A 43-year-old man with alcohol use disorder presented to the emergency department with abdominal distension and weight loss. Physical examination was notable for an abdominal fluid wave, pitting edema of both lower extremities, and spider angiomas on the upper chest and neck. Laboratory testing showed thrombocytopenia with a platelet count of 60 × 109/L (reference range 135–400), hypokalemia with a potassium level of 3.0 mmol/L (3.5–5.2), and hyponatremia with a sodium level of 109 mmol/L (136–145).
He was admitted to the intensive care unit, and hypertonic saline was started. The patient’s sodium level was 112 mmol/L after 24 hours and 120 mmol/L after 48 hours. He experienced agitation, which was attributed to alcohol withdrawal, and empiric lactulose was administered.
One week later, rhythmic movements of his extremities were observed. Electroencephalography showed cortical irritability in the right temporal region. Magnetic resonance imaging of the brain showed a “trident sign,” suggesting osmotic demyelination syndrome (Figure 1).
(A) There is a confluent trident-shaped lesion (arrow) in the central pons that is hyperintense on fluid-attenuated inversion recovery magnetic resonance imaging. (B) Additionally, the lesion (arrow) is hyperintense on diffusion-weighted imaging and (C) hypointense (arrow) on apparent diffusion coefficient imaging, consistent with restricted diffusion due to cytotoxic edema.
The patient’s seizures were controlled with the anticonvulsants levetiracetam, clobazam, and lacosamide. He was ultimately discharged to his home with rehabilitative services and medical therapy that included levetiracetam, lactulose, rifaximin, ciprofloxacin, and propranolol.
OSMOTIC DEMYELINATION SYNDROME
Osmotic demyelination syndrome describes the neurologic manifestations that may accompany sudden osmotic shifts in the brain, most commonly due to correction of chronic hyponatremia.1 Brain cells adapt to chronic hyponatremia by releasing electrolytes and organic osmolytes, causing water to move out of the cells and equalizing the solute concentration between the cell and the extracellular fluid.1 During correction of hyponatremia, osmolytes move into glia more slowly than electrolytes; rapid correction of hyponatremia creates an acute osmotic imbalance (rising sodium levels with lagging osmolar uptake) that results in myelin damage and cell death, classically in the pons.1
The presentation of osmotic demyelination syndrome is often biphasic. The initial encephalopathy that is related to severe hyponatremia improves with sodium correction, which is followed by neurologic deterioration up to 7 days later,1 as seen in our patient. Osmotic demyelination syndrome was once diagnosed by autopsy; however, magnetic resonance imaging has increased antemortem diagnosis and led to improved prognosis.2
Diagnostic clues
Diagnosis of osmotic demyelination syndrome relies on recognizing risk factors and typical imaging findings. Risk factors for osmotic demyelination syndrome include hypokalemia, chronic alcohol use disorder, malnutrition, and cirrhosis.1 Hypokalemia leads to downregulation of sodium-potassium adenosine triphosphatase, the enzyme that pumps sodium ions out of the cell and potassium ions in, so cells cannot readily respond to rapid sodium shifts. Alcohol use and malnutrition delay the regeneration of osmoles that the brain uses as buffers.1
Classic findings of osmotic demyelination syndrome on magnetic resonance imaging include confluent hypointensity on T1-weighted imaging, hyperintensity on T2-weighted imaging, and diffusion restriction within the central pons, in a trident configuration, sparing the periphery and corticospinal tracts.1,2 Changes in T1- and T2-weighted imaging can take 2 weeks to appear, but diffusion restriction may appear soon after clinical symptoms emerge.1 Magnetic resonance imaging findings may take weeks to improve but typically do not resolve.3
Cerebral spinal fluid, if obtained, is generally unremarkable.4
Differential diagnosis
The differential diagnosis in this patient included hepatic encephalopathy, posterior reversible encephalopathy syndrome, and Wernicke encephalopathy. Hepatic encephalopathy generally exhibits diffuse cerebral edema, sparing the perirolandic and occipital regions, and should improve with lactulose treatment. Posterior reversible encephalopathy syndrome is associated with blood pressure fluctuations (not prominent in this patient) and typically shows vasogenic edema in the parieto-occipital lobes or borderline zones and rarely involves the brainstem. Wernicke encephalopathy characteristically involves the mammillary bodies, dorsomedial thalami, quadrigeminal plate, periaqueductal gray matter, and hypothalamus, and presents with ophthalmoplegia and ataxia, which were not seen in our patient.5
There are radiographic mimics of osmotic demyelination syndrome that are also characterized by encephalopathy, seizures, and additional corticospinal or bulbar weakness. Restricted diffusion in acute pontine ischemia is typically unilateral rather than central. Demyelinating disease is usually also accompanied by demyelination in the posterior fossa and supratentorial brain regions. Brainstem encephalitis and tumors are typically expansile. Metabolic derangements usually also involve other regions of the brain.5
With no proven therapies, prevention is key
Guidelines recommend correcting serum sodium by less than 8 mmol/L in any 24-hour period in patients with risk factors for osmotic demyelination syndrome.6 Interestingly, osmotic demyelination syndrome is more correlated with the peak change in serum sodium and less with 24-hour changes.7
There are no proven therapies for osmotic demyelination syndrome; management includes supportive care and rehabilitation services. Favorable outcomes are reported in about half of patients, with many achieving full independence.2
DISCLOSURES
The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.
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