Improvement In Seizure Frequency Research Articles

Vagus Nerve Stimulation for Intractable Focal Epilepsy

Abstract Background Epilepsy is a common neurological condition affecting 0.5-1% of the population. Despite the advances in the medical management of epilepsy 25-35% of patients have poor control of their seizures or have unacceptable side effects from the medication. Aim and Objectives To make up-to-date recommendations for the value of vagus nerve stimulation (VNS) in patients suffering from intractable focal epilepsy and not candidates for surgical resection. Subjects and Methods Eight studies were included in the present meta-analysis. The flow diagram of the study selection processes. The total number of patients in the eight included studies was 266. The follow-up periods ranged from 12–124 months. Because of significant heterogeneity (I2 = 94 %) among the included studies, a sensitivity analysis was performed. Result 59.4% of all the included patients showed a 50% or greater reduction in seizure frequency after VNS. The patients with > 50% reduction in seizure frequency ranged from 25–66% among the eight included studies. Non-significant improvement in seizure frequency after VNS. Conclusion After VNS, the frequency of seizures was reduced by 50% in about 59.4% of the patients with intractable focal seizures. The present study's random effects forest plot, however, indicated that the reduction in seizure frequency following VNS was not statistically significant. The effectiveness of VNS in reducing seizure frequency in the population under study is therefore still unknown,.

Sulthiame use in children with pharmacoresistant epilepsies: A retrospective study.

This retrospective study aimed to assess the efficacy and tolerability of sulthiame as an add-on treatment in children with pharmacoresistant epilepsies. All patients with epilepsy who received sulthiame at Montreal Children's Hospital over an 11-year period were included. Medical charts were reviewed, and extracted data included patient age and sex, seizure types, epilepsy syndrome, electroencephalography (EEG) reports, brain imaging reports, antiseizure treatments trialed, starting and final dose of sulthiame, duration of sulthiame treatment, adverse events attributed to sulthiame, and seizure frequency before and after sulthiame treatment. EEG studies were also analyzed and spike-wave index (SWI) in the first 10 min of sleep was calculated. Sixteen patients were included, all of whom had pharmacoresistant epilepsies (mean of 9.9 trials of other antiseizure treatments). Six had genetic diagnoses, four had in utero/perinatal acquired brain injury, one had a suspected focal cortical dysplasia, and five were idiopathic. Ten patients had developmental and epileptic encephalopathy with spike-wave activation in sleep, three had Lennox-Gastaut syndrome, and one each had sleep-related hyperkinetic epilepsy, self-limited epilepsy with centrotemporal spikes, and mixed generalized and multifocal epilepsy. Of the 12 patients with uncontrolled seizures at the time of sulthiame initiation, 4 had improvement in seizure frequency, including 2 who became seizure free. Eight patients had EEG data available that allowed calculation of sleep SWI; from this group, SWI decreased from 81.1% +/- 17.6% to 45.1% +/- 36.5% (p = .007). The most common adverse events reported were somnolence/drowsiness, aggression, and increased seizure frequency. Of the patients with genetic etiologies, significant positive responses were seen in patients with pathogenic variants in NDUFS1 and SATB1. These data demonstrate the therapeutic potential of sulthiame, even in patients with highly pharmacoresistant epilepsy. Improvements may be seen in both seizure frequency and sleep SWI.

Breathing control training for functional seizures: A multi-site, open-label pilot study

There are no well-validated treatments for functional seizures. While specialist psychotherapy is usually recommended, the evidence for its benefit is qualified, and it can be difficult to obtain. Given the association between hyperventilation and functional seizures we explored an alternative modality, breathing control training, in a multi-site open label pilot trial. Participants with functional seizures over the age of 16 received an hour of breathing training from a respiratory physiotherapist, with a half-hour booster session a month later. Seizure frequency and Nijmegen scores (a measure of hyperventilation) were reported at baseline and follow-up, 3–4 months later. Eighteen subjects were recruited, and 10 completed follow-up. Seven of these 10 had improved seizure frequency, and 3 did not (Wilcoxon signed rank test, p = 0.09), with seizure frequency correlating with Nijmegen score (Spearman's rank correlation = 0.75, p = 0.034). The intervention was well tolerated, with no adverse events reported. These preliminary results support a potentially new approach to treating functional seizures that should prove cost-effective and acceptable, though require confirmation by a randomised controlled trial.

Effect of a ketogenic diet on decrease of seizures in refractory epilepsy among children (infancy to 14 years old) in Saudi Arabia: a cross-sectional study.

Refractory (intractable/pharmaco-resistant) epilepsy in children is considered if disabling seizures continue despite appropriate trials of two anti-seizure drugs, either alone or in combination. Ketogenic diets are used as a treatment option in many countries for children with refractory seizures; however, few patients have tried it in Saudi Arabia. Therefore, we examined the relationship between the exposure to a ketogenic diet and its effect in decreasing seizure frequency in infants and children up to 14 years who had refractory epilepsy and assessed factors that could improve the outcome of seizures. This cross-sectional study was conducted at King Fahad Medical City, Riyadh, Saudi Arabia. Data were collected by reviewing medical records of eligible children (infants and children up to 14 years old) with refractory epilepsy who were on ketogenic diets. Socioeconomic data of the parents (guardians) were collected via phone interviews after verbal consent from the parents (guardians). We recruited 95 children (aged 10 months to 14 years) with refractory epilepsy and on Ketogenic diets. Up to 44% of patients on 3:1 and 4.5:1 ratio ketogenic diets had decreased seizure frequency while patients on 1:1 and 2:1 ratio ketogenic diets showed no decrease in seizures. Patients with generalized epilepsy who were on ketogenic diets had the most improvement in seizure outcomes (56.1%) and patients on ketogenic diets who were ambulatory indoors and outdoors (66.7%) showed a high level of improvement in seizure outcomes compared to patients with who were non-ambulatory (21.9%). Lower improvements in seizure frequency in epileptic patients on ketogenic diets were associated with low education levels of parents (33.3% high school vs. 50% undergraduate school), low incomes [<11,400±7,560.864 Saudi riyal (SR)], and diagnosis of seizures in patients >8 years old. Ketogenic diets are a promising approach for treatment of refractory epilepsy among children. The improvement in seizure outcomes was associated with higher ratios of ketogenic diets (3:1 and 4.5:1), and higher physical activity. Sociodemographic factors, including parents' (guardians') education levels and income influenced the improvement of seizures.

Late-onset epilepsy with cognitive symptoms: Comparison of cognitive and imaging profiles with probable Alzheimer’s disease

ObjectiveWe aimed to (i) compare the clinical, neuropsychological, and neuroimaging characteristics of unprovoked late-onset epilepsy (LOE) patients with cognitive symptoms against probable Alzheimer’s disease (AD) patients; (ii) clarify how neurodegeneration and other processes could be implicated in the cognitive symptoms of unprovoked LOE patients; and (iii) characterize the longitudinal trajectory of unprovoked LOE patients with cognitive symptoms. MethodsTwenty-six unprovoked LOE patients with cognitive symptoms and 26 probable AD were retrospectively recruited from epilepsy and memory clinics at a single tertiary referral center. The patients underwent comprehensive clinical, neuropsychological, and 18Fluorodeoxyglucose PET-CT assessments. All LOE patients had clinical follow-up and a subset of 17 patients had repeat neuropsychological assessments. ResultsAt baseline, 18% of LOE patients with cognitive symptoms had dementia-range cognitive impairment and one received a diagnosis of probable AD. Compared with the probable AD group, the LOE group did not perform significantly better in global measures of cognition (total ACE-III), neuropsychological tests for fluency, working memory, language, attention, or executive function, but performed better in naming, memory, and visuospatial ability. The commonest patterns of cognitive impairment in the LOE group were frontal and left temporal, whereas all AD patients exhibited parietotemporal patterns. The AD group had more 18Fluorodeoxyglucose PET-CT hypometabolism in the parietal and occipital, but not the temporal and frontal lobes. During the 3.0 ± 3.2 years follow-up, improved seizure frequency in the LOE group covaried with improved total ACE-III score, there was no further conversion to probable AD and no group-level cognitive decline. ConclusionUnprovoked LOE patients with cognitive symptoms had varying severities of cognitive impairment, and different patterns of cognitive and imaging abnormalities compared with AD patients. They were rarely diagnosed with probable AD at presentation or follow-up. Cognitive outcome in LOE may be related to seizure control. Cerebral small vessel disease may play a role in LOE-associated cognitive impairment.

D-galactose Supplementation for the Treatment of Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE): A Pilot Trial of Precision Medicine After Epilepsy Surgery.

MOGHE is defined as mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Approximately half of the patients with histopathologically confirmed MOGHE carry a brain somatic variant in the SLC35A2 gene encoding a UDP-galactose transporter. Previous research showed that D-galactose supplementation results in clinical improvement in patients with a congenital disorder of glycosylation due to germline variants in SLC35A2. We aimed to evaluate the effects of D-galactose supplementation in patients with histopathologically confirmed MOGHE, with uncontrolled seizures or cognitive impairment and epileptiform activity at the EEG after epilepsy surgery (NCT04833322). Patients were orally supplemented with D-galactose for 6months in doses up to 1.5g/kg/day and monitored for seizure frequency including 24-h video-EEG recording, cognition and behavioral scores, i.e., WISC, BRIEF-2, SNAP-IV, and SCQ, and quality of life measures, before and 6months after treatment. Global response was defined by > 50% improvement of seizure frequency and/or cognition and behavior (clinical global impression of "much improved" or better). Twelve patients (aged 5-28years) were included from three different centers. Neurosurgical tissue samples were available in all patients and revealed a brain somatic variant in SLC35A2 in six patients (non-present in the blood). After 6months of supplementation, D-galactose was well tolerated with just two patients presenting abdominal discomfort, solved after dose spacing or reduction. There was a 50% reduction or higher of seizure frequency in 3/6 patients, with an improvement at EEG in 2/5 patients. One patient became seizure-free. An improvement of cognitive/behavioral features encompassing impulsivity (mean SNAP-IV - 3.19 [- 0.84; - 5.6]), social communication (mean SCQ - 2.08 [- 0.63; - 4.90]), and executive function (BRIEF-2 inhibit - 5.2 [- 1.23; - 9.2]) was observed. Global responder rate was 9/12 (6/6 in SLC35A2-positive). Our results suggest that supplementation with D-galactose in patients with MOGHE is safe and well tolerated and, although the efficacy data warrant larger studies, it might build a rationale for precision medicine after epilepsy surgery.

E.5 Large scale network changes immediately after Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy (MRgLITT) for hypothalamic hamartoma

Background: Hypothalamic hamartomas (HH) are a challenging cause of seizure in children, partly because the neural circuitry involved in ictogenesis is incompletely understood. We review our institutions’ use of magnetic resonance imaging-guided laser interstitial thermal therapy (MRgLITT) to treat hypothalamic hamartoma (HH) with resting-state fMRI performed immediately before and after ablation. Methods: Seed-based whole brain connectivity to thalamic regions of interest was performed immediately pre- and post- MRgLITT. Multivariable generalized linear models were used to correlate resting-state data with seizure outcomes. Results: Eight patients underwent MRgLITT treatments for HH, with a mean follow up of 29 months. Four patients (50%) were seizure free at 12 months and two (25%) had a significant improvement in seizure frequency. We identified reduced thalamocortical connectivity involving the anterior cingulate and posterior parietal regions, consistent with disconnection of the mammillothalamic tract and interruption of Papez circuit. Large-scale thalamocortical connectivity changes were driven by children who subsequently became seizure free. Conclusions: Disconnection of the mammillothalamic tract and interruption of thalamic circuitry in patients undergoing MRgLITT for HH appears to be associated with improved seizure outcomes. The ability to assess network changes immediately post- MRgLITT could enable operative adjustments to be made mid-procedure to optimize seizure outcome in real time.

Responsive Neurostimulation for the Treatment of Children With Drug-Resistant Epilepsy in Tuberous Sclerosis Complex

BackgroundTo review seizure outcomes in children with tuberous sclerosis complex (TSC) and drug-resistant epilepsy (DRE) treated with the responsive neurostimulation (RNS) System. MethodsWe retrospectively reviewed children (<21 years old) with TSC implanted with the RNS System at Texas Children's Hospital between July 2016 and May 2022. ResultsFive patients meeting the search criteria were identified (all female). The median age of the RNS implantation was 13 years (range: 5 to 20 years). The median epilepsy duration before the RNS implantation was 13 years (range: 5 to 20 years). Surgeries before RNS implantation included vagus nerve stimulator placement (n = 2), left parietal resection (n = 1), and corpus callosotomy (n = 1). The median number of antiseizure medications tried before RNS was 8 (range: 5 to 12). The rationale for the RNS System implantation included seizure onset in eloquent cortex (n = 3) and multifocal seizures (n = 2). The maximum current density for each patient ranged between 1.8 and 3.5 μC/cm2, with an average daily stimulation of 2240 (range: 400 to 4200). There was an 86% median seizure reduction (range 0% to 99%) at a median follow-up duration of 25 months (range: 17 to 25 months). No patient experienced implantation or stimulation-related complications. ConclusionsWe observed a favorable improvement in seizure frequency in pediatric patients with DRE secondary to TSC treated with the RNS System. The RNS System may be a safe and effective treatment for DRE in children with TSC.

Incidental Detection of Anti-IgLON5: A Diagnostic and Therapeutic Dilemma (P5-5.021)

<h3>Objective:</h3> To report a patient in whom anti-IgLON5 was incidentally detected as part of work-up for possible autoimmune-associated epilepsy. <h3>Background:</h3> Anti-IgLON5 disease has recently been characterized. Core manifestations include sleep disturbances, bulbar dysfunction, gait instability, chorea and cognitive decline, while seizures are not typical. Response to immunotherapy is usually suboptimal and prognosis is frequently poor, although early treatment could improve outcomes. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 49-year-old woman had an 18-year-history of temporal lobe epilepsy that developed after cervical cancer. Brain MRI was unremarkable but EEG showed right temporal epileptiform discharges and PET showed right temporal hypometabolism, compatible with right temporal seizure origin. Due to seizure refractoriness and history of cancer, comprehensive neural antibody testing for possible autoimmune-associated epilepsy was pursued and revealed anti-IgLON5 in serum and cerebrospinal fluid. On directed history, the patient reported snoring and insomnia that had developed two years prior, which were symptoms she had not initially volunteered because she felt they were mild and stable. Neurologic examination was unremarkable. The patient received a six-week trial of corticosteroids, without improvement in seizure frequency or sleep disturbances. Polysomnography revealed minimal sleep disordered breathing, mild arousals from slow wave sleep, unusually prominent beta activity in REM sleep, and excessive fragmentary myoclonus, which may represent early anti-IgLON5 disease. <h3>Conclusions:</h3> Diagnostically, we hypothesize that anti-IgLON5 is unrelated to chronic temporal lobe epilepsy in our patient, which we suspect is idiopathic. However, this antibody may explain sleep findings, and the mildness of her symptoms referable to anti-IgLON5 disease creates a unique therapeutic dilemma. In discussion with the patient, we have opted to monitor clinically and with polysomnography, and to consider institution of further immunotherapy if there is demonstrable disease progression. Future study into the natural history of anti-IgLON5 disease is needed to determine the optimal management of patients with mild symptoms. <b>Disclosure:</b> Dr. Alkabie has nothing to disclose. The institution of Dr. Murray has received research support from Wake Up Narcolepsy. Dr. Murray has received publishing royalties from a publication relating to health care. Dr. Budhram has nothing to disclose.

Efficacy and Quality of Life Outcome of Combined Epilepsy Surgery with RNS Placement (P5-1.002)

<h3>Objective:</h3> Retrospectively review clinical outcomes in patients treated with resection or Laser interstitial Thermal Therapy (LiTT) immediately (≤ 90 days) after implantation of RNS. <h3>Background:</h3> Surgical resection and LiTT are standard treatments for refractory epilepsy, but these options can be limited by eloquent cortex and seizure multifocality. Previous studies have suggested RNS may be used in conjunction with resective surgery (RNS+R) or LiTT (RNS+LiTT) as a new combination of treatments. Besides seizure control, quality of life and psychiatric symptoms including depression and anxiety are considered as important outcome evaluation after epilepsy surgery. <h3>Design/Methods:</h3> 34 patients that had RNS+R or RNS+LiTT at our center were reviewed and 10 were excluded. The decision of dual procedures was made prior to surgery. Patients received RNS+R had both resective surgery and RNS placement in the same procedure. Patients received RNS+LiTT had several weeks gap between the RNS placement and LiTT due to neurosurgical logistics. Clinical follow-ups were performed at 12, 18, 24, 36 and 48 months for evaluation of seizure frequency. Patient health questionnaire-9 (PHQ-9) is used as a depression assessment. Quality of life in epilepsy questionnaire (QOLIE-31) was used as scoring for evaluation of general quality of life. <h3>Results:</h3> Among the 24 patients that had RNS+R or RNS+LiTT, 22 patients (91.6%) showed improved seizure frequency at the last follow up. Fourteen patients had PHQ-9 evaluation and the average score was 5.85±6.29 (mean±SD), among which nine were between 0–4 (minimal depression), one was between 5–9(mild depression), three were between 10–14(moderate depression), one was 15–19(moderately severe depression) and none was 20–27(severe depression). QOLIE-31 done in eight patients showed average score of 65.61 ± 18.09 (mean±SD) in last follow-up visit. <h3>Conclusions:</h3> Our study showed significant seizure control rate of RNS+R or RNS+LiTT therapy in refractory epilepsy patients. It also suggestive for promising psychiatric outcomes and quality of life scoring after surgery. <b>Disclosure:</b> Dr. Pan has nothing to disclose. Dr. Mirza has nothing to disclose. Dr. Agostini has nothing to disclose. Dr. Alick-Lindstrom has nothing to disclose. Dr. Das has received personal compensation for serving as an employee of Concentra. Dr. Das has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for janicek. The institution of an immediate family member of Dr. Das has received research support from NIH. The institution of Dr. Ding has received research support from National Institute of Aging. The institution of Dr. Ding has received research support from NINDS. Dr. Doyle has nothing to disclose. Dr. Dieppa has nothing to disclose. Dr. Hays has nothing to disclose. Dr. Harvey has received personal compensation for serving as an employee of RSC Diagnostics. The institution of Dr. Harvey has received research support from GW Pharmaceuticals. The institution of Dr. Harvey has received research support from Cerevel Pharmaceuticals. The institution of Dr. Harvey has received research support from UCB Pharmaceuticals. The institution of Bradley Lega has received research support from NIH. irina podkorytova has nothing to disclose. Dr. Zepeda Garcia has nothing to disclose. Dr. Perven has nothing to disclose.

Efficacy of Cannabidiol in Pediatric Patients: Postmarket Experience at a Single Center

AbstractThe purpose of this research was to determine the postmarket efficacy and safety of cannabidiol in pediatric patients with Lennox–Gastaut's syndrome (LGS), Dravet's syndrome (DS), and other drug-resistant epilepsy (DRE). This was a single-center, retrospective cohort study in pediatric patients who received prescription cannabidiol at a single center. The primary outcome was the reduction in seizure frequency of all seizure types as measured by the Engel outcome scale at 3 months after initiation of cannabidiol. Thirty-six patients were included. The most common outcome in all three groups was an Engel Class III outcome 3 months following initiation of cannabidiol. Most patients in all groups experienced some clinical benefit and only 33% of patients experienced no clinical benefit. The maximum tolerated dose of cannabidiol at 3 months ranged from 5 to 31 mg/kg/d with a median of 17.9, 13.2, and 18.0 mg/kg/d in the LGS, DS, and DRE (other) groups, respectively. Eight patients discontinued cannabidiol at 3 months and only two patients were hospitalized after initiation of therapy. Seventy-five percent of patients did not report any adverse side effects. Based on the Engel outcome scale utilized within this study, pediatric patients with LGS, DS, and DRE (other) may experience a worthwhile improvement in seizure frequency while on cannabidiol. Further studies are needed to determine the long-term efficacy and safety of cannabidiol and discern predictors of response to therapy.

A six-month prospective, randomised, double-blinded, placebo-controlled, crossover, dietary trial design to investigate the potential of psychobiotics on seizure semiology and comorbidities in canine epilepsy: study protocol

BackgroundEpilepsy is the most common chronic neurological disease in dogs. More than two-thirds of these patients suffer from associated behavioural comorbidities. The latter could have their origin in partially overlapping pathomechanisms, with the intestinal microbiome as a potential key link between them. The current arsenal of drugs for epilepsy management remains limited. Most canine patients continue to have seizures despite treatment and the occurrence of comorbidities is not sufficiently addressed, limiting quality of life of affected dogs and owners. Therefore, novel additional epilepsy management options are urgently needed. The microbiome-gut-brain axis may serve as a new target for the development of innovative multimodal therapeutic approaches to overcome current shortcomings in epilepsy management.MethodsA six-month prospective, randomised, double-blinded, placebo-controlled, crossover, dietary trial was designed to investigate the potential of the psychobiotic Bifidobacterium longum on behavioural comorbidities in canine epilepsy. Seizure semiology will be evaluated as a secondary outcome measure. Thirty-four privately owned dogs are planned to be included in the ongoing study meeting the following inclusion criteria: Dogs displaying increased anxiety/fear behaviour since the start of the idiopathic epilepsy. Tier II confidence level of the International Veterinary Epilepsy Task Force for the diagnosis of idiopathic epilepsy, with a maximum seizure interval of 3 month and a minimum of three generalised seizures within that period and chronically treated with at least one antiseizure drug without improvement in seizure frequency Each dog will receive the allocated supplement (probiotic vs. placebo) alongside its normal diet for a 3-month period. After a three-week wash out period, the second phase starts by administering the respective other supplement for another 3 months.DiscussionThe current study considers modern high-quality standards for epilepsy medication trials. Common biasing effects should be limited to a possible minimum (regression-to-the mean effect, placebo effect, observer effect), ensuring a high validity and accuracy of the acquired results, thus enabling a representative nature of the efficacy of Bifidobacterium longum as add-on supplement for dogs suffering from epilepsy and its comorbidities. This publication should provide a description of the study procedure and data acquisition methods, including prognosed statistical analysis.

Magnetic resonance imaging-guided stereotactic laser ablation therapy for the treatment of pediatric epilepsy: a retrospective multiinstitutional study.

The authors of this study evaluated the safety and efficacy of stereotactic laser ablation (SLA) for the treatment of drug-resistant epilepsy (DRE) in children. Seventeen North American centers were enrolled in the study. Data for pediatric patients with DRE who had been treated with SLA between 2008 and 2018 were retrospectively reviewed. A total of 225 patients, mean age 12.8 ± 5.8 years, were identified. Target-of-interest (TOI) locations included extratemporal (44.4%), temporal neocortical (8.4%), mesiotemporal (23.1%), hypothalamic (14.2%), and callosal (9.8%). Visualase and NeuroBlate SLA systems were used in 199 and 26 cases, respectively. Procedure goals included ablation (149 cases), disconnection (63), or both (13). The mean follow-up was 27 ± 20.4 months. Improvement in targeted seizure type (TST) was seen in 179 (84.0%) patients. Engel classification was reported for 167 (74.2%) patients; excluding the palliative cases, 74 (49.7%), 35 (23.5%), 10 (6.7%), and 30 (20.1%) patients had Engel class I, II, III, and IV outcomes, respectively. For patients with a follow-up ≥ 12 months, 25 (51.0%), 18 (36.7%), 3 (6.1%), and 3 (6.1%) had Engel class I, II, III, and IV outcomes, respectively. Patients with a history of pre-SLA surgery related to the TOI, a pathology of malformation of cortical development, and 2+ trajectories per TOI were more likely to experience no improvement in seizure frequency and/or to have an unfavorable outcome. A greater number of smaller thermal lesions was associated with greater improvement in TST. Thirty (13.3%) patients experienced 51 short-term complications including malpositioned catheter (3 cases), intracranial hemorrhage (2), transient neurological deficit (19), permanent neurological deficit (3), symptomatic perilesional edema (6), hydrocephalus (1), CSF leakage (1), wound infection (2), unplanned ICU stay (5), and unplanned 30-day readmission (9). The relative incidence of complications was higher in the hypothalamic target location. Target volume, number of laser trajectories, number or size of thermal lesions, or use of perioperative steroids did not have a significant effect on short-term complications. SLA appears to be an effective and well-tolerated treatment option for children with DRE. Large-volume prospective studies are needed to better understand the indications for treatment and demonstrate the long-term efficacy of SLA in this population.

Highly purified cannabidiol improves stability and postural tone in adult patients with Lennox-Gastaut syndrome: A case series.

Lennox-Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy associated with numerous neurological signs and symptoms. Altered postural tone and the need for a caregiver-assisted wheelchair are features characterizing patients with LGS. Highly purified cannabidiol (CBD) is a novel antiseizure medication (ASM) recommended for seizure treatment, in combination with clobazam, in patients with LGS. Adding CBD to the previous ASM treatment helps in reducing seizure frequency, specifically drop seizures, in patients with LGS in both clinical trials and real-world studies. However, no data about drug effects on postural tone, motor activity, gait, and stability are available. In this case series, three adult patients diagnosed with LGS were treated with CBD as an add-on. During the follow-up, a slight improvement in seizure frequency was observed. Unexpectedly, an amelioration in postural tone and stability, measured using the validated Gross Motor Function Classification System, was also detected. Our case series suggests that CBD may help in managing patients with LGS regarding seizure control and in improving other aspects of the clinical spectrum of the disease, such as postural tone and stability. The mechanisms at the basis of this improvement may be related, other than seizure reduction, to the drug's effect on the brain locomotor centers, as demonstrated in animal model studies.

Clinical Outcome Data of Children Treated with Cannabis-Based Medicinal Products for Treatment Resistant Epilepsy-Analysis from the UK Medical Cannabis Registry.

There is a paucity of high-quality evidence of the efficacy and safety of cannabis-based medicinal products in treatment of treatment-resistant epilepsy (TRE) in children. A case series of children (<18 years old) with TRE from the UK Medical Cannabis Registry was analyzed. Primary outcomes were ≥50% reduction in seizure frequency, changes in the Impact of Pediatric Epilepsy Score (IPES), and incidence of adverse events. Thirty-five patients were included in the analysis. Patients were prescribed during their treatment with the following: CBD isolate oils (n = 19), CBD broad-spectrum oils (n = 17), and CBD/Δ9-THC combination therapy (n = 17). Twenty-three (65.7%) patients achieved a ≥50% reduction in seizure frequency. 94.1% (n = 16) of patients treated with CBD and Δ9-THC observed a ≥50% reduction in seizure frequency compared to 31.6% (n = 6) and 17.6% (n = 3) of patients treated with CBD isolates and broad-spectrum CBD products, respectively (p< 0.001). Twenty-six (74.3%) adverse events were reported by 16 patients (45.7%). The majority of these were mild (n = 12; 34.2%) and moderate (n = 10; 28.6%). The results of this study demonstrate a positive signal of improved seizure frequency in children treated with Cannabis-based medicinal products (CBMPs) for TRE. Moreover, the results suggest that CBMPs are well-tolerated in the short term. The limitations mean causation cannot be determined in this open-label, case series.

Nutritional Interventions for Patients with Mitochondrial POLG-Related Diseases: A Systematic Review on Efficacy and Safety.

Ketogenic diet is recommended as a treatment to reduce seizure frequency in patients with intractable epilepsy. The evidence and safety results are sparse for diet interventions in patients with pathogenic polymerase gamma (POLG) variants and intractable epilepsy. The aim of this systematic review is to summarize the efficacy of diet treatment on seizure frequency, clinical symptoms, and potential deleterious effect of liver involvement in patients with mitochondrial diseases caused by pathogenic POLG variants. Literature was searched in PubMed, Embase; and Cochrane in April 2022; no filter restrictions were imposed. The reference lists of retrieved studies were checked for additional literature. Eligibility criteria included verified pathogenic POLG variant and diet treatment. Overall, 880 studies were identified, providing eight case-reports representing nine patients eligible for inclusion. In eight of nine cases, clinical symptoms were improved; six out of nine cases reported improvements in seizure frequency. However, increasing levels of liver enzymes after initiating ketogenic diet were found in four of the nine cases, with one case revealing decreased levels of liver enzymes after initiating long-chain triglyceride restriction. Viewed together, the studies imply that ketogenic diet can have a positive impact on seizure frequency, but may induce progression of liver impairment in patients with pathogenic POLG variants.

Efficacy of pulse intravenous methylprednisolone in epileptic encephalopathy: a randomised controlled trial

BackgroundHigh-level evidence for using steroids in epileptic encephalopathy (EE), other than West syndrome (WS), is lacking. This study investigated the efficacy and safety of pulse intravenous methylprednisolone (IVMP) in EE...

Replacement of Valproic Acid with New Anti-Seizure Medications in Idiopathic Generalized Epilepsy.

Highlights What are the main findings? Replacement of VPA with new ASMs provided the same or better seizure control.Replacement of VPA with new ASMs provided better myoclonus control.Subsets of the monotherapy group achieved better seizure control with new ASMs. What is the implication of the main finding? This study showed the non-inferiority of new ASMs compared to VPA in terms of seizure control.Better seizure control was achieved using new ASMs in the PER monotherapy sub-group among patients with IGE.Background: Little is known regarding the non-inferiority of new anti-seizure medications (ASMs) in terms of replacing valproic acid (VPA) in patients with idiopathic generalized epilepsy (IGE). We hypothesized that replacement of VPA with new ASMs would offer non-inferior or better control of seizure frequency. The purpose of this study was to compare epileptic seizure frequency between the subset of patients with IGE who were on VPA and the subset of patients with IGE who replaced VPA with new ASMs. Methods: Patients with IGE who were on or had been on VPA between January 2016 and March 2022 were divided into a group that replaced VPA with new ASMs (VPA-replace group) and a group that remained on VPA (VPA-continue group). We then compared the groups in terms of seizure frequency and myoclonus. Results: Of the 606 patients on VPA between January 2016 and March 2022, 156 patients with IGE were enrolled to this study (VPA-replace group, n = 68; VPA-continue group, n = 88). The VPA-replace group included significantly more females than the VPA-continue group (p < 0.001). The VPA-replace group also showed significantly higher seizure frequency before replacement (p < 0.001), but not after replacement (p = 0.074). Patients on monotherapy displayed improved seizure frequency with new ASMs (p < 0.001). Among the new ASMs, perampanel (PER) significantly improved seizure frequency (p = 0.002). Forty-two patients in the VPA-replace group who had myoclonus achieved significant improvements (p < 0.001). Among these, patients on PER monotherapy (p < 0.001) or PER + lamotrigine (0.016) showed significantly improved myoclonus scale scores. Conclusions: This study shows the non-inferiority of new ASMs compared to VPA, with better seizure control using new ASMs in subsets of patients with IGE on monotherapy.

The Interaction Between Sleep and Epilepsy.

To review the mutual interactions between sleep and epilepsy, including mechanisms of epileptogenesis, the relationship between sleep apnea and epilepsy, and potential strategies to treat seizures. Recent studies have highlighted the role of functional network systems underlying epileptiform activation in sleep in several epilepsy syndromes, including absence epilepsy, benign focal childhood epilepsy, and epileptic encephalopathy with spike-wave activation in sleep. Sleep disorders are common in epilepsy, and early recognition and treatment can improve seizure frequency and potentially reduce SUDEP risk. Additionally, epilepsy is associated with cyclical patterns, which has led to new treatment approaches including chronotherapy, seizure monitoring devices, and seizure forecasting. Adenosine kinase and orexin receptor antagonists are also promising new potential drug targets that could be used to treat seizures. Sleep and epilepsy have a bidirectional relationship that intersects with many aspects of clinical management. In this article, we identify new areas of research involving future therapeutic opportunities in the field of epilepsy.

The Long-Term Effectiveness and Safety of Cannabidiol-Enriched Oil in Children With Drug-Resistant Epilepsy

BackgroundSeveral retrospective studies on pediatric epilepsy reported positive effects of cannabidiol-enriched artisanal cannabis oil and pure cannabidiol oil on seizure reduction. MethodsThis is a retrospective study of children and adolescents with refractory epilepsy caused by various etiologies who were treated with artisanal cannabis oil during January 2014 to June 2019, with at least one year follow-up. ResultsOf 114 patients, 84 (73.3%) reported some improvement in seizure frequency at some point during treatment. Fifty-one (59%) of the 86 patients who continued treatment for at least one year showed >50% improvement in seizure frequency. Seizure etiology, seizure type, and patients' age and sex were not found to be associated with the response to cannabidiol-enriched cannabis oil. Side effects were minor, and positive effects beyond seizure reduction were noted. ConclusionsArtisanal cannabidiol-enriched cannabis may be an effective and safe long-term treatment for refractory epilepsy.