N

Neurology
Eduard Bercovici, Lauren Gerard and Ognjen Papic, chapter editors
Lawrence Aoun and Sam Silver, associate editors
Jeremy Adams, EBM editor
Dr. Cheryl Jaigobin and Dr. Liesly Lee, staff editors
Basic Anatomy Review 2
Differential Diagnosis of Common
Presentations
Review of Neurological Examination
Lesion Localization
3
Diagnostic Investigations
Lumbar Puncture
6
Altered Level of Consciousness
Evaluation of Patient
Coma
Persistent Vegetative State
Brain Death
7
Seizure Disorders and Epilepsy
Seizure
Status Epilepticus
8
Behavioural Neurology
Acute Confusional State/Delirium
Dementia
Alzheimer's Disease
Lewy Body Disease
Frontotemporal Dementia
Normal Pressure Hydrocephalus
Aphasia
Dysarthria
Dysphagia
Apraxia
Agnosia
13
Cranial Nerve Deficits 20
Neuro-Ophthalmology
Acute Visual Loss
Optic Neuritis
Anterior Ischemic Optic Neuropathy
Amaurosis FugaxfTlA
Optic Disc Edema
Abnormalities of Visual Field
Abnormalities of Eye Movements
Disorders of Lateral Gaze
Internuclear Ophthalmoplegia (INO)
Diplopia
Abnormalities of Pupils
Relative Afferent Pupillary Defect
Horner's Syndrome
Anisocoria
24
Movement Disorders
Localization of Extrapyramidal Disorders
Function of the Basal Ganglia
Parkinsonism
Parkinson's Disease (PO)
Wilson's Disease
Tremor
Essential Tremor
Chorea
Huntington's Disease
Dystonia
Myoclonus
Tic Disorders
Tourette's Syndrome
29
Toronto Notes 2008
Neuromuscular Disease 38
Overview
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Other Motor Neuron Disease
Peripheral Neuropathies
Clinical Approach
Mononeuropathy Multiplex
Diffuse Symmetric Polyneuropathies
Guillain-Barre Syndrome (GBS)
Diabetic Neuropathies
Para neoplastic Neuropathies
Neuromuscular Junction Diseases
Clinical Approach
Myasthenia Gravis
Lambert Eaton Myasthenic Syndrome
Myopathies
Clinical Approach
Polymyositis/Dermatomyositis
Myotonic Dystrophy
Duchenne and Becker Muscular Dystrophy
Cerebellar Disorders 47
Approach to Cerebellar Disorders
Acquired Cerebellar Disorders
Hereditary Ataxias
Vertigo 48
Gait Disturbances 49
Disorders of Balance
Disorders of Locomotion
Pain Syndromes 50
Approach to Pain Syndromes
Neuropathic Pain
Tic Douloureux
Postherpetic Neuralgia
Complex Regional Pain Syndromes
Thalamic Pain (Dejerine Roussy Syndrome)
Headache 54
Clinical Approach to Headaches
Migraine Headaches
EpisodicTension-Type Headache
ChronicTension-Type Headache
Cluster Headache
eNS Infections 107
Spinal Cord Syndromes NS24
Stroke 57
Ischemic Stroke
Hemorrhagic Stroke
Treatment of Stroke
Multiple Sclerosis 64
Common Medications 66
Summary Key Questions 67
References 68
Neurology Nl
N2 Neurology Basic Anatomy Review Toronto Notes 200S
See functional Neuroanatomy
software Basic Anatomy Review
see also Neurosurgery, NS21 for Dennatome/Myotome infonnation
sensory cortex
upper motor neurons
in I1KItor
spinothalamic traci

Figure 1. Corticospinal Motor Pathway
" I
{lower limb & tn.<l'Ikl _ ftr.>l-order
of ....')
sensory neuron ""..-I '.,1.'
second-order
(uppelhmbl
cortex
sensory neuron within 12 spinal levels of their entry.
axons offirsl order neurons synapse onto
second order neurons, whose aXOIlS
then decussate before ascending as
the spinothalamic tract
Figure 5. SpinothalamicTract
o Cerebrocerebellum
Culmen
[J} Spinocerebellum
Vestibulocerebellum
onpUlfrom
upper limb
dorlillloot
grKlhs
ganghon
5
hmb&trunk @)
Figure 2. DiscriminativeTouch Pathway From Body
sensory cortex
face region
,Sagittal section through brainstem and cerebellum Flocculus Tormls Nodulus
Anre,ia, view
Figure 6. Cerebellum
chIef sensory
trlgenunal nucleus
Figure 3. DiscriminativeTouch Pathway From Face
Pons Midbrain Medulla
I. Corticosplnaltraet Ponril'lt"l'lucleus 1. InterpeduflCuiarfossa
1. Llteralsploolhalam,ctracr Abducens nerve fibres 2. Occulomotor lilt) nerve fibres
sensory corte"
and spinotectaillbres Corticosplnallract and 3. Cerebral peduncle
facE." region
3. Decussation 01 l'lle<h;,llemnivus cOrtkOI'lUcleilrfibtes 4 .'iubslanl,an'gr<l
... Reticularfolm.tlIon . 5. Rednucleu5
S. Nucleus of spinallracl S. Nucleus of fadal (VII) nerve (mOlor) 6. Edinger_estphal nucleI
lV) nerve (descending) 6. Facial (Villnervefib.es 7. OCculomotor (III) nucleus
6. Spinal IIKI of trigeminal (Vl nerve 7. rflgeminal {V) nerve fibres complex {motofl
7. Nucleuscul'lealus II Nucleus of abducens (VI) nerve 8. MedlallemruS(us
8. FaseJculuscunealus 9. Nucleus of spinal lracl of 9. Spinothillamiclraet
9. Nucleus groJcllr.; lrlgemlnal (V) nerve 10.
10. Fasckulus9facilis 10. lateral wstlbular nucleus 11. SuperlOfcolliculus
11. Central canal
11. Middle cerebellar peduncle
11.. Art:uatefibres
12. tv ventricle
Frances Yeung 2005
Figure 4. Spinothalamic Pain Pathway from Face
Figure 7. Brainstem
Toronto Noles 2008 Differential Diagnosis of Common Presentations Neurology N3
Differential Diagnosis of Common .
Presentations
1. Headache
migraine
tension-type
cluster
subarachnoid hemorrhage
meningitis
increased intracranial pressure
temporal arteritis
2. WeaknesslParalysislParesis/Loss of Motion
stroke
tumour
Parkinson's disease
Wilson's Disease
multiple sclerosis
myasthenia gravis
Guillain-Barre syndrome
amyotrophic lateral sclerosis
peripheral neuropathies
myopathies
3. Sensory Complaints/Numbness/Paresthesia
stroke
tumour
multiple sclerosis
peripheral neuropathies
B12 deficiency
4. Facial Pain
sinusitis
dental disease
tic douloureux (Trigeminal Neuralgia)
trigeminal neuropathic pain (2 to trigeminal nerve injury or disease)
glossopharyngeal neuralgia
postherpetic neuralgia
atypical facial pain
MS
compression of trigeminal roots from tumours or aberrant vessels
5. Facial Weakness
upper motor neuron
TIA/stroke
post-ictal hemiparesis
tumour
infection: otitis media, mastoiditis, Epstein-Barr virus (EBV), herpes zoster
virus (HZV), Lyme disease, HIV
lower motor neuron
infection: otitis media, mastoiditis, Epstein-Barr virus (EBV), herpes zoster
virus (HZV), Lyme disease, HIV
idiopathic (Bell's palsy)
sarcoid
neuropathy (DM)
parotid gland
6. Altered Mental Status
drug toxicity/overdose (i.e. opioids, benzodiazepincs, alcohol etc.)
trauma
stroke
hypertensive encephalopathy
space occupying lesion (sub-arachnoid hemorrhage, subdural hematoma,
tumour, abscess, hydrocephalus)
post-ictal state
delirium (see Psychiatry. PSI?)
dementia (see Psychiatry. PSI8)
metabolic abnormalities (i.e. hepatic encephalopathy, uremia, electrolyte
disturbances, acid-base disturbances)
endocrine (i.e. hypoglycemia, diabetic ketoacidosis)
infectious (i.e. bacterial meningitis, viral encephalitis, abscess, empyema)
psychiatric disease (i.e. depression)
N4 Neurology Differential Diagnosis of Common Presentations Toronto Notes 2008
~
7. Acute Loss of Vision
central retinal artery occlusion (retinal infarct)
ophthalmologic (retinal detachment, glaucoma; see 0rhthalmology. OP27, OP30)
anterior ischemic optic neuropathy (arteritic/tempora arteritis or
nonarteritic/atherosclerosis)
TIA/amaurosis fugax
stroke (hemianopsia/quadrantanopsia)
pseudotumour cerebn (advanced stage)
8. Diplopia
cranial nerve III/IVNI Palsies (OM, tumour, trauma, aneurysm)
brainstem pathology (stroke, tumour, MS)
thyroid opnthalmopathy
cavernous sinus pathology
myasthenia gravis
Wernicke encephalopathy
loptomeningeaf disease (e.g. meningitis)
Gullain-Barre syndrome (e.g. Miller-Fisher Variant)
9. Ptosis
cranial nerve III palsy
myasthenia gravis (uni/bilateral)
Horner's syndrome
congenital/idiopathic
myotonic dystrophy (bilateral)
mitochondnal disease
10. Vertigo
brainstem lesions (stroke, MS)
cerebellar lesions
vertebrobasilar insufficiency
neurosyphilis
drugs/arcohol
peripheral causes (see Otolaryngology. OT6)
Review of Neurological Examination
Vitals: pulse (especially rhythm), BP, temperature
Head & Neck: look for meningismus, bruises/injuries/trauma to head (i.e. battle
sign/raccoon eyes) tongue biting may suggest seizures
CardiaclVascular: auscultate for bruits (e.g. carotid), murmurs
Neurological:
General Approach
1) State of Consciousness/Arousal
Glasgow Coma Scale (GCS) (Eye, Verbal, Motor)
reflexes: responses to pain may include decerebrate and decorticate posturing
see Altered Level of Consciousness, N7
2) Mental Status (see Psychiatry. PS2)
appearance, behaviour, mood, affect, speech, thought process, thought
content, perceptions, insight, judgement
assess as is appropriate throughout the interview
3) Cognition
Mini-Mental Status Exam (MMSE), clock drawing, Baycrest
Neurocognitive Assessment
frontal lobe testing for perseveration
4) Cranial Nerve Examination (see Table 2)
5) Motor Examination
inspection: bulk, accessory movements, tremor, fasciculations, etc.
tone (assess for rigidity, spasticity, clonus)
power (0-5, 0: no contraction, 1: flicker, 2: active movement with gravity
eliminated, 3: active movement against gravity, 4-,4, 4+: active
movement against gravity and resistance,S: full power)
reflexes (0 - 4+, 0: absent with reenforcement, 1+: reduced, 2+: normal,
3+: increased, 4+: clonus present)
6) Sensory Examination
posterior columns (vibration, proprioception, light touch)
spinothalamic (pain, temperature)
cortical sensation (graphesthesia, stereognosis, extinction, 2-point
discrimination)
7) Co-ordination
finger to nose, heel to shin, rapid alternating movements
8) Stance & Gait
Romberg, tandem gait
Toronto Notes 2008 Differential Diagnosis of Common Presentations Neurology N5
Lesion Localization (WHERE is the lesion?)
----........-_...
Table 1. Anatomic Approach to Neurological Disorders, Symptoms and Signs
Location of the lesion General Symptoms Common Disorders
Cortex & Contralateral sensory & motor deficits Seizure disorder (cortex only)
Intemal capsula Cortical lesions: associated with aphasia, neglect, extinction, Coma
agraphaesthesia, astereognosia, visual loss Stroke
(higher level dysfunctions)
Internal capsule lesions: associated with pure motor, pure
sensory losses, incoordination, absence of cortical features
Cerebellum & Incoordination Cerebellar degeneration
Basal ganglia ~ Abnormal intentional movements for Parkinson's disease
cerebellar lesions (ipsilaterall Stroke
~ tremor, bradykinesia, involuntary movements for
basal ganglia lesions
Brainstam (unilatarall Contralateral UMN paralysis, contralateral proprioceptive Cranial nerve palsies
(midbrain CN 3-4; and pain temperature loss below the head and ipsilateral Stroke
pons CN 6-7; CN defects. CN defects and sensory/motor deficits are on
medulla CN 8-10) opposite sides in brain stem lesions - "crossed-signs"
MIDBRAIN: diplopia, ptosis, unreactive pupil
PONS: LMN facial weakness, quadriparesis in bilateral pontine
lesions, pinpoint pupils
MEDULLA: lateral or medial medullary syndromes
Spinal cord (unilateral) Ipsilateral paralysis and proprioceptive loss, contralateral Spinal cord syndromes
pain-temperature loss below the level of the lesion -
"crossed-signs"
Sensory level, bowellbladder dysfunction
paraparesis
Brown-Sequard syndrome
Nerve root Radicular pain +sensory/motor deficits Nerve root compression
or absent reflex Disk herniation
Paripheral nerve Ipsilateral motor and sensory deficits along Neuropathies
a nerve distribution. Presence of LMN signs
Neuromuscular junction Proximal & symmetrical muscle weakness without Myasthenia gravis
sensory loss, fatigability or fasciculations Lambert-Eaton syndrome
Diplopia, ptosis, bulbar weakness Botulism
Muscle Proximal & symmetrical muscle weakness without Muscular dystrophies
sensory loss Myopathies including polymyositis
Dermatomyositis
Table 2. Some helpful findings on physical examination
Cranial Nerves
CN1 Unilateral loss of smell suggests frontal lobe lesion (avoid irritative stimuli which stimulate CN51
CN2 Look at optic discs for edema and optic atrophy
CN3'4i6 Look for pupillary abnormalities, ptosis, abnormal eye movements
Drug reactions:
bilaterally dilated fixed pupils with anticholinergics le.g. atropine, 'mushrooms'). but also seen in herniation
bilaterally small fixed pupils with morphine and related drugs, but also seen in pontine lesion
Horner's syndrome: ptosis, miosis (anisocoria), anhydrosis Idue to interrupted sympathetic nerve supplyl
CN3 palsy: ptosis, eye is down and out, +/- impaired pupillary response (suggests astructural/compressive cause)
CNS Absent corneal reflex may be CN5 (sensory deficit) or CN7(motor deficit)
CN7 Forehead sparing: upper motor neuron lesion
CN9'10 Dysarthria
Motor System
Ataxia may be due to cerebellar disease, proprioceptive abnormality
Ataxia with eyes closed only is apositive Romberg's sign suggesting aloss of joint position sense/peripheal neuropathy
Ataxia with eyes open or closed suggests cerebellar disease
Pronator drift suggests hemiparesis or loss of position sense
Spasticity indicates upper motor neuron disease
Atrophy and fasciculations indicates lower motor neuron disease
Cogwheel rigidity is seen in extrapyramidal processes le.g. Parkinson's Diseasel
Symmetrical weakness of proximal muscles suggests myopathy; of distal muscles suggests polyneuropathy
Sensory System
Hemisensory loss with sensory level or dissociation loss suggests spinal cord lesion
Symmetrical distal sensory loss suggests polyneuropathy
Loss of vibretion sense suggests peripheral neuropathy or posterior column lesion
Impaired graphesthesia and stereognosis with intact primary sensation indicates parietal lesion
Reflexes
Increased in upper motor neuron disease
Decreased/absent in lower motor neuron disease, myopathies or neuromuscular junction disorders
Slow relaxation of ankle reflex is seen in hypothyroidism ('hung reflexes')
Babinski sign suggests an upper motor neuron lesion but may be seen following aseizure
Other
"Doll's eye" movement, if absent, suggests pons or midbrain lesion or very deep coma
Loss of vestibulo-ocular reflex with caloric stimulation suggests brain stem lesion or drug toxicity
Absence seizures can be precipitated by hyperventilation
Characteristic skin lesions are seen in neurocutaneaous syndromes (e.g. neurofibromatosis, tuberous sclerosis complex, Sturge-Weber
syndrome). non-blanching petechiae are seen in meningitis, ThromboticThrombocytopenic Purpura (TIP)
N6 Neurology Diagnostic Investigations Toronto Notes 2008
Diagnostic Investigations
Lumbar Puncture
Indications
suspected meningitis, sub-arachnoid hemorrhage (SAH) (CT negative), encephalitis,
CNS neoplasm (lymphoma, meningeal spread), work up of demyelinating diseases
and CNS vasculitis, mtrathecal drug injection
Contraindications
increased intracranial pressure (ICP)
must do cr first to rule out increased intracranial pressure (ICP)
do not attempt if mass lesion associated with papilledema, decreased level of
consciousness (LOC), or focal neurolOgical defiClt
coagulopathy, thrombocytopenia, anticoagulation
infection over lumbar puncture (LP) site
uncooperative patient
Complications
immediate: tonsillar herniation
delayed
post-LP headache (20-25%) - worse when upright, better supine
management: keep patient supine, po fluids, analgesia, blood patch
spinal epidural hematoma
infection
Table 3. Lumbar Puncture Interpretation
Condition Colour Protein Glucose Cells Other
Infectious
Viral infection Clear or opalescent Normal <0.45-1 gil Normal <100Oxl1J6/L
or slightly increased >3.0 mmoVL Lymphocytes mostly,
some PMNs
Bacterial infection Opalescent yellow, may clot >1 giL Decreased >100OxllJ6/L PMNs
(usually <2.0 mmoVL)
Granulomatous infection Clear or opalescent Increased but usually <5 giL Decreased lusually <1000xllJ6/L
(tuberculosis, fungal) <2.Q.4.0 mmol/LI Lymphocytes Low CSF glucose in TB
Neurologic
GuillainBarre Syndrome Clear or cloudy Markedly increased Normal Normal
Mulliple Sclerosis Clear Normal or increased Normal o-20x11J6/L lymphocytes Oligoclonal banding
Pseudotumour Cerebri Clear Normal Normal Normal Elevated opening pressure
Other
Neoplasm Clear or xanthochromic Normal or increased Normal or decreased Normal or increased Cytology pcsitive
lymphocytes
Traumatic tap Bloody, no xanthochromia Normal Slightly increased RBCs =peripheral blood,
less RBCs in tube 4than tube 1
Subarachnoid hemorrage Bloody, or xanthochromia Increased Normal WBClRBC ratio same as blood
after 28 h
What to send LP for
Tube #1: Cell Count and Differential
RBCs
WBCs and differential (normal: <3.0 x 106/L)
bacterial: predominantly polymorphonuclear leukocytes (PMNs)
viral: predominantly lymphocytes
xanthochromia (yellow in colour)
supernatant should be clear; if yellow, implies recent bleed into
cerebrospinal fluid (CSF)
traumatic tap does not give xanthochromia
Tube #2: Chemistry
glucose
must compare to simultaneously drawn serum glucose
bacterial: < 2.0 mmol/L or < 25% serum glucose
viral: CSF glucose is approximately 60% serum glucose ( >3.0 mmol/L)
protein
normal: <450 mgfL
bacterial: >1000 mg/L
viral: <1000 mgfL
albuminocytological dissociation: increased protein with normal cell
count implies Guillan-Barre syndrome (GBS)
additional tests: protein electrophoresis showing oligoclonal banding
may signify multiple sclerosis (MS)
CSF IgG: increased in MS and demyelinating neuropathies
Toronto Notes 2008 Diagnostic Investigations!Altered Level of Consciousness Neurology N7
Tube #3: Microbiology
gram stain
C&S
specific tests depending on clinical situation/suspicion
viral: PCR for herpes simplex virus (HSV)
bacterial: polysaccharide antigens of HJlu, N.meningitides,
Pneumococcus
fungal: Cryptococcal antigen, India ink stain (cryptococcus), culture
TB: Acid-Past stain, TB culture, TB PCR
Tube #4: Cytology (for evidence of malignancy)
Tube 1/5: RBCs (cell count) - similar to tube 111
if RBCs in tube #1 is RBCs in tube #5 then consider traumatic tap
in SAH, RBCs in tubes #1 and #5 should be approximately equal
Altered Level of Consciousness
see Neurosurgery, NS29
~ ~ _ ~ _ . ~ __...... ..,......l
Evaluation of Patient
History
previous/recent head injury (hematomas)
sudden collapse (ICH, SAH)
cardiovascular surgery, prolonged cardiac arrest (hypoxia)
limb twitching, incontinence, tongue biting (seizures, post-ictal state)
recent infection (meningitis)
other medical problems (diabetes mellitus (DM), renal failure, hepatic encephalopathy)
psychiatric illness (drug overdose)
telephone witnesses, read ambulance report, check for medic-alert bracelet
neurologic symptoms (headache, visual changes, focal weakness)
Physical Examination
Glascow Coma Scale
pupils - reactivity and symmetry, papilledema (increased ICP)
reflexes
corneal reflex: Normal =bilateral blinking response
gag reflex: Normal = gag
oculocephalic reflex (doll's eye): Normal = eyes move in opposite direction of
head, as if trying to maintain fixation of a point
vestibulocochlear response (cold caloric): Normal =nystagmus fast phase away
from stimulated ear
deep tendon reflexes
plantar reflex: Normal = flexor plantar response
tone
spontaneous involuntary movements
assess for meningeal irritation, increased temperature
assess for head injury, battle sign, racoon eyes, skin rashes, and joint abnormalities
that may suggest vasculitis
Coma
Definition
a state in which patients show no meaningful response to environmental stimuli, from
which they cannot be roused; umousable unresponsiveness
Pathophysiology
coma can be caused by lesions affecting the cerebral cortex bilaterally, the reticular
activating system (RAS) or their connecting fibres
focal supratentorial lesions do not alter consciousness except by herniation (with
compression on the brainstem or on the contralateral hemisphere) or by precipitating
seizures
Classification
structural lesions (tumor, pus, blood, infarction, CSF); 1/3 of comas
supratentorial mass lesion - leading to herniation as outlined above
infratentorial lesion - compression oT or direct damage to the RAS or its projections
..... ,,
~ ~ - - - - - - - - - - ,
~ r - - - - - - - - - - - - - ,
Glasgow Coma Scale
Eyes Open
Spontaneously 4
To voice 3
To pain 2
No response 1
Best Verbal Response
Answers questions appropriately 5
Confused, disoriented 4
Inappropriate words 3
Incomprehensible sounds 2
No verbal response 1
Best Motor Response
Obeys commands 6
Localizes to pain 5
Withdraws from pain 4
Decorticate (flexion) 3
Decerebrate (extensionI 2
No response 1
..... ' ,
Caloric Reflexes COWS
Cold Opposite, Warm Same
N8 Neurology Altered Level of Consciousness/Seizure Disorders and Epilepsy Toronto Notes 2008
metabolic disorders/diffuse hemispheric damage; 2/3 of comas
deficiency of essential substrates (e.g. oxygen, glucose, vitamin B12)
exogenous toxins (e.g. drugs, heavy metals, solvents)
endogenous toxins/systemic metabolic diseases (e.g. uremia, hepatic
encephalopathy, electrolyte imbalances, thyroid storm)
infections (meningitis, encephalitis)
trauma (concussion, diffuse shear axonal damage)
Investigations and Management
ABCs
labs: electrolytes, TSH, LFTs, Cr, BUN, Ca, Mg, PO<v tox. screen, glucose
CT/MRI, LP, EEG
consult neurosurgery if required
Persistent Vegetative State
Definition
a condition of complete unawareness of the self and the environment accompanied by
sleep-wake cycles with either complete or partial preservation of hypothalamic and brain
stem autonomic function
'awake but not aware'
follows comatose state
EtiologylPrognosis
most commonly caused by cardiac arrest or head injury
due to irreversible loss of cerebral cortical function BUT with intact brainstem function
average life expectancy 2-5 years
Brain Death
see also Neurosurgery. NS32
Seizure Disorders and Epilepsy
Seizure
Definition
seizure = paroxysmal alteration of behaviour and/or EEG changes that results from
abnormal, excessive activity of neurons
epilepsy = condition characterized by recurrent, unprovoked seizure activity
ictal =seizure
post-ictal = state of confusion/somnolence that can occur after some seizure types
inter-ictal = epileptic discharges that can be seen on EEG occuring between seizures
Classification
Table 4. Classification of Seizures
Partial (focal) seizures Generalized seizures
Simple partial seizures (without altered LOC) Absence Atonic
with motor signs typical Unclassified
with somatosensory or special sensory signs atypical
with autonomic signs Clonic
with psychic symptoms Myoclonic
Complex partial seizures (with altered LOCI 'Tonic
Partial seizure evolving to a 2' generalized seizure 'Tonic-c1onic
Etiology
Generalized
infectiolls/inllammatory
encephalitis, meningitis, neurocystercercosis
toxic/traumatic
medications (tricyclic antidepressants (TCAs), monoamine oxidase
inhibitors (MAOls), neuroleptics, cyclosporine, theophylline, isoniazid)
drugs (alcohol withdrawal, cocaine, amphetamines)
Toronto Notes 2008 Seizure Disorders and Epilepsy Neurology N9
anatomic
diffuse cerebral damage (anoxia, storage diseases)
metabolic
hypoxia
electrolytes (hypocalcemia, hypoglycemia, hyponatremia, hypernatremia,
hyperosmolality)
end-stage organ failure (renal, hepatic)
other (e.g. porphyria)
neonatal causes
idiopathic
epilepsy
Partial (focal)
vascular
cerebral hemorrhage, cortical infarcts, arteriovenous malformations
(AVMs), cavernous malformations, subdural hematoma
infectious/inflammatory
meningitis, encephalitis, cerebral abscess, subdural empyema, syphilis,
tuberculosis (1'8), HIV
sarcoidosis, systemic lUpus erythematosus (SLE)
toxic/trauma
cerebral trauma (subdural hematoma)
anatomic
hippocampal sclerosis
cortical dysplasias
neoplastic
primary or metastatic CNS tumours
neonatal
birth injury (e.g. hypoxia), IVH
idiopathic
epilepsy
Epidemiology
in developed countries, 2% to 4% of all persons have recurrent seizures at some period
in their lives; higher incidence in developing countries (i.e. cysticercosis is one of the
most common causes)
incidence highest among young children and elderly
age of onset: primary generalized seizures rarely begin <3 or >20 years of age
M:P = 1.5:1
epilepsy affects about 45 million people worldwide
Risk Factors
stroke risk factors (see Stroke, N57)
past history of neurological insult: birth injury, head trauma, stroke, CNS infection,
drug use/abuse
past history of seizures
family history of seizures
malignancy
Precipitants
sleep deprivation, drugs/alcohol, TV screen, strobe, emotional upset
fever: febrile seizures affect 4% of children between 3 months - 5 years of age;
benign if brief, solitary, generalized tonic-clonic seizure lasting less than 15 minutes
and not more frequent than once/24 hours (see Pediatrics. P80)
Signs and Symptoms (Table 5, Table 6)
during seizure
unresponsiveness or impaired LOC
nature of neurological features suggests location of focus
motor =frontal lobe
visual/olfactory/gustatory hallucinations = temporal lobe
salivation, cyanosis, tongue biting, incontinence, loud cry
Jacksonian march: one body part is initially affected, followed by spread to
other areas (e.g. fingers to hand to arm to face)
adversive: head or eyes are turned forcibly to the contralateral frontal eye field
automatisms: patterns of repetitive activities that look purposeful
(e.g. chewing, walking, lip-smacking)
temporal lobe epilepsy: behavioural disturbances, automatisms, olfactory or
gustatory hallucinations
1
9
'
Stroke is the most common cause of
lateonset (>50 years of agel epilepsy,
accounting for 5080% of cases.
NIO Neurology Seizure Disorders and Epilepsy Toronto Notes 2008
.... '
..
I
Motor andlor sensory partial
seizures indicate structural disease
until proven otherwise.
duration: ictus is seconds to minutes, post-ictus can be long
(minutes to hours)
after seizure
post-ictal symptoms: limb pains, tongue soreness, headache, drowsiness,
Todd's paralysis (paresis)
Table 5. Partial Seizures
Simple motor arise in precentral gyrus Imotor cortex!. affecting contralateral faceJtrunkJ1imbs
ictus
no dlange in consciousness
rhythmical jerking or sustained spasm of affected parts
dlaracterized by forceful turning of eyes and head to side opposite the discharging focus ladversive seizures)
may start in one part and spread "uP/down the cortex'IJad<sonian mardl- remember the homunculus)
duration usually seconds to minutes !Todd's may last hoursl
arise in sensory cortex (postcentral gyrus), affecting contralateral faceJtrunkilimbs
Simple sensory somatosensory
numbnessltinglingl"electric" sensation of affected parts
a"mardl' may occur
other forms include: visual, auditory, gustatory, vertiginous (may resemble schizophrenic hallucinations but patient
recognize the unreality of phenomena)
Simple autonomic epigastric disconfort, pallor, sweating, flushing, piloerection, and pupillary dilatation
Simple psychic disturbance of higher cerebral function
symptoms rarely occur without impairment of consciousness and are mudl more commonly experienced as complex partial
seizures
Complex partial seizures causing aherations of mood, memory, perception
lternporallobe epilepsy, common form of epilepsy, with increased incidence in adolescents, young aduhs
psychomotor epilepsy)
ictus
automatisms occur in 90% of patients Idlewing, swallowing, lipsmacking, scratdling, fumbling, running, disrobing,
continuing any complex act initiated prior to loss of consciousness)
aura of secondsminutes
forms include:
dysphasic, dysmnesic (deja vU), cognitive Idreamy states, distortions of time sense),
affective Ilear, anger), illusions (macropsia or micropsia), structured hallucinations Imusic, soenes, taste, smells),
epigastric fullness
then patient appears distant, staring, unresponsive (can be brief and confused with absence seizuresl
recovery is dlaracterized by confusion headadle
can resemble schizophrenia, psydlotic depression lif complex partial statusl
Table 6. Generalized Seizures
Absence onset in dlildhood
(Petit Mal) hereditary
autosomal dominant
incomplete penetrance 1-1/4 will get seizures, -113 will have dlaracteristic EEG findings)
3Hz spike and slow-wave ectivity on EEG
ictus
, dlild will stop activity, stare, blink/roll eyes, be unresponsive; lasting approximately 5-10 seconds or so, but may occur
hundreds of times/day
may be induced by hyperventilation
often associated with poor sdlolastic pertormance
Myoclonic ictus
sudden, brief, generalized muscle contractions lrapid jerking movementsl
most common disorder is juvenile myoclonic epilepsy lonset after puberty, does not remit with agel
also occurs in degenerative and metabolic disease le.g. hypoxic encephalopathyl
Toni:lonic common
(Grand Mal) all of the classic features do not necessarily occur every time
prodrome of unease, irritability hourso{jays before attack
ictus
aura lif secondarily from apartial onset) seconds to minutes before attack of olfactory hallucinations, epigastric
discomfort, deja vu, jerking of alimb, etc.
tonic phase: tonic contraction of muscles, with arms flexed and adducted, legs extended, respiratory muscles in spasm ("cry'
as air expelledl, cyanosis, pupillary dilatation, loss of consciousness, patient often "thrown' to the ground; lasting 10-30 seconds
clonic phase: clonus involving violent jerking of face and limbs, tongue biting, and incontinence; duration variable
postictal phase of decreased level of consciousness, with flaccid limbs and jaw, extensor plantar reflexes, loss of comeal reflexes; lasts
hours; headadle, confusion, adling muscles, sore tongue, amnesia; serum CK elevated for hours
Investigations
CBC, sodium, glucose, Ca, Mg, Cr, BUN, LFTs
CXR, ECG
EEG (bursts of sharp and slow waves represent epileptiform activity; focal epileptiform
in secondarily generalized; spikes and slow waves at 3Hz in absence) - interictal EEG is
normal in 60% of cases
prolactin-increased post-ictally with generalized tonic-clonic seizure (compare with
baseline level)
CT/MRI except for definite primary generalized epilepsy
LP if signs of infection and no papilledema or midline shift of brain structures
(generally done after CT or MRI, unless suspicious of meningitis)
tox screen
Toronto Notes 200S Seizure Disorders and Epilepsy Neurology Nll
Differential Diagnosis
syncope (see Table 7)
note: syncope may induce a seizure - this is not epilepsy
pseudoseizure (see Table 8)
anxiety: hyperventilation, panic disorder
TIA
hypoglycemia
movement disorders: myoclonus, episodic ataxias
alcoholic blackouts
migraine: confusional, vertebrobasilar
narcolepsy (cataplexy)
Table 7. Seizures versus Syncope
Characteristic Seizura Syncope
Time of onset day or night day
Position
any
upright, not recumbent
Onset sudden or brief graduallvasodepressorl
Aura possible specific aura diuiness, visual blurring, lightheadedness
COlour normal or cyanotic (tonic-elonicl pallor
Autonomic features uncommon outside of ictus common
diaphoresis
Duration brief or prolonged brief
Urinary incontinence common rare
Post-ictal symptoms can occur with tonic-clonic or complex partial' rare
Motor activity can occur occasional brief jerks
Injury common, tongue biting rare, from fall
Automatisms can occur with absence or complex partial none
EEG frequently normal, but may be abnormal normal
Table 8. Seizures versus Pseudoseizures (non-epileptic "seizures"'conversion disorder)
Characteristic Epileptic Seizure Psaudoseizure
Age any any, less common in elderly
M=F F>M
Triggers uncommon emotional disturbances
Duration brief may be prolonged
Motor activity automatisms in complex partial seizures opisthotonos
stereotypic rigidity
synchronous movements forced eye closure
irregular extremity movements
side-to-side head movements
pelvic thrusting
crying
Timing day or night usually day
usually other people present
Physical injury may occur non-serious
Urinary incontinence may occur
rare
Reproduction of attack spontaneous suggestion, or stimuli plus suggestion
EEG inter-ictal discharges frequent normal
Prolactin increased normal
Treatment
psychosocial
educate patients and family
advise about swimming, boating, locked bathrooms, operating dangerous
machinery, climbing heights, chewing gum
pregnancy issues: counselling and monitoring blood levels closely,
teratogenicity of anticonvulsant drugs, folate 4-6 mg/day (throughout
child-bearing years), vitamin K (at time of delivery)
evaluate for fetal neural tube defects
inform of prohibition to drive and requirements to notify Ministry of
Transportation
support groups, Epilepsy Association
follow-up visits to ensure compliance, evaluate changes in symptoms/seizure
type (re-investigate)
N12 Neurology Seizure Disorders and Epilepsy Toronto Notes 2008
o
pharmacologic (Table 9)
begin with one major anticonvulsant with a simple dosage schedule
adjust dose to achieve plasma level in therapeutic range
if no seizure control, increase dose until maximum safe dose or side effects
become intolerable
if still no seizure control, change to or add second drug
non-pharmacologic treatment
for selected cases of complex partial epilepsy and/or identifiable focus
vagal nerve stimulator
ketogenic diet
surgical resection
Table 9. Major AntiEpileptic Drugs
Type of Seizure Medication Dosing Schedule Therapeutic ranges
Partial or carbamazepine carbamazepine: start at 100-200 mg PO OD-bid, increase by 17-50 umoVL
2' generalized phenytoin 200mgld q2d up to 800-1200 mg/d lin divided dosesl if needed
valproate (mechanism. antkonvulsant, voltage dep. block of Na channelsl
phenytoin: if loading necessary -300 mg PO q4h x3doses, 40-80 umol/L
l' generalized valproate then 300 mg PO hs. Serum levels should be monitored if giiven IV do not exceed
lTonic-Clonicl phenytoin (mechanism voltage dependant block of Na channelsl 50 mglmin
(Grand Mall carbamazepine
va/praate. start at 15 mgt1<g/d PO increasing by 5-10 mgt1<g1d qweekly 350-700 umoVL
until seizures are controlled or intolerable side effects. Maximum daily
dose is 60 mgt1<g/d Imechanism unknown; GABA enhancingl
Absence ethosuximide ethosuximide: start 500 mg daily PO in divided doses, increasing by 280-710 umoVL
IPetitMal1 valproate 250 mgld q4-7days pm up to amaximum dose of 1500 mgld
Imechanism: inhibits NADPH-linked aldehyde reductase necessary
for the formation of GABAI
Myoclonic clonazepam clonazepam: 0.5 mg PO tid, increase by 0.5-tO mg/d q3d pm
valproate up to 20 mgld (in divided doses)
(mechanism: benzodiazepine; GABA enhancerl
Source: Clinician's Pocket reference 9lb Gomella LG &Haist SA Eds, McGraw-Hili, NewYork, 2002.
Pharmacological Treatment of Diseases, Pressaco J &Yu HEds, Urban Angel Medical Books, Toronto, 1996.
other adjuncts: clobazam, gabapentin, pregabalin
newer anticonvulsants: lamotrigine, topiramate, levetiracetam
Status Epilepticus
a life-threatening state (5-10% of epileptics) with either a continuous seizure lasting at
least 30 minutes or a series of seizures occurring without the patient regaining full
consciousness between attacks
complications: repetitive grand mal seizures impair ventilation, resulting in anoxia,
cerebral ischemia and cerebral edema; sustained muscle contraction can lead to
rhabdomyolysis and renal failure
Initial Management
ABCs
lateral semi-prone position, mandible pushed forward; use
oropharyngeal tube with high-flow oxygen
monitor vitals, including temperature
pulse oximetry
start intravenous lines
interrupt status (proceed through steps if seizure continues):
1. give 50 mL 50% glucoseN and thiamine 100 mg IM
2. [orazepam (0.1 mglkg IV at 2 mg/min)
3. ehenytoin (15 mglkg IV at maximum of 50 mg/min) or fosphenytoin
(20 mglkg PE IV at 150 mg/min), monitor cardiac rhythm and BP
4. additional phenytoin (5-10 mglkg IV at maximum of 50 mg/min can give up to a
total dose of phenytoin of 20 mg/kg) or fosphenytoin (5-10 mglkg PEN at 150 mg/min)
5. phenobarbita1 (20 mglkg IV at 50 mg/min); watch for hypotension and
respiratory depression (high dose IVbarbiturates requires central line to monitor
CVP)
6. if seizures continuing at this point, consider additional phenobarbital
(5-10 mg/kg IV at 50 mg/min) or proceed directly to 7
7. anesthesia with midaz01am or propofol (in ICU)
take focused history and examine patient
trauma
known seizure disorder
focal neurological signs
history or signs of medical illnesses, especially infection
check for neck stiffness, signs of head injury
Toronto Notes 2008 Seizure Disorders and Epilepsy/Behavioral Neurology Neurology N13
investigate cause of the status
CBC, electrolytes (including Ca), liver enzymes, Cr, BUN
glucose level (rule out hypoglycemia)
ABG
draw metabolic and drug screen (most common is alcohol)
measure anticonvulsant levels
CXR, EEG and consider STAT CT or MRI if first seizure or if focal neurological
deficits elicited
LP to evaluate for infection and subarachnoid hemorrhage if CT normal
Behavioural Neurology
see Psychiatry, PS17
Acute Confusional StatelDelirium
o
Table 10. Clinical Features of the Acute Confusional State
Level of consciousness " alertness, " attention, " concentration; fluctuating; worse at night. "sundowning" .... ' ,
.}--------------,
Psychomotor stetus psychomotor retardation
Delirium is characterized by acute
psychomotor agitation
onset, disorientation, marked vari-
Emotional status anxietyflrritability ability, altered level of conscious-
depression/apathy
ness, poor attention, and marked
psychomotor changes.
Perception illusions and hallucinations (usually visual and tactilel
gustatOly and olfactory hallucinations suggest temporal lobe epilepsy
Cognition memory disturbance (registration, retention, and recall)
disorientation
Table 11. Selected Intracranial Causes of Acute Confusion
Etiology Key Clinical Features Investigations
Vasculer Subarachnoid hemorrhage thunderclap headache CT (non-contrast)
'1' ICP 'LP
meningismus
StrokernA focal neurological signs CT (non-contrastl
Infectious Meningitis fever, headache, nausea, photophobia
LP
meningismus
Encephalitis focal neurological signs 'LP;MRI
fever, headache, t seizure
Abscess '1' ICP CT with contrast
focal neurological signs (often ring enhancing lesionI
Traumatic Diffuse axonal shear, trauma Hx CT Inon-eontrastl
Epidural hematoma, '1' ICP 'MRI
Subdural hematoma focal neurological signs
Autoimmune Acute CNS vasculitis skin rash, active joints ANA; ANCA; RF .... ' ,
) - - ~ = = = = - - - - - ,
MRI
angiography
Visual Hallucinations more com-
Neoplestic Mass effect/edema, '1' ICP CT (non-contrast)
monly indicate organic disease.
Hemorrhage, focal neurological signs 'MRI
Seizure papilledema
Seizure Status epilepticus see Seizure Disorders and Epilepsy, NB 'EEG
Todd's phenomenon
Primery psychiatric Psychotic disorder no organic signs or symptoms no specific tests
Mood disorder
Anxiety disorder
N14 Neurology Behavioral Neurology Toronto Notes 200S
Table 12. Selected Extracranial Causes of Acute Confusion - "HIT ME"
~ )
Etiology Key Clinical Features Investigations
'
Hypoxia Respiratory failure cyanosis, tacl1ypnea, tacl1ycardia 'ABG;CXR
Etiology of Delirium
Heart failure '5&50fCHF ABG; CXR; ECG
Carbon monoxide ICO) Hx CO exposure 'ABG
Infectious
poisoning
Withdrawal from drugs
Infectious Septicemia systemic S&S septicemia blood C&S
Acute metabolic disorder Pneumonia cough; respiratory distress 'CXR
Trauma UTI irritative urinary S&S urine R&MlC&S
eNS pathology
Hypoxia
ToxinSiMeds Alcohol see Emergency Medicine, ERSt toxicology screen
Benzodiazepines drug levels
Betablockers
Deficiencies in vitamins
Anticl10linergics
Endocrinopathies
Acute vascular insults
Metabolic Hepaticlrenal failure 5&S acute hepatic/renal failure liver enzymes; LFTs
Toxins see Gastroenterology, G32 , Nephrology, NP29 electrolytes, BUN, Cr
Heavy metals Electrolyte imbalance ' s e e ~ N P 9 electrolytes
'Ca panel
B" deficiency peripheral neuropathy; subacute combined serum 8
12
degeneration; glossitis 'CBC
Endocrine 1'/01- thyroid S&S hyper/hypothyroidism 'T5H,T3,T4
1'/01- glucose S&S DMihypoglycemia serum glucose
1'/01- cortisol S&S Cushing'siAddison's disease serum cortisol
Management of Acute Confusion - General Measures
well-lit room
hearing aids and glasses
orienting stimuli (clocks, calendars)
avoid restraints or catheters
stop all unnecessary medications
treat underlying cause, antipsycotics
~ Dementia
See Psychiatry, PS18
Definition
an acquired, generalized and (usually) progressive impairment of cognitive
function (i.e. memory, recall, orientation, language, abstraction etc.)
affects content, but not level of consciousness
affects 5-20"10 of people over age 65
Epidemiology
15"10 of those> 65 years of age have dementia
common etiologies: 60-80"10 Alzheimer's Disease (AD); 10-20"10 vascular dementia
<5"10 reversible: hypothyroid, normal pressure hydrocephalus (NPH), nutritional
deficiencies, depression and infection
History
'll' geriatric giants
incontinence/falls/polypharmacy
ADI.s IDEATH) IADLs ISHAFT) memory and safety (wandering, leaving doors unlocked, leaving stove on,
Dressing Shopping losing objects)
Eating Housekeeping behavioural (mood, anxiety, psychosis, suicidal ideation, personality
Ambulating Accounting changes, aggression)
Toileting Food preparation cardiovascular, endocrine, neoplastic
Hygiene Transportation EtOH, smoking
OTes, herbal remedies, compliance, accessibility
collateral history is usually very helpful
history of vascular disease
Physical Examination
hearing and vision
neurological exam
as directed depending on risk factors and history
MMSE
+ clock drawing
+ frontal lobe testing (go/no-go, word lists, similarities, proverb)
+ Baycrest NeurocognitiVE' Assessment
Toronto Notes 2008 Behavioral Neurology Neurology N15
Investigations
depend on suspected etiologies (see Tables 13 and 14)
CBC (note MCV), glucose, TSH, B12, folate
electrolytes LFTs renal function
CT head if Hx of TIA, stroke, focal neurological deficit, <65 years old,
rapid progression (weeks to months), immunocompromised, Hx of
neoplasm that can metastasize to brain, anticoagulant use
MRI as indicated
as clinically indicated - VDRL, HlV, ANA, anti-dsDNA, ANCA,
ceruloplasmin, copper, cortisol, toxicology, heavy metals
issues to consider
failure to cope
fitness to dnve
caregiver education and stress
respite services and day programs
power of attorney
wills
advanced directives (DNR)
Table 13. Common Causes of Dementia
Etiology Key Clinical Features Investigations
Primary degeneratiue Alzheimer's disease memory impairment CT or MRI, SPECT
aphasia, apraxia, agnosia
Lewy body disease hallucinations CT or MRI, SPECT
parkinsonism
fluctuating cognition
frontotemporal dementia disinhibition 'MRI, SPECT
(e.g. Pick's diseasel wsocial awareness
wpersonal hygiene
memory relatively spared
Huntington's disease chorea molecular testing
Vascular multi-infarct dementia abrupt onset MRI, SPECT
stepwise deterioration
systemic vasculopathy
CNS vasculitis systemic S&S of vasculitis ANA; ANCA; RF
'MRI
angiography
Table 14. Acquired Causes of Dementia
Etiology Key Clinical Features Investigations
Infectious chronic meningitis fever; headache; nausea LP +investigations
meningismus
localizing neuro deficits
chronic encephalitis fever; headache 'LP; MRI
chronic abscess '1' ICP CT with contrast
localizing neuro signs
HIV see Infectious Disease ID28 HIV serology
Creutzfelt-Jacob disease rapidly progressive 'EEG
syphilis ataxia, myoclonus
LP
'VDRL
Traumatic diffuse axonal shear, trauma Hx CT (non-contrast)
epidural hematoma, '1' ICP, papilledema
subdural hematoma localizing neuro signs
Rheumatologic SLE see RH9 MRI; ANA, anti-dsDNA
Neoplastic mass effect/edema, '1' ICP CT with contrast
hemorrhage, localizing neuro signs 'MRI
seizure
paraneoplastic encephalitis systemic S&S of cancer anti-Hu antibodies
Table 15. Reversible Causes of Dementia
Etiology Key Clinical Features Investigations
ToxinsIMeds Wernicke-Korsakoff anterograde amnesia no specific test
confabulation trial of thiamine
ataxia, ophthalmoplegia
benzodiazepines, see Emergencv Medicine, ER51 toxicology screen
Il-blockers, drug levels
anticholinergics
heavy metals S&S heavy metal toxicity urine heavy metals
Metabolic hepatidrenal failure S&S acute hepatidrenal failure liver enzymes; LFT's
see Gastroenterology. G32, Nephrology, NP29 electrolytes, 8UN, Cr
Wilson's disease KayserFleischer rings serum ceruloplasmin, Cu
hepatic failure
8" deficiency peripheral neuropathy; subacute combined serum Bl2
degeneration; glossitis
Endocrine 1'/,), thyroid S&S hyper/hypothyroidism 'TSH,T
3
,T,
1'/,), glucose S&S DMlhypoglycemia serum glucose
1'/,), cortisol S&S Cushing'siAddison's disease serum cortisol
Structural NPH gait apraxia 'CT
inconlinence
LP
dementia measure opening pressure
Primary Psychiatric depression (pseudodementia) no organic S&S no specific tests
N16 Neurology Behavioral Neurology Toronto Notes 2008
Alzheimer's Disease
Definition
progressive cognitive decline interfering with social and occupational functioning
characterized by the following
1) anterograde amnesia - impaired ability to learn new information
2) one of the following cognitive disturbance
a. Aphasia - language disturbance
b. Apraxia - impaired ability to carry out motor activities despite intact motor
function
c. Agnosia - failure to recognize or identify objects despite intact sensory function
d. Disturbance in executive function - planning, organizing, sequencing,
abstracting
Pathophysiology
genetic factors
a minority 7%) of AD cases are familial, autosomal dominant
3 major genes for autosomal dominant AD have been identified:
amyloid precursor protein (chromosome 21)
presenilin 1 (chromosome 14)
presenilin 2 (chromosome 1)
the E4 polymorphism of apolipoprotein E is a susceptibility genotype
pathology (although not necessarily specific for AD)
gross pathology
diffuse cortical atrophy, especially frontal, parietal, and temporal lobes
microscopic pathology
senile plaques (amyloid made from derived from cleaved
amyloid precursor protein)
neurofibrillary tangles (intracytoplasmic paired helical filaments with
and hyperphosphorylated Tau protein)
biochemical pathology
50-90% reduction in action of choline acetyltransferase
Epidemiology
1/12 of population 65-75 years of age
1/3 of population >85 years of age
accounts for 60-80% of all dementias
Risk Factors
FHxofAD
head injury
low education level
smoking
aluminum
Downs syndrome
Signs and Symptoms
cognitive impairment
memory impairment for newly acquired information (early)
memory impairment for remote events
deficits in language, abstract reasoning, and executive function
psychiatric manifestations
major depression (5-8%)
psychosis (20%)
motor manifestations (late)
parkinsonism (consider Lewy body disease)
Investigations
perform investigations to rule out other causes of dementia as necessary
EEG: generalized slowing (nonspecific)
MRI: dilatation of lateral ventricles; widening of cortical sulci, small infarcts (amyloid
angiopathy) nonspecific changes
SPECT: hypometabolism in temporal and parietal lobes
Treatment
acetylcholinesterase inhibitors have been shown to improve cognitive function
donepezil (Aricept)
rivastigrnine (ExelonTM)
galantamine (ReminyJTM)
other - although efficacy not proven
ginkgo biloba
tacrine
Toronto Notes 2008 Behavioral Neurology Neurology N17
Vit E
NMDA receptor agonist - memantine (Ebixa)
symptomatic management
low dose neuroleptic
trazodone for sleep disturbance
antidepressants
Prognosis
progressive
mean duration of disease 10 years
Lewy Body Disease (LBO)
- - - - - - - - - - - - - - - ~ - - - - -
Definition
progressive cognitive decline interfering with social or occupational function; memory
loss mayor may not be an early feature
one (for possible LBO) or two (for probable LBO) of the following:
fluctuating cognition with pronounced variation in attention and alertness
recurrent visual hallucinations
parkinsonism
Etiology and Pathogenesis
Lewy bodies (eosinophilic cytoplasmic inclusions) found in both cortical and
subcortical structures
Epidemiology
15-25% of all dementias
Signs and Symptoms
fluctuation in cognition with progressive decline
visual hallucinations
parkinsonism
repeated falls
sensitivity to neuroleptic medications (develop rigidity, neuroleptic malignant
syndrome, and extrapyramidal symptoms)
REM sleep disorder
Treatment
acetylcholinesterase inhibitors (e.g. donepezil)
Prognosis
typical survival 3-6 years
Frontotem oral Dementia
Definition
progressive dementia characterized by personality change, speech disturbance,
inattentiveness, and extrapyramidal signs
Etiology and Pathogenesis
gross pathology
atrophy of frontal and temporal poles
microscopic pathology
Pick bodies (intraneuronal inclusions containing abnormal Tau proteins)
Epidemiology
10% of all dementias
Signs and Symptoms
core features
insidious onset and gradual progression
early decline in social interpersonal conduct
early impairment in regulation of personal conduct
early emotional blunting
early loss of insight
behavioural disorder
decline in personal hygiene and grooming
mental rigidity/inflexibility
perseverative and stereotyped behaviour
speech and language
altered speech output (economy or pressure of speech)
echolalia/perseveration
N18 Neurology Behavioral Neurology Toronto Notes 2008
physical signs
primitive retlexes (i.e. pout, grasp, palmo-mental, glabellar)
parkinsonism
Investigations
MRljSPECT - frontotemporal atrophy/hypometabolism
Normal Pressure Hydrocephalus
------------'
see Neurosurgery. NS7
Definition
an acquired disturbance of language characterized by errors in speech production,
writing, comprehension, or reading
Neuroanatomy of Aphasia
Broca's area (posterior inferior frontal lobe) involved in speech production (expressive)
Wernicke's area (posterior superior temporal lobe) used for comprehension of
language
angular gyrus is responsible for relaying written visual stimuli to Wernicke's area for
reading comprehension
the arcuate fasciculus association bundle connects Wernicke's and Broca's areas
>99% of right-handed people have left hemisphere language representation
70% of left-handed people have left hemisphere language representation, 15% have
right hemisphere representation, and 15% have bilateral representation
Assessment of Language
.... ' , assessment of context
,,}-------------,
handedness (writing, drawing, toothbrush, scissors)
Aphasia localizes the lesion to the
education level
dominant cerebral hemisphere.
native language
learning difficulties
assessment for aphasia
1. spontaneous speech
fluency
\',
paraphasias: semantic ("chair" for "table"), or phonemic ("dable" for "table")
The left hemisphere is dominant for
2. repetition
3. naming
language in almost all right-handed
4. comprehension (auditory and reading)
people and 70% of left-handed people.
5. writing
6. neologisms
Approach to Aphasias
Table 16. Fluent Aphasias
Wernicke's Conduction Anomie SensoryTranscortical-
Lesion - posterior superior - arcuate fasciculus - numerous possible locations 1. subcortical temporoparietal
temporal lobe 2. temporoparietal watershed
11s1 temporal gyrus) between MCA and PCA
territories
Comprehension - poor 'good -good poor
Repetition - poor poor good
- good
Naming - relatively spared poor - poor - relatively spared
'Transcortical aphaSias are typically associated with cerebral anoxia (e.g. post-MI, CO poisoning, hypotension)
Table 17. Non-fluent Aphasias
Broca's Global MotorTranscortical' MixadTranscortical'
Lesion posterior inferior frontal lobe posterior inferior frontal lobe AND a. frontal lobe watershed between oombined sensory and motor
posterior superior temporal lobe MCA and ACA tenitories transoortical
b. white matter lesions deep to lal
Compt'ehension 'good poor 'good 'poor
Repetition poor poor 'good good
Naming poor 'poor poor poor
'Transcortical aphasias associated with cerebral anoxia le.g. post-MI, CO poisoning, hypotensionl
Toronto Notes 2008 Behavioral Neurology Neurology N19
Prognosis
most recovery from stroke-related aphasia occurs in first three months, but may
continue for>1 year
with recovery, the type of aphasia may evolve
poor prognosis: global aphasia
Dysarthria
Definition
inability to produce understandable speech due to impaired phonation (laryngeal
sound production) and/or resonance (the alteration of sounds in the cavity between
the larynx and the lips/nares) secondary to impaired motor control over peripheral
speech organs
Classification of Dysarthria
Table 18. Classification of Dysarthria
Classification Characteristics of Speech Etiologies'
Flaccid 'slurred, indistinct speech , motor neuron (e,g, ALSI
ILMN dysarthria or bulbar palsy) 'particular difficulty with vibratory "R"
'difficulty with lingual consonants produced by , peripheral nerve le,g, GBSI
tongue and labial consonants produced by lips , neuromuscular junction (e,g, MGI
, myopathy (e,g, dermatomyositis/polymyositis)
Spastic , slow and monotonous 'stroke
(upper motor neuron (UMN) dysarthria or 'strained or strangled 'tumour
pseudobulbar palsy) 'harsh , demyelination
, low pitched , degeneration
Ataxic , slow/akered rhythm 'cerebellar disease
improper stress , cerebellar outflow tract disease
, staccato speech
Extrapyramidal Hypokinetic , low-pitched , Parkinson's disease
, monotonous other causes of parkinsonism (see Movement
'decrescendo volume Disorders, N29)
Hyperkinetic Choreiform , Huntington's disease
, prolonged sentence segments , Dystonia musculorum deformans
intermixed with silences 'other hyperkinetic extrapyramidal disorders
'variable, improper stress (see Movement Disorders, N29)
'bursting quality
Dystonic
'slow speaking rate
'prolonged individual phonemes
'Abbreviations: ALS -amyotrophic lateral sclerosis; GBS - Guillain-Barre syndrome; MG -myasthenia gravis; OM -dermatomyositis; PM - polymyositis,
ysphagla
see Gastroenterology, G4
Apraxia
--------------------------'
Definition
inability to perform skilled voluntary motor sequences that cannot be accounted for by
weakness, ataxia, sensory loss, impaired comprehension, or inattention
Clinicopathological Correlations
Table 19. Apraxia
Description Tasts Hemispheres
Ideomotor 'inability to perform skilled learned motor 'blowing out amatch; left
sequences combing one's hair
Ideational 'inability to sequence actions ' preparing and mailing an envelope ' right and left
ConstnJctional' , inability to draw or construct ' copying afigure ' right and left
Dressing' 'inability to dress 'dressing , right
Refers specifically to the inability to carry out the learned movements involved in construction, drawing, or dressing; not merely the inability to
construct, draw, or dress, Many skills aside from praxis are needed to carry out these tasks,
N20 Neurology
..... '
.
,
.)-------------,
Lesions of the dominant parietal lobe
are characteriNd by Gerstmann's
Syndrome: acalculia, agraphia, finger
agnosia, and left-right disorientation.
Lesions of the non-dominant parietal
lobe are characterized by neglect,
anosognosia, and cortical sensory loss.
Behavioral Neurology/Cranial Nerve Deficits Toronto Notes 200S
Agnosia
Definition
disorder in the recognition of the significance of sensory stimuli in the presence of
intact sensation and naming
Clinicopathological Correlations
Table 20. Agnosias
Description Lesion
Aperceptive visual agnosia' inability to name or demonstrate the use of an object bilateral temporo-occipital cortex
presented visually 2' to distorted visual perception
recognition by touch remains intact
Associative visual agnosia' inability to name an object presented visually 2' to bilateral inferior temporo-occipital junction
disconnect between visual cortex and language areas
visual perception is intact as demonstrated by
visual matching
Prosopagnosia inability to recognize familiar faces in the presence of bilateral occipitotemporal areas or right inferior
intact visual perception and intact auditory recognition tempora-occipital region
Colour agnosia inability to perceive colour bilateral inferior temporlHlccipitallesions
Astereognosis inability to identify objects by touch anterior parietal lobe in the hemisphere opposite the
affected hand
Finger agnosia inability to recognize, name, and point dominant hemisphere parietal-occipital lesions
to individual fingers
Cranial Nerve Deficits
CN I: Anosmia
Clinical Features
absence of sense of smell
usually associated with a loss of taste sense; if taste is intact, consider malingering
usually not recognized by patient if it is unilateral
Classification
nasal: odours do not reach olfactory receptors because of physical obstruction
heavy smoking, chronic rhinitis, sinusitis
olfactory neuroepithelial: destruction of receptors or their axon filaments
influenza, herpes simplex, hepatitis virus, atrophic rhinitis (leprosy)
central: olfactory pathway lesions
congenital: Kallman syndrome (anosmia and hypogonadotropic
hypogonadism), albinism
head injury, cranial surgery, SAH, chronic meningeal inflammation
meningioma, aneurysm
Parkinson's disease
CN II: Optic Nerve
see Neuro-Ophthalmology, N24
CN III: Oculomotor Nerve Palsy
--"------_.......
Clinical Features
ptosis, eye is "down and out" (depressed and abducted), divergent squint, pupil
dilated (mydriasis)
pupillary constrictor fibres are on periphery of nerve
external compression of the oculomotor nerve results in umeactive pupil with
subsequent progression to extraocular muscle paresis
vascular infarction results in extraocular muscle paresis with sparing of the
pupil
Common Lesions
midbrain (infarction, hemorrhage)
may/may not affect pupil, may be bilateral with pyramidal signs contralaterally
Toronto Notes 200B Cranial Nerve Deficits Neurology N2I
posterior communicating artery aneurysm
..... ' ,
.l--------------,
pupil involved early, headache
cavernous sinus (internal carotid aneurysm, meningioma, sinus thrombosis)
Pupil sparing in CN III palsy suggests a
CN IV, V1 and V2/ and VI also travel in the cavernous sinus, pain and proptosis
vascular lesion.
may occur
Pupillary involvement in CN III palsy
ischemic (DM, temporal arteritis, HTN, atherosclerosis)
suggests external nerve compression.
pupil often spared
CN IV: Trochlear Nerve Palsy
-----------_.....
Clinical Features
diplopia, especially on downward and inward gaze
patient may complain of difficulty going down stairs or reading
patient may hold head tilted to side opposite of palsy to minimize diplopia
(Bielschowski head tilt test)
Common Lesions
trauma
ischemic (DM, HTN) most common
cavernous sinus (carotid aneurysm, thrombosis)
CN III and VI usually involved as well
orbital fissure (tumour, granuloma)
at risk during neurosurgical procedures in the midbrain because of long intracranial
course
only CN that exits posteriorly and crosses midline; left side symptom = right CN
pathology
CN V: Trigeminal Nerve
Trigeminal Nerve Lesions
Common Lesions
pons (vascular, neoplastic, demyelinating, syringobulbia)
petrous apex (petrositis)
orbital fissure, orbit, cavernous sinus (Ill, IV, VI also affected)
skull base (nasopharyngeal or metastatic carcinoma, trauma)
cerebellopontine angle
VII, VIll
acoustic neuroma, trigeminal neuroma, subacute or chronic
meningitis
other causes (DM, SLE)
herpes zoster
usually affects ophthalmic division (VI)
tip of nose involvement watch out for corneal involvement
(Hutchinson's sign)
Trigeminal Neuralgia (Tic Douloureux)
o
Definition
excruciating paroxysmal shooting pains in trigeminal root territory
Etiology
redundant or tortuous blood vessel in the posterior fossa, irritating the origin of the
trigeminal nerve
tumours of cerebellopontine angle (rare)
Clinical Features
characterized by: a series of severe, sharp, short, stabbing, unilateral shocks
usually in V3 distribution Vl' V2
pain typically lasts only a few seconds to minutes, and may be so intense that the
patient winces (hence the term tic)
may be brought on by triggers: touching face, eating, talking, cold winds
lasts for days/weeks followed by remission of weeks/months
F > M; usually middle-aged and elderly
physical examination is normal (if abnormal, think trigeminal neuropathy)
Investigations
clinical diagnosis (make sure no sensory loss over CN V)
sensory loss in trigeminal distribution suggests structural lesion (consider
demyelination, tumour)
N22 Neurology
.... ' ,
9')-------------,
CN VI has the longest intracranial
course and is vulnerable to increased
ICP, creating afalse localizing sign.
.... ' ,
9}-o-----------,
Forehead is spared in a UMN CN
Vlliasion.
Cranial Nerve Deficits Toronto Notes 2008
Treatment
medical
carbamazepine
c1onazepam, phenytoin, gabapentin and baclofen may also be beneficial
surgical (all methods are 80% effective, for -5 years)
microvascular decompression of redlUldant blood vessel at origin of trigeminal
nerve
percutaneous thermocoagulation
injection of glycerol/phenol into trigeminal ganglion
CN VI: Abducens Nerve Palsy
Clinical Features
inability to abduct the eye on the affected side
patient complainS of horizontal diplopia, which is worse on lateral gaze to the affected
side
Common Lesions
pons (infarction, hemorrhage, demyelination)
may be associated with facial weakness and contralateral pyramidal signs
tentorial orifice (compression, meningioma)
may be a false localizing sign in increased ICP
cavernous sinus (carotid aneurysm, thrombosis)
vascular - may be secondary to OM, HTN, or temporal arteritis
congenital- Duane's syndrome
CN VII: Facial Nerve
Clinical Features
LMNlesion
the entire face on ipsilateral side is weak
taste dysfunction to ant 2/3
both vollUltary and invollUltary movements are affected
impaired lacnmation, decreased salivation, numbness behind auricle,
hyperacusis
UMNlesion
weakness of contralateral lower face; frontalis is spared
Investigations
look for associated brainstem or cortical symptoms and signs to help localize lesion
Differential Diagnosis
idiopathic =Bell's Palsy
trauma
infection (otitis media, mastoiditis, Ebstein-Barr virus (EBV), herpes zoster virus
(HZV), HIV)
other
sarcoidosis, Group B Streptococcus, OM mononeuropathy, parotid gland
pathology
Bell's Palsy
see Otolaryngology, OT23
Definition
an idiopathic benign lower motor neuron (LMN) facial nerve palsy
Clinical Features
acute onset of unilateral (rarely bilateral) LMN facial weakness
diagnosis of exclusion
must rule out symptoms and signs of brainstem and hemispheric dysfunction
and systemic disease
etiology
lUlknown: thought to be due to swelling and inflammation of facial nerve in its
canal within the temporal bone
associated features which may be present
pain behind ipsilateral ear (often precedes weakness)
prodromal; viral upper respiratory tract infection (URII)
hyperacusls
decreased taste sensation
abnormal tearing (decreased lacrimation)
------------------
Toronto Notes 2008 Cranial Nerve Deficits Neurology N23
Treatment
patient education and reassurance
eye protection (because of inability to close eye)
artificial tears, lubricating oinhnent
patch eye at night
steroids (weigh risks and benefits)
start early after onset of symptoms (within 12 hours)
typical regime is prednisone 40-60 mg tapered over 7-10 days
acyclovir
controversial but used in the setting of a recent viral infection
Prognosis
spontaneous recovery in 85% over weeks to months
poor outcome
if complete paralysis lasts 2-3 weeks
if elderly or HTN
if symptoms of hyperacusis, abnormal tearing
Hemifacial Spasm
Definition
segmental myoclonus of facial muscles innervated by CN VII
Clinical Features
usually presents in the 5
th
or 6
th
decade of life
almost always presents unilaterally, beginning as myoclonus of orbicularis oculi
and can spread to other muscles after a few years
clonic movements eventually progress to tonic contractions of involved muscles
Etiology
majority of cases due to chronic irritation of facial nerve nucleus or nerve
(causing aberrant transmission within the nerve)
most common cause is idiopathic, caused by aberrant AICA artery compressing
facial nerve within the cerebellopontine angle
other causes
compressive lesions - tumor, AV malformation
non-compressive lesions - MS, stroke
Investigations
EMG - observe high frequency discharges of motor unit potentials that correlate
with clinically observed facial movements
MRl - detailed analysis of posterior fossa (especially with FIESTA sequence) to
obeserve aberrant blood vessels overlying the facial nerve
Treatment
carbamazapine and benzodiazepines (i.e. clonazepam) very useful in early/mild stages
botox injections - latency 3 - 5 days; duration 6 months
surgery - useful when idiopathic or compressive - treat with decompression of the
aberrant blood vessels - usually very favourable results
eN VIII: Vestibulocochlear Nerve
see Otolaryngology. OTl2
eN IX: Glossopfiaryngeal Neuralgia
Clinical Features
brief, sharp, attacks of pain affecting posterior pharynx
pain radiates toward ear and triggered by swallowing
taste dysfunction in post 1/3 of tongue
Treatment
carbamazepine
surgical lesion of CN IX
eN X: Va us Nerve
vagus nerve lesions result in
palatal weakness: affects swallowing
pharyngeal weakness: affects swallowing
laryngeal weakness: affects speech
..... '
.:\-------------,
An isolated cranial nerve defect,
especially of eN VI or VII, is most
likely the result of aperipheral,
and not abrainstem, lesion.
.... ,,
.l------------,
When screening for the presence of
dysphagia and assessing risk for aspi
ration, the presence of agag reflex is
inslJfficient. Rather the correct screen
ing test is to observe the patient drink
ing water from acup and looking for
coughing, choking, or "wetness" of
voice.
N24 Neurology Cranial Nerve DeficitsfNeuro-Ophthalmology Toronto Notes 2008
CNXI: Accessory Nerve
accessory nerve lesions
this nerve is vulnerable to damage during neck surgery
results in shoulder drop on the affected side, and weakness when turning the
head to the opposite side
CN XII: Hypoglossal Nerve
tongue fasciculation
deviation towards side of lesion
Ot er Differentials of [ower (c-N r , X, XI
and XII) Cranial Nerve Lesions
- - - - - - ~ - - - -
..... ' ,
,1----------,
intracranial/skull base
meningiomas, neurofibromas, metastases, osteomyelitis, meningitis
Clinical signs and symptoms sug-
brainstem
gesting lesions of both acranial
infarction, demyelination, syringobulbia, poliomyelitis, tumours (astrocytoma)
nerve and long tract signs imply a
brainstem localizing disease.
neck
trauma, surgC:'ry, tumours
Neuro-Ophthalmology
Acute Visual Loss
Etiology
ophthalmologic (seE' Ophthalmology, OP3)
corneal edema
glaucoma
vitreous hemorrhage
retinal detachment
optic nerve
optic neuritis
acute ischemic optic neuropathy (AlON)
arteritic
non-arteritic
compression by space occupying lesion (e.g. aneurysm)
vascular
TIA/amaurosis fugax
retinal artery occlusion
retinal vein occlusion
eNS
infarction/hemorrhage involving occipital lobe, optic radiations in temporal!
parietal lobe
lesions in optic tract/chiasm
Optic Neuritis
see also Optic Disc Edema, N25
most common etiology is multiple sclerosis (MS)
signs .
ipsilateral relative afferent pupillary defect (RAPD)
swollen disc if anterior optic neuritis (- 33% of cases), not seen in retrobulbar
optic neuritis (-66% of cases)
treatment
acute treatment consists of coursE' of N methylprednisolone - reduces time to
maximal recovery; does not affect dE'gree of recovery
Anterior'lschemic Optic Neuropathy
~ . - . : : _ - . . . . . . , ; = - - - - - - - , . - -
see also Optic Disc Edema, N25
non arteritic
atherosclerotic variety
most common in elderly
no evidence of systemic diseasE'
diagnosis and treatment: similar to secondary stroke prevention
(e.g. anti-platelet thE'rapy, lipid lowE'ring)
Toronto Notes 2008 Neuro-Ophthalmology Neurology N25
arteritic
.... '
..\------------,
,
most common cause is giant cell arteritis (see Rheumatology. RH17)
diagnosis: elevated ESR; if suspect giant cell arteritis, must do temporal artery If you suspect the diagnosis of
biopsy Giant Cell Arteritis do not wait for
treatment - high dose steroids biopsy results!
recovery of visual loss usually poor Begin treatment immediately!
Amaurosis FugaxfrlA
"----------------------"
central retinal artery occlusion: complete loss of vision
branch retinal artery occlusion: altitudinal loss of vision
can be transient (amaurosis fugax) or permanent (retinal infarct)
diagnosis and treatment: see Stroke, N57
O ~ t i c Disc Edema
Table 21. Causes of Optic Disc Edema
Optic Neuritis Papilledema Anterior Ischemic Neuropathy
rapidly progressive central vision loss usually no visual loss until late acute field defects
acuity affected possible transient obscuration decreased colour vision
decreased colour vision variable acuity
normal colour vision
Other symptoms tender globe, painful on motion headacne typically unilateral
rarely bilateral in adults nausea
may alternate eyes in multiple sclerosis vomiting
focal neurological deficits
Pupil no anisocoria no anisocoria no anisocoria
RAPD present 'no RAPD RAPD present
Fundus anterior have disc swelling variable disc swelling and retinal hemorrhages pale segmental disc edema with
variable papillitis absent venous pulsations retinal dot andlor flame hemorrhages
Etiologies MS, viral infection increased ICP le.g. mass lesion pseudotumour giant cell arteritis
associated with MS in 74% cerebril, malignant hypertension
of females and 34% of males
Treatment 'IV methylprednisolone may shorten treat specific cause of increased ICP consider ASA for non-arteritic
attacks; oral prednisone may increase
relapse rate
Other Causes of Disc Edema
central retinal vein occlusion
systemic illness
HTN, vasculitis, hypercapnia
toxic/metabolic/nutritional deficiency
infiltration
neoplastic: leukemia, lymphoma, glioma
non-neoplastic: sarcoidosis
pseudotumour cerebri
idiopathic signs and symptoms of increased ICP, with a normal CT
usually in obese young women
compressive
meningioma, hemangioma, thyroid ophthalmopathy
Abnormalities of Visual Field
Visual Field Defects
lesions anywhere in the visual system, from the optic nerve to the occipital cortex will
produce characteristic visual field defects (see Figure 8)
Definitions
monocular
scotoma: an area of absent or diminished vision within an otherwise intact
visual field
binocular
hemianopsia: loss of half of the visual field
homonymous: loss of either the right or left half of the visual field in both eyes
bitemporal: loss of both temporal visual fields (lesion of chiasm)
quadrantanopsia: loss of one quarter of the visual field
N26 Neurology
.... ' I
.}------------,
A lesion in acerebral hemisphere
causes eyes to "look away from
the hemiplegia.
A lesion in the brainstem causes
the eyes to "'oak toward" the side
of the hemiplegia.
Neuro-Ophthalmology Toronto Notes 2008
--.... --.... Visual Field Defects
right anopsia
(right optic nerve lesion)
right anopsia and left upper
quadrantanopsia (junctional sco-
tomal
optic nerve bitemporal hemianopsia
(chiasmaI lesion)
optic chiasm -..:....
optic tract--;;:;"
left homonymous hemianopsia
temporal ':'
(right optic tract lesion)
radiation ,,_ .............
(Meyer's loop) \\ LGB
left upper quadrantanopsia
"..
(right temporal lesion)
..
radiation ','('calcarine left lower quadrantanopsia
r fissure
(right parietallesionl
(lGB =lateral geniculate body)
Figure 8. Characteristic Visual Field Defects with Lesions Along the Visual Pathway
Abnormalities of Eye Movements
Disorders of Lateral Gaze
Etiology
brainstem infarcts
multiple sclerosis
tumours
Pathophysiology
voluntary eye movements are triggered in the frontal eye fields, located anterior to the
precentral gyrus, bilaterally in the frontal lobes
each frontal eye field controls voluntary saccades to the contralateral side via
connections to the contralateral paramedian pontine reticular formation (PPRF)
a unilateral lesion in one frontal eye field: prevents voluntary saccades to the opposite
side, eyes deviate toward the side of the lesion (may also occur with a large parietal
lobe lesion)
can be overcome with doll's eye maneuver
a unilateral lesion in the pons: prevents voluntary saccades to the ipsilateral side, eyes
deviate away from the lesion (because the corticopontine pathways cross)
cannot be overcome with doll's eye maneuver
seizure involving a frontal eye field: cause eye deviation towards the opposite side
Internuclear Ophthalmoplegia (lNO)

Etiology
MS (most common; see Multiple Sclerosis, N64)
vascular disease
neoplasm
Wernicke's encephalopathy
Pathophysiology
results from a lesion in medial longitudinal fasdculus (MLF) which causes
disconjugate gaze (see Ophthalmology, OP36) .
MLF links CN VI in pons with the contralateral CN III in midbrain
Clinical Features
on gaze away from the side of the lesion, adduction of ipsilateral eye is impaired but
there is full excursion of the contralateral eye in abduction with abduction nystagmus
cannot be overcome by caloric testing
accommodation reflex intact
may be bilateral
up beating nystagmus on upward gaze often present
Toronto Notes 2008 Neuro-Ophthalrnology Neurology N27
Diplopia
Monocular
most due to relatively benign optical problems (refractive error, cataract, functional)
Binocular
etiology
cranial nerve palsy (see CraniaL Nerves, N20)
CN III
- diabetes, aneurysm, tumour, trauma
- isolated CN III palsy with pupil sparing usually due to DM and
most will resolve spontaneously in several months
- isolated CN III palsy with pupil involved usually indicates
compressive lesion (especially posterior communicating
artery aneurysm)
CNN
- diabetes, trauma
CNVI
- diabetes, tumour, trauma
muscle
thyroid eye exophthalmos
neuromuscular junction
myasthenia gravis (MG) (see Myasthenia Gravis, N44)
a useful test is the Tensilon (edrophonium) test
Tensilon is a drug that inhibits acetylcholinesterase
in myasthenia gravis, Tensilon administration will improve
muscle function immediately and transiently
other
orbital trauma, tumour
Wernicke's encephalopathy
Miller-Fischer variant of CBS
leptomeningial disease
clinical features
diplopia worse
at end of the day suggests myasthenia gravis (e.g. fatiguable)
if only diplopia on extremes of gaze, cover each eye in isolation during extremes
of gaze
the covered eye that makes the outermost image disappear is the one
with pathology
Abnormalities of Pupils
Relative J(fferent Pupillary Defect RAPD)
(Marcus-Gunn Pupil)
Definition
a failure of direct pupillary responses to light, caused by a defect in the visual afferent
pathway anterior to the optic chiasm
indicates damage to the afferent portion of the pupillary reflex arc
optic nerve (optic neuritis, ischemia, compression)
optic chiasm (severe compression, e.g. pituitary tumour)
optic tract to the pretectal nucleus
clinical testing
swinging light test
swing light from one eye to the other; both pupils should constrict
initially
when normal side is illuminated, both pupils constrict
when damaged side is illuminated, both pupils paradoxically dilate
pupil reacts poorly to light, and better to accommodation
differential diagnosis
optic neuritis is the most common cause of RAPD
other causes: optic nerve compression, large retinal detachment, central retinal
artery/vein occlusion, advanced glaucoma
N28 Neurology Neuro-Ophthalmology Toronto Notes 2008
Homer's Syndrome
Definition
a sympathetic defect
clinical features: may cause partial ptosis, miosis, anhidrosis, and apparent
enophthalmos occur anywhere along the sympathetic pathway on the affected side
1st-order neuron (central): hypothalamus, medulla (brainstem stroke), spinal
tumour, MS, intracranial tumours, syringomyelia
2nd-order neuron (preganglionic): apical lung cancer (Pancoast's tumour),
paravertebral mass, carotid artery dissection
3rd-order neuron (postganglionic): cluster headache, migraine, cavernous sinus
mass, trauma (including surgical)
clinical confirmation with cocaine test: cocaine does not dilate a miotic Homer's pupil
central vs. pre-ganglionic vs. post-ganglionic
paredrine (hydroxyamphetamine) will not dilate a post-ganglionic pupil, but
will dilate a pre-ganglionic or central lesion
no test to differentiate central from pre-ganglionic lesion
Ciliary ganglion
Short ciliary Sympathetic root
nerves of ciliary ganglion
Trigeminal
ganglion .,
Ophthalmic branch
of trigeminal ganglion
Internal carotid artery
External carotid artery
Lung
Thoracic sympathetic
trunk
Figure 9. Sympathetic Pathway
Anisocoria
definition - unequal size of the pupils
idiopathic anisocoria
round, regular, <1 mm difference
pupils reactive to light and accommodation
responds normally to mydiatrics/ rniotics
see Table 22 for other causes of anisocoria
Toronto Notes 2008 Neuro-OphthalmologylMovement Disorders Neurology N29
Table 22. Summary of Conditions Causing Anisocoria
FeatuI1l Site of Lesion Light IIld Anisocoria MydriaticII MioticI EIfect of Pilocarpine
Acc:onvnodation Reflex
Abnonnal Pupil Miotic [Impaired pupillary dilation)
ArgyIl-Robertson Irregular, Midbrain Poor to light; better to Dilates/Constricts
(syp/lilisl pupil usually bilateral accommodation
Homer's Syndrome Round, unilateral, Sympathetic system Both brisk Greater in dark Dilates I Constricts
ptosis,anhidrosis
pseudoenophthalmos
Abnonmal Pupil Mydriatic limpaired pupillary constriction)
Allie'sTonic pupil Irregular, larger in Ciliary ganglion Poor to light. better to Greoter in light Dilates /Constricts Constricts Ihypersensitivity
bright light accommodation to dilute pilocarpinel
CHIn Palsy Round CN III fixed l a c u t e ~ 1 at 7-9mm Grealer in light Dilates/Constricts Constricts
Mydriatic pupil Round, uni- or bilateral Iris sphincter Rxedat 7-8mm Greater in light No effect Will not constrict
Movement Disorders
Localization of Extrapyramidal Disorders
Table 23. Corticospinal vs. Extrapyramidal Lesions
Corticospinal (pyramidal) Extrapyramidal
Muscle tone spastic rigid or hypotonic
Involuntary movements absent present
Tendon reflexes increased normal
Plantar reflexes upgoing 'downgoing
Paralysislweakness present absent
Examples stroke Parkinson's disease
Function of the Basal Ganglia
the globus pallidus pars intema (GPi) prevents excessive movement by tonic inhibition
of the cortical motor areas via the thalamus
net effect of striatal activity is to inhibit the GPi and thus to promote movement
Motor Cortex
PremOlar Cortex
jSupplementary Motor Area
INDIRECT DIRECT PATHWAY
PATHWAY
globus palildus -GABA.
pars Interna
,------'"---------,
excitalory connections pedunculopontlne I
.. Inhibitory connections
nucleus .
Figure 10. Neural Connections of the Basal Ganglia
The cerebral cortex initiates movement via excitatory (Glutamatergic, Glu) projections to the striatum (Le. basal ganglial via two path-
ways: direct and indirect. Final common pathway is the ventral thalamus and its projections back to the motor cortex (thalamocortical)
Indirect: Cortex ~ Striatum ~ GPe ~ STN ~ GPi ~ Thalamus ~ motor cortex
Activation of this pathway causes inhibition 01 the thalamus and ultimately prevents movement
Direct: Cortex ~ Striatum ~ GPe ~ GPi ~ Thalamus ~ motor cortex
Activation of this pathway activates STN which removes the inhibitory effect of the GPi on the thalamus, thereby allowing movement
N30 Neurology
..... ' ,
.}-------------,
Ocular signs, absent rest tremor,
early postural instability, and poor
response to levodopa should
cause one to suspect secondary
parkinsonism or parkinson-plus
syndromes.
o
Summary of key symptoms: TRAP
Tremor
Rigidity
AkinesiaJbradykinesia
Postural instability
Movement Disorders Toronto Notes 2008
Parkinsonism
Table 24. Selected Causes of Parkinsonism+
l' PO" PSP MSA Vascular CBGO
l-dopa effect
Rest tremor
Postural instability Late Late
Dystonia
UMN S&S
Distribution Sym Unilateral
Dementia
Gaze dysfunction
Dysautonomia Lale +ISDS)
MRI Normal Midbrain atrophy ,j, striatum on T2 Multi-infarct Parietal atrophy
Other See below Pseudobulbar palsy Cerebellar dysfunction HTN Alien limb
(OPCA) Apraxia
Stridor (SNDI
+Abbreviations: PD -Parkinson's Disease; PSP - Progressive Supranuclear Palsy; MSA - Mulliple System Atrophy; CBGD -Cortical Basal Ganglionic
Degeneration; OPCA -Olivopontocerebellar Atrophy; SND -Striatonigral degeneration; SDS - Shy-Drager Syndrome
" Drug-induced PD can be clinically indistinguishable from primary PD
Other Important Causes of Parkinsonism
secondary parkinsonism
postencephalitic
toxic (Mg, CO, MPTP)
post-traumatic
neuroleptics
parkinson-plus syndromes (complex clinical presentations)
progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome)
early postural instability, ophthalmoplegia, rare tremor
multiple-system atrophy (Shy Drager syndrome); OPCA (see N48) striato-nigral
degeneration
autonomic symptoms/signs
diffuse Lewy body disease (see Dementia, NI7)
presence of dementia for 2:1 year before onset of Parkinsonism
frontotemporal dementia (see Dementia, N17) - cortico-basal ganglion
degeneration
hereditary diseases
Wilson's disease (see Wilson's Disease, N33)
juvenile Huntington's disease
Parkinson's Disease (PD)
---"'---"---------------'
Definition
syndrome characterized by tremor, bradykinesia, rigidity and postural instability
Etiology
genetic
many genes identified but account for small minority of PO
earlier onset --+ more likely genetic role
environmental toxins
MJYrP, pesticides
oxidative stress/mitochondrial DNA mutations
Pathophysiology (Figure 11)
-..v striatal dopamine (OA) --+ disinhibition of globus pallidus pars intema and
substantia nigra pars reticulata .-> 1'inhibition of cortical motor areas
pathology: degeneration of dopaminergic neurons in the pars compacta of the
substantia nigra
presence of Lewy hodies in substantia nigra
Epidemiology
80% of all parkinsonism
prevalence 0.5-1 % in people 65-69 yrs old, 1-3% in people 2:80 yrs old
average age of onset is 60 yrs old; M:F=1.5:1
Toronto Notes 200S Movement Disorders Neurology N31
Signs and Symptoms
positive motor
rest tremor - most common initial finding
distal extremities; 4-5Hz
classic "pill-rolling" tremor of thumb and forefinger; also lips, chin, and
tongue, increased with distraction, decreased with movement
rigidity
cogwheeling - ratcheting of extremity during passive motion
smooth -lead pipe
flexed posture
negative motor
bradykinesia (slow movement; difficulty initiating movement; loss of automatic
movement)
facial- hypomimia (masked facies with -.ltblinking); drooling
(from failure to swallow automatically); dysphagia; wide eyes
vocal- hypophonia (soft speech), aprosody (monotonous speech),
dysarthria, and tachyphemia (inability to separate syllables clearly)
manual- micrographia (small and slow writing); difficulty shaving,
brushing teeth, combing hair; decremental amplitude of rapid successive
movements
gait - slow shuffling gait, short stride, -.ltarm swing
postural instability (late sign)
leads to falls
gait
- shuffling
- patient moves faster so as to move feet under the flexed body's
centre of gravity
freezing (transient inability to perform active movements)
commonly with walking
lasts a few seconds
triggers - beginning to walk, approaching a destination or barriers
overcome by visual cues
cognitive
bradyphrenia - slowness in responding to questions; inability to change mental
sets
dementia - generally occurs late
if occurs early (within 1 yr of diagnosis), consider Lewy body disease
behavioural
changed personality (dependent, fearful, indecisive, passive)
wspontaneous speech
avolition and depression
sleep disturbances
autonomic
constipation
inadequate bladder emptying
sexual dysfunction
Investigations
the diagnosis of PD is made mostly on clinical grounds
imaging not required in a typical presentation
N32 Neurology Movement Disorders Toronto Notes 2008
Treatment
Table 25. Medical Management of Motor Symptoms of Parkinson's Disease
Mode of Action Agents &Initial Dosages Comments
DA precursor CarbidopaA.evodopa: 251100 mg bid-qid, increase as
needed Imax 20012000 mgldl
Mainstay of treatment, this is the mosl widely used formulation
Excellent motor response
Peripheral dopa decarboxylase inhibitor lcarbidopa) decreases
peripheral OA resulting in less nausea and increasing
OA available in the CNS
DAagonist Bromocriptine: 1.25 mg PO bid
Pergolide: 0.05 mg PO 00, titrate q2-3d to desired
effect, usual maintenance is 3-6 mgld in
divided doses
Pramipexo/e: 0.125 mg PO tid, increase to 1.5-4.5 mgld
in divided doses
Overall less effective than levodopa
Longer half-life than levodopa and less likely to induce dyskinesias
Used mostly as adjuvant therapy to decrease levodopa
dose or to overcome fluctuations/dyskinesias
Can be used as monotherapy early on
RopinilO/e: 0.25 mg PO tid, increase weekly.
max dose 24 g1d
DA releaser I
NMDA antagonist
Amantadine: 100 mg PO 00 up to 100 mg PO qid Used in early PO
Rapid action
Short lived effect in advanced PO
MAO Binhibitor Se/egeline: 5mg PO bid
Rasagiline
Mild symptomatic effect
Used in early PO
Synergistic with levodopa
Anticholinergics Trihexyphenidy/: 1-2 mg PO 00, then 2-5 mg PO OD-qid
BenztlOpine: 0.5-6 mgld PO in divided doses
Less effective than OA agonists
Good for tremors, does not improve bradykinesia/rigidity
Adverse effects include cognitive deterioration and delirium
COMT inhibitors Entacapone: 200 mg administered concurrently with
each levodopalcarbidopa dose to amax of 8x/d
To/capone: 100 mg PO tid
Add to carbilfevo to extend half-life
Used to control fluctuations
Follow liver function, risk of fulminant liver failure
Worsening of dyskinesia 2' to levodopa, may need to ,),dose levodopa
.Abbreviations: OA - dopamine; COMT - catechol-O-methyllransferase
Table 26. Surgical Management of Motor Symptoms of Parkinson's Disease
Comments
Thalamotomylthalamic stimulation' 'good for contralateral intractable tremor
Paliidotomy/pBliidal stimulation' 'good for contralateral dopa-induced dystonia and chorea
'also good for bradykinesia and tremor
Subthalamic stimulation , best for contralateral bradykinesia and tremor
'can allow ,j, l,dopa dose - ,j, dopa-induced complications
Embryonic dopaminergic transplantation 'for bradykinesia and rigidity in young patients
'Stimulation procedures involve permanent Implantation of electrodes whose stimulation parameters can be fine-tuned to suit the patients evolving clinical condition
Complications ofTherapv
Table 27. Levodopa Related Fluctuations
Management
Delayed onset of response 'give l,dopa before meals
, reduce protein content of meals
El1lkf-dose deterioration ("wearing-off")' , ,j, dose of l,dopa with dopamine agonists
, slow-release carbidopaJl,dopa
, COMT inhibitors
Random oscillation ("on-off"j 'symptomatic relief of 'off" periods with dissolved l,dopa in carbonated water Ifast absorptionl or
injected apomorphine Isoluble OA agonistl
'COMT inhibitors
'Retum of parkinsonian symptoms wnhin 4hours of last dose
Table 28. Levodopa Related Dyskinesias
Timing Management+
Paak-dose dyskinesias' 'at height of anti parkinsonian benefit ',j, size and l' frequency of l,dopa dosing
'slow-release l,dopa
',j, l,dopa and add Selegeline or OA agonist
Diphasic dyskinesias' beginning and end of dosing intelVal ''I' dose of l,dopa Ibut beware peak-dose dyskinesiasl
'use OA agonist as major antiparkinsonian with only adjunctive l,dopa
"Off" Dystonia+ 'painful cramps appearing during 'off" states 'limit 'off" periods by using OA agonist as major antiparkinsonian with
only adjunctive l,dopa
'Can be chorea, dystonia, or ballism .ean also manage symptomatically le.g. manage dystonia with muscle relaxant baclofenl Abbreviations: DA -dopamine
Toronto Notes 2008 Movement Disorders Neurology N33
Wilson's Disease (a.k.a. hepatolenticular de eneration)
Pathophysiology
defect in copper metabolism resulting in accumulation of copper in brain (specifically
basal ganglia, cerebellum), kidneys, liver, corneas
autosomal recessive inheritance of mutation of ATP7B protein on chromosome 13
Epidemiology
1 in 35 000-100 000 live births, gene frequency 0.56%
children most commonly present with liver cirrhosis (average age 11 years)
young adults most commonly present with neurological sequelae
(average age 19 years)
lethal if left untreated
Signs and Symptoms
neurological
polyneuropathy - often presenting symptom, may be reversed with treatment
movement abnormalities - parkinsonism, dysarthria, tremor (rest or action),
facial dystonia, chorea, dysdiadochokinesia, incoordination, ataxia, abnormal
eye movements, respiratory dyskinesia (may present as unusual cough)
psychiatric
personality changes - hyperkinetic behaviour, emotional lability, irritability,
anger, mood disorders
psychosis
difficulty concentrating, memory impairment
ophthalmological
Kayser-Fleischer rings - yellow/brown rings at corneal limbus (requires slit
lamp examination)
sunflower cataracts
hepatic
signs/symptoms of liver cirrhosis
other
skeletal or joint abnormalities
Diagnostic Criteria
patients presenting with neurological abnormalities
extrapyramidal symptoms, Kayser-Fleischer rings, low ceruloplasmin level,
high serum copper, high urinary copper
patients presenting with liver abnormalities
Kayser-Fleischer rings, low serum ceruloplasmin level, high urinary copper
excretion
Management
restriction of dietary copper
copper chelators - penicillamine, trientine, zinc acetate
siblings of affected patients should be screened for asymptomatic disease
Prognosis
neurological symptoms begin to improve at 5-6 months after treatment, and do so
until 2 years
persistent neurological deficits after 2 years of treatment are likely to be permanent
psychiatric symptoms often resolve completely
in patients with fulminant liver failure, mortality rate up to 70%
N34 Neurology Movement Disorders
Tremor
Table 29. Approach to Tremors
Body flirt
Characteristics of tremor
.... ' ,
8aIt 18811 with
.'"'------------,
Alcohol dampens essential tremor.
AaIociated features
Alcohol potentiates intention tremor.
Differantial diagnosis
Traatment
"-lcinIonian TI1lIl1Of
' distal upper extremity (head rare)
'307Hz
, pill rolling
, flexiorVextension
, pronatiorVsupination
, at rest
, hands resting in lap while concentrating
on another task
, rigidity
, bradykinesia
, postural instability
, primary Parkinson's disease
, Wilson's Disease'
, Parkinsonism
'Levodopalcarbidopa
'anti-dlolinergics
, pallidotomy
'electrophysiologic surgery
Toronto Notes 2008
EstentiaWostural Tremor Intention Tremor
, upper extremitylhead , anywhere
'6012Hz '<5 Hz
'fine tremor coarse
, with arms and hands outstretched 'absent at rest
(posturall , worse at end of movement
'arms and hands outstretched 'finger to nose test
family history , dysdiadochokinesia
, dysmetria
, dysarthria
, physiological 'any cerebellar disorder'
, drug-induced 'Wilson's Disease'
, hyperthyroid' , pathology of the red nucleus
, hyperglycemic' 'alcohol intoxication
' m u ~ i p l e sclerosis
'propranolol 'treat underlying cause
'anticonvulsants
'In young patient 1<451, must doTSH (thyroid disease!. ceruloplasmin (Wilson's diseasel, CTIMRI (cerebellar disease) as indicated by type of tremor
Essential Tremor
Etiology and Pathogenesis
genetic - can be autosomal dominant
can also be sporadic
can be physiologic or pathologic
Epidemiology and Risk Factors
overall prevalence 1-4%; higher if >65 years old
Signs and Symptoms
6-12Hz postural and kinetic tremor of the arms
can also involve the head and voice
tremor improves with alcohol consumptions
Treatment
f3-blockers and primidone are the mainstay of therapy
other drugs used include clonazepam, topiramate, trihexyphenidyl
stereotactic thalamotomy or thalamic stimulation if severe and intractable
Prognosis
>90% never require medical attention
Toronto Notes 2008 Movement Disorders Neurology N35
Chorea
Definition
semi-purposeful flowing movements that are continuous, random, and can move from
one part of the body to another
Table 30. Choreiform Disorders'
Movement Disorder Associeted Features Investigetions
Huntington's Disease jerking chorea dementia molecular testing
psychosis CT It ventricles, atrophy at caudate nucleus)
Neuroacanthocytosis mild chorea peripheral neuropathy blood smear (acanthocytesl
tics feeding dystonia tCK
tongue biting
SLE local chorea; periodic see Rheumatology, RH9 'ANA,APLA
APlA Syndrome chorea migraine t aPTT
dementia Lupus anticoagulant
spontaneous abortions Anticardiolipin antibodies
thromboses
Raynaud's phenomenon
Wilson's Disease arm-flapping tremor Kayser-Fleischer rings ceruloplasmin, Cu++
chorea hepatic dysfunction liver biopsy
Vasculer Ballism hemiballismus MRI- infarcts in the subthalamic nucleus
Tardive Dyskinesia oral- buccal dyskinesia history of L-dopa or neuroleptic use no specific tests
Senile Chorea mild chorea late onset genetic testing to rule out Huntington's disease
no FHx 'APLA
no dementia
Syndenham's morea chorea rheumatic fever ESR,ASOT
'Abbreviations: APLA -anti phospholipid antibody; - levodopa
Huntington's Disease
o
Etiology and Pathogenesis
genetics
autosomal dominant CAG-repeat disorder with anticipation of Huntington
gene leading to accumulation of defective protein in neurons
pathology
global cerebral atrophy with the neostriatum particularly involved
Epidemiology
North American prevalence 4-8/100,000
mean age onset 35-44 yrs
Signs and Symptoms
chorea
purposeless and abrupt involuntary movements potentially involving any
skeletal muscle
begin as movements of eyebrows and forehead, shrugging of shoulders, and
parakinesiae (pseudopurposeful movements to mask involuntary limb jerking)
can progress to a dance-like gait or ballism
in the terminal stages, chorea can be replaced by dystonia and rigidity
cognitive and psychiatric manifestations
dementia
progressive memory impairment and loss of intellectual capacity
mood changes
irritability or depression, loss of interest
impulsiveness and bouts of violence
psychosis
can mimic schizophrenia
N36 Neurology Movement Disorders Toronto Notes 2008
typical progression
onset 35-40 years (range 5-70)
insidious onset (clumsiness, dropping objects, fidgetiness, irritability)
progression over 15 years to frank dementia, psychosis, and chorea
Investigations
MRI - enlarged ventricles, atrophy of cerebral cortex and caudate nucleus
genetic testing
Treatment
no disease altering treatments
symptomatic management of depression and psychosis with antidepressants and
antipsychotics
symptomatic management of chorea with neuroleptics, benzodiazepines
Prognosis
progressive course over 15-20 years
Dystonia
Definition
sustained involuntary muscle contractions ---> twisting motions or abnormal postures
co-contraction of agonist and antagonist muscles
Epidemiology
most common movement disorder encountered in movement disorder clinics after
parkinsonism
General Feature of Dystonias
worsened by fatigue, stress, and emotion
relieved by sleep (unless severe)
can be relieved by specific tactile or proprioceptive stimuli - "geste antagoniste"
(e.g. placing a hand on the side of the face in cervical dystonia)
younger onset ---> more likely to progress and generalize
leg dystonia -+ more likely to progress and generalize
Etiologic Classification of Dystonias
primary dystonias
familial (e.g. Oppenheim dystonia)
sporadic (e.g. torticollis, blepharospasm, writer's cramp, etc.)
dystonia-plus syndromes
dopa-responsive dystonia (DRD)
myoclonus-dystonia
secondary dystonias
trauma/surgical (e.g. thalamotomy)
focal lesions (e.g. stroke, tumour, focal demyelination)
PNS injury (e.g. trauma, electrical injury)
drugs/toxins (e.g. L-dopa, neuroleptics, anticonvulsants, Mn, CO, cyanide,
methanol)
heterodegenerative dystonias
Parkinsonian disorders (e.g. juvenile parkinsonism, PD, PSP, MSA, CBGD)
metabolic disorders (e.g. Wilson's disease, Lesch-Nyhan syndrome)
other movement disorders (e.g. Huntington's disease)
Treatment of Dystonias
medical
local
local injection of botulinum toxin
systemic
anticholinergics (e.g. trihexyphenidyl)
muscle relaxants (e.g. baclofen)
benzodiazepines (e.g. clonazepam, diazepam)
antidopaminergics (e.g. reserpine, neuroleptics)
dopamine for DRD
surgical
local
selective surgical denervation of affected muscles
systemic
stereotaxic thalamotomy (for unilateral dystonia)
posteroventral pallidotomy
Toronto Notes 2008 Movement Disorders Neurology N37
Myoclonus
Definition
brief, lightening-like involuntary muscle jerks due to either positive muscle
contractions or sudden brief lapses of contraction (e.g. asterixis)
Clinical Features
single or repetitive
focal, segmental, or generalized
can be stimulus sensitive (induced by noise, movement, light, visual threat, or
pinprick)
Treatment
treat underlying disorder
symptomatic trealment- sodium valproate, clonazepam, primidone, piracetam
Tic Disorders
Definitions
tic: a compulsive, rapid, repetitive, stereotyped movement or vocalization
simple tic: contraction of only 1 group of muscles
complex tic: sequence of movements or linguistically meaningful utterances
Clinical Classification of Tics
four types: Tourette's disorder, chronic motor/vocal tic disorder, transient tic disorder,
tic disorder not otherwise specified
motor tics
simple (blinking, head jerking)
dystonic (bruxism; abdominal tensing; sustained mouth opening)
complex (copropraxia - obscene gestures; echopraxia - imitating gestures;
throwing; touching)
vocal tics
simple (blowing, coughing, grunting, throat clearing)
complex (coprolalia - shouting obscenities; echolalia - repetition of others'
phrases; palilalia - repetition of one's own phrases)
Etiology
chromosomal abnormalities: Down syndrome, Fragile X syndrome
developmental syndromes: autism, POD, Rett syndrome
drugs: anticonvulsants, stimulants (e.g. amphetamines, cocaine, methylphenidate)
infections: encephalitis, post-rubella syndrome
high association with obsessive compulsive disorder (OCD) and ADHD
Etiologic Classification of Tic Disorders
primary tic disorders
transient tic disorder (in childhood, duration < 1 year)
chronic tic disorder
Gilles de la Tourette syndrome
adult onset or senile tic
secondary tic disorders
infections (e.g. encephalitis, Creutzfeld-Jakob disease, Sydenham's chorea)
head trauma
drugs (e.g. anticonvulsants, levodopa, stimulants, neuroleptics)
mental retardation syndromes (including chromosomal abnormalities)
Treatment
dopamine blockers (e.g. fluphenazine, haloperidol, clonidine tetrabenazine)
Tourette's Syndrome (a.k.a. Gilles de laTourette's Syndrome)
Definition (DSM-IV)
1. both multiple motor and l phonic tics must be present at some time during illness,
not necessarily concurrently
2. tics occur many times per day, nearly everyday or intermittently throughout a
period of 1 year, with no tic-free period of 3 consecutive months
3. onset prior to 18 years of age
4. the disturbance is not due to the effecs of a substance or general medical condition
..... ' ~
. } - - - - - - - - - - - ~
Normal forms of myoclonus
include hiccups and muscle jerks
experienced while falling asleep.
L
N38 Neurology Movement DisorderslNeuromuscular Disease Toronto Notes ZOOS
Etiology and Pathogenesis
both genetic and environmental
Epidemiology and Risk Factors
prevalence among adolescents - 3-5/100,000 (M>F)
Signs and Symptoms
tics
wide variety of tics that wax and wane in both type severity
tics can be voluntarily repressed for a time
tics are preceded by an unpleasant sensation that is relieved by carrying out
the tic
psychiatric
compulsive ideation (often associated obsessive-compulsive disorder, ADHD)
hyperactive behaviour
Treatment
clonidine
clonazepam
Prognosis/Course
begin at 5 years
increase until 10 years
decline thereafter (50% tic-free by 18 years)
Neuromuscular Disease
Overview
Table 31. Overview of Neuromuscular Diseases
Motor Neuron Disease Peripharal Neuropathy Neuromuscular Junction Myopathy
IMyasthenia Gravis)
SiS Weakness segmental and asymmetrical, distal (except GBSI proximal and fatiguable proximal
distal ~ proximal
Fasciculations 'yes yes 'no
no
Reflexes increased decreased/absent normal normal luntillatel
Sensory yes 'no
no no
Autonomic' 'no yes 'no
no
Tests EMG denervation and reinnervation signs of demyelination decremental response small, short motor potentials
axonal loss jitter on single fibre EMG
NCS normal abnormal normal normal
Muscle Enz normal normal normal increased
e.g. orthostatic hypotension, anhidrosis, visual blurring, urinary hesitancy or incontinence, constipation, erectile dysfunction
Abbreviations: GBS -Guillain-Barre Syndrome
Motor Neuron Disease
Amyotrophic Lateral Sclerosis (ALS)
o
Definition
.... ,,
disease with progressive degeneration of the motor neurons featuring both upper and
.."}-----------.,
lower motor neuron symptoms and signs; also called Lou Gehrig's disease
Motor Neuron Diseases are char-
Etiology
acterized by UMN and/or LMN
genetic
signs and symptoms.
5-10% of ALS cases are familial (e.g. SOD1 mutation)
indirect evidence for viral, autoimmune, paraneoplastic etiologies, and glutamate
toxicity
idiopathic
Pathology
degeneration and loss of motor neurons with astrocytic gliosis
Bunina bodies found in 70% of patients at autopsy
eosinophilic hyaline intracytoplasmic inclusions
disorder of anterior hom cells of spinal cord and cranial nerve nuclei and cortico spinal
tract
Toronto Notes 2008 Neuromuscular Disease Neurology N39
Epidemiology
frequency 5 cases per 100,000 population
age of onset 40-60, earlier with familial form
Signs and Symptoms
motor
limb findings - segmental and asymmetrical UMN and LMN signs
bulbar findings - dysarthria, dysphagia, tongue atrophy and fasciculations
ocular muscles and sphincters spared
death results from respiratory failure
no sensory findings
Investigations
bloodwork
CK should be normal, can be mildly elevated
E ~ I G
evidence of denervation (fibrillation, positive sharp waves, complex repetitive
discharges) in 3 limbs and paraspinal muscles
evidence of reinnervation (l'amplitude and duration of motor units)
fasciculations
muscle biopsy
small angulated fibres (evidence of denervation)
fiber type grouping
rule out cervical cord disease/compression with CT or MRl
Management
disease specific
riluzole (glutamate antagonist) prolongs survival by 3-6 months
symptomatic
cramping - baclofen, quinine, phenytoin
sialorrhea - anticholinergics
supportive
ventilatory support (e.g. BiPAP)
Prognosis
median survival 3 years after diagnosis (can be much longer with ventilatory support)
...::..-0............... ---'
Other Motor Neuron Diseases
Table 32. Other Motor Neuron Diseases*
Characteristic Features
Progressive muscular atrophy I Progressive bulbar palsy '510% of patients in ALS centers
, LMN S&S only
'asymmetric weakness
'later onset
Spinal muscular atrophy , LMN S&S only
'symmetric weakness
, hypotonia, weakness, eN palsies
'younger onset
Primary lateral sclerosis I , 510% of patients in ALS centers
Progressive pseudobulbar palsy , UMN S&S only
, later onset
PostllOlio syndrome 'documented history of paralytic poliomyelitis
'residual asymmetric muscle weakness, atrophy, and areflexia
Abbreviations: ALS amyotrophic lateral sclerosis; LMN lower motor neuron; UMN -upper motor neuron
Peripheral Neuropathies
see also Neurosurgery, NS27
N40 Neurology Neuromuscular Disease Toronto Notes 2008
..... ' ,
,or----------,
Clinical Approach to Peripheral Neuropathies
Axonal neuropathies feature
amplitudes on nelVe conduction
Clinical Classification
studies while demyelinating neu-
ropathies feature velocities.
Table 33. Anatomic Classification of Peripheral Neuropathies
Mononeuropathy distribution of asingle peripheral nerve
Mononeuropathy multiplex motor, sensory, and reflex affecting multiple nerves
stepwise progression; asymmetrical
can eventually summate to asymmetric stocking-glove pattern
Polyneuropathy diffuse. symmetric, distal stocking-glove pattern; distal hyporeflexia
presentation
I
c1inicaViabS/EDS'
I
EDS electrodiagnostic studies
Figure 11. Classification of Peripheral Neuropathies


Multi lex
-i"!- '"
Table 34. Differential Diagnosis of Mononeuropathy Multiplex
Etiology Pathophysiology Key Investigations
Vascular
SLE
RA
ischemic (vasculitisl
ischemic
ischemic (vasculitisl
p-ANCA
LP end 1'protein!
nerve biopsy
hepati1is serology
ANA. anti-ds DNA
nerve biopsy
'ANA,RF
nerve biopsy
HW
Lyme disease
Syphyllis
mixed
'infiUrative
HW serology
Lyme serology
'VDRL
Endocrine Diabetes ischemic fasting glucose
HbA1C
Immune Chronic inflammatory demyelinating polyradiculoneuropathy
Sarcoidosis
, demyelination
'infiltrative
EMG (demyelinationl
LP loligoclonal banding on
'1'serumACE
nerve biopsy
Hereditary liability to pressure palsies demyelination EMG -multifocal oonduetion blodt
Lymphoma
Paraproteinemias
'infiUrative imaging
nerve biopsy
serum and unne immuno electrophoresis
TCIIic Lead toxioty NT abnonmalities 'serum lead level
'Abbreviations: SLE systemic lupus erythromatosus; RA rheumatoid arthritis; EMG electromyography/nerve cooduction studies; NT neurotransmitter
Toronto Notes 200S Neuromuscular Disease Neurology N41
Diffuse Symmetric Polyneuropattiies
Table 35. Differential Diagnosis of Symmetric Polyneuropathy-
Etiology+ Mechanism Coune Modalities
Vascular PAN isc!lemic cI1ronic SIM
SLE 'isc!lemic 'cI1ronic SIM
RA 'isc!lemic 'cI1ronic SIM
Infectious HIV axonaUdemyelination 'cI1ronic SlA
Leprosy infiltrative 'cI1ronic SlA
Lyme axonaUdemyelination 'cI1ronic M
Immune GBS demyelination acute
M
ClOP demyelination 'cI1ronic SIM
Hereditary HMSN axonaUdemyelination cI1ronic SIM
Neoplastic Para neoplastic axonal/demyelination 'cI1ronic SIM
Osteolytic Myeloma axonaUdemyelination 'cI1ronic SIM
Osteosclerotic Myeloma' demyelination
Lymphoma
Monoclonal
gammopathy
axonal
demyelination
Toxin EtOH
Heavy Metals
Medications
axonal
axonal
axonal
Metabolic Diabetes
Hypothyroidism
Renal failure
isc!lemiclaxonal
axonal
axonal
Nutritional 8
12
Deficiency axonal
Other Porphyria
Amyloid
axonal
axonal
'cI1ronic SlM
'cI1ronic M
'cI1ronic SlM
sub-acute SIM
sub-acute SIM
sub-acute SIM
'cI1ronic SlA
'cI1ronic SIM
'cI1ronic SlA
sub-acute SIM
sub-acute M
sub-acute S
Investigations
pANCA; hepatitis serology
LP 11' protein; l' cellsl
nerve biopsy
'ANA
nerve biopsy
'ANA, RF
nerve biopsy
HIV serology
leprosy serology
nerve biopsy
Lyme serology
LP 11' protein; no l' cells)
LP 11' proteinl
genetic testing
'anti-Hu
'SPEP
skeletal bone survey
'SPEP
skeletal survey
SPEP, bone marrow biopsy
'SPEP
bone marrow biopsy
'GGT
urine heavy metals
drug levels
fasting glucose, HbA1C, 2hr OGTT
'TSH,T3,T4
'Iytes, Cr, BUN
vitamin B"
urine parphyrins
nerve biopsy
'Abbreviations: GBS - Guillain-Barre Syndrome; PAN - polyarteritis nodosa; SLE -systemic lupus erythromatosus; RA - rheumatoid arthritis; ClOP -cI1ronic
inflammatory demyelinating polyradiculoneuropathy; HMSN - hereditary motor sensory neuropathy; SPEP -serum protein electrophoresis;
S- sensory; M. motor; A- autonomic
.Most commonflmportant etiologies in boldface type
Guillain-Barre Syndrome (GBS)
Definition
a heterogeneous set of acute, rapid evolving polyradiculoneuropathies consisting of 3
subtypes:
1. acute inflammatory demyelinating polyneuropathy (AIDP) - 90%
2. acute motor-sensory axonal neuropathy (AMSAN)
3. acute motor axonal neuropathy (AMAN)
Etiology and Pathophysiology
AIDP
focal inflammation and demyelination of nerve roots and distal peripheral nerve
fibres resulting in conduction slowing or conduction block
AMSAN and AMAN
focal inflammatory axonal degeneration of ventral (AMAN) or ventral and
dorsal (AMSAN) roots
Epidemiology
annual incidence 1-2/100,000
bimodal distribution with peaks in young adulthood and elderly persons
Risk Factors
Table 36. Events Observed to Precede GBS
Viral Infections
EBV
CMV
HfV
Herpes
West Nile Virus
Bacterial Infections
Campy/obaeter jejuni
Mycoplasma pneumoniae
HaemophtYus influenzae
Borrelia burgdorferi
Vaccinations
Rabies
Vaccinia
Meningitis
Influenza
Guillian-Barre Syndrome is a neuro-
logical emergency due to the risk of
imminent respiratory failureI
N42 Neurology
..... ' ,
.}-------------,
Ototoxic drugs (e.g. aminoglyco-
sides) should not be given to dia
betics. Sensory neuropathies of
the feet prevent them from ade-
quately compensating for foss of
vestibular function!
Neuromuscular Disease Toronto Notes 2008
Signs and Symptoms
motor
weakness
begins in proximal muscles of lower extremities and ascends
loss of deep tendon reflexes (DTRs)
AMAN may be associated with UMN findings
sensory
paresthesiae (distal and symmetric)
objective sensory loss (vibration and proprioception)
pain (deep and poorly localized)
autonomic
blood pressure dysregulation (hypertension; orthostatic hypotension)
cardiac arrhythmias
bladder dysfunction
Miller-Fisher variant
ophthalmoplegia
ataxia
areflexia
Investigations
CSF analysis
albuminocytological dissociation consistent with demyelination (1' protein with
normal white ce11 count)
often absent in first few days and absent in 10% of all CBS
EMC/NCS
conduction block, differential slowing, or focal slowing on NCS
(motor> sensory)
wF-wave
Treatment
supportive care (most important)
admit all patients with suspected CBS
risk of rapid deterioration
respiratory failure (30% of all CBS patients; due to phrenic nerve involvement)
monitor vital capacity and intubate if <15 ml/kg
dysautonomia (ICU management)
paroxysmal hypertension
- short acting IV l3-blockers
orthostatic hypotension
- isotonic fluid replacement
cardiac arrhythmias
- absence of beat-to-beat pulse variation indicates vagal
denervation
- nonsinus bradycardia transvenous pacing
sinus tachycardia ~ fluid replacement
pain
ASA
antidepressants and anticonvulsants ineffective
specific therapy
IVIg
plasmapheresis (within 1st week)
no effect on mortality or relapse
more rapid improvement, less intensive care and ventilation required
Prognosis
typical course
nadir of symptoms at 2-3 weeks
considerable resolution at 4-6 weeks
long term outcomes
5% overall mortality (15-20% if ICU)
75% recover without serious residual deficit; maximal recovery by 18 months
7-15% have permanent substantial deficits (bilateral foot drop, intrinsic hand
muscle weakness, sensory ataxia, dysesthesiae)
Diabetic Neuropathies
see Endocrinology. ElO
Diabetic Distal Symmetric Polyneuropathy
pathophysiology
stocking-glove "dying back" axonal neuropathy with longest nerves affected first
clinical features - most commonly seen neuropathy
symptoms start in distal lower extremity
small sensory fibre disruption ~ loss of pain and temperature perception;
dysesthesiae
Toronto Notes 2008 Neuromuscular Disease Neurology N43
large sensory fibre disruption -+ loss of proprioception, vibratory perception,
and reflexes
motor fibre disruption -> intrinsic muscle weakness and wasting
Cranial Neuropathy
pathophysiology
peripheral nerve ischemia
clinicaf features
oculomotor neuropathy
III>IV>VI
pupillary sparing in 80-90% of CN III palsies (pupillary fibres are
superficial and therefore not as prone to ischemia)
Focal Mononeuropathy
pathophysiology
impaired glucose tolerance is associated with small fibre sensory neuropathy
compression/entrapment or ischemia
ischemia presents acutely and painfully and has poorer recovery
clinical features
upper extremity
carpal tunnel syndrome
ulnar neuropathy at the elbow
lower extremity
common peroneal neuropathy at the fibular head (foot drop)
Diabetic Polyradiculopathy
pathophysiology
axon loss at the root level affecting Single or contiguous roots (may be
inflammatory)
clinical features - most commonly seen neuropathy
diabetic amyotrophy
L2-L4 and occasionally LS
rapid development of pain and weakness preferentially affecting the
anterior thigh
wasting of the quadriceps with loss of the knee jerk
diabetic thoracoabdominal neuropathy
mid- to lower thoracic roots
Diabetic Autonomic Neuropathy
autonomic neuropathy alone is rare
pupils (miosis and sluggish reaction)
CVS (resting tachycardia and orthostatic hypotension)
CI (constipation, gastroparesis)
CD (erectile dysfunction, ejaculation failure)
Paraneoplastic Neuropathies
Table 37. Paraneoplastic Polyneuropathies
Syndrome Pathology Associated Tumour Associated Ab
Sensorimotor axonal/demyelination small cell lung
none
Pure sensory' dorsal root ganglionitis 'small cell lung, breast antiHu
Pure motor motor neuron disease ' lymphoma , paraprotein (IgG, IgM)
'Painful paresthesiae, sensory ataxia, and areflexia preceding tUJT10ur symptoms
Treatment
steroids
IVlg
plasmapheresis
treat underlying malignancy
N44 Neurology
..... ' ,
.}------------,
Diseases of the neuromuscular
junction typically feature promi-
nent fatiguability.
Mvasthenia Gravis is a neurologi-
cal emergency due to the risk of
imminent respiratory failure I
Neuromuscular Disease Toronto Notes 2008
Neuromuscular Junction Diseases
Clinical Approach to Disorders of the
Neuromuscular Junction
Table 38. Common Disorders of the Neuromuscular Junction
Myasthenia Gravis Lambert-Eaton Botulism
Ocularlbulbar parasis + ++ (early!
Limb weakness + +
Fatiguability + +
Post-ilxercisa enhancement + +
Reflexes N -.l- -.l-
Autonomic anticholinergic 5&5 + ++
Sensory 5&5
Associated conditions Thymoma Small cell carcinoma GIS&S
EMG response to repetitive stimulation
"
l' (rapid stimulation! l' (rapid stimulationl
-.l- (slow stimulation) -.l- (slow stimulation)
Myasthenia Gravis
-------------.....;.----------"
Etiology and Pathophysiology
damage and blockade of post-synaptic acetylcholine receptors by specific antibodies
15% of patients with myasthenia gravis have associated thymic neoplasia, 85% have
thymic hyperplasia
autoimmune disorder
Epidemiology
bimodal age of onset - 20's (mostly women) and 60's (mostly men)
Signs and Symptoms
see also Table 38
fatiguability and weakness of skeletal muscles without reflex, sensory, or coordination
abnormalities
typically ocular (diplopia/ptosis) -> bulbar (dysarthria/dysphagia) -+ neck flexors/
extensors -+ proximal limbs
respiratory muscle weakness may lead to respiratory failure
Investigations
edrophonium (Tensilon) test - can result in respiratory difficulty so have crash cart
nearby
1. fatigue patient with easily assessed sign (ptosis, vital capacity, slurred speech)
2. inject edrophonium
3. assess for improvement over 2 minutes
EMG
repetitive stimulation -+ decremental response
single fibre electromyography shows l' jitter (80-100% sensitivity)
anti-acetylcholine receptor antibody assay (70-80% sensitivity)
MUSK antibody, anti-agrin and anti-titin my also be seen
CT/MRI to screen for thymoma/thymic hyperplaSia
Treatment
thymectomy
85% of patients show improvement or remission
symptomatic relief
acetylcholinesterase inhibitors (e.g. pyridostigmine)
do not affect primary pathologic process -+ rarely result in control of disease
when used alone
immunosuppression
steroids are mainstay of treatment - 70-80% remission rate
azathioprine, cyclophosphamide and mycophenolate as adjuncts to steroids or
as steroid sparing therapy
short-term immunomodulation (for crises)
IVIg and plasmapheresis
Prognosis
30% eventual spontaneous remission
Toronto Notes 2008 Neuromuscular Disease
Lambert-Eaton Myasthenic Syndrome (LEMS)
Etiology and Pathophysiology
downregulation of presynaptic voltage-gated Ca channels 2 to specific
channel-binding antibody
50-66% are ultimately associated with small cell carcinoma of the lung
Signs and Symptoms
weakness of skeletal muscles without sensory, or coordination abnormalities
reflexes are diminished or absent, but increase after active muscle contraction
bulbar and ocular muscles affected in 25%
prominent anticholinergic autonomic symptoms
(dry mouth> impotence> constipation> blurred vision)
Investigations
edrophonium test (see Myasthenia Gravis, N44)-> no response
EMG
rapid (> 10Hz) repetitive stimulation --+ incremental response
screen for malignancy, especially small cell lung cancer
post-exercise facilitation - an incremental response to repetitive stimulation due to
presynaptic calcium accumulation
Treatment
tumour removal
acetylcholine modulation
1'acetylcholine release (3-4 diaminopyridine)
wacetylcholine degradation (pydridostigmine)
immunomodulation
steroids, plasmapheresis, IVlg
Myopathies
Clinical ~ ~ r o a c h to Muscle Diseases
Table 39. Myopathies
Etiology Key Clinical Features Key Investigations
Inflammatory Polymyositis myalgias "!'CK
pharyngeal involvement biopsy: endomesial infiltrates;
cardiomyopathy, lung fibrosis necrosIs
systemic autoimmune disease
Dermatomyositis 'myalgias tCK
similar to polymyositis biopsy: perifascicular atrophy
characteristic rashes
can be paraneoplastic
Sarcoidosis see Respirology, R13 'ACE level
biopsy: granulomas
Endocrine Thyroid (1' or -J,) see Endocrinology, E2l TSH, serum cortisol, calcium panel
Cushing's syndrome
Parathyroid It or-J,I
Toxic Medication medication or toxin history toxicology screen
Critical illness myopathy 'ICU patient biopsy: selective loss of thick
Hx steroids and nondepolarizing myosin filaments
taaralyzing agents
ailure to wean from ventilation
Infectious Parasitic, bacterial, or viral
mlialgias l' myoglobin
in lammatory myopathy
Hereditary dystrophy Duchenne early onset IDuchenne and Beckerl biopsy: abnormal dystrophin staining
Becker progressive proximal muscle weakness
calf pseudohypertrophy
Myotonic dystrophy distal myopathy genetic testing
myotonia
genetic anticipation
Hereditary metabolic McArdle's exercise-related myalgias, cramping, '1' lactate
and myoglobuminuria l' serum/urinary myoglobin
post-exercise
Hereditary periodic Periodic paralysis episodic weakness tor-J,K
paralysis normal between attacks
Hereditary mitochondrial MERRF ptosis, ophthalmoparesis common '1' lactate
MELAS biopsy: ragged red fibres
Keams Sayre
Neurology N45
... ' ,
,)-------------,
Lambert-Eaton myasthenic syn-
drome can be differentiated from
myasthenia gravis by the phenom-
enon of post-exercise facilitation.
... ,,
,)-----------,
Myopathies are characterized by promi-
nent symmetric proximal weakness and
absent sensory changes.
'Abbreviations: MERRF -mitochondrial encephalomyopathy with ragged red fibers; MELAS -mitochondrial encephalomyopathy, lactic acidosis, and
stroke-like episodes
N46 Neurology Neuromuscular Disease Toronto Notes 2008
see Rheumatology. RH13
Etiology and Pathophysiology
autoimmune: muscle microvasculature (DM); muscle fibres (PM)
Epidemiology
cancer association
9% (PM) and 15% (DM)
60% of adults >40 years with DM have concomitant neoplasm
common concurrent inflammatory disorders
RA, SLE, mixed connective tissue disease, Sjogren's syndrome, scleroderma
Signs and Symptoms
myopathic features
myalgias and muscle tenderness
proximal> distal; abductors> adductors; extensors> flexors
dysphagia and neck flexor weakness with progression
cutaneous features (DM)
photosensitive heliotrope (blue-purple) periorbital rash
erythematous rash on extensor surfaces of limbs and joints
V sign - anterior neck and chest rash
shawl sign - rash over shoulders
Gottran's papules
systemic features
Raynaud's phenomenon
pulmonary fibrosis
electrocardiographic abnormalities
pericarditis
Investigations
blood tests
CK
anti-nRNP; PM-ScI, antisynthetases, anti-Jo-1
aldolase
EMG
myopathic motor units (small/short motor potentials, full interference
pattern)
fibrillations
muscle biopsy
PM: endomesial infiltrates, necrosis and atrophy
DM: perifascicular atrophy
Treatment
immunosuppression
prednisone (mainstay)
azathioprine (for steroid sparing)
immunomodulation
IVIg is safe and effective
plasmapheresis is ineffective
Prognosis
favourable prognosis - 10 year survival up to 90%
Duchenne and Becker Muscular Dystrophy
see Pediatrics. P44
--a
Myotonic
Etiology and Pathophysiology
unstable trinucleotide repeat in DMK gene (rrotein kinase) at 19q13.3
number of repeats correlates with severity 0 symptoms
Epidemiology
most common adult muscular dystrophy
prevalence 3-5/100 000
Toronto Notes 2008 Neuromuscular Disease/Cerebellar Disorders Neurology N47
Signs and Symptoms
skeletal muscle
weakness
face, jaw, neck> distal extremities
myotonia
delayed relaxation of muscles after exertion (elicit by tapping on thenar
muscles with hammer)
facial (long and thin; wasted muscles of mastication ---+ sunken cheeks;
sternocleidomastoid wasting -> swan neck)
cardiac
90% have conduction defects (1 heart block; atrial arrhythmias)
respiratory (hypoventilation 2 to muscle weakness)
ocular
subcapsular cataracts
retinal degeneration
Wintraocular pressure
frontal balding
Investigations
EMG
subclinical myotonia -long runs with declining frequency and amplitude
muscle biopsy
l' central nuclei, nuclear chains, ringed fibres, type I fibre atrophy
molecular diagnosis
slit lamp examination (for cataracts)
Treatment
no cure
management of myotonia
phenytoin
management of systemic problems
cardiac (EeG and pacing if necessary)
Cerebellar Disorders
Approach to Cerebellar Disorders
Clinico-Anatomic Correlations
rostral midline -> stance and gait disturbances
caudal midline -> disturbances of axial posture and equilibrium
hemispheric -> ipsilateral limb ataxia
Symptoms and Signs of Cerebellar Dysfunction
nystagmus - observe on extra-ocular movement testing (most common is gaze-evoked
nystagmus)
dysarthria - elicit scanning/telegraphic/slurred speech on spontaneous speech (see
Dysarthria, N19)
ataxia -look for dysmetria, dysdiadochokinesia, and ataxia on finger-to-nose and
heel-to-shin testing ipsilateral to side of lesion
postural instability -look for truncal ataxia on sitting; look for difficult tandem gait
and broad based gait
intention tremor - elicit on finger-to-nose testing (typically horizontal)
hypotonia
other features: pendular patellar reflex (knee reflex causes pendular motion of leg),
rebound phenomenon (with both arms extended ---+ pushing both will cause one to
rebound up if there is lesion on that side), and flaccid tone
N48 Neurology Cerebellar Disorders Toronto Notes 2008
o
Acquired Cerebellar Disorders
Table 40. Acquired Cerebellar Disorders
Onset Etiology Key Features Investigations
Vascular Acute infarctionlTlA brainstem S&S 'CT/MRVMRA
hemorrhage brainstem S&S; l' ICP 'CTIMRI
basilar migraine brainstem S&S
Infectious Subacute bacterial abscess fever 'CT/MRI
viral encephalitis fever 'CT/MRI
ToxinsIMeds (Sublacute anticonvulsants drug Hx Drug levels
alcohol' S&S chronic EtOH
LFT
Autoimmune Subacute multiple sclerosis see Multiple Sclerosis section MRI; LP; Evoked potentials
Miller-Fisher GBS arefiexia; ataxia; oculoparesis 'EMGINCS
Metabolic Chronic hypothyroid see Endocrinology, E26 'TFT
'Wilson's disease Kayser-Fleischer Rings ceruloplasmin
thiamine deficiency Wernicke syndrome'
Neoplastic Subacute medulloblastoma children MRI/CT
astrocytoma children MRVCT
hemangioblastoma VHL syndrome*' 'MRVCT
Chronic paraneoplastic lung, breast, ovarian tumour Anti-Yo Ab; CXR
'Preferentially affects gait; limb coordination preserved
+Ophthalmoparesis, gait ataxia, dementia
"Von Hippel Lindau syndrome - hemangioblastomas Icerebellum, brainstem, spinal cord, retinal. renal cysts, renal cell carcinoma
Hereditary Ataxias
Friedreich's Ataxia
onset 5-20 years
affects cerebellum, spinal cord, peripheral nerve, and heart
cerebellar S&S: gait ataxia progressine; to limb ataxia
leg S&S: weakness, arefleXIa, Babinski; impaired proprioception and vibration
prognosis: death from cardiomyopathy or kyphoscoliotic pulmonary restriction in
10-20 years
AtaxiaTelangiectasia
multisystem disorder
progressive cerebellar ataxia presents in infancy
telangiectasia of conjunctiva, nose dl1d ears develops later
death usually occurs in 2nd or 3rd decade of life due to infection or malignancy
Olivopontocerebellar Atrophy (OPCA)
progressive neurodegeneration of brainstem that is either familial or sporadic
prevalance = 3-5/100,000 or approximately 5-8% of atypical parkinsonism
mean age =53 years, M:F =2:1 for familial but equal for sporadic
bulbar - dysphagia, dysarthria, ophthalmoplegia and optic atrophy
cerebellar and extrapyramidal S&S - ataxic gait, parkinsonism
other - peripheral neuropathy, dementia of varymg degrees
Spinocerebellar Ataxia
adult-onset
ataxia, dysarthria, sensory loss
many genetic syndromes identified (most common SCA 2,3,6)
Machado-Joseph disease (SCA3) (cerebellar, extrapyramidal, and pyramidal S&S)
Vertigo
Definition
an illusion of movement of self or surroundings (usually rotatory or spinning) often
associated with impulsion (sensation of hody being pulled in space) or oscillopsia
(visual illusion of moving back and forth)
see 0T12 for further details on Etiology, Pathophysiology,
Investigations, an Treatment
Etiology
central: brainstem or cerebellar
vascular disease
vertebrobasilar system ischemia (VBI)
TIA
Toronto Notes 2008 Vertigo/Gait Disturbances Neurology N49
neurosyphilis
multiple sclerosis
migraine
drugs - anticonvulsants, hypnotics, alcohol
peripheral
see Otolaryngology. OT6
Signs and Symptoms
see Table 41
Table 41. Peripheral vs. Central Vertigo
Peripheral Central
Vertigo severe. often rotational usually mild
always present often absent
Nystagmus horizontal, sometimes torsional vertical or rotatory
increased when looking away from the occurs in >1 direction
side of lesion, always 1direction only
Caloric testing abnormal on side of lesion may be normal
Brainstam or CN signs absent often present
Hearing loss and tinnitus often present absent
Nausea and vomiting usually present usually absent. can be present if 1'ICP
Falis often falls toward side of lesion often falls toward side of lesion but may be variable in direction
Visual fixation inhibits nystagmus no change in nystagmus
Gait Disturbances
Approach to Gait Disturbances
1. Length of stride short
Parkinson's (posture is stooped with no arm swing)
Marche apetit pas (Parkinson's/"Parkinson's plus" multi-infarct state)
"magnetic gait" in NPH
2. If (1) normal, look at width of stance
crossing over: think spastic paresis
wide based: cerebellar ataxia
wide with high stepping, slapping feet: sensory ataxia
3. If (1) and (2) normal, look at knees
high knees: foot drop/ LMN
4. If (1) to (3) normal, look at pelvis and shoulders
waddling gait (e.g. proximal muscle myopathy)
normal pressure hydrocephalus (feet barely leave ground)
5. Look at whole movements
disjointed movements: apraxic gait (cortical lesion from NPH, CVD)
bizarre, elaborate and inconsistent: functional gait
6. Look for asymmetry
think of pain (antalgic gait), bony deformity, or weakness
Disorders of Balance
Cerebellar
etiology
see CerebeLLar Disorders, N48
clinical features
wide based gait, ataxia, trunk sways forward
Sensory
etiology
vestibular causes (see Otolaryngology. OT6)
proprioceptive deficits (may have positive Romberg sign)
visual disturbances
clinical features
wide based stance and gait, high steppage, positive Romberg Sign
(proprioceptive)
NSO Neurology Gait DisturbancesIPain Syndromes Toronto Notes 2008
Disorders of Locomotion
----------------'
Weakness Disorders
LMN disease
high steppage, distal weakness
myopathy
proximal weakness with difficulty rising from chair or climbing stairs
Parkinsonism
parkinsonian gait
stooped posture, shuffling gait, difficulty initiating and terminating steps,
require many steps to tum
Higher Level Disorders
hemiparesis/focal brain injury
spastic extended leg and flexed arm, circumduction of affected foot
paraparesis/spinal cord injury
toe walking or scissoring gait, bilateral circumduction
apraxia; hydrocephalus or frontal lobe injury
magnetic gait (feet barely leave ground), shuffling, difficulty initiating steps
cerebral palsy; congenital or perinatal brain injury
scissoring gait, spastic extended legs and flexed arms, adventitial movements
movement disorders (e.g. chorea, athetosis, dystonia)
lurching gait, may have adventitial movements
Musculoskeletal Disorders
antalgic gait
Pain Syndromes
Approach to ain Syndromes
-----------------"
Definitions
Table 42. Common Terms Used in Discussing Pain Syndromes
Tenn Definition
Nociceptive pain pain arising from normal activation of peripheral nociceptors
Neuropathic pain pain arising from direct injury to neural tissue, bypassing nociceptive pathways
Spontaneous pain unprovoked burning, shooting, or lancinating pain
Paresthesiae spontaneous or evoked abnormal nonpainful sensations (e.g. tinglingl
Dysesthesiae spontaneous or evoked pain with inappropriate quality or excessive quantity
Allodynia adysesthetic response to anonnoxious stimulus
Hyperalgesia an exaggerated pain response to anoxious stimulus
Approaches to Pain Control
Table 43. Medical Approaches to Pain Control
Role Class Examples
Primary analgesics nonopiates NSAIDs
acetaminophen
opiates codeine
meperidine
morphine
Adjuvant analgesics antidepressants tricyclics (nortriptyline, amitriptyline, etc.)
SSRl's (f1uoxetine, paroxetine, etc.)
anticonvulsants gabapentin
carbamazepine
GABA agonists baclofen
oral local anesthetics mexiletine
sympatholytics phenoxybenzamine
",adrenergic agonists c10nidine
pregabalin (Lyrica T"I
Toronto Notes 2008 Pain Syndromes Neurology N51
Table 44. Selected Surgical Procedures for Pain Control
Classification Procedure Principle Selected Indications
Direct delivery of l' implantable morphine pump deliver morphine intrathecally or 1. failure of pain control with supratherapeutic
analgesics epidurally to activate oral meds
peripheral opiate receptors 2. inability to tolerate systemic narcotic
side effects
Central ablation stereotactic thalamotomy ablation of spinoreticular relay HEENT malignancy
spinal tractotomy' stereotactic radiofrequency coagulation intractable pain in terminal malignancy
of neural fibres in ventrolateral spinothalamic
tract at C1C2
dorsal root entry lesions' ablation of dorsal roots at entry into cord deafferentation pain (e.g. brachial plexus
avulsion)
Peripheral ablation nerve blocks' ablation of peripheral nerves with to provide dermatomal pain relief
neurolytics Ipermanent)
or local anesthetics Itemporary)
facet joint denervation cut posterior ramus of spinal nerves degenerative back pain
Stimulatory deep brain stimulation stimulation of electrodes in peri ventricular intractable pain; central pain
gray matter, thalamus, or internal capsule
dorsal column stimulation percutaneous electrodes in peridural space intractable pain
'Complication: ipsilateral leg weakness
+Complication: loss of motor and sympathetic function
Neuropathic Pain
Definition
pain resulting from a disturbance of the central or peripheral nervous system
Symptoms and Signs
hyperalgesia
allodynia
subjectively described as - burning, heat/cold, pricking, electric shock, perception of
swelling, numbness (i.e. stocking/sock distribution)
can be spontaneous or stimulus evoked
distribution may not fall along classical neuro-anatomicallines
Associated Issues
sleep difficulty
mood alteration
anxiety
stress
sexual dysfunction
Causes of Neuropathic Pain
peripheral neuropathy
systemic disease - diabetes, thyroid disease, renal disease, rheumatoid arthritis
nutritional/toxicity - alcoholism, pernicious anemia, chemotherapy
infectious - HIV
trauma - post surgical, nerve injury
nerve root
post-herpetic
cervical and lumbar radiculopathies
tic douloureux (see Tregeminal Nerve, N21)
plexopathies
central
MS
post-stroke
phantom limb
Complex Regional Pain Syndrome
CRPS type I (reflex sympathetic dystrophy)
CRPS type II (causalgia)
malignancy
N52 Neurology Pain Syndromes Toronto Notes 2008
TREATMENT
Pharmacotherapy
1. oral- tricyclic antidepressants (e.g. amitriptyline), antiepileptic medication
(e.g. gabapentin), pregabalin (Lyrica), duloxetine (SNRI), opioids (only long acting)
2. topical-lidocaine (if localized), or capsaicin cream
3. local
a. intrathecal- opioids, clonidine
b. botox injection
c. nerve block
Surgical Therapies
1. dorsal column neurostimulator
2. deep brain stimulator (thalamus)
OtherTherapies
1. neuropsychiatry - cognitive-behaviour theraphy, psychotherapy
2. rehabilitation - physiotherapy
3. CAM - acupuncture, meditation, massage therapy, TCM
Tic Douloureux
---------------------'
see Cranial Nerves, N21
Postherpetic Neuralgia
Definition
pain persisting beyond 3 months in the region of a cutaneous outbreak of herpes zoster
Etiology and Pathogenesis
destruction of the sensory ganglion neurons (e.g. dorsal root, trigeminal, or geniculate
ganglia) secondary to reactivation of herpes zoster infection
Epidemiology
10-15% of all patients with cutaneous herpes zoster
> 80% of herpes zoster infected patients> 80 years old
Signs and Symptoms
types of pain
1. constant deep ache or bum
2. intermittent spontaneous lancinating/jabbing pain
3. allodynia
distribution of post-herpetic neuralgia
thoracic> trigeminal> cervical> lumbar> sacral
Treatment
acute herpes zoster
acyclovir (rapid relief of acute herpes zoster pain, doesn't prevent
post-herpetic neuralgia)
post-herpetic neuralgia - medical
tricyclic antidepressants, pregabalin, gabapentin
opiates, topical lidocaine patch
intrathecal methylprednisolone
post-herpetic neuralgia - surgical
spinal tractotomy
dorsal root entry zone lesion
Com lex Regional Pain S ndrames (CRPS)
Definitions
CRPS is a pain syndrome characterized by the following:
1. presence of an initiating noxious event
2. continuing pain, allodynia, or hyperalgesia with pain disproportionate to
inciting event
3. evidence at some time of edema, changes in skin blood flow, or abnormal
vasomotor activity
4. absence of conditions that would otherwise account for degree of pain
and dysfunction
Toronto Notes 2008 Pain Syndromes Neurology N53
Classification
CRPS type I (reflex sympathetic dystrophy)
minor injuries of limb or lesions in remote body areas precede onset of Sx
CRPS type II (causalgia)
injuries of peripheral nerve precede the onset of symptoms
Signs and Symptoms
stage I (acute)
pain
disproportionate to initial injury
burning or aching
autonomic
edema
temperature inequality
stage II (dystrophic)
pain
constant
l' by stimulus to affected part
autonomic
cool, hyperhydrotic skin
hair loss and cracked/brittle nails
osteoporosis
stage III (atrophic)
pain
paroxysmal spread
autonomic
thin, shiny skin
thickened fascia with contractures
bony demineralization
Investigation
diagnosis is clinical
trial of differential neural blockade may be helpful
Treatment
medical
phenoxybenzamine (sympatholytic)
surgical
paravertebral sympathetic ganglion blockade
definite but transient improvement
paravertebral sympathetic ganglionectomy
for patients for whom ganglionic blocks provide only transient benefit
Thalamic Pain (De-erine Houss
Etiology and Pathogenesis
injury to ventral posterolateral (VPL) and ventral posteromedial (VPM) nuclei of the
thalamus
ischemic stroke
hypertensive vascular hemorrhage
Signs and Symptoms
begins with hemianesthesia
then persistent spontaneous burning contralateral to lesion
altered response to light cutaneous and deep painful stimuli
Treatment
medical: amitriptyline, anti-convulsants
surgical: stereotactic thalamic stimulation (may l'sensory deficit)
N54 Neurology Headache Toronto Notes 2008
The IlIlicllIII CInicII EumiIlIlion: Does lIiI
pIlient with heIdIdIe '-.nignine or llIId
1I8IIIlDging7
J<WA 2006; 296:1274-83
Does lIiI pIlient with heIdIdIe '-.
miPnl7
The most useful panel of questions for diagnosing
migraine is summariled bv the POUNDing mnemonic:
P - Pulsatile quality
0- duration of 4-n hOurs
U- Unilaterallocalion
N- Nausea or vomiting
D- Disabling intensity
The LA for definite or possible migraine diagnosis
varies with the number of features present with
and features, the LRs are 24 (1.5-llS), 3.5 (1.3-9,2j
and 0,4110.32.0,521 respedively,
Does lIiI pIlient willi heIdIdIe llIId
11IIIllinIging7
The prevalence of significant intracranial palhoIogy
Ipretest probabilityl varies by population, In those with
headad1e the prevalence is 12% (O,n-1.8%), In
adutt onset 1>40 yrsl migraine{ype headad1e the
prevalence is 0,0% 10,().5.3%), However, in those pre-
senting with new or changed headad1e the prevalence
is 32% (24q,(,), and in those presenting with thunder-
clap headad1e the prevalence is 43% l2().58%j,
In these different populations, no clinical feature was
found to be useful in ru6ng out significant intracranial
palhoIogy in a However, several indi-
'IiduaI clinical features were found to be predictive of
significant intracranial pathology:
clustel-type headad1e 10.7 (22-521
abnormal neurological exam 5.3(2,4-12)
undefined.type headad1e 3.8 (2.lHll
InorHensionImigrain&'tlusteHype)
headad1e with aura 3.2 (1.&MI
aggravated by exertiOlVValsalva 2.3 (1.4-3,81
headache with vomiting 1.8 (12-2,61
S&S of serious headaches include 1I
the sudden onset of asevere headache;
21 accompanying impaired mental sta-
tus, fever, seizures, or focal neurologic
deficits; or 3) new headaches beginning
after age 50,
Headache
Clinical Approach to Headaches
Table 45. Headaches Benign
Tension-Type Migraine (see Migraine, N56) Cluster
Prevalence '70% '12% 1<1%
Age of onset '15-40 "0-30
20-40
Sex bias 'F> M 'F> M 'M >F
Family History
none +++
'+
Location bilateral frontal unilateral>bilateral retroorbital
nuccho-occipital
Duration minutes - days hours - days 10 min - 2 hours
OnsetlCourse gradual: worse in PM gradual; worse in PM daily headache for weeks
months, nocturnal
Quality band-like: constant throbbing constant, aching, stabbing
Severity mild-moderate moderate-severe severe (wakes from sleep)
Provoking depression noise light
anxiety light EtOH
noise straining
hunger coughing
sleep deprivation activity
Palliating
rest rest walking around
Associated Sx no vomiting nausea/vomiting red watery eye
no photophobia photo/phonophobia stuffy nose
-aura unilateral Horner's
Physical signs muscle tension in scalp/neck muscle tension in scalp/neck red watery eye. rhinorrhea
tender scalp arteries swelling
Management Non-pharmacological Acute Rx
psychological counseling triptans O2
physical modalities (e,g, heat. massageI ergotamine
Pharmacological Prophylaxis
simple analgesics Ca-channel blockers
tricyclic antidepressants methylsergide
lithium
prednisone
Table 46. Headaches - Serious
Meningiallrritation +Intracranial Pressura Temporal Arteritis
Incidence -1%
Age of onset 'anyage any age '>60
Sex bias no bias no bias no bias
Location generalized; stiff neel< any location temporal
Duration variable
chronic
variable
OnsetlCourse meningitis: hours-days gradual; worse in AM variable
SAH: thunderclap onset
Quality variable unlike any previous headache throbbing
Severity - severe 1 severe variable; can be severe
Provoking head movement lying down
Valsalva
head low
1 exertion
Palliating rest and immobility standing/sitting
Associated Sx neck stiffness nausealvomiting polymyalgia rheumatica
photophobia focal neuro Sx jawltongue claudication
focal deficits le,g, CN palsiesl -J, level of consciousness visual loss
Physical signs Kernig's sign focal neuro Sx Temporal artery changes:
Brudzinski's sign papilledema firm, nodular, incompressible
tender
Management CT/LP CT/MRI and treat appropriately prednisone
see also Neurosurgery NS4 see also Rheumatology, RH17
Etiology meningitis, SAH tumour, IIH, malignant hypertension vasculitis IGCAj
SAH - subarachnoid hemorrhage; IIH - idiopathic intracranial hypertension; GCA - giant cell arteritis
Investigation
good history and physical should be able to rule out serious causes of headache
LP/CT if
new-onset headache
different/more severe headache (especially if the worst headache ever)
sudden onset ("thunderclap" headache)
Toronto Notes 2008 Headache
headache associated with
fever
meningismus
altered level of consciousness
focal neurological symptoms
recent head injury
optic disc edema
headache worst in morning or associated with early morning nausea
or vomiting
Migraine Headaches
Definition (common migraine)
?5 attacks fulfilling each of the following criteria
4-72h duration
2 of the following:
unilateral or predominantly unilateral
pulsating
moderate-severe, interfering with daily activity
aggravated by routine physical activity
1 of the following:
nausea/vomiting
photophobia/phonophobia/osmophobia
Epidemiology
18% females, 6% males suffer from migraines
frequenL)' typically decreases with age
Etiology and Pathophysiology
vascular theory of migraine (controversial)
vasoconstriction -> migraine aura (2 to ischemia)
vasodilation -> headache
triggers
mood - stress, sleep excess/deprivation
chemical/hormonal- medications (estrogen, NTC), hormonal changes
(ovulation, pregnancy)
diet - caffeine withdrawal, chocolate, tyramines (e.g. red wine),
nitrites (e.g. processed meats)
Signs and Symptoms
stages of uncomplicated migraine
i) prodrome (hours to days before headache onset)
ii) aura
iii) headache (see Table 46 for description of typical headache)
iv) postdrome
aura
fully reversible symptom of focal cerebral dysfunction lasting <60 minutes
examples:
homonymous visual disturbance (fortification spectra - zigzags;
scintillating scotomata - spots)
unilateral paresthesiae and numbness
unilateral weakness
aphasia
prodrome/postdrome
appetite changes
autonomic symptoms
altered mood and psychomotor agitation/retardation
classification of migraines
common migraine
no aura
classic migraine
migraine with aura (headache follows reversible aura within 60 minutes)
complicated migraine
migraine with severe or persistent sensorimotor deficits
examples:
- basilar-type migraine (occipital headache with diplopia, vertigo,
ataxia, and altered level of consciousness)
- hemiplegic/hemisensory migraine
- ophthalmoplegic migraine
Neurology N55
o
,
9}------------,
The oral contraceptive pill is con-
traindicated with complicated
migraine due to risk of stroke.
... ' ,
9)-------------,
Migraine auras can mimic other
causes of transient neurological
deficits (e.g. TIAs and seizures).
Pharmacological treatments for &Cute
migraine - Pain 2002: 97:24757
Study: Meta-analysis of 54 double-blind, placebo-
controlled RCTs of pharmacologic treatment of
acute migraine of moderate to severe intensity
(21,022 patients in totall.
DBtB extracIion: Number of patients, dosing
regimes, details of study design, and timing or
type of rescue medication. Outcomes included
headache relief at 1and 2hours, freedom from
pain at 2hours, sustained relief for 24 hours, and
adverse effects within 24 hours
Msin Results: Oata were available for 9oral
medications, 2intranasal medications, and subcu
taneous sumatriptan, For HA relief at 2h, all inter
ventions were effective except Cafergot", with
, NNTs ranging from 2.0 for sumatriptan 6mg s.c to
5.4 for naratriptan 2.5 mg. The lowest NNT for oral
medication was 2.6 for eletriptan BOmg. For
patients pain free at 2h, the lowest NNT was 2,1
for sumatriptan 6mg s.c, with the lowest NNT for
oral medication being 3.1 for Rizatriptan 10mg.
For sustained relief over 24h NNT ranged from 2.8
for eletriptan 80 mg to 8.3 for rizatriptan 5mg.
Side effects could not be analyzed systematically,
There were no drugto-drug comparisons.
Conclusion Overall, most treatments were effec
tive. Subcutaneous sumatriptan and oral triptans
were most effective,
N56 Neurology Headache Toronto Notes 2008
acephalgic migraine (aka migraine equivalent)
aura without headache
Management
avoid triggers
mild to moderate migraine treatment:
1
st
line treatment: NSAIDS - ASA, ibuprofen, naproxen
moderate to severe migraine treatment:
triptans (most effective):
oral triptans: naratriptan, rizatriptan, sumatriptan, zolmitriptan
sumatriptan nasal spray, sumatriptan S.c. injection
ergots: dihydroergotamine (DHE) nasal spray
acetaminophen + codeine
migraine prophylaxis:
anticonvulsants: divalproex, topiramate
tricyclic antidepressants: amitryptiline, nortriptyline
propranolol
5-HT antagonists: methylsergide
riboflavin (vitamin B2)
Note: A prophylactic agent is recommended only if migraine attacks are severe
enough to cause impairment of a patient's quality of life or if a patient has >3
migraines/month that have not responded adequately to treatment
Source: Sliverstein SD et al.120001 Practice parameter: Evidence-based guidelines for migraine headacl1e Ian evidence based reviewl. Neurology, 55:754-63.
E isodicTension-Type Headache
._-------------'
Diagnostic Criteria
1. at least 10 previous headache episodes fulfilling criteria 2 through 4; number of days
with such headaches: less than 180 days per year
2. headache lasting from 30 minutes to 7 days
3. at least two of the following pain characteristics
a. pressing or tightening (nonpulsating) quality
b. mild or moderate intensity
c. bilateral location
d. no aggravation by walking stairs or similar routine physical activity
4. both of the following:
a. no nausea or vomiting (anorexia may occur)
b. photophobia and phonophobia are absent, or one but not the other is present
ChronicTension-Type Headache
Diagnostic Criteria
1. average headache frequency of more than 15 days per month for more than 6 months
fulfilling the following criteria:
2. at least 2 of the following pain characteristics:
a. pressing/tightening (nonpulsating) quality
b. mild or moderate intensity (may inhibit but does not prohibit activities)
c. bilateral location
d. no aggravation from climbing stairs or similar routine physical activity
3. both of the following:
a. no vomiting
b. no more than one of the following: nausea, photophobia, or phonophobia
4. secondary headache types not suggested or confirmed
Cluster Headache
Diagnostic Criteria
1. at least five attacks fulfilling criteria 2 to 4 below
2. severe unilateral, supraorbital and/or temporal pain lasting 15 to 180 minutes (untreated)
3. headache associated with at least one of the following on the pain side
a. conjunctival injection or lacrimation (ipsilateral)
b. nasal congestion or rhinorrhea
c. forehead and facial sweating
d. miosis or ptosis (ip'silateral)
e. eyelid edema (ipsilateral)
f. a sense of restlessness or agitation
4. not attributed to another disorder
can have up to 8 attacks per day
Toronto Notes 2008 CNS Infections/Spinal Cord Syndromes/Stroke Neurology N57
CNS Infections
see Infectious Disease. ill7
Spinal Cord Syndromes
see Neurosurgery. NS24
Stroke
Definition
a clinical syndrome characterized by sudden onset of a focal neurological deficit
preswned to be on a vascular basis, and without an alternative explanation
StrokeTerminology
Transient Ischemic Attack (TIA)
stroke syndrome with neurological symptoms lasting from a few minutes to as
much as 24 hours, followed by complete functional recovery
following TIA, between 10-15% will develop infarction in the first 3 months of
follow-up, irrespective of territory involved
risk of infarction is greatest within 2-3 months of initial TIA
Amaurosis Fugax, Transient Monocular Blindness (TMB)
retinal ischemia due to embolism to ophthalmic and retinal arteries resulting in
a sudden, and frequently complete, transient loss of vision in one eye or an
altitudinal defect (superior or inferior)
Reversible Ischemic Neurological Deficit (RIND)/Minor Stroke
neurological abnormalities similar to acute completed stroke, but the deficit
disappears after 24-36 hours, leaving few or no detectable neurological sequelae
Completed Stroke (CS)
stroke syndrome with a persisting neurological deficit
Progressing Stroke (Stroke In Evolution)
neurological deficits begin in a focal or restricted distribution but over the
ensuing hours spread gradually in a pattern reflecting involvement of more and
more of the particular vascular territory (may be due to several factors i.e.
propogation of thrombus, cerebral edema, secondary hemorrhage, etc)
Risk Factors
age
hypertension
smoking (risk of stroke within 3-5 years of quitting =risk of non smoker)
myocardial infarction
atrial fibrillation
diabetes mellitus
hyperhomocysteinemia
obesity
hypercholesterolemia
drugs (i.e. sympathomimetics, oral contraceptive pill, cocaine, etc.)
Differential Diagnosis - HasThe Patient Had a Stroke?
not all acute focal neurological deficits are secondary to ischemic stroke
differential diagnosis
vascular
hypertensive encephalopathy
subdural hematoma, subarachnoid hemorrhage, intracranial hemorrhage
infectious/inflammatory
abscess
encephalitis (e.g. herpes simplex)
vasculitis
anatomic
demyelinating diseases (e.g. Multiple Sclerosis)
Bell's Palsy
mononeuropathy
plexopathies
N58 Neurology Stroke Toronto Notes 2008
seizure
focal seizure (post ictal weakness)
other
migraine, hypoglycemia
confusion, dementia, and coma (without focal signs) are rarely modes of presentation
for strokes and usually suggests diffuse disturbance of cerebral function
Signs and Symptoms - Where is the lesion and what is the blood supply?
What is the lesion?
cortical lesion (see Figure 12 and Table 48)
examples of cortical lesions include
MCA
ACA
PCA
brainstem stroke
examples of syndromes include
Vertebrobasilar Insufficiency (VBI) - transient neurological dysfunction
- nystagmus
- limb and/or truncal ataxia (pt falls to one side)
- contralateral impairment in pain + temperature sensation
- ipsilateral limb and trunk numbness (with contralateral weakness)
- visual field deficits (abnormal eye movements)
subclavian steal syndrome - VBI due to stenosis at the subclavian artery -
increased arm use diverts blood down from vertebral artery into left arm
- symptoms include vertigo, headaches, left arm claudication assoc
with arm use
lateral medullary (Wallenberg) syndrome - infarct involving PICA or
vertebral artery territory
- ipsilateral facial pain and numbness;
- contralateral impairment of pain and temperature sensation (body
+/- face)
- ipsilateral ataxia (pt falls to one side)
- vertigo, N/V
- ipsilateral homer's syndrome
- dysphagia, dysarthria, hiccups
medial medullary syndrome - infarct involving spinal artery territory
- contralateral arm and leg weakness - sparing the face
- contralateral impairment of proprioception and vibration
- ipsilateral tongue weakness
locked-in syndrome - caused by basilar artery occlusion
- paralysis or weakness in all four limbs (quadriplegia or
quadriparesis), dysarthria or anarthria
- horizontal gaze paresis (vertical eye movement is spared)
- patient awake and alert because of sparing of reticular activating
system but unable to respond verbally or move
cranial nerve findings of brainstem stroke include
diplopia, gaze palsy, nystagmus
dizziness and vertigo
dysarthria
dysphagia
cerebellar findings of brainstem insults include
ataxia
incoordination
sensory findings of brainstem insults include
sensory deficits on ipsilateral side of face, contralateral side of body
(crossed sensory findings)
motor findings of brainstem insults include
crossed or bilateral motor deficits
indeterminate presentation of brainstem stroke may include
hemisyndromes: hemiparesis, hemisensory loss, dysarthria
lacunar infarct (see Stroke Etiologies, N59)
ischemic vs. hemorrhagic
important to distinguish ischemic from hemorrhagic stroke (see Table 48)
Toronto Notes 2008 Stroke Neurology N59
dllterlorcerebf81ancry
anterior cerebral anery
lenticulostriate
arteries
posterior cerebral artery anterior choroidal artery
Transverse view Sagittal view
Figure 12. VascularTerritories of Major Cerebral Arteries
Table 47. Anterior vs. Middle YS. Posterior Cerebral Arteries
Anterior Cerebral Artery Middle Cerebral Artary Posterior Cerebral Artery
tmotor motor contralateral homonymous hemianopsia,
contralateral hemiplegia (lower extremityl contralateral hemiplegia lupper extremity and facel or quantrontinopsia Iblindness lif bilaterall
sensory sensory if dominant hemisphere affected with posterior
contralateral hemianesthesia Ilower extremityl contralateral hemianesthesia corpus callosum lesion
gaze preference laway from hemiparesis, lupper extremity and face) alexia without agraphia
towards the side of the lesionl homonymous hemianopsia or quantrontinopsia if thalamus affected
behavioural and memory disturbances if dominant hemisphere affected contralateral hemisensory loss
abulia aphasia, Gerstmann's syndrome spontaneous pain
if non-dominant hemisphere affected if non-dominant hemisphere affected if subthalamic
constructional apraxia neglect hemiballismus
presence of primitive reflexes if midbrain IWeber's syndromel
grasp, snout, palmomental ipsilateral CN III palsy
urinary incontinence contralateral motor deficits
'Top of basilar syndrome (bilateral PCA intact)
If cerebral peduncle
contralateral hemiparesis
Table 48. Ischemic YS. Hemorrhagic Stroke
Ischemia Hemorrhage
Hypertension often present usually present
PrecedingTIA 30% of cases no
Course static lean be stepwise) rapidly progressive
Increased ICP7 'yes
no
CT Scan Result normal, or consistent with infarct shows blood
Etiology - What is the Pathogenesis? (guides acute and chronic treatment)
ischemic vs hemorrhagic
..0-__-"- _
Ischemic Stroke (80
0
/0)
ischemic stroke results from focal ischemia leading to cerebral infarction
strokes can be due to embolus from heart or large arteries, in-situ thrombosis of
diseased arteries or because of hematological disease predisposing to thrombosis
core of infarct includes electrically silent and necrotic brain tissue that cannot be
revived using revascularazation
penumbra is the tissue surrounding the infarct that contains electrically silent neurons
that can be revised if revascularized (reperfused)
surrounding region becomes edematous 2-5 days post stroke due to stasis - may lead
to initial worsening of symptoms
cerebrovascular thrombosis (40% of all strokes)
gradual, stuttering progression of S&S
caused by formation of in-situ clot on atherosclerotic lesion
may cause in-situ thrombosis or embolize to distal segment and disrupt blood
flow
large vessel thrombosis - occur within carotid, basilar and intracranial segments of
cerebral arteries
risk factors
hypertension
diaoates mellitus
cigarette smoking
hyperhomocysteinemia
hypercholesterolemia
Carotid endarterectomy for symptomatic
C8IOlid It8noIiI
Cochrane Database of Systematic Reviews 1999;
Issue 3
Study: Meta-analysis of 2RCTsINASCET &ECST,
5950 patients) comparing carotid endarterectomy
and medical treatment vs. medical treatment alone
in surgically fit patients with symptomatic carotid
stenosis.
lletults: Compared to those who receive only
medical therapy, endarterectomy in patients with
severe stenosis IECST>BO%or NASCET>70%)
reduced the RR of disabling stroke or death by 48%
ICI: 27-73%1. The NNT to prevent one disabling
stroke or death with carotid endarterectomy in this
group was 15 (CI: 11l-31 I. Endarterectomy in
patients with less severe stenosis (ECST 71l-79% or
NASCET 50-69%1 reduced the RR of disabling
stroke or death by 27% 10: 15-44%1. In this case,
the NNT to prevent one disabling stroke or death
with carotid endarterectomy was 21 (0: 11-1251. In
patients with lesser degrees of stenosis IECST
<70% or NASCET <50%), endarterectomy led to an
increased risk of disabling stroke or death by 20%
(CI: ().44%1 with aNNH of 45 (CI: 22-infinityl.
CorIcuIsionI: When pertonned by surgeons with
complication rates less than 6%, carotid endarterec-
tomy reduces the risk of disabling stroke or death
in symptomatic patients with moderate to severe
carotid stenosis.
CIfOlid endarterectomy for asymptomatic
C8IOtid stenosis
Cochrane Database of Systematic Reviews 2005;
Issue 34
Study. Meta-analysis of 3RCTs (VACS, ACAS &
ACST, 5223 patientsl comparing carotid endarterecto-
my and medical treatment vs. medical treatment
alone in patients with asymptomatic carotid stenosis.
IlesuIts: Compared to those who received only med-
ical therapy, there was anet excess of perioperative
stroke or death of 2.9% in those who undelWent
carotid endarterectomy. However, over mean follow-
up periods ranging from 2.7 to 4.0 years, the RR of
perioperative stroke or death or any subsequent
stroke Ithe primary outcomel was 0.6910: 0.57-{1.00)
in those who undelWent endarterectomy; the ARRs
ranged from 1to 3.1% over the same periods. The RR
of any stroke or death was 0.92ICI: 0.83-1.021 in the
surgical group but was not statistically
Based on insufficient data, there were no significant
differences in treatment effect estimates in patients
with different grades of stenosis.
Concullions: Carotid endarterectomy reduces the
risk of stroke by approximately 30% over 3years in
patients with asymptomatic carotid
However, this procedure also increases the risk of
perioperative stroke or death by approximately 3%.
Furthermore, the NNT to realize this benefit over the
long term is between 33 and 100, and there was only
a trend towards reduction in any stroke
or death over the same period.
N60 Neurology Stroke Toronto Notes 2008
long term management
control of atherosclerotic risk factors
carotid endarterectomy in selected patients (see below)
antiplatelet agents - aspirin, clopidogrel (Paxil), dipyridarnole/ASA
(Aggrenox)
small vessel thrombosis - lacunar infarcts - small (<20 rnrn) deep infarcts
involving yenetrating branches of the large cerebral arteries
majority 0 infarcts are < 5 rnm; only 1% are> 10 rnrn
risk factors
chronic HTN
DM
increasing age
pathology - lipohyalinosis of small penetrating arteries within basal ganglia +/-
brainstern; junctional plaques - atherosclerosis of parent vessel blocking entry of
penetrating vessels
management - control HTN and add antiplatelet agents
embolic origin (rapid onset of symptons) (30% of all strokes)
cardioembolic origin
risk factors: increased a ~ e , atrial fibrillation (most common), LV
aneurysm, LV dysfunction, CHF
valvular etiology: valvular vegetations (i.e. infection, tumour), valvular
heart disease, prosthetic valves
paradoxical embolus - patent foramen ovale (PFO/ASD/atrial septal
aneurysm)
other emboli
air emboli: during surgery or diving
fat emboli (e.g. from long bone fractures)
long term treatment
risk of embolization can be decreased with anticoagulation (heparin or
warfarin)
do CT scan prior to starting anticoagulation to exclude presence of
bleeding (due to increased risk of secondary hemorrhage into a
cardioembolic infarct)
if moderate sized infarct, delay anticoagulation
lacunar infarction
small 20 rnrn) and deep infarcts involving penetrating
branches of large cerebra1 artery
risk factors
HTN (chronic)
DM
increasing age
pathology
lipohyalinosis of small penetrating arteries of basal ganglia and brain
stem; rnicroatheroma; junctional plaques (atherosclerosis of parent vessel
blocking orifices of penetrating vessels)
common sites: putamen, internal capsule, thalamic, ventral pons
5 characteristic syndromes
Table 49. Characteristics Lacunar Stroke Syndromes
Type Neurological Findings
Pure Motor (66%) Contralateral aarm, leg, face weakness
Dysarthria
Pure Sensory (10%) Contralateral sensory loss in arm, leg, face of al modalities
Mixed Motor and Sensory Contralateral sensory loss and weakness in arm, leg, face
Clumsy Hand and Dysarthria 120%) Contralateral paresis and clumsiness of arm/hand
Contralateral faceltongue weakness
Dysarthria/dysphagia
Ataxic hemiparesis Contralateral ataxia/weakness
long term treatment
control HTN
use antiplatelet drugs
other causes
large artery diseases
vasculitis (polyarteritis nodosa, Takayasu arteritis, meningovascular
syphilis)
other (SLE, Behcet's)
arterial dissection
Toronto Notes 2008 Stroke Neurology N6l
hematological coagulopathy: hypercoagulable states, sickle cell anemia,
homocystinuria, APLA, protein CIS deficiency
venous infarction (cortical vein or sinus thrombosis)
seen in "hypercoagulable states" (see Investigations, below) and results
in cortical infarction, often complicated by secondary hemorrhage and
seizures
migraine
vasospasm (drug induced, subarachnoid hemorrhage)
water shed due to systemic hypopulsion
Hemorrhagic Stroke (20%)
see also Table 48 and Neurosurgery. NS14
abrupt onset with focal neurological deficits, due to spontaneous (non-traumatic)
bleeding into the brain
includes ICH and SAH (90% ICH; 10% SAH)
hemorrhage into an area of cerebral infarction is a hemorrhagic infarct which should be
classified as ischemic stroke complicated by secondary hemorrhage
Symptoms
signs of increased ICP (headaches, N/V, seizure)
signs of meningismus
decreased LOC
focal neurologic deficits
INVESTIGATIONS
All Patients
CBC, electrolytes, creatinine, PT, PTT, glucose, lipids
CT head (unenhanced CT head is imaging method of choice)
ECG, echocardiogram
carotid dopplers if carotid territory, or MR angiography if posterior circulation territory
Selected Patients
ESR, VDRL, hypercoagulability work-up (Factor V Leiden, antiphospholipid antibody
syndrome, deficiencies of protein C and protein S and antithrombin-III, fasting
homocysteine)
MRI
magnetic resonance angiography
transesophageal echocardiogram
Holter monitor
ischemic stroke - all patients
CT+/- MRI
assess risk factors (BP, fasting glucose, HbAlC, festing lipids)
ECG, echocardiogram
carotid dopplers if carotid territory stroke
MRA if vertebrobasilar stroke, some carotid territory strokes if indicated
hemorrhage
CT (noncontrast)
LP if suspect SAH
cerebral angio, CT angio, MRA if suspect aneurysm!AVM
if hypertensive hemorrahge - repeat CT head in 6-8 wks to rule out underlying lesion
Treatment of Stroke
A) Acute Stroke Management
Goals
ensure medical stability
limit or prevent neuronal death
Practical guidelines
general
ensure the ABC's, check glucose, urgent CT to rule out hemorrhage and assess
infarct
other labs: CBC, PT, PTT, INR, ECG
N62 Neurology
t.f'A in acute stroke - NlNDS trial
NEJM 1995;333:15817
Study: Randomized, doubleblind, placelJo.con-
trolled trial (3 month follow-upl.
PItients: 624 patients (mean age 76 y, 58% men,
65% whitel with ischemic stroke of recent onset,
and no evidence of intracranial hemorrhage on
CT. Exclusions included hx of recent stroke or
recent surgery, symptoms of
SAH, recent GI or GU hemorrhage, seizure with
onset of stroke, and recent use of anticoagulants.
llIt8MJntion: IV t-PA (0.9 mglkgl or placebo with-
in 180 minutes of the onset of symptoms.
Main outcomes: Neurologic deficit at 24 hours
INIHSS scale) and functional outcome at 3
months (composite score).
Results: There was no significant difference
between groups at 24 hours. At 3months, there
were more patients in the t-PA group with mini-
malar no disability 150% vs. 38%, p=O.031.
Intracerebral hemorrhage was more common in
the tPA group Ip<O.OOll. There was no significant
difference in mortality.
Conclusion: IV t-PA given within 3hours of onset
of acute ischemic stroke improves functional out-
come at 3months. The risk of intracerebral bleed-
ing is increased.
Addendum:When re-assessed at 12 months
from the time of treatment, patients in the t-PA
group were 30% more likely to have minimal or
no disability, with no significant difference in mor-
tality or rate of recurrent stroke (NEJM 1999:
340:1781-7).
Aspirin and heparin in acute stroke -
International StrokeTrial
Lancet 1997;349:158!l-81
Study. Randomized, open trial with 6month fol-
lOW-Up.
Patients: 19,435 patients 154% menl with suspect-
ed acule ischemic stroke of recent onset lIess than
<18 hI, with no evidence of intracranial hemor
rhage, and no clear indications for, or contraindi-
cations to, heparin or aspirin.
InteMHltion: Half the patients were allocated
unfractionated heparin (SOOO or 12,SOO IU bid!,
and half were never allocated heparin: Similarly,
half were allocated aspirin 300 mg daily. Thus
patients were randomly assigned to receive
aspirin, heparin, both, or neither.
Outcomes: Death within two weeks, and death or
dependency al6 months.
Results: For both heparin vs. no heparin and
aspirin vs. no aspirin, there was no significant dif-
ference in death at 2weeks, or death or depend-
ency at 6months. Both aspirin and heparin-allo-
cated patients had significantly fewer recurrent
ischaemic strokes within 14 days, but this benefrt
was completely offset by asimilarsized increase
in hemorrhagic stroke in those receiving heparin.
After adjustment for predicted prognosis, the
aspirin group showed adecreased risk of death or
dependence at 6months (14 per 1000 fewer,
p=O.03).
ConclusiOfl:The 1ST suggests that aspirin should
be started immediately after the onset of ischemic
stroke.
... ' ,
.}------------,
The leading causes of death during the
first month following a stroke are:
pneumonia, pulmonary embolus, car
diac disease, and from the stroke itself.
Leading causes of death beyond the
first week are usually unrelated to the
stroke itself.
Stroke Toronto Notes 2008
diagnosis
make the correct etiological diagnosis so you have a rational approach
for secondary prevention of stroke
consider transfer to stroke center if patient seen in first few hours for
neuroprotective or thrombolytic therapy (have been proven effective in clinical
tests)
thrombolysis
rt-PA (recombinant tissue plasminogen activator) within 3 hours of acute
ischemic stroke onset (NINDS trial)
treated patients were 30% more likely to have minimal or no disability at 3
months
6.4% of pafients had a symptomatic intracerebral hemorrhage (0.6% in
placebo group)
treatment did not affect mortality compared to placebo but patients
with severe strokes were more likely to have favourable outcomes if
treated with rt-PA, benefits of rt-PA were sustained at 12 months
anti-platelet therapy
given at presentation or after 24h if patient treated with tPA
in patients not receiving thrombolysis or anticoagulation, ASA therapy is
recommended within 48 hours of stroke onset (however optimal dose uncertain,
no compelling evidence that any specific doses more effective)
give antiplatelet agents if ASA not suitable or if already taking ASA
clopidogrel (75 mg/d) preferred over ticlopidine (increased risk of neutropenia)
should not combine ASA I- dopidogrel (MATCH trial)
more powerful antipbtelE't agents (glycoprotein lIb/lIla platelet receptor
antagonists) are currently being evaluated in ischemic stroke patients
blood pressure control
do not lower the blood pressure unless the hypertension is severe
antihypertensive therapy is withheld for at least 10 days after
thromboembolic stroke unless there is cardiac failure, aortic dissection, or
sBP above 220 mmHg, or dBP above 120 mmHg
acutely elevated BP is necessary to maintain brain perfusion
most patients with an acute cerebral infarct are initially hypertensive and their
BP will fall spontaneously within 1-'2 days
IV labetalol is usually first line if needed
blood sugar
avoid hyperglycemia which will increase the degree of lactic acidosis in
ischemic tissue. increase the infarct size
B) Other Management Issues
prevent complications
NPO if swallowing difficulty
DVT prophylaxis if limb weakness
initiate rehabilitation
therapy (see also Primary and SeconJary Prrvt'ntion, N63)
investigate to determine the vascular territory and etiology, then treat
accordingly
for carutid territory event, carotid endarterectomy benefits those with
symptomatic severe stenosis (>70%), and is less beneficial for those with
symptomatic moderate stenosis (50-69%). See Neurosurgery, NS19
lower temperature if febrile
Toronto Notes 2008 Stroke Neurology N63
PRIMARY AND SECONDARY PREVENTION
CarotidTerritory Event
carotid endarterectomy benefits those with symptomatic severe stenosis (70-99%), and
is less beneficial for those with symptomatic moderate stenosis (50-69%),
see Neurosurgery, NS19
Asymptomatic Carotid Bruit
suggests the presence of atherosclerotic stenosis and signifies increased risk for both
cerebral and myocardial infarction
modify risk factors, antiplatelet therapy
if stenosis> 60%, risk of stroke is 2% per year; carotid endarterectomy reduces the risk
of stroke by 1% per year (but 5% risk of complications)
Hypertension
primary prevention
antihypertensives reduce the risk of ischemic stroke in elderly patient with
isolated systolic hypertension (SHEP trial)
ramipril lOmg 00 is effective in patients at high risk for
cardiovascular disease (HOPE-Stroke trial)
ACEI reduce the risk of stroke beyond their antihypertensive effect
secondary prevention
ACEI and thiazide diuretics are useful in patients with a Hx of strokeffIA
(PROGRESS trial)
Anti-Platelet Therapy
primary prevention
current evidence has not firmly established a protective role for antiplatelet
agents for low-risk patients without a prior strokefflA
secondary prevention
genera]]y aspirin is chosen as the initial antiplatelet of choice for stroke
prevention
other agents (ASA+dipyridamole; clopidogrel) are reserved for
those who suffer cerebrovascular symptoms while on aspirin
warfarin is generally reserved for specific indications in stroke prevention,
dissection, cardiac/atrial fibrillation, venous thrombosis
Hypercholesterolemia
primary prevention
statins reduce the risk of stroke in patients with CAD or at high risk for
cardiovascular events, even with normal cholesterol (CARE study)
secondary prevention
more evidence is needed for high-risk patients with symptomatic
cerebrovascular disease, but statins are generally used in these patients as well
Atrial Fibrillation
primary and secondary prevention
warfarin is the first-line agent
Smoking
primary prevention
smoking increases risk of stroke in a dose-dependent manner
secondary prevention
after smoking cessation, the risk of stroke decreases to haseline within 2-5 years
Physical Activity
regular physical activity is an important lifestyle measure in stroke prevention and this
effect has a dose-response in terms of both intensity and duration of activity
STROKE REHABILITATION
individualized based on severity and nature of impairment, may require inpatient
program and continuation through home care or outpatient services
multidisciplinary approach includes
dysphagia assessment and dietary modifications
communication rehabilitation
cognitive and psychological assessments including screen for depression
therapeutic exercise programs
assessment of ambulation and evaluation of need for assistive devices, splints
or bracing
vocational rehabilitation
ACE inhibitor in stroke prevention HOPE trial
NEJM 2000;342:145-53
Study Randomized, blinded, placebo-controlled
trial. Mean follow-up 5years.
I'ati6nts 9297 patients 55 years of age or older
Imean age 66 y, 73"10 menl who had evidence oj
vascular disease or diabetes plus one other cardia-
vaSCtJlar risk factor and who were not known to
have alow ejection fraction or heart failure.
1trt8twnDon: Ramipril10 mg once daily orally vs.
matching placebo.
Main Outcomes: Stroke, myocardial infarction, or
death from cardiovascular causes
Results:
Outcome__.lJJRR""RLl>I95!>L'k""oC",-II.,...---JN",fllTllJ>(C,,-iI
Stroke 32% 116 to 441 67 (43 to 145)
Ml, stroke, or 22% 114 to 301 26119 to 43)
()/ mortality
AII-eause 16% (5 to 251 56 (32 to 195)
mortality
Treatment with ramipril reduced the risk of stroke
13.4 percent vs. 4.9 percent; RR 0.68; p<O.OOl).
Conclusion: In adults at high risk for cardiovascu-
lar events, ramipril reduced the risk of stroke, as
well as other vascular events and overall mortality.
Statins in stroke prevention
- MRC9HF Heart Plotection S1udy
Lancet 2002; 360:7-22
Study: Randomized, double-blind, placebo-con-
trolled trial with mean follow-up of 5years.
Patienllr. 20 536 patients aged 40 to 80 years (28%
Yof age, 75% menl with nonfasting total cho-
lesterol mmollL, who were considered to be at
substantial5-year risk of death from coronary heart
disease because of cardiovascular disease, dia-
betes, or treated hypertension. 16% of patients had
known cerebrovascular disease. Exclusions includ-
ed chronic liver disease, evidence of abnormal liver
or kidney function, muscle disease, and others.
1trt8twnDon: Runin treatment involved 4weeks
of placebo followed by 4-6 weeks of afixed dose of
40 mg simvastatin daily. Patients were then ran-
domized to simvastatin 40 mgld or placebo.
Main Outcomes Included all-eause and vaSCtJlar
mortality, major coronary events, and stroke.
ResuIlE
RRR 195%CIl--..!:OOJQL
Stroke 25% (15 to 341 73151101311
Major coronary 27% 121 to 331 33126 to 46)
event
AII-eause 13"/0 (6 to 191 58137 to 1281
mortality
Conclusion: Simvastatin safely reduced the risk of
stroke, major coronary events, and all-eause mor-
tality in patients at significant 5year risk of coro-
nary heart disease.
0rgMised inpatient (stroke unit) care for stroke
(S1Joke UnitTriafistl' CoIaIIcntionI
The Cochrane Database of Reviews 2001;
Issue 3.
PuIpOSe: Assess the effect of stroke unit care compared
with other models of care.
Study Charac:teristic: 23 trials, 1141 or
quasrandomized studies 191 invoMng 4911 patients.
Pncipenls: Patients admitted to hospital wIio had suf
fered astroke, defined as afocal neurological deficit due
to cerebrovascular disease, excluding subaradmoid
hemorrhage and subdural hematoma,
IntIMintion: Organised inpatient stroke un" care with
muffidisciplinal'( teams that manage stroke
patients in adedicated ward, with amobile team, or
within ageneric disability service, compared with aher
native forms of care, ageneral medical ward.
Primary Outcomes: Death, dependency Irequire assis
tance for activities of living). and the require-
ment for institutional care at the end of follow-up.
Results:The NNT to prevent one death is 33195% 0, 20-
100), to prevent one patient being unallie to live at home
was 20 (95% CI, 12-501, and to prevent one patient failing
to regain independence was 20 195%0,11501.
CooduIions: stroke patients cared for in an
organized stroke un" with amuffidisciplinary care team
are more to survive t!lejr stroke, return home and
make agood recovery.
N64 Neurology Multiple Sclerosis Toronto Notes 2008
Multiple Sclerosis
Definition
a demyelinating and inflammatory disease of the CNS characterized by multiple and
varied neurological signs and symptoms over time
lesions/attacks must be separated in both space and time
Classification (based on pattern and course of illness)
relapsing-remitting MS (80% of patients early in the course of the illness, F>M)
clearly defined attacks/relapses with complete recovery or some residual defect
on recovery; no progression of disease between relapses
primary progressive MS
progressive clinical course from onset (F=M)
secondary progressive
initial relapsing-remitting course, which becomes progressive +/- occasional
relapses
Etiology
unknown; thought to involve triggering of the immune system by an agent e.g. virus
(EBV), bacteria, chemicals, in genetically predisposed adults
Pathology
multiple discrete lesions of myelin dt'struction (plaques)
common plaque sites include optic nerve, periventricular areas, corpus callosum,
brainstem, spinal cord
Epidemiology
onset usually age 17-35, but can be younger or older
F:M=3:2
incidence rate 1.5-11 per 100,000, may be increasing
prevalence 50-100 per 100,000, higher prevalence in higher latitudes
genetic predisposition: 3% risk for first degree relatives, 30% concordance for identical
twins, HLA-DR2 and DW2 association
Signs and Symptoms
hyperreflexia, ataxia, nystagmus, spasticity, limb weakness
paresthesia, gait disorder, weakness (e.g. hemiparesis, paraparesis), incoordination,
visual loss (optic neuritis) and diplopia, incontinence, fatigue
Charcot's triad (nystagmus, intention tremor and scanning speech)
Common Features
optic neuritis
internuclear ophthalmoplegia (INO): demyelination in medial longitudinal fasciculus
(MLF) causing failure of adduction of the ipsilateral eye and nystagmus of the
abducting eye on attempted lateral gaze
Lhennitte's sign: forward flexion of the neck causes electric shock sensation down the
back to limbs, indicative of cervical cord lesion
Uhthoffs phenomenon: worsening ot symptoms with heat (e.g. hot bath, exercise)
trigeminal neuralgia in young patient
transverse myelitis: inflammation of spinal cord producing weakness and sensory loss
(dennatomal levels)
Investigations
MRI (test of choice to support a clinical diagnosis of MS)
demyelinating plaques appear as hyperintense lesions on T2 weighted MRI in
periventricular distribution
contrast (gadolinium) identifies active plaque
classic finding of periventricular lesions perpendicular to the lateral ventricles
(Dawson's fingers)
CSF
oligoclonallg bands in 90% ot patients with MS, increased IgG concentration,
mild lymphocytosis and increased protein
evoked potentials (visual/auditory/somatosensory)
slowing may be seen
Toronto Notes 200S Multiple Sclerosis
Treatment
patient education and counselling
disclosure, future expectations, prognosis
refer to MS society and support groups for patient and partner/family
psychosocial issues - relationship distress, depression and suiddality
not uncommon; refer to social work if necessary
acute treatment
corticosteroids are indicated in the treatment of disabling relapses with objective
findings of neurological impairment to speed recovery
IV methylprednisolone 500-1000 mg od for 3-7 days +/- short oral prednisone
taper
disease-modifying therapy (DMT)
(Betaseron, Avonex TM, RebifT
M
) and glatiramer acetate
(Copaxone), natalizumab (Tysabri)
clinically isolated syndrome
emerging thought is that early treatment with DMT in patients with a
single attack may delay second attack e.g. Avonex can be considered
for use in patients with single attack and abnormal brain MRI
relapsing-remitting MS
interferon-(3 and glatiramer acetate about equally effective in reducing
relapse rate by -30%; attacks are also shorter and less disabling
secondary progressive MS
interferon-(3 may slow the progression of disability
primary progressive MS
immunosuppressive agents eg: methotrexate 7.5mg q weekly
symptomatic treatment
spasticity (baclofen, tizanidine, dantrolene, benzodiazepines)
bladder dysfunction (oxybutynin)
pain (TCA, carbamazepine, gabapentin)
fatigue (amantadine, modafinil, methylphenidate)
depression (antidepressants)
physiotherapy, speech therapy, occupational therapy, nutrition
Prognosis
good prognostic indicators - female, young, relapsing-remitting disease, presenting
with optic neuritis, low disease burden on MRI at presentation, low rate of relapses
early in course of illness
primary progressive MS - poorest prognosis, higher rates of disability, poor response
to therapy
no response to disease modifying therapy
Neurology N65
..... ' ,

Multiple Sclerosis is acommon
cause of internuclear ophthalmoplegia.
z

Mechanism of ActionIC1ass Generic name Trade name Dosing Indications Contraindications Side effects
Z
ro

Dopamine precursor levodopa +carbidopa SinemetT'.' Carbidopa 25 mgllevodopa 100 mg PO tid Disease narrowangle glaucoma, use of MAO inhibitor nausea, hypotension, hallucinations,
6"
Maximum 200 mg carbidopa and 2000 mg in last 14 days, history of melanoma or dyskinesias

levodopa per day undiagnosed lesions
Dopamine agonist bromocriptine Parlode!''' 1.25 mg PO bid, increase by Parkinson's Disease conoomitant use of potent inhibrtors of CYP3A4, hyotension, nausea, dizziness, oonstipation,
2.5 mgld q24wks, up to 1o-3D mg PO tid uncontrolled hypertension, isd1emic heart disease, diarrhea, vomrting, abdominal cramps, headache,
peripheral vascular disease. Caution with renal or nasal congestion, drowsiness, hallucinations
hepatic disease
MAO Binhibitor selegiline Eldepryl'" 5mg PO bid Parkinson's Disease ooncomitant use of meperidine or tricyclic headache, insomnia, dizziness, nausea, dry mouth, hallucinations,
antidepressants confusion, orthostatic hypotension, increased risk of
hypertensive crisis with tyramine-;:ontaining foods
MAO Binhibitor pyridostigmine MestinonH.I 600 mgld PO divided in 5-6 doses Myasthenia Gravis GI or GU obstruction nausea, vomiting, diarrhea, abdominal cramps, increased
Range 60-1500 mgld peristalsis, increased salivation, increased bronchial secretions,
miosis, diaphoreses, muscle cramps, fasciculations,
muscle weakness
Triptan sumatriplan Imitrex'" 25-100 mg PO pm, maximum 200 mg1d Migraine hemiplegiclbasilar migraine, isd1emic heart dizziness, sensation of heat hypertensive crisis,
disease, peripheral vascular disease.
cerebrovascular disease, uncontrolled hypertension,
use of agonist in past 24 hours,
use of MAO inhibitor in last 14 days, severe hepatic
disease
coronary artery vasospasm, cardiac arrest, nausea,
vomiting, headache, hyposalivation, dizziness, drowsiness
a
(j
0

0
::s

Ergot dihydroergotamine Migrana!n: nasal spray 0.5 mg/spray, maximum 4sprays Migraine hemiplegiclbasilar migraine, high-dose />SA therapy,
uncontrolled hypertension, ischemic heart disease,
peripheral vascular disease, severe hepatic or renal
ooronary artery vasospasm, transient myocardial isd1emia,
myocardial infarction, ventricular tachycardia, ventricular
fibrillation. May cause significant rebound headache
ro
e:
"
'" =-.
0
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dysfunction, use of triptans in last 24 hours; use of
MAO inhibitors in last 14 days, oonoomitant
Anticonvulsant carbamazepine Tegretol" start at 100200 mg PO O[)'bid, Epilepsy partial +/. 2' history of bone marrow depression, hepatic disease, CNS disturbances {drowsiness, headache, unsteadiness,
(Carbatrol, Epitol in USA) increase by 200 mg/d up to 800-1200 mgld generalization; hypersensitivity to the drug, or known sensitivity to dizziness), nausealvomiting, skin rash, agranulocytosis/aplastic
(individual doses) if needed generalized tonic-elonic tricyclic oompounds such as amitriptyline anemia (rare)
Cholinesterase Inhibitor donepezil Aricept" 5mg PO 00, may increase Mild to moderate hypersensrtivity to donepezil or to piperidine derivatives nausea, vomiting, diarrhea, insomnia, muscle cramps,
to 10mg PO 00 afler 4-6 weeks Alzheimer's Disease, fatigue, and anorexia
Lewy Body Disease
Immunomodulator interteron beta' b Betaseron 0.25 mg 18 MIUI SC every other day RelapsingRemitting and pregnancy, hypersensitivity to natural or reoombinant injection site reactions, injection site necrosis, flulike symptoms
Secondary Progressive interteron beta (fever, chills, myalgia) tend to decrease over time
Mulitple Sclerosis
Muscle Relaxant
Antispastic
baclofen Lioresal, Lioresal
j
'" Up to 20 mg PO qid, variable for
intrathecal
Spasticity (i.e. MS)
intrathecal route
hypersensitivity to baclofen
(Spinal Cord Injuryl
transient drowsiness, daytime sedation, dizziness, weakness,
fatigue, convulsions, hypotonia
-

g
Antispasmodic
Anticholingergic
oxybutynin chloride Ditropan'" 5mg PO bid Uninhibited neurogenic
bladder or reflex
neurogenic
glauooma, GI obstruction, megaoolon, severe colitis,
myasthenia gravis, obstructive uropathy,
hypersensitivity to oxybutinin
headache, pain, dry mouth, constipation, unnary retention,
diarrhea, nausea, dyspepsia, dizziness

8"
Z
0
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Toronto Notes 2008 Summary Key Questions Neurology N67
Summary Key Questions
Question
1. What are the clinical features of lic Douloureux?
2. What are afew examples of Hereditary Ataxias?
3. How does Cranial Nerve III palsy present?
4. What is the management for Bell's Palsy?
5. What is the presentation of Ataxia-Telangiectasia?
6. Describe aParkinsonian gait.
7. Describe agait due to spastic hemiparesis
i.e. Cerebral Palsy
8. What are two types of Complex Regional
Pain Syndrome?
9. What are oral pharmacological treatment options for
neuropathic pain?
10. What is aTIA?
11. What are risk factors for stroke?
12. What is the initial anti platelet of choice for secondary
stroke prevention?
13. What are the hallmark S&S of Parkinson's Disease?
14. What is the pathophysiology of Wilson's Disease?
15. What is the inheritance pattem of
Huntington's Disease?
16. What is the most common tic disorder?
17. What is the biggest worry with
Guillain-Barre Syndrome?
18. What types of neuropathies are seen in
diabetes mellitus?
19. What is the commonly associated tumour with
myasthenia gravis?
20. What is the hallmark of Myasthenia Gravis?
21. What disease is Lambert-Eaton myasthenic syndrome
associated with?
22. How can Lambert-Eaton myasthenic syndrome be
differentiated from myasthenia gravis?
23. In vertigo, it nystagmus is seen in more than
one direction, what does that tell you?
24. What causes of headache are serious and must
be ruled out?
25. What classes of drugs can be used for
migraine prophylaxis?
26. Where can CNS lesions be located and
result in coma?
Answer
Sharp pain in V3 t/- V1 and V2, pain lasts few seconds to minutes, may cause wincing (ticl,
may be brought on by triggers, lasts for days to weeks followed by remission of weekslmonths
Friedreich's Ataxia, Ataxia-Telangiectasia, Olivopontocerebellar Ataxia, Spinocerebellar Ataxia
Ptosis, eye down and out, pupil dilated t/- unreactive pupiVextraocular muscle paresis
Education, reassurance, eye protection (artificial tearsllubricating ointment'patching)
tl-steroid sfacyclovi r
Progressive cerebellar ataxia in infancy, followed by telangiectasias of conjunctivae, nose
and ears at alater stage.
Stooped posture, shuffling gait, difficulty initiating and tenminating steps
Scissoring gait, spastic extended legs and flexed arms, adventitial movements
Type 1- reflex sympathetic dystrophy
Type II- causalgia
Rrst line - tricyclic antidepressants, gabapentin
Second line - SSRI, opioids
Stroke syndrome with neurological symptoms lasting from afew minutes to as much as
24 hours, followed by complete functional recovery.
Age, hypertension, smoking, DM, hypercholestrolemia, atrial fibrillation, obesity,
hyperhomocysteinemia, drugs, cardiac pathology
ASA
Tremor, rigidity, akinesia, postural instability
Abnonmality in copper metabolism
Autosomal d o m i n a n ~ with anticipation
Gilles de la Tourette's Syndrome
Risk of imminent respiratory failure
Cranial neuropathies, focal mononeuropathies, polyradiculopathies, distal symmetric
polyneuropathies, autonomic neuropathies
Thymoma
Fatiguability
Small cell lung cancer
Post-exercise facilitation
The etiology must be central
SAH, meningitis, increased intracranial pressure, temporal arteritis
Anticonvulsants, tricyclic antidepressants, beta-blockers, 5-HT antagonists, riboflavin
Ivitamin B21
Bilateral cerebral cortex, RAS Ibrainsteml, focal brain lesions causing herniation, or diffuse
axonal injury
N68 Neurology Summary Key Questions/References Toronto Notes 2008
Iluestion Answer
27. What makes apartial seizure complex versus simple? Complex seizures involve level of awareness
28. What is the most common cause of late-onset Stroke
(>50 years of agel epilepsy?
29. What investigations can help differentiate an EEG and serum Prolactin
epileptic seizure from apseudoseizure?
30. In delirium, what are the most common Visual and tactile
types of hallucinations expenenced?
31. In dementia, what are indications for <65 years old, rapid progression [weeks to months!. hx of TIA/CVA, focal neurological defici!is),
ordering aCT head? hx of neoplasm that can metastasize to brain, immunocompromised, anticoag use
32. List the main dementia syndromes? Alzheimer's Disease, dementia, Lewy body disease, frontotemporal dementia
33. What are the cardinal features of Horner's syndrome? Ptosis, miosis and anhidrosis
34. How does hydroxyamphetamine help localize Hydroxyamphetamlne will only cause dilation if the lesion is pre-ganglionic or central
the lesion in Horner's syndrome?
35. Left upper quadrantanopsia. Where is the lesion? Right temporal lobe- Meyer's loop
36. What are common presentations in MS? Optic neuritis, transverse myelitis, diplopia, vertigo
37. What imaging modality should be used MRI
to support aclinical diagnosis of MS?
References
Brain Death
Wijdicks Enhe Diagnosis of Brain Death. NEJM2001; 3441161: 1215-1221.
Coma
Bhidayasiri R, Waters MF, Giza CC (2005). Neurological differential diagnosis: aprioritized approach. Massachusettes: Blackwell Publishing, Inc., pp.71-72.
Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds 120051. Harrison's principles of internal medicine, 16th edition. Toronto: McGraw-Hili Companies, Inc,
pp. 1629-30.
Common Presenting Complaints
Bhidayasiri R, Wate,s MF, Giza CC 12005). Neurological differential diagnosis: aprioritized approach. Massachusettes: Blackwell Publishing, Inc, pp. 12-13, 305-314.
Headache
Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 2nd edition. Cepahalagia. 2004; 24IS11:9-
160. htto:/lwww.ihs-ciassification.org.
Multiple Scterosis
Ambati BK, Smith WT, Azer-Bentsianov MT 12001). Residents manual of medicine. Hamilton: BC Decker, pp. 211-213.
Carpenter CCJ, Grigys RC, Loscalzo J, eds 12001). Cecil Essentials of medicine, 5th edition. Philadelphia: WB Saunders Co, pp. 973976.
Ferri FF 120011. Practical gUide to the care of the medical patient. St. Louis: Mobsy Inc, pp. 654-656.
Noseworthy JH, C, Rodriguez M, Weinshenker BG. Multiple sclerosis. NEJM2000; 343113): 938-52.
Olek MJ, ed (2005j. Muitiple sclerosis: etiology, diagnosis, and new treatment strategies. New Jersey: Humana Press Inc, pp. 36-40, 57, 131,222-23.
Samuels MA, Feske SK, eds 120031. Office practice of neurology, 2nd edition. Philadelphia: Elsevier Science, pp. 410-11.
Persistent Vegetative State
Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds 120051, Harrison's principles of internal medicine, 16th edition, Toronto: McGraw-Hili Companies, Inc,
pp.1625,
Seizures and Epilepsy
Ambati BK, Smith WT, Azer-Bentsianov MT (20011. Residents manual of medicine, Hamilton: BC Decker, pp. 203-205,
Ferri FF 12001). Practical guide to the care of the medical patient. St. Louis: Mobsy Inc, pp. 617-619.
Carpeoter CCJ, Griggs RC, Loscalzo J, eds (2001j, Cecil Essentials of medicine, 5th edition. Philadelphia: WB Saunders Co, pp, 956-964.
Spinal Cord Syndrome
Wagner R, Jagoda A, Neurologic Emergencies: Spinal cord syndromes. Emerg Med Clin;c North America 1997; 15(3): 699-711.
Status Epilepticus
Lowarstein DH, Alldredge BK. Status epilepticus. NEJM 1998; 338(14): 970-976.
Stroke
lindsay K, Bone L, 2003 Neurology and Neurosurgery Illustrated, Philadelphia: Churchililivingstone p, 244
W, Silver J12002) Essentials nf Physical Medicine and Rehabilitation. Philadelphia: Hanley and Beltus Inc., p. 778-782
Organized Inpatient Istroke unit) care for stroke (Stroke UnitTrialists' Collaboration). The Cochrane Database of Systematic Reviews 2001; Issue 3
Neuropathic Pain
Marcus, D. (20051, Chronic Pain - APrimary Guide to Practical Management. New Jersey: Human. Press, p. 111-128
Wilson's Disease
Ammoff MJ, Greenberg DA, Simon RP. Lange: Clinical Neurology, 6th edition. Toronto: McGraw-Hili Companies, Inc. pp. 254-56.