Well-controlled Epilepsy Research Articles

Evaluation of QT dispersion in epileptic patients and its association with SUDEP risk

BackgroundMortality in epileptic patients was attributed to sudden unexpected death in epilepsy (SUDEP). The precise pathophysiology of SUDEP is not fully understood, yet prolongation of ventricular repolarization particularly QTc interval suggested to be one of the contributing risk factor for SUDEP. ObjectivesWe aimed at evaluation of QTc and QT dispersion (QTD) in patients with epilepsy (both refractory and well-controlled epilepsy) and their association with the epileptic severity and sudden unexplained death (SUDEP) risk. Patients and methodsThe study included eighty epileptic patients (40 controlled epileptic patients and 40 refractory epileptic patients) compared to thirty non-epileptic volunteers as the control group (patients with history of cardiovascular comorbidities or exposure to antiarrhythmic drugs were excluded from the study). All participants were subjected to clinical evaluation including detailed epileptic history with assessment of SUDEP 7 risk, severity scale, 12 leads surface ECG to measure QTc & QTD, 24 h Holter monitoring to assess heart rate variability (HRV) parameters. ResultsControlled and refractory epileptic patients demonstrated increased average QTc and QTD values compared to control group (450.1 ± 18.9 vs. 412.3 ± 12.3 ms, p < 0.0001, 452.1 ± 19.0 vs. 412.3 ± 12.3 ms, p < 0.0001 respectively) (45.6 ± 14.9 vs. 15.4 ± 6.8 ms, p < 0.001, 70.6 ± 18.1 vs. 15.4 ± 6.8 ms, p < 0.0001 respectively). Refractory epileptic patients had a significantly higher incidence of abnormal QTD > 50 ms compared to controlled epileptic patients (32.5% vs. 90%, p < 0.005). Refractory epileptic patients with generalized form had significantly higher severity scale in addition to significantly impaired rMSSD and pNN50 compared to those with focal form (1072.7 ± 722.7 vs. 429.1 ± 180.4, p < 0.03, 17.11 ± 4.6 vs. 26.4 ± 7.9 ms, p < 0.004 and 2.9 ± 1.8 vs. 7.8 ± 4.1%, p < 0.003 respectively). Among refractory epileptic patients, the duration of epilepsy, rMSSD and QTD significantly correlated with SUDEP-7 risk (r2 =0.199, p < 0.005, r2 =0.623, p < 0.0001 and r2=0.44, p < 0.0001 respectively). ConclusionsThe current study stands out the importance of evaluating QTc and QTD in 12-lead ECG recordings in epileptic patients and signifying their association with SUDEP-7 risk among refractory epileptic patients.

P.120 Case series: Clinical and genetic spectrum of SCN8A-related disorders in British Columbia

Background: Children with pathogenic variations in SCN8A can present with early infantile epileptic encephalopathy-13, benign familial infantile seizures-5 or intellectual disability alone without epilepsy. In this case series, we discuss six children with variants in SCN8A managed at BC Children’s Hospital. Methods: We describe clinical and genetic results on six individuals with SCN8A variants identified via clinical or research next-generation sequencing. Functional consequences of two SCN8A variants were assessed using electrophysiological analyses in transfected cells. Results: Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Phenotypes and genotypes in our cohort are described in the table below. Functional analysis supported gain-of-function in P2 and loss-of-function in P4. Conclusions: Our cohort expands the clinical and genotypic spectrum of SCN8A-related disorders. We establish functional evidence for two missense variants in SCN8A, including LoF variant in a patient with intellectual disability, and autism spectrum disorder without seizures.

Seizure recurrence after prolonged seizure control: Patterns and risk factors

ObjectiveTo identify the patterns and possible predictors of seizure recurrence after durable seizure freedom during maintenance of anti-seizure medication (ASM) treatment. MethodsWe conducted a retrospective longitudinal study that identified all adult individuals with epilepsy (IWE) at the George Washington University outpatient epilepsy clinic between 1/1/2014 and 12/31/2016 who had been seizure free for at least 2 years. We followed up the patients until 5/30/2020 for seizure recurrence. The data were analyzed using survival analysis, univariate analysis, and multivariate regression with Cox proportional hazard model. Outcomes were dichotomized into seizure relapse and seizure freedom. The total number of relapses and triggers of the initial relapse for individual patient were also analyzed. ResultsThis single-center cohort consisted of 220 IWE (age 21–80) of whom 99 patients had been seizure free for 2–3 years and 121 patients had been seizure free for more than 3 years. In this cohort, 48 patients (22%) experienced at least one seizure relapse during the span of the study. Of the relapsing patients, 25 (52%) had a single seizure relapse, and 8 (15%) had frequent seizure relapses (n ≥ 5) and developed pharmacoresistance. Half of the initial seizure relapses occurred without a trigger. Among those with at least one year of follow-up after relapsing (n = 33), 29 (86%) regained seizure freedom for at least 1 year. Among 26 patients with at least 2 years of follow-up, only 14 (55%) regained at least 2 years of seizure freedom. Previous longer duration of seizure freedom and ASM monotherapy predicted less chances of seizure relapse and fewer seizure numbers after relapse. No difference in prognosis was noted among relapsing patients between those with or without triggers. SignificancePatients with well-controlled epilepsy may have seizure relapses with or without identifiable triggers. Most patients regained at least 1-year seizure freedom after the initial relapse, whereas about half patients reachieved 2-year seizure remission. About 15% of the relapsing patients may subsequently develop pharmacoresistance. Prognostic factors of seizure recurrences include duration of initial seizure remission and the number of ASMs used during remission. The presence of identifiable triggers for the initial seizure relapse does not predict future outcome.

Interleukin-33 and oxidative stress in epilepsy patients

Objectiveİnflammation and oxidative stress plays an important role in the etiology of epilepsy. Interleukin-33 (IL-33), a new member of the cytokine family associated with interleukin-1 (IL-1), has been found to play a role in pathogenesis of central nervous system diseases and cause the production of proinflammatory cytokines and oxidative stress molecules. Our aim was to investigate IL-33 and oxidative stress values (total antioxidant capacity (TAS), total oxidant capacity (TOS), and oxidative stress index (OSI)) in patients with epilepsy and to evaluate their relationship with each other. MethodsThe study included 60 patients with epilepsy and 35 healthy controls. The group of patients with epilepsy consisted of 21 patients with treatment-resistant epilepsy and 39 patients with well-controlled epilepsy. The patients with epilepsy were also classified as monotherapy and polytherapy group according to the number of antiepileptic drugs they used, and focal and generalized epilepsy group according to the seizure type. Serum IL-33, TAS, TOS and OSI levels were measured in the patients with epilepsy and the control group. ResultsThe mean serum TAS level was significantly lower in the all patients with epilepsy group compared to the control group, and the mean serum IL-33, TOS, and OSI levels were significantly higher. The mean serum TOS and OSI levels were significantly lower and TAS levels were significantly higher in the patients with well-controlled epilepsy than the patients with treatment-resistant epilepsy. While there was a positive correlation between serum IL-33 and OSI levels in the all patients with epilepsy group, a negative correlation was shown between IL-33 and TAS levels. ConclusionThe IL-33/ST2 pathway may represent a new promising therapeutic strategy both for the treatment and the prevention of the disease.

Abnormal night melatonin level in a patient with well-controlled epilepsy without sleep disturbances – could it be associated with levetiracetam therapy: A case report

Abnormal night melatonin level in a patient with well-controlled epilepsy without sleep disturbances – could it be associated with levetiracetam therapy: A case report

Abnormal night melatonin level in a patient with well-controlled epilepsy without sleep disturbances – could it be associated with levetiracetam therapy: A case report

We present a case report of a 23-year old male with newly diagnosed epilepsy manifested with generalized tonic seizures. Levetiracetam (LEV) was started and the patient was seizure free. The patient demonstrated intermediate chronotype determined by the Morningness-Eveningness Questionnaire (MEQ). There was no epileptiform activity on electroencephalography (EEG) and polysomnography (PSG), sleep architecture disturbances (PSG) or daytime sleepiness (Epworth sleepiness score, Multiple sleep latency test) at the onset and after 3 months of LEV therapy. The melatonin serum levels after 3 months of LEV treatment were 22.00 pg/ml at 3 a.m. and 23.60 pg/ml at 8 a.m. - there was no normal night peak concentration. This abnormality may be associated with a later night peak melatonin concentration, the treatment with levetiracetam being a possible explanation. We consider the presented clinical case of special interest because of the combination of absence of normal night peak melatonin concentration, normal sleep parameters and non-extremely presented chronotype. We suggest that such patients could benefit from add-on therapy with melatonin.

Evaluation of IL-10, IFN-γ, and thiol-disulfide homeostasis in patients with drug-resistant epilepsy.

This study compared dynamic thiol-disulfide homeostasis (an oxidative stress marker), anti-inflammatory interleukin-10 (IL-10) levels, and proinflammatory interferon gamma (IFN-γ) levels in drug-resistant epilepsy patients with those in patients with well-controlled epilepsy and healthy controls. This prospective cross-sectional study enrolled 89 people: 27 with drug-resistant epilepsy, 30 with well-controlled epilepsy, and 32 healthy controls matched in demographic characteristics. The mean serum IL-10 levels were significantly lower and the mean serum IFN-γ levels significantly higher in the drug-resistant epilepsy patients compared to the well-controlled epilepsy and healthy control groups. The mean serum native thiol (SH) and total thiol (TT) levels were significantly lower, and the disulfide (SS) levels were significantly higher in the drug-resistant group than in the other two groups. The significant differences in thiol-disulfide homeostasis and IL-10 and IFN-γ levels in the drug-resistant epilepsy group suggest that these markers indicate a poor prognosis in epilepsy.

CARDIOVASCULAR RISK PROFILE IN YOUNG PATIENTS WITH EPILEPSY

Abstract Objective: The risk of premature deaths in patients with epilepsy (approx. 50 mln. patients worldwide) is about 2–3 times higher as compared to general population. This phenomenon is mainly explained by cardiovascular causes as well as sudden unexpected deaths in epilepsy (SUDEP). Epilepsy is associated with sympathetic overdrive and renin-angiotensin-system abnormalities all of which may be implicated in organ damage (both directly and indirectly via high blood pressure; BP). In our study, we aimed at the evaluation of several cardiovascular risk factors and organ damage in patients with epilepsy; its’ relation to disease control and comorbid hypertension. Design and method: A total of 48 patients and matched controls were included in the study. Anthropometry, biochemical assessment, office and ambulatory blood pressure, structural and/ or functional vascular changes were recorded. One-way ANOVA and ANCOVA were employed (mean ± SE). Results: Patients were comparable in terms of age and BMI. Hypertensives were aware of high BP in 50% of cases. Study subgroups were comparable in terms of heart rate, serum uric acid, triglicerides, HDL, glucose, serum creatinine and eGFR, serum potassium (P = NS for all comparisons). Total cholesterol was the lowest in well-controlled epileptic patients which was followed by refractory disease and epilepsy with comorbid hypertension (167.6 ± 6.7 vs. 196.9 ± 7.4 vs. 223.5 ± 8.9; respectively). Patients with refractory epilepsy had comparable serum LDL and PWV to hypertensive well-controlled epileptics; both contrasted with values recorded in patients with well-controlled epilepsy who were free of hypertension (LDL: 121.7 ± 6.8 vs. 140.9 ± 8.2 vs. 99.2 ± 6.1; respectively, and PWV: 6.4 ± 0.24 vs. 6.8 ± 0.30 vs. 5.5 ± 0.22; respectively). Reported differences were valid after adjustment for age and BMI. Conclusions: Except for BP values, patients with refractory epilepsy who are free of hypertension have similar CV risk profile to patients with high BP. These findings along with underdiagnosed hypertension may explain higher CV mortality and morbidity documented in epilepsy.

Neurodevelopmental Co morbidities of Poorly-Controlled Childhood Epilepsy: A Case-Control Study

Introduction: The epilepsy associated co morbidities are often underestimated, consequently, undertreated. The aim of the present study was to determine neurodevelopmental co morbidities associated with poorly controlled childhood epilepsy.&#x0D; Materials and Methods: This retrospective study was performed from January 2007 to December 2008 at Paediatric Neurology outpatient department in Bangabandhu Sheikh Mujib Medical University, Dhaka, among the children with epilepsy of 7 months to 15 years age who had history of at least 6 months treatment with rational antiepileptic drugs daily with adequate compliance. There were two groups of patients; group 1, consisted of 50 poorly controlled epilepsy patients and group 2, comprised 50 well-controlled epilepsy patients. We retrospectively reviewed EEGs and medical records from these children. Features of neurolodevelopmental co morbidities were compared between the two groups.&#x0D; Results: In this study, initial EEG was abnormal significantly in poorly controlled group (OR= 5.27; p=0.025). Co morbidities- cerebral palsy, language and speech delay, motor delay, microcephaly and cognitive disability were significantly higher in poorly-controlled epilepsy group compared to well-controlled epilepsy group (60.0% vs. 24.0%, p &lt;0.001; 74.0% vs. 38%, p &lt;0.001; 72% vs. 40%, p &lt;0.01; 60% vs. 30.0%, p &lt;0.01; 70% vs 32%, p &lt;0.001 respectively).&#x0D; Conclusion: The study showed several neurodevelopment co morbidities that can be identified early in the course of childhood epilepsy which can predict development of poor seizure control. Knowledge of these co morbidities will help us to discriminate our patient and can inform therapeutic choices.&#x0D; Medicine Today 2021 Vol.33(1): 65-70

B-waves are present in patients without intracranial pressure disturbances.

Intracranial pressure (ICP) B-waves are defined as short, repeating elevations of ICP of up to 50mmHg with a frequency of 0.5-2 waves/min. The presence of B-waves in overnight recordings is regarded as a pathological phenomenon. However, the physiology of B-waves is still not fully understood and studies with transcranial Doppler, as a surrogate marker for ICP, have suggested that B-waves could be a normal physiological phenomenon. We present four patients without known structural neurological disease other than a coincidentally found unruptured intracranial aneurysm. One of the patients had experienced well-controlled epilepsy for several years, but was included because ICP under these conditions is unlikely to be abnormal. Following informed consent, all four patients had a telemetric ICP probe implanted during a prophylactic operation with closure of the aneurysm. They underwent overnight ICP monitoring with simultaneous polysomnography (PSG) sleep studies at 8weeks after the operation. These patients exhibited nocturnal B-waves, but did not have major structural brain lesions. Their ICP values were within the normal range. Nocturnal B-waves occurred in close association with sleep-disordered breathing (SDB) in rapid eye movement (REM) and non-REM sleep stages. SDB during REM sleep was associated with ramp-type B-waves; SDB during non-REM sleep was associated with the sinusoidal type of B-wave. We propose that B-waves are a physiological phenomenon associated with SDB and that the mechanical changes during respiration could have an essential and previously unrecognised role in the generation of B-waves.

Increased frequency of proinflammatory CD4 T cells and pathological levels of serum neurofilament light chain in adult drug-resistant epilepsy.

Adult drug-resistant epilepsy (DRE) is associated with significant morbidity. Infiltration of immune cells is observed in DRE epileptic foci; however, the relation between DRE and the peripheral immune cell compartment remains only partially understood. We aimed to investigate differences in immune cell populations, cytokines, and neurodegenerative biomarkers in the peripheral blood of subjects with epilepsy versus healthy controls, and in DRE compared to well-controlled epilepsy (WCE). Peripheral blood mononuclear cells and serum from >120 age- and sex-matched adults suffering from focal onset epilepsy and controls were analyzed by multipanel flow cytometry, multiplex immunoassays, and ultrasensitive single molecule array. Using a data-driven analytical approach, we identified that CD4 T cells in the peripheral blood are present in a higher proportion in DRE patients. Moreover, we observed that the frequency of CD4 T cells expressing proinflammatory cytokines interleukin (IL)-17A, IL-22, tumor necrosis factor, interferon-γ, and granulocyte-macrophage colony-stimulating factor, but not anti-inflammatory cytokines IL-10 and IL-4, is elevated in the peripheral blood of DRE subjects compared to WCE. In parallel, we found that Th17-related circulating proinflammatory cytokines are elevated, but Th2-related cytokine IL-4 is reduced, in the serum of epilepsy and DRE subjects. As Th17 cells can exert neurotoxicity, we measured levels of serum neurofilament light chain (sNfL), a marker of neuronal injury. We found significantly elevated levels of sNfL in DRE compared to controls, especially among older individuals. Our data support that DRE is associated with an expansion of the CD4 Tcell subset in the peripheral blood and with a shift toward a proinflammatory Th17/Th1 CD4 Tcell immune profile. Our results further show that pathological levels of sNfL are more frequent in DRE, supporting a potential neurodegenerative component in adult DRE. With this work, we provide evidence for novel potential inflammatory and degenerative biomarkers in DRE.

SLEEP ABNORMALITIES AND POLYSOMNOGRAPHIC PROFILE IN CHILDREN WITH DRUG-RESISTANT EPILEPSY

PurposeThis study aims to assess the prevalence of sleep abnormalities in children with drug-resistant epilepsy (DRE) and characterize their polysomnographic profile and to further compare it with well-controlled epilepsy (WCE) and age-matched typically developing children (TDC). MethodsA cross-sectional study consisting of 40 children in each group (DRE, WCE, and TDC) was conducted. Children’s sleep habits questionnaire (CSHQ) and modified pediatric Epworth daytime sleepiness scale (MPEDSS) were administered to all three groups. Thirty-five children each in the DRE and WCE group and 17 TDC underwent single night polysomnography (PSG). ResultsThe prevalence of sleep abnormalities by the administration of CSHQ in DRE group was 72.5% (95% C.I-58.7 to 86.3%, mean score: 47.5 ± 7.1) compared to 32.5% (42.4 ± 6.2) and 15% (37.3 ± 5) in WCE and TDC groups respectively (P = 0.01). On MPEDSS, 52.5% of children in the DRE group had excessive daytime sleepiness compared to 12.5% in WCE and 5% in TDC groups respectively (p-0.03).On overnight PSG, sleep efficiency and REM sleep duration were significantly reduced in the DRE group in comparison to WCE and TDC. N2 duration, REM latency, arousal, and apnea-hypopnea index were significantly increased in the DRE group when compared to WCE and TDC groups. ConclusionSleep-related problems are major comorbidity in up to three-fourths of patients with DRE and sleep architecture is significantly affected particularly in the DRE group.

Clinical Predictors of Poorly-Controlled Childhood Epilepsy: A Case-Control Study

Introduction:The aim of the present study was to determine clinical factors associated with poorly controlled epilepsy.&#x0D; Materials and Methods: This retrospective study was performed from January 2007 to December 2008 at Paediatric Neurology outpatient department in Bangabandhu Sheikh Mujib Medical University, Dhaka, among the children with epilepsy of 7 months to 15 years age who had history of at least 6 months treatment with rational antiepileptic drugs daily with adequate compliance. There were two groups of patients; group 1, consisted of 50 poorly controlled epilepsy patients and group 2, comprised 50 well-controlled epilepsy patients. We retrospectively reviewed EEGs and medical records from these children. Features of clinical findings were compared between the two groups.&#x0D; Results: In this study, age of onset of initial seizure before 1 year, mixed type of seizure, infantile spasm, high initial seizure frequency (daily seizure), symptomatic etiology, mental retardation, neonatal seizure and more than 20 seizures before starting treatment were also found to be significant clinical predictors of poorly controlled epilepsy. Multivariate analysis detected 2 independent clinical predictors of poorly controlled epilepsy: mixed seizures and more than 20 seizures before starting treatment.&#x0D; Conclusions: The study showed several clinical factors that can be identified early in the course of childhood epilepsy which can predict development of poor seizure control. Knowledge of these factors will help us to discriminate our patients and pay more attention to those at risk of developing poorly controlled epilepsy.&#x0D; Medicine Today 2020 Vol.32(2): 85-90

Behavioral aspects of executive functions in young adults with well-controlled epilepsy

ABSTRACT Executive function (EF) skills involve higher-level cognitive functions, such as planning, goal formation, goal-directed behavior, and effective performance. Previous research has shown that these aspects of EF are essential for successful functioning in everyday life. This study aimed to examine differences in the behavioral aspects of EF between young adults with epilepsy and healthy controls. The study involved 62 young adults, aged 18 to 30 years, divided into two groups: a study group of young adults with well-controlled epilepsy and a control group of healthy young adults. The groups were matched according to basic sociodemographic characteristics. The Behavior Rating Inventory of Executive Function – Adult version was used to assess the behavioral aspects of executive functions. A significant difference between groups was only observed on the Organization of Materials scale, where the group with epilepsy achieved better performance. Our findings suggest that self-assessed behavioral control of EF is almost the same in healthy young adults and young adults with epilepsy who have no comorbidities and have good control of the disease as well as preserved intellectual ability and functionality in everyday activities.

Seizure as the presenting symptom of COVID-19: A retrospective case series

BackgroundCoronavirus Disease 2019 (COVID-19) has rapidly become a global pandemic, with over 1.8 million confirmed cases worldwide to date. Preliminary reports suggest that the disease may present in diverse ways, including with neurological symptoms, but few published reports in the literature describe seizures in patients with COVID-19. ObjectiveThe objective of the study was to characterize the risk factors, clinical features, and outcomes of seizures in patients with COVID-19. MethodsThis is a retrospective case series. Cases were identified through a review of admissions and consultations to the neurology and neurocritical care services between April 1, 2020 and May 15, 2020. SettingThe study setting was in a tertiary care, safety-net hospital in Boston, MA. ParticipantsPatients presenting with seizures and COVID-19 during the study period were included in the study. ResultsSeven patients met inclusion criteria (5 females, 71%). Patients ranged in age from 37 to 88 years (median: 75 years). Three patients had a prior history of well-controlled epilepsy (43%), while 4 patients had new-onset seizures, including 2 patients with prior history of remote stroke. Three patients had no preceding symptoms of COVID-19 prior to presentation (57%), and in all cases, seizures were the symptom that prompted presentation to the emergency department, regardless of prior symptoms of COVID-19. ConclusionsProvoking factors for seizures in patients with COVID-19 may include metabolic factors, systemic illness, and possibly direct effects of the virus. In endemic areas with community spread of COVID-19, clinicians should be vigilant for the infection in patients who present with seizures, which may precede respiratory symptoms or prompt presentation to medical care. Early testing, isolation, and contact tracking of these patients can prevent further transmission of the virus.

A Novel de novo Frameshift Mutation in the BCL11A Gene in a Patient with Intellectual Disability Syndrome and Epilepsy

Intellectual disability syndrome (IDS) associated with a hereditary persistence of fetal haemoglobin (HbF), also known as Dias-Logan syndrome, is commonly characterised by psychomotor developmental delay, intelectual disability, language delay, strabismus, thin upper lip, abnormalities of external ears, microcephaly, downslanting palpebral fissures. Sporadically, autism spectrum disorders and blue sclerae in infancy have been reported in IDS. Rarely, IDS-affected patients present with epilepsy and/or epileptic syndromes. It has been shown that a haploinsufficiency of the B cell leukaemia/lymphoma 11A gene (BCL11A) is responsible for IDS. Herein, we identified a novel de novo frameshift deletion (c.271delG; p.E91Afs*2) in the BCL11A gene in a boy affected with IDS. Interestingly, this heterozygous loss-of-function BCL11A mutation was also associated with a generalised idiopathic epilepsy and severe language delay observed in the patient. Moreover, our study showed that the combination of molecular genetic analyses with the monitoring of HbF was essential to make the final diagnosis of Dias-Logan syndrome. Because our patient suffered from well-controlled epilepsy, we propose to include the BCL11A gene in routinely used molecular genetic epilepsy-related gene panels. Additionally, many of the clinical features of IDS overlap with symptoms observed in patients with suspected alcohol spectrum disorders. Therefore, we also suggest monitoring HbF levels in patients with these syndromes to further facilitate clinical diagnosis.

Focal segmental glomerulosclerosis and mild intellectual disability in a patient with a novel de novo truncating TRIM8 mutation

Mutations in the TRIM8 gene have been described in patients with severe developmental delay, intellectual disability and epilepsy. Only six patients have been described to date. All the previous mutations were truncating variants clustered in the C-terminus of the protein. A previous patient with TRIM8-related epileptic encephalopathy was reported to have nephrotic syndrome. Here we describe the clinical, radiological and histological features of an 8-year-old male patient with a TRIM8 mutation who, in contrast to previous patients, had only mild intellectual disability and well-controlled epilepsy. The patient was found to have proteinuria at 2 years of age. Renal biopsy findings were suggestive of focal segmental glomerulosclerosis. His kidney function declined and peritoneal dialysis was started at 5 years of age. He underwent renal transplant at 7 years of age. Trio-based whole genome sequencing identified a novel de novo heterozygous frameshift mutation in TRIM8 (NM_030912.2) c.1198_1220del, p.(Tyr400ArgfsTer2). This patient is further evidence that TRIM8 mutations cause a syndrome with both neurological and renal features. Our findings suggest the spectrum of TRIM8-related disease may be wider than previously thought with the possibility of milder neurodevelopmental problems and/or a more severe, progressive renal phenotype. We highlight the need for proteinuria screening in patients with TRIM8 mutations.

Course and prognosis of adult-onset epilepsy in Brazil: A cohort study

BackgroundMost of the epilepsy longitudinal studies have analyzed children. However, in endemic regions, such as Brazil, neurocysticercosis accounts for many adult-onset epilepsy cases. So, the main objective of this study was to identify the clinical predictors associated with drug-resistant adult-onset epilepsy in Brazil during a long-term follow-up. MethodsWe followed 302 individuals with adult-onset epilepsy for 9.8 years in our University Hospital. Structured questionnaires about drug-resistant epilepsy were applied. The presence of drug-resistant epilepsy was the primary outcome. We used multilevel linear modeling in our data analysis. ResultsOverall 47 (15.6%) individuals presented drug-resistant epilepsy and the etiology was structural in 70.2% of them, while infectious etiology was present in 8.5% of this group. Infectious etiology occurred in 25.9% (n = 66) of the patients from the nondrug-resistant group. Those with developmental delay were two times more likely to present seizures. Structural epilepsy etiology was associated with an increased chance of relapsing. Poor school performance and abnormal electroencephalogram were also associated with an increased chance of seizures. ConclusionThe course of epilepsy was favorable in the majority of our patients, and drug-resistant epilepsy rates were similar to those found in other studies, although we evaluated older individuals with higher levels of infectious etiology. Also, we found that neurocysticercosis was associated with well-controlled epilepsy, while structural epilepsy was directly related to the occurrence of seizures. We also hypothesized that the smaller size of lesions found in neurocysticercosis could contribute to better treatment response.

Quality of life and its association with comorbidities and adverse events from antiepileptic medications: Online survey of patients with epilepsy in Australia

ObjectiveThis study aimed to explore the quality of life (QoL) of adult patients with epilepsy (PwE) in Australia and its relationship with comorbidities and adverse events (AEs) from antiepileptic drugs (AEDs). MethodsCross-sectional surveys were completed by PwE, or carer proxies, recruited via the online pharmacy application MedAdvisor and Australian PwE Facebook groups from May to August 2018. Data were collected on demographics, epilepsy severity and management, AEs, comorbidities, and QoL (using the Patient-Weighted Quality of Life in Epilepsy Inventory [QOLIE-10-P] total score). Two linear regression models were constructed to explore associations between AEs or comorbidities and QOLIE-10-P score, with possible confounders determined using stepwise selection. ResultsNine hundred and seventy-eight of 1267 responses were eligible (mean age of respondents: 44.5 years, 64% female, 52% employed). Recent AED use was reported by 97%; 47% were on AED monotherapy, 35% had ≤2 lifetime AEDs, and 55% were seizure-free for >1 year. After stepwise selection, control variables included in both models were time since diagnosis, employment status, seizure frequency, number of currently prescribed AEDs, and number of general practitioner (GP) visits per year. In the model for comorbidities, “psychiatric disorders” was associated with the largest QOLIE-10-P score decrease (−23.14, p < 0.001). In the model for AEs, which additionally controlled for depression and anxiety disorder, self-reported “memory problems” was associated with the largest decrease in QOLIE-10-P score (−14.27, p < 0.001). ConclusionsIn this survey of Australian PwE, many of whom had relatively well-controlled epilepsy, psychiatric and self-reported memory problems were common and associated with the greatest detrimental impact on QoL. Further research is needed to better understand the underlying causes of impaired QoL and thereby improve its management.

EEG as a Predictor of Poorly- Controlled Childhood Epilepsy

Introduction:The aim of the present study was to determine electroencephalographic factors associated with poorly controlled epilepsy.&#x0D; Materials and Methods: This retrospective study was performed from January 2007 to December 2008 at Paediatric Neurology outpatient department in Bangabandhu Sheikh Mujib Medical University, Dhaka, among the children with epilepsy of 7 months to 15 years age who had history of at least 6 months treatment with rational antiepileptic drugs daily with adequate compliance. There were two groups of patients; group 1, consisted of 50 poorly controlled epilepsy patients and group 2, comprised 50 well-controlled epilepsy patients. We retrospectively reviewed EEGs and medical records from these children. Features of initial EEGs findings were compared between the two groups.&#x0D; Results: Significant electroencephalographic predictors of poorly controlled epilepsy were: abnormal initial EEG (p=0.025), EEG background abnormality (p&lt;0.001), frequent sharp wave/spike (p&lt;0.001) and hypsarrhythmia (p=0.046). No significant difference was noticed between the two groups in respect to the location of spikes/ sharp waves. With multiple logistic regression, independent predictors of poor seizure control were EEG background abnormality and frequent sharp wave/spike.&#x0D; Conclusion: The study showed several Electroencehalographic factors that can be identified early in the course of childhood epilepsy which can predict development of poor seizure control. Knowledge of these factors will help us to discriminate our patients and pay more attention to those at risk of developing poorly controlled epilepsy.&#x0D; Medicine Today 2020 Vol.32(1): 15-20