Antiseizure Medicines Research Articles

Characterizing Cerebral Imaging and Electroclinical Features of Five Pseudohypoparathyroidism Cases Presenting with Epileptic Seizures.

Objective To characterize the cerebral imaging and electroclinical features and investigate their etiological contributions to seizures in pseudoparathyroidism (PHP). Methods The clinical symptoms, biochemical imaging by magnetic resonance imaging (MRI) and computed tomography (CT) tests, and electroencephalogram (EEG) manifestations of five PHP patients with seizures were retrospectively collected and analyzed. Results Physical examination showed an average stature in cases 2~4 and short stature in cases 1 and 5. X-ray tests suggested ectopic calcification in four patients. The seizures in four cases were effectively controlled with antiseizure medicines (ASMs). Cerebral CT scans showed extensive brain calcifications in the bilateral basal ganglia (all five cases), cerebellum (cases 1, 3, and 5), thalamus (case 4), and cerebral cortex. Cerebral MRI showed short T1 signals mainly in the basal ganglia. EEG records revealed focal EEG abnormalities, including abnormal slow waves and epileptiform discharges, mainly over the temporal and frontal lobes. The brain areas with focal EEG abnormalities and calcification did not always coincide. Conclusion The seizures in PHP can be focal to bilateral tonic–clonic. ASMs are effective in epilepsy combined with PHP. Intracranial calcification is not a reliable etiological cause of epilepsy in PHP patients.

Risk Factors and Incidence of Epilepsy after Severe Traumatic Brain Injury.

We determined the incidence of post-traumatic epilepsy after severe traumatic brain injury. Of 392 patients surviving to discharge, cumulative incidence of post-traumatic epilepsy was 25% at 5 years and 32% at 15 years, an increase compared with historical reports. Among patients with one late seizure (>7 days post-trauma), the risk of seizure recurrence was 62% after 1 year and 82% at 10 years. Competing hazards regression identified age, decompressive hemicraniectomy, and intracranial infection as independent predictors of post-traumatic epilepsy. Patients with severe traumatic brain injury and a single late post-traumatic seizure will likely require long-term antiseizure medicines. ANN NEUROL 2022;92:663-669.

Can Old Animals Reveal New Targets? The Aging and Degenerating Brain as a New Precision Medicine Opportunity for Epilepsy.

Older people represent the fastest growing group with epilepsy diagnosis. For example, cerebrovascular disease may underlie roughly 30–50% of epilepsy in older adults and seizures are also an underrecognized comorbidity of Alzheimer's disease (AD). As a result, up to 10% of nursing home residents may take antiseizure medicines (ASMs). Despite the greater incidence of epilepsy in older individuals and increased risk of comorbid seizures in people with AD, aged animals with seizures are strikingly underrepresented in epilepsy drug discovery practice. Increased integration of aged animals into preclinical epilepsy drug discovery could better inform the potential tolerability and pharmacokinetic interactions in aged individuals as the global population becomes increasingly older. Quite simply, the ASMs on the market today were brought forth based on efficacy in young adult, neurologically intact rodents; preclinical information concerning the efficacy and safety of promising ASMs is not routinely evaluated in aged animals. Integrating aged animals more often into basic epilepsy research may also uncover novel treatments for hyperexcitability. For example, cannabidiol and fenfluramine demonstrated clear efficacy in syndrome-specific pediatric models that led to a paradigm shift in the perceived value of pediatric models for ASM discovery practice; aged rodents with seizures or rodents with aging-related neuropathology represent an untapped resource that could similarly change epilepsy drug discovery. This review, therefore, summarizes how aged rodent models have thus far been used for epilepsy research, what studies have been conducted to assess ASM efficacy in aged rodent seizure and epilepsy models, and lastly to identify remaining gaps to engage aging-related neurological disease models for ASM discovery, which may simultaneously reveal novel mechanisms associated with epilepsy.

Trends in the prescription of anti-seizure medicines for pregnant women outpatients with epilepsy during 2016–2020 in Japan

PurposeThe temporal trends in prescribing anti-seizure medicines (ASMs) for pregnant women with epilepsy are unclear. In this study, we investigated the trends in ASM prescriptions in pregnant Japanese women with epilepsy. MethodsAdministrative data (as of December 2021), pertaining to Japanese pregnant outpatient women with epilepsy, aged 16–49 years, who visited hospitals between January 1, 2016 and December 31, 2020 were included in the study. Annual prescription trends in ASMs during this period were calculated based on the proportions. The Cochran–Armitage trend test was used to evaluate the proportion of prescriptions for each ASM. ResultsThe numbers of pregnant women with epilepsy were 404, 421, 368, 378, 386 for the years 2016, 2017, 2018, 2019, and 2020, respectively. As of 2020, levetiracetam had the highest proportion of prescriptions, followed by lamotrigine and valproic acid. From 2016 to 2020, the proportions of levetiracetam and lamotrigine prescribed for pregnant women with epilepsy have increased significantly from 19.1% to 30.8% and from 12.1% to 18.4%, respectively. In contrast, there was no temporal change in the proportion of valproic acid prescribed, which was 12.4% in 2016 and 10.1% in 2020. ConclusionOur findings suggest that the trends in the prescription of ASMs in Japanese pregnant women outpatients with epilepsy have shifted toward ASMs with a lower teratogenic risk.

Bacillus subtilis plays a role in the inhibition of transporter ABCB1 in Caco-2 cells

BackgroundsThe mechanism of drug-resistant epilepsy has been incompletely understood, and the transporter hypothesis is one of the most cited theories. The association between gut microbiome and epilepsy is increasingly recognized but the mechanism remains unclear. We hypothesize that gut microbiome plays a role of pharmacokinetics of antiseizure medicines (ASMs) through transporters at the host-microbe interface. This study aimed to screen the key subspecies of gut microbiota related to drug-resistant epilepsy and explore their effects on the ASMs resistance mechanism through the regulation of transporter ATP-binding cassette B1 (ABCB1). MethodsThree groups of participants were designed, 10 drug-resistant epilepsy patients (DR group), 10 non-drug-resistant epilepsy patients (NDR group), and 19 healthy controls (Control group). Fresh stool samples were collected. Based on the 16S rRNA sequencing results of their fecal samples, we selected the Bacillus subtilis (B. subtilis) to explore its effect on the ASMs efflux mediated by transporter ABCB1 whose expression were detected through quantitative PCR and Western blot analysis in Caco-2 cell model. Further, we conducted the Rhodamine 123 accumulation assay to evaluate the activity of the transporter ABCB1 in Caco-2 cell and the high-performance liquid chromatography (HPLC) to measure the concentrations of ASMs. ResultsWe found that the Phylum Firmicutes were enriched in the patients with drug-resistant epilepsy (70.82%) and picked up B. subtilis as the key type of bacteria relevant to drug-resistant epilepsy. The B. subtilis not only downregulated the expression level and the efflux activity of ABCB1 in Caco-2 cells treated with ASMs (P < 0.01), but also reduced the carbamazepine efflux in the Caco-2 cells (P < 0.05). ConclusionOur study identified B. subtilis as the key bacterial type associated with patients affected by drug-resistant epilepsy and revealed that it also ameliorated resistance to ASMs by downregulating the transporter ABCB1.

Clinical characteristics and treatment experience of individuals with SCN8A developmental and epileptic encephalopathy (SCN8A-DEE): Findings from an online caregiver survey.

SCN8A developmental epileptic encephalopathy (SCN8A-DEE) is a rare and severe genetic epilepsy syndrome characterized by early-onset developmental delay, cognitive impairment, and intractable seizures. SCN8A gene variants are associated with a broad phenotypic spectrum and variable disease severity. A caregiver survey, solicited by the advocacy group The Cute Syndrome Foundation (TCSF), was conducted to gather information on the demographics/disease presentation, seizure history, and treatment of patients with SCN8A-related epilepsies. A 36-question online survey was developed to obtain de-identified data from caregivers of children with SCN8A-related epilepsy. The survey included questions on genetic diagnosis, disease manifestations/comorbidities, seizure severity/type, current/prior use of antiseizure medicines (ASMs), and best/worst treatments per caregiver perception. In total, 116 survey responses (87 USA, 12 Canada, 12 UK, 5 Australia) were quantitatively analyzed. Generalized tonic/clonic was the most common seizure type at onset and time of survey; absence and partial/focal seizures were also common. Most patients (77%) were currently taking ≥2 ASMs; 50% had previously tried and stopped ≥4 ASMs. Sodium channel blockers (oxcarbazepine, phenytoin, lamotrigine) provided the best subjective seizure control and quality of life. The SCN8A-DEE patient population is heterogeneous in seizure characteristics and ASMs taken and is difficult to treat, with high seizure burden and multiple comorbidities. The high proportion of patients who previously tried and stopped ASMs indicates large unmet treatment need. Further collaboration between families, caregivers, patient advocates, clinicians, researchers, and industry can increase awareness and understanding of SCN8A-related epilepsies, improve clinical trial design, and potentially improve patient outcomes.

NBI-921352, a first-in-class, NaV1.6 selective, sodium channel inhibitor that prevents seizures in Scn8a gain-of-function mice, and wild-type mice and rats.

NBI-921352 (formerly XEN901) is a novel sodium channel inhibitor designed to specifically target NaV1.6 channels. Such a molecule provides a precision-medicine approach to target SCN8A-related epilepsy syndromes (SCN8A-RES), where gain-of-function (GoF) mutations lead to excess NaV1.6 sodium current, or other indications where NaV1.6 mediated hyper-excitability contributes to disease (Gardella and Møller, 2019; Johannesen et al., 2019; Veeramah et al., 2012). NBI-921352 is a potent inhibitor of NaV1.6 (IC500.051 µM), with exquisite selectivity over other sodium channel isoforms (selectivity ratios of 756 X for NaV1.1, 134 X for NaV1.2, 276 X for NaV1.7, and >583 Xfor NaV1.3, NaV1.4, and NaV1.5). NBI-921352is a state-dependent inhibitor, preferentially inhibiting inactivatedchannels. The state dependence leads to potent stabilization of inactivation, inhibiting NaV1.6 currents, including resurgent and persistent NaV1.6 currents, while sparing the closed/rested channels. The isoform-selective profile of NBI-921352 led to a robust inhibition of action-potential firing in glutamatergic excitatory pyramidal neurons, while sparing fast-spiking inhibitory interneurons, where NaV1.1 predominates. Oral administration of NBI-921352 prevented electrically induced seizures in a Scn8a GoF mouse,as well as in wild-type mouse and ratseizure models. NBI-921352 was effective in preventing seizures at lower brain and plasma concentrations than commonly prescribed sodium channel inhibitor anti-seizure medicines (ASMs) carbamazepine, phenytoin, and lacosamide. NBI-921352 waswell tolerated at higher multiples of the effective plasma and brain concentrations than those ASMs. NBI-921352 is entering phase II proof-of-concept trials for the treatment of SCN8A-developmental epileptic encephalopathy (SCN8A-DEE) and adult focal-onset seizures.

Metabolomics Provides Novel Insights into Epilepsy Diagnosis and Treatment: A Review.

Epilepsy is one of the most common diseases of the central nervous system. The diagnosis of epilepsy mainly depends on electroencephalograms and symptomatology, while diagnostic biofluid markers are still lacking. In addition, approximately 30% of patients with epilepsy (PWE) show a poor response to the currently available anti-seizure medicines. An increasing number of studies have reported alterations in the blood, brain tissue, cerebrospinal fluid and urine metabolome in PWE and animal models of epilepsy. The aim of this review was to identify potential metabolic biomarkers and pathways that might facilitate diagnostic, therapeutic and prognostic determination in PWE and the understanding of the pathogenesis of the disease. The PubMed and Embase databases were searched for metabolomic studies of PWE and epileptic models published before December 2020. The study objectives, types of models and reported differentially altered metabolites were examined and compared. Pathway analyses were performed using MetaboAnalyst 5.0 online software. Thirty-five studies were included in this review. Metabolites such as glutamate, lactate and citrate were disturbed in both PWE and epileptic models, which might be potential biomarkers of epilepsy. Metabolic pathways including alanine, aspartate and glutamate metabolism; glycine, serine and threonine metabolism; glycerophospholipid metabolism; glyoxylate and dicarboxylate metabolism; and arginine and proline metabolism were involved in epilepsy. These pathways might play important roles in the pathogenesis of the disease. This review summarizes metabolites and metabolic pathways related to epilepsy and provides a novel perspective for the identification of potential biomarkers and therapeutic targets for epilepsy.

New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) of unknown aetiology: A comparison of the incomparable?

PurposeThe discussion is ongoing whether new-onset refractory status epilepticus (NORSE) in adults and febrile infection-related epilepsy syndrome (FIRES) in children are one syndrome if the aetiology is unknown. In this study we will compare an adult cohort with NORSE and a paediatric cohort with FIRES in order to determine if they are similar or different. MethodsWe retrospectively compared 18 adults with NORSE versus 48 children with FIRES, both cohorts without identifiable cause despite extensive investigations. We analyzed demographic and clinical data using Mann-Whitney-U and χ2- tests. ResultsNORSE affected more women (78% vs. 42%; P = 0.009) than in FIRES. Median acute hospital stay was longer in FIRES (35 days [interquartile range, IQR=36] vs. 20 days [IQR=19]; P<0.001). FIRES was treated more frequently with coma therapy (82% vs. 28%; P<0.001) and with a higher median number of antiseizure medicines (7 [IQR=5] vs. 4 [IQR=2]; P<0.001). Children with FIRES showed a higher cerebrospinal fluid (CSF) cell count (10 cells/μl; P = 0.002) but a lower CSF protein level than adults with NORSE (48 mg/dl; P = 0.028). Immunotherapy was administered more frequently in FIRES (73% vs. 22%; P<0.001) than in NORSE. Group differences in number of antiseizure medicines after hospital stay (P = 0.229) and in overall mortality (P = 0.327) were not significant. ConclusionIn our explorative comparison, differences prevailed. NORSE and FIRES should be compared prospectively in age-matched cohorts.

Current Concepts in the Management of Idiopathic Generalized Epilepsies.

Idiopathic generalized epilepsies (IGEs) are a group of epilepsies characterized by an underlying genetic predisposition and a good response to antiseizure medicines (ASMs) in the majority of the patients. Of the various broad-spectrum ASMs, valproate is the most effective medicine for the control of seizures in IGEs. However, with the availability of many newer ASMs and evidence showing the high teratogenic potential of valproate, the choice of ASMs for IGEs has become increasingly difficult, especially in women of the child-bearing age group. In this article, we review the current evidence regarding the efficacy and safety of various ASMs in patients with IGEs and provide practical guidelines for choosing appropriate ASMs in various subgroups of patients with IGEs.

Epilepsy: management

Pharmacy teams in both primary and secondary care can support people with epilepsy, the vast majority of whom will be taking one or more anti-seizure medicines (ASMs) to manage their condition. This article is the second in a series and focuses on the management of epilepsy. Information relating to symptoms and diagnosis can be found […]

Influence of nanoparticle size on blood-brain barrier penetration and the accumulation of anti-seizure medicines in the brain.

Anti-seizure medicines constitute a common yet important modality to treat epilepsy. However, some of them are associated with serious side effects including hepatotoxicity and hypersensitivity. Furthermore, the blood-brain barrier (BBB) is an insurmountable obstacle for brain drug delivery. Fortunately, the introduction of the nanoparticles for drug delivery is a feasible approach to overcome these obstacles. Encapsulating drugs into nanoparticles and delivering them to specific sites shows great potential for improving the efficiency of drug delivery and reducing systemic toxicity. Several in vivo studies have investigated the effect of nanoparticle size on biodistribution in mice, but very few have investigated its effects on efficient drug delivery while crossing the BBB. Therefore, we designed a methoxy poly(lactide-co-glycolide)-b-poly(ethylene glycol) methyl ether (mPEG-PLGA) nanoparticle delivery system and explored the cell uptake efficiency of nanoparticles with different sizes and their ability to penetrate the BBB while carrying carbamazepine (CBZ). CBZ-loaded nanoparticles could significantly reduce the cytotoxicity of CBZ to L929 cells at high concentrations. Results from the endocytosis experiment involving human cerebral microvessel endothelial cell/D3 showed that the DiR-loaded mPEG5K-PLGA10K nanoparticles possessed the highest cell uptake efficiency. The endocytosis efficiency was 90% at 30 min, which far exceeded that of the other groups. Moreover, similar results were obtained from subsequent experiments where fluorescence images of the isolated organs of the mice were acquired. To summarize, our study demonstrated that drug delivery to the brain using nanocarriers is size dependent. Nanoparticles with the smallest particle size can be internalized more effectively, and easily penetrate the BBB, and accumulate in the brain.

Alpha-lipoic acid analogues in the regulation of redox balance in epilepsy: A molecular docking and simulation study

ObjectiveOxidative stress is one of the pathophysiological mechanisms implicated in drug-resistant epilepsy. Recurrent seizures and prolonged treatment with anti-seizure medicines (ASMs) can produce reactive oxygen species (ROS) resulting in neuronal cell damage, cell toxicity, and cell death. This damage may contribute to the loss of efficacy of anti-seizure medicines. Add-on therapy with antioxidants, neuroimmunophilins, and polyphenols may thus be beneficial in drug-resistant epilepsy. In vitro and in vivo studies have shown a significant improvement in drug efficacy and seizure suppression using co-treatment of anti-seizure medication with naturally available antioxidants including alpha-lipoic acid (α-lipoic acid) from walnut; however, the underlying mechanisms of action remain to be fully understood. MethodsWe undertook molecular docking and molecular dynamics simulations to determine whether alpha-lipoic acid and related analogues interacted with the human manganese superoxide dismutase (MnSOD) protein, a member of the oxidative metabolic pathway. The 3D structure of the compounds and the protein were retrieved from protein and chemical databases, binding sites were identified and ligand-protein interactions were performed. ResultsAlpha-lipoic acid and various analogues docked within a human MnSOD binding region. Docking results were validated by molecular dynamic simulation. The CMX-2043 analogue showed strong binding with MnSOD compared to alpha-lipoic acid and other analogues. SignificanceOur findings provide new insights into additional mechanisms of action, which may in part, account for the antioxidant properties associated with alpha-lipoic acid and related analogues. The results support further in vitro and in vivo evaluation of these compounds to better understand their potential as add-on therapy for ASM treatment in epilepsy.

Novel treatments in epilepsy guided by genetic diagnosis.

In recent years, precision medicine has emerged as a new paradigm for improved and more individualized patient care. Its key objective is to provide the right treatment, to the right patient at the right time, by basing medical decisions on individual characteristics, including specific genetic biomarkers. In order to realize this objective researchers and physicians must first identify the underlying genetic cause; over the last 10years, advances in genetics have made this possible for several monogenic epilepsies. Through next generation techniques, a precise genetic aetiology is attainable in 30-50% of genetic epilepsies beginning in the paediatric age. While committed in such search for novel genes carrying disease-causing variants, progress in the study of experimental models of epilepsy has also provided a better understanding of the mechanisms underlying the condition. Such advances are already being translated into improving care, management and treatment of some patients. Identification of a precise genetic aetiology can already direct physicians to prescribe treatments correcting specific metabolic defects, avoid antiseizure medicines that might aggravate functional consequences of the disease-causing variant or select the drugs that counteract the underlying, genetically determined, functional disturbance. Personalized, tailored treatments should not just focus on how to stop seizures but possibly prevent their onset and cure the disorder, often consisting of seizures and its comorbidities including cognitive, motor and behaviour deficiencies. This review discusses the therapeutic implications following a specific genetic diagnosis and the correlation between genetic findings, pathophysiological mechanisms and tailored seizure treatment, emphasizing the impact on current clinical practice.

Completion Posterior Quadrant Disconnection After Failed Temporal Lobectomy: 2-Dimensional Operative Video

Epilepsy is a chronic seizure disorder that affects about 1% of the global population.1 When seizure freedom cannot be obtained solely through antiseizure medicines (ASMs), the condition is termed medically refractory epilepsy (MRE).2,3 Though posterior quadrant disconnection (PQD) is underutilized in our experience, it is a highly effective surgical procedure for MRE restricted to the temporal, parietal, and/or occipital lobes.4-12 In this operative video, we demonstrate a right-sided completion PQD following failed temporal lobectomy in an 8-yr-old female with focal MRE. We review technical nuances, including (1) extension/revision of prior scalp incision, (2) placement of subdural strip for the identification of phase reversal and central sulcus, (3) disconnection of parietal and occipital lobes, (4) extension of the corticectomy to the pia overlying the falcotentorial junction and into the prior temporal lobectomy defect, and (5) posterior disconnection of the corpus callosum. Postoperatively, the patient experienced subtle left-arm weakness and central fever, both of which resolved. An external ventricular drain (EVD) was placed in the ventricle/operative cavity and left for 3 to 4 d until the draining cerebrospinal fluid (CSF) cleared. As of 3-mo follow-up, she has been seizure-free without complications. In summary, PQD is a safe and effective treatment option for MRE that can be utilized not only as an initial operation but also after failed surgery. Appropriate patient consent was obtained to perform this procedure and present this clinical case and surgical video for academic purposes. Image at 4:00 licensed under CC BY-2.5, 2006, modified from http://upload.wikimedia.org/wikipedia/commons/7/70/Lateral_head_skull.jpg (flipped and rotated). Image at 4:42, Public Domain: Gray H. Anatomy of the Human Body. 1918. Bartleby.com, https://commons.wikimedia.org/wiki/File:Lobes_of_the_brain_NL.svg; flipped, modified. Image at 6:42, Public Domain: House EL, Pansky B. A Functional Approach to Neuroanatomy. 1960. McGraw-Hill Book Company; https://upload.wikimedia.wikipedia.commons/5/52/Lawrence_1960_2.3.png; modified.

Disorders of Neuronal Migration/Organization Convey the Highest Risk of Neonatal Onset Epilepsy Compared With Other Congenital Brain Malformations

BackgroundAlthough seizures in neonates are common and often due to acute brain injury, 10-15% are unprovoked from congenital brain malformations. A better understanding of the risk of neonatal-onset epilepsy by the type of brain malformation is essential for counseling and monitoring. MethodsIn this retrospective cohort study, we evaluated 132 neonates with congenital brain malformations and their risk of neonatal-onset epilepsy. Malformations were classified into one of five categories based on imaging patterns on prenatal or postnatal imaging. Infants were monitored with continuous video EEG (cEEG) for encephalopathy and paroxysmal events in addition to abnormal neuroimaging. ResultsSeventy-four of 132 (56%) neonates underwent EEG monitoring, and 18 of 132 (14%) were diagnosed with neonatal-onset epilepsy. The highest prevalence of epilepsy was in neonates with disorders of neuronal migration/organization (9/34, 26%; 95% confidence interval [CI] = 13-44%), followed by disorders of early prosencephalic development (6/38, 16%; 95% CI = 6-31%), complex total brain malformations (2/16, 13%; 95% CI = 2-38%), and disorders of midbrain/hindbrain malformations (1/30, 3%; 95% CI = 0-17%). Of neonates with epilepsy, 5 of 18 (28%) had only electrographic seizures, 13 of 18 (72%) required treatment with two or more antiseizure medicines (ASMs), and 7 of 18 (39%) died within the neonatal period. ConclusionOur results demonstrate that disorders of neuronal migration/organization represent the highest-risk group for early-onset epilepsy. Seizures are frequently electrographic only, require treatment with multiple ASMs, and portend a high mortality rate. These results support American Clinical Neurophysiology Society recommendations for EEG monitoring during the neonatal period for infants with congenital brain malformations.

Tolerability of antiseizure medicines using Lithuanian version of the Liverpool Adverse Events Profile

ObjectivesTo develop and validate a Lithuanian version of the Liverpool Adverse Events Profile (LT-LAEP), and to evaluate the main demographic, clinical, and pharmacological determinants of its score. Materials and methodsWe developed the LT-LAEP and examined its psychometric properties. People with epilepsy (PWE) were asked to fill in the LT-LAEP, the Generalized Anxiety Disorder scale-7 (GAD-7), the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), and a questionnaire addressing key demographic and clinical information. Antiseizure medicine (ASM) burden was expressed as a number of ASM and total drug load. Multiple linear regression analysis was used to determine the influence of various variables on LAEP results. ResultsThe data of 157 participants with the established diagnosis of epilepsy and stable ASM regimen were included in the final analysis. The mean LT-LAEP score was 48.72 ± 13.65. High internal consistency (Cronbach’s α = 0.912) and test–retest reliability (ICC = 0.801) were demonstrated. The most common adverse effects (AEs) were tiredness (24.8%) and memory problems (23.6%). Lithuanian version of the Liverpool Adverse Events Profile score significantly correlated with NDDI-E (r = 0.635, p < 0.001) and GAD-7 (r = 0.640, p < 0.001) scores. The correlation between LT-LAEP score and total drug load was weak (r = 0.243, p = 0.002). The significant predictors of higher LT-LAEP score were female sex (β = −4.768, p = 0.003), higher seizure frequency (β = 4.757, p < 0.001), and higher NDDI-E (β = 1.457, p < 0.001) and GAD-7 scores (β = 0.610, p = 0.007) (F(4,152) = 43.975, R2 = 0.536, p < 0.001). ConclusionsThe LT-LAEP is a reliable and valid instrument for the evaluation of the AEs of ASM. A higher score of LT-LAEP is predicted by female sex, seizure frequency, and anxiety and depression levels rather than total drug load.

The “newest” AEDS - are they gamechangers?

The newest ASMs: Are they gamechangers? Much has been written recently about the failure of several decades worth of newly approved antiseizure medicines (ASMs) to be able to reduce the number of treatment resistant epilepsy patients, despite the approval of over a dozen new therapies. Recent studies have suggested that the likelihood that epilepsy will be resistant to anti-seizure medicines has changed very little over the last several decades. Clinicians turned to surgery and devices as the best tools for providing a substantial seizure reduction. However, in the last several years there appears to finally be evidence that substantial progress is possible from ASMs. Some of this turnaround has arisen from a renewed interest in treatment of orphan epilepsies associated with developmental and epileptic encephalopathy (DEE). One example of a “gamechanging” ASM is fenfluoramine, which has been approved for the treatment of Dravet syndrome. Cenobamate, recently approved for use in focal epilepsy, also performed extremely well, both in short-term randomized placebo-controlled trials, and in long-term follow-up studies, where observed seizure freedom rates of over 20% at the highest dose far surpass the seizure freedom rates seen with devices such as the responsive neurostimulator and the deep brain stimulator. These recent drug approvals have provided an excellent demonstration that we should not count out the benefits of anti-seizure medications in the fight to eliminate treatment resistant epilepsy. The next few years will bring trials of disease modifying treatments including precision therapies targeted at epilepsies caused by specific gene mutations.

Treatment outcomes in drug resistant juvenile myoclonic epilepsy: Valproate resistance may not be the end of the road

ObjectiveTo determine treatment responses to various antiseizure medicines (ASMs) in patients with drug resistant juvenile myoclonic epilepsy (DRJME) MethodsWe reviewed records of all JME patients attending epilepsy clinics at 5 centers during a 5-year period. We used International Consensus Criteria to diagnose JME and International League Against Epilepsy Criteria to define drug resistance and sustained seizure freedom. We only used broad spectrum medicines which included valproate, lamotrigine, topiramate, levetiracetam, clobazam, phenobarbitone, clonazepam, and zonisamide. We considered an ASM successful if patient achieved seizure freedom within 3 months of attaining maintenance dose. ResultsWe studied 116 patients (61 males) with DRJME. At terminal followup, 82 (70.7%) patients had achieved sustained seizure freedom with a mean followup of 3.2 ± 1.3 years after last dose change. In patients where valproate failed as first- or second-line ASM (n=70; 60.3%), 49(70%) became seizure-free. In this group, 33(67%) patients became seizure-free after addition of lamotrigine. Success rate of lamotrigine and valproate combination was 69% as compared to 9% with all other combinations (p = 0.001). In patients who were not exposed to valproate as initial therapy (n=46), 33 (71.7%) became seizure-free, 30 (91%) after adding valproate. At last follow-up, 75 (90%) seizure-free patients were receiving valproate including 45 (55%) patients with a combination of valproate and lamotrigine. Only one of 24 patients became seizure-free after failing valproate and lamotrigine combination. ConclusionSeizure freedom can be achieved in two-thirds of patients with DRJME. A combination of valproate and lamotrigine is the most effective duotherapy.

Impact of COVID-19 pandemic on pediatric patients with epilepsy in Jordan: The caregiver perspective

ObjectivesThe recent COVID-19 pandemic has disrupted care systems around the world. We assessed the impact of COVID-19 lockdown on the care of pediatric patients with epilepsy in Jordan. Potential predictors for seizure control during COVID-19 outbreaks were investigated. MethodsA cross- sectional survey was conducted on pediatric patients with epilepsy in Jordan, between January and February 2021, via online questionnaires. The collected data included demographic information, epilepsy-related characteristics, views of caregivers and changes in seizure control during COVID-19 outbreak. ResultsA total number of 672 subjects were screened, 276 were eligible, and 154 completed the questionnaire adequately. Two thirds of caregivers (66.2%) reported that the COVID -19 outbreaks prevented their child from getting proper epilepsy care and 28.6% reported difficulty giving the drugs to their child on time because of loss of daily routine. In addition, more than half (55.8%) reported difficulty obtaining antiseizure medicines (ASMs). On the other hand, 77.3% of caregivers reported that seizure status remained unchanged or improved for their children during the COVID-19 and 22.7% reported worsened seizure control. The number of antiseizure medicines taken by patients (p < 0.001), age (p = 0.032), residency area (p = 0.013) and the difficulty in giving the medicine during COVID-19 pandemic (p = 0.002) were the major factors influencing the seizure worsening experienced by patients. ConclusionAlmost one of every five patients reported worsened seizure control during the outbreak of COVID-19 in Jordan. Moreover, two thirds of caregivers reported poor epilepsy care. This finding highlights the need to implement organized and efficient telemedicine programs devoted to epilepsy care.