Professional Documents
Culture Documents
Nephrology
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
Nephrology NPI
NPl Nephrology
1'oroDio
2011
( ) L.oapdiul'ltics
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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)
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
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
--------------(Yilc:eral
z. Bawmln'SipiiCI
3.
epilhalium)
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!
GFR - K, 1M' - Alii r, = ultnlillndion caallicilnt AP = hylhstJdic pnmnn All = DlmotiC PIIIISUIII
Nit ouMwd pr811Uf8
NP4 Nephrology
1'oroDio
2011
renal autoregulation maJntains a constant GFR over a range of mean arterial pressures (70 to 180 m.mHg). 2 mechanisms of autoregulatl.on: myogenic mechanism: release of vasoactive factors in response to alterations in perfusion
pressure. E.g. rise ln perfusion pressure causes afferent arteriolar coll8trlctl.on, 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, normal = 0.2 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
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kidney
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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, NP34) an elevated ACR or 2.8 mglmmol is the earliest sign of diabetic nephropathy composition of normal total urine protein 60% filtered plasma protein: 50% albumin, 15% Ig, 25% other 40% Tamm-Horsfall mucoprotein secreted from tubular cells
tm
....
,,
I Proteinuria I
Physiologic Orthostlllic Absence of protainuria overnight Usually resolves spontaneously (exercise, fever, CHF}
PATHOLOGIC PIQ11:1NUIIA
+ htllaiDail:
o..
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.d l'labsorplion and incraased exJ:relion af LMW proteins Albumin {>60 kDI is NOT affected Thus, edema is partly secondary to salt and Wlll8r l'lltllntion
2.Giom.-r No111111lly, the 111ntion barrier is selectively penneable to SIZE {<60 kDI and CHARGE {repels nagativa particles). Thus, albtnin is NOT filtarud through a nonmlll giDIJIIIIIIuS Damage to any component of tha QIDIIIIIIIIar filtration barriar mulls in loss of albumin and other high MW proteins. Thus. 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. GN Post-strap. GN lgA nephropBihy
wti,.
Second1ry SystEmic disease Sl.E, diabetes, vasculitis Infectious disease HIV, Hap Band C, bllctarial endocarditis Hlllditary/Jnelllbolic Alport's, Fabry's, sickle cell, polycystic kidney disease Medications NSAIOs, gold, heavy melllls Cancer {carcinoma,lymphomal Lymphom1, solid tumour Others Cryoglobulinemia, hypertansiva nephrosclerosis
<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
3.11vartlaw production of LMW proteins which axceeds the reabsorptive capacity of the proximal 1ub\Q Plasma cllll dyscmiu: produce light chain lg myeloma, W.ldanstrom'a macroglobulinemia, monoclonl gammopathy of undanninad significiii'ICII
C111 be seen with glornerulll' clsease; i.e. mild glomerular disease can lead to a
mild dagrae of proteinuria, prolifllllltive lasioos may also be associlllad with scrne
degree of proteinuria
Investigations
urine R&M, C&S, urea, Cr further workup (if degree of proteinuria >0.5 glday, casts and/or hematuria) CBC, glucose, electrolytes, 24-hr urine protein and Cr urine and serum immunoelectrophoresis, abdominal!pelvic ultrasound serology: ANA, RF, p-ANCA, c-ANCA, Hep B, Hep C, HIY, ASOT indications for nephrology referral ACR >30-1000 mglmmol nephrotic syndrome: marked proteinuria >3.5 g/1.73m2/daywith hypoalbuminemia (<35 giL)
NP6 Nephrology
Hematuria
Definition presence ofblood or RBCs in urine gross hematuria: pink, red, or tea-coloured urine in gross hematuria, the urine should be centrifuged it is hematuria only if the sediment is red. If the supernatant is red. test for heme with a dipstick - if +ve for heme: myoglobinuria or hemoglobinuria - if -ve for heme: pseudohematuria. Consider medications (e.g. rifampin), food dyes (e.g. beets) or metabolites (e.g. porphyria) microscopic hematuria: normal coloured urine, >2-3 RBCs/HPF on microscopy
H1111aluria
"
...
+ve dipllick, no RBCI
Myoglobin (rhabdomyolysis)
Prilllllry
..
Urologic Nephrolithiasis, 1rauma, tumour. pro.tatitis, urethritis Dysuria or flank pain common Isomorphic RBCs, no casts Blood at beginning (lni!Yitis) or end [prostate, bladder) of stre1111
"
Second1ry
..
GN Post-51rap. GN Rapidly-progressive GN nephritis (ICuta and chronic) Papillary necrosis lgA naphroplllhy
Comective tissue diseases (CTDJ Waganar's, Goodpastura's, SLE, Ct.Jrg-Stnluss, HSP Infection Pyelonephritis Heneditary AIport's, polycystic kidnsy disaasa (PCKD)
Investigations for Hematuria Hx and Px: family history of nephrolithiasis, hearing loss (Alpert's), cerebral aneurysm (PCKD), diet, recent URTI, irritative and obstructive urinary symptoms (UTI) urine R&M, C&S, urea, Cr 24-hr urine stone workup: calcium, oxalate, citrate, magnesium, uric acid, cysteine further workup (if casts and/or proteinuria): CBC, electrolytes, 24-hr urine protein and Cr, serology (.ANA, RF, C3, C4, p-ANC.A, c-.ANCA, .ASOT), abdo/pelvic ultrasound, cystoscopy urology consult
,,
er-=cr_
[Cr),.,,.. x GFR = [CrJ..t..., x urin flow ms(ml/min) GFR - ICrJ.m. x urjne !low r11!: [Cr)-
.....
,,t----------------.
There is an inverse relati011ship between sarum Cr concentration and CrCI at steady state.
Ways to Estimate GFR I. Calculate creatinine clearance (CrCl) calculation provides reasonable estimate of GFR measure plasma [Cr], 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, particularly in azotem.ic patients incomplete urine collection can underestimate true GFR; over-collection of urine overestimates it
Nephrology NP7
2. Cockcroft-Gault formula serum Cr used along with age, gender and weight (kg) to estimate GFR (see sidebar) nonnal range is >90 ml/min (> 1.5 ml/s) 3. MDRD (Modification of Diet in Renal Disease) formula most common way in which GFR is estimated complex formula incorporating age, gender, serum Cr, Mrican descent GFR is reported as ml/min/L73m2 body surface area Limitations of Using Serum Cr Measurements I. must be in steady state constant GFR and rate of production of Cr from muscles sudden injury may reduce GFR substantially, but it takes time for Cr to accumulate and then re-establish steady state 2. GFR must fall substantially before plasma [CrI rises above normal laboratory range with progressive renal failure, remaining nephrons compensate with hyperfiltration GFR is relatively preserved despite significant structural damage 3.plasma [CrI is influenced by the rate of Cr production lower production with smaller muscle mass (ie. female, elderly, low weight) e.g. consider plasma [Crl oflOO f!InOl!L (1.13 mgldL) in both of these patients 20 year-old man who weighs 100 kg, GFR = 144 mUmin 80 year-old woman who weighs 50 kg, GFR = 30.6 mUmin 4. contribution of tubular secretion to Cr excretion is increased when GFR is low CrCl overestimates GFR certain drugs (cimetidine, trimethoprim) interfere with Cr secretion 5. 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.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; increased protein intake or catabolism (sepsis, trauma, 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, 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), and 14:1 in US units (urea expressed as BUN in mgldl and Cr in mgldL)
...
Cockcroft-Gault Fonnlll
....
}-----------------,
Function
incruH in Urwa Volume depletion (prarenalezotemial Gl hemonllage High protlin diet
Sepsis
Urinalysis
use dipstick in freshly voided urine specimen to assess the following:
1. Specific Gravity ratio of the mass of equal volumes of urine/H 20 normal range is 1.001 to 1.030 values <1.010 reflect dilute urine, values >1.020 reflect concentrated urine value usually 1.010 in end stage renal disease (isosthenuria)
2. pH urine pH is normally between 4.5-7.0; if persistently alkaline, consider: renal tubular acidosis UTI with urease-producing bacteria (e.g. Proteus)
.....
}----------------,
Z4 hour Urinll Callectian 1. lliscllld first morning $JI&Cim&n 2. Collect all subsequent urina for lila
next24 hi"$ 3. IWripra.. bltwnn voids 4. Collect second morning CIIJIIy: Cloudilass may indicate infection Colour: usually pllla yallow or lllllbar. but may be colourtess (dillllellls insipidus, excess Wlt8r intalal], bright yallow (due to ribofiiMn ingestion or vitamin ..bllllll). or dlllt yaUow (conciiTII'IDd urina in inlnMiscu!er volume depletion]
3. Glucose freely filtered at glomerulus and reabsorbed in proximal tubule causes of glucosuria include 1. hyperglycemia >9-11 mmol/L (>160-200 mg!dl) leads to filtration that exceeds tubular resorption capacity 2. increased GFR (e.g. pregnancy) 3. proximal tubule dysfunction (e.g. Fanconi's syndrome) 4. Protein dipstick only detects albumin; other proteins (e.g. Bence-Janes, lg, Tamm-Horsfall) may be missed microalbuminuria (defined as 30-300 mglday) is not detected by standard dipstick (see Diabetes and the Kidney, NP34) sulfosalicylic acid detects all protein in urine by precipitation gold standard: 24-hr urine collection for total protein
....
Eslinwting Urillll DIIIIDI..ity Lut 2 digits of lila specific g111Yity x 30 = urine osmolality approximatEly e.g. specific gravity of 1.020
= 600m0sm
NP8 Nephrology
5o Leukocyte Esterase
enzyme found in WBC and detected by dipstick presence ofWBCs indicates infection (e.g. UTI) or inflammation (e.g. AIN) nitrates in urine are converted by bacteria to nitrites high specificity, low sensitivity for UTI +ve dipstick for leukocyte esterase and nitrites is 94% specific for diagnosing a UTI
6. Nitrites
....
.. ,
o
7. Ketones
positive in alcoholic/diabetic ketoacidosis, prolonged starvation, fasting
Tnninolagy
B. Hemoglobin
Red 1)111 calls WlitiCIIcasts
QllllljwQt
o
nil
Aly 111 or
ltplne
... lllllwilfl
inoopr
positive in hemoglobinuria (hemolysis), myoglobinuria (rhabdomyolysis) and true hematuria (RBCs seen on microscopy)
Urine Microscopy
centrifuge urine specimen for 3-5 minutes, discard supernatant, resuspend sediment and plate on slide shaking tube vigorously may disrupt casts
Reduced
1. 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.g. proliferative glomerulonephritis) isomorphic RBCs, no casts suggest extraglomerular bleeding (e.g. 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.e. negative culture), consider: chronic urethritis, prostatitis, interstitial nephritis, calculi, papillary necrosis, renal TB, viral infections
Eosinophils
detected using Wright's or Hansel's stain (not affected by urine pH) consider allergic interstitial nephritis, atheroembolic disease
Oval Fat Bodies renal tubular cells filled with lipid droplets seen in heavy proteinuria (e.g. nephrotic syndrome) 2. CASTS cylindrical structures formed by intratubular precipitation of Tamm-Horsfall mucoprotein; cells may be trapped within the matrix of protein
Table 3. Interpretation of Casts
Hyaline casls
Red blood cell casts White blood call casls
Physiologic (concenlnrted urile, fever, exercise] Glomerulll' bleedilg (glomerulonephritis, vasculitis} lnfeclian (pyelaneplritis] lnllanmrtion (interstitial nephritis} Acute tubulll" necrosis Glomerulonephritis, interslitial nelllritis Heavy proteiruria (>3.51fday]
Pigmented gnmlar casts (heme grarular casls, muddy brown] Fatty casts
3. CRYSTALS
uric acid- consider acid urine, hyperuricosuria (e.g. gout) calcium phosphate - alkaline urine calcium oxalate - consider hyperoxaluria. ethylene glycol poisoning sulfur - sulfa-containing antibiotics
Nephrology NP9
Urine Electrolytes
can use to evaluate the source of an electrolyte abnormality or grossly assess tubular function commonly measure: Na, K. Cl. osmolality and pH no 'normal' values; electrolyte excretion depends on intake and current physiological state therefore results must be interpreted in the context of a patient's current state, e.g. 1. 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. daily urinary potassium excretion rate should be decreased (<20 mmolJd) in the setting of hypokalemia if higher than 20 mmolJd, 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
......
,
INal"'- x [Crlurilo
Fractional Excrwlion of Sodium FEti, = .. X ICrl- X 1DO Many fonnuills uud in nephrology 11111 derived from 1he division of two frllctiDRI, each of which urine and plasma concentmian (e.g. U,IP, + Wl'2l In 1he cqe of it is UNJPNo + UcJPc. which 1hln givls the above equation.
Examples of Common Urine Electrolyte Abnormalities high urine Na (>20 mmolJL) in the setting of acute renal failure: indicates renal disease vs. pre-renal high urine Na (>40 mmolJL) in the setting of hyponatremia: generally from causes such as diuretics, tubular disease (e.g. Bartter's syndrome), SIADH additionally, urine pH is useful to grossly assess renal acidification "low" pH (<5.5) in the presence oflow serum pH is an appropriate renal response a high pH in this setting might indicate a renal acidification defect (e.g. RTA)
Electrolyte Disorders
Sodium Homeostasis
Introduction hyponatremia and hypernatremia are disorders of water balance hyponatremia suggests too much water in the extracel.l.ular fluid relative to Na hypernatremia is too little water in the extracel.l.ular fluid relative to Na both can be associated with normal, decreased or increased total body Na solutes (such as Na, glucose, 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, ECF volume is determined by Na content, 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. Clinical Assessment of ECF Volume (Total Body Na)
Fllid Campartmall: Hypovolllllic Decreased Orlho6tatic op
..... ,
Co..
Sodium [Na) 135145 mmaVL (K) 3.S.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. serum pruteil
NP10 Nephrology
mectrotyte Disorders
Hyponatremia
hyponatremia: serum [Na] <136 mmol!L can be associated with increased, normal or decreased (most common) serum osmolality
Mechanisms of Hyponatremia
1. Hyponatremia despite dilute urine (U0 ..,.<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.g. schizophrenia) ability to excrete water is compromised in people with low solute excretion (particularly urea) e.g. elderly women with "tea and toast" diet low protein intake, low urea excretion
2. Hyponatremia with concentated urine (Uoam>200) if urine remains concentrated. 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, GI, urine, blood or 3rd spacing effective volume depletion: CHF and cirrhosis pathological ADH release: SIADH and endocrine deficiency SIADH - many causes including medications, lung disease, neurological disease, ectopic production, stress (pain, nausea, surgery); see Table 5 adrenal insufficiency (decreased volume and co-secretion ofADH and CRH) hypothyroidism (decreased cardiac output, decreased GFR)
.....
, ...-----------------.
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
Hypo-Osmol (dilutionall Most common cause of hyponatremia Excess water in relidion to sodium stores which can be decreased, 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.g. 11111nnitoll Pseudohyponatramia -lab artnct seen with severe hyperlipidemia or panaprotainamia (e.g multiple myelomaI
HypaP.OIIIIIolar (transloc:ati-11 Extra osmol us in ECF <h.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..<2Q/anuric CHF Cirrhosis and ascites Pregnancy
y
Euvulemic u_>1DD SIADH [normlll U.J Altalal insufficiency Hypothyroidism U_<10D "-Ychogenic polydipsia Traat1111nt Tnaat with water restriction Tnaat with salt and wlllllr (i.a. nonmal salina)
y
Hypovulemic U,..>20 lliurelics Salt-wasting nephropathy U..<10 Diarrhea Excessive sweating Third spacing (e.g. pancnaatitis, 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 ..
ARF, CRF
TrNtmlllt Treatment golll is Naloss with ralatively mora water loss Treat with sahnd water restriction and sometimes diurelics
mectrolyte Disorders
Nephrology NP11
Complications
seizures, coma, respiratory arrest, pennanent brain damage, brainstem herniation, death risk of brain cell shrinkage with rapid correction of hyponatremia can develop osmotic demyelination of pontine and extrapontine neurons, which may be irreversible (e.g. central pontine myelinolysis: cranial nerve palsies, quadriplegia, decreased LOC)
Risk Fac:tors for Osmotic Demyelination rise in serum [Na] with correction >8 mmolJL/d if chronic hyponatremia
associated hypokalemia and/or malnutrition if patient with hyponatremia and hypovolemia is given large volume of isotonic fluid (ADH is stimulated by hypovolemia; when hypovolemia is corrected, the ADH level falls suddenly causing sudden brisk water diuresis, and therefore rapid rise in serum Nalevel) patient with psychogenic polydipsia, deprived of water
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. Definitely Arote (known to have developed over <24-48 hours) commonly occurs in hospital (dilute IV fluid+ reason for ADH excess e.g. post-operative) less risk from rapid correction since adaptation has not fully occurred if symptomatic correct rapidly with 3% NaCll-2 cc/kglh up to serum Na=125-130 mmolJL may need furosemide to address volume overload if asymptomatic, treatment depends on severity if marked fall in plasma [Na], treat as symptomatic B. Chronic or Unknown 1. 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. if asymptomatic water restrict to< 1 Uday fluid intake consider IV 0.9% normal saline (NS) + furosemide (reduces urine osmolality, augments excretion of electrolyte-free Hp) consider NaCl tablet or Oxocubes as a source ofNa 3. refractory furosemide and IV NS demeclocyline 300-600 mg PO bid (antagonizes effect of ADH on collecting duct; avoid if cirrhosis or congestive heart failure as nephrotoxic in these settings) extra osmoles- give oral urea (increases loss ofwater without Na; 30-60 g/day) slow rate of IV 3% NaCI (e.g. 10 cclhr = 120 mmol/day of sodium which will increase serum [Na] by about 3 mmol/Uday)
....
'..,
ea-ntratlon of Na in Common
lnfuut.Na in 0.45% NaCI = 77 mmoi/L Na in O.K NaCI = 154 mmoi/L Na in 3'11. NeCI = 513 mmaVL Na in 5% NeCI - 855 mmaVL Na in Ringer's = 130 mmolll Na inD5W = 0
IV)
....
,..__________________ ,
HzO Dlllcit 1nd TBW Eqllllti1.1BW = O.Bxwt (kg) man; TBW = 0.5 x wt (kg) women
NP12 Nephrology
mectrotyte Disorders
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SlADH} 1. urine that is inappropriately concentrated for the serum osmolality 2. high urine sodium (>20-40 mmol/L) 3.highFENa
Table 5. Disorders Associated with SIADH
Tumaur
Small ceiiCa Bronchog111ic Ca AdenoCa of panCI'I!IIS disease
Pulm11111ry
Pneumonia Lung abscess
Drugs
MiiCIIIueaus
Thymoma
Dill DDAVP
Oxytocin Nicotine
Hypernatremia
hypernatremia: serum [Na] >145 mmol/L too little water relative to total body Na; always a hyperosmolar state usually due to net water loss, rarely due to hypertonic Na gain results from problems with water intake (access, 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
...
HypiMIIImic (raN) IIII'O!renic [hypertonic salina or NaHCO,) Cushing's syndrorna Hyparald01111ronism Traat wi1h salt restriction, diuretics, wmer replacement Dialysis if ranal failure
Nan-llypemlamlc
...
Is patient putting out a small volume [500 mlJd) of miXimaly [ > 8DD mOsnv\u) Ll'ina?
...
No Is urine osmole excretion rme > 750 mOsm/d 1
...
I
v..
Diuretics [loop) Osmotic diurasis Hyparglycamia Endoganous[uraa with axcass NG protein faads)
\W Insensible water loss Respinrtory, skin Gl [dianhaa) Osmotic (lactulosa, malabsorption) Remota renal loss
...
D1
...
01
Complications
increased risk of vascular rupture resulting in intracranial hemorrhage rapid correction may lead to cerebral edema due to ongoing brain hyperosmolarity
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, 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, use formula to calculate water deficit: H20 deficit= TBW x (serum rNa! - 140) [TBW = 0.6 x wt(kg) for men, 0.5 x wt(kg) for women] 140 replace free water deficit; "free water" is water without sodium encourage patient to drink pure water, as oral route is preferred for fluid administration if unable to replace PO or NG, correct H2 0 deficit with hypotonic IV solution lL DSW approximately equals 1 L free water 11 0.45% NS approximately equals 500 mL free water use formula (see Hyponatremia, 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 (0.5 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 0.5 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), then replace water deficit using D5W DIABETES INSIPIDUS (DI}
....
,,
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, granulomatous diseases, trauma, vascular events, and malignancy nephrogenic DI: lithium (most common), hypokalemia. hypercalcemia. and congenital
Diagnosis
urine osmolality inappropriately low in patient with hypematremia (UDIIn <300 mOsm!kg) serum vasopressin concentration may be absent or low (central), or elevated (nephrogenic) dehydration test: HzO deprivation until loss of 3% of body weight or until urine osmolarity rises above plasma osmolarity; 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, 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), thiazides may help as well (reduced ECF volume stimulates proximal tubular reabsorption of sodium and water, leading to less delivery of glomerular filtrate to ADH sensitive parts of renal tubule, and therefore lower urine volume: results)
Potassium Homeostasis
approximately 98% of total body K stores are intracellular normal serum K ranges from 3.5-5.0 mEq/L in response to K load, rapid removal from ECF is necessary to prevent life-threatening hyperkalemia insulin, 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, causing Na reabsorption and K excretion metabolic alkalosis hypomagnesemia increased non-reabsorbablc: anions in tubule: lumen: HC03, penicillin, salicylate
NP14 Nephrology
mectrotyte Disorders
Hypokalemia
serum [K] <3.5 mEq/L
Approach to Hypokalemia 1. emergency measures: obtain ECG; if potentially life threatening. begin treatment immediately 2. rule out transcellular shifts ofK as cause ofhypokalemia 3. assess contribution of dietary K intake 4. 24-hr K excretion or spot urine K 5. TTKG =transtubular potassium gradient =(UJJPJ/(Uoom/PomJ 6. if renal K loss, check BP and acid-base status 7. may also assess plasma renin and aldosterone levels, serum [Mg]
Hypokalemia
DICQIIsedlnhlq Limited diatary in!Bb Cll.y ingll&lion
U. <25 mEq/day
TTKG <3
KG
I
into C.lls Mlllllbolic alkalosis {IQH axchanqa across call mambrana) I111LJin {llimulatus NII/I( AlPBse) Catacholaminas, Ji1-egonills {v.ntolin ), 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
I I
Hypo- or -motaivl
...
Aclclamlc
...
llyparlllni11 1" hyperakloslllrnnism {e.g Conn's syndrome) 2 (renovascular disease, reni1 tumour} Non.,aldoslllrnne mineralocorticoid [Cushing's, exogenous)
...
Alhlemic Diurulics (furosemide, hydrnchloruthilllide) ranall01111 duatll hyparaldoslllrnnism and mlllllbolic alkalosis) Inherited renal tubular lesions - Bartter's {loop of Henle dyafunction: furosemide-lib effect) - Gitelman's (disbl convoluted tlb.lle
DKA
RTA
TTl(G =
Trant-Tubolllr KGraclent
Signs and Symptoms usually asymptomatic, particularly when mild (3.0-3.5 mmol/L) nausea, vomiting, fatigue, generalized weakness, myalgia, muscle cramps, and constipation if severe: arrhythmias, muscle necrosis, and rarely paralysis with eventual respiratory impairment arrhythmias occur at variable levels of K; more likely if digoxin use, hypomagnesemia, 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, wide QRS, arrhytlmtias; increases risk of digitalis toxicity
mectrolyte Disorders
Nephrology NP15
Treatment treat underlying cause if urine output and renal function are impaired, correct with extreme caution risk of hyperkalemia with potassium replacement especially high in elderly, diabetics, and patients with decreased renal function beware of excessive potassium repletion, especially if transcellular shift caused hypokalemia if true K deficit, potassium repletion (decrease in serum [K] of 1 mEq is very roughly 100-200 mEq of total body loss) oral sources- food, tablets (K-Dur-), KClliquid solutions IV - usually KCl in saline solutions, avoid dextrose solutions (may exacerbate hypokalemia via insulin release) max. 40 mmol/L via peripheral vein, 60 mmolJL via central vein, max. infusion 20 mmo!Jhr o K-sparing diuretics (triamterene, spironolactone, amiloride) can prevent renal Kloss restore Mg if necessary
Hyperkalemia
serum [K] >5.0 mEq!L
Approach to Hyperkalemia 1. emergency measures: obtain ECG, if life threatening begin treatment inunediately 2. rule out factitious hyperkalemia; repeat blood test 3. hold exogenous K, and any K retaining medications 4. assess potential causes of transcellular shift 5. estimate GFR (calculate CrCl using Cockcroft-Gault) 6. if normal GFR, calculate TTKG = (Uk/PJ<)/(U0 om/P01111) TTKG <7 = decreased effective aldosterone function TTKG >7 = normal aldosterone function
Table 6. Causes of Hyperkalemia
hctitious lnc....ad lntaq
Cellular Releue
Intravascular hemolysis Rhabdomyolysis Insulin deficiency Hyperosmolar states (e.g. 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
Hyporeninemic, hypaaldosteranism o Associated with DM2, NSAIDs, chronic interstitial nephritis, HIV
Adrenal insufficiency ol any cause (e.g. Addison's diseasa, AIDS, 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, tacrolimus o Pseudohypoaldosteronism (rare inherited tubular disardnl
Signs and Symptoms usually asymptomatic but may develop nausea. palpitations, muscle weakness, muscle stiffness, paresthesias, areflexia, ascending paralysis, 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
NP16 Nephrology
....
.. ,
In patients with dilbetes and increued [K+] and hypervfycamia, often jUI! giving insulin to mtore euglycamia is sufficient to correct the hyperkalemia.
Normal
T W11W
Peaking
T W11W
Paaksd
1 g
Treatment
acute therapy is warranted ifECG changes are present, or if patient is symptomatic tailor therapy to severity ofincrease in [K] and ECG changes [K] <6.5 and normal ECG tn:at underlying cause, stop K intake, increase the loss ofK via urine and/or GI tract (see below) [K] between 6.5 and 7.0, no ECG changes: add insulin to above n:gimen [K] >7.0 and/or ECG changes: first priority is to protect the heart, add Ca gluconate to above
Tnilllllenl of Hypllllcelemll
SEE BIG KDROP SEE - Calcium gluconata
BIG- BIIQDnist. Bicllb, Insulin, Glucosa
I- Ka.,.xaim11
DIOP- Diuretics, Dialysis
1. Protect the Heart Ca gluconate 1-2 amps (10 mL of10% solution} IV antagonizes cardiac toxicity of hyperkalemia, protects cardiac conduction system, no effect on serum [K] onset within minutes, lasts 30-60 minutes
2. Shift K into Cells regular insulin (Insulin R) 10-20 units IV; with 1-2 amp DSOW (give DSOWbefon:insulin) onset of action 15-30 min, 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 of7.5% or 8.4% NaHC03 in lL D5W) onset of action 15-30 min, transient effect, drives K into cells in exchange for H (Ventolin) in nebulized form (dose= 2 cc or 10 mg inhaled) or 0.5 mg IV onset of action 30-90 min, stimulates Na/K ATPase caution if patient has heart disease as tachycardia may result from this high dose ofbeta2 agonist 3. Enhance K Removal from Body
via urine (prefern:d approach) furosemide mg IV), 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, and controversial how much K is actually n:moved - 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:, 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, n:spiratory, metabolic and CNS function see Respirolo!O" R5 for mon: information on respiratory acidosis/alkalosis normal concentration ofHC03 = 24 mEq!L normal pC02 = 40 mmHg each add base disorder has an appropriate compensation inadequate compensation or overcompensation indicates the presence of a second acid-base disorder e.g. in metabolic acidosis, inadequate compensation means there is also respiratory acidosis; overcompensation means there is also respiratory alkalosis
Acid-Due Disorders
Nephrology NP17
Reepiratury acidoi Acute: 1' 10 PCO, = 1' 1 HCO, Chronic: 1' 10 PCO, = 1' 3 HCO,
a.piratury alludosi Acute: "- 10 PCO, = "- 2 HCO, Qlranic: "- 10 PCO, = "- 5 HCO,
Metabolic Acidosis
Identify Main Disturbanc), then:
1. Evaluate compensation (Figure 12)
......
.. "
+
2. Calculate plasma anion gap (PAG) PAG = Na- (HC03 + Cl) baseline= 12, range 10-14 PAG can be altered by plasma albumin level: for each 10 giL fall in albumin, lower baseline PAG by 3 (e.g. is plasma [albumin]= 20 giL, expect PAG = 6)
3. If PAG elevated. compare increase in PAG with decrease in HC03 if increase in PAG < decrease in HC03, there is a coexisting non-AG metabolic acidosis if increase in PAG > decrease HC03, there is a coexisting metabolic alkalosis 4. Calculate osmolar gap osmolar gap = measured osmolality- calculated osmolality calculated osmolality= (2 x Na) + urea+ glucose (all units are in mmolJL) normal osmolar gap < 10 if gap> 10, consider: methanol poisoning, ethylene glycol poisoning, OR another cause of acidosis plus ethanol ingestion
2. Olmoillr Gap = mea&ured OIITiolality - calculided osmolality (normal < 1Dl 3. Calculated Osmolality = 2[Na]
IUreal + (Glucose]
Etiology and Pathophysiology 1. lncreaJed PAG Metabolk Acidosis (4 types) 1. Lactic acidosis (2 types)
L-lactic acid - Type A: due to tissue hypoperfusion (any cause of shock), ischemic bowel, profound hypoxemia - Type B: failure to metabolize normally produced lactic acid in the liver due to severe liver disease, excessive alcohol intake, thiamine deficiency, or metfonnin accumulation (metformin interferes with electron transport chain) D-lactic add: rare syndrome characterized by episodes of encephalopathy and metabolic acidosis, requires carbohydrate malabsorption (e.g. short bowel syndrome), colonic bacteria that produce D-lactic acid. a carbohydrate load, diminished colonic motility and impaired D-lactate metabolism 2. Ketoacidosis diabetic starvation alcoholic (decreased carbohydrate intake and vomiting) 3. Toxins methanol (toxic to brain and retina, can cause blindness and brain death)- metabolized to formic acid ethylene glycol (toxic to brain and kidneys)- metabolized to oxalic acid (envelope shaped crystals in urine) salicylate 4. Advanced renal failure (i.e. serum Cr increased at least Sx above baseline - a very low GFR causes anion retention, and renal disease leads to impaired bicarbonate production)
Ill:'
or
ASA
ICARMEL Ketoacidosis
NP18 Nephrology
Add-Due Disorders
It'
RTA*
Diarrhea* Urehlroenteric fi5tulll Pancreaticoduodenal fistulil increased *Most Common
2. Normal PAG Metabolic Acidosis (Hyperc.hlorem.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, reabsorption type IV RTA: defective ammoniagenesis due to decreased aldosterone, hyporesponsiveness or hyperkalemia to help distinguish renal causes from non-renal causes, use Urine Anion Gap= (Na + K) - Cl calculation establishes the presence or absence of unmeasured +ve ions (e.g. NH 4) in urine if <0, suggests adequate Nlf.t in urine (likely nonrenal cause: diarrhea) if >0, suggests problem is lack ofNlf.t in urine (e.g. distal RTA)
.....
,...----------------. ,
Metabolic Alkalosis
Pathophysiology
requires initiating event and maintenance factors initiating event GI (vomiting. NG tube) or renal loss ofH exogenous alkali (oral or parenteral administration), milk alkali syndrome diuretics (contraction alkalosis): decreased excretion ofHC03, decreased ECF volume, therefore increased [HC03 ] post-hypercapnia: renal compensation for respiratory acidosis is HC03 retention, 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, aldosterone also promotes hypokalemia hypokalemia: transcellular K/H exchange, stimulus for ammoniagenesis and HC03 generation
...
U0 <20 mEq/1.. Salina 1111ponsiva
+
+
I I
...
U >20 mElJIL 0
II
...
Diundic . .
II +
Salina resislllnt
ICheck blood
Hyperten.ivll 1 hyperaldosteronism 2 hyperaldosteronism Cushing's syndrome
+ +
I
I
...
Nllllllllnllin Exogenous alkali S8\111'8 hypokalemia Bartter's, Gilelm1111's
Nephrology NP19
Treatment
treat underlying cause correct underlying disease, replenish K and Mg deficits, and possibly K-sparing diuretic saline sensitive metabolic alkalosis (most common) treabnent: volume repletion carbonic anhydrase inhibitor (e.g. 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, severity of insult, adaptation to nephron loss/ dysfunction, treatment of reversible disease process
1. Volume Overload
due to increase in total body Na content signs: weight gain, H1N, pulmonary or peripheml edema
2. Electrolyte Abnormalities
high K (decreased renal excretion, increased tissue breakdown) P04 (decreased renal excretion, increased tissue breakdown) Ca (rare; happens during recovery phase after rhabdomyolysis-induced acute kidney injury or in settings where hypercalcemia contributes to renal failure, such as in multiple myeloma or sarcoidosis) uricacid low Na (failure to excrete excessive water intake) Ca (decreased Vit D activation, hyperphosphatemia, hypoalbuminemia) HC03 (especially with sepsis or severe heart failure)
3. Uremic Syndrome
retention of urea and other metabolites as well as deficiencies of hormones, causing the manifestations of uremic syndrome
Complications
CNS: decreased LOC, stupor, seizure CVS: cardiomyopathy, CHF, arrhythmia, pericarditis, atherosclerosis GI: peptic ulcer disease, gastroduodenitis, AVM hematologic: anemia, bleeding tendency (platelet dysfunction), infections endocrine: decreased testosterone, estrogen, progesterone increased FSH, LH metabolic: renal osteodystrophy: secondary increased PTH due to decreased Ca, high P04 and low active vitamin D osteitis fibrosa cystica hypertriglyceridemia, accelerated atherogenesis decreased insulin requirements, increased insulin resistance dermatologic: pruritus, ecchymosis, hematoma, calciphylaxis (vascular Ca deposition)
NP20 Nephrology
abrupt decline in renal function leading to increased nitrogenous waste products formerly known as Acute Renal Failure (ARF)
Clinical Features
azotemia (increased BUN, Cr) abnormal urine volume (anuria, oliguria, polyuria)
, ..)-----------------.
CI111111D Pn_.lllll Elialllgy Clinical: Dlc111uad BP, incrtuad HR, lrld orthostatic HR and BP chlngas I11C11181ad [u11a] > > lncraaad [Cr] Urine [Na] <10-20 mmoVI. Urina ollllllllllli1y >500 mOsmfkv Fractional uxcrvtion af Na <1'lr. Cllllll to Rlnal Etiology Appropriate dinical contaxt Urinalysis positive for casts: Pigmented g111nular- ATN WBC-AIN RBC-GN Cl11111 to PDit-B-1 EtiDIIIIIt' Known solitary kidney Olderman Rucunt retroperito1181111 surgury Anuria Palpablubladder Ultrasound shows hydronephrosis
...
NSAID5
"nil
...
lllypavolemill
..
....
,,
I'N-nlll rN
Normal RBC, pigmenlld
gnnullrCIIII
'lllacull.r Vasculitis Malignant HTN Thrombotic microangiopatily Cholastarolamboli Large vessel disease
..
. ..
llri1l (NI]
Approach to AKI
Investigations
--------------------------------------------
llrileiCTWAI FeNa
llrileOSIIIIIIIily >500
blood: CBC, electrolytes, Cr, urea (think prerenal if increase in urea is relatively greater than increase in Cr), Ca, P04 urine volume, C&S, R&M: sediment, casts, crystals urinary indices Foley catheterization (rule out bladder outlet obstruction) fluid challenge (ie. fluid bolus to rule out most pre-renal causes) imaging: abdo U/S (assess kidney size, hydronephr06is, post-nmal obstruction) indications for renal biopsy diagnosis is not certain prerenal azotemia or ATN is unlikely oliguria persists >4 weeks
Treatment
1. preliminary measures pre-renal correct prerenal factors: optimize volume status and cardiac performance, hold ACEI/ARB renal exclude reversible renal causes: die nephrotoxic drugs, treat infection, and optimize electrolytes post-renal consider obstruction: structural (stones, strictures) vs. functional (neuropathy) treat with Foley catheter, indwelling bladder catheter, nephrostomy, stenting 2. treat complications fluid overload NaCl restriction high dose loop diuretics hyperkalemia (refer to Treatment of Hyperkalemia, NP16) adjust dosages of medications cleared by kidney 3. definitive therapy depends on etiology note: renal transplant is not a therapy for AKI
Nephrology NP21
Prognosis
high morbidity and mortality in patients with sustained AKI and multi-organ failure
......
,
42.!1%
26.4%
Diabetes
HypartBIIIion
Interstitial nephriti&'
Cystir/HirediiB!y/Congenital SecondllfY GNI\Iasculitis
GlomenJonephrilis OtharJ\!nknown
9.!1%
7.7%
4.Dl(, 3.1% 2.4%
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
Slqe4
Stqe5
15-29
NEPHION
between meals Ito increased Cal and with mills (1D bind and decreased POJ
N - NIJihrotoxins: IMiid IIIPhnrtaxic drugs [ASA, gentamicin) end adjust doses of renally excreted
medications
IIIII_.,.
diselle.
llril...,... Clnli-o.-..in
sa.dy . . . .: Rlndomillld I:GIIbGied lrilll111d llllly!ld CV CIUII:omll il pDIIII Mdl cllanic ijctluy diMIIIICXIIVprgOOJril lllllad with RAS
inhibillnl
blockll$i.llerin lfiQiallnlil IIWiflm bb:kldt-buld 1hlllpyMil pllceba lllllllllllfnll (bell-lllocklr, Cltill!lchlnnal bbclan 11111 ot111r ll'llillyparllllsNe-bllld thenvfl theavt illhe slid\'. llllldti:Twanty-!Mirilll{N = 457!iiiWIIII incblld. Can1llrld ID plabo, liAS blacbdl raOOcad IIIII rilk al hllllllai1111 in peliellts with diablli: Pllilnls with no!Miilbelic CKD, liAS bloc:bde dectelsed CV oulcGme CGirj1llld ID llllllfnll111npy. C...._: RAS blocbde llduced CV aull:omes in dilbatic nepllropllhv Will u no!Miilbelic
em
NP22 Nephrology
Pericarditis
Encephalopathy
Edema!pulm01111ryl
or Acidosis (rulnctory)
Eleclrolylll imbalance lrefractoryl
lhmia
Encephl.lopaltly, pericarditis,
...
,.-----------------. .,
Type (e.g. FBDI
un111
>35-50mM
length le.g. 4h 3 1irnaflwk or 2h daly) Q Blood Flow (Max 4011 cc/min) Ultnlfitration (e.g. 2L or to target dry
weightI Na 140 lean budjusted by stilling II: 155 and "rampilg" down to
Serum K Dilllysllhl 4-6 1.5
<3.5 Ca I.Z5
HC!la 40
3.5
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, neuropathy, seizures) uremic pericarditis refractory accelerated hypertension clinically significant bleeding diathesis persistent severe nausea and vomiting plasma Cr >1060 IUDOl!L (12 mg!d.L) or BUN >36 mmol/L (100 mg/dL; 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, solutes, excess fluid (ultrafiltration), and restoring buffering agents to the bloodstream available as intermittent (e.g. three times per week), continuous {CVVHD) or sustained low efficiency (SLED) peritoneal dialysis: peritoneum acts as a semipermeable membrane similar to hemodialysis filter advantages: independence, fewer stringent dietary restrictions, better rehabilitation rates available as continuous ambulatory (CAPD; four exchanges per day) or cyclic (CCPD; 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, the serum Cr level quoted as >350 IUDoliL (>4.0 mg!d.L), 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. Peritoneal Dialysis VI. Hemodialysis
,,., .-----------------.
Whta lnitiltll DIALYSIS
Rate
l.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; if not acandidll:e far diaysis, 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
NOTE
Cockcroft-Gault equation (or
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, in order to avoid dialysis
kidney func:tion
Young, ligh functioning. residual renal functian Bed-bound, co-morbidities, no renal function Success depends on presence of residual renal function Residual renal function not as important
Ftom: Nlllionll
......
....
Renal Transplantation
preferred modality of RRT, 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, living donor (related or unrelated) kidney transplanted into iliac fossa, transplant renal artery anastomosed to external iliac artery of recipient 1 year renal allograft survival rates
,,.-----------------, '
.
Nephrology NP23
Antiprvlifwmivlt 11111dic.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, malignancy (skin, Kaposi's sarcoma, post-transplant lymphoproliferative disorder) acute rejection: graft site tenderness, rise in Cr, oliguria, fever de novo glomerulonephritis (usually membranous) new-onset diabetes mellitus (often due to prednisone use) cyclosporine or tacrolimus nephropathy (refer to Small Vessel Disease, NP32) chronic allograft nephropathy early allograft damage caused by episodes of acute rejection and acute peritransplant injuries immunologic and nonimmunologic factors (HTN, hyperlipidemia, age of donor, quality of graft, 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
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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. endothelial, parietal epithelial), 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
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Clinical/Lab Features proteinuria (but <3.5 g/1.73 m 2 /day) abrupt onset hematuria (microscopic or macroscopic) azotemia (increased Cr and urea)
NP24 Nephrology
Glomerular Disease
RBC casts and/or dysmorphic RBCs in urine oliguria HTN (due to salt and water retention)
It'
puffyeyes
smoky urine
Proteinuria
Hematuria
Etiology
etiology can be divided into low and normal complement levels (Table 10) frequently immune-mediated, with Ig and C3 deposits found in GBM outcome dependent on etiology
Table 10. Etiology of Nephritic Syndrome
Nonnll Camplamant Lartl lgA nephropathy Anti.{iBM disaasa PolyariErilis nodosa Wegener's granulomatosis Henoch.Schonlein pLrpura Goodpasue's synrtome
Slf
Endocarditis Abscess or shunt neplritis Cryoglobulinemia
....
, ...----------------.
2. NEPHROTIC SYNDROME
Clinical/Lab Features heavy proteinuria (>3.5 g/1.73m2/d) hypoalbuminemia edema hyperlipidemia (elevated LDL cholesterol),lipiduria (fatty casts and oval fat bodies on microscopy) hypercoagulable state (due to antithrombin III, 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) - i.e. 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. Naphrotic Syndroma Minimal
Prwentation -' Nepllratie Syndnlme 1. Sevn proteinuria (>3.5 Qfdl 2. Hypollbumilemia 3. Edama 4. Hyperlipidemia, lipiduria 5. Oval fat bodies (microscopy( 6. Hypereoag!Jahle stile (antithrombin Ill, protein Cand pnrtein S lost in urineI
Change
Hodgkin's lymphoma
NSAIDs
Gold, penicillamine Heroin Recllce BP, ACB, &teroids Steroids, ACEVARB fur proiBinuria Aspirin, ACEI, dipyridamole Treat undBriying controversial cause
Steroids
Naphritic
Hamatu.ria, "-
[ Protainara
FSGS Membranous gtomarulopathy
Minimal change Membranoproliferative GN Focal proliferative GN lgA nephropllhy ldioplllhic membranoprolifenrtive GN
Glomerular Disease
Nephrology NP25
RPGNTpl: AJrti.GBM m iltld .. %111RPGNC. 15% of cases lmmuno.ftuorncence Linear pattern due to lgG 111d SUing Pattem C3 deposition along capillary loops
Antibodies against type IV collagen in GBM
Primuyc....
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
s-nduvc....
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urinalysis: RBCs, WBCs, casts, protein 24-hr urine for protein and CrCl radiology CXR (infiltrates, CHF, pleural effusion) renal ultrasound renal biopsy (percutaneous or open) ifheavyproteinuria or renal insufficiency, and cause not obviously diabetic nephropathy urine immunoelectrophoresis for Bence-Jones protein if proteinuria present
NP26 Nephrology
Glomerular Disease
............ ..._..
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Amyloidosis nodular deposits of amyloid in mesangium, 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, TB, rheumatoid arthritis, 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
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Figure 16. International Society of Nephrology/Renal Pathology Society Classification of Lupus Nephritis 2003 HIV-Assoc:iated Renal Disease 1. direct nephrotoxic effect ofHIV infection, antiretroviral drugs (e.g. tenofovir, indinavir) and other drugs used to treat HIV-assodated infections 2.HIV-assodated nephropathy histology: focal and segmental glomerular collapse with mesangial sclerosis, "collapsing FSGS" tubular cystic dilation and tubule-reticular inclusions clinical features: predominant in black men, heavy proteinuria, progressive renal insufficiency prognosis: kidney failure within one year without treatment therapy: short-term, high dose steroids, ACEI, HAART Henoch-Schonlein Purpura (HSP) seen more commonly in children purpura on buttocks and legs, abdominal pain, arthralgia and fever glomeruli show varying degrees of mesangial hypercellularity IgA and C3 staining of mesangiwn usually benign, self-limiting course; 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, 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, cyclophosphamide, 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, prednisone or sulfa may prevent recurrence
Nephrology NP27
Cryoglobulinemia cryoglobulin&: monoclonal IgM and polyclonal IgG presents as purpura, 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. plasmapheresis overall prognosis: 75% renal recovery
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. proximal tubule (e.g. multiple myeloma, heavy metals) Fanconi syndrome: decreased reabsorption in proximal tubule causing glycosuria, aminoaciduria, phosphaturia, hypouricemia proximal RTA (decreased bicarbonate absorption): Type II RTA 2. distal tubule (e.g. amyloidosis, obstruction) distal RTA (Type I RTA) Na-wasting nephropathy hyperkalemia. type N RTA 3. collecting duct (e.g. sickle cell anemia. analgesics, 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
NP28 Nephrology
'IUbulointerstitial Diseaae
Etiology hypersensitivity I. antibiotics: beta-lactams, sulfonamides, rifampin, quinolones, cephalosporins 2. other: NSAIDs, allopurinol, furosemide infections bacterial pyelonephritis, Streptococcus, brucellosis, Legionella, CMY, EBV, toxoplasmosis, leptospirosis immune SLE, acute allograft rejection,Sjogren'ssyndrome,sarcoidosis,mixedessentialcryoglobulinemia idiopathic Pathophysiology acute inflammatory cell infiltrates into renal interstitium
Investigations urine sterile pyuria, WBC casts, mild proteinuria, hematuria eosinophils if allergic interstitial nephritis blood increased Cr and urea eosinophilia if drug reaction normal PAG metabolic acidosis (renal tubular acidosis) hypophosphatemia, hyperkalemia, hyponatremia gallium scan shows intense signal due to inflammatory infiltrate renal biopsy definitive Treatment treat underlying cause (e.g. stop offending medications, antibiotics if pyelonephritis) corticosteroids (may be indicated in allergic or immune disease) Prognosis recovery within 2 weeks if underlying insult can be eliminated
2. CHRONIC TUBULOINTERSTrTIAL NEPHRITIS Definition characterized by slowly progressive renal failure, 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), acetaminophen cisplatin, lithium, cyclosporine, tacrolimus heavy metals (lead, cadmium, copper), lithium, mercury, arsenic radiation chinese herbs endogenous hypercalcemia, hypokalemia, oxalate, uric acid nephropathy vascular disease: ischemic nephrosclerosis, atheroembolic disease malignancies: multiple myeloma granulomatous: TB, sarcoidosis, Wegener's granulomatosis immune: SLE, Sjogren's, cryoglobulinemia, Goodpasture's, amyloidosis, renal graft rejection hereditary: cystic diseases of the kidney, sickle cell disease others: radiation, Balkan (endemic) nephropathy
Tubulointeratitial DiAease
Nephrology NP29
Pathophysiology fibrosis of interstitium with atrophy of tubules, mononuclear cell inflammation Signs and Symptoms tubular dysfunction (e.g. acidosis, 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, P04) and anemia Findings which Suggest Chronic Tubulointerstitial Nephritis normal PAG metabolic acidosis hyperkalemia (out of proportion to degree of renal insufficiency) polyuria, nocturia partial or complete Fanconi's syndrome urine: mild proteinuria, few RBCs and WBCs, no RBC casts ultrasound: shrunken kidneys with irregular contours
--------------------------
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. sepsis, rhabdomyolysis, or administration of nephrotoxic drug urine: high FEN., pigmented-granular casts Complications hyperkalemia: can occur rapidly and cause serious arrhythmia metabolic acidosis, decreased Ca, increased P04> hypoalbuminemia Investigations blood: CBC, eletrolytes, Cr, urea, Ca, P04> blood gases urine: R&M, electrolytes, osmolality ECG abdominal ultrasound
[ Acute Tubular Nacrosis [
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- Methotrexate
Conti'IISt madill Haavymlltals Other - Fluorinated anaesthstic - E1ilylena glvcol
NP30 Nephrology
......
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
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, ACE inhibitors, cyclosporine on morning of procedure if possible
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Analgesic Nephropathies
1. Vasomotor Acute Kidney Injury (AKI)
normally prostaglandins vasodilate renal arterioles to maintain blood flow NSAIDs act by blocking cycloo.xygenase enzyme, thereby preventing prostaglandin synthesis and causing renal ischemia more common in elderly, underlying renal disease, hypovolemia (diuretics, CHF, cirrhosis, nephrotic syndrome) clinically: develop prerenal azotemia within a few days of starting NSAID treatment: discontinue NSAID, dialysis rarely needed
Etiology
abdominal trauma, surgery, embolism, vasculitis, extrarenal compression, hypercoaguable state, aortic dissection kidney transplant more vulnerable
Nephrology NP31
Investigations
renal arteriography (more reliable but risk of contrast-mediated ATN, atheroembolic renal disease) contrast-enhanced CT or magnetic resonance angiography, duplex Doppler studies (operator dependent)
Treatment
prompt localization of occlusion and restoration of blood flow anticoagulation, thrombolysis, percutaneous angioplasty or clot extraction, surgical thrombectomy
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2. 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. atherosclerosis - more common in elderly 2. fibromuscular dysplasia - more common in females, age 30-50
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Treatment
medical therapy, percutaneous angioplasty + stent, surgical revascularization little or no benefit if therapy is late Le. kidney is already shrunken. However, therapy can be considered to save the opposite kidney if normal
Etiology
hypercoagulable states (e.g. nephrotic syndrome, especially membranous), ECF volume depletion, extrinsic compression of renal vein, significant trauma, malignancy (e.g. RCC), sickle cell clinical presentation determined by rapidity of occlusion and formation of collateral circulation acute: nausea/vomiting, flank pain, hematuria, elevated plasma LDH, rise in Cr, sudden rise in
proteinuria
chronic: increasing proteinuria and/or tubule dysfunction
Investigations
renal venography (gold standard), CI' or MR angiography, duplex Doppler U/S
Treatment
anticoagulation with heparin then warfarin (1 yr or indefinitely, depending on risk factors)
NP32 Nephrology
3. THROMBOTIC MICROANGIOPATHY
a spectrum which includes HUS, TTP, DIC, 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, corticosteroids (splenectomy and rituximab if refractory) avoid platelet transfusions and ASA
.... ..........
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4. SCLERODERMA
50% scleroderma patients have renal involvement (mild proteinuria, high Cr, HTN) histology: media thickened, "onion skin hypertrophy of small renal arteries, fibrinoid necrosis of afferent arterioles and glomeruli 10-15% scleroderma patients have a "scleroderma renal crisis": malignant liTN (usually within the first few years), ARF, microangiopathy, volume overload, visual changes, HTN encephalopathy renal involvement usually occurs early in the course of illness treatment BP control with ACEI slows progression of renal disease
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Nephrology NP33
Hypertensive Nephrosclerosis
Tabla 13. Chronic vs. Malignant Nephrosclerosis
Mlllipnt Nephl"llld_. Slow vascular sclerosis with ischemic changes affacting Fibrinoid namsis of arterioles, disn.,tion of vascular intralobular and all&rent arterioles endothelium Clinil:<ll Pll:lure African American, undllllyilg chronic kidllll'f disease, chronic hypertensive disease Uri111lpia Mid pnrtainuria. normal urine sedinant
Therapy
Blood pr8S$U18 control, frequent follow-up Can progress to renal fllilure despite patient adherence
Lower dBP tu 1Q0.1 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, 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
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
NP34 Nephrology
as well as investigations for renovascular HTN, additional tests may include 24-hour urinary estimations of Cr clearance and protein excretion imaging {U/S, CT, radionuclide scan) serology for collagen-vascular disease renal biopsy
Treatment
most chronic renal disease is irreversible, but treatment of HTN can slow the progression of renal insufficiency control ECF volume: Na restriction (88 mmol/day intake), diuretic, dialysis with end-stage disease ACE inhibitor and/or ARB may provide added benefit (monitor K and Cr)
Multiple Myeloma
futuiW of Mulliplll ,.,.._.
CARU
Calcium (elevated) Anemia llanlll Failure Lytic Bon l.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, can progress rapidly to kidney failure
oMIDD
deposits of monoclonal Ig in kidney, liver, heart and other organs mostly light chains (85-90%) causes nodular glomerulosclerosis (similar to diabetic nephropathy) lab features: increased BUN, 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, diffuse tubular obstruction chemotherapy (especially cisplatin): ATN or chronic TIN pelvic tumours/mets: post-renal failure secondary to obstruction 2 amyloidosis radiotherapy (radiation nephritis)
....
, ...----------------.
..... , .----------------.
Abnonnll Urine ACR Values from 20D8 Canadian Diabetes Association CPG > 2.0 m!Vmmol in males > Z.B m!Vmmol in f811111es
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; rapidly rising Cr, short duration ofDM family history of nondiabetic renal disease (e.g. PCKD, Alpert's) DIABETIC RENAL COMPLICATIONS
(Urine Prolllin)
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0 ---
fE
Time
1. Progressive Glomerulosclerosis
classic diabetic glomerular lesion: Kimmelstiel-WII.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) 2.0-20 mg/mmol in men (18-180 mgld), 2.8-28 mglmmol in women (25-250 mg/d) increased mesangial matrix stage 3 macroalbuminuria (>300 mgl24h); ACR in men >20 mglmmol, (> 180 mg/d); in women, ACR is >28 mg/mmol (>250 mg/d) clinically detectable proteinuria, +ve urine dipstick normalGFR very expanded mesangial matrix stage4 increased proteinuria (>500 mgl24hr) decreased GFR <20% glomerular filtration surface area present sclerosed glomeruli
....
,,
2. Accelerated Atherosclerosis
common finding decreased GFR may increase Angiotensin II production resulting in increased BP increased risk of ATN secondary to contrast media
3. Autonomic Neuropathy
affects bladder leading to functional obstruction and urinary retention residual urine promotes infection obstructive nephropathy
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4. 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.g. 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, rule out nondiabetic renal disease avoid unnecessary potential nephrotoxins (NSAIDs, aminoglycosides, dye studies)
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NP36 Nephrology
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011
dillllicl, ClrmlyiiCtirG IIQIIIISI. lhllrndlln: t.llln 50 mg 1'0 OO(t:Ud Ill doubled lflll4 Mlks) VI. pllcaho. a....: l'rinlly endpoilts ilcUied iblbli'G rl swn Ct ESRil, 01 dllth. S.Candlly lllldpoinll ilcbled IIIJIIIidily llld lllllltllj;yfmm CW CIUIBS. .....: incillnct rl doublng rl swn Cr {IUIZS\IIIId ESRD !RR but hid 110 1111 rilkof dlllll. Harllit IICIIIdllllt.t lllll'llullbil b BP cliqn abiL Slcoadlly 11'111 poi'dl- similr,lllhlllqlllt8 of hDijlitlilltion for hllrtfliU. WIS tignificlnttv lowarv.illl
!CCII.
*'
c:.lllian: LDIIflln carllfTid rnl benelils in patients will!. 2dilllleles 1111 118pi'Riplllly, IIIII was Qllllllll'{ WIII1Diarat8d.
Priorities in the Management of Patients with DM 1. vascular protection for all patients with diabetes ACEI, antiplatelet therapy (as indicated) BP control, glycemic control, lifestyle modification, lipid control 2. optimization ofBP in patients who are hypertensive treat according to hypertension guidelines 3. renal protection for DM patients with nephropathy (even in absence ofliTN) Type 1 DM: ACEI 2 DM: CrCl >60 mL/min: ACEI or ARB- CrCl <60 mL/min: ARB 2 line agents: nondihydropyridine calcium channel blockers (diltiazem, 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, usually stabilizes after 2-4 weeks, monitor for significant worsening of renal function or h!ferkalemia if >30% rise in serum Cr or hyperkalemia, discontinue medication and consider 2 line agent consider holding ACEI, ARB and/or diuretic with acute illness and in women before becoming pregnant consider referral to nephrologist if ACR >60 mg/mmol, eGFR <30 mUmin, progressive kidney function loss, unable to achieve BP targets or unable to stay on ACEI or ARB
........: To review
rlllay
llllierU willl Type I cilbetes no eftect on Gill was IMQd il the bNrmin diet group.
Signa and Symptoms often asymptomatic; discovered incidentally on imaging or by screening those with FHx acute abdominal flank pain/dull lumbar back pain hematuria (microscopic frequently initial sign, gross) nocturia (urinary concentrating defect) rarely extra-renal presentation (e.g. ruptured berry aneurysm, diverticulitis) HTN (increased renin due to focal compression ofintrarenal arteries by cysts) (60-75%) palpable kidneys Common Complications
urinary tract and cyst infections, HTN, CRF, nephrolithiasis (5-15%), 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- best accomplished by renal U/S (enlarged kidneys, multiple cysts throughout renal parenchyma, increased cortical thickness, splaying of renal calyces) cr abdo with contrast (for equivocal cases, occasionally reveals more cystic involvement) gene linkage analysis for PKD1 for asymptomatic carriers Cr, BUN, urine R&M (to assess for hematuria)
Nephrology NP37
Treatment goal: to preserve renal function by prevention and treatment of complications educate patient and family about disease, 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, ciprofloxacin: able to penetrate cyst walls, 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
Sita Dl Acciol
llick Df Loop Df Han Ia
IIIIICIIian
Doli!a
Advana EfllcCs
QO
Nl!ii(I2CI1Tinsport renal and VIISDdilltary lllhlc1s (Kloss; 1' Hsacretion; 1' Casxmdion)
lA ad111111 secandllry tD CHF, fu1111amida: Allarw in sLMB-1111siiMI individuals naplrrutic synd111ma, cinliDtic ascites; ada11111- zo.ao IVJIM/PD q&-Sh Elactrolytl abniiiTTIIIIitia; lrfpok*ni11, hyponatnmia, 1' fnle Wltar claarance in SIAIJIJ.induced (ITIIX 600 mlfd) until dsii!ld rtllipon118 lrfpocalcemi11, hypemllciLI'ia (with i1llne furmation) lrfponatremia), BP (less affiCtiv8 due tD Valuma deplltion with matabolic abiosis lfTN - 20-80 rngld PO 00/hid nrtaction) Pracipitmas ldtacks
.f
e.
1:1"
Tliazide Diurllica
hydrochloruthiazida (HCTZ) chlaruthillzide (Dilliltj (Lozule, Lozideltj matDiaz!llla (Zir=lyn., chlorthalidona (fWvton8) spi!IIRolllctona(AidiC!Dne] triamtlnlna([)yrlnium) amiloride (MUnorS)
In
1st lila fur eaantillllfTN Treatment Df edema Idiopathic hypert:alciuriaand stonea [ia.bataslnsipidus RII!Wcas K caused by other loss
fllamB/hyparvDIInia
HCTZ: ede11111- 25-100 00 lfTN -12.5-25 PO DO (m11X 50 rngld) 2&-200 mlfday Oil/bid dosing lfTN: 50-200 mlfday Oil/bid doling Hyparaldosteronism- 10[1.400 mlfday Oil/bid amilorida: &-10 DO
Hypok*nia I11C1181ed serum lillie levels PracipitDs gooty idtacks, hypacllllcenia EIMtdlipids Gklc011eintuiiJiliiCI Hyperkalemia (elUtion with ACE irilibi!Dr) TriamiiAinl can ba naphru!Dxic (rn) Neplrlllijhia Gyna1111111ia (IIS!rDgllic efltct Df spironollclonl)
Patnaillt-spalilg
SMni CHF.IICitea [iipironra:tuna), cystic fibrosis (amiIoride vilco&ity of secretions) Combina ACE-irilibitar fDr syrJIIII,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..Diii:O..I'IIIil:l
ltiC8TDI
UAII
To "- intnacrenial or jllii'IOcQjillr prassu111 NOIHillbsorilabla solutn incriiiSil osmDtic prassUrl Df filtratl MobilizllliDnDIIIKCISSfllid - 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
i
Na, oJ./1' IQ
ACB
Tissuas dillull81r
Pr-m
PO DD/Did
c..q.
Astllna Hyperkalamia A!pnulocyiDsis (captapril) Acute kidney injny
t ..
ARB
IOII8rtln (Comare) candasartan (AtiCind<tj irbesrrtan [Avap111., valsarttll(Diovan") !Wnisartan (ro.tcardisiiJ eprusartan (TMten., olmasartan [0.-runaciiJ aliskimn (llasitaze]
Vascular smoolh mllll:kl, adrenal inhiMor at1he qiotnin lfTN cortax, 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 .,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
Rlllin Altlpisa
antagonist
HTN
llliskimn 15!l-JOD
PO DD
Hyperkalemia
... ...
Nephrology NP39
Rlftnlce
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, BP, renal or cardiovascular events, or mortality and carries significant operative risks The ARB telrniser1lln and the ACEI enalaprilare etJllllly effective in slowing ranal function delarioralion in type 2 diabatas with mild to moderate hyp811Bnsion and aar1y naptropathy S1lnlard irrmunosuppresion therapy in ranal tnn;plant patients low dosetacrolimus is superior to cyclosporina and sirolifllls in reduction of acute rejection, rnainll!nance of ranallunction, 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. 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, 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. 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, MMF, steroids and low-dose tacrolifllls effectively maintail stable renal function following renal transplantation, without the nagativa Blfacts on renal function commonly reported for standard CNI regimens
BENEDICT
NEJM2004; 351:1941-1951
,6SIRAL
NEJM2009; 361:1953-62
DETAIL
NEJMZ004; 351:1952-61
ELITE
HEMO
NEJM2002; 347:2010-19
ROAD
JASN2001; 18:1889-1898
SYMPHONY
NEJMZ001; 357:2562-75
NP40 Nephrology
References
References
Adler SG, S.hmt DJ.(2003I. An au1tn8 aiSAIIItiiiiDpiCi in gtlmarullr 111d lr8llrrrmt for naphrology1Rina&L Amaril:ln Jaulllli of Killll'f lise-, Val 42: 3!5-418. Andreoli TE at Cecil Essentials of Medicine, 6111 ad. Saundlr Publisq Philllllllphia. Andi'D!Iue HJ. Mlliu NM. (1999]. Ma1111gement of ife threlterirG acid-base disorders pill I. WM. Vol. 338 !11: 2&-33. Andi'D!Iua HJ. Mllias NM. (1 999]. Mallllgamant of ill thraatarirQ acid-bela disordara pill II. NEJM. Val 338(21: 107-11. Andi'D!JU8 HJ. Mllias NE.(2Wll. HypoMtremia. Vol 342(201: 1483-1499, 1581-1589. 1lndl All, Bain SC,IIau1iir P, Klrllerv B. Madsllld S. Jerwll J. et II. AJ9o1nin-lleceplor Blockllde VIISU5 Converting.fnzyme Wilition in Type 2Diabe11s and Naplnap11hy, NEJM. Vol. 351(1t,1952-61. Bramar BM, Caopar ME, da Zaluw D. Kaine WF. Mitch WE, Blli.{2001l. Effac:tJ of IDArlln anlilnll Crial'lscul in l'ltiants with Type 21ilbatas111d
Nephropathy, NEJM, Vol. 345(121; 861-861. Churchill DN,Iilllcka PG, Jindal KK. TDII*lira EB, Gold ate in MB. (19991 CiMca1 pnctic8 tuillllilas lor initiatian al dialysis. Canadian Society of Nephrabgy. JAm SGc Nephrol; Vol. 10 S231H1. DanadioJII. GrandeJP.(2ll02). Medi:al J1119111: lgAnephropathy. NEJM. Vol. 347:738-748. Gabow PA. (1 9931. Aullllomal domin1nt di- NEJM. Vol. 329(51:332-342. Grerierg. Artlv. Primer on Kidney liseues. 3rd ed. San llego: Academic Pless, 2001. Hakim R.Limus M (1995].1niliBiion DfDi.._ JAm Soc NlplrGI, Vol&, 131S.13Z8. Hliperin Ml. GDidatain MB, KatsayR, llll (198111. Fluid, alactmlyla,and scidblsa pllysiDiogy: I problam.JIIsad IPJIRIICh, lrd ad. HarcourtBlaca & Co.: New Yort. Halperin M. Kimel K. (1998].1'atJssirm. The Lancet, Vol352: 13HO. Hns SB. MIIIIDr SJ. 2l111111n 8.(19981. NIW 1hl m111111g1m11nt of diab111s: aphysicilll's tuida. St.ring CormiUII for thllilvision Dfthl Ham ph ill RR at II. Rll\'iiW ai!IQQ !IRIII fliU.. http;l/lw.w.embblfcl)lllicr/Jflrf.html. Hudson BG. Trwii\Uon K, SundUimoorthy M. Nei111111 EG.(2ll031. Mechllilms of Disease: Alport's Synd!ame, Goodpaslire's Syndrome, lAd Type NCollagen. NEJM, Vol. 348: 2543-2556. John lUll CA. L8vey AS, Cor.h J, Levin A, Lau J, llcnoyln. G.(2ll041. CiMca1 pmcb clnrie di&eue in adults: Pill l Gbmarul fittmion rata, prulli11ria, ud ather rrartn. American Familyl'hysicillls. Johnson RJ. Ftahally J.lds Comprallnivl clinical naphrology. Mosby: Naw Yort. 100001 clinicallfiCiice Quidelnes lor clllanic disease: evalurlion, clmification, ud stRtlication: 2ll00 wcutive updale.http;lfwww. dDGVtdo!lilloc.htm Kalina WF. Gnllled E. (19991. Protairama. alilllrruril, rist USIISII!IInt, dBIIctian, elimination (I'ARA!lE): 1 pOiition pepar altha Nltio1llll Kidney Famdltion. A J mar Killis, Vol. 33[51: 1004-1010. Llwis EJ. Hunsicbl LG, l!llin RP. Rohda Tha Elllcts of AngiJtlnsii-Corrnrting Enl'l"la ..libition on liabatic NIJRapethy. NEJM. Vol. Mcfarllna P. lalla S. Houldan R, Hams S.(2ll031. Napllapalhy: Canadi1n Dilllllll Allocillian clinical prlctica tuidalinll axpart commit!IL Mtp//lw.w.diabltll.ct/ Mallzar, Sat al. (19!181. Clinicall'rlctice Guidalinll fol tha Managamant of Dilllllll in Canida. CMAJ.
Myn, A. Madici111141h ld. Baltimora: Wililma & 21)01. ONTARGET m.tigi!Dn. (2ll081 T*isnn, or bath in patients 111igh risk lomsculu IMII1li. NEJM, 358, 1547-59. Slbltina M.(2ll041. Pucket Melil;ina: Tba Ganaralllolpital Handbook of hlamal Madicina. 2nd ad. CllajQr 4. 1-21).
LippincllttWillau. &
Wlins. Schiftl H,Lang SM. Fischer R.(2ll021. Daily Hamodialysis and 1hl Outcome of Aaa Renal FaiU.. NEJM. Vol. 346{5t3DS.1D. Schreiber M. Samnara lor 3 clinical clsrkllan medicine: hyponatremia and hypamatramia. Dclallar 29, 2ll02. Smith, Kinsey. Renal Diseese: AConcl!plual ApJiroach. New Ywk: Cland1ill.ivingstone, 1987. Thldhani R,l'llscual M,llonwntra.Jil (1 9961. kuteranal fliU.. NEJM. Vol. 334(221:14481460.
Neurology
Mina Atia, Tara Rutin and Courtney Scott, chapter editors Doreen Ezeife and Nigel Tan, associate editors Steven Wong, EBM editor Dr. David Chan, staff editor
The Neurological Exam ................... 2 General Exam and Mental Status Cranial Nerves Exam Motor Exam Sensory Exam Coordination Exam and Gait Basic Anatomy Review ................... 4 Lumbar Puncture ........................ 7 Seizure Disorders and Epilepsy . . . . . . . . . . . . 8 Seizure Status Epilepticus Behavioural Neurology .................. 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 . . . . . . . . . . . . . . . . . . . 17 NEURO-OPHTHALMOLOGY Abnormalities of Vision .. 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 ............. 21 Abnormalities of Eye Movements ......... 22 Disorders of Lateral Gaze Internuclear Ophthalmoplegia (I NO) Diplopia Nystagmus Abnormalities of Pupils .. 23 Relative Afferent Pupillary Defect (RAPD) Horner's Syndrome Anisocoria Movement 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 .................. 29 Amyotrophic Lateral Sclerosis (ALS) Other Motor Neuron Diseases
Toronto Notes 2011
Peripheral Neuropathies . . . . . . . . . . . . . . . . . 30 Neuro-oncology ....................... 32 Paraneoplastic Syndrome Tumours of the Nervous System Neuromuscular Junction Diseases ......... 32 Clinical Approach Myasthenia Gravis (MG) Lambert-Eaton Myasthenic Syndrome (LEMS) Myopathies............................ 34 Clinical Approach Polymyositis/Dermatomyositis Myotonic Dystrophy Duchenne and Becker Muscular Dystrophy Cerebellar Disorders . . . . . . . . . . . . . . . . . . . . 35 Wernicke-Korsakoff Syndrome Cerebellar Ataxias Vertigo ............................... 36 Galt Disturbances ...................... 36 Pain Syndromes ........................ 36 Approach to Pain Syndromes Neuropathic Pain Tic Douloureux Postherpetic Neuralgia (PHN) Complex Regional Pain Syndromes (CRPS) Thalamic Pain (Dejerine Roussy Syndrome) Headache ............................. 39 Clinical Approach to Headaches Migraine Headaches Episodic Tension-Type Headache Chronic Tension-Type Headache Cluster Headache Sleep Disorders ........................ 42 Overview of Sleep Disturbances of Alertness and Sleep CNS Infections ......................... 44 Spinal Cord Syndromes ................. 44 Stroke ................................ 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) .. 49 Common Medications ................... 51 Landmark Neurology Trials............... 52 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Neurology Nl
N2 Neurology
Neurological
mental status: WC (AVPU scale, Glasgow Coma Scale) cognition: Folstcin Mini-Mental Status Exam (MMSE), clock drawing, frontal lobe testing (for perserveration) clock drawing: give patient a blank piece of paper and tell them to draw the face of a clock. put in all the numbers, and set the hands to 'ten after eleven'.
/5 /3 /5 /3 /2 /1 /3
/1
Place: Counlly, Province, City, Building. Floor lmmediilte Recall: 3 wnlated items
Spell 'WORLD' backwards or do Sarial7s
Delayed recall af previous 3 items Naming: Pen, Watch Repetition: 'No ifs, ands, or buts' 3-Step Command: "take this paper in your left hand, fuld it in half, and place it on the floor with your right hand." Read and obey: 'CLOSE YOUR EYES' Writing: Write afull sentence Copy:
/1
DI'IWing
TOTAL
/1 /30
Pentagons (1 0
Zbisecting!
....
----(_.,
CNIII with pupil1paring -Think vascular caus1s likl diabetic ophthalmoplagia CNIII with pupil involvement- Think
compressive lesions.
Caloric!WielQis
cows
Cold
Oppositll
WIII"TI1
Same
N4 Neurology
Sensory Exam
primary sensation spinothalamic tract: pain and temperature dorsal column: proprioception and vibration cortical sensation graphesthesia, stereognosis, extinction, 2 point discrimination
119,
Romberg Stable with eyes open and closed = normal Stable with eyes open, falls with eyes closed = +ve Romberg, suggesting loss of joint position sense Falls with eyes open and closed = cerebellar or vestibular syndromes
Medulla
1. Corticospinal tract 2. Lateral spinothalamic tract and spinotectal fibres 3. Decussation of medial lemniscus 4. Reticular fonnation 5. Nucleus of spinal tract of trigeminal (V) nerve (descending) 6. Spinal tract of trigeminal (V) nerve 7. Nucleus cuneatus B. Fasciculus cuneatus 9. Nucleus gracilis 1D. Fasciculus gracilis 11. Central canal 12. Arcuate fibres
Pons
1. Pontine nucleus 2. Abducens nerve fibres 3. Corticospinal tract and corticonuclear fibres 4. Medial lemniscus 5. Nucleus of facial (VII) nerve (motor) 6. Facial (VII) nerve fibres 7. Trigeminal (V) nerve fibres B. Nucleus of abducens (VI) nerve 9. Nucleus of spinal tract of trigeminal (V) nerve 1D. Lateral vestibular nucleus 11. Middle cerebellar peduncle 12. IV ventricle
Midbrain
1. Interpeduncular fossa 2. Occulomotor (1111 nerve fibres 3. Cerebral peduncle 4. Substantia nigra 5. Red nucleus 6. Edinger-westphal nuclei 7. Occulomotor (Ill) nucleus complex (motor) B. Medial lemniscus 9. Spinothalamic tract 1D. Central canal 11. Superior colliculus
'
Figure 1. Brainstem
Vermis
Flocculus Tonsils
Nodulus
Neurology NS
il matar cariJDI:
Alcill
\1 }
oJ
Axial muld"
4. Spi1Dihlllmic Tnct
Triguminal ganglion
. ]f0/-\ l
Thelanu \ ,
- \ It
V',
1\'
[ .....
'\.
,__
I
J face
SENGryi:Gitsx
rsgian
'\
1 Mediallemniscus
ttrigeminllllemniscus)
I 'f, Chillf
Figun 5. Discriminatin Touch Pltlway
!
o
Spinal triguminalrM:Iu
.s
0
e.:
..
Axial muld" l
. IJj
\!1
Alcill m111cl88
N6 Neurology
Sympathatic
1'oroDio
2011
Paruympathlllic
II
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 L34, L4-5, or L5.S1
inlnpacas.
\,
The volume of CSF removed during a lurnb11r puncture i& ruplsni&hed within
one hour.
.....
,..,
needle
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)
\,
RBC in tuba #1 > >#5 -1r8umatic tap RBC in tube #1
SAH
Condition
NORMAL INFECTIOUS Viral Infection
Colour
Cle.-
Proteil
<0.45 gil
Glucose
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
BIU:ta'iallnfaction
Decreased ( < 25% serum glc or <2.0 mmoi/L) llecraasad (usually <2.0-4.0 mmoi/L)
Granulomatoullnlection fun;jal)
<11XXlx1o'!L Lymphocyllls
N8 Neurology
11,
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
Classifieation
SeiZU111
UnpriiVOksd
...
I
Provoked
...
t.
I
...
I
Complex
...
...
Abet nee
Motor Sensory
Autonomic
Pwychiatric
...
Convulsive
...
I
Clonic
Tonic
+ +
Tonio-Cionic
Myoclonic
+ ...
Atonic
Etiology
idiopathic identifiable etiology: vascular, congenital, neurodegenerative or other neurologic disorders, neoplasm, trauma, childhood epilepsy syndromes, infection, metabolic, toxins, genetic cryptogenic
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
Neurology N9
complex (alteration of mood, memory, perception) forms: dJ5phasic, dysmnesic (deja vu), cognitive (disorientation of time sense), affective (fear, anger), illusions, structure hallucinations (music, scenes, taste, smells), epigastric fullness automatism (chewing, swallowing, lip-smacking, scratching, fumbling, running, disrobing, continuation of actions prior to decreased LOC) followed by distant staring unresponsiveness
Table &. Classic Factors Differentiating Seizure versa Syncope
"-{,
Complex partial s!ll1us can resemble ll:hizophnmia or pl'jl:hotic daprvuion.
....
Srii:OPB
Day
Upright, not recuntent Gradual
or motor plwnam111.
Aura
Colaur Duration lncoll:inanca
"-\.1
Dllfwentill DiltP*il of Connlslons Syncope, pseudoll8izurv,
hyperv8ntilatian. panic disordlr. 11A, hypoglycemia, movement disorder, alcoholic blackouts, mig111inn !confusional, verlebrabesilarl, narcolepsy (r;alapi8X'fl
Briuf or prolonged
Common Occurs in tonic-clonic or co1J111ex partial Common Common. tongue biting Common i1 absence or conlJiex partial Normal or Abnonnal
Past-ictal
Motllr ActMty Injury
Autumatilllll
"-\.,
....
EEG
Nota thllt frontal saiZIDI (raral can look. lib a puudasG!n WilD odd mo1Dr activity that may occur.
Trigg en Duration
Uncommon
Emotionel disturbance
Brief or prolonged
Synchronous. S181'8Dlypic. automatisms
May be prolonged
Opisthotonos, rigidity, forced eye closure, irragular axtnmity moVIITI8nts, shakilg heed, pelvic thrust crying
Motllr ActMty
l'ngncy I MUll TIIBIIIQIInicity of anticonwlunts due 1D increased risk of open neural tuba dafvct. Advisa patient pregnancy 1D take 5 mgfday of folic acid. Consider switching medicatio111.
Timing
Day or Night
May occur May occur
Spontaneous Dftan intsr-iclill di&chqas Increased
PhpiCIIInjury
lncoll:inanca llepraduction af Attac:k
....
.l------------------,
MinistJy of T111nsportation must be conllcted by law far Ill patients who have had auizurl. Patients will hiM
license suspended Llltil seizure free for
EEG
Prolldil
'l'wloleiBJres do IIIII
&month&.
Investigations
.... ,l------------------, ;
Antic--Ill Mlldi:ltiBraad spectrum (germalized from onsll and partial onset seizures): felb.mate, lamolrigina,lavelinlcebrm, nlfinamida, topinsmate, Wl)roate, zonisamide
'
evaluation of new onset seizures: history and physical, complete neurologic exam, CBC, electrolytes, FBG, calcium, magnesium, ESR, creatinine, urea, liver function tests, EEG, MRI (if suggestion of focal deficit, progression or >25 years of age)
Treatment
anticonvulsant& psychosocial issues: stigma of seizures, educate patient and family, advise of dangerous activities including driving, pregnancy issues surgical treatment if focal
Narrow spectrum {simple partial, complex partial and secondarily u-ndized 118izurl: clllbarnllz8pine, gabapenlin. laco11mide, oxcarblmpine, phanob.tlillll, ph1111ytuin. PfliUIIbelin,
primidone, tiagabine, vigabatrin
Abnncasaizurn (a type of gan8111lizad seizure): ethosuximide
Status Epilepticus
initial measures: ABCs, vitals, ECG, nasal 0 2, IV with NS, glucose 50 ml IY, thiamine 100 mg IY.EEG bloodwork: electrolytes, calcium, magnesium glucose, CBC, toxicology screen and alcohol level, anticonvulsant levels focused history general physical exam (once seizures controlled): LOC, vital signs, HEENT (tongue biting, papilledema), neck stiffness, signs of neurocutaneous disorders, decreased breath sounds, cardiac murmurs or arrhythmias, urinary incontinence, aphasia, motor exam
NIO Neurolo8Y
it,
Reflex asymmeby or unilatel'll Babinski aign may bs indicativa of afuc:all85ion.
Convulsive Seizure
Tf11111:115
Stllbll Epileptic
..._,,
.l-----------------,
l.ABCs
Kfvwr or meningismus
spib.wave compiiXIS.
4. Glucose 50 mliV
5. lor'IIZapam 0.1-2 (or Diazepam 10 mg IV over 2 mini
Lumbar Punc:ture with Gram stain and Treat pl'llllmptivllly with anliliotics
....
,.Jr-----------------, ,
20-59% of first EEG are positive in epilepsy, 59-92% of epilepsy is picked wilh repeated EEGs.
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
12h (Tihctay SE)
Behavioural Neurology
..M
Delirium is a medical emergency CBrT'finU significant risk of morbidity and mortality.
....
,,
Vacular
Subarachnoid hemormage
marbd variability,
Stroke/IIA
w.ctiDUI
Menilgitis Encephalitis Abscess TI'IUIIIIIic Difluse axonal shear, epidural hematoma, subdural hematoma
lP
LP;MRI CT wilh contrast (often ring enhancing lesion) CT (non-contrast) MRI ANA; ANCA; RF MRI Angiography CT (non-contrast) MRI
j'\.,
..M
Visual hallucilations more indicate organic diseas1.
Etiology of Delirium I WATCH DEATH lnfuctious Withdrawal from drugs Acute matabolic: dilllnlar Trauma
CNS pdlology Hypoxia
Autoimmune
Neapllltic
Mass eh:t/edema, hemorrhage, seizure Status epilepticus Todd's phenornanon Psychotic disorder, mood disorder, IIIXiaty disorder
Increased ICP Focal neurological signs Papiladema See Seizure Disorders andEpilepsy, NB No organic signs or svn.rtoms
Saizunl
PriiiiiiiY Psychilbic
EEG
No specific tests
Behavioural Neurology
Neurology Nil
Dementia
see Psychiatry. PSIS
Definition
an acquired, generalized and (usually) progressive impairment of cognitive function (i.e. memory, recall, orientation, language, abstraction, etc.) affects content. but not level of consciousness
Epidemiology
15% ofthose >65 years of age have dementia common etiologies: 60-SO% Alzheimer's Disease (AD); 10-20% vascular dementia <5% reversible: hypothyroid, normal pressure hydrocephalus (NPH), nutritional deficiencies, 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, beta-blockers, anticholinergics), heavy metals, hepatic or renal failure, Wilson's Disease, B12 deficiency, 1'/-.l.- glucose, 1'/.J.. cortisol, thyroid dysfunction, NPH, depression (pseudodementia), brain tumour, subdural hematoma must rule out delirium
History
geriatric giants incontinence/falls/polypharmacy memory and safety (wandering, leaving doors unlocked, leaving stove on, losing objects) behavioural (mood, anxiety, psychosis, suicidal ideation, personality changes, aggression) ADLs and IADLs cardiovascular, endocrine, neoplastic, renal alcohol, smoking OTCs, herbal remedies, medications (sedative hypnotics, antipsychotics, antidepressants, anticholinergics), compliance, accessibility history of vascular disease, history of head trauma collateral history is usually very helpful
ADLI "DEATH"
Dressing
IADU "SHAFT"
Shopping
Houubaping
Eating
Ambulating Toileting Hygiene
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, word lists, similarities, proverb) + Baycrest Neurocognitive Assessment
Investigations
depends on suspected etiologies (see Tables 9 and 10) CBC (note MCV for evidence of alcohol use), glucose, TSH, B12o RBC folate electrolytes, LFTs, renal function, lipids, serum calcium CThead MRI as indicated as clinically indicated- VDRL, HIY, ANA, anti-dsDNA, ANCA, ceruloplasmin, copper, cortisol, toxicology, 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. anorexia, pallor, SOB
Ftltigue
wills
N12 Neurolo8Y
Behavioural Neurolo8Y
Etiology
Primuy llegananrliVB
Allheiner's disease
Lewy body disease
Memory impairment Aphasia, apraxia, agnosia Hallucinations Parkinsonism Fluctuating Disinhibition, 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
(hulld injury)
MRI,SPECT
Huntington's, CJDJ
VQCUIIIr
dumunlia)
Endocrine (hypathyruid)
Space occupying lesion (chronic
hematoma)
Toxic (alcohol)
eNS vasculitis
Infectious
Chronic meningitis
LP + investigetions
Traumatic:
Diffuse axonal shear, epidural hematoma, &Ubdural hematoma SlE Mass effect/edema, hemorrhage, seillft Paraneoplastic
Neaplutic
4 A"lllllf IIIII D If AD
Anterograde amnesia
Aphasia ApiiiXil
Agnosia
Disturbance in uecutiva function
Behavioural Neurology
Neurology N13
pathology (although not necessarily specific for AD) gross pathology diffuse cortical atrophy, especially frontal, parietal, 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
cognitiveimpairment memory impairment for newly acquired information (early) deficits in language, abstract reasoning, 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; widening of cortical sulci SPECT: hypometabolism in temporal and parietal lobes
Treatment
acetylcholinesterase inhibitors have been shown to improve cognitive function donepezil rivastigmine (Exelon), galantamine (Reminyl) relative contraindications: bradycardia, arrhythmia, CHF, CAD, asthma, COPD, ulcers, 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 - although efficacy not proven ginkgo biloba Vit E (caution: >400 IU/day associated with excess mortality; Ievell evidence) symptomatic management low dose neuroleptic trazodone for sleep disturbance antidepressants
Prognosis
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
Nl4 Neurolo8Y
Behavioural Neurolo8Y
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.uctuation in cognition with progressive decline visual hallucinations parkinsonism repeated falls sensitivity to neuroleptic medications (develop rigidity, neuroleptic malignant syndrome, extrapyramidal symptoms) REM sleep disorder Treatment acetylcholinesterase inhibitors (e.g. donepezil) Prognosis typical survival3-6 years
Neurology NlS
Clinical Presentation sparadk CJD: rapidly progressive demenling illness causing death within months, associated
with myoclonus
cerebellar ataxia cxtrapyramidsl signs aldnelk mutism and cortical bUndness sometimes occur
fatalwlthinlyear EEG: triphasic compleus
Diagnosis
rule out treatable dementia, neurologic exam, EEG, MRI only wsr.y to confirm diagnosis is brain biopsy/autopsy
1\fpes
sparadk CJD: most common form (8596), 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, InJections (human growth hormone
products), electrodes
variant: earlier onset, more psychiatric symptoms, Longer duration, ab&ence of triphasic
.....
Prion prollins have 11 normll fonn and 111 irnc:lioua form. The inflctio1111orm iJ aln:nmally fDided and leads tD abnormal fDidina af no11111l prian pra1Ji111. Thae
aln:lrmally fDided prgteinIIVIII'8glllll
compleus on EEG (Le. Mad Cow disease) kuru: historically due to cannabalism in Papua New Guinea
panencephalopathic form: primarily seen in Japan, progresses over years Histopathology sponglform changes, astrocytosls and neuronal. loss occur sporadically Treatment no known treatment
A11DciWA!nxil af Damantia
h:DIIIilmce
Aphasia
Definition
-----------------------------------------------
\,
Th&laft: han. . . ia domir-.ntftw
an acquired disturbance of language characterized by errom in speech production, writing, comprehension. or reading
Neuroanatomy of Aphasia Broca's area (posterior inferior frontal lobe) involved in speech production (expressive) Wemick.e's area (posterior superior temporal. 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.culus association bundle connects Wernicke's and Broca's areas >9996 of right-banded people have left hemisphere language representation 7096 ofleft-handed people have left hemisphere language representation, 1596 have right hemisphere representation, and 15% have bilateral representation
Assessment of Language asseaament ofcontext handedness (writing, drawing, toothbrush. sdsllors) education level native language learning difficulties assessment for aphasia 1. spontaneous speech fluency paraphasia&: semantic ("cbm for "tablej, or phonemic ('"clable" for "table") 2. repetition 3.namlng 4. comprehension (auditory and reading) 5. writing 6. neologism&
W.micb's area: poetllrior apect af 1" tampan! IJYIUII
Nl6 Neurolo8Y
Behavioural Neurolo8Y
-t,
,u
Apbasilllocalizes 111e lesion to the dominant cerabral bemllpbare.
lllpalitian
Good Good Poor Good
Broca"
No...ftuent No...nuent
MaturTCA
1. Fronlllllobe watershed between MCA and ACA territories 2. \1\otita matter lesions deep to (1)
Combined sensory and motor tllnscortical Posterior infaior frontal lobe AND posterior superior temporal lobe
MixadTCA
Poor
Global
Wernicke"
Canduc:tion Scn.aryTCA
Alomic
Fluent
Good
Good
lt:A=T11llS4:Grlic:IIIPhasil
Prognosis
most recovery from stroke-related aphasia occurs in first three months, but may continue for >1 year with recovery, 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, ataxia, sensory loss, impaired comprehension, or inattention
Hemi1pheres Lalt
Right and left Right and left Right
!Ill merely tile illlbiily Ia canstruct. cRw, dresl.
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; combing one's hair Preparilg and mailing an envalope Copying afigure Dressing
specilil:llyla the inllbily Ia c.ryoutthe lelmed ..-nts iMJiwd in conslnrjjon, drMing, M11yskilll uida from plllliln naedad to canyiMthesaiiSb.
Agnosia
Definition
disorder in the recognition of the significance of sensory stimuli in the presence of intact sensation and naming
Neurology Nl7
Clinicopethologic:l Correl.tions
Tillie 13. AaDiils
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
... ' ,
Pariml '-ii!M Lssians of1he dominant Pllrietalloba n chnctlrizBd by Gamnlll!"a Syndro1111: acak:ulia, agraphia,. m;.r agnDBia, and lsft-right llsarianbdiDR. l.eliOM of1ha pwillll IDIIe are clwBI:IIrized by 11111111et. .,D81Jt1naaia. and cartical 1111n111ry lOIS.
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...l pen:eptian and inllct auditory IIICO(Jitian
tampa10-accipitll ragian
Anlaillr pll'ietal llbe in 1he llmsphere app01ita tha lffactad hind
Alllnlt_,.
Figar Aplasia
lnaiJiily to idediy objects by touch lnaiJiily to racagniza, 11111111, and pailt to Dial filga!s
llaminant hemisphara
''..,
msta. considrr rnailglring.
If 1111111mill il nlll: UlociiiiBd wi1h loa af
\.,
lf.lllmanrflsyndrorne ila conganitll dilordrr of ..,..,. and
hypoganiiiiDinlpil: hypogan..ilm.
SR
LJt
IR
'./'
10
\ JR
Mit
ii'
LR
..... SO
0 Shiny H. Lai Zllll&
Clinic:al Features E.lci!Macle ptosis, resting eye position is down s.nd out'" (depressed s.nd abducted), pupil dilated (mydriasis)
Common Lealona
midbrain: bilateral with contralateral pyramidal signs mydrlasls posterior commwlicating artery aneurysm: early mydrlasis then CNm palsy cavernous sinus (internal carotid aneurysm, meningioma, slnua thrombosis) ischemia ofCNIII (DM, temporal arteritis, HTN, atherosclerosis): pupil sparing
["\.,
Pupry cOMiril:blrfibiVII&re on lha par1ohalllllllpiCI: af CNIII au cornprlllion of the neml... to mydriQia while infan:lion (mr.cting canlnl of CIIUIII pupilllry
....
Jlii/fi----111
.....
',
L.eeions iRVGivilg tha C'8V8111DU8 liar1 111M pallliea of Ill. 1\f. Ill. V1 and V2 as Wflllas pain and proptosis.
IBid 1o
i
0
Nl8 Neurolo8Y
-"{.,
CN IV is the only mnill nerve that exits pcmaio!ly 111d cro111111 thu midlinu. A CN IV lesion may cause a con1nllateral
deficit.
..... ,
CN IV is at ri&k of 1rlluma during
CDUfM.
CN V: Trigeminal Nerve
Lesions trigeminal neuralgia, herpes zoster, cavernous sinus, orbital fissure, trauma. cerebellopontine angle tumours, demyelination, syringobulbia, metastatic infiltration of nerve, ipsilateral brainstem lesion, contralateral parietal lesion Trigeminal Neuralgia (Tic Douloureux) excruciating unilateral paroxysmal shooting "electricn pains in trigeminal root territory usually in V3 distribution V 1, V 2 normal sensory exam etiologies: idiopathic, compression by tortuous blood vessel (SCA), cerebellopontine angle tumour (5%), multiple sclerosis (5%) pain lasts seconds/minutes over days/weeks; remits for weeks/months triggers: touching face, eating, talking, cold wind, shaving, applying make-up F > M; usually middle-aged and elderly medical treatment carbamazepine; narcotics do not help if medical treatment fails (order increasingly invasive): gamma knife, invasive percutaneous denervation (radiofrequency/glycerol), percutaneous balloon microcompression, microvascular decompression rule out structural lesion, multiple sclerosis or vascular lesion with MRI
....
,,.)-----------------, ,
Forehlllld i15p11recl in a UMN CN VII lasion due to bilateral innervation from cerabral hemispheres.
Neurology Nl9
rt,
CN IX: Glossopharyngeal Nerve
Clinical Features sharp paroxy8l1l8l pain of posterior pha.rynx radlating to ear. triggered by swallowing taste dysfunction in posterior 113 oftongue
absent gag re:flex (dysphagia)
wt.IICI'IIIIi!g for th8 Prlll8nce D1 and - i n g rillk fill' IIPildian. tha p181811CB rJ I gllg raftM ia illlll'icillnt llltlur. the cornet tilt il1o DIIIIMI tha plltillll Ginldng WIQr !rum a. c:up a.nd IDDting for coughing. choking. or "wtlness" Df vaice.
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.
I'IIIUrD!Inmll, miiBibllll,
IIIIBDrrrj!llilil, meningitis lniaiiMI: strDU, demy11inlltion. IYrinaotutil, poliomyelilit. llllroeytuma Nadc trau11111, .urgary, tumour11
----t,
NDITIIII is inilillhld when lh IDIIfJI 1h1'8W1a bolus blt:lt
Mo1Dr ne1.1111 (e.g. Al.S) f'a1Dnl niiVI (a.g. GBSI NIUUIII&CUIIr junction (8.11- MG) Myapathv (a.g. DMfMI
by CN XII. Tha bolus slimuiiiiBs tha 10ft palal8 to slsva18 llld the bolu is dlllldlld into 1ha Of1IPiwynx. tt.c1: the
phlryngalll conslric1Dn cunnct, tha
Straka
TIDID.. Demyelination DlgenaretiCII
'-Ynx
Ha1111
Lawpilched
llld the weal conls clo11. SWIIowing diiPBnda on liferent inlarmllion vii CN V, IX, and X and mo1or action via CN v; VIL IX. X. and XII.
N20 Neurolo8Y
Low.ptched
Monotonous
DealiSCendo volume
Hyperkinetic
ChD1'8iform
Prolonged senlllnce segments intermixed with silences Variable, improper stn!ss
Bursting quality
Dystonic Slow speaking rate Prolonged individual phonemes
"Abbmiatians: ALS- amyrAJopliic lltllllscllrolis; GBS -Guillain-Bami l','lllroma; MG -llftllllhril gmis; IJ.l-dlnni!Dmyasitis; PM-polymyositis
NEURO-OPHTHALMOLOGY
Abnormalities of Vision Acute Visual Loss
ophthalmologic: acute angle closure glaucoma, vitreous hemorrhage, retinal detachment optic nerve: optic neuritis, anterior ischemic optic neuropathy (arteritic, non-arteritic), compression by space occupying lesion (e.g. aneurysm) vascular: TWamaurosis fugax, central retinal artery or vein occlusion, carotid-cavernous sinus fistula CNS: stroke, optic tract/chiasm lesion, migraine infectioD}inflammation: endophthalmitis
Optic Neuritis
see
......
---------------
If you ill'll8Cl the diagnolis of qiant cen arteritis do not wait for biopsy rasLJts. Beqin treatment immediatelyl
see also Optic Disc Edema, 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. RH17)
Amaurosis Fugax
see Qphthalmology. OP37 and Stroke section, N44
Neuro-Opbl:halmoloBf
Neurology N21
Plplllllml
AIDN
CIIVO
<50
llld cohu vision Pail (esp with eye
movanent}
Alrr
'mion
SynpiMs
If GCA: headache,
. .I
fii!IM
RAPD
!liC
if llllerior
RAPD No RAI'Il Pale llll!rnenllll diiC ad111111, Swollen diac, V8IIDUJ relilal Ct. flml 11191f98111R, retiMI hemanhages hlllllllhllge
Ghlll cell arteritis
Associated with vascUopathy
Etlalaal
Tralnlam
MS. vial
IV(ratcnl)
lnCI1!BSI!d ICP
one
Tf8Bimusa
Calsidar ASA I non..taritic; optimim risk factors.l8duce mrnids I arteritic lOP. :t laser
hemianopsia: loss ofhalfof the visual field homonymoWI: loss of either the right or left half of the visual field in both eyes bitemporal: loss of both temporal visual fields (lesion ofclrlasm) quadr.mtanopsJa: loss ofone quarter of the visual :field
BrTEMPORAL HEMIANOPSIA chiasmallesion in clilldren: craniopharyngioma In middle aged: pituitary mass in elderly: meningioma
HOMONYMOUS HEMIANOPSIA
retrochiasmallesion the more congruent. the more porterior the lesion check all hemiplegic patients fur ipsilateral homonymous hemianopsia (e.g. left hemisphere -+right visual field defect)
i Q
Figun 1&. Cherlll:telistic Visl Field Dlfecbi with 1.81iaas Alal!g the Viull Plthvny
N22 Neurology
Neuro-Ophthalmology
....
,,
A lesion in a cerebral hemisphere causes eyes to "look away" from the hemiplegia, and to look towards the lesion. A lesion in the brainstem causes the eyes to "look toward" the side of the hemiplegia, and to look away from the lesion.
Right {normal}
Clinical Features on gaze away from the side of the lesion: I) adduction ofipsilateral eye is impaired; 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, cataract, functional) Binocular cranial nerve palsy (see Cranial Nerves, N17) CN III (oculomotor) DM, aneurysm, tumour, 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,trauma CN VI (abducens) DM, tumour, trauma, raised ICP (false localizing sign) muscle Graves' ophthalmopathy neuromuscular junction myasthenia gravis (MG) (see Myasthenia Gravis, N32) other orbital trauma, tumour Wernicke's encephalopathy Miller-Fischer variant of GBS leptomeningial disease
Vergence {normal}
Shelley Wall 2003
11,
Diplopia worse at end of the day suggests myasthenia gravis {e.g. fatiguable}.
If only diplopia on extremes of gaze, cover each eye in isolation during extremes of gaze. The covered eye that makes the outermost image disappear is the one with pathology.
Neuro-Ophthalmology
Neurology N23
Nystagmus
definition: rapid. involuntary, 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, jerking, rotatory, coarse) or as normal vs.
pathological
Abnormalities of Pupils
Relative Afferent Pupillary Defect (RAPD) (Marcus-Gunn Pupil)
see also Ol!hthalmolop. OP33
Definition a fallure ofdirect pupillary responses 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, both pupils should constrict initially when normal side is illuminated. both pupils constrict
when damaged side is Illuminated, both pupils paradoxically dilate because the damaged
eye perceives less light relative to normal eye pupil reacts poorly to light. and better to accommodation
differential diagnosis
optic neuritis is the most common cause of RAPD other causes: optic nerve compression, large retinal detachment. central retinal artery/vein
ry....,_.
CGn81riction of
lllmulltad f10J8
----
N24 Neurology
Neuro-Ophtbalm.olOBY
1'oroDio
2011
Horner's Syndrome
Definition
..... '
H-' Sylllnne PIDIIil
lliollis
Anhydrasis
a sympathetic defect clinical features: partial ptosis (drooping eyelid), miosis (conrtricted pupil), anhydrosis (lack of sweating), and apparent enophthalmos lesions occur anywhere along the sympathetic pathway on the affected side 1st-order neuron (central): hypothalamus, medulla (brainstem stroke), spinal tumcnu; MS, intracranial tumoUIS, syringomyelia 2nd-order neuron (preganglionic): apical lung cancer (Pancoast's tumour), paravertebral mass, carotid artery dissection 3rd-order neuron (postganglionic): cluster headache, cavernous sinus IIlllli8, trauma (lncluding surgical) clinical confirmation with cocaine test cocaine does not dilate a miotic Homer's pupiL Cocaine blocks the reuptake of nora.dtenaline. which dJlates a normal pupil central vs. pre-ganglionic vs. post-ganglionic paredrine (hydraxyamphetamlne. stimulates noradrenaline release) will not dilate in a case of post-ganglionic lesion, 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.rvical u-I'Giion
.,
D
E
0
of Pupilary Dlatian
Anisocoria
clefiDltion: unequal size of the pupJls see Qphtha1moloo OP31
Movement Disorders
Neurology N25
Movement Disorders
Overview of Movement Disorders
Tabla , 6. Muvamant Disorder Definitions
Aladhisia Altlrilil
A1hltolis Subjective restlessness relieved by stereotypic movements (e.g. squinnilgl Loss of rruscle contraction (negative myodonusl Slow writhing movements, especially distally Slow ami/or small alflllilude movements Rapid jerky movarnentthat looks semipuposeful Excessive movements associated with neuroleptics Co-corrtnlction of and antagonists causing sustained twisting movements Episodes of halted mCJIDr action. aspacially cllrilg walking Unilateral violent flingir4 movement Briel muscle group contraction 1hat is either focal, segmental, or generalized Muscle quivering Acceleration of movements Stereotyped actions due to inner urge; can be suppressed Rhythmic alternating movements
....
,,
Bridyldniill
Charea
Dpldnllil
Dysblnil Free.dng
disordersl
[i.e. bradykinesia and freezingl
H1111iballism
Myoclonus Myukimil
Tachykini
TICS
....
,'
Tl'llllllr
Soma myoclonus is rtim!Ws sensitive and can be induced by noise, movement, light, vi11UIIl1hreat, or
pinprick.
PATltWAY
DIRECT
- --- -- --
N26 Neurology
Movement Disorders
',.l-------------------, '
In a young patient ( <45) must do TSH (thyroid disease), ceruloplasmin (Wilson's disease), and CT/MRI (cerebellar disease) as indicated by type of tremor.
11,
Alcohol dampens essential tremor. Alcohol potentiates intention tremor.
',..)-------------------. '
>90% of essential tremor does not need treatment.
Differential Diagnoses 1. Tremor: a. Postural: physiologic, anxiety, sedative/alcohol withdrawal, drug toxicity, heavy metal poisoning, carbon monoxide poisoning, thyrotoxicosis, benign essential tremor, cerebellar, Wilson's disease benign essential tremor is a common autosomal dominant trait that presents as a bilateral postural tremor of the vertical axis, especially in the upper extremities b. Intention: brainstem lesion, cerebellar lesion, alcohol, anticonvulsants, sedatives, Wilson's disease c. Resting: Parkinsonism, Wilson's disease, mercury poisoning
Table 17. Approach to Tremors
Resting Body Part Characteristics Worse with Associated Sx DDx Distal UE 3-7Hz pill rolling Rest while concentrating "TRAP" IPD, Parkinsonism, Wilson's disease Sinemet, anticholinergics, surgery, DBS Postural Uf/head/voice 612Hz fine tremor Sustained posture (outstretched arms}
Autosomal dominant FHX
Intention Anywhere <5Hz coarse tremor Finger to nose Cerebellar findings Cerebellar disorders, Wilson's disease, alcohol, MS Treat underlying cause
11,
Most common cause of chorea is drug therapy for Parkinson's disease.
Treabnent
2.Chorea: Huntington's disease, neuroacanthocytosis, SLE, APLA syndrome, Wilson's disease, cerebrovascular disease, tardive dyskinesia, senile chorea, Syndenham's chorea, pregnancy chorea 3.Dystonia a. Primary dystonia: familial, sporadic (torticollis, blepharospasm, writer's cramp) b. Dystonia-plus syndromes: dopa-responsive dystonia, myoclonus-dystonia c. Secondary dystonia: thalamotomy, stroke, CNS tumour, demyelination, PNS injury, drugs/toxins (L-dopa, neuroleptics, anticonvulsants, Mn, CO, cyanide, methanol) d. Heterodegenerative dystonias: Parkinsonian disorders, Wilson's disease, Huntington's disease 4.Tics a. Primary tic disorders: transient tic disorder, chronic tic disorder, Gilles de la Tourette, adult onset or senile b. Secondary tic disorders: encephalitis, CJD, Syndenham's chorea, head trauma, drugs, mental retardation syndromes c. Association with OCD and ADHD
Movement Disorders
Neurology N27
-----------------------------------
Etiology sporadic: combination of oxidative stress to dopaminergic neurons, environmental toxins (e.g. pesticides), accelerated aging, genetics famllial (10%): autosomal dominant a-synuclein mutations, autosomal recessive Parkin gene or DJ-1 gene mutation Ouvenile onset) .MPTP (neurotoxin) Pathophysiology loss of dopaminergic neurons in pars compacta of substantia nigra, 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, especially hands rigidity: lead-pipe hypertonus; cogwheeling due to superimposed tremor negative motor bradykinesia: slow small amplitude movements, difficulty initiating movement related findings: masked facies, hypophonia, aprosody (monotonous speech), dysarthria, micrographia, shuffling gait with decreased arm swing freezing: occurs with walking triggered by initiating stride or barriers/destinations, lasts seconds postural instability: late finding of falls, shuffling gait with acceleration and flexed body cognition: bradyphrenia (slow to think/respond), late finding of dementia behavioural: personality change, decreased spontaneous speech, depression, sleep disturbances,
anxiety
ley Pukionim
Ftur
TW
lllJIIIor Rigidity
....
,,
Conlldw an Alterllldve Dilgnasis If Atypical Parlcirwo.U.m Poor ruponu to Ldopa Abrupt onset of symptmns
Rapid progression Earlylalls Early autonomic dysfunction
disonln
Re1:ent diagnosis af psychiabic dillllsa History of encephalitis UnUSUII toxin axpDSUI'B ExUnsiv. tlliVII histDry
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; especially affects the striatum, leading to increased activity of the direct pathway and decreased activity of the indirect pathway
N28 Neurolo8Y
Epidemiology
Movement Disorders
North American prevalence 4-8/100,000 mean age of onset 35-44 years; but varies with degree of anticipation from 5-70
Signs and Symptoms
typical progression: insidious onset with clumsiness, fidgetiness, irritability progressing over 15 years to frank dementia, psychosis and chorea chorea: begins as movement of eyebrows and forehead, shrugging of shoulders, and parakinesia (pseudopurposeful movement to mask involuntary limb jerking) progresses to dance-like or ballism, and in late stage is replaced by dystonia and rigidity dementia: progressive memory impairment and loss of intellectual capacity mood changes: irritability, depression, anhedonia, impulsive, 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, 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, stress, emotions; relieved by sleep or specific tactile/proprioceptive stimuli ('geste antagoniste: e.g. 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.
local medical: botulinum toxin systemic medical: anticholinergics, muscle relaxants (Baclofen), benzodiazepines, antidopaminergics (reserpine, neuroleptics); dopamine for dopa-responsive dystonia surgical: surgical denervation of affected muscle, stereotaxic thalamotomy (unilateral dystonia), posteroventral pallidotomy
Tic Disorders
Clinical Classification
motortics simple: blinking, head jerking dystonic: bruxism, grinding teeth, abdominal tension, sustained mouth opening complex: copropraxia (obscene gestures), echopraxia (imitate gestures), throwing, touching vocal tics simple: blowing, coughing, grunting, throat clearing complex: coprolalia (shout obscenities), echolalia (repeat others' phrases), palilalia (repeat own phrases)
Treatment
dopamine blocker
Neurology N29
il'' inconllittlnt with ALS IW FilaSen110ry ax, predomirnnt p11in, bowel or bladder incontinence, cognitive
mllld& wallkm!H.
',
Denuvation on EMG Fibrillations, lhlrp wavas,
N30 Neurolo8Y
,, ,
DDx of M-neuropltllr Mljlipllll Vasculitis (e.g. PAN), OM, leprosy, ureoidosis, HIV.Iymphoma. Lvm- diMUI, pr8SIIn palsy predisposition (herediWy), multifocal motor neuropathy (pun motor), chronic inflammatory demyeli111.1ing polynauropllhy (ClOP).
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.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, idiopathic neuritis, tumour infiltration, radiation, thoracic outlet syndrome (i.e. cervical rib) lumbosacral plexopathy (rare, especially unilateral) DDx: idiopathic neuritis, infarction (i.e. diabetes), compression mononeuropatby: single nerve deficit carpal tunnel syndrome (most common): compression of median nerve at wrist symptoms: wrist pain, paresthesia first 3 digits, radiation to elbow, worse at night signs: Tinel's sign, thenar muscle wasting, 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}, median (at pronator teres), Saturday night palsy (radial nerve entrapment at spiral groove of humerus), obturator (from childbirth), peroneal (due to crossing legs or surgical positioning), 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.e. stocking-glove distribution}, hypotonia; progression of dysesthesia early, weakness later most polyneuropathies are due: to medical conditions like diabetes, renal disease:, substances, toxins, or are hereditary other important etiologies: SLE, mv; leprosy, alcohol, B12 deficiency, 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, IVIg, and asathioprine critical illness polyneuropathy associated with sepsis and multisystem organ failure; severe sensorimotor axonal neuropathy
Table 18. Diffarential Diagnosis of Symmetric Polyneuropathy Etiology+ V.Cul
..._,,
Dlabellc Neara,.dlles 1. Axonal (most common): pain> mDior 2. Autonomic: anhydrosis, onhcmatic hypotension, impotence, gaslroplnsis, bowel and blldd1r dysfunction 3. Mononeuropllthy multiplex: ll8MI
4. Cranial niURipelhy: CNIII (pupil sparing) > IV > VI
infarct or compression
..._', ..
DDx of o.r,.llnllting Ntluropllthy GBS, CIDP. paraprotBinemia. dipthlria, amiodarone, storage disaue.. prassura paiiJY predisposition. paraneoplaslic.
..._,,
Axonal neuropatllies hiiVI decr.ased
amplitude on NCS; dlll'll'(llinlling neuroplllhin hiiVI dlc11111Sed velocity on NCS.
----t,
should not be given to diabetic&. Sensory neuropattw of feet pr8Y8nt them from adequately compeiiSiting for lass of vestibular function.
ea...
Ischemic Ischemic Ischemic AxonaVdemyelination lnfillrative AxonaVdemyalination Demyelination Demyelination Clrunic Clrunic Ctronic Clrunic Clrunic Clrunic
Acute
Madlliliel
lmllltiptisee
PAN
SlE
RA
RH17 RH&
sae BtlllliTIIIIIllagy. RH9 see HIV serology Laprosy serology Nerve biopsy Lyme serology LP (1' protsin; no 1' cells) LP (1' protein)
HIV
Leprosy
Lyme Immune
GBS
CIDP
Ctronic
SAY!
Peripheral Neuropathies
Neurology N31
Maclllnism
AxonaVdamyalination AxonaVdemyelination AxonaVdemyelination Axonal Demyelination Axonal Axonal Axonal lschemio'axanal Axonal Axonal Axonal Axonal Axonal
Caune
Chronic Chronic Chronic Chronic Chronic
Modllitia
Hnditarr
Neaplallic
HMSN
Paraneoplastic
EtDH
Heavy metals Medications
Drug levels
Metabali:
Diabetes
Hypothyroidism Ranal hlikuu
Nlllrilionlll
Brz deficiency
Othllll'
Porphyria Amyloid
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
....
,,
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
2. Ataxia 3. Arvllexil
....
,,
N32 Neurolo8Y
Neuro-oncology
Paraneoplastic Syndromes
Definition
uncommon complication of cancer; often is the presenting complaint
Pathophysiology
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
Investigations
antibodies commonly ordered include anti-Hu, anti-Ri and anti-Yo
Treatment
unsatisfactory and often palliative. Options to consider are steroids, IVIg, plasmapheresis and treatment of malignancy
OculluAiulblr pamis
+
+ +
N
++(early)
.....
', ..
Limb WIIDISS
htiguablity
+ + + +
+ +
+
++
GISSx
SansarySx
Associated conditions
Rapatilivll EMG stimulatilll
Thymoma
"'
hyperplasia
autoimmune disorder
Epidemiology
bimodal age of onset - 20's (mostly women) and 60's (mostly men)
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
....
,, ,,
Investigations
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
....
Treatment
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
Prognosis
3096 eventual spontaneous remission
....
,,
Lambert-Eaton myas1hanic syndrome can be differentiated from myasthenia Qlllvis, by 1ha phenomenon of postexercise facilitlltion.
Investigations
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
N34 Neurolo8Y
Myopathiea
Myopathies
Clinical Approach to Muscle Diseases
Table 20. Myopathies
Etiology lnlllmmiiDry Polymyositis Mya[gies Pharyngeal involvement Mya[gias Similar to polymyositi& Characteri&tic r.&les Can be paraneoplastic
Ksr lnvatigations
1' CK Biopsy: endomesial Necrosis 1' CK Biopsy: parifasciculll' atrophy
....
',
rnsen.tion
Dermatomyositis
1' CK Biopsy: ilclusion bodias TSH, serum cortisol, calcium panel Toxicology Biopsy: selective loss of thick Myosin filaments
.....
',
Endoc:rin1
Thyroid (1' or -1-) Cushing's syndrome Parathyroid (1' or -1-) Medication Critical illness myopathy
.....
',
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, cramping, and myoglobumimria Episodic W8ilkness between attacks
wen-s
Legs: climbing slllirl, stand from sit Anna: n111ch above hlllld, wash hair
Becksr
Myotonic dystrophy
.....
',
Hereditary Mltlbolic
McArdle's
1' lactate 1' serurnturinary myoglobil Pllst-sxen:ise 1'cr-I-K Increased lactate Biopsy: ragged red fibres
Mitochandriil
Polymyositis/Dermatomyositis
see RH13
Myotonic Dystrophy
Etiology and Pathophysiology unstable trinucleotide repeat in DMK gene (protein kinase} at 19ql3.3 number of repeats correlates with severity of symptoms; autosomal dominant Epidemiology most common adult muscular dystrophy prevalence 3-5/100 000 Signs and Symptoms appearance: ptosis, bifacial weakness, frontal baldness {including women), triangular face giving a drooping/dull appearance
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; atrial arrhythmias) respiratory: hypoventilation 2 to muscle: weakness ocular: subcapsular cataracts, retinal degeneration, decreased intraocular pressure EMG: subclinical myotonia -long runs with declining frequency and amplitude
Cerebellar Disorders
Clinico-Anatomic Correlations vermis: trunk/gait ataxia cerebellar lobe (i.e. lateral): tremor, rebound phenomenon, dysarthria, dysdiadochokinesis, 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- elicit scanning/telegraphic/slurred speech on spontaneous speech (see Dysarthria, Nl9) ataxia: broad-based, uncoordinated, lurching gait dysmmetria: irregular placement ofvoluntary limb or ocular movement dysdiadochokinesis: unable to perform rapid alternating movements (e.g. pronationsupination task) postural instability: look for truncal ataxia on sitting (titubation =rhythmic rocking of trunk and head); look for difficult tandem gait and broad based gait intention tremor: elicit on finger-to-nose testing- typically orthogonal to intended movement, and increases as target is approached hypotonia: decreased resistance to passive muscular extension- 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, confusion, decreased EOM, 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. 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.g. Arnold-Chiari malformation, Dandy-Walker cysts) Hereditary Ataxias autosomal recesaive: includes Friedreich's ataxia, ataxia telangiectasia, vitamin E deficiency Friedreich's ataxia: prevalence 2/100 000; onset between 8 and 15 years signs: gait and limb ataxia, weakness, areflexia, extensor plantar reflex, impaired proprioception and vibration death in 10-20 years from cardiomyopathy or kyphoscoliotic pulmonary restriction autosomal dominant: spinocerebellar ataxias (SCA.s) of which 30 exist, most are CAG repeats
N36 Neurolo8Y
Acquired Ataxias neurodegeneration (e.g. multiple system atrophy) systemic: alcohol, celiac sprue, hypothyroidism, Wilson's, thiamine deficiency toxins: carbon monoxide, heavy metals, lithium, phenytonin, solvents vascular: infarct, bleed, basilar migraine autoimmune: MS, Miller-Fischer (GBS) children: tumours, post-viral
Vertigo
see Otolaryngology, OT12
Gait Disturbances
Approach to Gait Disturbances I. Length of stride if small paces - look at posture if stooped with no armswing- Parkinsonian gait look for other signs of extrapyramidal disorders if upright with exaggerated armswing - Marche a petit pas due to diffuse infarction of both cerebral hemispheres (lacunar)
r-t,
CENTRAL MOTOR SYSTEMS 3 compnnb tu til cantrol af pit 1. Pyramidal: main ouUiow from cor1ex to spinal cord 2. Extrapyramidal: bani ganglia inhibita BJa:llll mCMimanb; 3. Clrlblllum: afflcts coordination of
2. If normal stride length, look at width between feet if wide-based- ataxia if high stepping and positive Romberg- sensory ataxia loss of joint position sense (+ve Romberg) if wide based without high stepping - cerebellar ataxia veers to side of the lesion if scissoring of legs or toe walking- spastic gait bilateral circumduction due to spastic paraparesis from cerebral palsy, multiple sclerosis or cord compression 3. If normal width, look for height of step if high stepping bilaterally- bilateral foot drop if feet barely leave ground or disjointed movement - magnetic/apraxic gait frontal lobe pathology due to normal pressure hydrocephalus or cerebrovascular disease
4. If no high stepping, lookfor stabllity of pelvis if rotation of pelvis - waddling gait
6. If movement is elaborate and inconsistent, especially when being observed. conaicler functional pit rule out an odd gait due to chorea from Huntington's disease
Pain Syndromes
Approach to Pain Syndromes
...._,,
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. bypassing nociceptive pathways Spontaneous pain: unprovoked burning, shooting, or lancinating pain Paresthesiae: spontaneous or evoked abnormal nonpainful sensations (e.g. 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
Pain Syndromes
Neurology N37
Neuropathic Pain
Definition
pain resulting from a disturbance of the central or peripheral nervous system
Associated Issues
sleep difficulty anxiety/stress/mood alteration sexual dysfunction
Treatment pharmacotherapy: TCA. SNRI, anticonvulsant, long acting opiate, topical lidocaine, capsaicin
cream, intrathecal opioid or clonidine, Botox, nerve block surgical therapies: dorsal column neurostimulator, DBS (thalamus) other therapies: neuropsychiatry - cognitive behavioural theraphy, psychotherapy rehabilitation - physiotherapy CAM - acupuncture, meditation, massage therapy, TCM
Epidemiology
10-15% of all patients with cutaneous herpes zoster >80% of herpes zoster infected patients >80 years old
N38 Neurolo8Y
Pain Syndromes
Signs and Symptoms types of pain: constant deep ache or burning. intermittent spontaneous lancinating/jabbing pain, allodynia distribution: thoracic > trigeminal > cervical > lumbar > sacral Treatment acute herpes zoster early treatment with antiviral agents (acyclovir; longer-acting famciclovir and valaciclovir more effective) may prevent PHN in patients over 50 years PHN medical: TCA, pregabalin, gabapentin, opiate, lidocaine patch, intrathecal methylprednisolone surgical: spinal tractotomy, dorsal root entry zone lesion
Thalamic Pain (Dejerina Roussy Syndrome) - -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)
Headache
Neurology N39
a.lllliaal cmc.J Eumilllllign: O.llil Pllilnt wilb 11Hdde .... a..,. Nllll
JWA 2006; 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, pupils (symmetry), fundi (papilledema, retinal hemorrhages), pronator drift, meningismus, deep tendon reflexes and Babinski, gait indications for a new-onset headache, worst headache of life, thunderclap headache, headache with worrisome symptoms (fever, meningismus, altered LOC, focal neurologic deficits, trauma, papilledema, morning headache) if CT is negative but suspicion of SAH or meningitis, perform a lumbar puncture
N......,
nnmanic: p-
Dnltlil!lllillllwilb ........... The most of..- for dilgnosing nipile i$ .urrrrm.d by 11-. P(Utling
'*"
u-
a - 4inl1ion of 4-72
UnilideriiiOCIIion
cr
..............,
ThaiR far dafiW or polllil1i n-i11111inl dill!jlllllii VlrillwM!I U.lllmblr rlfiiUM pr8I8IE Mdl 3111d feiW U.Llls ... 24 {1.5-3181. 3.5 {1.3-9.2111111 0.41 {0.32-0.521 TllpiC1ivltf. Dnlllil , . . .... h...... IIIII
Clustar <1%
20-40
70%
15-40 F>M Nona Bilateral frontal MinLIII!s-days lndual; worse in PM Band-like; constant Mild-modarata Depression
Anxiety
Aga of Ollllt
SexBia Family HistaiY
M>F
+++
Uniateral>bilateral Fronto-tenwal Haurs-days Gradual; 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. haurs
l.ocatiCII
Dul'llion Onset/CGune
The prawlence rl ii'Uicllnill pllllology {!111111 problliiitylwrias lnlll011 v.1lh dlronic helldldle 1he plellllence is l.l'J. {0.77-1.11\).ln Ylll niglint-typl lllldlclw the prMiince is Howavll. inlhose prasal1ing wi1h new lllldlclw the prMiince is 32'Jo in 1hose jiiUidiiQ Ylilll t!UIIIarcllp hlllldlchl the prMimct is 43\ {211-611\). Ill th8le dilllrant popullbs. 110 clinical flllfln was found lo hlllllful inlllivJ imcrlrill pethoQ in a 1118111iniiUMYHawM!. -a indivi!UI c1inicll IIU.ns Will luund 1o 1xt ]IIICictive of lignili:lnt petholoQr.
c:QI8r-tp haadache
abnonnlllraJroiDQicll1111111
111ddneli-typl hlldlch1
Duality
Severity Pravoldng
IQUIMbld
EtOH
Noise Hunger Slaap deprivation Pallating Rest No vomiting No photophobia Muscle tension i'1 Non1)harmacological Psychological counseling Physical modalities (e.g. heat, massage) Phannacological Simple analgesics Tricyclic antidepressants
Walking around
ARoc:iltad Sx
Red watery eve Nasal congestion or rhinoi'Thea Unilateral Homer's Red watery eye, rhinorrhea Eyaid !hop
Acute Rx Oz Sumatriptan (IIIISII or injection) Prophylaxis Verapamil Lithium Methylsergide Pnmisolone
headache;
Pllysicll Signs
MIRII!IIdllnt
fl-.
Te11poral Arteritis <<1% >60 No bias Ten'flOIBI Variable Variable Tt.-obbing Variable; can be severe
<1%
Any age
No bias Generalized; stiff neck Variable Meningitis: oours-days SAH: thunderclap onset Variable S8\111'8
Snfty
N40 Neurolo8Y
Headache
lnci'IIISid
Lying down Valsalva H81ldlow Exertion Standing/sitting
Pressure
Tempol'll Arllrilis
PrCMIIcing
Head movement
Pllllilting
Associltld Sx
Rest and
Neck stiffness
.....
',
Etialagy
Photophobia
Nausel/vomiling Focal neuro Sx DecriiiiSad lewl of consciousness Focal neuro Sx Pupilledeme CTJMRI and treat appropriatl!ly See also Neurosuroerv. NSS
Polymyalgia rheumatica
Jaw/tongue claucication
Visual loss
artery change&: Finn. nodular, incompressible Tender
Dura
Pretlisone
See also Rheumatology. RH17
Meningitis, SAH
(GCA)
Headaches with serious risk to life or function subarachnoid hemorrhage (SAH), meningitis, herniation (from space-occupying lesion),
temporal arteritis, venous sinus thrombosis
Migraine Headaches
Definition (common migraine) <?:5 attacks fulfilling each of the following criteria
4-72 h duration 2 of the following: unilateral, pulsating, moderate-severe (interfers with daily activity), aggravated by routine phy5ical activity 1 of the following: nausea/vomiting, photophobia/phonophobia/osmophobia
1hB 01111 contracapliva pill il con1rlindicmd with complicat.d migraine due to risk of stroke.
Epidemiology
18% females, 6% males; frequency decreases with age {especially at menopause)
.....
',
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, sleep excess/deprivation, drugs (estrogen, nitroglycerin), hormonal changes, caffeine withdrawal, chocolate, tyramines (e.g. red wine), nitrites (e.g. processed meats) auras are felt to be due to a wave of excitation/depression leading to the symptoms experienced in an aura (e.g. visual symptoms due to wave through occipital cortex)
Headache
Neurology N41
Phi!R:IIIGgiell'h................ !'lin 2002; 91:241-51 lludr. dll!lbii-IJind, pilctillctanrollld IItTs of piwn'abgc 1nltment of lade mignrine rl1111de!ati.! to IIMII i1llnily {21,022 pllilla in 1111111. Dllllllhdilll: Nunarrl patients, iiDiirG ..gm., dutdl of lludy IIIII liming or \ypll rlresc:ue medication. M:omes inc:bled heldac:l!e ...Wat 111111 2holn, ITeedorn frgm plin II 2 tan, IJiflilld fllilffor 24 botn.llld lflm1l llffildJ will*l24 baurs. Mlin lids; Dill Will Millila for I Dill medicDns, 2ilbanml melbtions,llld IUbcullnlous FGr IIA 11lilf d 211. 111 intelwrmans wm ellectiw u:ept CftgG!4'. wi111NNTIIII1gi11Qfrom2.0for lll1lltripiM 6mg s.eto 5.41arnmiptM2.5 mg. The l:iwestlf for 0111 madi:atian -2.6 far UilripiM IIJl mg. For prilllll pain 1111111211. ttw lilwllt NNT 2.11ar IUI'I1atriplln 6 mg I.C, Mhlla IDMt NNT for 0111 madi:atian beilg 3.1 far RizlllriptJn 10 mg. For susllined 11!111- 24b NNT r111ged fTom U
ellec:ts cauld 1111 be 1111md IVSflntilaly. There W8l'll no drug-11Hirug complrilanl.
llffilctivt. Subcutnauslll11llriptln IIIII IIIII 1riptn- 1111111 llllctivt.
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: - basilar-type migraine (occipital headache with diplopia, vertigo, ataxia, and altered level of consciousness) - hemiplegiclhemisensory migraine - ophthalmoplegic migraine acephalgic migraine (aka migraine equivalent): aura without headache
Management
avoid triggers mild to moderate migraine treatment 1st line treatment: NSAIDS - ASA, ibuprofen, naproxen moderate to severe migraine treatment triptans (most effective), ergots (dihydroergotamine, DHE), Tylenol #3 migraine prophylaxis: anticonvulsant& (divalproex, topiramate), TCA (amitryptiline, nortriptyline), propranolol, SHT antagonists (methylsergide), calcium channel blocker (verapamil)
Cenclian:
!Mrl' most
lrellllnenl$ were
.....
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. Su:a: SlivBrlllin SO at l.l'llc:tice p11111181ar:
{1111 evidence t.ed ,....,. Nartqy 200);
Evidance-1111811
55:754-63
-----------------------
Diagnostic Criteria 1. average headache frequency of more than 15 days per month for more than 6 months fulfilling
the following criteria 2. at least 2 of the following pain characteristics a. pressing/tightening (nonpulsating) quality b. mild or moderate intensity (may inhibit but does not prohibit activities) c. bilateral location d no aggravation from climbing stairs or similar routine physical activity 3. both of the following a. no vomiting b. no more than one of the following: nausea, photophobia, or phonophobia 4. secondary headache types not suggested or confirmed
Cluster Headache
Diagnostic Criteria 1. at least five attacks fulfilling criteria 2 to 4 below
2. severe unilateral, supraorbital and/or temporal pain lasting 15 to 180 minutes (untreated) 3. headache associated with ipsilateral (to pain): conjunctival injection or lacrimation, nasal congestion or rhinorrhea, facial sweating, miosis or ptosis, eyelid edema, restlessness/agitation 4. not attributed to another disorder
N42 Neurolo8Y
Sleep Disorders
Sleep Disorders
,, ,
................
1. 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),located in the anterior hypothalamus, receives afferents from the retina and possibly from the lateral geniculate body; it projects not only to other hypothalamic nuclei, but also to the basal forebrain, thalamus, and periaquaductal gray Sleep Stages Stage 1: 50% of alpha waves get replaced by theta waves (4-7 Hz), slow rolling eye movements, high muscle tone Stage 2: vertex K complexes, beta waves (> 13 Hz), and high voltage (positive and negative) discharges with spindles on EEG; eye movement is still; high muscle tone Stage 3 and 4 (Delta sleep): slow wave (<2 Hz) but high voltage activity on EEG, still eye movements, low muscle tone, increased GH release, decrease in BP/HR/CO/RR Rapid Eye Movement (REM) sleep: mixed frequencies on EEG with low voltage and sawtooth waves, rapid eye movements, muscle paralysis, cholinergic brain state, dreaming
2. Slaap debt of somnogens {possibly adanosina) Iiiii wi1h tina spent awaka
,, ,
3 Cablgur!R of DyaDIIIJiilla 1. lnlrinsic sleep disorders 2. Exbinsic aeap disorde.-. 3. Circadian llllllllld disordn
Coma see
NS35
....
,..,
Alcohol shorten& llaap latency and promotes drowsiness. but I&ads to poor sleep mainteniiiCe duma second half olllnp.
Insomnia defi.oition: subjective complaint of poor sleep quality, non-restorative categoriea sleep onset: diffi.culty falling asleep; rule out disordered breathing, restless leg syndrome, and anxiety maintenance: waking up; rule out intrinsic sleep disorder with sleep study sleep offset: early morning awakening; rule out depression or disordered breathing non-restorative sleep differential diagnosis primary insomnia psychophysiologic hyperarousal from efforts to fall asleep - treatment: improve sleep hygiene sleep state misperception: normal sleep demonstrated despite complaint of poor sleep idiopathic insomnia - treatment: benzodiazepine receptor agonists or heterocyclic antidepressants sleep apnea - obstructive sleep apnea: refer to Respirology. R32 - central sleep apnea: no effort to breath over 10 seconds - DDx: heart failure, syringobulbia, lateral medullary syndrome, brainstem dysfunction restless leg syndrome (RLS) and periodic limb movement disorder (PLMD) - RLS: unpleasant sensations creeping along leg leads to need to move legs leading to problems with sleep initiation - PLMD: repetitive leg movements in sleep, 90% of RLS - DDx: spasticity; radiculopathy. neuropathy. pregnancy; alcohol, iron deficiency - treatment: iron supplement. dopamine agonist l-2h prior to bed secondary insomnia poor sleep hygiene transient situation: associated with major life change or stressful event - resolves on its own secondary to psychiatric disorders (80% ofpsychiatric patients) - depression has been shown to be associated with short REM latency secondary to neurologic disorders - examples: dementia, Parkinson's disease, hemiballism, Huntington's disease, atlantoaxial subluxation, myotonic dystrophy secondary to drugs/toxins - examples: caffeine, alcohol, nicotine, amphetamines, cocaine, antidepressants, glucocorticoids, sedative (withdrawal of night), arsenic, copper, lead, mercury fatal familial insomnia: rare degenerative prion disease of increasing sleep - onset insomnia leading to death within 7 to 13 months - associated symptoms: fever, excess salivation, sweating others: environmental, altitude (lower FI02 )
Sleep Disorders
Neurology N43
Narcolepsy irresistible desire to sleep in inappropriate circumstances and places clinical features: cataplexy, sleep paralysis (unable to move upon wakening for 2-3 minutes), 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, prevalence 1:2000, onset in adolescence/early adult symptoms can become less troublesome with age but it is a life-long disorder etiology: post head injury, multiple sclerosis, hypothalamic tumours; rarely familial diagnosis: based on clinical history+ EEG findings of REM in <15 min of sleep onset; seen on 2/4 naps during a multiple sleep latency test
....
', ',
Cltlplexy: brief episodes of muscle p111111y$is in 181PDfll8 IXJ exceA emotion (l.g. lllll!lhDrl.
....
htllophyW!agy
treatment
lifestyle modification ("cat naps) can occassionally be effective management on their own; certain activities are restricted (e.g. driving) modafinal (non-amphetamine stimulant) amphetamines avoided because of their propensity for habituation selegilene (metabolized in part to amphetamine), is a stimulant that also reduces cataplexy symptoms. others: moxindol, pemoline, 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, amnesia treatment: self-limiting, diazepam confusional drunkneas: partial arousal from slow wave sleep associated with confusion and startling, resistance to being consoled, and appearance of being awake aggravated by napping in narcolepsy, stress/anxiety, fever, excess exercise, night terror predominantly in children somnambulism: sleep walking (ranges from sitting up in bed to violent sleep behaviour) 1-15% of population, with greatest frequency in childhood clinical presentation: agitation, automatisms, walkinglrunning, completion of complex tasks, verbalization, open eyes, choreiform movements, enuresis, difficult to arouse associated with fever, sleep deprivation, sleep apnea, urinary retention, external noise, medications increases the risk of psychoneurosis in adults, but not in children. night terror: abrupt awakening associated with fear and autonomic stimulation in children (ages 2 to 4), resolves by adolescence clinical presentation: child awakes suddenly, sits up in bed and screams, eyes open, dilated pupils, sympathetic activity, increased muscle tone, child is not consolable, agitation, vocalizations, enuresis different from other slow wave sleep arousals, night terrors can occur at any time of the night associated with fever, bladder distention, sleep deprivation, medications Circadian Abnormalities familial advanced sleep phase syndrome autosomal dominant condition of early morning awakening (i.e. "morning larksu) pathophysiology: codon mutation of Per gene leads to a 4 hours advance of sleep, 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. injurious behaviour during sleep 2. movement associated with dreaming state 3. at least 1 of: potentially harmful behaviours in sleep acting out dreams disruption of sleep due to activities 4. polysomnograph shows: excess chin tone on EMG and/or excess chin or limb twitching on EMG 1 of: excess limb/body jerking, injurious behaviours, no epileptic activity rule out psychiatric or other sleep disorders
....
'..._---------------, ,
Slow WBVe sleep arousal is 11$50Cillted with confusion and amiiBiia; REM sleep aroUSBI is IISSIICimd wilh rapid awekanilg 111d vivid draam recan.
N44 Neurolo8Y
fibromyalgia: associated with pain, nonrefreshing sleep, fatigue, muscle tenderness and trigger points
CNS Infections
see Infectious Diseases, ID6
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
Thrombotic
Embolic
lntnlcnbral
Subarachnoid
Subdural/Epidural
Approach to Stroke
Initial AslleiSDleDt Goals 1. Has the patient had a stroke? 2. Is the patient a candidate for tPA? Onset: time when last known to be awake and symptoms free Mimics to rule out: post-ictal, hypoglycemia, systemic infection, tumours, conversion disorder
Stroke
Neurology N45
Assessment NIH Stroke Scale (NIHSS- see sidebar) applies mainly to MCA territory CT signs of acute stroke loss of cortical white-grey differentiation sulcal effacement (i.e. 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, lentiform, insula, internal capsule, MCA 1, 2, 3, 4, 5, 6 Treatment if no hemorrhage on cr and there is a clinical indication, tPA may be offered to the patient within the appropriate time limits (see Emergency Medicine, ER38 for more tPA details)
....
,.l------------------, ,
31 Motor systam
41 Sensory system 5ll.angUIIge abiities Scoring (l!/421: O=no stroke H=mild stroke 5-15=moderate stroklil 1520=moderate to 111verutroke 21-42=18111118 stroke tPA should be considered if scoru 6 or greater.
Stroke Syndromes
Stroke Syndromes According to Vascular Territory ACA: contralateral paresis and sensory loss, 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, Broca's (expressive) aphasia (if in dominant hemisphere) inferior division: contralateral homonymous hemianopsia (esp. inferiorly), contralateral agraphesthesia and astereognosis, anosognosia, contralateral neglect, Wernicke's (receptive) aphasia (if in dominant hemisphere) Internal carotid: premonitory TIA or transient monocular blindness (amaurosis fugax), asymptomatic or similar to MCA occlusion PCA: contralateral homonymous hemianopsia (especially superiorly), midbrain findings (vertical gaze palsy, CN III palsy, INO), occipital findings (anomia, alexia without agraphia, visual agnosia) ifbilateral: cortical blindness or prosopagnosia Basilar artery proximal (usually thrombosis) occlusion: CN VI palsy, impaired horizontal EOM impairment, vertical nystagmus, reactive myosis, hemi- or quadriplegia, coma, locked-in syndrome distal (usually embolic) occlusion (aka Top of the Basilar Sydrome): decreased LOC, CN III palsy, decerebrate or decorticate posturing PICA (Lateral Medullary or Wallenburg Syndrome): ipsilateral ataxia, ipsilateral Homer's, ipsilateral facial sensory loss, contralateral limb impairment of pain and temperature, nystagmus, vertigo, NN, dysphagia, dysarthria, hiccup Lacunar Infarcts (basal ganglia, thalamus, posterior limb internal capsule) pure motor hemiparesis: contralateral arm, leg, and face pure sensory loss: hemisensory loss (usually thalamic) ataxic hemiparesis: ipsilateral ataxia and leg paresis dysarthria-clumsy hand syndrome: dysarthria, facial weakness, dysphagia, mild hand weakness and clumsiness
.....
,_._________________ ,
Cerebralnnos..us thrombosis should be considered in the differential diagnosis of stroke and headache. It is an uncommon cause of either, but iSIIUOCiK!Bd with high morbidity and morllllity. Patients often present with headache alone, but can also have seizures, focal neurological deficits, or cranial narva plllsies. MRI with gadolinium is the bast diagnostic t11st. Treatment is typically anticoagulation with heparin initially, than llansition to
Wllfllm.
Ischemic Stroke
Etiology thrombosis: stepwise deficits, preceded by TIAs embolus: abrupt onset, no warning TIA, maximal at onset, multifocal if cardiac origin, seizure more likely Conditions Associated with Increased Risk of Cerebral Ischemia 'VUcular disorders: atherosclerosis, vasculitis, SLE, syphilis, AIDS, carotid or vertebral dissection, drug abuse (cocaine, amphetamines, heroin), migraines, venous or sinus thrombosis, lacunar infarcts (due to chronic HTN) cardiac disorders: mural thrombus, rheumatic heart disease, arrhythmia. endocarditis, mitral valve prolapse, prosthetic heart valves hematologic disorders: thrombocytosis, polycythemia. sickle cell disease, leukocytosis, hypercoagulable states
....
,_._________________, ,
N46 Neurolo8Y
Stroke
......
t-----------------,
,
,
Hemorrhagic Stroke
Etiology
intraurebral (ICH): hypertensive, amyloid angiopathy, or other cause subarachnoid (SAH): aneurysm, AVM, or other cause epidural/subdural hematoma
......
t-----------------,
Investigations
bloodwork: CBC, ESR, VDRL, serum glucose, 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
Vartabrobasilar insufficiency dua stenosis associated with left arm 1118 causing vertigo, headaches, left arm daudication.
Hypertensive Stroke
Etiology
BP above upper limit of autoregulation of cerebral blood flow (normal is 150-200 mmHg), chronic HTN, acute HTN chronic HTN stimulates cerebral blood vessels causing adaptive changes like hyalinization and lipidosis to preserve the blood-brain barrier. 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, focal neural Sx, NN, visual disturbances and change in WC due to microinfarctions and petechial hemorrhages pathology: hemorrhages occur from rupture of damaged blood vessels, likely at the site of Charcot-Bouchard aneurysms most common sites: putamen, thalamus, cerebellum, and pons
.....
, ,t-----------------,
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), corticosteroids for vasogenic edema
NULf 1995; 333:1581-7 Study: lllndanilld, d!IIHI-illnd, pabocunbaled lrill(3 month Pllilllt: &24 plli8llls (llllllllag& 76 y, 58'JI. man. 65\ v.tiltl Mill iscllenic: slrolce rl reced onset, IIIII IIIIINidlncB rl inlnlmllilll bllllliiiiNga an Cl Excmians inckllld hx rl racant linD or racant 11J'Q81r. SBP=1B5,1111'=110. DISAH, racant Gl or GU lllmorrhage, lliBifl v.rilli anlll rl
Treatment of Stroke
A. ACUTE STROKE MANAGEMENT
Goals
ensure medical stability limit or prevent neuronal death
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 6.4% of patients had a symptomatic intracerebral hemorrhage (0.6% 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, benefits of rt-PA were sustained at 12 months
340:1781-71.
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)
....
',
Anticoagulation
Thrombolytic
Endwrectomy
Carotid Stanalis
TIA Cardiac Carotid or
noncamprauibla silll, sBP >185, dBP >110,aggressiveRx to d8CI'88Sa BP. uncontroUad serum glucose,1hrombacytopenia, PMH ICH, Sx of SAIVparicllldiliili/'MI, pregnant.
Alllollllll Cantraindicltio to tPA Improving Sx. minor Sx, hemorrhage or mns an CT. high INR or aPTT, uizln at &troks annt, 111cent ITllljar &llfllllry or tnluma, recent Gl or urinaty hamonhaga, recant LP or arterial punctu11111t
+ (carotidl
StralaHHvalulion
Strob
Antiplltelet:
o
o
....
+
+ (carotidl
',
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.PAI for ischemic stroke within 3h of stroke onset Get 24h CT to 1\10 ICH. Also aptian of intra-erterial tPA for specific dinical silliBtians
Rlllti11 contrlindicltion to tPA Early signs of I111Q8 cnbral inflllrc;tion, NIHSS >22. resistant HlN, >85, Hx AVM or ansury&m.
Carotid Endartereclllmy: 50-99% stenosis with law risk of periapellltive death or disabling strDks
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. renal failure, aortic dissection, sBP above 220 mmHg. 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
....
,,
BP llllllt be lowered to sBP < 185 and dBP < 11 0 before IPA is given.
,.._
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, then treat accordingly lower temperature if febrile
-----------------
carotid endarterectomy benefits those with symptomatic severe stenosis (70-99%), and is less beneficial for those with symptomatic moderate stenosis (50-69%), see Neurosw:w:y. NS21
Asymptomatic Carotid Bruit
suggests the presence of atherosclerotic stenosis and signifies increased risk for both cerebral and myocardial infarction modify risk factors, antiplatelet therapy if stenosis >60%, risk of stroke is 2% per year; carotid endarterectomy reduces the risk of stroke by 1% per year (but 5% risk of complications)
Hypertension primary prevention
'-dllge.111d 110 clair ildicllions lor, 111 CGIIIIU!dicdons ID, heparin 111 aspiin. lnl!rvenlion: Hlll111e patients- IIOI:IIed ldraclianlllcl hl,.m 15000 ar 12,500 Rl bidL IIJid hd- -lllaCitBd baplrin; Similllly, hill wn llloCIIBd :m mg daily. 1M pllilnls wn lllllomly ID riCIM apirin, hlplrin, halh, Cllllllilllar. o.th Mthin IMYMb, ud dlltll ar deplndiiiC:y It 6manllll. blalll: FGr ba1ll hepllil vs. 110 heparin and aspiril vs.110 lll'iill. lher8 WISIIO 'aniiCIIt diffniCI in d8l1h Ill ZwnQ. or dNth dlpendlncy 116 manllll. Bath aspirin and bupuiHIIaCitBd pllilabi hid raaDII ilchumic lfnlbl \'lithil 14 days, aflsll byalimila'-lilld i.._. in hlllllllllllgic lllab il t!ae M,lrin. Afflr llljlltmeol fw prudielld ]RQIIIIIil, liltJ 8ipirin gnllp I decrelled list of delllll 01 depellllence d 6111rils 1141* 1000 18wir, p=D.ll31. Canlbin: TheiST IUIIQIIIJ thlt 11piin slaJid be lllftad inrnednly llftaollle onset rl ilch8mic
llnlb.
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)
N48 Neurolo8Y
Stroke
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; clopidogrel) are reserved for those who suffer cerebrovascular symptoms while on ASA warfarin is generally reserved for specific indications in stroke prevention, dissection, cardiac!atrial fibrillation, venous thrombosis
RRR (MC!J
CVmomity Al-c:IUIIII rn!ltlly
100 fC!]
evm.
TNIImaotwMh llllliprillWdUCid the rill: of IIIW (3A piiRII'IIvs. 4.1 piii'CIIII; 11ft 0.&8; Clldlsla1: 1n lilts atliah rilkfor ClldwasaW mri1ri reU:ed !be risk rA slroke. as wd II oii'411W MID and 01'81111 mor111ty,
Hypercholesterolemia primary prevention statins reduce the risk of stroke in patients with CAD or at high risk for cardiovascular events, even with normal cholesterol (CARE study) secondary prevention more evidence is needed for high-risk patients with symptomatic cerebrovascular disease, 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, 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
Stroke Rehabilitation
individualized based on severity and nature of impairment; 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, splints or bracing vocational rehabilitation
....
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,I1lljorC011111ryMIIIS,IIId lklusa Tnlltlly ill pelilnts llliPICUII5 yaw risk rJ CUftlllllryhelrtdi-e.
Neurology N49
l!
""
c
I ,.
::J
Progressive
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, inflammation, and necrosis Acute Disseminated Encephalomyelitis (ADEM): monophasic demyelinating disorder with multifocal neurologic symptoms seen mainly in children often following infection or vaccination
Etiology
genetic polygenetic: the HLA-DR2 gene has been demonstrated to be a genetically susceptible area. 30% concordance for monozygotic twins, 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, in particular an association with EBV has been found
Epidemiology
onset 17-35, 3F:1M, 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, new gadolinium enhancing lesion 3 months later, or new T2lesions > 1 month after first attack Dissemination in Space: clinical evidence of 2 or more lesions; or three of [1 gadolinium enhancing or 9 T2lesions], [1 infratentoriallesion], [1 juxtacorticallesion], [3 periventricular lesions]
Features symptoms in order of frequency: fatigue, depression, numbness, weakness, visual disturbance, bladder dysfunction, spasticity, impaired gait, cognitive disturbance, 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. intention tremor) symptoms not commonly found in MS: visual field defects, aphasia, apraxia, progressive hemiparesis
.....
,,
Investigations
MRI: demyelinating plaques appear as hyperintense lesions on T2 weighted MRI, with active lesions showing enhancement with gadolinium typical locations: periventricular, corpus callosum, cerebellar peduncles, brainstem, juxta cortical region, and dorslateral spinal cord Dawson's fingers: periventricular lesions extending superiorly into corpus callosum CSF: oligoclonal bands in 90%, increased IgG concetration evoked potentials (visua1Jauditory/somatosensory): delayed but well-preserved wave forms
N50 Neurolo8Y
.............................
,.lllial:
Aaltllllt. D.a,iq c-.ian llflbllftl E.-lllblliplllc:ln* Codnle Brtllllse Sytt Rer 2008; 2:Cil005218. SlUr. Coclme rjSllmltic !Miw. 2 RtT and qulli.ftct 1160 pilieals with fiest ridarnywlrm wilh lnin MRI (cliicllly ilolllled syndromes, CS).
plabo. (No IIIJpraprilll glllinrnlr ICitllllrilll W8llllaurJ).
11116: Apooled odds 111iD (OR) rl 0.53 [(5\ Cl 0.10.71, p<D.Wll)forpatilllts an fNV811US It one M'O odds ndiowu 0.52 (95\, D.llll.71l, Tbara
1llllmlntCIIdlliy prog181si011
Treatment acute treatment: methylprednisolone 500-1000 mg IV daily X 3-7 days taper diseue modifying therapy (DMT): interferon-beta (Betaseron, Avonex, RebW), glatiramer acetate (Copaxone) and natalizumab (Tysabri) CIS: early treatment with Avonex may delay potential second attack RRMS: DMT reduces rate of relapse by 30%; attacks shorter and less severe SPMS: interferon-beta may slow progression PPMS: immusuppressant therapy (e.g. Methotrexate) symptomatic treabnent spasticity: baclofen, tizanidine, dantrolene, benzodiazepine bladder dysfunction: oxybutynin pain: TCA, carbamazepine, gabapentin fatigue: amantidine, modafinil, methylphenidate education and coUD8eling: MS society, support groups, psychosocial issues Prognosis good prognostic indicators: female, young, RRMS, presenting with optic neuritis, low burden of disease on initial MRI, low rate of relapse early in disease PPMS: poor prognosis, higher rates of disability, poor response to therapy
Al:tioWCI
TriiiBNU18
IIDiiiiJI
Carbidopa 25 ml)'levodopa 100 mg PO 1id Maxinum 200 mg carbidopa and 2000 mg levodupa per day
Canlrlildicatiuns
N51UW-Ingle glaucoma. use of MAO inhibitor
Side Ellecll
Nausea, hypotension, hlllklcillllions, dyt;kinesias in last 14 days, hiSIOry of melanoma or undiagnosed skin lesions Hypotension. 1111usea. dizziness, constiplllion. diarrllea, vomiting, abdominal cramps, headache, nasal congestion, chwsiness, halklcinations Headache, insomnia, dizziness, nausea, dry mouth, hallucinlllions, confusion, orthostlllic hypotension, increased akinesia. risk of hypertensive crisis with tyramine-containing foods Nausea, diarrllea. abdominal cramps, increased periistalsis, increased salivation, increased bronchial seavtions, miosis, diaphoresis, muscle cRimps, fascicullllions, muscle weakness Dizziness, senurtion of hlllll. hypertllnsiva aisis, disease. peripheral vascular disease, coronary artery vasospasm, cardiac anest. nausea, vomHing, headache, hyposalivation, drowsiness Coronary artery vasospasm, transient myocardial ischemia, myocardial infarction. vtntricular tachyclldia, vantricU&r fibrilllllion. May caue significant rebound headache CNS disturbances (drowsiness, headache, unsteadiness, dizziness!, 1111usea/vomiting, skin rash, anamia Nausea, dianhea, insomnia, muscle cRimps, fillip, and anorexia Injection II!ICiions. injection site necrosis. flu-like symptoms (fever, chills, myalgia) tend to decrease overtime Transient drowsiness. daytime sedation, dizziness, Makness. fatip, convulsions, hypotonia, hypersensitivity to donepszil or to piperidine
Dupwine ptVCUr&llr
Dop511ine agonist
bromucriptine
P!lrlodeP
Partanson's Disease
Concomitant use of potent inhibitors of CYP3A4, uncontrolled hypertension, ischemic heart disease, peripheral vascular disease. Caution with renal or hepatic diseil5e Concomitant use of meperidine or tricyclic IIIJiid8pniiiSanl8
J
... ...
C)
MAOBimibitor
selegiline
EldepryP
SmgPObid
Partanson's Disease
MAOBimibitor
pyridostigmine
Mestinon111
Myastlllllia Gravis
Gl or GU obstruction
Triptlm
surnatriptan
Mi!Jlline
Ergot
dihydroergotamine
Mig
ran'
Hemiplegiclbasilar migraine, ischemic heert disease; cnl!rovascdar disease. uncontroled hypertension. use of in past 24 hours, use of MAO inhibitor in last 14 days, SMre hepatic disease Hemiplegiclbasilar migraine, higiKiose ASA therapy, uncontrolled hypertension, ischemic heart disease, peripheral vascular disease, IIIMII8 hepatic or ranal dysfmction, use of triptans in last 24 hours; use of MAO inhibHors in last 14 days Hisllly d bone llllllllW depression, hepatic disease, hypersensitivity to the drug, or known sensitivity to tricyclic compounds such as Hypersensitivity to dunepezil or 1o piperidine derivatives Pregnancy, hypersensitivity to nllllnl or recombinant interferon beta Hypersensitivity 1o baclofen (Spinal Cord lnjlry)
Migraine
Anticonvulsn
carbamazepile
Tegrr!Die
[Carbatrol.
EpitolinUSAI Cholinesterue lnhibHor donepszil
Epilepsy- partial :!: 2" generalillltion; ganeralizlld tonic-i:lonic Mild to moderatll Alzheimer's Oisease, Lewy Body Disease Relapsing.&mitting and Secondary Progressive Mulitple Sclerosis Spasticity (i.e. MS)
I
ll:l
5mg PO OD, may increase to 10mg PO OD altar 4-6 Meks Betaseron111 0.25 mg (8 MU) SC every other day
lmmunomodulator
interferon bet&-, b
baclolen
Lioresall
derivatives
Antispasmodic Anticholingergic oxybutynin clbide Ditropen111 SmgPObid neurogeric bladder or reftex neurogenic bladder Glaucoma, Gl obstruction, megacolon, severe rnylsthenia pis, obstructive uroplllhy, hypersensitivity to Cllybutinin Headache, pain, dry mouth. constiplllion, urinllrV retention, diarrhea, nausea. dyspepsia, dizziness
l
...
N52 Neurolo8Y
Refei'IIICI
NEJM 1991; 7:445-53 NEJM 1995; 333:1581-7 NEJM 2008; 359:1317-29 NEJM 2008; 359:1238-51 NEJM 2006; 355:549-59 NEJM 2001; 345:311-8
Results
Patienl1 with sy111:1tama1ic cellllid stenosis of 71}.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 4.5 hours of aculll ischemic strokB
References
Bnil Dlllh Wjdicu EF. Tha
Br11in Dallth. NFJM 2001; 344116): 1215-21.
ea.
Blidayasiri R, Waters MF. Gila CC 12005). Neurological dillarill dillgllOiis: a prioritized IPIIfDlCh. M1111clllletles: Blactwel Publisliing. pp.712. Kaaper II. hnvald E. lUi AS. HM1181 Sl. LDrQo DL. Jamalltlll JL.Ids 12005). Harrison's inlllmll medicioa, 16th ldition. TGIOI11D: McGtaw-Hill pp. 162&-30. C1111111an Prasanting !'.on1111illll Blidayasiri R, Waters MF. Gila CC 12005). Neurological dillarill dillgllOiis: a prioritized ljlpiOICh. MISSicl'llletles: Blactwel Publisliing, pp. 12-13,
H8ldlchl
Amblti BK. Slmh WT, Azer-Benlsilnov MT 120011. Residents manull of medicine. Hamilton: BC Declalr, pp. 211-13. Carpenter CCJ, Gri!IIIS RC. Losc:alill J. eds 120011. Cecil Essentials ci metile. 5th edition. Viii! Saunders Ca. pp. 97U. FeTri FF 12001 1'rlelical to lila c1111 medical plllient St Ur.is: Mabsy Inc. pp. 654-656. NOKWOrlllv Jlll!Jcdinetli C. Rodri!Ja M. Weilshe!U BG. t.Uiiple sclerosis. NEJM 2000; 343l131: 938-52. Dlak MJ, ad (2005). t.Uiipluclerosis: lllialagy, dilgnasis, and newtrt811Nnt 111111gits. New Jersev: Humana Prea Inc, 3640, 57, 131, 22223. Slllllllls MA. Feslil SK. eds DHice ]IIICiice of niiiiUIDgy. 2nd dian. Plillldei!Da: Else\lier Sc:iell:e. pp. 410-11. Palmln CH, ltlinglil SC. dan ll. Filippi M. Harlq HP, Kappas I, IIIII. Dilgnasli: critmia far multiple sclllr111is: 2005 ravilianstothe "Mcllanlld Crilaril". Ann Naurol 2005 Dac;58t6l:840-6. Parsistant V8ga1ativa State II. hnvald E. Fu:i AS, HIUSel' Sl. lDrQo DL. Jamelltlll JL. eds 12005). Harrison's rl internal medil:ine, 16th edition. TGIOI11D: McGtaw-Hill pp. 1625.
Sc--
2004;
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llizlnlallld Efilaply Amblti BK. Slri1h WT, MT 12001). Rlllidilnts manull of medicine. Hamilton: BC Declalr, pp. 203mi. Ferri FF 1200n 1'rlelical !ollie care lithe medical plllient St Ur.is: Mobiy Inc. pp. 617-9. Carpen!Br CCJ, Gri!IIIS RC. Losc:alill J. ads (2001). Cacil Essentials ci rnlliciie. 5th edition. Viii! Saundln Co, pp. 95U4. Griggs RC Cecil EsSIIIIials of Mldicine7th Edition Andraall CaTpenr. Griggs, Barjllrjn. Saundi!S EI18Vill pp 1120-41.
IMitul E,ilptic lcMtanstlii Dll Ailrldgl BK. Statuupllplicus. NEJM 1998;338114):970-6. Spinal CGrd .,.._ W.Ur R, Jarjodll A. Naurulogie Spill! t:Qid l'j!JIIllllllll. Enlll'g Med Cfric North Arraica1897; I513): 69&-711.
S1llb lildsay K. Bane L. 2003 Neu10bgy and 1Jstr1ted. Cluchii.Ningstone p. 244. Fnmllnl W, Silver J. (20021 Eslllnlills of Physical Mliiciia and lllhebililllian. Philldllphia: Hlriay and Beluslnc., p. 171-782. Drganimd Qatiellllstroke 111i1j care lor stroke (Stroke Unnrialis11' Colllbora1ian). The Coclme Da!Bbne ci Systematic Reviews2001; IBie 3. Johnston SC, RIIIIIMII PM, MN, Gills MF. Bkins JS, Bamrlllin Allll al. Validlliln IIIII raiDrnant of scarasto p!lldict vary 111rt, stroke risk llftar
EpiiiPIJ
N...,....cPain
Cllvnic Pain- APrimary Guile to l'nlctical Mlnag...rt. Nlw JllrWf. llnna111 Praa. p. 111-28.
Willal'sDIII
Aminal! MJ. Graenb1111 1:\\ Simon RP.I.ai9: Clnical 61h lditian. TGIOI11D: Mcllllw-llill Campania, Inc. pp. 254-56. 1ilardars Motor Syslam Marshlll FJ. Cecil Essentials ol Medicine 7111 <ianAndreoli, Carpenter, Griggs, Benjanin. Salrlders BseWer pp 1090-100. Dlllllllil Patler1011 C. Feighlner JW, Garcia A, GY. MacKnight C, Sadolmick AD. Diagnosis and 1relllmelll ol dementia: 1. Risk assessment and primary prevention ci Alzhllimardil8u8. CMAJ. 2008 Fab 26;178151:548-S&.Reviaw. Feldman Hll Jacava C. Robilard A. Garcil A. Chow t Berrie M, et al and 1relllmelll rl dementia: 2. Diagnosis. CMAJ. 2008 Mardi 25; 118(7):825-36.
Review.
and l'rMIIilll....,.lltiC Nualgia: An CIINII rilk llcl1n ullfll il ciical 'ractil:l? CD811 PG. Sc:utt F, Lllldlllm-Gr&llll Mlit al. Chi]J!er 24 Nuak9:11sarders Yamada KA. AMdlllll S. The Washington Mlnualci Madi:al Tharspllllics, 3111 Edition. UppincDI W.ms rnl WAins J1P 531534.