Epilepsy Status Research Articles

Functional patterns of neural activation during vocal emotion recognition in youth with and without refractory epilepsy

Epilepsy has been associated with deficits in the social cognitive ability to decode others’ nonverbal cues to infer their emotional intent (emotion recognition). Studies have begun to identify potential neural correlates of these deficits, but have focused primarily on one type of nonverbal cue (facial expressions) to the detriment of other crucial social signals that inform the tenor of social interactions (e.g., tone of voice). Less is known about how individuals with epilepsy process these forms of social stimuli, with a particular gap in knowledge about representation of vocal cues in the developing brain. The current study compared vocal emotion recognition skills and functional patterns of neural activation to emotional voices in youth with and without refractory focal epilepsy. We made novel use of inter-subject pattern analysis to determine brain areas in which activation to emotional voices was predictive of epilepsy status. Results indicated that youth with epilepsy were comparatively less able to infer emotional intent in vocal expressions than their typically developing peers. Activation to vocal emotional expressions in regions of the mentalizing and/or default mode network (e.g., right temporo-parietal junction, right hippocampus, right medial prefrontal cortex, among others) differentiated youth with and without epilepsy. These results are consistent with emerging evidence that pediatric epilepsy is associated with altered function in neural networks subserving social cognitive abilities. Our results contribute to ongoing efforts to understand the neural markers of social cognitive deficits in pediatric epilepsy, in order to better tailor and funnel interventions to this group of youth at risk for poor social outcomes.

Microemulsion for Simulataneous Intransal Delivery of Carbamazepine and Vitamin B6 for Treatment of Epilepsy

<p style="text-align: justify;"><strong>Background: </strong>Status epilepsy is a neurological emergency characterized by severe bouts of seizure. It has been reported that combination of antiepileptic drug with Vitamin supplements reduce the drug resistance and rapid improvement was also observed in epilepsy patients. In this study, we tried to develop novel intranasal microemulsion for simultaneous delivery of carbamazepine and Vitamin B₆ for treatment of epilepsy. <strong>Materials and Methods: </strong>For simultaneous estimation of Carbamazepine and Vitamin B₆, second derivative spectroscopy method was developed and validated. The ME containing CBZ, in lipophilic phase and Vitamin B₆ in aqueous phase was studied for physicochemical characters and ex vivo diffusion through sheep nasal mucosa. The maximal electroshock (MES)- induced seizure models was used to establish the pharmacodynamic credentials of the microemulsion. <strong>Results: </strong>The wavelength selected for Carbamazepine and Vitamin B₆ were 231 nm and 250 nm respectively. It was found that prepared microemulsion is stable with globule size of 395+12 nm. Diffusion across sheep nasal mucosa followed zero order kinetics for carbamazepine and Vitamin B₆ in the prepared microemulsion. It was found that the hind limb extension time and the recovery time were significantly different from control group (<em>p</em>&lt;0.05). The microemulsion remained stable after dilution, centrifugation and freeze thaw cycle as tested for particle size, zeta potential and percentage transmission. <strong>Conclusion:</strong> The proposed microemulsion should form the basis for treatment of epilepsy which warrants co-administration of micronutrients. <strong>Key words:</strong> Carbamazepine, Intranasal Microemulsion, Pharmacodynamic, Simultaneous Delivery, Vitamin B₆.

Epileptogenic Zone Location of Temporal Lobe Epilepsy by Cross-Frequency Coupling Analysis.

Epilepsy is a chronic brain disease with dysfunctional brain networks, and electroencephalography (EEG) is an important tool for epileptogenic zone (EZ) identification, with rich information about frequencies. Different frequency oscillations have different contributions to brain function, and cross-frequency coupling (CFC) has been found to exist within brain regions. Cross-channel and inter-channel analysis should be both focused because they help to analyze how epilepsy networks change and also localize the EZ. In this paper, we analyzed long-term stereo-electroencephalography (SEEG) data from 17 patients with temporal lobe epilepsy. Single-channel and cross-channel CFC features were combined to establish functional brain networks, and the network characteristics under different periods and the localization of EZ were analyzed. It was observed that theta–gamma phase amplitude coupling (PAC) within the electrodes in the seizure region increased during the ictal (p < 0.05). Theta–gamma and delta–gamma PAC of cross-channel were enhanced in the early and mid-late ictal, respectively. It was also found that there was a strong cross-frequency coupling state between channels of EZ in the functional network during the ictal, along with a more regular network than interictal. The accuracy rate of EZ localization was 82.4%. Overall, the combination of single-channel and multi-channel cross-band coupling analysis can help identify seizures and localize EZ for temporal lobe epilepsy. Rhythmic coupling reveals a relationship between the functional network and the seizure status of epilepsy.

Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice.

Chondroitin sulfate is a proteoglycan component of the extracellular matrix (ECM) that supports neuronal and non-neuronal cell activity, provides a negative domain to the extracellular matrix, regulates the intracellular positive ion concentration, and maintains the hypersynchronous epileptiform activity. Therefore, the present study hypothesized an antiepileptic potential of chondroitin sulfate (CS) in pentylenetetrazole-induced kindled epilepsy and pilocarpine-induced status epilepticus in mice. Levels of various oxidative stress markers and inflammatory mediators were estimated in the brain tissue homogenate of mice, and histopathological changes were evaluated. Treatment with valproate (110 mg/kg; i.p.) as a standard drug and chondroitin sulfate (100 & 200 mg/kg, p.o.) significantly (p < 0.01) and dose-dependently prevented the severity of kindled and spontaneous recurrent seizures in mice. Additionally, chondroitin sulfate showed its antioxidant potential by restoring the various biochemical levels and anti-inflammatory properties by reducing NF-kB levels and pro-inflammatory mediators like TNF-alpha, IL-1β, and IL-6, indicating the neuroprotective effect as well as the suppressed levels of caspase-3, which indicated a neuroprotective treatment strategy in epilepsy. The proteoglycan chondroitin sulfate restores the normal physiology and configuration of the neuronal tissue. Further, the molecular docking of chondroitin sulfate at the active pockets of TNF-alpha, IL-1β, and IL-6 showed excellent interactions with critical amino acid residues. In conclusion, the present work provides preclinical evidence of chondroitin sulfate as a new therapeutic approach in attenuating and preventing seizures with a better understanding of the mechanism of alteration in ECM changes influencing abnormal neuronal activities.

P.119 Emergency Department Use in Children with Cerebral Palsy: A Data Linkage Study

Background: Improved understanding of factors predictive of emergency department (ED) visits in children with cerebral palsy (CP) can help optimize healthcare use. We sought to identify the pattern of ED consultations in these children. Methods: Data from the Registre de paralysie cérébrale du Québec and provincial administrative databases were linked. The CP cohort was comprised of children born between 1999 and 2002. Data pertaining to ED presentations between 1999 and 2012 were obtained. Relative risks were calculated to identify factors associated with increased ED visits. Peers without CP were selected from administrative databases and matched in a 20:1 ratio. Chi-square tests and Student’s T-tests were used to compare the two cohorts. Results: 301 children with CP and 6040 peer controls were selected. Ninety-two percent (92%) of the CP cohort had at least one ED visit, compared to 74% amongst controls. Children with CP had an increased risk of high ED use compared to peers (RR 1.40 95% CI 1.30-1.52). Factors predictive of high ED use were comorbid epilepsy, severe motor impairment and low socioeconomic status. Conclusions: Children with CP have a higher need for urgent health assessments than their peers, resulting in increased use of ED services. System factors and barriers should be investigated.

Measurement of Sleep Behaviors in Chromosome 15q11.2-13.1 Duplication (Dup15q Syndrome).

Duplication of chromosome 15q11.2-q13.1 (dup15q syndrome) results in hypotonia, intellectual disability (ID), and autism symptomatology. Clinical electroencephalography has shown abnormal sleep physiology, but no studies have characterized sleep behaviors. The present study used the Children's Sleep Habits Questionnaire (CSHQ) in 42 people with dup15q syndrome to examine the clinical utility of this questionnaire and quantify behavioral sleep patterns in dup15q syndrome. Individuals with fully completed forms (56%) had higher cognitive abilities than those with partially completed forms. Overall, caregivers indicated a high rate of sleep disturbance, though ratings differed by epilepsy status. Results suggest that clinicians should use caution when using standardized questionnaires and consider epilepsy status when screening for sleep problems in dup15q syndrome.

Influence of Different Antiepileptic Drugs on Blood Ammonia and Homocysteine Levels in Children with Epilepsy.

In this study, we performed a study on 106 children with epilepsy who were treated with sodium valproate (the VPA group, n = 37), oxcarbazepine (the OXC group, n = 34), or levetiracetam (the LEV group, n = 35). In addition, the clinical data of epileptic children who were newly diagnosed in the same period without antiepileptic drug (AED) treatment (the untreated group, n = 35) and normal children who received physical examination in our hospital (the healthy group, n = 35) were selected as controls. We analyzed the efficacy and safety of different AEDs, used blood ammonia and homocysteine levels as the observation indicators, and calculated the incidence of hyperammonemia (VAH) and hyperhomocysteinemia (HHcy) treated with different AEDs. And, based on the effect of epilepsy status on the cognitive function of patients, we also analyzed the effect of different AED treatments on children's cognitive function. Our results show that sodium valproate, oxcarbazepine, and levetiracetam are all effective in the treatment of children with epilepsy and can be used as the first-line choice of antiepileptic treatment for children with epilepsy. However, compared with sodium valproate, levetiracetam and oxcarbazepine have a lower incidence of adverse drug reactions and do not cause an increase in blood ammonia and Hcy levels, so they have higher safety of drug treatment. In addition, compared with sodium valproate, levetiracetam and oxcarbazepine have better recovery of cognitive function in children with epilepsy and so they have better application value.

Neurodevelopmental Outcomes in Infants Fed with Soy Formula: A Retrospective, National Population-Based Observational Cohort Study

BackgroundSoy-based infant formulas are increasingly popular, but data regarding their effects on neurodevelopmental outcomes during early childhood is scanty. ObjectiveThis study investigated the effect of consuming soy-based infant formula at 9–12 mo after birth on the subsequent development of epilepsy, neurodevelopmental disorders, and developmental status. MethodsThis nationwide retrospective administrative study used health screening examinations and linked insurance claims data of children born in Korea during 2008 and 2009. Infants who received soy formula were compared with those who received cow's milk formula using propensity score matching that considered birth history, economic status, clinical conditions, and drug prescription records. Exposure was defined as soy formula feeding determined from questionnaires completed by the parents when children were 9–12 mo old. Outcomes were epilepsy, attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental status. Children were followed until 31 December, 2017. ResultsA total of 153,841 eligible participants were enrolled; 11,535 (7.5%) children received soy formula, while 142,864 (92.5%) received cow's milk formula. The incidence rate of epilepsy during the follow-up period was 29.8 per 100,000 person-years (95% CI: 19.90, 42.73) in the soy formula group and 22.6 per 100,000 person-years (95% CI: 16.40, 30.32) in the cow's milk formula group, with no significant difference (aHR: 1.318; 95% CI: 0.825, 2.106). The 2 groups also had no difference based on prespecified analysis using different definitions of epilepsy. Likewise, no significant associations of soy formula with ADHD (aHR: 1.26; 95% CI: 1.00, 1.60) or ASD (aHR: 0.99; 95% CI: 0.54, 1.83), or delays of developmental stages were observed. ConclusionsFeeding with soy formula rather than cow's milk formula had no apparent association with increased risks of epilepsy, ADHD, ASD, and developmental status, according to this cohort composed of a general pediatric population.

Case Report: Hypopituitarism Presenting With Nonconvulsive Status Epilepticus

Introduction: Hypopituitarism is defined as one or more partial or complete pituitary hormone deficiencies. Nonconvulsive status epilepticus (NCSE) refers to a state of continuous or repetitive seizures without convulsions. In this paper, we review a case of an old female patient with hypopituitarism who presented with NCSE, which is rare in the clinic.Case Report: This paper describes a 67-year-old female patient with hypopituitarism who presented as NCSE. She had surgical resection of pituitary tumor half a year before the seizures and did not get regular hormone replacement therapy. She presented general convulsive status epilepsy as the initial symptom and got sedation and antiepileptic drug in the emergency room. The seizure was terminated but the patient fell in coma in the following days. The patient had magnetic resonance imaging (MRI) and other inspects, and EEG showed epileptic discharges. Combining these clinical symptoms and examinations, we made the diagnosis of NCSE. Finally, she regained consciousness after the treatment with diazepam.Conclusion: This case report and literature review investigated the possible mechanism of hypopituitarism presenting with NCSE.

Cortical and Subcortical Network Dysfunction in a Female Patient With NEXMIF Encephalopathy

The developmental and epileptic encephalopathies (DEE) are the most severe group of epilepsies. Recently, NEXMIF mutations have been shown to cause a DEE in females, characterized by myoclonic–atonic epilepsy and recurrent nonconvulsive status. Here we used advanced neuroimaging techniques in a patient with a novel NEXMIF de novo mutation presenting with recurrent absence status with eyelid myoclonia, to reveal brain structural and functional changes that can bring the clinical phenotype to alteration within specific brain networks. Indeed, the alterations found in the patient involved the visual pericalcarine cortex and the middle frontal gyrus, regions that have been demonstrated to be a core feature in epilepsy phenotypes with visual sensitivity and eyelid myoclonia with absences.

Whole Genome Sequence Data From Captive Baboons Implicate RBFOX1 in Epileptic Seizure Risk.

In this study, we investigate the genetic determinants that underlie epilepsy in a captive baboon pedigree and evaluate the potential suitability of this non-human primate model for understanding the genetic etiology of human epilepsy. Archived whole-genome sequence data were analyzed using both a candidate gene approach that targeted variants in baboon homologs of 19 genes (n = 20,881 SNPs) previously implicated in genetic generalized epilepsy (GGE) and a more agnostic approach that examined protein-altering mutations genome-wide as assessed by snpEff (n = 36,169). Measured genotype association tests for baboon cases of epileptic seizure were performed using SOLAR, as well as gene set enrichment analyses (GSEA) and protein–protein interaction (PPI) network construction of top association hits genome-wide (p < 0.01; n = 441 genes). The maximum likelihood estimate of heritability for epileptic seizure in the pedigreed baboon sample is 0.76 (SE = 0.77; p = 0.07). Among candidate genes for GGE, a significant association was detected for an intronic SNP in RBFOX1 (p = 5.92 × 10–6; adjusted p = 0.016). For protein-altering variants, no genome-wide significant results were observed for epilepsy status. However, GSEA revealed significant positive enrichment for genes involved in the extracellular matrix structure (ECM; FDR = 0.0072) and collagen formation (FDR = 0.017), which was reflected in a major PPI network cluster. This preliminary study highlights the potential role of RBFOX1 in the epileptic baboon, a protein involved in transcriptomic regulation of multiple epilepsy candidate genes in humans and itself previously implicated in human epilepsy, both focal and generalized. Moreover, protein-damaging variants from across the genome exhibit a pattern of association that links collagen-containing ECM to epilepsy risk. These findings suggest a shared genetic etiology between baboon and human forms of GGE and lay the foundation for follow-up research.

Safety and tolerability of the novel 2019 coronavirus disease (COVID-19) vaccines among people with epilepsy (PwE): A cross-sectional study

BackgroundPeople with epilepsy (PwE) were concerned about the safety of the novel 2019 Coronavirus Disease (COVID-19) vaccines. ObjectiveThis study aimed to assess the side effects experienced by PwE following vaccination with COVID-19 vaccines and to identify the causes of vaccine hesitation. MethodsWe administered a questionnaire to PwE, who visited the epilepsy clinic at Ibn Sina Hospital in Kuwait during the first two working weeks of April 2021. It included socio-demographic, epilepsy status, and vaccination data. In addition, we asked those who were not vaccinated yet about the reasons and their plan. ResultsA total of 111 PwE were surveyed, with 82 being vaccinated and 29 being unvaccinated. Out of the 82 vaccinated, 66 (80.5%) reported at least one side effect. Patients who received the Pfizer BioNTech mRNA vaccine (BNT162b2) (first, second dosage); and the Oxford-AstraZenecaa chimpanzee adenovirus-vectored vaccine (ChAdOx1nCoV-19) (first dose) had the following reactions: Pain at the injection site (40%, 67.6%), 43.8%, fatigue (47%, 32.4%), 46.9%, Headache (33.3%, 35.3%), 34.4% and Myalgia (40%, 35%), 50% respectively. Local site effects, including pain (67.6% vs. 40%, p = < 0.001) and redness (26.5% vs 6.7%, p = 0.019), were more statistically significantly after the second dose of BNT162b2 vaccine compared to the first dose of the same vaccine. While there was no significant difference in systemic side effects frequencies between the two doses of the BNT162b2 vaccine. The systemic side effects were more statistically significantly after the first dose of ChAdOx1nCoV-19 compared to the first dose of the BNT162b2 vaccine and those included fever (56.3% vs 13.3%, p = < 0.001), chills (37.5% vs 6.7%, p = < 0.001), myalgia (50% vs 40%, p = < 0.001) and arthralgia (25% vs 6.7%, p = 0.021). The local site reactions were not significantly different between the first doses of both vaccines. Among the subgroup who had vaccine-related side effects, 66.7% were females, 90.9% were 55 or younger, 63.6% were on polytherapy, 74% had side effects for one day or less, and 95% were symptoms free by the end of the first-week post-vaccination. Symptoms were mild in 68% of the patients and moderate in 29.3%. Most patients (93.9%) did not report seizure worsening after vaccination. The relative risk of seizure worsening after the first and second doses of BNT162b2 and the first dose of ChAdOx1nCoV-19 vaccines was 1.027 (95% CI 0.891–1.183), 1.019 (95% CI 0.928-1.119), and 1.026 (95% CI 0.929–1.134) respectively. After the first dose of BNT162b2, one patient reported the development of status epilepticus. Among the non-vaccinated group, 34.9% were still indecisive, while 37.9% rejected the vaccination. Fear of adverse effects (42.9%) and fear of epilepsy worsening (23.8%) were the main reasons for vaccine hesitation. ConclusionsThis study shows that the two vaccines under consideration (BNT162b2 and ChAdOx1nCoV-19) have a good safety profile and a low risk of epilepsy worsening among a cohort of PwE in Kuwait.

The applicability of magnetic resonance imaging classification system (MRICS) for cerebral palsy and its association with perinatal factors and related disabilities in a Croatian population-based sample

AimTo investigate the association of cerebral palsy motor disorders, perinatal factors, and related disabilities with brain magnetic resonance imaging classification score (MRICS)-based groups in a population-based sample.MethodsThe study enrolled children with cerebral palsy born from 2003 to 2015 treated at Split University Hospital who underwent brain MRI scanning. Perinatal data (plurality, birth weight, gestational age, and Apgar score) were collected from hospital records. Motor disorders of cerebral palsy (gross and fine motor function) and the related disabilities (intellectual status, speech and eating ability, epilepsy, vision and hearing status) were evaluated with neurological status assessment. Neuroimaging findings were presented as MRICS-based groups.ResultsOf 115 enrolled children, an abnormal finding on brain MRI was confirmed in 95%, including white matter injury (66%), maldevelopments (13.9%), gray matter injury (9.6%), and miscellaneous findings (6.1%). Gross and fine motor function were not significantly associated with MRICS-based group. All related disabilities and perinatal factors, except Apgar score, were significantly associated with MRICS-based group.ConclusionBrain MRICS-based groups were associated with perinatal risk factors and related disabilities of cerebral palsy, but not with common motor disorders. MRI classification score is a reliable diagnostic tool, which strongly correlates with perinatal factors and related disabilities of cerebral palsy.

Deep brain stimulation in patients with long history of drug resistant epilepsy and poor functional status: Outcomes based on the different targets

BackgroundDeep brain stimulation (DBS) is a widely used surgical procedure for the treatment of patients with drug resistant epilepsy (DRE) and several anatomical target have been described. Indications for DBS includes patients with focal, partial seizure and those for which resective or disconnective surgery are contraindicated, such as involvement of eloquent cortex or significant comorbidities. Despite the SANTE trial has clearly indicated the efficacy of DBS of anterior nucleus of the thalamus (ANT), specific indications regarding the best anatomical target and outcome in patients with severe disability are lacking. Here we described our case series of patients underwent DBS of three different target including ANT, centromedian thalamic nucleus (CMN) and subthalamic nucleus (STN). MethodSix patients with DRE have been treated with DBS of ANT (n = 3), STN (n = 2) and CMN (n = 1). Outcome has been expressed as seizures frequency reduction and patients functional status after surgery with a follow-up of 5–11 years. ResultsFour out of six patients show no reduction of seizures frequency after DBS implant with one case of increasing atypical absence. Two cases, one ANT and one CMN, show a significant reduction of seizures frequency of 50–60%. No patients improve relative to functional outcome and one showed psychiatric symptoms worsening. ConclusionsFor patients with DRE and severe functional disability, DBS may reduce seizure frequency in some cases, but it does not improve functional outcome.

Sleep duration and quality among U.S. adults with epilepsy: National Health Interview Survey 2013, 2015, and 2017

BackgroundEpilepsy is associated with a high prevalence of sleep disturbance. However, population-based studies on the burden of sleep disturbance in people with epilepsy are limited. This study assessed sleep duration and sleep quality by epilepsy status in the general U.S. adult population aged ≥ 18 years. MethodsWe pooled data of cross-sectional National Health Interview Surveys in 2013, 2015, and 2017 to compare the prevalence of sleep duration and quality among those without epilepsy (N = 93,126) with those with any epilepsy (a history of physician-diagnosed epilepsy) (N = 1774), those with active epilepsy (those with a history of physician-diagnosed epilepsy who were currently taking medication to control it, had one or more seizures in the past year, or both) (N = 1101), and those with inactive epilepsy (those with a history of physician-diagnosed epilepsy who were neither taking medication for epilepsy nor had had a seizure in the past year) (N = 673). We also compared these measures between those with active and those with inactive epilepsy. The prevalences were adjusted for sociodemographics, behaviors, and health covariates, with multivariable logistic regression. We used Z-tests to compare prevalences of sleep duration and quality at the statistical significance level of 0.05. ResultsAdults with any epilepsy reported significantly higher adjusted prevalences of short sleep duration (<7 h) (36.0% vs. 31.8%) and long sleep duration (>9 h per day) (6.7% vs. 3.7%) but a lower prevalence of healthy sleep duration (7–9 h per day) (57.4% vs.64.6%) than those without epilepsy. In the past week, adults with any epilepsy reported significantly higher adjusted prevalences than adults without epilepsy of having trouble falling asleep (25.0% vs. 20.3%), staying asleep (34.4% vs. 26.3%), nonrestorative sleep (adults did not wake up feeling well rested) (≥3days) (50.3% vs. 44.3%), and taking medication to help themselves fall asleep or stay asleep (≥1 times) (20.9% vs. 13.5%). However, adults with active epilepsy did not differ from adults with inactive epilepsy with respect to these sleep duration and quality measures. ConclusionsAdults with epilepsy reported more short or long sleep duration and worse sleep quality than those without epilepsy. Neither seizure occurrence nor antiepileptic drug use accounted for these differences in sleep duration and quality. Careful screening for sleep complaints as well as identifying and intervening on the modifiable risk factors associated with sleep disturbances among people with epilepsy could improve epilepsy outcomes and quality of life.

No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy.

Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with Onchocerca volvulus. Here, we screened serum and CSF samples of persons with nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) and African and European controls for leiomodin-1 antibodies by a cell-based assay (CBA) and Western blot (WB). These samples were also investigated for the presence of auto-antibodies cross-reacting with rat brain tissue by immunohistochemistry (IHC). Additionally, IHC was used to detect the leiomodin-1 protein in post-mortem brain samples of persons with OAE who died. Leiomodin-1 antibodies were detected by CBA in 6/52 (12%) and by WB in 23/54 (43%) persons with OAE compared to in 14/61 (23%) (p = 0.113) and 23/54 (43%) (p = 0.479) of controls without epilepsy. Multivariable exact logistic regression did not show an association between O. volvulus infection or epilepsy status and the presence of leiomodin-1. Leiomodin-1 antibodies were not detected in 12 CSF samples from persons with OAE or in 16 CSF samples from persons with acute-onset neurological conditions, as well as not being detected in serum from European controls. Moreover, the leiomodin-1 protein was only detected in capillary walls in post-mortem brain tissues and not in brain cells. IHC on rat brain slides with serum samples from persons with OAE or controls from persons with or without O. volvulus infection revealed no specific staining pattern. In conclusion, our data do not support OAE to be an autoimmune disorder caused by leiomodin-1 antibodies.

Facilitation of drug-resistant epilepsy and catastrophic status epilepticus in children with combined pituitary hormone deficiency.

Clinicians and researchers often focus on the primary cause of seizures and epilepsy, but outcomes in individual patients also depend on multiple other variables, which might be easy to adjust. Previous studies suggest mutual interactions between endocrine disorders and epilepsy. We therefore hypothesized that combined pituitary hormone deficiency (CPHD) facilitates seizures and epilepsy. This is a retrospective study from a pediatric center. We determined the proportion of CPHD patients with epilepsy and examined basic clinical features in this group. Patients with super-refractory status epilepticus (SRSE) were reviewed to identify subjects with co-morbid CPHD. Those cases were analyzed in detail. 12 of 73 CPHD patients (16%) also had epilepsy. Various etiologies of CPHD were represented, though five subjects had a cranial tumor or cortical malformation. Epilepsy was drug resistant in all but one patient. Among 12 identified patients with SRSE, 4 were unexpected new-onset cases. Three of these subjects also had CPHD with ACTH deficiency and a febrile infection prior to SRSE. Another common feature was the devastating clinical course: In all three patients, initial MRI already suggested severe neuronal damage, SRSE persisted for at least one week with ongoing need for anesthetic coma, and outcome was poor (two patients survived with major sequelae, one child deceased during the episode). Our findings indicate that CPHD may predispose for drug-resistant epilepsy and refractory seizures with catastrophic outcome. We suggest that in children with new-onset SRSE, screening for CPHD should be considered.

CSNK2B: A broad spectrum of neurodevelopmental disability and epilepsy severity.

CSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow-up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures.

Examining brief and ultra-brief anxiety and depression screening methods in a real-world epilepsy clinic sample

ObjectiveRecent epilepsy quality measure recommendations for depression and anxiety screening endorse ultra-brief screeners, the Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2). Thus, it is important to assess how symptom detection may be affected using ultra-brief screeners compared with slightly longer, well-validated instruments: Neurological Disorders Depression Inventory-Epilepsy (NDDI-E) and Generalized Anxiety Disorder-7 (GAD-7). The objective was to compare symptom detection by brief versus ultra-brief depression and anxiety screeners in a large real-world epilepsy clinic sample. MethodsThis was a prospective, cross-sectional assessment of consecutive patients in an adult tertiary epilepsy practice who completed the GAD-7 and NDDI-E with embedded ultra-brief scales (GAD-2; GAD-Single Item: GAD-SI; NDDI-E 2 item: NDDIE-2) on a tablet and had clinic staff administered ultra-brief PHQ-2 (yes/no version) documented in the medical record at the same visit. Prevalences of positive anxiety and depression screens were calculated for each instrument overall, and by epilepsy status. Concordance correlation coefficients (CCC) were calculated comparing the ultra-brief with brief anxiety and depression instruments, and receiver operating curves (ROC) were calculated using the longer instruments as alternative standards. ResultsAmong N = 422 individuals the prevalence of positive anxiety screen by GAD-7 was 24% and positive depression screen by NDDI-E was 20%. Positive anxiety and depression screens were significantly less prevalent among seizure-free individuals than those with continued seizures. The verbally administered yes/no PHQ-2 had only 1 positive screen (0.2%). Other than poor concordance between the PHQ-2 and NDDI-E, the screener pairs had acceptable concordance (CCC 0.79 to 0.92). Areas under the ROC curves were acceptable for the NDDIE-2, GAD-2 and GAD-SI (0.96, 0.98, and 0.89, respectively). SignificanceIn this sample, clinic staff interview-administered yes/no PHQ-2 had exceedingly low sensitivity compared with the NDDI-E self-reported on a tablet. Further investigation is warranted to assess if poor detection is due to characteristics of this PHQ-2 in epilepsy samples, or method of administration in this clinic. The other ultra-brief anxiety and depression instruments demonstrated good concordance with the longer, well-validated instruments and may be useful in clinical practice.

An epidemiological survey of epilepsy in tropical rural areas of China.

ObjectiveEpilepsy is a chronic neurological disease that is characterized by seizures. Seizure episodes, stigma, and high medical costs associated with this condition caused significant psychological distress. This study aimed to evaluate epidemiological characteristics and treatment status of epilepsy in individuals existing in the tropical rural areas of Hainan Province of China.MethodsA household survey on epilepsy was conducted among the rural population of Chengmai County, Danzhou City, Baoting Autonomous County (Li and Miao nationalities), and Dingan County in Hainan Province, China. A screening questionnaire based on the standard screening questionnaires of the World Health Organization (WHO) was designed and a screening instrument of International Community‐based Epilepsy Research Group was used. Individuals suspected or previously diagnosed with epilepsy were reexamined by an experienced neurologist. Further clinical data were collected from subjects with confirmed diagnosis of epilepsy.ResultsThis study included 16 676 subjects with 8827 men (52.93%) and 7849 women (47.07%). Majority of the study subjects included were of Han Chinese (N = 13 145, 78.83%), and the remaining were of Li minority ethnicity. The incidence of epilepsy was 0.24 per 1000, and the total prevalence of active epilepsy was 2.33 per 1000. The prevalence of epilepsy in the Han and Li nationalities was 3.27 and 2.27 per 1000, respectively, which was shown to be higher in people aged ≥ 60. The initial onset of epilepsy tended to trigger among children aged between 0 and 9 years old. Initial assessment revealed that the treatment gap for active epilepsy was 58.97%, and stroke is shown as the most common cause of symptomatic epilepsy.SignificanceThe prevalence and incidence of epilepsy in tropical rural areas of Hainan Province were close to those of the earlier findings that are reported in other regions of China and lower than those remaining in the tropical areas around the world. There exists a huge treatment gap for active epilepsy, which indicates an urgent need for a rational intervention strategy.