What are the differences between central pontine myelinolysis (CPM), botulism, and locked-in syndrome in terms of clinical presentation, diagnosis, and management?

Distinguishing Central Pontine Myelinolysis, Botulism, and Locked-In Syndrome

These three conditions can present with quadriplegia and bulbar dysfunction, but consciousness, pupillary responses, and temporal progression distinguish them clinically—botulism shows descending paralysis with unreactive pupils over hours to days, central pontine myelinolysis develops days after rapid sodium correction with preserved consciousness, and locked-in syndrome (whether from CPM or other causes) presents with complete motor paralysis except vertical eye movements while consciousness remains fully intact.

Clinical Presentation Differences

Botulism

• Descending flaccid bilateral paralysis beginning with cranial nerve palsies (ptosis, ophthalmoplegia, diplopia) followed by progressive weakness of respiratory, extremity, and axial muscles over hours to a few days 1
• Unreactive or dilated pupils are expected findings, though reported in only 25% of confirmed cases 1
• Symmetric neurologic deficits affecting proximal before distal muscles, with preserved consciousness throughout 1
• Early symptoms include dysphagia, blurred vision, slurred speech, dry mouth, and diplopia 1
• Gastrointestinal symptoms (nausea, vomiting) occur in 50% of foodborne cases 1

Central Pontine Myelinolysis (CPM)

• Delayed onset occurring days to weeks after rapid correction of hyponatremia (typically >10-12 mEq/L in first 24 hours) 2, 3
• Progressive spastic quadriparesis, dysarthria, pseudobulbar palsy developing over days, not hours 2, 4
• Preserved consciousness in most cases, though encephalopathy can occur 4
• May present with neuropsychiatric manifestations (acute psychosis, personality changes, hallucinations) as the primary feature, even without focal neurologic deficits 4
• Symmetric demyelination in central basis pontis on MRI, appearing as hyperintense signal on T2/FLAIR sequences 3, 5

Locked-In Syndrome

• Complete quadriplegia and bulbar palsy with only vertical eye movements and blinking preserved 3, 6
• Fully preserved consciousness and cognition—patients are alert and aware but cannot move or communicate except through eye movements 3, 5
• Represents the most severe manifestation of CPM when it occurs from pontine pathology 6
• Can result from CPM following rapid sodium correction, presenting 1-2 weeks after the electrolyte disturbance 3

Diagnostic Approach

Key Distinguishing Features on Examination

• Pupillary response: Unreactive in botulism 1; normal in CPM and locked-in syndrome 3
• Consciousness: Preserved in all three conditions typically, but botulism patients can follow commands while locked-in patients cannot move to demonstrate this 1, 3
• Pattern of weakness: Descending in botulism (cranial nerves → trunk → limbs) 1; ascending or simultaneous in CPM 2, 3
• Temporal relationship: Hours to days in botulism 1; days to weeks after sodium correction in CPM 2, 3

Diagnostic Testing

• Botulism: Clinical diagnosis confirmed by mouse bioassay or toxin detection in serum/stool; EMG shows characteristic decremental response at low-frequency stimulation with incremental response at high-frequency 1
• CPM: MRI brain showing symmetric T2/FLAIR hyperintensity in central pons, though initial MRI may be normal with changes appearing 1-2 weeks later 3, 4
• History of rapid sodium correction (>10-12 mEq/L in 24 hours) strongly suggests CPM in appropriate clinical context 2, 3

Management Priorities

Botulism

• Immediate consultation with CDC botulism clinical service and administration of botulinum antitoxin as soon as diagnosis is suspected 1, 7
• Supportive care with mechanical ventilation for respiratory failure 1
• Monitor for upper airway compromise from pharyngeal collapse even before diaphragmatic weakness develops 1

Central Pontine Myelinolysis

• Prevention is paramount: Correct hyponatremia slowly (≤8-10 mEq/L in first 24 hours) in high-risk patients (alcoholics, malnourished, chronic liver disease, transplant recipients) 2, 3
• Once CPM develops, treatment is supportive with intensive rehabilitation over months to years 3, 6
• Consider adjusting immunosuppression (switching from tacrolimus to sirolimus) in transplant-related cases 6
• Prognosis varies from complete recovery to persistent locked-in syndrome depending on severity 3, 6

Locked-In Syndrome

• Establish communication system using eye movements immediately upon recognition 3
• Intensive, prolonged rehabilitation (>2 years) can result in significant functional recovery even from complete quadriplegia 3
• Supportive care including mechanical ventilation, nutrition, prevention of complications 3, 6

Critical Pitfalls to Avoid

• Do not assume altered mental status excludes botulism—consciousness is typically preserved, and reported altered mental status may reflect inadequate examination 1
• Do not rely on initial MRI to exclude CPM—imaging may be normal in first 1-2 weeks, requiring repeat imaging if clinical suspicion persists 4
• Do not mistake locked-in syndrome for coma or unresponsiveness—test vertical eye movements and blinking specifically to establish communication 3, 5
• Consider botulism when myasthenia gravis or Guillain-Barré syndrome are suspected, as these are the most common misdiagnoses 1
• Perform thorough serial neurologic examinations including pupillary responses, pattern of weakness progression, and cranial nerve function to distinguish these conditions 1