Increased Seizure Activity Research Articles

Increase in seizure activity is associated with change to daylight savings time as identified by an implanted thalamic neurostimulator in bilateral thalamic centrum medianum nuclei

Increase in seizure activity is associated with change to daylight savings time as identified by an implanted thalamic neurostimulator in bilateral thalamic centrum medianum nuclei

Benefits And Challenges for Young Australians with Epilepsy Transitioning Into Adult Healthcare: A scoping review

Transitioning from paediatric healthcare into an adult healthcare system is a high-risk time for people with complex epilepsy. This can be a period of significant upheaval as a young person moves away from familiar and safe paediatric environments into unfamiliar adult healthcare. This is compounded by normal adolescent development, the challenges of epilepsy and the lifestyle conditions it demands, including restrictions on driving and levels of independence. Such factors can contribute to suboptimal health engagement which result in increased seizure activity, hospital admissions and reduction in community participation. Effective, well implemented transition programs are key to reducing risks, however little is known about which features of transition pathways define success or best practice. A scoping review was used to examine a broad range of peer-reviewed literature published between 2017 and 2022. This review examined evidence-based literature relating to experiences of people with epilepsy as they transitioned between paediatric and adult healthcare environments. Specifically, exploring practices that offered benefits, recognising barriers, and identifying findings to inform future research and advance transition practices. This review found that key to reducing transition-related health impacts for young people was patient-centred, engaging care that acknowledges their psychosocial and mental health needs specific to their level of development. Evidence suggests that engagement is built through multidisciplinary clinics that facilitate education and self-management. This review found that successful programs can deliver this by focusing on four key areas; relationships and continuity, capacity building, processes, and health services and systems. At a paediatric level this involves timely, age-appropriate preparation that builds skills and knowledge through tailored care-plans. At the transfer phase this means coordinated teams that work together across systems to ensure handover continuity, reduce stressors, and to aid navigation. At the adult level, care-teams that welcome young patients with protocols for continued capacity building are required.

Myasthenia gravis in a pediatric patient with Lennox-Gastaut syndrome following responsive neurostimulation device implantation: illustrative case.

Myasthenia gravis (MG) is an autoimmune disorder in which the postsynaptic acetylcholine receptor of the neuromuscular junction is destroyed by autoantibodies. The authors report a case of MG in a pediatric patient who also suffered from Lennox-Gastaut syndrome (LGS) and is one of a limited number of pediatric patients who have undergone placement of a responsive neurostimulation (RNS) device (NeuroPace). A 17-year-old female underwent placement of an RNS device for drug-resistant epilepsy in the setting of LGS. Five months after device placement, the patient began experiencing intermittent slurred speech, fatigue, and muscle weakness. Initially, the symptoms were attributed to increased seizure activity and/or medication side effects. However, despite changing medications and RNS settings, no improvements occurred. Her antiacetylcholine receptor antibodies measured 62.50 nmol/L, consistent with a diagnosis of MG. The patient was then prescribed pyridostigmine and underwent a thymectomy, which alleviated most of her symptoms. The authors share the cautionary tale of a case of MG in a pediatric patient who was treated with RNS for intractable epilepsy associated with LGS. Although slurred speech, fatigue, muscle weakness, and other symptoms might stem from increased seizure activity and/or medication side effects, they could also be due to MG development.

ULTRASTRUCTURAL CHANGES OF THE PINEAL GLAND IN EPILEPSY

Circadian mechanisms modulate neuronal excitability at several levels, and their destruction can cause excessive uncontrolled excitability. Previous studies have shown that epilepsy is associated with melatonin levels. Melatonin is a powerful chronobiotic secreted from the pineal gland; helps to maintain normal circadian rhythms and is used to treat some neurological and psychiatric disorders. Circadian rhythms and sleep/wake mechanisms play role in the epilepsy. Melatonin deficiency can decrease seizure threshold, and hence could increase seizure activity. The aim of the study was to identify ultrastructural changes in the pineal gland in an experimental model of epilepsy. Materials and methods. The experiment was carried out on Wistar rats, 5-6 months of age, weight of about 200 g, 36 experimental and 10 control animals. Electrically provoked experimental epileptic seizures model in rats was reproduced. The rats developed spontaneous generalized seizures after 9-14 stimulations. Material for histological examinations was taken after stable formation (for >1 month) of repeated seizures. Ultrathin sections, after contrast with Reynolds lead citrate, were studied under an electron microscope at an accelerating voltage of 75 kV. The increase was selected adequate to the study and ranged from 20,000 to 60,000 times. Results. Experimental studies have confirmed the presence of stable dystrophic, up to apoptosis of some cells, morphological changes of the pineal gland in the experimental model of epilepsy in rats, which is the reason for the decrease in its functional activity. Conclusions. Our experimental data on the morphological changes of the pineal gland confirm the conclusion about a stable, possibly irreversible, decrease in gland function in epilepsy due to damage and disruption of the structure of its cells. Given the polyfunctionality of melatonin, its deficiency can be one of the causes of changes in neural networks, impaired permeability of synaptic membranes, and as a consequence, increased epileptic activity of neurons.

New Onset Seizures in a Child Taking 0.01% Atropine Drops

Introduction: Myopia is a refractive disorder commonly diagnosed in childhood that follows a progressive course. It is considered a global epidemic with nearly 23% of the world’s population being diagnosed with this condition. Moreover, myopia is increasing in prevalence worldwide, demonstrated by studies in Asian and Western populations. This has important implications as myopic progression to high myopia is associated with significant morbidity and visual disability if left untreated. Of these treatments, the pharmacologic agent atropine has demonstrated the greatest efficacy in reducing myopia progression. Case report: This is a case report of an 11-year-old male treated with 0.01% atropine drops for myopia progression that developed new-onset seizures. The seizures were characterized as benign epilepsy with central temporal spikes and ceased when drops were discontinued. Discussion: Atropine 1% drops have previously been associated with new or increased seizure activity in a handful of case reports, however, it is our knowledge that this is the first report associated with 0.01% drops. This is important given the growing use of 0.01% drops as well as higher concentrations such as 0.025 % and 0.05% for the treatment of pediatric myopia. Conclusion: While it cannot be proven that the drops were causative in the seizure events, it is important to consider prior seizures as a relative contraindication to the use of these drops. Atropine has the potential to exacerbate seizure activity, so it is possible that the 0.01% atropine drops played a role in the patient’s seizures. Also, any diagnosis of new-onset seizures in pediatric patients should prompt discontinuation of drops at seizure onset.

Alzheimer risk-increasing TREM2 variant causes aberrant cortical synapse density and promotes network hyperexcitability in mouse models

The R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2) increases the risk of Alzheimer's disease (AD). To investigate potential mechanisms, we analyzed knockin mice expressing human TREM2-R47H from one mutant mouse Trem2 allele. TREM2-R47H mice showed increased seizure activity in response to an acute excitotoxin challenge, compared to wildtype controls or knockin mice expressing the common variant of human TREM2. TREM2-R47H also increased spontaneous thalamocortical epileptiform activity in App knockin mice expressing amyloid precursor proteins bearing autosomal dominant AD mutations and a humanized amyloid-β sequence. In mice with or without such App modifications, TREM2-R47H increased the density of putative synapses in cortical regions without amyloid plaques. TREM2-R47H did not affect synaptic density in hippocampal regions with or without plaques. We conclude that TREM2-R47H increases AD-related network hyperexcitability and that it may do so, at least in part, by causing an imbalance in synaptic densities across brain regions.

Vaccination against COVID-19 and potential protective effects on seizure recurrence in children with epilepsy: A cross-sectional survey.

Despite strong evidence on the safety and tolerability of the COVID-19 vaccine, data on vaccination in children with epilepsy, particular younger children with specific epilepsy syndromes, are limited. The protective effects of vaccination against seizure increase upon COVID-19 infection also remain to be elucidated. Questionnaire surveys were distributed online via an established WeChat group for patient management as well as in our outpatient clinic. The data collected included demographics and clinical information related to COVID-19 vaccination and infection. Detailed information related to epilepsy diagnosis and treatment was also collected from our patient database. Logistic regression analysis was performed to determine the factors associated with non-vaccination. The characteristics of seizures following COVID-19 infection were described. In total, 354 suitable questionnaires were included in the study. The median age at survey was 6 years (interquartile range 4, 9). The most common epilepsy syndrome was self-limited epilepsy (n = 153, 43.2%), followed by developmental and/or epileptic encephalopathy (D/EE, n = 81, 22.9%) and genetic generalized epilepsy (n = 59, 16.7%). The vaccine uptake rate was 43.8% (n = 155), and all related side-effects (n = 11, 7.1%) remitted spontaneously. Younger age (odds ratio [OR] = 0.877, P = 0.001), D/EE (OR = 5.096, P = 0.008), and less than six months seizure-freedom before vaccination (OR = 3.026, P = 0.005) were associated with unwillingness to be vaccinated. There were no significant differences in the rate of COVID-19 infection (33.7% vs 32.7%, P = 0.879) and resultant increased seizure activity following infection between the vaccinated and unvaccinated groups after propensity score matching (9.1% vs 15.6%, P = 0.428).Three unvaccinated cases of Dravet syndrome developed status epilepticus following COVID-19 infection. Vaccination against COVID-19 is safe and well tolerated in children, even in younger patients with D/EE. Although the risk of worsening seizures following COVID-19 infection may not be reduced by immunization, education focused on increased vaccination in pediatric epilepsy is still warranted.

Transcranial electric motor evoked potential monitoring during scoliosis surgery in children with cerebral palsy and active seizure disorder: is it feasible and safe?

Use of spinal cord monitoring in children with cerebral palsy (CP) and neuromuscular scoliosis is challenging. The previous reports suggest low success rates in the setting of CP, and it is unclear if transcranial electric motor evoked potentials (TcMEP) monitoring is contraindicated in patients with an active seizure disorder. The purpose of this study was to determine (1) are patients with CP able to be appropriately monitored with TcMEP? and (2) does TcMEP cause an increase in seizure activity? This was an institutional review board-approved retrospective cohort study observing 304 patients from 2011 to 2020. Inclusion criteria included all patients with CP undergoing posterior spinal fusion during this time. Intraoperative data were examined for the ability to obtain monitoring and any intraoperative events. Patients were followed for 3months postoperatively to determine any increase in seizure activity that could have been attributed to the TcMEP monitoring. Of the 304 patients who were observed, 21% (20.8%) were unable to be monitored due to lacking baseline signals from the extremities. Seventy-seven percent (77.5%) were successfully monitored with TcMEP. For these patients, no increased seizure activity was documented either intra- or postoperatively. A high percentage of children (77.5%) with CP were able to be successfully monitored with TcMEP during posterior spinal fusion. Furthermore, the concerns about increased seizure activity after TcMEP were not supported by the data from this cohort. Technical details of successful neuromonitoring in these patients are important and included increased stimulation voltage requirements and latency times. III retrospective comparative study.

Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy

ObjectiveEpidiolex® (CBD) is FDA-approved for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC). Phase III studies suggest that certain adverse effects (AEs), possibly linked to pharmacokinetic/pharmacodynamic (PK/PD) interactions may be therapy-limiting. We sought to identify these factors that contribute to treatment success and retention of therapy. MethodsA single-center, retrospective review of patients with refractory epilepsy taking Epidiolex® was performed. Kaplan-Meier analysis was performed to describe Epidiolex® retention, as a measure of overall effectiveness. ResultsOne hundred and twelve patients were screened; 4 were excluded due to loss to follow-up or never starting Epidiolex®. Of 108 patients, mean age was 20.3 years (13.1, range 2 to 63), and 52.8% were female. Mean initial and maintenance doses were 5.3 mg/kg/day (1.3) and 15.3 mg/kg/day (5.8), respectively. At the final evaluation, 75% of patients remained on Epidiolex®. The 25th percentile for discontinuation was 19 months. 46.3% of patients experienced at least one treatment-emergent adverse effect (TEAE) with 14.5% d/c Epidiolex® due to treatment emerging adverse effects (TEAE). The most common reasons for discontinuation were lack of efficacy (37%), increased seizure activity (22%), worsened behavior (22%), and sedation (22%). One out of 27 discontinuations was due to liver function test (LFT) elevations (3.7%). At initiation, 47.2% were concurrently taking clobazam, and 39.2% of those patients had an initial clobazam dose decrease. 53% of patients were able to either discontinue or lower the dose of at least one other antiseizure medication. SignificanceEpidiolex® is generally well-tolerated and the majority continued long-term treatment. Patterns of adverse effects were similar to clinical trials, however gastrointestinal complaints, and significant LFT elevations were less common. Our data suggest most patients discontinue within the first several months of treatment and suggest that further studies designed to evaluate early identification and potential mitigation of adverse effects and including drug interactions are warranted.

Значение герпесвирусов в постковидном периоде у детей

Aim: to assess the prevalence of detection of confirmed herpes virus infections (HVI) in children who had a previous COVID-19 infection, characterize specific clinical manifestations of the disease under the new conditions (post-COVID syndrome), and to provide a rationale for the administration of drug therapy. Patients and Methods: of 456 patients who received medical consultations from September 2021 to July 2022, the authors selected 72 (15.8%) children (42 boys and 30 girls) who had a previous SARS-CoV-2 infection confirmed by serological tests or polymerase chain reaction and in whom herpes viruses were found during serological evaluation. Results: most of the children (81.4%) visited the polyclinic within the first six months after the COVID-19 infection. Epstein-Barr virus (EBV) was the most prevalent finding among herpesviruses detected in children with post-COVID-19 sequela — it was detected in 44 (61.1%) cases. Human herpesvirus (HHV) 6 and cytomegalovirus (CMV) were less common in this group and found in 41 (56.9%) and 30 (41.7%) children, respectively. HHV-1 and HHV-2 were detected more rarely — in 11 (15.3%) children. Monoinfection was diagnosed in 41 (56.9%) cases and a combination of viruses was found in 31 children, in 22 (71.0%) of them it comprised two viruses, in 6 (19.3%) — three viruses, and in 3 (9.7%) — four viruses. The presence of herpesvirus infections underpinned the main reasons why parents of the ill children were seeking for outpatient care, in particular: a prolonged subfebrile condition (18.0%), fatigue and sleep disorders (27.7%), rashes (16.6%), lymphadenopathy (16.7%), ENT diseases (33.3%), more frequently occurring respiratory diseases (33.3%), and the increase in seizure activity in children with epilepsy (8.3%). In addition to herpes viruses, pathogenic agents were detected in 18% of patients, including intracellular pathogens, which were found in 13.9% of 72 children. Taking into consideration the obtained results and established clinical diagnoses, the authors conducted a review and provided a rationale for the administered drug therapy, including medications for herpes treatment. Conclusion: a prior COVID-19 infection induces immunosuppression and, as a result, the activation of herpesvirus infections as long-term effects of COVID-19 (post-COVID conditions). The presence of mixed viral and bacterial pathogens is an indication for administering antivirals, immunomodulators, antibacterial agents, and probiotics. KEYWORDS: post-COVID conditions, herpesvirus infections, children, clinical symptoms, treatment. FOR CITATION: Savenkova M.S., Sotnikov I.A., Afanasieva A.A. et al. Importance of herpes viruses in children with post-COVID conditions. Russian Journal of Woman and Child Health. 2023;6(1):39–44 (in Russ.). DOI: 10.32364/2618-8430-2023-6-1-39-44.

EFFECT OF TAURINE ON MANIFESTATION OF AUDIOGENIC EPILEPSY IN RATS WITH PENDULUM MOVEMENTS

A decrease of taurine in hippocampus of the line of rats with pendulum movements (PM), predisposed to audiogenic epilepsy, was shown. Taurine (aminoethanesulfonic acid) is known to be an anticonvulsant drug. The aim of the present work was to verify the predictive validity of taurine in rats with pendulum movements (PM). In neonatal period the exogenous taurine administration did not influence a convulsive activity at the age of 1.5 and 3 months in PM rats. The increase in the number of audiogenic seizures after taurine injections was found in adolescent period in 1.5 months and in prolonged point – in 3 months. The number of abortive seizures decreased under acute injection of taurine in adult PM rats, but the level of ictal and postictal indicators restored one month later, at the age of 4 months. Obtained results indicate the absence of effect of taurine administered to rats in the neonatal age, while at the long-term scale, the rats showed the increasing seizure activity under the action of taurine in adolescent period and confirm the predictive validity of this drug in adult PM rats.

Lack of UBE3A-Mediated Regulation of Synaptic SK2 Channels Contributes to Learning and Memory Impairment in the Female Mouse Model of Angelman Syndrome.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe developmental delay, motor impairment, language and cognition deficits, and often with increased seizure activity. AS is caused by deficiency of UBE3A, which is both an E3 ligase and a cofactor for transcriptional regulation. We previously showed that the small conductance potassium channel protein SK2 is a UBE3A substrate, and that increased synaptic SK2 levels contribute to impairments in synaptic plasticity and fear-conditioning memory, as inhibition of SK2 channels significantly improved both synaptic plasticity and fear memory in male AS mice. In the present study, we investigated UBE3a-mediated regulation of synaptic plasticity and fear-conditioning in female AS mice. Results from both western blot and immunofluorescence analyses showed that synaptic SK2 levels were significantly increased in hippocampus of female AS mice, as compared to wild-type (WT) littermates. Like in male AS mice, long-term potentiation (LTP) was significantly reduced while long-term depression (LTD) was enhanced at hippocampal CA3-CA1 synapses of female AS mice, as compared to female WT mice. Both alterations were significantly reduced by treatment with the SK2 inhibitor, apamin. The shunting effect of SK2 channels on NMDA receptor was significantly larger in female AS mice as compared to female WT mice. Female AS mice also showed impairment in both contextual and tone memory recall, and this impairment was significantly reduced by apamin treatment. Our results indicate that like male AS mice, female AS mice showed significant impairment in both synaptic plasticity and fear-conditioning memory due to increased levels of synaptic SK2 channels. Any therapeutic strategy to reduce SK2-mediated inhibition of NMDAR should be beneficial to both male and female patients.

Negative effects of brain regulatory T cells depletion on epilepsy

The infiltration of immune cells is observed in the epileptogenic zone; however, the relationship between epilepsy and regulatory T cells (Tregs) remains only partially understood. We aimed to investigate brain-infiltrating Tregs to reveal their underlying role in epilepsy. We analyzed the infiltration of Tregs in the epileptogenic zones from patients with epilepsy and a pilocarpine-induced temporal lobe epilepsy (TLE) model. Next, we evaluated the effects of brain Treg depletion on neuroinflammation, neuronal loss, oxidative stress, seizure activity and behavioral changes in the pilocarpine model. We also explored the impact of Treg expansion in the brain on seizure activity. There were a large number of Tregs in the epileptogenic zones of human and experimental epilepsy. The number of brain Tregs was negatively correlated with the frequency of seizures in patients with epilepsy. Our further findings demonstrated that brain Treg depletion promoted astrocytosis, microgliosis, inflammatory cytokine production, oxidative stress, and neuronal loss in the hippocampus after status epilepticus (SE). Moreover, brain Treg depletion increased seizure activity and contributed to behavioral impairments in experimental chronic TLE. Interestingly, intracerebroventricular injection of CCL20 amplified Tregs in brain tissue, thereby inhibiting seizure activity. Taken together, our study highlights the therapeutic potential of regulating Tregs in epileptic brain tissue.

Regulation of Potassium and Chloride Concentrations in Nervous Tissue as a Method of Anticonvulsant Therapy

Under some pathological conditions, such as pharmacoresistantepilepsy, status epilepticus or certain forms of genetic abnormalities,spiking activity of GABAergic interneurons may enhance excitationprocesses in neuronal circuits and provoke the generation of ictaldischarges. As a result, anticonvulsants acting on the GABAergicsystem may be ineffective or even increase seizure activity. Thisparadoxical effect of the inhibitory system is due to ionic imbalancesin nervous tissue. This review addresses the mechanisms of ictaldischarge initiation in neuronal networks due to the imbalance ofchloride and potassium ions, as well as possible ways to regulateionic concentrations. Both the enhancement (or attenuation) of theactivity of certain neuronal ion transporters and ion pumps andtheir additional expression via gene therapy can be effective insuppressing seizure activity caused by ionic imbalances. The Na+–K+-pump,NKCC1 and KCC2 cotransporters are important for maintaining properK+ and Cl– concentrationsin nervous tissue, having been repeatedly considered as pharmacologicaltargets for antiepileptic exposures. Further progress in this directionis hampered by the lack of sufficiently selective pharmacologicaltools and methods for providing effective drug delivery to the epilepticfocus. The use of the gene therapy techniques, such as overexpressingof the KCC2 transporter in the epileptic focus, seems to be a more promisingapproach. Another possible direction could be the use of optogenetictools, namely specially designed light-activated ion pumps or ionchannels. In this case, photon energy can be used to create therequired gradients of chloride and potassium ions, although thesemethods also have significant limitations which complicate theirrapid introduction into medicine.

Neuropilin-2 Signaling Modulates Mossy Fiber Sprouting by Regulating Axon Collateral Formation Through CRMP2 in a Rat Model of Epilepsy

Programmed neural circuit formation constitutes the foundation for normal brain functions. Axon guidance cues play crucial roles in neural circuit establishment during development. Whether or how they contribute to maintaining the stability of networks in mature brains is seldom studied. Upon injury, neural rewiring could happen in adulthood, of which mossy fiber sprouting (MFS) is a canonical example. Here, we uncovered a novel role of axon guidance molecule family Sema3F/Npn-2 signaling in MFS and epileptogenesis in a rat model of epilepsy. Dentate gyrus-specific Npn-2 knockdown increased seizure activity in epileptic animals along with increased MFS. Hippocampal culture results suggested that Npn-2 signaling modulates MFS via regulating axon outgrowth and collateral formation. In addition, we discovered that Sema3F/Npn-2 signal through CRMP2 by regulating its phosphorylation in the process of MFS. Our work illustrated that Npn-2 signaling in adult epilepsy animals could potentially modulate seizure activity by controlling MFS. MFS constitutes the structural basis for abnormal electric discharge of neurons and recurrent seizures. Therapies targeting Npn-2 signaling could potentially have disease-modifying anti-epileptogenesis effects in epilepsy treatment.

Recognizing seizure clusters in the community: The path to uniformity and individualization in nomenclature and definition.

Seizure emergencies experienced by patients with epilepsy include status epilepticus and seizure clusters. Although an accepted definition of status epilepticus exists, no clear consensus definition of seizure clusters has emerged; this is further complicated by the appearance in the literature of various empirically based definitions that have been developed for clinical trial study designs. In general, patients with intractable epilepsy have been shown to have a significant risk for acute episodes of increased seizure activity called seizure clusters (also referred to as acute repetitive seizures, among other terms) that differ from their usual seizure pattern. Duration (e.g., number of hours or days) is often included in the definition of a seizure cluster; however, the duration may vary among patients, with some seizure clusters lasting ≥24 h and requiring long-acting treatment for this period. In addition to seizure cluster duration, the time between seizures and possible acceleration in seizure frequency during the cluster may be important variables. The recognition and treatment of seizure clusters require urgent action because episodes that are not quickly and appropriately treated may lead to injury or progress to status epilepticus or potentially death. Most seizure clusters occur outside a medical facility (in the community) and treatment is usually administered by nonmedical individuals; therefore, health care providers may benefit from a clear description of these potential seizure emergencies that they can then use to educate patients and caregivers on the prompt and appropriate identification of seizure clusters and administration of rescue therapy. Here we explore why greater uniformity is needed in the discussion of seizure clusters. This exploration examines epidemiologic studies of seizure clusters and status epilepticus, inconsistencies in nomenclature and definitions for seizure clusters, practical application of seizure cluster terminology, and the potential use of acute seizure action plans and patient-specific individualized definitions in the clinical setting.

COVID-19 vaccine in patients with Dravet syndrome: Observations and real-world experiences.

ObjectiveVaccination against the SARS‐CoV‐2 virus is a primary tool to combat the COVID‐19 pandemic. However, vaccination is a common seizure trigger in individuals with Dravet syndrome (DS). Information surrounding COVID‐19 vaccine side effects in patients with DS would aid caregivers and providers in decisions for and management of COVID‐19 vaccination.MethodsA survey was emailed to the Dravet Syndrome Foundation's Family Network and posted to the Dravet Parent & Caregiver Support Group on Facebook between May and August 2021. Deidentified information obtained included demographics and vaccination status for individuals with DS. Vaccine type, side effects, preventative measures, and changes in seizure activity following COVID‐19 vaccination were recorded. For unvaccinated individuals, caregivers were asked about intent to vaccinate and reasons for their decision.ResultsOf 278 survey responses, 120 represented vaccinated individuals with DS (median age = 19.5 years), with 50% reporting no side effects from COVID‐19 vaccination. Increased seizures following COVID‐19 vaccination were reported in 16 individuals, but none had status epilepticus. Of the 158 individuals who had not received a COVID‐19 vaccination, 37 were older than 12 years (i.e., eligible at time of study), and only six of these caregivers indicated intent to seek vaccination. The remaining 121 responses were caregivers to children younger than 12 years, 60 of whom indicated they would not seek COVID‐19 vaccination when their child with DS became eligible. Reasons for vaccine hesitancy were fear of increased seizure activity and concerns about vaccine safety.SignificanceThese results indicate COVID‐19 vaccination is well tolerated by individuals with DS. One main reason for vaccine hesitancy was fear of increased seizure activity, which occurred in only 13% of vaccinated individuals, and none had status epilepticus. This study provides critical and reassuring insights for caregivers and health care providers making decisions about the safety of COVID‐19 vaccinations for individuals with DS.

CaV2.1 channel mutations causing familial hemiplegic migraine type 1 increase the susceptibility for cortical spreading depolarizations and seizures and worsen outcome after experimental traumatic brain injury.

Patients suffering from familial hemiplegic migraine type 1 (FHM1) may have a disproportionally severe outcome after head trauma, but the underlying mechanisms are unclear. Hence, we subjected knock-in mice carrying the severer S218L or milder R192Q FHM1 gain-of-function missense mutation in the CACNA1A gene that encodes the α1A subunit of neuronal voltage-gated CaV2.1 (P/Q-type) calcium channels and their wild-type (WT) littermates to experimental traumatic brain injury (TBI) by controlled cortical impact and investigated cortical spreading depolarizations (CSDs), lesion volume, brain edema formation, and functional outcome. After TBI, all mutant mice displayed considerably more CSDs and seizures than WT mice, while S218L mutant mice had a substantially higher mortality. Brain edema formation and the resulting increase in intracranial pressure were more pronounced in mutant mice, while only S218L mutant mice had larger lesion volumes and worse functional outcome. Here, we show that gain of CaV2.1 channel function worsens histopathological and functional outcome after TBI in mice. This phenotype was associated with a higher number of CSDs, increased seizure activity, and more pronounced brain edema formation. Hence, our results suggest increased susceptibility for CSDs and seizures as potential mechanisms for bad outcome after TBI in FHM1 mutation carriers.

Examining the role of astrogliosis and JNK signaling in post-traumatic epilepsy

ObjectivePost-traumatic epilepsy is a devastating complication of traumatic brain injury that has no targeted pharmacological therapy. Previous literature has explored the role of the c-Jun N-terminal kinase (JNK) pathway in epilepsy and the creation of epileptogenic foci by reactive astrogliosis; however, the relationship between reactive astrogliosis and the c-Jun N-terminal kinase signaling pathway in the development of post-traumatic epilepsy has not been thoroughly examined.MethodsFour experimental groups, consisting of c57/b16 male mice, were examined: (1) control, (2) traumatic brain injury of graded severity (mild, moderate, severe), (3) sub-convulsive kainic acid alone without traumatic brain injury (15 mg/kg i.p.), and (4) sub-convulsive kainic acid administered 72 h after moderate traumatic brain injury. Modified Racine scale from 1 to 72 h and total beam breaks at 72 h were used to assess seizure activity. Immunohistochemistry and western blot were utilized to examine astrogliosis (GFAP), microglia activation (IBA-1), and phosphorylated JNK in prefrontal cortex samples collected from the contracoup side at 72 h post-injury.ResultsAstrogliosis, measured by GFAP, was increased after traumatic brain injury and increased commensurately based on the degree of injury. Mice with traumatic brain injury demonstrated a four-fold increase in phosphorylated JNK: p < 0.001. Sub-convulsive kainic acid administration did not increase seizure activity nor phosphorylation of JNK in mice without traumatic brain injury; however, sub-convulsive kainic acid administration in mice with moderate traumatic brain injury did increase phosphorylated JNK. Seizure activity was worse in mice, with traumatic brain injury, administered kainic acid than mice administered kainic acid.ConclusionsReactive astrocytes may have dysfunctional glutamate regulation causing an increase in phosphorylated JNK after kainic acid administration. Future studies exploring the effects of JNK inhibition on post-traumatic epilepsy are recommended.

Increasing Seizure Activity During Radiation Treatment for High-grade Gliomas - Final Results of a Prospective Interventional Study.

Little is known regarding seizures during radiotherapy for brain tumors. This prospective study investigated seizure activity in patients irradiated for high-grade gliomas. Using a seizure diary, progression of seizure activity was evaluated in 22 patients receiving chemoradiation for grade III (n=1) or IV (n=21) gliomas. Progression was defined as increased frequency of any and/or generalized seizures (>50%) or increased anti-epileptic medication (≥25%). Patients' satisfaction with the diary was assessed using a questionnaire (six scales of 1-7 points). Uni- and multivariable analyses were performed including baseline seizure activity, age, sex, resection, tumor site, performance score, and history of epilepsy/seizures. Ten patients (45%) experienced progression of seizure activity during their radiotherapy course, mainly due to increased seizure frequency (nine patients=41%). Mean values of patients' satisfaction scores ranged between 3.92 and 4.92 points. Radiotherapy of high-grade gliomas can increase seizure activity. Patients require close monitoring to initiate or adjust anti-epileptic medication.