Osmotic demyelination syndrome after bone marrow transplantation

1Nephrology and Kidney Transplantation Ward, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran 2Hematology, Oncology Research Center and Stem Cell Transplantation (HORCST), Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran 3Endocrinology and Metabolism Research Institute (EMRI), Tehran University of Medical Sciences, Tehran, Iran #Equally contributed as first authors.


Introduction
Hyponatremia is one of the most common electrolyte abnormalities in patients referred to the hospital. Clinical symptoms and signs of hyponatremia depend on the severity of hyponatremia (1)(2)(3). Hyponatremia commonly indicates weakness, nausea, headache, muscle cramps, cognitive disorders, confusion, lethargy, seizure, and coma (1,(4)(5)(6). Focal neurologic signs are scarce (6). The approach to first therapy of hyponatremic patients depends upon hyponatremia severity, the presence, and severity of symptoms, the presence of preexisting intracranial pathology, and the prevention of quick correction of hyponatremia (7)(8)(9). A 14-year-old boy with the past-medical history of common variable immunodeficiency (CVID), ulcerative colitis, and lichen planus was referred to the emergency department with loss of consciousness and seizure two hours ago. Considering CVID about 6 weeks ago, he had undergone bone marrow transplantation (BMT). He took some medications, involving cyclosporine, acyclovir, risperidone, citalopram, mesalamine, voriconazole, and prednisolone.
Lumbar puncture was handled and the results of cerebrospinal fluid (CSF) were normal.
A spiral brain computerized tomography (CT) scan (without contrast) and magnetic resonance imaging (MRI) was done and found normal. MRI repeated 2 weeks later, and T2-weighted image indicated the bilateral symmetric hyperintense lesions in basal ganglia ( Figure 1). His neurologic abnormalities in MRI relatively recovered about two months later (Figure 2).
The existence of concomitant metabolic derangements,   involving hypoglycemia, hypokalemia, hypophosphatemia, and hypomagnesemia may disrupt the normal activity of active transport pumps at the cell membrane included in the regulation of intracellular osmolarity, restricting the ability of brain to respond to osmotic stress (17). Moreover, the correction of hypokalemia or other metabolic disorders may cause a quick increase in serum Na through cellular Na + /K + exchange and other mechanisms. Serum Na must be closely controlled when correcting these abnormalities (17)(18)(19).
Moreover, low pre-transplant serum cholesterol was associated with ODS in post liver transplantation. It may show the malnutrition or increase the susceptibility to calcineurin inhibitor toxicity in the post-liver transplantation which was associated with ODS in case reports (11,16,19,20) ODS's clinical manifestations are typically delayed for two to six days after the rapid elevation of the serum sodium concentration has occurred (9,10). The symptoms involve dysarthria, dysphagia, paraparesis or quadriparesis, behavioral disturbances, movement disorders, seizures, lethargy, confusion, disorientation, obtundation (10,11).
Strictly influenced the patients may become "locked in"; they are awake, but cannot move or verbally communicate. They can commonly move their eyes and blink (10,12).
In patients with pontine involvement, speech abnormalities early occur and persist, and patients often become mute. Corticospinal signs (hyperreflexia and bilateral Babinski signs) and corticobulbar signs (brisk jaw jerk) are usual. Swallowing dysfunction may result in the aspiration pneumonia and respiratory failure (9,11).
Other usual physical findings involve increased muscle tone, facial weakness, and snout, grasp, or rooting reflexes. Extra-pontine involvement can lead to various findings, involving the psychiatric disturbances, catatonia, postural limb tremor, myoclonic jerks, and a parkinsonian picture with choreoathetosis or dystonia, which responds to the dopaminergic treatment (10)(11)(12)(13).

Conclusion
Considering the severity, permanent adverse consequences, and high mortality rate of ODS, the inhibition is necessary. Among the patients with hyponatremia more than two days or with hyponatremia of unknown duration, we proposed that the serum sodium must not increase 6 to 8 mEq/L in any 24-hour period to inhibit ODS. ODS risk is highest in the patients with serum sodium of ≤120 mEq/L, especially if hyponatremia is associated with hypokalemia, low-plasma osmolality, and other electrolyte disorders.

Authors' contribution
Initial draft and data gathering was handled by Farnoosh Tavakoli. Fatemeh Yaghoubi and Davood Babakhani presented the case and contributed to case discussion and figures. Manuscript was edited by Farnaz Tavakoli. All authors read and signed the final version.