Effect Of Antiseizure Drugs Research Articles

Incidence and Characteristics of Cerebellar Atrophy/Volume Loss in Children with Confirmed Diagnosis of Tuberous Sclerosis Complex.

Objectives: The goal of our study was to determine the incidence of cerebellar atrophy, assess the imaging findings in the posterior fossa and determine the incidence of hippocampal sclerosis in a cohort of pediatric patients with confirmed tuberous sclerosis complex (TSC). Material and methods: MRI studies of 98 TSC pediatric patients (mean age 7.67 years) were evaluated for cerebellar atrophy, cerebral/cerebellar tubers, white matter lesions, subependymal nodules, subependymal giant cell astrocytomas, ventriculomegaly, and hippocampal sclerosis. Clinical charts were revisited for clinical symptoms suggesting cerebellar involvement, for seizures and treatment for seizures, behavioral disorders and autism. Results: Cerebral tubers were present in 97/98 cases. In total, 97/98 had subependymal nodules, 15/98 had SEGA, 8/98 had ventriculomegaly and 4/98 had hippocampal sclerosis. Cerebellar tubers were found in 8/98 patients (8.2%), whereas cerebellar atrophy was described in 38/98 cases (38.8%). In 37/38 patients, cerebellar volume loss was mild and diffuse, and only one case presented with left hemi-atrophy. Briefly, 32/38 presented with seizures and were treated with anti-seizure drugs. In total, 8/38 (21%) presented with behavioral disorders, 10/38 had autism and 2/38 presented with seizures and behavioral disorders and autism. Conclusions: Several studies have demonstrated cerebellar involvement in patients with TSC. Cerebellar tubers differ in shape compared with cerebral tubers and are associated with cerebellar volume loss. Cerebellar atrophy may be focal and diffuse and one of the primary cerebellar manifestations of TSC, especially if a TSC2 mutation is present. Cerebellar degeneration may, however, also be secondary/acquired due to cellular damage resulting from seizure activity, the effects of anti-seizure drugs and anoxic-ischemic injury from severe seizure activity/status epilepticus. Further, prospective studies are required to identify and establish the pathogenic mechanism of cerebellar atrophy in patients with TSC.

Functional and structural networks decoupling in generalized tonic-clonic seizures and its reorganization by drugs.

To investigate potential functional and structural large-scale network disturbances in untreated patients with generalized tonic-clonic seizures (GTCS) and the effects of antiseizure drugs. In this study, 41 patients with GTCS, comprising 21 untreated patients and 20 patients who received antiseizure medications (ASMs), and 29 healthy controls were recruited to construct large-scale brain networks based on resting-state functional magnetic resonance imaging and diffusion tensor imaging. Structural and functional connectivity and network-level weighted correlation probability (NWCP) were further investigated to identify network features that corresponded to response to ASMs. Untreated patients showed more extensive enhancement of functional and structural connections than controls. Specifically, we observed abnormally enhanced connections between the default mode network (DMN) and the frontal-parietal network. In addition, treated patients showed similar functional connection strength to that of the control group. However, all patients exhibited similar structural network alterations. Moreover, the NWCP value was lower for connections within the DMN and between the DMN and other networks in the untreated patients; receiving ASMs could reverse this pattern. Our study identified alterations in structural and functional connectivity in patients with GTCS. The influence of ASMs may be more noticeable within the functional network; moreover, abnormalities in both the functional and structural coupling state may be improved by ASM treatment. Therefore, the coupling state of structural and functional connectivity may be used as an indicator of the efficacy of ASMs.

Effects of antiseizure drugs on epileptic activity and synaptic and cognitive dysfunction in transgenic mice expressing A53T human α‐synuclein

AbstractBackgroundAbnormal α‐synuclein (αS) plays an important role in the pathology of Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB). New evidence shows network hyperexcitability can accelerate synaptic and cognitive deficits in PDD and DLB. While 90% of epileptiform activity is detected during sleep in Alzheimer’s disease (AD), epileptiform activity during sleep in PDD or DLB is poorly understood. There are currently no known treatments to delay PDD or DLB progression. Although antiseizure drugs (ASDs) have been used to improve memory deficits in AD, this treatment approach has not been investigated in α‐synucleinopathies.MethodsTo explore the effect of ASDs in attenuating αS‐dependent seizure activity, we used transgenic mice expressing the A53T mutant human α‐synuclein (TgA53T) as a model of motor and cognitive decline in PDD and DLB. We have begun screening FDA‐approved ASDs using cortical electroencephalography with electromyography to examine epileptic events 24 hours before and after intraperitoneal injection. The two ASDs exhibiting the strongest efficacy in reducing epileptic activity across sleep‐wake states will be tested for effects on cognitive function and synaptic plasticity following chronic administration. We are also quantifying pathological high frequency network oscillations (HFOs), biomarkers of epileptogenesis.Results3‐4‐month‐old TgA53T mice experienced epileptiform events but had normal long‐term potentiation (LTP) and memory, indicating that epileptic activity onset precedes αS‐induced synaptic and cognitive deficits. Starting at 6 months of age, TgA53T hippocampal slices show the absence of LTP, with reduced c‐fos and calbindin and increased neuropeptide Y indicating alterations in hippocampal inhibitory circuitry. In behavioral testing, TgA53T mice exhibit impairment in fear conditioning, Y‐maze spatial recognition, and Barnes maze spatial learning and memory with age. Preliminary studies indicate lacosamide and brivaracetam as the most effective of ASDs tested in reducing epileptic myoclonus and interictal epileptiform events. We also found more HFOs in TgA53T mice and TgA53T mice with tau ablation.ConclusionSuppression of epileptic activity by ASDs would support ASDs as a novel treatment for reducing or preventing cognitive dysfunction in DLB and PDD. Furthermore, ASD‐induced reversal of synaptic and cognitive deficits would provide evidence that epileptic activity plays a causal role in αS‐dependent pathology.

Evaluation of Bone Metabolism in Children Using Antiseizure Drugs: A Single-Center Experience and Review of the Literature

AbstractThe effect of anti-seizure drugs (ASDs) on bone mineral density (BMD) is a controversial topic. This study investigated the effect of monotherapy and polytherapy drugs separately. Patients with a history of epilepsy treated with the same ASDs for more than 6 months were included in the study. Data regarding patient demographics, biochemical markers related to bone metabolism (calcium, phosphorus, alkaline phosphatase, parathyroid hormone, vitamin D), and BMD with dual-energy X-ray absorptiometry (DXA) were collected and compared. In total, 104 children with epilepsy using valproic acid (VPA), levetiracetam (LEV), carbamazepine (CBZ) alone or in combination and 22 healthy controls were evaluated. The ages of the children (64 boys, 62 girls) ranged between 2 and 17, with a mean of 9.50 ± 4.03 years. BMD or Z-scores did not differ among the monotherapy groups or between them and the polytherapy group. The lowest mean Z-score was in the VPA group but without statistical significance. Alkaline phosphatase levels were significantly higher in the group using CBZ. Calcium levels significantly differed between the groups (p = 0.001). The CBZ and LEV groups had the lowest calcium levels. However, phosphorus and vitamin D measurements did not significantly differ by ASDs used. Unfortunately, low vitamin D levels were evident in all children with epilepsy and even among controls. Physical activity, sun exposure, and calcium intake might be recommended in children treated with ACDs and in combination with additional risk factors monitoring via DXA should be considered. Further studies in a large population are necessary to judge which ASDs are more at risk to reduce bone mineralization than others.

Cannabidiol modifies the seizure expression and effects of antiseizure drugs in a rat model of recurrent severe seizures

PurposeTo evaluate the effects of cannabidiol alone or in combination with antiseizure drugs in the expression of recurrent generalized seizures in a rat model. MethodsGroup A: Male Wistar rats received 3-mercaptopropionic acid (MP) every 12 h for 5 days to induce recurrent generalized seizures. Thereafter, the animals were submitted to a crossover protocol to receive different treatments with cannabidiol, phenytoin and phenobarbital, alone and in combination. Group B: Rats were manipulated as group A, but they received cannabidiol during the induction of recurrent seizures. ResultsMinor and major seizures were induced after each MP administration. Status epilepticus (SE) detected during the last MP administrations was considered a sign of high seizure severity. Cannabidiol did not modify the expression of the MP induced seizures but reduced the prevalence of SE in both experimental groups. Phenytoin decreased the expression of major seizures but did not modify the prevalence of SE (groups A and B). Cannabidiol combined with phenytoin did not modify these effects. Phenobarbital diminished the expression of major seizures, an effect more evident when combined with cannabidiol (groups A and B). The combination of phenobarbital and cannabidiol reduced the expression of SE of group B. The mortality rate of groups A and B at the end of the crossover protocol was 30% and 9%, respectively (p=0.2). ConclusionCBD associated with appropriate antiseizure drugs reduces the severity and prevalence of generalized seizures. In contrast, CBD alone reduces the seizure severity, but does not avoid the expression of generalized seizures.