Experienced Status Epilepticus Research Articles

Subdural Empyema Secondary to Sinusitis: Presenting with Cluster-like Headache, Status Epilepticus, and Orbital Apex Syndrome

A 67-year-old man suffered cluster-like headache for 8 months. He underwent endoscopic sinus surgery 2 months prior to the onset of headache. The patient experienced status epilepticus 7 months after the onset of cluster-like headache, and 8 months after its onset, orbital apex syndrome developed. Brain magnetic resonance imaging (MRI) showed subdural empyema. This case emphasizes the association between subdural empyema caused by sinusitis and the potential manifestation of various neurological symptoms, including cluster-like headache, status epilepticus, and orbital apex syndrome.

Epilepsy phenotypes across the different age-ranges in IQSEC2-related encephalopathy: An Italian multicentre retrospective cohort study

BackgroundEpilepsy is a hallmark of IQSEC2-related encephalopathy within a phenotypic variability ranging between early onset epileptic and developmental encephalopathy and X-linked intellectual disability with epilepsy. Patients and MethodsData including demographic aspects, gene variants, seizure semiology and timing, EEG features, neuroimaging and response to therapy were retrospectively collected in patients with IQSEC2-related epilepsy referring to 8 Italian tertiary centres. ResultsThe reported cohort included 11 patients (8 males and 3 females). Mean age at the onset of epilepsy was 3.90±2.80 years. No cases were reported in the first year of life. No specific epileptic syndromes were recognized. Predominant seizure-types in the age range 12–36 months included focal onset tonic seizures with impaired awareness, myoclonic seizures, and late onset spasms. Generalized motor seizures were predominant in patients between 3 and 6 years and between 12 and 18 years while focal motor seizures with impaired awareness were the most represented types between 6 and 12 years. No patients experienced status epilepticus. EEG patterns included a delayed maturation of EEG organization, irregular focal or diffuse slow activity, multifocal or diffuse epileptiform abnormalities. No structural epileptogenic lesions were detected at MRI. Valproate, lamotrigine, clobazam, topiramate and levetiracetam were the most used antiseizure medication. Complete seizure freedom was achieved only in 2 patients. ConclusionsOnset of epilepsy after the first year of age, predominance of focal seizures with impaired awareness and generalized motor seizures, no pathognomonic underlying epileptic syndrome and infrequent occurrence of status epilepticus emerged as the main features of IQSEC2-related epilepsy phenotype.

Continuous cardiac monitoring in epilepsy: an implantable loop manual activation algorithm for improving ECG signal acquisition accuracy

BackgroundThe muscle artifacts, caused by prominent muscle contractions, mimicking cardiac arrhythmias, might compromise the ECG signal quality and the implantable loop recorder memory capacity in patients with epilepsy. We developed an epileptic seizures clinical pattern-based implantable loop recorder manual activation algorithm, presenting its real-world efficacy here.MethodsOne hundred ninety-three patients (18–60 years) with drug-resistant focal epilepsy were consecutively enrolled and underwent a subcutaneous loop recorder implantation. Patients with focal onset-aware seizures and patients with focal impaired awareness seizures /bilateral tonic-clonic seizures without aura were recommended to use the activator once - just after the episode. Patients with focal impaired awareness seizures/bilateral tonic-clonic seizures with aura, the caregivers of patients experiencing status epilepticus, were advised to use the activator twice - during the aura and after the episode/ regaining consciousness.ResultsSix thousand four hundred ninety-four ECG traces (4826 - auto-triggered events, 1668 - person-activated events) were recorded and analyzed. The rate of true positive events in the person-activated group was statistically higher than in the autoactivation group (72.5% vs.19.4%, p < 0.0001). Person-activated false-positive events were observed in 30.5% of patients with focal impaired awareness seizures and 27.7% in patients with bilateral tonic-clonic seizures. The highest rate of false-positive events (61.5%) was detected in patients undergoing epileptic status, and the lowest rate (3.8%) - was in patients with focal onset aware seizures. The rate of false-positive events was significantly higher in patients with impaired awareness seizures without aura both in focal impaired awareness (45.5% vs. 19.3%, p < 0.0001) and bilateral tonic-clonic seizure groups (38.8% vs. 5.9%, p < 0.0001).ConclusionsArrhythmias with varying clinical outcomes are expected in epilepsy patients and have been monitored continuously. The specified loop recorder external activation algorithm can improve the clinically relevant cardiac arrhythmia detection accuracy in epilepsy patients and the value of future studies.

Disease Impact and Burden in Patients with SCN2A-Related Developmental and Epileptic Encephalopathy (P11-9.012)

<h3>Objective:</h3> Explore the burden of <i>SCN2A</i>-DEE on patients and caregivers using clinical data generated via a novel, patient-consented, real-world data platform. <h3>Background:</h3> <i>SCN2A</i>-related DEE comprises a subset of rare neurodevelopmental genetic disorders characterized by significant heterogeneity and limited understanding of disease burden and progression. <h3>Design/Methods:</h3> Real-world clinical data were extracted from patients with an <i>SCN2A</i> variant using Invitae’s Ciitizen platform, which employs a proprietary approach combining machine learning and expert human review to streamline generation of research-grade data from unstructured health records spanning ~10 years. Extracted data (seizure history, medications, comorbidities, developmental milestones) were classified by phenotype based on age at seizure onset, type of seizure at initial presentation, variant type and functional characterization using dynamic action potential clamp analysis. <h3>Results:</h3> 45 patients (92%) had data available for analyses. Four phenotypes were identified across three groups: early onset (EO, 33.5%), late onset (LO, 42%), and autism without epilepsy (AO, 24.5%). The LO group contained two distinct phenotypes based on age and type of seizure at onset: the first, characterized by initial seizure presentation with infantile spasms (LOIS, 20%); the second characterized by seizures other than infantile spasms and presenting later in life (LO, 22%). Mean patient age across cohorts was 8 years (0.8–23.3), with similar percentages of males and females. Mean age at seizure onset was 5.1 days (1–44) in the EO group. 53% of patients with seizures experienced status epilepticus at least once. Mean number of medications prescribed over a patient’s lifetime was 18.1 (0–58). Patients had multiple comorbidities, with global developmental delay the most common (97%), and hypotonia, GERD, autism, and sleep disorders reported in &gt;50%. All patients did not meet at least one critical developmental milestone. <h3>Conclusions:</h3> Using a novel real-world data platform and functional variant characterization, we provide unprecedented insight into clinical phenotypes, disease burden and treatment patterns in <i>SCN2A</i>-DEE. <b>Disclosure:</b> Kelley Dalby has received personal compensation for serving as an employee of Praxis Precision Medicines. Kelley Dalby has stock in Praxis Precision Medicines. Kelley Dalby has stock in RogCon. Mr. Snyder has received personal compensation for serving as an employee of Praxis Precision Medicines. Mr. Snyder has received stock or an ownership interest from Praxis Precision Medicines. Dr. G Matthews has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Praxis Precision Medicines. Dr. G Matthews has stock in Praxis Precision Medicines. Ms. Brimble has received personal compensation for serving as an employee of Invitae. Ms. Brimble has stock in Invitae. Ms. Brimble has stock in Ciitizen. Mr. Beek has received personal compensation for serving as an employee of invitae. Mr. Beek has stock in invitae. Ms. Berk has received personal compensation for serving as an employee of Invitae. Ms. Berk has stock in Invitae. Dr. Oldham has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Souza has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Souza has stock in Praxis Precision Medicines. Steven Petrou has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Praxis Precision Medicines. Steven Petrou has stock in Praxis Precision Medicines. The institution of Steven Petrou has received research support from Praxis Precision Medicines. The institution of Steven Petrou has received research support from Medical Research Future Fund. Steven Petrou has received intellectual property interests from a discovery or technology relating to health care. Steven Petrou has received intellectual property interests from a discovery or technology relating to health care.

Re-appraisal of callosotomy: rates and predictors of short-term seizure outcome in pediatric epileptic encephalopathy

BackgroundEpilepsy is a chronic debilitating disease especially in pediatric population. Most of reported studies for corpus callosotomy as a palliative surgery in drug-resistant cases are on limited number of cases and there is scarcity in literature for outcomes reported from developing countries. Here, we present our study on a large series of cases with analysis of potential predicators outcomes in the era of more expensive devices like vagal nerve stimulation to give a litany on a universal epilepsy surgery procedure which had been missed in the literature through the last decade.ResultsAn observational retrospective study was done reviewing 129 patients with PEE underwent open microscopic corpus callosotomy. Total and drop attack seizure outcomes were studied after surgery. Potential outcomes predictors studied are: preoperative EEG and MRI. Preoperative IQ impairment epilepsy duration, age at diagnosis, MRI finding, IQ score, EEG findings, history of infantile spasm and extent of callosotomy done. All the recorded outcomes were substantially improved after callosotomy in our study population of 129 pediatric patients. The median (IQR) preoperative drop attack frequency was 70 (21–140) which decreased to 3 (0–14) postoperatively. Similarly, the number of anti-epileptics used by patients had a median of 3 (2–4) which decreased to 2 (2–3) after the surgery. All patients were experiencing status epilepticus which disappeared in 72% of the patients after callosotomy. Preoperative normal MRI was a predictor for drop attack favorable outcome and mild preoperative impairment of IQ was a predictor of favorable total seizure and drop attack outcome.ConclusionsCorpus callosotomy is a well-tolerated palliative procedure for drug-resistant generalized epilepsy notably, drop attacks which had its notorious effect on quality of life of pediatric patients and their families, no appreciable prognostic factors for favorable outcome were clearly observed except for normal preoperative MRI, mild preoperative IQ affection, and complete callosotomy.

Comparison of neurological manifestation in children with and without coronavirus 2019 experiencing seizures with fever

Whether neurologic symptoms due to SARS-CoV-2 differ from those of non-SARS-CoV-2 viral infection is unclear. We aimed to describe these neurological manifestations and compare the clinical characteristics and treatments in children with seizures and fever with or without COVID-19. We retrospectively analyzed data from 105 hospitalized children (<18 years) with clinical seizures and fever between September 2021 and August 2022. We compared the clinical characteristics and treatments between the COVID-19 (n = 20) and non-COVID-19 (n = 85) groups. Patients with COVID-19 were older than those without (32.5 [20–86] months vs. 20 [16–32] months, p = 0.029). Seizure type and duration and impaired consciousness duration did not differ between groups. Six and 32 patients experienced status epilepticus lasting 30 min in the COVID-19 and non-COVID-19 groups, respectively. Most treatments did not differ between groups; however, electroencephalography was used less frequently for COVID-19. Neurological sequelae occurred in one and four patients in the COVID-19 and non-COVID-19 groups, respectively. In conclusion, seizures with fever due to SARS-CoV-2 were more common in older children. Seizure characteristics and neurologic sequelae did not differ in children with and those without COVID-19. In general, electroencephalography was used less during COVID-19 for infection control measures.

Status Epilepticus in Pediatric Patients in Saudi Arabia: A Systematic Review

Children frequently experience status epilepticus (SE), a neurologic emergency. Based on current findings in the medical literature, this systematic review aimed to review the published literature of the updates in epidemiology of Status epilepticus in pediatric patients in Saudi Arabia. Because they are reliable sources, PubMed and EBSCO Information Services will be used as the search databases for the publications used in the study. Status epilepticus (SE), seizures, mental health issues, and

Fructose 1,6-bisphosphate is anticonvulsant and improves oxidative glucose metabolism within the hippocampus and liver in the chronic pilocarpine mouse epilepsy model

Glucose metabolism is altered in epilepsy, and this may contribute to seizure generation. Recent research has shown that metabolic therapies including the ketogenic diet and medium chain triglycerides can improve energy metabolism in the brain. Fructose 1,6-bisphosphate (F16BP) is an intermediate of glycolysis and when administered exogenously is anticonvulsant in several rodent seizure models and may alter glucose metabolism. Here, we showed that F16BP elevated the seizure threshold in the acute 6-Hz mouse seizure model and investigated if F16BP could restore impairments in glucose metabolism occurring in the chronic stage of the pilocarpine mouse model of epilepsy. Two weeks after the pilocarpine injections, mice that experienced status epilepticus (SE, “epileptic”) and did not experience SE (no SE, “nonepileptic”) were injected with vehicle (0.9% saline) or F16BP (1 g/kg in 0.9% saline) daily for 5 consecutive days. At 3 weeks, mice were injected with [U-13C6]-glucose and the % enrichment of 13C in key metabolites in addition to the total levels of each metabolite was measured in the hippocampal formation and liver. Fructose 1,6-bisphosphate increased total GABA in the hippocampal formation, regardless of whether mice had experienced SE. In the hippocampal formation, F16BP prevented reductions in the % 13C enrichment of citrate, succinate, malate, glutamate, GABA and aspartate that occurred in the chronic stage of the pilocarpine model. Interestingly, % 13C enrichment in glucose-derived metabolites was reduced in the liver in the chronic stage of the pilocarpine model. Fructose 1,6-bisphosphate was also beneficial in the liver, preventing reductions in % 13C enrichment of lactate and alanine that were associated with SE. This study confirmed that F16BP is anticonvulsant and can improve elements of glucose metabolism that are dysregulated in the chronic stage of the pilocarpine model, which may be due to reduction of spontaneous seizures. Our results highlight that F16BP may be therapeutically beneficial for epilepsies refractory to treatment.

Genotype-phenotype correlation of CACNA1A variants in children with epilepsy.

To explore the genotypes and phenotypes of CACNA1A variants in children with epilepsy. Eighteen children (six males, 12 females) with CACNA1A variants were identified using next-generation sequencing. There were 14 missense variants, two nonsense variants, one frameshift variant, and one splice site variant. Sixteen variants were de novo. Age at seizure onset ranged from 1 day to 8 years; median age was 8 months. Multiple seizure types were observed, including focal, generalized tonic-clonic, myoclonic, and absence seizures, as well as epileptic spasms and tonic seizures. Focal motor status epilepticus occurred in 10 individuals and generalized motor status epilepticus occurred in two individuals. All 18 children showed developmental delay. Focal motor status epilepticus resulted in cerebral atrophy in five individuals, mainly on the contralateral side. Interictal electroencephalogram showed focal discharges in 12 individuals, whereas five individuals had generalized discharges. Three individuals were seizure-free, whereas 15 still had seizures and five had recurrent status epilepticus at last follow-up. Most children with epilepsy and CACNA1A variants had early seizure onset and developmental delay. Focal seizure was the most common seizure type. Most patients experienced status epilepticus. Unilateral cerebral atrophy could occur after focal motor status epilepticus. Patients with CACNA1A variants located in the transmembrane region may be at high risk of status epilepticus.

Caligula: a neuropsychiatric explanation of his madness.

Gaius Julius Caesar Augustus Germanicus, better known as Caligula, (12 CE to 41 CE) was the third Roman emperor and ruled only four years. Throughout his life he experienced several traumatic events, and, in addition, historians mention some premorbid conditions that could cause him to become the monster that most historians know today. When Caligula was 25 years old, he suffered a near-fatal illness that turned his story around. One possible cause was lead poisoning due to the high consumption of wine, which contained lead, by Roman patricians. On the other hand, it is plausible that Caligula experienced epilepsy that began in childhood, later experienced status epilepticus in 37 CE, which triggered an epileptic psychosis with the consequent psychopathic and paranoid changes that led him to the madness noted by historians.

Topiramate rectal suspensions in pediatric patients

We report our experience with topiramate rectal suspensions in a single center case series of three patients <1 year of age from 2017 to 2020 who received topiramate per rectum after being placed nil per os (NPO) status at a free standing children’s hospital. The objective was to describe the compounding methods and clinical outcomes of three of the youngest patients to receive topiramate rectal suspensions. All three patients received topiramate per rectum for 2–4 days. No adverse effects or increase in seizure frequency were noted. For patients placed on NPO status, there is currently no alternative to oral topiramate. No studies describe per rectum topiramate use in pediatrics. Rectal administration of topiramate is not only useful in times when patients are NPO, but may also be useful when patients on topiramate experience status epilepticus. The formulation of topiramate suppositories should be explored in the future. Until further information is available, dose substitution should be done carefully with close supervision by a healthcare provider.

Emergency seizure management

Seizures are a common presentation in both emergency departments and general pediatric practices. Epilepsy affects more than 3.4 million people nationwide, of which approximately 500,000 are children, with greater than 200,000 first-time seizures each year.1 Of the affected individuals, as many as 100,000 are estimated to experience status epilepticus (SE). Both general practitioners and neurologists alike must be able to define, recognize and treat seizure emergencies. This review article defines and describes SE, discusses the emergency evaluation and management of SE that is both new-onset and breakthrough in people with epilepsy, reviews the current treatment recommendations for SE in both the home and hospital settings, and introduces special populations that may be at high risk for SE or other seizure emergencies.

Idiopathic epilepsy in dogs: insights into factors that may predict upcoming seizure activity

Idiopathic epilepsy (IE) is the most common chronic neurological disorder in dogs. Most dogs with IE first experience seizures when they are under six years old, and they usually require...

The Neuroprotective Effects of Histamine H3 Receptor Antagonist E177 on Pilocarpine-Induced Status Epilepticus in Rats.

Epilepsy is a multifaceted neurological disorder which severely affects neuronal function. Some patients may experience status epilepticus (SE), a life-threatening state of ongoing seizure activity linked to cognitive dysfunction, necessitating an immediate intervention. The potential of histamine H3 receptors in several neuropsychiatric diseases including epilepsy is well recognized. In the current study, we aimed to explore the effect of H3R antagonist E177 on prevention and termination of pilocarpine (PLC)-induced SE in rats as well as evaluating the effects of E177 on the levels of oxidative stress in hippocampus tissues. The results showed that the survival rate of animals pretreated with E177 (5 and 10 mg/kg, intraperitoneal (i.p.)) was significantly increased during the first hour of observation, and animals were protected from SE incidence and showed a prolonged average of latency to the first seizure when compared with animals pretreated with PLC (400 mg/kg, i.p.). Moreover, the protective effect of E177 (10 mg/kg) on SE was partially reversed when rats were co- administered with H3R agonist R-(α)-methylhistamine (RAM) and with the H2R antagonist zolantidine (ZOL), but not with the H1R antagonist pyrilamine (PYR). Furthermore, pretreatment with E177 (5 and 10 mg/kg) significantly decreased the abnormal levels of malondialdehyde (MDA), and increased levels of glutathione (GSH) in the hippocampal tissues of the treated rats. However, E177 failed to modulate the levels of catalase (CAT), superoxide dismutase (SOD), or acetylcholine esterase activity (AChE). Our findings suggest that the newly developed H3R antagonist E177 provides neuroprotection in a preclinical PLC-induced SE in rats, highlighting the histaminergic system as a potential therapeutic target for the therapeutic management of SE.

Novel SZT2 mutations in three patients with developmental and epileptic encephalopathies

BackgroundThe seizure threshold 2 (SZT2) gene encodes a large, highly conserved protein that lowers seizure threshold and may also enhance epileptogenesis. In this study, three patients diagnosed with SZT2‐related developmental and epileptic encephalopathies (DEEs) were reviewed aiming to expand knowledge of the genotype and phenotype of SZT2 mutations.MethodsTargeted next‐generation sequencing was performed to identify pathogenic mutations in 205 cases with DEEs of unknown etiology. Detailed clinical and genetic data were collected from SZT2‐associated patients.ResultsFour novel mutations were found (c.1626 + 1G>A, c.5772dupA, c.4209C > A, c.7307_7308insG) in three patients. All the variants were inherited from their parents. Two patients were siblings and harbored the same mutations and presented developmental delay prior to the onset of seizures. All the individuals were diagnosed as DEEs, drug refractory epilepsy, and experienced status epilepticus (SE); one patient died of SE. One subject showed subependymal nodules as similar as those of tuberous sclerosis complex (TSC) in cranial magnetic resonance imaging (MRI).ConclusionOur results expand the genotype and phenotypes of SZT2‐related DEEs, suggesting that SZT2 mutations play a role in developmental delay and epileptic encephalopathy, with high susceptibility to SE and relatively specific MRI findings.

Seizures and epilepsy in multiple sclerosis: epidemiology and prognosis in a large tertiary referral center.

Seizures and epilepsy may substantially add to the burden of disease in multiple sclerosis(MS), whereas the exact prevalence and prognosis of seizures and epilepsy in patients with MS remains largely unknown. We aimed to investigate the epidemiology and prognosis of seizures and epilepsy in MS. We retrospectively analyzed a cohort of 4078 MS patients from a single tertiary referral clinic. After excluding 37 patients with unconfirmed MS and alternative seizure etiologies, we found seizures attributable to MS in 1.5% and epilepsy in 0.9% of patients. 40.4% of patients with a follow-up of at least twelve months experienced only a single seizure and 59.6% had recurring seizures. 39% of patients with recurrent seizures were considered drug-resistant, with 9.7% experiencing status epilepticus. Seizure recurrence after a first seizure depended significantly on the MS subtype and was seen more often if the first seizure occurred simultaneously with a MS relapse than in the absence of a relapse. Our study shows a lower number of seizures and epilepsy in MS than previously reported. While a single seizure in MS usually has a good prognosis, relapse-associated seizures and established epilepsy in MS may not be as benign as previously assumed.

Attenuating M-current suppression in vivo by a mutant Kcnq2 gene knock-in reduces seizure burden and prevents status epilepticus-induced neuronal death and epileptogenesis.

The M-current is a low-threshold voltage-gated potassium current generated by Kv7 subunits that regulates neural excitation. It is important to note that M-current suppression, induced by activation of Gq-coupled neurotransmitter receptors, can dynamically regulate the threshold of action-potential firing and firing frequency. Here we sought to directly examine whether M-current suppression is involved in seizures and epileptogenesis. Kv7.2 knock-in mice lacking the key protein kinase C (PKC) phosphorylation acceptor site for M-current suppression were generated by introducing an alanine substitution at serine residue 559 of mouse Kv7.2, mKv7.2(S559A). Basic electrophysiologic properties of the M-current between wild-type and Kv7.2(S559A) knock-in mice were analyzed in primary cultured neurons. Homozygous Kv7.2(S559A) knock-in mice were used to evaluate the protective effect of mutant Kv7.2 channel against chemoconvulsant-induced seizures. In addition, pilocarpine-induced neuronal damage and spontaneously recurrent seizures were evaluated after equivalent chemoconvulsant-induced status epilepticus was achieved by coadministration of the M-current-specific channel inhibitor, XE991. Neurons from Kv7.2(S559A) knock-in mice showed normal basal M-currents. Knock-in mice displayed reduced M-current suppression when challenged by a muscarinic agonist, oxotremorine-M. Kv7.2(S559A) mice were resistant to chemoconvulsant-induced seizures with no mortality. Administration of XE991 transiently exacerbated seizures in knock-in mice equivalent to those of wild-type mice. Valproate, which disrupts neurotransmitter-induced M-current suppression, showed no additional anticonvulsant effect in Kv7.2(S559A) mice. After experiencing status epilepticus, Kv7.2(S559A) knock-in mice did not show seizure-induced cell death or spontaneous recurring seizures. This study provides evidence that neurotransmitter-induced suppression of M-current generated by Kv7.2-containing channels exacerbates behavioral seizures. In addition, prompt recovery of M-current after status epilepticus prevents subsequent neuronal death and the development of spontaneously recurrent seizures. Therefore, prompt restoration of M-current activity may have a therapeutic benefit for epilepsy.

Acute Lidocaine Toxicity; a Case Series.

Parenteral form of lidocaine is the best-known source of lidocaine poisoning. This study aimed to evaluate the characteristics of acute lidocaine toxicity . In this retrospective cross-sectional study, demographics, clinical presentation, laboratory findings, and outcome of patients intoxicated with lidocaine (based on ICD10 codes) admitted to Loghman Hakim Hospital, during April 2007 to March 2014 were analyzed. 30 cases with the mean age of 21.83 ± 6.57 year were studied (60% male). All subjects had used either 6.5% lidocaine spray or 2% topical formulations of lidocaine. The mean consumed dose of lidocaine was 465 ± 318.17 milligrams. The most frequent clinical presentations were nausea and vomiting (50%), seizure (33.3%), and loss of consciousness (16.7%). 22 (73.3%) cases had normal sinus rhythm, 4 (13.3%) bradycardia, 2 (6.7%) ventricular tachycardia, and 2 (6.7%) had left axis deviation. 11 (36.6%) cases were intubated and admitted to intensive care unit (ICU) for 6.91 ± 7.16 days. Three patients experienced status epilepticus that led to cardiac arrest, and death (all cases with suicidal intention). Based on the results of this study, most cases of topical lidocaine toxicity were among < 40-year-old patients with a male to female ratio of 1.2, with suicidal attempt in 90%, need for intensive care in 36.6%, and mortality rate of 10%.

The phenotype of bilateral hippocampal sclerosis and its management in "real life" clinical settings.

There is little detailed phenotypic characterization of bilateral hippocampal sclerosis (HS). We therefore conducted a multicenter review of people with pharmacoresistant epilepsy and bilateral HS to better determine their clinical characteristics. Databases from 11 EPIGEN centers were searched. For identified cases, clinicians reviewed the medical notes, imaging, and electroencephalographic (EEG), video-EEG, and neuropsychometric data. Data were irretrievably anonymized, and a single database was populated to capture all phenotypic information. These data were compared with phenotyped cases of unilateral HS from the same centers. In total, 96 patients with pharmacoresistant epilepsy and bilateral HS were identified (43 female, 53 male; age range = 8-80years). Twenty-five percent had experienced febrile convulsions, and 27% of patients had experienced status epilepticus. The mean number of previously tried antiepileptic drugs was 5.32, and the average number of currently prescribed medications was 2.99; 44.8% of patients had cognitive difficulties, and 47.9% had psychiatric comorbidity; 35.4% (34/96) of patients continued with long-term medical therapy alone, another 4 being seizure-free on medication. Sixteen patients proceeded to, or were awaiting, neurostimulation, and 11 underwent surgical resection. One patient was rendered seizure-free postresection, with an improvement in seizures for 3 other cases. By comparison, of 201 patients with unilateral HS, a significantly higher number (44.3%) had febrile convulsions and only 11.4% had experienced status epilepticus. Importantly, 41.8% (84/201) of patients with unilateral HS had focal aware seizures, whereas such seizures were less frequently observed in people with bilateral HS, and were never observed exclusively (P=.002; Fisher's exact test). The current work describes the phenotypic spectrum of people with pharmacoresistant epilepsy and bilateral HS, highlights salient clinical differences from patients with unilateral HS, and provides a large platform from which to develop further studies, both epidemiological and genomic, to better understand etiopathogenesis and optimal treatment regimes in this condition.

P.018 Forced normalization after vagal nerve stimulation in a case of intractable Lennox-Gastaut syndrome

Background: Forced normalization is the development of psychiatric symptoms in a patient experiencing remission of intractable seizures. The mechanism of this phenomenon is unknown. We present a complex case of Lennox Gastaut syndrome that experiences forced normalization after vagus nerve stimulation (VNS). Methods: This case details a 31-year-old male with seizures since early childhood. The patient has intractable epilepsy and failed AEDs, VNS, and a partial callosotomy. Results: The patient was in remission from 2-12 years old, when seizures returned at a frequency of 2-5 per day. He has multiple types of seizures including drop attacks, absences, and tonic-clonic seizures. Patient experienced status epilepticus multiple times. Twelve AEDs were failed before VNS was started in 2010, which helped curb the severity of seizures and the potential for clusters. Forced normalization developed over the course of treatment with VNS. The patient behavior was characterized by aggression, paranoia, and hallucinations. VNS was turned off late in 2010 and then re-started in January of 2011. Patient proceeded to cycle between several days of seizures without psychiatric symptoms and several days of psychosis without seizures. Conclusions: Vagus nerve stimulation gave way to forced normalization, characterized here as aggressive behaviour and psychosis. Forced normalization is seen commonly after epilepsy surgery, but rarely following VNS.