Course Of Epilepsy Research Articles

The short-term prognostication of characteristics of course and optimization of tactics of medical care support of patients with epilepsy

In clinical practice the identification of the dynamics of course of focal epilepsies on the basis of available clinical and neurophysiological indices (prognostication) is of great importance. The purpose of the study is the short-term prognostication of the course of focal frontal and temporal epilepsy. The materials and methods. The control (42 patients) and clinical (70 patients) groups were examined. The complex clinical physiological examination was carried out using electroencephalography, cognitive evoked potential, cardiac rhythm variability and the Schulte test. The cluster analysis was applied to allocate the observable patients into groups according to the dynamics of seizures frequency. The artificial neural networks technology based on physiological characteristics was applied to classify patients into groups with different course of disease. The results. The spectral characteristics of electroencephalographic signal had the greatest value for short-term prognostication of course of disease in the group of patients with focal frontal epilepsy. In patients with focal temporal epilepsy, the most significant predictors were the characteristics of cognitive evoked potential and characteristics of function of coherence of electroencephalogram. The conclusions. The developed algorithm of prognostication of unfavorable course of focal frontal epilepsy has high sensitivity, but lower specificity. Contrariwise, in case of temporal epilepsy, high specificity of the proposed algorithm is demonstrative, but its sensitivity is lower. It is recommended to apply these algorithms and to accentuate attention on characteristics of potential parameters at organization of diagnostic process in case of focal epilepsy.

Problems of diagnosing focal cortical dysplasia

Focal cortical dysplasia (FCD) is one of the most common causes in developing pharmacoresistant epilepsy. We present the clinical case of the patient with generalized seizures. Routine electroencephalography (EEG) data registered diffuse epileptiform activity that allowed to diagnose genetic eneralized epilepsy and pharmacoresistant course of seizures.After performing magnetic resonance imaging using the epileptological program and video-EEG-monitoring, the diagnosis was revised: structural focal epilepsy with seizures with focal onset with oroalimentary, gesture automatisms in the right hand, bilateral tonic-clonic, uncompensated by levetiracetam monotherapy (1500 mg/day). Background disease: congenital malformation of the brain: FCD in the basal parts of the left temporal lobe. Lacosamide was added to the therapy in the drug dose 300 mg/day, and the frequency of epileptic seizures decreased. Differential diagnosis between genetic generalized epilepsy and structural epilepsy with FCD usually poses no obstacles. However, in some cases, structural epilepsy occurs under the “mask” of generalized epilepsy. Hence, this clinical case demonstrates the importance of diagnostic measures in the differential diagnostics of various forms of epilepsy to determine further tactics of patient management.

Psychiatric disorders in patients with resistant temporal lobe epilepsy two years after undergoing elective surgery. A longitudinal study

PurposePsychiatric morbidity in temporal lobe epilepsy (TLE) is frequent and negatively affects patients’ life quality. Surgery is the procedure of choice when treating seizures, although the effects on psychiatric disorders remain unclear. We evaluate the effect of surgery on psychiatric disorders in patients with TLE two years after the intervention, to then shed light on how these are related to anxiety and depression symptoms, and Interictal Dysphoric Disorder (IDD). MethodsWe included data from 65 patients with TLE whose psychiatric evaluations were performed according to DSM-IV criteria. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) test. ResultsAt 2-year follow-up, anxiety and depressive disorders decreased, and psychotic disorders augmented without statistical significance. Baseline psychiatric disorders predisposed to psychiatric pathology at 2-year follow-up and did not correlate with epilepsy outcome after surgery. Postoperative psychiatric disorders correlated with the seizure incidence two years after the intervention, suggesting that epilepsy and psychiatric disorders were associated in processes such as surgery. De novo psychiatric disorders represented 52% of postoperative psychiatric pathology, 62% being psychotic disorders. De novo psychiatric disorders became more frequent from the first year of surgery, occurring mainly in patients free of seizures. The HADS test scores and IDD correlated with psychiatric disorders at 2-year follow-up. ConclusionsBaseline psychiatric disorders did not influence surgery outcome, but correlated with psychiatric disorders’ prevalence two years after surgery. Despite not finding statistical significance, surgery reduced the prevalence of psychiatric disorders, and de novo psychiatric disorders were associated with an improvement in the epilepsy course at 2-year follow-up.

Unusual drug-resistant psychotic state with epilepsy manifestations, cognitive deterioration and muscular atrophy - case report

Introduction This article will focus on the case of patient whose disease manifested after episode of dehydration at 16 years of age and within 8 years led to his death. During the eight years of illness, the patient suffered from polymorfic psychotic states accompanied by various types of epileptic seizures, including absence and grand-mal seizures, resistant to drug therapy. In addition, he suffered from multiple motor disorders, skeletal and mimiс muscle atrophy, as well as progressive cognitive decline from very high level of cognitive functions to level of moderate deterioration. Despite repeated evaluations, there was no unequivocal diagnosis of his disorder.ObjectivesMale, born in 1994, without a known hereditary pathology in the field of neurology or psychiatry. Pregnancy and childbirth proceeded without features and the early stages of cognitive-motor development were marked as normative, with the exception of a single epileptic seizure at the age of 3 years (according to the description of the parents). Until the age of 16, the patient was not under the supervision of a neurologist or psychiatrist, developed on a par with his peers, successfully attended school with high marks in the exact sciences, and went in for sports.MethodsCase reportResultsCase reportConclusionsA patient is considered with a non-standard course of psychosis and epilepsy, which was accompanied by multiple neurological and psychiatric symptoms.In Israel there are only 13 patients with a resemble clinical picture and there is no diagnosis or group of diagnoses in ICD, DSM or any neulogical classificatin tha can describe his disease.

Juvenile myoclonic epilepsy: Long-term prognosis and risk factors

ObjectiveOur goal was to investigate the long-term clinical course of juvenile myoclonic epilepsy (JME) in a cohort of patients and to identify prognostic factors for refractoriness and seizure relapse after anti-seizure medications (ASMs) withdrawal. A literature review is also presented to consolidate and compare our findings with the previously reported cases. MethodsWe retrospectively studied a series of patients diagnosed with JME with 15 years or more of evolution. We collected clinical, neurophysiological and neuroimaging data from patients who met defined inclusion and exclusion criteria. ResultsStudy involved 61 patients (65.5% female) with mean age at study of 37.6 years, and mean age at its outset of 14.8 years. Median follow-up was 31.0 years (mean 28.9, range 15–53). They presented more frequently with a combination of myoclonic and generalized tonic-clonic seizures (GTCS) (65.6%). Sixty-five percent of patients (n = 40) had a 5-year terminal remission with a mean age at last seizure of 27.4 years. Thirty-two percent of seizure-free patients (n = 13) withdrew ASMs: 6 out of 13 had a recurrence of the seizures while 7 remained seizure-free (mean age at ASMs withdrawal 21.0 versus 35.7 years, p < 0.05). In the multivariate model, a high GTCS frequency at onset (p = 0.026) was a prognostic factor of drug resistance. ConclusionJME is often regarded as a benign epileptic syndrome, although a quarter of the individuals have refractory epilepsy. The possibility of withdrawing ASMs in patients who have been free of seizures over an extended time seems feasible.

Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders.

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel Kv1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants.

Two decades of research towards a potential first anti-epileptic drug

The basic mechanisms by which brain insults, such as trauma, stroke or status epilepticus produce epilepsy are not completely understood, and effective preventive measures and treatment are still not available in the clinical setting. Over the last 2 decades we have conducted several studies with animal models of epilepsy (rodents and non-human primates) and demonstrated that drugs that modify neuronal plastic processes, such as anticholinergic agents (e.g., antimuscarinic compounds), if administered soon after brain injury and over a period of 10–20 days, have the potential to modify the natural course of post-traumatic epilepsy. To that end treatment with scopolamine showed promising results as a candidate agent in both the pilocarpine and kainate models. We then showed that biperiden, yet another cholinergic antagonist acting in the muscarinic receptor, that is widely used to treat Parkinson's disease, also decreased the incidence and intensity of spontaneous epileptic seizures, delaying their appearance in the pilocarpine model of epilepsy. In other words, biperiden showed to be a potential candidate to be further investigated as an antiepileptogenic agent. Accordingly, we tested the safety of biperiden in a small group of patients (as a small phase II safety assessment) and confirmed its safety in the context of traumatic brain injury (TBI). Now, we provide information on our ongoing project to evaluate the efficacy of biperiden in preventing the development of epilepsy in patients that suffered TBI, in a double blind, randomized, placebo-controlled trial.

Status epilepticus of focal impaired-awareness seizures. Russkiy zhurnal detskoy nevrologii

Background. The status epilepticus of focal impaired-awareness seizures (SE FIAS) is a series of focal seizures with loss or change of consciousness, between which there is no complete recovery of consciousness. This status epilepticus occurs in patients with temporal (especially with hippocampal sclerosis) and frontal epilepsy. It is important to differentiate SE FIAS with the absence status epilepticus, with psychiatric disorder, with postictal confusion. As a rule, this status epilepticus is self-terminate, without special treatment.Objective: to study the features of epidemiology, etiology, diagnosis, therapy and prognosis in patients with SE FIAS.Materials and methods. The study included 1350 consecutive patients diagnosed with epilepsy.Results and discussion. A history of SE FIAS was found in 20 patients (14 women and 6 men), it occurred in the age range from 5 to 66 years. 13 patients (65 %) had mesial temporal lobe epilepsy, 5 patients (25 %) had frontal lobe epilepsy, and 2 patients (10 %) had lateral temporal lobe epilepsy. Only in 80 % of patients treatment was adequate before the development of SE FIAS, in 20 % of patients it was inadequate and subsequently caused the development of status epilepticus. In 40 % of patients the occurrence of SE FIAS is associated with their own non-compliance; in 30 % of patients the development of status epilepticus had iatrogenic causes. Measures to prevent the development of status epilepticus were ineffective only in patients with pharmacoresistant symptomatic epilepsy and in non-compliant patients.Conclusions. SE FIAS occurs in 1 % of patients with epilepsy. Among patients, women with temporal or frontal epilepsy dominate; status epilepticus occurs at any age and is often triggered by changes in therapy due to doctors’ recommendations or patient non-compliance. Usually the status is self-terminating. To prevent its recurrence, adequate antiepileptic therapy is necessary. The prognosis in patients with SE FIAS is favorable; however, the general prognosis remains serious due to the severity of the course of epilepsy.

The effect of rehabilitation treatment on the electroencephalography results and the course of epilepsy in children with cerebral palsy

Introduction. Cerebral palsy is often combined with epilepsy and epileptiform electroencephalographic (EEG) activity. Currently, the question of how rehabilitation with cerebral palsy is dangerous in relation to the provocation of epileptic seizures is relevant. Objective: to study the effect of cerebral palsy rehabilitation on epilepsy in a standard rehabilitation center. Material and methods. We examined 80 children with various forms of cerebral palsy and epileptiform EEG activity. The patients were divided into two groups: children of Group 1 never had epileptic seizures, children of Group 2 had a history of epileptic seizures of more than 6 months ago. The follow-up was 12 months during which children underwent EEG before and after rehabilitation courses. Depending on the risks associated with provoking epileptic seizures, patients were prescribed rehabilitation procedures of various intensities: Vojta kinesiotherapy, massage, physiotherapeutic treatment in the form of transcranial micropolarization and paraffin therapy. Results. During the study, epileptic seizures developed in 5 patients (12.5%) from Group 1 and in 7 children (17.5%) from Group 2. In all cases, rare focal seizures were recorded (1–2 times a year). All patients with seizures during our study had a history of seizures under the age of 1 year. The onset of seizures was quickly stopped by the basic antiepileptic drugs in monotherapy. Epileptic seizures developed in children with moderate to severe cerebral palsy on GMFCS (Gross Motor Function Classification System) and a history of neonatal seizures. We attributed both of these to risk factors. In children with cerebral palsy and epilepsy in remission of 6 months or more, massage and Vojta therapy did not provoke epileptic seizures. The effect of epileptiform activity on the severity of motor status and on cognitive functions in cerebral palsy has not been established in our study. Conclusion. According to our data, rehabilitation measures do not have a significant impact on the risk of developing 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

Peculiarities of formation and clinical course of symptomatic epilepsy as a result of cranial injury

Post-traumatic epilepsy (PTE) is a formidable and frequent consequence of traumatic brain injury (TBI) in the long term. 41 patients with PTE were examined, mostly men of working age. The time of formation of PTE after was 14.3 ± 1.4 months, which decreased depending on the severity of brain injury, the average frequency of seizures was 2.93 ± 0.8 per month.Focal seizures were mainly registered (63.4%, p &lt;0.05), and taking into account the focal onset in bilateral tonic-clonic seizures, this figure reached 90.2% (p &lt;0.05). Among the selected syndromes, except for direct PTE, autonomic dysfunctions (87.8%) with paroxysmal course (58.5%) prevailed, especially in persons with moderate trauma (r = 0.51, p &lt;0.05).Typical comorbid symptoms in people with PTE were cognitive deficits, which correlated with the severity of TBI, as well as depressive and anxiety symptoms. Depressive layers were more often observed in the presence of the focal component of seizures (94.7%, p &lt;0.05), temporal localization of the pathological process and predominant vagotonia. Anxiety manifestations affected all types of attacks on the background of sympathicotonia (83.3%, p &lt;0.05), which in our opinion improved the implementation of crisis conditions, which were observed in 66.7% of cases.

Peculiarities of formation and clinical course of symptomatic epilepsy as a result of cranial injury

Peculiarities of formation and clinical course of symptomatic epilepsy as a result of cranial injury

ОСЬ КИШЕЧНИК–МОЗГ И РЕЦЕПТОРЫ, АКТИВИРУЕМЫЕ ПЕРОКСИСОМНЫМИ ПРОЛИФЕРАТОРАМИ КАК ФАКТОРЫ РЕГУЛЯЦИИ ЭПИЛЕПТОГЕНЕЗА

A large proportion of patients with epilepsy suffer from pharmacoresistant forms of the disease, and this makes the search for new treatments urgent. The possible role of gut-brain interactions in the pathogenesis of epilepsy is widely discussed. Recent experimental and clinical studies show a correlation between the balance of gut microbiota and the severity of epileptogenesis. Various methods to modify the microbiota composition demonstrate its significant impact on the clinical course of epilepsy. Nevertheless, the question remains open as to the basic receptor element of the gut-brain axis, a sort of an interface between the gut microorganisms and the body's regulatory systems. This review aims to analyze the pathways and levels of gut microbiota involvement in the pathogenesis and sanogenesis of epilepsy. Among these pathways, the neural, metabolic, immune, and endocrine pathways are distinguished. Analysis of the data obtained to date shows a significant role for peroxisome proliferator-activated receptors (PPARs) in these processes. The expression of these receptors in the main structures of the gut-brain axis, the presence of their ligands among the metabolites of microbiota, as well as anticonvulsant and/or neuroprotective activities described for some PPAR agonists, allow a hypothesis to be proposed on the role of PPARs as the above-mentioned signaling interface in the gut-brain axis. Separate attention is paid to the therapeutic potential of PPAR agonists in epilepsy treatment.

Antiepileptic and cognition-enhancing effects of Citrus aurantium peel extract in animal model of epilepsy

Background: History of epilepsy is intertwined with the chronicles of humankind, with millions of people worldwide living with epilepsy, still the current available antiepileptic drugs (AEDs) only suppress seizures without correcting the natural course of epilepsy. Growing limitations of available AEDs have motivated this study to divert our attention towards other safe and natural resources available for the treatment of epilepsy. Aim and Objective: This study aims to investigate the antiepileptic and cognition-enhancing effects of Citrus aurantium (CA) in a mouse model of pentylenetetrazole (PTZ)-induced generalized tonic–clonic seizures. Materials and Methods: Kindling was induced by administering 35 mg/kg PTZ to 6-month-old Swiss albino mice for 28 days. Mice were divided into following groups: PTZ control group; CA peel extract group, and Valproic acid (VA) group. The methods used for validating the antiepileptic and cognition-enhancing effects were Behavioral seizure evaluation and Cook’s pole climbing apparatus. Results: Acute treatment with CA effectively attenuated the seizures induced by PTZ. The antiepileptic and cognition-enhancing effects of CA peel extract were comparable with the standard treatment, that is, VA. Conclusion: CA showed remarkable antiepileptic and memory-enhancing effects in PTZ-induced seizures and the effects were comparable to VA.

Dravet syndrome

This review will illustrate the electroclinical description of Dravet syndrome, highlighting the difficulty to understand the correlation between the SCN1A mutation and clinical characteristics, including the frequent comorbidities. Therefore, the efficacy of the new treatment options, which now become available, should not only focus on seizure frequency reduction but also on the long-term effects on these comorbidities, such as intellectual disability, motor and sleep problems. Comprehensive guidelines for a more standardized treatment in children with Dravet syndrome have been published. First-line and second-line treatments actually include only a few antiseizure medications, such as valproate, clobazam, stiripentol, topiramate and bromide. Cannabidiol and fenfluramine were shown to be very effective drugs and will become standard second-line drugs in Dravet syndrome. There are preliminary data showing that both drugs also have a positive effect on quality of life and on cognitive functioning. Genetic treatments in Dravet syndrome most likely will dramatically change the natural course of this refractory epilepsy syndrome. A better understanding of the full clinical picture is necessary to understand the potential value of new treatment options in Dravet syndrome. Treatment nowadays with the newer drugs becomes much more standardized and effective, and this will have a positive effect on long-term overall outcome.

Pro-inflammatory cytokines, but not brain- and extracellular matrix-derived proteins, are increased in the plasma following electrically induced kindling of seizures

BackgroundThe aim of the study was to evaluate the brain-derived proteins, extracellular matrix-derived protein and cytokines as potential peripheral biomarkers of different susceptibility to seizure development in an animal model of epilepsy evoked by chronic focal electrical stimulation of the brain.MethodsThe plasma levels of IL-1β (interleukin 1β), IL-6 (interleukin 6), UCH-L1 (ubiquitin C-terminal hydrolase 1), MMP-9 (matrix metalloproteinase 9), and GFAP (glial fibrillary acidic protein) were assessed. The peripheral concentrations of the selected proteins were analyzed according to the status of kindling and seizure severity parameters. In our study, increased concentrations of plasma IL-1β and IL-6 were observed in rats subjected to hippocampal kindling compared to sham-operated rats.ResultsAnimals that developed tonic–clonic seizures after the last stimulation had higher plasma concentrations of IL-1β and IL-6 than sham-operated rats and rats that did not develop seizure. Elevated levels of IL-1β and IL-6 were observed in rats that presented more severe seizures after the last five stimulations compared to sham-operated animals. A correlation between plasma IL-1β and IL-6 concentrations was also found. On the other hand, the plasma levels of the brain-derived proteins UCH-L1, MMP-9, and GFAP were unaffected by kindling status and seizure severity parameters.ConclusionsThe plasma concentrations of IL-1β and IL-6 may have potential utility as peripheral biomarkers of immune system activation in the course of epilepsy and translational potential for future clinical use. Surprisingly, markers of cell and nerve ending damage (GFAP, UCH-L1 and MMP-9) may have limited utility.

Length Polymorphism and Methylation Status of UPS29 Minisatellite of the ACAP3 Gene as Molecular Biomarker of Epilepsy. Sex Differences in Seizure Types and Symptoms.

Epilepsy is a neurological disease with different clinical forms and inter-individuals heterogeneity, which may be associated with genetic and/or epigenetic polymorphisms of tandem-repeated noncoding DNA. These polymorphisms may serve as predictive biomarkers of various forms of epilepsy. ACAP3 is the protein regulating morphogenesis of neurons and neuronal migration and is an integral component of important signaling pathways. This study aimed to carry out an association analysis of the length polymorphism and DNA methylation of the UPS29 minisatellite of the ACAP3 gene in patients with epilepsy. We revealed an association of short UPS29 alleles with increased risk of development of symptomatic and cryptogenic epilepsy in women, and also with cerebrovascular pathologies, structural changes in the brain, neurological status, and the clinical pattern of seizures in both women and men. The increase of frequency of hypomethylated UPS29 alleles in men with symptomatic epilepsy, and in women with both symptomatic and cryptogenic epilepsy was observed. For patients with hypomethylated UPS29 alleles, we also observed structural changes in the brain, neurological status, and the clinical pattern of seizures. These associations had sex-specific nature similar to a genetic association. In contrast with length polymorphism epigenetic changes affected predominantly the long UPS29 allele. We suppose that genetic and epigenetic alterations UPS29 can modify ACAP3 expression and thereby affect the development and clinical course of epilepsy.

Evaluation of serum high-mobility group box 1 concentration in dogs with epilepsy: A case-control study.

BackgroundHigh‐mobility group box 1 (HMGB1) is a key mediator of neuroinflammation and there are increased HMGB1 levels in laboratory animal models of epilepsy and human patients with epilepsy.ObjectivesTo determine serum HMGB1 levels in dogs with epilepsy.AnimalsTwenty‐eight epileptic dogs, 12 dogs with nonepileptic brain diseases, and 26 healthy dogs.MethodsIn this case‐control study, serum HMGB1 concentrations were estimated using the canine‐specific enzyme‐linked immunosorbent assay kit. Diagnosis of dogs with epilepsy was based on medical history, physical and neurological examination findings, laboratory test results, magnetic resonance image, and cerebrospinal fluid analysis.ResultsSerum HMGB1 levels were significantly higher in epileptic dogs (median = 0.41 ng/mL; range, 0.03‐5.28) than in healthy dogs (median = 0.12 ng/mL; range, 0.02‐1.45; P = .002). In contrast, serum HMGB1 levels of dogs with non‐epileptic brain diseases (median = 0.19 ng/mL; range, 0.03‐1.04) were not significantly increased compared to those of healthy dogs (P = .12). Regarding idiopathic epilepsy, dogs with an epilepsy course of >3 months showed a higher serum HMGB1 concentration (median = 0.87 ng/mL; range, 0.42‐2.88) than those with that of ≤3 months (median = 0.26 ng/mL; range, 0.03‐0.88; P = .02).Conclusions and Clinical ImportanceSerum HMGB1 could be a biomarker of epilepsy.

Developmental and epilepsy spectrum of KCNB1 encephalopathy with long-term outcome.

We aimed to delineate the phenotypic spectrum and long-term outcome of individuals with KCNB1 encephalopathy. We collected genetic, clinical, electroencephalographic, and imaging data of individuals with KCNB1 pathogenic variants recruited through an international collaboration, with the support of the family association "KCNB1 France." Patients were classified as having developmental and epileptic encephalopathy (DEE) or developmental encephalopathy (DE). In addition, we reviewed published cases and provided the long-term outcome in patients older than 12years from our series and from literature. Our series included 36 patients (21 males, median age = 10years, range = 1.6months-34years). Twenty patients (56%) had DEE with infantile onset seizures (seizure onset = 10months, range = 10days-3.5years), whereas 16 (33%) had DE with late onset epilepsy in 10 (seizure onset = 5years, range = 18months-25years) and without epilepsy in six. Cognitive impairment was more severe in individuals with DEE compared to those with DE. Analysis of 73 individuals with KCNB1 pathogenic variants (36 from our series and 37 published individuals in nine reports) showed developmental delay in all with severe to profound intellectual disability in 67% (n=41/61) and autistic features in 56% (n=32/57). Long-term outcome in 22 individuals older than 12years (14 in our series and eight published individuals) showed poor cognitive, psychiatric, and behavioral outcome. Epilepsy course was variable. Missense variants were associated with more frequent and more severe epilepsy compared to truncating variants. Our study describes the phenotypic spectrum of KCNB1 encephalopathy, which varies from severe DEE to DE with or without epilepsy. Although cognitive impairment is worse in patients with DEE, long-term outcome is poor for most and missense variants are associated with more severe epilepsy outcome. Further understanding of disease mechanisms should facilitate the development of targeted therapies, much needed to improve the neurodevelopmental prognosis.

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