What is the differential diagnosis and approach for a 40-year-old patient with sudden onset monoparesis (monoparesis), presenting with loss of power, sensation, and areflexia (absence of reflexes) in the right arm, elbow, and distal (distal) areas?

Acute Monoparesis of the Right Arm: Differential Diagnosis and Approach

This 40-year-old patient with sudden onset right arm monoparesis, complete sensory loss, and areflexia most likely has either a peripheral nerve injury (brachial plexopathy or multiple mononeuropathies) or, less commonly, a cortical stroke affecting the motor and sensory cortex—immediate neuroimaging with MRI is essential to distinguish between these etiologies, as the combination of motor, sensory, and reflex loss in a single limb is atypical for pure cortical stroke.

Key Distinguishing Clinical Features

The clinical presentation provides critical diagnostic clues:

• Sudden onset suggests vascular etiology (stroke) or acute nerve injury/compression 1, 2
• Complete sensory loss is unusual for pure cortical stroke, which typically spares sensation or causes only mild sensory deficits 3, 4
• Areflexia strongly suggests peripheral nerve pathology rather than upper motor neuron lesion, where reflexes are typically preserved or increased 2, 3
• Involvement of entire arm (proximal and distal) indicates either extensive cortical lesion or brachial plexus/multiple nerve involvement 3, 4

Primary Differential Diagnoses

1. Brachial Plexopathy (Most Likely Given Clinical Features)

This is the most probable diagnosis given the combination of motor, sensory, and reflex loss:

• Acute brachial plexus injury can cause complete monoparesis with sensory loss and areflexia in the affected limb 5
• Etiologies include trauma, compression, inflammatory (neuralgic amyotrophy), or vascular compromise 5
• The sudden onset suggests either traumatic injury (even without recalled trauma), vascular insult to the plexus, or acute inflammatory process 5

2. Cortical Stroke (Less Likely but Must Be Excluded)

While less consistent with the complete clinical picture, stroke must be urgently excluded:

• Monoparetic stroke comprises less than 1% of all strokes but can present with isolated arm weakness 4
• Most monoparetic strokes involve the precentral gyrus or middle cerebral artery branch territory with cortical (80.6%) and often multiple (64.5%) lesions 2, 3
• Critical distinguishing features against stroke: Pure cortical strokes typically preserve or only mildly affect sensation, and reflexes are usually normal or increased (not absent) 2, 3, 4
• Only 35.5% of monoparetic stroke patients show upper motor neuron signs initially 2
• Distal arm monoparesis from stroke is clearly delineated on MRI/DWI as superficial small cortical infarcts 4

3. Guillain-Barré Syndrome Variant (Consider if Bilateral or Progressive)

While GBS typically presents with ascending bilateral weakness, variants exist:

• Pure motor variant (5-70% of cases) can present with motor weakness without sensory signs, but this is typically bilateral and ascending 5, 6
• Areflexia is characteristic of GBS, with decreased or absent reflexes in most patients at presentation 6
• Recent infection history (within 6 weeks) is present in about two-thirds of GBS patients 6
• Key distinguishing feature: GBS is almost always bilateral and progressive over hours to days, not isolated to one limb 5, 6

4. Multiple Mononeuropathies or Vasculitic Neuropathy

• Sudden onset of multiple nerve involvement can mimic monoparesis 5
• Consider if patient has systemic symptoms, fever, or risk factors for vasculitis 5

Immediate Diagnostic Approach

Step 1: Emergency Neuroimaging (Within 1 Hour)

Obtain MRI brain with DWI/FLAIR sequences immediately:

• MRI with DWI is superior to CT for detecting acute cortical infarcts causing monoparesis 4
• FLAIR and T2 imaging can identify small hemorrhages and perifocal edema 7
• If stroke is identified, it will appear as superficial cortical lesion in precentral gyrus or MCA territory 2, 3, 4
• Paramedian pontine lesions can rarely cause pure brachial monoparesis 1

Step 2: Focused Neurological Examination

Assess for features that distinguish central from peripheral pathology:

• Test all cranial nerves: Facial weakness, diplopia, or dysphagia suggest GBS or brainstem pathology 8, 5
• Examine contralateral limb: Any bilateral findings strongly suggest GBS 5, 6
• Assess for upper motor neuron signs: Babinski sign, spasticity (though may be absent acutely in stroke) 2
• Detailed sensory examination: Map exact distribution of sensory loss to determine if it follows dermatomal (plexus), peripheral nerve, or cortical pattern 5
• Palpate brachial plexus region: Check for masses, tenderness, or signs of trauma 5
• Assess respiratory function: Measure vital capacity if GBS suspected, as 20% develop respiratory failure 5, 6

Step 3: Targeted History

Obtain specific information to narrow differential:

• Trauma history: Even minor trauma can cause plexus injury 5
• Recent infection: Within 6 weeks suggests GBS (two-thirds of cases) 6
• Vascular risk factors: Hypertension, diabetes, hyperlipidemia increase stroke probability 8, 2
• Pain characteristics: Radicular pain suggests plexus or nerve root pathology; muscular pain can occur in GBS 5, 6
• Progression pattern: Stroke is maximal at onset; GBS progresses over hours to days; plexopathy may worsen initially then stabilize 6, 2

Step 4: Initial Laboratory Testing

If GBS is being considered:

• Complete blood count, glucose, electrolytes, kidney and liver function to exclude metabolic causes 5
• Serum creatine kinase (elevated suggests muscle involvement) 5
• Consider Lyme serology if in endemic area 8

Do not delay neuroimaging for laboratory results 5

Step 5: Electrodiagnostic Studies (Within 24-48 Hours)

Nerve conduction studies and EMG are essential for definitive diagnosis:

• Can distinguish between cortical (normal nerve conduction), plexus (abnormal in distribution of plexus), or GBS (diffuse abnormalities with demyelinating features) 5
• In GBS, look for reduced conduction velocities, reduced amplitudes, temporal dispersion, or conduction blocks 5
• "Sural sparing pattern" (normal sural with abnormal median/ulnar) is typical for GBS 5
• Studies may be normal in first few days after symptom onset 5

Step 6: Lumbar Puncture (If GBS Suspected)

Perform after neuroimaging rules out mass lesion:

• Look for albumino-cytological dissociation (elevated protein with normal cell count) characteristic of GBS 5
• Important caveat: CSF protein can be normal in first week of GBS—do not dismiss diagnosis based on this alone 5
• Marked CSF pleocytosis should prompt reconsideration of GBS diagnosis 5

Critical Pitfalls to Avoid

• Do not assume peripheral nerve injury without neuroimaging: Cortical strokes can present with minimal upper motor neuron signs initially and may be misdiagnosed as peripheral neuropathy 2, 4
• Do not dismiss stroke based on absent reflexes: While unusual, some stroke patients have decreased reflexes acutely 3
• Do not wait for complete diagnostic workup before treatment: If stroke is identified on imaging, initiate acute stroke protocols immediately; if GBS is suspected clinically, do not wait for antibody results or CSF confirmation before starting treatment 5
• Do not overlook bilateral findings: Even subtle contralateral weakness suggests GBS rather than unilateral pathology 5, 6
• Do not assume good prognosis without proper diagnosis: While monoparetic stroke has better functional outcomes, recurrent stroke risk is 14% over 1.7 years, similar to other strokes 2, 4

Disposition and Monitoring

• Admit all patients for observation and definitive diagnosis 5, 6
• ICU-level care if: Respiratory compromise suspected (GBS), acute stroke with potential for deterioration, or rapidly progressive weakness 5, 6
• Serial neurological examinations every 2-4 hours to detect progression 5, 6
• Continuous cardiac monitoring if GBS suspected due to dysautonomia risk 5, 6