Question 5.2

A 75-yr-old woman on Indapamide for Hypertension presented with seizures after a 7- day history of increasing lethargy. She was unwell, had dry mucus membranes and decreased skin turgor with a BP 88/50. Her serum sodium was 103 mmol/L.

By day 5 of her admission, the serum sodium has increased to 141 mmol/L. The antihypertensive therapy was adjusted and she was discharged home. Ten days after the initial presentation, she is readmitted with ataxia and confusion. On examination, the following findings were noted:

  • Afebrile GCS E4, M6, V4. 
  • No neck stiffness 
  • Tremor++, ataxia ++. 
  • Drooling of saliva + 
  • Brisk jaw jerk, bilaterally brisk reflexes, extensor plantar reflexes.
  • Full blood count: Nil significant 
  • LFT: normal. 

You are called to the ED to assess this patient as there are concerns that she might be an aspiration risk. 

a) List 2 likely differential diagnoses for her presentation. 
b) List 4 underlying predisposing conditions

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College Answer


Pontine demyelination is a differential given the recent history of rapid sodium replacement.

Brainstem stroke is an alternative explanation.


Patients at increased risk of osmotic demyelination:

  • Alcoholics
  • Malnourished patients
  • Hypokalemic patients
  • Burns patients
  • elderly women on thiazide therapy


Brainstem stoke? Really? But I suppose one must offer a differential.

A good article on pontine myelinolysis suggests that the pons is not unique and you can myelinolyse anywhere there is myelin. Typically, the early symptoms are dysartheria and dysphagia. They are followed by a flaccid quadriparesis.

The key issue is rate of correction. If the hyponatremia has lasted longer than 48 hours, we would be forced to call it "chronic". It takes brain cells about 48 hours to get rid of idiogenic osmoles and become isotonic with the hyponatremic extracellular fluid. However, once lost, those organic molecules take much longer to synthesise.

In short, your adaptation to hyponatremia is rapid, but your adaptation to a rising sodium is sluggish.

The result of bathing your neurons in a hypertonic solution is a shrinkage of those neurons. Water will easily cross the membrane into the hypertonic extracellular fluid, and the cells of the brain parenchyma will shrink and die.

The article mentioned above concludes with the sage advice that perhaps there is no such thing as a "maxiumum safe rate of replacement) but that most neurologists carry the figure of 10mmol/day in their head.

Risk factors for pontine myelinolysis?

Well. The first study (1959) which described this syndrome found it among alcoholic and malnourished patients. Later works extended the range of risk factors. In summary, they are as follows:

  • Alcoholism
  • Malnutrition
  • Other electrolyte disturbances (esp. hypokalemia)
  • Use of diuretics
  • Liver transplantation


R J Martin Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes J Neurol Neurosurg Psychiatry 2004;75:iii22-iii28 doi:10.1136/jnnp.2004.045906

For all electrolyte abnormality questions, I refer to the Electrolyte Quintet series from the Lancet. In the sodium article by Kumar, there is a table (Panel 2) from which the college answer seems to be derived (with a couple of changes). I have used that panel as my model answer.

Sumit Kumar, Tomas Berl. Sodium.  The LancetVolume 352, Issue 912318 July 1998Pages 220-228

Laureno, Robert, and Barbara Illowsky Karp. "Myelinolysis after correction of hyponatremia." Annals of Internal Medicine 126.1 (1997): 57-62.

Lee, Eun Mi, et al. "Risk factors for central pontine and extrapontine myelinolysis following orthotopic liver transplantation." European neurology 62.6 (2009): 362-368.

Adams, Raymond D., MAURICE VICTOR, and ELLIOTT L. MANCALL. "Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients." AMA Archives of Neurology & Psychiatry 81.2 (1959): 154-172.

Brown, William D. "Osmotic demyelination disorders: central pontine and extrapontine myelinolysis." Current opinion in neurology 13.6 (2000): 691-697.

Harris, Cheryl P., J. J. Townsend, and J. Richard Baringer. "Symptomatic hyponatraemia: can myelinolysis be prevented by treatment?." Journal of Neurology, Neurosurgery & Psychiatry 56.6 (1993): 626-632.