Osmotic Demyelination Syndrome

Osmotic demyelination syndrome is a non-inflammatory demyelinating disorder of the pons (central pontine myelinolysis) and extrapontine regions, caused by rapid shifts in serum osmolality, most often over rapid correction of hyponatraemia. It causes quadriparesis, dysarthria, dysphagia and, in severe cases, the locked in syndrome.

It is rare, and it occurs in about 0.5 to 2% of patients with severe hyponatraemia who are over corrected. Alcohol use disorder, malnutrition, liver transplantation and hypokalaemia increase risk.

Risk factors. Serum sodium under 105 mmol/L, chronic hyponatraemia for over 48 hours, increase in sodium of more than 8 to 10 mmol/L in 24 hours, alcohol use disorder, malnutrition, liver disease, hypokalaemia and use of thiazide diuretics.

Timing. Symptoms appear 2 to 6 days after correction, often after initial improvement (a biphasic course).

Pathophysiology.

Rapid rise in extracellular tonicity shrinks brain cells that have lost osmolytes to adapt to chronic hyponatraemia, and they cannot recover osmolytes fast enough.

Endothelial injury, breakdown of the blood brain barrier and oligodendrocyte apoptosis cause demyelination, most in areas with a high ratio of grey to white matter in the pons.

• Initial improvement of encephalopathy after sodium correction, then deterioration after 2 to 6 days.
• Dysarthria, dysphagia, flaccid then spastic quadriparesis, pseudobulbar palsy and ataxia.
• Locked in syndrome in severe disease, with preserved vertical eye movements and blinking.
• Extrapontine features: parkinsonism, dystonia, tremor, catatonia, behavioural and mood change.
• Altered consciousness, seizures or coma in some.

Red flags.

• Over rapid sodium rise in any patient (more than 8 mmol/L in 24 hours).
• New dysphagia, quadriparesis or reduced consciousness after correction.
• Seizures or respiratory failure.

• Clinical diagnosis from the history of hyponatraemia and rapid correction with the latent interval and typical syndrome.
• MRI of the brain: T2 and FLAIR hyperintensity in the central pons (the "trident" or "piglet" sign) and extrapontine regions, with diffusion restriction early; MRI may be normal in the first 1 to 2 weeks and should be repeated.
• Serial serum sodium, potassium, osmolality, urine sodium and osmolality; liver, renal and thyroid function; glucose.
• Exclude stroke, Wernicke encephalopathy, hepatic encephalopathy and demyelinating diseases.

Differential diagnosis. Basilar artery occlusion and pontine infarction, Wernicke encephalopathy, multiple sclerosis, pontine glioma, hepatic encephalopathy, Guillain-Barré syndrome with brainstem involvement and Bickerstaff encephalitis.

• Prevention is the main treatment. Correct chronic hyponatraemia slowly: aim for a rise of 4 to 6 mmol/L in 24 hours, with a limit of 8 mmol/L in 24 hours in those at high risk (limit 10 to 12 mmol/L in 24 hours in others), and check sodium every 2 hours initially.
• Severe symptoms (seizure, coma): 3% sodium chloride 150 mL intravenously over 20 minutes, repeated once or twice to raise sodium by 5 mmol/L, then stop. Maximum 3 doses. Monitor sodium every 20 minutes to 2 hours, urine output, and neurological state. Avoid fluid overload in heart failure and renal impairment.
• Over correction (rise of more than 8 mmol/L in 24 hours, or urine output over 100 mL/hour): relower sodium with desmopressin 2 micrograms intravenously every 8 hours together with 5% glucose 3 mL/kg intravenously over 1 hour, repeated as needed. Maximum 8 micrograms in 24 hours. Monitor sodium hourly, glucose and urine output. Avoid in fluid overload and with severe hypernatraemia; use caution in heart failure.
• Correct potassium deficiency, and give thiamine 200 to 500 mg intravenously every 8 hours for 3 to 5 days in patients with alcohol use disorder or malnutrition. Maximum 1500 mg daily. Monitor for anaphylaxis and give with resuscitation facilities available.
• Supportive care in intensive care: airway protection, nutrition, swallowing management and ventilation.
• Immunoglobulin, corticosteroids and plasma exchange are used in some case reports, but benefit is unproven.
• Rehabilitation: physiotherapy, speech therapy and occupational therapy.

Monitoring. Sodium every 2 hours during correction, then daily; neurological checks; repeat MRI at 2 weeks if the first scan is normal; review at 1, 3 and 6 months.

Referral and escalation. Intensive care and nephrology or endocrinology; neurology; neurorehabilitation.

Special groups. Alcohol use disorder, malnutrition and liver disease: lower correction targets (6 mmol/L in 24 hours). Women and older adults: higher risk during correction.