An Italian family affected by Nasu-Hakola disease with a novel genetic mutation in the TREM2 gene

Abstract

LETTERS Central pontine myelinolysis temporally related to hypophosphataemia Central pontine myelinolysis (CPM) is known to be associated with the rapid correction of severe hyponatraemia. However, there have been case reports of CPM occurring in normonatraemic patients. 1 Here we describe two patients in whom chronic alcohol abuse led to profound hypophosphataemia that was closely temporally related to the development of CPM. Case 1 A 29 year old woman was admitted for investigation of painless jaundice of 10 days' duration. She had consumed 100-140 units of alcohol a week for the preceding 18 months and had been noted to have mildly deranged serum transaminase levels one year previously. On admission she was fully oriented with normal speech and gait. She had a mild postural tremor but no asterixis. A plasma biochemical profile showed her sodium to be 122 mmol/l, potassium 2.1 mmol/l, and urea 5.9 mmol/l. Serum creatinine was 182 µmol/l, phosphate 0.65 mmol/l, magnesium 0.59 mmol/l, and total corrected calcium 2.18 mmol/l. She was immediately given potassium and magnesium supplements, chlo-rdiazepoxide, and intravenous vitamins including vitamin K and thiamine. Three days after admission she developed a Staph aureus septicaemia secondary to a peripheral venous cannula infection. This required treatment with intravenous cefuro-xime and flucloxacillin. She subsequently became drowsy and by day 10 had developed a severe spastic dysarthria and profound spastic tetraparesis. There was a bilateral lower motor neurone pattern of facial weakness and gaze evoked nystagmus. The clinical suspicion of CPM was supported by magnetic resonance imaging of the brain, which showed symmetrical signal hyperintensity in the pons on T2 weighted images, as well as generalised cerebral atrophy. A review of the biochemistry results during her admission showed that the maximum increase in serum sodium concentration over a 24 hour period was only 7 mmol/l (from 123 to 130 mmol/l). Potassium and magnesium concentrations were corrected to the lower end of their normal ranges. However, she developed profound hypophosphataemia (0.16 mmol/l at nadir) which was rapidly corrected to 0.8 mmol/l within 72 hours. The rapid rise in plasma phosphate coincided with the onset of the patient's neurological deterioration. With supportive care she made a gradual recovery such that two months after admission she was safe to be discharged, with only a mild residual left hemiparesis and slight spastic dysarthria, which were improving. Case 2 A 44 year old woman was admitted with a three day history of progressive dysarthria, seven days of difficulty in walking, and dysaesthesia affecting all four limbs and the perioral region. She had consumed at least 80 units of alcohol a week for several months before presentation. Examination on admission revealed a mild tetraparesis, dysarthria, and subjective sensory loss in both legs and the left arm. Her admission blood profile revealed a plasma sodium concentration of 136 mmol/l and potassium of 3.4 mmol/l. The serum phosphate concentration was profoundly low at 0.13 mmol/l. T2 weighted and FLAIR sequence MRI done three days after admission showed abnormal signal within the central brain stem suggestive of CPM (fig 1). She was treated with oral thiamine, multi-vitamins, and minerals including phosphate. She made a rapid improvement such that her dysarthria had resolved and gait improved sufficiently for her to be discharged 11 days after admission. Comment