Reversible splenial lesion syndrome associated with SARS-CoV-2 infection in two children

BackgroundReversible splenial lesion syndrome (RESLES) is characterized by a temporary lesion in the splenium of the corpus callosum, emerging related to encephalitis, seizures, antiepileptic drug withdrawal, or metabolic disturbances. Among RESLES, mild encephalitis/encephalopathy with reversible splenial lesion (MERS) has been defined as a distinct clinicoradiologic syndrome associated with viral infections.Case presentationWe report two children with multisystem inflammatory syndrome-children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who developed RESLES during the disease course. Encephalopathy was the main central nervous system symptom. Both of the children showed a rapid recovery, and brain magnetic resonance imaging revealed complete resolution of the splenial lesion within 1 week.ConclusionThe complete resolution of the splenial lesion and rapid recovery from encephalopathy in RESLES associated with SARS CoV-2 were similar to observed in MERS.     

Comparison of fiber tract low frequency stimulation to focal and ANT stimulation in an acute rat model of focal cortical seizures

BackgroundCurrent implementations of direct brain stimulation for epilepsy in patients involve high-frequency (HFS) electrical current and targeting of grey matter. Studies have shown that low-frequency (LFS) fiber-tract stimulation may also prove effective. To compare the efficacy of high-frequency grey matter stimulation to the low-frequency fiber tract stimulation technique a well-controlled set of experiments using a single animal model of epilepsy is needed.ObjectiveThe goal of this study was to determine the relative efficacy of different direct brain stimulation techniques for suppressing seizures using an acute rat model of focal cortical seizures.Methods4-AP was injected into the S1 region of cortex in rodents over 3 h. LFPs were recorded from the seizure focus and mirror focus to monitor seizure frequency during the experiments. CC-LFS, HFS-ANT, Focal-HFS, or a transection of the CC was applied.ResultsStimulation of the CC yielded a 65% ±14% (p = 0.0014) reduction of seizures in the focus and a 97% ±15% (p = 0.0026) reduction in the mirror focus (n = 7). By comparison transection of the CC produced a 65% ±18% reduction in the focus and a non-statistically significant reduction of 57% ±18% (p = 0.1381) in the mirror focus (n = 5). All other methods of stimulation failed to have a statistically significant effect on seizure suppression.ConclusionsLFS of the CC is the only method of stimulation to significantly reduce seizure frequency in this model of focal cortical seizures. These results support the hypothesis that LFSof fiber tracts has significant potential for seizure control.     

The voltage-gated calcium channel CaV1.2 promotes adult oligodendrocyte progenitor cell survival in the mouse corpus callosum but not motor cortex

Throughout life, oligodendrocyte progenitor cells (OPCs) proliferate and differentiate into myelinating oligodendrocytes. OPCs express cell surface receptors and channels that allow them to detect and respond to neuronal activity, including voltage-gated calcium channel (VGCC)s. The major L-type VGCC expressed by developmental OPCs, CaV1.2, regulates their differentiation. However, it is unclear whether CaV1.2 similarly influences OPC behavior in the healthy adult central nervous system (CNS). To examine the role of CaV1.2 in adulthood, we conditionally deleted this channel from OPCs by administering tamoxifen to P60 Cacna1c ^fl/fl (control) and Pdgfrα-CreER:: Cacna1c ^fl/fl (CaV1.2-deleted) mice. Whole cell patch clamp analysis revealed that CaV1.2 deletion reduced L-type voltage-gated calcium entry into adult OPCs by ~60%, confirming that it remains the major L-type VGCC expressed by OPCs in adulthood. The conditional deletion of CaV1.2 from adult OPCs significantly increased their proliferation but did not affect the number of new oligodendrocytes produced or influence the length or number of internodes they elaborated. Unexpectedly, CaV1.2 deletion resulted in the dramatic loss of OPCs from the corpus callosum, such that 7 days after tamoxifen administration CaV1.2-deleted mice had an OPC density ~42% that of control mice. OPC density recovered within 2 weeks of CaV1.2 deletion, as the lost OPCs were replaced by surviving CaV1.2-deleted OPCs. As OPC density was not affected in the motor cortex or spinal cord, we conclude that calcium entry through CaV1.2 is a critical survival signal for a subpopulation of callosal OPCs but not for all OPCs in the mature CNS.     

经纵裂-透明隔间腔入路胼胝体切开术治疗难治性癫痫的手术方法及临床疗效

目的探讨经纵裂-透明隔间腔入路胼胝体切开术治疗药物难治性癫痫的手术方法和临床疗效。方法回顾性分析2014年1月至2019年1月上海交通大学医学院附属仁济医院功能神经外科收治的23例难治性癫痫患者的临床资料。患者均采用梯形小骨窗开颅,分别经纵裂-透明隔间腔入路行胼胝体前2/3切开术或一期胼胝体全节段切开术。术前行磁共振静脉成像(MRV)和图像三维重建辅助设计切口和骨窗。术后定期行影像学随访,采用Montreal神经研究所和医院Oguni等胼胝体切开术后疗效分级标准评估疗效。结果23例患者均顺利完成胼胝体切开手术,其中11例行胼胝体前2/3切开术,12例行一期胼胝体全节段切开术。23例患者中,22例沿中线切开胼胝体至透明隔腔,仅1例患者因脑发育畸形,术中探查透明隔腔缺失,改用经侧脑室入路切开胼胝体。患者术后均无颅内出血、脑积水和感染,无遗留长期神经功能障碍和并发症。MRI或弥散张量成像复查证实胼胝体切开范围达到要求。所有患者的中位随访时间为1.8年(0.5~5.2年)。术后疗效分级结果:A级4例、B级6例、C级6例、D级7例、E级0例,总有效率为69.6%(16/23)。结论经纵裂-透明隔间腔入路行胼胝体切开术可保持正中的手术路径,从而减少副损伤和并发症的发生,提高手术疗效。     

A familial Sonic Hedgehog (SHH) stop-gain mutation associated with agenesis of the corpus callosum,mild intellectual disability and facial dysmorphism

BackgroundAgenesis of the corpus callosum (ACC) is a relatively common brain malformation in children with developmental disabilities, caused by mutations in many genes. These genetic causes are characterized by their extreme heterogeneity with more than 300 causative genes identified to date.Case reportWe describe two new cases from a three-generation family with ACC and a de novo mutation of the sonic hedgehog (SHH) gene. The affected family members had mild intellectual disability, broad forehead, and widely spaced eyes. A next-generation sequencing (NGS) approach revealed a stop-gain mutation (NM_000193.2:c.1300_1301insA p.Trp434Ter) of the SHH gene; it is the first family to report ACC associated with a single SHH gene mutation.ConclusionACC with mild intellectual disability and facial dysmorphism may be caused by a mutation in SHH, but further research investigating the genotype-phenotype correlation of SHH mutations is required.     

Novel BRPF1 mutation in a boy with intellectual disability,coloboma, facial nerve palsy and hypoplasia of the corpus callosum

Mutations in the chromatin regulator gene BRPF1 were recently associated with the Intellectual Developmental Disorder With Dysmorphic Facies And Ptosis (IDDDFP). Up till now, clinical data of 22 patients are reported. Besides intellectual disability (ID), ptosis and blepharophimosis are frequent findings, with refraction problems, amblyopia and strabism as other reported ophthalmological features. Animal studies indicate BRPF1 as an important mediator in brain development. However, only 5 of 22 previously reported patients show structural brain abnormalities.We report on an additional patient harboring a novel de novo nonsense mutation p.(Glu219*) in BRPF1. He presented with ID, bilateral iris colobomas, facial nerve palsy and severe hypoplasia of the corpus callosum. Our findings support previous findings of brain abnormalities in BRPF1-mutations and indicates coloboma and facial nerve palsy as possible additional features of IDDDFP syndrome.