FXTAS: new insights and the need for revised diagnostic criteria.

OBJECTIVE: Fragile X-associated tremor ataxia syndrome (FXTAS) is defined by FMR1 premutation, cerebellar ataxia, intentional tremor, and middle cerebellar peduncle (MCP) hyperintensities. We delineate the clinical, neurophysiologic, and morphologic characteristics of FXTAS. METHODS: Clinical, morphologic (brain MRI, (123)I-ioflupane SPECT), and neurophysiologic (tremor recording, nerve conduction studies) study in 22 patients with FXTAS, including 4 women. RESULTS: A total of 43% of patients had no family history of fragile X syndrome (FXS), which contrasts with previous FXTAS series. A total of 86% of patients had tremor and 81% peripheral neuropathy. We identified 3 electroclinical tremor patterns: essential-like (35%), cerebellar (29%), and parkinsonian (12%). Two electrophysiologic patterns evocative of non-length-dependent (56%) and length-dependent sensory neuropathy (25%) were identified. Corpus callosum splenium (CCS) hyperintensity was as frequent (68%) as MCP hyperintensities (64%). Sixty percent of patients had parkinsonism and 47% abnormal (123)I-ioflupane SPECT. Unified Parkinson's Disease Rating Scale motor score was correlated to abnormal (123)I-ioflupane SPECT (p = 0.02) and to CGG repeat number (p = 0.0004). Scale for the assessment and rating of ataxia correlated with dentate nuclei hyperintensities (p = 0.03) and CCS hyperintensity was a marker of severe disease progression (p = 0.04). CONCLUSIONS: We recommend to include in the FXTAS testing guidelines both CCS hyperintensity and peripheral neuropathy and to consider them as new major radiologic and minor clinical criterion, respectively, for the diagnosis of FXTAS. FXTAS should also be considered in women or when tremor, MCP hyperintensities, or family history of FXS are lacking. Our study broadens the spectrum of tremor, peripheral neuropathy, and MRI abnormalities in FXTAS, hence revealing the need for revised criteria.

A possible hypophosphatemia-induced, life-threatening encephalopathy in diabetic ketoacidosis: a case report.

Hypophosphatemia, a common metabolic disorder, is usually silent and diagnosed by blood tests. However, misdiagnosis may result in delayed phosphate repletion, responsible for significant morbidity and potential mortality. We report an exceptional case of hypophosphatemia-related, life-threatening encephalopathy. A 49-year-old type-1 diabetic woman was admitted to our intensive care unit with coma and severe ketoacidosis. Initial neurologic impairment worsened despite improvement in acid-base disturbances and glucose levels. The electroencephalogram showed bilateral spikes with a background theta wave rhythm. Profound hypophosphatemia <0.20 mmol/L (<0.6 mg/dL) was diagnosed. No other cause of encephalopathy was found. Prompt phosphate repletion resulted in progressive and complete recovery. This observation allowed us to study the relations between the coma depth, the electroencephalographic findings, and the serum phosphate concentrations. Our data strongly suggest that phosphate depletion-induced encephalopathy probably originates from direct impairment of cerebral electrophysiological activity rather than from cardiac flow alteration.