Critical Care Medicine-Neurologic Disorders>>>>>Inflammatory and Demyelinating
Question 3#

A homeless 35-year-old alcoholic male with a body mass index of 18 kg/m2 is admitted for seizures, encephalopathy, and dysarthria. On presentation, he had a serum sodium of 108 mmol/L, potassium 2.4 mmol/L, chloride 98 mmol/L, alanine aminotransferase 356 IU/L, aspartate aminotransferase 450 IU/L, and gamma-glutamyl transpeptidase 1200 IU/L. He was started on lactulose, thiamine replacement, and saline infusions. CT scan of brain was unremarkable. He recovered within 36 hours, coincident with a sodium correction to 130 mmol/L. The patient then deteriorated on day 6 to a catatonic state with flaccid paralysis of all extremities.

Which of the following MOST LIKELY caused his deterioration?

a. Administration of thiamine before glucose
b. Nonconvulsive status epilepticus
c. Aggressive nutritional support and elevated phosphate
d. Saline infusion

Correct Answer is D

Comment:

Correct Answer: D

Rapid correction of serum sodium with saline infusions (or hypertonic saline) in patients with chronic hyponatremia can cause central pontine myelinolysis (CPM) or osmotic demyelination syndrome. CPM was originally described in 1959 as a disease associated with malnourished alcoholics. Extrapontine myelinolysis was recognized in 1962, and the link with rapid correction of hyponatremic patients was found in 1982. It remains a rare disease with a biphasic presentation. Patients typically are encephalopathic or seizing upon presentation. Laboratory testing usually reveals profound hyponatremia (Na <120 mmol/L). The rapidity of sodium correction is thought to cause the damage to the myelin sheath. There is an initial period of symptom improvement before deterioration which may include corticobulbar fiber involvement (dysarthria and dysphagia), corticospinal tract involvement (flaccid quadriparesis followed by spasticity), and pupillary or oculomotor changes from tegmentum/pontine extension. The appearance of “locked-in syndrome” may also occur. Extrapontine involvement may be characterized by psychiatric, behavioral, parkinsonism, dystonia, catatonia, mutism, and movement disorders. There is no absolute “safe” limit for rate of sodium correction. A 10 mmol/L rise per 24 hours was previously recommended; however, now experts recommend a correction rate of <8 mmol/L per 24 hours. Clinical improvement or stability should not be considered evidence that sodium correction has not occurred too rapidly. Clinical symptoms of CPM, which are usually irreversible, most commonly occur 2 to 6 days following rapid sodium correction. 

Hypophosphatemia rather than hyperphosphatemia is the hallmark and primary etiology of refeeding syndrome that can occur in severely malnourished patients following initiation of nutritional support. Refeeding syndrome most commonly involves multiorgan dysfunction and can result in neurologic symptoms due to electrolyte abnormalities and fluid shifts. Thiamine deficiency can result in a Wernicke encephalopathy and is associated with chronic alcoholics. Clinical manifestations include encephalopathy, ataxia, and oculomotor deficits.

References:

  1. Martin RJ. Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes. J Neurol Neurosurg Psychiatry. 2004;75(suppl 3):iii22-iii28.
  2. Jonathan Graff-Radford JEF, Kaufmann TJ, Mandrekar JN, Rabinstein AA. Clinical and radiologic correlations of central pontine myelinolysis syndrome. Mayo Clin Proc. 2011;86:1063-1067.
  3. Gautam D, Khan SA. Current concepts in pontine myelinolysis: review of literature. Transl Biomed. 2015;4.
  4. Dhrolia MF, Akhtar SF, Ahmed E, Naqvi A, Rizvi A. Azotemia protects the brain from osmotic demyelination on rapid correction of hyponatremia. Saudi J Kidney Dis Transpl. 2014;25:558-566.