Neuromuscular Disorders
Ping-Wei Chen
PGY – 2
Emergency Medicine Resident
April 8, 2010
Thanks: Dr. Walker, Dr. Burton-MacLeod, Dr. Oster, Dr. Brownell
Weakness
• Non-Neuromuscular
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Cardiovascular
Respiratory
Infectious
Metabolic
Endocrine
Toxicologic
• Neuromuscular
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Brain
Spinal Cord
Anterior Horn Cell
Peripheral Nerve
Neuromuscular Junction
Muscle
Localizing the Lesion: UMN vs LMN
• Upper motor neuron
– Unilateral symptoms
– If bilateral symptoms, associated
• Altered mental status
• Cranial nerve abnormalities
– If bilateral symptoms and normal mental status
• THINK spinal cord
Localizing the Lesion: UMN vs LMN
Reflexe
s
Spasticity
Atrophy
Fasciculations
Babinski’s
Nerve
Conduction
Testing
Weakness
Upper
Motor
Neuro
n
hyper
yes
no
no
upgoing
normal
yes
Lower
Motor
Neuro
n
hypo
no
yes
yes
downgoing
abnormal
yes
Myelopathy
• Pathology of the spinal cord
• Clinically:
– UMN signs
– Ascending weakness
– Bowel/Bladder involvement
– Sensory involvement (define level)
Anterior Horn Cell
• UMN synapses with LMN here
• Clinically:
– Both UMN/LMN signs
– Little/No sensory involvement
– Bulbar symptoms (ALS)
• Speech
• Swallowing
• Chewing
Neuropathy
• Peripheral nerve pathology
• Clinically:
– LMN signs
– Distal to proximal involvement
• “glove and stocking” pattern
– Varied sensory involvement
Neuromuscular Junction
• Connection between CNS and muscles
• Clinically:
– Variable presentations of weakness
• Fatigability
• Proximal
• Ascending vs Descending
– No sensory involvement
Myopathy
• Muscle pathology
• Clinically:
– LMN signs
– Proximal > Distal
– ±muscle tenderness
Case
• 65M with weakness.
– 2x visits to GP in last 3 months for same.
– Notices:
• sometimes chokes on food
• Blurry vision when tired
• Generalized fatigue
– “Enough is enough”
• O/E:
– Normal PERL
– Rapid neurological exam otherwise normal.
• Any thoughts?
Myasthenia Gravis
• RARE
• Rarely diagnosed in ED
• Bi-modal age of onset
– Women 20-40
– Men 50-70
Neuromuscular Junction
Myasthenia Gravis
• Autoantibodies against Nicotinic ACh
receptors
– Decreased number of post-synaptic ACh receptors
– Compete for binding on ACh receptors with ACh
Myasthenia Gravis
• Clinically:
– Fatigability of voluntary muscles
• BEWARE – respiratory muscles
– Ocular symptoms first
• Ptosis, diplopia, blurred vision
– Normal sensation
– No pain
Myasthenia Gravis
• Diagnosis
– Clinical + Further Testing
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Edrophonium/Ice Bag Test
Anti-ACh Receptor Antibody
Muscle Specific Receptor Tyrosine Kinase Antibody
Electrophysiologic Tests
Myasthenic Crisis
• MG + Respiratory failure requiring intubation
– 15%-20% MG patients
• Precipitants
– Infection (most common)
– Medication changes
– Surgery
– Pregnancy/Childbirth
– Unidentified (30%)
Back to our patient
• When to intubate?
Caution: Don’t rely on work of breathing!
•Spirometry
•FVC ≤ 1L = intubate
•Rate of decrease in FVC
•“sooner rather than later”
Cholinergic Crisis
• Excessive anticholinesterase medication
– Too much Acetylcholine
Acetylcholine
Succinylcholine
Myasthenic VS Cholinergic Crisis
• May be difficult to differentiate
– Response to Edrophonium/Ice Bag Test
– Presence of muscarinic symptoms
• Cholinergic crisis rare unless >> dose ingested
– ie: pyridostigmine >120mg every 3 hours
• Assume weakness 2o worsening MG
Edrophonium/Tensilon Test
• Edrophonium
– 135mg IV
– Response 30-90s?
– Adverse effect?
• Max dose 10mg IV
• Caution
– Asthmatics/COPD
• Atropine at bedside!!
• Measure distance
between upper and
lower eyelid in most
affected eye
Ice Bag Test
• Apply ice to most
affected eye X 2 mins
• Measure distance
between upper and
lower eyelid in most
affected eye
Myasthenia Gravis
• Management
– Emergency Department
• Identify
• Supportive
– Early intubation for respiratory failure
– Neurology/ICU
• Anti-cholinesterase Medications
– Pyridostigmine
• Immunomodulation
– Plasmapheresis, IVIG
– Glucocorticoids, Azathioprine, Mycophenolate Mofetil,
Cyclosporine
• Thymectomy
Clinical Pearls
• Do spirometry!
– Insidious respiratory failure
– FVC ≤1L = ICU consult, FVC≤500cc
• Sick Myasthenia Gravis patient?
– *Continue acetylcholinesterase inhibitor meds*
• Admitting Myasthenia Gravis patient?
– Neurology consult
Case
• 62M with known small cell lung Ca
– Generalized leg weakness
– Difficulty climbing stairs
• Could this be Lambert-Eaton Syndrome?
Lambert-Eaton Syndrome
• RARE
• Strong association with neoplasm (SCLC)
• Auto-antibodies to Voltage Gated Ca channels
– Decreased release of ACh from pre-synaptic
terminal
Lambert-Eaton Syndrome
• Clinically:
– Proximal muscle weakness (<MG) ± soreness
– Autonomic dysfunction (anti-cholinergic)
– Variable bulbar involvement
• Differentiation from MG
– Weakness improves with use of muscle
– Autonomic involvement
Case
• 41yo male with nausea and diarrhea X 24 hrs
• “really weak”
– Difficulty holding head up for long periods
– Arms weak
• Blurred vision, dry mouth
• ? “food poisoning”
– moloha
• Any thoughts?
Botulism
• Clostridium botulinum
– Obligate anaerobe
– Spore forming
– Toxin producing
• Mechanism of Action
– Irreversible binding to presynaptic membrane of
peripheral and cranial nerves
• inhibiting ACh release
– Disperses widely via vascular system regardless of
portal of entry
Botulism
• Clinical Entities
1.
2.
3.
4.
Food-borne
Infantile
Wound
Adult Enteric Infectious Botulism/Adult
Infectious Botulism of Unknown Source
5. Inhalational
Botulism
• Clinically:
– Both voluntary and autonomic involvement
– Symptom onset 6-48hrs post-ingestion of toxin
• Descending, symmetrical paralysis
• ±GI tract symptoms (N/V/D, abdo cramps, constipation)
• ±Anti-cholinergic symptoms
– Pupils dilated and non-reactive to light*
• No sensory involvement
• No pain
• No fever
*differentiates from myasthenia gravis
Infantile Botulism
• Clinically:
– Constipation
– Weak Cry
– Feeding difficulties/Anorexia
– Descending/Global Hypotonia
– Lethargy
Botulism
• Diagnosis
– Clinical Diagnosis (exclude other pathology)
• Home canned foods, contaminated aquatic products, honey (infants)
• Vegetables
– Centre for Disease Control and Prevention 1998
• Suspect in
• Adult with acute onset dysfunction of
– GI tract
– Autonomic nervous system (anticholinergic symptoms)
– Cranial nerve dysfunction
• Infant with acute onset of
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Poor feeding
Diminished crying ability
Weakness
Respiratory distress
Botulism
• Diagnosis
– Laboratory tests rarely helpful in initial
management
• Toxin/Spore Analysis
– Serum, Stool, Vomitus, Food
• Wound Cultures
Management
• Supportive Care
– Early intubation for respiratory failure
– Equine Trivalent Anti-toxin
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>1 year old
Decrease mortality, disease duration (if given early)
Unclear effect on ventilator dependence
Side effects: serum sickness, anaphylaxis
– Human Botulism Immune Globulin (BIG-IV)
• <1 year old
– Antibiotics in Wound Botulism
• Penicillin G or Metronidazole (allergy)
Case
• 9yo male
• 1 day history of:
– Tripping when walking
– Legs “feeling tight”
• Seen by GP earlier; clinic note faxed
– Neuro exam abnormalities
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4+/5 strength bilaterally in lower extremities
Sensation grossly normal
Able to ambulate but “clumsy”
Bloodwork normal
– Go to ED if gets worse
Case
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Now back: can’t walk or sit up independently
“A cold” 3 weeks ago
Otherwise healthy, IUTD
O/E:
– Normal cranial nerves
– No sensory level
– Decreased DTRs
Video Exam
Case
• Bloodwork unremarkable
– Electrolytes normal
– No increased WBC
• Other investigations?
• Any thoughts?
Guillain-Barre Syndrome
• Most common cause of acute symmetrical
weakness in developed countries
• 1-2 per 100,000 worldwide
• All ages affected
– Peaks in young adults and elderly
Guillain-Barre Syndrome
• Heterogeneous syndrome with several variant
forms
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Acute Inflammatory Demyelinating Polyneuropathy
Miller-Fisher Syndrome
Acute Motor Axonal Neuropathy
Acute Sensorimotor Axonal Neuropathy
• Autoimmune response to preceeding infection
– Molecular mimicry
– Campylobacter
– HIV, EBV, CMV, H. influenza, E. coli
Guillain-Barre Syndrome
• Clinically:
– Progressive, relatively symmetric muscle weakness
• Usually ascending, then generalized
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Distal paresthesias
Decreased/Absent deep tendon reflexes
Dysautonomia
Variable involvement
• Facial muscles
• Bulbar muscles
• Cranial Nerves
• Investigations:
– Increased protein in CSF; normal white cell count
Guillain-Barre Syndrome
• Management
– Emergency Department
• Supportive
– Early intubation for respiratory failure (15-30%)
– Hemodynamic monitoring (autonomic dysfunction)
– Neurology/ICU
• Plasmapheresis
• IVIG
• No role for steroids
Tick Paralysis
• Summer months
• Tick Endemic Areas
– Pacific Northwest (BC)
– Rocky Mountains
• Injection of ixovotoxin with tick feeding
– Diminish release of ACh
– Slow nerve conduction velocity
• Clinically:
– Early: restless, irritable, hand/feet paresthesia
– 24-48hrs:
• ascending, symmetrical, flaccid paralysis
• ±cerebellar dysfunction
Tick Paralysis
• Diagnosis:
– Clinical; no diagnostic laboratory measure
• Management:
– Supportive Care
• Early intubation for respiratory failure
– Tick Removal
Case
• 46yo woman with ALS
– 5 days of productive cough (clear, now green)
– Fever 38.9oC today
– No GI/GU symptoms
• O/E:
•HNT – normal
•CV – tachycardic (115bpm)
•Resp – RR46, SCM use, crackles R lung field
•Abdo – soft, nontender, no CVA tenderness
•MSK – no rashes
Intubate?
Amyotrophic Lateral Sclerosis
• 1-3 per 100,000
• Sporadic and Familial forms
• Increasing incidence after 40yo; peaks 7080yo
• Clinically:
– Progressive UMN/LMN symptoms (months/years)
– Asymmetric weakness (distal to proximal)
– No sensory findings
Amyotrophic Lateral Sclerosis
• Management
– Supportive Care
– Advanced Directive?
• Moss et al. Chest. 1996
– Case Series (n=75)
» 72% ALS patients aware of disease progression to
respiratory failure
» 48% ALS patients learned this from MD
» 42% ALS patients made decision re: long term ventilation
prior to crisis
Questions?