Search Results (7)

Periventricular nodular heterotopia (PVNH) is a genetically heterogeneous malformation of cortical development with variable neurological outcomes. Among recessive forms, ARFGEF2-related disorder is uniquely characterised by the association of diffuse PVNH and progressive microcephaly. We describe a two-year-old boy born to consanguineous parents who presented with severe developmental delay, hypotonia, progressive microcephaly, and infantile-onset epileptic spasms with developmental regression. Brain MRI showed extensive bilateral PVNH associated with callosal hypoplasia and ventriculomegaly. EEG revealed dysmature background activity with multifocal epileptiform discharges and runs of asynchronous fast activity during sleep. Genetic testing identified a novel homozygous nonsense variant in ARFGEF2. The clinical course was characterised by drug-resistant epilepsy and multisystemic involvement, including feeding difficulties and recurrent respiratory infections. To contextualise this case, we performed a comprehensive review of previously reported patients, further delineating the clinical, neuroradiological, and electroclinical spectrum of ARFGEF2-related disorder. This case highlights progressive microcephaly as a key distinguishing feature of ARFGEF2-related PVNH and underscores the importance of early genetic diagnosis to guide targeted surveillance for extra-CNS complications and multidisciplinary care. Full article

The closed-loop control of pathological brain activity is a challenging task. In this study, we investigated the sensitivity of continuous epileptiform short discharge generation to electrical stimulation applied at different phases between the discharges using an in vitro 4-AP-based model of epilepsy in rat hippocampal slices. As a measure of stimulation effectiveness, we introduced a sensitivity function, which we then measured in experiments and analyzed with different biophysical and abstract mathematical models, namely, (i) the two-order subsystem of our previous Epileptor-2 model, describing short discharge generation governed by synaptic resource dynamics; (ii) a similar model governed by shunting conductance dynamics (Epileptor-2B); (iii) the stochastic leaky integrate-and-fire (LIF)-like model applied for the network; (iv) the LIF model with potassium M-channels (LIF+KM), belonging to Class II of excitability; and (v) the Epileptor-2B model with after-spike depolarization. A semi-analytic method was proposed for calculating the interspike interval (ISI) distribution and the sensitivity function in LIF and LIF+KM models, which provided parametric analysis. Sensitivity was found to increase with phase for all models except the last one. The Epileptor-2B model is favored over other models for subthreshold oscillations in the presence of large noise, based on the comparison of ISI statistics and sensitivity functions with experimental data. This study also emphasizes the stochastic nature of epileptiform discharge generation and the greater effectiveness of closed-loop stimulation in later phases of ISIs. Full article

Back ground: Children with epilepsy are affected by several factors, including clinical and social variables. Among these variables, cognitive decline and behavioral disturbances, perceptions of stigma, and fatigue can lead to reductions in quality of life (QOL). Epileptic activities, including seizure severity, frequent seizures, and status epilepticus (SE), have been identified as important predictors of QOL. In addition, the frequency of interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) may also be an important predictor of QOL, because IEDs can lead to cognitive decline and behavioral disturbances. Moreover, frequent seizures and/or IEDs may play a role in emotional mediators, such as stigma and fatigue, in childhood epilepsy. Seizure severity and/or IEDs are, therefore, important QOL-related factors in childhood epilepsy. Seizure severity as a QOL-related factor: Frontal lobe dysfunctions, such as cognitive decline and behavioral disturbances, can result in reduced QOL for both the child and their family. Frontal and prefrontal lobe growth disturbances can be present during active-phase epilepsy in some children with neuropsychological impairments. Recovery from prefrontal lobe growth disturbances may depend on the active seizure period. Children with a shorter active seizure period can recover from disturbances in prefrontal lobe growth more rapidly. In contrast, recovery may be delayed in children with a longer active seizure period. Moreover, frequent seizures can lead to seizure-associated headaches, perceptions of self-stigma and parental stigma, and fatigue. Accordingly, severe seizures can lead to neuropsychological impairments in association with prefrontal lobe growth disturbances in children with epilepsy. EEG abnormalities as QOL-related factors: IEDs on EEG, representing persistent pathological neuronal discharges, may be associated with several pathological aspects. Frontal IEDs can be a risk factor for recurrent seizures, cognitive decline, and behavioral disturbances, and they may also play a role as emotional mediators similar to stigma. In addition, behavioral disturbances may result in the presence of secondary bilateral synchrony (SBS) on EEG. Behavioral disturbances can be improved in association with a reduction in IEDs in children with frontal IEDs and SBS. Therefore, EEG abnormalities, such as frontal IEDs and SBS, can also lead to neuropsychological impairments in children with epilepsy. Therapeutic strategies in children with epilepsy: Seizure severity and IEDs on EEG may be associated with neuropsychological impairments, leading to QOL reduction. Therapeutic management may be desirable to reduce seizures and EEG abnormalities, such as frontal IEDs and SBS, as early as possible to improve QOL in children with epilepsy. During antiseizure medication (ASM) selection and adjustment, physicians should strategize the therapeutic approach to controlling seizures and suppressing EEG abnormalities in children with epilepsy. Among various ASMs, novel ASMs, such as levetiracetam and perampanel, may suppress both clinical seizures and IEDs on EEG; thus, these novel ASMs may represent an important addition to the treatments available for epileptic children presenting with frontal IEDs and SBS. Full article

Heterozygous variants in the ATP1A3 gene are linked to well-known neurological phenotypes. There has been growing evidence for a separate phenotype associated with variants in residue Arg756—fever-induced paroxysmal weakness and encephalopathy (FIPWE) or relapsing encephalopathy with cerebellar ataxia (RECA). With only about 20 cases being reported, the clinical features associated with mutations at Arg756 have not been fully elucidated. We report a case of FIPWE with a p.Arg756Cys change in the ATP1A3 gene and a comparison of the clinical features, including electrophysiological examination, with previous cases. The 3-year-old male patient had normal psychomotor development, presenting with recurrent symptoms of generalized hypotonia with loss of gait, mutism, and dystonic movements only during febrile illnesses since 19 months of age. At 2.7 years of age, a third neurological decompensation episode occurred, during which electroencephalography (EEG) did not reveal high voltage slow waves or epileptiform discharge. Nerve conduction studies (NCS) also did not show latency delay or amplitude reduction. ATP1A3 exon sequencing showed a heterozygous p.Arg756Cys mutation. While the patient experienced repeated encephalopathy-like episodes, including severe hypotonia during febrile illness, EEG and NCS did not reveal any obvious abnormalities. These electrophysiological findings may represent an opportunity to suspect FIPWE and RECA. Full article

Objective: To determine the predictors and the long-term outcomes of patients with seizures following surgery for dysembryoplastic neuroepithelial tumors (DNTs); Methods: Clinical data were collected from medical records of consecutive patients of the Department of Neurosurgery of Sanbo Brain Hospital of Capital Medical University with a pathological diagnosis of DNT and who underwent surgery from January 2008 to July 2021. All patients were followed up after surgery for at least one year. We estimated the cumulative rate of seizure recurrence-free and generated survival curves. A log-rank (Mantel–Cox) test and a Cox proportional hazard model were performed for univariate and multivariate analysis to analyze influential predictors; Results: 63 patients (33 males and 30 females) were included in this study. At the final follow-up, 49 patients (77.8%) were seizure-free. The cumulative rate of seizure recurrence-free was 82.5% (95% confidence interval (CI) 71.8–91.3%), 79.0% (95% CI 67.8–88.6%) and 76.5% (95% CI 64.8–87.0%) at 2, 5, and 10 years, respectively. The mean time for seizure recurrence-free was 6.892 ± 0.501 years (95% CI 5.91–7.87). Gross total removal of the tumor and a short epilepsy duration were significant predictors of seizure freedom. Younger age of seizure onset, bilateral interictal epileptiform discharges, and MRI type 3 tumors were risk factors for poor prognosis; Conclusions: A favorable long-term seizure outcome was observed for patients with DNT after surgical resection. Predictor analysis could effectively guide the clinical work and evaluate the prognosis of patients with DNT associated with epilepsy. Full article

Temporal lobe epilepsy (TLE) is one of the most common types of focal epilepsy, characterized by recurrent spontaneous seizures originating in the temporal lobe(s), with mesial TLE (mTLE) as the worst form of TLE, often associated with hippocampal sclerosis. Abnormal epileptiform discharges are the result, among others, of altered cell-to-cell communication in both chemical and electrical transmissions. Current knowledge about the neurobiology of TLE in human patients emerges from pathological studies of biopsy specimens isolated from the epileptogenic zone or, in a few more recent investigations, from living subjects using positron emission tomography (PET). To overcome limitations related to the use of human tissue, animal models are of great help as they allow the selection of homogeneous samples still presenting a more various scenario of the epileptic syndrome, the presence of a comparable control group, and the availability of a greater amount of tissue for in vitro/ex vivo investigations. This review provides an overview of the structural and functional alterations of synaptic connections in the brain of TLE/mTLE patients and animal models. Full article

Background: The conversion of glutamic acid into γ-aminobutyric acid (GABA) is catalyzed by the glutamic acid decarboxylase (GAD). Antibodies against this enzyme have been described in neurological disorders, but the pathophysiological role of these antibodies is still poorly understood. We hypothesized that anti-GAD autoantibodies could diminish the GABA content in the slice and facilitate epileptic activity. Methods: Cerebrospinal fluids (CSF) from two patients containing anti-GAD (A and B) were injected into the rat hippocampus in vivo. Hippocampal slices were prepared for electrophysiological field potential recordings in order to record recurrent epileptic discharges (REDs) in the CA1 region induced by the removal of Mg²⁺ and/or by adding gabazine. As control groups, we injected an anti-GAD-negative human CSF or saline solution, and we used non-operated naive animals. Results: RED frequencies were significantly higher in the Mg²⁺-free solution than in the gabazine-containing solution. The average frequency of REDs in the last 10 min and the average duration of REDs in the last 5 min did not show significant differences between the anti-GAD-B-treated and the control slices, but in the Mg²⁺-free solution, anti-GAD-A had significantly higher epileptic activity than anti-GAD-B. Conclusions: These results indicate that anti-GAD has distinct effects on the development of spontaneous epileptic activity. Full article