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XP-13 Nephrology Toronto Xotcs 2023

Common Medications

Table 19. Common Medications in Nephrology

Classification Examples Site of Action Mechanism of Action

(Secondary Effect)

Indication Dosing Adverse Effects

Na <K 72CI-transport trenal Management oledema

and peripheral vasodllalory secondary to CHf.

effects (K'

loss:t H'secretion: nephrotic syndrome.

» Cat'excretion) cirrhotic ascites;

t free water clearance

(eg.in SIADKinduccd

hyponatremia).

*

BP

(less effective due to

short action)

loop Diuretics furoscmide (Lasix *

)

bumctanide (8umer< 7

Burner 1

)

ethacrynate (EdecrinJ)

torsemide (Demader!

)

Thick ascending

limb olloop of

Henle

forosemide:

edema:20-80 mgIV/IM/PO q6 8h

(mar 600 mg/d) until desired

response

NTH:20- 80 mg/dP0 once daily/

BIO dosing

Allergy in sulfa- sensitive

individuals

Electrolyte abnormalities;

hypokalemia,

hyponatremia,

hypocalcemia.

hypercalciuria (with stone

formation)

Volume depletion with

metabolic alkalosis

Precipilales goul attacks

Hypokalemia

Increased serum urate

levels

Precipitates gout attacks,

hypercalcemia

Elevated lipids

Glucose intolerance

Inhibit Na /CI -transporter (K '

loss; t H«- secretion;

*

Ca!'

ercrelion)

Distal convoluted

tubule

Thiaiidc Diuretics hydioclilorolhiande 1st line lor essential HCI2:

IHCI2)

chlorothiazide (Diuril 1

)

indapamide (LCMOI

Loaide

melolazone (Zaroiolyn')

chlorthalidone

(Hygrolon-)

Potassium-Sparing spironolactone

(Aldactonc '

)

triamterene (Dyrcnium'

)

amiloride (Midamor 1

)

edema:25-100 mg P0 once daily

HTH:12.5-25 mg P0 once daily

(mar SO mg/d)

nephrolilhiasis/hypercalciuria:

25 100 mg once daily

HIN

treatment of edema

Idiopathic

hypercalciuria and

stones

Diabetes insipidus

(nephrogenic)

Cortical collecting

dud(« Na'

reabsorption)

Aldosterone antagonist

(spironolactone)

Block Na channels (triamterene Edema /hypervolemia

and amiloride)

Seduces K'loss caused spironolactone:25-200 mg/d once Hyperkalemia (caution

with ACEl)

Triamterene can be

nephrotoxic (rare)

Hyperaldosteronism:100-400 mg/d Nephrolithiasis

once daily/BIO dosing

amiloride:edema/HTH:5 10 mg P0 effect of spironolactone)

once daily

Diuretics daily/BIO dosing

H1H: 50- 200 mg/d once daily/BIO

dosing

by other diuretics

Severe CHF,ascites

(spironolactone),

cystic fibrosis

(amiloride » viscosity

of secretions)

Gynecomastia (estrogenic

Combination olACEl and thiazide Combine K'

-sparing

have a synergistic effect drug with thiazide lo

reduce hypokalemia

Combination

Agents

Dyazide - (triamterene

- HCI2)

Aldadazide -

(spironolaclone

’

HCIZ)

Moduietlc ' (amiloride

* HCIZ)

Vaseretic'5 (enalaptil

- HCIZ)

Zestorctic® (lisinopril

•HCIZ)

mannitol (Osmitrol :

)

glycerol

Osmotic Diuretics Renal tubules

(proximal and

collecting dud)

Hon-reabsorbable solutes

increase osmotic pressure of

glomerular filtrate -inhibits

reabsorption of water and

t urinary excretionol toxic

material

Inhibits angiotension converting HTN

enzyme,preventing formation Cardioprotective

of angiotensinII

Prevents angiotensin It

vasoconslriding vascular

smooth muscle net

vasodilation » BP

Prevents angiotensin It

mediated aldosterone release

horn adrenal cortex and action

on proximalrenal tubules

-»

*

Na+ and HiO excretion

* *

BP

Reduces fibrosis and

atherogenesis

Competitive inhibitor atthe

angiotensin It receptor:prevents Cardioprotective

angiotensin llvasoconslriding elfeds

action on vascular smooth

muscle •»

*

8P

Prevents angiotensin It

mediated aldosterone release

horn adrenal cortex and action

on proximalrenal tubules -*

t

Ha*

and H20 excretion

Inhibits renin production and

activity

Cardioprotective and

renopiotedivc abilities being

evaluated

lo « intracranial or

intraocular pressure

Mobilization of excess

fluid in renal failure or

edematous stales

mannitol:

*

ICP:0.25-2 g/kg IV over 30-60

Transient volume

expansion

Electrolyte abnormalities

|t/t Nrr. aft K '|

urea min

ramipril:HTN:2.5-20 mg POonce

daily/BIO dosing

renoproledivcuse;10 mgP0

once daily

tiandolapril:HTN;1-4mg P0 once

Cough

Asthma

Hyperkalemia

Angioedcma

Agranulocytosis

Icaptopril)

Lungs

Tissues diffusely

ACEI ramipril (Altace -)

enalaptil (Vasotec:

)

lisinopril (Prinivit '

)

tiandolapril (Mavik )

captoprit (Capoten:

)

elfeds

Renoprolcctivecllccls

daily

AKt

Teratogenic

tosartan (Cozaan )

candesartan

(Atacand -

)

irbesartan (Avapro )

valsartan (Diovan !

)

telmisartan (Micardis - )

eprosartan (Teveten- )

olmesartan (Olmelec )

ARB Vascular smooth

muscle,adrenal

cortex,proximal

tubules

HTN Hyperkalemia

tosartan 25-100 mg PO once daily Caution -reduce dose in

candesartan 8-32 mg PO once daily hepatic impairment

irbesartan 150-300 mg POonce AKt

NTH:

Renoprolcdive effects

daily Teratogenic

valsartan 80 -320 mg PO once daily

telmisartan 20 - 80 mg PO once daily

eprosartan 400 800 mg P0 once

r -i

l L J

.11 .

olmesartan 20- 40 mg PO once daily

Renin Antagonists aliskiren (Rasilez aliskiren150-300 mg PO once daily Hyperkalemia 5) Oiredrenin

antagonist

HTN +

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NP'1‘1 Nephrology Toronto Notes 2023

Landmark Nephrology Trials

Trial Name Reference Clinical Trial Details

ELECTROLYTE DISTURBANCES

SALT-1 NEJM 2006:16:2099 112 Title:lolvaptan. a Selective Oral Vasopressin V2- Receptor Antagonist, lor Hyponatremia

Purpose: Investigate whether lolvaptan migilt be of benefit in hyponatremia.

Methods:Patients with cuvolemic or hypervolemic hyponatremia were randomized to oral lolvaptan ISmg daily or oral matched placebo.Ihe

primary endpoints were changes in daily aiea-uiidcr-lhe-curvc for serum Naconcenlralions.

Results:Serum Na" concentrations increased more in the lolvaptan group than placebo during the first 4 d (P- 0.001) and after 30 d (P* 0.001).

Side effects included dry mouth,thirst,and increased urination.

Conclusions:In patients with euvolemic or hypervolemic hyponatremia, lolvaptan.an oral vasopressin V2-receplor antagonist,was effective in

increasing serum Na concenlralions.

Title:Patiromor in Palienls with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors

Purpose: Assess the safely and efficacy of patiromcr. a K binder,in treating hyperkalemia.

Methods:Patients with CKD receiving RAAS inhibitors with serum Klevels of S.1to 6.5 mmol/ received patiromcr lor 4 wk.Ihe primary efficacy

endpoint wasIhe mean change in serum Klevels from baseline to week 4.Subsequently,107 patients were randomly assigned to patiromer or

placebo for Iherandomized withdrawal phase.

Results:The median increasein K-levels from baseline was greater with placebo than with patiromer (P'

0.001).A recurrence of hyperkalemia

occurred in60% of placebo palienls compaied with15% in the patiromer group.

Conclusions:In CKD palienls receiving RAAS inhibitors and who had hyperkalemia,patiromer treatment was associated with a decrease in

serum K’lcvels and a reductionin hyperkalemia recurrence.

OPAL HK NEJM 2015:372:211-21

DIABETIC NEPHROPATHY

ACEI and Diabetic NEJM 1993:329:1456-62 Title:The Effect of Angiotensin-Converting-Enzyme Inhibition onDiabetic Nephropathy

Purpose:Determine whether captoprit has kidney-protecting properties independent of BP control in patients with diabetic nephropathy.

Methods:Patients with insulin-dependent DM were randomized to caplopril or placebo.The primary endpoint was a doubling of Ihe baseline

serum Cr.

Results:Ihe associated risk reductions of Ihe primary endpoint was 48%in Ihe caplopril group.Serum Cr concentrations doubled in 25 palienls

in Ihe caplopril gioup compared to 43 palienls In Ihe placebo group. Ihe mean rate of decline inCr clearance was 11% per yr inIhe caplopril

group and 17% in the placebo group.

Conclusions:Caplopril protects against deterioration in renal function in insulin- dependent diabetic nephropathy and is significantly more

effective than BP control alone.

Title:Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes

Purpose:Determine whether aliskiren would reduce CV events in palienls with T2DM and CKD.

Methods:8561palienls were randomized lo aliskiren 300 mg daily or placebo as an adjunct to ACEI or AR 8.Iheprimary endpoint was a

composite of time lo CV death,cardiac arrest with resuscitation,nonfalal Ml,nonfatal stroke, or UA hospitalization.

Results:Ihe primary endpoint occurred in 18.3% of patients assigned lo aliskiren.compared with 17.1% in the placebo group (hazard ratio1.08:

95% Cl 0.98 lo1.20;P-0.12).Effects on secondary renal outcomes were similar between groups.Ihe proportion of patients with hyperkalemia

|11.2% vs.7.2%) and hypotension (12.1% vs.8.3%) were higher in the aliskiren group.

Conclusions:Combining aliskiren with ACEI or ARB in high-risk patients withI2DM leads to increased incidence of nonfatal stroke,

hyperkalemia,and hypotension.

Title:Preventing Microalbuminuriain Type 2 Diabetes

Purpose: Assess whether ACEI and non-diliydropyridine calcium channel blockers (CCBs),alone or in combination,prevent microalbuminuria in

patients with H1N and 120M.

Methods:1204 patients were randomized to 3 yr of treatment with trandolapril 2 mg daily plus verapamil SR 180 mg daily,trandolapril alone,

verapamil alone,or placebo.The primary endpoint was the development of persistent microalbuminuria.

Results:The primary outcome was reached in 5.7% of combination patients.6% of trandolapril patients.11.9% of verapamil patients,and10% of

placebo patients.Serious adverse events were similar among all treatment groups.

Conclusions:Treatmcnl with ACEI trandolapril alone or trandolapril combined with verapamil decreased Ihe incidence of microalbuminuria in

patients with12DM and HIM with notmoalbuminuria.

Title: Angiotensin-Receptor Blockade versus Converting-Enzyme Inhibitionin Type 2 Diabetes and Nephropathy

Purpose:Compare renoprolective elfeels of ARBs and ACEIs in patients with T2DM.

Methods:250 patients withT2DM and early nephropathy were randomized to either telmisartan 80 mg daily or enalapril 20 mg daily.The

primary endpoint was a change in GFR between baseline and last available value,during Ihe 5 yr study period.

Results:At 5 yr,the change in Of R was -17.9 ml/min/1.73 mtvilh telmisartan,compared with14.9ml7minf1.73 m 2with enalapril (difference -3.0

mL/min/1.73 m?;9S% Cl -7.6 to 1.6).

Conclusions:Ihe ARB telmisartan and Ihe ACEI enalapril arc equally effective in slowing renal function deterioration inI2DM with mildlo

moderate NIN and early nephropathy.

Title:RenoprolectiveEffect of Ihe Angiotensin-Receptor Antagonist Irbesarlan inPatients with Nephropathy Due to Type 2 Diabetes

Purpose:Assess whether the ARB irbesarlan or the CCS amlodipine slow progression of nephropathy inpatients withI2DM independently of BP

effects.

Methods:1715 hypertensive patients with nephropathy due to T2DM were randomized to irbesarlan 300 mg daily,amlodipine10mg daily,or

placebo.Ihe primary endpoint was a composite of the doubling of baseline serum Cr. development ol ESRD. or all- cause mortality.

Results:Treatment wilhirbesarlan was associated with a rate ol primary endpoints 20% lower than placebo (P*0.02) and 23% lower than

amlodipine (P'0.006). Treatmcnl wilhirbesarlan wasassociated wilh a RR of ESRD 23% lower than that in both oilier groups (P’0.07 lor both

comparisons).These differences were not explained by BP changes.

Conclusions:Treatment with irbesarlan reduced the risk of developing ESRD and worsening renal function in patients withI2DM and diabetic

nephropathy.

Title:Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes andNephropathy

Purpose:Assess the role of AR 8 losartan in slowing progression of renal disease,in patients with T 2DM and nephropathy.

Methods:1513 palienls were randomized to losartan 50-100 mg daily or placebo,in additionlo conventional anlihypertcnsivc treatments.Ihe

primary outcome was a composite of the doubling olserum Cr.ESRD. or mortality.

Results:327 palienls in the losartan group, compared with 359 in Ihe placebo group,achievedIhe primary endpoint (risk reduction 16%:

P-0.02).Losartan reduced the incidence of the doubling of serum Cr (risk reduction 25%;P-0.006) and ESRD (risk reduction 28%;P-0.002),wilh

no effect onmortality.

Conclusions:Losartan conferredsignificant renal benefits in patients with T20M and nephropathy,and was generally well-tolerated.

ALTITU0E NEJM 2012:367:2204-13

BENEDICT NEJM 2004;351:1941-51

DETAIL NEJM 2004:351:1952 61

IDNI NEJM 2001:345:851 60

RENAAL NEJM 2001;345:861-69

r "i

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NP-15 Nephrology Toronto Notes 2023

Trial Name Reference Clinical Trial Details

ROADMAP HEJM 2011:364:907-17 Title: Olmesarlan lor the Delay or PreventionolMicroalbuminuria inType 2 Diabetes

Purpose:Assess whether treatment with an ARB would prevent the occurrence of microalbuminuria in T2DM patients with normoalbuminuria.

Methods:4447 patients with T 2DM were randomized to receive olmesarlan 40 mg 00 or placebo.Additional hypertensives were used as needed

to meet the target BP of <130/80 mmHg.The primary outcome was the time until the first onset of microalbuminuria.

Results:Microalbuminuria developed in 8.2% of olmesarlan-treated patients,and 9.8% in the placebo group. The time to onset of this increase

was increased by 23% with olmesarlan (hazard ratio 0.77;95%Cl 0.63 to 0.94;P'

0.01).

Conclusions: The use ol the ARB olmesarlan was more effective than placebo in delaying the onset of microalbummutia in patients with T2DM,

normoalbuminuria.and goodBP control.

Title:Canagllflozin Slows Progression ol RenalFunction Ocdine Independently of Glycemic (fleets

Purpose: Determine whether canagliflocin decreases albuminuria and reduces renal function decline independently of its glycemic effects.

Methods: 1450 patients with 12DM receiving mcllormm were landomizcd lo canaglillozin 100 mg.canagliflocin 300 mg.or glimepiridc al6 8

mg.Primary endpoints weie annual change in eGFR and albuminuria over 2 yr follow-up.

Results: Glimepinde.canagliflocin100 mg and canaglillozin 300 mg had eGFR declines of 3.3ml/min/1.73 m /per yr (95% Cl 2.8 to 3.8).0.5 ml/

min/1.73 m (95% Cl 0.0 to1.0).and 0.9 mL/min/1.73 m /|95% Cl 0.4 to 1.4),respectively.Patients receiving these treatmentshad reductions in

HbA1c of 0.81%,0.83% and 0.93%,respectively.

Conclusions;Canagliflocin.anSGLT2 inhibitor,slowed the progression of renal disease over 2 yr in patients with T2DM.and may confer

renoprotective effects independently of glycemic control.

Canagliflocin Slows JASN 2017;28:368-75

Progression ol Renal

Function Decline

Independently of

Glycemic Effects

PARENCHYMAL KIDNEY DISEASES

AASK JAMA 2001:285:2719 28 Title:Effect of Ramiprilvs.Amlodipine on Renal Outcomes inHypertensive Nephrosclerosis

Purpose:Compare the effects of an ACEI,a dihydropytidine CCS and p-blocker on hypertensive renal disease progression.

Methods:1094patients with hypertensive renal disease were randomized to amlodipine 5 10 mg/d.meloprolol 50-200 mg/d or ramipril 2.5-10

mg/d.with other agents. The primary outcome was the rate of change ol GFR.

Results: Ihe ramipril group had a 36% slower mean declineinGFR (P'0.006) vs.the amlodipine group|95% Cl 20% to 66%). There were no

significant dilferencesin Ihe mean GFR decline from baseline lo 3 yr between treatment groups.

Conclusions:Ramipril,compared with amlodipine.slows progression of hypertensive renal disease and proteinuria,and may benefit patients

without proteinuria as well.

Title:Efficacy and safety of vodosporin versus placebo for lupus nephritis (AURORA1):a double-blind,randomised,multicentre,placebocontrolled.phase 3 trial

Purpose:Evaluate the safety and efficacy of vodosporin inthe treatment of lupus nephritis.

Methods:Adults diagnosed with systemic lupus erythematosus with lupus nephritis (biopsy class lll

-V) were randomized (1:1ratio) to receive

oral vodosporin or placebo,in addition to standard therapy.The primary outcome at wk 52 was a complete renal response (urine protein:Cr ratio

<0.5 mg/mg. stable renal function (eGFR >60 ml/min/1.73 m2 or <20% decrease from baseline eGFR).and no rescue therapy).

Results: At endpoint wk 52.significantly morepatients in the vodosporin group had a complete renalresponse,as compared to Ihe placebo

group (41% vs.23%;OR 2.65:95% Cl11.64 4.27;P<0.0001). The adverse event profile was similar between groups (21%vs. 21%) withno deaths

attributable to study- related treatments.

Conclusions: Patients who received vodosporin in addition to standard therapy had a higher rate of complete renal response lhan those

receiving standard Iherwpy alone.

Title: Two Year.Randomized.Controlled trial olBelimumabin lupus Nephritis

Purpose:Elucidate the efficacy and safety of IV belimumab as compared with placebo,when added to standaid therapy of mycophenolate

mofetil orcydophosphamide-azathioprine.

Methods:Adults with biopsy-proven,active lupus nephritis were randomized (1:1ratio) to receive IV belimumab (10 mg/kg) or matching placebo,

in addition to standard therapy.The primary outcome at week104 was a primary efficacy renal response (urinary protein:Cr ratio <0.7.eGFR no

<20% pre-flare value,or >60ml/min and no use of rescue therapy).

Results: At endpoint wk104.significantly more patients inIhe belimumab group had a primary efficacy response,as compared to the placebo

group (43% vs.32%;OR 1.65:95% Cl1.1 to 2.5; P'

0.02).The risk of a renal-related event«death was lower among patients who received

belimumab than placebo(hazard ratio 0.51;95% Cl 0.34 to 0.77;P'0.001).

Conclusions: Patients who received belimumab in addition lo standard therapy had a higher rale of primary efficacy response lhan (hose who

received standard therapy alone.

Title:Stenting andMedical Therapy for Atherosclerotic Renal Artery Stenosis

Purpose:Study the usefulness of renal artery stenting for the prevention of major adverse renal and CV events in patients with atherosclerotic

renal artery stenosis.

Methods:947 patients with atherosclerotic renal artery stenosisand either systolic HTN or CKO were randomized to medical therapy plus

stenting,or to medical therapy alone.The primary outcomes were occurrence of adverse CV and renal events.

Results: The rate of primary events did not differ significantly between participants who underwent stenting or medical therapy alone (35.1%vs.

35.8%;hazard ratio 0.94;95% Cl 0.76 to1.17;P'0.58).There wereno significant differences in other components of the primary endpoint.

Conclusions:Renal-artery stenting did not confer a significantbenefit with respect to Ihe prevention of renal or cardiac events when added to

comprehensive,multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease.

Title: Rituximab versus Azathioprine for Maintenancein ANCA Associated Vasculitis

Purpose:Assess whether riluximab helpsmaintain remission of ANCA-associalcd vasculitis.

Methods: Patients with newly diagnosed ANCA associated vasculitides in complete remission were randomized lo either rituximab 500mgor

daily azathioprine.Ihe primary endpoint al 28 mo was Ihe rale of ma|Ot relapse.

Results: At 28 mo. ma|or relapse occurred in 29% of patients in the azathioprine group,compared to 5% olpatients in the rituximab group

(hazard ratio 6.61;95%Cl 1.56 to 27.96;P'0.002). The frequency ol serious adverse events was comparable between groups.

Conclusions:More patients with ANCA-associaled vasculitis had sustained remission at 28 mo with rituximab than with azathioprine.

Title:Renal Outcomes with Telmisartan. Ramipril,or Both,inPeople at High Vascular Risk

Purpose:Investigate the renal effects of ACEI.ARB and combination,in patients with atherosclerotic vascular disease for the reduction of

proteinuria.

Methods:25 620 patients were randomized to ramipril10 mg daily,telmisartan 80 mg daily,or a combination.The primary renal outcome was a

composite of dialysis,doubling of serum Cr,and mortality.

Results: The number of primary events were similar for telmisartan (13.4%) and ramipril (13.5%),(hazard ratio1.00;95% Cl 0.92 lo1.09) but

were increased with combination therapy (14.5%;hazard ratio1.09;95% Cl 1.01to 1.18, P'0.037).

Conclusions: Telmisartan and ramipril monotherapy reduced proteinuria and Cr increase in patients with high vascular risk.

Title: Renoprotective Properties ol ACE-inhibition inNon diabetic Nephropathies with Non Nephrotic Proteinuria

Purpose: Assess the renoprotective effects olACE inhibitioninnon-diabetic nephropathies with non-ncphrotic proteinuria.

Methods: 186 patients were randomized lo ramipril or control(placebo plus conventional antihypertensive). The primary endpoints were change

in GFR and time lo overt proteinuria.

Results: The decline in monthly GFR was nolsignificantlydillerent|0.26 ml/min/1.73 m^in ramipril group vs.0.29 ml/min/1.73 m (n the

control group).Progression to ESRD was significantly less common with ramipril than control,for a RR of 2.72 (95% Cl1.22 to 6.08),likewise for

progression lo overt proteinuria (RR 2.40;95% Cl1.27 to 4.52).

Conclusions:In non-diabetic nephropathy.ACEI were renoprotective in patients with non-nephrotic range proteinuria.

AUR0RA1 Lancet 2021;397(10289):

2070-80

BLISS IN NEJM 2020:383:1117 28

CORAL NEJM 2014:370:13- 22

MAINRITSAN HEJM 2014:371:1771-80

0NTARGET Lancet 2008:372:547-53

r ~i

L J

REIN Lancet 1999:354:359 64

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NP-16 Nephrology Toronto Notes 2023

Trial Name Reference Clinical Trial Details

REIN2 lancet 2005;365:939-46 Title; Blood-Pressure Control for Renoprotection in Patients with Non-diabetic Chronic Renal Oisease

Purpose: Assess effects of intensified vs. conventional BP control with ACEt on progression to ESRO.

Methods: Patients with non-diabetic nephropathies receiving background treatment were randomized to either conventional(diastolic <90

mmHql 01 intensified |

'

t30 mmHg) BP control. The primary outcome was lime to ESRO over 36 mo.

Results:Patients assigned to intensified BP control progressed lo ESR 0 at a rale of 23% compared lo 20% in the control group.

Conclusions: In patients with non- diabetic nephropathy already on ACEI. there was no further benefit from intensified 8P control by adding CCB

vs.conventional BP control on ACEI alone.

Title:Renoprotection of Optimal Antiproteinuric Doses

Purpose:Determine whether titration of benazepril or losartan would improve renal outcomes inchronic renal insufficiency.

Methods: 360 patients without DM.who had proteinuria and chronic renal insufficiency were randomized to benazepril 10mgfd.benazepril 20

mg/d.losartan 50 mg/d. or losartan 100 mg/d.The primary endpoint was time to a composite of doubling serum Cr.ESRO. or mortality.

Results: Up-titration of benazepril and losartan were associated with a 51% and 53% reduction in the primary endpointrisk (P'0.028 and 0.022

respectively!. There was no significant difference in the rates of major adverse events between treatment groups.

Conclusions: Up titrationol either ACEI benazepril or ARB losartan lo optimal anti-proteinuria doses conferred benefit on renal outcome In

patients without DM who had proteinuria and renal insufficiency.

Title:Prophylactic Hydration to Protect Renal Function from Intravascular lodinaled Contrast Material in Patients at High Risk of ContrastInduced Nephropathy

Purpose: Assess clinical effectiveness of prophylactic hydration in preventing contrast-induced nephropathy in patients with compromised renal

function.

Methods: High-risk adult patients undergoing an elective procedure requiring iodinated contrast were randomized to IV NaCI 0.9% or no

prophylanis. Ihe primary outcome was incidence of contrast-induced nephropathy.

Results: Contrast-induced nephropathy was recorded in 2.6% olnon- hydrated patients and 2 7% of hydrated patients.

Conclusions: No hydration prophylanis was non inferior and cost saving in preventing contrast induced nephropathy compared with IV

hydration.

ROAD JASN 2007:18:1889-98

AMACING Lancet 2017:389:1312-22

CHRONIC KIDNEY DISEASE

CHOIR NEJM 2006:355:2085-98 Title:Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease

Purpose:Determine the optimal level of Hb correction in CKD with erythropoietin (EP0) deficiency as a complication.

Methods:1432 patients with CKD were randomized to receive epoetin alfa (human recombinant EP0) targeted to Hb 13.5 g/dl. or those receiving

epoetin alfa targeted to Hb 11.3 g/dl. The primary endpoint was a composite of death. Ml.hospitalization for CHF, and stroke.

Results:125 primary events occurred in Ihe high-Hb group compared to 97 events in Ihe low- Hb group (hazard ratio 1.34:95% Cl 1.03 to 1.74:

P'0.03). More patients In the high- Hb group had at least one serious adverse event.

Conclusions: A higher Hb correction target resulted in Increased ralesol infarction, hospitalization for CHF. and stroke.

Title: Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease

Purpose:Understand the safely and efficacy of thiazide diuretic chlorthalidone for the treatment olHIN in patients with advanced CKD.

Methods:160 patients with stage 4 CKD and poorly controlled HTN were randomized (1:1ratio) to receive chlorthalidone or placebo.Ihe primary

outcome measure was the change in 24-h ambulatory s8P from baseline to 12 wk post-treatment.

Results:Patients with advanced CKD and poorly controlled CKD receiving chlorthalidone experienced a greater reduction in sBP than those

receiving placebo therapy (-11.0 mmHg vs. -0.5 mmHg;P<0.001).Adverse events,including hypokalemia,hyperglycemia,dizziness,and

hyperuricemia occurred more frequently in patients receiving chlorthalidone.

Conclusions : In patients with advanced CKD and poorly controlled HTN, chlorthalidone more effectively teduces sBP than placebo, however,

adverse events must becarefully considered.

Title: Normalization of Hemoglobin level in Patients with Chronic Kidney Disease and Anemia

Purpose:Establish whether correction of anemia in stage 3 or 4 CKD improves CV outcomes.

Methods:603 patients with eCFR 15.0 to 35.0 ml/min/1.73 m2 and mild-moderate anemia were randomized to a normal target Hb (13-15 g/dL) or

a subnormal target range (10.5-11.5 g/dl).The primary endpoint was a composite of 8 CV events.

Results:Complete correction of anemia did not affect the likelihood of a first CV event (hazard ratio 0.78:95% Cl 0.53 to 1.14;P'0.20).The mean

eGFR was 24.9 ml/min/1.73 m4n the complete group,and 24.2 ml/min/1.73 m2 in the incompletegroup,decreasingby 3.6 and 3.1 ml/min/1.73

mi /yr,respectively.

Conclusions: In patients with CKO. complete correction of Hb didnot reduce the risk of CV events or incidence of hypertensive episodes.

Title: Canaglillozin and Renal Outcomes in Type 2 Diabetes and Nephropathy (CREDENCE)

Purpose: Since few effective treatments are available for diabetic nephropathy,this study aims to assess renal outcomes in patients treated with

SGLT 2 inhibitor canaglillozin.

Methods:Patients with type 2 diabetes and albuminuric CKD were randomized to receive canaglillozin 100 mg daily,or placebo.All patients had

an estimated GFR of 30 to <90 mL/min/1.73 nP and albuminuria >300 to 5000. and were treated with RAAS blockade.The primary outcome was

a composite of ESRD (dialysis,transplantation, or sustained eGFR <15mL/min/1.73 m). a doubling of serum Cr,or death from renal orCV (CV)

causes.

Results: Of 4401 randomized patients with a median follow-up of 2.62 yr, the RR of primary outcome was 30% lower in Ihe canaglillozin group

than in the placebo group (hazard ratio 0.70; 95% Cl 0.59 Io0.82:P'0.00001). The canaglillozin group also had a lower risk of CV death. Ml or

stroke (hazard ratio 0.85; 95% Cl 0.67 to 0.95;P'0.01|.

Conclusions; In patients with T 2DM and kidney disease,the risk of kidney failure and CV events was lower In the canaglillozin group Ilian In the

placebo group.

Title: Oapagliflozin in Patients with Chionic Kidney Oisease

Purpose:Elucidate the safety of dapagliflozin in patients with CKD with or withoutI2DM.

Methods:4304 patients with CKD (eGFR 25-73 mL/min/1.73 nPand ACR 200-5000) were randomized to receive dapagliflozin or placebo. The

Methods outcome was a composite of >50% reduction in eGFR.ESRD, and death from cardiorenal causes.

Results:The primary outcome occurred less frequently in patients receiving dapagliflozin compared to those receiving placebo (9,2% vs.14.5%;

HR 0.61: 95% Cl 0.51-0.72;P<0.001; NNT lo prevent one primary outcome event 19; 95% Cl 15-27). This trial was slopped early because of

efficacy.

Conclusions: Patients receiving dapagliflozin are less likely lo experience a composite of *50% reduction in eGFR, ESRO. or death from

cardiorenal causes compared lo those receiving placebo.Oapagliflozin Is safe in patients with CKO.

Title: Effect ol Finerenone on Chionic Kidney Disease Outcomes in Type 2 Diabetes

Purpose: Understand the effects of finerenone on kidney and cardiovascular outcomes in patients with CKD and T2DM.

Methods:5734 patients with CKO (diabetic retinopathy urine ACR 30-300- eGFR 25-60ml/min/1.73 m2or urine ACR 300-5000- eGFR 25 -75

ml/min/1.73 m2 ) and T2DM v/ere randomized (1:1ratio) to receive finerenone or placebo.The primary outcome measure was a composite of

kidney failure, >40% reduction in eGFR. and death from renal causes.

Results:The primary outcome occurred less frequently in patients receiving finerenone compared to those receiving placebo (17.8% vs. 21.1%;

HR 0.82:95% Cl 0.73-0.93;P'0.001). The frequency of adverse events was comparable between gioups. though hyperkalemia-related

discontinuation of therapy occurred more frequently in patients receiving finerenone.

Conclusions: Patients receiving finerenone are less likely lo experience a composite of kidney failure, e40% reduction incGf R, and death from

renal causes compared to those receiving placebo.

CLICK NEJM 2021; 385:2507 -19

CREATE NEJM 2006:355:2071 84

CREDENCE NEJM 2019;380:2295-306

DAPA- CKD NEJM 2020: 383:1436 -46

FIDEIIO OKD NEJM 2020:383:2219 29.

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NP‘

17 Nephrology Toronto Notes 2023

Trial Name Reference Clinical Trial Details

SHARP Lancet 2011;377:2181-92 Title:The Effects of Lowering LDL Cholesterol with Simvastatin plus Ezetimibe in Patients with Chronic Kidney Disease

Purpose:Assess safety and efficacy of low-density lipoprotein (LDL) -lowering with simvastatin plus ezetimibe in patients with CKD.

Methods: 9270 patients withmoderate-severe CKO with nohistory of Ml or coronary revascularization were randomized to simvastatin 20 mg

plus ezetimibe 10 mg daily,or to matching placebo.The primary outcome was the first major atherosclerotic event.

Results: Combination therapy resultedIn a 17% reduction in fiist major atherosclerotic events (11 3% vs.13.4%;RR 0.83;95% Cl 0.74 to 0.94;

P'0.0021). There were significant reductions innon-hemorrhagic strokes (2.8% vs. 3.8%;RR 0.75;95% Cl 0.60 to 0.94: P'0.01) and arterial

revascularization (6.1% vs. 7.6%;RR 0.79;95% Cl 0.68 to 0.93;P'0.0036).

Conclusions:In patients with CKD and no history of Ml or coronary revascularization.20 mg simvastatin plus10 mg ezetimibe daily,compared to

matchingplacebo,reduced the incidence of major atherosclerotic events.

Title:A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease

Purpose:Assess clinical outcomes with darbepoetin alfa among patients with T20M and CKD.

Methods: 4038 patients with diabetes,CKD and anemia were randomized to darbepoetin alfa at13 g/dL, or to placebo.The primary endpoints

were the composite outcomes ol death, CV event,death,or ESRO.

Results: Death or CV events occurred in 632 patients treated with daibepoelin alfa and 602 placebo-matched patients (hazard ratio 1.05;95% Cl

0.94 to 1.17;P'0.41).Oeath or ESRO occurred in 652 patients treated with daibepoelin alfa and 618 placebo- matched patients (hazard ratio1.06:

95% Cl 0.95 to 1.19;P'

0.29).

Conclusions: Oarbepoebn alia did not reduce the risk of death,a CV event,or a renal event,and was associated with an increased risk of stroke.

Title:Effect of Cinacalcet on Cardiovascular Disease in Patients Undergoing Dialysis

Purpose:Assess the effects of calcimimelic agent cinacalcet in reducing mortality risk and nonfata!CV events in patients withCKD.

Methods:3383 patients with moderate-severe hyperparathyroidism undergoing hemodialysis wererandomized to cinacalcetor placebo.The

primary composite endpoint was time until death.Ml.hospitalization for unstable angina (UA),HE.or a peripheral vascular event.

Results: The primary endpoint was reached in 48.3% of cinacalcet-treated patients and 49.2% of placebo-matched patients (hazard ratio 0.93;

95% Cl 0 85 to 1.02;P'0.11).

Conclusions:Cinacalcet did not significantly reduce the risk of death or major CV events in patients with moderale- to- severe secondary

hyperparathyroidism who were undergoing dialysis.

TREAT NEJM 2009;361:2019-32

EVOLVE HEJM 2012: 367:2482 94

CYSTIC 0ISEASE5 OF THE KI0NEV

REPRISE NEJM 2017:377:1930 42 Title: Tolvaptan inLater-Stage Autosomal Dominant Polycystic Kidney Disease

Purpose:Assess the efficacy and safety of tolvaptan inpatients with later-stage autosomal dominant polycystic kidney disease (ADPCKD).

Methods:1370 patients with ADPCKD with eOFR 25 to 44ml/minfl.73m Awere randomized (1:1ratio) to tolvaptan or placebo for 12 mo.The

primary endpoint was a change in eGfR from baseline to follow-up.

Results: The change from baseline eGFR was -2.34 mUmin/1.73 mJin the tolvaptan group (95%Cl-2.81to -1.87) compared with -3.61mL /

min/1.73 m2 in the placebo group (95% Cl -4.08 to -3.14):(difference1.27; 95% Cl 0.86 to1.86;P«0.001|.

Conclusions: Tolvaptan treatment in patients with later-stage ADPKD resulted in a slower decline in eGFR over a1yr period,compared to the

placebo group.

RENAL REPLACEMENT THERAPY

lancet 2003:361:2024 31 Title: Effect ol Fluvaslatm on Cardiac Outcomes in Renal Transplant Recipients

Purpose:Evaluate the safety and efficacy of fluvastatin on cardiac and renal endpoints in renal transplant recipients.

Methods: 2102 renal transplant patients were randomized to fluvastatin or placebo.The primary endpoint was the occurrence of a major CV

event, including cardiac death,nonfatal Ml, or coronary intervention.

Results: Risk reduction in primary events was not significant with fluvastatin (risk ratio 0.83:95% Cl 0.64 to 1.06;P*0.139).There were fewer

cardiac deaths and nonfatal Ml in the fluvastatin group thanin the placebo group (risk ratio 0.60:95% Cl 0.48 to 0.88:P'

0.005).

Conclusions:The use of fluvastatin in renal transplant recipients did not significantly decrease the risk of occurrence of a major adverse cardiac

event,however,there wasa significant reduction in cardiac deaths or nonfatal Ml.

Title: Rosuvaslatin and Cardiovascular Events in Patients Undergoing Hemodialysis

Purpose: Assess the benefit ol statin therapy In patients undergoing hemodialysis for reduction of CV risk.

Methods: 2776 patients undergoing maintenance hemodialysis were randomized lo rosuvastatm 10 mg daily or placebo. The primary cndpoinl

was death from CV causes,nonfatal Ml. or stroke.

Results: 9.2% and 9.5% of patients reached the primary endpoint,in the rosuvastatin and placebo groups,respectively (hazard ratio 0.96;95%

Cl 0.84 to1.11;P'

0.59).Rosuvastatin had no effect on irtdrvidual components of the primary endpoint.

Conclusions:In patients receivingmaintenance hemodialysis,rosuvastatin had no significant effect on CV risk.

Title: Reduced Exposure to Calcineurin Inhibitors in Renal Transplantation

Purpose:Evaluate the efficacy and relative toxic effects of four immunosuppressive agents in renal transplant recipients.

Methods: 1645 renal-transplant recipients were randomized lo receive standard- dose cyclosporine plus mycophenolate mofetit plus

corticosteroids,or daclizumab induction plus mycophenolate molehl plus corticosteroids,both groups in combination witheither low- dose

cyclosporine,low dose tacrolimus, or low- dose slrolimus.Ihc primary endpoint was eGFR 12 mo alter transplantation.

Results: The mean eGFR was higher in patients receiving low- dose tacrolimus|65.4 mUmin/1.73m7) than in the 3 other groups (ranging from

56.7 mUmin/1.73 m4o 59.5ml/min(1.73 m 7 ).Serious adverse events were more common in low dose sirolimus than the other groups (53.2% vs.

a range of 43.4% to 44.3%).

Conclusions:Daclizumab induction,mycophenolate moletil.corticosteroids,and low-dose tacrolimus effectively maintain stable renal function

following renal transplantation,withoutthe negative effects on renal function commonly reported for standard calcineurin inhibitor|CNI)

regimens.

Title:Hemodialysis Six Times per Week versus Three Times per Week

Purpose: Determine whether increasing the fieguency of in-center hemodialysis wouldbe beneficial.

Methods: Patients were randomized to undergo hemodialysis 6x /wk or 3x/wk. The primary composite outcomes were death or change in left

ventricular (LV) mass,and death or change in physical health scores.

Results: Frcguenl hemodialysis was associated with significant benefits with respect lo both primary outcomes (hazard ratio lor IV mass 0.61;

95% Cl 0.46 lo 0.83;hazard ratio for physical health 0.70:95% Cl 0.53 to 0.92). Frequent hemodialysis was also associated with improved HIH

and hyperphosphatemia control.

Conclusions:Frequent hemodialysis,versus conventional hemodialysis,is associated with favourable patient outcomes.

Title:Effect of Dialysis Dose and Membrane Flux inMaintenance Hemodialysis

Purpose:Assess the effects on morbidity and mortality of dialysis dose and level of flux,in patients undergoing maintenance hemodialysis.

Methods:1846 patients undergoing thrice-weekly dialysis wererandomized to high-dose dialysis and lo a low- or high-flux dialyzer.The primary

outcome was all

- cause mortality.

Results: The primary outcome was not influenced by the dose or flux assignment;(RR 0.96:95%Cl 0.84 to 1.10:P'

0.53) lor a comparison of the

high- dose group with standard- dose,and (RR 0.96:95%Cl 0.81to 1.05; P'0.23) for a comparison of high- and low-llux dialyzer assignments.

Conclusions:Use of high dose dialysis or high flux membranes vs. standard dose or low flux in 3x/wk dialysis does not improve survival or

outcomes.

ALERT

AURORA NEJM 2009:360:1395 407

ELITE-SYMPHONY NEJM 2007;357:2562-75

FHN NEJM 2010:363:2287-300

ri

HEMO NEJM 2002;347:2010 -19 i

_ j

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NP18 Nephrology Toronto Notes 2023

Trial Name Reference Clinical Trial Details

IDEAL NtJM 2010:363:609 19 Title: A Randomized,Controlled Trial olEarly versus laic Initiationol Dialysis

Purpose:Examine effects of timing dialysis initiation on survival inpatients with CKO.

Methods:Patients with CKD and eGFR 10 to15 mL/min/1.73 m2 were randomized to early initiation (eGFR 10.0 to14.0 mL/min/1.73 m2 ) or late

iniliation (eGFR SO to 7.0 mL/min/1.73 m2). The primary outcome was allcause mortality.

Results: A total of 37 6% of patients in the early initiation group and 36.6% of patients in the lale-mitiation group died within 3.59 yr (hazard

ratio1.04:95% Cl 0.83 lo1.30: P'0.75).There were no significant differences in the frequency of adverse events.

Conclusions:In patients withprogressive CKD,early initiation of dialysis was not associated with an improvement in survival or clinical

outcomes.

Title:Conversion from Calcineutin Inhibitors loSirolimus Maintenance Therapy in Renal Allograft Recipients

Purpose:Evaluate the efficacy and safety of converting maintenance renal transplant patients from CNIs lo sirolimus.

Methods:830 renalallograft recipients were randomized to continue CNI or convert from CNI to sirolimus.Primary endpoints were GFR and the

rates of biopsy-confirmed acute rejection (BCAR),graft loss, or death at 12 mo.

Results:Intenlion- lo-treat analysis showed no significant difference in GFR, while on therapy analysis showed higher GFR at 12 and 24 months

after sirolimus conversion.Rales of other primary endpoints were similar between groups.Malignancy rales were significantly lower at 12 and

24 months in patients who underwent sirolimus conversion.

Conclusions:At 2years,conversion of maintenance therapy in renal transplant patients from CNIs lo sirolimus was associated with excellent

palient and grail survival.

CONVERT Transplantation

2009;87:233- 42

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McFarlane P.TobeS.Houlden R.etal.Nephropathy:Canadian Diabetes Association clinical practice guidelines expert committee.2003.

Mehta R.Kellum JA,Levin A.From acute renal failure ID acute kidney injury:what's changed?.Nephrology Self-Assessment Program 2O07:6(5):28t.

Mehta RL.Kellum JA,Shah SV.et al.Acute Kidney Injury Network:report of aninitiative toimprove outcomes in acute kidney injury.Crit Car 2007;11(2):R31.

Mliter TR.Urinary Diagnostic Indices in Acute Renal Failure:A Prospective Study.Ann Intern Med1978:89(1):47.

Miller IR,Anderson RJ.Linas SL,etal.Urinary diagnostic indices in acute renal failure:a prospective study. Ann Intern Med1978:89|1):47.

Moist LM,Troyanov S,White Cl,et al.Canadian Society olNephrology Commentary onthe 2012 K0I60 Clinical PracbceGuideline for Anemia in CKD. Am J Kidney Dis 2013:62(5):860- 73.

Moore KL. Persaud IVN. The Developing Human:ClinicallyOriented Embryology. Saunders.

Moore KL. Before We Are Born: Basic Embryology andBirthDefects. Saunders.

MoriliML. Ayus JC. The pathophysiology and treatment of hyponatremic encephalopathy:an update. Nephrol Oial Transplant 2003:18(12): 2486.

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Neurology

Lauren Kanee, Thomas Milazzo, and Maleeha A.Qazi, chapter editors

Karolina Gaebe and Alyssa Li, associate editors

Wei hang Dai and Camilla Giovino, KBM editors

Dr. Charles Kassardjian, Dr. Alexandra Muccilli, and Dr. Liza Pulcine,staff editors

Movement Disorders

Function of the Basal Ganglia

Overview of Movement Disorders

Movement Disorders

Parkinson's Disease

Other Parkinsonian Disorders

Huntington’s Disease

Wilson's Disease

Dystonia

Tic Disorders

Tourette’s Syndrome (Gilles de la Tourette Syndrome) N35

Cerebellar Disorders

Wernicke-Korsakoff Syndrome

Cerebellar Ataxias

Vertigo

Motor Neuron Disease

Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease)

Other Motor Neuron Diseases

Peripheral Neuropathies

Diagnostic Approach to Peripheral Neuropathies

Classification

Guil!ain-Barr£ Syndrome

Neuromuscular Junction Diseases.

Clinical Approach to Disorders of the Neuromuscular Junction

Myasthenia Gravis

Lambert-Eaton Myasthenic Syndrome

Botulism

Myopathies

Clinical Approach to Muscle Diseases

Myotonic Dystrophy Type L

Pain Syndromes

Approach to Pain Syndromes

Neuropathic Pain

Trigeminal Neuralgia

Postherpetic Neuralgia

Painful Diabetic Neuropathy

Complex RegionalPain Syndromes

Headache

Migraine Headaches

Sleep Disorders

Overview of Sleep

Coma

Insomnia

Sleep Apnea

Restless Legs Syndrome andPeriodic Limb Movement inSleep

Narcolepsy

Parasomnias

Central Nervous System Infections

Spinal CordSyndromes

Stroke

Terminology

Pathophysiology

Assessment of Acute Ischemic Stroke

Treatment of Acute Ischemic Stroke

Primary and Secondary Prevention of Ischemic Stroke

Cerebral Hemorrhage

Neurocutaneous Syndromes

Multiple Sclerosis

Common Medications

Landmark Neurology Trials

References

Acronyms

Approach to the Neurological Complaint

Lesion Localization

The NeurologicalExam

General Exam and Mental Status

Cranial Nerve Exam

Motor Exam

Sensory Exam

Coordination Exam and Gait

Basic Anatomy Review

Lumbar Puncture

Approach to CommonPresentations

Weakness

Numbness/Altered Sensation

Gait Disturbance

Cranial Nerve Deficits

CNI: Olfactory Nerve

CNII: Optic Nerve

CN III:Oculomotor Nerve

CN IV:Trochlear Nerve

CN V:Trigeminal Nerve

CN VI: Abducens Nerve

CN VII:Facial Nerve

CN VIII:Vestibulocochlear Nerve

CN IX:Glossopharyngeal Nerve

CN X:Vagus Nerve

CN XI: Accessory Nerve

CN XII:Hypoglossal Nerve

Neuro-Ophthalmology

Optic Neuritis

Anterior Ischemic Optic Neuropathy

Amaurosis Fugax

Optic Disc Edema

Optic Disc Atrophy

Abnormalities of Visual Field

Abnormalities of Eye Movements

Disorders of Gaze

Internudear Ophthalmoplegia

Diplopia

Nystagmus

Abnormalities of Pupils

Nutritional Deficiencies and Toxic Injuries

Seizure Disorders andEpilepsy

Seizure

Status Epilepticus

Behavioural Neurology

Acute Confusional State/Delirium

Mild NeurocognitiveDisorder (Mild Cognitive Impairment)

Major Neurocognitive Disorder (formerly Dementia)

Major or Mild Neurocognitive Dementia due to Alzheimer’s

Disease

Major or Mild Neurocognitive Dementia with Lewy Bodies

(formerly Dementia with Lewy Bodies)

Major or Mild Frontotemporal Neurocognitive Dementia (formerly

Frontotemporal Dementia)

Major or Mild Vascular Neurocognitive Dementia

Creutzfeldt-Jakob Disease

Aphasia

Apraxia

Agnosia

Mild Traumatic Brain Injury

Neuro-Oncology

Paraneoplastic Syndromes

Tumours of the Nervous System

N2 ,N30

N2

N3

,N34

N34

N6 ,N35

N9

N36

N37

,N11

N37

N38

N40

N14

,N42

.N42

N43

N15

N15

N46

N17

N48

N18

N21

N51

N51

N51

r n

L J

N55

N29

,N55

N30

N57 +

N59

N61

Toronto Notes 202J

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XI Neurology

N2 Neurology Toronto Notes 2023

Acronyms

aPTT activated partial thromboplastin FDG -PET 18 Ffluoiodeoxyglucose

time

ACA anterior cerebral artery

ACEI angiotensin converting enzyme FTD

inhibitor

ACh acetylcholine

Alzheimer's disease

ADL activities of dally living

Atl) antiepileptic drugs

AION acute ischemic optic neuropathy FI/A

amyotrophic lateral sclerosis FID

absolute risk increase

AVM arteriovenous malformation

AVPU alert,verbal,pain, unresponsive

BPPV benign paroxysmal positional ICH

vertigo

CIDP chronic inflammatory

demyelinatingpolyneuropathy INO

Creutzfeldt-Jakob disease

cranial nerve

CNS central nervous system

CRPS complex regional pain syndrome JCV

CRVO central retinal vein occlusion LEMS

CTV cerebralCT venography

CVD cerebrovascular disease

DBS deep brain stimulation

dementia with Lewy bodies

EOM extraocular movement

IR lateralrectus

MAOI monoamine oxidase inhibitors

MCA middle cerebral artery

myasthenia gravis

MLF medial longitudinal fasciculus RAPD

MMSE mini mental status examination REM

MoCA Montreal cognitive assessment RLS

medial rectus

MRA magnetic resonance

angiography

MRV magnetic resonance venography SAH

MS multiple sclerosis

MSA multiple systems atrophy

MuSK muscle specific kinase

NCD ncurocognitivc dementia

NCS nerve conduction studies

NMJ neuromuscular junction

NPH normal pressure hydrocephalus SR

OA osteoarthritis

PComm posterior communicating artery

PD Parkinson's disease

PPRF paramedian pontine reticular

formation

progressive supranuclear palsy

polysomnogram

relative afferent pupillary defect

rapid eye movement

restless legs syndrome

range of motion

recombinant tissue plasminogen

activator

subarachnoid hemorrhage

subdural hematoma

substantia nigra pars compacta

substantia nigra pars reticulata

serotonin andnorepinephrine

reuptake Inhibitors

superior oblique

superior rectus

selective serotonin receptor

inhibitors

subthalamic nucleus

traumatic brain injury

tricyclic antideprcssanl

transient ischemic attack

upper motor neuron

vascular endothelial growth

factor

varicella zoster virus

positron emission tomography

frontal eye field

frontotemporal dementia

GuillainBarie syndrome

giant cell arteritis

Glasgow coma scale

globus pallidus pars externa

globus pallidus pars interna

headache

FEF PSP

MG PSG

GBS

GCA

AD GCS

civ MR ROM

Gl

’

i rtPA

ALS Huntington's disease

Huntingtin gene

instrumental activities of daily

living

intracranial hemorrhage

idiopathic Intracranial

hypertension

internudear ophthalmoplegia

inferior oblique

inferior rectus

intravenous immunoglobulin

John Cunningham virus

lambert-Eaton myasthenic

syndrome

lateral geniculate body

louver motor neuron

levelof consciousness

lumbar puncture

ARI HTT SDH

IADL SNc

SNr

SNRI

IIH

SO

CJD 10 SSHli

CN IR

IVIG STN

PHN postherpetic neuralgia

PICA posterior Inferior cerebral artery TCA

I

'

LMS periodic limb movement in sleep TIA

PML progressive multifocal

leukoencephalopathy

PPA primary progressive aphasia

T8I

LGB UMN

LMN VEGF

DLB LOC

LP VZV

Approach to the Neurological Complaint

Lesion Localization

•(.

'NS vs. PNS lesion

CNS: cortical,subcortical, brainstem/bulbar (midbrain, pons, medulla), cerebellum, spinal cord,

anterior horn cells

PNS:anterior horn cells, nerve root, plexus, peripheral nerve, NM), muscle

see Table 3,N5 for UMN (motor neurons originating in cerebral cortex and travelling to

brainstem or spinal cord) and LMN (motor neurons originating in spinal cord and travelling to

muscles or glands) signs

• cortical

contralateral hemiparesis(with differential effect on face and arm vs. leg)

cortical sensory loss:hemisensory loss, position sense, two-point discrimination, graphesthesia,

stereognosis

• dominant hemisphere: aphasia, alexia, agraphia, acalculia, left-right disorientation

• non-dominant hemisphere: hemineglect, dysprosody, amusia, constructional apraxia, alien hand

syndrome

homonymous hemianopia/quadrantanopia

gaze deviation

seizure

• agnosia (visual, auditory)

• ideomotor and ideational apraxia

• subcortical

internal capsule: contralateral hemiparesis with equal face, arm, and leg involvement

without sensory/cortical deficits (pure motor); contralateral hemiparesis and sensory deficit

(sensorimotor); contralateral dysmetria/clumsiness and paresis (ataxic hemiparesis); dysarthria

and ataxia of the hand (clumsy hand-dysarthria syndrome)

• basal ganglia: pill-rolling tremor, bradykinesia. festinating gait, hemiballismus, chorea, dystonic

posture

thalamus: dense sensory loss, contralateral severe pain, visual field cut, cognitive impairment,

altered level of awareness

• brainstem/bulbar (midbrain, pons, and medulla)

crossed hemiplegia or sensory loss (i.e. ipsilateral face, contralateral body)

• ipsilateral ataxia (dysmetria, rapid alternating movements)

nystagmus, diplopia, INO (impaired adduction on contralateral gaze), pupillary abnormalities,

gaze impairment

dysphagia, dysarthria

hearing loss, vertigo

hiccups

ipsilateral Horner’

ssyndrome

r n

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X3 Neurology Toronto Notes 2023

• cerebellum

ipsilateral ataxia (unsteadiness, incoordination)

dysmetria, intention tremor

dysdiadochokinesia

head/truncal titubation, wide-based gait (staggering, reeling,lurching)

scanning speech (explosive speech with noticeable pauses and accentuated syllables)

nystagmus, distorted smooth pursuit, oscillopsia

• pendular reflexes, hypotonia

• spinal cord

bilateral motor and/orsensory deficits below the lesion without facial involvement

sensory level (line below which there is decreased sensation);suspended “cape-like” sensory level

(in central cord lesions)

LM N signs at level of lesion; UM N signs below lesion

bowel, bladder,sexual dysfunction

saddle anesthesia (i.e. conus medullaris)

sensory ataxia

• nerve root

multiple peripheral nerve involvement

myotomal/dermatomal deficits

back /neck pain radiating to leg/arm

saddle anesthesia (i.e. cauda equina)

• peripheral nerve

length dependent (“stocking-glove distribution”) or non-length dependent sensory loss (see

Peripheral Neuropathies, N38)

weakness orsensory loss respecting the distribution of a specific nerve (e.g. median nerve, ulnar

nerve, radial nerve)

• neuromuscular junction

fluctuating/fatiguable symptoms

facial and limb weakness, bulbar (dysarthria/dysphonia/dysphagia), ocular (diplopia/ptosis),

respiratory distress (see Neuromuscular Diseases, NS )

• reflexes usually preserved unlesssevere/advanced or LEMS

• muscle

usually symmetric proximal weakness (e.g.climbing stairs, getting up from chair) without

sensory deficits

asymmetric myopathic weakness seen in distal myopathies, myositis, glycogen storage diseases,

and facioscapulohumeral dystrophy

muscle tenderness

• muscle atrophy

See

s

Online Atlasfor Cranial Nerves

Exam, Motor Exam,and Sensory Exam

Techniques

Battle'ssign -mastoid ecchymosis

Raccoon eyes- periorbital ecchymosis

The Neurological Exam

If patient has not brought their glasses,

have them look through a pinhole for

General Exam and Mental Status best corrected vision

• vitals: pulse (especially rhythm), BF, UR, temperature

• H&N: meningismus ( nuchal rigidity/Brudzinski sign /Kernig sign), head injury/bruises (signs of basal

skull fracture:Battle'ssign, raccoon eyes, hemotympanum,CSF rhinorrhea/otorrhea), tongue biting

• CVS:carotid bruits, heart murmurs

• mentalstatus:orientation (person, place, time), LOG (GCS) (see Emergency Medicine, ER4)

• GCS/15 - Motor/6, Verbal/5 (T= intubated), Eyes/4

When testing CNI. avoid noxious smells

like ammonia, asthistests CN V

Screening Neurologic Exom

• Mental status: orientation (person,

place, time), obeys commands,GCS

• Head and neck:examine for

lacerations, contusions, deformities,

signs of basal skull fracture,flex neck

for meningismus if c-spine injury has

been ruled out

• CN exam: visual fieldslfundoscopy.

pupil size and reactivity. EOM.facial

strength, hearing tofinger rub

• Motor:tone, power in deltoids,

biceps,triceps, wrist extensors, hand

interossei. iliopsoas, hamstrings,

ankle dorsiflexors. pronator drift

• Coordination:linger lapping,fingerto-nose, heel-knee-shin

• Gait:tandem gait, heel walking

• Reflexes:biceps, triceps, patellar,

ankle, plantar (Babinski)

• Sensation: pain/temperature,

vibration

Table1, Glasgow Coma Scale

Points Eyes Verbal Motor

No eye opening

Eye opening topain

Eye opening lo verbal stimulus

Eye opening spontaneously

1 No verbalresponse

Incomprehensible sounds

Inappropriate words

Confused

Oriented

Ho motor response

Extension to pain

Flexion topain

Withdraws from pain

Localizes pain

Obeys commands

2

3

4

S

6

n

L J

• mentalstatus examination

• Folstein MMSE -/30 (normal: 2:24, mild impairment: 19-23, moderate impairment: 10-18,severe

impairment:<10 (note:dementia is not diagnosed by cognitive testing alone)

MoCA -/30 (normal: >26)

frontal lobe testing:test for executive function (e.g. go/no-go test,Luria stest, F-word list

generation, trails test, and frontal release signs e.g. grasp, pout-and-snout, rooting, palmomental,

glabellar tap)

• clock drawing ( note: no single scoring system is clearly superior, and simple subjective assessment

as “normal” or “abnormal ” is sufficient)

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Cranial Nerve Exam

Table 2. Cranial Nerve Examination and Associated Deficits

Cranial Nerve Recommended Physical Exams Signs/Symptoms of Deficit

Olfactory (CNI) Odour sensation:test each nostril separately

Optic|CN ll|

Anosmia (can be associated withloss ol taste)

Visual acuity:test each eye individually:best corrected Central vision loss,peripheral vision loss,absence

of lightrellexes,RAPD,enlargedblind spot,colour

Test visual fields:peripheral visual fields (counting desaturalion (especially red)

lingers,while pin),central visual field,and blind spol

(red pin)

Assess pupils:direct and consensual pupillary reaction

(afferent component),swinging flashlight test (for

RAPD)

fundoscopy:optic disc edema and pallor,venous

pulsations,hemorrhages

Colour vision testing (Ishihara plates)

v s on

Oculomotor (CM III) Assess EOM and nystagmus Eye deviation (e.g.one eye deviated down and out).

Assess pupils:direcl and consensual pupillary reaction ophthalmoparesis.plosis.can demonstratemydriasis

(cllerenl component),sire and shape

Accommodation reflex and saccadic eye movements

lest for ptosis (levator paipebrae superioris)

CN Innervation of EOM

IR:CN VI. SO:CN IV.Other:CN III

Trochlear (CM IV) Test movement of SO muscle Vertical diplopia, may tilt head towardsunaffected

side (Bielschowsky head till test), affected eye cannot

turn inward and downward

Test sensation above supraorbital ridge [VI).maxilla or Ipsilateral lacial sensory abnormality and absent

comeal reflex on stimulation ipsilaterally, weakness

and wasting of muscles ol mastication, deviation ol

open jaw to ipsilateral side, trigeminal neuralgia

Trigeminal (CN V)

cheeks (V2),mandible|V3)

Test corneal reflex (afferent limb)

Assess motor function: temporalis, inasseter,

pterygoids,jaw jerk reflex

Contraction of the left

sternocleidomastoid turns the head right

Abducens (CNVI) Test movement of LR muscle Horizontal diplopia, esotropia (convergent

strabismus), and abductor paralysis of ipsilateral eye,

leading to difficulty looking laterally with diplopia

LMN lesion ~ ipsilateral facial weakness,involving

forehead.Loss of tacrimation.decreased salivation,

dry mouth,loss of taste in anterior 2/3 of the tongue

ipsilaterally.hyperacusis

UMN lesion - contralateral facial weakness,sparing

the forehead

Calorics:Brainstem Test

Describe nystagmus by direction of fast

component

Facial (CN VII) lest muscles ol facial expression

Test corneal reflex (efferentlimb)

Assess taste in anterior 2/3 of the tongue

Visceral motor nerve function to salivary and lacrimal

glands COWS

Cold

Opposite

Warm

Vestibular function:nystagmus, caloric reflexes Vertigo,disequilibrium,nystagmus,sensoiineural Same

Cochlear lunction: whisper test. Rmne test,Weber lest hearing loss

Assess vocal cord function (phonation) and gag reflex

(afferent limb)

Assess ta ste in posterior1/3 of the longue (biller and of gag reflex,dysphagia

sour tasle)

Assess vocal cord lunction:guttural (“ga") and palatal Loss ol gag reflex,dysphagia,hoarse voice,paralysis

|"ka") articulation

Assess gag reflex (efferent limb)

Observe uvula deviation and palatal elevation

Assess swallowing

Vestibulocochlear (CN VIII)

Glossopharyngeal (CN IX) Dysarthria,dysphonia

Loss oitaste in posterior 1/3 of ipsilateral tongue,loss

UMN Tests

Plantar (Babinski) reflex: 'Up-going'

big toe ± fanning of toes indicates an

UMN lesion

Hoffmann's reflex:Involuntary flexion

of the thumb or index finger when

tapping/flicking the nail of the middle

finger downwards may indicate an

UMN lesion and corticospinal pathway

dysfunction,potentially due to cervical

spine cord compression,if asymmetrical

Pronator drift:Unable to maintain full

arm extension and supination:side of

forearm pronation reflects contralateral

pyramidal tract lesion:closing eyes

accentuates effect

Unilateral lesion is rare

Vagus (CN X|

of soft palate (failed elevation),deviation of uvula to

contralateral side of lesion, anesthesia of pharynx and

larynx ipsilaterally

Ipsilateral shoulder shrug weakness and turninghead

to opposite side

Wasting olIpsilateral tongue muscles and deviation to

ipsilateral side on protrusion

Accessory (CN XI) Assess strength of trapezius (shoulder shrug) and

sternocleidomastoid muscles (head turn)

Inspect longuelor signsol atrophy,fasciculations.

asymmetry olmovement and strength,lateral

deviation with protrusion

Hypoglossal(CN XII)

Motor Exam

• bulk: atrophy, asymmetry

• tone: hypotonia (flaccid ), hypertonia (spasticity, rigidity, paratonia ), cogwheeling

• power: Medical Research Council muscle strength scale, pronator drift, forearm rolling test (satellite

sign)

• reflexes: deep tendon reflexes, abdominal reflexes, primitive reflexes, Babinski sign, Hoffmannssign,

clonus

• abnormal movements:tremors, chorea, dystonia, dyskinesia, hemiballism, myoclonus, athetosis, tics,

fasciculations, myokymia

• abnormal posturing:decorticate (upper extremity flexion, lower extremity extension), decerebrate

(extremity extension)

Pyramidal Pattern ol Muscle Weakness

(i.e.UMN)

Weaker arm extensors: shoulder

abduction,elbow extension,wrist

extension,finger extension,finger

abduction

Weaker leg flexors: hip flexion,knee

flexion,ankle dorsiflexion

r n

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Primitive Reflexes

Grasp,palmomental,root,glabellar

tap.snout

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N5 Neurology Toronto Notes 2023

Table 3. Localization of Motor Deficits

LMN UMN Extrapyramidal

Muscle Tone Flaccid

Fasdculallons

Spastic Rigid Medical Research Council Muscle

None Tremor,chorea,ballism.

myoclonus

Normal

Up-going (extensor,i.e.Babinski Down-going (flexor)

Involuntary Movements Strength Scale

S Full power

4 Submaumal power against

resistance (rangrrg 4».4,4-)

3 Full ROM against gravity without resistance

2 Full ROM with grartyremoved

1 Muscle flicker

0 No mastie contraction

Decreased

Down-going (flexor)

Reflexes Increased

Plantar Rellex

sign)

Pattern of Muscle Weakness Proximal,distal,or local Pyramidal pattern;look for

hemiparetic gait (flexed arm.

extended legs)

Upper extremities; extensors

weaker than flexors

Lower extremities: flexors

weaker thanextensors

None

Deep Tendon Reflexes Table 4. Overview of Neuromuscular Diseases

Root MusdeTendon

C5/6 Biceps brachii

C( Brachioradialis

C7 Triceps brachii

C8 Finger flexors

12/3 Nip adductors

13/4 Knee extensors

Peripheral

Neuropathy

Motor Neuron

Disease (e.g. ALS)

Neuromuscular

Junction

Myopathy

SIGNS AND SYMPTOMS

Weakness Segmental and

asymmetrical,distal to

proximal

Distal (except GBS) but

may beasymmetrical

Proximal and latigable

(e.g. MG), or weak then

recovers (e.g.LEMS)

Proximal (with some

exceptions)

Fasciculations

Reflexes

Yes Yes No No

S1J2 Ankle (Achilles)

Mixture of hyperreflexia

and decreased/absent

reflexes

Decreased/absent Normal Normal(until late)

Sensory

Autonomic*

No Yes No No

No Yes No (except LEMS) No Deep Tendon Reflex Scoring

D Absent

Depressed - elicited with reinforcement

TESTS

1* Signs of demyelination

and/or axonal loss

Small,short motor

potentials

EMG Denervation and

reinnervation

Decremental response

on repetitivenerve

stimulation,jitter on

single fibre EMG

Normal

Normal

only

2* Normal

Increased

Increased with clonus |

-4 beats)

3-

Routine NCS 4*

Muscle Enzyme

Normal orabnormal Abnormal

Normal or mildly elevated Normal

Normal

Increased (early/rmd

stage)

Normal/decreased (late

stage)

Interpreting a Slow or Uncoordinated

Rapid Alternating Movement (RAM)

• Slow RAMs v/ithout fatiguing is

suggestive of weakness (especially If

it is asymmetric)

• Slow RAMs with fatiguing (i.e.

decreasing amplitude over time) is

suggestive of Parkinsonism

• Uncoordinated RAM is suggestive

of cerebellar disorder (i.e.ataxia

and irregularly irregular rhythm) or

ideomotor apraxia

’e.g. orthostatic hypotension,anhidrosis,visual blurring,urinary hesitancy or incontinence,constipation,erectile dysfunction

Table 5. Approach to Strength Testing of Radiculopathies vs. Peripheral Neuropathies

How lo use this table:For each nerve root,learn two (or more) peripheral nerves (and their associated musclcs/movements).Inradiculopathies,

all associated peripheral nerves landIheir movements) willbe impaired,whereas inperipheral neuropathies,only one ol the nerves (and its

movement) will be impaired,sparing the other nerve. Particularly useful peripheral nerve "pairs" are boldedlor emphasis

Root Peripheral Nerve Movement Muscle

C5 Axillary

Musculocutaneous (C5/6)

Radial (C6)

Shoulder abduction

Elbow flexion

Wrist extension

Deltoid

Biceps brachii

Brachioradialis

Extensor carpi radialis longus

Triceps brachii

Extensor digitorum communis

Pronator feres

Flexor carpiradialis

Flexor pollicis longus

Abductor pollicisbrevis (look lor thenar

wasting)

Opponens pollicis (look for thenar wasting)

First dorsal interosseus (look for wastingin

first dorsal webbed space)

Iliopsoas

Adductor muscles

Quadriceps

Tibialis anterior

Tensor fascia lata

Hamstring

Tibialis posterior

Peroneus muscles

Tibialis anterior

Extensor hallucis longus

Gluteus maximus

Hamstring muscles

Gastrocnemius and solcus

C6

a Radial

Posterior interosseus

Median

Elbow extension

Finger extension

Forearm pronation

Wrist llexlon

Thumb llexion

Thumb abduction

Opposition

Common Cerebellar Findings

Frontal executive dysfunction/

disinflation,scanning speech,

nystagmus,hypermetric saccades,

hypotonia,pendular reflexes,intention

tremor,ataxicfinger-nose/heel-shin/

tandem,wide based stance and gait,

positive rebound

Midline cerebellar diseases:truncal

ataxia

Lateral cerebellar hemisphere diseases:

limb ataxia

C8. T1 Median

Ulnar Finger abduction

L2.3. 4 Femoral

Obturator

Femoral (13/41

Deep peroneal (L4/5)

Superior glutealnerve (L5,S1)

Sciatic (15.SI)

Superficial peroneal

Deep peroneal

Hip flexion

Hip adduction

Knee extension

Oorsillexion

Hip abduction

Knee flexion

Ankle inversion

Ankle eversion

Big toe extension

13.4

LJ

15

Tibial

Romberg Test +

Stable with eyes open and closed -

normal

Stable with eyes open,falls with eyes

dosed positive Romberg,suggesting

loss of joint position sense

S1 Inferior gluteal nerve

Sciatic

libial

Hip extension

Knee flexion

Plantar llexion

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N'6 Neurology Toronto Notes 2023

Sensory Exam

• primary sensation

• spinothalamic tract: crude touch,pain,

temperature

• dorsal column-medial lemniscus pathway:fine touch,vibration,proprioception

• cortical.sensation

graphesthesia,stereognosis, extinction (tactile, visual, auditory), 2-point discrimination

Note: If primary sensation is not intact, this precludes the testing of cortical sensation. Deficits in

cortical sensation are typically a sign of contralateral parietal lobe lesions

Coordination Exam and Gait

• coordination exam

finger-to-nose, heel-to-shin, knee taps, rapid alternating movements

• stance and gait

Romberg test

pull test or push and release test for postural instability

gait: antalgic, hemiplegic, ataxic, apraxic, Parkinsonian,steppage, broad-based

• tandem gait (heel-to-toe test)

Basic Anatomy Review

Medulla Midbrain

23 Interpeduncular lossn

24 Oculomotor (III) nerve fibres

25 Cerebral peduncle

26 Substantia nigra

27 Red nucleus

23 Edinger-Wcstphal nuclei

29 Oculomotor (III) nucleus s

complex (motor)

30 Cerebral aqueduct

31 Pretectal area

32 Superior colliculus

1 Corticospinal tract

2 Spinothalamic tract

3 Medial lemniscus

4 Reticular formation

5 Nucleus of spinal tract of

trigeminal (V) nerve (descending)

6 Spinal tract of trigeminal IV) nerve

7 Nucleus cuncatus

8 Fasciculus cuncatus

9 Nucleus gracilis

10 Fasciculus gracilis

11 Central canal

12 Arcuate fibres

13 Pontine nucleus

14 Abducons (VII nerve fibres

15 Nucleus ol facial (VII) nerve (motor)

16 Facial IVII) nerve fibres

17 Trigeminal (V) nerve fibres

18 Nucleus of abduccns (VI) nerve

19 Nucleus of spinal tract of

trigeminal (V) nerve

20 Lateral vestibular nucleus

21 Middle cerebellar peduncle

22 Fourth ventricle

r

:

-

£

y

Figure 1. Brainstem (axial view)

ROSTRAL Anterior cerebral artery (AC Al

Anterior communicating artery(AComiii)

\ Optic rkorvo <CN II)

Intomol coiotid arlory <ICA>

Middle cerebral artery (MCA)

Posterior communicating artery(PComm)

Posterior cerebral artery (PCA)

Oculomotor nerve (CNIII)

Trochloar nervolCN IVI

Trigeminalnorvo (CN V )

Superior cerebellar ortery(SCA)

Basilar ar tory AtxJucens nerve (CN VI)

Facialnerve<CN VII)

r1

L J

Anterior inferior cerebellar artery!AICAI

Vestibulocochlear nerve (CN VIII)

Glossopharyngeal nerve (CNIX)

Hypoglossalnervo(CN XII)

Vagus norvo (CNX)

Posteior inferior cereballararteiylPICA) Ft +

Iu

Voitabiiilartiiiy

4,

AccossoiyneivelCN XI) Anteriot spinal artery

Figure 2. Brainstem (posterior view)

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X7 Neurology Toronto Notes 2023

Sensory cortex Third-order

Sensory cortex

lloworlimb and trunk)

sensory neuron

Sensory cortex

(upperlimb)

Putamcn

Putamcn

Internal

\

\T"—'y/

'Internal

V’*- ^ capsule

‘

|—Medial lemniscus

capsule

Thalamus

IVP nucleus!

Thalamus -Spinal lemniscus

IVPnucleus!

Nucleus

cuncatus

-Spinothalamic tract

i

Fasciculus Internal arcuate fibres Second-order

cuneatus Dorsalroot

ganglion

sensory neuron

Nucleus gracilis

Input from

upperlimb S

.

Dorsalroot

ganglion

r

Fasciculus gracilis 5

iAy £

a

IB

BQ

First-order

sensory neuron

Inputfrom

lowerlimb

and trunk

Within 1-2spinal levels of their entry,axons

of first order neurons synapse onto second

order neurons,whoso axons then decussate

before ascending asthc spinothalamic tract u

Figure 3. Discriminative touch pathway (dorsal column) from body Figure 4. Spinothalamic tract from body

InternaT

capsule

InternaT

capsule 2 Thalamus 2

1

Thalamus M

.7, 7

cv Sensory cortex

faceregion Sensory cortex o

faceregion I

I

1

f

Trigeminal

ganglion

Input from face J

—1

Tract ol the spinal

trigeminal nucleus

Trigeminal .

'

ganglion

Input fromlace

_

i

2 Spinal lemniscus

(trigeminal lemniscus)

Medial lemniscus

(trigeminal lemniscus)

Chief sensory

trigeminal nucleus

- -

; 7

- -

7

Spinal trigeminal

nucleus -

0 0

Figure 5. Discriminative touch pathway (dorsal column) from face Figure 6.Spinothalamic tract pathway from face

Upper motor neurons

inmotor cortex

Internal

capsule

Decussation of the

pyramids

(medulla)

Lateral

corticospinal

tract

Lower motor

neuron

I Pyramids

f

Medial

corticospinal

tract

r n

L J

Limb muscles Lower motor neuron

77

Axial +

muscles

Axial

muscles

Figure 7. Corticospinal motor pathway

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N8 Neurology Toronto Notes 2023

Sympathetic Parasympathetic Pupil

<®-

0

Dilation Constriction

Lacrimal and salivary glands

/r>,Pteryaopalatine g llacrimationl

JjfiFSOtic g.(parotid secretion)

IIIV'

Modulate

secretion ubmaxillarv g.(salivation)

.VII

IX

X il

Superior Lungs and trachea

cervical

ganglion

Bronchodilation

Coronary arteries and

heart rate

Vasodilation,

acceleration ^

-^

Vasoconstriction,

^

deceleration

£

< $ e

Glycogen utilization Secretion

TjJi Gl tract

•>

Symulate

Xr-rtotility and

enzyme

^

—secretion

Inhibit \

motility \

and enzyme

secretion

S2

Adrenal

y medulla

Y.Release^

-'

’

-V epipapfirine

Bladder

Inhibit

constriction

Q

Reproductive system CM

£

crEjaculation|

(ect|oa

Swear

glands*

: emulate

_

§—

©

Figure 8. Sympathetic and parasympathetic pathways

C2

Myotomes

C6 C5 - Shoulder abduction and e ItemInc

C6 -Elbow fte»J0a andmat eitension

C? -Elbow extension and finger extension

C8-Finger fleikn

II

- Finger abduction

12-9 -Intercostal labdommal ielleies|

1910 - Upper abdomeals

Tit-12 - Lower abdominals

L2- Hip Demon

L3 - Hip adduction

14 - Knee extension and ankle dorsitlexioo

15 - Ankle doisiHeiion and b.g toe extension

$1-Plantarflenw

C7—C8

r »

L J

IN

a

c

g

o +

5

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