Familial occurrence of seizure disorders across MRI defined structural focal epilepsy etiology.

BACKGROUND: Previous studies have established familial occurrence of epilepsy and seizure disorders and early age of epilepsy onset as predictors of genetic epilepsy, but have not evaluated the rate of their occurrence in patients with different epilepsy etiology. Our study determines the distribution of familial occurrence and age of epilepsy onset across structural focal epilepsy (FE) etiology in a large FE cohort. METHODS: Records of 1354 consecutive patients evaluated for epilepsy and seizure disorders in The Neurology Clinic, University Clinical Center of Serbia from 2008 to 2019 were screened for FE. Structural etiology, lobar diagnosis, familial occurrence, and age at epilepsy onset were determined. Patients with a. nonlesional focal epilepsy (NLFE), b. hippocampal sclerosis (HS) and c. congenital or perinatal etiology (CPE) were classified as NAFE, while patients with an identified acquired focal epilepsy (AFE) constituted the control group. RESULTS: We identified 965 patients with FE, 329 (34.1 %) with NLFE, 213 (22.1 %) with HS, 174 (18.0 %) with CPE and 249 (25.8 %) with AFE. Familial occurrence was identified in 160 (16.6 %), 19.1 % of patients with NAFE and 9.2 % of AFE (p = 0.003). Patients with NAFE had a younger age of epilepsy onset (13 vs. 18 years, p < 0.001). The highest proportion of familial occurrence was found in patients with NLFE (23.7 %), while the youngest median age of epilepsy onset was identified in patients with HS (12 years) and CPE (11 years). CONCLUSION: Patients with NAFE frequently have familial occurrence of epilepsy and have an earlier age of epilepsy onset than patients with AFE.

[Benefit of surgery in a case of negative motor focal epileptic seizures secondary to parietal cortical dysplasia]. / Beneficio de la cirugía en un caso de crisis epilépticas focales motoras negativas secundarias a displasia cortical parietal.

Focal atonic seizures are recognized rarely as ictal phenomena, they can correspond to both generalized epilepsy and focal epilepsy. The areas of the brain involved in the management of this type of seizure are: the negative motor area and the primary motor and primary somatosensory cortices, although the neurophysiology that generates them is still unclear. We present the case of a patient with focal atonic seizures in the left upper limb, refractory to drug treatment. Neuroimaging was performed, a parietal cortical lesion was diagnosed. A scalp Video EEG and then a Stereo EEG was performed, defining the epileptogenic area and its relationship with eloquent areas. Surgical resection of the lesion was performed, achieving complete seizure control.

Las crisis atónicas focales son poco reconocidas como fenómenos ictales, pueden corresponder tanto a una epilepsia generalizada como a una epilepsia focal. Las áreas del cerebro implicadas en la gestión de este tipo de crisis son: el área motora negativa y las cortezas motora primaria y somatosensitiva primaria, aunque aún la neurofisiología que las genera no está aclarada. Presentamos el caso de un paciente con crisis atónicas focales farmacorresistentes en miembro superior izquierdo. Se realizó resonancia de cerebro con diagnóstico de displasia cortical parietal, se monitoreó con video EEG de scalp y luego a video EEG con electrodos profundos. Se definieron el área epileptógena y su relación con áreas elocuentes, se realizó resección quirúrgica de la lesión, logrando el control completo de las crisis.

Longitudinal evolution of electroencephalogram (EEG): Findings over five years of follow-up in children with Zika-related microcephaly from the Microcephaly Epidemic Research Group Pediatric Cohort (2015-2020).

OBJECTIVE: To assess the longitudinal evolution of EEG findings in children with Zika related-microcephaly (ZRM) and to evaluate the associations of these patterns with the children's clinical and neuroimaging characteristics. METHODS: As part of the follow-up of the Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC) in Recife, Brazil, we performed serial EEG recordings in a subgroup of children with ZRM to evaluate changes in background rhythms and epileptiform activity (EA). Latent class analysis was used to identify patterns in the evolution of EA over time; clinical and neuroimaging findings were compared across the identified groups. RESULTS: Out of the 72 children with ZRM who were evaluated during 190 EEGs/videoEEGs, all participants presented with abnormal background activity, 37.5% presented with an alpha-theta rhythmic activity, and 25% presented with sleep spindles, which were less commonly observed in children with epilepsy. EA changed over time in 79.2% of children, and three distinct trajectories were identified: (i) multifocal EA over time, (ii) no discharges/focal EA evolving to focal/multifocal EA, and (iii) focal/multifocal EA evolving to epileptic encephalopathy patterns (e.g., hypsarrhythmia or continuous EA in sleep). The multifocal EA over time trajectory was associated with periventricular and thalamus/basal ganglia calcifications, brainstem and corpus callosum atrophy and had less focal epilepsy, whereas the children in the trajectory which evolved to epileptic encephalopathy patterns had more frequently focal epilepsy. SIGNIFICANCE: These findings suggest that, in most children with ZRM, trajectories of changes in EA can be identified and associated with neuroimaging and clinical features.

Epilepsy in hypothalamic hamartomas: semiology spectrum and predictor analyses of 78 patients.

OBJECTIVE: To assess seizure semiology and disease evolution in a large number of hypothalamic hamartoma (HH) patients. METHODS: Seizure semiology and associated medical records for 78 patients with HH-related epilepsy were retrospectively reviewed. Potential predictors of seizure types were assessed through univariate and binary logistic regression analyses. RESULTS: 57 (73.1%) patients presented with gelastic seizures at the onset of epilepsy, of whole 39 (68.4%) experienced additional seizure types with a mean latency interval of 4.59 years. Automatism, version, and sGTCs were increasingly common with disease evolution. The intraventricular size of HH was significantly negatively correlated with the disease evolution interval (r = -0.445, p = 0.009). A significantly higher rate of patients with automatism in the DF-II group relative to the DF-III group was found in both χ2 (X = 6.07, p = 0.014) and logistic regression analyses (B = 3.196, p = 0.020). INTERPRETATION: Gelastic seizures are the most common initial seizure type in HH patients, but variable semiologies occur with disease evolution. The intraventricular HH lesion size is an important determinant of epilepsy evolution. DF-II HH lesions contribute to a higher chance of automatism evolution. The present study furthers our understanding of the dynamic organization of the seizure network affected by HH.

Epileptic nystagmus as clinical manifestation of self-limited focal epilepsy: Rethinking etiology and prognostic value and literature review.

Epileptic nystagmus (EN) is an uncommon ictal clinical manifestation characterized by rapid, repetitive eyeballs movements. Few cases of EN have been reported and, in most cases, electro-clinical correlation showed a focal EEG activity, mainly in the occipital and temporo-occipital areas. Although EN occurs both in idiopathic and non-idiopathic epilepsy, the most frequent cause appears to be inborn or acquired alteration of brain structures. We report of a 12-year-old girl with EN as ictal manifestation of self-limited focal seizures. We described clinical manifestations, electroencephalographic features, treatment, and follow-up, presenting the ictal video-EEG phenomenon. Alongside, we reviewed the reported clinical features of the few pediatric cases (seven patients) with idiopathic epileptic nystagmus through a systematic literature review. Isolated Epileptic Nystagmus (IEN) is much rarer than EN, as it is more frequently associated with other types of seizures, and can be idiopathic, especially in children. Epilepsy prognosis is usually favorable with appropriate treatment, and ASM discontinuation seems to be successful after few years of treatment.

Stereo-EEG Evaluation and Surgical Treatment in Patients With Drug-Resistant Focal Epilepsy Associated With Nodular Heterotopia.

PURPOSE: Nodular heterotopia (NH) is a common cause of drug-resistant epilepsy. Only limited studies detail the treatment of NH with laser interstitial thermal therapy and none analyze the relation between epileptogenicity and NH location. METHODS: We retrospectively studied nine patients with drug-resistant epilepsy and NH who underwent stereoelectroencephalography and subsequent epilepsy surgery. Nodular heterotopia in the frontal lobes or along the bodies of the lateral ventricles was classified as anterior NH. Nodular heterotopia in the trigones, temporal or occipital horns, or temporal lobes was classified as posterior NH. Nodular heterotopia in both anterior and posterior locations was classified as diffuse NH. Interictal and ictal stereoelectroencephalography were analyzed, and patients were followed postoperatively to assess outcomes. RESULTS: Of the six patients who underwent nine laser interstitial thermal therapy procedures either in isolation or in combination with other surgical therapies, four patients were Engel Ia, one was Engel IIb, and one was Engel IIIa, with an average follow-up of 22.8 months. All patients with posterior NH had interictal epileptiform abnormalities and seizures originating from the posterior NH. None of the patients with anterior NH had epileptiform activity recorded from their NH. CONCLUSION: Laser interstitial thermal therapy alone or in combination with other surgical therapies is an effective treatment in those with drug-resistant epilepsy because of NH, even in those with extensive NH and broad seizure onset. We observed a trend suggesting that posterior NH are more likely to be epileptogenic compared with anterior NH and recommend that in patients with anterior NH, alternative epilepsy etiologies and stereoelectroencephalography implantation strategies be considered.

Repeated long sessions of transcranial direct current stimulation reduces seizure frequency in patients with refractory focal epilepsy: An open-label extension study.

OBJECTIVE: Although clinical trials have demonstrated that cathodal transcranial direct current stimulation (tDCS) is effective for seizure reduction, its long-term efficacy is unknown. This study aimed to determine the long-term effects of repeated cathodal long tDCS sessions on seizure suppression in patients with refractory epilepsy. METHODS: Patients were recruited to participate in an extended phase of a previous randomized, double-blind, sham-controlled, three-arm, parallel, multicenter study on tDCS. The patients were divided into an active tDCS group (20 min of tDCS per day) and an intensified tDCS group (2 × 20 min of tDCS per day). Each tDCS session lasted 2 weeks and the patients underwent repeated sessions at intervals of 2 to 6 months. The cathode was placed over the epileptogenic focus with the current intensity set as 2 mA. Seizure frequency reduction from baseline was analyzed using the Wilcoxon signed-rank test for two related samples. A generalized estimating equation model was used to estimate group, time, and interaction effects. RESULTS: Among the 19 patients who participated in the extended phase, 11 were in the active tDCS group and underwent 2-16 active tDCS sessions, and eight were in the intensified tDCS group and underwent 3-11 intensified tDCS sessions. Seizure reduction was significant from the first to the seventh follow-up, with a median seizure frequency reduction of 41.7%-83.3% (p < 0.05). Compared to the regular tDCS protocol, each intensified tDCS session substantially decreased seizure frequency by 0.3680 (p < 0.05). One patient experienced an increase of 8.5%-232.8% in the total number of seizures during three treatment sessions and follow-ups. CONCLUSION: Repeated long cathodal tDCS sessions yielded significant and progressive long-term seizure reductions in patients with refractory focal epilepsy.

Mesenchymal stem cell therapy for focal epilepsy: A systematic review of preclinical models and clinical studies.

Drug-resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE. Medline, Ovid EMBASE, Scopus, and the Cochrane Databases were searched electronically from their dates of inception to November 2021 using the following keywords: (("mesenchymal") AND ("stem cell")) AND (("epilepsy") OR ("convulsion") OR ("seizures")). This review followed Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. The initial query identified 488 studies representing 323 unique manuscripts. After application of selection criteria, 15 studies were included in this systematic review; 11 were preclinical studies and 4 were clinical studies. All preclinical studies were performed in rodents and all clinical studies were phase 1 trials. Thus far, therapy with MSCs appears to be safe for use in humans, as no severe adverse events related directly to the therapy were reported. Furthermore, MSC therapy appears to provide a statistically significant clinical benefit by reducing the seizure burden of patients, reducing the electrophysiological biomarkers of epilepsy, and improving their comorbidities, such as depression and anxiety. In addition, animal studies reveal that the therapy exerts its effect by reducing aberrant mossy fiber sprouting (reduce excitatory pathways) and increasing γ-aminobutyric acid (GABA)ergic interneurons (increase inhibitory pathways). Both preclinical and clinical studies have shown MSC therapy to be safe and preliminary effective, thus warranting further studies to investigate its therapeutic potential.

Brain tumor-related epilepsy and risk factors for metastatic brain tumors: analysis of 601 consecutive cases providing real-world data.

OBJECTIVE: It is necessary to accurately characterize the epidemiology and trends of brain tumor-related epilepsy (BTE) in patients with metastatic brain tumors. This study aimed to determine the incidence of BTE associated with metastatic brain tumors and retrospectively investigate the risk factors for BTE. METHODS: This retrospective analysis included 601 of 631 consecutive patients with metastatic brain tumors who received treatment, including surgery, radiotherapy, and/or other treatments. BTE and the clinical course were examined retrospectively. Logistic regression multivariate analyses were performed to identify risk factors for BTE. RESULTS: BTE was reported in 148 (24.6%) of 601 patients during the entire course. Of these 148 patients, 81 (54.7%) had first-onset epilepsy (13.5% of all patients). Of the 520 cases of nonepileptic onset, 53 were in the prophylactic antiepileptic drug (AED) group. However, 12 of these patients and 55 of the no-prophylactic AED group developed epilepsy during the course of the study. Including these 67 patients, 148 patients were examined as the group of all epilepsy cases during the entire course. In 3 patients, the seizure progressed to status epilepticus. In most patients, the BTE (n = 83, 56.1%) manifested as focal aware seizures. Logistic regression analysis identified young age (p = 0.037), male sex (p = 0.026), breast cancer (p = 0.001), eloquent area (p < 0.001), peritumoral edema (p < 0.001), dissemination (p = 0.013), and maximum tumor volume (p = 0.021) as significant risk factors for BTE. BTE was more common with tumor volumes greater than the cutoff value of 1.92 ml. CONCLUSIONS: BTE appears to be more likely to occur in cases with young age, male sex, breast cancer, tumors involving eloquent areas, brain edema, dissemination, and giant tumors.

Epilepsy Is Heterogeneous in Early-Life Tuberous Sclerosis Complex.

BACKGROUND: Epilepsy in tuberous sclerosis complex (TSC) typically presents with early onset, multiple seizure types, and intractability. However, variability is observed among individuals. Here, detailed individual data on seizure characteristics collected prospectively during early life were used to define epilepsy profiles in this population. METHODS: Children aged zero to 36 months were followed longitudinally. Caregivers kept daily seizure diaries, including onset and daily counts for each seizure type. Patients with >70% seizure diary completion and >365 diary days were included. Developmental outcomes at 36 months were compared between subgroups. RESULTS: Epilepsy was seen in 124 of 156 (79%) participants. Seizure onset occurred from zero to 29.5 months; 93% had onset before age 12 months. Focal seizures and epileptic spasms were most common. Number of seizures (for median 897 days) ranged from 1 to 9128. Hierarchical clustering based on six metrics of seizure burden (age of onset, total seizures, ratio of seizure days to nonseizure days, seizures per seizure day, and worst seven- and 30-day stretches) revealed two distinct groups with broadly favorable and unfavorable epilepsy profiles. Subpopulations within each group showed clinically meaningful differences in seizure burden. Groups with higher seizure burden had worse developmental outcomes at 36 months. CONCLUSIONS: Although epilepsy is highly prevalent in TSC, not all young children with TSC have the same epilepsy profile. At least two phenotypic subpopulations are discernible based on seizure burden. Early and aggressive treatments for epilepsy in TSC may be best leveraged by targeting specific subgroups based on phenotype severity.

[Temporal pole encephalocele, a surgical treatable cause of drug-resistant epilepsy]. / Encefalocele del polo temporal: una causa tratable quirúrgicamente de epilepsia farmacorresistente.

INTRODUCTION: Encephaloceles are herniation of brain parenchyma through a bony skull defect that can cause drug-resistant epilepsy. In these cases, a surgical approach should be considered. CASE REPORT: 38-year-old man with drug-resistant epilepsy and 1.5 T magnetic resonance imaging performed with no relevant findings. After video-electroencephalogram, 3 T magnetic resonance imaging and F-18-fluoro-deoxy-glucose positron emission tomography, a right temporal encephalocele was confirmed. A right temporal polar resection was performed four years ago and the patient remains seizure-free. DISCUSSION: Anterior temporal encephaloceles are an underdiagnosed cause of epilepsy, and a 3 T magnetic resonance imaging reviewed by an epilepsy expert radiologists is key to diagnosis. CONCLUSION: In drug-resistant cases with presurgical evaluation compatible with the location, surgical treatment must be considered.

TITLE: Encefalocele del polo temporal: una causa tratable quirúrgicamente de epilepsia farmacorresistente.Introducción. Los encefaloceles son herniaciones del parénquima cerebral consecuencia de un defecto óseo. Si producen epilepsia farmacorresistente, hay que plantearse un abordaje quirúrgico. Caso clínico. Varón de 38 años con epilepsia farmacorresistente y estudio estándar de resonancia magnética de 1,5 T sin hallazgos. Tras realizar un videoelectroencefalograma, una resonancia magnética de 3 T y una tomografía por emisión de positrones con fluorodesoxiglucosa, se confirmó la presencia de un encefalocele del polo temporal derecho. Se efectuó una resección de ese polo temporal y cuatro años después el paciente continúa libre de crisis. Discusión. Los encefaloceles temporales anteriores constituyen una causa infradiagnosticada de epilepsia en cuyo estudio es clave la resonancia magnética de 3 T y la evaluación por un radiólogo experimentado en epilepsia. Conclusión. En casos farmacorresistentes y evaluación prequirúrgica de la epilepsia congruente con la localización, hay que considerar su tratamiento quirúrgico.

Gelastic seizures and the hypothalamic hamartoma syndrome: Epileptogenesis beyond the lesion?

The clinicoradiologic syndrome of hypothalamic hamartoma (HH) manifests with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, precocious puberty, behavioral disturbances, and cognitive impairment. Gelastic seizures are an early marker of epilepsy with HH in most of the cases. Despite a high variability, two major epilepsy phenotypes can be distinguished, based on electroclinical features: (i) focal seizures with epigastric or déjà-vu aura, loss of consciousness, and oroalimentary or gestural automatisms suggestive of temporal lobe involvement; and (ii) motor seizures with tonic, atonic, myoclonic, or versive phenomena, suggesting frontoparietal network involvement, with possible evolution toward an epileptic encephalopathy. The underlying physiopathologic mechanisms are not completely elucidated. The well-known intrinsic epileptogenicity of the HH represents the rationale for direct HH-aiming surgical procedures, with variable success in achieving seizure freedom. The concept of kindling-like secondary epileptogenesis has been suggested as a possible putative mechanism since the very beginnings of the hamartocentric era. Accordingly, a cortical area with enhanced epileptogenic properties due to an independent stage of secondary epileptogenesis would be responsible for seizures persisting after hamartoma ablation. However, recent intracerebral stereotactic EEG (SEEG) explorations demonstrated more complex, both reciprocal and hierarchical, relationships within the hypothalamo-cortical epileptogenic networks. Network formation may be due to either secondary epileptogenesis or widespread epileptogenicity present at the outset. A short time window from epilepsy onset to surgery seems to be crucial to cure epilepsy by direct surgery addressing a hamartoma. SEEG exploration may be reasonably proposed in cases where clinical data suggest an extension of the epileptogenic zone outside the limits of the HH, especially in focal seizures with impaired awareness and absence of gelastic seizures, or after a failure of the direct HH-aiming procedure.

Etiology-specific response to antiseizure medication in focal epilepsy.

OBJECTIVE: In focal epilepsy, data on the etiology-specific response to antiseizure medication (ASM) are surprisingly sparse. In this study, we sought to reappraise whether seizure outcome of pharmacological treatment is linked to the underlying etiology. Furthermore, we assessed ASM load with respect to the cause of epilepsy. METHODS: Data were retrospectively obtained from the electronic database of the three sites of an academic adult epilepsy outpatient clinic. For each patient, presumed cause of epilepsy was categorized into one of nine etiological groups. Individual drug loads were calculated according to the 2020 World Health Organization Center for Drug Statistics Methodology ATC/DDD Index. Univariate and multivariate analyses were conducted to explore the association between different etiologies and outcome regarding 12-month seizure freedom as well as ASM load. RESULTS: A total of 591 patients with focal epilepsy were included in the final analysis. Ischemic stroke was the etiology with the highest rate of 12-month terminal seizure freedom (71.2%, 95% confidence interval [CI] = 57.9-82.2) and, considering all etiological groups, was an independent predictor of seizure freedom (odds ratio = 2.093, 95% CI = 1.039-4.216). The lowest rates of seizure freedom were observed in patients with hippocampal sclerosis (28.2%, 95% CI = 15.0-44.9) and malformation of cortical development (16.7%, 95% CI = 2.1-48.4). In patients with ischemic stroke, median ASM load (1.0, interquartile range [IQR] = .5-1.8) was significantly lower compared to that in patients with hippocampal sclerosis (median = 1.8, IQR = 1.2-3.0, p = .008) and brain tumors (median = 1.7, IQR = .7-3.2, p = .049). SIGNIFICANCE: Response to treatment with ASM is highly etiology-specific and best in patients with epilepsy due to ischemic stroke. Interestingly, this most favorable treatment outcome can be achieved by the lowest ASM load considering all etiological groups. In focal epilepsy, etiology should be taken into account when counseling patients about their expected seizure outcome with pharmacological treatment and when tailoring initial ASM doses.

Meningioangiomatosis: an uncommon cause of focal epilepsy with characteristic neuroimaging and neuropathology.

A 3-year-old boy presented with acute onset of prolonged right sided focal seizures with secondary generalisation. The investigation findings were suggestive of a neoplastic process more than an inflammatory process. Decision to perform brain biopsy from the lesion to establish the precise nature of lesion was undertaken.

[Go-induced epilepsy treatment with levetiracetam successfully prevented seizures].

There are only a few reports on Go-induced epilepsy. We hereby report a case of Go-induced epilepsy and its ictal electroencephalography (EEG) findings, and treatment. A 71-year-old man reported to our hospital for seizures that lasted for several minutes after he had played Go for approximately an hour. Ictal EEG showed focal to bilateral tonic-clonic seizures of right parietal origin. He was administered levetiracetam 500 mg before the games, and he participated without seizures for more than a year. Go-induced epilepsy is considered to have a focal onset, and it may be controlled with antiepileptic drugs before the games.

Frequent SLC35A2 brain mosaicism in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE).

Focal malformations of cortical development (MCD) are linked to somatic brain mutations occurring during neurodevelopment. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a newly recognized clinico-pathological entity associated with pediatric drug-resistant focal epilepsy, and amenable to neurosurgical treatment. MOGHE is histopathologically characterized by clusters of increased oligodendroglial cell densities, patchy zones of hypomyelination, and heterotopic neurons in the white matter. The molecular etiology of MOGHE remained unknown so far. We hypothesized a contribution of mosaic brain variants and performed deep targeted gene sequencing on 20 surgical MOGHE brain samples from a single-center cohort of pediatric patients. We identified somatic pathogenic SLC35A2 variants in 9/20 (45%) patients with mosaic rates ranging from 7 to 52%. SLC35A2 encodes a UDP-galactose transporter, previously implicated in other malformations of cortical development (MCD) and a rare type of congenital disorder of glycosylation. To further clarify the histological features of SLC35A2-brain tissues, we then collected 17 samples with pathogenic SLC35A2 variants from a multicenter cohort of MCD cases. Histopathological reassessment including anti-Olig2 staining confirmed a MOGHE diagnosis in all cases. Analysis by droplet digital PCR of pools of microdissected cells from one MOGHE tissue revealed a variant enrichment in clustered oligodendroglial cells and heterotopic neurons. Through an international consortium, we assembled an unprecedented series of 26 SLC35A2-MOGHE cases providing evidence that mosaic SLC35A2 variants, likely occurred in a neuroglial progenitor cell during brain development, are a genetic marker for MOGHE.

Clinical and electrographic features of persistent seizures and status epilepticus associated with anti-NMDA receptor encephalitis (anti-NMDARE).

Based on a multicenter cohort of people with anti-NMDA receptor encephalitis (anti-NMDARE), we describe seizure phenotypes, electroencephalographic (EEG) findings, and anti-seizure treatment strategies. We also investigated whether specific electrographic features are associated with persistent seizures or status epilepticus after acute presentation. In this retrospective cohort study, we reviewed records of children and adults with anti-NMDARE between 2010 and 2014 who were included in the Rare Epilepsy of New York City database, which included the text of physician notes from five academic medical centers. Clinical history (e.g., seizure semiology) and EEG features (e.g., background organization, slowing, epileptiform activity, seizures, sleep architecture, extreme delta brush) were abstracted. We compared clinical features associated with persistent seizures (ongoing seizures after one month from presentation) and status epilepticus, using bivariate and multivariable analyses. Among the 38 individuals with definite anti-NMDARE, 32 (84%) had seizures and 29 (76%) had seizures captured on EEG. Electrographic-only seizures were identified in five (13%) individuals. Seizures started at a median of four days after initial symptoms (IQR: 3-6 days). Frontal lobe-onset focal seizures were most common (n=12; 32%). Most individuals (31/38; 82%) were refractory to anti-seizure medications. Status epilepticus was associated with younger age (15 years [9-20] vs. 23 years [18-27]; p=0.04) and Hispanic ethnicity (30 [80%] vs. 8 [36%]; p=0.04). Persistent seizures (ongoing seizures after one month from presentation) were associated with younger age (nine years [3-14] vs. 22 years [15-28]; p<0.01). Measured electrographic features were not associated with persistent seizures. Seizures associated with anti-NMDARE are primarily focal seizures originating in the frontal lobes. Younger patients may be at increased risk of epileptogenesis and status epilepticus. Continuous EEG monitoring helps identify subclinical seizures, but specific EEG findings may not predict the severity or persistence of seizures during hospitalization.

Improved seizure burden and cognitive performance in a child treated with responsive neurostimulation (RNS) following febrile infection related epilepsy syndrome (FIRES).

Responsive neurostimulation (RNS) is an emerging therapy for patients with refractory focal epilepsy who are not candidates for surgical resection, with limited published experience in the pediatric population. We report a case of refractory multifocal epilepsy following febrile infection related epilepsy syndrome (FIRES) in which surgical resection was not feasible due to multifocal independent seizures and risk of cognitive deficit, and RNS was pursued. Relevant RNS data and neuropsychological testing results were reviewed. By eight months after implantation, decreased frequency and severity of clinical seizures were noted, and RNS data revealed decreased "long episodes," reduced spread of electrographic seizures, and fewer detections. Neuropsychological assessment, though potentially confounded by stimulant medication, revealed significant improvement in multiple cognitive domains, particularly working memory and processing speed, at six months. These findings illustrate success in detecting and aborting seizures, and additionally suggest a neuromodulatory effect of RNS stimulation. Our case demonstrates feasibility, efficacy and safety of RNS in a pediatric patient with FIRES, with evidence to also suggest cognitive improvement.

Longitudinal analysis of structural connectivity in patients with newly diagnosed focal epilepsy of unknown origin.

OBJECTIVES: The aim of this longitudinal study was to clarify whether significant alterations in structural connectivity occur over time in patients with newly diagnosed focal epilepsy of unknown origin. METHODS: A total of 40 patients with newly diagnosed focal epilepsy of unknown origin and with normal brain magnetic resonance imaging (MRI) on visual inspection were enrolled. All subjects underwent MRI twice involving three-dimensional volumetric T1-weighted imaging, which were suitable for structural volume analysis. Gray matter volumes were obtained using the FreeSurfer image analysis suite, and structural connectivity analyses were performed using Matlab-based BRain Analysis using graPH theory software. RESULTS: The median interval between the two MRI scans was 18.5 months in patients with epilepsy. There was a general tendency toward decreased gray matter volumes on the second scan compared with the initial scan. However, the volumes of the right and left thalamus and brainstem on the second MRI scan had an increased tendency compared with those on the initial MRI scan. In measures of connectivity, there were significant differences between the two MRI scans. The mean clustering coefficient, global efficiency, local efficiency, and the small-worldness index were significantly increased, whereas the characteristic path length was decreased on the second MRI scan compared with the initial MRI scan. CONCLUSIONS: The structural connectivity in patients with newly diagnosed focal epilepsy of unknown origin increases over time in the initial stage. These alterations and increases in structural connectivity may be related to underlying epileptogenicity in the initial stages of epilepsy.