Neuromuscular Disorders

Rebecca Burton-MacLeod

R4, Emergency Med

April 26th, 2007

Objectives • Discuss pathophys

• Classification schemes

• Specific disorders

• Cases

• A few fun pics…

Main concerns

• Respiratory compromise!!!!

• Altered vision

• Difficulty swallowing

• Difficulty speaking

• Motor failure

Bulbar symptoms

Determining level

• Brainstem and above:– Unilateral weakness

usually

– If bilateral weakness then associated CN involvement or altered mental status

• CNS o/e: – Spasticity– Hyperreflexia– Positive Babinski– No fasciculations

• PNS:– Dec muscle tone– Hyporreflexia– Atrophy– Fasciculations– Negative Babinski

Definitions

• Myelopathies—involve spinal cord

• Radiculopathies—involve nerve roots as they leave spinal cord

• Neuropathies—involve peripheral nerves

• Myopathies—involve muscles

Neuromuscular junction

• Link between CNS and MSK• Depolarization of neuron causes release of

neurotransmitters at nerve terminal (Ach), which binds to muscle fiber receptor and initiates another wave of depolarization causing muscle contraction

• Must have: sufficient quantity of neurotransmitters AND adequate number of receptors on postsynaptic membrane

NMJ

• Nicotinic synapse:– Muscle weakness

– Disorders of postsynaptic membrane

• Muscarinic synapse:– Anticholinergic

symptoms

– Presynaptic and synaptic disorders

Etiologies

• Congenital—congenital MG, Achesterase deficiency

• Infectious—botulinum • Autoimmune—MG, Lambert-Eaton s/o• Toxins—snake/scorpions,

organophosphates• Drugs—Mg, aminoglycosides,

fluoroquinolones

NMJ disorders

Presynaptic Synaptic Postsynaptic

Lambert-Eaton s/o

Organophosphate poisoning

Myasthenia gravis

Botulism Ach-esterase deficiency

Congenital MG

HyperMg Snake venom

Scorpion/spider toxin

History—specific features

• General:– Cranial muscle

weakness

– Proximity muscle weakness

– Resp muscle involvement

• Presynaptic:– Improvement after

initiation of activity

– Autonomic involvement

• Postsynaptic:– Improvement in

strength after rest

Clinical characteristics Hx Strength DTR Sensation Wasting

Myelopathy

Motor neuron dis

Neuropathy

NMJ dis

Myopathy

Clinical characteristics cont’d

Hx Strength DTR Sensation Wasting

Myelopathy Trauma, infx, ca

N to dec Inc N to dec No

Motor neuron dis

Neuropathy

NMJ dis

Myopathy

Clinical characteristics cont’d

Hx Strength DTR Sensation Wasting

Myelopathy Trauma, infx, ca

N to dec Inc N to dec No

Motor neuron dis

Progressive prob swallow, speak, walk

Dec Inc N Yes

Neuropathy

NMJ dis

Myopathy

Clinical characteristics cont’d

Hx Strength DTR Sensation Wasting

Myelopathy Trauma, infx, ca

N to dec Inc N to dec No

Motor neuron dis

Progressive prob swallow, speak, walk

Dec Inc N Yes

Neuropathy Recent infxn N to dec

Dist>prox

Dec Dec Yes

NMJ dis

Myopathy

Clinical characteristics cont’d

Hx Strength DTR Sensation Wasting

Myelopathy Trauma, infx, ca

N to dec Inc N to dec No

Motor neuron dis

Progressive prob swallow, speak, walk

Dec Inc N Yes

Neuropathy Recent infxn N to dec

Dist>prox

Dec Dec Yes

NMJ dis Food, ticks, easy fatigue

N to fatigue

N N No

Myopathy

Clinical characteristics cont’d Hx Strength DTR Sensation Wasting

Myelopathy Trauma, infx, ca

N to dec Inc N to dec No

Motor neuron dis

Progressive prob swallow, speak, walk

Dec Inc N Yes

Neuropathy Recent infxn N to dec

Dist>prox

Dec Dec Yes

NMJ dis Food, ticks, easy fatigue

N to fatigue

N N No

Myopathy Thyroid dis, prev similar

Dec

prox>dist

N N yes

Case

• 65M who has been noticing difficulty swallowing. 2x visits to ED in last 3months for esophageal obstructions due to food boluses. Also notices double vision after reading for a while, generalized fatigue.

• O/e: ptosis of L eye. Normal PERL. Rapid neuro screen otherwise normal.

• Any thoughts?

Myasthenia gravis

• Causes fluctuating, fatigable weakness of voluntary muscles

• Incidence 14/100,000

• Bimodal distribution—2nd/3rd decades (F), and then 6th/7th decades (M)

• Association with thymic hyperplasia (70% pts), thymoma (15% pts)

MG pathophys

• Ach-R loss due to:– Accelerated endocytosis and degradation of

receptors– Complement-mediated damage– Functional blockade of Ach-R (minor

contributor)

Clinical course

• 85% pts generalized weakness within 1yr

• 85% pts have max severity of illness within 5yrs of onset of symptoms

• <50% pts have remissions

• Extremely variable course of illness

Severity classification

• Bella and Chad’s classification:– Class 1—any ocular muscle weakness, but

other strength is normal– Class 2—mild weakness other than ocular

muscles– Class 3—moderate weakness other than ocular– Class 4—severe weakness other than ocular– Class 5—intubation

S/S MG

Ptosis, diplopia, blurred vision 53%

Limb weakness (arms>legs; symmetrical; proximal)

10%

Generalized fatigue 10%

Dysphagia 5%

Slurred/nasal speech 5%

Difficulty chewing 5%

Diagnosis

• Physical exam:– Normal reflexes, sensation, coordination– Asymmetrical ptosis– Symmetrical, fluctuating EOM weakness– Normal PERL– Fatigability

• Tests:– Tensilon test– Ice test – Immune testing – EP studies

Tensilon test

• IV edrophonium 1-5mg IV (tensilon) provides rapid (within 30sec) and short acting (~5min) improvement of ocular symptoms in pts with MG

• Edrophonium is Ach-esterase inhibitor

• **always have atropine at bedside as may cause bradycardia!!

Ice test

• Cooling improves MG symptoms, heat exacerbates

• Measure distance b/w upper and lower eyelids

• Apply icepack x2min then measure again (should improve >2mm for positive MG)

• Positive in 80% of pts with MG

Other tests

• Ach-R Ab levels (present in 90-95% pts)

• EP studies—repetitive nerve stimulation shows decremental response in MG

Mgmt

• Anticholinesterase agents (pyridostigmine first-line; lose efficacy over time)

• Immunosuppression (steroids reduce levels of Ach-R Ab; transient exacerbation after initiation so should be hospitalized)

• Thymectomy (59% pts show sustained improvement post-op)

• Plasmapheresis• IVIG

Disposition

• Any suspected MG case requires neuro consult / close f/u

Case

• 43F brought in by EMS after sudden resp failure at work. Hx from colleagues of “muscle disorder” and taking steroids, which were recently d/c. Also doubled the dose of her other med “?” 1wk ago.

• Pt unable to speak, only nods head slightly. Obviously shallow resps. ++salivation, incontinent, bradycardic.

• Any thoughts?

Myasthenic crisis

• True emergency!• Often underlying precipitating event (infection, changes

in meds)• Weakness due to MG progression or else complication

of anticholinesterase therapy (cholinergic crisis)• Thus d/c all anticholinesterase meds if suspect

myasthenic crisis• Support ventilation, ICU admission,

plasmapheresis/IVIG, high-dose steroids (only if airway secured)

Case

• 62M with known SCC lung Ca. c/o generalized leg weakness. Difficulty climbing stairs. Also c/o dry mouth and erectile dysfxn.

• O/e: testing grip strength—initially weak, then strengthens, then weakens again; hyporeflexia in LE

• Any thoughts?

Lambert-Eaton s/o

• Rare autoimmune condition

• Primary cause, also paraneoplastic d/o (3% of pts with SCC of lung…may precede diagnosis)

LES pathophys

• Insufficient release of neurotransmitter at presynaptic terminal

• Ab-blockade of voltage-gated Ca channels results in dec Ca influx and deficient neurotransmitter release

LES diagnosis

• Classic triad—muscle weakness (legs, prox), hyporeflexia, autonomic symptoms

• EP studies—resting action potential is low, decrement with slow repetitive stimulation; with rapid stimulation causes doubling from baseline amplitude

Mgmt

• R/o underlying Ca• Anticholinesterase agents (pyridostigmine)• Neurotransmitter enhancers

(aminopyridines):– K-channel blockers prolongs AP and keeps Ca

channels open longer resulting in inc Ca influx and neurotransmitter release

• Immunosuppression

Case

• 6mo M presented to ED with parents• 3day hx of URTI symptoms

– Small cough, Congestion,Tactile fever, Symptoms worsening today, Friend with similar URTI symptoms week prior

• Normally BF, pt has been refusing any fluids for 2days

• No BM x 2days• PMHx: healthy

Case cont’d

• O/E:– 37.9C 142 52 87% r/a – Child appears lethargic– Lungs—wheezing L>R– Pt mildly dehydrated

• Any thoughts?

Case cont’d

• During ICU stay:– Hx of poor sucking prior to admission

– Pt being given “bactrex”—homeopathic supplement containing a wealth of ingredients to ‘boost the immune system’

– Noted to have profound generalized muscle weakness on exam

– No BM x2weeks despite aggressive bowel routine

– Pulmonary, ID, Neurology involved in care

Botulism

• 5 types of botulism:– Food-bourne (ingestion of pre-formed heat

labile toxin)– Infant (ingestion of spores with in vivo toxin

produced)– Wound (IVDU)– Unclassified– Inadvertent (botox injections)

Pathophys

• Most cases caused by strains A, B, E (7 strains exist) of clostridium botulinum

• Most potent biologic toxins known– Doses of 0.05-0.1mcg can cause death in adults

• Toxin transported from GI tract/wound to neuron, toxin irreversibly binds to presynaptic nerve membrane and internalized, blocks release of Ach resulting in neuromuscular blockade

• Primarily occurs at cholinergic synapses of CN, autonomic nerves, NMJ

MoA

Horowitz BZ. Botulinum toxin. Crit Care Clinic. 2005.

Diagnosis

• CN findings in presence of GI symptoms and associated anticholinergic symptoms

• Onset usually within 12-36hrs after ingestion• Symmetrical, descending, rapidly progressive

weakness (may occur within 24hrs)• Suspect wound botulism in IVDU with bulbar

findings

Diagnosis

• C. botulinum toxin positive in stool (60% of pts)

• Normal nerve conduction studies

• EMG may show findings consistent with acute denervation; rapid repetitive nerve stimulation shows incremental response

Fox CK et al. Recent advances in infant botulism. Pediatr Neurol. 2005.

Mgmt

• Supportive measures• Although sepsis on differential, avoid use of

aminoglycosides– Have neuromuscular blocking activity which may

exacerbate botulinum blockade

– Study of 99 infantile botulism pts, 61% required mechanical ventilation if received aminoglycoside vs. 26% if no aminoglycoside given

Wilson R et al. Clinical characteristics of infant botulism in the US. Ped Infect Dis. 1982.

Antitoxin ?

• BabyBIG– Approved in 2003 by FDA for cases of proven

infantile botulism– Ig prepared from plasma of donors immunized

with botulinum toxoid– Cost is $45,000 US per infant, shipped from the

US – Significantly decreases LOS hospital/ICU,

length of mechanical ventilation

Case

• 28F G1P0 develops eclampsia in Cranbrook. Call to STARS. Pt retrieved, treated en route with Mg 5gm IV. Undergoes stat C-section on arrival at FMC. Post-op, unable to extubate pt.

• Any thoughts?

Medications causing NM d/o

• D-penicillamine causes iatrogenic MG

• Aminoglycosides, chloroquine, and fluoroquinolones all may have pre- and post-synaptic effects

• Mg…

HyperMg

• Mg regulates Ca in presynaptic membrane thru voltage-gated Ca channels by blocking Ca influx

• Prevents exocytosis of neurotransmitter

• Also causes anticholinergic symptoms

• Also potentiates action of NMB agents to produce prolonged respiratory weakness

Case

• 22F comes to ED with difficulty raising arms—noticed while fixing hair over last couple of weeks. Also c/o pain in shoulders bilaterally.

• O/e: periorbital heliotrope rash!!

• Any thoughts?

Dermatomyositis

• Weakness, pain, tenderness of involved muscles

• Inflammatory myopathy (also polymyositis)– PM does not have classic skin findings

• Associated inc risk of ca—breast, ovary, lung, GI, lymphoproliferative

Diagnosis

• R/o metabolic cause with lytes (inc/dec K, Ca, dec Ph, Mg)

• Check CK– Interpret with clinical picture!– Should not be sufficient rhabdo to cause renal

failure

• EMG, muscle biopsies

Mgmt

• Prednisone 1-2mg/kg/d

• Cytotoxic drugs for acute exacerbations:– Azathioprine– Methotrexate