⚠️ Must-Not-Miss Diagnoses
Stroke (focal sudden weakness), Guillain-Barré (ascending weakness + areflexia), myasthenic crisis (respiratory compromise), spinal cord compression (bilateral weakness + sensory level), hypokalemic periodic paralysis, botulism.
Differential Diagnosis by Key Features
| Clinical Feature | Think Of | Priority |
|---|---|---|
| Sudden focal weakness, face/arm/leg, speech change | Stroke/TIA | HIGH |
| Ascending weakness days-weeks, areflexia, after infection | Guillain-Barré syndrome | HIGH |
| Bilateral leg weakness + sensory level + bowel/bladder dysfunction | Spinal cord compression | HIGH |
| Fatigable weakness — worse with use, ptosis, diplopia | Myasthenia gravis | Moderate |
| Proximal muscle weakness, rash, elevated CK | Inflammatory myopathy | Moderate |
| Fatigue, cold intolerance, weight gain, constipation | Hypothyroidism | Moderate |
| Generalized fatigue, pallor, exertional symptoms | Anemia | Low-moderate |
Systematic Approach
Localize
Upper vs lower motor neuron, neuromuscular junction, muscle
UMN (stroke, MS): spasticity, hyperreflexia, Babinski. LMN (GBS, ALS): flaccidity, hyporeflexia, fasciculations. NMJ (myasthenia): fatigable weakness, normal reflexes. Muscle (myopathy): proximal > distal, elevated CK.
Pattern
Focal vs generalized, proximal vs distal, acute vs chronic
Focal acute = stroke until proven otherwise. Ascending = GBS. Proximal = myopathy or NMJ. Distal = peripheral neuropathy. Fatigable = myasthenia. Episodic = channelopathy, TIA.
Respiratory
Assess in GBS and myasthenic crisis
NIF (negative inspiratory force) and FVC are more sensitive than SpO2 for impending respiratory failure in neuromuscular disease. NIF worse than -25 cmH2O or FVC <1L → ICU monitoring.
Workup
Guided by localization
Stroke → CT/MRI brain. GBS → LP (albuminocytologic dissociation), nerve conduction studies. Myasthenia → AChR antibodies, edrophonium test, CT chest (thymoma). Myopathy → CK, EMG, muscle biopsy. Thyroid → TSH.
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