Yep, it usually looks as cookie cutter as that. Right smack in the middle of the pons. But not always…
Osmotic demyelination syndrome, previously known as central pontine myelinolysis, is a rare but terrifying condition of the central nervous system where susceptible regions of brain tissue are stressed to the point of nearly irreversible injury. Half the time this occurs in the pons, hence the term central pontine myelinolysis, but there is some substantial overlap with sites of extrapontine myelinolysis. Today, on BrainWaves, we will be talking with Dr. Joshua VanDerWerf, from our prior episode on the History of American Neurology, about this unusual clinical condition.
Clinically, ODS is described as the progression of initially flaccid quadriparesis, dysarthria, dysphagia, pseudobulbar affect, and possibly coma or locked-in syndrome over the course of several hours to days. All of these features are attributable to the pontine location of injury. In cases with extrapontine involvement, it is recognized that patients may have prominent movement disorders such as parkinsonism or dystonia, as well as neurobehavioral symptoms including anything from akinetic mutism and catatonia to severe agitation. Essentially, if a chronically ill patient develops these features or if you are unable to otherwise explain lack of expected improvement in a patient after critical illness, ODS should be something clinicians keep on the differential.
We used to think of this as a disease afflicting alcoholics and malnourished patients. With the flurry of reports in the following decades it was recognized that electrolyte disturbances, and mainly hyponatremia, seemed to be associated with ODS. In the 1980s, animal studies confirmed that the
rapid correction of chronic hyponatremia, and not the hyponatremia itself, causes ODS. The thought is that the stress of rapid shifts in osmolality, in the setting of a chronically hypo-osmolar state, can lead to the death of oligodendrocytes, and therefore the loss of myelin in certain brain regions. Because of this, in chronic hyponatremia (>48hrs duration) clinicians should not raise the serum sodium level by more than 1-2mmol/L/hr or >8mmol/L/day. Keep in mind however, that these values are based solely on animal models and clinical experience. Many experts maintain that there may be no absolutely “safe” rate of sodium correction in chronic hyponatremia. However, in acute hyponatremia (<48hrs duration), it is safe to rapidly correct sodium levels, with the use of hypertonic saline if necessary. The caveat being, that if there is any doubt as to the chronicity of a patient’s hyponatremia, one should proceed with caution, and correct slowly.
Besides chronic alcoholism and primary electrolyte disturbances, other causes of ODS include liver transplantation, burns, malignancy, pulmonary infections, acute brain injury, DKA and HHS, hemodialysis, and AIDS. What’s even more interesting is that there are several reported cases of ODS occurring without hyponatremia–which Josh and I wrote about last year in Neurovirology. Although the key driver of osmotic stress is often related to sodium derangements, there are several other potentials causes of osmotic shifts.
So there’s a lot more to it than rapid correction of hyponatremia and pontine demyelination. Even though this probably accounts for the majority of the cases you’ll see. Check out the episode for more information about this mysterious process and the theories behind the demyelination.
The content in this episode was vetted and approved by Joshua Levine.
- Adams RA, Victor M, Mancall EL. Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholics and malnourished patients. Arch Neurol Psychiatry 1959;81:154–72.
- Gocht A, Colmant HJ. Central pontine and extrapontine myelinolysis: a report of 58 cases. Clin Neuropathol. 1987 Nov-Dec;6(6):262-70.
- Kleinschmidt-Demasters BK, Rojiani AM, Filley CM. Central and extrapontine myelinolysis: then…and now. J Neuropathol Exp Neurol. 2006 Jan;65(1):1-11.
- Martin RJ. Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes. J Neurol Neurosurg Psychiatry. 2004;75 Suppl 3:iii22-8.
- Menger H, Jorg J. Outcome of central pontine and extrapontine myelinolysis. J Neurol 1999;246:700–5.
- Siegler JE, Wang AR, Vanderwerf JD. Normonatremic osmotic demyelination in the setting of acquired immune deficiency syndrome and malnutrition: case report and literature review. J Neurovirol. 2016 Jul 12.
- Wright DG, Laureno R, Victor M. Pontine and extrapontine myelinolysis. Brain. 1979 Jun;102(2):361-85.