Blood work should only delay treatment

if patient is on anticoagulants, low

platelet count suspected, abnormal

electrolytessuspected, or any bleeding

abnormality suspected

vascular

Suspect an alternate diagnosis if fever,

decreased LOC,fluctuating symptoms,

gradual onset, no focal neurological

symptoms, and/or positive symptoms

r t

L J

+

Infarcted area of brain tissue can

often appear normal on CT during the

first several hours after stroke onset,

especially if in posterior circulation

Activate Windows

Go to Settings to activate Windows.

N52 Neurology Toronto Notes 2023

• PCA

contralateral hemianopia or quadrantanopia

« midbrain findings:CN 111 and IV palsy/pupillary changes, hemiparesis

thalamic findings:sensory loss, amnesia, decreased LOC

if bilateral:cortical blindness or prosopagnosia

hemiballismus

• basilar artery

« proximal (usually thrombosis): impaired EOM, vertical nystagmus, reactive miosis, hemi- or

quadriplegia, dysarthria, ataxia, locked-in syndrome, coma

distal (usually embolic, i.e. top of the basilar syndrome):somnolence, memory and behaviour

abnormalities, oculomotor deficit

• PICA (lateral medullary or Wallenberg syndrome):ipsilateral ataxia, ipsilateral Horners, ipsilateral

facial sensory loss, contralateral limb impairment of pain and temperature sensation, nystagmus,

vertigo, N/V,dysphagia, dysarthria, hiccups

• medial medullary infarct (anteriorspinal artery, which can be associated with anterior cord infarct):

contralateral hemiparesis (facial sparing), contralateral impaired proprioception and vibration

sensation,ipsilateral tongue weakness

• lacunar infarcts(deep hemispheric white matter; involving deep penetrating arteries of MCA, circle of

Willis, basilar and vertebral arteries): contralateral face, arm, leg hemiparesis

• Common lacunarsyndromes:

sensorimotorstroke: weakness and numbness of the face/arm/leg without other cortical signs (i.e.

aphasia, apraxia, visual loss)

pure motor hemiparesis (posterior limb of internal capsule or ventral pons): contralateral arm,

leg, and face

pure sensory loss (ventral thalamic): hemisensory loss

• ataxic hemiparesis (ventral pons or internal capsule):ipsilateral ataxia and leg paresis

dysarthria-clumsy hand syndrome (ventral pons or genu of internal capsule):dysarthria,facial

weakness, dysphagia,mild hand weakness, and clumsiness

See Landmark Nmrobgr trialsfor note information

on tire ARISTOTLE triaL It detailsthe efficacy of

a pirtaban.an oraldrectfactorXa inhibitor,in

reducing the risk of stroke,as compared to warfarin.

The National Institute of Health

Stroke Scale (NIHSS) is a standardized

clinical examination that determines the

severity of an acute stroke:it can also be

used to monitor response to treatment

over time

The scale uses 11 items that evaluate:

. LOC

• Visual system

• Motor system

• Sensory system

• Language abilities

Scoring (x/42):

0-

no stroke

1-4-mild stroke

5-15-moderate stroke

16'20-modcrate to severe stroke

21-42-severe stroke

Aspect Score:10-Point Quantitative

Score to Assess Ischemic Changes on

CT Scan

• 10/10 is normal and <4/10 signifies

high-risk of bleed with rtPA

• Subtract 1point for each of following

structures if abnormal within the

ischemic hemisphere: caudate,

lentiform.insula, internal capsule.

MCA 1,23,4.5. 6regions

Cortical Vascular Territories: Left Hemisphere

O Area of anterior cerebral artery IACA)

G Area of middle cerebral artery (MCA)

Branches of ACA G Area of posterior cerebral artery (PCA)

If rtPA is given at stroke onset,delay

acute antiplatelet/anticoagulation

Branches ol treatment by 24 h

Cortical Vascular Territories: Vontral Surface Absolute Contraindications to rtPA

Any source of active hemorrhage,

any hemorrhage on brain imaging,

any condition that could increase the

risk of major hemorrhage after rtP A

administration

Q Area of anterior cerebral artery { ACA)

I I Area of middle cerebral artery (MCA)

Q Area of posterior cerebral artery (PCA)

BranchesofACA -

(

Branches of MCA A

(fy PCA

<L y I

/

I

1

A

*

1-i

©

r

LJ

Figure 26. Vascular territories

+

Activate Windows

-Go to Settings toaetivate Windows.

X53 Neurology Toronto Notes 2023

Assessment of Acute Ischemic Stroke

Relative Contraindications to rtPA

Historical:history of ICH. stroke or

serious head/spinal trauma in the

preceding 3 mo. major surgery in

the preceding 14 d (risk varies by

procedure),arterial puncture at a noncompressible site in the previous 7 d

Clinical: suspicious for SAH, suspicious

for another non ischemic acute

neurological condition (e.g. post ictal

Todd's paralysis, focal neurological signs

due to severe hypo- or hyperglycemia),

elevated BP (sBPi180 mmHg, dBP ilOb

mmHg) refractory to treatment, current

use of direct oral anticoagulant

Imaging: early signs of extensive

infarction

Laboratory: blood glucose <2.7 mmol/L

or >22.2 mrnolfl, elevated aPTT.INR >1.7,

platelet count <100 x 103/mm3

General Assessment

• ABCs, full vital sign monitoring, capillary glucose (Accu-Chek*), urgent CODE STROKE if <4.5 h from

symptom onset (for possible thrombolysis), N1 HSS

• LOC (knows age, month; obeys commands), dysarthria, dysnomia (cannot name objects)

• gaze preference, visual fields, facial palsy

• arm drift, leg weakness, ataxia

• sensation to pinprick, extinction/neglect

• history

onset: time when last known to be awake and symptom free

• mimics to rule out: seizure/post-ictal, hypoglycemia, migraine, conversion disorder

• investigations

« neuroimaging: non-contrast CT head (STA1) to rule out hemorrhage, M Kl

vascular imaging: CT angiogram (STAT), carotid dopplers ultrasound, MUA ECCi

• ECCi, Holter monitor, transthoracic echocardiogram: to rule out cardioemholic causes such as

atrial fibrillation

• CBC, electrolytes, creatinine, partial thromboplastin time (PTT)/INR, blood glucose, lipid profile

• imaging (i.e. CT ± MR or CT angiography) signs of stroke

• loss of cortical white-grey differentiation

• sulcal effacement (i.e. mass effect decreases visualization of sulci)

hypodensity of parenchyma

insular ribbon sign

hyperdense MCA sign

calculate ASPECTS score for CT

See Lard-narkBeurologyTrialsfor mote information

oo tte OSH triaL It deta Is the efficacy anilsafety

<f endovascular thrombectomy performed mote

than 6 boom after tbe onset of ischemic stroke in

patentswho were well 6-24 h earlier with a mismatch

between clinical deficit end infarct

Treatment of Acute Ischemic Stroke

1. Neuroprotective strategies

• BP, glucose, temperature control (exact targets will depend on clinical scenario)

2. Thrombolysis

• rtPA should be given within 4.5 h of acute ischemic stroke onset provided there are clinical indications

and no contraindicationsto use (see sidebar)

3. Intra-Arterial Mechanical Thrombectomy

• early endovascular treatment of proximal anterior circulation occlusion has significant benefit on

outcomes

26 hours: with small-to-moderate ischemic core on CT

6-24h:CT perfusion used to select patients with large mismatch volume

l

'

or basilar occlusions: weigh risks and benefits

• current standard of care is IV tPA t mechanical thrombectomy

4. Anti-Platelet Therapy

• loading dose of antiplatelets at presentation of '

llA or stroke if rtPA not received

• loading dose of ASA: recommended dose 160 mg chewed

if patient intolerant to ASA, use another antiplatelet agent (e.g. dopidogrel 300 mg)

• IfTIA or minor stroke ( NIHSS 24), load with ASA and dopidogrel and treat with dual antiplatelet

therapy for 21 d / 3 wk (ASA 8I mg and dopidogrel 75 mg)

• ASA 81 mg or dopidogrel 75 mg daily should be continued indefinitely for secondary prevention

• Dual antiplatelets should not be continued for >90 d as risk of hemorrhage is significantly

increased beyond this point

5. Acute Anti-Coagulant Therapy

• delay initiation/hold oral anticoagulation depending on size of infarct and presence of petechial/frank

hemorrhage

Other Acute Management Issues

• avoid hyperglycemia which can increase the infarct size

• lower temperature if febrile (febrile stroke: think septic emboli from endocarditis)

• prevent complications

NPO if dysphagia (to be reassessed by SLP)

• DV T prophylaxis if bed-bound

• initiate rehabilitation early

SeeLacdmarkdeurologyTrialsfor more information

oa tbe SPAfiCL triaLIt details whether statins reduce

the risk of strokeafter a recentstroke or II

*

.

Evalualiag for Occult Atrial Fibrillation - CRYSTAL

IF Trial

ICJU 2014:370:2473 SS

Purpose lo investigate optimal methodsfor using

E(C to detect If ib alter ciyptogenic stroke.

Methods:«1 patens >40 yr with no evidence of

*

f Ib during >24 h ECG nronrloring lece red long tein

monitoring with an mseitable cardiac monitor (ICM )

or comrtntionelfollow- up (control).

Results incidence of (Fib detection in the ICM group

*

S.the contiol groupwas8.9% vs.1.4% at G mo

(haiard ratio.6.4:9S% Cl. 1.9 21.7; P

-0.0011, and

12.4% n.2.0% at 12 mo (7.3 (2.0-20.8); P<0.001|.

respectrrefy.

Conclusion FoUowmgciyp.'ogenic stroke. ECO

monitoring with ICM was more effective than

cooientional follow-up lor detecting

*

f ib.

Carotid endarterectomy needs to be

done within 2 wk of the ischemic event

for the most benefit

r i

L j

+

Activate Windows

Go to Settings to activate Windows.

N5

-1Neurology Toronto Notes 2023

Blood Pressure Control

• do not lower the blood pressure unless the HTN is severe

• antihypertensive therapy is withheld for 48-72 h (permissive hypertension) after non-thrombolysed

ischemic stroke unlesssBP >220 mmHg or dBP >120 mrnHg, or in the setting of acute Ml, renal

failure, aortic dissection (IV labetalol first-line if needed)

if patient receives tPA, target BP 180/105 mmHg

• acutely elevated BP is necessary to maintain brain perfusion to the ischemic penumbra

• most patients with an acute cerebral infarct are initially hypertensive but their BP will improve within

1-2 d

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 assistive devices,splints or

braces, vocational rehabilitation CHADS2

St roke risk stratification for patients

with atrial fibrillation

CHF (1point)

HIN sBP >160 mmHgftreated HTN (1

point)

Age >75 yr (1point)

DM (1point)

Prior Stroke or TIA|2 points)

Primary and Secondary Prevention of Ischemic Stroke

Anti-Platelet Therapy

• primary prevention

no firm evidence of a protective role for antiplatelet agents in low-risk patients without a prior

stroke/TIA

• secondary prevention

initial choice:ASA,but other antiplatelet agents reasonable alternatives (clopidogrel or ASA/

dipyridamole)

longer-term use of combined ASA and clopidogrel not recommended forsecondary prevention

unless there is an alternate indication (e.g.coronary drug-eluting stent requiring dual antiplatelet

therapy),due to increased risk of bleeding and mortality

ABCD;

Score

To predict/identify individuals at highrisk of stroke following TIA

Age:1point for age >60 yr

Blood pressure (at presentation):

1point for HTN

(>140/90 mmHg at initialevaluation)

Clinical features:2 points for unilateral

weakness.1point for speech

disturbance without weakness

Duration of symptoms:1point for

10-59 min.2 points for >60 min

DM:1point

Stroke risk:0-3:low-risk.4-5:

moderate risk.6-7: high-risk

Carotid Stenosis

• primary prevention (asymptomatic)

carotid endarterectomy is controversial:if stenosis >60%, risk ofstroke is 2% per yr; carotid

endarterectomy reduces the risk ofstroke by 1% per yr (but 5% risk of complications)

• secondary prevention (previousstroke/ TIA in carotid territory)

carotid endarterectomy clearly benefits those with symptomatic severe stenosis(70-99%), as well

Surgery. VS9

• according to the CREST trial, endarterectomy and carotid stenting have similar benefits in a

composite endpoint of reduction of stroke, Ml, and death; however, in the periprocedural period,

stenting results in a higher rate ofstroke, while endarterectomy results in a higher rate of Ml

Atrial Fibrillation

• primary and secondary prevention with anticoagulation

classical risk stratification used CH Al)S2 score (0-6), but Stroke 2014 guidelines recommend that

virtually all patients with atrial fibrillation without contraindication be anticoagulated

0 (low-risk, 1.9% annualstroke risk): antiplatclet

I (intermediate risk. 2.8% annual stroke risk): anticoagulant or antiplatelet- patient specific

decision

See laadnurk Nevtology lullsfor IBOIC Mounition

on the MMMMBurn.It complies the efficacy ol

p eruUMOcnliiiuluniMl angioplasty and stenting

(PUS) 1«aggiessire ordeal management in

Intracraaialarterial stenosis.

Endovascular Thrombectomy after large-VCssel

Ischemic Stroke:AMeta-Analysis olIndividual

f alien!DataIron fivt landomiitdTrills

Lancet 2016:387:1723-1731

Faipcst:To compare theefficacy of endovascular

thrombectomy to standard medical care In patients

nidiacute ischemic stroke doe to occlusion olthe

ptosnalinterior circulation.

Study: A neta-analysis of individual patient data from

5 BCTs (US UEAN.ESCAPE,REVASCJI.SWIFT PRIME,

andEXTENDIA).

Results: De:a fion128? indrvidual patents (634

assigned to endorascular thrombectomy and653

assigned to control) were analyzed.The number

needed to treat to reduce dsabildyfor one patient by

at least one level on the modified Rankin Scale,which

measures dsabiity and dependencein activities of

dally bring,was 2.6.Mortality at 90 d and risk of

parenchymal hematoma andsymptomatic ICH didnot

differ between the endorascular thrombectomy and

controlgroups.

Conclusion:Most pabents—irrespective of patient

characteristics or geographical location—with aente

setemc stroke caused by occlusion of lireprmimal

anterior circnlation benefit from endovascular

thrombectomy.

* >2 (high- risk, 4-18.2% annual stroke risk): anticoagulant

• anticoagulation therapy

*

warfarin (titrate to INR 2-3)

* direct oral anticoa

PO BID), rivaroxa

gulants(DOAC):dabigatran (110 or 150 mg PO BID), apixaban (2.5 or 5 mg

ban (15 or 20 mg PO once daily), or edoxaban (30 or 60 mg once daily) may

be alternatives to warfarin and generally have a lower risk of ICH

- Praxbind* reversal agent for dabigatran if necessary

- Andexanet’reversal agent for apixaban and rivaroxaban if necessary

- do not use DOAC in patients with mechanical heart valves or AT with valvular heart

disease

Hypertension

• primary prevention

targets:BP <140/90 mmHg (sBP <120 mmHg for high-risk without diabetes (SPRINT trial) or

<130/80 mmHg for diabetics or renal disease)

ACE1:ramipril 10 mg PO once daily is effective in patients at high-risk for cardiovascular disease

(HOPE trial)

• secondary prevention

combination of ACEI and thiazide diuretics are recommended in patients with previousstroke/

TIA ( PROGRESS trial)

r

L J

+

Activate Windows

Go to Settings to activateWindows.

N55 Neurology Toronto Notes 2023

Hypercholesterolemia

• primary prevention

statinsin patients with CAD or at high-risk for cardiovascular events, even with normal

cholesterol (CARE trial)

• secondary prevention

target LDL <2 mmol/L (or 50% reduction in LDL); high dose atorvastatin (SPARCL trial) but

lower doses may be adequate if intolerable

Type 1 and Type 2 Diabetes

• HbAlc <7%,fasting blood glucose 4-7 mmol/L,2 h postprandial plasma glucose target 5-10 mmol/L

Smoking

• primary prevention:smoking increases risk of stroke in a dose-dependent manner

• secondary prevention:combination of pharmacological therapy and behavioural therapy should be

considered in all smoking cessation programs; aftersmoking cessation, the risk ofstroke decreases to

baseline within 2-5 yr

Physical Activity

• beneficial effect of regular physical activity has a dose-related response in terms of intensity and

duration of activity

ACE Inhibitor in Stroke Prevention - HOPE Trial

NEJM 2000:342:145-153

Study:Randomined. blinded, placebo-controlled

trial.Mean follow-upSyr.

Patients: 929? patients >55 yr (mean age 66 yr.73%

men) wbo had evidenceof vascular d sease or OH plus

oneother carctiwascutar risk factor and who were not

known to haie a low ejection fraction or heartfailure.

Intervention:lamipril 10 mg POonce dady n.

matching placebo.

Main Outcomes:Stroke.Ml.or dealt from

cardiovascular causes.

Results:

Cerebral Hemorrhage

• definition:intracranial bleeding into brain parenchyma or epidural,subdural orsubarachnoid spaces

• etiology:head trauma, aneurysm,AVM, cavernous malformation, brain tumour, hemorrhagic stroke

Investigations

• general investigations:see Assessment and Treatment of Acute Ischemic Stroke, N53

• further investigations, when clinically indicated:

LP (ifsuspect SAH despite negative CT)

may require cerebral angiogram if suspecting aneurysm or AVM

if typical location for hypertensive hemorrhage, repeat CT head in 4-6 wk after hemorrhage has

resolved to rule out an underlying lesion

Outcome RRR (95%CI| HNT (Cl)

Stroke 32% (16-44) 67(43-145)

Ml,stroke, or 26 (19-43) 22% (W-30|

CV modality

M-cause

modality

16% (5-25) 56 (32-195)

Treatment

• medical

anti-hvpertensives: no conclusive BP target ranges for managing 1CH exist; 2020 Canadian

Stroke Best Practice Guidelines suggest that SBP<140-I60 mmHg for the first 24-48h post-lCH is

reasonable

• 1CP lowering medical management (if necessary):see Neurosurgery, NS8

• surgical:see Neurosurgery, NS25

Ireatmtntwith ramipril reduced the riskofstroke

(3.4% vs.4.9%: RR 0.68;M.001).

Conclusions:In admits at high-risk for cardiovascular

fronts,ramipril reduced the risk of stroke,as well

as other vascular events and overall modally.In

addition.ACEI reduce risk of stroke beyond their

hypertensive effect.

Neurocutaneous Syndromes Relapsing

remitting |

~|

n 11 l

~l l

~

l

. see Paediatrics, P89

r

l Progressive f|n

Multiple I

Sclerosis 8 1“

Progressive

S

Definition

• a chronic inflammatory disease of the CNS characterized by relapsing-remitting or progressive

neurologic symptoms due to inflammation, demyelination, and axonal degeneration

Epidemiology

• global prevalence -2.8 million

• onset 17-35 yr; l

;

:M=3:l

• genetic

• polygenetic: the HLA-DRB1 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 regions with less sun exposure and lowerstores of vitamin D (Europe,

Canada, US, New Zealand, Southeast Australia)

MS has also been linked to certain viruses (e.g. EBV)

Clinical Patterns

• clinically isolated syndrome (CIS):first clinical episode that is suggestive of MS

• relapsing-rcmitling (RRMS) 85%, primary progressive (PPMS) 10%, progressive relapsing (PRMS) 5%,

secondary progressive (SPMS)

• most RRMS goes on to became SPMS

Progressive

relapsing

Time

Figure 27.Clinical patterns of MS

Most symptoms in MS are due to cord,

brainstem, and optic nerve lesions

1

J

Chronic Cerebrospinal Venous

Insufficiency (CCSVI)

A theory proposed in 2008 described

abnormal venous blood flow in patients

with MS: while some RCTs are still

underway, recent studies have largely

discredited this highly controversial

theory. That is. studies indicate no

connection between CCSVI and MS

+

Activate Windows

Go to Settings to activat Wi

N56 Neurology Toronto Notes 2023

Clinical Features

• an MS relapse/attack/exacerbation is characterized by the onset of new neurological symptoms lasting

more than 24 h, in the absence of fever or infection

symptoms typically peak over days to weeks, followed by variable improvement over weeks to

months

in KKMS, average 0.4-0.6 relapses per yr, but higher disease activity in first yr of disease

• symptoms include numbness, visual disturbance (optic neuritis), weakness,spasticity, diplopia (e.g.

1NO), impaired gait, vertigo, bladder dysfunction

• Lhermitte'

ssign: llexion of neck causes electric shock sensation down back into limbs suggestive of a

dorsal cervical cord lesion

• UhthotT’s phenomenon: worsening of symptoms in heat

• SPMS:classically presents with progressive weakness and gait dysfunction with cerebellar findings

of arms (i.e. intention tremor); associated features: fatigue, depression,subtle cognitive dysfunction,

autonomic dysfunction

• symptoms not commonly found in MS:visual field defects, aphasia, apraxia, progressive hemiparesis

• negative prognostic factors include age >40 at onset, male sex, non-White ethnicity, frequent relapses,

moderate orsevere relapse, multi-system relapse (motor,sensory, cerebellar, brainstem, etc.),

incomplete recovery, high MRI lesion burden, presence of brainstem and/or spinal cord lesions

Diagnosis

• demonstration of both dissemination in time and space based on the revised McDonald criteria (2017)

• dissemination in time:>2 attacks (lasting at least 24 h with 30 d between the 2 attacks),

simultaneous presence of gadolinium enhancing and non-enhancing MKI lesions at any time,or

a new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, presence of CS1

;

oligoclonal

bands

dissemination in space:>1 T2 lesions on MRI in at least 2 of the 4 CNS regions (periventricular,

cortical/juxtacortical, infratentorial, orspinal cord) or developing a second attack that implicates

a different CNS region

MS Variants

• Devic’

s = neuromyelitis optica (NMO):severe optic neuritis and longitudinally extensive transverse

myelitis extending >3 vertebral segments (aquaporin-4 antibody positive)

• tumefactive MS:solitary lesion >2 cm mimicking neoplasms on MRI

• fulminant MS (Marburg):rapidly progressive and fatal MS associated with severe axonal damage,

inflammation, and necrosis

• paediatric MS:onset of MS before the age of 18

epidemiology:rare (1.35-2.5 in 100000 children)

presentation: more likely to present with isolated optic neuritis,isolated brainstem syndrome,or

symptoms of encephalopathy compared to adults

course:98% have RRMS

diagnosis and treatment similar to adult MS

differential diagnosis: in the setting of nonspecific CS1

:

abnormalities and MRI evidence of white

matter lesion, rule out ADEM (acute disseminated encephalomyelitis), optic neuritis, transverse

myelitis, neuromyclitis optica,CNS malignancies,stroke, leukodystrophies, and mitochondrial

disease

• ADEM: monophasic demyelinating disorder with multifocal neurologic symptoms with

encephalopathy seen mainly in children, often following infection

Investigations

• MKI: demyelinating plaques appear as hyperintense lesions on T2-weighted MKI, with active lesions

sometimes showing enhancement with gadolinium

typical locations: periventricular, corpus callosum, cerebellar peduncles, brainstem, juxtacortical

region, and dorsolateral spinal cord

Dawson'

s fingers: periventricular lesions extending into corpus callosum

• T1 “black holes"

cranial MKI is more sensitive than spinal MRI

• CSE: oligoclonal bands in 90%, increased IgG concentration

• evoked potentials(visual/auditory/somatosensory): delayed but well-preserved wave forms

Treatment

• acute treatment:methylprednisolone 1000 mg IV daily x 3-7 d (no taper required) or prednisone 1000-

1250 mg PO daily x 3-7 d (no taper required);if poor response to corticosteroids, may consider plasma

exchange

• long-term treatment:vitamin D 4000 units/d

• disease modifying therapy (DMT)

goals:decrease relapse rate,decrease progression of disability,slow accumulation of MRI lesions

first line:teriflunomide, interferon-(3 (injection:Betaseron*, Avonex",RebiP),glatiramer acetate

(injection:Copaxone*),dimethyl fumarate (Tecfidera*)

second line: natalizumab (Tysabri*) (monthly IV infusion),fingolimod (Gilenya*), ocrelizumab

(Ocrevus*), alemtuzumab (Lemtrada*), cladribine (Mavendad*), ofatumumab (Kesimpta*)

increased risk of PML associated with natalizumab; PML may also described with fingolimod,

dimethyl fumarate, and ocrelizumab,but to a lesser degree

The Expanded Disability Status Scale

(EDSS) is used as a measure of disability

progression and is scored from 0 to

10 based on the neurologic exam and

ambulation

Fingolimod for Retapsiag-ilemKting Multiple

Sclerosis

Cochrane 08SystIn201S;4:C00093)1

Purpose Systematic literature leview of the evidence

for fingo'rod in treatment of relapsing remitting US.

Study:Ueta -analysisod sin RCIs (n-S51S2|

inresbgatiog the be-ehts and harmsof fingolimod

andother disease modifying drugs in the treatment of

relapsmgremitbng US.

Results:Co*

pared to placebo and interferon

9-la.tngokmod increasesthe proba bitty of being

relapse Iteeat 24 m o (RR 1.

(4 vs. placebo,RR 1.18

vs.interferon J-la) but haslittle to no effect on

drsabiHy progression|RR1.0) us.placebo.RR 1.02

us.interferon 8-1|a .Fingolimod usewas associated

with a higher incidence of adverse events and

: V.:-. :- A :

"

6 - :

Conclusions:fingolimod significantly redeces

disease activity m relapse-remitting US compared

to placebo bnt does not prevent disability.Its use is

associated winadverse eventsand requiresdose

patient monitoring, particularly within the first 6

mo.Furtherstudy is needed to assessthe benefits of

fingofimod vs.ether disease modifying drugs.

RecoubinantInterferon 8or Glatiramer

Acetate for DelayingConversion of the first

Demyelinating Kentlo Multiple Sclerosis

Cochrane 08Syst Rer 2008:2

*

00052)8

Study:Meta analysis of RCIs investigating clinically

isolated syndrome (CIS) paleintstreated with

immunomodulatory drugs.

Priaaiy Oatcomes Proportion of pilienll

converting to clinically definite US and adverse

effects

Resalts:Ibree trills|n*1l60) tested the efficacy of

interferon beta (IFH) and no trial lasted glatiramer

acetaie|GA) Ihe pooled odds ratio (OR)lor patents

on FA vs. placebo al1yt was 0.S3(9$% Cl 0.40-0.71.

P<0.0001).Ihe 2 yr follow up OR was 0.52 (95%

Cl 0.38 0.20.P

-0.0001) Ibeie was no significant

increase ia adverse eventsfor those on IfH.

Conclusions KK treatment can delay progression lo

cboicaly definite US In patients with CIS over 2 yt.

See lanfcrait neurology Inalsfor more information

on the PreCISe trial.It detailstheefficacy ol early

bailment with glatiramer acetate ia delaying onset

of clinically definite multiple sclerosis (MS).

+

“

Activate Windows

Go to Settingsto activateWindows,

N57 Neurology Toronto Notes 2023

CIS:early treatment may delay potential second attack; glatiramer acetate, interferons, and

teriflunomide all with RCT data

RRMS:first-line DMT reduces rate of relapse by about 30%;second-line by 50-90%

miS:ocrelizumab infusion (ORATORIO trial 2017)

• SPMS:siponimod (Mayzent*)

•symptomatic treatment

• spasticity: baclofen, tizanidine. dantrolene, benzodiazepine, botulinum toxin

• bladder dysfunction: oxybutvnin, mirabegron

pain: 1CA, carbamazepine, gabapentin

fatigue: amantadine, modafinil, methylphenidate

• depression: antidepressant,lithium

constipation: high fibre intake,stool softener, laxatives

• sexual dysfunction:sildenafil (Viagra*), tadalafil (Cialis*), vardenafil (Levitra*,Staxyn*)

•education and counselling:MS Society,support groups, psychosocial issues

Prognosis

•good prognostic indicators:female,young, RRMS, presenting with optic neuritis, low burden of

disease on initial MR1, low rate of relapse early in disease

•FPMS:poor prognosis, higher rates of disability, poor response to therapy

Common Medications

Table 26. Common Medications - Major Issues

Indications Mechanism of

Action/Class

Generic Name Trade

Name

Dosing Contraindications Side Effects

Parkinson's

Disease

Dopamine precursor levodopa *

carbidopa

Sinemet 1 Carbidopa 25 mgjlevodopa Use of MAO inhibitor in

100 mg POTID

Maximum 200 mg

carbidopa and 2000 mg

levodopa/d

Initial:0.125 mg 110 Hypersensitivity

Maximum: 4.5 mgld

Initial:0.25 mg 110

Maximum: 8 mg

5 mg P0 BIO

1mg P0 once daily

Nausea, hypotension, hallucinations,dyskinesias

last14 d

Ooparninc agonist pramipcxole

ropinirole

roligoline

Mitpaex '

Rcquip '

Hcupro -

Hdllucinalions, nausea, dirtiness, headache,

insomnia,somnolence, application site reactions

(roligoline)

MA0B inhibitor Concomitant use of

meperidine or tricyclic

antidepressants

MA0B inhibitor Eldepryl ;

Acilect:

H/A. insomnia,dirtiness,nausea, dry mouth,

hallucinations,confusion, orthostatic hypotension,

increased akinesia, risk of hypertensive crisis with

tyraminecontaining foods

N /V.diarrhea , abdominal cramps, increased

peristalsis, incicascd salivation, increased bronchial

secretions, miosis, diaphoresis,muscle cramps,

fasciculalions, muscle weakness, bradycardia

Hemiplegic /basilar migraine, Vertigo, chest pain, flushing,sensation of heat,

ischemic heart disease, CVD. hypeitensive crisis, peiipheral vascular disease,

uncontrolled BIN, use of coronary artery vasospasm, cardiac arrest, nausea,

ergotamine/5'HT1agonist vomibng. HiA. hyposalivation.fatigue

in past 24 h. use of MAO

inhibitor in last 14 d,severe

hepatic disease

Nasalspray 0.5 mg/spiay. Hemiplegiclbasilar migraine, Coronaiy aitcry vasospasm, transient myocardial

maximum 4 sprays/d high dose ASA therapy. ischemia. Ml. ventricular tachycardia.vcntriculai

uncondoned H1N ,ischemic fibrillation: may cause significant rebound HIA

heart disease, peripheral

vascular disease,severe

hepatic orrenal dysfunction,

use of triptansin last 24

h.use of MAO inhibitors in

last14 d

Myasthenia

Gravis

Mestinon ’

600 mg/d P0 divided in

5-6 doses

Range 601500 mg Id

Acetylcholinesterase pyridostigmine Gl or GU obstruction

inhibitor

Imitrex '

25100 mgP0 PRH,

maximum 200 mg/d

Acute Migraine Iriptan (selective sumatriptan

5-hydroxylryptamine

receptoragonist)

drhydroergolamine Migranal Ergot 5 (5- HT1D

receptoragonist)

Migraine

Prophylaxis

Topamax Sedation, mood disturbance, cognitive dysfunction,

anorexia, nausea, diarrhea, paresthesias, metabolic

acidosis, glaucoma. SJS/ IEN

80 mgld divided every 6 8 Uncompensated CNF.severe fatigue,cognitive dysfunction, disturbed sleep,

h;increase by 20- 40 mg! bradycardia or heart block. rashes,dyspepsia,dry eyes, heart failure,

dose every 3-4 wk to max severe C0PD or asthma bronchospasm,risk of acute tachycardia and BIN if

160-240 mg/d in divided withdrawal

doses q6-8 h

25 mg P0 (in evening); Nephrolithiasis

may increase weekly by 25

mgld to a max 50 mg 810

Anticonvulsant topiramate

Inderal '

0- blocker propranolol

r T

L J

SJS:Stevens-Johnson Syndrome.TES:toxic epidermal necrolysis