Osmotic Demyelination Syndrome

Aka: Osmotic Demyelination Syndrome, Cerebral Demyelination Syndrome, Central Pontine Myelinolysis

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II. Incidence

  1. Rare Incidence: <0.05% (0.5% of neurology admissions)

III. Pathophysiology

  1. CNS cells are unable to freely move Sodium across cell membranes
    1. CNS Cells (esp. oligodendrocytes) are uniquely sensitive to shifts in plasma Sodium
      1. Oligodendrocytes are concentrated in the Pons, but are found throughout the CNS
    2. Rapid Serum Sodium drops result in brain cell swelling
    3. Rapid rise in Serum Sodium results in brain cell dessication
  2. Potentially lethal Cerebral edema from rapid Electrolyte correction
    1. Over-correction of Serum Sodium when <125 mEq/L
    2. Too rapid correction of Serum Sodium (>0.5 mEq/hour)
  3. Related to chronicity of Electrolyte disturbance
    1. Associated with rapid Sodium correction in chronic Hyponatremia (present >48 hours)
      1. Do not replace Serum Sodium more than 8 mEg/L per 24 hours
    2. Not associated with correction of acute Hyponatremia (esp. <24 hours)
      1. Severe symptomatic Hyponatremia (esp. <120 mEq/L) requires rapid Sodium replacement

IV. Risk Factors

  1. Chronic Hyponatremia (present >48 hours)
  2. Serum Sodium <105 mEq/L (severe Hyponatremia)
  3. Severe Malnutrition (cancer, elderly)
  4. Alcohol Use Disorder
  5. Comorbid Hypokalemia
  6. Hyperemsis Gravidarum

V. Findings

  1. Symptoms onset may be delayed as much as 7 days after rapid Sodium shift
  2. Altered Mental Status
  3. Severe Muscle Weakness (quadriparesis)
  4. Dysphagia
  5. Dysarthria
  6. Coma or Locked-In Syndrome in severe cases

VI. Prognosis

  1. Full recovery may occur in up to 60% of patients
  2. Severe Disability or death in 33-55% in some studies

VII. Prevention

  1. Chronic Hyponatremia and other risk factors above are higher risk for Osmotic Demyelination Syndrome
    1. Slow Sodium correction rates are important for prevention
    2. In chronic Hyponatremia, do not correct Sodium >0.5 mEq/h or >8 mEq/day
    3. Some recommend limiting daily maximum correction to 6 mEq/day
  2. Acute Hyponatremia (<48 hours) has pardoxically higher mortality with very low correction rates (<6 mEq/day)
    1. In contrast, faster correction (>10 mEq) were associated with lower mortality
    2. Ayus (2025) JAMA Intern Med 185(1):38-51 +PMID: 39556338 [PubMed]
    3. MacMillan (2023) NEJM Evid 2(4):EVIDoa2200215 +PMID: 38320046 [PubMed]
    4. Seethapathy (2023) NEJM Evid 2(10):EVIDoa2300107 +PMID: 38320180 [PubMed]
  3. Recognize overcorrection early and manage aggressively
    1. Stop Sodium replacement
    2. Reverse Sodium overcorrection
      1. Replace urinary water loss with free water orally (or D5W at 3 ml/kg/hour) OR
      2. Desmopressin 2 to 4 mcg IV every 8 hours

VIII. References

  1. Swaminathan and Willis (2026) Hyponatremia Management, EM:Rap, 4/20/2025
  2. Le and Drogell (2015) Crit Dec Emerg Med 29(11): 13-19
  3. Miller (2023) Am Fam Physician 108(5): 476-86 [PubMed]

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