What are the possible causes of acute onset ptosis with motor and sensory symptoms and neck drop?

Acute Onset Ptosis with Motor/Sensory Symptoms and Neck Drop: Differential Diagnosis

The combination of acute onset ptosis, motor and sensory symptoms, and neck drop most strongly suggests myasthenia gravis (particularly generalized form), though botulism and immune checkpoint inhibitor-related neurologic toxicity must be urgently excluded based on clinical context.

Primary Diagnostic Considerations

Myasthenia Gravis (Most Likely)

Myasthenia gravis presenting with neck drop ("head drop") indicates generalized disease involving bulbar, limb, and potentially respiratory muscles, which can lead to life-threatening respiratory failure. 1

Key Clinical Features:

• Fatigable weakness that worsens with sustained activity and improves with rest 2
• Variable ptosis that worsens with fatigue (prolonged upgaze) and may show Cogan lid-twitch sign 1
• Neck weakness/head drop indicates involvement of large motor groups beyond ocular muscles 1
• Difficulty with chewing, swallowing, slurred speech 1
• Slow ocular saccades 1
• Pupils typically not affected (distinguishes from third nerve palsy) 1

Immediate Diagnostic Steps:

• Ice pack test: Apply ice pack over closed eyes for 2 minutes—reduction of ptosis by ~2mm is highly specific for myasthenia gravis 1
• Acetylcholine receptor antibody testing: 80-88% sensitivity for generalized MG, 98-100% specificity (gold standard serological test) 2
• Assess respiratory function immediately: Myasthenic crisis can be life-threatening 2
• Consider Tensilon test (95% sensitive for generalized MG) if performed in monitored setting with atropine available 1

Critical Pitfall:

50% of patients with ocular myasthenia develop generalized systemic myasthenia within a few years, and the presence of neck drop indicates this progression has already occurred. 1 This requires urgent neurology consultation and potential ICU monitoring for respiratory compromise.

Botulism (Must Exclude)

Botulism can present with symmetric cranial nerve palsies including ptosis, descending paralysis, and respiratory failure, though sensory symptoms are typically absent. 1

Distinguishing Features:

• Descending pattern: Cranial nerves affected first, then descending to trunk and extremities 1
• Symmetric cranial nerve palsies with or without paresis of other muscles 1
• Pupils may show impaired or slow responses (unlike myasthenia) 1
• Sensory examination should be normal in classic botulism—presence of sensory symptoms makes this less likely 1
• History of contaminated food, wound, or injection drug use 1

Immediate Action:

If botulism suspected, immediately contact local/state health department emergency staff for expert consultation and botulinum antitoxin from CDC. 1

Immune Checkpoint Inhibitor-Related Neurologic Toxicity

If patient has cancer treatment history, checkpoint inhibitor-induced myasthenia gravis or myasthenic syndrome must be considered, with median onset 4 weeks (range 1-68 weeks). 1

Presentation:

• Fatigable/fluctuating muscle weakness, ptosis, double vision, dysphagia, dysarthria, facial weakness, head drop or neck weakness 1
• May overlap with myositis 1
• Can be life-threatening and requires immediate immunosuppression 1

Secondary Considerations

Guillain-Barré Syndrome

• Typically presents with ascending progressive weakness (feet to head), not descending 1
• Sensory symptoms (numbness, tingling, burning pain) are common 1
• CSF protein often elevated by second week 1
• Neck drop can occur but ptosis is less characteristic 1

Lambert-Eaton Myasthenic Syndrome

• Proximal muscle weakness with autonomic dysfunction 1
• Reflexes typically diminished/absent (unlike myasthenia where reflexes preserved) 2
• Less commonly presents with prominent ptosis 1

Diagnostic Algorithm

1. Immediate assessment:

   • Respiratory function (vital capacity, negative inspiratory force)
   • Pupillary examination (equal and reactive suggests myasthenia; abnormal suggests other pathology) 1, 3
   • Sensory examination (normal in myasthenia and botulism; abnormal suggests GBS or other neuropathy)

2. Bedside testing:

   • Ice pack test (2 minutes over closed eyes) 1
   • Assess for fatigability with prolonged upgaze 1
   • Look for Cogan lid-twitch sign 1

3. Laboratory/Imaging:

   • Acetylcholine receptor antibodies (first-line) 2
   • Anti-MuSK antibodies if seronegative 2
   • Repetitive nerve stimulation or single-fiber EMG 2
   • Chest CT to screen for thymoma (10-15% of MG patients) 2
   • Stool/serum for botulinum toxin if epidemiologically appropriate 1

4. Urgent neurology consultation for any patient with neck drop and ptosis 1

Critical Management Points

The presence of neck drop with ptosis indicates generalized neuromuscular disease requiring ICU-level monitoring for respiratory failure. 1 Do not delay treatment while awaiting confirmatory testing if clinical suspicion is high—empiric treatment with anticholinesterase drugs (pyridostigmine) can be diagnostic and therapeutic for myasthenia gravis. 4