.022 pllilla in 1111111.ophthalmoplegic migraine • acephalgic migraine (aka migraine equivalent): aura without headache Management • avoid triggers • mild to moderate migraine treatment • 1st line treatment: NSAIDS . and altered level of consciousness) .

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

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

muscle tenderness and trigger points CNS Infections • see Infectious Diseases. 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. endocrine. Has the patient had a stroke? 2. coughing. especially during non-REM sleep • triggers: sleep deprivation • treatment of sleep disorders decreases seizures. arthritis • mood disorders • alcohol abuse • cerebral degenerative disorders • trauma • dementia: insomnia associated with wandering. hypoglycemia. metabolic. Parkinson's disease. wheezing and SOB can interrupt sleep • GERD • fibromyalgia: associated with pain.N44 Neurolo8Y Sleep Disorden/CNS Infections/Spinal Cord Syndroma/Stroh Toronto Notes 2011 Medical Disorder Affecting Sleep • nocturnal leg cramps: DM. Is the patient a candidate for tPA? • Onset: time when last known to be awake and symptoms free • Mimics to rule out: post-ictal. Classification of Stroke Approach to Stroke • Initial AslleiSDleDt Goals 1. exercise.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. pregnancy. verbalization. systemic infection. tumours. conversion disorder . fatigue. and treatment of epilepsy improves sleep • astluna/COPD: lower airway obstruction. aggression. ID6 Spinal Cord Syndromes • see Neurosu. nonrefreshing sleep.

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

drug HUH.t-----------------. VDRL. DISAH. All rnri1l. anticoagulation. •t-----------------. check glucose. Clllllbia1: Nt. PTT.... focal neural Sx. d!IIHI-illnd.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. acute HTN • chronic HTN stimulates cerebral blood vessels causing adaptive changes like hyalinization and lipidosis to preserve the blood-brain barrier. The classic sits of hypar111nsiva hamorrhagn is 1h1 bual ganglia. cardiac arrest) • when hypotension is less severe.031. ESR.-llfiCH ffTN. benefits of rt-PA were sustained at 12 months na dillebiily. serum glucose.. ACUTE STROKE MANAGEMENT Goals • ensure medical stability • limit or prevent neuronal death linD. likely at the site of Charcot-Bouchard aneurysms • most common sites: putamen.1111'=110.N46 Neurolo8Y Stroke Toronto Notes 2011 ... Mlllndm: Whea IHSieSied It 12 months flumtile lima rJ . left arm daudication. .tiltl Mill iscllenic: slrolce rl reced onset... p=0. .g.. NN. lhelt were more !lllieniJ il the t. 333:1581-7 Study: lllndanilld. urgent CT to rule out hemorrhage and assess infarct • other labs and tests: CBC.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.. 58'JI. thalamus.4% of patients had a symptomatic intracerebral hemorrhage (0. Investigations • • • • • • • bloodwork: CBC. 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.. AVM. cerebellum. corticosteroids for vasogenic edema Global Cerebral Ischemia • etiology: inadequate blood flow to brain to meet metabolic demands (e. •. inthll3. AVM. morll8y or rail rJ 11am111 strolrl 'IEJIJ 1 999. lliBifl v. 1rauma. Practical Guidelines • general • ABC's. INR.. willlll!llignifil:ant difln1ce in 340:1781-71. SBP=1B5. 65\ v. 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. headaches. pabocunbaled lrill(3 month Pllilllt: &24 plli8llls (llllllllag& 76 y.nm carrman in 1111 (p<O. and llllrnlllial: IVt. a.rilli anlll rl Treatment of Stroke A. plliam. lumoUili.OOII. racant Gl or GU lllmorrhage... IIIII IIIIINidlncB rl inlnlmllilll bllllliiiiNga an Cl Excmians inckllld hx rl racant linD or racant 11J'Q81r. coagulopathias. 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). carubllll amyloid angiopathy. or other cause • subarachnoid (SAH): aneurysm.fA P41 Mill milnl or na dillebiily 38%. chronic HTN.. amyloid angiopathy. Theru wu no ll9ifart dillaiiiiC8 in morllily.. hemorrhaoe in cmlnl irfin:ll. . visual disturbances and change in WC due to microinfarctions and petechial hemorrhages • pathology: hemorrhages occur from rupture of damaged blood vessels.ulll: l1wl wn na significlnt cltflnace 1124 hOUII.fA (OJlllAI arpllcabaMhin Mlin outcomll: NuW:Igic dllfili 1124 iiDin INI!SS sc*land functiansl oull:ome 1131111111hs (CIIII'flllilllllllllj. Hemorrhagic Stroke Etiology • intraurebral (ICH): hypertensive. . and pons . or other cause • epidural/subdural hematoma c.. 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. lntm:nblll hiii"IIIIIIIIQI. MCA and PCA 1-I'A in AMI Slniii-IINDS Tlilll NULf 1995.. Hypertensive Stroke Etiology • BP above upper limit of autoregulation of cerebral blood flow (normal is 150-200 mmHg). •t-----------------. man.

Sx of SAIVparicllldiliili/'MI.MCtlt 1997. 111cent ITllljar &llfllllry or tnluma. OTHER MANAGEMENT ISSUES ..tion..-lllaCitBd baplrin. heparin 111 aspiin.ll31.. 110 heparin and aspiril vs.. blalll: FGr ba1ll hepllil vs. .. tidopidine. >85.110 lll'iill. '. Table 23. pregnant. liltJ 8ipirin gnllp I decrelled list of delllll 01 depellllence d 6111rils 1141* 1000 18wir. uizln at &troks annt.S1 lludy: llllndDniled. • avoid hyperglycemia which will increase the infarct size B. then treat accordingly • lower temperature if febrile Primary and Secondary Prevention Carotid Territory Event ----------------- • carotid endarterectomy benefits those with symptomatic severe stenosis (70-99%).. minor Sx.IIOI:IIed ldraclianlllcl hl. or dNth «dlpendlncy 116 manllll.lrin. . NS21 Asymptomatic Carotid Bruit • suggests the presence of atherosclerotic stenosis and signifies increased risk for both cerebral and myocardial infarction • modify risk factors. Canlbin: TheiST IUIIQIIIJ thlt 11piin slaJid be lllftad inrnednly llftaollle onset rl ilch8mic 1Jm1111n 48 hL willl110 ll'idlnCI!i illnmnill llnlb. dopidagrel + ± .. risk of stroke is 2% per year. 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) . .1hrombacytopenia. . recent Gl or urinaty hamonhaga. C11J1111rilh'lith 6munlll . ± antiplatelet therapy • if stenosis >60%. in hlllllllllllgic lllab il t!ae M. 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 . Also aptian of intra-erterial tPA for specific dinical silliBtians Rlllti¥11 contrlindicltion• to tPA Early signs of I111Q8 cnbral inflllrc.PAI for ischemic stroke within 3h of stroke onset Get 24h CT to 1\10 ICH. + + (carotidl '.. dBP >110. . carotid endarterectomy reduces the risk of stroke by 1% per year (but 5% risk of complications) Hypertension • primary prevention '-dllge. NIHSS >22. 111 CGIIIIU!dicdons ID.aggressiveRx to d8CI'88Sa BP.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•) . 1M pllilnls wn lllllomly ID riCIM apirin.. aortic dissection. resistant HlN._.. PMH ICH. Alllollllll Cantraindicltio• to tPA Improving Sx. hemorrhage or mns an CT.m 15000 ar 12... 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. 341:15i.. Similllly. o. Afflr llljlltmeol fw prudielld ]RQIIIIIil. halh. Sinllllrill I.._ 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. see Neurosw:w:y.. lher8 WISIIO 'aniiCIIt diffniCI in d8l1h Ill ZwnQ.. BP llllllt be lowered to sBP < 185 and dBP < 11 0 before IPA is given. hill wn llloCIIBd :m mg daily.500 Rl bidL IIJid hd.. Treatment Condition Antiplatelet Anticoagulation Thrombolytic Endwrectomy ± Carotid Stanalis TIA Cardiac Carotid or + ± + ± ± noncamprauibla silll. high INR or aPTT. aflsll byalimila'-lilld i. uncontroUad serum glucose.th Mthin IMYMb. p=D. sBP >185. Cllllllilllar. Hx AVM or ansury&m. .. + 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. . lnl!rvenlion: Hlll111e patients. hlplrin.111d 110 clair ildicllions lor. . renal failure. Bath aspirin and bupuiHIIaCitBd pllilabi hid raaDII ilchumic lfnlbl \'lithil 14 days. ud dlltll ar deplndiiiC:y It 6manllll. sBP above 220 mmHg. recant LP or arterial punctu11111t + ± + (carotidl StralaHHvalulion Strob • Antiplltelet: o o Cardiac Carotid or vertibmbasilar dipyramole.

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 .IIId lklusa Tnlltlly ill pelilnts llliPICUII5 yaw risk rJ CUftlllllryhelrtdi-e. 1I'IISCie disuse... 75\ l1lllll willl nomtlilg 111111 \'olio were CDIIIidenid 1D be IIIUbPnlillS. as wd II oii•'411W• MID and 01'81111 mor111ty. dilbetJs.af21)02. Hypercholesterolemia • primary prevention • statins reduce the risk of stroke in patients with CAD or at high risk for cardiovascular events.&8.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. TNIImaotwMh llllliprillWdUCid the rill: of IIIW (3A piiRII'IIvs.d kraw t:erebravlscullt diseue.J dDsl rA 40 llrJ lirrwu11tii dUy.. Clldlsla1: 1n lilts atliah rilkfor ClldwasaW mri1ri reU:ed !be risk rA slroke. cardiac!atrial fibrillation. venous thrombosis RRR (MC!J CVmomity Al-c:IUIIII rn!ltlly 100 fC!] S1roka 32\ (1 61u 441 67(431u 1451 ML slnlb.-: RurHn1lllllm8nt 4wll8b rA piiCibo fallowld bv 4-6 Mlb rJ I ro. 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.. 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.llld oO!ers. 380:7-22 S1ully: llltldani1ld. ar Z2\(141D3Ill Z6{191D431 16\ (5tu 251 56 {321u 1SSI evm.1 piii'CIIII.. . clopidogrel) are reserved for those who suffer cerebrovascular symptoms while on ASA • warfarin is generally reserved for specific indications in stroke prevention. Mlil Ou1amll: lnclJded lkuallld vacull Tnlltlly.. 111 trOd hv1ftnllion. pllllllbocanballd trill Mil ...RtiiiF Hurt t.. rill: rJ d81111 frlln CD101111Y MlllciualbecUirA dilllll. dissection. 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..._ . IIIUII: Stroke Rehabilitation • individualized based on severity and nature of impairment. falicJw. . 11ft 0.I1lljorC011111ryMIIIS. llllj01 CDIDI1IIY events. diUIIII-illild. IK rJ pdlllll 1-. Eldlsions ilcludld clmc lwr rA lllnornl lim 111 flllction.. even with normal cholesterol (CARE study) • secondary prevention • more evidence is needed for high-risk patients with symptomatic cerebrovascular disease. 4. . Pl&ra were111eri !lllbnimd 1D lm-tllin 40 II1IVd 01 pllcabo.-.. splints or bracing • vocational rehabilitation . .. 1. 20 538 plllienls aged 40 tl80 ¥1811 (28\ rA 1Q8.llp rA 5Ylll'. 11d slnlb.

[1 juxtacorticallesion]. primary progressive (PPMS) 10%. visual disturbance. cerebellar peduncles. brainstem. 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. intention tremor) • symptoms not commonly found in MS: visual field defects.. [1 infratentoriallesion]. corpus callosum. progressive hemiparesis . 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. or progressive. 30% concordance for monozygotic twins.. secondary progressive (SPMS) • RRMS can become SPMS l! i "" c I . or new T2lesions > 1 month after first attack • Dissemination in Space: clinical evidence of 2 or more lesions. spasticity. Investigations • MRI: demyelinating plaques appear as hyperintense lesions on T2 weighted MRI. . juxta cortical region. increased IgG concetration • evoked potentials (visua1Jauditory/somatosensory): delayed but well-preserved wave forms . or three of [1 gadolinium enhancing or 9 T2lesions]. and necrosis • Acute Disseminated Encephalomyelitis (ADEM): monophasic demyelinating disorder with multifocal neurologic symptoms seen mainly in children often following infection or vaccination Figure 23.. depression. Clinical Patterns of MS Etiology • genetic • polygenetic: the HLA-DR2 gene has been demonstrated to be a genetically susceptible area. in particular an association with EBV has been found Epidemiology • onset 17-35. bladder dysfunction. ::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. new gadolinium enhancing lesion 3 months later. numbness. impaired gait.. apraxia. aphasia. [3 periventricular lesions] Features • symptoms in order of frequency: fatigue. progressive relapsing (PRMS) 5%. weakness. 3F:1M. with active lesions showing enhancement with gadolinium • typical locations: periventricular. and dorslateral spinal cord • Dawson's fingers: periventricular lesions extending superiorly into corpus callosum • CSF: oligoclonal bands in 90%. 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. cognitive disturbance. inflammation.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.. neurologic symptoms due to demyelination and early relative sparing ofaxons Relapsing Remitting Clinical Patterns of MS (Figure 23) • relapsing remitting (RRMS) 85%.. Mort aymptoms in MS n duiiD cont brainsbm and optic nerve lesions.

... methylphenidate • education and coUD8eling: MS society. and ..71l.tvene lfllcts..lllial: Aaltllllt. Avonex•. glatiramer acetate (Copaxone•) and natalizumab (Tysabri•) • CIS: early treatment with Avonex may delay potential second attack • RRMS: DMT reduces rate of relapse by 30%.-lllblliplllc:ln* Codnle Brtllllse Sytt Rer 2008. support groups.g. presenting with optic neuritis.iq c-.. carbamazepine..53 [(5\ Cl 0. low rate of relapse early in disease • PPMS: poor prognosis...limlfllml. 2:Cil005218. RRMS. Methotrexate•) • symptomatic treabnent • spasticity: baclofen.. CS). p<D. gabapentin • fatigue: amantidine. attacks shorter and less severe • SPMS: interferon-beta may slow progression • PPMS: immusuppressant therapy (e.IS. Coclme rjSllmltic !Miw... poor response to therapy 1D lilicdv delnile t. COIM!rtiag 1D liliclly deliile t.tS • pllienls Mil em in • _..«1·0.ftct 1160 pilieals with fiest ridarnywlrm wilh lnin MRI (cliicllly ilolllled syndromes.ian llflbllftl E. D.. dantrolene.. low burden of disease on initial MRI.. higher rates of disability. 11116: Apooled odds 111iD (OR) rl 0.71.llll. modafinil.Wll)forpatilllts an fNV811US It one M'O odds ndiowu 0.N50 Neurolo8Y Multiple Sclerosis (MS) Toronto Notes 2011 . SlUr.. benzodiazepine • bladder dysfunction: oxybutynin • pain: TCA.. D. Tbara 1llllmlntCIIdlliy prog181si011 Treatment • acute treatment: methylprednisolone 500-1000 mg IV daily X 3-7 days ± taper • diseue modifying therapy (DMT): interferon-beta (Betaseron•. plabo.. .52 (95\..a...... RebW).. tizanidine..... young.. . (No IIIJpraprilll glllinrnlr ICitllllrilll W8llllaurJ).. psychosocial issues Prognosis • good prognostic indicators: female.. 2 RtT and qulli.

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

The 1nllmatimal Claaificatian rl Headadle Disoolen. Drganimd Qatiellllstroke 111i1j care lor stroke (Stroke Unnrialis11' Colllbora1ian). Kaaper II. Gri!IIIS RC. w. 359:1317-29 NEJM 2008. Plillldei!Da: Else\lier Sc:iell:e. Lllldlllm-Gr&llll Mlit al. 5th edition. MN. 410-11. et al and 1relllmelll rl dementia: 2. 118(7):825-36. LDrQo DL.. TGIOI11D: McGtaw-Hill pp. 654-656. NOKWOrlllv Jlll!Jcdinetli C.Uiipluclerosis: lllialagy.l/wMY. Harrison's rl internal medil:ine. Chi]J!er 24 Nuak9:11sarders Yamada KA. Slri1h WT. Filippi M... Fu:i AS. and newtrt811Nnt 111111gits. Cecil Essentials ci metile. NEJM 2000. IIIII. TGIOI11D: Mcllllw-llill Campania. IBie 3. MacKnight C.is: Mabsy Inc. Hamilton: BC Declalr. Robilard A. Ferri FF 1200n 1'rlelical !ollie care lithe medical plllient St Ur. http. Carpenter. eds 12005). Willal'sDIII•• Aminal! MJ. pp. pp. Carpenter CCJ. Hamilton: BC Declalr. IMitul E.178151:548-S&. Graenb1111 1:\\ Simon RP. NFJM 2001. CMAJ. 3111 Edition. Gills MF. Parsistant V8ga1ativa State II. Tha Br11in Dallth. llizlnlallld Efilaply Amblti BK.Ids 12005). 171-782. Saundi!S EI18Vill pp 1120-41. Bane L. stroke risk llftar EpiiiPIJ lrMsienl ischlemic lllllck. pp.Reviaw. FeTri FF 12001 1'rlelical to lila c1111 medical plllient St Ur.ai9: Clnical 61h lditian. Enlll'g Med Cfric North Arraica1897. 355:549-59 NEJM 2001. CMAJ. N. 2nd dian. Kappas I. 254-56.. Weilshe!U BG. The Washington Mlnualci Madi:al Tharspllllics. Risk assessment and primary prevention ci Alzhllimardil8u8..ils-cllllificatian.. Jarjodll A. Naurulogie Spill! t:Qid l'j!JIIllllllll. MISSicl'llletles: Blactwel Publisliing. Azer-Benlsilnov MT 120011. M1m11s. Spinal CGrd . S1llb lildsay K. Bkins JS. pp. RIIIIIMII PM. 57.org. Griggs RC Cecil EsSIIIIials of Mldicine7th Edition Andraall CaTpenr. llnna111 Praa.lltiC Nualgia: An CIINII rilk llcl1n ullfll il ciical 'ractil:l? CD811 PG... HM1181 Sl. Neurological dillarill dillgllOiis: a prioritized ljlpiOICh. Bamrlllin Allll al. Carpen!Br CCJ.. ea. UppincDI W. 1ilardars Motor Syslam Marshlll FJ. New Jersev: Humana Prea Inc.368:283-92. 36·40.58t6l:840-6. pp. ad (2005). 2008 Fab 26. pp. 359:1238-51 NEJM 2006. lUi AS. Cacil Essentials ci rnlliciie. Jamelltlll JL. Rlllidilnts manull of medicine. pp. 5th edition. 203·mi.I. Garcia A. Rodri!Ja M.._ W. Feslil SK. Diagnosis and 1relllmelll ol dementia: 1. Inc. 2nd edition. Palmln CH. Gri!IIIS RC. Harrison's inlllmll medicioa. I513): 69&-711..cPain Cllvnic Pain. Benjanin. 97U.. 12-13. Chow t Berrie M. t..ilptic• lcMtanstlii Dll Ailrldgl BK. Nlw JllrWf. ads (2001). t. Dlak MJ. Ann Naurol 2005 Dac. 222·23. ltlinglil SC. p. 162&-30. Silver J. Salrlders BseWer pp 1090-100. 131. 95U4. Gila CC 12005).Ur R. ··Sc-- Claaificatian Subcammitlee rl the 24IS11:9-160. 16th ldition. 244.on1111illll Blidayasiri R.Uiiple sclerosis. lDrQo DL. 2004. eds DHice ]IIICiice of niiiiUIDgy.338114):970-6. Lancet2001. Griggs. Waters MF. Validlliln IIIII raiDrnant of scarasto p!lldict vary 111rt. Dlllllllil Patler1011 C. Dilgnasli: critmia far multiple sclllr111is: 2005 ravilianstothe "Mcllanlld Crilaril". p. 7:445-53 NEJM 1995. pp. and l'rMIIilll. 333:1581-7 NEJM 2008. Fnmllnl W. Statuupllplicus. HIUSel' Sl. dilgnasis. .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. Slmh WT.. Garcil A. Waters MF. Blidayasiri R. NEJM 1998.. AMdlllll S. 16th edition. Neurological dillarill dillgllOiis: a prioritized IPIIfDlCh. 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