We conducted a systematic review investigating the efficacy and tolerability of adrenocorticotropic hormone (ACTH) and corticosteroids in children with epilepsies other than infantile epileptic spasm syndrome (IESS) that are resistant to anti-seizure medication (ASM). We included retrospective and prospective studies reporting on more than five patients and with clear case definitions and descriptions of treatment and outcome measures. We searched multiple databases and registries, and we assessed the risk of bias in the selected studies using a questionnaire based on published templates. Results were summarized with meta-analyses that pooled logit-transformed proportions or rates. Subgroup analyses and univariable and multivariable meta-regressions were performed to examine the influence of covariates. We included 38 studies (2 controlled and 5 uncontrolled prospective; 31 retrospective) involving 1152 patients. Meta-analysis of aggregate data for the primary outcomes of seizure response and reduction of electroencephalography (EEG) spikes at the end of treatment yielded pooled proportions (PPs) of 0.60 (95% confidence interval [CI] 0.52-0.67) and 0.56 (95% CI 0.43-0.68). The relapse rate was high (PP 0.33, 95% CI 0.27-0.40). Group analyses and meta-regression showed a small benefit of ACTH and no difference between all other corticosteroids, a slightly better effect in electric status epilepticus in slow sleep (ESES) and a weaker effect in patients with cognitive impairment and \"symptomatic\" etiology. Obesity and Cushing\'s syndrome were the most common adverse effects, occurring more frequently in trials addressing continuous ACTH (PP 0.73, 95% CI 0.48-0.89) or corticosteroids (PP 0.72, 95% CI 0.54-0.85) than intermittent intravenous or oral corticosteroid administration (PP 0.05, 95% CI 0.02-0.10). The validity of these results is limited by the high risk of bias in most included studies and large heterogeneity among study results. This report was registered under International Prospective Register of Systematic Reviews (PROSPERO) number CRD42022313846. We received no financial support.

Mutations in the SZT2 gene have been associated with developmental and epileptic encephalopathy-18, a rare severe autosomal recessive neurologic disorder, characterized by psychomotor impairment/intellectual disability, dysmorphic facial features and early onset of refractory seizures. Here we report the generation of the first induced pluripotent stem cell (iPSC) lines from a patient with treatment-resistant epilepsy, carrying compound heterozygous mutations in SZT2 (Mut1: c.498G>T and Mut2: c.6553C>T), and his healthy heterozygous parents. Peripheral blood mononuclear cells were reprogrammed by a non-integrating Sendai virus-based reprogramming system. The generated human iPSC lines exhibited expression of the main pluripotency markers, the potential to differentiate into all three germ layers and presented a normal karyotype. These lines represent a valuable resource to study neurodevelopmental alterations, and to obtain mature, pathology-relevant neuronal populations as an in vitro model to perform functional assays and test the patient’s responsiveness to novel antiepileptic treatments.

The Duke-Davidoff-Masson syndrome (DDMS) is a rare neurological condition with unknown prevalence, globally. To date, <100 cases have been reported worldwide. We report the case of an 18-year-old patient admitted for status epilepticus seizure, and who presented a right hemiparesis, body asymmetry, joints ankylosis, and mental retardation. Brain CT-scan revealed left hemisphere atrophy, skull bone thickening, and hyperpneumatization of the frontal sinuses; all consistent with DDMS. Seizures improved remarkably on Levetiracetam and Valproate. This is the first report of an unusual DDMS in Mali, and the diagnosis delay highlights the challenges for the management of these diseases in resource-limited settings.

Objective: The ketogenic diet (KD) is a high-fat, adequate-protein, and low-carb diet. Ketone bodies increase in the blood due to low carbohydrate content and high-fat content in the diet. The most important feature of the ketogenic diet is that it causes the production of ketone bodies in the liver. Ketone bodies are an alternative fuel to glucose for the brain and form the structure necessary for the cell membrane and biosynthesis of triglycerides. The ketogenic diet provides evidence on seizure control with anticonvulsant effects. In this review, the positive/negative effects of KD on seizure control, place, importance, quality of life, cognition, and behavior in the treatment of resistant epilepsy were examined.Methods: Scientific information on the subject was obtained from the literature accessed through databases such as MEDLINE, Embase, Web of Science, Cochrane Central, www.ClinicalTrials.gov, PubMed, Science Direct, and Google Scholar.Results: Although it has started to be used as a treatment method in many diseases today, the main area of effect of KD is drug-resistant epilepsy. In order for the ketogenic diet to be successful in these patients, it is necessary to choose the appropriate patient, medical treatment and diet plan, inform the patient sufficiently, and perform frequent monitoring in accordance with the follow-up criteria. It is argued that KD is one of the most effective treatments for epilepsy.Conclusion: The fact that KDs generally have a restricted diet pattern, the need for supplementation, biochemical findings and possible side effects raise the issue of diet sustainability. More clinical studies are needed to generalize.

Childhood absence epilepsy (CAE) is a common pediatric generalized epileptic syndrome. Although it is traditionally considered as a benign self-limited condition, the apparent benign nature of this syndrome has been revaluated in recent years. This is mainly due to the increasing evidence that children with CAE can present invalidating neuropsychological comorbidities that will affect them up to adulthood. Moreover, a percentage of affected children can develop drug-resistant forms of CAE. The purpose of this review is to summarize the most recent studies and new concepts concerning CAE treatment, in particular concerning drug-resistant forms of CAE. A Pubmed search was undertaken to identify all articles concerning management and treatment of CAE, including articles written between 1979 and 2021. Traditional anticonvulsant therapy of CAE that is still in use is based on three antiepileptic drugs: ethosuximide which is the drug of choice, followed by valproic acid and lamotrigine. In the case of first line treatment failure, after two monotherapies it is usual to start a bi-therapy. In the case of absence seizures that are refractory to traditional treatment, other antiepileptic drugs may be introduced such as levetiracetam, topiramate and zonisamide.

UNASSIGNED: Epilepsy is characterized as a tendency towards recurrent seizures and it is a significant health problem in the world and one of the most common severe neurologic disorders among children. This study aims to evaluate the outcome of magnetic resonance imaging in determining the etiology in patients with refractory epilepsy and to reveal pathologies that may have the potential to be treated with methods, such as epileptic surgery.
UNASSIGNED: Data were obtained from the patient files of the patients diagnosed with epilepsy and monitored for at least two years between 01.01.2009-12.31.2012 in the Uludag Faculty of Medicine, the Division of the Pediatric Neurology. File records of the patients, age, sex and MRI findings of the patients were recorded.
UNASSIGNED: One hundred twenty were girls (49%) and 125 were male (51%) of the cases. The age range ranged from 1 to 18 years and the median value was 8.3 (1-18) years. One hundred twenty of the 245 patients who met the diagnostic criteria for resistant epilepsy was found as well controlled. In patients with resistant epilepsy, the findings of these two groups of patients were compared concerning MR findings. Among all patients, 154 (62.8%) patients were found to have MR pathology. Of these patients, 83 (53.9%) were in the resistant group and 71 (46.1%) were in the well-controlled group. There was no significant difference in the presence of MR findings between the two groups (p=0.354). The highest incidence (24.8%) of the encephalomalacia in patients in the resistant group may explain the association of perinatal hypoxia with resistance development.
UNASSIGNED: If patients with epilepsy can be predicted early in the disease, which group of the patients will not respond well to medical treatment; unlike other patients, different treatment modalities, such as antiepileptic use, vagal nerve stimulation, ketogenic diet and epilepsy surgery, can be applied to this group of the patients. We think that clinicians can guide the planning of treatment of the MR findings.

Treatment resistant epileptic encephalopathy (EE) in childhood in a significant amount due to genetic damage or congenital abnormalities of the brain. The literature described a rare microcephalic-capillary malformation syndrome (Microcephaly-capillary malformation, MIC-CAP), manifested from the first month of life by the early onset of treatment-resistant epilepsy, severe progressive microcephaly, spastic tetraparesis, severe delay in psychomotor development, multiple, small-sized capillary angiomas on the body and underdevelopment of the fingers. The boy was diagnosed with a previously described variant of the nucleotide sequence in exon 2 of the STAMBP chr2 gene:74058171rs781694797 188A>G in the homozygous state, leading to the replacement of the amino acid p.Tyr63Cys in 63 protein position. This type of mutation chr2:74058171rs781694797 188A>G was also detected in the father and mother in the heterozygous state. This variant is considered as pathogenic, related to the patient\'s phenotype. The article presents a literature review of this syndrome and the case report.
Резистентные к лечению эпилептические энцефалопатии в детском возрасте в большинстве случаев обусловлены генетическими поломками или врожденными аномалиями развития головного мозга. В литературе описан редкий микроцефально-капиллярный мальформационный синдром (Microcephaly-capillary malformation, MIC-CAP), проявляющийся с первого месяца жизни ранним началом резистентной к терапии эпилепсии, тяжелой прогрессирующей микроцефалией, спастическим тетрапарезом, грубой задержкой психомоторного развития, множественными малыми капиллярными ангиомами на туловище и недоразвитием пальцев. У мальчика был диагностирован ранее не описанный вариант нуклеотидной последовательности во 2-м экзоне гена STAMBP chr2:74058171rs781694797 188A>G в гомозиготном состоянии, приводящий к замене аминокислоты p.Tyr63Cys в 63-й позиции белка. Данный вид мутации chr2:74058171rs781694797 188A>G также был выявлен у отца и матери в гетерозиготном состоянии. Данный вариант рассматривается как патогенный, имеющий отношение к фенотипу пациента. В статье приведен обзор литературы с описаниями данного синдрома и собственное наблюдение.

The refractory epilepsy adds to the global burden of epilepsy as about 25 % of all patients with epilepsy present drug-resistant epilepsy. The P-glycoprotein (P-gp) plays a vital role in the mechanism of resistance in epilepsy. The AED levels in the brain are regulated by the P-gp transport. The upregulation of P-gp results in low concentration of AEDs inside the brain parenchyma and thus leads to resistance. There are three main conditions which lead to decrease transport of AEDs in refractory epilepsy. First being AEDs as substrate of P-gp; secondly, the elevated expression of P-gp in patients with drug resistant epilepsy as compared to drug-responsive patients; thirdly, the low brain AED concentration in refractory epilepsy in comparison to drug-responsive epilepsy. Therefore, determination of P-gp substrate should be a criterion for the selection of new AED for management of refractory epilepsy. This review highlights various tools which help in identification of P-gp substrates and also illustrates a concept of using various novel non-P-gp substrates which can cross the blood brain barrier and leads to enhanced accumulation inside the brain. Hence, these non P-gp substrates can be used as an add on treatment for the management of resistant epilepsy.

Antiepileptic drugs (AEDs) are routinely withdrawn during long-term video-electroencephalography (EEG) monitoring (LTM), to record sufficient number of seizures. The efficacy of rapid and slow AED taper has never been compared in a randomized control trial (RCT), which was the objective of this study.
In this open-label RCT, patients aged 2-80 years with drug-resistant epilepsy (DRE) were randomly assigned (1:1) to rapid and slow AED taper groups. Outcome assessor was blinded to the allocation arms. Daily AED dose reduction was 30% to 50% and 15% to <30% in the rapid and slow taper groups, respectively. The primary outcome was difference in mean duration of LTM between the rapid and slow AED taper groups. Secondary outcomes included diagnostic yield, secondary generalized tonic-clonic seizure (GTCS), 4- and 24- hour seizure clusters, status epilepticus, and need for midazolam rescue treatment. The study was registered with Clinical Trial Registry-India (CTRI/2016/08/007207).
One hundred forty patients were randomly assigned to rapid (n = 70) or slow taper groups (n = 70), between June 13, 2016 and February 20, 2017. The difference in mean LTM duration between the rapid and slow taper groups was -1.8 days (95% confidence interval [CI] -2.9 to -0.8, P = .0006). Of the secondary outcome measures, time to first seizure (2.9 ± 1.7 and 4.6 ± 3.0 days in the rapid and slow taper groups respectively, P = .0002) and occurrence of 4-hour seizure clusters (11.9% and 2.9% in the rapid and slow taper groups, respectively, P = .04) were statistically significant. None of the other safety variables were different between the 2 groups. LTM diagnostic yield was 95.7% and 97.1%, in rapid and slow taper groups respectively (P = .46).
Rapid AED tapering has the advantage of significantly reducing LTM duration over slow tapering, without any serious adverse events.

BACKGROUND: To date, an increasing number of pet owners, especially in the USA, are using cannabis-derived products containing generally delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) to help their animals\' health. Unfortunately, studies on the clinical use of cannabinoids in veterinary medicine are still limited, and the application of analytical methodologies for the determination of cannabinoids in animal (especially dog) biological matrices such as plasma, is still missing.
METHODS: A reliable, fast, accurate, simple gas chromatography-mass spectrometry (GC-MS) method was developed and validated for the quantification of THC and CBD in plasma samples of eight dogs under therapeutic treatment for epilepsy and receiving oral administration of medical cannabis (Bediol).
RESULTS: The method was linear for both the analytes under investigation with coefficients of determination (r2) of at least 0.99. Absolute analytical recovery (mean ± SD) ranged from 80.6 ± 6.2% for THC and 81.7 ± 4.3% for CBD. The matrix effect showed less than 10% analytical suppression due to endogenous substances for both the analytes. The intra-assay and inter-assay precision values ranged from 4.9% to 12.7%, and from 5.2% to 8.7% respectively. The intra-assay and inter-assay accuracy values ranged from 2.3% to 9.6% and from 3.4% to 13.0%, respectively.
CONCLUSIONS: The validated method was successfully applied to real samples; moreover, to assess the potential of the method applicability and robustness in future veterinary clinical studies on cannabinoids therapy, we attempted to follow the kinetic of THC and CBD in the plasma of two dogs under therapy at different times after Bediol administration.