Autism Spectrum Disorder: Correlation between aberrant behaviors, EEG abnormalities and seizures

The relationship between epilepsy, epileptiform discharges, cognitive, language and behavioral symptoms is not clearly understood. Since difficulties with socialization and maladaptive behaviors are found in children with Autism Spectrum Disorder (ASD), we inquired whether epileptiform activity and seizures are associated with adverse behavioral manifestations in this population. We reviewed our EEG database between 1999–2006, and identified 123 children with ASD. EEG abnormalities were found in 39 children (31%). A control group of age and gender matched ASD children with normal EEG’s was obtained. Packets of questionnaires including the Vineland Adaptive Behavior Scale II (VABS), Aberrant Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS) were sent by mail. Out of 21 packets received, 11 had normal and 10 had abnormal EEG’s. There were no statistically significant differences in behavior between the two groups. Statistical analysis of discharge location and frequency did not reveal a significant trend. However, children with ASD and seizures had statistically significant lower scores in VABS daily living (P=0.009) and socialization (P=0.007) as compared to those without seizures. ASD children with seizures had higher ABC levels of hyperactivity and irritability. Differences in irritability scores nearly reached statistical significance (P=0.058). There was no significant difference in the degree of CARS autism rating between the groups. Our study did not reveal statistically significant differences in behaviors between ASD children with and without EEG abnormalities. However, ASD children with seizures revealed significantly worse behaviors as compared to counterparts without seizures

Assurance Cases for Proofs as Evidence

Proof-carrying code (PCC) provides a 'gold standard' for establishing formal and objective confidence in program behavior. However, in order to extend the benefits of PCC - and other formal certification techniques - to realistic systems, we must establish the correspondence of a mathematical proof of a program's semantics and its actual behavior. In this paper, we argue that assurance cases are an effective means of establishing such a correspondence. To this end, we present an assurance case pattern for arguing that a proof is free from various proof hazards. We also instantiate this pattern for a proof-based mechanism to provide evidence about a generic medical device software

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes

Autism Spectrum Disorder: Correlation between aberrant behaviors, EEG abnormalities

The relationship between epilepsy, epileptiform discharges, cognitive, language and behavioral symptoms is not clearly understood. Since difficulties with socialization and maladaptive behaviors are found in children with Autism Spectrum Disorder (ASD), we inquired whether epileptiform activity and seizures are associated with adverse behavioral manifestations in this population. We reviewed our EEG database between 1999-2006, and identified 123 children with ASD. EEG abnormalities were found in 39 children (31%). A control group of age and gender matched ASD children with normal EEG’s was obtained. Packets of questionnaires including the Vineland Adaptive Behavior Scale II (VABS), Aberrant Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS) were sent by mail. Out of 21 packets received, 11 had normal and 10 had abnormal EEG’s. There were no statistically significant differences in behavior between the two groups. Statistical analysis of discharge location and frequency did not reveal a significant trend. However, children with ASD and seizures had statistically significant lower scores in VABS daily living (P=0.009) and socialization (P=0.007) as compared to those without seizures. ASD children with seizures had higher ABC levels of hyperactivity and irritability. Differences in irritability scores nearly reached statistical significance (P=0.058). There was no significant difference in the degree of CARS autism rating between the groups. Our study did not reveal statistically significant differences in behaviors between ASD children with and without EEG abnormalities. However, ASD children with seizures revealed significantly worse behaviors as compared to counterparts without seizures

Ketogenic diet: Predictors of seizure control

Background: The ketogenic diet is an effective non-pharmacologic treatment for medically resistant epilepsy. The aim of this study was to identify any predictors that may influence the response of ketogenic diet. Methods: A retrospective chart review for all patients with medically resistant epilepsy was performed at a tertiary care epilepsy center from 1996 to 2012. Patient- and diet-related variables were evaluated with respect to seizure reduction at 1, 3, 6, 9 and 12-month intervals and divided into four possible outcome classes. Results: Sixty-three patients met inclusion. Thirty-seven (59%) reported >50% seizure reduction at 3 months with 44% and 37% patients benefiting at 6-month and 12-month follow up, respectively. A trend toward significant seizure improvement was noted in 48% patients with seizure onset >1 year at 12-month (p = 0.09) interval and in 62% patients with >10 seizure/day at 6-month interval (p = 0.054). An ordinal logistic regression showed later age of seizure to have higher odds of favorable response at 1-month (p = 0.005) and 3-month (p = 0.013) follow up. Patients with non-fasting diet induction were more likely to have a favorable outcome at 6 months (p = 0.008) as do females (p = 0.037) and those treated with higher fat ratio diet (p = 0.034). Conclusion: Our study reports the effectiveness of ketogenic diet in children with medically resistant epilepsy. Later age of seizure onset, female gender, higher ketogenic diet ratio and non-fasting induction were associated with better odds of improved seizure outcome. A larger cohort is required to confirm these findings

MRI segmentation analysis in temporal lobe and idiopathic generalized epilepsy

BACKGROUND: Temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) patients have each been associated with extensive brain atrophy findings, yet to date there are no reports of head to head comparison of both patient groups. Our aim was to assess and compare between tissue-specific and structural brain atrophy findings in TLE to IGE patients and to healthy controls (HC). METHODS: TLE patients were classified in TLE lesional (L-TLE) or non-lesional (NL-TLE) based on presence or absence of MRI temporal structural abnormalities. High resolution 3 T MRI with automated segmentation by SIENAX and FIRST tools were performed in a group of patients with temporal lobe epilepsy (11 L-TLE and 15 NL-TLE) and in15 IGE as well as in 26 HC. Normal brain volume (NBV), normal grey matter volume (NGMV), normal white matter volume (NWMV), and volumes of subcortical deep grey matter structures were quantified. Using regression analyses, differences between the groups in both volume and left/right asymmetry were evaluated. Additionally, laterality of results was also evaluated to separately quantify ipsilateral and contralateral effects in the TLE group. RESULTS: All epilepsy groups had significantly lower NBV and NWMV compared to HC (p < 0.001). L-TLE had lower hippocampal volume than HC and IGE (p = 0.001), and all epilepsy groups had significantly lower amygdala volume than HC (p < = 0.004). In L-TLE, there was evidence of atrophy in both ipsilateral and contralateral structures. CONCLUSIONS: Our study revealed that TLE and IGE patients demonstrated similar overall tissue-specific brain atrophy, although specific structures differences were appreciated. L-TLE also appeared to behave differently than NL-TLE, with atrophy not limited to the ipsilateral side