Initial Workup for Generalized Weakness

History and Physical Examination

The American Heart Association recommends assessing the pattern and severity of weakness, including proximal vs. distal distribution, symmetric vs. asymmetric involvement, and acute vs. chronic onset 3, 4, 5
Documenting the patient's ability to perform routine and desired activities of daily living is crucial, as well as assessing for orthostatic blood pressure changes, which may indicate volume depletion or autonomic dysfunction 1, 2
Evaluating for cardiac and non-cardiac disorders that might cause or contribute to weakness is essential, and obtaining a careful history of current and past use of medications, alcohol, illicit drugs, and alternative therapies that could cause weakness is also important 1, 2

Complete blood count, urinalysis, serum electrolytes, blood urea nitrogen, serum creatinine, fasting blood glucose, lipid profile, liver function tests, and thyroid-stimulating hormone are recommended as part of the initial workup for generalized weakness 1, 2
Consider creatine kinase (CK) if myopathy is suspected, and inflammatory markers (ESR, CRP) if inflammatory or rheumatologic conditions are suspected 3, 5

A twelve-lead electrocardiogram and chest radiograph are recommended to evaluate for cardiac abnormalities and cardiopulmonary disease 1, 2
Consider echocardiography if heart failure is suspected, to assess left ventricular ejection fraction, size, wall thickness, and valve function 1, 2
Electromyography (EMG) and nerve conduction studies may be considered if neuromuscular causes are suspected, and MRI of affected areas if focal weakness or structural abnormalities are suspected 3, 5, 6

For suspected myasthenia gravis, AChR and anti-striated muscle antibodies should be considered, as well as MuSK and LRP4 antibodies if AChR antibodies are negative 4, 5
For suspected Guillain-Barré syndrome, lumbar puncture for CSF analysis is recommended, typically showing elevated protein with normal cell count 6
For suspected heart failure, consider coronary arteriography if angina or significant ischemia is present 1, 2
For suspected myositis, check CK, aldolase, and consider muscle biopsy if diagnosis remains unclear 3, 5

Normal laboratory values early in the disease course do not rule out serious conditions, and repeat testing may be necessary if symptoms persist 6
Certain medications can cause or exacerbate weakness and should be reviewed carefully, and electrolyte abnormalities may be subtle but clinically significant causes of weakness 1, 2, 3, 4