Discharges With Triphasic Morphology as Marker of the Risk of Death in Acute Encephalopathy.

Introduction. In clinical practice, it is difficult to define the prognosis of patients with acute encephalopathy; a syndrome characterized by cognitive dysfunction and altered sensorium. Discharges with triphasic morphology (DTM) are an electroencephalographic pattern that might be useful to establish the risk of death. The aim of this study was to define the prognostic value of DTM regarding mortality in patients with acute encephalopathy. Methods. We conducted an observational retrospective cohort study including patients with acute encephalopathy with and without DTM paired by age and gender in a 1:2 ratio. We calculated the odds ratio (OR) to determine the association between DTM and mortality. In addition, we calculated sensibility, specificity, and predictive values. Results. We included 72 patients, 24 with DTM and 48 without DTM. Mortality was higher in patients with DTM (41.6% vs 14.5%, P = .01). Factors associated with a higher risk of death were DTM (OR = 4.1, 95% confidence interval [CI] 1.3-13, P = .01) and sequential organ failure assessment score (OR = 1.3, 95% CI 1.04-1.67, P = .02). A higher Glasgow coma scale score was associated with a lower risk of death (OR = 0.65, 95% CI 0.51-0.83, P = .001). The sensibility and specificity of DTM were 59% and 75%, respectively. Positive and negative likelihood ratios were 2.36 and 0.55. Discussion. Our results revealed high mortality in patients with acute encephalopathy and DTM. This electroencephalographic pattern was associated with 4 times higher risk of death. However, its usefulness for predicting death was limited.

Identification of a somatic mutation in the RHEB gene through high depth and ultra-high depth next generation sequencing in a patient with Hemimegalencephaly and drug resistant Epilepsy.

Malformations of cortical development are a frequent cause of drug-resistant Epilepsy and developmental delay. Hemimegalencephaly is a Malformation of cortical development characterized by enlargement of all or a part of one cerebral hemisphere. Germline and somatic mutation in genes belonging to the Mammalian Target of Rapamycin (mTOR) pathway has been identified in patients suffering from epilepsy secondary to Hemimegalencephaly and focal cortical dysplasia. We present here a patient suffering from severe neonatal Epilepsy since 3 h of life secondary to Hemimegalencephaly, requiring an anatomic hemispherectomy surgical procedure for seizure control, where by means of next-generation sequencing at an ultra-high depth coverage, we were able to identify a novel somatic mutation in the RHEB gene (NM_005614: c.119A > T: p. Glu40Val). The histopathological diagnosis was Cortical Dysplasia type IIB determined by the presence of dysmorphic neurons of variable size with nuclear alteration and balloon cells in the context of Hemimegalencephaly, which are similar to that have been demonstrated in hyperactivating RHEB models. This is the first report of a somatic mutation in RHEB gene in a patient suffering from Epilepsy secondary to Hemimegalencephaly. It highlights different current topics in the fields of genetics of Malformations of cortical development: a-somatic mosaicism is not uncommon in these neurodevelopmental disorders; b-the molecular diagnostic approach should involve the use of state-of-the-art methods and the sampling of different tissues; c-new findings might facilitate therapeutics discoveries while providing an improved understanding of normal brain development.