What is the approach to diagnosing and managing a patient with generalized weakness?

Approach to Associated History in Generalized Weakness

Critical Red Flags to Identify Immediately

The most urgent historical features to elicit are respiratory symptoms (dyspnea, shortness of breath), bulbar dysfunction (difficulty swallowing, slurred speech, facial weakness), and rapidly ascending weakness, as these indicate potentially life-threatening conditions requiring immediate intervention. 1, 2

Life-Threatening Presentations Requiring Urgent Assessment:

• Respiratory compromise: Ask specifically about shortness of breath, difficulty breathing when lying flat, or feeling unable to take a deep breath—these suggest impending respiratory failure in myasthenia gravis crisis or Guillain-Barré syndrome 1, 2
• Bulbar symptoms: Inquire about difficulty swallowing (dysphagia), slurred speech (dysarthria), or facial weakness, which may precede respiratory compromise 1, 2
• Rapidly ascending weakness: Determine if weakness started in the legs and is moving upward, characteristic of Guillain-Barré syndrome 2
• Autonomic instability: Ask about blood pressure fluctuations, heart rate abnormalities, or bowel/bladder dysfunction 2

Essential Temporal and Pattern Characteristics

Onset and Progression:

• Acute onset (hours to days): Consider Guillain-Barré syndrome, myasthenia gravis crisis, or electrolyte disturbances 2, 3
• Subacute onset (days to weeks): Think myasthenia gravis, inflammatory myopathies, or ICU-acquired weakness 2, 4
• Chronic progression (weeks to months): Consider chronic inflammatory demyelinating polyneuropathy or muscular dystrophies 5

Fluctuation Pattern:

• Worsens with activity, improves with rest: Highly suggestive of myasthenia gravis—specifically ask if symptoms are worse at end of day or after repetitive activities 6, 2
• Variable day-to-day: Also characteristic of myasthenia gravis 6
• Constant and progressive: More consistent with Guillain-Barré syndrome or myositis 2

Distribution and Localization Questions

Pattern of Weakness:

• Proximal vs. distal: Proximal weakness (difficulty rising from chair, lifting arms overhead, climbing stairs) suggests myopathy or myositis, while distal weakness suggests peripheral neuropathy 2, 5
• Symmetrical vs. asymmetrical: Symmetrical weakness is typical of Guillain-Barré syndrome and ICU-acquired weakness, while asymmetrical patterns suggest focal nerve or root lesions 6, 2
• Ascending pattern: Weakness starting in legs and moving upward is classic for Guillain-Barré syndrome 2

Specific Muscle Group Involvement:

• Ocular symptoms: Ask about double vision (diplopia) or drooping eyelids (ptosis)—50% of myasthenia gravis patients present with ocular symptoms only 6, 2
• Facial weakness: Inquire about difficulty with facial expressions, chewing, or keeping mouth closed 6
• Neck weakness: Ask if patient has difficulty holding head up—common in myasthenia gravis 6

Associated Symptoms to Systematically Assess

Sensory Symptoms:

• Paresthesias or numbness: Presence suggests peripheral nerve involvement (Guillain-Barré syndrome) rather than neuromuscular junction or muscle disease 2
• Pain: Muscle pain or tenderness points toward myositis, while radicular pain suggests nerve root involvement 2

Systemic Symptoms:

• Fever: May indicate infectious myositis or systemic inflammatory process 6
• Weight loss: Consider malignancy-associated paraneoplastic syndromes 6, 2
• Fatigue: Protracted fatigue is common in coccidioidal infection and may persist long after active infection resolves, eventually becoming a deconditioned state 6

Critical Contextual History

Recent Medical Events:

• ICU admission or prolonged mechanical ventilation: ICU-acquired weakness occurs in 33% of critically ill patients, with higher incidence after >7 days of mechanical ventilation (43% vs. 33% with <5 days) 6
• Recent infection: Guillain-Barré syndrome often follows respiratory or gastrointestinal infection by 1-3 weeks 2
• Recent surgery or hospitalization: Consider critical illness polyneuropathy or myopathy 6, 4

Medication History—Specifically Avoid These in Myasthenia Gravis:

• Beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, macrolide antibiotics: All can worsen myasthenia gravis 6, 1
• Immune checkpoint inhibitors: Can cause immune-related myasthenia gravis, myositis, or Guillain-Barré syndrome 6, 2

Comorbidities:

• Autoimmune thyroid disease or thymoma: Increased risk for myasthenia gravis 6
• Malignancy: Consider paraneoplastic syndromes 6, 2
• Sepsis or multiorgan failure: Risk factor for ICU-acquired weakness 6

Functional Impact Assessment

Activities of Daily Living:

• Self-care limitations: Determine if patient can dress, bathe, or feed themselves—Grade 3-4 weakness limits self-care and warrants aggressive intervention 6
• Mobility: Ask if patient can walk independently, needs assistance, or is bedbound 6
• Occupational impact: Document inability to work or perform usual activities, as medical release may be justified during recovery 6

Special Populations

Transplant Patients:

• In transplant patients with generalized weakness, consider calciphylaxis, which can mimic collagen vascular diseases and requires multidisciplinary diagnostic approach including electrodiagnostics, vascular studies, and skin biopsy 7

Adolescents:

• In young patients, specifically ask about eating disorders and use of ipecac for self-induced vomiting, which can cause profound weakness requiring cardiac monitoring 8

Critical Illness Context:

• The hospital setting significantly narrows the differential diagnosis—most cases of generalized weakness in hospitalized patients are not due to primary neurologic diseases but rather complications of critical illness, medications, or metabolic derangements 4