Chalfont Seizure Severity Scale Research Articles

Effects of L-Carnitine Supplementation on Gastric Emptying in Children with Drug Resistant Epilepsy on Ketogenic Diet

Abstract Background The ketogenic diet (KD) is a high fat, low carbohydrate, and adequate protein (1 g/kg) diet with a demonstrated efficacy in the treatment of drug-resistant epilepsy (DRE) in infants and children. Gastrointestinal (GI) disturbances are often related to scarce tolerance of the diet that results in a significant resistance to the ketogenic diet and even blunting its efficacy. In addition, ketogenic diet’s high-fat content prolongs the gastric emptying time thus favoring gastro-esophageal reflux disease, nausea and vomiting. Objectives The objective of the study was to assess the effect KD on Chalfont seizure severity scale and the effect of L-carnitine supplementation on gastric emptying in children with drug resistant epilepsy (DRE) on ketogenic diet (KD). Patients and Methods This was a randomized controlled clinical trial that was conducted on thirty children newly diagnosed with DRE. The patients were divided randomly into 2 groups (15 patients received KD with L-carnitine supplementation and the rest received KD only). Patients were assessed at baseline and 3 months of starting KD. Assessments of children included Chalfont Seizures Severity Scale and the antral length by ultrasound. Results The mean age of the studied children was 4.5 years in KD with L-carnitine supplementation group and 3.5 years in KD only group, 33.35% of the children were females and 66.65% were males. Our study showed that there was a highly significant increase in weight and height/length for age z-scores in all patients after intervention with p-value=0.002. Our results also showed marked improvement of seizures activity for epileptic children in both groups after 3 months of intervention. Our study proved that the patients who received KD with L-carnitine supplementation showed highly significant increase in HDL level after intervention. A comparison between the two studied groups regarding the antral length by ultrasound showed that there was no statistically significant difference between both groups at time of enrolment and after intervention. Conclusion KD is an effective, safe, and tolerable therapy for children with DRE. Although antral length didn’t reach statistically significant difference between both groups initially and after KD therapy, L- carnitine supplementation had a positive effect on fasting lipid profile.

The Beneficial Effect of Probiotics as an Adjuvant Treatment in Childhood Drug Resistant Epilepsy

Abstract Background Epilepsy is the most frequent chronic neurologic condition in children and every year >4.9 million people develop new-onset epilepsy. The foundation of treatment in epilepsy is drug therapy with anti- seizure medications (ASM). However, about one-third develop drug resistant epilepsy (DRE) due to inability to achieve seizure control despite the use of appropriate ASM. Recent studies indicate that gut dysfunction/dysbiosis is presumably involved in the pathogenesis of and susceptibility to epilepsy. The reconstruction of the intestinal microbiome through probiotic intervention has shown beneficial effects on DRE. Aim of the Work The aim of this study is to study safety and effectiveness of probiotics in controlling epileptic seizures in DRE patients by decreasing frequency and severity of seizures. Patients and Methods This study is a prospective study – Single arm Clinical Trial (Pilot study) conducted on 35 DRE patients at the neurology outpatient clinic, Pediatric Neurology Unit, Ain Shams University, from January to August, 2023, of which 14 (40%) dropped out due to socioeconomic reasons and non-compliance while 21 (60%) patients completed this clinical trial. All the results were calculated based on the 21 patient who completed the study. Patients were supplemented with probiotics for 4 months and assessed pre and post probiotics intake by the following tools: seizure assessment by Chalfont seizure severity scale, a blood sample taken to measure serum sCD14 as an inflammatory marker, an EEG was done and QOLIE-31 was used to asses quality of life. Probiotics (spores of antibiotic resistant Bacillus clausii; Enterogermina 2 Billion @ SANOFI) were used with the following doses daily for 4 months (as per SANOFI’s dose prescribtion): ages 1 year to 2 years: 1 vial per day, ages 2 years to 18 years: 2 vials per day. Results Our study included 21 participants; the median age at the time of the study was 11 years ranging from 2.5 to 15 years of age and the median age of onset of seizure was 7 ranging from 6 months to 12 years. The majority of participants were found to be female 15 (71.4%) and the rest were male 6 (28.4%). This clinical trial shows that probiotics could be a useful supplement in the treatment of DRE where 42.9% of our patients achieved the Therapeutic goal of reduction (≥50%) in the number of seizures & improvement in seizure severity (p-value < 0.001) and frequency (p-value < 0.005). Serum sCD14 levels were withdrawn as an inflammatory marker to understand the potential cause of the improvement in epileptic seizures and their levels were outstandingly improved between pre and post probiotics intake with p-value < 0.001. We also found that quality of life was significantly improved as measured by questionnaire QOLIE31 between pre and post probiotics intake in our patients in all its aspects with total score <0.001. We compared between our 2 main diagnoses (The GDD and Genetic epilepsy) and found that there was higher quality of life in the genetic group than the global developmental delay group with p-value < 0.001 mostly attributing this to the fact that most of the genetic patients had a higher starting point than their counterpart in their developmental history and other aspects. Our patients were also sub-divided into 2 groups based on the effectiveness of the probiotics in improving seizures frequency 50% or more and it was found that the effective group had a lower median age (7 years) than the non-effective group (12.5 years) delineating that younger age responds better to probiotics or management in general. Conclusion This study revealed that probiotics decrease the frequency and severity of seizures and improve the quality of life of drug resistant epilepsy patients. Since this is a pilot study and there are deficient data in this area, more studies are needed to evaluate the applicability, safety and the mechanism of action of probiotics.

Compliance and Ketones Levels in Relation to Seizure Control in Children with Drug Resistant Epilepsy Treated with Ketogenic Diet

Abstract Background The ketogenic diet (KD) is a high-fat, adequate-protein, low-carbohydrate diet. Ketogenic diet therapy (KDT) has become an important option in the management of drug- resistant epilepsy and some of the inborn errors of metabolism in children, with increasing evidence of its favorable effects. Objective To evaluate patient's compliance to KD in children with drug resistant epilepsy (DRE) and the effect of KD on course and outcome of DRE. Methodology This cross-sectional study included 42 children whose age ranged between 1 month and 18 years with drug resistant epilepsy (DRE) on ketogenic diet for at least 3 months. They were recruited from the Ketogenic Diet Clinic, Children’s hospital, Ain Shams University, Cairo, Egypt. They were assessed for anthropometric measurements, betahydroxybutyrate (BHB) in blood,and acetone in urine, fasting lipid profile,serum random blood sugar;The frequency and severity of convulsions were assessed using chalfont severity scale before and after applying KD and correlated with the laboratory markers measured. Results Beta hydroxybutarate levels in blood ranged from (0.1 - 4.6) achieving ketosis in 37patient (BHB>2 mmol/L). As regard frequency of convulsions per day there was highly significant decrease after 3 month of KD with p < 0.001 compared to that before using the KD. On applying chalfont seizure severity scale on our patients there was highly significant decrease in the severity of the seizure with p < 0.001 after KD. Regarding the frequency of possible complications associated with KD, 69% of the patients had no complication, while 26.2% had constipation, 26.2% had hyperlipidemia, 2.4 % had vomiting, 2.4 % had kidney stones, and 2.4 % had urinary gravels. Conclusion KD is an effective, safe, and tolerable therapy for children with DRE where significant improvement in both frequency and severity of seizures after KD were found.

An exploratory study of brain temperature and choline abnormalities in temporal lobe epilepsy patients with depressive symptoms.

Epilepsy and depression share neurobiological origins, and evidence suggests a possible bidirectional relationship that remains poorly understood. This exploratory, cross-sectional study aimed to investigate this relationship by employing magnetic resonance spectroscopic imaging (MRSI) and thermometry (MRSI-t) in patients with temporal lobe epilepsy (TLE) with comorbid depressive symptoms and control participants. This is the first study to combine MRSI and MRSI-t to examine brain temperature and choline abnormalities in regions implicated in seizure onset and depression. Twenty-six patients with TLE and 26 controls completed questionnaires and underwent imaging at 3T. Volumetric echo-planar MRSI/MRSI-t data were processed within the Metabolite Imaging and Data Analysis System (MIDAS). Choline (CHO) was quantified as a ratio over creatine (CRE; CHO/CRE). Brain temperature (TCRE ) was calculated based on the chemical shift difference of H2 O relative to CRE's stable location on the ppm spectrum. The Hospital Anxiety and Depression Scale measured anxiety and depressive symptoms. The Chalfont Seizure Severity Scale measured seizure severity in patients with TLE. Two sets of voxelwise independent sample t tests examined group differences in CHO/CRE and TCRE maps. Voxel-based multimodal canonical correlation analysis (mCCA) linked both datasets to investigate if, how, and where CHO/CRE and TCRE abnormalities were correlated in TLE participants and controls. Compared to controls, patients with TLE reported more depressive symptoms (P = 0.04) and showed CHO/CRE and TCRE elevations in left temporal and bilateral frontal regions implicated in seizure onset and depressive disorders (pFWE < 0.05). For the TLE group, CHO/CRE levels in temporal and frontal cortices were associated with elevated TCRE in bilateral frontal and temporal gyri (r = 0.96), and decreased TCRE in bilateral fronto-parietal regions (r = -0.95). Abnormalities in TCRE and CHO/CRE were observed in seizure-producing areas and in regions implicated in depression. These preliminary findings suggest that common metabolic changes may underlie TLE and depression. Our results suggest further investigations into the proposed bidirectional mechanisms underlying this relationship are warranted.

Epilepsy Surgery and Health Education Improved Quality of Life in Children with Drug Resistant Epilepsy

Background Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite introduction of recent antiepileptic drugs (AEDs), there's about one-third of patients that suffer from epilepsy also have seizures refractory to pharmacotherapy. Aim of the Work To study the effect of epilepsy surgery and health education on seizure control, sleep, and quality of life in children with drug resistant epilepsy (DRE) postoperative. Patients and Methods This was an observational study that relied on data collection, health education on 30 children operated upon for DRE and their families throughout a 6-month period. Data collected included Chalfont Seizure severity scale (CSSS), Quality of life (QOL) questionnaire, IQ assessment, total sleep habits questionnaire (CQHQ), EEG and Engel scale after epilepsy surgery. Results Enrolled children age ranged between 4-18 years with a mean age of 7.8 ± 3.8 years, of which (65.6%) were males. There was a significant reduction in CSSS after surgery from (78.5 ± 30.1) to (60.3 ± 33.6), quality of life from (91.3 ± 20.9) to (80.5 ± 18.1), and in CSHQ from (33.7 ± 10.2) to (25.1 ± 8.3). IQ increased after surgery from (46.7 ± 15.7) to (50.2 ± 16.5); P value &amp;lt;0.001 for all. Mean reduction of Chalfont scale was 24.73% (range from 0 % to 70%). Quality of life was 10.98% (range from 0% to 36.2%), CSHQ was 23.03% (range from 0% to 70%) and mean IQ increase was 8.31% (range from 0% to 50%). There was an improvement in seizure control as Engel classification postoperatively. In Engel (I) 3.1% were A and 3.1% were D. In Engel (II) 3.1% were A, 3.1% were B and 3.1% were D. In Engel (III) 28.1% were A and 3.1% were D. In Engel (IV) 15.6% were A, 28.1% were B and 9.4% were C. Conclusion Epilepsy surgery can effectively improve QOL in children with medicationresistant seizures, through sustained seizure freedom, which was associated with the greatest improvement in life quality, IQ and sleep habits.

The effect of cannabidiol on seizure features and quality of life in drug-resistant frontal lobe epilepsy patients: a triple-blind controlled trial.

Treatment-resistant epileptic seizures are associated with reduced quality of life (QoL). As polypharmacy with routine antiseizure medications has many side effects, novel add-on treatments are necessary. Recent research showed the efficacy of add-on therapy by cannabidiol (CBD) on refractory epilepsy. We attempted to extend data on the efficacy and safety profile of CBD in patients with frontal lobe treatment-resistant epilepsy. A total of 27 patients were recruited into two CBD (n = 12) and placebo (n = 15) groups. The CBD group received a highly purified liposomal preparation of the drug in addition to routine antiseizure medications. The placebo group only received antiseizure medications. This experiment followed a triple-blinding protocol. Outcome measures were seizure frequency, the Chalfont seizure severity scale (CSSS), and the quality of life questionnaire score (QOLIE-31) assessed at baseline, 4 weeks, and 8 weeks. At 4 weeks, results indicated that a higher fraction of patients in the CBD group (66.67%) showed improvement in seizure, compared to the placebo group (20.00%). Before-after comparison revealed that CBD, unlike routine ADEs, was effective in reducing the occurrence of seizures at the study's final timepoint [mean difference 45.58, 95% CI (8.987 to 82.18), p = 0.009]. Seizure severity was not affected by study groups or time intervals (repeated-measures ANOVA p > 0.05). Post-hoc tests found that the QoLI-31 score was improved at 8 weeks compared to baseline [mean diff. -5.031, 95% CI (-9.729 to -0.3328), p = 0.032]. The difference in cases who experienced enhanced QoL was meaningful between the CBD and placebo groups at 8 weeks [RR: 2.160, 95% CI (1.148 to 4.741), p = 0.018] but not at 4 weeks (p = 0.653). A positive finding for QoL improvement was associated with a positive finding for seizure frequency reduction [r = 0.638, 95% CI (0.296 to 0.835), p = 0.001]. Interestingly, limiting the correlation analysis to cases receiving CBD indicated that QoL improvement was not linked with seizure parameters such as severity and frequency (p > 0.05). The present study suggests the benefit of a purified and highly efficient preparation of CBD for seizure frequency reduction and improvement of QoL in refractory frontal lobe epilepsy. Further study with longer follow-ups and larger sample size is advised. https://www.irct.ir/trial/56790, identifier: IRCT20210608051515N1.

Evaluation of Heart Rate Variability Parameters During Awake and Sleep in Refractory and Controlled Epileptic Patients.

BackgroundAlterations of heart rate variability (HRV) in epileptic patients were the field of interest of several studies for many reasons, particularly the contribution toward sudden unexpected death in epilepsy (SUDEP).AimWe aimed at evaluation of autonomic dysfunction in epileptic patients during awake and sleep in addition to studying the association between SUDEP risk with different Holter parameters.Patients and MethodsThe study included eighty epileptic patients (40 controlled epileptic patients and 40 refractory epileptic patients) compared to 30 volunteers as control group. They underwent detailed epileptic history, Chalfont seizure severity scale, sudden unexpected death in epilepsy (SUDEP)-7 risk score and 24 hour Holter monitoring to assess HRV parameters.ResultsPatients with refractory epilepsy had longer duration of epilepsy with increased number of used AEDs compared to controlled epileptic group. Both controlled and refractory epileptic patients had significantly higher average heart rate (AV.HR), sympatho-vagal ratio (low-frequency/high-frequency (LF/HF) ratio in 24 hours, daytime, and nighttime), and LF and HF values compared to controls. The rMSSD (the root mean square of difference between successive normal intervals), Tri.Index (triangular index), and pNN50 (percentage of the number of pairs of consecutive beat-to-beat intervals that varied by 50 ms) were significantly reduced in both epileptic groups compared to controls. Among refractory epileptic patients, patients with generalized epilepsy had significantly higher severity epileptic scale, average heart rate, minimum heart rate, and LF/HF night, in addition to lower rMSSD and pNN50 compared to patients with focal epilepsy. We found positive correlation between the following Holter indices (LF/HF 24, LF/HF day, and LF/HF night) and the duration of the epilepsy, while negative correlations between Tri.Index, LF, and HF and the epileptic duration were detected. SUDEP-7 risk was negatively correlated with pNN50 and rMSSD; meanwhile, it was positively correlated with LF/HF 24. The severity of epilepsy among refractory epileptic patients was positively correlated with average heart rate but negatively correlated with pNN50 and rMSSD. Using linear regression analysis, we found that pNN50 and rMSSD could predict SUDEP-7 risk and severity of epilepsy in refractory epileptic patients.ConclusionEpileptic patients (particularly refractory patients with generalized EEG findings and long duration) had reduced heart rate variability and hence impairment of parasympathetic activity with increased susceptibility for adverse outcomes. Moreover, pNN50 and rMSSD could be used as predictors for SUDEP-7 risk as well as severity of epilepsy in refractory epileptic patients.

Clinico-radiological Profile in Children with Drug Resistant Focal Epilepsy

Abstract Objective To assess the clinical and neuroimaging findings of pediatric patients with drug-resistant focal epilepsy, comparing conventional MR technique to the "essential 6” protocol. Methods An observational study of 18 children with drug resistant focal seizures identified both clinically and/or by EEG findings. Available clinical data as well as EEG and MRI data in patients’ files at the pediatric neurology clinic at Ain Shams University was retrospectively evaluated and documented. All patients then underwent a new MRI study using a novel MR technique - the essential six sequence protocol to determine whether the latter technique was superior to standard at picking subtle anatomical abnormalities in children with drug resistant focal epilepsy. Results 18 children (10 males and 8 females) with a mean age of 8.49 ±3.20 years were enrolled. The mean age at onset of epilepsy was 3.24 ±2.79 years. 15 out of 18 patients (83%) had an abnormal EEG. The mean Chalfont Seizure Severity Scale Score was 63.71 ±34.35. There was no statistically significant difference in Chalfont seizure severity scores between patients with normal vs abnormal EEG, and with normal vs abnormal MRI. The novel MRI technique could pick on an abnormality in 12 out of the 18 cases (66%), which is six times more than what could be identified using the baseline/conventional MRI technique. Conclusions The essential 6 MRI protocol is superior to conventional MRI protocols at picking structural abnormalities in patients with drug resistant focal epilepsy.

Epilepsy O-EP002. Epileptic adolescents and Ramadan fasting: A prospective cohort study

Introduction . The prevalence of epilepsy in childhood is 3 to 5.5/1000 worldwide and 8/1000 in Arab countries, including Egypt. All healthy Muslims are obligated to fast the month of Ramadan when they reach puberty as Ramadan fasting is one of the five pillars of Islam. Aim: To evaluate the effect of Ramadan fasting on seizure control in epileptic adolescents. Methods . A prospective cohort study that included 56 epileptic patients aged 11–18 years. Patients were followed-up in the pediatric neurology clinic at Tanta University Children's Hospital during Ramadan 2019. Seizures frequency and severity, measured by Chalfont Seizure Severity Scale, during Ramadan fasting were compared to those in the month before Ramadan. Results . Before Ramadan, 43/56 patients were controlled and seizure-free. Meanwhile, 13/56 patients were uncontrolled and had seizure frequency of 1–6 seizures in the month before Ramadan. There was no significant difference in seizure frequency during Ramadan compared to before Ramadan (p = 0.132), whereas seizure severity was significantly reduced during Ramadan (p = 0.028). Both seizure frequency and severity were significantly lower during Ramadan in uncontrolled epileptic patients compared to before Ramadan (p = 0.02 & 0.005). Conclusion . Ramadan fasting is safe in adolescents with epilepsy. Fasting is not a precipitating factor for seizures in epileptic adolescents, provided compliance to anti-epileptic drugs, and could be beneficial for seizure control in uncontrolled epilepsy.

Seizure after Subdural Hematoma Treated with Combination Western-Korean Medicine

Combined Western-Korean medicine treatments were given to a 67-year-old woman with late onset seizures who underwent surgical drainage of a subdural hematoma. Clonazepam and herbal medicine was prescribed. Acupuncture, moxibustion, cupping, chuna, and physical therapy were also performed. The frequency and intensity of seizures was assessed using the Chalfont Seizure Severity Scale. The seizure index score improved from 25 at admission to 0 at discharge. Pain in the right upper extremity reduced from 10 to 0 on the visual analogue scale and muscle strength increased from Grade 3 to 5 in Medical Research Council Scale for the Manual Muscle Test. At the time of hospitalization, the manual muscle strength tests for the affected shoulder, elbow, wrist, and grip strength were 30%, 60%, 10%, 5%, respectively, which improved almost 100% by discharge. Further studies using combined Western-Korean medicine for seizures after strokes are necessary to determine the most effective treatment.

Epileptic Adolescents and Ramadan Fasting: A Prospective Cohort Study

AbstractThis study aimed to evaluate the effect of Ramadan fasting on seizure control in epileptic adolescents. A prospective cohort study that included 56 epileptic patients aged 11 to 18 years. Patients were followed-up in the pediatric neurology clinic at Tanta University Children's Hospital during Ramadan 2019. Seizures frequency and severity, measured by Chalfont seizure severity scale, during Ramadan fasting were compared with those in the month before Ramadan. Before Ramadan, 43/56 patients were controlled and seizure free. Meanwhile, 13/56 patients were uncontrolled and had seizure frequency of one to six seizures in the month before Ramadan. There was no significant difference in seizure frequency during Ramadan compared with before Ramadan (p = 0.132), whereas seizure severity was significantly reduced during Ramadan (p = 0.028). Both seizure frequency and severity were significantly lower during Ramadan in uncontrolled epileptic patients compared with before Ramadan (p = 0.02 and 0.005). Ramadan fasting is safe in adolescents with epilepsy. Fasting is not a precipitating factor for seizures in epileptic adolescents, provided compliance to antiepileptic drugs, and could be beneficial for seizure control in uncontrolled epilepsy.

Cannabidiol normalizes resting-state functional connectivity in treatment-resistant epilepsy

ObjectiveResting-state (rs) network dysfunction is a contributing factor to treatment resistance in epilepsy. In treatment-resistant epilepsy (TRE), pharmacological and nonpharmacological therapies have been shown to improve such dysfunction. In this study, our goal was to prospectively evaluate the effect of highly purified plant-derived cannabidiol (CBD; Epidiolex®) on rs functional magnetic resonance imaging (fMRI) functional connectivity (rs-FC). We hypothesized that CBD would change and potentially normalize the rs-FC in TRE. MethodsTwenty-two of 27 participants with TRE completed all study procedures including longitudinal pre-/on-CBD rs-fMRI (8M/14F, mean age = 36.2 ± 15.9 years, TRE duration = 18.3 ± 12.6 years); there were no differences in age (p = 0.99) or sex (p = 0.15) between groups. Assessments collected included seizure frequency (SF), Chalfont Seizure Severity Scale (CSSS), Columbia Suicide Severity Rating Scale (C-SSRS), Adverse Events Profile (AEP), and Profile of Mood States (POMS). Twenty-three healthy controls (HCs) received rs-fMRI and POMS once. ResultsParticipants with TRE showed average decrease of 71.7% in SF (p < 0.0001) and improved CSSS, AEP, and POMS confusion, depression, and fatigue subscores (all p < 0.05) on-CBD with POMS scores becoming similar to those of HCs. Paired t-tests showed significant pre-/on-CBD changes in rs-FC in cerebellum, frontal areas, temporal areas, hippocampus, and amygdala with some of them correlating with improvement in behavioral measures. Significant differences in rs-FC between pre-CBD and HCs were found in cerebellum, frontal, and occipital regions. After controlling for changes in SF with CBD, these differences were no longer present when comparing on-CBD to HCs. SignificanceThis study indicates that highly purified CBD modulates and potentially normalizes rs-FC in the epileptic brain. This effect may underlie its efficacy. This study provides Class III evidence for CBD's normalizing effect on rs-FC in TRE.

Drug–drug interactions with cannabidiol (CBD) appear to have no effect on treatment response in an open-label Expanded Access Program

ObjectiveWe have previously shown that cannabidiol (CBD; Epidiolex®) significantly affects levels of clobazam/N-desmethylclobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine. In the present study, we tested whether the presence of concomitant clobazam affected seizure frequency and severity (treatment response) 12 weeks after initiation of therapy with CBD in patients with treatment-resistant epilepsy (TRE). The secondary questions were whether the presence of any of the other antiepileptic drugs (AEDs) had an effect on seizure frequency or severity at 12, 24, or 48 weeks after therapy initiation. MethodsOne hundred and thirty-two adults and children with TRE receiving CBD were studied prospectively. Participants were separated into two groups — either taking (CBD + clobazam) or not taking concomitant clobazam (CBD − clobazam). In the secondary analyses, participants were divided into groups depending on whether they were taking at least 1/4 of the other AEDs shown to interact with CBD (iAED). Seizure counts and Chalfont Seizure Severity Scale (CSSS) were obtained at baseline, 12, 24, and 48 weeks. Groups were compared at each respective time point in the study using generalized estimating equations (GEE) analyses. ResultsAll groups demonstrated statistically significant reductions in seizure frequency and severity from baseline (all P < 0.05). When participants on CBD + clobazam were compared with CBD − clobazam, there were no significant differences in seizure frequency and severity reduction between the groups at 12 weeks (both P > 0.05). When comparing groups with iAEDs vs. group without iAEDs, independent of coadministration of clobazam, no differences in treatment response were observed (all P > 0.05). Longitudinal analyses up to 48 weeks after therapy initiation did not reveal any differences in treatment response between groups. ConclusionThese analyses suggest that concomitant to CBD, AEDs may not have an effect on reducing seizure frequency and severity in patients with TRE.

Cognitive functioning following long-term cannabidiol use in adults with treatment-resistant epilepsy

Cognitive dysfunction is a common comorbidity in adults with treatment-resistant epilepsy (TRE). Recently, cannabidiol (CBD) has demonstrated efficacy in epilepsy treatment. However, our understanding of CBD's cognitive effects in epilepsy is limited. We examined long-term cognitive effects of CBD in adults with TRE as part of an ongoing prospective, open-label safety study. Twenty-sevenadults with TRE (mean age: 34[SD +14], female 52%) enrolled in the UAB CBD program completed standardized cognitive testing (NIH Toolbox Cognition Battery (NIHTB-CB)) at pre-CBD administration baseline and at one-yearfollow-up. Participants were receiving stable CBD dose at the time of one-year testing (mean=36.5mg/kg/day). The NIHTB-CB consisted of two global composite scales (Fluid and Crystallized) and seven individual tests measuring aspects of working memory, episodic memory, executive function, processing speed, and language. All participants had recorded Chalfont Seizure Severity Scale (CSSS) scores at each visit. Statistical analyses consisted of t-test, Pearson correlation coefficient, and linear regression. At baseline, cognitive test performance was below average for both global composite scales (Fluid: 71 [±18] range: 46–117) and Crystallized (76 [±15] range: 59–112)]. Longitudinal analysis revealed no significant group change across the two global composite scales. Of the seven individual cognitive tests, none changed significantly over time. No correlation was found between the cognitive change scores and CBD dose (all P's≥0.21). Change in cognitive test performance was not associated change in seizure severity rating. These findings are encouraging and indicate that long-term administration of pharmaceutical grade CBD is overall cognitively well-tolerated in adults with TRE.

FMRI study of cannabidiol-induced changes in attention control in treatment-resistant epilepsy

Patients with treatment-resistant epilepsy (TRE) frequently exhibit memory and attention deficits that contribute to their poor personal and societal outcomes. We studied the effects of adjunct treatment with pharmaceutical grade cannabidiol (CBD) oral solution (Epidiolex®; Greenwich Biosciences, Inc.) on attention control processes related to stimulus conflict resolution in patients with TRE. Twenty-two patients with TRE underwent 3 T magnetic resonance imaging (MRI) before receiving (PRE) and after achieving a stable dose of CBD (ON). Functional MRI (fMRI) data were collected while patients performed 2 runs of a flanker task (FT). Patients were instructed to indicate via button press the congruent (CON) and incongruent (INC) conditions. We performed t-tests to examine with FT attention control processes at PRE and ON visits and to compare the 2 visits using derived general linear model (GLM) data (INC – CON). We performed generalized psychophysiological interaction (gPPI) analyses to assess changes in condition-based functional connectivity on FT. Median time between fMRI visits was 10 weeks, and median CBD dose at follow-up was 25 mg/kg/d. From PRE to ON, participants experienced improvements in seizure frequency (SF) (p = 0.0009), seizure severity (Chalfont Seizure Severity Scale (CSSS); p < 0.0001), and mood (Total Mood Disturbance (TMD) score from Profile of Mood States (POMS); p = 0.0026). Repeated measures analysis of variance showed nonsignificant improvements in executive function from 34.6 (23.5)% to 41.9 (22.4)% CON accuracy and from 34.2 (25.7)% to 37.6 (24.4)% INC accuracy (p = 0.199). Change in CON accuracy was associated with change in INC accuracy (rS = 0.81, p = 0.0005). Participants exhibited CBD-induced increases in fMRI activation in the right superior frontal gyrus (SFG) and right insula/middle frontal gyrus (MFG) and decrease in activation for both regions at ON relative to PRE (corrected p = 0.05). The subset of patients who improved in FT accuracy with CBD showed a negative association between change in right insula/MFG activation and change in accuracy for the INC condition (rS = −0.893, p = 0.0068). The gPPI analysis revealed a CBD-induced decrease in condition-based functional connectivity differences for the right SFG seed region (corrected p = 0.05). Whole-brain regression analysis documented a negative association of change in right insula/MFG condition-based connectivity with change in INC accuracy (corrected p = 0.005). Our results suggest that CBD modulates attention control processing in patients with TRE by reducing right SFG and right insula/MFG activation related to stimulus conflict resolution and by dampening differences in condition-based functional connectivity of the right SFG. Our study is the first to provide insight into how CBD affects the neural substrates involved in attention processing and how modulation of the activity and functional connectivity related to attentional control processes in the right insula/MFG may be working to improve cognitive performance in TRE.

Seizure severity is associated with poor quality of life in people living with epilepsy (PLWE) in Uganda: A cross-sectional study

RationaleThere is a paucity of information about the association of seizure severity and quality of life (QoL) in people living with epilepsy (PLWE) in sub-Saharan Africa. We evaluated the relationship between seizure severity and health-related quality of life (HRQoL) of patients with epilepsy being followed up in an outpatient neurology clinic in urban central Uganda. MethodsForty-eight PLWE who met the study inclusion criteria were enrolled. The study questionnaire was comprised of the Chalfont Seizure Severity Scale (CSSS) and the Quality of Life Inventory in Epilepsy (QOLIE-31). Spearman's rank correlation coefficient was used to determine the association between seizure severity and QoL score. ResultsThe median age of the study participants was 25 years, with median age (interquartile range (IQR)) of epilepsy onset of 12 (6–18) years. Over 57.4% of the study participants were unemployed. The mean (standard deviation (SD)) of QOLIE-31 and Seizure Severity Score was 62.5 (14.5) and 62.4 (1.6), respectively. There was no gender difference in the seizure severity scores (p = 0.451). An inverse relationship existed between seizure severity and the total QOLIE-31 score (Spearman's rank correlation coefficient, r = −0.48, p = 0.001), and seizure worry (r = −0.31, p = 0.030). ConclusionsIn this Ugandan sample, seizure severity is unacceptably high and directly impacts the life of PLWE. Interventions that reduce seizure severity are urgently needed in our settings to reduce seizures and improve the QoL in PLWE.

Quality of life in adults enrolled in an open-label study of cannabidiol (CBD) for treatment-resistant epilepsy

Treatment-resistant epilepsy (TRE) is associated with low quality of life (QOL). Cannabidiol (CBD) may improve QOL, but it is unclear if such improvements are independent of improvements in seizure control. Our aim was to compare QOL at baseline and after 1 year of treatment with CBD. We hypothesized that QOL would improve independent of changes in seizure frequency (SF) or severity, mood, or adverse events. We assessed QOL using Quality of Life in Epilepsy-89 (QOLIE-89) in an open-label study of purified CBD (Epidiolex®) for the treatment of TRE. All participants received CBD, starting at 5 mg/kg/day and titrated to 50 mg/kg/day in increments of 5 mg/kg/day. We collected QOLIE-89 in adult participants at enrollment and after 1 year of treatment, or at study exit if earlier. We analyzed if the change in QOLIE-89 total score could be explained by the change in SF, seizure severity (Chalfont Seizure Severity Scale, CSSS), mood (Profile of Moods States, POMS), or adverse events (Adverse Event Profile, AEP). Associations among the variables were assessed using bivariate tests and multiple regression. Fifty-three participants completed enrollment and follow-up testing, seven at study termination. Mean QOLIE-89 total score improved from enrollment (49.4 ± 19) to follow-up (57 ± 21.3; p = .004). We also saw improvements in SF, POMS, AEP, and CSSS (all p ≤ .01). Multivariable regression results showed QOLIE-89 at follow-up associated with improvements in POMS at follow-up (p = .020), but not with AEP, CSSS, or SF (p ≥ .135). Improvement in QOL after treatment with CBD is associated with better mood but not with changes in SF, seizure severity, or AEP. Cannabidiol may have beneficial effects on QOL and mood that are independent of treatment response.

A preliminary study of the effects of cannabidiol (CBD) on brain structure in patients with epilepsy.

Cannabis use is associated with changes in brain structure and function; its neurotoxic effects are largely attributed to Δ9-tetrahydrocannabidiol. Whether such effects are present in patients with epilepsy exposed to a highly-purified cannabidiol isolate (CBD; Epidiolex®; Greenwich Biosciences, Inc.) has not been investigated to date. This preliminary study examines whether daily CBD dose of 15–25 mg/kg produces cerebral macrostructure changes and, if present, how they relate to changes in seizure frequency. Twenty-seven patients with treatment-resistant epilepsy were recruited from the University of Alabama at Birmingham CBD Program. Participants provided seizure frequency diaries (SF), completed the Chalfont Seizure Severity Scale (CSSS) and Adverse Events Profile (AEP), and underwent MRI before CBD (baseline) and after achieving a stable CBD dosage (on-CBD). We examined T1-weighted structural images for gray matter volume (GMV) and cortical thickness changes from baseline to on-CBD in 18 participants. Repeated measures t-tests confirmed decreases in SF [t(17) = 3.08, p = 0.0069], CSSS [t(17) = 5.77, p < 0.001], and AEP [t(17) = 3.04, p = 0.0074] between the two time-points. Voxel-level paired samples t-tests did not identify significant changes in GMV or cortical thickness between these two time-points. In conclusion, short-term exposure to highly purified CBD may not affect cortical macrostructure.

Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study

The objective of this study was to characterize the changes in adverse events, seizure severity, and frequency in response to a pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex®) in a large, prospective, single-center, open-label study. We initiated CBD in 72 children and 60 adults with treatment-resistant epilepsy (TRE) at 5 mg/kg/day and titrated it up to a maximum dosage of 50 mg/kg/day. At each visit, we monitored treatment adverse events with the adverse events profile (AEP), seizure severity using the Chalfont Seizure Severity Scale (CSSS), and seizure frequency (SF) using seizure calendars. We analyzed data for the enrollment and visits at 12, 24, and 48 weeks. We recorded AEP, CSSS, and SF at each follow-up visit for the weeks preceding the visit (seizures were averaged over 2-week periods). Of the 139 study participants in this ongoing study, at the time of analysis, 132 had 12-week, 88 had 24-week, and 61 had 48-week data. Study retention was 77% at one year. There were no significant differences between participants who contributed all 4 data points and those who contributed 2 or 3 data points in baseline demographic and AEP/SF/CSSS measures. For all participants, AEP decreased between CBD initiation and the 12-week visit (40.8 vs. 33.2; p < 0.0001) with stable AEP scores thereafter (all p ≥ 0.14). Chalfont Seizure Severity Scale scores were 80.7 at baseline, decreasing to 39.2 at 12 weeks (p < 0.0001) and stable CSSS thereafter (all p ≥ 0.19). Bi-weekly SF decreased from a mean of 144.4 at entry to 52.2 at 12 weeks (p = 0.01) and remained stable thereafter (all p ≥ 0.65). Analyses of the pediatric and adult subgroups revealed similar patterns. Most patients were treated with dosages of CBD between 20 and 30 mg/kg/day. For the first time, this prospective, open-label safety study of CBD in TRE provides evidence for significant improvements in AEP, CSSS, and SF at 12 weeks that are sustained over the 48-week duration of treatment.

The impact of anxiety, seizure severity, executive dysfunction, subjectively perceived psychological deficits, and depression on social function in patients with epilepsy.

The impact of anxiety, seizure severity, executive dysfunction, subjectively perceived psychological deficits, and depression on social function in patients with epilepsy (PWE) was analyzed. A brief cognitive screening test (EpiTrack) and an estimation of the last 6 months' cumulative seizure severity (Chalfont seizure severity scale) were performed, and questionnaires on subjectively perceived cognitive deficits (c.I.-Skala), anxiety (State-Trait Anxiety Inventory, STAIX1 and STAIX2), depression (Self Rating Depression Scale, SDS), and social function (Soziale Aktivität Selbstbeurteilungsskala, SASS) were completed. Forty PWE (aged 41.8 years, SD 16; 24 female, 16 male) were analyzed. Thirty-eight point 5 percent had a score signifying depression in the SDS; 20% had a pathological result in at least one of the anxiety scores. The ANOVA revealed that only anxiety as a trait symptom (STAIX2) had a significant influence on social function apart from the other factors (p<0.004). Additionally there was a trend for a significant influence of depressive symptoms (SDS) on social functioning (p=0.093). Symptoms of anxiety impair the social function of patients with epilepsy apart from depression, cognitive function, and seizure severity. They should be taken into account in the treatment of patients with epilepsy.