Comorbidity Of Epilepsy Research Articles

RTID-06. ENHANCING TUMOR TREATING FIELDS THERAPY FOR RECURRENT GLIOBLASTOMA WITH TARGETED AND INDIVIDUALIZED SKULL REMODELING SURGERY. A MULTI-CENTER RANDOMIZED PHASE 2 TRIAL

Abstract BACKGROUND We present an upcoming(Sep. 2020) randomized, comparative, multi-center, investigator-initiated, interventional, phase 2 trial testing the efficacy of a novel therapeutic concept for recurrent glioblastoma(GBM). The intervention combines personalized targeted skull remodeling surgery(SR-surgery) with Tumor Treating Fields(TTFields) and best practice medical oncological therapy. SR-surgery involves strategically placed burr holes to strengthen the electric field in the tumor region. Preclinical studies indicate that SR-surgery provides a marked and focal enhancement(~100%) of TTFields. We recently concluded a phase 1 safety/feasibility study indicating promising clinical efficacy and no clinically significant toxicity related to the intervention. This subsequent randomized, comparative phase 2 trial aims to validate superior efficacy of the treatment. METHOD We will utilize a comparative, 1:1 randomized, minimax two-stage phase 2 design with an expected sample size of 70 patients, interim futility analysis at 1-yr follow-up of the first 52 patients and a maximum sample size of 84 patients. Patients will receive either 1)TTFields and best practice medical oncological treatment(control arm) or 2) SR-surgery plus TTFields and best practice medical oncological treatment (interventional arm). Major eligibility criteria include age ≥ 18 years, supratentorial GBM, Karnofsky performance score(KPS) ≥ 70, focal tumor, and lack of uncontrollable epilepsy or significant co-morbidity. The study is designed to detect a 20% increase in the overall survival rate 12 months(OS12) assuming OS12=40% in the control group and OS12= 60% in the intervention group. Secondary endpoints include hazard ratio of overall survival and progression-free survival, objective response rate, QoL, KPS, steroid dose, and toxicity. Patients will be followed for the whole trial period(36 months). The average expected follow-up is 18 months and includes regular assessment of toxicity, response and QoL. Endpoint data will be collected at the end of the trial, occurrence of suspected unexpected serious adverse reactions(SUSARs) or unacceptable serious adverse events(SAEs), withdrawal of consent, or loss-to-follow-up.

Clinical outcomes of COVID-19 in long-term care facilities for people with epilepsy

In this cohort study, we aim to compare outcomes from coronavirus disease 2019 (COVID-19) in people with severe epilepsy and other co-morbidities living in long-term care facilities which all implemented early preventative measures, but different levels of surveillance.During 25-week observation period (16 March–6 September 2020), we included 404 residents (118 children), and 1643 caregivers. We compare strategies for infection prevention, control, and containment, and related outcomes, across four UK long-term care facilities. Strategies included early on-site enhancement of preventative and infection control measures, early identification and isolation of symptomatic cases, contact tracing, mass surveillance of asymptomatic cases and contacts. We measured infection rate among vulnerable people living in the facilities and their caregivers, with asymptomatic and symptomatic cases, including fatality rate.We report 38 individuals (17 residents) who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive, with outbreaks amongst residents in two facilities. At Chalfont Centre for Epilepsy (CCE), 10/98 residents tested positive: two symptomatic (one died), eight asymptomatic on weekly enhanced surveillance; 2/275 caregivers tested positive: one symptomatic, one asymptomatic. At St Elizabeth’s (STE), 7/146 residents tested positive: four symptomatic (one died), one positive during hospital admission for symptoms unrelated to COVID-19, two asymptomatic on one-off testing of all 146 residents; 106/601 symptomatic caregivers were tested, 13 positive. In addition, during two cycles of systematically testing all asymptomatic carers, four tested positive. At The Meath (TM), 8/80 residents were symptomatic but none tested; 26/250 caregivers were tested, two positive. At Young Epilepsy (YE), 8/80 children were tested, all negative; 22/517 caregivers were tested, one positive.Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic individuals are identified through enhanced surveillance at resident and caregiver level. We observed a low rate of morbidity and mortality, which confirmed that preventative measures with isolation of suspected and confirmed COVID-19 residents can reduce resident-to-resident and resident-to-caregiver transmission. Children and young adults appear to have lower infection rates. Even in people with epilepsy and multiple co-morbidities, we observed a high percentage of asymptomatic people suggesting that epilepsy-related factors (anti-seizure medications and seizures) do not necessarily lead to poor outcomes.

Psychiatric Comorbidities in Pediatric Epilepsy.

Psychiatric comorbidities are close to 5-times higher in children and youth with epilepsy (CYE) compared to general population. With epilepsy being one of the most common neurological disorders in children, we provide a timely review of psychiatric issues in CYE. A meta-analysis found a pooled prevalence of anxiety in 18.9% and depression in 13.5% of CYE. Attention deficit hyperactivity disorder (ADHD) is 2.5 to 5.5 times higher in CYE compared to healthy counterparts. Recent evidence highlights that behavioral adverse effects may lead to discontinuation of anti-epileptic drugs (AEDs) in more than 10% of CYE. Up to 70% CYE shows elevation in baseline psychological symptoms after AED initiation. Identifying psychiatric symptoms can be easily accomplished by the routine use of psychiatric screening instruments in CYE clinics, which is associated with improved health-related quality of life (HRQOL). Psychoeducation is a key component for any visit with CYE. There is some evidence of the effectiveness of behavioral psychological interventions for CYE. There are no therapeutic trials of psychotropics in CYE, but treatment recommendations based on the experience in adults with epilepsy and general population are applicable. Early diagnosis and management of psychiatric comorbidities leads to improvement in HRQOL of CYE. This requires routine screening and a multidisciplinary teamwork.

Implication of sestrin3 in epilepsy and its comorbidities.

Epilepsy is a serious neurological disorder affecting about 1% of the population worldwide. Epilepsy may arise as a result of acquired brain injury, or as a consequence of genetic predisposition. To date, genome-wide association studies and exome sequencing approaches have provided limited insights into the mechanisms of acquired brain injury. We have previously reported a pro-epileptic gene network, which is conserved across species, encoding inflammatory processes and positively regulated by sestrin3 (SESN3). In this study, we investigated the phenotype of SESN3 knock-out rats in terms of susceptibility to seizures and observed a significant delay in status epilepticus onset in SESN3 knock-out compared to control rats. This finding confirms previous in vitro and in vivo evidence indicating that SESN3 may favour occurrence and/or severity of seizures. We also analysed the phenotype of SESN3 knock-out rats for common comorbidities of epilepsy, i.e., anxiety, depression and cognitive impairment. SESN3 knock-out rats proved less anxious compared to control rats in a selection of behavioural tests. Taken together, the present results suggest that SESN3 may regulate mechanisms involved in the pathogenesis of epilepsy and its comorbidities.

Psychiatric Comorbidity and Quality of Life in patients with Epilepsy

Foundation: The epilepsies are persistent neurological issues in which groups of nerve cells, or neurons, in the mind now and then sign strangely and cause seizures. During a seizure, numerous neurons fire (signal) simultaneously – upwards of 500 times each second, a lot quicker than ordinary. This flood of extreme electrical action occurring simultaneously causes automatic developments, sensations, feelings, and practices and the impermanent unsettling influence of typical neuronal action may cause lost mindfulness. Epilepsy influences patients, all things considered, races, and ethnic foundations. As indicated by the National Institute of Neurological Diseases and Stroke (NINDS), about 2.3 million grown-ups and in excess of 450,000 kids and teenagers in the United States have epilepsy. Point of the Work: to evaluate the mental comorbidity and personal satisfaction in patients with epilepsy through poll 30 patients at the Neurology Unit in Pediatric Department in Benha University.Patients and Methods: At the Neurology Unit, Pediatric Department, Benha University Hospitals, the variables adding to mental comorbidity in epilepsy and to survey the effect of mental co-grimness on personal satisfaction were resolved in 30 patients with epilepsy and 30 benchmark group . The essential end purpose of this investigation is to distinguish the mental comorbidity and personal satisfaction in patients with epilepsy and their effect on personal satisfaction. Results: there is huge distinction between the contemplated bunches with respect to the downturn and tension evaluations, where 86.7% of the controls had no downturn contrasted with 0% of the patients, while just 13.3 % of them had gentle evaluation contrasted with 43.3% of the patients. Then again, 30% and 26.7% of patients endured moderate and extreme sorrow individually contrasted with 0% of the controls. End: mental comorbidity has solid effect on personal satisfaction in persistent with epilepsy.

Development and validation of a screening questionnaire for psychogenic nonepileptic seizures

ObjectiveEpilepsy and psychogenic nonepileptic seizures (PNES) are serious conditions, associated with substantial morbidity and mortality. Although prompt diagnosis is essential, these conditions are frequently misdiagnosed, delaying appropriate treatment. We developed and validated the Anxiety, Abuse, and Somatization Questionnaire (AASQ), a quick and clinically practical tool to differentiate PNES from epilepsy. MethodWe retrospectively identified psychological variables that differentiated epilepsy from PNES in a discovery cohort of patients admitted to a video-electroencephalography monitoring (VEM) unit from 2002 to 2017. From these findings, we developed the AASQ and prospectively validated it in an independent cohort of patients with gold-standard VEM diagnosis. ResultsOne thousand two hundred ninety-one patients were included in the retrospective study; mean age was 39.5 years (range: 18–99), 58% were female, 67% had epilepsy, and 33% had PNES. Psychometric data for 192 instrument items were reviewed, receiver operating characteristic curves were computed, and a 20-item AASQ was created. Prospective validation in 74 patients showed that a one-point increase in the AASQ score was associated with 11 times increase in the odds of having PNES compared with epilepsy. Low scores on the AASQ were associated with a low probability of PNES with a negative predictive value of 95%. SignificanceThe AASQ is quick, inexpensive, and clinically useful for workup of seizure disorders. The AASQ excludes PNES with a high degree of confidence and can predict PNES with significance when combined with basic clinicodemographic variables. Future research will investigate diagnostic performance of the AASQ in relevant clinical subgroups, such as patients with comorbid epilepsy and PNES.

Psychosocial long-term outcome in patients with psychogenic non-epileptic seizures

PurposeTo evaluate psychosocial long-term outcome in patients diagnosed with psychogenic nonepileptic seizures (PNES) and to predict outcome of PNES, economic status, and quality of life (QoL) at follow-up. MethodsPatients diagnosed with PNES in the video-EEG-monitoring unit at our Epilepsy center between 2002–2016 were contacted by phone 1–16 years after communicating the diagnosis. Patients underwent a structured interview asking for current PNES status, psychosocial situation (economic status, marital status, setting of living, driving), depression, and QoL. ResultsOf 70 PNES patients without comorbid epilepsy (age: 41.1 ± 13.5 years; 74 % female, follow-up: 5.2 ± 4.2 years), 23 patients (33 %) reported to be free of PNES during the last 12 months. Patients with cessation of PNES were younger at PNES onset (p < .01) and diagnosis (p < .01) and had a higher education (p < .05). At follow-up, the proportion of economically active patients only increased in individuals with cessation of PNES (p < .001) while an increased number of patients with persisting PNES relied on governmental support (p < .001). Cessation of PNES was associated with better mood (p < .01) and QoL (p < .001). In multiple regression models, cessation of PNES was only predicted by younger age at onset, while good economic outcome was determined by younger age and good economic status at diagnosis and cessation of PNES at follow-up. Good QoL at follow-up was predicted by low depressive symptoms, freedom of PNES, and economic activity at follow-up. ConclusionLong-term outcome in patients with PNES remains to be poor and the majority of patients continue to have PNES. Cessation of PNES was associated with good economic outcome, mood, and QoL.

Disrupted White Matter Integrity and Structural Brain Networks in Temporal Lobe Epilepsy With and Without Interictal Psychosis.

Background: Despite the importance of psychosis as a comorbidity of temporal lobe epilepsy (TLE), the underlying neural mechanisms are still unclear. We aimed to investigate abnormalities specific to psychosis in TLE, using diffusion MRI parameters and graph-theoretical network analysis.Material and Methods: We recruited 49 patients with TLE (20 with and 29 without interictal schizophrenia-like psychosis) and 42 age-/gender-matched healthy controls. We performed 3-tesla MRI scans including 3D T1-weighted imaging and diffusion tensor imaging in all participants. Among the three groups, fractional anisotropy (FA), mean diffusivity (MD), and global network metrics were compared by analyses of covariance. Regional connectivity strength was compared by network-based statistics.Results: Compared to controls, TLE patients showed significant temporal and extra-temporal changes in FA, and MD, which were more severe and widespread in patients with than without psychosis. We observed distinct differences between TLE patients with and without psychosis in the anterior thalamic radiation (ATR), inferior fronto-occipital fasciculus (IFOF), and inferior longitudinal fasciculus (ILF). Similarly, for network metrics, global, and local efficiency and increased path length were significantly reduced in TLE patients compared to controls, but with more severe changes in TLE with psychosis than without psychosis. Network-based statistics detected significant differences between TLE with and without psychosis mainly involving the left limbic and prefrontal areas.Conclusion: TLE patients with interictal schizophrenia-like psychosis showed more widespread and severe white matter impairment, involving the ATR, IFOF and ILF, as well as disrupted network connectivity, particularly in the left limbic and prefrontal cortex, than patients without psychosis.

Incremental burden of mental health conditions in adult patients with focal seizures

IntroductionClinical research has consistently established mental health conditions (MHCs) as frequent comorbidities of epilepsy. However, the extent of economic burden of comorbid MHC in patients with focal seizures has not been systematically investigated. This retrospective cohort analysis of health plan claims compared healthcare use and costs among adult patients with focal seizures with and without comorbid MHC. MethodsWe utilized the Inovalon Medical Outcomes Research for Effectiveness and Economics (MORE2) Registry, longitudinal data from over 150 commercial, Medicare Advantage, and managed Medicaid health plans for the analysis, and identified a cohort of patients with focal (partial-onset) seizure with relevant ICD9/10 diagnosis codes with and without MHC. Mental health conditions were defined as diagnoses for anxiety, bipolar condition/mania, attention-deficit conduct condition, major depression, schizophrenia, and other psychotic conditions, and patients without MHC were propensity score-matched to patients with preexisting MHC on baseline patient characteristics. The assessment examined a series of outcomes, including 1) direct healthcare resource utilization and 2) total provider reimbursement. ResultsPatients with preexisting MHC were more likely to receive adjunctive epilepsy therapy as well as broad-spectrum antiepileptic drugs/antiseizure medications (ASMs). Additionally, patients with focal seizures and MHC were significantly more likely to utilize high-cost healthcare services. The presence of MHC was associated with approximately 50% greater utilization of emergency department (ED), physician, and inpatient services. Consequently, healthcare expenditures were significantly higher among patients with MHC ($17,596 vs. $10,857; 62% higher, p < 0.001), with the trend consistent across all care settings. ConclusionsThis analysis illustrates the health service utilization and cost implications of MHC among patients with focal seizures. The data suggest that patients with MHC have a greater overall clinical burden, which may be associated with higher healthcare resource use and expenditures. Because of the potential burden and costs associated with MHC, neurologists should consider screening patients with focal seizures for mental health disorders to identify and initiate treatment for comorbid mental health disorders.

Multimorbidity and fit note receipt in working-age adults with long-term health conditions.

Research on sickness absence has typically focussed on single diagnoses, despite increasing recognition that long-term health conditions are highly multimorbid and clusters comprising coexisting mental and physical conditions are associated with poorer clinical and functional outcomes. The digitisation of sickness certification in the UK offers an opportunity to address sickness absence in a large primary care population. Lambeth Datanet is a primary care database which collects individual-level data on general practitioner consultations, prescriptions, Quality and Outcomes Framework diagnostic data, sickness certification (fit note receipt) and demographic information (including age, gender, self-identified ethnicity, and truncated postcode). We analysed 326 415 people's records covering a 40-month period from January 2014 to April 2017. We found significant variation in multimorbidity by demographic variables, most notably by self-defined ethnicity. Multimorbid health conditions were associated with increased fit note receipt. Comorbid depression had the largest impact on first fit note receipt, more than any other comorbid diagnoses. Highest rates of first fit note receipt after adjustment for demographics were for comorbid epilepsy and rheumatoid arthritis (HR 4.69; 95% CI 1.73-12.68), followed by epilepsy and depression (HR 4.19; 95% CI 3.60-4.87), chronic pain and depression (HR 4.14; 95% CI 3.69-4.65), cardiac condition and depression (HR 4.08; 95% CI 3.36-4.95). Our results show striking variation in multimorbid conditions by gender, deprivation and ethnicity, and highlight the importance of multimorbidity, in particular comorbid depression, as a leading cause of disability among working-age adults.

A conjoint analysis of epilepsy and migraine through network-and-pathway-based method.

Epilepsy and migraine are both considered as paroxysmal neurologic disorders. Previous studies have reported some cases with comorbidity of these two diseases. As the underlying molecular mechanism remains unclear, we performed a network-and-pathway-based method with candidate gene sets of epilepsy and migraine to explore it. : Comparing the candidate genes between epilepsy and migraine, we identified 21 common genes. Functional enrichment analysis indicated that epilepsy and migraine are dysfunctional in the similar biological processes, such as glutamatergic transmissions, channel activities, and transporter activities. We also explored many shared pathways between these two diseases such as neuroactive ligand-receptor interaction. By combining systematical analysis and previous studies review, we finally identified six essential genes associated with the comorbidity of epilepsy and migraine. This is the first time to address the common ground of epilepsy and migraine by a systematic biology method. The present study provides a novel way to explain the potential mechanisms of these two diseases and a new set of therapeutic targets.

Convulsive seizures and some behavioral comorbidities are uncoupled in the Scn1aA1783V Dravet syndrome mouse model.

Dravet syndrome (Dravet) is a severe childhood epileptic encephalopathy. The disease begins with a febrile stage, characterized by febrile seizures with otherwise normal development. Progression to the worsening stage features recurrent intractable seizures and the presentation of additional nonepileptic comorbidities, including global developmental delay, hyperactivity, and motor deficits. Later in life, at the stabilization stage, seizure burden decreases, whereas Dravet-associated comorbidities persist. To date, it remains debated whether the nonepileptic comorbidities result from severe epilepsy or represent an independent phenotypic feature. Dravet mice (DS) faithfully recapitulate many clinical aspects of Dravet. Using wild-type (WT) and DS at different ages, we monitored multiple behavioral features as well as background electroencephalogram (EEG) activity during the different stages of Dravet epilepsy. Behavioral tests of WT and DS demonstrated that some deficits manifest already at the pre-epileptic stage, prior to the onset of convulsive seizures. These include motor impairment and hyperactivity in the open field. Deficits in cognitive functions were detected at the onset of severe spontaneous seizures. Power spectral analysis of background EEG activity, measured through development, showed that DS exhibit normal background oscillations at the pre-epileptic stage, a marked reduction in total power during the onset of severe epilepsy, and a subsequent smaller reduction later in life. Importantly, low EEG power at the stage of severe frequent convulsive seizures correlated with increased risk for premature death. Our data provide a comprehensive developmental trajectory of Dravet epilepsy and Dravet-associated comorbidities in mice, under controlled settings, demonstrating that the convulsive seizures and some nonepileptic comorbidities may be uncoupled. Moreover, we report the existence of an inverse correlation, on average, between the power of background EEG and the severity of epileptic phenotypes, suggesting that such measurements may potentially serve as a biomarker for Dravet severity.

Neurodevelopmental Outcomes of High-Risk Preterm Infants: A Prospective Study in Japan.

To determine the neurodevelopmental outcomes of very-low-birth-weight infants (VLBWIs, birth weight <1,500 g) after 9 years of follow-up. This study prospectively recruited 224 VLBWIs born from 2003 to 2009 in Kyushu University Hospital, Japan. Comorbidities of neurocognitive impairment, epilepsy, and autism spectrum disorder or attention-deficit hyperactivity disorder (ASD/ADHD) were assessed at age 3, 6, and 9 years. Neurodevelopmental profiles were obtained from 185 (83%), 150 (67%), and 119 (53%) participants at age 3, 6, and 9 years, respectively. At age 9 years, 25 (21%) VLBWIs showed intelligence quotient (IQ) <70, 11 (9%) developed epilepsy, and 14 (12%) had a diagnosis of ASD/ADHD. The prevalence of epilepsy was higher in children with an IQ <70 at age 9 years than in those with an IQ ≥70 (44% vs 0%). In contrast, ASD/ADHD appeared at similar frequencies in children with an IQ <70 (16%) and ≥70 (11%). Perinatal complications and severe brain lesions on MRI were considered common perinatal risks for developmental delay and epilepsy but not for ASD/ADHD. Male sex was identified as a unique risk factor for ASD/ADHD. These data suggest that VLBWIs showed a higher prevalence of developmental delay, epilepsy, and ASD/ADHD at age 9 years than the general population. Distinct mechanisms might be involved in the pathogenic process of ASD/ADHD from those of developmental delay and epilepsy.

Epilepsy and drug-resistant epilepsy in children with cerebral palsy: A retrospective observational study

PurposeThe objective of this study was to determine risk factors for epilepsy and drug-resistant epilepsy (DRE) development in children with cerebral palsy. MethodTwo hundred twenty-nine patients presenting to the pediatric neurology clinic and diagnosed as having cerebral palsy between November 2016 and November 2019 were included in the study. Medical histories and clinical, laboratory, and radiological findings were examined retrospectively from patient records in the hospital data system. ResultsGirls represented 103 patients (45%) and boys 126 (55%). The patients' mean age was 8.39 ± 4.54 years. Epileptic seizures were present in 120 (52.4%) patients and drug-resistant seizures in 64 (27.9%). The risk of epilepsy was significantly higher in patients with motor or speech impairment, with hearing impairment, or undergoing first seizure in the neonatal period. We also observed a higher risk of epilepsy in patients with psychiatric comorbidity, particularly autism spectrum disorder. The risk of epilepsy was also higher in patients with microcephaly or quadriplegic cerebral palsy and in patients with focal and generalized epileptiform abnormality on electroencephalograms (EEGs). However, no significant difference was identified when all these factors were evaluated in terms of the risk of developing DRE. ConclusionPatients with cerebral palsy have high comorbid epilepsy rates. We think that the risk of epilepsy may be higher in patients undergoing first seizure in the neonatal period, with microcephaly, with quadriplegic type cerebral palsy, and with additional psychiatric comorbidity. The rate of DRE development was very low in patients with normal EEG findings or with only background rhythm abnormalities on first EEGs during neonatal seizures. This may be regarded as a good prognostic factor for nondevelopment of DRE.

Role of inflammation in childhood epilepsy and ADHD comorbidity

Epilepsy is a heterogeneous disorder that is not limited to experiencing seizures but also includes multiple neuropsychiatric squeal (i.e. attention-deficit/hyperactivity disorder (ADHD), depression and anxiety) that adversely impact a child quality of life. However, the underlying mechanism linking both disorders is not yet thoroughly explored. Our objective was to assess pro-inflammatory cytokines levels in children with seizure controlled epilepsy and explore the association between pro-inflammatory cytokines and the co-occurrence of ADHD in such children. A cross-sectional study included 50 children with controlled epilepsy for at least one year, in addition to 30 neurotypical children as controls. All children were assessed by the Conner parent scale for ADHD. Serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were measured and correlated to clinical data. In the present study, 23 out of 50 children with epilepsy also had ADHD (46%). Children with ADHD have been found to have a significantly lower age of onset, longer duration of epilepsy, and a higher serum level of IL-6 and TNF-α than those without ADHD. The Conner's parent rating scale overall total score yielded significant negative correlations with the age of onset of epilepsy and a significant positive correlation with the duration of epilepsy and pro-inflammatory cytokine levels. In addition to active seizures, the presence of elevated circulating inflammation markers may be associated with increased frequency of ADHD in children with epilepsy aged 6-14 years.

Idiopathic epilepsy in dogs: insights into factors that may predict upcoming seizure activity

Idiopathic epilepsy (IE) is the most common chronic neurological disorder in dogs. Most dogs with IE first experience seizures when they are under six years old, and they usually require...

Cannabinoids for People with ASD: A Systematic Review of Published and Ongoing Studies

The etiopathogenesis of autism spectrum disorder (ASD) remains largely unclear. Among other biological hypotheses, researchers have evidenced an imbalance in the endocannabinoid (eCB) system, which regulates some functions typically impaired in ASD, such as emotional responses and social interaction. Additionally, cannabidiol (CBD), the non-intoxicating component of Cannabis sativa, was recently approved for treatment-resistant epilepsy. Epilepsy represents a common medical condition in people with ASD. Additionally, the two conditions share some neuropathological mechanisms, particularly GABAergic dysfunctions. Hence, it was hypothesized that cannabinoids could be useful in improving ASD symptoms. Our systematic review was conducted according to the PRISMA guidelines and aimed to summarize the literature regarding the use of cannabinoids in ASD. After searching in Web of KnowledgeTM, PsycINFO, and Embase, we included ten studies (eight papers and two abstracts). Four ongoing trials were retrieved in ClinicalTrials.gov. The findings were promising, as cannabinoids appeared to improve some ASD-associated symptoms, such as problem behaviors, sleep problems, and hyperactivity, with limited cardiac and metabolic side effects. Conversely, the knowledge of their effects on ASD core symptoms is scarce. Interestingly, cannabinoids generally allowed to reduce the number of prescribed medications and decreased the frequency of seizures in patients with comorbid epilepsy. Mechanisms of action could be linked to the excitatory/inhibitory imbalance found in people with ASD. However, further trials with better characterization and homogenization of samples, and well-defined outcomes should be implemented.

An acute seizure prior to memory reactivation transiently impairs associative memory performance in C57BL/6J mice

Memory deficits significantly decrease an individual's quality of life and are a pervasive comorbidity of epilepsy. Despite the various distinct processes of memory, the majority of epilepsy research has focused on seizures during the encoding phase of memory, therefore the effects of a seizure on other memory processes is relatively unknown. In the present study, we investigated how a single seizure affects memory reactivation in C57BL/6J adult mice using an associative conditioning paradigm. Initially, mice were trained to associate a tone (conditioned stimulus), with the presence of a shock (unconditioned stimulus). Flurothyl was then administered 1 h before, 1 h after, or 6 h before a memory reactivation trial. The learned association was then assessed by presenting a conditioned stimulus in a new context 24 h or 1 wk after memory reactivation. We found that mice receiving a seizure 1 h prior to reactivation exhibited a deficit in memory 24 h later but not 1 wk later. When mice were administered a seizure 6 h before or 1 h after reactivation, there were no differences in memory between seizure and control animals. Altogether, our study indicates that an acute seizure during memory reactivation leads to a temporary deficit in associative memory in adult mice. These findings suggest that the cognitive impact of a seizure may depend on the timing of the seizure relative to the memory process that is active.

Abstract CT184: Optimizing Tumor Treating Fields therapy for recurrent glioblastoma with targeted and individualized skull remodeling surgery. A multi-center randomized phase 2 trial

Abstract Background: We will initiate (March 2020) a randomized, comparative, multi-center, investigator-initiated, interventional, phase 2 trial (NCT04223999) testing the efficacy of a potentially new treatment modality for recurrent glioblastoma (GBM). The new treatment modality combines individualized targeted skull remodeling surgery (SR-surgery) with Tumor Treating Fields (TTFields) and best practice medical oncological therapy. The aim of SR-surgery is to enhance the electric field in the tumor region, by removing bone with burrholes. Preclinical research indicate that this modality provides a marked and focal enhancement (~100%) of TTFields. We concluded (April 2019) a phase 1 safety/feasibility trial indicating improved overall survival without additional toxicity from the intervention. The following randomized, comparative phase 2 trial aims to validate superior efficacy of the intervention. Method: The trial is designed as a comparative, 1:1 randomized, minimax two-stage phase 2 with an expected 70 patients to a maximum sample size of 84 patients. After 12-months follow-up of the first 52 patients an interim futility analysis will be performed. The two trial arms will consist of either a) TTFields, best practice oncological treatment (control arm) or b) SR-surgery, TTFields and best practice oncology (interventional arm).Major eligibility criteria include age ≥ 18 years, supratentorial GBM, Karnofsky performance score (KPS) ≥ 70, focal tumor, and lack of uncontrollable epilepsy or significant co-morbidity. Study design aims to detect a 20% increase in the overall survival rate 12 months (OS12) assuming OS12 = 40% in the control group and OS12= 60% in the intervention group. Secondary endpoints include hazard rate ratio of overall survival and progression-free survival, objective response rate, quality of life, KPS, steroid dose, and toxicity. Patient follow-up is until death or 36 months (trial duration). Expected average for follow-up is 18 months. Every 3. month there will be an assessment of toxicity, response and QoL. Endpoint data will be collected at the end of the trial, occurrence of suspected unexpected serious adverse reactions (SUSARs) or unacceptable serious adverse events (SAEs), withdrawal of consent, or loss-to-follow-up. Citation Format: Nikola Mikic, Anders R. Korshøj. Optimizing Tumor Treating Fields therapy for recurrent glioblastoma with targeted and individualized skull remodeling surgery. A multi-center randomized phase 2 trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT184.

Heart Rate Variability Parameters During Psychogenic Non-epileptic Seizures: Comparison Between Patients With Pure PNES and Comorbid Epilepsy.

Introduction: Psychogenic non-epileptic seizures (PNES) may resemble epileptic seizures. There are few data about ictal ANS activity alterations induced by PNES in patients with pure PNES (pPNES) compared to PNES with comorbid epilepsy (PNES/ES). We aimed to compare heart rate variability (HRV) parameters and hence autonomic regulation in PNES in epileptic and non-epileptic patients.Methods: We obtained HRV data from video-electroencephalography recordings in 22 patients presenting PNES (11 pPNES and 11 PNES/ES) in awake, and supine states. We calculated HRV parameters in both time and frequency domains including low frequency (LF) power, high frequency power (HF), LF/HF ratio, square root of the mean of the sum of the squares of differences between adjacent R wave intervals (RMSSD) and the standard deviation of all consecutive R wave intervals (SDNN). We also evaluated approximate entropy (ApEn), cardiosympathetic index (CSI), and cardiovagal index (CVI). Four conditions were considered: basal condition (BAS), before PNES (PRE), during PNES (ICT) and after PNES (POST).Results: HRV analysis showed significantly higher ICT LF and LF/HF ratio vs. each condition. We also found higher POST HF vs. PRE and BAS, lower RRI in ICT vs. each condition and PRE vs. BAS. POST RMSSD was significantly higher compared to all other states. ICT CSI was significantly higher compared to all other states, whereas CSI was significantly lower in POST vs. PRE and PRE CVI lower than ICT and higher in POST vs. BAS and PRE. Also, ICT ApEn was lower than in all other states. Higher LF in pPNES vs. PNES/ES was also evident when compared across groups.Significance: A few studies examined HRV alterations in PNES, reporting high sympathetic tone (although less evident than in epileptic seizures). Our data suggest a sympathetic overdrive before and during PNES followed by a post-PNES increase in vagal tone. A sympathovagal imbalance was more evident in pPNES as compared to PNES/ES.