Prospective study of epilepsy with generalized tonic-clonic seizures alone: Clinical features, response to treatment, and likelihood of medication withdrawal.

OBJECTIVE: This prospective study aimed to delineate the demographics, natural progression, and treatment response of patients newly diagnosed with epilepsy with generalized tonic-clonic seizures alone (EGTCA). Furthermore, our objective includes assessing the seizure recurrence rate post antiseizure medication (ASM) discontinuation within this cohort, alongside exploring predictive factors for seizure relapse. METHODS: The study cohort, derived from an ongoing, prospective, multicenter investigation on children and adults with new-onset unprovoked seizures, included consecutive patients enrolled between March 2010 and March 2020, and meeting mandatory ILAE criteria for EGTCA diagnosis. Participants underwent a 3-h sleep-deprived video-EEG recording along with an epilepsy protocol brain magnetic resonance imaging (MRI) with repeat EEG at each follow-up. Cumulative time-dependent probabilities of seizure recurrence were calculated using Kaplan-Meier survival analysis. Logistic regression identified variables associated with seizure recurrence following ASM taper. RESULTS: Eighty-nine patients with a median age of 16 years were included, constituting 31% of those diagnosed with an idiopathic generalized epilepsy. Regarding the circadian distribution of seizures, 59.6% of patients exclusively experienced diurnal seizures, 12.4% exclusively nocturnal, and 28.1% experienced both diurnal and nocturnal seizures. Generalized spike-wave discharges (GSWD) were present in the initial EEG of 88% of patients. A GTC recurred in 14% of patients treated with ASM compared with 73% of untreated patients (p < 0.00001). ASM discontinuation was attempted in 50 patients after a median treatment duration of 3 years, with 44% experiencing a recurrence. Patient-initiated taper and a mixed circadian seizure pattern independently predicted a higher likelihood of recurrence post-ASM discontinuation. SIGNIFICANCE: Our findings underscore the importance of prompt treatment upon the diagnosis of EGTCA. Notably, lifelong treatment may not be imperative; patients seizure-free for at least 2 years, with the absence of GSWD on EEG, often maintained seizure freedom after ASM withdrawal, especially with physician-initiated tapering. PLAIN LANGUAGE SUMMARY: Seizures in individuals diagnosed with "epilepsy with generalized tonic-clonic seizures alone" (EGTCA) typically start during adolescence and often respond well to antiseizure medications. An electroencephalogram, which measure brain waves, will show abnormal discharges in most patients with EGTCA. Lifelong treatment with antiseizure medication is not necessary for everyone with EGTCA; approximately, 40% can successfully stop treatment without facing seizure recurrence. Patients who stop medication on their own have a higher risk of seizures returning compared with those who undergo cessation under a doctor's supervision.

Case report: Rapid recovery after intrathecal rituximab administration in refractory anti-NMDA receptor encephalitis: report of two cases.

Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is one of the most prevalent etiologies of autoimmune encephalitis. Approximately 25% of anti-NMDAR encephalitis cases prove refractory to both first- and second-line treatments, posing a therapeutic dilemma due to the scarcity of evidence-based data for informed decision-making. Intravenous rituximab is commonly administered as a second-line agent; however, the efficacy of its intrathecal administration has rarely been reported. Case summary: We report two cases of severe anti-NMDAR encephalitis refractory to conventional therapies. These patients presented with acute-onset psychosis progressing to a fulminant picture of encephalitis manifesting with seizures, dyskinesia, and dysautonomia refractory to early initiation of first- and second-line therapeutic agents. Both patients received 25 mg of rituximab administered intrathecally, repeated weekly for a total of four doses, with no reported adverse effects. Improvement began 2-3 days after the first intrathecal administration, leading to a dramatic recovery in clinical status and functional performance. At the last follow-up of 6 months, both patients remain in remission without the need for maintenance immunosuppression. Conclusion: Our cases provide evidence supporting the intrathecal administration of rituximab as a therapeutic option for patients with refractory anti-NMDAR encephalitis. Considering the limited penetration of intravenous rituximab into the central nervous system, a plausible argument can be made favoring intrathecal administration as the preferred route or the simultaneous administration of intravenous and intrathecal rituximab. This proposition warrants thorough investigation in subsequent clinical trials.

Early predictors of remission in children and adolescents with new-onset epilepsy: A prospective study.

PURPOSE: This study aims to identify predictive factors of a two-year remission (2YR) in a cohort of children and adolescents with new-onset seizures based on baseline clinical characteristics, initial EEG and brain MRI findings. METHODS: A prospective cohort of 688 patients with new onset seizures, initiated on treatment with antiseizure medication was evaluated. 2YR was defined as achieving at least two years of seizure freedom during the follow-up period. Multivariable analysis was performed and recursive partition analysis was utilized to develop a decision tree. RESULTS: The median age at seizure onset was 6.7 years, and the median follow-up was 7.4 years. 548 (79.7%) patients achieved a 2YR during the follow up period. Multivariable analysis found that presence and degree of intellectual and developmental delay (IDD), epileptogenic lesion on brain MRI and a higher number of pretreatment seizures were significantly associated with a lower probability of achieving a 2YR. Recursive partition analysis showed that the absence of IDD was the most important predictor of remission. An epileptogenic lesion was a significant predictor of non-remission only in patients without evidence of IDD, and a high number of pretreatment seizures was a predictive factor in children without IDD and in the absence of an epileptogenic lesion. CONCLUSION: Our results indicate that it is possible to identify patients at risk of not achieving a 2YR based on variables obtained at the initial evaluation. This could allow for a timely selection of patients who require close follow-up, consideration for neurosurgical intervention, or investigational treatments trials.

Risk of recurrence in patients with an unprovoked tonic-clonic seizure and generalized epileptiform discharges on EEG.

OBJECTIVE: The decision to initiate treatment in patients with a first unprovoked seizure remains controversial. Studies have reported a recurrence rate ranging from 21%-50%, but most have included patients with different etiologies, electroencephalography (EEG) findings, and seizure types. This study aimed to determine the risk of recurrence in patients with a first unprovoked generalized tonic-clonic (GTC) seizure with evidence of generalized spike-wave discharges (GSWDs) on EEG and compare the efficacy of antiseizure medications (ASMs) in preventing recurrence. METHODS: This prospective study included consecutive patients who presented with a single GTC seizure, evidence of GSWDs on EEG, and a follow-up period of at least 1 year. All patients underwent extensive evaluation, including a 3-hour sleep-deprived video-EEG recording and an epilepsy protocol brain magnetic resonance imaging (MRI). Treatment with ASMs was recommended for all patients. The decision regarding the specific ASM to be used was left to the treating physician's discretion. RESULTS: A total of 57 patients with a median age of 19 years were included. A total of 41 patients agreed to be started on an ASM while 16 declined. Seizure recurred in 6 of 41 patients (14.6%) in the treated group compared to 11 of 16 (68.8%) in the untreated group (p = .00006). Valproate was significantly more efficacious than levetiracetam or lamotrigine (p = .04). Of the 15 patients who discontinued ASM treatment after remaining seizure-free for an average of 30 months, 6 (40%) experienced a seizure recurrence. SIGNIFICANCE: Patients with a first unprovoked GTC seizure and evidence of GSWDs on EEG have a high risk of recurrence if left untreated. Valproate is the most efficacious ASM for preventing recurrence in this population. A sizeable proportion of patients can be successfully tapered off medication after a period of seizure freedom. This study provides valuable information for guiding treatment decisions in this patient population.

Role of Early Intravenous Immunoglobulins in Halting Clinical and Radiographic Disease Progression in Rasmussen Encephalitis.

BACKGROUND: Rasmussen encephalitis (RE) is a rare progressive presumed autoimmune disorder characterized by pharmacoresistant epilepsy and progressive motor and cognitive deterioration. Despite immunomodulation, more than half of the patients with RE ultimately require functional hemispherotomy. In this study, we evaluated the potential beneficial effects of early initiation of immunomodulation in slowing disease progression and preventing the need for surgical interventions. METHODS: A retrospective chart review over a 10-year period was conducted at the American University of Beirut Medical Center to identify patients with RE. Data were collected on seizure characteristics, neurological deficits, electroencephalography, brain magnetic resonance imaging results (including volumetric analyses for an objective assessment of radiographic progression), and treatment modalities. RESULTS: Seven patients met the inclusion criteria for RE. All patients received intravenous immunoglobulins (IVIGs) as soon as the diagnosis was entertained. Five patients with only monthly to weekly seizures at the time of IVIG initiation had favorable outcomes without resorting to surgery, along with a relative preservation of the gray matter volumes in the affected cerebral hemispheres. Motor strength was preserved in those patients, and three were seizure free at their last follow-up visit. The two patients who required hemispherotomy were already severely hemiparetic and experiencing daily seizures at the time of IVIG initiation. CONCLUSIONS: Our data suggest that the early initiation of IVIG as soon as a diagnosis of RE is suspected, and particularly before the appearance of motor deficits and intractable seizures, can maximize the beneficial effects of immunomodulation in terms of controlling seizures and reducing the rate of cerebral atrophy.

Standardized reporting of complications of epilepsy surgery and invasive monitoring: A single-center retrospective study.

OBJECTIVE: Monitoring adverse effects related to epilepsy surgery is essential for quality control and for counseling patients prior to the procedure. The aim of this study was to analyze the rates of complications related to epilepsy surgery following invasive monitoring and to classify them according to the recently proposed protocol by the E-pilepsy consortium. METHODS: This is a retrospective study of collected data extracted from our routinely updated epilepsy surgery database which consisted of 173 surgical procedures: 89 surgeries for insertion of subdural grids, strips, and/or depth electrodes, and 84 resective surgeries. According to the protocol, complications were defined as unexpected postoperative adverse events and were stratified into transient (lasting less than 6 months) and permanent deficits (lasting 6 months or longer). In addition, we reported patients with postoperative psychiatric disturbances and calculated the rates of transient and permanent postoperative sequelae which were defined as expected postoperative deficits deemed inherent to the surgical procedure. RESULTS: Six potentially life-threatening complications requiring acceleration of the planned resective surgery occurred during invasive monitoring. Following resective surgery, 12 transient sequelae (8 motor deficits, three language deficits, and one transient dyscalculia) and 10 permanent sequelae (5 mild memory disturbances, four visual field cuts, and one contralateral dysesthesia) occurred. In addition, 7 patients experienced transient motor complications. Four permanent postoperative neurological complications (4.8%) occurred: motor deficits in three patients and a partial peripheral facial palsy in one. Finally, five patients developed de novo psychiatric disturbances (transient in four and permanent in one). CONCLUSIONS: This is the first study to classify complications of epilepsy surgery according to the E-pilepsy consortium protocol. Our findings demonstrate that epilepsy surgery following invasive monitoring is safe and associated with low morbidity when performed in specialized centers. Monitoring these complications according to a unified definition and using a multidimensional protocol will allow for a direct comparison across epilepsy surgery centers, will provide the epileptologists and surgeons with objective percentages to share with their patients and will help in identifying risk factors and improving the safety of epilepsy surgery.

Refractory Morvan syndrome responsive to rituximab: a case report and review of the literature.

Morvan Syndrome (MoS) is an autoimmune disorder characterized by peripheral nerve hyperexcitability, autonomic dysfunction, and encephalopathy. We describe the case of a man with a history of thymoma diagnosed with a paraneoplastic MoS with a severe painful neuropathy refractory to immunoglobulins and steroids who had a dramatic and lasting response following treatment with rituximab. We also reviewed the clinical features, comorbidities, laboratory findings, treatment responses, relapses, and long-term outcomes of all published cases of MoS treated with rituximab. This drug appears promising for the treatment of patients with MoS who failed first line therapy with immunoglobulins and steroids.

Brain magnetic resonance imaging findings and brain volumetric differences in a large series of benign rolandic epilepsy.

BACKGROUND: Several studies with a small sample size have investigated the relationship between structural and functional changes on MRI and the clinical and natural history of BRE. We aim to assess the frequency of incidental epileptogenic lesions on brain MRI in a large cohort of patients diagnosed with BRE and to assess the difference in volumetric brain measurements in BRE patients compared to healthy controls. METHODS: The case-control study includes 214 typical BRE cases and 197 control children with non-epileptic spells. Brain MRIs were evaluated for abnormalities which were classified into normal and abnormal with or without epileptogenic lesions with categorization of epileptogenic lesions. Brain segmentation was also performed for a smaller group of BRE patients and another healthy control group. Pearson's chi-squared test and two-tailed independent samples t-test were used. RESULTS: In patients with BRE, 7% had an epileptogenic lesion on their MRI. The frequency of epileptogenic lesion in the control group was 10.2% and not significantly different from those with BRE (p= 0.2). Significantly higher intracranial and white matter volumes were found in BRE patients compared to the healthy group while lower gray matter volume was found in BRE patients. Cortical and subcortical regions showed either higher or lower volumes with BRE. Interestingly, altered subcallosal cortex development which has a known association with depression was also found in BRE. CONCLUSIONS: Our findings confirm the absence of any association between specific brain MRI abnormalities and BRE. However, the altered cortical and subcortical development in BRE patients suggests a microstructural-functional correlation.

COVID-19-Associated Acute Asymmetric Hemorrhagic Necrotizing Encephalopathy: A Case Report.

Background: Coronavirus disease 2019 (COVID-19) has been associated with many neurological complications affecting the central nervous system. Purpose: Our aim was to describe a case of COVID-19 associated with a probable variant of acute necrotizing encephalopathy (ANE). Results: A 60-year-old man who presented with a 3-day history of dyspnea, fever, and cough tested positive for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Five days following his admission, the patient was intubated secondary to respiratory failure. Following his extubation 16 days later, he was found to have a left-sided weakness. Magnetic resonance imaging (MRI) of the brain showed hemorrhagic rim-enhancing lesions involving the right thalamus, left hippocampus, and left parahippocampal gyrus. These lesions showed decreased relative cerebral blood flow on MR perfusion and restricted on diffusion-weighted imaging. These neuroimaging findings were consistent with ANE. The left-sided weakness gradually improved over the subsequent weeks. Conclusions: We concluded that COVID-19 can be associated with ANE, a condition believed to be the result of an immune-mediated process with activation of the innate immune system. Future studies must address whether biological drugs targeting the pro-inflammatory cytokines could prevent the development of this condition.

Bilateral Reappearance of the N20 Potential in a Normothermic Young Woman Post-Anoxic Brain Injury.

SUMMARY: Hypoxic-ischemic brain injury is a well-known consequence of cardiac arrest and providing an accurate prognostication remains a challenge, especially in decisions related to withdrawal of care. Bilateral absence of the cortical response (N20 potential) on median somatosensory evoked potentials, on days 1 to 3 after the return of spontaneous circulation, is widely considered as the most reliable predictor of poor outcome with a high specificity and a low false-positive rate. The authors describe the case of a young comatose woman after hypoxic injury because of cardiac arrest whose initial median somatosensory evoked potentials revealed bilateral absence of the N20 response associated with evidence of selective injury to both perirolandic cortices and basal ganglia on brain MRI. This patient made a substantial recovery associated with bilateral reappearance of the N20 potential and resolution of the neuroimaging abnormalities.This case revealed that an acute selective and reversible hypoxic injury to both perirolandic cortices may lead to a temporary loss of the N20 responses and an inaccurate prediction of poor outcome after cardiac arrest. It emphasizes on the importance of adopting a multimodal approach in the prognostic assessment of survivors of cardiac arrest.

New-onset refractory status epilepticus as an early manifestation of multisystem inflammatory syndrome in adults after COVID-19.

Multisystem inflammatory syndrome in adults (MIS-A) is a rare hyperinflammatory complication with multi-organ involvement that manifests a few weeks after recovering from a typically mild coronavirus disease 2019 (COVID-19) infection. Although encephalopathy and seizures can occur in the acute phase of COVID-19, the nervous system is infrequently involved in patients with MIS-A. Herein, we describe the case of a young woman who presented with new-onset refractory status epilepticus (NORSE) following a mild COVID-19 infection associated with symptoms, signs, and laboratory findings that satisfy the updated Centers for Disease Control and Prevention (CDC) definition of MIS-A. Magnetic resonance imaging of the brain revealed symmetric T2-signal increase involving both orbitofrontal lobes, insulae, and hippocampi. One of the notable findings in our patient was the quick response and significant clinical recovery that occurred following initiation of treatment with intravenous methylprednisolone and intravenous immunoglobulin. Our case expands the clinical spectrum of MIS-A and documents the occurrence of NORSE as one of its early clinical manifestations. A routine comprehensive clinical and laboratory assessment is needed to screen for this underdiagnosed condition, especially in patients with post-COVID-19 inflammatory complications.

Predicting the occurrence of thrombocytopenia from free valproate levels: A prospective study.

PURPOSE: The likelihood of valproate (VPA) induced thrombocytopenia increases with higher VPA levels. In critically ill patients, the biological active free VPA level cannot be predicted from the total serum level. In this study, we evaluated the relationship between trough free VPA serum levels and concomitant platelet counts and assessed risk factors for the development of thrombocytopenia with the aim of generating a formula specifying the probabilities of developing thrombocytopenia based on trough free serum VPA levels. METHODS: Trough free VPA levels and concomitant platelet counts were collected from a large cohort of patients who participated in a prospective VPA monotherapy trial. Significant variables associated with thrombocytopenia in a univariate analysis were evaluated in a multivariate model. A receiver operator curve was performed to compute the trough free VPA levels with the greatest discriminating power in predicting thrombocytopenia. RESULTS: 844 trough free VPA levels and concomitant platelet counts obtained from 264 patients were analyzed. In a multivariate analysis, trough free VPA levels, gender, and baseline platelet counts were significantly associated with thrombocytopenia. Using stepwise regression and multivariate logistic regression analyses, we generated gender-specific formulas for predicting platelet counts and probabilities of developing thrombocytopenia. The trough free VPA with the greatest discriminating power to predict platelet values ≤ 100,000/µL was 16.65 µg/mL. CONCLUSIONS: The generated model was based on trough free VPA levels and achieved high sensitivity and specificity. Our results are therefore generalizable and can be applied to estimate the probability of developing thrombocytopenia in critically ill patients.

The importance of acknowledging diagnostic uncertainty in patients with new-onset paroxysmal spells.

OBJECTIVE: The aims of this study were to evaluate the frequency of paroxysmal spells of indeterminate nature (PSIN) in a large cohort of children and adults with suspected new-onset seizures, to evaluate the reasons for including patients in this category, and to calculate the rate of erroneous diagnoses if the epileptologists were compelled to label those events as epileptic seizures or nonepileptic paroxysmal spells. METHODS: Patients identified for this study participated in a prospective study evaluating patients with suspected new-onset unprovoked seizures. The workup included a detailed history and a thorough description of the spells, a 3-hour video EEG recording, and an epilepsy protocol brain MRI. Based exclusively on a detailed description of the ictal events, two epileptologists were asked to independently classify each patient into those with a definite diagnosis of unprovoked seizures or a definite diagnosis of a nonepileptic paroxysmal spells (group 1) and those with PSIN (group 2). RESULTS: A total of 1880 consecutive patients were enrolled with 255 (13.6%) included in the PSIN group. Patients with PSIN were significantly younger than those with a definite diagnosis, and PSIN were significantly more frequent in children with developmental delay. The most common reason for including patients in the PSIN group was the inability to categorically discriminate between a seizure and a nonepileptic mimicker. When the raters were compelled to classify the spells in the PSIN group, the frequencies of erroneous diagnoses ranged between 32% and 38%. The final diagnoses on those patients were made based on the results of the EEG, MRI, and follow-up visits. SIGNIFICANCE: Our data indicate that a diagnostic category of PSIN should be recognized and ought to be used in clinical practice. Acknowledging this uncertainty will result in lower frequencies of erroneous diagnoses, possible stigma, and potential exposure to unnecessary antiseizure medications.

Depression and anxiety in patients from Lebanon with new onset functional seizures.

OBJECTIVES: To prospectively compare the frequencies of depression and anxiety in patients with new onset functional seizures versus two age and gender-matched control groups consisting of patients with new onset epileptic seizures and normal individuals. METHODS: Consecutive patients, 16 years and older, enrolled in a prospective study for suspected new onset epileptic seizures and diagnosed with documented functional seizures were included. We compared the depression and state and trait anxiety scores using the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI) between patients with functional seizures and the other two control groups. RESULTS: The 33 patients with functional seizures had significantly higher depression and anxiety scores compared to those with epileptic seizures and normal controls. Twenty patients (60.6%) in the functional seizures group scored in the "depression" range compared to 5/33 (15.2%) in the epileptic seizures and 1/33 (3%) in the control groups. In the functional seizures group, 14/33 (42.4%) had scores in the "state anxiety" range compared to 6/33 (18.2%) and 2/33 (6.1%) in the epileptic seizures and normal control groups, respectively. Similarly, 15/33 (51.5%) of patients in the functional seizures group had scores in the "trait anxiety" range compared to 4/33 (12.1%) and 1/33 (3%) in the epileptic seizures and normal control groups, respectively. CONCLUSIONS: Our results indicate that patients with new onset functional seizures frequently suffer from depression and anxiety at the time of their initial evaluation. These findings underscore the importance of screening for depression and anxiety in that patient population.

A novel possible familial cause of epilepsy of infancy with migrating focal seizures related to SZT2 gene variant.

Seizure threshold-2 (SZT2) gene variants have been associated with a decrease in seizure threshold resulting in variable phenotypic expressions ranging from mild-moderate intellectual disabilities without seizures, to an early-onset epileptic encephalopathy with severe cognitive impairment. In addition, hypotonia and distinctive facial dysmorphism, including a high forehead and to a lesser extent ptosis and down-slanting palpebral fissures, were present in the majority. We herein report a novel SZT2 variant in one of two siblings both diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). This report is the fourth to document a possible familial case in EIMFS, a condition that was not previously associated with SZT2 variant. This report expands the phenotypic expression of SZT2, corroborates the importance of genetic counseling in some cases of EIMFS, and highlights the efficacy of potassium bromide in controlling the seizures associated with this condition.

Case Report: Distinctive EEG Patterns in SCARB-2 Related Progressive Myoclonus Epilepsy.

Action myoclonus-renal failure syndrome (AMRF) is a rare, recessively inherited form of progressive myoclonus epilepsy (PME) caused by mutations in the SCARB2 gene and associated with end-stage renal failure. In addition to severe progressive myoclonus, the neurological manifestations of this syndrome are characterized by progressive ataxia and dysarthria with preserved intellectual capacity. Since its original description, an increasing number of "AMRF-like" cases without renal failure have been reported. We describe the case of a 29-year-old woman with progressive disabling myoclonus associated with dysarthria and ataxia who was found to have a novel homozygous frameshift mutation in the SCARB2 gene. In addition, this report emphasizes the presence of two EEG patterns, fixation-off phenomenon, and bursts of parasagittal spikes exclusively seen during REM sleep that appear to be characteristic of this condition.

Current role of carbamazepine and oxcarbazepine in the management of epilepsy.

Epilepsy is one of the most common neurological disorders, affecting approximately 50 million people worldwide. Despite a dramatic increase in treatment options over the past 30 years, it still ranks fourth in the world's disease burden. There are now close to 30 antiepileptic drugs (AEDs), with more than two thirds introduced to the market after carbamazepine (CBZ) and one third after its derivative, oxcarbazepine (OXC). Following the introduction of these newer AEDs, the role of CBZ and OXC in the therapeutic armamentarium for seizure control and effective epilepsy management needs to be reviewed. The main guidelines list both CBZ and OXC as first-line options or second-line alternatives for the treatment of focal-onset epilepsy and primary generalized tonic-clonic seizures. While evidence suggests that overall AEDs have similar efficacy, some newer AEDs may be better tolerated than CBZ. In line with this, there have been changes in treatment patterns, with many variations across different countries. However, CBZ remains among the two or three most prescribed drugs for focal epilepsy in many countries, and is widely used across Europe, Africa, South America, and Asia, where it represents a good compromise between cost, availability, and effectiveness. OXC is among the first-choice options for the initial treatment of focal-onset seizures in several countries, including the US and China, where the oral suspension is commonly prescribed. This review provides guidance on the optimal use of these two drugs in clinical practice, including in children, the elderly, and in pregnancy.

FARS2 Mutations: More Than Two Phenotypes? A Case Report.

FARS2, a nuclear gene, encodes the mitochondrial phenylalanyl-tRNA synthetase (mtPheRS). Previous reports have described two distinct phenotypes linked to FARS2 gene mutation: an early onset epileptic encephalopathy and spastic paraplegia. This report describes a distinctive phenotype of FARS2-linked, juvenile onset refractory epilepsy, caused by a hemizygous mutation in a compound heterozygous state (p.V197M and exon 2 microdeletion). A 17-year- old woman with normal development presented with a super refractory focal motor status epilepticus. Only an emergency life-saving surgery aborted her status after all therapeutic interventions, including anesthesia, failed to control her seizures. Pathological and biochemical activities on muscle biopsy showed mitochondrial proliferation with enhanced isolated activities of complexes II and IV, suggestive of a compensatory mechanism for the bioenergetic deficiency. Postoperatively, the patient started experiencing focal aware motor seizures originating from the contralateral hemisphere after being seizure free for a few months. This report suggests a third phenotypic manifestation of FARS2 gene mutation.

Coma With Absent Brainstem Reflexes and a Burst Suppression on EEG Secondary to Baclofen Toxicity.

Baclofen, a muscle relaxant prescribed for the alleviation of symptoms of spasticity acts primarily at the spinal level but with high doses, it penetrates the blood-brain barrier and can result in prominent central nervous depression. Baclofen toxicity has been associated with a variety of symptoms ranging from dizziness to deep coma. We report the clinical course, management, and outcome of a case of baclofen overdose who presented in deep coma with loss of brainstem reflexes and a burst suppression (BS) pattern on his electroencephalogram (EEG). In addition, we reviewed the presentation and outcomes of all reported cases of baclofen toxicity with a BS pattern on EEG to evaluate if those cases share a common clinical presentation and for the presence of signs and symptoms that would help the clinician to consider this diagnosis. There appears to be a common clinical picture associated with severe baclofen toxicity consisting of deep coma associated with loss of all brainstem reflexes including pupillary reactivity, frequent association with seizures/myoclonic jerks, and a BS pattern on EEG. The outcome is generally good, and serial EEGs are recommended to document a reversal of the abnormal electrographic features.

Treatment of generalized convulsive status epilepticus: An international survey in the East Mediterranean Countries.

PURPOSE: Three Chapters of the Commission of the East Mediterranean Affairs (CEMA) of the ILAE conducted a survey to assess the availability of drugs used for the treatment of generalized convulsive status epilepticus (GCSE) across the CEMA countries and to evaluate the treatment choices of adult and pediatric neurologists for the treatment of this condition. METHOD: The web-based survey consisted of two similar vignettes of GCSE in a child and an adult. The questions evaluated the sequential drugs of choice based on drug availability and with the assumption that all drugs were at the disposition of the neurologists. The neurologists were also asked about the timing of introduction of anesthetic drugs and how they monitor patients in drug induced coma. RESULTS: Our data showed that the availability of drugs differ substantially across CEMA countries. A benzodiazepine and phenytoin/phenobarbital were the initial drugs of choice for the majority of adults and pediatric neurologists. In cases of refractory status, most neurologists would use a third agent before proceeding to treatment with an anesthetic agent. Although the vast majority would prefer to monitor patients in drug-induced coma with continuous EEG, only 38% are using this modality because of its unavailability at their institutions. CONCLUSIONS: Our data emphasize that an algorithm for the treatment of GCSE in the CEMA countries should be flexible and should propose different treatment options at each step of the protocol that are based on the best available data while taking into consideration the drug availability across the CEMA countries.