Intractable Seizures and Limbic Encephalitis, Unaccounted Complications of Type 1 Diabetes Autoimmunity

Glutamic acid decarboxylase 65kD autoantibody (GAD65Ab) is frequently detected in patients with refractory epilepsy and stiff person syndrome (SPS). In contrast to T1D, the pathological role of GAD65Ab in neurological disorders is still debatable. As a result, the implementation of possible immunotherapy is usually delayed. This report presents two cases of GAD65Ab associated brain autoimmunity and their different management. We present clinical data and discuss management based on available evidence in the reviewed literature. Both cases presented with acute on chronic neurological symptoms and were GAD65Ab positive. Case 1, a 30-year-old man with a history of early-onset T1D at 14 months, followed by cryptogenic temporal epilepsy at 11 years of age, presented with intractable seizures. Case 2, a 48-year-old woman, presented with a history of recurrent severe headaches, cognitive impairment, decreased memory, and behavioral symptoms. GAD65Ab was detected in both patients’ sera. CSF GAD65Ab was only checked and positive in case 1. Case 2 was diagnosed with limbic encephalitis, treated with immunotherapy, and showed a remarkable clinical improvement. Case 1 with refractory epilepsy failed multiple AEDs and Responsive-Stimulator System (RNS) treatments. He was finally diagnosed with autoimmune epilepsy. The delay in diagnosis resulted in a lost opportunity for early immunotherapy. In conclusion, autoantibody screening and early initiation of immunotherapy should be considered to manage GAD65Ab associated neurological disorders.

A Retrospective Analysis of Psychiatric Presurgical Evaluation of Children and Adolescents Evaluated for Epilepsy Surgery in a Comprehensive Epilepsy Care Unit of Mumbai

Background Epilepsy being one of the most prevalent neurological diseases in children is associated with psychopathology and academic concerns. Epilepsy surgery is considered for refractory epilepsy at some centers in India and hence this study was undertaken to find out prevalence and type of psychopathology in children and adolescents with refractory epilepsy before epilepsy surgery. Methods All data were analyzed from the records of patients undergoing preepilepsy surgery protocol workup in comprehensive center of epilepsy care at a general municipal hospital in Mumbai. A record of 150 children and adolescents in the age group of 3 to 18 years over a period of 10 years was taken and all details of demographics, epilepsy, and psychopathology were recorded. Results The mean age for our sample was 11.4 ± 3.4 years and a male preponderance was seen. Majority (80%) of the children were pursuing education. The duration of seizure disorder was approximately 4.41 + 2.36 years and complex partial seizures were seen commonly in 50% of the children. Both magnetic resonance imaging (MRI) and video electroencephalography (VEEG) findings revealed right sided lateralization followed by left in majority of the patients. Psychopathology was seen in 70 (46%) patients with mental retardation, hyperkinetic disorders affecting attention and activity and oppositional defiant disorder, and unspecified mental disorder due to underlying brain damage being the type of International Classification of Disease-10th Revision (ICD-10) disorders seen. Patients with psychopathology showed a left-sided predominance on their MRI and VEEG findings for laterality of the epileptogenic focus as compared with right side. Conclusion Refractory seizures and associated psychopathology impact family life, friendships, and academics and worsen prognosis and quality of life. Screening for psychopathology in children with epilepsy would therefore lead to better outcomes especially prior to epilepsy surgery.

A study of brain functional network and alertness changes in temporal lobe epilepsy with and without focal to bilateral tonic–clonic seizures

Background Temporal lobe epilepsy (TLE) is commonly refractory. Epilepsy surgery is an effective treatment strategy for refractory epilepsy, but patients with a history of focal to bilateral tonic-clonic seizures (FBTCS) have poor outcomes. Previous network studies on epilepsy have found that TLE and idiopathic generalized epilepsy with generalized tonic-clonic seizures (IGE-GTCS) showed altered global and nodal topological properties. Alertness deficits also were found in TLE. However, FBTCS is a common type of seizure in TLE, and the implications for alertness as well as the topological rearrangements associated with this seizure type are not well understood. Methods We obtained rs-fMRI data and collected the neuropsychological assessment data from 21 TLE patients with FBTCS (TLE- FBTCS), 18 TLE patients without FBTCS (TLE-non- FBTCS) and 22 controls, and constructed their respective functional brain networks. The topological properties were analyzed using the graph theoretical approach and correlations between altered topological properties and alertness were analyzed. Results We found that TLE-FBTCS patients showed more serious impairment in alertness effect, intrinsic alertness and phasic alertness than the patients with TLE-non-FBTCS. They also showed significantly higher small-worldness, normalized clustering coefficient (γ) and a trend of higher global network efficiency (gE) compared to TLE-non-FBTCS patients. The gE showed a significant negative correlation with intrinsic alertness for TLE-non-FBTCS patients. Conclusion Our findings show different impairments in brain network information integration, segregation and alertness between the patients with TLE-FBTCS and TLE-non-FBTCS, demonstrating that impairments of the brain network may underlie the disruptions in alertness functions.

Localizing Epileptic Foci Before Surgery in Patients With MRI-Negative Refractory Epilepsy Using Statistical Parameter Mapping and Three-Dimensional Stereotactic Surface Projection Based on 18F-FDG PET

Patients with refractory epilepsy are not only free of seizures after resecting epileptic foci, but also experience significantly improved quality of life. Fluorine-18-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) is a promising avenue for detecting epileptic foci in patients with magnetic resonance imaging (MRI)-negative refractory epilepsy. However, the detection of epileptic foci by visual assessment based on 18F-FDG PET is often complicated by a variety of factors in clinical practice. Easy imaging methods based on 18F-FDG PET images, such as statistical parameter mapping (SPM) and three-dimensional stereotactic surface projection (3D-SSP), can objectively detect epileptic foci. In this study, the regions of surgical resection of patients with over 1 year follow-up and no seizures were defined as standard epileptic foci. We retrospectively analyzed the sensitivity of visual assessment, SPM and 3D-SSP based on 18F-FDG PET to detect epileptic foci in MRI-negative refractory epilepsy patients and obtained the sensitivities of visual assessment, SPM and 3D-SSP are 57, 70 and 60% respectively. Visual assessment combined with SPM or 3D-SSP can improve the sensitivity of detecting epileptic foci. The sensitivity was highest when the three methods were combined, but decreased consistency, in localizing epileptic foci. We conclude that SPM and 3D-SSP can be used as objective methods to detect epileptic foci before surgery in patients with MRI-negative refractory epilepsy. Visual assessment is the preferred method for PET image analysis in MRI-negative refractory epilepsy. When the visual assessment is inconsistent with the patient’s electroclinical information, SPM or 3D-SSP was further selected to assess the epileptic foci. If the combination of the two methods still fails to accurately locate the epileptic foci, comprehensive evaluation can be performed by combining the three methods.

Sodium Valproate Combined With Topiramate vs. Sodium Valproate Alone for Refractory Epilepsy: A Systematic Review and Meta-Analysis

Background: Among antiepileptic drugs (AEDs), sodium valproate alone or in the combination of topiramate (TPM) for treating refractory epilepsy was controversial. This meta-analysis aimed to systematically evaluate the clinical effects of these two regimens in this population.Methods: Relevant studies up to August 2021 were identified through systematic searches of CNKI, Wanfang, PubMed, and Embase databases. We assessed the effectiveness and the frequency of absence seizures, atonic seizures, and tonic–clonic seizures. The included literature's risk of bias was evaluated using the Cochrane Collaboration's Risk of Bias tool. Sensitivity analysis was conducted to confirm the results' stability. STATA 15.0 was utilized for all pooled analyses in the included studies.Results: Totally 10 articles were determined for our meta-analysis, involving 976 patients with epilepsy in total (combined group, n = 488; monotherapy group, n = 488). The results of this meta-analysis indicated that the total effective rate of sodium valproate combined with TPM was higher than that of sodium valproate alone (random-effect model: OR = 3.52; 95% CI 1.47 to 8.47; p < 0.001; I2 = 73.8%). The frequency of absence seizures in the combined group was lower (fixed-effect model: WMD = −6.02; 95% CI −6.50 to −5.54; I2 = 0.0%) than that in the monotherapy group, with a statistical difference (p < 0.05). The combined group had lower frequency of atonic seizures (WMD = −4.56, 95% CI −6.02 to −3.10; I2 = 82.6%) and lower frequency of tonic–clonic seizures (WMD = −3.32; 95% CI −4.75 to −1.89; I2 = 96.4%). In addition, the distinct difference of adverse events was non-existent between two groups.Conclusions: Sodium valproate combined with TPM was more effective than sodium valproate alone for epilepsy therapy. This meta-analysis provides feasibility data for a larger-scale study on AED therapy of refractory epilepsy and may contribute to better therapy strategies for epilepsy clinically.

Reducing VNS stimulation parameters: is it safe?

Introduction Vagal nerve stimulation (VNS) is an adjuvant therapy used in the treatment of patients with refractory epilepsy who are not candidates for resective surgery or who have limited results after surgical procedures. Currently, there is enough evidence to support its use in patients with various types of epilepsy. Therefore, the present study was conducted to explore the possibility of optimizing therapy by reducing the consumption of the system's battery. Methods The prospective and double-blind analysis consisted in the evaluation of 6 patients submitted to VNS implantation for 3 months, followed by adjustment of the stimulation settings and continuity of follow-up for another month. The standard protocol was replaced by another with a frequency value of 20 Hz instead of 30 Hz to increase battery life. The safety of this procedure was evaluated through the assessment of two main variables: seizures and side effects. Results The stimulation at 20 Hz showed 68% reduction in the incidence of seizures (p = 0.054) as well as low incidence of side effects. Conclusion The present study suggests that the reduction of the stimulation frequency from 30 to 20 Hz is a safe procedure, and it does not compromise the effectiveness of therapy.

Clinical and Social Findings of Childhood Epilepsy

Background: Seizures are defined as a transient occurrence of signs and symptoms due to the abnormal, excessive, or synchronous neuronal activity in the brain characterized by abrupt and involuntary skeletal muscle activity. Seizure is related to specific risk factors like positive family history, fever, infections, neurological comorbidity, premature birth, mother’s alcohol abuse, and smoking in pregnancy. Epilepsy is the most frequent chronic neurologic condition in children. Studies have suggested declining incidence rates of childhood epilepsy in high-income countries during the last decades. Objective: To describe the clinical features and social findings of epilepsy in children, and to evaluate some risk factors associated with control of epilepsy. Patients and Methods: This cross-sectional study was conducted in the pediatric department of Albatool teaching hospital in Diyala province, Iraq. A total of 100 children were included in the study from February 2020 to May 2020. All children diagnosed with epilepsy in this study. Results: One hundred children with epilepsy, their mean age was 5.96± 3.33 years (range 1-14 years). Of the 48(48%) children were male and 52(52%). Of the total patients, 79% were free from seizure on AED, 21% of them were refractory to treatment.Patients without developmental delay (88.7%, p=0.012) can be controlled by AED. Patients who had idiopathic seizures (87.5%, p=0.04) can be controlled by AED. Patients who had seizure attacks can be controlled by AED more than patients who had weekly or monthly seizure attacks (97.4%) (p<0.001). Patients who had been treated by monotherapy (94.7%, p=0.012) can be controlled more than patients who were treated by multidrug therapy. Affected social interaction and need more supervision were factors that detected more in patients with refractory epilepsy, p=0.04, 0.01 respectively. While there was no association between frightened other people and epilepsy control. Conclusion: Most of the patients are characterized by: treatment approach monotherapy, less affected by social interaction and need less supervision. Patients with refractory epilepsy had opposite factors. Keywords: Epilepsy, Albatool teaching hospital.

ESTUDO SOBRE O CANABIDIOL: UMA ALTERNATIVA AO TRATAMENTO DE DOENÇA EPILÉTICA

Objetivo: descrever os efeitos terapêuticos e sobre a utilização do cannabidiol no tratamento da epilepsia. Métodos: O presente estudo se caracteriza como sendo uma revisão de literatura do tipo integrativa, com abordagem qualitativa.Resultados: Foram localizadas 118 produções cientificas. Sendo excluídos produções realizadas em um período maior que dez anos e aquelas que não estavam disponíveis ao acesso gratuito. Os estudos demonstraram melhora na frequência das crises. Não foi encontrada associação entre o percentual de redução das frequências das crises e tempo de tratamento. Os efeitos adversos mais encontrados foram sonolência, hiporexia, diarreia, vômitos alterações comportamentais e tonturas. Considerações finais: It is concluded that the therapeutic use of cannabidiol was associated with a decrease in the frequency of epileptic seizures, as well as an improvement in the quality of life in individuals with refractory epilepsy.

Dietary therapies for epilepsy in low resource settings: challenges and successes

The Ketogenic Diet (KD) is a high fat, low carbohydrate and restricted protein diet which has been used for the treatment of drug resistant epilepsy in children. It is considered the treatment of choice for refractory nonsurgical epilepsy in children. However, despite this being a very useful and relatively simple treatment, children from developing countries have not been able to benefit as much as their counterparts in more privileged settings. In this article, the challenges faced by pediatric neurologists and parents who wish to use the diet in children with refractory epilepsy are discussed, and also the simple low cost innovations which can be used to overcome these challenges are suggested. The evolution from the use of the classic ketogenic diet to the flexible use of the modified Atkins diet in low resource settings will be discussed.