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X39 Neurology Toronto Notes 2023

chronic inflammatory demyelinating polyneuropathy (C1DP)

• chronic relapsing sensorimotor polyneuropathy or polyradiculopathy with increased protein

in CSF and demyelination (shown on EMG/NCS)

• course is fluctuating, in contrast with the acute onset of GBS

• treatment: first-line is prednisone; alternatives are plasmapheresis, 1V1G, and azathioprine

Table 19. Differential Diagnosis of Symmetric Polyneuropathy

Etiology Mechanism Course Modalities Investigations

Vascular Chronic S/M SiI-Hi : lIn M]

* PAN Ischemic

RH 2 I Evaluation of Distal Symmetric Polyneuropathy:

Hole cllaboratory and Genetic Testing

Meuro'ogy 2005.12:185192

Screening laMests:flood glucose, serum Dr

mil) metabolites,serum protemimmunohication

electrophoresis.

Genetic Testing Indicated for urPtogenic

poTyneuropathy eitnhitingclassic hereditary

neuropathy phenotype.Screen lor CMI1A duplication/

deletion hnd Ci32 mutations.

SIE Chronic Si Ischemic 'M See Rheumaloloqy.

RH11

RA Ischemic Chronic SIM Soc Rheumatology.

RH8

Chronic

Acute

Infectious HIV Aional S/A HIV serology

leprosy serology

Nerve biopsy

lyme serology

IP|t ptolein. no t

cells)IMG

IPIt protein) EMC

Genetic testing

Paraneoplastic

antibodies

leprosy Inliltralive S/A

Chronic

Acute

tyme Atonal

Demyelination

M

Immune* GBS M

CI0P Demyelination Chronic S/ M

Atonal/demyelinalron Chronic

Atonal/dcmyelinalron Chronic

HMSN

Paraneoplastic

Hereditary S /M

Neoplastic S/M

Myeloma Aional/demyelination Chronic S/M SPEP

Skeletal bone survey

lymphoma Atonal Chronic M SPEP

8one marrow biopsy

Monoclonal Aional /Demyelination Chronic S/M

gammopathy

SPEP

Bone marrow biopsy

Toxin EtOH Atonal GGT, MCV

Atonal

Sub-acute

Sub-acute

S/M

Heavy metals(e.g. S/M

lead)

Medications

Urine heavy metals

Atonal Sub-acute S/M Drug levels

Easting glucose.

HbAIc, 2h 0GTT

ISH. T3. T4

Electrolytes.Cr. BUM

Vitamin Bu

Urine porphyrins

Metabolic DM Ischemic/axonal Chronic S/A

Chronic

Chronic

Hypothyroidism S/M

Renal failure

Budeficiency

Porphyria

Amyloid

Atonal

Atonal S/A

Nutritional

Other

Sub-acute

Sub-acute

Atonal S/M

Atonal M

Sub-acute to chronic Si Atonal 'M SPEP

Nerve biopsy

A = autonomic:CIDP = chronic irillumrnutory demyelinating polyneuropathy:GGT = gamma-glutamyl transferase; HMSN = hereditary motor sensory

neuropathy:

M = motor; OGTT - oral glucose tolerance test:PAN

- polyarteritis nodosa: RA = rheumatoid arthritis:S= sensory;SLE = systemic lupus

erythematosus:

SPEP = serum protein electrophoresis

* Neuropathies of vascular etiology usually present as mononeuropathy multiplex

* Neuropathies of Immune etiology usually piesent as polyradiculopathy

Guillain-Barre Syndrome

Definition

• acute (evolving over 4 wk or less) rapidly evolving demyelinating inflammatory

polyradiculoneuropathy that often starts in the distal lower limbs and ascends

Etiology

• autoimmune attack and damage to peripheral nerve myelin

• usually preceded by viral/bacterial infections

Signs and Symptoms

• sensory:distal and symmetric paresthesias, loss of proprioception and vibration sense, neuropathic

pain

• motor:weaknessstarting distally in legs and progressing proximally, areflexia

• autonomic: blood pressure dysregulation, arrhythmias, bladder dysfunction

In GBS. IVIG and plasmapheresis lead to

mote rapid improvement, less intensive

care and less ventilation, but do not

change mortality or relapse rate

ri

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GBS is a neurological emergency due to

risk of imminent respiratory failure

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Investigations

• CSF:albuminocytologic dissociation (high protein, normal WBC)

• EMG/NCS:conduction block, differential or focal (motor>sensory) slowing, decreased 1 -wave,sural

sparing

Treatment

• 1VIG or plasmapheresis, pain management, monitor vitals and vital capacity

Prognosis

• peak ofsymptoms at 2-3 wk, plateau or resolution at 4-6 wk

• 5% mortality (higher if require 1CU), up to 15°u have permanent deficits

The most commonly identified antecedent

infection in GBS is Campylobacter jejuni

Miller-Fischer Variant of GBS- Triad

• Ophthalmoplegia

• Ataxia

. Areflexia

Neuromuscular Junction Diseases

Clinical Approach to Disorders of the Neuromuscular

Junction

Table 20. Common Disorders of the Neuromuscular Junction

Ocular;Buliar Paresis

Myasthenia Gravis Lambert

-Eaton Botulism

(early) Neuromuscular

o

Junction Disease

• Diseases of the NMJ typically feature

prominent fatigability

• Fatigability can be tested by holding

the arms out or by holding the ga2e

in the upward position (especially

in MG)

• Muscle weakness due to fatigability

will improve with rest and/or ice

limb Weakness

Fatigability

Post-Eiercise Enhancement

Reflexes

Anticholinergic Si

Sensory Si

Associated Conditions

N « «

++

Small cell carcinoma GISSS

Incrementalresponse

Thymoma

Repetitive EMG Stimulation Decremental response t (rapid stimulation)

(slow stimulation)

Myasthenia Gravis Ca:

'channel

Etiology and Pathophysiology

• autoimmune disorder of the NM ), commonly associated with anti-AChR or MuSK antibodies

• 15% of patients with \1G have associated thymic neoplasia,85% have thymic hyperplasia

Epidemiology

• bimodal age of onset, 20s (mostly women) and 60s(mostly men)

Clinical Features

• fatigable,symmetric,or asymmetric weakness without reflex changes,sensory changes,or

coordination abnormalities

• ocular (diplopia/ptosis), bulbar (dysarthria/dysphagial, and /or proximal limb weakness

• symptoms may be exacerbated by infection, pregnancy, menses, and various drugs

• respiratory muscle weakness may lead to respiratory failure

Investigations

• repetitive stimulation: decrement in amplitude >10%

• single fibre electromyography:shows increased jitter (80-100% sensitivity)

• spirometry:forced vital capacity may be used to monitor adequacy of respiratory effort over time

• AChR antibody assay (50-90% sensitivity); anti-MuSK antibody may be used if seronegative for antiAChR antibody

• CT/MR1 chest:screen for thymoma/thymic hyperplasia

• edrophonium (Tensilon*) test:assessfor improvement over 2 min following edrophonium injection

(no longer performed)

NO CONTRACTION

® Minyan Wang 2012V

Figure 24. Myasthenia gravis

Tensilon

G!

is a drug that inhibits

acetylcholinesterase.It improves muscle

function immediately in MG, but not in a

cholinergic crisis. This test is infrequently

used asthis drug is no longer available .

but if performed, a crash cart should be

nearby as respiratory difficulty and/or

bradycardia may occur +

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Treatment

• acetylcholinesterase inhibitors(e.g. pyridostigmine):first line treatment

• corticosteroids (e.g. prednisone):mainstay of treatment if acetylcholinesterase inhibitors not effective

• short-term immunomodulation (e.g.1V1G and plasmapheresis):for crisis

• long-term immunosuppression (e.g.azathioprine, cyclophosphamide, mycophenolate):can be used as

steroid-sparing therapy

• Newer medications that are more disease specific:Eculizumab (complement inhibitor), Efgartigimod

(neonatal l

'

c receptor blocker)

• thymectomy:option in non-thymomatous AChR-antibody-positive generalized MG (85% remission

rate)

Prognosis

• 30% eventual spontaneous remission

• with treatment, life expectancy is equal to that of a person without MG, but quality of life may vary

Randomized Trial of Thymectomy in Myasthenia

Gravis

MEJH 2016;375:511-22

Purpose: Toconaa -ethe efficacyollkymectoniypMs

prednisone vs. prednisone done in the treatment

of M .

Methods:126 patients with generalized

oonthynomatoos M6 Icliitical class H IV disease <5

years duration and elevated acetylcholine-receptor

antibody) received extended transsternal thymectomy

plus alternate-day prednisone or alternate-day

prednisonealone.

Results: Over 3 years, thymectomy was associated

with a lower time-weighted average Onantitative

HC score as compared to prednisone alone (6.15 vs.

8.99.P'

0.001). and a lower average requirement for

dternate-day prednisone (44 mg vs.60 mg. P’

O.OOt).

Immunosuppression was required by fewer patients

intbe thymectomy group (1Avs.48%, P<0.001):

they were also hospitalized less frequently for

exacerbations (9% vs. 37%.P<0.001|.

Conclusion: In patients with nonthymomatous MO.

thymectomy improved clinica I outcomes.

Lambert-Eaton Myasthenic Syndrome

Etiology and Pathophysiology

• autoimmune disorder due to antibodies against presynaptic voltage-gated calcium channels,causing

decreased ACh release at the NMJ

• 50-66% are associated with small cell carcinoma of the lung

Clinical Features

• weakness ofskeletal muscles withoutsensory or coordination abnormalities,proximal and losver

muscles more affected

• reflexes are diminished or absent,but increase after active muscle contraction

• bulbar and ocular muscles affected in 25% (vs.90% in MG)

• prominent anticholinergic autonomic sy mptoms(dry mouth>impotence>constipation>blurred

vision)

Investigations

• edrophonium test: no response

• rapid (>10 Hz) repetitive nerve stimulation:incremental response

• EMG:incremental response with exercise

• screen for malignancy, especially small cell lung cancer

Treatment

• tumour removal

• ACh modulation

increased ACh release (3,4-diaminopyridine)

decreased ACh degradation (pyridostigmine)

• immunomodulation:steroids,plasmapheresis,IVIG

|c«

»

o

°

o

^

4nti-Ca channel

antibodies

a;

-channel

tCh

*

NoAChrelease

NO CONTRACTION

© Minyan Wang 2012J

Figure 25. Lambert-Eaton Botulism myasthenic syndrome

Etiology and Pathophysiology

• caused by a toxin produced by spores of Clostridium botulinum bacteria, which can enter through

wounds or by ingestion

• infantile botulism is the most common form and is usually from ingestion of honey or corn syrup

Clinical Features

• occur 6-48 h after ingestion

• bilateral cranial neuropathies: ptosis, extraocular muscle weakness,dilated poorly reactive pupils,

dysarthria, jaw weakness, dysphagia

• symmetric descending weakness with paralysis and absent/decreased reflexes

• autonomic dysfunction: nausea, orthostatic hypotension, constipation (paralytic ileus), bladder

distension

• anticholinergic symptoms:dry mouth, constipation, urinary retention

• pattern of paresis often starts with GIsymptoms -> extraocular muscle weakness -> dysphagia > limbs

and respiratory involvement

• without prompt treatment, respiratory muscle weakness can lead to respiratory failure

Investigations

• blood test for toxin,stool culture

• CT7MRI to rule out intracranial lesion (normal in botulism)

Treatment

• botulinum anti-toxin:good prognosis with prompt treatment

• supportive therapy as required (monitor respiratory status and assess need for intubation)

r *i

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Myopathies

Clinical Approach to Muscle Diseases

Table 21. Myopathies

Etiology Key Clinical Features Key Investigations

Myalgias

Pharyngeal involvement

Inflammatory Polymyositis (see Rheumatology.

RH16)

tCK

Biopsy;endomysial infiltrates,

necrosis

Dermatomyositis (see

Rheumatology.RH16)

Myalgias tCK

Characteristic rashes

Can be paraneoplastic

SeeRespirology.815

Biopsy:perifascicular atrophy

Sarcoidosis ACE level

Biopsy;granulomas

Weak quadriceps and deep finger » CK

flexors

Inclusion body myositis

B opsy;inclusion bodies

Endocrine Thyroid (t or See Endocrro ogy.E25 TSH

*

)

Cushing's syndrome

Parathyroid|t or »|

Medication

Critical illness myopathy

Serum cortisol

Calcium panel

Toxic Medication or toxin history Toxicology screen

ICU patient

Hx steroids and nondepolarizing myosin filaments

paralyzing agents

Failure to wean fromventilabon

Biopsy;selective loss of thick

Myalgias

Inflammatory myopathy

Early onset (Duchenne and Becker) Dystrophin analysis:absent

Genetic testing

Dystrophin analysis:reduced

Genetic testing

Infectious Parasitic,bacterial,or viral t myoglobin

Hereditary Dystrophy Duchenne (see Medical Genetics.

MG8)

Becker Progressive proximal muscle

weakness

Calf pseudohypertrophy

Distal myopathy

Myotonia

Genetic anticipation

Exercise-related myalgias,

cramping,and myoglobuminuri

Myotonic dystrophy Genetic testing

Hereditary Metabolic McArdle's t lactate

t serumj’urinary myoglobin

post-exercise

Normal t or

*

K’

Hereditary Periodic Paralysis “Channelopathy" Episodic weakness -

Normal between attacks

Myoclonus,generalized seizures,

dementia,myopathy

Paediatric onset,stroke-like

symptoms,episodic vomiting,

dementia

Progressive ophthalmoplegia,

retinal pigment degeneration,

cardiac conduction abnormalities

Hereditary Mitochondrial MERRF Biopsy,raggedred fibres

Increased lactate

MELAS

Kearns Sayre

MELAS:mitochondrial encephalomyopathy,lactic acidosis,and stroke-like episodes:MERRF:mitochondrial encephalomyopathy with ragged red

fibres

CK: creatine kinase

Myotonic Dystrophy Type1

Etiology and Pathophysiology

• unstable trinucleotide (CTG) repeat in myotonic dystrophy kinase gene (protein kinase) at I9ql3.3,

number of repeats correlates with severity ofsymptoms, autosomal dominant

Epidemiology

• most common adult muscular dystrophy, prevalence 3-5 in 100000

Clinical Features

• appearance

ptosis, bifacial weakness, frontal baldness (including women), triangular face giving a drooping/

dull appearance

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•physical exam

» distribution of weakness:distal weaker than proximal (in contrast to other myopathies),steppage

gait

myotonia:delayed relaxation of muscles after exertion (elicit by tapping on thenar muscles with

hammer)

• cardiac:90% have conduction defects (1° heart block;atrial arrhythmias)

• respiratory: hypoventilation 2°to muscle weakness

• ocular:subcapsular cataracts,retinal degeneration, decreased intraocular pressure

• other: DM, infertility, testicular atrophy

EMG: electrical myotonia (waxing and waning discharges,sound like “dive-bomber")

Treatment

•management of myotonia:mexiletine,phenytoin

Prognosis

•no cure, progressive,death usually around 50 yr

Pain Syndromes

Approach to Pain Syndromes

Definitions

• nociceptive pain:pain arising from stimulus causing potential or actual non-neural tissue injury

• neuropathic pain:pain arising from lesion or disease affecting the somatosensory system

• spontaneous pain: unprovoked burning,shooting, or lancinating pain

• paresthesia:spontaneous abnormal non-painful sensation (e.g. tingling)

• dysesthesia: evoked pain with inappropriate quality or excessive quantity

• allodynia: pain response to a non-noxiousstimulus

• hyperalgesia:exaggerated pain response to a noxiousstimulus

Non-Pharmacological Management

• physical (PT, acupuncture,chiropractic manipulation, massage)

• psychoeducational (CBT,family therapy, education, psychotherapy)

Medical Pain Control

• combination multi-modal therapy is important

• primary analgesics: acetaminophen, NSAIDs (often used forsoft tissue injuries,strains,sprains,

headaches, and arthritis), opiates

• adjuvants: antidepressants(TCAs,SSRls), anticonvulsants(gabapentin, carbamazepine, pregabalin),

baclofen,sympatholvtics(phenoxybenzamine), a2-adrenergic agonists (clonidine)

Surgical Pain Control

• peripheral ablation: nerve blocks,facet joint denervation

• direct delivery:implantable morphine pump

• central ablation:stereotactic thalamotomy,spinal tractotomy,or dorsal root entry lesion

• DBS or dorsal column stimulation

• Pinprick sensation mediated by A6

lives

• Pain due to tissue damage is

mediated by C fibres

WHO Pain Ladder

Mild Pain: Non-opioid (acetaminophen

and/or NSAID) ± adjuvant

Moderate Pain:Opioid for mild to

moderate pain (codeine/oxycodone) +

non-opioid z adjuvant

Severe Pain:Opioid for moderate to

severe pain (morphine’hydromorphone)

+ non-opioid:adjuvant

Axonal regeneration is directed by intact

nerve sheaths.If the nerve sheath is

damaged,axons grow without direction,

become tangled,and form a neuroma.

This can result in ectopic electrical

Neuropathic Pain impulses and neuropathic pain

Epidemiology

• affects up to 6% of people (2 million Canadians)

Symptoms and Signs

• hyperalgesia, allodynia

• subjectively described as burning,heat/cold, pricking, electric shock, perception ofswelling,

numbness

• can be spontaneous orstimulus evoked,distribution may not fall along classical neuro-anatomical

lines

• associated issues:sleep difficulty, anxiety/stress/mood alteration

Causes of Neuropathic Pain

• sympathetic:CRPS

• non-sympathetic:damage to peripheral nerves

systemic disease:DM,thyroid disease,renal disease,rheumatoid arthritis, MSA

nutritional/toxicitv:alcoholism, pernicious anemia, chemotherapy

infectious: post-herpetic,HIV

trauma/compression:nerve entrapment, trigeminal neuralgia, post-surgical, nerve injury,

cervical/lumbar radiculopathy, plexopathy

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