Summary Objective GABRA1 mutations have been identified in patients with familial juvenile myoclonic epilepsy, sporadic childhood absence epilepsy, and idiopathic familial generalized epilepsy. In addition, de novo GABRA1 mutations were recently reported in a patient with infantile spasms and four patients with Dravet syndrome. Those reports suggest that GABRA1 mutations are associated with infantile epilepsy including early onset epileptic encephalopathies. In this study, we searched for GABRA1 mutations in patients with infantile epilepsy to investigate the phenotypic spectrum of GABRA1 mutations. Methods In total, 526 and 145 patients with infantile epilepsy were analyzed by whole‐exome sequencing and GABRA1‐targeted resequencing, respectively. Results We identified five de novo missense GABRA1 mutations in six unrelated patients. A p.R112Q mutation in the long extracellular N‐terminus was identified in a patient with infantile epilepsy; p.P260L, p.M263T, and p.M263I in transmembrane spanning domain 1 (TM1) were identified in three unrelated patients with West syndrome and a patient with Ohtahara syndrome, respectively; and p.V287L in TM2 was identified in a patient with unclassified early onset epileptic encephalopathy. Four of these mutations have not been observed previously. Significance Our study suggests that de novo GABRA1 mutations can cause early onset epileptic encephalopathies, including Ohtahara syndrome and West syndrome.

Purpose: Intratumoral metabolism and synthesis of estrogens are considered to play important roles in the pathogenesis and/or development of human endometrial carcinoma. Steroid sulfatase hydrolyzes biologically inactive estrogen sulfates to active estrogens, whereas estrogen sulfotransferase sulfonates estrogens to estrogen sulfates. However, the status of steroid sulfatase and/or estrogen sulfotransferase in human endometrial carcinoma has not been examined.Experimental Design: We first examined the expression of steroid sulfatase and estrogen sulfotransferase in 6 normal endometrium and 76 endometrial carcinoma using immunohistochemistry to elucidate the possible involvement of steroid sulfatase and estrogen sulfotransferase. We then evaluated the enzymatic activity and the semiquantitative analysis of mRNA using reverse transcription-PCR in 21 endometrial carcinomas. We correlated these findings with various clinicopathological parameters including the expression of aromatase, 17␤-hydroxysteroid dehydrogenase type 1 and type 2.Results: Steroid sulfatase and estrogen sulfotransferase immunoreactivity was detected in 65 of 76 (86%) and 22 of 76 (29%) cases, respectively. Results of immunoreactivity for steroid sulfatase and estrogen sulfotransferase were significantly correlated with those of enzymatic activity and semiquantitative analysis of mRNA. No significant correlations were detected among the expression of the enzymes involved in intratumoral estrogen metabolism. There was a significant correlation between steroid sulfatase/estrogen sulfotransferase ratio and clinical outcomes of the patients. However, there were no significant differences between steroid sulfatase or estrogen sulfotransferase and estrogen receptor, progesterone receptor, Ki67, histologic grade, or clinical outcomes of the patients.Conclusions: Results of our study demonstrated that increased steroid sulfatase and decreased estrogen sulfotransferase expression in human endometrial carcinomas may result in increased availability of biologically active estrogens and may be related to estrogen-dependent biological features of carcinoma.

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Summary:Purpose: To investigate spatial and temporal cortical activity during clusters of naturally occurring epileptic spasms in patients with West syndrome (WS) by using multichannel near-infrared spectroscopy (mNIRS).Methods: Conventional magnetic resonance imaging (MRI) and interictal and ictal single-photon emission computed tomography (SPECT) were carried out in three patients with WS. Thereafter, cortical hemodynamics during naturally occurring epileptic spasms were measured by mNIRS with simultaneous video/electroencephalographic (EEG) monitoring.Results: Ictal SPECT revealed multiple hyperperfused areas within the cortex. With the use of mNIRS, an increase in regional cerebral blood volume (CBV) was observed in these areas, which is representative of cortical activation. The increase in CBV was accompanied by an increase in the concentrations of both oxy-and deoxyhemoglobin. The following heterogeneous regional changes in CBV during ictus were observed: (a) transient increases that were synchronized with spasms; (b) a gradual increase during an ictal event that fluctuated in synchrony with spasms; and (c) a combination of transient and gradual increases. An increase in regional CBV occurred in multiple areas that were activated either simultaneously or sequentially during an ictal event. Topographic changes in CBV were closely correlated with the phenotype of the spasm.Conclusions: During ictal events, multiple cortical areas were activated simultaneously or sequentially. The pattern of cortical activation closely affected the phenotype of the spasm, which suggested that the cortex was involved in the generation of spasms. Key Words: West syndrome-Infantile spasm-Nearinfrared spectroscopy.West syndrome (WS) is an age-dependent epileptic syndrome that occurs during infancy. WS is characterized by clustering epileptic spasms, electroencephalographic (EEG) hypsarrhythmia, and arrested psychomotor development (1,2). Although the pathophysiology of WS remains unknown, subcortical structures such as the lentiform nuclei and brainstem are thought to be involved (3,4). In addition, magnetic resonance imaging (MRI) and functional neuroimaging have revealed that a considerable number of children with WS possess focal cortical abnormalities (5-7). Surgical resection of the affected area can eliminate the spasms (8), suggesting (at least in such patients) that the abnormal cortex may play a crucial role in the pathogenesis of spasms in patients with WS. Positron emission tomography (PET) and singlephoton emission computed tomography (SPECT) have suggested that abnormal cortical areas are hyperperfused during ictal periods, implying that these areas of the cortex are activated during a cluster of spasms (9,10). However, because of the insufficient time resolution of PET and SPECT for rapidly progressing and repeatedly occurring spasms, it is impossible to discriminate between the cerebral perfusion changes during spasms and those at intervals of spasms, and postictal changes might contaminate the results. A differen...