Journal of epilepsy research最新文献

Background and purpose: Seizures are common presentation of cerebral vascular malformation (CVM). Topography and haemodynamic alterations are proposed as mechanisms for epileptogenesis, but the role of glial/neuronal alterations in perilesional tissue has not received much attention. Identification of the exact pathophysiologic basis could have therapeutic implications. To evaluate whether angioarchitectural factors of CVM or alterations in neuroglial/stroma of the adjacent cortex contribute to seizures.

Method: The clinical, imaging and histological characteristics of arteriovenous malformation (AVM) and cerebral cavernous malformation (CCM) with and without seizures was evaluated using neuroimaging imaging and digital subtraction angiography parameters and histopathology by morphology and immunohistochemistry.

Results: Fifty-six cases of CVM were diagnosed over a 2-year study period. Of these, 32 had adequate perilesional tissue for evaluation (AVM, 24; CCM, 8). Seizures at presentation was seen in 12/24 (50%) of AVM and 5/8 (62.5%) CCM. In AVM, hemosiderin deposition and gliosis in parenchyma (p=0.01) had significant association with seizure. Siderotic vessels in the adjacent cortex was exclusively seen only in CCM with seizures (p=0.018). Angioarchitectural features of CVM on imaging and neuronal alterations in adjacent cortex on histology failed to show any statistically significant difference between the two groups (p>0.05).

Conclusions: We propose that changes in adjacent cortex appear to be epileptogenic rather than the malformation per se. Reactive gliosis and hemosiderin deposits in perilesional tissue in AVM and siderotic vessels in CCM were associated with seizure. This explains the better outcomes following extended lesionectomy that includes epileptogenic perilesional tissues.

After the coronavirus disease 2019 (COVID-19) pandemic emerged, the development of vaccines was accelerated. Neurologic complications of COVID-19 vaccination had been reported, which included encephalitis. In this study, we report a very rare case of a female with anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma that would be triggered by BNT162b2 m-RNA COVID-19 vaccination.

Background and purpose: The literature is still controversial in relation to therapeutic differences between innovative, generic, and similar anti-seizures medications (ASM). Topiramate (TPM) is an ASM used in the treatment of various seizure types and in different epileptic syndromes, as well as in other groups of morbidities, and it is available in many generic and similar forms, besides the innovator. The aim of this translational work was to compare different brands of TPM by using animal models of seizures induced by pentylenetetrazole (PTZ).

Methods: Five brands of TPM (one reference, two similar and two generics) were tested in mice. Animals were previously treated with TPM (n=6/brand) and latencies from PTZ injection to onset of manifestations, first seizure and death were measured and compared between groups. Experiment was conducted in two settings: acute seizure model (PTZ 80 mg/kg) and kindling model (PTZ 20, 30, and 40 mg/kg in 8 alternate days).

Results: The experiment did not demonstrate significant differences between the TPM brands regarding the protective effect in the acute seizure and kindling models.

Conclusions: In conclusion, results can be explained by true therapeutic equivalence or insufficiency of the PTZ model to reveal differences among brands.

The calcium voltage-gated channel subunit alpha 1 H (CACNA1H) is a gene present in eukaryotic cells located on chromosome 16 that encodes the T-type calcium channels, which are important for calcium influx and depolarization of cells. Pathogenic variants in CACNA1H cause autosomal dominant susceptibility to idiopathic generalized epilepsy 6 (OMIM: 611942), which is a broad term that encompasses several common seizure phenotypes. In this article, we reported a Saudi female with a heterozygous variant in the CACNA1H gene (OMIM: 607904) who had epilepsy and hearing loss. This is the first case to report the association of epilepsy and hearing loss with a variant in CACNA1H. We believe that variant may be the reason for developing both epilepsy and sensorineural hearing loss. Further studies are needed to identify the role of CACNA1H in the physiology of the ear to allow for a better understanding of the effects of mutations. In children who present with early childhood hearing loss, genetic studies in highly selected cases including those with a strong family history of hearing loss and epilepsy may help detect a CACNA1H variant early and help with the early screening and diagnosis of other associated disorders including subclinical epilepsy.

Background and purpose: Psychiatric comorbidities (PC) occur more frequently in patients with epilepsy than in the general population. To determine the main PC associated with epilepsy and its association with demographic data and clinical features of epilepsy.

Methods: A retrospective study was carried out on patients with epilepsy at the Medical Specialties Center of the Municipal Health Department. Demographic data, crisis onset, time range of seizures evolution, type of epileptic seizures, types of epilepsy, etiology, brain injury, topographic location, hemispheric location, type of antiepileptic drugs (AEDs), use of monotherapy or polytherapy, control of epileptic seizures and the PC were recorded.

Results: One hundred forty adult patients were studied 51.4% male, mean age 44.9 years, time of evolution of the crises was 14 years, focal crisis 88.6%, mesial temporal sclerosis 42%, controlled 92.4%, monotherapy 66.1%, and the most used AEDs were carbamazepine (33.1%), valproic acid (28.2%), and phenobarbital (10.4%). The PC present in 67.1% of the patients was depression (22.8%), anxiety disorder (AD) (17.8%), psychosis (10%), dementia (9.2%) and bipolar affective disorder (BAD) (8.5%). The relationship between PC and crisis control was significant (p<0.009).

Conclusions: Schooling was lower than that reported in the general population in Brazil, and we found a low rate of unemployment or retirement. Epilepsy is associated with PC, the most frequent being depression, AD, psychosis, dementia and BAD. The absence of a relationship between depression and brain damage; anxiety disorder with education, types of epilepsy and etiology; psychosis with sex and time of epilepsy evolution were significant.

Background and purpose: Patients over the age of 75 are more likely to develop epilepsy than children under the age of 10. Patients of all ages are prescribed anti-epileptic drugs; however, those over the age of 65 are the most typically prescribed group.

Methods: This is a retrospective study of geriatric cases admitted to the Neurosurgery Department in Khoula Hospital from January 1, 2016 to December 31, 2019. A medical records of 669 patients were identified. Patients' demographics, risk factors, usage of anti-epileptic drug (AED), type of tumor, tumor location, neuro-vital signs diagnosis, Glasgow coma scale on arrival, treatment types, and length of stay (LOS) were recorded.

Results: The prevalence of AEDs use was 19%. Patients with traumatic brain injury (TBI) were found to have a higher rate of using AEDs (32.1%) followed by patients with oncological and vascular pathologies, respectively (30.1% and 21.6%). There was a significant relationship between the utilization of AEDs among different neurological diseases investigated (p<0.05). Patients who received surgical interventions were using AEDs much more than patients with conservative management (p=0.001). There was a significant difference in the LOS and the usage of AEDs. Added to that, the results signify a relationship between the intensive care unit (ICU) admission and the utilization of AEDs in which the majority of the patients who were not on AEDs were not admitted to the ICU (p<0.05). Phenytoin was the most commonly used AED among different neurosurgical pathologies in the present study (n=110).

Conclusions: AEDs are used as prophylaxis to prevent seizures before most neurosurgical procedures and were commonly prescribed in TBI patients. Phenytoin was found to be the commonest AEDs utilized among the different neurosurgical categories followed by levetiracetam.

Background and purpose: FAME (Fycompa^® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074), a previously reported single-arm, phase IV study, showed that perampanel improved seizure control as first add-on to failed anti-seizure medication (ASM) monotherapy in 85 South Korean patients aged ≥12 years with focal-onset seizures (FOS) with/without focal to bilateral tonic-clonic seizures. We present results of three post hoc analyses of FAME that further assessed the efficacy and safety of perampanel.

Methods: Patients were stratified by low- (4, 6 mg/day) versus high- (8, 10, 12 mg/day) dose maintenance perampanel, perampanel added to first- versus second-line ASM monotherapy, and concomitant background ASM monotherapy and perampanel dose. The primary endpoint was the proportion of patients with a ≥50% reduction in total seizure frequency during the 24-week maintenance period. Safety was assessed by the descriptive incidence of treatment-emergent adverse events (TEAEs).

Results: In post hoc analyses, 50% responder rates were significantly higher for low- versus high-dose maintenance perampanel (88.6% vs. 40.0%; p<0.001) and when added to first- versus second-line ASM monotherapy (83.5% vs. 33.3%; p=0.013). By concomitant background ASM and perampanel maintenance dose, 50% responder rates were 100% for perampanel 4 mg/day added to carbamazepine, oxcarbazepine, lamotrigine, or valproic acid, and 85% when added to levetiracetam. Add-on perampanel improved 75% and seizure-free responder rates, and median percent changes from baseline seizure frequency per 28 days. Perampanel was well tolerated when added to ASM monotherapy, with dizziness being the most common TEAE.

Conclusions: Post hoc analyses of FAME provide supportive data for the use of perampanel as an effective and well-tolerated first add-on treatment to a broad spectrum of ASM monotherapies in patients with FOS.

Background and purpose: Perampanel is approved for the adjunctive treatment of focal-onset seizures (FOS) with or without secondary generalized seizures. The FAME (Fycompa^® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074) study evaluated the efficacy and safety of perampanel added to monotherapy in patients with FOS with or without secondary generalized seizures (SGS). Post hoc analyses of the FAME study assessed potential predictors of response and an in-depth evaluation of the safety and efficacy of perampanel.

Methods: Efficacy was assessed by reduction of total seizure frequency by ≥50%, ≥75% or 100%, and safety by incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. Univariate and multivariate logistic regression analyses for treatment response were performed.

Results: Most patients (82/85) received perampanel doses of 4-8 mg/day during maintenance therapy and the highest efficacy rates were achieved with 4 mg/day, irrespective of efficacy outcome. Doses of 4 or 6 mg/day in patients with FOS with SGS (n=16) produced comparable efficacy outcomes. In multivariate analysis, total perampanel dose was predictive of 50% and 75% response rates; longer total perampanel administration period with 50% response; and concomitant non-anti-seizure medication with a 100% response. Patients developed a TEAE more frequently during the 12-week titration period (60.2%) than the 24-week maintenance period (28.4%), including dizziness (45.5% vs. 9.1%), somnolence (10.2% vs. 0%), and headache (4.5% vs. 3.4%).

Conclusions: Post hoc analyses show that even low doses of perampanel may be effective and TEAEs are usually self-limited or well-tolerated.

Lennox-Gastaut syndrome (LGS) is a pharmacoresistant epileptic encephalopathy. Herein reported is a case of LGS that combination therapy with levetiracetam, lamotrigine and valproate culminated in control of all seizure types and resolution of epileptic discharges in electroencephalography. This case indicates that logical combination therapy may provide seizure control and improvement of electroencephalographic pattern in patients with LGS even in cases at which epileptic surgery fails.