Tonic-clonic Research Articles

Centromedian region thalamic responsive neurostimulation mitigatesidiopathic generalized and multifocal epilepsy with focal to bilateral tonic-clonic seizures.

Although >30% of epilepsy patients have drug-resistant epilepsy (DRE), typically those with generalized or multifocal disease have not traditionally been considered surgical candidates. Responsive neurostimulation (RNS) of the centromedian (CM) region of the thalamus now appears to be a promising therapeutic option for this patient population. We present outcomes following CM RNS for 13 patients with idiopathic generalized epilepsy (IGE) and eight with multifocal onsets that rapidly generalize to bilateral tonic-clonic (focal to bilateral tonic-clonic [FBTC]) seizures. A retrospective review of all patients undergoing bilateral CM RNS by the senior author through July 2022 were reviewed. Electrodes were localized and volumes of tissue activation were modeled in Lead-DBS. Changes in patient seizure frequency were extracted from electronic medical records. Twenty-one patients with DRE underwent bilateral CM RNS implantation. For 17 patients with at least 1 year of postimplantation follow-up, average seizure reduction from preoperative baseline was 82.6% (SD = 19.0%, median = 91.7%), with 18% of patients Engel class 1, 29% Engel class 2, 53% Engel class 3, and 0% Engel class 4. There was a trend for average seizure reduction to be greater for patients with nonlesional FBTC seizures than for other patients. For patients achieving at least Engel class 3 outcome, median time to worthwhile seizure reduction was 203.5 days (interquartile range = 110.5-343.75 days). Patients with IGE with myoclonic seizures had a significantly shorter time to worthwhile seizure reduction than other patients. The surgical targeting strategy evolved after the first four subjects to achieve greater anatomic accuracy. Patients with both primary and rapidly generalized epilepsy who underwent CM RNS experienced substantial seizure relief. Subsets of these patient populations may particularly benefit from CM RNS. The refinement of lead targeting, tuning of RNS system parameters, and patient selection are ongoing areas of investigation.

Early Symptoms and Treatment Outcomes in Neuronal Ceroid Lipofuscinosis Type 2: Croatian Experience.

Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative disease that generally appears in children between 2 and 4 years old, leading to seizures and a progressive loss of language and motor functions. As the disease progresses, affected individuals typically experience blindness and ultimately pass away in late childhood. Treatment with intracerebroventricular cerliponase alfa has been shown to slow the deterioration of motor and language functions compared to the natural progression of the disease. We aim to highlight the early symptoms of CLN2 which help with early diagnosis and timely treatment initiation in children with specific medical indications, as well as identify medical contraindications for enzyme replacement therapy. We describe five Croatian patients and one Bosnia and Herzegovinian patient with CLN2 disease, analyzing the clinical characteristics, neuroimaging findings, electroencephalogram results, genetic analysis, treatment indications and contraindications, and disease progression. All six patients presented with seizures: focal seizures (n = 1), myoclonic-atonic seizures (n = 1), febrile seizures (n = 2), and tonic-clonic seizures (n = 2), along with language delay (n = 6). Despite this, one patient refused treatment, two were initially included in the clinical trial and then continued treatment, one did not indicate starting treatment, and three continued treatment. One patient, after 4.5 years of treatment, no longer had medical indications for the therapy, which was discontinued. The other two patients who received treatment had a significant slowing of disease progression. The early onset of seizures between ages 2 and 4, alongside delayed language development, is a defining characteristic of CLN2 disease. Enzyme replacement therapy using cerliponase alfa represents the initial treatment for neuronal ceroid lipofuscinosis type 2, targeting the underlying cause of the disease. It effectively delays the progression of language and motor decline in patients diagnosed with this condition.

Critical Management of Recurrent Seizure at 16-Year-Old Primigravida with Atypical Eclampsia: A Case Report

Background: Atypical eclampsia, characterized by seizures without the classic signs of hypertension and proteinuria, presents a diagnostic and therapeutic challenge in the critical management aspect. This case report highlights the critical management of recurrent seizures in a young primigravida with atypical eclampsia. Case presentation: A 16-year-old primigravida at 38 weeks gestation presented with recurrent generalized tonic-clonic seizures. Despite initial magnesium sulfate therapy, seizures persisted postpartum. The patient was managed with a combination of midazolam and dexmedetomidine for seizure control and sedation. After five days of intensive care, the patient recovered without further complications. Conclusion: This case underscores the importance of considering atypical eclampsia in pregnant women presenting with seizures, even in the absence of typical preeclampsia symptoms. The successful use of midazolam and dexmedetomidine in this case suggests their potential as alternative therapeutic agents for refractory seizures in eclampsia. Further research is needed to validate these findings and establish optimal treatment protocols for atypical eclampsia.

Clinical features and underlying etiology of children with Lennox-Gastaut syndrome.

Lennox-Gastaut Syndrome (LGS) is characterized by the presence of multiple seizure types and encompasses a heterogenous group of etiologies. The aim of our study was to evaluate the etiological profile of LGS and investigate seizure outcomes based on different clinical variables. The clinical features, neuroimaging findings, genetic testing and other testing results of LGS patients were systematically reviewed. The identifiable etiology was categorized as either acquired or nonacquired. Univariate and multivariate regression analyses were performed to explore the association between clinical variables and seizure outcome at the last follow-up. We enrolled 156 patients diagnosed with LGS, of whom 66% were male. The mean age of patients was 34.2months and the median follow-upduration was 29.5months (interquartile range = 14-56.25months). The initial seizure type was epileptic spasm in 61 patients, among which 33 of them met the criteria for infantile epileptic spasm syndrome. All patients underwent neuroimaging test, with 25% falling into the acquired structural category. Etiology could be identified in 84 individuals, including pathogenetic variants found in 34 out of 117 patients with nonacquired etiology. CHD2 mutations were most frequently observed among these pathogenetic variants. At the last follow-up, favorable outcomes were observed in 27 patients. The identification of etiology emerged as a significant determinant influencing LGS outcome; specifically, patients with unknown etiology had a higher likelihood of experiencing favorable outcomes compared to those with known cause (p = 0.041). Early onset age and longer epilepsy duration significantly increased the odds of an unfavorable outcome (p = 0.006 and 0.024). We present novel data on the clinical and etiological spectrum of LGS, with determined etiology observed in over half of the patients. Epileptic spasms were found to be more prevalent than tonic seizures as seizure onset types in LGS. The presence of a known etiology, earlier age at onset, and longer duration of epilepsy were associated with a poorer long-term epileptological outcome.

Causal links between serum micronutrients and epilepsy: a Mendelian randomization analysis.

Micronutrient levels play a critical role in epilepsy. This study investigates the impact of micronutrient levels on epilepsy via Mendelian randomization (MR). A two-sample MR framework evaluated the genetic association between 15 serum micronutrients and epilepsy phenotypes. The analysis included calcium, iron, zinc, selenium, copper, magnesium, potassium, folate, vitamins B6, B12, C, D, E, retinol, and carotene against all epilepsy, generalized epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), generalized tonic-clonic seizures alone and with spike-wave electroencephalography (GTCS), and various focal epilepsy phenotypes [with hippocampal sclerosis (HS), lesions other than HS, lesion-negative]. The random-effects inverse-variance weighted (IVW) model was the primary method used, supported by heterogeneity and pleiotropy assessments. Multivariable Mendelian randomization analyses (MVMR) were used to identify micronutrients that are significantly causally associated with different epilepsy subtypes and to confirm the most potential causal risk factors for these subtypes. Zinc conferred an increased risk of focal epilepsy with HS (OR = 1.01; p = 0.045). Carotene was similarly linked to higher risks of lesion-negative cases (OR = 1.129; p = 0.037). Conversely, vitamin B6 was associated with reduced risks of focal epilepsy with HS (OR = 0.949; p = 0.020), and vitamin D was linked to decreased risks of both CAE (OR = 0.976, 95% CI: 0.959-0.993, p = 0.006) and JAE (OR = 0.986, 95% CI: 0.973-0.999, p = 0.032). These associations were robust, showing minimal heterogeneity and no evidence of pleiotropy across various sensitivity analyses. After adjustment using MVMR, significant causal relationships between vitamin D and both CAE and JAE remained. Furthermore, the causal relationship between zinc and vitamin B6 on focal epilepsy with HS became non-significant, while carotene shifted from a risk factor to a protective factor for focal epilepsy lesion-negative after adjusting for vitamin D. MR estimates provide robust evidence for the causal effects of vitamin D on reducing the risk of CAE, and JAE, which might provide alternative treatment strategies.

Effect of Antiseizure Medication on the Salience Network in Patients with Epilepsy with Generalized Tonic-Clonic Seizures Alone.

This study aimed to investigate the effects of antiepileptic drugs on salience network regions in patients with epilepsy with generalized tonic-clonic seizures alone (EGTCSa). A retrospective observational case-control study was performed on 40 patients diagnosed with epilepsy with EGTCSa and 40 healthy age-matched controls. In LORETA, a voxel-by-voxel analysis between regions from the salience network was performed for both hemispheres, specifically between the anterior cingulate (BA 32 and BA 24) and the sublobar insula (BA 13). Subsequently, a Wilcoxon rank-sum test (the Mann-Whitney U test) was conducted for the equality of medians in the transformation matrix. A comparison was then made between each region of interest as defined by the salience network and the controls. Marked differences were found in the brain regions assessed in patients with EGTCSa treated with valproic acid and carbamazepine compared to the control group; few differences in patients treated with levetiracetam; and no difference was found in the group without treatment compared with those in the control group. These results suggest that ASMs can influence cognitive processes, which provide novel insights toward understanding the neural mechanisms underlying the effects of ASMs administration.

Vitamin D deficiency and effect of treatment on seizure frequency and quality of life parameters in patients with drug-resistant epilepsy: A randomized clinical trial.

This study was undertaken to assess the effect of treatment of vitamin D deficiency in drug-resistant epilepsy. We conducted a multicenter, double-blind, placebo-controlled, randomized clinical trial, including patients aged ≥15 years with drug-resistant focal or generalized epilepsy. Patients with 25-hydroxyvitamin D (25[OH]D) < 30 ng/mL were randomized to an experimental group (EG) receiving vitamin D3 (cholecalciferol, 100 000 IU, five doses in 3 months) or a control group (CG) receiving matched placebo. During the open-label study, EG patients received 100 000 IU/month for 6 months, whereas CG patients received five doses in 3 months then 1/month for 3 months. Monitoring included seizure frequency (SF), 25(OH)D, calcium, albumin, creatinine assays, and standardized scales for fatigue, anxiety-depression, and quality of life (Modified Fatigue Impact Scale [M-FIS], Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy [QOLIE-31]) at 3, 6, and 12 months. The primary efficacy outcome was the percentage of SF reduction compared to the reference period and CG at 3 months. Secondary outcomes were SF and bilateral tonic-clonic seizure (BTCS) reduction, scale score changes, and correlations with 25(OH)D during the follow-up. Eighty-eight patients were enrolled in the study (56 females, aged 17-74 years), with median baseline SF per 3 months = 16.5 and ≥2 antiseizure medications in 88.6%. In 75 patients (85%), 25(OH)D was <30 ng/mL; 40 of them were randomly assigned to EG and 34 to CG. After the 3-month blinded period, SF reduction did not significantly differ between groups. However, during the open-label period, SF significantly decreased (30% median SF reduction, 33% responder rate at 12 months). BTCSs were reduced by 52%. M-FIS and QOLIE-31 scores were significantly improved at the whole group level. SF reduction correlated with 25(OH)D > 30 ng/mL for >6 months. Despite no proven effect after the 3-month blinded period, the open-label study suggests that long-term vitamin D3 supplementation with optimal 25(OH)D may reduce SF and BTCSs, with a positive effect on fatigue and quality of life. These findings need to be confirmed by further long-term studies. ClinicalTrials.gov identifier: NCT03475225 (03-22-2018).

Clinical profile of epilepsy in western Algeria

BackgroundEpilepsy is one of the most common neurological diseases that affects people of different ages, ethnicities, and geographical locations. The objective of the present study was to determine the demographic and clinical characteristics of epilepsy in west Algerian population.Patients and methodsWe enrolled 226 patients with epilepsy and collected data from medical records. We analyzed socio-demographic data, personal and family history, age at onset, seizure types, neurological and psychological findings, etiologies, syndromic classification and comorbidities.ResultsIn our cohort, the mean age was 27.26 ± 17.57 years and there was no gender predominance. The mean age of seizure onset was 17.11 ± 16.27 years. Genetic epilepsy was the most observed (45.13%). Focal seizures (69.02%) were more frequent than generalized seizures which were mostly represented by absence and tonic–clonic seizures. We reported 51.45% of patients with comorbidities and 16.65% with a history of traumatic brain injury.ConclusionThis is the first report describing the clinical profile and the socio-demographic features in a cohort of patients with epilepsy in the western Algeria. Our results could help to offer personalized care to our patients based on the clinical particularities of their epileptic disorders.

Familial mesial temporal lobe epilepsy phenotype is associated with novel LGI1 variants: A report of two families

ObjectiveTo expand the clinical phenotype and mutation spectrum of familial mesial temporal lobe epilepsy (FMTLE) and provide a new perspective for exploring the pathological mechanisms of epilepsy caused by leucine-rich glioma inactivated 1 (LGI1) variants. MethodsWe reported clinical data from two families with FMTLE and screened patients for variants in the LGI1 gene using Whole-exome sequencing and Sanger sequencing. The clinical features of FMTLE were analysed. The pathogenicity of the causative loci was assessed according to the American College of Medical Genetics and Genomics guidelines, and potential pathogenic mechanisms were predicted through multiple bioinformatics and molecular dynamics software. ResultsWe identified two novel LGI1 truncating variants within two large families with FMTLE: LGI1 (c.1174C>T, p.Q392X) and LGI1 (c.703C>T, p.Q235X). Compared to previous reports, we found that focal to bilateral tonic-clonic seizures are a common type of seizure in FMTLE. The clinical phenotypes of patients with FMTLE caused by LGI1 variants were relatively mild, and all patients responded well to valproic acid. Bioinformatics analyses and molecular dynamics simulations showed that protein structure and interactions were considerably weakened or damaged as a result of both variants. ConclusionThis study presents the first report identifying LGI1 as a potential novel pathogenic gene within FMTLE families, thereby broadening the mutation spectrum associated with FMTLE. The findings of this study offer novel insights and avenues for understanding the intricate molecular mechanisms underlying LGI1 variants and their correlations with patient phenotypes. This study proposes the possibility of familial focal epilepsy syndromes overlapping.

A pH-sensitive closed-loop nanomachine to control hyperexcitability at the single neuron level

Epilepsy affects 1% of the general population and 30% of patients are resistant to antiepileptic drugs. Although optogenetics is an efficient antiepileptic strategy, the difficulty of illuminating deep brain areas poses translational challenges. Thus, the search of alternative light sources is strongly needed. Here, we develop pH-sensitive inhibitory luminopsin (pHIL), a closed-loop chemo-optogenetic nanomachine composed of a luciferase-based light generator, a fluorescent sensor of intracellular pH (E2GFP), and an optogenetic actuator (halorhodopsin) for silencing neuronal activity. Stimulated by coelenterazine, pHIL experiences bioluminescence resonance energy transfer between luciferase and E2GFP which, under conditions of acidic pH, activates halorhodopsin. In primary neurons, pHIL senses the intracellular pH drop associated with hyperactivity and optogenetically aborts paroxysmal activity elicited by the administration of convulsants. The expression of pHIL in hippocampal pyramidal neurons is effective in decreasing duration and increasing latency of pilocarpine-induced tonic-clonic seizures upon in vivo coelenterazine administration, without affecting higher brain functions. The same treatment is effective in markedly decreasing seizure manifestations in a murine model of genetic epilepsy. The results indicate that pHIL represents a potentially promising closed-loop chemo-optogenetic strategy to treat drug-refractory epilepsy.

Study of Inflammatory Markers in Patients with Uncontrolled Generalized Motor Tonic–Clonic Seizures

Abstract Background Epilepsy is a multifaceted chronic neurological disease characterized by recurrent spontaneous seizures. It affects almost 70 million patients around the globe, making it one of the most common chronic causes of neurological morbidities. Aim of the Work detect an association between some inflammatory markers {C-reactive protein (CRP), Neutrophil-lymphocyte ratio (NLR), and Platelet-lymphocyte ratio (PLR)}and epilepsy in order to detect a pathogenic relation that in turn can influence the course and management of epilepsy. Patients and Methods the current body of evidence recognizes the association between inflammation and epilepsy. Several inflammatory markers have been investigated in relation to different types of epilepsy. This study chose CRP as a convenient and widely used inflammatory marker, together with NLR and PLR, the two novel, readily available indices of inflammation that are yet to be fully investigated in relation to epilepsy. We included 50 patients with uncontrolled generalized motor tonic–clonic seizures. Ages ranged from 18 – 45 years and both genders were represented. Patients were compared with 50 controls of same age and gender. Strict inclusion and exclusion criteria were applied to all volunteers. Results In this study, levels of CRP, NLR and PLR in 50 patients with epilepsy were significantly higher than controls. These results add to the pool of evidence that support the association between epilepsy and inflammatory processes. This study managed to investigate the correlation between inflammatory markers and specific independent variables such as frequency of seizures, time interval between last seizure and presentation, number of status epilepticus per year, number of anti-epileptic medications, duration of postictal confusion, age of onset of seizures, duration of illness, and EEG findings, in addition to age and gender differences. This study found increased levels of CRP, NLR, and PLR in patients with high frequency seizures compared to those with intermittent seizures. Similar results were obtained with increased number of episodes of status epilepticus, number of anti-epileptic medications and shorter time interval between last reported seizure and sample withdrawal. Longer duration of postictal confusion was associated with high values of NLR and PLR. Conclusion systemic inflammatory response has been detected in patients with uncontrolled generalized motor tonic–clonic seizures, which confirms the association between inflammation and epilepsy. This association is specifically correlated to higher seizure frequency, shorter duration between last seizure and blood sample withdrawal, higher number of status epilepticus in the last 12 months, higher number of anti-epileptic medications, longer duration of post-ictal confusion and female gender.

Prevalence of Seizures in Children Diagnosed With Neurodevelopmental Disorders.

Introduction Neurodevelopmental disorders (NDDs) typically emerge in early childhood and have a profound impact on the development of the nervous system, leading to various neurological challenges in cognition, communication, social interaction, motor skills, and behavior. These disorders arise from disruptions in brain development mechanisms. NDDs include conditions such as cerebral palsy (CP), global developmental delay (GDD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), with ADHD and ASD being the most prevalent. However, there is a lack of comprehensive research on the causes of NDDs in children receiving care at tertiary hospitals in Saudi Arabia. Therefore, in this study, we aimto investigate the characteristics of patients with NDDs and explore the association between NDDs and seizures. It also focuses on identifying specific risk factors that may influence the relationship between NDDs and seizures. Methods We conducted a retrospective cross-sectional study at the pediatric neurology and developmental assessment clinic of King Abdulaziz University Hospital in Jeddah, Saudi Arabia. The study involved a review of electronic medical records from January 2021 to May 2023 for 200 pediatric patients who attended the clinic for NDD and seizures. Descriptive statistics summarized the data, using frequencies and percentages for categorical variables, and mean ± standard deviation for quantitative variables. The chi-square test identified differences between qualitative variables, with a significance threshold of p < 0.05. Results The study sample comprised 200 children ranging in age from one month to 14 years, with the majority of patients being from Jeddah city. Participants were categorized into four age groups: 17.0% (n=34) were aged between one month and three years, 18.5% (n=37) were aged between three and six years, 55.0% (n=110) were aged between six and 12 years old, and 9.5% (n=19) were aged between 12 and 14 years. The NDD subtypes identified were ASD 9.5%, ADHD 16.0%, CP 8.5%, GDD 30.5%, ID 5.5%, and 30% had multiple types of NDD. Generalized tonic-clonic seizures were the most common type observed. Conclusion Children with NDDs exhibit a high prevalence of seizures, with the age of the patient and consanguinity emerging as significant influencing factors in this correlation. Among the key findings is an emphasis on the importance of early detection and intervention for children with NDDs at higher risk of developing seizures. Overall, the study sheds light on the characteristics of NDD patients and their association with seizures, contributing to a better understanding of the complex relationship between NDDs and seizure occurrence. It also emphasizes the need for comprehensive assessment and management strategies that consider seizures in children with NDDs.

Not All Patients with a Headache need a CT Scan, but they should be Listened to, and also with a Stethoscope: A Report of a Large Arteriovenous Malformation with a Loud Cranial Bruit.

Arteriovenous malformations (AVMs) are abnormal direct connections between arterial and venous systems, without an interposed capillary bed. This permits high-flow arteriovenous shunting, which precipitates structural changes in the afferent and efferent vessels, namely arterial smooth muscle hyperplasia and thinning of venous walls. Patients with intracranial AVMs typically present with a haemorrhage, headache or seizure. Treatment is either via medical management aimed at control of seizures, headache and blood pressure, or interventional via surgical, radiation or radiologically guided embolisation. We report the case of a woman in her early 40s presenting with a tonic-clonic seizure against a background of a 31-year history of migraine and an 18-month history of tremors in her right arm. The clinical examination was remarkable for an extremely loud cranial bruit and a right homonymous hemianopia. Imaging diagnosed an 8 cm Martin-Spetzler grade V intracranial arteriovenous malformation in her left parietal lobe, which was deemed unsuitable for operative or radiotherapy-based intervention. The patient was managed through observation and relatively good control of her breakthrough seizures was achieved through the addition of brivaracetam to her lamotrigine and carbamazepine-based therapy, six years after her initial presentation. Arteriovenous malformations may go undetected for decades.The presence of a cranial bruit is an important sign and tool in diagnosing an intracranial arteriovenous malformation. The presence of a homonymous hemianopia, of which a patient may be unaware, helps to localise an intracranial lesion.The risks of operative or radiological intervention must be balanced with the risks of haemorrhage or refractory seizure when adopting a strategy for the treatment of an intracranial arteriovenous malformation. Good control of epileptic symptoms in those deemed not suitable for operative or radiological intervention can be achieved by careful titration of anti-seizure medications.

A Cross Sectional Study on Prescription Pattern of Antiepileptic Medication among Children of Southern Rajasthan in a Tertiary Care Teaching Hospital

Background: Drug utilization studies are powerful exploratory tools for establishing the role of drugs in society and also effective methods for assessing the prescribing pattern of clinicians. Around 4-10% of children suffer at least one seizure episode at 16 years of age. Even after the availability of several Antiepileptic drugs (AEDs), choosing the correct drug with accurate dosing will produce seizure-free generation. Hence, this study aims to examine the prescription patterns of drugs in epileptic children. Methods: This study was a cross sectional observational study. Children &lt;16 years old visiting neurology department with a history of epileptic seizures and already on antiepileptic drug therapy were included in the study. The data comprised of demographic details, disease history, type of seizure, diagnosis, investigations done, along with prescribed medication noted in case record form. The total study duration was 13 months. Results: In this study, the maximum epilepsy encountering age in male and female children was below the 12-year age group, male predominance was higher than females (male 60.83% vs. female 39.16%). The majority of children were diagnosed with generalized tonic colonic seizures, 54.17%, followed by focal/or partial seizures, 39.17%. Sodium valproate 19.16%, carbamazepine 14.17%, oxcarbazepine 16.67%, and levetriacetam 13.33% were the most commonly prescribed single drug regimens for treating both types of seizures, followed by clobazam added as second and third adjuvant drug in resistant epilepsy to valproate 12.5%, oxcarbazepine 6.67%, and levetriacetam plus carbamazepine combination 5% respectively. Conclusion: Monotherapy was majorly followed in 70% of pediatric patients for maintaining better patient compliance. Both old and new AEDs regimens are prescribed for maintaining the quality of life in patients.

Epilepsy and Cognition in GM2-Gangliosidosis B1 Variant – Experience of a Tertiary Hospital

Introduction: GM2 gangliosidosis B1 variant (GM2B1) is an autosomal recessive disorder due to deficiency of β-hexosaminidase A, leading to the lysosomal storage of GM2 gangliosides in neuronal tissue and neuronal death. Symptoms include progressive motor coordination impairment and neurodegeneration, in children with previously normal development, leading to early death. Objective: Clinical characterization of patients with GM2B1 with a focus on epileptic manifestations. Methods: A descriptive retrospective study was conducted, analyzing clinical records of patients diagnosed with GM2B1 and followed at our Hospital Neuropediatric Department in the decade 2013-2022. Results: Four patients (three female) from three families diagnosed with GM2B1 were identified. The median age at diagnosis was 70 months. The most frequent symptoms at presentation were developmental regression (all children), language impairment (three), and epileptic seizures (two). Enzymatic deficiency in leukocytes and pathogenic variants in the HEXA gene were demonstrated in all cases. The pathogenic variant c.533G&gt;A(p.R178H) in exon 5 was present in seven of the eight alleles. All patients experienced language impairment (Md=42 mos) with complete language loss (Md=78 mos). Loss of walking ability occurred in three patients (Md=96 mos). All patients experienced epileptic seizures during the course of the disease, with a median onset of seizures at 55 months. Initial seizures were classified as atypical absences (two), tonic seizures (one) and myoclonic seizures (one). Electroencephalographic evaluation revealed slow basal rhythm and focal paroxysmal activity in all cases. All were treated with antiseizure medication, two requiring a combination of three drugs. Conclusion: GM2B1 encompasses a wide clinical spectrum, with heterogenous age of symptom onset, clinical presentation and disease progression. Epilepsy is a common comorbidity in GM2B1, with variable seizure type and severity, and may be difficult to control. Timely diagnosis, coupled with multidisciplinary clinical follow-up, is crucial to improve quality of life of patients and enable genetic counseling.

New-Onset Seizures and Seizure Worsening in the Course of COVID-19 Infection.

The aim of our study is to assess the clinical manifestations, investigation results, and outcomes in Bulgarian patients with seizures in the course of COVID-19 infection. We performed an open, prospective study during a 12-month period from January 2021 with the participation of 290inpatients and outpatients with seizures whoattended the Clinic of Neurology at the University Hospital in Plovdiv, Bulgaria. After a detailed anamnesis, they underwent neurological examination, EEG, neuroimaging, and lumbar puncture when needed. There was a prospective one-year follow-up regarding seizure frequency, EEG, and treatment. In 18 (5.9%) patients, seizures were related to COVID-19 infection. Nine (3.1%) patients had new-onset seizures, and in nine (3.1%) participants with epilepsy, there was a worsening of seizure frequency. New-onset seizures were more likely to occur inpeople above 65 years of age, within one to two months from the infection diagnosis. In one participant, seizures were related to fever. The most common seizure types were generalized tonic-clonic and focal motor seizures with/without loss of awareness. Antiseizure medications were started in seven participants. Viral encephalopathy was confirmed in two patients, one of them died. EEG showed focal epileptiform activity in four participants. The one-year prospective observation showed a favorable outcome in five patients who were without seizures, had normal EEG, and three were without treatment. Seizure frequency increase or seizure recurrence was typically observed for a short period of time in the epilepsy group. EEG was worsened in one patient and treatment changes were needed in five participants. In conclusion, our study results provide evidence about the progress and possible relationshipbetweennew-onset seizures and seizure worsening with COVID-19 infection.

Robot-assisted, CT-guided placement of responsive neurostimulator system with bilateral centromedian thalamus depth electrodes for multifocal intractable epilepsy.

The responsive neurostimulator system has become increasingly popular in the surgical management of refractory epilepsy, with targeting of various thalamic nuclei showing promising results in select patients. A 42-year-old female presented for evaluation of refractory epilepsy consisting of generalized tonic-clonic and focal seizures with preserved awareness. Phase I and II monitoring suggested multifocal bilateral epilepsy with bilateral frontal onset, and the patient underwent robot-guided bilateral centromedian thalamic placement of the RNS System. In this operative video, the authors share their institutional experience and protocol utilizing the ExcelsiusGPS robot in the placement of the RNS System in the thalamus. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID243.

Valproate-induced leucocytoclastic vasculitis: A rare case report

ABSTRACT Drug-induced vasculitis is essentially a small-vessel vasculitis. Histopathological changes in this condition are characterised by neutrophilic leucocytoclasia of the small vessels. To label it leucocytoclastic vasculitis, one must exclude other types of vasculitis where autoimmune workup comes into play. Antiepileptics, although rare, are also known to have such a presentation. We present a case of a 35-year-old male, a known case of hypertension and seizure disorder (on regular treatment), with a recent history of generalised tonic–clonic seizures, leading to a change in his antiepileptics. This was followed by extensive rash development, predominantly on his lower limbs, which was diagnosed as leucocytoclastic vasculitis, with sodium valproate (VPA) being the aetiology for the same. The offending drug was removed, and after treatment with steroids, the patient’s condition significantly improved.

Posterior Reversible Encephalopathy Syndrome After Inadvertent Dural Puncture Vs Bupivacaine-Induced Adverse Drug Reaction: A Case Report

A case involving a 29-year-old female patient with a known case of hypothyroidism at 38 weeks gestation. She developed a fronto-occipital, postural type of headache. This ensued on the second postoperative day after undergoing an unintended dural puncture with the introducer needle during spinal anesthesia for an elective cesarean section. It was initially treated as a post-dural puncture headache until she developed generalized tonic–clonic seizures the next day. Magnetic resonance imaging (MRI) of the brain exhibited features of posterior reversible encephalopathy syndrome (PRES). With anticonvulsants and antibiotics, the neurological symptoms subsided, and the patient was discharged home symptom-free. We call attention to the importance of suspecting PRES in obstetric cases with an inadvertent dural puncture in a normotensive patient. Neuroimaging plays a crucial role in making a diagnosis of headaches, especially during the peripartum period. Lastly, keeping in view, the potential medicolegal implications in such cases, further research seems vital, especially in the Asian population.

Seizure Outcome and Predicting Factors in Adult Patients with Phenylketonuria: Single-center Experience

ABSTRACT Objective: Phenylketonuria (PKU) is one of the most common metabolic disorders worldwide. If left untreated, it causes neuropsychiatric sequelae, with seizures being a common occurrence. There is little information about the clinical features of epilepsy, electroencephalography (EEG) findings, and factors related to seizure outcomes in adult patients. We aimed to investigate these variables in adult PKU patients. Methods: We conducted a retrospective search in our database using the keywords “PKU and epilepsy” for the period between 2008 and 2022. Demographic, clinical, EEG, and cranial magnetic resonance imaging (MRI) findings of the patients were extracted from the electronic health records. Scalp EEG and MRI findings were reassessed. Phenylalanine (Phe) levels of the cases were retrieved. The potential correlation between seizure outcome and laboratory findings was analyzed. Results: Ten patients (4 females; aged: 19–55 years) were included. Seizure onset was various. The most common seizure type was bilateral tonic-clonic. Nine patients were on antiseizure medications (ASMs); seven were seizure-free. EEG background activity was slow in four patients, with paroxysmal discharges in eight individuals. The most frequent MRI finding was periventricular white matter hyperintensity. No correlation existed between seizure outcome and clinical, EEG, MRI results, or Phe levels. Seizure freedom was more common in patients with good dietary compliance. Conclusion: Bilateral tonic–clonic seizures were the most common type of seizure, accompanied by frequent paroxysmal activity in EEG. MRI scans revealed periventricular white matter hyperintensity. Seizure freedom was commonly achieved with ASMs, irrespective of blood Phe levels. Nevertheless, dietary compliance may play a role in seizure control.