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 – Cardiovascular – Respiratory – Infectious – Metabolic – Endocrine – Toxicologic Neuromuscular – 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 SpasticityAtrophyFasciculationsBabinski’sNerve Conduction Testing Weakness Upper Motor Neuro n hyperyesno upgoingnormalyes Lower Motor Neuro n hyponoyes downgoingabnormalyes

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 – 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 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 2 o 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.Food-borne 2.Infantile 3.Wound 4.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 – 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 >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 4+/5 strength bilaterally in lower extremities Sensation grossly normal Able to ambulate but “clumsy” Bloodwork normal – Go to ED if gets worse

Case 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 – 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 – 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 38.9 o C 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 yo 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 – 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?