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  • Updated 05.08.2024
  • Released 04.14.2003
  • Expires For CME 05.08.2027

Osmotic demyelination syndromes



Spastic quadriparesis, pseudobulbar palsy, and pseudobulbar affect occurring several days following a rapid rise in serum osmolality are the classical signs of osmotic demyelination syndrome. The author reviews the classic clinical signs and pathophysiology of osmotic demyelination syndrome and includes updates from literature on methods of prevention and potential future treatment options for this infrequent but preventable iatrogenic disease.

Key points

• All patients with severe hyponatremia receiving intravenous fluids should have serum sodium measured every 4 hours to allow for adjustments in fluid and electrolyte administration if serum sodium should rise at a rate greater than 0.5 mEq/ml per hour.

• Use of desmopressin to limit water diuresis during correction of severe hyponatremia should be considered to prevent overcorrection.

• Vaptans are efficacious and safe in treating hypervolemic and normovolemic hyponatremia.

• Because patients with severe hyponatremia and concomitant hypokalemia are at greater risk of developing osmotic demyelination syndrome, a slower correction than 12 mEq/ml in a 24-hour period should be considered.

• Treatment of osmotic demyelination syndrome is mainly supportive; no large clinical trials have been performed to examine the efficacy of therapeutic relowering of serum sodium, steroids, plasma exchange, or IVIG.

Historical note and terminology

The factors that led to the appearance of osmotic demyelination syndrome during the 1950s were the introduction of diuretics, the liberal use of intravenous fluids, and the ability to rapidly measure serum electrolytes (151).

The original description of osmotic demyelination syndrome was by Raymond Adams (1911-2008), Maurice Victor (1920-2001), and Elliott Mancall (1927-2013) in 1959 (02). During their studies of the neuropathology of alcoholism, they recognized a peculiar and unique pattern of demyelination occurring in the central pons of four individuals with alcoholism and malnutrition. They labeled this disorder “central pontine myelinolysis.”

The initial suggestion that an “electrolyte imbalance may be a contributing factor” in the development of central pontine myelinolysis was made by Canadian neuropathologist Kenneth Berry (1932-2006) and Polish-Canadian neuropathologist Jerzy Olszewski (1913-1964) (22).

In 1969, American internist Alfredo Paguirigan and American neurologist Edward B Lefken noted that acute cases of central pontine myelinolysis only developed in hospitalized patients who were being hydrated (142).

American neuropathologists Kevin O Leslie and Michael D Norenberg, along with British-American neurologist Andrew S Robertson (106; 136) noted that in 12 cases of acute central pontine myelinolysis, there had been a recent rapid rise of serum sodium in each patient; they suggested that central pontine myelinolysis “is an iatrogenic disorder that in most cases is caused by a rapid correction of serum sodium rather than by hyponatremia per se.”

Subsequently, demyelination in other areas of the central nervous system associated with osmotic stress has been described (ie, extrapontine myelinolysis), encouraging the use of the more general term “osmotic demyelination syndrome” rather than the more restrictive term “central pontine myelinolysis” (151; 117). In addition, osmotic demyelination has been observed with other electrolyte disorders, including hypernatremia, hypokalemia, hypophosphatemia, and hyperammonemia, as well as the hyperosmolar hyperglycemic state.