Higher Seizure Rates Research Articles

Advances in epileptic network findings of hypothalamic hamartomas.

Hypothalamic hamartomas (HHs) are congenital developmental malformations located in the hypothalamus. They are associated with a characteristic clinical manifestation known as gelastic seizures (GS). However, the traditional understanding of HHs has been limited, resulting in insufficient treatment options and high recurrence rates of seizures after surgery. This is consistent with the network hypothesis of focal epilepsy that the epileptogenic zone is not only limited to HH but may also involve the distant cerebral cortex external to the HH mass. The epilepsy network theory, on the other hand, provides a new perspective. In this study, we aim to explore HH-related epilepsy as a network disease, challenging the conventional notion of being a focal lesional disease. We analyze various aspects of HHs, including genes and signaling pathways, local circuits, the whole-brain level, phenotypical expression in terms of seizure semiology, and comorbidities. By examining HHs through the lens of network theory, we can enhance our understanding of the condition and potentially identify novel approaches for more effective management and treatment of epilepsy associated with HHs.

Collegiate Athletes With Diabetes: Baseline Medical Comorbidities and Preseason Concussion Testing Performance.

People with diabetes mellitus (DM) are at increased risk for adverse health events and complications throughout their lifetime. Whether DM significantly affects collegiate athletes' concussion baseline testing performance remains unclear. To (1) describe the prevalence of DM and associated comorbidities and (2) compare concussion baseline testing performance between student-athletes with DM and student-athletes without DM (NoDM). Retrospective, cross-sectional study. University. Using the Concussion, Assessment, Research and Education (CARE) Consortium research database, we matched athletes with self-reported DM (N = 229) by institution, sex, age, sport, position, testing year, and concussion history to athletes with NoDM (N = 229; total sample mean age = 19.6 ± 1.4 years, women = 42%). Descriptive statistics and χ2 tests of independence with subsequent odds ratios were calculated. Independent-samples t tests compared baseline symptoms, neurocognitive testing, and balance performance between athletes with DM and athletes with NoDM. Effect sizes were determined for significant group differences. At baseline, athletes with DM had higher rates of self-reported pre-existing balance disorders, sleep disorders, seizure disorders, motion sickness, learning disorders, vision and hearing problems, psychiatric disorders, depression, bipolar disorder, nonmigraine headaches, and meningitis than athletes with NoDM (P values < .05). We found balance differences between groups (P = .032, Cohen d = 0.17) such that, on average, athletes with DM had 1 additional error on the Balance Error Scoring System (DM = 13.4 ± 6.5; NoDM = 12.1 ± 5.9). No other comparisons yielded significant results. Although athletes with DM had high rates of self-reported balance disorders, sleep disorders, seizures, and meningitis, their baseline neurocognitive testing results were largely identical to those of athletes with NoDM. Our findings suggested that nonclinically meaningful differences were present in concussion baseline balance testing but no significant differences were noted in cognitive testing; however, the effect of DM on concussion recovery remains unknown.

Classification System for Predicting Emergent Epilepsy Phenotype in the Intra-amygdala Kainic Acid Mouse Model of Epilepsy.

Animal models of drug-resistant epilepsy represent an important resource for discovering new drug targets and testing experimental medicines. Intra-amygdala microinjection of kainic acid in mice is one of the most widely regarded models of drug-resistant epilepsy. Mice develop acute status epilepticus, which diminishes after a few hours and then, within a few days, mice display spontaneous seizures (epilepsy). The frequency of spontaneous seizures varies between mice, with some developing low or high seizure rates. The ability to predict soon after status epilepticus, which mice will go on to develop a normal frequency of seizures, would enable a significant reduction in resources and EEG reviewing time and lead to humane early end-points for the mice with low or high seizure rates. In this study, we developed two machine learning models, a feature-based and transfer learning-based approach, for predicting the emergent spontaneous seizure rates in the intra-amygdala kainic acid model based on the acute EEGs recorded in mice during status epilepticus lasting 40 minutes. The method was trained on data from 28 mice and subsequently tested on data from 16 mice. The feature-based and transfer learning-based models achieved accuracies of 69% and 75%, respectively on the test set in classifying emergent epilepsy as normal or outlier (i.e. low-frequency or high-frequency seizure rate). A limitation of the intra-amygdala kainic acid model has been the loss of time and resources from generating mice with low or high rates of spontaneous seizures. To date, no other research has attempted to predict emergent spontaneous seizure rates. The feature-based and transfer learning-based models will assist researchers in identifying mice with a normal frequency of seizures before the onset of spontaneous seizures. We have implemented this approach as a web server, which can potentially reduce the time and resources spent analysing the EEGs of mice who develop low-frequency or high-frequency seizure rates. This will enable the early humane endpoint of outlier mice, which aligns with the principles of the responsible use of animals in research and simultaneously speeds up preclinical anti-epilepsy drug discovery.

NCMP-23. EVALUATION OF IMMUNOTHERAPY EFFECTS IN CANCER PATIENTS ON EPILEPTIFORM ACTIVITY

Abstract BACKGROUND/OBJECTIVE Immune checkpoint inhibitors are associated with increased risk of autoimmune neurologic conditions, both in the peripheral and central nervous system. Increased activation of the immune system can lower seizure threshold, potentially increasing a patient’s risk of seizures. We hypothesize that patients treated with immune checkpoint inhibitors have a higher rate of seizures. METHODS We retrospectively reviewed 465 cancer patients undergoing electroencephalography (EEG) monitoring performed at Memorial Sloan Kettering Cancer Center from January 2022 to March 2023. Data was gathered from an EEG RedCap database containing patient demographic and seizure data. Patients were separated based on whether they had received immune checkpoint inhibitors (+ICI) prior to seizure occurrence or were never exposed to immune checkpoint inhibitors (-ICI) and had a seizure. Patient cancer type and presence of brain lesions (primary or metastases) were also reviewed. RESULTS Out of 465 patients, 109 received immune checkpoint inhibitors (+ICI) during their treatment. Seven of those patients were reported to have had at least one seizure (7/109, 6.42%) following treatment with ICI. The remaining 356 patients did not undergo immune checkpoint inhibitor treatment (-ICI), of which 30 were reported to have had at least one seizure (30/356, 8.43%). Of the +ICI patients who were experiencing seizures, 5 of them had brain lesions; 4 had primary brain tumors and 1 had brain metastases. Of –ICI patients, 21 patients had brain lesions; 15 had primary brain tumors and 6 had brain metastases. DISCUSSION Although immune checkpoint therapy may lead to increased activation of the immune system, our data did not reveal a higher incidence of seizures. Limitations to our study include its retrospective design, low number of patients, and low overall number of seizures captured on EEG.

Interaction between valproic acid and meropenem or ertapenem in patients with epilepsy: clinical relevance and results from pharmaceutical intervention

ObjectiveThe literature has described the interaction between valproic acid and carbapenems. This interaction leads to decreases in plasma concentrations of valproic acid. The main objectives of this study were to assess its relevance in clinical practice, to identify variables associated with increased seizure episode rates, and to analyse the impact of pharmaceutical intervention on avoiding the effects of this interaction. MethodAn observational retrospective study of inpatients with epilepsy admitted between 2016 and 2020. Their pharmacological treatment throughout admission was recorded, and the presence of other interactions leading to decreased plasma concentrations of valproic acid was reviewed. The seizure rate during the year prior to admission was compared to that during the interaction period. For every episode in which the interaction was detected, an intervention was conducted by providing the prescriber with information on the interaction and suggesting a change of antibiotherapy as well as the pharmacokinetic monitoring of valproic acid. Results37 episodes were included. 58.1% of the patients were male and median age was 70 years. In total, 56.8% of the patients received meropenem and 43.2% received ertapenem. The median duration of concomitant treatment with valproic acid and carbapenem was 4 days. The incidence rate ratio was 2.60 (95% confidence interval: 1.61-4.21). Thus, this interaction was associated with a higher seizure rate. A statistically significant association was found between higher seizure rates and patients treated with more than one anti-epileptic drug. Hospital pharmacists detected 24 episodes (64.9%). In total, 17 interventions (70.8%) were accepted and 13 combinations were discontinued. Pharmacokinetic monitoring was conducted in 13 episodes (35.1%) and infratherapeutic levels were found in all of them. ConclusionsThe interaction between valproic acid and meropenem or ertapenem is clinically relevant. It is recommended that this combination should be avoided provided that a viable alternative is available. Pharmaceutical intervention may contribute to preventing seizures associated with this combination.

Risk of seizures in a population of women with BRCA-positive metastatic breast cancer from an electronic health record database in the United States

BackgroundIncidence and risk factors for seizures among women with advanced breast cancer (BC) and brain metastases are not well characterized across treatment-related or clinical subtypes. This study leveraged a large real-world dataset to describe incidence and risk factors for seizures in BRCA-associated metastatic breast cancer.MethodsThe Optum® de-identified electronic health records database was used. Females with a BC diagnoses between 2008 and 2018, with clinic visits 12 months before BC index date, evidence of BRCA mutation (BRCA+), evidence of metastasis, and no previous cancers were included. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR- (human epidermal growth factor 2/hormone receptor), HER2−/HR+, HER2+/HR+, and triple negative BC (TNBC; HER2−/HR-). Seizures were identified using diagnosis codes and natural language processing. Incidence, occurrence rates, and cumulative incidence of seizures from the diagnosis of metastasis to the end of follow up were calculated. Comparisons were made between phenotypes and stratified on PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsants use before BC. All comparisons included age at metastasis, number of prior lines of treatment, and metastasis location as covariates.Results27.8% of 7941 BRCA+ patients had ≥1 seizure over a mean follow-up time of 2.35 years. Incidence and occurrence rates were 11.83 (95% CI: 11.35–12.33) and 201.3 (95% CI: 198.05–204.50), respectively, per 100 person-years. HER2−/HR+ and TNBC patients had the lowest and highest seizure incidence rates, respectively (10.94 [95% CI: 10.23–11.71] and 16.83 [95% CI: 15.34–18.46]). With HER2−/HR+ as the reference group in a competing risk analysis, TNBC (hazard ratio, HR = 1.35; 95%CI: 1.21, 1.52; p < 0.001) and HER2+/HR- (HR = 1.29; 95%CI: 1.07, 1.56; p < 0.01) patients had a greater risk of seizures. Patients with diagnosed brain metastases or a history of seizures had higher seizure rates. Incidence trended higher with PARP inhibitor use, but patient numbers were low.ConclusionsThis study provides novel real-world evidence on seizure incidence rates in BRCA+ BC patients, even those without diagnosed brain metastases, and underscores the need to understand patients’ tumor phenotypes when assessing seizure risk. These findings may have implications for clinical practice and assessment of benefit-risk ratios of new therapeutic agents.

Quality of epilepsy care in a rural and deprived Scottish population.

Epilepsy is among the commonest neurological disorders globally. Appropriate prescription and good adherence to anticonvulsants can achieve seizure freedom rates of 70%. Scotland is an affluent nation with free at point-of-access health care but there remain significant healthcare inequalities, particularly associated with deprivation. Anecdotally, epileptics in rural Ayrshire rarely engage with healthcare services. We describe the prevalence and management of epilepsy in a deprived and rural Scottish population. Electronic records were used to obtain the following for patients with coded diagnoses of 'Epilepsy' or 'Seizures' within a general practice list of 3500 patients: demographics; diagnosis; seizure types; date and level (primary, secondary) of last review; last seizure date; anticonvulsant prescription; adherence; and any clinic discharge due to non-attendance. 92 patients were coded as above. 56 had a current diagnosis of epilepsy (prev 16.1/100,000). 69% had good adherence. 56% had good seizure control, with adherence associated with control. Of the 68% managed by primary care, 33% were uncontrolled and 13% had had an epilepsy review in the previous year. 45% of patients referred to secondary care were discharged for non-attendance. We demonstrate a high prevalence of epilepsy, low anticonvulsant adherence and sub-optimal rates of seizure freedom. These may be linked to poor attendance at specialist clinics. Management in primary care is challenging as evidenced by low review rates and high rates of ongoing seizures. We propose that the synergistic factors of uncontrolled epilepsy, deprivation and rurality make it difficult to attend clinics, with resultant health inequalities.

Seizures as treatment-emergent adverse events during glioblastoma clinical trials.

e14018 Background: Seizures are not an uncommon presenting symptom of glioblastoma (GBM), and may occur following surgery for GBM. Such seizures typically can be controlled with anti-epileptics, and the risk of seizures seems to decrease after concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ). However, the risk of seizures theoretically might be increased in association with a therapeutic intervention designed to enhance local inflammation at the GBM site. 33% of patients experienced one or more seizures as a treatment-emergent-adverse-event (TEAE) during a phase II clinical trial of AV-GBM-1, patient-specific dendritic cell vaccines that consist of autologous dendritic cells loaded with autologous tumor associated antigens derived from a short-term culture of self-renewing tumor cells, that were injected subcutaneously for up to six months after recovery following concurrent RT/TMZ (Bota DA et al. 2021 Society for Immunotherapy of Cancer (SITC) late-breaking abstract #952, 2021 Society of Neuro-Oncology abstract #CTIM-33). A literature search was conducted to determine reported rates of seizures as TEAE in primary GBM patients in clinical trials. Methods: Phase III trials of systemic treatment of primary GBM, and published during 2005 to 2021, were identified by searches of clinicaltrials.gov and PubMed. Published reports were reviewed for data describing the frequency of seizures reported as TEAE in text and/or summary tables. Only trials that had at least 50 patients in a standard treatment arm of surgical resection, RT/TMZ and maintenance TMZ were included. Chi square test was used to compare proportions of patients experiencing seizures in these trials. Results: Eight such randomized trials were identified. Five trials did not mention seizures as TEAE. One trial provided data only for grade 3 and 4 events: 13/229 (5.7%). The other two trials reported all seizures regardless of grade, but were limited to patient populations with O6-methylguanine-DNA-methyltransferase promoter methylation in one, and epidermal growth factor receptor amplification in the other. The rates of seizures in those two trials were much lower than the 19/57 (33.0%) reported with AV-GBM-1: 28/258 (10.9%, p &lt; 0.0001), and 69/372 (15.4%, p = 0.0136). Conclusions: The frequency of seizures that occur in GBM patients receiving standard RT/TMZ is not well-documented in publications of large, randomized trials. AV-GBM-1 may be associated with a higher rate of seizures because of treatment-induced inflammation at the tumor site, but a randomized trial would be needed to determine this.

Perinatal Outcomes and Factors Associated with Ethnic Group in cases of Preterm Birth: the Multicenter Study on Preterm Birth in Brazil.

To investigate the characteristics of women who had preterm birth (PTB) and related outcomes according to ethnicity. A secondary analysis of a multicenter cross-sectional study conducted in Brazil. Women who had PTB were classified by self-report as white and non-white. Clinical, pregnancy, and maternal data were collected through postpartum interviews and reviews of medical charts. The sociodemographic, obstetric and clinical characteristics of the women, as well as the mode of delivery and the neonatal outcomes among different ethnic groups were compared through a bivariate analysis. Of the 4,150 women who had PTB, 2,317 (55.8%) were non-white, who were more likely: to be younger than 19 years of age (prevalence ratio [PR]: 1.05; 95% confidence interval [95%CI]: 1.01-1.09); to be without a partner; to live on low income; to have lower levels of schooling; to have ≥ 2 children; to perform strenuous work; to be from the Northeastern region of Brazil rather than the from Southern region; to have a history of ≥ 3 deliveries; to have an interpregnancy interval < 12 months; to have pregnancy complications such as abortion, PTB, preterm premature rupture of membranes (pPROM), and low birth weight; to initiate antenatal care (ANC) visits in the second or third trimesters; to have have an inadequate number of ANC visits; to be under continuous overexertion; to smoke in the first and second or third trimesters; and to have anemia and gestational hypertension. The maternal and neonatal outcomes did not differ between the groups, except for the higher rate of low birth weight (73.7% versus 69.0%) in infants born to non-white women, and the higher rate of seizures (4.05% versus 6.29%) in infants born to white women. Unfavorable conditions were more common in non-whites than in whites. Proper policies are required to decrease inequalities, especially in the context of prematurity, when women and their neonates have specific needs.

Genetics and clinical correlation of Dravet syndrome and its mimics – experience of a tertiary center in Taiwan

Dravet syndrome is a severe developmental and epileptic encephalopathy characterized by the onset of prolonged febrile and afebrile seizures in infancy and SCN1A gene mutations. In some cases, non-SCN1A gene mutations can present with a phenotype very similar to that of Dravet syndrome. The aim of this study was to compare phenotypes of patients with SCN1A and non-SCN1A gene mutation-related Dravet syndrome. Thirty-six patients with Dravet syndrome-like phenotypes were followed from July 2017 to December 2019. We retrospectively analyzed their clinical profiles and genetic surveys. Of the 36 enrolled patients, 15 (41.7%) had SCN1A mutations, one (2.8%) had an SCN8A mutation, one (2.8%) had an STX1B mutation, and five females (13.9%) had PCDH 19 mutations. The median age at first seizure onset was 7 months in those with SCN1A mutations, 1.3 years in those with PCDH19 mutations, and 10 months for the remaining patients. The majority of the patients with SCN1A mutations had status epilepticus (80% vs. 20%) and fever-sensitive seizures (76% vs. 31%) compared to those with PCDH19 mutations. The patients with SCN1A-related seizures had a higher rate of focal seizures as first seizure type than those without SCN1A mutations. Three of five (60%) patients with PCDH19 mutations had brain magnetic resonance imaging abnormalities. The three most commonly used antiseizure medications were sodium valproate, levetiracetam, and clobazam. Seven of the 15 patients with SCN1A mutations used stiripentol. The median time from seizure onset to genetic diagnosis was 6.6 years (range 4 months-22.3 years). The patients with SCN1A mutations in this study had high rates of fever-sensitive seizures, status epilepticus, seizure onset with focal seizure type, and relatively young age at seizure onset. The patients with PCDH19 mutations had a relatively high rate of abnormal brain magnetic resonance imaging findings.

Clinical features, treatments, and outcomes of patients with anti-N-methyl-D-aspartate encephalitis-a single-center, retrospective analysis in China.

Objective: To describe the clinical features, laboratory data, treatment, and outcomes of anti-N-methyl-D-aspartate (NMDAR) encephalitis in Chinese patients. Methods: This retrospective study included hospitalized patients definitively diagnosed with anti-NMDAR encephalitis and positive for anti-NMDAR antibodies in the cerebrospinal fluid (CSF) in Shenzhen People's hospital, between November 2015 and February 2020. The clinical manifestation, laboratory data, treatments and outcomes were collected retrospectively. Patients were followed up for more than 1 year. Results: The study included 31 patients (15 men, 48.4%) with a median age of 31 years (interquartile range 21-48). The most common clinical presentations were psychosis (n = 23, 74.2%), seizures (n = 20, 64.5%), and memory impairment (n = 20, 64.5%). Total magnetic resonance imaging abnormalities were found in 11 patients (35.5%), with the medial temporal and frontal lobes as the most commonly involved. Abnormal electroencephalogram was observed in 16 patients (51.6%). Five out of 31 patients (19.5%) were diagnosed as neoplasm, including five females with ovarian teratoma and one male with a central nervous system tumor. Multiple immune antibodies, including anti-SSA antibody in four patients (15.4%), anti-Ro52 antibody in four (15.4%), antinuclear antibody (ANT) in four (15.4%), anti-thyroglobulin antibodies (TGAb) in five (17.2%), and thyroid peroxidase antibodies (TPOAb) in three (10.3%) were present. All patients received first-line immunization therapy (intravenous immunoglobulin, glucocorticoids, or plasmapheresis alone or combined), and only two patients (7.3%) received second-line immunization therapy (rituximab). Mechanical ventilation was more necessary in women (37.5%) than in men (6.7%) (p = 0.04), and 29 (93.5%) had favorable clinical outcomes. At more than 12 months of follow-up, the median modified Rankin Scale score decreased from 4 to 0. Conclusions: Patients with anti-NMDAR encephalitis in China had high rates of psychosis and seizures, with low rates of underlying neoplasms. A higher proportion of female patients required mechanical ventilation. Complications with other positive autoimmune antibodies were a common clinical symptoms of anti-NMDAR encephalitis. Majority of the patients obtained satisfactory outcomes in combination with early first-line and long-term immunization therapy.

Advances and Future Directions of Diagnosis and Management of Pediatric Abusive Head Trauma: A Review of the Literature.

Abusive head trauma (AHT) is broadly defined as injury of the skull and intracranial contents as a result of perpetrator-inflicted force and represents a persistent and significant disease burden in children under the age of 4 years. When compared to age-matched controls with typically single occurrence accidental traumatic brain injury (TBI), mortality after AHT is disproportionately high and likely attributable to key differences between injury phenotypes. This article aims to review the epidemiology of AHT, summarize the current state of AHT diagnosis, treatment, and prevention as well as areas for future directions of study. Despite neuroimaging advances and an evolved understanding of AHT, early identification remains a challenge for contemporary clinicians. As such, the reported incidence of 10–30 per 100,000 infants per year may be a considerable underestimate that has not significantly decreased over the past several decades despite social campaigns for public education such as “Never Shake a Baby.” This may reflect caregivers in crisis for whom education is not sufficient without support and intervention, or dangerous environments in which other family members are at risk in addition to the child. Acute management specific to AHT has not advanced beyond usual supportive care for childhood TBI, and prevention and early recognition remain crucial. Moreover, AHT is frequently excluded from studies of childhood TBI, which limits the precise translation of important brain injury research to this population. Repeated injury, antecedent abuse or neglect, delayed medical attention, and high rates of apnea and seizures on presentation are important variables to be considered. More research, including AHT inclusion in childhood TBI studies with comparisons to age-matched controls, and translational models with clinical fidelity are needed to better elucidate the pathophysiology of AHT and inform both clinical care and the development of targeted therapies. Clinical prediction rules, biomarkers, and imaging modalities hold promise, though these have largely been developed and validated in patients after clinically evident AHT has already occurred. Nevertheless, recognition of warning signs and intervention before irreversible harm occurs remains the current best strategy for medical professionals to protect vulnerable infants and toddlers.

The burden and clinical manifestation of hospitalized influenza among different pediatric age-groups in the tropics.

IntroductionIn tropical Singapore, influenza occurs all year‐round. This study of influenza‐confirmed hospitalized pediatric patients compared clinical characteristics and complications by age‐group and differences between influenza A and B.MethodsThis was a retrospective study of pediatric inpatients from January 2013 to December 2014. Patients were grouped into: <6 months, 6 months to <5 years, 5‐ to <10‐year and ≥10 years. Complications were classified into neurologic, pulmonary, and other. We also calculated the incidence of hospitalized influenza cases per 100 000 age‐related population.ResultsThere were a total of 1272 patients with a median age of 37 months. The highest hospitalization rates were in the <6 months age‐group. Majority (75.2%) had no comorbidity; 25.6% had complications: neurologic 11.9%, pulmonary 9.6%, other 4.1%. Patients with other complications were older, male, and had the highest influenza B rates and the longest length of stay. Influenza A comprised 76.9% of cases and had higher complication rates especially neurologic, compared to influenza B. Influenza B patients were older and were more likely to develop other complications. The 6‐month to <5‐year‐age‐group had the highest complication rate (30.6%), especially neurologic. However, ≥10 years old had the highest other complications, ICU/ high‐dependency admissions and influenza B Victoria rates.ConclusionsInfants <6 months had the highest hospitalization rates for influenza. The 6‐month to <5‐year‐age‐group had the highest complication rate especially neurologic. Influenza A patients were younger, had higher seizure rates and complications compared to influenza B.

Prophylactic antiepileptic treatment with levetiracetam for patients undergoing supratentorial brain tumor surgery: a two-center matched cohort study.

Guidelines on the administration of prophylactic antiepileptic drugs (AED), and specifically levetiracetam, for brain tumor surgery are still lacking. In this two-center matched cohort study, we aim to compare the proportion of postoperative seizures during follow-up after supratentorial tumor surgery in patients receiving no seizure prophylaxis, and those treated with levetiracetam perioperatively. Three hundred sixteen consecutive patients undergoing supratentorial tumor surgery, without history of seizures were included: 207 patients did not receive AED (no AED group), and 109 patients received levetiracetam perioperatively (levetiracetam group). The primary outcome measure was the rate of postoperative seizures. Additionally, uni- and multivariate analyses assessing possible risk factors for postoperative seizures were performed. No statistically significant difference for the occurrence of postoperative seizures was found between the two groups (10.1%, n = 21 in the no AED group vs. 9.2%, n = 10, in the levetiracetam group; p = 0.69, OR 0.9 [0.4-2.0), NNT 103 [12.9-17.1]). After propensity score matching, the primary outcome was observed in 13 patients (12.4%) from the no AED group and in 9 patients (8.6%) from the levetiracetam group (p = 0.50, OR 0.7 [0.3-1.6], NNT 26.3 [8.3-22.4]). Among all analyzed possible risk factors for postoperative seizures, only postoperative infarction showed a statistically significant association with higher seizure rates in multivariate analysis (OR 8.2 [1.1-60.6], p = 0.04). Prophylactic treatment with levetiracetam after brain tumor surgery showed no statistically significant effect in preventing postoperative seizures. However, in case a postoperative infarction occurs, its administration might be indicated.

Safety and Effectiveness of Bis-Chloroethylnitrosourea Wafer Chemotherapy in Elderly Patients with Recurrent Glioblastoma

Objective: To assess the safety and effectiveness of bis-chloroethylnitrosourea (BCNU) wafers in elderly patients with recurrent glioblastoma (GBM). Methods: Patients with recurrent GBM operated on between 2007 and 2014 were divided into 3 groups: >65 years with BCNU wafer implantation, >65 years without BCNU wafer implantation, and ≤65 years with BCNU wafer implantation. We compared survival and complications. Results: A total of 79 patients were identified: 24 in the older BCNU group (median age 68.2 years, 33.3% with a methylated MGMT promoter), 16 in the older non-BCNU group (median age 68.6 years, 31.3% with a methylated MGMT promoter), and 39 in the younger BCNU group (median age 56.8 years). Survival after progression was 9.2 months in the elderly BCNU group and 7.6 months in the elderly non-BCNU group (p = 0.34); overall survival was 17.2 and 15.9 months, respectively (p = 0.35). We found a tendency toward a higher rate of seizures and pneumonia in the older BCNU group. Conclusion: BCNU wafer implantation after resection of recurrent GBM is a reasonably safe treatment in patients aged >65 years. Seizures and systemic infections may occur more frequently, but the trade-off is still favorable as survival may be influenced positively. Higher age should not be regarded as a contraindication for BCNU wafers.

Characterizing regression in Phelan McDermid Syndrome (22q13 deletion syndrome)

PurposeTo describe the frequency and characteristics of developmental regression in a sample of 50 patients with Phelan McDermid Syndrome (PMS) and investigate the possibility of association between regression, epilepsy, and electroencephalogram (EEG) abnormalities and deletion size. MethodsThe Autism Diagnostic Interview-Revised (ADI-R) was used to evaluate regression in patients with a confirmed diagnosis of PMS. Information on seizure history and EEGs was obtained from medical record review. Deletion size was determined by DNA microarray. ResultsA history of regression at any age was present in 43% of all patients. Among those exhibiting regression, 67% had onset after the age of 30 months, affecting primarily motor and self-help skills. In 63% of all patients there was a history of seizures and a history of abnormal EEG was also present in 71%. No significant associations were found between regression and seizures or EEG abnormalities. Deletion size was significantly associated with EEG abnormalities, but not with regression or seizures. ConclusionThis study found a high rate of regression in PMS. In contrast to regression in autism, that often occurs earlier in development and affects language and social skills, we found regression in PMS most frequently has an onset in mid-childhood, affecting motor and self-help skills. We also found high rates of seizures and abnormal EEGs in patients with PMS. However, a history of abnormal EEG and seizures was not associated with an increased risk of regression. Larger deletion sizes were found to be significantly associated with a history of abnormal EEG.

Clinical correlation and prognostic implication of periodic EEG patterns: A cohort study

ObjectiveDespite increasing amounts of research on periodic discharges (PDs), large clinical studies regarding their prognostic value are lacking. The aim of the current study was to evaluate the clinical implications and prognostic value of PDs. MethodsIn this single-center retrospective cohort study, we included patients who underwent electroencephalographic recording either during hospitalization or from our outpatient clinics. Demographic data, associated seizure events, use of antiepileptic drugs, and outcomes at discharge were analyzed. Multivariate logistic regression analysis was used to evaluate associations between clinical factors and functional outcomes. ResultsFour hundred and twenty patients were enrolled during a 17-year period, with a mean age of 66 years. The main etiologies included systemic infection (24%), anoxia (15%), and ischemic stroke (12%). Recent seizures were identified in 283 patients (67%), of whom 84 (30%) had status epilepticus. One hundred and fifty-four patients (37%) did not survive to hospital discharge. In multivariate analysis, old age (>65years; OR=2.55; 95% CI=1.57–4.16; P<0.001) was the strongest predictor of mortality, followed by systemic infection, anoxic encephalopathy, cefepime encephalopathy, and the occurrence of status epilepticus. Conversely, the use of antiepileptic drugs was negatively associated with mortality (OR=0.50; 95% CI=0.28–0.87; P=0.02). ConclusionsPDs were associated with high rates of comorbidities and recent seizures, while the use of antiepileptic drugs was associated with a lower rate of mortality.

Effects of cerebrolysin on functional recovery in patients with severe disability after traumatic brain injury: A historical cohort study

ObjectiveTo determine the effects of cerebrolysin on functional recovery in patients with severe disability after traumatic brain injury (TBI). MethodsThis was a retrospective cohort study being performed during a 2-year period in a level I trauma center in Southern Iran including all the adult patients (>16years) with severe disability (GOS of 2 and 3) 1-month after trauma. We excluded those with posttraumatic seizures and those with meningitis or current infections. Some patients received cerebrolysin (n=65) and some did not (n=64). Cerebrolysin was administered intravenously in 10mL dosage daily for 30days. Patients in two study groups were matched regarding the baseline characteristics including age, gender, GCS on admission, pupil reactivity and Rotterdam score. The administered cerebrolysin dosage was 10mL intravenously daily for 30days. The 3- and 6-month Glasgow Outcome Scale Extended (GOSE) was recorded. The outcome scales were compared between two study groups. ResultsOverall we included 129 patients with severe disability 1-month after TBI. The baseline characteristics were comparable between groups. We found that GOSE at 3-month (p=0.017) and 6-month (p=0.009) was significantly higher in those receiving cerebrolysin. Cerebrolysin administration was associated with lower mortality rate, and higher good recovery after 6 month of therapy (p=0.024). Cerebrolysin administration was also associated with higher favorable and lower unfavorable outcome (p=0.043). Cerebrolysin was associated with higher seizure rate (p=0.042). ConclusionCerebrolysin administration in patients with severe disability after TBI is associated with improved functional recovery, decreased mortality rate and increased favorable outcome. Seizure is important side effect of cerebrolysin administration in TBI patients.

305 Medical, Traumatic, and Psychological Emergencies in Incarcerated Patients

The purpose of this research is to gather data on incarcerated individuals who present to the emergency department and their rates of medical, psychological, and traumatic disease. We conducted a retrospective medical record review of all incarcerated patients seen at the adult Erlanger Baroness Emergency Department in Chattanooga, TN, from January 2012 to December 2014. Data collected included age, race, sex, diagnosis, disposition, and whether access to care was cited as a contributing factor to presentation to the ED. Additionally in trauma patients we collected data on cause and mechanism of injury, need for procedures and specialty consults. There were 894 visits from incarcerated persons. 578 visits (64.65%) were medical, 37 visits (4.1%) were psychiatric, and 279 visits (31.2%) were for trauma. 129 patients had multiple visits. The most common medical comorbidities were hypertension (149 or 25.91%), COPD (77 or 13.39%), and seizures (67 or 11.65%). 247 (42.96%) of patients reported psychiatric comorbidities. 353 (61.39%) reported tobacco use. 238 (41.39%) reported alcohol and/or drug addictions. In 38 of the 894 visits (4.26%) access to care was cited as a contributing factor to their need for emergency care. In medical patients the most common diagnosis was neurological (.23 per patient visit). The most common causes of traumatic injuries included 118 (42.45%) accidental, 89 (32.02%) due to assault, 43 (15.47%) self-inflicted. The most common mechanisms of injury included 118 (42.45%) with blunt objects/punch/kick, 84 (30.22%) falls, and 30 (10.79 %) with knife/sharp object. 84 trauma patients (30.10%) had procedures performed by the emergency physician, 27 (9.71%) had an in ED procedure performed by a specialist, 4 (1.43%) had multiple procedures by multiple providers, and 2 (0.72%) went to the operating room. The most common final diagnoses in trauma 120 (0.43 per patient visit) with contusions/hematomas/abrasions, 97 (0.35 per patient visit) laceration/avulsion/bite/puncture wounds, 83 (0.30 per patient visit) bone fractures. Incarcerated patients presenting to the ED have high rates of medical comorbidities, especially hypertension and seizures. This population also has high rates of psychiatric disease and substance abuse. Patients with medical complaints were more likely to require admission than those with traumatic injuries. In 4.5% (38) of visits, access to care was specifically cited as a contributing factor. The real number is likely much higher when lack of documentation, noncompliance, and other factors are assessed. Medical patients most commonly presented for neurological disease processes. 32% of traumatic injuries were the result of physical assault sustained by the inmate. Most trauma occurred by falls or blunt trauma. Most traumatic injuries did not require specialist consult, but orthopedic surgery was the most commonly placed consult. Most procedures were performed by the emergency physician.

Legal enforcement against illegal imitation in developing countries

This study investigates the effect of intellectual property rights (IPR) enforcement in a developing country on imitation, innovation, economic growth, and welfare using a North–South quality ladder model. Unlike existing studies, this study explicitly distinguishes IPR protection and IPR enforcement by incorporating illegal imitation and seizure activity into the model. The four main results are, first, a higher seizure rate does not always decrease imitation rate in the South. Second, a higher seizure rate does not always encourage innovation in the North. Third, although a sufficiently high seizure rate is required to enhance economic growth, such a policy reform would deteriorates welfare in both the North and South. Finally, unlike seizure, prohibiting imports of illegal imitations from the South always lowers illegal imitation.