The adult motor phenotype of Dravet syndrome is Associated with Mutation of the STXBP1 Gene and Responds Well to Cannabidiol Treatment

Dravet syndrome is a terrible disease generally caused by mutations of the SCN1A gene. Recently others genes such as STXBP1 have been involved in the pathogenesis of the disease. The STXBP1 mutation in patients with Dravet Syndrome may additionally causes several parkinsonian features usually attributed to carriers of the SCN1A mutation. Management continues to be difficult; that is why Cannabidiol emerged as valid option for treatment of this condition.

Effects of Valproate on Reproductive Endocrine Function in Male Patients with Epilepsy: A Systematic Review and Meta-Analysis

CONCLUSIONS: This meta-analysis indicates that VPA may lead to a significant decrease in the levels of FSH and testosterone and alter the concentrations of LH, DHEAS, SHBG, and ADION to some extent, which might contribute to the reproductive endocrine dysfunction in male patients with epilepsy. It is important for clinical neurologists to be cautious when prescribing VPA to reproductive-aged male patients with epilepsy.

BACKGROUND: Valproate (VPA) is a broad spectrum antiepileptic drug (AED) that is generally used as a first line agent for most idiopathic and symptomatic generalized epilepsies. Many studies have indicated that AEDs cause reproductive endocrine disorders in males, but the exact etiology underpinning these dysfunctions is not clear. This meta-analysis and systematic review was intended to evaluate the effect of VPA on reproductive endocrine function in male patients with epilepsy.

METHODS: A literature search was performed using electronic databases up to December 2017 for eligible studies. The differences in the levels of the reproductive factors, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione (ADION) in the male patients with epilepsy treated with VPA (treatment group) were compared with the those of the healthy controls (control group) by the use of the Standardized mean difference (SMD) with 95% confidence intervals (CIs).

RESULTS: Six publications with a total of 316 subjects were identified. The result revealed that the levels of FSH (SMD?=?-1.33, 95% CI: -2.60 to -0.07, P?=?0.039) and testosterone (SMD?=?-0.45, 95% CI: -0.87 to -0.03, P?=?0.038) of the treatment group were decreased significantly compared with the healthy controls. There was an increase in the levels of SHBG (SMD?=?0.41, 95% CI: -0.21 to 1.03, P?=?0.197), DHEAS (SMD?=?0.20, 95% CI: -0.06 to 0.45, P?=?0.126) and ADION (SMD?=?0.73, 95% CI: -0.10 to 1.57, P?=?0.086), and a decrease in that of LH(SMD?=?-0.71, 95% CI: -1.49 to 0.07, P?=?0.075) in the male patients with epilepsy treated with VPA, but the differences did not reach statistical significance (P?>?0.05).

Improving Compliance in Adults with Epilepsy on a Modified Atkins Diet: A Randomized Trial

PURPOSE: To determine whether use of a ketogenic formula during the first month of the modified Atkins diet (MAD) in adults with drug-resistant epilepsy (DRE) improves seizure reduction and compliance compared to MAD alone.

METHODS: Eighty adults (age ?18 years) with DRE and ?4 reliably quantifiable seizures/month were enrolled. All participants were trained to follow a 20?g/day net carbohydrate limit MAD. Patients were randomized to receive one 8-ounce (237?mL) tetrapak of KetoCal®, a 4:1 ketogenic ratio formula, daily in combination with MAD during the first month (treatment arm) or second month (control/cross-over arm). Patients recorded urine ketones, weight, and seizure frequency and followed up at 1 and 2 months.

RESULTS: By 1 month, 84% of patients achieved ketosis (median of 4-4.5 days). At 1 month, the treatment arm had a significantly higher ketogenic ratio and more patients with a ?1:1 ketogenic ratio compared to the control arm. There was no difference in median seizure frequency, proportion of responders (?50% seizure reduction), or median seizure reduction from baseline between groups. However, patients treated with KetoCal® during the first month were significantly more likely to continue MAD for 6 months or more.

CONCLUSION: Although supplementing MAD with a ketogenic formula in the first month did not increase the likelihood of reducing seizures compared to MAD alone, significantly more adults remained on MAD long-term with this approach. This suggests a potential strategy for encouraging compliance with MAD in adults with DRE.

Correlation Between Clinical and Cognitive Aspects and Nutritional Indicators of Elderly Patients with New-Onset Epilepsy

OBJECTIVE: Nutritional indicators were correlated with cognitive and clinical aspects of 25 elderly patients with new-onset epilepsy (EPWE). The nutritional indicators of the EPWE were compared with those of a similar control group at a significance level of p?<?0.05.

RESULTS: There was lower cognitive performance, greater risk of malnutrition and muscle tissue depletion, and higher waist circumference (WC) in the EPWE. Longer epilepsy duration was correlated with loss of muscle mass (Pearson’s correlation: 0.433; p?=?0.044). Performance in the verbal fluency test, in the clock-drawing test, and in the immediate memory test was negatively associated with body fat. Better performance in the image recognition test was negatively associated with the indicators of muscle reserve.

CONCLUSION: There was lower cognitive performance, higher risk of malnutrition, and high abdominal obesity in new-onset epilepsy. Cognitive performance was related to adiposity. Cognitive impairment and longer disease duration are related to increased nutritional risk.

Characteristics of the Knowledge and Attitudes of Parents about Epilepsy

AIM: The aim of the study was to identify the knowledge and attitudes of parents about epilepsy.

METHODS: Our study was conducted as a questionnaire study with 1200 parents. The demographic information of the participants, their answers to general questions about epilepsy, and their self-reported epilepsy knowledge scale and epilepsy attitude scale data were evaluated.

RESULTS: A total of 746 (62.2%) mothers and 454 (37.8%) fathers participated in the study. The mean age was 36.3?±?9.2?years. The educational level was high school or higher in 65.3%. The mothers and the fathers had similar epilepsy knowledge levels and epilepsy attitude characteristics. The highest epilepsy knowledge level and the best attitudes about epilepsy according to the educational level was in the “university or higher” group. Moreover, a positive correlation was found between the epilepsy knowledge level and positive epilepsy attitudes of the parents.

CONCLUSION: A more positive attitude and better knowledge about epilepsy with increasing educational level indicate that negative attitudes are caused by lack of information. Positive attitudes in the society toward patients with epilepsy would be expected to increase by ensuring a sufficient level of knowledge about epilepsy.

Elevated Cerebrospinal Fluid Protein in POLG-Related Epilepsy: Diagnostic and Prognostic Implications

SIGNIFICANCE: Our results indicate that there is disruption of the blood brain barrier in POLG-related disease, as evidenced by a raised cerebrospinal fluid protein and a raised CSF/serum ratio of albumin. We also find that raised cerebrospinal fluid protein is a common finding in patients with POLG disease. Our data suggest that the presence of blood brain barrier dysfunction predicts a poorer outcome, and elevated cerebrospinal fluid protein may therefore be an additional biomarker both for early diagnosis and to identify those at high risk of developing epilepsy.

OBJECTIVE: Epilepsy is common in individuals with mutations in POLG, the gene encoding the catalytic subunit of the mitochondrial DNA polymerase gamma. Early recognition and aggressive seizure management are crucial for patient survival. Disruption of the blood-brain barrier (BBB) is implicated in various neurological disorders including epilepsy. The aim of this study was to assess whether POLG-related disease is associated with BBB dysfunction and what clinical implications this has for patients.

METHODS: Our retrospective study used data from 83 patients with pathogenic POLG mutations from 4 countries–Norway, Sweden, Finland, and the United Kingdom. Data were collected using a structured questionnaire. We used the presence of raised cerebrospinal fluid (CSF) protein and a raised CSF/serum ratio of albumin (Q-alb) to evaluate the integrity of the blood-CSF barrier.

RESULTS: Raised CSF protein was found in 70% of patients (n = 58/83) and appeared to be associated with the most severe phenotypes. In those in whom it was measured, the Q-alb ratio was markedly elevated (n = 18). The majority of those with epilepsy (n = 50/66, 76%) had raised CSF protein, and this preceded seizure debut in 75% (n = 15/20). The median survival time from symptom onset for those with raised CSF protein was decreased (13 months) compared to those with normal CSF protein (32 months).

New Technique Fine-Tunes Treatment for Severe Epilepsy Cases

One of three epilepsy patients experience no relief from drugs and are candidates for surgery. An advance by researchers at Yale and the Cleveland Clinic will enable surgeons to more precisely target areas of the brain causing debilitating symptoms in a subset of these patients.

The technology called magnetoencephalography or MEG measures small amounts of magnetic-electrical activity on the surface of epileptic brain areas, and the researchers have developed a novel way to employ it.

Recording of seizures during routine MEG in some surgical candidates can help precisely identify affected areas of the brain and, in a few cases, even negate the need to conduct invasive intracranial EEG evaluations prior to surgery, the authors say. Lead author of the study published June 11 in the journal JAMA Neurology is Dr. Rafeed Alkawadri, assistant professor of neurology at Yale and director of Yale Human Brain Mapping Program. Dr. Andreas Alexopoulos of the Cleveland Clinic is senior author of the paper.

Inadequate Regulation Contributes to Mislabeled Online Cannabidiol Products

Researchers from the University of Pennsylvania, Veterans Affairs San Diego, RTI international, Americans for Safe Access, Palo Alto University, and Johns Hopkins University analyzed the content of 84 cannabidiol (CBD) products purchased on the internet and compared the results to their advertised concentrations. Products were mislabeled with 26% containing less CBD than labeled and 43% containing more, indicating a high degree of variability and poor standardization of online products.

Notably, the oil-based products were more likely to be accurate (45% compared to 25% for tincture and 12.5% for vaporization liquid) and had a smaller percentage of deviation. Oil based products also had a higher range of concentration. In addition to CBD mislabeling, ?-9-tetrahydrocannabibolic acid (THC) was detected in 21% of samples. This study also notes that products containing THC could have sufficient enough concentrations to produce intoxication in children.

Transcutaneous Vagal Nerve Stimulation (t-VNS): An Adjunctive Treatment Option for Refractory Epilepsy

PURPOSE: The aim of this trial was to investigate the efficacy and safety of transcutaneous vagal nerve stimulation (t-VNS) in the palliative treatment of drug resistant epileptic patients ineligible for surgery.

METHODS: Twenty adult patients received four hours of t-VNS per day for six months (T1), followed by a two-month washout period (T2). The frequency and type of seizures recorded at T1 and T2 were compared with those occurring in the three months preceding study entry (T0). Responders (>30% reduction in the total number of seizures) subsequently received two hours of t-VNS per day for further six months (T3). All patients underwent electroencephalography (EEG) and completed the Quality of Life in Epilepsy questionnaire at baseline and T1.

RESULTS: At T1 six patients were considered responders. In these patients, at T3 the average reduction in seizure frequency was 60% compared to T0 (p?=?0.043), and 51% compared to T2 (p?=?0.043). Responders had more often seizures with falls (5 of 6; 83.3%) compared with non-responders (3 of 14; 21.4%) (p?=?0,010) and t-VNS reduced their frequency by a percentage ranging from 47.5 to 100%. There was no change in responders’ EEG findings after stimulation. At the end of the trial, three responders continued t-VNS, one implanted VNS.

CONCLUSIONS: t-VNS had no or minimal side effects and significantly reduced seizures in about one third of the enrolled patients. Further studies should be planned to assess whether t-VNS is a suitable tool to predict the efficacy of implanted VNS.

Specificity, Versatility, and Continual Development: The Power of Optogenetics for Epilepsy Research

Optogenetics is a powerful and rapidly expanding set of techniques that use genetically encoded light sensitive proteins such as opsins. Through the selective expression of these exogenous light-sensitive proteins, researchers gain the ability to modulate neuronal activity, intracellular signaling pathways, or gene expression with spatial, directional, temporal, and cell-type specificity. Optogenetics provides a versatile toolbox and has significantly advanced a variety of neuroscience fields.

In this review, using recent epilepsy research as a focal point, we highlight how the specificity, versatility, and continual development of new optogenetic related tools advances our understanding of neuronal circuits and neurological disorders.