What is the approach to a patient presenting with weakness?

Approach to a Patient with Weakness

The evaluation of a patient presenting with weakness requires a systematic neurological assessment to identify the underlying cause, with priority given to potentially life-threatening conditions such as Guillain-Barré syndrome (GBS) and myasthenia gravis (MG). 1

Initial Assessment

• Determine if the weakness is true motor weakness (loss of power) versus fatigue (general tiredness without loss of motor function) 2
• Assess pattern of weakness: bilateral vs unilateral, proximal vs distal, symmetrical vs asymmetrical 3
• Evaluate onset and progression: acute (hours to days), subacute (days to weeks), or chronic (weeks to months) 1, 3
• Check for associated symptoms: sensory changes, pain, autonomic dysfunction, respiratory symptoms 1
• Examine reflexes: decreased/absent reflexes suggest peripheral nervous system involvement 1

Diagnostic Algorithm

Step 1: Identify Red Flags Requiring Immediate Intervention

• Respiratory compromise: assess negative inspiratory force (NIF) and vital capacity (VC) 1
• Bulbar symptoms: dysphagia, dysarthria, facial weakness 1
• Rapidly ascending weakness: may indicate GBS requiring close monitoring 1
• Autonomic instability: blood pressure fluctuations, heart rate abnormalities 1

Step 2: Localize the Lesion Based on Clinical Features

A. Neuromuscular Junction (e.g., Myasthenia Gravis)

• Fluctuating weakness that worsens with activity 1
• Ocular symptoms (ptosis, diplopia) 1
• Normal sensation 1
• Diagnostic tests:
  • AChR and anti-striated muscle antibodies (if negative, consider MuSK and LPR4 antibodies) 1
  • Electrodiagnostic studies with repetitive stimulation 1

B. Peripheral Nerves (e.g., Guillain-Barré Syndrome)

• Ascending weakness (typically starts in legs) 1
• Areflexia or hyporeflexia 1
• Sensory symptoms (paresthesias, numbness) 1
• Diagnostic tests:
  • Lumbar puncture (elevated protein with normal cell count) 1
  • MRI spine to rule out compressive lesions 1
  • Electrodiagnostic studies (NCS/EMG) 1
  • Antiganglioside antibody testing 1

C. Muscle (e.g., Myositis)

• Proximal weakness (difficulty rising from chair, lifting arms) 1
• Muscle pain or tenderness 1
• Normal sensation 1
• Diagnostic tests:
  • CPK, aldolase, transaminases 1
  • Inflammatory markers (ESR, CRP) 1
  • EMG/NCS 1
  • Consider muscle biopsy in unclear cases 1

D. Intensive Care Unit-Acquired Weakness

• History of critical illness, prolonged mechanical ventilation 1
• Symmetrical limb weakness 1
• Reduced or absent deep tendon reflexes 1
• Diagnostic tests:
  • Manual muscle testing 1
  • Electrophysiological studies 1

Step 3: Laboratory and Diagnostic Testing

• Basic metabolic panel: electrolyte abnormalities (especially K+, Mg2+, Ca2+) 4
• Complete blood count: anemia, infection 4
• Thyroid function tests: hypo/hyperthyroidism 5
• Inflammatory markers: ESR, CRP 1
• Specific testing based on suspected diagnosis:
  • Autoimmune: ANA, RF, anti-CCP, myositis-specific antibodies 1
  • Paraneoplastic: anti-Hu (ANNA-1), anti-MAG antibodies 1
  • Infectious: HIV, Lyme disease, hepatitis 1

Management Principles

• For Guillain-Barré syndrome:

  • Admit to hospital with capability for ICU monitoring 1
  • Initiate IVIG (0.4 g/kg daily for 5 days) or plasma exchange (200-250 ml/kg for 5 sessions) 1
  • Monitor respiratory function closely 1

• For Myasthenia Gravis:

  • Pyridostigmine (starting at 30 mg PO TID, max 120 mg QID) 1
  • Corticosteroids (prednisone 0.5 mg/kg daily) 1
  • For severe cases: IVIG or plasmapheresis 1
  • Avoid medications that can worsen MG: beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, macrolides 1

• For Myositis:

  • Corticosteroids (prednisone 0.5-1 mg/kg/day) 1
  • For severe cases: consider IVIG, rituximab, or other immunosuppressants 1
  • NSAIDs for pain management 1

Special Considerations

• In elderly patients, weakness may present atypically and can be the only manifestation of serious underlying conditions 5
• Distinguish between true weakness and fatigue; fatigue is common but requires different management approaches 6
• Consider immune-related adverse events in patients on immune checkpoint inhibitors 1
• Weakness may be the initial presentation of a paraneoplastic syndrome requiring malignancy workup 1