What are the potential causes of sudden onset proximal arm weakness and distal leg weakness?

Sudden Onset Proximal Arm and Distal Leg Weakness: Differential Diagnosis

The most critical immediate consideration is acute stroke, particularly involving the anterior cerebral artery (ACA) territory or internal capsule, which can produce atypical weakness patterns including leg-predominant weakness with variable arm involvement. 1

Life-Threatening Causes Requiring Immediate Evaluation

Stroke (Most Urgent)

• Sudden onset is the hallmark of vascular etiology and should trigger immediate stroke protocol activation 1
• ACA territory strokes can cause contralateral leg-predominant weakness with proximal arm involvement, particularly when affecting the medial premotor cortex and supplementary motor area 1
• Internal capsular lesions account for approximately 29% of leg-predominant strokes and can produce variable patterns affecting both proximal and distal muscles 1
• Immediate brain imaging (CT or MRI) must be completed within 24 hours for any sudden unilateral weakness 2
• Look for: sudden onset (minutes to hours), unilateral distribution, associated facial weakness, speech disturbance, or sensory changes 2

Checkpoint Inhibitor-Induced Myositis (If Applicable)

• Carries 20% mortality risk due to concurrent myocarditis and requires immediate recognition 3
• Presents with proximal weakness but can have atypical patterns 3
• Requires immediate withdrawal of immunotherapy and high-dose glucocorticoids, IVIG, and/or plasma exchange 3

Inflammatory/Autoimmune Causes (Subacute to Acute Onset)

Idiopathic Inflammatory Myopathy

• While typically insidious (66.4% of cases), IIM can present acutely in 4.6% of cases 2
• The atypical pattern of proximal arm with distal leg weakness is unusual for classic IIM, which typically shows proximal > distal weakness in legs 2
• Assess immediately for respiratory muscle weakness, dysphagia, or dysarthria - these represent medical emergencies requiring ICU admission 4, 3
• Check creatine kinase (CK) urgently - markedly elevated CK (>10x normal) suggests inflammatory myopathy 4, 3
• Look for: skin manifestations (heliotrope rash, Gottron's papules/sign), symmetric weakness, elevated CK, positive myositis antibodies (anti-Jo-1, anti-SRP) 2, 4

Mixed Connective Tissue Disease

• Can produce atypical muscle involvement patterns affecting facial, neck, wrist, or finger muscles in addition to proximal weakness 5
• Associated with esophageal dysmotility affecting both striated and smooth muscle 5
• Generally has good therapeutic response to immunosuppression 5

Neuromuscular Causes (Consider if Pattern Persists)

Spinal Muscular Atrophy Variants

• Congenital autosomal dominant distal SMA can present with distal leg weakness and mild proximal arm weakness 6
• X-linked spinal and bulbar muscular atrophy can rarely present with prominent distal atrophy without typical proximal involvement 7
• These are chronic progressive conditions, not truly sudden onset 6, 7

Critical Diagnostic Algorithm

Step 1: Rule Out Stroke (First 24 Hours)

• If symptom onset is within 48 hours with unilateral weakness, immediately send to emergency department 2
• Obtain urgent brain imaging (CT or MRI) and vascular imaging (CTA/MRA from aortic arch to vertex) within 24 hours 2
• Complete ECG without delay 2

Step 2: Assess for Respiratory Emergency

• Check vital capacity, negative inspiratory force, and oxygen saturation immediately 4, 3
• Bulbar symptoms (dysphagia, dysarthria, dysphonia) indicate severe disease requiring urgent high-dose methylprednisolone 3

Step 3: Laboratory Evaluation

• Creatine kinase (CK) - if >10x normal, suspect inflammatory myopathy 4, 3
• Thyroid function tests (TSH, free T4) - hypothyroidism causes proximal weakness 3
• Inflammatory markers (ESR, CRP) if inflammatory myopathy suspected 3
• Myositis-specific antibody panel (anti-Jo-1, anti-SRP) 4, 3

Step 4: Advanced Imaging if Non-Vascular

• Muscle MRI identifies inflammation and guides biopsy site 3
• EMG shows myopathic vs neurogenic patterns 3, 6

Common Pitfalls to Avoid

• Do not assume symmetric involvement is required for stroke - atypical patterns occur in 4% of stroke cases 1
• Do not delay stroke workup based on unusual weakness distribution - leg-predominant or monoparesis patterns can be cortical 1, 8
• Do not wait for definitive investigations before treating respiratory muscle weakness - treatment should not be delayed 9
• Do not attribute sudden weakness to peripheral nerve disorders without imaging - distal arm monoparesis from stroke is often misdiagnosed as peripheral neuropathy 8