Figure 9. Dermatome map

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Lumbar Puncture

Indications

• diagnostic:CNS infection (meningitis, encephalitis), inflammatory disorder (MS,GBS, vasculitis),

SAH (ifCT negative), CNS neoplasm (neoplastic meningitis),IIH

• therapeutic:to administer anesthesia, chemotherapy, contrast media

• to decrease IGP (IIH, NPH, cryptococcus meningitis)

Contraindications

• masslesion causing increased 1CP could lead to cerebral herniation;CT first if suspect masslesion or

any neurologic deficit

• LP causes acute pressure gradient that can result in downward displacement of brain

• infection over LP site/suspected epidural abscess

• moderate thrombocytopenia (<50 x 10 y

/L), ongoing anticoagulant therapy (high 1NR or aPTT), or

coagulopathy (e.g. hemophilia)

• uncooperative patient

• acute confirmed/suspected spinal trauma or congenital spinal abnormalities

Complications

• tonsillar herniation (rare)

. SDH (rare)

• transient 6th nerve palsy (rare)

• post-LP headache (5-40%):worse when upright,bettersupine;generally, onset within 24 h

prevention:smaller gauge (i.e. 22) needle, reinsert stylet prior to needle removal, blunt-ended

needle

• symptomatic treatment:oral analgesics, antiemetics, caffeine and sodium benzoate injection

definitive treatment:epidural blood patch (autologous)

• spinal epidural hematoma

• infection

The needle for a IP is inserted into one

of L3-4, L4- 5. or L5-S1 interspaces

<8>

Do not delay antibiotics while waiting for

a LP if infection issuspected

LP Tubes

• tube #1: cell count and differential: RBCs, VVBCs, and differential

xanthochromia (yellow bilirubin pigmentation implies recent bleed into CS1

;

,diagnostic of SAH)

• tube #2:chemistry:glucose (compare to serum glucose) and protein

• tube #3:microbiology:Gram stain and C&S

• specific tests depending on clinical situation/suspicion

viral: PGR for herpessimplex virus ( HSV ) and other viruses

bacterial: polysaccharide antigens of H. influenzae, N. meningitidis,S. pneumoniae

fungal:cryptococcal antigen, culture

TB:acid-faststain,TB culture,TB PGR

• tube #4:cytology:for evidence of malignant cells. If clinical suspicion is low for neoplasm and

concerned about SAH,send final tube for cell count

RBCs in lube #1»»5 » traumatic tap

RBCs in tube

*

1'

#5 and elevated » SAH

Table 6. Lumbar Puncture Interpretation (Normal vs. Various Infectious Causes)

Condition Colour Protein Glucose White Blood Cells

Normal Clear <0.459a 60% of serum glucose or 0-5 >10 VI

>3.0 mmolfl

Normal <1000110Vl lymphocytes

mostly,some PMNs

Decreased (<25% serum >1000 >10Vl PMNs

glucose or <2.0 mmol/l)

Decreased (usually <2.0- <1000 x10VI lymphocytes

4.0 mmol/l)

Viral Infection Clear or opalescent Normal or slightly

increased <0.45-1g/L

Bacterial Infection Opalescent yellow, may >1g/L

-Jet

Granulomatous Infection Clear or opalescent

(tuberculosis, fungal)

Increased bul usually

<5g/l

Approach to Common Presentations

Weakness

Approach

• mode of onset:abrupt (vascular, toxic, metabolic),subacute (neoplastic, infective, inflammatory'

),

insidious(genetic, degenerative, endocrine, neoplastic)

• course: worse at onset (vascular), progressive ( neoplastic, degenerative, infective, genetic), episodic

(vascular, inflammatory), activity dependent (NM), muscular)

• pattern: objective vs.subjective, generalized vs. localized, asymmetric vs.symmetric, proximal vs.

distal, UMN vs.LMN, peripheral vs. myotomal

• associated symptoms:sensory, cortical, autonomic,spinal (i.e. bowel/bladder dysfunction),signs/

symptoms specific to various etiologies

• history:family history, developmental history, medications, risk factors, recent/preceding exposures

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•investigationsfor LMN: NCS/EMG

•investigations for UMN: imaging (brain and/orspinal cord)

•investigations for suspected myopathy: muscle biopsy, CK level, NCS/EMG

•investigations for suspected neuromuscular junction disorder: NCS/EMG (with repetitive nerve

stimulation and single fiber EMG), antibodies (e.g. anti-acetylcholine receptor (AChR) antibodies and

anti-MuSK antibodiesfor MG,voltage-gated calcium channel antibodies for LEMS)

Differential Diagnosis

•objective muscle weakness; also, ditferentiate between true muscle weakness vs.fatigue

• generalized

myopathy (proximal > distal weakness)

- endocrine: hypothyroidism, hyperthyroidism,Cushing’s syndrome

- rheumatologic: dermatomyositis, polymyositis, vasculitis

- infectious:HIV, influenza

- other:collagen vascular disorders,steroids,statins, alcohol, electrolyte disorders

NM|(MG, botulism, LEMS, organophosphate poisoning)

polyradiculopathy (infection, malignancy, GBS, C1DP)

cachexia

localized

UMN (vasculitis, abscess, brain tumour, vitamin Bi:deficiency, MS,stroke)

• radicular pain (i.e. nerve root)

• anterior horn cell (spinal muscular atrophy, ALS, polio, paraneoplastic)

peripheral neuropathy (peroneal muscle atrophy, GBS,leprosy, amyloid, myeloma,DM,lead

toxicity)

•no objective muscle weakness

chronic illness (cardiac, pulmonary, anemia, infection, malignancy)

depression

• deconditioning

Numbness/Altered Sensation

Approach

• positive sensory symptoms: paresthesia/dysesthesia = tingling, pins and needles, prickling,burning,

stabbing

• negative sensory symptoms:hypoesthesia/anesthesia = numbness, reduction/absence of feeling

• determine distribution ofsensory loss:

nerve root vs. peripheral nerve

• symmetric stocking-glove pattern (indicative of distal symmetric polyneuropathy)

dissociated sensory loss:dorsal column (fine touch, proprioception, vibration) vs.spinothalamic

tract (pain and temperature)

• investigations: NCS, blood glucose, vitamin B12 levels, imaging based on associated findings

Differential Diagnosis

• cerebral:stroke,demyelination,tumour

symptoms:hemiplegia,aphasia, apraxia

• brainstem:stroke, demyelination, tumour

symptoms: diplopia, vertigo, dysarthria, dysphagia, crossed sensory and/or motor findings

• spinal cord/radiculopathy:cord infarction, tumour, MS,syringomyelia, vitamin B12 deficiency, disc

lesion

symptoms:back/neck pain, weakness (paraparesis or Brown-Sequard pattern), bowel and bladder

dysfunction

• neuropathy:focal compressive neuropathy (based on location and distribution), DM, uremia,

vasculitis, vitamin B12 deficiency, HIV, Lyme disease,alcohol, paraneoplastic, amyloid

polyneuropathy (length-dependent neuropathy) will have a stocking-glove distribution ofsensory

abnormalities

• other: dermatological (e.g. herpes zoster, angioedema), psychiatric disorders (e.g. panic attacks)

Gait Disturbance

Approach

1.Characterize the gait disturbance

posture,stride length, width between feet, height ofstep,stability of pelvis,symmetry, arm

swing, difficulty turning, tremor,elaborate/inconsistent movements,standing from sitting

2.Identify accompanying neurologic signs

• full neurological exam required (diagnosis often can be made by physical exam alone)

3.Identify'

red flags

• sudden onset, cerebellar ataxia, paresis (hemi

-. para-, or quadri-), bowel/ bladder incontinence

A. Workup

based on etiology -requires blood work,neuroimaging, and urgent neurologist referral

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Table 7. Types of Gait Disturbance

Location Description Disorder

Visual Loss Broad based gait with tentative steps Cataractsurgery without lensreplacement

Sensory atama:wide- based with high stepping Demyclinatlng neuropathies, paraneoplastic

syndrome, tabes dorsalis. MS, compiesslve

myelopathy. B12 deficiency

Proprioceptive loss

posture and positive flomberg

Peripheral Vestibular lesion

1, Acute

2. Bilateral

Peripheral Nerve Disorder

1. Foot drop

2. lumbosacral radiculopathy

Myopathies

1.Vestibular ataxia

2. Disequilibrium

1. Tumour,trauma, infectious, Meniere'

s

disease

2. Ototoxic drugs

Acquired/hereditary peripheral neuropathy,

compressive peroneal neuropathy.L4-5

radiculopathy

Waddling gait: broad based,short stepped Muscular dystrophy,inflammatory myopathy

gait with pronounced lumbar lordosis,rotation

of pelvis

Spastic gait:spastic loot drop, circumduction. Unilateral:stroke (ischemic/hemonhaglc)

scissoring of legs or toe walking with bilateral Bilateral: cervical spondylosis, cerebral palsy.

spinal cord tumour, combined spinal cord

degeneration. MS. motor neurondisease

Steppage gait

Pyramidal/Corticospinal Tract Lesion

t. Unilateral

2.Bilateral circumduction

Basal Ganglia 1.Parkinsonian gait:small paces, stooped

posture, reduced arm swing

2.Choreic/hemiballislic/dystonic gait

Infarct.PD.PSP, MSA. Huntington'

s,

Sydenham's chorea.Wilson’s disease, SLE,

neuroleptic medications, polycythemia vera,

genetic dystonia

Primary and secondary neoplasm,toxins

{alcohol), vitamin E deficiency, hypothyroid,

hypoxia, hypoglycemia, paraneoplastic

syndrome, vascular lesion

Cerebellar Disorder Cerebellar ataxic gait,wide- based without

high stepping:veers toside of lesion

Alcoholic gait

Cranial Nerve Deficits

CN I:Olfactory Nerve

If anosmia is not associated with loss of

taste, consider conversion disorder

Clinical Features

• anosmia associated with a loss of taste

Differential Diagnosis

• nasal: physical obstruction

heavy smoking, chronic rhinitis,sinusitis, neoplasms,septal deformity, choanal atresia,

vestibular stenosis, foreign body

• olfactory neuroepithelial:destruction of receptors or their axon filaments

influenza, herpessimplex, interferon treatment of hepatitis virus, atrophic rhinitis (leprosy),

C:0V1D-19

• central:lesion of olfactory pathway

Kallmann syndrome, albinism, head injury, cranial surgery, SAH, chronic meningeal

inflammation, meningioma,aneurysm, PD, MS

SR 1010 SR

\ /

-(

•h

LH MB

irfsoso'ih / \

g

'

ShanyH L012006J

Figure 10. Diagnostic positions of

gaze toisolate the primary action of

each muscle

CN II:Optic Nerve

Kallmann syndrome is a congenital

disorder of anosmia and

• see Neuro-Ophthalmology,A'14 hypogonadotropic hypogonadism

CN III:Oculomotor Nerve

Pupillary constrictor fibres run along

outside of nerve, whereas vasculature is

contained within nerve

For CN III palsy with a reactive pupil,

think ischemic cause ("pupil sparing")

For CN III palsy with mydriasis,think

compressive lesion

Clinical Features

• ptosis, resting eye position is “down and out" (depressed and abducted ), pupil dilated (mydriasis)

• vertical and horizontal diplopia; paralysis of adduction, elevation, and depression

Differential Diagnosis

• PComm aneurysm: early mydriasis, then CN III palsy

• cavernous sinus (internal carotid aneurysm, meningioma,sinus thrombosis):associated with deficits

in other CNs within the cavernoussinus

• midbrain lesion: complete unilateral CN 111 palsy with bilateral weakness of the SR and ptosis with

contralateral pyramidal signs ± mydriasis

• orbital lesion:associated with optic neuropathy, chemosis,proptosis

• other: inflammatory (e.g. MS with brainstem lesion), infection, ischemia, neoplasia, uncal herniation,

trauma

r T

L J

Lesions involving the cavernous sinus

can lead to cranial nerve palsies of III.

IV. VI. VI. and V2 as well as orbital pain

and proptosis

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Optic chiasm

DDx of CN III Palsy Pituitary gland

IV iCAM

ischemic

Cavernous sinus

Aneurysm (PComm.internal carotid)

Midbrain lesion

Internal carotid artery Dura mater

8

=

= Sphenoid air sinus I

Figure 11. Cavernous sinus (coronal view)

CN IV: Trochlear Nerve

CN IV is the only cranial nerve that

decussates at rnidline and exits

posteriorly

A CN IV lesion may cause a contralateral

deficit if lesion affects the nucleus

Clinical Features

• vertical and torsional diplopia; defect of intorsion and depression

patient may complain of difficulty going down stairs or reading

Differential Diagnosis

• common: ischemic (DM, H I N ), idiopathic, trauma (TBI or surgical), congenital

• other; cavernoussinus lesion,superior orbital fissure (tumour, granuloma)

CN IV is at risk of trauma during

neurosurgical procedures involving the

midbrain because of its long intracranial

course

CN V: Trigeminal Nerve

Clinical Features

• ipsilateral loss of facial sensation and corneal reflex,weakness of muscles of mastication (V3 only)

with pterygoid deviation towards the side of the lesion

Differential Diagnosis

• brainstem:ischemia, tumour,syringobulbia, demvelination

• peripheral: tumour, aneurysm, chronic meningitis, metastatic infiltration of nerve

• trigeminal ganglion: acoustic neuroma, meningioma,fracture of middle fossa

• cavernous sinus:carotid aneurysm, meningioma,sinus thrombosis

trauma

• note: other CN V lesions that cause facial pain = trigeminal neuralgia, herpes zoster

Distinguishing CN III.IV.and VI Lesions

III IV VI

Diplopia Oblique Vertical Honiontal

Exacerbating Near looking faitaiget

target down

Up and Down Rotated

rotated and towards

away flexed

Head Til

away CN VI: Abducens Nerve

Clinical Features

• resting inward deviation (esotropia)

• horizontal diplopia;defect of lateral gaze

Differential Diagnosis

• pons (infarction, hemorrhage,demyelination, tumour): facial weakness and contralateral pyramidal

signs

• tentorial orifice (compression,meningioma, trauma):false localizing sign of increased ICP

• cavernoussinus:carotid aneurysm, meningioma,sinusthrombosis

• ischemia ofCN VI:DM, temporal arteritis, HTN, atherosclerosis

• congenital: Duane'

ssyndrome

Jaw deviation is towards the side of a

LMNCNV lesion

CN VI has the longest intracranial course

and is vulnerable to increased ICP.

creating a false localizing sign

CN VII:Facial Nerve

Forehead is spared in a UMN CN VII

lesion due to bilateral innervation of CN

VII nuclei from cerebral hemispheres to

the frontalis

Clinical Features

• LMN lesion:ipsilateral facial weakness (facial droop, flattening of forehead, inability to close eyes,

flattening of nasolabial fold)

• UMN lesion: contralateral facial weakness with forehead sparing (due to bilateral frontalis

innervation)

• impaired lacrimation, decreased salivation, numbness behind auricle, hyperacusis, taste dysfunction

of anterior 2/3of tongue

Differential Diagnosis

• idiopathic: Bell'

s palsy, 80-90% of cases (see Otolaryngology. 0123)

most often related to HSV, but other viruses may be implicated (CMV, herpes zoster, HBV )

• other:temporal bone fracture, HBV, Ramsay Hunt (VZV ), otitis media/mastoiditis,sarcoidosis, DM

mononeuropathy, parotid gland disease, Lyme meningitis, HIV

When screening for dysphagia and

assessing aspiration risk,the presence

of a gag reflex is insufficient:the

correct screening test is to observe the

patient drinking water from a cup while

observing for any coughing,choking,or

“wetness" of voice

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A. Facial nerve lesion (Bell's palsy)

Motor cortex .

_

B. Supranuclear lesion

s

Supranuclear Facial Nerve Branch Memory Aid

L A To Zanzibar By Motor Car

Temporal

Zygomatic

Buccal

Mandibular

Cervical

Internal

capsule M

•A f•

'

Nucleus

ofCNVIl

Lesion in

facialnerve Facial nerve Differential Diagnosis of Lower Cranial

Nerve Deficits (CNIX,X,XI.XII)

Intracranial/Skull Base:meningioma,

neurofibroma,metastases.

osteomyelitis,meningitis

Brainstem: stroke,demyelination.

syringobulbia,poliomyelitis,astrocytoma

Neck:trauma,surgery,tumours

Normal swallowing is initiated when

the tongue moves a bolus back into the

palatal archway. Tongue movements

are innervated exclusively by CN XII.

The bolus stimulates the soft palate to

elevate, and the bolus is deflected into

the oropharynx

Next the pharyngeal constrictors

contract,the larynx elevates,and the

vocal cords close.Swallowing depends

on afferent information via CN V,IX, and

X and motor action via CN V.VII,IX,X,

and XII

Connections in the nucleus of the tractus

sotitarius in the medulla (in proximity

to the respiratory centre) act as the

swallowing centre.Swallowing and

breathing are coordinated to prevent

aspiration

Figure 12. LMN vs. UMN facial nerve palsy

CN VIII: Vestibulocochlear Nerve

• see Otolaryngology, 0114

CN IX:Glossopharyngeal Nerve

Clinical Features

• unilateral lesion is rare

• taste dysfunction in posterior 1/3 of tongue, absent gag reflex, and dysphagia

Disorders

• glossopharyngeal neuralgia:sharp paroxysmal pain of posterior pharynx radiating to ear, triggered by

swallowing

treated with carbamazepine or surgical ablation of CN IX

CN X: Vagus Nerve

Clinical Features

• oropharyngeal dysphagia (transfer dysphagia) due to palatal and pharyngeal

• bulbar dysphagia (brainstem)

other causes of dysphagia:see Gastroenterology, G8

• dysarthria:inability to produce understandable speech due to impaired phonation and/or resonance

weakness

Uvula deviation is away from the side

of a LMN CN X lesion due to impaired

ipsilateral palatal elevation

CN XI:Accessory Nerve

Clinical Features

• LMN lesion: paralysis of ipsilateral trapezius and sternocleidomastoid (ipsilateral shoulder drop,

weakness on turning head to contralateral side)

• UMN lesion: paralysis of ipsilateral sternocleidomastoid and contralateral trapezius

CN XI is vulnerable to damage during

neck surgery

CN XII:Hypoglossal Nerve

r1

Clinical Features

• LMN lesion: tongue deviation towards lesion, ipsilateral tongue atrophy, and fasciculations (if chronic)

• UMN lesion: tongue deviation away from lesion, absence of atrophy and fasciculations, and slowed

tongue movement

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Neuro-Ophthalmology

Optic Neuritis

• see Optic Oise Edema, below and Multiple Sclerosis,N55

Anterior Ischemic Optic Neuropathy

• see Optic Disc Edema and Multiple Sclerosis, S55

• non-arteritic (NAION):due to atherosclerosis, diabetes, hyperlipidemia, hypertension

• arteritic (AAION): due to GCA (see Rheumatology. RH 22)

NAION can be caused by use of sildenafil

(Viagra'

) in rare case

Amaurosis Fugax

• see Ophthalmology. OP36 and Stroke, SSI

Optic Disc Edema

If you suspect the diagnosis of GCA,

do not wait for biopsy results:begin

treatment immediately

Table 8. Common Causes of Optic Disc Edema

Optic Neuritis Papilledema AION CRVO

>50 yr but usually >70 yt >50 yr

Painless unilateral acute Painless unilateral variable

field defect over h lo d with vision loss

•colour vision

Age <50 yr

Acute lo subacute

monocularfbinocular

central vision loss(a

acuity and colour vision)

with recovery

Pain with F0M

Any

Vision tale visual loss

HIA, N/V,focal neurological GCA: H 'A,scalp

tenderness, jaw

claudication, systemic

(weight loss,fatigue,

fever), polymyalgia

rheumatica

RAPD

Bilateral disc swelling, Pale segmental disc

retinal hemorrhage, no edema, retinal dot,flame

venous pulsationsjonly hemorrhages

true if combined with other

fundal findings)

Symptoms Painless, monocular,

blurry vision, with sudden

onset

deficits

t RAPD

Swollen disc, venous

engorgement, retinal

hemorrhage

Pupil

Fundus

RAPD

Disc swelling if anterior

NoRAPD

(1/3)

Normal disc in acute stage

if retrobulbar (2/3)

Will goon to develop optic

disc pallor in the chronic

phase in both

MS. neuromyelitis optica,

other inflammatory and

infectious diseases

Etiologies Increased ICP see table 24. Arteritic:GCA

Headaches. H47,IIH if CT/V Non-arteritic:

rules oul space- occupying atherosclerosis,

lesion and venous

thrombosis

Emergent CT and

CT-venogram:LPifCT

is normal to measure

opening pressure

Associated with

vasculopathy.thrombus.

Cardiovascular risk

DM. hyperlipidemia, factors. DM. glaucoma. SIE

hypertension

CBC.ESR.CRP, temporal

artery biopsy. MRI orbits

with gadolinium

Investigations MRI brain and orbits with

gadolinium

Fluorescein angiogram and

coherence tomography;

trombophilia work-up if no

cause lor CRVO identified

(younger patients)

Optimize nskfactors,

reduce lOP.t laser, tVEGF

inhibitors

Treatment High-dose IV or

P0 corticosteroids

(accelerates recovery of

vision, does not improve

long-term outcome)

Treat cause (acetazolamide Arteritic:steroids

Non-arteritic:no proven

treatment

for IIH )

Optic Disc Atrophy

r t

i J

• etiologies: glaucoma, AION, compressive tumour, optic neuritis,Leber'

s hereditary optic neuropathy,

congenital

• presentation:disc pallor,low visual acuity, vision defect, decreased colour vision

• treatment: none (irreversible), aim to prevent

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Abnormalities of Visual Field Bitemporal Hemianopsia DDx by Age

• Children: craniopharyngioma

• Middle aged (20s to 50s):pituitary

mass

• Elderly (>60 yr):meningioma

Visual Fields Defects

« i

»

omRight anopsia

(right optic nerve lesion)

1

©

•

* Right anopsia and left upper

quadrantanopsia (junctional scotoma)

2

t

J In homonymous hemianopsia,more

congruent deficits are caused by more

posterior lesions:macular sparing may CO occur with occipital lesions

3 Bitemporal hemianopsia

(chiasmal lesion)

i|

Optic nerve'

-

Optic chiasm

Optic tract_

/

.

Temporal

-

^

.,‘

‘

,. 4

radiation ;{

(Meyers loopl \\

w —

I

I

4-2

a? ccLeft homonymous hemianopsia

(right optic tract lesion)

5

L6B 6

•©«

A destructive lesion (e.g. stroke) In a

cerebral hemisphere causes eyes to

"look away" from the hemiplegia, and to

look towards the lesion

A destructive lesion (eg.stroke) in the

brainstem causes the eyes to "look

toward"the side of the hemiplegia, and

to look away from the lesion

Lett upper quadrantanopsia

(right temporal lesion)

:

5

_

•0©

Parietal

radiation \'

•

Calcarine-/

/

r

fissure

(Primary visual cortex ’ )

Left lower quadrantanopsia

(right parietal lesion) 5

0 J

Figure 13.Characteristic visual field defects with lesions along the visual pathway

Abnormalities of Eye Movements Check all hemiplegic patients for

homonymous hemianopsia (ipsilateral to

side of hemiplegia)

Disorders of Gaze

Pathophysiology

• horizontal gaze: FEE > contralateral PPRE (pons) -> eyes saccade away from FEE

• vertical gaze: cortex > rostral interstitial nucleus in the MLE (midbrain)

Clinical Features

• unilateral lesion in one FEE > eyes deviate toward the side of the lesion

• can sometimes be overcome with doll’s eye maneuver

• unilateral lesion in the PPRE -> eyes cannot look toward side of lesion, thus producing a pseudodeviation to the contralateral side

• cannot he overcome with doll’s eye maneuver if CN VI nucleus lesion as well

• seizure involving a EEE: eyes deviate away from the focus

Etiology

• common:infarcts (frontal or brainstem), MS,tumours

"Negative lesions" that eliminate

function/cause malfunction of FEF (i.e.

stroke/tumour) cause the eyes to deviate

to the side of the lesion:

"positive

lesions"that cause ovcractive function

of PEE (i.e. seizure) focus cause the eyes

to deviate away from the focus

IF

To

medial

'

'

rectus m.

CN III

'

CNIII

-

1

nucleus

o :u

ijo lateral Internudear Ophthalmoplegia rectusm

o

Pathophysiology

MLF e.

• results from a lesion in the MLE which disrupts coordination between the CN VI nucleus in the pons

and the contralateral CN III nucleus in the midbrain -> disrupts conjugate horizontal gaze

Clinical Features

• horizontal diplopia on lateral gaze, oscillopsia (objects in visual field appear to oscillate)

• ipsilateral adduction defect and horizontal abducting nystagmus in the contralateral, abducted eye

• cannot be overcome by caloric testing

• accommodation reflex intact

• may be bilateral (especially in MS)

Etiology

• common: MS, brainstem infarct or tumour

CNVi -

nucleus CNVI

PPRE

Right Left

Right Lett

Standard (normal)

<cc\ ZE>

Right gaze Inormall Investigations

• MR1

OS £J> ri

L J

Left gaze ( abnormal-INO)

Vergence (normal!

+

^

©Sherry An 2022 after N Bmacliynsky 2012 J

Figure14. internudear

ophthalmoplegia

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Diplopia

Etiology - Monocular

• mostly due to benign optical problems (refractive error, cataract, dry eye) or functional causes

Diplopia worse at the end of the day

suggests MG fi.e.fatigable). in addition

to mbed (horizontal and vertical

diplopia) that resolves when one eye

is closed

Etiology - Binocular (due to ocular misalignment)

• muscle:Graves’ophthalmopathy, EOM restriction/entrapment

• neuromuscular junction: MG (see Myasthenia Gravis, N40)

• cranial nerve palsy (see Cranial Nerve Deficits, Nil)

• INO (see Internuclear Ophthalmoplegia, N 15)

• other

• orbital trauma (orbital floor fracture), tumour,infection, inflammation

Miller-Fisher variant of GBS

Wernicke’s encephalopathy

leptomeningeal disease

If diplopia is only on extremes of gaze,

cover each eye in isolation during

ertremes of gaze

The covered eye that makesthe lateral

image disappear is the pathological one

Approach to Diplopia

• monocular (diplopia when one eye open) vs. binocular (diplopia when both eyes open )

• horizontal (CN VI palsy if worse at distance, convergence insufficiency if worse when near) vs. vertical

vs. oblique diplopia

• direction of gaze that exacerbates diplopia

• corrective head movements

Left CN III (complete)

Eye position down and out (with

ptosis and pupillary dilation)

Workup

• may observe isolated CN IV or CN VI palsy for a few weeks, but workup if persistent or other

symptoms develop

• consider ESR/CRP if symptoms of GCA and diplopia

• indicationsfor neuroimaging

bilateral or multiple nerve involvement

progressive worsening

severe sudden onset headache (rule out aneurysm)

other neurological deficits on examination

any findings of CN 111 palsy (e.g. unequal pupils with mydriasis + /- down and out)

any findings of Horner’

s syndrome: ptosis, miosis, anhidrosis

Left Sympathetic Pathway

Homer'

ssyndrome:ptosis, miosis, and

anhydrosis

Nystagmus

• rapid, involuntary,small amplitude movements of the eyes that are rhythmic in nature

• begins with a slow phase movement,followed by a quick more obvious phase

• nystagmus is described in relation to the quick phase of the eye movement

• can be categorized by movement type (pendular, jerking,rotatory, coarse) or as physiological vs.

pathological

Table 9. Nystagmus Features

CN IV

Difficulty looking down and in

(Le.looking down at a golf ball-think

CN Fore!)

Peripheral (Vestibular) Central (Brainstem)

Unidirectional,last phase away from thelesion May be bilateral/unidirectional

Usually horizontal-rotary

Direction

Nystagmus Can be any type:usually vertical,horizontal,

pendular or jerk:may change direction

Does not suppress nystagmus

Left CN VI

fiaze Fixation Difficulty looking laterally

Vertigo

Auditory Symptoms

Other Neurological Signs

Suppresses nystagmus

Severe

Common

Mild

Extremely rare

Often present

MS. vascular (brainstem/cerebellar),

neoplastic/paraneoplastic,medications

Absent

DDx BPPV, vestibular neuritis, Meniere's disease,

toxicity,trauma.Ramsay Hunt syndrome

Left Medial Longitudinal Fasciculus

Internuclear ophthalmoplegia UNO):

Difficulty adducting ipsilateral eye and

horizontal nystagamusin abducted

contralateral eye

Abnormalities of Pupils

• see Ophthalmology. OB30

£ Minyan Wang 2012 j

Figure 15. Abnormal eye movement

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X17 Neurology TorontoNotes 2023

Nutritional Deficiencies and Toxic Injuries

• sufficient nutritional intake is required for optimal functioning of the nervous system; deficiencies in

the following nutrients may result in central and peripheral nervoussystem abnormalities (potential

neurological symptoms are provided)

Table 10.Nutritional Deficiency Features and Management

Vitamin Deficiency Neurological Clinical

Manifestation

Investigation Treatment"

Paresthesias and sensory ataxia Serum cobalamin

are Ihe most common initial

symptoms

Myelopathy (subacute compined

degeneration),peripheral

neuropathy

Neuropsychialric:memory

impairment,change in

personality,delirium,and

psychosis

Optic neuropathy

Myelopathy,peripheral

neuropathy

May be clinically indistinguishable

(rom vitamin Bu deficiency

Neuropsychiatric symptoms

Myelopathy,myeloneuropathy. Serum copper andceruloplasmin;

sensory ataxia, spastic gait urinary copper:MRI spine;EMG/

(similar to vitamin Bit deficiency) NCS

Severe sensory loss

Ophthalmoplegia,retinopathy. Serum vitamin E;ratio serum Vitamin E 2200 mg/kgfdP0 or IM

spinocerebellar syndrome with vitaminE tosum of cholesterol

peripheral neuropathy (with signs and triglycerides:EM6 NCS

of cerebellar ataxia),psychomotor

impairment

Three manifestations include: Clinical diagnosis:brain MRI

beriberi (dry and wet),infantile

beriberi,Wernicke.Korsakoff

syndrome,seeCerebellar

Disorders. N36

Painful sensorimotor peripheral Semm pyndoxa!phosphate;EEG in Pyridoxine 50-100 mg daily

neuropathy,intractable epilepsy infants and children;EM&'MCS

ininfants,confusion

Pellagra:encephalopathy,

dementia,and peripheral

neuropathy

VitaminBu Vitamin Bu1000 pg IM for 5 d.

Serum methylmalonic acid then 1/mo or P0Bu1000 pg'd

Serum homocysteine

MRIspme.EMG. NCS

Serum folate

Homocysteine

Folate Folate1mg TID P0initially.1mg

once daily thereafter

Discontinue tine;copper 8 mg/d

P0 for 1wk,6 mg/d lor 1wk.4

mg/d for 1wk. 2 mg/d thereafter

Copper

Vitamin E

Thiamine100 mg IV followed

by 50-100 mg IV orIMuntil

nutritional status stable

Thiamine

Pyridoxine(VitaminB6)

Niacin (Vitamin 83) Nicotinic acid 25-SO mg daily P0

or IM.When supplementing,be

aware of "niacin flush”insome

patients

• also consider occupational neurotoxic syndromessecondary to exposure to pesticides,solvents,

and metals.Encephalopathy, extrapyramidal features, neurodegenerative diseases, and peripheral

neuropathy are commonly encountered. Onset and progression of neurological diseasesshould be

temporally related to neurotoxin exposure. Main toxins associated with neurotoxicity are listed below

Table 11. Selected Occupational Neurotoxic Syndromes

Toxin Associated Occupations Characteristic Neurological Findings

Printer,spray painters,industrial cleaners,

paint or glue manufacturers,graphic industry,

electronic industry,plastic industry

Organic Solvents Nausea,H/A,concentration difficulty

Long-term exposure may lead to'chronic solvent-induced encephalopathy." characterized by

mild-to-sevete cognitive impairment

Agricultural work,pesticide manufacturing and Pesticide exposure may increase the risk of PD

formulating,highway and railway workers,green

house,forestry and nursery workers

Battery andmetalproduction (e.g.solder,

pipes),chemical andelectronic application

industries,steel manufacturing,welders,

alloy workers,transportation,packaging,

construction

Pesticides|e.g.insecticides,fungicides,

rodenticides.fumigants,herbicides)

Lead:delayed/reversed development,permanentlearmng disabilities,peripheral neuropathy

(commonly presenting withradial neuropathy resulting in wrist drop),seizures, coma,death from

encephalopathy (rare)

Mercury: psychiatric disturbances,atana.trerrov.visual loss,heating loss,tiredness,memory

disturbances, peripheral neuropathy

Manganese: psychiatric symptoms,hanimations ('manganese madness"),extrapyramidal

features,dystonia,parkinsonism (mangamsm)

Aluminum:implicated in Alzheimer's pathogenesis.AIS

Arsenic: sleeplessness/sleepiness.irritabilrty.H/A.spasms in muscleextremities and muscle

fatigue,peripheral neuropathy

Thallium: ataxia,seizures,motor neuropathy,brain edema

Tin:mental status changes withpersistent neuropsychological abnormalities

Cognitive/behavioural and emotional symptoms,parkinsonian syndromes

Nitrous oxide misuse may resultin a functional Si2 deficiency and thus symptoms of subacute

combined degeneration

Heavy Metals|e.g.lead,mercury,

manganese,aluminum,arsenic,tin.thallium)

L J

Gases|e.g.carbon dioxide,nitrous oxide,

formaldehyde)

Anesthesia, disinfection,manufacture of

illuminating gas andwater-gas

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N18 Neurology Toronto Notes 2023

Neurologic Complications due to Toxic Injuries Related to Bariatric Surgery

• deficiencies of both fat- and water-soluble vitamins may occur following malabsorptive bariatric

surgery

• patients who have undergone malabsorptive surgery should be monitored for late metabolic

complications (e.g. B12 and copper deficiency) and neurological manifestations (e.g.peripheral

neuropathy)

Seizure Disorders and Epilepsy

Seizure

Definitions

• seizure: transient occurrence ofsigns and/or symptoms due to abnormal hyper-synchronization of

neurons

can be a symptom of acute insult to the brain such as:alcohol and illicit drug use/withdrawal;

brain injury/abnormality (tumour, trauma, vascular);CNS infection;fever (children); metabolic

(hypoglycemia, electrolyte abnormalities, liver/renal failure); medications; or be a genetic or

inherited cause

• epilepsy: disorder of the brain characterized by an enduring predisposition to generate epileptic

seizures, and by the neurobiologic, cognitive, psychological, and social consequences of this condition

diagnosis of epilepsy requires:

1. at least two unprovoked seizures occurring more than 24 h apart

2. one unprovoked seizure and a probability of further seizures similar to the general recurrence

risk (at least 60%) oftwo unprovoked seizures, occurring over the next 10 yr

3. diagnosis of an epilepsy syndrome

etiologies: genetic;structural (e.g. prior stroke, tumour, meningo/encephalitis, perinatal insult,

vascular malformation, malformation of cortical development, neurodegenerative); or unknown

Classification

Stroke isthe most common cause of

lateonset (>50 yr) seizures, accounting

for 50-80% of cases

Seizure

I

Seizures and Dementia

Neurodegenerative diseases can

underlie seizures.Conversely,seizures

can be a cause of dementia

Focal Onset Generalized Onset Unknown Onset*

I

'

A.v=re In p=

rej A.' -. d ’e =:;

i

Nonmotor FocalUnilateral Motor

tonic-clonic

i 1

’.Uni Nonmotor

(absence)

MOW Nonmotor Unclassified -

i I l 1 I i

Tonic-clonic

Clonic

Tonic

Myoclonic

Myclonic-tonic-clonic Myoclonia

Myoclonic-atonic

Atonic

Epileptic spasms

Typical Tonic-clonic Behaviour ariest

Atypical Epileptic spasms

Myoclonic

Eyelid

Automatisms

Atonic

Clonic

Epileptic spasms Emotional

Hyperkinetic Sensory

Myoclonic

Tonic

Autonomic

Behaviour arrest

Cognitive

'Unknown Onset may be reclassified into focal or generalized onsetwith further information or future observed seizures

I Unclassified comprises both seizures with patternsthat do not fit other categories or lack information

Figure 16. International League Against Epilepsy (ILAE) 2017 seizure classification

Clinical Features

• focal (partial)seizures

focal can secondarily generalize or remain focal

focal without impaired awareness (i.e.

“simple partial seizures") 4 focal with impaired awareness

(i.e.

“complex partial seizures”

) 4 secondarily generalized seizures

focal aware (formerly simple partial)

motor: dystonic posturing, clonic movements, forceful turning of eyes and/or head, focal

muscle rigidity/jerking ± Jacksonian march (spreading to adjacent muscle groups)

sensory: unusual sensations affecting vision, hearing, smell, taste or touch

» autonomic: epigastric discomfort, pallor, sweating, flushing, piloerection, pupillary dilatation

• focal impaired awareness (formerly complex partial)

patient may appear to be awake but with impairment of awareness

classic complex seizure is characterized by automatisms such as chewing,swallowing, lipsmacking,scratching, fumbling, running, disrobing, and other stereotypic movements

other forms: dysphasic, dysmnesic (deja vu), cognitive (disorientation of time sense), affective

(fear, anger), illusions,structured hallucinations (music,scenes, taste,smells), epigastric

fullness

Temporal lobeseizures are suggested

by an aura of fear,olfactory or gustatory

hallucinations, and visceral or deja vu

sensations

Frontoparietal cortex seizures are

suggested by contralateral focal sensory

or motor phenomena

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X19 Neurology Toronto Notes 2023

• generalized seizures

absence (petit mal): usually seen in children, unresponsive for 5-10 s with arrest of activity,

staring, blinking or eye-rolling, no post-ictal confusion;3 Hz spike and slow wave activity on EEG

• donic:whole body repetitive rhythmic jerking movements

• tonic: whole body muscle rigidity in flexion or extension

• tonic-clonic (grand mal)

• may have prodrome of unease or irritability hoursto days before

tonic ictal phase:muscle rigidity

clonic ictal phase: repetitive violent jerking of face and limbs, tongue biting, cyanosis,

frothing, incontinence

• post-ictal phase:flaccid limbs, extensor plantar reflexes, headache, confusion, aching

muscles,sore tongue,amnesia,elevated serum CK lasting hours,may have focal paralysis

(Todd’s paralysis)

• myoclonic:sporadic contractions localized to muscle groups of one or more extremities

• atonic: loss of muscle tone leading to drop attack

AntiepBeptic Drug Monothfrspjfor Epilepsy:A

Hetwork Meta-Analysis ofIwlividualParticipant

Data

Cocltra*

D!Syst to201?:C0011412

Purpose: To conparethe Its;to wt-drawal of

&ea:nert.ioe!oremission.EdSueto first seizure

of 10 enoep-leptic drug treatneits for adults and

childrec wifi partial onset seizures

Methods Articles were iden:Sed ront Cochrane

Epilepsj'sSoeoaltsed Register.CERTRAL. MEDLINE.

SCOPUS,ard two clinical trialregisters.Indn-dua

patient data was identified for cetworic-meta analysis

Results: Urhamarepine and least:g ne are suited e

first- fine treatments for partial onset seizureswith

leretraceam asa suitable a te-atse.Evidence

supports sodium valproate as first-hoe treatment for

generalized tonic-clonic seizures

*

ft lamotrigine and

leuetiracemm as suitable alteroatres.particularly for

females of child-hearing age

Table 12. Classic Factors Differentiating Seizure, Syncope and Pseudoseizure

Characteristic Seizure Syncope Pseudoseizure*

(Psychogenic non-epileptic

seizure)

Timing Day or night (especially front Day Day, other peoplepresent

sleep) DDx of Convulsions

Syncope, psychogenic non-epileptic

seizures, hyperventilation, panic

disorder. TIA. hypoglycemia,movement

disorder,alcoholic blackouts,migraines

(confusional, vertebrobasilar),

narcolepsy (cataplexy)

Gradual,upright position (not

recumbent)

Lightheadedness,pallor,

diaphoresis,tunnel vision

Provokedby emotional

disturbance or suggestion

Variable

Onset Sudden, in any position

Early Symptoms or Signs Possible specific aura

Duration Brief orprolonged

Common

Confusion,aphasia,Todd's Ho

paresis,fatigue

Synchronous,stereotypic. Occasional briel tonic stiffening,

automatisms (common In complex can have'convulsive syncope'

partial),lateral tonguebiting,

eyes open or eyes rolled back

Brief Often prolonged

Incontinence

Post-ictal

Possible butrare Rare

Variable,often none

Note thatseizures originating in the

frontal lobes may look like psychogenic

non-epileptic spells due to an abundance

of repetitrve hyperkinetic movements:

they often occur during sleep

Motor Activity Prolonged episodes,

opisthotonos,eye closure.

Irregular extremity movements,

shakinghead,pelvic thrust

crying,tonguebiting atthe tip

Injury Common Rare unless fromfall Rare

EEG Usually abnormal tinierictal

discharges

Normal Normal

By law.the Ministry of Transportation

in most provinces must be contacted

for all patients who have had a

seizure, patients will have their license

suspended until seizure free for 6 mo.

commercial driversface a longer wait

‘Pseudosei-zures do not rule out seizures (rot Lrcommon to have both)

•alcoholic withdrawal seizures may occur up to 2 d from the last exposure to alcohol (see Emergency

Medicine. EU54 )

Investigations

•CBC, electrolytes,Ca -+,Mg2+ POt -5 ,fasting blood glucose,Cr,liver enzymes, CK, prolactin

• toxicology screen, EtOH level, AED level (if applicable)

•CT/MK1 (if new seizure without identified cause or known seizure history with new neurologic signs/

symptoms)

(Note:Neuroimaging may be normal in up to 90% of cases following the first unprovoked seizure)

•LP (if fever or meningismus)

•EECi ( Note: EEC isspecific but not sensitive)

Treatment

•avoid precipitating factors

•prognosis: risk ofseizure recurrence increases with the number of unprovoked seizures at initial

presentation, abnormal EEG, and presence of a neurological disorder

•indications for AED: EEG with epileptiform activity, remote symptomatic cause (organic brain

disease, prior head injury, or CNS infection), abnormal neurologic examination or findings on

neuroimaging, nocturnal seizure, recurrent unprovoked seizure

•psychosocial issues:stigma ofseizures, education of patient and family,status of driver’

slicense,

pregnancy issues

•safety issues: driving, operating heavy machinery, bathing,swimming alone

•appropriate follow-up; refer for evaluation for possible surgical treatment if focal and refractory

EEG findingssuggestive of

predisposition to epilepsy:spike and

wave discharges, polyspike and wave

discharges,spike-wave complex

discharges

EEG has a 17% sensitivity and 95%

specificity after first unprovoked seizure,

sensitivity increasesto 51% if EEG is

performed within 24 h

If the first routine EEG is normal, a

sleep-deprived sleep EEG should be

considered to increase the likelihood of

detecting an abnormality

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N20 Neurology Toronto Notes 2023

Status Epilepticus

•definition: medical emergency involving unremitting seizure or successive seizures without return to

baseline state of >5 min

•complications: anoxia, cerebral ischemia and cerebral edema.Ml, arrhythmias, cardiac arrest,

rhabdomyolysis and renal failure, aspiration pneumonia/pneumonitis,death (20%)

•initial measures: ABCs, vitals, monitors, capillary glucose (SEAT),ECG, nasal O’

, IV NS,IV glucose,

IV thiamine, ABCs (if respiratory distress/cyanotic)

•blood work: electrolytes,Ca Mg 2

'

, POt3 , glucose,CBC, toxicology screen, EtOH level, AED levels

•focused history: onset, past history of seizures, drug and alcohol ingestion, past medical history,

associated symptoms, witnesses/collateral history

•physical exam (once seizures controlled): LOG, vitals, HEENT (nuchal rigidity, head trauma,tongue

biting, papilledema), complete neurological exam,signs of neurocutaneous disorders,decreased

breath sounds, cardiac murmurs or arrhythmias, urinary incontinence, MSK exam (rule out injuries)

•post-treatment stabilization:CT head,EEC, Eoley catheter to monitor urine output, urine toxicology

screen, monitor for rhabdomyolysis,and IV fluids to maintain normal cerebral perfusion pressure

Antiepileptic Drugs

•focal and most generalized seizures

• valproate (Depakene*),lamotrigine (Lamict.nl*), levetiracetam (Keppra*), topiramate (Topamax*),

phenobarbital (Phenobarb'

l

, primidone, zonisamide, rufinamide (Banzel*),felbamate,

benzodiazepines

•primarily focal seizures (± 2° generalization)

carbamazepine (Tegretol*), phenytoin (Dilantin*), gabapentin (Neurontin*), lacosamide

(Vimpat*), oxcarbazepine (Trileptal*), eslicarbazepine acetate (Aptiom*), pregabalin (Lyrica*),

tiagabine (GabitriP), vigabatrin (Sabril*)

•absence seizure:ethosuximide (Zarontin")

Medical Emergency:Status epilepticus

can cause irreversible brain damage

without treatment

The most common causes of status

epilepticus in adults are failure to take

AEDs, remote symptomatic causes, and

stroke

Despite being a common cause of

seizures. EtOH withdrawal is a rare

cause of status epilepticus

Consider non-convulsive status

epilepticus in a patient who has a

persistent decreased level of awareness

>20 min after a generalized seizure:

order an EEG if unsure

Complex partialstatus epilepticus can

resemble schizophrenia or psychotic

depression

Convulsive seizures

i

>5 min

Treat asstatus epilepticus

I Teratogenicity of anticonvulsants

includes neural tube defects,deft

palate , urogenital malformations, and

heart defects.Advise patient planning

pregnancy to take1-4 mgd of folic add.

Optimize AEDs with lowest possible

dose associated with good seizure

control, preferably monotherapy if

possible. The risk of fetal malformations

with AEDs is 2x the general population:

highest risk associated with valproic acid

and/or 2+ concurrent AEDs.Consider

pre-conception AED levels if patient is

well-controlled, monthly serum levels

during pregnancy, and titrate AED to

maintain pre-conception serum levels.

Refer to high-risk OB for intrapartum

fetalscreening

1.ABCs

2. Vital signs

3.Laboratory investigations

4. Glucose 50 mL IV

5. Lorazepam 0.1 mgkg IV at 2mg/min

If fever or

meningismus CT.lumbar puncture with Gram stain,

* treat pre-emptively with antibiotics

I

Fosphenytoin 1000-1500 mg IV at 150 mg/min

or

phenytoin 20 mg/kg IV up to 30 rnglrg at a maximum rate of 50 mg/min

1

1.ICU

2.Continuousinfusion of midazolaRVpropofoVpentobarfaital

3.Burstsuppression (on EEG)

Figure17.Status epilepticustreatment algorithm

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Behavioural Neurology

• see Psychiatry. PS23

Acute Confusional State/Delirium

Table 13. Selected Causes of Acute Confusion <8>

Delidum Is a medical emergency

carrying significant risk of morbidity and

mortality. It is diagnosed when feature

1AND 2 as well asfeature 3OR 4 are

present:

• Feature1: acute onset and

fluctuating course

• Feature 2:inattention

• Feature 3:disorganized thinking

• Feature 4:altered LOC

Etiology Key Clinical Features Investigations

SAH Thunderclap H/A. increased

ICP. menmgismus, loss of

consciousness

Vascular CUP

Angiography il CT and LP negative

Stroke/TIA (ischemic or CT.MRI

hemorrhagic)

Meningitis

Focal neurologicalsigns

Infectious Fever.H/A.nausea, photophobia. CT.IP

meningismus

Fever. H/A.tseizure

Focal neurological signs

Increased ICP

Focal neurologlealsigns

Trauma H«

Increased ICP

Focal neurologicalsigns

Skin rash, active joints

Encephalitis CUP

It is often diagnosed using the Confusion

Assessment Method

MRI

Abscess CT with contrast (often ring

enhancing lesion)

traumatic Diffuse axonal shear, epidural

hematoma. SDH

Cl

MRI

Autoimmune AcuteCHS vasculitis ANA.ANCA. RF

MRI

Angiography

Serum and CSF (test for presence

of antibodies),seaich for primary

neoplasm

Paraneoplastic or autoimmune

encephalitis(anti- NMDA -R )

Onset:psychiatric features,

memory loss,seizures

Delayed:movement disorder,

and changes in BP, HR, and

temperature

Increased ICP

Focal neurologlealsigns

Papilledema

Primary or secondary CHS CT

neoplasm

Neoplastic

MRI

Search lor primary neoplasm il

metastatic disease

Seizure Focalseizure with impaired

awareness, non-convulsive status

epileplicus, post ictal contusion

Psychotic, mood, and anxiety

disorder

Illicit drug use (e.g. cocaine)

SeeSeizure Disorders and

Cpilepsy.N18

FFG

CT or MRI

Workup forseizure triggers

Primary Psychiatric Ho organicsigns orsymptoms Ho specific tests

Other Vital signs

Serum chemisliy and electrolyte

analysis

Serum and urine toxicology

screen

Flushing,dry skin and mucous Serum chemistry and electrolyte

membranes, mydriasis with loss of analysis

accommodation

Antipsychotic medication use

Muscle rigidity

Hyperthermia

Autonomic instability

Chest pain, cough with black

sputum, newonset seicure. HIN.

increased ICP. dyspnea

Medications (e.g.anticholinergic

side effects, benzodiazepines)

Serum chemistry and electrolyte

analysis

Neuroleptic Malignant Syndrome

Mild Neurocognitive Disorder (Mild Cognitive Impairment)

Prevalenccof Dcptessionin Patients with Mild

Cognitive Impairment: A Syslemalic Review and

Meta-Analysis

JAMA Psychiatry 2017;74:58-67

Purpose:to estimate the prevalence of depression in

L-idnnduatsinrith mild cognitive impairment.

Methods:Review of articles with patients with

mdd cognitive impairment as a primary study

group,reported depression /depressive symptoms

usvig a ta'dated tool, and reported die prevalence

of depression in patients with mild cognitive

impairment.

tesnlts: Pooled prevalence of depression patients

•nth add cognitive Impairment was 3ft (SS\Cl

2/-3ft|. Pievalencein community-based populations

(25%.95% C119-30) wassignificantly lower than

clime-based populations(40%. 95% Cl 32-48).

Conclusions: P-evalenceof depression in patients

with mild cognitive impairment is high.

Definition

• cognitive changes with measurable deficits in one or more cognitive domains

• preservation of independence or minimal impairment in ADLs and lADLs and not meeting criteria

for major NCD

• amnestic (precursor to AD) vs. non-amnestic

Epidemiology

• mild NCD: 2-10% at age 65 and 5-25% by age 85

Risk Factors

• non-modifiable: age. history of stroke or heart disease, and apolipoprotein E (APOE) E4 genotype

• modifiable: educational level and vascular risk factors (e.g. hypertension, diabetes mellitus, obesity)

Clinical Features

• cognitive impairment with different subtypes

• single domain vs.multiple domains (e.g. memory, visual spatial function, attention, executive

function, language)

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amnestic (memory impairment) vs. nonamnestic (memory function preserved)

• amnestic subtype is the most common and most associated with AD pathology

important to ascertain that memory complaints represent change from baseline

•neuropsychiatric symptoms:depression (50%), irritability, anxiety, aggression, and apathy

Investigations

•establish a baseline for follow-up

•clinical interview with patient and caregivers is the cornerstone of mild NCD evaluation, including

detailed family history

•neuropsychological testing

MMSE (not sensitive to early cognitive change) or MoCA (more sensitive);should be done in

conjunction with a history and neurological exam or with other neurocognitive tests

• if abnormal, follow-up in one year to monitor cognitive and functional decline

•neuroimaging

• role uncertain; a non-contrast brain CT is often ordered to evaluate for structural abnormalities

(CVD,SDH, Nl

’

H, or mass lesion);a MK1 is helpful to establish baseline and to look for other

possible reversible causes of cognitive impairment

•other testing to exclude treatable conditions (e.g. B •-

deficiency, hypothyroidism,seizures,

autoimmune encephalitis) and underlying psychiatric conditions (e.g. depression)

Treatment

•non-pharmacologic management:exercise training for 6 mo is likely to improve cognition; insufficient

evidence to support or refute cognitive intervention, it may improve outcome on select cognitive

measures

•pharmacologic management: monitoring and management of hypertension and other vascular risk

factors is recommended

•no evidence for cholinesterase inhibitors, anti

-inflammatory agents

Prognosis

•development of major NCD for age £65 is 14.9% after 2 yr

•relative risk of major NCD is 3.3 after 2-5 yr

—r

Mild

SSi

vs

|

. Major

—

I

NCD duo to

Alzheimer's disease

• Frontotemporal

• NCO withLcwy

• Vascular NCO

• Other causes o< NCO

(traumatic braininjury.

substance mcdicatcn

use,HIVinfection,

prion disease,

Parkinson s disease,

Huntington s disease)

NCO

bod N

ussagw

V

Frontal lobo Temporal lobe

|

Executive 8chaviour

function • Apathy

Language Memory

• Semanbc

• Oisinhibbon dementia

• Non-fluent

progressive

aphasia

Figure 18. Major NCD classification

Major Neurocognitive Disorder (formerly Dementia)

Sensitivity and Specificity

Tool Sensitivity Specificity

• see Psychiatry. PS24 MMSE 81% 82%

Clinical 85%

Judgment

82%

Definition

• acquired, generalized, and (usually) progressive impairment of cognitive function associated with

impairment in ADLs/IADLs (e.g.shopping, food preparation, finances, medication management)

• diagnosis of major NCD requires presence of significant cognitive decline from a previous level of

performance in one or more cognitive domains(complex attention, executive function, learning and

memory,language, perceptual-motor, or social cognition) based on:

a) concern of the individual or a knowledgeable informant AND

b) substantial impairment in cognitive performance either documented by standardized

neuropsychological testing or quantified clinical assessment

. see Psychiatry, PS24

• in comparison, mild NCD does not affect ADLs

mild NCD represents an intermediate stage between major NCD and normal aging

Epidemiology

• major NCD:1-2% at age 65 and reaching as high as 30% by age 85

• major NCD due to AD is uncommon before age 60

• major NCD due to frontotemporal lobar degeneration has an earlier onset and represents a

progressively smaller fraction of all NCDs with increasing age

Etiology

• see Table 14, N23

• reversible causes:alcohol (intoxication or withdrawal, Wernicke’s encephalopathy), medication

(benzodiazepines, anticholinergics),heavy metal toxicity, hepatic or renal failure,Bi2 deficiency,

glucose, cortisol, thyroid dysfunction, NPH, depression (pseudodementia), intracranial tumour, SDH,

and hypercalcemia

• must rule out delirium

OSMN 76% 80%

Vitamin Biz Deficiency Symptoms

• Macrocytic anemia,pallor.SOB,

fatigue, chest pain,palpitations

• Confusion or change in mental status

(if advanced)

• Decreased vibration sense

• Distal numbness and paresthesia

• Weakness with UMN findings

• Diarrhea,anorexia

<§>

Major NCD Considerations for

Management

ABCDs

Aff ective disorders. ADLs

Behavioural problems

Caretaker,Cognitive medications and

stimulation

Directives. Driving

Sensory enhancement (glasses/hearing

aids) History

• “geriatric giants”

confusion/incontinence/falls

memory and safety (wandering,leaving doors unlocked, leaving stove on, losing objects, driving)

• behavioural (mood, anxiety, psychosis,suicidal ideation, personality changes, aggression)

polypharmacy and compliance (sedative hypnotics, antipsychotics, antidepressants,

anticholinergics)

• ADLs and IADLS

• cardiovascular, endocrine, neoplastic, renal KOS, head trauma history

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Most common causes of rapidly

progressive neurodegenerative

dementia are CJD,frontotemporal lobar

dementia,tauopathies. diffuse Lewy

body disease,and AD

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N23 Neurology Toronto Notes 2023

• alcohol,smoking

• collateral history

• family history'

Physical Exam

• blood pressure

• hearing and vision

• neurological exam with attention to signs of parkinsonism, UMN findings

• general physical exam with focus on CVD, patient-specific risk factors, and history

• MMSE or MoCA, clock drawing, frontal lobe testing ( go/no-go, word lists, similarities, proverb)

Investigations

• rule out reversible causes

• CBC ( note MCV for evidence of alcohol use and Bt:deficiency), glucose, T

'

SH, BID, RBC folate

• electrolytes, Ll'

Ts, renal function, lipids,serum calcium

CT head, MRI as indicated, SPECT (optional)

as clinically indicated: VDRL, HIV, ANA, anti-dsDNA, ANCA, ceruloplasmin, copper, cortisol,

toxicology, heavy metals

• issues to consider

failure to cope, fitness to drive, caregiver capacity and wellbeing, power of attorney,legal will,

advanced medical directives, patient and caregiver safety

Features of Early Major NCD vs.

Normal Aging

Early Signs of

Major NCD

Normal Aging

Forgetting Hie

names of close

relations

Increased frequency

of forgetting

Repeating phrases'

stories in the same

conversation

Unpredictable mood

changes

Forgetting the names

of acquaintances

Briefly forgetting part

ofaneipenence

Not putting away

tingsproperty

Mood changes

in response to

appropriate causes

Changes inusual

interests

Decreased interest

in activities and

difficulty making

choices

Table 14.Selected Causes of Major NCD (Dementia)

Etiology Key Clinical Features Investigations

PRIMARY DEGENERATIVE

AUhemet'

s disease Cholinesterase Inhibitorsfor Dementia with lewy

Bodies (OlBj.Parkinson'

s Disease Dementia

( POD) and CognitiveImpairmeut ihParkinsoo'

s

Disease (CIHDPD)

Cochrane DB Syst Per 2012;3:CD0065M

Purpose: Ic assessBedhaq :‘

rMMt «itcholmesterase inhibitorsin Dll.POD.and CIND-PD

Methods: Review of erodes hoc databases

including NEDLINE.EMEASE.PsyrINFO,and DMAHL

Results: ThesihesrrI2i5 l ddkdtd

demonstrated therapeutic beseht of choinesterase

inhibitorsfor globel assessment cognitive function,

behavioural disturbance,cndadrwtmsof daify

living.Chniinesterase iih&tmswe-? associated

with increased adierse events(OR161) and drop out

(OR 1.94).Adverse events were more corn on with

rivastigmne but not*

to doeepezl Fewer deads

occurred in the treatment goto(OR 0.21)

Conclusion: Cur.-ea er deace swsorts use of

cholinesterase m -oitorsfor patents wits POO.baths

role in 0 L8 and CINO PO rssti!: .-deaMemory impairment CT or Itfil.FOS PEI orSPECT

Aphasia, aprama. agnosia

Visual hallucinations

Parkinsonism

Fluctuating cognition

REM sleep behaviour disorder

Severe neurolepticsensitivity

Behavioural presentation:disrnhibrtion. perseveration.

decreased social awareness,mental rigidity,memory relatively spared

Language presentation:progressiva non-fluent aphasia,semantic dementia

Chnrea

Neurapsychiatnc symptoms

Dementia with Lewy bodies CT or MRI.SPEC!

Frontofenporal dementia (e.g. Pick '

s

disease)

CT or MRI.SPEC!

Huntington Genetic testing '

s disease

VASCULAR

Vascular cognitive impairment (previously Bradyphreuia wrtboet features of parkinsonism (slow thinking,slow rate of CT or IttLSPECT

learning,slow gait)

Dyseiecntive syndrome

May be abrupt onset

Stepwisedeterioration dclass*

but progressive deterioration is most

common

Systemic signs and symptoms of vasculitis

Mufti- rafarct dementia)

CHS vascu’

rtis ANA:ANCA:RF

Cl or MRI

Angiography

INFECTIOUS

Chronic meningitis Fever. HA.nausea (triad ofteo absent m cases of chronic meningitis)

Meningismns

Localizing neurological deficits

Fever.FLA

Increased ICP

Localizing neurological def ats

CT.MR1.IP

Chronic encephalitis

Chronic abscess

CTorMSI

Owth contrast.MRI

Seelnfect ccs Osrait: 1327 KIV serology

Rapidly progressive, nyocloaits.akinetic mutism, parkinsonism,or cortical EEC.Cl or MRI.IP

symptoms

Ataiia. myoclonus,tabesdorsalis

HIV

Crer.ttfe:dt-Jakob disease

SypteSs IP.CT.or MRI

VDRL

TRAUMATIC

DrPose aioualshear.epidural hematoma,

subdural hematoma

Trauma Hi

Increased ICP.papilledema

Localizing neurological signs

0.MRI

RHEUMATOIOGIC

SLE See Rheumatology,Shill MRI

A*

A

_ anti- dsONA

r m

NEOPLASTIC

Primary or secondary brain lumour

(metastasis).

paraneoplastic encephalitis

L.J

Increased ICP Cl with contrast

Localizing neurologicalsigns

Systemic symptomsotcaccer

MRI

Paraneoplastic antibodies

OTHER

Normal pressure hydrocephalus Gail disturbances +

Urinary incontinence

SeeNeurosL-tp;- y. »S9

CTotMRL

large volume IP

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N24 Neurology Toronto Notes 2023

Major or Mild Neurocognitive Dementia due to Alzheimer’s

Disease

*