What is the initial workup for a patient presenting with generalized weakness?

Initial Workup for Generalized Weakness

The initial workup for a patient presenting with generalized weakness should include a thorough history and physical examination, complete blood count, urinalysis, serum electrolytes (including calcium and magnesium), blood urea nitrogen, serum creatinine, fasting blood glucose, lipid profile, liver function tests, thyroid-stimulating hormone, electrocardiogram, and chest radiograph. 1

History and Physical Examination

• Distinguish true weakness (loss of strength) from fatigue or asthenia, which have different etiologies but can coexist with weakness 2
• Assess the pattern and severity of weakness, including:
  • Proximal vs. distal distribution
  • Symmetric vs. asymmetric involvement
  • Acute vs. chronic onset
  • Fluctuating vs. persistent symptoms 2
• Document the patient's ability to perform routine and desired activities of daily living 1
• Assess for orthostatic blood pressure changes, which may indicate volume depletion or autonomic dysfunction 1
• Measure weight, height, and calculate body mass index 1
• Perform a complete neurological examination, including muscle strength testing, deep tendon reflexes, and sensory assessment 2
• Evaluate for cardiac and non-cardiac disorders that might cause or contribute to weakness 1
• Obtain a careful history of current and past use of medications, alcohol, illicit drugs, and alternative therapies that could cause weakness 1

Laboratory Testing

• Complete blood count to evaluate for anemia, infection, or malignancy 1
• Urinalysis to screen for renal disease or infection 1
• Serum electrolytes, including calcium and magnesium, to identify electrolyte disturbances 1
• Blood urea nitrogen and serum creatinine to assess kidney function 1
• Fasting blood glucose (or glycohemoglobin) to screen for diabetes 1
• Lipid profile to assess cardiovascular risk 1
• Liver function tests to evaluate for hepatic disease 1
• Thyroid-stimulating hormone to screen for thyroid dysfunction 1
• Consider creatine kinase (CK) if myopathy is suspected 1, 2
• Consider inflammatory markers (ESR, CRP) if inflammatory or rheumatologic conditions are suspected 1

Diagnostic Imaging and Other Studies

• Twelve-lead electrocardiogram to evaluate for cardiac abnormalities 1
• Chest radiograph (posterior-anterior and lateral) to assess for cardiopulmonary disease 1
• Consider echocardiography if heart failure is suspected, to assess left ventricular ejection fraction, size, wall thickness, and valve function 1
• Consider electromyography (EMG) and nerve conduction studies if neuromuscular causes are suspected 1
• Consider MRI of affected areas if focal weakness or structural abnormalities are suspected 1

Additional Considerations Based on Clinical Suspicion

• For suspected myasthenia gravis: AChR and anti-striated muscle antibodies; consider MuSK and LRP4 antibodies if AChR antibodies are negative 1
• For suspected Guillain-Barré syndrome: lumbar puncture for CSF analysis (typically shows elevated protein with normal cell count) 1
• For suspected heart failure: consider coronary arteriography if angina or significant ischemia is present 1
• For suspected myositis: check CK, aldolase, and consider muscle biopsy if diagnosis remains unclear 1
• For suspected endocrine disorders: consider additional thyroid function tests, cortisol levels 3, 4

Common Pitfalls and Caveats

• Failure to distinguish between true weakness and fatigue/asthenia can lead to inappropriate testing and delayed diagnosis 2
• Normal laboratory values early in the disease course do not rule out serious conditions; repeat testing may be necessary if symptoms persist 1
• Certain medications (e.g., statins, beta-blockers, fluoroquinolones) can cause or exacerbate weakness and should be reviewed carefully 1
• Electrolyte abnormalities may be subtle but clinically significant causes of weakness 1
• Consider cardiac and hepatic interactions, as dysfunction in one system can affect the other 5

By following this systematic approach to the workup of generalized weakness, clinicians can efficiently identify the underlying cause and initiate appropriate management to improve patient outcomes.