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OBJECTIVEThe potential loss of motor function after cerebral hemispherectomy is a common cause of anguish for patients, their families, and their physicians. The deficits these patients face are individually unique, but as a whole they provide a framework to understand the mechanisms underlying cortical reorganization of motor function. This study investigated whether preoperative functional MRI (fMRI) and diffusion tensor imaging (DTI) could predict the postoperative preservation of hand motor function.METHODSThirteen independent reviewers analyzed sensorimotor fMRI and colored fractional anisotropy (CoFA)–DTI maps in 25 patients undergoing functional hemispherectomy for treatment of intractable seizures. Pre- and postoperative gross hand motor function were categorized and correlated with fMRI and DTI findings, specifically, abnormally located motor activation on fMRI and corticospinal tract atrophy on DTI.RESULTSNormal sensorimotor cortical activation on preoperative fMRI was significantly associated with severe decline in postoperative motor function, demonstrating 92.9% sensitivity (95% CI 0.661–0.998) and 100% specificity (95% CI 0.715–1.00). Bilaterally robust, symmetric corticospinal tracts on CoFA-DTI maps were significantly associated with severe postoperative motor decline, demonstrating 85.7% sensitivity (95% CI 0.572–0.982) and 100% specificity (95% CI 0.715–1.00). Interpreting the fMR images, the reviewers achieved a Fleiss’ kappa coefficient (κ) for interrater agreement of κ = 0.69, indicating good agreement (p < 0.01). When interpreting the CoFA-DTI maps, the reviewers achieved κ = 0.64, again indicating good agreement (p < 0.01).CONCLUSIONSFunctional hemispherectomy offers a high potential for seizure freedom without debilitating functional deficits in certain instances. Patients likely to retain preoperative motor function can be identified prior to hemispherectomy, where fMRI or DTI suggests that cortical reorganization of motor function has occurred prior to the operation.

Introduction: KCNMA1 encodes, the alpha subunit of the voltage, and calcium-sensitive potassium channel, predominantly expressed in the central nervous system. Therefore abnormal function in this gene may occur neurological conditions.Materials and Methods: We report 15-year-old patient who was born at term with healthy conditions. Motor signals were delayed, and also seizures started at the age of 18 months. EEG revealed generalized spike-wave activities. Brain MRI performed, atrophy of the cerebellum was detected. Recent clinical examination; contractures on the large joints, and dyskinetic tremor. Whole exome sequencing (WES) was performed and in-slico analyses were conducted. MCF7 and 293T cells transfected with either wild-type or mutant expression vectors. Cellular distribution was determined by immunofluorescence. Functional analysis was performed using electrophysiological approach based on whole-cell patch-clamp.Results: WES revealed homozygous variation (NM_001161352.1:c.1372C>T, p.Arg458Ter). The variant was not observed in publicly available or in-house databases. Immunofluorescent staining revealed that novel variant is not interfering with the synthesis of KCNMA1 however mutation exhibit dominant-negative effect on cell viability when compared to wild-type. 293T and MCF7 cells transfected with homozygous p.Arg458Ter mutation showed markedly increased KCNMA1 currents compared to controls on patch-clamp recording, and these data support loss-of-function effect of all KCNMA1 mutants.Conclusions: Herein we report a 15-year old boy who has neurological conditions. A novel homozygous stop-gain mutation detected by WES and confirmed by conventional sequencing. Afterward, functional characterization was conducted using two step-approach, immunostaining to detect subcellular effect of the variation and patch-clamp to detect a difference between mutant vs. wild-type of the protein. Homozygous mutation was considered as causative for this clinical condition. This study was supported by Bezmialem Vakif University, Scientific Research Projects Unit, Project No:2.2019/7.