Partial Seizures Research Articles

Study on Factors Associated with Poor Seizure Control in Epileptic Patients during Pregnancy

The management of epilepsy during pregnancy is always challenging. This study aims to analyze the factors associated with poor seizure control during pregnancy and to describe the most commonly used antiseizure drugs in these patients. We conducted a casecontrol study of pregnant patients with epilepsy between 2017 and 2022. 50 pregnant women with poorly controlled epilepsy were taken as cases and 50 pregnant women with well-controlled epilepsy were taken as controls. Patients were evaluated in the first and second trimesters of pregnancy and after delivery. Patients’ mean age was 32.6 years. 53% had focal epilepsy, 40% had generalized epilepsy and 5 % had undetermined epilepsy. The factors associated with poor control of seizure during pregnancy were duration of epilepsy, poor seizure control in the year prior to pregnancy, treatment with 2 or more antiseizure drugs, untreated epilepsy, missed medication dosages, decline in plasma concentrations of antiepileptic drug, presence of focal activity in EEG and abnormal imaging findings. Anti-seizure medications most widely used in monotherapy were lamotrigine, levetiracetam, carbamazepine, and valproate. EWMCJ Vol. 12, No. 1&2, January-July 2024: 99-103

[11C]Metoclopramide PET can detect a seizure-induced up-regulation of cerebral P-glycoprotein in epilepsy patients

BackgroundP-glycoprotein (P-gp) is an efflux transporter which is abundantly expressed at the blood-brain barrier (BBB) and which has been implicated in the pathophysiology of various brain diseases. The radiolabelled antiemetic drug [11C]metoclopramide is a P-gp substrate for positron emission tomography (PET) imaging of P-gp function at the BBB. To assess whether [11C]metoclopramide can detect increased P-gp function in the human brain, we employed drug-resistant temporal lobe epilepsy (TLE) as a model disease with a well characterised, regional P-gp up-regulation at the BBB.MethodsEight patients with drug-resistant (DRE) TLE, 5 seizure-free patients with drug-sensitive (DSE) focal epilepsy, and 15 healthy subjects underwent brain PET imaging with [11C]metoclopramide on a fully-integrated PET/MRI system. Concurrent with PET, arterial blood sampling was performed to generate a metabolite-corrected arterial plasma input function for kinetic modelling. The choroid plexus was outmasked on the PET images to remove signal contamination from the neighbouring hippocampus. Using a brain atlas, 10 temporal lobe sub-regions were defined and analysed with a 1-tissue-2-rate constant compartmental model to estimate the rate constants for radiotracer transfer from plasma to brain (K1) and from brain to plasma (k2), and the total volume of distribution (VT = K1/k2).ResultsDRE patients but not DSE patients showed significantly higher k2 values and a trend towards lower VT values in several temporal lobe sub-regions located ipsilateral to the epileptic focus as compared to healthy subjects (k2: hippocampus: +34%, anterior temporal lobe, medial part: +28%, superior temporal gyrus, posterior part: +21%).Conclusions[11C]Metoclopramide PET can detect a seizure-induced P-gp up-regulation in the epileptic brain. The efflux rate constant k2 seems to be the most sensitive parameter to measure increased P-gp function with [11C]metoclopramide. Our study provides evidence that disease-induced alterations in P-gp expression at the BBB can lead to changes in the distribution of a central nervous system-active drug to the human brain, which could affect the efficacy and/or safety of drugs. [11C]Metoclopramide PET may be used to assess or predict the contribution of increased P-gp function to drug resistance and disease pathophysiology in various brain diseases.Trial registrationEudraCT 2019-003137-42. Registered 28 February 2020.

Infantile Intraparenchymal Brain Abscess due to Streptococcus pyogenes

Introduction Group A ß-hemolytic streptococcus (GABHS) are the most common bacterial cause of tonsillitis, and can cause noninvasive diseases such as pharyngitis and impetigo, as well as more severe invasive diseases. The incidence of invasive disease is 1-3/100,000 per year, and the morbidity and mortality rate is high. GABHS is rarely lead to brain abscesses. Case Report Acute phase reactants were found to be high in a 40-day-old patient who presented with fever, irritability and focal seizures. Acute phase reactants were high. Transfontanel ultrasonography showed increased thickness, echo and blood supply in the meninges. Brain magnetic resonance imaging (MRI) and diffusion MRI revealed a thick-walled abscess in the right cerebral hemisphere and parietooccipital parenchyma with diffusion restriction on diffusion-weighted images. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) test revealed S. pyogenes,and S. pyogenes grown in CSF culture. Initially, meropenem, vancomycin, metronidazole antibiotherapy was applied. Treatment was revised to cefotaxime and vancomycin after culture antibiogram and was completed for 8 weeks. Seizures regressed. Control brain imaging showed improvement. Restriction in left lower extremity movements remained. Physical therapy and rehabilitation was recommended and he was discharged. Conclusion GABHS, which is the causative agent of acute tonsillitis, rarely causes invasive disease which has high mortality and morbidity.

Quantitative EEG biomarkers for STXBP1-related disorders.

EEG patterns and quantitative EEG (qEEG) features have been poorly explored in monogenic epilepsies. Herein, we investigate regional differences in EEG frequency composition in patients with STXBP1 developmental and epileptic encephalopathy (STXBP1-DEE). We conducted a retrospective study collecting electroclinical data of patients with STXBP1-DEE and two control groups of patients with DEEs of different etiologies and typically developing individuals matched for age and sex. We performed a (1) visual EEG assessment, (b) qEEG analysis, and (c) electrical source imaging (ESI). We quantified the relative power (RP) of four frequency bands (α β, θ, δ), in two electrode groups (anterior/posterior), and compared their averages and dynamics (standard deviation [SD] over time). The ESI was performed by applying the standard Distributed Source Modeling algorithm. We analyzed 42 EEG studies in 19 patients with STXBP1-DEE (10 female), with a median age at recordings of 9.6 years (range 9 months to 29 years). The δRP was higher in recordings of STXBP1-DEE (p < .001) compared to both control groups, suggesting the pathogenicity and STXBP1-specificity of these findings. In STXBP1-DEE, the δRP was significantly higher in the anterior electrode group compared to the posterior one (p = .003). There was no correlation between the anterior δRP and the epilepsy focus, age at recordings, and concomitant medications The ESI modeling of this activity showed a widespread involvement of the dorsomesial frontal cortex, suggesting a large corticosubcortical pathologic network. Finally, we identified two groups of recordings: cluster.1 with higher anterior δRP and low dynamics and cluster.2 with lower δRP and higher dynamics. Patients in cluster.1 had a more severe epilepsy and neurological phenotype compared to patients in cluster 2. The qEEG analysis showed a predominant frontal slow activity as a specific STXBP1 feature that correlates with the severity of the phenotype and may represent a biomarker for prospective longitudinal studies of STXBP1-DEE.

Meningeal Dissemination and Drop Metastasis From Glioma Presenting With Non-Epileptic Myoclonus and Minipolymyoclonus

We describe the case of a 36-year-old woman with a past medical history of low grade right frontal lobe glioma and focal epilepsy presenting with subacute, progressive, multifocal myoclonus and neck and back pain. Unlike her typical seizures, the myoclonus exhibited a distinct semiology, involving both positive and negative muscle jerks affecting multiple limb muscles while sparing the face. In addition, neurological examination revealed low-amplitude, arrhythmic movements of the hands and fingers, resembling minipolymyoclonus. There were no other neurological exam findings, including mental status changes, extrapyramidal signs or signs of myelopathy. Brain and spine MRI indicated leptomeningeal and spinal “drop” enhancing lesions, suggesting likely malignant evolution of the glioma. EEG ruled out a cortical origin of the myoclonus. Pharmacological trials with benzodiazepines and other antiepileptic medications were ineffective. The patient’s myoclonus was most likely spinal segmental in origin from meningeal spread of glioma. The spinal roots or anterior horns of the spinal cord may have represented a focus of hyperexcitability responsible for generating minipolymyoclonus. Our case expands the etiological spectrum of non-epileptic myoclonus and minipolymyoclonus to encompass meningeal carcinomatosis and drop metastases from glioma. These cases may occur even without overt signs of myelopathy. Recognizing such presentations holds significance due to the poor prognosis associated with meningeal spread of glioma and the limited response of non-epileptic myoclonus to symptomatic treatments.

Impact of the socioeconomic crisis in Lebanon on people with epilepsy.

The economic crisis in Lebanon, which began in 2019, has affected the healthcare system and patients' incomes. The aim of this study was to analyze the obstacles faced by people with epilepsy (PWE) during this crisis and to assess its impact on their quality of life. The method used was a cross-sectional study conducted among PWE aged 18-65 years, who were asked to complete a comprehensive questionnaire covering sociodemographic aspects, clinical aspects, the impact of the economic crisis, and the QOLIE-31 (version 1.0), validated in English and Arabic, which assesses the quality of life of PWE. 71 patients were included in the study with an average age of 35.2 years [23.5; 62.5] (53.5% were males). Their average QOLIE-31 score was 50.3 (+/- 17.9). A significant proportion (71%) of patients reported difficulties during the crisis, with 25% reporting having had seizure-related injuries in the years 2022-2023 and 36.6% reporting an increase in seizure frequency compared to that prior to 2020. Moreover, many patients had to change (33.8%) or discontinue (18.3%) antiseizure medications, due to drug shortages, rising costs, and high gas prices. To mitigate these challenges, patients sought solutions such as obtaining medications from abroad (34%) or through donations (8%) or purchasing from the black market (8%). Low quality of life was associated with unemployment, low education level, the presence of focal seizures with impaired awareness or generalized seizures, polytherapy, seizure-related injuries, and medication changes during the economic crisis. These results highlight the considerable challenges faced by PWE in Lebanon during the economic crisis, emphasizing the negative effect of the crisis on their quality of life and seizure control. This study analyzed the obstacles faced by 71 people with epilepsy during Lebanon's economic crisis and showed that many patients had to change (33.8%) or discontinue (18.3%) antiseizure medications, due to drug shortages, rising costs, and high gas prices. To mitigate these challenges, patients sought solutions such as obtaining medications from abroad (34%) or through donations (8%) or purchasing from the black market (8%). This affected their quality of life. In fact, low quality of life was associated with unemployment, low education level, focal seizures with impaired awareness or generalized seizures, polytherapy, seizure-related injuries, and medication changes.

Somatic variant analysis of resected brain tissue in epilepsy surgery patients.

We studied the distribution of germline and somatic variants in epilepsy surgery patients with (suspected) malformations of cortical development (MCD) who underwent surgery between 2015 and 2020 at University Medical Center Utrecht (the Netherlands) and pooled our data with four previously published cohort studies. Tissue analysis yielded a pathogenic variant in 203 of 663 (31%) combined cases. In 126 of 379 (33%) focal cortical dysplasia (FCD) type II cases and 23 of 37 (62%) hemimegalencephaly cases, a pathogenic variant was identified, mostly involving the mTOR signaling pathway. Pathogenic variants in 10 focal epilepsy genes were found in 48 of 178 (27%) FCDI/mild MCD/mMCD with oligodendroglial hyperplasia and epilepsy cases; 36 of these (75%) were SLC35A2 variants. Six of 69 (9%) patients without a histopathological lesion had a pathogenic variant in SLC35A2 (n = 5) or DEPDC5 (n = 1). A germline variant in blood DNA was confirmed in all cases with a pathogenic variant in tissue, with a variant allele frequency (VAF) of ~50%. In seven of 114 patients (6%) with a somatic variant in tissue, mosaicism in blood was detected. More than half of pathogenic somatic variants had a VAF < 5%. Further analysis of the correlation between genetic variants and surgical outcomes will improve patient counseling and may guide postoperative treatment decisions.

Epilepsy Demystified: Symptoms, Seizures, Types and Treatment Options

Epilepsy is a long-term neurological condition where seizures recur due to abnormal electrical signals in the brain. These seizures can vary, with focal seizures starting in one area of the brain and generalized seizures affecting the brain more broadly. Diagnosing epilepsy involves looking at your medical history, symptoms, and tests like EEG or brain scans to get a clear picture. Treatment usually includes medications to control seizures, lifestyle adjustments, and sometimes surgery. If you remain seizure-free for 2 to 4 years, your doctor might gradually lower your medication and consider stopping it altogether.

Multimodal and quantitative analysis of the epileptogenic zone network in the pre-surgical evaluation of drug-resistant focal epilepsy

Surgical resection for epilepsy often fails due to incomplete Epileptogenic Zone Network (EZN) localization from scalp electroencephalography (EEG), stereo-EEG (SEEG), and Magnetic Resonance Imaging (MRI). Subjective interpretation based on interictal, or ictal recordings limits conventional EZN localization. This study employs multimodal analysis using high-density-EEG (HDEEG), Magnetoencephalography (MEG), functional-MRI (fMRI), and SEEG to overcome these limitations in a patient with drug-resistant MRI-negative focal epilepsy. A 17-year-old with drug-resistant epilepsy underwent evaluation. HDEEG, MEG, fMRI, and SEEG were used, with a novel HDEEG-cap facilitating simultaneous EEG-MEG and EEG-fMRI recordings. Electrical and magnetic source imaging were performed, and fMRI data were analysed for homogenous regions. SEEG analysis involved spike detection, spike timing analysis, ictal fast activity quantification, and Granger-based connectivity analysis. Non-invasive sessions revealed consistent interictal source imaging results identifying the EZN in the right anterior cingulate cortex. EEG-fMRI highlighted broader activation in the right cingulate cortex. SEEG analysis localized spikes and fast activity in the right anterior and posterior cingulate gyri. Multi-modal analysis suggested the EZN in the right frontal lobe, primarily involving the anterior and mid-cingulate cortices. Multi-modal non-invasive analyses can optimise SEEG implantation and surgical decision-making. Invasive analyses corroborated non-invasive findings, emphasising the importance of individual-case quantitative analysis across modalities in complex epilepsy cases.

Pattern of Injuries in Children with Epilepsy: A Hospital-Based Case-Control Study

Abstract Objective The aim of this study is to examine the profile and pattern of injuries in children with epilepsy (CWE) as compared with healthy controls. Methods This prospective, cross-sectional study conducted over 1 year in a tertiary care pediatric center included consecutive CWE aged 4 to 16 years who had active seizures during the preceding 1 year. A similar number of age- and sex-matched healthy controls were enrolled. Children with acute symptomatic seizures or degenerative neurologic disorders were excluded. Standardized scales were used to assess intelligent quotient, psychopathology, seizure severity, and restriction of daily activities. Results Two hundred and eight CWE (mean age: 107 ± 37months; range: 3.5–16 years) and an equal number of healthy controls (mean age: 108 ± 43 months; range: 3.5–16 years; p = 0.07) were evaluated. The majority of CWE had generalized epilepsy (n = 117, 59.6%) followed by focal epilepsy (n = 84, 40.3%). The mean duration of epilepsy was 47.4 ± 36.3 months. The prevalence of injury was significantly greater in CWE (n = 118/208, 56.7%) compared with controls (n = 56/208, 26.9%; p &lt; 0.001). CWE suffered significantly greater number of 293 injuries in the past 1 year in contrast to 83 injuries in controls (p &lt; 0.001). In CWE, the majority of injuries were unrelated to seizures (n = 85/118, 72%, 211 injuries), while only one-third (n = 33/118, 27.9%, 82 injuries) suffered seizure-related injuries. The incidence of injures unrelated to seizures and that of seizure-related injuries were similar (2.48 seizure-related injuries per person per year). Among CWE, a comparison of the injury versus noninjury group showed a significantly longer duration of epilepsy (53 ± 34 vs. 40 ± 38 months, p &lt; 0.007), higher prevalence of underlying structural etiology in generalized epilepsy (34.7 vs. 13.3%, p &lt; 0.001), higher mean seizure severity and restriction of daily activity scores, and higher prevalence of hyperactivity (36.4 vs. 18.9%, p = 0.006) and intellectual disability (35.6 vs. 10%, p &lt; 0.001) in the injury group. Injuries on the head, face, and upper limb were significantly more in CWE as compared with controls, and tongue injuries were found only in CWE (p =&lt; 0.05), and were seen significantly more as seizure-related injury (n = 7 vs. 1, p &lt; 0.001) compared with non-seizure-related injuries. The majority of injuries in children with CWE and controls were mild in nature (n = 112, 53.8% vs. n = 54, 26%; p &lt; 0.001). Conclusions The prevalence of injuries among CWE aged between 4 and 16 years is high and is significantly greater than in healthy controls, although the majority of injuries are mild in severity in both and are non-seizure-related injuries. Longer duration of epilepsy, higher seizure severity, and restriction of daily activities, and higher prevalence of underlying structural etiology, hyperactivity, and intellectual disability are associated with injuries in CWE.

Integrating standard epilepsy protocol, ASL-perfusion, MP2RAGE/EDGE and the MELD-FCD classifier in the detection of subtle epileptogenic lesions: a 3 Tesla MRI pilot study.

Malformations of cortical development (MCDs) in children with focal epilepsy pose significant diagnostic challenges, and a precise radiological diagnosis is crucial for surgical planning. New MRI sequences and the use of artificial intelligence (AI) algorithms are considered very promising in this regard, yet studies evaluating the relative contribution of each diagnostic technique are lacking. The study was conducted using a dedicated "EPI-MCD MR protocol" with a 3 Tesla MRI scanner in patients with focal epilepsy and previously negative MRI. MRI sequences evaluated included 3D FLAIR, 3D T1 MPRAGE, T2 Turbo Spin Echo (TSE), 3D T1 MP2RAGE, and Arterial Spin Labelling (ASL). Two paediatric neuroradiologists scored each sequence for localisation and extension of the lesion. The MELD-FCD AI classifier's performance in identifying pathological findings was also assessed. We only included patients where a diagnosis of MCD was subsequently confirmed on histology and/or sEEG. The 3D FLAIR sequence showed the highest yield in detecting epileptogenic lesions, with 3D T1 MPRAGE, T2 TSE, and 3D T1 MP2RAGE sequences showing moderate to low yield. ASL was the least useful. The MELD-FCD classifier achieved a 69.2% true positive rate. In one case, MELD identified a subtle area of cortical dysplasia overlooked by the neuroradiologists, changing the management of the patient. The 3D FLAIR sequence is the most effective in the MRI-based diagnosis of subtle epileptogenic lesions, outperforming other sequences in localisation and extension. This pilot study emphasizes the importance of careful assessment of the value of additional sequences.

Clinical and Radiological Parameters Affecting the Yield of Routine Electroencephalography in Various Indications.

To highlight the significance of various clinical and radiological parameters in association with specific electroencephalographic (EEG) patterns in order to prioritize EEG referrals. This retrospective, cross-sectional study was conducted in the neurology department of King Fahad University Hospital, Alkhobar, and involved a review and analysis of EEG and medical records pertaining to 604 patients referred for routine EEG. The data were analyzed using SPSS version 22. An association between various parameters and EEG yield was established. Factors associated with the yield of abnormal EEG patterns were diverse, like generalized tonic-clonic seizures (GTCs) (P =.05), status epilepticus (SE) (P =.05), altered level of consciousness (ALC) (P =.00), abnormal movement (P =.00), cardiac arrest (P =.00), prior history of epilepsy (P =.04), chronic renal disease (CRD) (P =.03), abnormal neurological exam (P =.00), and cortical lesions on brain imaging (P =.00). Among the abnormal EEG patterns, epileptiform activity (EA) in EEG was associated with focal seizures (P =.03), GTCs (P =.00), falls (P =.05), cardiac arrest (P =.00), a history of epilepsy (P =.00), and hypoxic ischemic injury (P =.03). Encephalopathy in EEG was also associated with focal sz (P =.02), GTCs (P =.00), SE (P =.01), ALC (P =.00), cardiac arrest (P =.00), history of stroke (P =.01), and epilepsy (P =.00). Among the studied parameters, patient level of consciousness, neurological exam findings, and neuroimaging findings, with some discrepancies, were found to be the most consistent in predicting the EEG yield. The study demonstrated the value of a proper neurological exam and careful selection of patients to gain the optimum benefit from the routine EEG.

Case report: A rare secondary systemic candidiasis as a bite wound complication in a dog

An 11-year-old, 4.8 kg, intact male mixed-breed dog was evaluated for a bite wound that had occurred a day prior to consultation. On examination, the patient exhibited signs of early to-late decompensatory shock, hemothorax, pneumothorax, and rib fractures. Initial shock management and resuscitation were performed. After several days of stabilization, exploratory thoracotomy, thoracic wall reconstruction, culture sampling, and antibiotic susceptibility tests were conducted. Empirical antimicrobial treatments were performed while pending culture results. Despite aggressive antimicrobial therapy, the patient had focal seizures and wound dehiscence, presumably due to the worsening of infection and inflammation. Necrotic tissues adjacent to the dehiscence were debrided, and the wound was opened. A previous analysis of wound and blood cultures identified Candida glabrata, and itraconazole was initiated in accordance with the culture results. Successful treatment was achieved, and the wound was closed. The patient remained healthy after 2 months of monitoring. To the best of our knowledge, this was the first case report of systemic candidiasis in a dog secondary to a bite wound diagnosed via blood culture. Additionally, this case highlights successful treatment with itraconazole.

Insights from Ecstatic Epilepsy: From Uncertainty to Metacognitive Feelings.

Ecstatic epilepsy is a rare form of focal epilepsy linked to the anterior insula in which patients experience a blissful state with a unique set of symptoms, including a feeling of physical well-being, mental clarity, a sense of oneness with the universe, and time dilation. In this chapter, we reflect on how these symptoms coincide with our current knowledge of the insula's functions and explore how this stunning natural model can further inform our understanding of the insula's role in the sentient self, uncertainty and surprise monitoring, and metacognitive feelings.

TRANscranial direct current stimulation for FOcal Refractory epilepsy in mitochondrial disease (TRANSFORM): delayed-start, randomised, double-blinded, placebo-controlled study

BackgroundFocal epilepsy is common in children and adults with mitochondrial disease. Seizures are often refractory to pharmacological treatment and, in this patient group, frequently evolve to refractory focal status epilepticus (also known as epilepsia partialis continua). Where this occurs, the long-term prognosis is poor. Transcranial DC stimulation (tDCS) is a promising, non-invasive, adjunctive treatment alternative to common surgical procedures. Limited recruitment of study participants with this rare disease and the ethical challenges of administering a treatment to one group and not another, while maintaining strict methodological rigour can pose challenges to the design of a clinical study.MethodWe designed the first delayed start, double-blinded, sham-controlled study to evaluate the efficacy of tDCS as an adjunctive treatment for focal epilepsy. We will include participants with a genetically confirmed diagnosis of mitochondrial disease with drug-resistant focal epilepsy aged ≥ 2 years, aiming to collect 30 episodes of focal status epilepticus, each treated for a maximum period of 14 days. The early start intervention arm will receive tDCS from day 1. The delayed start intervention arm will receive sham stimulation until crossover on day 3. Our primary endpoint is a greater than 50% reduction from baseline (on day 0) in seizure frequency assessed by 3x daily reporting, accelerometery, and video monitoring. Changes in the underlying epileptogenic focus within the brain related to the tDCS intervention will be assessed by magnetic resonance imaging (MRI) and/or electroencephalography (EEG).DiscussionStudy results in favour of treatment efficacy would support development of tDCS into a mainstream treatment option for focal epileptic seizures related to mitochondrial disease.Trials registrationISRCTN: 18,241,112; registered on 16/11/2021.

Crossed Wernicke’s Aphasia With Focal Clonic Cluster Seizures With Secondary Generalization Mimicking Faciobrachial Seizures Following a Right Middle-Cerebral-Artery Ischemic Stroke: A Novel Phenotypic Presentation

Crossed Wernicke’s aphasia (CWA) following a stroke is a rare clinical phenomenon, particularly when associated with seizures. This case report presents a unique instance of crossed CWA accompanied by focal clonic cluster seizures affecting the left arm and face, with secondary generalization, in a monolingual Bengali-speaking patient following a right middle cerebral artery ischemic stroke. The patient, a 70-year-old male from rural India, presented with acute behavioral abnormalities and language impairment. He experienced left-sided focal motor-onset clonic seizures with impaired awareness, followed by fluent yet unintelligible speech, characterized by phonemic and semantic paraphasias, as well as neologistic jargon. Neuroimaging revealed a right parieto-occipital infarct. Although initially misdiagnosed and treated for acute psychosis, thorough clinical evaluation ultimately led to the diagnosis of CWA—a rare form of aphasia in a right-handed individual after a right hemisphere stroke. This case underscores the diagnostic challenges associated with stroke-related language disorders and highlights the importance of recognizing variations in language lateralization. Furthermore, the occurrence of CWA in a Bengali-speaking individual emphasizes the potential impact of linguistic and cultural factors on brain organization and language processing. This case also adds to the limited body of literature regarding the co-occurrence of post-stroke seizures and aphasia, particularly in atypical presentations such as CWA.

Stiripentol for the treatment of refractory status epilepticus

BackgroundStatus epilepticus (SE) is one of the most common neurological emergencies and an acutely life-threatening condition characterized by high mortality and morbidity. Despite the well-established staged therapy of status epilepticus, especially stages 1 and 2, more than one third of patients develop (super-) refractory SE. Despite a large variety of potential treatment options for super-refractory SE, there is an unmet clinical need of potential new treatment ideas in this often desperate clinical situation.A number of studies have demonstrated the safety and efficacy of stiripentol (STP) in patients with Dravet syndrome (DS) and in children with focal epilepsy and generalized epilepsies. Some smaller series and case reports have documented the use of STP in the treatment of status epilepticus in adult patients.MethodsWe retrospectively analyzed all patients who were admitted to the Department of Neurology at Marburg University Hospital between 2013 and 2023 with a diagnosis of (super)-refractory status epilepticus and who received additional treatment of SE with STP. All patients who received STP during the SE were included, regardless of previous medication.ResultsSE ceased in 64% of 25 patients (13 female and 12 male). The mean age was 58.6 ± 21.9 years (mean ± SD). 72% had a structural epilepsy. In 20% of patients, SE was terminated by the administration of STP alone in 32% of cases, while in a further 32% of patients, the simultaneous administration of multiple anti-seizure medications (ASMs) including STP was potentially responsible for the cessation of the SE, with valproic acid (VPA), benzodiazepines and STP, being the most frequently implicated ASMs. In 12% of patients, there was at least a temporary improvement in the electroencephalogram (EEG). Stiripentol had to be discontinued in three cases due to a reduction in vigilance or hypercalcemia.ConclusionsStiripentol may represent a promising additional treatment option for refractory and super-refractory status epilepticus. The tolerability of this treatment has already been demonstrated in previous studies, and was also reflected in these data. Further prospective investigation in larger patient populations are necessary to ascertain the efficacy of stiripentol in SE.Trial registrationNCT06540378, retrospectively registered.

Clinical features of KCNB1 gene variation related developmental and epileptic encephalopathy

Objective: To summarize the clinical features of epilepsy and (or) developmental delay associated with KCNB1 gene variants in children. Methods: A case series study was conducted on 24 children with KCNB1 gene variants associated with epilepsy and (or) developmental delay who were treated at the Children's Medical Center of Peking University First Hospital and the Department of Neurology of Shenzhen Children's Hospital from July 2015 to June 2024. The manifestations of seizures, electroencephalogram (EEG) and genetic test results of those children were analyzed. Results: All the KCNB1 gene variants were de novo, involving 20 different variation, including 15 missense variations, 3 frameshift variations and 2 nonsense variations. There were 7 novel variations. Among the 24 developmental and epileptic encephalopathy children, there were 14 boys and 10 girls. The last follow-up age ranged from 9 months to 13 years and 9 months. Seizures were present in 21 children (88%), with onset ranging from 1 month to 7 years, and 76% (16/21) began before 2 years of age. The seizure types included focal seizures in 15 children (71%), epileptic spasms, myoclonic seizures, and generalized tonic-clonic seizures in 6 children respectively, atypical absence seizures in 4 children, and myoclonic atonic seizures in 1 child. Seventeen children (81%) had a cluster of seizures and 5 had a history of focal status epilepticus with impaired consciousness. All 24 children had varying degrees of developmental delay, with 3 presenting solely developmental delay. EEG abnormalities were present in all the 21 children with seizures, including focal or multifocal discharges in 20 children, generalized discharges in 10 children, hypsarrhythmia in 2 children, and electrical status epilepticus during sleep in 3 children. Magnetic resonance imaging abnormalities were found in 5 of the 24 children. Among the 21 children with seizures, 57% (12/21) achieved seizure control. Conclusions: KCNB1 gene variants are predominantly de novo missense variation. Most affected children present with epilepsy, though some may exhibit only developmental delay. Epilepsy often begins before 2 years of age, with focal seizures being the most common type. About 80% of patients experience clustered seizures. Although most patients achieve seizure control, they still exhibit varying degrees of developmental delay, consistent with developmental epileptic encephalopathy.

A 7-year-boy with Recurrent Acute Disseminated Encephalomyelitis: A Case Report

Acute Disseminated Encephalomyelitis (ADEM) is one form of inflammatory demyelinating disorder of central nervous system affecting the children following an idiopathic course of onset and usually monophasic. Recurrent ADEM is a rare entity and will arise a confusion about its diagnosis. There is no definite clinical criteria and treatment protocol for the management of ADEM. Here we report a case of recurrent ADEM where a 6 year old boy presented with recurrent episodes of low grade fever, difficulty in walking, altered sensorium and focal seizure. MRI of brain showed reappearance of demyelinating lesion on the previous site. The gap between first and second episode was six months. After the first attack of ADEM patient were completely recovered both clinically and neuroradiologically with immunotherapy. But after 7 months of disease free remission, patient again developed same features. So we diagnosed the baby as recurrent ADEM based on the consensus criteria of International Pediatric MS study group (IPMSSG). BANGLADESH J CHILD HEALTH 2023; VOL 47 (1) : 51-54

Hippocampal microscopic fractional anisotropy is reduced in temporal lobe epilepsy

Abstract Surgical resection is the method of choice for treating drug-resistant focal temporal lobe epilepsy (TLE). Postsurgical outcomes are better when magnetic resonance imaging (MRI) findings can localize the seizure focus for resection. However, many patients are MR-negative, meaning the focus cannot be differentiated from normal tissue in relaxation-weighted MRI. Diffusion MRI shows promise as a preoperative marker of neuronal abnormalities due to its sensitivity to cellular changes such as axon damage, indexed by fractional anisotropy. Microscopic fractional anisotropy is a recently introduced diffusion MRI metric that is sensitive to axon integrity regardless of axon orientation in both grey and white matter. In contrast, regular fractional anisotropy is only sensitive to axon integrity in coherently oriented bundles of fibers. This work investigated whether microscopic fractional anisotropy is sensitive to hippocampal abnormalities in drug-resistant TLE. Diffusion MRI was performed on a 3T scanner in 19 patients (age = 31±10 years) with drug-resistant TLE (of which 10 were MR-negative) and 18 healthy volunteers (age = 38±15). A deep-learning method was employed to segment the hippocampus into smaller subregions corresponding to the subiculum, cornu ammonis (CA) 1, CA2/3, and CA4 plus dentate gyrus (DG). Mean measurements of subregion volume, diffusivity, fractional anisotropy, and microscopic fractional anisotropy were compared between cohorts. In a subset of the TLE cohort suspected to have unilateral pathology (n=15, age = 32±10 years), the percentage differences between measurements ipsilateral and contralateral to the epileptogenic zone were evaluated to assess asymmetry. Microscopic fractional anisotropy was reduced in the hippocampus of drug-resistant TLE patients relative to healthy volunteers. In subregion-specific analysis, microscopic fractional anisotropy was significantly reduced in only the CA4/DG region in patients compared to healthy volunteers, after corrections for multiple comparisons. In the 15 patients with suspected unilateral pathology, microscopic fractional anisotropy was reliably and statistically lower in the ipsilateral CA4/DG region compared to the contralateral side. Significant differences were not observed between TLE patients and healthy volunteers, or between hemispheres for patients with suspected unilateral pathology, for the fractional anisotropy or volume metrics. Diffusion MRI may complement standard imaging procedures by detecting abnormalities in MRI-negative patients. Due to its ability to detect abnormality regardless of axon orientation, microscopic fractional anisotropy may improve seizure focus localization in surgical candidates.