Neuromuscular Disorders: Pattern, Then Antibody
Separate the neuromuscular junction from nerve and muscle
Fatigable weakness that worsens through the day points to the neuromuscular junction. Proximal weakness with normal sensation and reflexes points to muscle. Distal symmetric sensory loss with reduced reflexes points to neuropathy. Mixed upper and lower motor neuron signs point to ALS.
Myasthenia gravis causes fluctuating ptosis, diplopia, bulbar symptoms, and proximal weakness, sparing pupils and often sparing reflexes. Repetitive nerve stimulation shows decrement; single-fiber EMG is most sensitive. Acetylcholine receptor antibodies are positive in most generalized cases, with MuSK and LRP4 antibodies in some seronegative patients. Thymoma requires resection, and thymectomy is considered in acetylcholine receptor positive generalized disease. Myasthenic crisis requires monitoring of vital capacity and noninvasive ventilation; avoid aminoglycosides, fluoroquinolones, and magnesium.
Lambert-Eaton syndrome shows proximal weakness, hyporeflexia, autonomic symptoms, and an incremental response to high-frequency stimulation; it is strongly associated with small cell lung cancer. Botulism produces descending flaccid paralysis with autonomic features.
Guillain-Barre syndrome presents with ascending symmetric weakness, areflexia, and albuminocytologic dissociation, with nadir by 2 to 4 weeks. Miller Fisher variant shows ophthalmoplegia, ataxia, and areflexia. Treatment is IVIG or plasma exchange; corticosteroids are not effective. Monitor vital capacity and autonomic instability.
Myopathy clues. Dermatomyositis adds heliotrope rash and Gottron papules; inclusion body myositis shows distal finger flexor and quadriceps weakness in older adults and responds poorly to immunomodulation; statins cause proximal myopathy and rhabdomyolysis.
Rule of thumb: decrement on repetitive stimulation means myasthenia, increment means Lambert-Eaton.