Related Epilepsy Research Articles

Application of high-dose Diazepam in epileptic children with electrical status epilepticus during sleep

Objective To explore the therapeutic effects and adverse reaction of high-dose Diazepam (DZP) in patients with electrical status epilepticus during sleep (ESES). Methods Nine patients in the Outpatient of the Department of Pediatrics, Peking University First Hospital from October 2016 to May 2017 with ESES were treated with high-dose DZP.Oral DZP was administered in a dose of 0.75-1.00 mg/kg(maximum: 40 mg) during the first night followed by 0.5 mg/(kg·d) (maximum: 20 mg) from the second night for 1-3 months and tapered over next 1-3 months.The seizures, electroencephalogram (EEG) changes and adverse reactions were observed before and after DZP treatment. Results Six of 9 patients were male and 3 were female.The age of onset was ranged from 1 year and 6 months to 10 years.Benign childhood epilepsy with central temporal spike was diagnosed in 5 cases, epileptic encephalopathy with continuous spike-and-wave during sleep in 1 case, and ESES related epilepsy in 3 cases.Age of onset DZP treatment ranged from 4 years and 4 months to 12 years, and the duration of DZP treatment was ranged from 1 to 5 months (1 case only for the first night). The follow-up interval was 6-12 months.The efficiency of DZP on seizures: intent effective in 5 patients, effective in 2 patients and ineffective in 2 patients, and the effective rate was 78% (7/9 cases). The efficiency of DZP on EEG (1 month after DZP treatment): intent effective in 2 patients (EEG norma-lized), effect in 3 patients and no effect in 2 patients, and the effective rate was 71% (5/7 cases), while 2 patients did not receive EEG examination.Four of 7 patients (57%) with intent effect and effective of DZP on seizures had seizures relapse during drug reduction and after drug withdrawal, and the EEG deteriorated simultaneously.Adverse reactions of DZP included 3 patients (33%) with adverse reactions, bed-wetting in 2 patients and snoring on the first night in 1 patient who withdrew DZP later. Conclusions The high-dose of DZP has a certain effect on seizures control and ESES suppression in patients with ESES, but also has a certain recurrence rate.The adverse reactions are mild and self-limiting.High-dose DZP treatment could be a choice for refractory patients with ESES to alleviate disease. Key words: Electrical status epilepticus during sleep; Diazepam; Epilepsy

Outcomes of tumour related epilepsy in a specialised epilepsy surgery unit

IntroductionSeizures are an important cause of morbidity in patients with low grade gliomas with approximately 40% of cases drug resistant. The pathogenesis is quite complex and poorly understood. The treatment aims vary between almost purely epilepsy considerations and those that are primarily oncologic. AimTo determine whether patients who present with seizures and are found to have a low grade glioma have better outcomes when managed through a specialized epilepsy unit compared to the general neurosurgical service. MethodsA review of the prospectively collected database was performed over a 10 year period to identify 48 adult patients who present with a seizure and were subsequently found to have a low grade glioma. These patients were analysed with respect to management through the specialized epilepsy service or the general neurosurgical service. The primary outcome was Engel classification between the two groups. Secondary outcomes included recurrence, postoperative deficits, delay to surgery, histology, grade and extent of resection. OutcomesThe patients managed through the epilepsy service had significantly higher rate of favourable Engel outcomes (I and II) compared to the general neurosurgery service (OR: 13.2, 95% CI: 1.239–140.679; P = 0.033). The epilepsy surgery group patients had a significantly higher delay to surgery (P < 0.001). The patients in the epilepsy service had a significantly higher resection ratio compared to the general neurosurgery service (73% vs 127%, P = 0.014). Rates of recurrence were not different between the two groups. ConclusionPatients with tumour related epilepsy who undergo an intensive presurgical evaluation may obtain better seizure related outcomes.

Mosaicism and incomplete penetrance of PCDH19 mutations

BackgroundMutations in the PCDH19 gene have mainly been reported in female patients with epilepsy. To date, PCDH19 mutations have been reported in hundreds of females and only in 10 mosaic...

Seizure predictors and outcome after Onyx embolization in patients with brain arteriovenous malformations.

Brain arteriovenous malformation (bAVM)-related epilepsy can significantly affect patient quality of life. We aimed to identify the factors associated with seizures occurrence and evaluate the long-term outcome following Onyx embolization in bAVM patients. Between July 2014 and July 2016, 239 consecutive patients underwent treatment for bAVMs in our institute and were respectively analyzed. Demographics, seizure status and bAVM morphologic characteristics were recorded. Modified Engel classification was used to evaluate the long-term seizure outcomes. Of 239 bAVM patients, 68 (28.5%) initially presented with seizures. Seizure occurrence was associated with cerebral hemorrhage history, frontal-temporal location and arterial borderzone location. Of the 37 patients who presented with initial seizures and were treated with Onyx embolization, 23 (62.2%) were treated with antiepileptic drugs (AEDs) before Onyx embolization. At the last follow-up visit, 19 (51.4%) of the 37 patients reached modified Engel class I outcome. Of the 23 patients who had ever been treated with AEDs, 12 (52.2%) were still taking AEDs at the last follow-up visit. Single-factor analysis showed that arterial borderzone location was significantly correlated with higher modified Engel class outcome ( p = 0.046). Patients with bAVM hemorrhage history, frontal-temporal location and arterial borderzone location were associated with seizure occurrence. Seizure-free status was not obtained in AVM patients with arterial borderzone after embolization, though it may have benefits in other ways. The seizure-free mechanism of bAVM with Onyx embolization is worth further study.

Sleep Related Epilepsy and Pharmacotherapy: An Insight.

In the last several decades, sleep-related epilepsy has drawn considerable attention among epileptologists and neuroscientists in the interest of new paradigms of the disease etiology, pathogenesis and management. Sleep-related epilepsy is nocturnal seizures that manifest solely during the sleep state. Sleep comprises two distinct stages i.e., non-rapid eye movement (NREM) and rapid eye movement (REM) that alternate every 90 min with NREM preceding REM. Current findings indicate that the sleep-related epilepsy manifests predominantly during the synchronized stages of sleep; NREM over REM stage. Sleep related hypermotor epilepsy (SHE), benign partial epilepsy with centrotemporal spikes or benign rolandic epilepsy (BECTS), and Panayiotopoulos Syndrome (PS) are three of the most frequently implicated epilepsies occurring during the sleep state. Although some familial types are described, others are seemingly sporadic occurrences. In the present review, we aim to discuss the predominance of sleep-related epilepsy during NREM, established familial links to the pathogenesis of SHE, BECTS and PS, and highlight the present available pharmacotherapy options.

P01.008 Feasibility of a structured tumor related epilepsy education intervention in adult gliomas

P01.008 Feasibility of a structured tumor related epilepsy education intervention in adult gliomas

Relationship of electrophysiological dysfunction and clinical severity in SCN2A-related epilepsies.

Variants in the SCN2A gene cause a broad spectrum of epilepsy syndromes of variable severity including benign neonatal-infantile epilepsy (BFNIE), developmental and epileptic encephalopathies (DEE), and other neuropsychiatric disorders. Here, we studied three newly identified variants, which caused distinct phenotypes observed in nine affected individuals of three families, including BFNIE, and DEE with intractable neonatal seizures. Whole cell patch-clamp recordings of transfected tsA201 cells disclosed an increased current density and an increased subthreshold sodium inward current upon an action potential stimulus (p.(Lys908Glu)), a hyperpolarizing shift of the activation curve (p.(Val208Glu) and p.(Thr773Ile)), and an increased persistent current (p.(Thr773Ile)). To evaluate genotype-phenotype correlations, we next developed scoring systems for both the extent of the electrophysiological dysfunction and the severity of the clinical phenotype and applied those to 21 previously and newly functionally characterized SCN2A variants. All inherited variants were associated with a mild clinical phenotype and a lower electrophysiological score compared to those occurring de novo and causing severe phenotypes. Our results thus reveal a nice correlation between the extent of channel dysfunction and the clinical severity.

Lack of response to quinidine in KCNT1-related neonatal epilepsy.

To evaluate the clinical efficacy and safety of quinidine in patients with KCNT1-related epilepsy of infancy with migrating focal seizures (EIMFS) in the infantile period and to compare with the effect of quinidine on mutant channels in vitro. We identified 4 patients with EIMFS with onset in the neonatal period, pathogenic variants in the KCNT1 gene, and lack of response to AEDs. Patients were prospectively enrolled, treated with quinidine, and monitored according to a predefined protocol. Electroclinical, neuroimaging, and genetic data were reviewed. Two patients had novel variants in the KCNT1 gene that were modeled in Xenopus oocytes with channel properties characterized using electrophysiology recordings. Three of four patients were treated with quinidine early in their disease course, prior to 6 months of age. No significant side effects were noted with quinidine therapy. In addition, there were no significant changes in electroencephalography (EEG)-confirmed seizure burden during therapy, and patients had near hourly seizures before, during, and after treatment. Two patients had previously reported gain-of-function mutations, which demonstrated sensitivity to high levels of quinidine in the oocyte assay. Two patients with novel variants, showed characteristic gain-of-function and were thus predicted to be pathogenic. Of interest, these variants were essentially insensitive to high levels of quinidine. Patients had no reported benefit to quinidine therapy despite age at treatment initiation. Pharmacogenetic results in oocytes were consistent with clinical treatment failure in 2 patients, suggesting that single-dose pharmacologic assessment may be helpful in predicting which patients are exceedingly unlikely to achieve benefit with quinidine. In the 2 patients who had a lack of therapeutic benefit despite sensitivity to high concentrations of quinidine with in vitro oocyte assay, it is likely that the achievable exposure levels in the brain were too low to cause significant in vivo channel blockade.

Clinical phenotypes of TBC1D24 gene related epilepsy

Objective: To summarize the clinical features of TBC1D24 gene mutations associated with epilepsy. Methods: All the patients with TBC1D24 gene compound heterozygous mutations were retrospectively collected at the Pediatric Department of Peking University First Hospital from March 2015 to July 2017, and the features of clinical manifestations, electroencephalogram, and neuroimaging were analyzed. Results: Eighteen cases with TBC1D24 gene compound heterozygous mutations were included. The age of seizure onset was 1 day to 8 months, and the median age was 90 days. Seizure types included generalized tonic-clonic seizures (GTCS) in 3 cases, focal seizures in 18 cases, myoclonus in 18 cases, and 17 cases had focal myoclonus and myoclonus status. The focal myoclonus involving one or multiple muscle groups, sometimes migrating and alternating, lasting up to minutes to several days, and could be terminated by sleep or sedation drugs. In 11 cases, myoclonus was exacerbated by fever or infections, and 2 cases developed into myoclonic status during infection, in a severe case with the loss of consciousness. The magnetic resonance imaging (MRI) of seven patients was abnormal, including cerebral atrophy or cerebellar atrophy with abnormal signals. Segment myoclonus was captured in 10 patients, but without correlated epileptiform discharges. There were ten cases had varying degrees of developmental delay, 7 were normal, and one patient died of status epilepticus at the age of 4 months. Three cases had hearing disorders. In the 18 patients, the clinical phenotype of 4 cases consisted of epilepsy of infancy with migrating focal seizures, 2 with progressive myoclonus epilepsies, 1 with Dravet syndrome, 1 with DOORS syndrome, and 3 with unclassified epileptic encephalopathy. Conclusions: The clinical feature of TBC1D24 gene mutation related epilepsy was focal myoclonus, and tended to develop into myoclonic status epilepticus, and could be aggravated by infections, and terminated by sleep or sedation drugs. Mental retardation involved or not, neuroimaging could present with cerebral atrophy or cerebellar atrophy with abnormal signals.

Role of Diffusion Tensor Imaging in Detection and Lateralization of Temporal Lobe Epilepsy

AbstractBackground: Temporal lobe epilepsy (TLE) is the most common localization related epilepsy syndrome. Diffusion tensor imaging (DTI) is a new imaging technique that is sensitive to the structural integrity changes of cerebral tissue in patients with TLE who have been evaluated for epilepsy surgery.Aim of Study: To demonstrate the role of diffusion tensor imaging in the diagnosis of temporal lobe epilepsy.Patients and Methods: This is a prospective study included 40 patients diagnosed clinically as having TLE and twenty control subjects. The patients and control groups are examined by conventional magnetic resonance imaging (MRI ) followed by DTI and tractography. EEG examination, was performed to 36 patients only, the remaining 4 were missed during follow-up. It was done to support the clinical diagnosis of TLE and to help in the lateralization of the site of seizure focus to be compared with DTI results.Results: The calculated cut off value regarding fractional anisotropy (FA )difference between both hippocampi was 0.014. Twenty eight patients with FA differences above this value were considered as DTI positive of hippocampal abnor-mality and 12 patients were below this value and were con-sidered as DTI negative. FA differences between both hippoc-ampi in patients' group were significantly increased as compared with the control group.Conclusion: DTI can detect hippocampal abnormalities even in patients with normal conventional MR, so it can be used to lateralize seizure side, thus increase the diagnostic accuracy before epilepsy surgery.

Return of individual results in epilepsy genomic research: A view from the field.

Genomic findings are emerging rapidly in 2 large, closely related epilepsy research consortia: the Epilepsy Phenome/Genome Project and Epi4K. Disclosure of individual results to participants in genomic research is increasingly viewed as an ethical obligation, but strategies for return of results were not included in the design of these consortia, raising complexities in establishing criteria for which results to offer, determining participant preferences, managing the large number of sites involved, and covering associated costs. Here, we describe the challenges faced, alternative approaches considered, and progress to date. Experience from these 2 consortia illustrates the importance, for genomic research in epilepsy and other disorders, of including a specific plan for return of results in the study design, with financial support for obtaining clinical confirmation and providing ongoing support for participants. Participant preferences for return of results should be established at the time of enrollment, and methods for allowing future contacts with participants should be included. In addition, methods should be developed for summarizing meaningful, comprehensible information about findings in the aggregate that participants can access in an ongoing way.

Ketogenic diet for febrile infection related epilepsy syndrome: case report and literature review

目的 总结热性感染相关性癫痫综合征(FIRES)的临床特征、病因及生酮饮食(KD)治疗的作用。 方法 分析1例入住四川大学华西第二医院儿科重症监护室的FIRES患儿临床表现、诊断及KD治疗经过，随诊1年观察预后，综合文献资料，总结该病临床特征、病因、诊断标准及KD治疗效果。 结果 患儿为学龄前期儿童，起病急骤，表现为发热、意识障碍及药物难控制的癫痫持续状态。脑电图示背景慢化，额、颞及顶叶尖波发放，头颅磁共振成像示双侧脑室周围白质异常信号。经KD治疗1周后，成功撤停丙泊酚并转入普通病房，出院后继续口服抗癫痫药物及KD治疗，随访1年期间，未再出现癫痫持续状态，认知水平较住院期间改善，但较病前明显落后。相关文献显示该病好发于既往健康的学龄儿童，常伴发热，病因与炎症介导的免疫反应可能有关，早期KD治疗的患者有1/4～1/3发作减少，有利于尽早撤停静脉麻醉剂，随访显示大部分患者认知损害有改善，癫痫发作频率及出现癫痫持续状态减少。 结论 FIRES病因不明，好发于学龄儿童，常伴发热，癫痫发作呈暴发性、药物难治性，早期KD治疗对控制急性期癫痫发作及改善远期预后有益。

Phenotype study of SCN2A gene related epilepsy

Objective: To summarize the phenotype of epileptic children with SCN2A mutations. Methods: Epileptic patients who were treated in the Pediatric Department of Peking University First Hospital from September 2006 to October 2017 and detected with SCN2A mutations by targeted next-generation sequencing were enrolled. Clinical manifestations of all patients were analyzed retrospectively. Results: A total of 21 patients (16 boys and 5 girls) with SCN2A mutations were collected. Twenty-one SCN2A mutations were identified. Ten patients had mutations inherited from one of their parents and 11 patients had de novo mutations. The age of epilepsy onset was from 2 days to 2 years and 6 months: six patients with seizure onset in neonates (29%) , six patients with seizure onset between 1 month and 3 months of age (29%), three patients with seizure onset between 4 months and 6 months of age, two patients with seizure onset between 7 months and one year of age, and four patients with seizure onset beyond one year of age. Multiple seizure types were observed. The focal seizure was the most common seizure type which was observed in 18 patients (86%) . Spasm seizure was observed in 6 patients (29%) . Other seizure types were rare. In 19 patients, seizures manifested in clusters (90%) . In 3 patients, seizures manifested fever-sensitive. Nine of ten patients with inherited SCN2A mutations had normal development. However, all patients with de novo SCN2A mutations had mild or severer development delay. In 21 patients with SCN2A mutations, five were diagnosed with benign familial infantile epilepsy, 3 with benign familial neonatal-infantile epilepsy, 3 with Ohtahara syndrome, 3 with West syndrome, 2 with encephalopathy with early infantile onset epilepsy, one with febrile seizures plus, one with Dravet syndrome, one with encephalopathy with childhood-onset epilepsy, one with autism with epilepsy and one with intellectual disability with epilepsy. Conclusions: The clinical features of patients with SCN2A mutations include that main seizure onset is the neonate and early infancy, and the main seizure type is the focal seizure, manifested in clusters. The large spectrum of SCN2A-related epilepsy, which not only includes epilepsy with a comparatively favorable prognosis, but also epileptic encephalopathy. De novo mutations often lead to severe phenotype with development delay.

Research progress in genetic studies of genetic epilepsy with febrile seizures plus

Genetic epilepsy with febrile seizures plus(GEFS+ ) is a genetically related epilepsy syndrome, characterized by a distinctive pattern of phenotypic heterogeneity and genetic heterogeneity.An increasing number of studies illustrate that a variety of pathogenic variations participate in the pathogenesis of GEFS+ , but the pathogenesis and genetic mechanisms are not fully understood, and most families can not find pathogenic genes.With the improvement of genetic techniques, the pathogenesis of GEFS+ will be better explained and a new basis will be provided for its diagnosis and precision treatment.This article discusses the clinical manifestation, genetic research, diagnosis and treatment of GEFS+ , aiming at raising awareness of the disease. Key words: Genetic epilepsy with febrile seizures plus; Hereditary; Clinical manifestation; Diagnosis; Treatment

Elevated cerebrospinal fluid protein in POLG-related epilepsy: Diagnostic and prognostic implications.

Epilepsy is common in individuals with mutations in POLG, the gene encoding the catalytic subunit of the mitochondrial DNA polymerase gamma. Early recognition and aggressive seizure management are crucial for patient survival. Disruption of the blood-brain barrier (BBB) is implicated in various neurological disorders including epilepsy. The aim of this study was to assess whether POLG-related disease is associated with BBB dysfunction and what clinical implications this has for patients. Our retrospective study used data from 83 patients with pathogenic POLG mutations from 4 countries--Norway, Sweden, Finland, and the United Kingdom. Data were collected using a structured questionnaire. We used the presence of raised cerebrospinal fluid (CSF) protein and a raised CSF/serum ratio of albumin (Q-alb) to evaluate the integrity of the blood-CSF barrier. Raised CSF protein was found in 70% of patients (n = 58/83) and appeared to be associated with the most severe phenotypes. In those in whom it was measured, the Q-alb ratio was markedly elevated (n = 18). The majority of those with epilepsy (n = 50/66, 76%) had raised CSF protein, and this preceded seizure debut in 75% (n = 15/20). The median survival time from symptom onset for those with raised CSF protein was decreased (13 months) compared to those with normal CSF protein (32 months). Our results indicate that there is disruption of the BBB in POLG-related disease, as evidenced by a raised CSF protein and Q-alb ratio. We also find that raised CSF protein is a common finding in patients with POLG disease. Our data suggest that the presence of BBB dysfunction predicts a poorer outcome, and elevated CSF protein may therefore be an additional biomarker both for early diagnosis and to identify those at high risk of developing epilepsy.

Magnetic resonance imaging of tuberous sclerosis complex with or without epilepsy at 7T.

This study was conducted to determine the benefit of magnetic resonance imaging (MRI) at 7T in detecting structural lesions and previously unidentified abnormalities in patients with tuberous sclerosis complex (TSC). Thirteen patients with TSC (8-36years, seven males) previously diagnosed by 3T MRI underwent additional imaging at 7T, which included T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE), T2-weighted turbo spin echo (TSE), SPACE fluid attenuated inversion recovery (FLAIR), susceptibility weighted imaging (SWI), white matter suppressed (WM-suppressed), and gray-white matter tissue border enhancement (GW-TBE) MPRAGE sequences. Subtle lesions, tuberal morphology, and perituberal cortex abnormalities were examined and compared to those observed at 3T MRI using standard sequences. Improved visualization of TSC lesions was achieved in all subjects at 7T compared to 3T imaging, and three subjects received resective surgery. The 7T T1- and T2-weighted images had high spatial resolution and provided a clear delineation of the perituberal cortex. SWI revealed abnormal blood vessel morphology. WM-suppressed and GW-TBE protocols, adjusted specifically for TSC imaging, aided in visualizing lesions and uncovered more extensive subtle lesions and abnormalities beyond the conventionally detected tubers. Due to its high spatial resolution and powerful new imaging protocols, 7T MRI provided a better evaluation of subtle lesions and perituberal details compared with conventional MRI at 3T, with potential implications for diagnosis and operative treatment of TSC and its related epilepsy.

T18. High dose phenobarbital is safe and effective treatment for SCN2A related epilepsy

Introduction Voltage-gated sodium channels play major role in neuronal excitability. Nav1.1, Nav1.2, Nav1.3 and Nav1.6 sodium channels found in the brain differ in α -subunits, encoded by SCN1A, SCN2A, SCN3A, and SCN8A genes respectively. NaV1.2 Channels is the only sodium channel expressed during early development at nodes of Ranvier and in the axon initial segment (AIS) in developing and mature neurons, particularly cortical glutamatergic pyramidal cells. NaV1.2 channel has relatively high exictation threshold. NaV1.2 is regulated developmentally by alternative splicing to produce ‘neonatal’ and ‘adult’ isoforms. ‘Neonatal’ form is less excitable than ‘adult’ conferring reduced neuronal excitability and seizure susceptibility. Most dominantly inherited missense genetic variants of NaV1.2 manifests as familial epilepsy while de novo mutations as severe epileptic encephalopathy, both have gain of function with increased excitability and lowered seizure threshold. Cortical pyramidal neurons AIS receives exclusively inhibitory GABA-ergic input from specific set of interneurons called chandelier cells. Methods A FT, WF child born via planned caesarian to a healthy 27 yr G2P2A0L2 with APGAR 8, 9 at 1, 5 min at OSH. On DOL 2, developed seizure manifested as chocking, left arm forced flexion with leftward head deviation, right arm extension evolve into whole body jerking with apnea. Ictal EEG documented left frontal-temporal onset focal seizure. She received two loading doses of Phenobarbital followed by maintenance of 5 mg/kg/day. At therapeutic level of 44 mcg/ml, seizures remained under controlled. On DOL 22, presented to OSH with right arm twitching. Random PHB level was 27.5 mcg/ml. She received load of PHB and Levetiracetam 20 mg/kg each. Seizures continued overnight leading to transfer to our institute. Patient physcial and neurologic exam was normal. Ictal EEG re-demonstrated left central onset rhythmic spike-wave seizure evolution pattern clinically manifesting wide-eyed gaze with right face and upper extremity clonic jerking. Patient received total dose of 40 mg/kg of levetiracetam without improvement. Later, two 10 mg/kg doses of PHB given at couple of hours interval stopped seizures. Maintenance dosing of PHB was increased to 6 mg/kg/day. PHB level obtained was 54.2mcg/ml. It was tolerated well without sedation, hypotonia or adverse effects. She has been weaned off PHB at 7 months of age and has been seizure free with normal development at 14 months of age. Gene DX Comprehensive Epilepsy Panel revealed pathogenic variant of the SCN2A gene (p. Val261Met). Results We described infant with de novo SCN2A mutation presenting as benign familial neonatal infantile epilepsy well controlled with high therapeutic phenobarbital level without experiencing adverse side effects. Conclusion Phenobarbital at very high therapeutic level exerted seizure control probably via inhibitory effects of Chanderlier cell counterbalancing increased excitability of genetic missense variant of NaV1.2 at the AIS.

Electroclinical characteristics and syndromic associations of “eye-condition” related visual sensitive epilepsies—A cross-sectional study

PurposeThe systematic study of visual phenomena such as eye closure (ECLS), eye-closed/fixation-off sensitivity (FOS) [terminology proposed as eye-condition sensitive (ECS) epilepsy] distinct from photosensitivity is rarely explored in literature. MethodsClinical, electroencephalographic (EEG) and imaging records of patients attending an epilepsy clinic were screened. Inclusion criterion was demonstrable electrographic visual sensitivitiy in the form of ECS parameters with/without photosensitivity. Subsequently, detailed analysis of their data was undertaken. ResultsFifty two patients had one or more ECS parameters. Mean age of onset of epilepsy of the cohort was 10.26 ± 7.79 yrs. A family history of seizures was noted in 17% of the cohort. ECLS, FOS, combination of both, co-existent scotosensitivity and photosensitivity were noted in 32.6%, 48.1%, 19.2%, 23.1% and 30.8% respectively. Epilepsy syndromes included late-onset childhood occipital epilepsy-Gastaut variant (23.1%), reflex occipital lobe epilepsy with ECS without photosensitivity (21.2%), idiopathic photosensitive occipital epilepsy (13.5%), genetic generalized epilepsy (13.5%) and symptomatic epilepsy (28.7%) predominated by patients with posterior cortex gliosis or who were imaging negative. The idiopathic group also had lower seizure score and marked sleep activation of epileptiform abnormalities. Co-existent phostosensitivity was associated with a significantly higher predisposition for female gender, ECLS, generalized seizures and spikes with lower prevalence of FOS and extra-occipital spikes. Parieto-occipital spikes were noted in 88.4% patients. ConclusionSyndromic heterogeneity is evident in ECS epilepsies. These form a unique subset of visual-sensitive epilepsy syndromes with focal or generalized seizure subtypes of idiopathic or symptomatic etiologies, with and without associated photosensitivity.

New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES): State of the art and perspectives.

We report the proceedings of the First International new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) Symposium. To promote awareness of this condition and foster research efforts, we conveyed the First International new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) Symposium. The conference was supported by The NORSE Institute (http://www.norseinstitute.org). This article summarizes the discussions that were held during the Symposium and presents our strategy to unravel the cause of these disorders and to improve patient care. The standardized definitions for these disorders that have been developed, are required to improve communication and facilitate the development of multicenter registries and biobanks. A distinction between childhood- and adult-onset forms of the syndrome is not supported by strong scientific evidence and it is argued that both should be studied together. Although the pathophysiology remains elusive, nascent evidence suggests a role for a postinfectious cytokine-mediated mechanism, which should be further investigated. It also appears important to develop tools for their early recognition and prompt treatment. Recent evidence suggests that specific electroencephalography (EEG) features might be helpful. The optimal treatment options remain to be determined; immune therapies are usually disappointing, but the ketogenic diet has proved effective in uncontrolled trials. NORSE and FIRES represent a very delicate clinical situation with specific communication issues between physicians and with patients and families. Standardized consensus definitions and a multidisciplinary multicenter strategy will help research efforts and improve clinical care for patients with NORSE and FIRES.

Clinical features and gene analysis of TBC1D24 gene mutation related early-onset focal myoclonic epilepsy

Objective: To investigate the clinical features and genetic characteristics of patients with TBC1D24 gene mutation related early-onset focal myoclonic epilepsy. Methods: Clinical data of 3 patients with TBC1D24 gene mutation related early-onset focal myoclonic epilepsy of Xuanwu Hospital from November 2016 to June 2017 was collected and analyzed.Candidate gene mutations were screened by second generation sequencing. Results: Among the 3 patients, 1 was male and 2 were females.Seizure onset age was 4 months, 3 years and 5 years after birth respectively. Two patients had family history of epilepsy.They all had prolonged episodes of focal myoclonus. Two patients had mental retardation.Scalp electroencephalograms (EEG) was recorded in all 3 cases and myoclonic seizures were captured.The ictal EEGs were normal in all cases. In one patient, the ictal EEG of generalized seizure showed alpha rhythm originating from left fronto-central region. Brain magnetic resonance imaging (MRI) was normal in 2 patients. Abnormal signal was found bilaterally in cerebellum in 1 patient. The gene screening showed that two patients carried compound heterozygous mutation of TBC1D24 gene and one carried homozygous mutation, all of which were de novo mutations.All the patients were treated with multiple antiepileptic drugs (AEDs) and seizures were uncontrolled in 2 patients. One patient was followed up for 10 months without recurrence. Conclusions: TBC1D24 gene related early-onset focal myoclonic epilepsy is clinically characterized by early onset, prolonged focal myoclonus which relieved with sleep, mental retardation and poor response to AEDs.The interictal and ictal EEG usually show normal. Genetic analysis can assist in diagnosis and genetic counseling.