Focal Discharges Research Articles

Epilepsy in Children with Tuberous Sclerosis Complex: A Prospective Observational Study in Bangladesh.

Background and PurposeEpilepsy is an important neurologic feature of patients with tuberous sclerosis complex (TSC). Most common seizure types are focal seizure and epileptic spasm. Seizure control often requires multiple antiepileptic drugs. This study has been done to evaluate the seizure types, electro-encephalography (EEG), neuroimaging features, and drug treatment of epilepsy in TSC.MethodsThis prospective observational study has been conducted on epilepsy patients with TSC at Bangabandhu Sheikh Mujib Medical University from 2011 to 2019.ResultsSeventy patients with a mean±standard deviation age of 5.64±3.96 years were identified and 57.1% were female. Most common type of seizure was focal seizure (46%). Epileptic spasm occurred in 17% of patients and all of them had seizure onset before 1 year. In 47% of patients EEG showed focal epileptic discharge; hypsarrhythmia was found in most of the patients with epileptic spasm. Majority of the patients needed more than one drug to control seizure. Only 34% of patients were seizure free for at least 12 months and 22.8% had drug resistant epilepsy.ConclusionsThis study highlights the pattern of seizure, treatment pattern, response to drug, and short-time outcome of children with TSC with epilepsy in a developing country like Bangladesh.

Long-term effects of vagus nerve stimulation in refractory pediatric epilepsy: A single-center experience

IntroductionVagus nerve stimulation (VNS) has been used as an adjunctive therapy for both children and adults with refractory epilepsy, over the last two decades. In this study, we aimed to evaluate the long-term effects and tolerability of VNS in the pediatric drug-resistant epilepsy (DRE) and to identify the predictive factors for responsiveness to VNS. MethodsWe retrospectively reviewed the medical records of pediatric patients who underwent VNS implantation between 1997 and 2018. Patients with ≥50% reduction of seizure frequency compared with the baseline were defined as “responders”. The clinical characteristics of responders and nonresponders were compared. ResultsA total of 58 children (male/female: 40/18) with a mean follow-up duration of 5.7 years (3 months to 20 years) were included. The mean age at implantation was 12.4 years (4.5 to 18.5 years). Approximately half (45%) of our patients were responders, including 3 patients (5.8%) who achieved seizure freedom during follow-up. The age of seizure-onset, duration of epilepsy, age at implantation, and etiologies of epilepsy showed no significant difference between responders and nonresponders. Responders were more likely to have focal or multifocal epileptiform discharges (63%) on interictal electroencephalogram (EEG), when compared to nonresponders (36%) (p = .07). Vocal disturbances and paresthesias were the most common side effects, and in two patients, VNS was removed because of local reaction. ConclusionOur series had a diverse etiological profile and patients with transition to adult care. Long-term follow-up showed that VNS is an effective and well-tolerated treatment modality for refractory childhood onset epilepsy. Age at implantation, duration of epilepsy and underlying etiology are not found to be predictors of responsiveness to VNS. Higher response rates were observed for a subset of patients with focal epileptiform discharges.

Alterations of intracerebral connectivity in epilepsy patients with secondary bilateral synchrony

IntroductionThe aim of our study was to evaluate intracerebral network changes in epilepsy patients demonstrating secondary bilateral synchrony (SBS) in EEG by applying a new Diffusion Tensor Imaging (DTI) method using an energy-based global tracking algorithm. Materials and methods10 MRI negative epilepsy patients demonstrating SBS in 10–20 surface EEG were included. EEG findings were analyzed for irritative zones characterized by focal interictal epileptiform discharges (IEDs) triggering SBS. In addition, DTI including an energy-based global tracking algorithm was applied to analyze fiber tract alterations in irritative zones. To measure the deviation of a certain cortical connection in comparison to healthy controls, normalized differences of fiber tract streamline counts (SC) and their p-values were evaluated in comparison to corresponding fibers of the control group. ResultsIn 6 patients the irritative zone initiating SBS was located in the frontal lobe, in 3 patients in the temporal lobe and in 1 patient in the region surrounding the right central sulcus. All patients demonstrated significantly altered SC in brain lobes where the irritative zone triggering SBS was located (p ≤ 0.05). Seven out of 10 patients demonstrated SC alterations in tracts connecting brain lobes between the ipsilateral and the contralateral hemisphere (p ≤ 0.05). ConclusionOur data demonstrate that alterations in fiber tracts in irritative zones triggering SBS are not necessarily associated with intracerebral lesions visible in high resolution MRI. Our study gives evidence that diffusion tensor imaging is a promising non-invasive additive tool for intracerebral network analyses even in MRI-negative epilepsy patients.

Pitfalls in the diagnosis of Jeavons syndrome: a study of 32 cases and review of the literature.

Jeavons syndrome (JS) is mainly characterized by eyelid myoclonia with or without absences. It is thought to be underdiagnosed rather than have a rare prevalence. We aimed to investigate the electroclinical features of JS to determine possible factors influencing the diagnosis. We retrospectively identified the medical records of 32 cases (0.55%) from 5,796 patients with epilepsy. The inclusion criteria were: (1) eyelid myoclonia with or without absences; (2) generalized paroxysmal activity on EEG; and (3) discharges triggered by eyelid closure and/or intermittent photic stimulation. Eighteen (56.2%) of the patients were female. The mean age at seizure onset was 8.7±5.3 years and the mean age at admission to hospital was 17.8±10.7 years. A family history of epilepsy was present in 15 (46.8%) patients. Eyelid myoclonias were noticed in six (18.7%) patients by themselves. Based on the analysis of video-EEG recordings, 26 (81.2%) patients were sensitive to eye closure, 22 (68.7%) had photoparoxysmal responses, and 16 (50%) presented with absence seizures. Ten (31.2%) patients had focal epileptic discharges. Eight (25%) patients were on monotherapy. Seven (21.8%) patients achieved seizure freedom. Three patients underwent ketogenic diet therapy, which was effective in two patients. A vagus nerve stimulator was implanted into three patients, one of whom reported seizure reduction. Eyelid myoclonias are the main seizure type of JS but are usually overlooked. The time interval between seizure onset and clinical diagnosis suggests that this syndrome continues to be under-recognized. The genetic heterogeneity and phenotypic variability are likely to be more extensive than currently recognized, making the diagnosis more phalangine. [Published with video sequence].

Novel and de novo point and large microdeletion mutation in PRRT2-related epilepsy.

BackgroundPoint and copy number variant mutations in the PRRT2 gene have been identified in a variety of paroxysmal disorders and different types of epilepsy. In this study, we analyzed the phenotypes and PRRT2‐related mutations in Chinese epilepsy children.MethodsA total of 492 children with epilepsy were analyzed by whole exome sequencing (WES) and low‐coverage massively parallel CNV sequencing (CNV‐seq) to find the single nucleotide variants and copy number variations (CNVs). And quantitative polymerase chain reaction was utilized to verify the CNVs. Their clinical information was followed up.ResultsWe found PRRT2‐related mutations in 19 patients (10 males and nine females, six sporadic cases and 13 family cases). Twelve point mutations, four whole gene deletion, and three 16p11.2 deletions were detected. The clinical features of 39 patients in 19 families included one early childhood myoclonic epilepsy (ECME), one febrile seizure (FS), two infantile convulsions with paroxysmal choreoathetosis (ICCA), six paroxysmal kinesigenic dyskinesias (PKD), 12 benign infantile epilepsy (BIE), and 17 benign familial infantile epilepsy (BFIE). All patients had normal brain MRI. Interictal EEG showed only one patient had generalized polyspike wave and five patients had focal transient discharges. Focal seizures originating in the frontal region were recorded in one patient, two from the temporal region, and two from the occipital region. Most patients were treated effectively with VPA or OXC, and the child with myoclonic seizures was not sensitive to antiepileptic drugs.Conclusion PRRT2 mutations can be inherited or de novo, mainly inherited. The clinical spectrum of PRRT2 mutation includes BIE, BFIE, ICCA, PKD, FS, and ECME. The PRRT2‐related mutations contained point mutation, whole gene deletion and 16p11.2 deletions, and large microdeletion mutations mostly de novo. It is the first report of PRRT2 mutation found in ECME. Our report expands the mutation and clinical spectrum of PRRT2‐related epilepsy.

Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS)

ObjectiveTo summarize and extend the phenotypic characterization of Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome, and to discuss genotype-phenotype correlations.MethodsCollecting clinical information of 17 patients with pathogenic variants in PIGN, PIGA, and PIGT. Genetic studies were performed on all patients.ResultsThere were 7 patients with 15 PIGN mutations (one patient carrying 3 mutations), 8 patients with 8 PIGA mutations, and 2 patients with 5 PIGT mutations (one patient carrying 3 mutations). All patients had epilepsy and developmental delay, with 71% of them showed hypotonia. And among these patients’ various seizure types, the focal seizure was the most common one. Eighty-two percent patients showed a significant relationship between seizures and fever. Serum ALP was elevated in one patient with PIGN mutations and in two patients with PIGA mutations. Brain MRI showed enlarged subarachnoid space in 56% of patients. Some other different characteristics had also been found in our patients: First, atypical absence seizures presented in three patients with PIGN mutations; Second, diffuse slow waves mixed with focal or multifocal discharges of interictal EEG in 88% cases with PIGA-deficient; Third, phenotypes of seven out of eight patients with PIGA mutations were difficult to be classified as severe or less severe group; Last, mild neurological symptoms and developmental status rather than severe conditions occurred in one patient with PIGT mutations.ConclusionWith epilepsy, developmental delay, and/or hypotonia as common features, the knowledge of MCAHS in terms of phenotype and genotype has been expanded. In cases with PIGN-deficient, we expanded the types of atypical absence seizures, and described one patient with elevated serum ALP. Focal seizures with diffuse slow waves mixed with focal or multifocal discharges on EEG rather than infantile spasms with hypsarrhythmia, which as previously reported were often seen in our patients with PIGA mutations. The classifications of phenotypes caused by PIGA mutations should be more continuous than discrete. The mild phenotype of one patient with PIGT mutations expanded the clinical presentation of MCAHS3.

The use of hepcidin and presepsin in diagnosis of neonatal sepsis and its neurological sequelae in a tertiary neonatal intensive care unit, Assiut, Egypt

Background Neonatal sepsis (NS) is a common neonatal disorder associated with high mortality and morbidity. Objective The present work aims to assess diagnostic value of hepcidin and presepsin in NS detection and their roles in associated morbidity (especially neurological defects) and mortality. Patients and methods A case–control study was conducted at the neonatal intensive care unit of University Children’s Hospital, Assiut, Egypt, in the period between June 2018 and June 2019. A total of 120 neonates with NS and 40 healthy neonates as control group were enrolled. Neonates were subjected to full history taking and thorough clinical evaluation. Blood picture, C-reactive protein (CRP), blood culture, and hepcidin and presepsin serum levels were measured. Only survivors were subjected to electroencephalography (EEG) and brain computed tomography (CT) evaluations. Results Neonates in NS group had significantly higher CRP, as well as hepcidin and presepsin serum levels versus control. Hepcidin and presepsin were significantly higher among nonsurvivors versus survivors and in neonates with neurological deficits versus neonates without neurological deficit. Sensitivity and specificity were 88.33 and 82.50%, respectively, for CRP; 93.33 and 90.00%, respectively, for hepcidin; and 91.67 and 90.00%, respectively, for presepsin. Of NS group, 66.7% had late-onset sepsis, 20.0% had neurological deficits, and 45.0% were survivors. Among survivors, the most frequent findings in EEG were focal epileptic discharge (57.4%) followed by continuous normal voltage (46.3%), and generalized periodic discharge with triphasic waves (42.6%), whereas in CT, the most frequent findings were mild hypoxia (37.0%) followed by periventricular hypoxia (33.3%). Conclusions Hepcidin and presepsin have an important role in prediction and diagnosis of NS with neurological sequelae and death. Moreover, brain CT and EEG must be performed in all survivor neonates following NS.

Novel and de novo mutation of PCDH19 in Girls Clustering Epilepsy.

Background PCDH19 has become the second most relevant gene in epilepsy after SCN1A. Seizures often provoked by fever.MethodsWe screened 152 children with fever‐sensitive epilepsy for gene detection. Their clinical information was followed up.ResultsWe found eight PCDH19 point mutations (four novel and four reported) and one whole gene deletion in 10 female probands (seven sporadic cases and three family cases) who also had cluster seizures. The common clinical features of 16 patients in 10 families included fever‐sensitive and cluster seizures, mainly focal or tonic‐clonic seizures, and absence of status epilepticus, normal intelligence, or mild‐to‐moderate cognitive impairment, the onset age ranges from 5 months to 20 years. Only four patients had multiple or focal transient discharges in interictal EEG. Focal seizures originating in the frontal region were recorded in four patients, two from the parietal region, and one from the occipital region.Conclusion PCDH19 mutation can be inherited or de novo. The clinical spectrum of PCDH19 mutation includes PCDH19 Girls Clustering Epilepsy with or without mental retardation, psychosis, and asymptomatic male. The onset age of PCDH19 Girls Clustering Epilepsy can range from infancy to adulthood. Sisters in the same family may be sensitive to the same antiepileptic drugs. And our report expands the mutation spectrum of PCDH19 Girls Clustering Epilepsy.

Interictal epileptiform activity in sleep and wakefulness in patients with temporal lobe epilepsy

Sleep is an important activator of epileptiform activity, with epileptiform discharge (ED) probability varying among sleep stages. The aim of our study was to analyze the association between epileptiform activity and sleep stages or wakefulness in adults with temporal discharges. We analyzed 32 long-term overnight EEG recordings. All focal discharges were marked, and the entire sleep was staged. Absolute general epileptiform discharge index (EDI), defined as a ratio of total ED number to the full recording time in hours, as well as absolute EDIs for REM, N1, N2 and N3 stages were calculated. The majority of patients (28) had the highest EDI in N3. EDI increased significantly while sleep progressed to deeper stages, reaching its peak in N3. In REM sleep, EDI sharply declined (p < 0.01) reaching the levels of wakefulness. Increasing synchronization of cortical neurons is thought to be the major mechanism of EDI rise in NREM sleep. Hence, N3 seems to be the most sensitive stage to capture EDs, which highlights the importance of deep sleep recording in patients with temporal epilepsy.

Clinical characteristics of PCDH19-female limited epilepsy

Objective: To analyze the clinical characteristics of patients with PCDH19-female limited epilepsy (PCDH19-FE). Methods: The clinical data of 60 female epilepsy patients with PCDH19 gene heterozygous variations at the Department of Pediatrics, Peking University First Hospital from October 2007 to December 2018 were collected and analyzed retrospectively, their clinical manifestations, accessory examination and follow-up treatment were summarized. Results: Data of a total of 60 cases of PCDH19-FE were collected. The seizure onset occurred between 4 and 42 months of age (median: 11 months of age). Focal seizures occurred in 47 patients (78%), generalized tonic-clonic seizures (GTCS) occurred in 30 patients (50%), and other rare types of seizures included atypical absence, myoclonic, clonic, tonic, and atonic seizures. Two or more seizures types existed in 24 patients (40%), and seven patients (12%) had attacks of status epilepticus. Sensitivity to fever was observed in 47 out of them (78%) and clustering of seizures as found in all patients. During the interictal phase, focal discharges were monitored in 22 cases (22/45, 49%), multifocal discharges in 12 cases (12/45, 27%), widely discharging in 2 cases (4%), and both focal and widely discharging in 9 cases (20%). Clinical seizures were detected in 30 patients during the electroencephalogram (EEG) recording, including focal seizures in 22 cases, GTCS seizures in 8 cases, tonic seizure in three cases, myoclonic seizure followed by GTCS in one case, and two types of seizures in four cases. Before seizure onset, 57 patients had normal development and three patients had delayed language development. After seizure onset, varied degrees of intelligence disability were present in 38 cases (63%), language delay in 36 cases (60%), and gait instability in 10 cases (17%). Autistic features occurred in 17 cases (28%); and other behavioral problems like learning difficulties, personality, or emotional disorders existed in 33 cases (55%). Age at last follow-up ranged from one year and 3 months to 22 years and 3 months of age, 17 patients (28%) were seizure-free for more than 2 years (5 to 22 years at the last follow-up). The efficiency of antiepileptic drugs were 65% (33/51) in sodium valproate, 63% (27/43) in levetiracetam and 59% (20/34) in topiramate. Conclusions: The clinical features of PCDH19-FE are characterized by clustering of seizures, focal seizures in most cases, sensitivity to fever mostly, focal discharges principally in EEG, varied degrees of intellectual disability or movement disorder, combined with autism spectrum disorders in partial and high efficiency in sodium valproate or levetiracetam treatment.

Clinical and genetic characteristics of focal epilepsy in children caused by GATOR1 complex gene variation

Objective: To summarize the clinical and genetic characteristics of focal epilepsy in children caused by GATOR1 complex gene variation. Methods: The clinical data, gene variation and treatment outcome of 12 children with focal epilepsy caused by GATOR1 complex gene variation admitted to Beijing Children's Hospital Affiliated to Capital Medical University from June 2016 to October 2018 were retrospectively analyzed. Results: There were 7 males and 5 females in 12 cases. The epilepsy onset age was 5.5 (3.0, 12.0) months, and from 11 days to 16 months of age. The epileptic seizure types were all focal motor seizures, and one case combined with epileptic spasms. The frequency of seizures in all patients was more than one time per day. Seven cases had frontal lobe epilepsy and two cases had lateral temporal lobe epilepsy. One case had a family history of febrile seizures and two had a family history of suspicious epilepsy. Epileptic form discharges were observed in 9 patients during the interictal phase by electroencephalograms (EEG), and all of them were focal discharges. Eight cases had clinical seizures detected by EEG, in 4 of whom the seizures were originated in frontal region. There were no abnormalities in brain magnetic resonance imaging in 11 cases whereas 1 case had malformation of cortical development of left frontal lobe. Eight patients had DEPDC5 gene variation, one had NPRL2 gene variation, three had NPRL3 gene variation. One case had de novo variation and the other 11 had hereditary variation. There were 11 types of gene variation, including 5 nonsense variations, 3 missense variations, 2 frame shift variations and 1 in frame deletion variation. There was no clear relationship between the clinical phenotype and the genotype. During the follow-up period from 6 months to 2 years and 6 months, 6 cases had seizure control, 3 of them were controlled by oxcarbazepine. The other 6 cases had drug-refractory epilepsy, 2 of them failed with vagus nerve stimulation and ketogenic dietary therapy as well, meanwhile combined with mental retardation. Conclusions: GATOR1 complex gene variation can lead to genetic focal epilepsy, which usually has early onset with frequent seizures. Most of the patients have focal epileptic form discharges on EEG, and there is usually no structural lesion in brain imaging. Most of the patients have hereditary loss-of-function variations. Approximately half of cases are drug-resistant epilepsy.

Atrial fibrillation and its arrhythmogenesis associated with insulin resistance

BackgroundInsulin resistance (IR) is considered as a risk factor for atrial fibrillation (AF) even before diabetes develops. The pathophysiology and underlying mechanism are largely unclear.MethodsWe investigated the corresponding mechanism in two IR models of rats fed 15-week high-fat (HFa) and high-fructose/cholesterol (HFr) diets. AF was evaluated and induced by burst atrial pacing. Isolated atrial myocytes were used for whole-cell patch clamp and calcium assessment. Ex vivo whole heart was used for optical mapping. Western blot and immunofluorescence were used for quantitative protein evaluation.ResultsBoth HFa and HFr rat atria were vulnerable to AF evaluated by burst atrial pacing. Isolated atrial myocytes from HFa and HFr rats revealed significantly increased sarcoplasmic reticulum calcium content and diastolic calcium sparks. Whole-heart mapping showed prolonged calcium transient duration, conduction velocity reduction, and repetitive ectopic focal discharge in HFa and HFr atria. Protein analysis revealed increased TGF-β1 and collagen expression; increased superoxide production; abnormal upregulation of calcium-homeostasis-related proteins, including oxidized CaMKIIδ, phosphorylated-phospholamban, phosphorylated-RyR-2, and sodium-calcium exchanger; and increased Rac1 activity in both HFa and HFr atria. We observed that inhibition of CaMKII suppressed AF in both HF and HFr diet-fed rats. In vitro palmitate-induced IR neonatal cardiomyocytes and atrial fibroblasts expressed significantly more TGF-β1 than did controls, suggesting paracrine and autocrine effects on both myocytes and fibroblasts.ConclusionsIR engenders both atrial structural remodeling and abnormal intracellular calcium homeostasis, contributing to increased AF susceptibility. The inhibition of CaMKII may be a potential therapeutic target for AF in insulin resistance.

Epilepsy in neurofibromatosis type 1: Diffuse cerebral dysfunction?

IntroductionNeurofibromatosis type 1 (NF1) is accompanied by epileptic seizures in 4–7% of patients. We examined clinical, electrophysiological, and radiological features associated with epilepsy in our NF1 series in order to identify risk factors. MethodsWe reviewed data of 641 pediatric patients with NF1 diagnosis according to National Institutes of Health (NIH) criteria in Hacettepe University records from January 2008–August 2018. Demographic features, NF1-related clinical and imaging characteristics, age at onset of epilepsy, seizure semiology, and frequency, electroencephalogram (EEG) findings, and response to treatment were noted. ResultsTwenty-six patients with NF1, 15 male, 11 female, had epilepsy. Age at seizure onset was 6 months to 13 years. Seizure semiology was focal with impaired awareness (n = 9, 34%), focal aware motor (n = 2, 8%), focal to bilateral tonic–clonic (n = 3, 12%), generalized tonic–clonic (n = 7, 28%), absence (n = 3, 12%), infantile spasms (n = 1), and unclassified type (n = 1). None had a history of status epilepticus. The EEG findings were normal for age in ten patients (38%). Others had focal (n = 8, 30%), generalized (n = 7, 27%), or multifocal (n = 1, 4%) discharges. On brain magnetic resonance imaging (MRI) signal intensity changes typical for NF1 (neurofibromatosis bright objects, NBOs) were the most common finding (80%), followed by normal MRI (20%). There was no relation between the localization of NBOs and discharges on EEG. Seventeen patients (65%) were seizure-free at the time of the study; 11 of them still under medication including four on multiple antiepileptic drugs. The rate of learning problems and NBO were significantly higher in patients with NF1 with epilepsy compared to those without. DiscussionEpilepsy in NF1 is associated with relatively infrequent seizures and good response to treatment. Learning disorders are markedly frequent in this group, irrespective of the severity of epilepsy. The absence of correlation between the localizations of epileptiform discharges and lesions on MRI support the role of cellular or synaptic mechanisms rather than structural causes in the pathogenesis of epilepsy.

Encefalitis por virus influenza B en un paciente adulto. Reporte de caso

Neurological manifestations associated with influenza virus infection include encephalitis, encephalopathy, acute necrotizing encephalitis, transverse myelitis, acute disseminated encephalomyelitis, mild encephalitis with reversible splenial syndrome (MERS), and Guillaín Barré syndrome. We report a 16-year-old female who was admitted at our emergency department with seizures, confusion, nystagmus and motor clumsiness five days after an upper a respiratory tract infection. Influenza type B virus infection was confirmed by chain polymerase reaction analysis. The initial electroencephalogram demonstrated a pattern of global slowness without epileptic discharges. One week later, it showed a progression to slow-wave focal bilateral discharges at both temporal and occipital lobes. The patient had a favorable evolution and was discharged 19 days after admission with phenytoin to prevent seizures.

Profile of intractable epilepsy in a tertiary referral center in upper Assam

Introduction: Epilepsy is a common and diverse disorder with many different causes.Outcomes are varied with 60—70% of newly diagnosed people rapidly entering remission after starting treatment, and 20—30% developing a drug-resistant epilepsy with consequent clinical and psychosocial distress. Methods: It is a Descriptive Cross-sectional study which was conducted in Assam Medical College and Hospital, Dibrugarh from April 2014 to April 2016. A total of 42 patients of IE attending the neurology, paediatrics and medicine department were included in the study. Results: Forty-two patients (males 24, females 18) with intractable epilepsy were included for the study. Maximum patients were in between 20-40 years of age (42.9%) and their mean duration of epilepsy was13.2 ± 7.13 years. The seizure frequency varied from once every month to more than 200 per (mean 26.2 ± 24.17) month. Twenty-six patients (61.9%) had partial seizures, 8 (19.1%) patients had generalized seizures and 8(19.1%) had multiple seizure semiology. Thirty-six patients had risk factors of intractable epilepsy. Seven (16.6%) patients were having family history of epilepsy and 4(9.5%) patients had history of febrile seizures. Mesial temporal lobe sclerosis (MTLS) and birth hypoxia are the two major risk factors for intractable epilepsy. EEG was abnormal in 66.7% cases, with generalized background slowing in 19.1%, focal slowing in 14.2%, generalized epileptiform discharges in 9.5% and focal epileptiform discharges in 23.8%. CT brain was abnormal in 18(42.9%) patients. MRI brains were abnormal in 25 out-off 36 patients (69.4%). Carbamazepine was the most commonly used drug (57.1%) followed by clobazam (47.6%). Phenytoin, levetiracetum, Phenobarbitone, oxcarbazepine, zonisemide, lacosemide are the other AEDs used in combination. Conclusion: This study showed, patients with partial seizures, birth hypoxia, history of febrile seizures, family history of seizures, structural brain abnormalities and background EEG abnormalities were the most common risk factors for development of intractable epilepsy.

Photosensitive tonic-clonic seizures:a continuum between focal and generalized seizures

To investigate whether the tonic-clonic seizure (TCS) induced by intermittent photic stimulation (IPS)was generalized tonic-clonic seizure (GTCS)or partial secondarily tonic-clonic seizure (PGTCS),and to analyze the relationship between them. Video-electroencephalogram (VEEG)database of Peking University First Hospital from March 2010 to October 2018 were reviewed. Fifteen cases with idiopathic epilepsy who had TCS induced by IPS were included in this study, and their clinical and electroencephalogram (EEG)characteristics were retrospectively analyzed. In this study, 4 of the 15 cases were boys and 11 were girls. The age of seizure onset ranged from 1 to 13 years. According to the medical records: 12 cases were considered as GTCS,while the remaining 3 cases were considered as PGTCS. The age at VEEG monitoring ranged from 2.5 to 16.0 years. All backgrounds of the VEEG were normal. Interictal discharges:generalized discharges in 11 cases, of which 4 cases coexisted with posterior discharges, 2 cases coexisted with Rolandic discharges, the other 5 cases merely had generalized discharges; merely focal discharges in two cases, one in the Rolandic area and the other in the posterior area; no interictal discharge in the remaining 2 cases. IPS induced photoparoxysmal response (PPR)results: 2 cases without PPR,the remaining 13 cases with PPR of generalized discharges, and 6 of the 13 cases coexisted with posterior discharges. IPS induced photoconvulsive response (PCR)results: GTCS in one case (contradictory to medical history),PGTCS in 11 cases (consistent with medical history),and GTCS and PGTCS hardly to distinguish in the remaining 3 cases. Of the three conditions above, there were generalized myoclonic seizures induced by IPS before TCS in 7 cases. The medical history was unreliable in determining whether TCS was generalized or focal. Myoclonic seizures can coexist with PGTCS, and sometimes GTCS was indistinguishable from PGTCS, indicating that the dichotomy of seizure types need to be improved. Photosensitive TCS should be regarded as a continuum between focal and generalized seizures.

Triggering Factors for Breakthrough Seizures among Epileptic Patients. Cross Sectional Study in Epileptic Patients Attending Epilepsy Clinic Mansoura University Hospital, Egypt

Background: The prevalence of breakthrough seizures in persons with epilepsy is very high in developing countries. Consequently, patients and physicians should be aware of the possible factors that may cause breakthrough seizures.
 Objective: The aim of our study is to determine the possible factors that may be a precipitating cause for breakthrough seizures in patients with epilepsy.
 Methods: This cross-sectional study included 100 persons with epilepsy with idiopathic epilepsy receiving antiepileptic drugs (AEDs). They were divided into two groups. Group 1 included 50 persons with epilepsy with a history of recent breakthrough seizures. Group 2 included 50 persons with epilepsy who had not experienced any recent breakthrough seizures. Patients were subjected to a thorough questionnaire addressing precipitating factors. All participants were subjected to an electroencephalogram (EEG) and the Morisky Medication Adherence Scale (MMAS).
 Results: There was no significant differences between group 1 and group 2 regarding age, sex, age of onset of epilepsy, occupation and marital status (P value range 0.5 – 0.2). The patients in group 1 were found to have longer durations of epilepsy, lower adherence to AEDs (P = 0.001), more missed doses of AEDs (P = 0.0001), more side effects of AEDs (P = 0.0005), more sleep deprivation, lower level of AEDs (P = 0.0006), more frequently on AED polytherapy (P = 0.0002), and more flickering lights (P = 0.04) than the participants in group 2. In terms of the EEG, group 1 showed a higher percentage of abnormal EEGs and more frequent focal epileptiform discharges (P = 0.003). Also, pathological findings in MRI brain were associated with higher breakthrough seizures (P = 0.005). No significant difference was found in both group1 and group 2 regarding emotional stress (P = 0.55), substitution of brand AEDs by generic one (P = 0.83), concurrent illness (P = 1), or the use of non AEDs (P = 0.79).
 Conclusion: The precipitating factors of breakthrough seizures are multifactorial and it is very important to educate patients about these precipitating factors to achieve better control of epilepsy.

Periodic focal epileptiform discharges

ObjectiveTo report intraoperative periodic focal epileptiform discharges (PFEDs) during awake craniotomy using high-density electrocorticography (HD-ECoG). MethodsWe retrospectively analyzed 81 patients undergoing awake craniotomy between 9/29/2016 and 7/5/2018. Intraoperative HD-ECoG was performed with direct electrocortical stimulation (DECS) for functional brain mapping. Real-time interpretation was performed and compared to scalp EEG when performed. Perioperative seizures, surgical complications, and characteristics of PFEDs were assessed. Results69/81 patients (mean age 48.5 years) underwent awake surgery; 55 operated for brain tumor, 11 for epilepsy and 3 for cavernomas. A focal abnormality on brain MRI was present in 63/69 (91.3%) patients. 43/69 (62.3%) patients had seizures preoperatively, 4/69 (5.7%) had seizures during DECS. PFEDs were identified in 11 patients (15.9%); 2 on depth recording and 9 during intraoperative HD-ECoG. 32 patients (46.3%) had preoperative EEG. HD-ECoG detected more epileptiform discharges (EDs) than standard EEG (32/43; 74.4% vs 9/32; 28.1%) (p = <0.001). Of 9/43 patients with PFEDs on HD-ECoG, 7 patients also had scalp EEG but only one case had EDs (p = 0.02), and 0/32 had periodic EDs. ConclusionsIntraoperative PFEDs are novel, highly focal EDs approximating a single gyrus. In patients with brain tumors, PFEDs did not demonstrate a relationship to pre-operative seizures though has similarities to other common waveforms in patients with epilepsy. SignificancePFEDs expand our understanding of the interictal-ictal continuum and highlight improved temporo-spatial information obtained from increasing sensor density during intracranial EEG recording.

Shall we treat patients with benign epileptiform discharges of childhood without epileptic seizures?

Benign epileptiform discharges of childhood are age-dependent electroencephalogram patterns associated with idiopathic benign focal epilepsy. Multiple studies have demonstrated that focal epileptiform discharges can be registered in patients without any clinical manifestations of epilepsy. Long-term follow-up of clinically healthy children with benign epileptiform discharges of childhood on electroencephalogram demonstrated that 14 % of them developed epileptic seizures with age and 50 % developed various cognitive and behavioral disorders. The question of whether or not to treat such patients (with benign epileptiform discharges of childhood on electroencephalogram but without epileptic seizure) is still being widely discussed. Individual decision making with the consideration of potential risks and benefits for a patient is preferable in this case. Valproic acid is the drug of first choice in these patients.

Clinical features of 19 children with Bickerstaff brainstem encephalitis

Objective: To summarize the clinical features of Bickerstaff brainstem encephalitis (BBE) in children. Methods: In this retrospective study, data of 19 patients with BBE (11 males and 8 females) were collected from Department of Neurology, Beijing Children's Hospital from October 2015 to January 2018. The clinical features, treatment and prognosis were analyzed. Results: The onset age of BBE ranged from 1 year and 8 months to 12 years and 11 months. There were 18 cases with preceding infection. The most common infection was upper respiratory tract infection (9 cases), followed by simple fever (5 cases). The most common initial neurological symptoms were lethargy or disturbance of consciousness (8 cases), followed by limb weakness (5 cases). There were 6 cases of simple BBE and 13 cases of BBE overlapping Guillain-Barré syndrome (GBS). Besides the characteristic triad of altered mental status, ataxia, and ophthalmoplegia, there were other symptoms including convulsion (5 cases), diplopia (3 cases), nystagmus (7 cases), facial muscular weakness (7 cases),bulbar palsy (13 cases) and autonomic nerve symptoms (9 cases). Hypo or areflexia was seen in 16 cases. Positive Babinski's signs were seen in 8 cases. Hyponatremia was present in 10 cases in whom 4 showed severe hyponatremia. Albumin-cytological dissociation of cerebrospinal fluid was seen in 10 cases. The autoimmune antibodies were examined in all 19 patients. Anti-ganglioside antibodies including anti-GM1 IgG antibody was positive in 2 patients and one of whom was also found with positive anti-GD1b IgG antibody. Anti-GQ1b IgG antibody was present in 2 patients. Electromyography was performed in 14 cases and 8 cases, who were all BBE overlapping GBS, showed neurological damage. A total of 16 cases were monitored by video electroencephalography and 8 cases showed slow waves of background. In addition to, interictal focal discharge was detected in 2 cases. T2 fluid-attenuated inversion recovery (FLAIR) sequence abnormal signals were detected in 3 of 18 cases performed brain magnetic resonance imaging (MRI), and lesions involved with brainstem, basal ganglia, thalamus, cerebellum, corpus callosum and cerebral cortex. Lesions involved cervical and thoracic spinal cord were found in 1 out of 11 cases for whom spinal cord MRI was performed. All of the 4 cases who underwent enhanced MRI of spinal had partial nerve roots enhancement. All of the 19 patients received 1 to 2 courses of intravenous immunoglobulin therapy, and 2 cases also received plasma exchange. Fifteen cases received steroid therapy. The following-up period ranged from 3 months to 2.5 years. Two cases were lost to follow-up. Twelve cases achieved a full recovery within 3 months. Three cases recovered within 6 months. One case still had slight limb weakness and ataxia after 1 year and 8 months of follow-up, and another case had left autonomic nerve symptoms in the follow-up of 2 years and 3 months. Both of them were BBE overlapping GBS. Conclusions: Children's BBE is similar to that in adults, and is frequently found overlapped with GBS. Furthermore, it is sometimes accompanied by central nervous system demyelination disease. The antiganglioside antibodies are not often detectable. Immunoglobulin therapy could usually achieve good response. The prognosis of simple BBE is good in most situations. For BBE overlapping GBS, the more severe the limb weakness during the peak of disease is, the slower the recovery would be.