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    • One week after the CCRT she was

    2019-06-21

    One week after the CCRT, she was brought to our emergency department due to fever, severe general weakness, and severe oral pain. Her Sicca syndrome-related xerostomia had worsened due to radiotherapy and was complicated with severe stomatitis, which made oral intake difficult. She took traditional Chinese medicine for symptomatic treatment. On physical examination, severe oral ulcers with crust, dry mucosa, decreased skin turgor, and no abnormality of breath sound were found. On neurological examination, there was no abnormality of mental status, cognition, cranial nerves palsy, nor muscle power of the four limbs. The complete blood count (CBC) included a white blood count of 300/mm3 (reference range 3500–9100/mm3) (58.0% neutrophils, 12.0% lymphocytes, 26.0% monocytes, and 2.0% eosinophils), hemoglobin was 11.5 g/dL (reference range 12.0–15.0 g/dL), and platelet, 56000/microL (reference range 157000–377000/microL). The level of sodium was 103 mmol/L (reference range 136–144 mmol/L), and level of potassium, 2.2 mmol/L (reference range 3.6–5.1 mmol/L). The levels of blood glucose, liver function test, renal function and urinalysis were normal. Chest plain film revealed no significant infiltration of lungs. Empirical antibiotic with piperacillin/tazobactam 3375 mg every 6 h for neutropenic fever (ANC of 174 cells/micro L), 3% sodium chloride pump at the rate of 20 ml/h for severe hyponatremia and 60 mEq potassium chloride were infused on the first day at the emergency department. Rapid rise of serum sodium level from 103 mmol/L to 117 mmol/L in 12 h was noted by follow-up vascular disrupting agent examination, so 3% sodium was discontinued and 0.9% sodium chloride was infused instead. After admission to the ward, we continued the use of antibiotic with piperacillin/tazobactam and added antifungal agent with amphotericin B for neutropenic fever. We also administered parenteral nutrition supplement and corrected severe multiple electrolytes imbalance (hypokalemia, hypomagnesemia, hypocalcemia) (Fig. 2) over a period of time. No further fever was noted after admission. However, symptoms such as slurred speech, limbs weakness, and slow response were observed since the 3rd day of admission. Drowsiness, tetraplegia, dysphagia, and dysarthria became gradually obvious. Additionally, staring gaze, mutism, stridor, locked-in syndrome like, intermittent muscle spasm over limbs, spasticity of joints and foot drop developed as well. Central pontine and extrapontine myelinolysis were diagnosed by brain magnetic resonance imaging study (on the 12th day of admission). There was symmetrically increased T2 weighted signal intensity involving bilateral parietal cortex, basal ganglia, thalami, and a star shape lesion in pons; they also showed water restriction on diffusion weighted images (Fig. 1). Brain EEG showed near continuous diffuse (wave at frequency of 5–7 Hz, and 30–45 UV in amplitude) rhythmic theta activity alternating with suppressed background.
    Discussion A rapid correction of hyponatremia creates the hyperosmotic stress that causes endothelial injury and then promotes opening of the blood-brain barrier. This results in the direct release (from endothelial injury) of myelinotoxic or oligodendroglial destructive factors and blood derived myelinolytic factors. The central pons has the greatest degree admixture of gray and white matter of all areas of the brain, with the fact that gray matter contained 10-times more capillaries than white matter which was enriched with myelin. Hence, pons face is the greatest risk of demyelination. Unlike acute hyponatremia in which osmotic equilibrium is restored following rapid correction of hyponatremia, in chronic hyponatremia, cells lose organic osmolytes (including myo-inositol, taurine, glutamine, glutamate, creatinine, phosphocreatine, glycerophosphorylcholine), other than Na+, K+, Cl− ions. Following infusion of hypertonic saline, ions reaccumalated into cells quickly but organic osmolytes take about 5 days to do so. High cerebral ion concentration with low concentrations of organic osmolytes may have interfered normal protein structure and function.