Tabular Comparison of Central Pontine Myelinolysis, Locked-In Syndrome, and Botulism
These three conditions can present with severe motor deficits but differ fundamentally in etiology, temporal progression, consciousness level, and pupillary findings—key distinguishing features that guide immediate management.
| Feature | Central Pontine Myelinolysis (CPM) | Locked-In Syndrome | Botulism |
|---|---|---|---|
| Etiology | Osmotic demyelination from rapid correction of hyponatremia, occurring in alcoholics, malnourished patients, chronic liver disease, or hyperglycemic hyperosmolar syndrome [1,2] | Pontine infarction (most common), hemorrhage, trauma, or severe CPM causing ventral pontine damage [3] | Botulinum neurotoxin blocking acetylcholine release at neuromuscular junctions from foodborne, wound, or inhalational exposure [4,5] |
| Temporal Progression | Develops days to 1-2 weeks after rapid sodium correction (>10-12 mEq/L in 24 hours), with biphasic pattern: initial improvement then sudden deterioration [1,3] | Acute onset over hours (stroke) or subacute over days to weeks (progressive CPM) [3] | Progressive descending paralysis evolving over hours to a few days from initial visual symptoms to complete paralysis [4,5] |
| Consciousness | Variable: ranges from alert to coma depending on lesion extent; altered mental status common initially [1,6] | Fully preserved consciousness and cognition—patient is alert, aware, listening, and comprehending despite inability to respond [3] | Fully preserved consciousness throughout—patients are cognitively intact, alert, and can follow commands despite appearing comatose [4,5] |
| Pattern of Weakness | Spastic quadriparesis or quadriplegia with upper motor neuron signs; symmetric involvement [2,3] | Complete flaccid quadriplegia with bilateral facial paralysis; only vertical eye movements and blinking preserved [3,7] | Descending flaccid bilateral paralysis: cranial nerves first (ptosis, ophthalmoplegia, bulbar palsy), then respiratory muscles, then proximal before distal limb muscles [4,5] |
| Pupillary Response | Normal or variable depending on brainstem involvement [6] | Normal pupillary responses preserved [3] | Unreactive or dilated pupils expected (though reported in only 25% of confirmed cases); sluggish, poorly reactive, or fixed pupils are characteristic [4,5] |
| Cranial Nerve Findings | Pseudobulbar palsy, dysarthria, dysphagia may occur [2,7] | Bilateral facial paralysis, loss of horizontal eye movements, but vertical gaze and blinking intact [3] | Early prominent cranial nerve palsies: ptosis, ophthalmoplegia, diplopia, blurred vision, dysphagia, slurred speech, dry mouth [4,5] |
| Reflexes | Hyperreflexia with extensor plantar responses (upper motor neuron pattern) [2] | Variable depending on level of lesion [3] | Normal or diminished reflexes (lower motor neuron pattern) [8] |
| Sensory Examination | Typically intact [6] | Intact sensation [3] | Completely intact—no sensory symptoms or deficits [8] |
| Associated Symptoms | May have ataxia, tremor, myoclonus (rare), confusion, behavioral changes [7,6] | None beyond motor deficits [3] | Autonomic dysfunction: dry eyes, dry mouth (or copious secretions from dysphagia), urinary retention, constipation, ileus; gastrointestinal symptoms (nausea, vomiting) in 50% of foodborne cases [4] |
| Respiratory Failure | Can occur with extensive pontine involvement [1] | Common due to bilateral corticospinal tract involvement [3] | Occurs in 42-46% of patients, typically within first 2 hospital days; pharyngeal collapse may precede diaphragmatic weakness [8] |
| MRI Findings | Diagnostic: symmetric hyperintense signal on T2/FLAIR in central pons (sparing periphery), may show extrapontine lesions; appears 1-4 weeks after symptom onset [1,2,6] | Ventral pontine infarction or hemorrhage on acute imaging [3] | Normal brain imaging [5] |
| Diagnostic Testing | MRI brain (may be normal initially for 72 hours, then shows characteristic pontine lesion); serum sodium history showing rapid correction [1,3] | MRI/CT showing pontine stroke or severe demyelination [3] | Mouse bioassay (gold standard) for botulinum toxin in serum/stool; EMG showing facilitation with rapid repetitive stimulation; clinical diagnosis based on CDC criteria [4,5] |
| Specific Treatment | No specific treatment—supportive care only; prevention through slow sodium correction (<8 mEq/L per 24 hours) [2] | No specific treatment—supportive care, rehabilitation [3] | Immediate botulinum antitoxin (BAT) from CDC—prevents progression if given within 24-48 hours but cannot reverse existing paralysis [5,8] |
| Supportive Care | Intensive care with mechanical ventilation if needed, physical therapy, management of spasticity [2] | Prolonged intensive care, establish communication system (eye blinks), aggressive rehabilitation for 2+ years [3] | Meticulous supportive care: mechanical ventilation (often for weeks to months), establish communication system, prevent complications (UTI, DVT, pressure ulcers), treat dry eyes/mouth, provide psychological support, explain procedures before performing them [4,8] |
| Prognosis | Variable: ranges from complete recovery to locked-in syndrome to death; severity does not correlate with lesion size on MRI [6]; mortality greatly reduced with modern intensive care [2] | Poor for functional recovery; most remain severely disabled; gradual improvement possible over years with intensive rehabilitation [3] | Mortality decreased from 70% to <5% with modern intensive care; recovery takes weeks to months; antitoxin prevents progression but does not reverse paralysis [8] |
| Key Distinguishing Features | History of rapid sodium correction in at-risk patient (alcoholic, malnourished, liver disease); biphasic clinical course; MRI shows pontine lesion after 1-2 weeks [1,2,3] | Preserved vertical eye movements and blinking with complete quadriplegia; acute vascular event on imaging [3] | Descending paralysis pattern; unreactive pupils; preserved consciousness; normal brain imaging; exposure history (food, wound, injection drug use) [4,5,8] |
Critical Clinical Pitfalls to Avoid
Do not assume altered mental status excludes botulism—facial paralysis, ptosis, and inability to speak can make alert patients appear comatose; always assess cognition carefully 4, 5
Do not wait for MRI confirmation before treating suspected botulism—contact CDC immediately for botulinum antitoxin if clinical suspicion is medium to high, as laboratory confirmation takes days and delayed treatment worsens outcomes 4, 8
Do not dismiss CPM based on normal initial brain imaging—MRI may show no abnormalities for 72 hours after symptom onset, with characteristic pontine lesions appearing only after 1-4 weeks 1, 3
Recognize that botulism is frequently misdiagnosed as myasthenia gravis, Guillain-Barré syndrome, or stroke—the descending pattern, unreactive pupils, and preserved consciousness distinguish botulism 5, 8
Establish communication systems immediately for both botulism and locked-in syndrome patients, as they are cognitively intact despite appearing unresponsive; explain all procedures before performing them 4, 3