GENERALIZED WEAKNESS

New or worsening diffuse muscle weakness or fatigue impairing function — broad differential requiring systematic localization and workup

SYMPTOMS / ASSOCIATED SX

  • Difficulty rising from chair, climbing stairs, lifting arms overhead (proximal myopathy)

  • Bilateral symmetric vs. asymmetric; descending vs. ascending pattern

  • Dysphagia, diplopia, ptosis (NMJ disease — myasthenia gravis)

  • Sensory deficits, back pain, bowel/bladder dysfunction (cord compression)

  • Rash (heliotrope, Gottron papules → dermatomyositis); fevers, weight loss

DENIES

  • Focal unilateral deficits (stroke — MRI brain/spine)

  • Bowel/bladder incontinence + saddle anesthesia (cauda equina — EMERGENT MRI)

  • Recent vaccination/GI illness preceding ascending weakness (GBS)

  • Statin or colchicine use (drug-induced myopathy)

SOCIAL HISTORY

  • Alcohol (alcoholic myopathy, neuropathy, thiamine deficiency); statin use

  • Recent illness or vaccination (GBS); occupational exposures (heavy metals)

MAIN ETIOLOGY

  • Metabolic/electrolyte: hypokalemia, hyponatremia, hypophosphatemia, hypomagnesemia, hypothyroidism, adrenal insufficiency

  • Infectious: sepsis (critical illness myopathy), Lyme, HIV, viral myositis

  • Inflammatory myopathy: polymyositis, dermatomyositis, inclusion body myositis

  • Drug-induced: statins, steroids, colchicine, hydroxychloroquine, alcohol

  • Neurologic: GBS (ascending), MG (fatigable), cord compression, stroke

  • Deconditioning/critical illness myopathy: common in ICU/hospitalized patients

MOST COMMON DDX

  • Stroke/TIA (focal deficit, acute onset, neuroimaging)

  • GBS (ascending weakness, areflexia, albumino-cytologic dissociation on LP)

  • Myasthenia gravis (fatigable ptosis, AChR/MuSK Ab, Tensilon test, RNS EMG decrement)

  • Hypokalemia (K <3.0, ECG changes, paralytic ileus)

  • Hypothyroidism (TSH elevated, slow-relaxing DTRs, proximal weakness)

  • Polymyositis/dermatomyositis (elevated CK/aldolase, myositis panel, EMG)

DATA

  • BMP + Mg + Phos; CBC; TSH; CK + aldolase; LFTs; ESR/CRP

  • ANA, anti-Jo-1, anti-MDA5, anti-Mi-2 (inflammatory myopathy panel)

  • AChR Ab, anti-MuSK (myasthenia gravis)

  • AM cortisol; ACTH stim test if Addison's suspected

  • MRI spine if bowel/bladder involved (emergent for cauda equina)

  • EMG/NCS (neurology-guided): nerve vs. muscle vs. NMJ localization

  • LP if GBS suspected (elevated protein, normal cells)

  • NIF if bulbar weakness or respiratory compromise

HOME MEDS

  • Statins — hold if CK elevated; reassess after resolution; HMGCR Ab if IMNM suspected

  • Colchicine/hydroxychloroquine — hold if drug-induced myopathy suspected

  • Pyridostigmine — continue if known MG; assess dose adequacy

PLAN

  • Correct electrolyte abnormalities (K, Mg, Phos, Na)

  • Inflammatory myopathy (PM/DM):

    • Prednisone 1 mg/kg/day PO (max 80 mg/day)

    • Steroid-sparing: azathioprine 2–3 mg/kg/day or mycophenolate 2–3 g/day — add early

    • IVIG 2 g/kg over 2–5 days for severe/refractory; rheumatology consult

  • GBS (Dutch GBS trial / PE-Sandoglobulin trial):

    • IVIG 0.4 g/kg/day IV ×5 days OR PLEX 5 exchanges over 10 days — equivalent efficacy

    • Serial NIF q4–6h; ICU if NIF <30 cmH2O or rapid progression

    • No role for steroids in GBS; neurology consult urgently

  • Myasthenia crisis:

    • Pyridostigmine 30–60 mg PO q4–6h (careful — cholinergic crisis risk)

    • IVIG 2 g/kg over 2–5 days or PLEX for crisis

    • Prednisone start low 10–20 mg/day, titrate slowly (initial worsening risk)

    • Avoid: fluoroquinolones, aminoglycosides, beta-blockers — precipitate crisis

  • Drug-induced myopathy: discontinue agent; CK trend q48–72h until normalizing

  • PT/OT — early mobilization key for all etiologies

  • Neurology consult for GBS, MG, cord compression; rheumatology for inflammatory myopathy

  • DISCHARGE:

    • Inflammatory myopathy: outpatient rheum; screen for ILD (PFTs, HRCT)

    • Statin myopathy: alternative statin at lower dose; CK recheck in 6–8 weeks

    • Dermatomyositis: malignancy screen (CT CAP + mammogram + colonoscopy — ~25% association)

RED FLAGS

  • Ascending weakness + areflexia → GBS; check NIF immediately; ICU if progressing

  • NIF <30 cmH2O or FVC <50% predicted → impending respiratory failure; intubate early

  • Dysphagia + weakness + ptosis → MG crisis; ICU respiratory monitoring

  • Saddle anesthesia + bowel/bladder dysfunction → cauda equina; emergent MRI + spine surgery

  • CK >10,000 → rhabdomyolysis; aggressive IVF and renal monitoring

SENIOR IM RESIDENT PEARLS

  • Localize first: UMN (spasticity, hyperreflexia, Babinski) vs. LMN (flaccid, areflexia, fasciculations) vs. myopathic (proximal, normal reflexes, high CK) vs. NMJ (fatigable, normal CK, RNS decrement)

  • 20-30-40 rule for GBS intubation: FVC <20 mL/kg, MIP <–30 cmH2O, MEP <40 cmH2O → intubate

  • HMGCR Ab-positive IMNM: does NOT resolve after stopping statin; requires prednisone + immunosuppression

  • Common mistake: attributing weakness to deconditioning without checking CK, TSH, electrolytes

  • Dermatomyositis: ~25% associated with occult malignancy — CT CAP + age-appropriate cancer screen

  • Common mistake: giving fluoroquinolones or aminoglycosides to undiagnosed MG — can precipitate crisis

  • Critical illness myopathy: develops after just 1 week in ICU; ABCDEF bundle is best prevention