What is the initial diagnostic approach and treatment plan for a patient presenting with weakness?

Evaluation of Weakness: Initial Diagnostic Approach and Treatment

Begin with a focused history targeting onset tempo, distribution pattern, and respiratory/bulbar symptoms, followed by objective strength grading using the MRC scale, then order CK, TSH, and basic metabolic panel as first-line laboratory tests. 1, 2

Immediate Red Flag Assessment

Identify life-threatening presentations first that require urgent intervention:

• Respiratory symptoms (shortness of breath, difficulty breathing) indicate impending respiratory failure in myasthenia gravis crisis or Guillain-Barré syndrome requiring immediate assessment 2
• Bulbar dysfunction (difficulty swallowing, slurred speech) may precede respiratory compromise 2
• Rapidly ascending weakness is characteristic of Guillain-Barré syndrome 2
• Severe rhabdomyolysis (CK >1000 U/L) requires urgent management 1

These patients need hospitalization and urgent neurology consultation. 1

Critical History Elements

Temporal Pattern and Onset

• Acute onset (hours to days): Consider Guillain-Barré syndrome, myasthenia gravis crisis, or electrolyte disturbances 2
• Subacute onset (days to weeks): Suggests myasthenia gravis, inflammatory myopathies, or ICU-acquired weakness 2
• Symptoms worsening with activity and improving with rest: Highly suggestive of myasthenia gravis 2

Distribution and Pattern

• Proximal weakness (difficulty rising from chair, lifting arms overhead): Indicates myopathy or myositis 2
• Distal weakness: Suggests peripheral neuropathy 2
• Symmetrical weakness: Typical of Guillain-Barré syndrome and ICU-acquired weakness 2
• Asymmetrical patterns: Suggest focal nerve or root lesions 2

Associated Symptoms

• Paresthesias or numbness: Indicate peripheral nerve involvement (Guillain-Barré) rather than neuromuscular junction or muscle disease 2
• Fever: May indicate infectious myositis or systemic inflammatory process 2
• Weight loss: Suggests malignancy-associated paraneoplastic syndromes 2

Critical Contextual Factors

• Recent ICU admission or prolonged mechanical ventilation: ICU-acquired weakness occurs in 33% of critically ill patients 2
• Recent infection (respiratory or gastrointestinal 1-3 weeks prior): May precede Guillain-Barré syndrome 2
• Medication history: Beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, macrolides, and immune checkpoint inhibitors can cause or worsen weakness 2
• Statin use: Critical for diagnosing medication-induced myopathy 1
• Family history: Essential for inherited myopathies, periodic paralysis, or muscular dystrophies 1

Physical Examination Approach

Objective Strength Documentation

Grade muscle strength using the MRC scale (0-5) in multiple muscle groups bilaterally rather than accepting subjective patient reports. 2 This provides quantifiable documentation and allows tracking of progression.

Essential Neurologic Survey

• Reflex examination: Diminished or absent reflexes with weakness suggest lower motor neuron, peripheral nerve, or neuromuscular junction disease 2
• Cranial nerve assessment: Test eye movements for oculomotor abnormalities and assess facial expression symmetry 2
• Motor neuron signs: Look for fasciculations, muscle atrophy, or tongue wasting suggesting amyotrophic lateral sclerosis 2

Functional Observation

Watch the patient's posture, gait, and spontaneous motor function before formal testing, as stressed examination may not reveal true functional capacity. 2

Initial Laboratory Testing

Order the following first-line tests to identify common and treatable causes: 1

• Creatine kinase (CK): CK >1000 U/L indicates rhabdomyolysis, muscular dystrophy, or severe myositis requiring urgent management 1
• Thyroid-stimulating hormone (TSH): Identifies thyroid-related weakness 1
• Basic metabolic panel: Hypokalemia, hypercalcemia, and hypomagnesemia cause reversible weakness 1
• Complete blood count: Evaluate for infection or hematologic abnormalities 1

Electrodiagnostic Testing

Perform EMG and nerve conduction studies to distinguish myopathy from neuropathy from neuromuscular junction disorders if the diagnosis remains unclear after initial laboratory testing. 1 This can be delayed in cooperative patients to see if abnormalities persist, but should be performed early in uncooperative ICU patients. 1

Treatment Approach Based on Etiology

For Immune-Mediated Myositis

• Hold immune checkpoint inhibitors permanently 1
• Initiate methylprednisolone 1-2 mg/kg IV 1
• Consider plasmapheresis for severe cases 1

Hospitalization Criteria

Admit patients with: 1

• Severe weakness limiting mobility
• Respiratory involvement
• Rhabdomyolysis

Urgent Consultation

Obtain urgent rheumatology and neurology consultation for patients with suspected myasthenia gravis or muscular dystrophy. 1

Common Pitfalls to Avoid

• Do not assume normal early examination rules out progressive conditions - repeat examination may be necessary as weakness evolves 2
• Do not rely solely on patient's subjective description - objective MRC grading is essential 2
• Do not overlook medication history - many drugs cause or worsen weakness 1, 2
• Do not delay assessment of respiratory function - respiratory failure in neuromuscular disease may be insidious until sudden decompensation 3