Tonic-clonic Status Epilepticus Research Articles

Distinct Clinical Courses and Shortened Lifespans in Childhood-Onset DNA Polymerase Gamma Deficiency.

DNA polymerase subunit gamma (POLG) deficiency is likely the most frequent cause of nuclear-encoded mitochondrial disorders. POLG-related disorders reportedly constitute a spectrum of overlapping phenotypes from infancy to late adulthood. We retrospectively reviewed natural histories for 40 children carrying biallelic pathogenic POLG variants. The patients were identified by the French coordinating center for mitochondrial disorders (CARAMMEL), making this a large monocentric series on childhood-onset POLG deficiency. Three patterns of clinical course and survival were observed, distinguished by main category of symptoms: neurologic, hepatic, and gastrointestinal. A total of 24 patients needed urgent neurointensive care for tonic-clonic seizures, myoclonic epilepsy, and status epilepticus, occasionally precipitated by valproate administration. Other neurologic symptoms included dystonia, cerebellar ataxia, and peripheral neuropathy. We report 6 POLG-deficient patients with polyradiculoneuropathy mimicking subacute Guillain-Barré syndrome and provide postgadolinium MRI evidence of diffuse cranial nerve root and cauda equina enhancement, suggesting these disorders have an inflammatory component. Children presenting with enteral nervous system involvement had vomiting, gastroparesis, and chronic intestinal pseudo-obstruction. They had later ages of onset and lived much longer. Primarily, hepatic presentations had the earliest onset and shortest survivals. Secondary hepatic failure was frequently precipitated by valproate administration given before diagnosis to patients with focal impaired awareness seizures or absence of seizures. These POLG deficiencies were often fatal, with age at death ranging from 3 months to 10 years, with a significant difference in survival between the 3 clinical forms; 6 of the 40 children did survive. No genotype-phenotype correlations were found for the 3 clinical course types. The study demonstrates the prevalence of neurologic presentation and the extent of central, peripheral, and autonomous nervous system involvement in 60% of patients. Most of the patients with early onset and rapidly fatal hepatic failure did not live long enough to develop neurologic symptoms. The study revealed a new clinical form of POLG deficiency presenting with neurodigestive symptoms with longer lifespan. We also propose that POLG deficiency should be considered in children presenting with unexplained polyradiculoneuropathy, demyelinating neuropathy, and elevated CSF protein. Finally, valproate administration remains a notable cause of avoidable death in POLG-deficient patients.

Developing a pathway to clinical trials for CACNA1A-related epilepsies: A patient organization perspective.

CACNA1A-related disorders are rare neurodevelopmental disorders linked to variants in the CACNA1A gene. This gene encodes the α1 subunit of the P/Q-type calcium channel Cav2.1, which is globally expressed in the brain and crucial for fast synaptic neurotransmission. The broad spectrum of CACNA1A-related neurological disorders includes developmental and epileptic encephalopathies, familial hemiplegic migraine type 1, episodic ataxia type 2, spinocerebellar ataxia type 6, together with unclassified presentations with developmental delay, ataxia, intellectual disability, autism spectrum disorder, and language impairment. The severity of each disorder is also highly variable. The spectrum of CACNA1A-related seizures is broad across both loss-of-function and gain-of-function variants and includes absence seizures, focal seizures with altered consciousness, generalized tonic-clonic seizures, tonic seizures, status epilepticus, and infantile spasms. Furthermore, over half of CACNA1A-related epilepsies are refractory to current therapies. To date, almost 1700 CACNA1A variants have been reported in ClinVar, with over 400 listed as Pathogenic or Likely Pathogenic, but with limited-to-no clinical or functional data. Robust genotype-phenotype studies and impacts of variants on protein structure and function have also yet to be established. As a result, there are few definitive treatment options for CACNA1A-related epilepsies. The CACNA1A Foundation has set out to change the landscape of available and effective treatments and improve the quality of life for those living with CACNA1A-related disorders, including epilepsy. Established in March 2020, the Foundation has built a robust preclinical toolbox that includes patient-derived induced pluripotent stem cells and novel disease models, launched clinical trial readiness initiatives, and organized a global CACNA1A Research Network. This Research Network is currently composed of over 60 scientists and clinicians committed to collaborating to accelerate the path to CACNA1A-specific treatments and one day, a cure.

Safety and efficacy of rapid withdrawal of anti-seizure medication during long-term video-EEG monitoring.

Anti-seizure medications (ASMs) are often withdrawn during long-term video-EEG monitoring (LTM) to allow pre-surgical evaluation. Herein, we evaluated the safety and efficacy of ultra-rapid withdrawal (URW) and rapid withdrawal (RW) of ASMs in an epilepsy monitoring unit (EMU). This retrospective study examined all consecutive patients admitted to our EMU between May 2021 and October 2022. Patients were classified into the URW and RW groups according to the way ASMs were withdrawn. We compared the efficacy and safety of the procedures used in the groups in terms of duration of LTM, latency to the first seizure, and incidence of focal to bilateral tonic-clonic seizures (FBTCS), seizure clusters (SC), and status epilepticus (SE). Overall, 110 patients (38 women) were included. The mean age of patients at the time of LTM was 29 years. All medications were stopped on admission for monitoring in the URW group (n = 75), while in the RW group (n = 35) ASMs were withdrawn within 1 day. In both groups, the duration of LTM was approximately 3 days: URW group (2.9 ± 0.5 days) and RW group (3.1 ± 0.8 days). The latency to the first seizure was significantly different between the two groups; however, there were no differences between the two groups in terms of the distribution of FBTCS, SC, or SE, number of seizures, and the requirement for intravenous rescue medication was low. The rapid withdrawal of ASMs to provoke seizures during monitoring for pre-surgical evaluation following the URW protocol was as effective and safe as with RW. Ultra-rapid ASM withdrawal has the benefits of reducing LTM duration and shortening the time to first seizure compared to rapid medication tapering.

Telemedicine in follow-up of pediatric status epilepticus: A resounding success story or just a farce?

ObjectivesStatus epilepticus is a life-threatening medical emergency that presents with a continuous seizure lasting for more than five minutes. Telemedicine can potentially play a role in follow-up care of such patients after discharge from the hospital at reduced patient costs. Whether it is efficacious and leads to patient satisfaction is controversial. Therefore, the primary objective of the present study was to compare video consultation with face-to-face consultation in children aged 1–12 years with tonic-clonic status epilepticus after seven days of discharge for any one of the following critical events-any breakthrough seizure, drug compliance, features of raised intracranial pressure and any adverse events. The secondary objective of the study was to compare cost and patient satisfaction of the two modalities. MethodsChildren aged 1–12 years attending Paediatric Emergency of a tertiary care hospital of Northern India with a diagnosis of status epilepticus were enrolled after written informed consent from the parents before completion of their hospital stay. The parents were contacted by the Paediatric Resident on their mobile phone through video calling one day before the scheduled hospital visit. Subsequently, the child was seen directly in hospital on the next day by faculty member/Resident. The information of both interactions was noted on a structured questionnaire. The diagnostic accuracy of telemedicine video consultation for identifying the Critical Clinical Events was estimated using Face-to-Face consultation as the gold standard. ResultsOut of the 108 enrolled patients, two patients were lost to follow up. The diagnostic performance of video consultation in identification of any of the Critical Events compared to Face-to-Face Consultation was as follows: Sensitivity: 42%, Specificity: 100%, PPV: 100%, NPV: 89% with overall Diagnostic Accuracy: 90%. The main discrepancy was seen in identification of the drug compliance. The reason for decreased sensitivity was the presence of different caregivers for video and face to face consultation. The average cost of coming to hospital was 362.73 INR whereas no additional cost was required for video consultation. Also, the average time of visiting the hospital was 4 hour and 26 min, whereas the average time of video consultation was 10 min. 100.0% of the participants agreed that the method of Video Consultation was cost effective and time Saving. Majority (92.5%) of the participants were Satisfied with Video Consultation and 82.1% of the participants were willing for the method of video consultation for further follow up of their children. SignificanceDiagnostic accuracy of video consultation compared to face to face consultation in children aged 1–12 years with tonic clonic status epilepticus after seven days of discharge is 90%. The cost effectiveness time and patient satisfaction seen with telemedicine are encouraging. Ensuring that the primary caregiver is present for both video and face to face consultation by a prior consent can improve the sensitivity and diagnostic accuracy of video consultation. Categories: Medical Education, Neurology, Pediatrics

Proper Therapy Selection Improves Epilepsy Outcomes in Patients With Multilobar Sturge-Weber Syndrome

BackgroundHemispherectomy is an optimal treatment for patients with Sturge-Weber syndrome (SWS) affecting the whole hemisphere; however, a consensus has not been reached regarding therapeutic choices for those with involvement of two to three lobes. In this study, we compared seizure and cognitive outcomes between medical and surgical treatment groups in patients with multilobar involvement. MethodsWe evaluated 50 patients with multilobar involvement. Surgical indications included (1) antiepileptic drug (AED)-resistant seizures; (2) developmental delay; and (3) cortical atrophy. Twenty-nine patients were classified in the medical treatment group (MTG), and 21 patients were in the surgical treatment group (STG). Seizure type and frequency, SWS electroencephalography score (SWS-EEGS), and pretherapeutic and posttherapeutic SWS neurological scores (SWS-NS) were compared between groups. Median ages at the initial evaluation of the MTG and STG were 4 and 2 years, and at the final evaluation were 13 and 17 years, respectively. ResultsThe STG had a higher incidence (76.2%) of focal to bilateral tonic-clonic seizures and status epilepticus, although no difference in SWS-EEGS. Seizure and cognitive subcategories of SWS-NS at initial evaluation were worse in the STG (P = 0.025 and P = 0.007). The seizure subcategory in MTG and STG improved after therapy (P = 0.002 and P = 0.001). Cognition was maintained in MTG and improved in STG (P = 0.002). The seizure-free rates in MTG and STG were 58.6% and 85.7%, respectively. ConclusionsAppropriate therapeutic choices improved seizure outcomes. Although patients who required surgery had more severe epilepsy and cognitive impairment, surgery improved both.

Brivaracetam or levetiracetam in status epilepticus?: Lessons from the photosensitivity model

First, a short history is given of the use of the EEG as a biomarker of efficacy in anti-seizure medication (ASM) development. The generalized epileptiform EEG response to Intermittent Photic Stimulation (IPS), the photoparoxysmal EEG response or PPR, in particular, is a reliable reproducible measure since the 1950s.Over time, a “Photosensitivity Model”, testing within the same patients the impact of potential new oral ASMs, along with dose-ranging data, on PPRs, has been developed successfully. The classical Photosensitivity Model consists of IPS and blood sampling for ASM measurement performed hourly between 8 AM and 5 PM over three consecutive days. This single-blind, placebo-controlled, pharmacokinetic-pharmacodynamic (PK/PD) Model is now commonly utilized as a Proof-of-Concept Phase 2a trial.For Generalized Tonic-Clonic Status Epilepticus (GTCSE), it is especially relevant to know the time for CNS entry and effect minutes after i.v. ASM treatment, since “time is brain”. We, therefore, adapted successfully the Model to a time-efficient Model with the determination of photosensitivity ranges in minutes after equivalent doses of iv brivaracetam (BRV) and levetiracetam (LEV). This modified design allows one to monitor the time to CNS effect (i.e., PPR elimination) of a quickly-acting FDA-approved ASM given i.v., a crucial element in status epilepticus treatment. This paper was presented at the 8th London-Innsbruck Colloqium on Status Epilepticus and Acute Seizures held in September 2022.

Mowat-Wilson syndrome: literature review and case series

Mowat-Wilson syndrome (MWS) is a rare genetic disorder characterized by a combination of the following signs: 1) facial dysmorphism (wide nose, broad medial eyebrows, pronounced chin, and open mouth); 2) mental retardation; 3) abnormalities of internal organs (congenital heart defects, Hirschsprung's disease, hypospadias/cryptorchidism). The disease is associated with a heterozygous pathogenic mutation in the ZEB2 gene. More than 80 % of MWS patients are diagnosed with epilepsy, the onset of which is usually observed in infancy. Patents have focal motor seizures, atypical absence seizures, generalized convulsive seizures. Epileptic seizures are often triggered by fever; some children are resistant to therapy. MWS patients have a specific phenotype (blue eyes, fair hair, wide-based gait, frequent laughter, limited or absent expressive language) that requires differential diagnosis with Angelman syndrome (caused by a mutation in the UBE3A gene). MWS was described in 1998, but there have been no case reports in the Russian literature yet. We report 4 cases of MWS in children aged 2 to 13 years treated in the Svt. Luka's Institute of Neurology and Epilepsy. In all of these patients, we identified a heterozygous de novo deletion in the ZEB2 gene. Epilepsy was observed in all patients. Mean age at onset was 13 months. All children had focal motor seizures and atypical absence seizures. None of them had tonic-clonic seizures or status epilepticus. The analysis of electroencephalograms showed that patients with a lower index of epileptiform activity tend to have better development and vice versa: children with a high index of epileptiform activity during sleep had more severe developmental delay.

Epilepsy P-EP001. Status epilepticus and intractable seizure in herpes simplex encephalitis patient: Case series

Introduction . Herpes Simplex Encephalitis (HSE) is a rare disorder caused by infection of the CNS by HSV that could have a potentially fatal outcome particularly with delayed treatment. The early presentation is relatively nonspecific consisting of fever, headaches, seizures and unconsciousness. Seizures have been associated with death in HSE. This case report aims to publish case series of status epilepticus and intractable seizure in HSE patient at Sardjito Hospital Yogyakarta. Results . CASE 1: A 26year-old male was admitted to the ER Sardjito Hospital in 2018 presented with GTCS and behavior changes. GCS of this patient was E4V4M6 and there were no signs of meningeal irritation, no weakness found in extremity but increase of physiological reflex indicating UMN sign. After being transferred to the ward, patient developed to status epilepticus, then patient was referred to ICU; midazolam & propofol were administered to reduce seizures. Laboratory, CSF analysis and MRI were consistent with HSE. After aggressive treatments with anti-edema, antiviral and multiple antiepileptic drug (AED), there was a reduction in seizure but sometimes patient still developed GTCS. He was discharged after 25 days treatments with full consciousness, reduction of seizure frequency but the focal aware seizures were still remained. CASE 2: A 29-year-old female was admitted to the ER Sardjito in 2019 presented with focal to bilateral tonic-clonic seizure and status epilepticus. The complaints begin with acute progressive headache, fever, visual hallucinations and weakness of the left limbs. GCS of this patient was E2VTM2 (on midazolam) and there were no signs of meningeal irritation. Laboratory and CSF analysis were consistent with HSE. CT scan showed cerebral edema. After treatments with anti-edema, antiviral and AED, the patient regained full consciousness and there was a reduction of seizure frequency but focal aware seizures were still remained. Conclusion . Seizures in HSE are reported to be intractable seizures and more likely to develop status epilepticus. The seizures are typically refractory to AED, often requiring combination and aggressive treatments.

Pharmacological management of seizures in patients with COVID-19: a systematic review

Background: Some patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported to exhibit neurological symptoms such as seizures and impaired consciousness. Our study reviews reported cases to assess the pharmacological approach to managing seizures in SARS-CoV-2 patients and associated outcomes. Methods: A systematic review of case reports on the incidence of seizures following coronavirus disease 2019 (COVID-19) among patients that reported use of antiepileptic drugs (AEDs) in management was performed by using the PRISMA (preferred reporting items for systematic reviews and meta-analysis) guidelines. Databases used included EMBASE, PubMed, SCOPUS, and Google Scholar. Data was presented as qualitative and descriptive data. Results: In total, 67 articles were selected for full-text assessment, of which 19 were included in the final review. Patients had a median age of 54 years, most of whom were male. Remdisivir, dexamethasone, Laminavir, hydroxychloroquine, azithromycin, and Lopinavir-ritonavir were common agents used in the management of COVID-19. Most patients presented with either generalized tonic-clonic seizures or status epilepticus. Most patients received levetiracetam as drug choice or as part of their regimen. Other AEDs commonly prescribed included midazolam and sodium valproate. Some patients received no antiepileptic drug therapy. Most of the patients who died had more than one comorbidity. Also, most of the patients who died received COVID-19 treatment drugs. None of the patients who received midazolam as drug choice or as part of their regimen developed recurrent seizures in contrast to patients who received levetiracetam and sodium valproate as drug choice or as part of their regimen. Interestingly, none of the patients who received no AEDs suffered recurrent seizures or died. Conclusions: Standard guidelines for managing seizures in COVID-19 patients may be required. A limitation of this review is that it involved the use of case reports with no controls and a small number of patients.

Absence of RNA-binding protein FXR2P prevents prolonged phase of kainate-induced seizures.

Status epilepticus (SE) is a condition in which seizures are not self‐terminating and thereby pose a serious threat to the patient's life. The molecular mechanisms underlying SE are likely heterogeneous and not well understood. Here, we reveal a role for the RNA‐binding protein Fragile X‐Related Protein 2 (FXR2P) in SE. Fxr2 KO mice display reduced sensitivity specifically to kainic acid‐induced SE. Immunoprecipitation of FXR2P coupled to next‐generation sequencing of associated mRNAs shows that FXR2P targets are enriched in genes that encode glutamatergic post‐synaptic components. Of note, the FXR2P target transcriptome has a significant overlap with epilepsy and SE risk genes. In addition, Fxr2 KO mice fail to show sustained ERK1/2 phosphorylation induced by KA and present reduced burst activity in the hippocampus. Taken together, our findings show that the absence of FXR2P decreases the expression of glutamatergic proteins, and this decrease might prevent self‐sustained seizures.

Acute withdrawal of new-generation antiepileptic drugs in epilepsy monitoring units: Safety and efficacy

IntroductionAcute withdrawal of antiepileptic drugs (AEDs) is a safe and effective approach to provoking seizures in order to complete video-electroencephalogram (V-EEG) studies in a timely manner. Previous studies have focused only on withdrawal from conventional AEDs, and the effects of withdrawal from new-generation AEDs have not been extensively studied. Materials and MethodsThis study examined adult patients with drug-resistant epilepsy admitted to an epilepsy monitoring unit between 2015 and 2018. Patients were classified according to whether they received conventional AEDs (Con; n = 13) or new-generation AEDs (N-Gen; n = 26). We then compared the effects of withdrawing these two types of AEDs over a period of one week in terms of efficacy (time to complete V-EEG monitoring) and safety, including the incidence of cluster seizures (CS), focal to bilateral tonic-clonic seizures (FBTCS) and status epilepticus (SE). ResultsIn both groups, approximately one week was required to complete V-EEG analysis: N-Gen group (5.6 days) and Con group (6.3 days). No differences were observed between the two groups in terms of the median number of seizures, the onset of the 1st seizure, the distribution of CS, FBTCS, or SE. Following acute withdrawal of medication, a high percentage of patients with a history of CS or FBTCS, respectively, presented CS or FBTCS. ConclusionsWe did not observe significant differences between patients taking new-generation AEDs and those taking conventional AEDs following withdrawal during V-EEG recording. In the current study, we employed a standard protocol for the rapid withdrawal of AEDs (daily dose reduction of 50%), which was sufficient for 80% of patients to complete V-EEG monitoring within one week.

Etiological Spectrum of Status Epilepticus in Ouagadougou, Burkina Faso: A Prospective Cross-sectional Multicenter Hospital Study

<i>Introduction</i>: In sub-Saharan Africa, cerebrovascular aetiologies of status epilepticus (SE) are on the rise alongside infectious brain lesions. The aim of our study was to describe the etiologic spectrum of SE in Ouagadougou, Burkina Faso, in a high risk SE setting. <i>Patients and methods</i>: This is a prospective, cross-sectional, descriptive, multicenter and hospital study of patients hospitalized consecutively in the university hospitals of the city of Ouagadougou, in Burkina Faso, from 01/01/2015 to 12/31/2019, for SE. The sociodemographic, clinical, paraclinical (biological, critical and / or intercritical EEG, neuroradiological) characteristics and the aetiological data of the patients were analyzed using the Epi-info 7.2.1.0 software: calculations of numbers, frequencies, averages. The significance rate was set at 0.05. <i>Results</i>: 91 patients hospitalized for SE were collected, with a male predominance (73.62%). The mean age was 36.6 years +/- 24.5 years (2 days and 86 years); 25 patients (27.5%) already had known epilepsy. Generalized tonic-clonic SE from the start and focal SE with convulsive bilateralization were the most common seizure types with 46 cases (50.5%) and 27 cases (29.7%), respectively. The average duration of an EME episode was 18 hours +/- 31 (5 minutes - 6 days). On admission, a focused motor deficit with 36 cases (46.7%) and fever in 28 patients (30.8%) were the main clinical signs; hyperleukocytosis with 23 cases (25.3) and anemia with 22 cases (24.2%), were the main laboratory abnormalities. On cerebral CT scan, sequelae with 33 cases (51.6%), acute stroke with 14 cases (21.9%) and acute meningoencephalitis with 8 cases (12.5%), were the most frequent. SEs symptomatic of acute brain disease, with 61 cases (67%), were dominated by infectious etiologies with 30 cases (33%) and acute strokes with 16 cases (17.6%). Among the non-acute or sequelae SEs of etiology, the sequelae of traumatic brain injury with 10 cases (11%) and the sequelae of stroke with 8 cases (8.8%) were the most represented. <i>Conclusion</i>: The aetiologies of SE are dominated in the Ouagadougou CHUs by CNS infections, acute or sequelae strokes and cranio-encephalic trauma. The fight against infectious diseases and the prevention of vascular risk factors will help reduce the frequency and severity of EMEs.

Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee.

Purpose:Established tonic–clonic status epilepticus (SE) does not stop in one-third of patients when treated with an intravenous (IV) benzodiazepine bolus followed by a loading dose of a second antiseizure medication (ASM). These patients have refractory status epilepticus (RSE) and a high risk of morbidity and death. For patients with convulsive refractory status epilepticus (CRSE), we sought to determine the strength of evidence for 8 parenteral ASMs used as third-line treatment in stopping clinical CRSE.Methods:A structured literature search (MEDLINE, Embase, CENTRAL, CINAHL) was performed to identify original studies on the treatment of CRSE in children and adults using IV brivaracetam, ketamine, lacosamide, levetiracetam (LEV), midazolam (MDZ), pentobarbital (PTB; and thiopental), propofol (PRO), and valproic acid (VPA). Adrenocorticotropic hormone (ACTH), corticosteroids, intravenous immunoglobulin (IVIg), magnesium sulfate, and pyridoxine were added to determine the effectiveness in treating hard-to-control seizures in special circumstances. Studies were evaluated by predefined criteria and were classified by strength of evidence in stopping clinical CRSE (either as the last ASM added or compared to another ASM) according to the 2017 American Academy of Neurology process.Results:No studies exist on the use of ACTH, corticosteroids, or IVIg for the treatment of CRSE. Small series and case reports exist on the use of these agents in the treatment of RSE of suspected immune etiology, severe epileptic encephalopathies, and rare epilepsy syndromes. For adults with CRSE, insufficient evidence exists on the effectiveness of brivaracetam (level U; 4 class IV studies). For children and adults with CRSE, insufficient evidence exists on the effectiveness of ketamine (level U; 25 class IV studies). For children and adults with CRSE, it is possible that lacosamide is effective at stopping RSE (level C; 2 class III, 14 class IV studies). For children with CRSE, insufficient evidence exists that LEV and VPA are equally effective (level U, 1 class III study). For adults with CRSE, insufficient evidence exists to support the effectiveness of LEV (level U; 2 class IV studies). Magnesium sulfate may be effective in the treatment of eclampsia, but there are only case reports of its use for CRSE. For children with CRSE, insufficient evidence exists to support either that MDZ and diazepam infusions are equally effective (level U; 1 class III study) or that MDZ infusion and PTB are equally effective (level U; 1 class III study). For adults with CRSE, insufficient evidence exists to support either that MDZ infusion and PRO are equally effective (level U; 1 class III study) or that low-dose and high-dose MDZ infusions are equally effective (level U; 1 class III study). For children and adults with CRSE, insufficient evidence exists to support that MDZ is effective as the last drug added (level U; 29 class IV studies). For adults with CRSE, insufficient evidence exists to support that PTB and PRO are equally effective (level U; 1 class III study). For adults and children with CRSE, insufficient evidence exists to support that PTB is effective as the last ASM added (level U; 42 class IV studies). For CRSE, insufficient evidence exists to support that PRO is effective as the last ASM used (level U; 26 class IV studies). No pediatric-only studies exist on the use of PRO for CRSE, and many guidelines do not recommend its use in children aged <16 years. Pyridoxine-dependent and pyridoxine-responsive epilepsies should be considered in children presenting between birth and age 3 years with refractory seizures and no imaging lesion or other acquired cause of seizures. For children with CRSE, insufficient evidence exists that VPA and diazepam infusion are equally effective (level U, 1 class III study). No class I to III studies have been reported in adults treated with VPA for CRSE. In comparison, for children and adults with established convulsive SE (ie, not RSE), after an initial benzodiazepine, it is likely that loading doses of LEV 60 mg/kg, VPA 40 mg/kg, and fosphenytoin 20 mg PE/kg are equally effective at stopping SE (level B, 1 class I study).Conclusions:Mostly insufficient evidence exists on the efficacy of stopping clinical CRSE using brivaracetam, lacosamide, LEV, valproate, ketamine, MDZ, PTB, and PRO either as the last ASM or compared to others of these drugs. Adrenocorticotropic hormone, IVIg, corticosteroids, magnesium sulfate, and pyridoxine have been used in special situations but have not been studied for CRSE. For the treatment of established convulsive SE (ie, not RSE), LEV, VPA, and fosphenytoin are likely equally effective, but whether this is also true for CRSE is unknown. Triple-masked, randomized controlled trials are needed to compare the effectiveness of parenteral anesthetizing and nonanesthetizing ASMs in the treatment of CRSE.

Essential oil-related status epilepticus: A small case series study.

ObjectiveEssential oils are plant‐derived oils and are widely used as an over‐the‐counter remedy for common ailments. Many essential oils are found to have proconvulsant effects. Here we report a small case series of 3 adults with eseential oil‐related status epilepticus.MethodsThis was an observational study conducted in a tertiary care hospital in south India from January 2018 to December 2019. We collected the demographic, clinical, and imaging features of all cases of status epilepticus resulting from exposure to essential oils. Cases of status epilepticus secondary to all other causes were excluded.ResultsThere were 3 young adults with essential oil‐related status epilepticus. Two had de novo generalized tonic–clonic status epilepticus, and 1 with posttraumatic occipital lobe epilepsy had focal‐impaired awareness status epilepticus. The first 2 cases presented with histories of ingestion of eucalyptus oil. The third case had focal‐impaired awareness status epilepticus after topical application of various balms containing eucalyptus and camphor.ConclusionsProconvulsant essential oils of eucalyptus and camphor can cause both generalized and focal status epilepticus. Physicians dealing with patients of status epilepticus should enquire about the exposure to proconvulsant essential oils.

Fatal metaldehyde poisoning in a dog confirmed by gas chromatography

BackgroundMetaldehyde is a toxic pesticide used mainly as a molluscicide, responsible for intoxication and deaths in both humans and animals. Accidental exposure to metaldehyde in dogs is considered rare, but severe. Data concerning clinical and veterinary forensic toxicology are largely incomplete, especially regarding case reports in dogs. The present work reports a complete and detailed description of a case from the history, clinical evolution, pathological exams and toxicological diagnosis in an accidental case of metaldehyde poisoning in dog.Case presentationAn eleven-month-old, 3.0 kg, male German Spitz was presented for emergency care with acute vomiting and seizures 3 hours after suspected accidental ingestion of commercial molluscicide containing 3% metaldehyde (Lesmax®). The animal was in lateral recumbency and showed stuporous mentation, salivation, tonic-clonic status epilepticus, systemic tremors, bilateral miosis, absent palpebral, corneal, oculovestibular and gag reflexes, severely depressed spinal reflexes, dyspnea and tachycardia. Despite treatment, the patient progressed to comatose mentation and died. Necropsy examination revealed discrete lesions in the liver and central nervous system, while stomach examination revealed content of feed, activated charcoal and blue-green granules, compatible to the commercial formula of metaldehyde. Histology examination revealed extensive hemorrhage and severe centrolobular necrosis of the liver and tumefaction of Kupfer cells. Brain samples showed discrete hemorrhage and hyperemia. In order to confirm the diagnosis, samples from feces, stomach content, spleen, liver, heart, kidneys and brain were submitted gas chromatography analysis. Results confirmed the presence of metaldehyde in all samples. We describe clinicopathological abnormalities of a fatal case of metaldehyde poisoning in a dog, as well as postmortem diagnosis using gas chromatography.ConclusionMetaldehyde poisoning is rarely reported, since the diagnosis is often difficult and the notifications scarce. To our knowledge, this is the first report describing clinical signs, pathological findings and chromatographic diagnosis. This report aims to contribute to the understanding of the pathogenesis of metaldehyde intoxication, to further explore veterinary forensic toxicology diagnosis.

Critical Care Management of Status Epilepticus at a Tertiary Care University Hospital.

Status epilepticus (SE) is a neurological emergency associated with significant morbidity and mortality. The objective of this study was to review the critical care management of patients with SE focusing on antiepileptic drugs (AEDs) as well as to determine the optimal dosing strategies of phenytoin (PHT) and predictors of its effectiveness. A retrospective chart review of adult patients with SE admitted to the University of Alberta Hospital, Canada, was conducted. Fifty-six admissions were included. Benzodiazepines (BDZs) were initially given in 89% of our patients. Following BDZs, PHT and levetiracetam were the most commonly initiated AEDs as first- and second-line agents and were deemed effective in 30/44 and 5/11 patients, respectively. Patients who received a PHT loading dose (LD) of 1000 mg were less likely to reach target levels compared with a weight-based LD ≥15 mg/kg (29% vs. 60%). Likewise, patients who received a maintenance dose (MD) of 300 mg/day were less likely to reach target compared with 400 mg/day or >5 mg/kg per day; however, this did not reach statistical significance. Three variables were found to be associated with PHT effectiveness: tonic-clonic SE (OR 5.01, 95% CI 1.02-24.7, p = 0.048), history of seizures and BMI <30 kg/m2 (OR 0.16, 95% CI 0.03-1.07, p = 0.059). Further studies of the predictors of PHT effectiveness, specifically obesity, are necessary to help individualize care. Finally, we suggest that PHT should be loaded according to the guidelines as 20 mg/kg followed by an MD of at least 400 mg/day or >5 mg/kg per day.

Status epilepticus in patients with genetic (idiopathic) generalized epilepsy.

Aim of the studyGenetic (idiopathic) generalized epilepsies (GGEs) account for nearly one-third of all epilepsies. The frequency of status epilepticus (SE) in patients with GGEs has been poorly studied. Therefore, this study aimed to evaluate the frequency of different forms of SE in a cohort of patients with GGEs.Materials and methodsAmong 153 patients with GGEs treated at the university epilepsy clinic in the period between 1998 and 2018, those with SE were retrospectively identified.ResultsAbsence SE was diagnosed in 8 patients (13 episodes), while myoclonic SE was found in 2 patients (2 episodes). No cases of tonic–clonic SE were detected in the study cohort. Most SE episodes were found to be provoked by ill-advised antiepileptic drugs or changes in drug regimen. In all the subjects, SE was stopped by intravenous administration of diazepam and/or valproate. Long-term outcome of epilepsy was good, with most patients (70%) being seizure-free.ConclusionStatus epilepticus is not a rare phenomenon in patients with genetic generalized epilepsies, with absence SE being the most common type. Most cases of SE are provoked by ill-advised AEDs or changes in drug regimen. Status epilepticus in GGEs can be easily treated with benozdiazepines and/or valproate. Status epilepticus in GGEs can be easily treated with benozdiazepines and/or valproate.

Treatment delay in status epilepticus \u2013 more effective prehospital symptom recognition warranted

BackgroundThe outcome of status epilepticus (SE) can be improved by facilitating early recognition and treatment with antiepileptic drugs. The purpose of this study was to analyze the treatment delay of SE in a prospectively recruited patient cohort. Improvements to the treatment process are suggested.MethodsConsecutive adult patients with SE were recruited in the emergency department of Kuopio University Hospital (KUH) between March 23 and December 31, 2015. SE was defined as a prolonged (> 5 min) epileptic seizure or recurrent tonic-clonic seizures (≥ 3 seizures within any 24 h). Diagnostic and treatment delays and the features of SE were subject to statistical analysis.ResultsWe recorded 151 cases of SE during the study period. First-line treatment was initiated outside of hospital in 79 cases (52.3%), with a significantly shorter median delay compared to intrahospital initiation (28 min vs. 2 h 5 min, p < 0.001). Forty-six episodes of SE (30.5%) were not recognized during the prehospital phase. The median delay in recognition of tonic-clonic SE (23 min) was significantly shorter than in focal aware (2 h 0 min, p = 0.045) or focal impaired awareness SE (2 h 25 min, p < 0.001). Second-line treatment was used in 91 cases (60.3%), with a median delay of 2 h 42 min. Anesthesia was used in seven cases (4.6%) with refractory SE, with a median delay of 6 h 40 min.ConclusionsSE is often not recognized during the prehospital phase of treatment, which delays the initiation of first-line treatment. Intrahospital delay could be reduced by streamlining patient transition between the three lines of treatment.

Status Epilepticus in Our Patients, 15-Years Follow-Up Study

Introduction: Status epilepticus (SE) is the second most frequent neurological emergency. The purpose of this study was to analyse clinical presentation, causes and outcome of SE. Aim of the Study: The aim was to establish clinical characteristics, etiology and the outcome of status epilepticus as well as sex and age distribution in patients hospitalized at the Clinic of Neurology UCC RS in a 15-year follow-up. Patients and Methods: In this prospective 15-year study, all patients with SE admitted to the University Clinical Center of Republic of Srpska, Clinic of Neurology, were treated in the period of 15 years (2003-2017). Demographic and clinical data were collected. Results: In the aforesaid period, 124 patients with SE were treated, and there were 71 man (57%) with mean age of 59 years and 54 woman (43%), with mean age of 52.5 years. Primarily generalized tonic-clonic SE was identified in 70 (56%) and 44 (35.2%) patients, retrospectively. Simple partial SE occurred in 10 (8%) patients. 62% of the patients had previously had epilepsy while 38% had not. The main underlying causes were noncompliance to treatment in the first group (n=56; 72%) and cerebrovascular disease (n=36; 75%) in the second group. Overall mortality rate was 11.2% , which correlated with acute symptomatic etiology and patients of older age (mean: 73 years). Conclusion: Epileptic patients are at greater risk to develop SE. However, in patients with no prior history of epilepsy and acute neurological problems SE may also occur. Cerebrovascular disease was the most common cause of SE in those with the initial seizure. Noncompliance to treatment was the major cause in patients with preexisting epilepsy.

S23. Mortality prediction with the status epilepticus severity score

Status epilepticus (SE) as a cause of impaired level of consciousness in intensive care unit (ICU) is reported in the international literature between 5% and 49%, probably underdiagnosed. The many different forms and stages of SE (Refractory SE, RSE and Super-Refractory SE, SRSE) are associated with neuronal injury and require optimal treatment. The Status Epilepticus Severity Score (STESS) was recently developed to predict outcome of SE. AIM: To determine the association between STESS scale and mortality in patients with epileptic status assisted in the ICU of a public hospital. Analytical, observational and retrospective study of cases of nontraumatic coma with clinical or electroencephalography criteria of SE (classified according to the International League Against Epilepsy, ILAE) admitted to the ICU in a tertiary care hospital in Buenos Aires, Argentina, over a three year period (2014–2017). The STESS scale was used. EEG was recorded using 21 electrodes placed according to the International 10–20 System, at least 60 min of artifact-free recording. We excluded cases with extra-axial brain compression lesions. The cohort consisted of 15 subjects who presented some type of SE, mean age was 49 years (± 18 years), 46% were women, time from ICU admission to first EEG: 2.5 days (±1.7 days). A total of 53% of patients had tonic-clonic SE, SRSE (40%) and RSE in the rest of the population. In-hospital mortality rate was 26%. The 86% presented acute brain injury (included stroke, hypoxic-ischemic encephalopathy, metabolic causes, autoimmune encephalitis and infectious encephalitis) and 13% was progressive causes (two patients with brain tumor). A total number of 13 cases (86%), presented with new onset SE without a history of epilepsy and 13% patients had active epilepsy on treatment. STESS scores were significantly higher in non-survivors compared to survivors (P-value = 0.0035). No statistically significant association was found between STESS scores and injury. Patients with STESS scores ⩽3 were found to survive. Follow-up with EEG was useful in 73% patients with SE who recover consciousness once the seizure has been aborted. Despite of the small sample size used in this study, the STESS scale at the admission could predict the evolution of SE. The STESS scores were found to be good predictor of mortality in UCI patients with SE. SE is a very heterogeneous condition in terms of clinical presentation and causes, the application of this scale can help to design better therapeutic regimens for the SE.