We describe an unusual case of hypoxic ischemic encephalopathy in a preterm female of 36 weeks who presented with status epilepticus and atypical abdominal myoclonus. The seizures were confirmed electrographically using video electroencephalography (EEG), while the abdominal myoclonus was demonstrated to be nonepileptic, as it had no EEG correlate. Other possible causes of neonatal seizures were excluded. The infant then responded to a gamut of antiseizure medications but the myoclonus persisted. To the best of our knowledge, this is the first report of atypical myoclonus in a preterm baby caused by hypoxic ischemic encephalopathy.

Objective: To explore the clinical and imaging features of acute encephalopathy with biphasic seizures and late reduced diffusion(AESD) in children. Methods: For the case series study, 21 children with AESD from Peking University First Hospital, Provincial Children's Hospital Affiliated to Anhui Medical University, Children's Hospital of Fudan University, and Shanxi Children's Hospital who were diagnosed and treated from October 2021 to July 2023 were selected. Clinical data were collected to summarize their clinical information, imaging, and laboratory tests, as well as treatment and prognostic characteristics. Descriptive statistical analysis was applicated. Results: Of the 21 cases with AESD, 11 were males and 10 were females, with the age of onset of 2 years and 6 months (1 year and 7 months, 3 years and 6 months). Of the 21 cases, 18 were typical cases with biphasic seizures. All typical cases had early seizures within 24 hours before or after fever onset. Among them, 16 cases had generalized seizures, 2 cases had focal seizures, and 7 cases reached the status epilepticus. Of the 21 cases, 3 atypical cases had late seizures in biphasic only. The late seizures in the 21 cases occurred on days 3 to 9. The types of late seizures included focal seizures in 12 cases, generalized seizures in 6 cases, and both focal and generalized seizures in 3 cases. Diffusion-weighted imaging (DWI) test on days 3 to 11 showed reduced diffusion of subcortical white matter which was named "bright tree sign" in all cases. The diffuse cerebral atrophy predominantly presented in the front-parietal-temporal lobes was found in 19 cases between day 12 and 3 months after the onset of the disease. Among 21 cases, 20 had been misdiagnosed as autoimmune encephalitis, central nervous system infection, febrile convulsions, posterior reversible encephalopathy syndrome, acute disseminated encephalomyelitis, and hemiconvulsion-hemiplegia-epilepsy syndrome. All the cases received high-dose gammaglobulin and methylprednisolone pulse therapy with poor therapeutic effect. By July 2023, 18 cases were under follow-up. Among them, 17 cases were left with varying degrees of neurologic sequelae, including 11 cases with post-encephalopathic epilepsy; 1 recovered completely. Conclusions: AESD is characterized by biphasic seizures clinically and "bright tree sign" on DWI images. Symptomatic and supportive treatments are recommended. The immunotherapy is ineffective. The prognosis of AESD is poor, with a high incidence of neurological sequelae and a low mortality.
Male ; Female ; Child ; Humans ; Infant ; Child, Preschool ; Posterior Leukoencephalopathy Syndrome/complications* ; Seizures/etiology* ; Brain Diseases/diagnostic imaging* ; Status Epilepticus ; Seizures, Febrile/diagnostic imaging*

Background: Status epilepticus (SE) is a neurological emergency requiring prompt evaluation and management to prevent disease refractoriness associated with significant mortality and morbidity. Thus, estimating costs attributable to the treatment of SE is important because of the severity of this disease. In the Philippines, healthcare provisions are mostly out-of-pocket expenses; hence the cost of treatment is a critical determinant for disease management. Unfortunately, the availability of data regarding the cost of illness of SE in developing countries is limited. Objectives: To determine the frequently used anticonvulsant drug regimen and direct inpatient costs of acute treatment for status epilepticus within five years in a private tertiary hospital in the Philippines. Methods: Records from patients diagnosed with SE who were admitted under or referred to the Adult Neurology Service in a private tertiary hospital from January 2015 to December 2019 were retrospectively evaluated. The SE type was classified as non-refractory (NRSE), refractory (RSE), and super refractory (SRSE). Demographic data, clinical features, SE type, etiology, antiepileptic drugs (AEDs) and anesthetic drugs used, total cost of AEDs and anesthetic drugs, total cost of 5-day hospitalization, and total cost of entire length of stay were recorded. Results: We retrieved the records of 61 patients admitted for SE. Of these patients, 23 were classified as nonrefractory, 20 as refractory, and 18 as super refractory. Diazepam was given to all SE patients as first-line treatment. Valproic acid and levetiracetam were used as second-line treatments. The most frequently given anesthetic drug was midazolam. The mean hospitalization cost per patient was ₱52,0982.3 for SE, ₱659,638.7 for RSE, and ₱134,1451 for SRSE. The mean cost of 5-day hospitalization was ₱193,572.3 for NRSE, ₱358,808.5 for RSE, and ₱652,781 for SRSE. The mean cost of medications was ₱18,546 for NRSE, ₱30,780 for RSE, and ₱128,263 for SRSE. Conclusion The direct cost of SE varied depending on subtype and response to treatment. Costs increased with disease refractoriness. Direct inpatient treatment costs for SRSE were twice as high as that of NRSE and RSE.
epilepsy ; status epilepticus ; hospitalization

OBJECTIVE: To explore the genetic etiology for an infant featuring convulsive status epilepticus, developmental delay and elevated plasma lactate. METHODS: Whole exome sequencing and mitochondrial D-loop sequencing were carried out for the infant. Candidate variants were verified by Sanger sequencing. Previously reported FARS2 gene variants were searched from the PubMed, Wanfang and CNKI databases. RESULTS: The infant was found to harbor compound heterozygous variants of the FARS2 gene, namely c.925G>A (p.G309S) and c.405C>A (p.H135Q), which were inherited from its mother and father, respectively. The former has been recorded by the HGMD as a pathogenic variant, whilst the latter was predicted to be likely pathogenic based on the guidelines of the American College of Medical Genetics and Genomics. A total of 30 COXPD14 cases were retrieved from the literature, with common mutations including missense variants, in-frame deletions, splice-site variants and large deletions. CONCLUSION The common manifestations of COXPD14 have included developmental delay (96%), status epilepticus (97%) and increased lactic acid (96%). The compound heterozygous variants of the FARS2 gene probably underlay the disorder in this child.
Female ; Humans ; Infant ; Genetic Testing ; Mitochondrial Diseases ; Mitochondrial Proteins/genetics* ; Phenylalanine-tRNA Ligase ; Status Epilepticus ; Exome Sequencing

INTRODUCTION: We performed a case series of all five (5) confirmed adult Filipino cases of Anti-N-Methyl-D-Aspartate receptor (anti-NMDA-R) encephalitis in a tertiary government hospital in the Philippines admitted in the past three years. Two cases were identified with unique features: (1) a 23-year old female who presented with combined refractory seizures and persistent chorea and orofacial dyskinesias; and (2) a 22-year old male who presented with refractory epilepsia partialis continuua. The rest of the patients were hereby presented. BACKGROUND: In the past years, anti-NMDA-R encephalitis has been considered a diagnosis of exclusion in lieu of other infectious causes of encephalitis. It is rare and an emerging disease with an incidence estimated at approximately 2-3 cases per million. Recent literature recorded severe cases of anti-NMDA-R encephalitis that presented as intractable first onset seizures, combined with hyperkinetic movement disorders, acute psychosis without a premorbid condition, and dysautonomia. OBJECTIVES: To present the clinicodemographic profile and to discuss the management and outcomes of patients with anti-NMDAR encephalitis in a tertiary hospital in the Philippines. RESULTS: Here, we report five confirmed cases of anti-NMDA-R encephalitis admitted in 2019-2021. The mean age is 23 years old, with 4:1 female to male ratio with a median length of hospitalization of 58 days. All patients presented with acute psychiatric symptoms without premorbid condition, focal and generalized seizures, decreased consciousness, dyskinesias, and autonomic instability. Four patients needed airway support for central hypoventilation, one had first onset seizure that developed into refractory epilepsia partialis continuua, one had persistent chorea and orofacial dyskinesia. Imaging studies of the brain included contrast-enhanced CT Scan and MRI with unremarkable findings. No female patients had an ovarian teratoma as revealed in the whole abdominal ultrasound. All CSF analysis for anti-NMDA-receptor was done in the same laboratory outside the hospital which revealed positive for NMDA-receptor antibodies, while CSF lymphocytic pleocytosis was only seen in 1/5 and protein elevation in 4/5. All of the patients underwent electroencephalogram (EEG) studies which revealed diffuse delta-theta slowing without epileptiform discharges. The patient who had persistent chorea and orofacial dyskinesias showed extreme delta brush, while one had normal EEG findings. They all received high-dose steroid and intravenous Immunoglobulin (IVIg); three patients were able to undergo Rituximab infusion. Only one female patient had mild deficits, one female was discharged fully functional and ambulatory from being weaned off from the mechanical ventilator, one female had aborted cardiac arrest and was discharged bedridden at GCS 10, and two died due to the other concomitant medical conditions. The Modified Rankin Scale (MRS) and Mini-mental Status Examination (MMSE) were used to assess the neurological and functional outcomes of our patients. CONCLUSION Anti-NMDA-R encephalitis is an emerging neurological disorder that warrants early identification as it impacts timeliness of management and long-term outcomes.
Anti-N-Methyl-D-Aspartate Receptor Encephalitis ; Status Epilepticus

Objective: To summarize the genetics and clinical phenotypes of epilepsy children with 2q24.3 microdeletion. Methods: All the patients with 2q24.3 microdeletion were retrospectively collected at the Pediatric Department of Peking University First Hospital from March 2017 to July 2022. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed. Results: There were 13 patients with 2q24.3 microdeletion were included. All 13 patients had de novo copy number variation (CNV) with a deletion size ranged 0.18-7.31 Mb. The main pathogenic genes in the region were SCN3A, SCN2A, TTC21B, SCN1A and SCN9A genes. Among the 13 patients, 7 were boys, and 6 were girls. The onset age of epilepsy was 3.3(2.5, 6.0) months. Multiple seizure types were observed, including focal seizures in 13 patients, generalized tonic-clonic seizures (GTCS) in 6 patients, myoclonic seizures in 3 patients, epileptic spasm in 2 patients, and tonic seizures in 2 patients. Seizures were fever sensitivity in 9 patients. Status epilepticus was observed in 6 patients. One case had normal mental motor development and 12 cases had different degrees of developmental delay. Six patients had craniofacial abnormality, 1 had six-finger deformity of the right thumb, and 1 had multiple system abnormalities. EEG showed focal discharge in 3 cases, multifocal discharges in 5 cases, multifocal and generalized discharges in 1 case. Brain magnetic resonance imaging (MRI) showed enlargement of subarachnoid spaces in the frontal and temporal region in 4 patients, enlargement of lateral ventricle in 4 patients and delayed myelination of white matter in 1 patient. Dravet syndrome was diagnosed in 5 cases. The age at the last follow-up were 2.5(1.4,5.5) years, 1 patient was seizure free longer than 1 year, and 12 patients still had seizures. Conclusions: The epilepsy associated with 2q24.3 microdeletion is mainly induced by the deletion of SCN3A, SCN2A and SCN1A genes. The seizure onset age of 2q24.3 microdeletion related epilepsy was in infancy. Multiple seizure types are observed and the common seizure types include focal seizures and GTCS. Most patients have fever sensitivity and status epilepticus. Most patients have developmental delay. The phenotype of patients with deletion of SCN3A and SCN2A gene is more severe than that of patients with deletion of SCN1A gene only.
Humans ; Abnormalities, Multiple ; Chromosomes ; DNA Copy Number Variations ; Epilepsies, Myoclonic ; Epilepsy ; Fever ; NAV1.7 Voltage-Gated Sodium Channel ; Phenotype ; Retrospective Studies ; Seizures ; Status Epilepticus ; Chromosomes, Human, Pair 2

OBJECTIVE: To systematically evaluate the efficacy and safety of levetiracetam (LEV) versus phenytoin (PHT) as second-line drugs for the treatment of convulsive status epilepticus (CSE) in children. METHODS: English and Chinese electronic databases were searched for the randomized controlled trials comparing the efficacy and safety of LEV and PHT as second-line drugs for the treatment of childhood CSE. RevMan 5.3 software was used for data analysis. RESULTS: Seven studies with 1 434 children were included. The Meta analysis showed that compared with the PHT group, the LEV group achieved a significantly higher control rate of CSE ( CONCLUSIONS LEV has a better clinical effect than PHT in the treatment of children with CSE and does not increase the incidence rate of adverse events.
Anticonvulsants/adverse effects* ; Child ; Humans ; Levetiracetam/therapeutic use* ; Pharmaceutical Preparations ; Phenytoin/adverse effects* ; Status Epilepticus/drug therapy*

OBJECTIVES: To study the effect of gap junction blockers, quinine (QUIN) and carbenoxolone (CBX), on hippocampal ripple energy expression in rats with status epilepticus (SE). METHODS: A total of 24 rats were randomly divided into four groups: model, QUIN, valproic acid (VPA), and CBX ( RESULTS: Ripple expression was observed in the hippocampal CA1, CA3, and dentate gyrus regions of normal rats. After 10 minutes of PILO injection, all groups had a gradual increase in mean ripple energy expression compared with 1 day before modeling, with the highest expression level before chloral hydrate injection in the model, VPA and CBX groups ( CONCLUSIONS The change in ripple energy can be used as a quantitative indicator for early warning of seizures, while it cannot predict seizures in the interictal period. Gap junction blockers can reduce ripple energy during seizures.
Animals ; Gap Junctions ; Hippocampus ; Pilocarpine ; Rats ; Seizures ; Status Epilepticus/drug therapy*

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.
Animals ; Astrocytes/metabolism* ; Complement C3/metabolism* ; Epilepsy ; Mice ; Neurons/pathology* ; Status Epilepticus ; TRPV Cation Channels/metabolism*

Regulator of calcineurin 1 (RCAN1) can be induced by an intracellular calcium increase and oxidative stress, which are characteristic features of temporal lobe epilepsy. Thus, we investigated the spatiotemporal expression and cellular localization of RCAN1 protein and mRNA in the mouse hippocampus after pilocarpine-induced status epilepticus (SE). Male C57BL/6 mice were given pilocarpine hydrochloride (280 mg/kg, i.p.) and allowed to develop 2 h of SE. Then the animals were given diazepam (10 mg/kg, i.p.) to stop the seizures and sacrificed at 1, 3, 7, 14, or 28 day after SE. Cresyl violet staining showed that pilocarpine-induced SE resulted in cell death in the CA1 and CA3 subfields of the hippocampus from 3 day after SE. RCAN1 immunoreactivity showed that RCAN1 was mainly expressed in neurons in the shammanipulated hippocampi. At 1 day after SE, RCAN1 expression became detected in hippocampal neuropils. However, RCAN1 signals were markedly enhanced in cells with stellate morphology at 3 and 7 day after SE, which were confirmed to be reactive astrocytes, but not microglia by double immunofluorescence. In addition, real-time reverse transcriptase–polymerase chain reaction showed a significant upregulation of RCAN1 isoform 4 (RCAN1-4) mRNA in the SE-induced hippocampi. Finally, in situ hybridization with immunohistochemistry revealed astrocytic expression of RCAN1-4 after SE. These results demonstrate astrocytic upregulation of RCAN1 and RCAN1-4 in the mouse hippocampus in the acute and subacute phases of epileptogenesis, providing foundational information for the potential role of RCAN1 in reactive astrocytes during epileptogenesis.
Animals ; Astrocytes ; Calcineurin ; Calcium ; Cell Death ; Diazepam ; Epilepsy ; Epilepsy, Temporal Lobe ; Fluorescent Antibody Technique ; Hippocampus ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Mice ; Microglia ; Neurons ; Neuropil ; Oxidative Stress ; Pilocarpine ; RNA, Messenger ; Seizures ; Status Epilepticus ; Up-Regulation ; Viola