Higher Prevalence Of Seizures Research Articles

Prevalence of Seizures in Children Diagnosed With Neurodevelopmental Disorders.

Introduction Neurodevelopmental disorders (NDDs) typically emerge in early childhood and have a profound impact on the development of the nervous system, leading to various neurological challenges in cognition, communication, social interaction, motor skills, and behavior. These disorders arise from disruptions in brain development mechanisms. NDDs include conditions such as cerebral palsy (CP), global developmental delay (GDD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), with ADHD and ASD being the most prevalent. However, there is a lack of comprehensive research on the causes of NDDs in children receiving care at tertiary hospitals in Saudi Arabia. Therefore, in this study, we aimto investigate the characteristics of patients with NDDs and explore the association between NDDs and seizures. It also focuses on identifying specific risk factors that may influence the relationship between NDDs and seizures. Methods We conducted a retrospective cross-sectional study at the pediatric neurology and developmental assessment clinic of King Abdulaziz University Hospital in Jeddah, Saudi Arabia. The study involved a review of electronic medical records from January 2021 to May 2023 for 200 pediatric patients who attended the clinic for NDD and seizures. Descriptive statistics summarized the data, using frequencies and percentages for categorical variables, and mean ± standard deviation for quantitative variables. The chi-square test identified differences between qualitative variables, with a significance threshold of p < 0.05. Results The study sample comprised 200 children ranging in age from one month to 14 years, with the majority of patients being from Jeddah city. Participants were categorized into four age groups: 17.0% (n=34) were aged between one month and three years, 18.5% (n=37) were aged between three and six years, 55.0% (n=110) were aged between six and 12 years old, and 9.5% (n=19) were aged between 12 and 14 years. The NDD subtypes identified were ASD 9.5%, ADHD 16.0%, CP 8.5%, GDD 30.5%, ID 5.5%, and 30% had multiple types of NDD. Generalized tonic-clonic seizures were the most common type observed. Conclusion Children with NDDs exhibit a high prevalence of seizures, with the age of the patient and consanguinity emerging as significant influencing factors in this correlation. Among the key findings is an emphasis on the importance of early detection and intervention for children with NDDs at higher risk of developing seizures. Overall, the study sheds light on the characteristics of NDD patients and their association with seizures, contributing to a better understanding of the complex relationship between NDDs and seizure occurrence. It also emphasizes the need for comprehensive assessment and management strategies that consider seizures in children with NDDs.

Association of Epileptiform Discharge and Autism Spectrum Disorder Severity in Children Attending the Outpatient Clinics, Child Welfare Teaching Hospital, Baghdad

Background: Subjects with Autism Spectrum Disorder (ASD) have a higher prevalence of seizures than the general population, according to a significant body of research. Also, seizure-free patients with ASD have been found to have a higher prevalence of epileptiform discharge abnormalities compared to healthy controls across investigations. Changes in the electroencephalogram (EEG) can manifest as sharp waves or spikes, sharp and slow waves, generally distributed or general area, or focused, and can manifest in various brain regions. There is a necessity to search for a distinctive EEG characteristic in ASD patients. Objectives: This study used electroencephalography to investigate the relationship between interictal epileptiform discharges and the severity of ASD in children. Patient and methods: The study involved a total of 65 children. The first group consisted of 30 children (seven females and 23 males, 2-12 years of age) recruited from the autism center and the pediatric neurology consultancy clinic in the Child Welfare Teaching Hospital / Medical City. The second group consisted of 35 age- and gender-matched normally-developed children (10 females 25 males, 2-12 years of age) recruited from the Pediatrics Consultation Clinics in the Child Welfare Teaching Hospital. The ASD children met the DSM-5 criteria for autism and the Childhood Autism Rating Scale was utilized to determine the severity of autism. The electroencephalography signals were recorded to detect epileptiform discharge. The data was collected during the period from 5th October 2022 to 1st April 2023. Result: A statistically significant association was found between the epileptiform discharges and the study group (ASD Vs normally developed children). The EEG records were normal in 20 (66.7%), abnormal in the form of focal epileptiform discharge in 5 (16.7%), and in the form of generalized epileptiform discharge in 5 (16.7%) of ASD children. The EEG findings and the CARS-measured autism severity showed a statistically significant association (P=0.05), as the EEG abnormalities increased with the severity of autism. Conclusion: The degree of autism was found to be associated with the abnormalities of the electroencephalogram and the degree of autism. Received: May,, 2023 Accepted: Sept, 2023 Published: Jan. 2024

The clinical spectrum of MELAS and associated disorders across ages: a retrospective cohort study.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a severe multisystemic disease, although some have a milder phenotype. We aimed to evaluate the clinical spectrum of this disease from MELAS patients to asymptomatic carriers and identify predictors of severity. We reviewed 81 patients, who had MELAS or had positive genetics without meeting clinical criteria. Patients who met criteria including lactic acidosis, encephalomyopathy, and stroke-like episodes (SLE) were categorized as MELAS, symptomatic non-MELAS, and asymptomatic. MELAS was further categorized as "standard-onset" if the first stroke-like episode (SLE) occurred before age 40 or "late-onset." Eighty-one patients were included: 42 MELAS (13 late-onset), 30 symptomatic non-MELAS, and 9 asymptomatic. MELAS patients had lower BMI at onset (mean 18.6 vs. 25.1 asymptomatic and 22.0 symptomatic non-MELAS, p < 0.05). There was a trend toward higher serum heteroplasmy in MELAS compared to symptomatic non-MELAS and asymptomatic (means 39.3, 29.3, and 21.8% p = 0.09). Symptomatic non-MELAS had more sensorineural hearing loss as first presenting symptom (51.6% vs. 24.4%, p < 0.05). MELAS had higher prevalence of seizures (88.1% vs. 16.7%, p < 0.05) and shorter survival from onset to death (50% mortality at 25 years vs. 10%, p < 0.05). Late-onset MELAS had longer disease duration from first symptom to first SLE (mean 16.6 vs. 9.3 yrs) and also lived longer (mean age at death 62 vs. 30). Standard-onset MELAS had more neurologic involvement at onset than late-onset (51.7% vs. 15.4%). Late-onset patients had more prevalent diabetes (69.2% vs. 13.8%) and nephropathy (53.8% vs. 10.3%). Patients with late-onset MELAS also had more organ systems involved (mean 4.1 vs. 2.7, p < 0.05). There was a trend toward higher heteroplasmy levels in standard-onset (mean 44.8% vs. 25.3%, p = 0.18). Our study highlights the spectrum of MELAS. The lower BMI in MELAS at presentation as well as higher rates of sensorineural hearing loss as initial symptom in symptomatic non-MELAS may be useful clinical markers. While many patients present before age 40 with SLE, some can present with SLE later in life. Standard onset MELAS is more likely to present with neurologic symptoms. Late-onset is more likely to suffer diabetes or nephropathy and have more organ systems involved.

Hyperexcitable Phenotypes in Induced Pluripotent Stem Cell–Derived Neurons From Patients With 15q11-q13 Duplication Syndrome, a Genetic Form of Autism

BackgroundChromosome 15q11-q13 duplication syndrome (Dup15q) is a neurogenetic disorder caused by duplications of the maternal copy of this region. In addition to hypotonia, motor deficits, and language impairments, patients with Dup15q commonly meet the criteria for autism spectrum disorder and have a high prevalence of seizures. It is known from mouse models that synaptic impairments are a strong component of Dup15q pathophysiology; however, cellular phenotypes that relate to seizures are less clear. The development of patient-derived induced pluripotent stem cells provides a unique opportunity to study human neurons with the exact genetic disruptions that cause Dup15q. MethodsHere, we explored electrophysiological phenotypes in induced pluripotent stem cell–derived neurons from 4 patients with Dup15q compared with 6 unaffected control subjects, 1 patient with a 15q11-q13 paternal duplication, and 3 patients with Angelman syndrome. ResultsWe identified several properties of Dup15q neurons that could contribute to neuronal hyperexcitability and seizure susceptibility. Compared with control neurons, Dup15q neurons had increased excitatory synaptic event frequency and amplitude, increased density of dendritic protrusions, increased action potential firing, and decreased inhibitory synaptic transmission. Dup15q neurons also showed impairments in activity-dependent synaptic plasticity and homeostatic synaptic scaling. Finally, Dup15q neurons showed an increased frequency of spontaneous action potential firing compared with control neurons, in part due to disruption of KCNQ2 potassium channels. ConclusionsTogether, these data point to multiple electrophysiological mechanisms of hyperexcitability that may provide new targets for the treatment of seizures and other phenotypes associated with Dup15q.

Emerging Gene and Small Molecule Therapies for the Neurodevelopmental Disorder Angelman Syndrome

Angelman syndrome (AS) is a rare (~1:15,000) neurodevelopmental disorder characterized by severe developmental delay and intellectual disability, impaired communication skills, and a high prevalence of seizures, sleep disturbances, ataxia, motor deficits, and microcephaly. AS is caused by loss-of-function of the maternally inherited UBE3A gene. UBE3A is located on chromosome 15q11–13 and is biallelically expressed throughout the body but only maternally expressed in the brain due to an RNA antisense transcript that silences the paternal copy. There is currently no cure for AS, but advancements in small molecule drugs and gene therapies offer a promising approach for the treatment of the disorder. Here, we review AS and how loss-of-function of the maternal UBE3A contributes to the disorder. We also discuss the strengths and limitations of current animal models of AS. Furthermore, we examine potential small molecule drug and gene therapies for the treatment of AS and associated challenges faced by the therapeutic design. Finally, gene therapy offers the opportunity for precision medicine in AS and advancements in the treatment of this disorder can serve as a foundation for other single-gene neurodevelopmental disorders.

Seizures and Phytotherapy: The Most Important Medicinal Plants Used for Seizures in Children and Adults in Iranian Ethnobotanical Documents

Due to the relatively high prevalence of seizures (8%), the cases of prescribing these drugs are very high and usually have many side effects, so in this review study, the use of medicinal plants in different regions of Iran in ethnobotanical documents was extracted and reported. In this study, for this purpose, keywords such as convulsion (seizure), medicinal plants, ethnobotany, identification of medicinal plants, region and Iran were performed. Databases such as ISI Web of Science, PubMed, Scopus, ISC, Magiran and Google Scholar were used to review articles and resources. Based on the results, Anthemis nobilis L., Leonurus cardiac L., Lotus corniculatus L., Hyoscyamus niger L., Salvia spp., Grammosciadium platycarpum Boiss. &amp; Hausskn., Nigella sativa L., Anethum graveolens L., Papaver fugax Poir., Lotus corniculatus L., Verbascum thapsus L., Ferula assa-foetida L., Ferula gumosa Boiss., Heracleum persicum Desf.ex Fischer., Angelica archangelica L., Vicia faba L., Verbascum pseudonobile Stoj &amp; Stef., Melissa officinalis L., Teucrium polium L., Datura stramonium L., Hymenocrater spp. and Melissa officinalis L., are medicinal plants that are used in different parts of Iran to treat seizures. The data collected in this study were analyzed using Microsoft Excel program. According to the results, the plants of this study belong to 11 plant families. The aerial part with 32% is the most plant part used for seizures. Also, most of the medicinal plants used to treat seizures were related to the northern region of Khuzestan. Ethnobotanical knowledge can provide pure ideas for modern pharmacological knowledge and lead to the production of effective natural anticonvulsant drugs.

Evaluation of Perineuronal Nets and Their Regulation by Serotonin 5‐HT 7 Receptors in a Juvenile Fmr1 Knockout Mouse Model of Fragile X Syndrome

Fragile X Syndrome (FXS) is the leading monogenic cause of autism and intellectual disability. Individuals with FXS also often experience several other neuropsychiatric symptoms, including seizures. FXS is caused by silencing of the FMR1 gene, preventing expression of FMRP, an RNA-binding protein that regulates protein synthesis. A widespread theory is that the lack of FMRP causes an imbalance in excitatory—inhibitory neurotransmission, leading to excessive excitatory tone, which may explain the relatively high prevalence of seizures in individuals diagnosed with FXS and autism. The central serotonin system can modulate symptoms of FXS, and certain serotonin receptors (5-HTRs) are functionally linked with proteins known to be altered in FXS, suggesting targeting them may be therapeutic for FXS. For example, reports show that activation of 5-HT7Rs increases activity of matrix metalloproteinase 9 (MMP-9), which is upregulated in the absence of FMRP; MMP-9 degrades perineuronal nets (PNNs) that form around parvalbumin-positive GABAergic interneurons, suggesting blockade of 5-HT7Rs may restore MMP-9 homeostasis, leading to enhanced inhibitory tone in FXS. The formation of PNNs coincides with the closing of juvenile plasticity. Previous studies show that PNN density in the auditory cortex is reduced in juvenile Fmr1 knockout mice, and coincident hyperexcitability of the auditory cortex may contribute to the audiogenic seizure (AGS) phenotype that is prominent in juvenile Fmr1 knockout mice. Recently, we reported that a novel serotonin receptor modulator, FPT, that has potent 5-HT7R competitive antagonist activity, completely blocks AGSs in juvenile Fmr1 knockout mice. Here we report that the selective 5-HT7R antagonist, SB-269970, reduced AGS lethality in juvenile Fmr1 knockout mice compared to vehicle, but effects were not statistically significant (P=0.21, N=12 each). Preliminary results support previous observations of reduced density of PNNs in the auditory cortex of juvenile Fmr1 knockout mice (N=8) compared to WT mice (N=8). Ongoing studies are investigating PNN density following semi-chronic administration of SB-269970 or FPT to determine the efficacy of 5-HT7R blockade or other pharmacological mechanisms of FPT to normalize PNN density in juvenile Fmr1 knockout mice to wild-type mice levels.

Pre-operative Seizures in Patients With Single Brain Metastasis Treated With Resection Plus Whole-Brain Irradiation and a Boost.

Seizures can be the initial symptom of brain metastases. This study investigated pre-treatment seizures in patients with a single lesion. Pre-operative seizures were analyzed in 104 patients with a single brain metastasis receiving resection plus whole-brain irradiation and a boost. Prevalence of seizures, risk factors and associations with survival (OS) were evaluated. Thirty patients (34.6%) had seizures prior to neurosurgery. Significant associations between seizures and investigated characteristics were not found. However, age ≤61 years showed a trend (p=0.117) for increased incidence of seizures. Time from diagnosis of malignancy until neurosurgery >12 months was significantly associated with improved OS on univariate analysis (p=0.003). Trends for a positive association with OS were found for no seizures (p=0.054), female gender (p=0.066) and breast cancer (p=0.098). On multivariate analysis, time until neurosurgery >12 months was independently associated (p=0.019) with better OS, and seizures showed a trend (p=0.119) for improved OS. Considering the high prevalence of seizures in this cohort, regular screening and monitoring of these patients appears reasonable. This applies particularly to patients aged ≤61 years.

Factors Associated With Lack of Vision Improvement in Children With Cortical Visual Impairment.

Improvement in vision has been noted in children with cortical visual impairment (CVI), resulting from disparate types of brain injury. The purpose of our study was to determine the risk factors associated with poor recovery of vision in this group of patients. Case records of children who were born before 2010 with at least 4 follow-up visits for CVI were reviewed for underlying etiologies of CVI, visual acuity (VA), and associated neurological and ophthalmological disorders. VA was assessed in 6 qualitative grades. Changes in VA were recorded as the difference between the grades of VA at presentation and the last follow-up visit. The outcome was calculated as a ratio of actual improvement to potential improvement in grades of qualitative VA. Multiple linear regression determined factors associated with lack of vision improvement in all children and based on etiology. Fifty-three children with CVI were identified. The median age at presentation was 13.6 months (range: 2.9-76.4 months) and the median follow-up was 5.8 years (1.1-16.3 years). CVI resulted from central nervous system (CNS) malformation (9.4%), hypoxic/inflammatory injury (15.1%), seizures (24.5%), and combined causes (51.0%). Vision improvement was noted in 83% of children. Lack of VA improvement was associated with older age at presentation in all children with CVI and within each etiological group except CNS malformation. None of the other investigated variables were associated with poor recovery of VA. Most of the children with CVI showed improvement in vision. Older age at presentation, but not etiology of CVI, was associated with poor improvement in VA.

Abusive Head Trauma and Mortality-An Analysis From an International Comparative Effectiveness Study of Children With Severe Traumatic Brain Injury.

Small series have suggested that outcomes after abusive head trauma are less favorable than after other injury mechanisms. We sought to determine the impact of abusive head trauma on mortality and identify factors that differentiate children with abusive head trauma from those with traumatic brain injury from other mechanisms. First 200 subjects from the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial-a comparative effectiveness study using an observational, cohort study design. PICUs in tertiary children's hospitals in United States and abroad. Consecutive children (age < 18 yr) with severe traumatic brain injury (Glasgow Coma Scale ≤ 8; intracranial pressure monitoring). None. Demographics, injury-related scores, prehospital, and resuscitation events were analyzed. Children were dichotomized based on likelihood of abusive head trauma. A total of 190 children were included (n = 35 with abusive head trauma). Abusive head trauma subjects were younger (1.87 ± 0.32 vs 9.23 ± 0.39 yr; p < 0.001) and a greater proportion were female (54.3% vs 34.8%; p = 0.032). Abusive head trauma were more likely to 1) be transported from home (60.0% vs 33.5%; p < 0.001), 2) have apnea (34.3% vs 12.3%; p = 0.002), and 3) have seizures (28.6% vs 7.7%; p < 0.001) during prehospital care. Abusive head trauma had a higher prevalence of seizures during resuscitation (31.4 vs 9.7%; p = 0.002). After adjusting for covariates, there was no difference in mortality (abusive head trauma, 25.7% vs nonabusive head trauma, 18.7%; hazard ratio, 1.758; p = 0.60). A similar proportion died due to refractory intracranial hypertension in each group (abusive head trauma, 66.7% vs nonabusive head trauma, 69.0%). In this large, multicenter series, children with abusive head trauma had differences in prehospital and in-hospital secondary injuries which could have therapeutic implications. Unlike other traumatic brain injury populations in children, female predominance was seen in abusive head trauma in our cohort. Similar mortality rates and refractory intracranial pressure deaths suggest that children with severe abusive head trauma may benefit from therapies including invasive monitoring and adherence to evidence-based guidelines.

Autism Spectrum Disorder in Fragile X Syndrome: Cooccurring Conditions and Current Treatment.

Individuals with fragile X syndrome (FXS) are frequently codiagnosed with autism spectrum disorder (ASD). Most of our current knowledge about ASD in FXS comes from family surveys and small studies. The objective of this study was to examine the impact of the ASD diagnosis in a large clinic-based FXS population to better inform the care of people with FXS. The study employed a data set populated by data from individuals with FXS seen at specialty clinics across the country. The data were collected by clinicians at the patient visit and by parent report for nonclinical and behavioral outcomes from September 7, 2012 through August 31, 2014. Data analyses were performed by using χ2 tests for association, t tests, and multiple logistic regression to examine the association between clinical and other factors with ASD status. Half of the males and nearly 20% of females met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for current ASD. Relative to the FXS-only group, the FXS with ASD (FXS+ASD) group had a higher prevalence of seizures (20.7% vs 7.6%, P < .001), persistence of sleep problems later in childhood, increased behavior problems, especially aggressive/disruptive behavior, and higher use of α-agonists and antipsychotics. Behavioral services, including applied behavior analysis, appeared to be underused in children with FXS+ASD (only 26% and 16% in prekindergarten and school-age periods, respectively) relative to other populations with idiopathic ASD. These findings confirm among individuals with FXS an association of an ASD diagnosis with important cooccurring conditions and identify gaps between expected and observed treatments among individuals with FXS+ASD.

The spectrum of epilepsy and electroencephalographic abnormalities due to SHANK3 loss-of-function mutations.

The coincidence of autism with epilepsy is 27% in those individuals with intellectual disability.1 Individuals with loss-of-function mutations in SHANK3 have intellectual disability, autism, and variably, epilepsy.2-5 The spectrum of seizure semiologies and electroencephalography (EEG) abnormalities has never been investigated in detail. With the recent report that SHANK3 mutations are present in approximately 2% of individuals with moderate to severe intellectual disabilities and 1% of individuals with autism, determining the spectrum of seizure semiologies and electrographic abnormalities will be critical for medical practitioners to appropriately counsel the families of patients with SHANK3 mutations. A retrospective chart review was performed of all individuals treated at the Blue Bird Circle Clinic for Child Neurology who have been identified as having either a chromosome 22q13 microdeletion encompassing SHANK3 or a loss-of-function mutation in SHANK3 identified through whole-exome sequencing. For each subject, the presence or absence of seizures, seizure semiology, frequency, age of onset, and efficacy of therapy were determined. Electroencephalography studies were reviewed by a board certified neurophysiologist. Neuroimaging was reviewed by both a board certified pediatric neuroradiologist and child neurologist. There is a wide spectrum of seizure semiologies, frequencies, and severity in individuals with SHANK3 mutations. There are no specific EEG abnormalities found in our cohort, and EEG abnormalities were present in individuals diagnosed with epilepsy and those without history of a clinical seizure. All individuals with a mutation in SHANK3 should be evaluated for epilepsy due to the high prevalence of seizures in this population. The most common semiology is atypical absence seizure, which can be challenging to identify due to comorbid intellectual disability in individuals with SHANK3 mutations; however, no consistent seizure semiology, neuroimaging findings, or EEG findings were present in the majority of individuals with SHANK3 mutations.

Ocena klinicznych czynników ryzyka wystąpienia padaczki lekoopornej u dzieci i młodzieży

Introduction: Epilepsy is one of the most common neurological illnesses occurring in children. In approximately 20–30% of cases it is drug-resistant. Aim of the research: To assess the already-known risk factors, analyse the rarely described ones, and find new causes of epilepsy drug resistance in children, taking into account the level of impact of each factor. Material and methods: The study comprised 152 of all 383 children hospitalised in 2012 at the Neurology Department of the Polish Mother’s Memorial Hospital in Lodz due to epilepsy. Based on medical documentation, neurological examination, and our own questionnaire, we divided patients into two groups: drug-resistant epilepsy or drug-sensitive epilepsy. We compared the type, level of influence, and prevalence of different factors. For statistical analysis, the χ2 test was used. Statistical significance was set at p < 0.05. Results: Drug-resistant epilepsy was found in 64 patients (42.1%), and drug-sensitive epilepsy was found in 88 patients (57.9%). Factors that were most probable to cause drug resistance included: high prevalence of seizures (Cramer’s V = 0.66), type of epileptic syndrome (V = 0.62), psychomotor developmental delay (V = 0.62), and occurrence of status epilepticus (V = 0.6). Factors such as infections of CNS in early childhood, repeated severe infections of airways in childhood, and mother’s infectious diseases with high fever during pregnancy were rare or non occurring (Cramer’s V = 0.41, 0.32, and 0.31, respectively). Conclusions: The study confirmed the previously known causes of drug resistance and indicated the significance of under estimated inflammatory and infectious factors involving pyrexia, in children and also in mothers during pregnancy.

Focal cortical dysplasias in autism spectrum disorders

BackgroundPrevious reports indicate the presence of histological abnormalities in the brains of individuals with autism spectrum disorders (ASD) suggestive of a dysplastic process. In this study we identified areas of abnormal cortical thinning within the cerebral cortex of ASD individuals and examined the same for neuronal morphometric abnormalities by using computerized image analysis.ResultsThe study analyzed celloidin-embedded and Nissl-stained serial full coronal brain sections of 7 autistic (ADI-R diagnosed) and 7 age/sex-matched neurotypicals. Sections were scanned and manually segmented before implementing an algorithm using Laplace’s equation to measure cortical width. Identified areas were then subjected to analysis for neuronal morphometry. Results of our study indicate the presence within our ASD population of circumscribed foci of diminished cortical width that varied among affected individuals both in terms of location and overall size with the frontal lobes being particularly involved. Spatial statistic indicated a reduction in size of neurons within affected areas. Granulometry confirmed the presence of smaller pyramidal cells and suggested a concomitant reduction in the total number of interneurons.ConclusionsThe neuropathology is consistent with a diagnosis of focal cortical dysplasia (FCD). Results from the medical literature (e.g., heterotopias) and our own study suggest that the genesis of this cortical malformation seemingly resides in the heterochronic divisions of periventricular germinal cells. The end result is that during corticogenesis radially migrating neuroblasts (future pyramidal cells) are desynchronized in their development from those that follow a tangential route (interneurons). The possible presence of a pathological mechanism in common among different conditions expressing an autism-like phenotype argue in favor of considering ASD a “sequence” rather than a syndrome. Focal cortical dysplasias in ASD may serve to explain the high prevalence of seizures and sensory abnormalities in this patient population.

Electroclinical phenotypes in a pedigreed baboon colony

This is the first large-scale epidemiological study evaluating the prevalence of interictal epileptic discharges (IEDs) and photosensitivity (PS) recorded by scalp EEG in a natural nonhuman-primate model of photosensitive, generalized epilepsy. Scalp EEG was used to characterize electroclinical phenotypes in a large baboon pedigree housed at the Southwest National Primate Research Center at the Texas Biomedical Research Institute (Texas Biomed) based upon IEDs and photosensitivity. Scalp EEG studies including intermittent light stimulation (ILS) were performed in 671 baboons. Clinical histories were available for 531 (79%) of the animals. The EEG studies lasted 53 (±11) min, during which the baboons were lightly sedated with intramuscular ketamine doses of 5.6 (±0.8) mg. The animals were further classified according to electroclinical phenotypes recorded by scalp EEG: presence or absence of IEDs, seizures and photoparoxysmal or photoconvulsive responses. Effects of age, gender, and species on EEG phenotypes were compared using (Chi-square, two-sided, α<0.05). Sensitivity and specificity of IEDs and photosensitivity to detect a history of seizures was calculated. Generalized IEDs and photosensitivity were identified in 324 (49%) and 156 (23%) pedigreed baboons, respectively. Only photosensitivity was associated with gender, significantly increased in males. Otherwise, while IEDs were marginally more prevalent among males, there were no other significant associations of IEDs or photosensitivity with age or subspecies. Photosensitivity was significantly associated with IEDs, with demonstrating a possible association with gender and subspecies. Of 531 baboons with histories of clinical events, 91 (17%) had witnessed seizures and 269 (51%) were asymptomatic. IEDs demonstrated sensitivity and specificity of 62% and 57%, and photosensitivity of 40% and 83%, for prediction of seizures, respectively. While these EEG findings mirror the high prevalence of seizures in the colony, the sensitivity and specificity of scalp EEG may have been affected by ketamine's ability to lower the threshold for IEDs and seizures, particularly in animals predisposed to epilepsy. Photosensitivity provides a specific biological marker for epilepsy in future epidemiological, genetic, behavioral and histopathological studies.

Seizures in systemic sclerosis

The aim of this study was to evaluate the frequency of seizures in systemic sclerosis (SSc) and to determine the clinical and laboratory features associated with their occurrence. Thirty-four SSc patients (ACR criteria) were analyzed by a standard interview, physical examination, and review of medical charts. Risk factors for seizures, clinical manifestations, associated co-morbidities and current treatment were evaluated. We identified 3 (8.8 %) SSc patients with seizures. A higher median age [61 (35-64) vs. 48 (27-71) years, p = 0.0005] and higher activity score [4.75 (4.5-5.0) vs. 2.5 (0-5-5) years, p = 0.006] were observed in SSc patients with seizures. No other clinical or laboratory feature was associated with the occurrence of seizure in this cohort. This study demonstrated a higher prevalence of seizures in SSc when compared to general population. Seizures were associated with older age and higher activity score in this cohort.

Pattern of neonatal seizures in Osogbo, south-western Nigeria

Objectives. A study to determine the pattern and outcome of neonatal seizures. Design. A prospective descriptive study. Setting. Special Care Baby Unit, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Nigeria. Subjects. All newborn infants with observed seizures admitted between January 2006 and December 2008. Results. Of 866 neonates admitted, 59 (6.8%) had seizures; of these 43 (72.9%) had been born outside our health facility (outborn). Babies with seizures had a higher birth weight than babies without seizures (p=0.008), and the incidence of seizures had a linear relationship increasing with the weights of the babies and inverse to their ages. Of the 59 babies with seizures, 37 (62.7%) were considered to have had birth asphyxia. Meningitis, hypoglycaemia, and hypocalcaemia occurred in 7 (11.9%), 6 (10.2%) and 2 (3.4%) of cases, respectively, and 7 (11.9%) had undiagnosed causes. Forty-two (71.2%) of the 59 babies had both subtle and generalised seizures. Twenty-seven babies with seizures died (45.8%) compared with 131 of 807 babies without seizures (16.2%, p=0.0001). Babies with seizures and asphyxia or who had been outborn had the highest risk of death (59.5% and 48.8%, respectively). Recommendations. The major causes of neonatal seizures and death are potentially preventable. Comprehensive and vigorous efforts are needed to achieve safe delivery, prevent birth asphyxia and improve care and transport of sick neonates at the primary care level. In view of the high prevalence of seizures among severely asphyxiated neonates and those with meningitis, anticonvulsant chemoprophylaxis is recommended in these groups.

HERPES SIMPLEX ENCEPHALITIS IN OLDER ADULTS

To the Editor: Herpes simplex encephalitis (HSE) is the most frequent cause of sporadic necrotizing encephalitis in adults.1,2 HSE has a bimodal distribution, with one-third of patients younger than 20 and half aged 50 and older.3,4 Nevertheless, few data have been reported about HSE in older adults.3,5 The aim of this study was to describe the characteristics of an elderly subgroup of a larger series of inpatient adults.6 Inpatients aged 65 and older with a consistent clinical profile and a positive polymerase chain reaction (PCR) for herpes simplex virus (HSV) in the cerebrospinal fluid (CSF) or compatible neuroimaging of the brain were included. A compatible clinical profile was established when patients showed symptoms or signs consistent with central nervous system dysfunction of acute or subacute onset and an altered level of consciousness or fever. Neuroimaging of the brain was considered positive in the presence of hypodense images on computed tomography (CT) or hyperintense lesions in the temporal lobes or the orbitobasal region of the frontal lobes (unilaterally or bilaterally) in T2 and fluid-attenuated inversion recovery sequences on magnetic resonance imaging (MRI). An electroencephalographic study (EEG) was defined as positive if it showed focal slow waves, spikes, or spike-waves. Functional status was measured using the Barthel Index for basic activities of daily living. Cognitive function was measured using the Pfeiffer questionnaire after 6 months of follow-up. The Charlson Index was used to measure overall comorbidity. Neurological sequelae were evaluated and measured using the modified Rankin scale (mRS) at discharge and after a follow-up period of 6 months. Patients were divided into two groups according to the mRS: good outcome (≤Grade 2) and poor outcome (≥Grade 3).7 Twelve patients were studied. Demographic and clinical characteristics, diagnostic tests, and clinical course of these patients are summarized in Table 1. No patients were at Stage 3 or higher on the Global Deterioration Scale (GDS), and no dementia had been diagnosed before admission. The temporal lobe was affected in all, and in two (16.6%) patients, the involvement was bilateral. All patients received acyclovir for a mean of 14 days (range 12–20 days), 11 (91.7%) also received antiepileptic drugs (in 7 patients as treatment and in 4 patients as prophylaxis), and five (41.7%) patients were treated with dexamethasone for intracranial hypertension. The mean duration between starting acyclovir and the first day of apyrexia was 11 days (range 3–21 days). Four patients (33.3%) required admission to the intensive care unit (ICU), all of them needing orotracheal intubation for mechanical ventilation. At discharge, nine (75%) patients were found to have poor outcome, with a hospital mortality of three (25%) patients. After 6 months, three (33.3%) patients continued to have poor outcome, without any new deaths, according to the mRS. This subgroup of elderly patients had characteristics similar to those found in other series, such as the predominance of temporal-frontal symptoms, disorientation, behavioral changes, and aphasia, reflecting the tropism for this anatomical level,2,8 but the mortality rate was higher than in the general population, in agreement with other studies that identified age as an independent prognostic factor.2–4,6 Main symptoms of neurological sequelae are neurological deficits such as aphasia, seizures, or other neuropsychological dysfunctions, especially memory disorders, which have been found to be common. Several studies have suggested that HSV-1 might be involved in the pathogenesis of Alzheimer's disease, being a susceptibility factor due to specific characteristics of the virus.9 Major symptoms observed in the current series, such as behavioral changes and disorientation, are common signs of many infectious diseases in older adults. Therefore, especially if not accompanied by seizures, many cases could be misdiagnosed as nonspecific infections, delaying the initiation of acyclovir. Because cranial CT in the emergency department has low sensitivity, if HSE is suspected, treatment with acyclovir should be started until PCR for HSV in CSF and MRI come back negative. In elderly patients with HSE, fever is usually present, and it may persist for some days, despite administration of acyclovir. HSE results in high morbidity and mortality, frequent ICU admission, and a long hospital stay. If HSE is suspected, treatment with acyclovir should not be delayed despite a normal CT. Because of the high prevalence of seizures, antiepileptic drugs, either for treatment or prophylaxis, should be used in these patients. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Antoni Riera-Mestre, Ana Requena, and Sergio Martínez-Yélamos: letter design, data acquisition and interpretation, letter preparation. Carmen Cabellos: data interpretation, letter preparation. Pedro Fernández-Viladrich: critical revision of the letter. Sponsor's Role: None.

Antiemetic Properties of the Antiepileptic Drug Levetiracetam

To the Editor: Chemotherapy-induced nausea and vomiting is an important problem in patients with brain tumors. Because of the high prevalence of seizures, most patients are given antiepileptic drugs. Motivated by a case report,1 we investigated whether levetiracetam can suppress chemotherapy-induced nausea and vomiting. We retrospectively evaluated 161 patients with glioblastoma who had undergone radiation therapy and started adjuvant chemotherapy; 66 patients were taking levetiracetam and 95 were not (for all numerical data, see Table 1 in the Supplementary Appendix, available with the full text of this letter at www.nejm.org). In a univariate analysis, use of levetiracetam and older age were . . .

Risk factors associated with development of seizures after use of iohexol for myelography in dogs: 182 cases (1998).

To determine prevalence of seizures after use of iohexol for myelography and identify associated risk factors in dogs. Retrospective study. 182 dogs that received iohexol for myelography in 1998. Medical records were reviewed for age, breed, sex, weight, dose and total volume of iohexol, injection site, number of injections, lesion type and location, total duration of anesthesia, duration from time of iohexol injection to recovery, presence and number of seizures, and whether surgery followed the myelogram. 39 (21.4%) dogs had at least 1 generalized seizure during or after myelography. Injection site was strongly associated with prevalence of seizures, and risk of seizure was significantly higher after cerebellomedullary injections, compared with lumbar injections. Mean total volume of iohexol administered to dogs that had seizures was significantly higher, compared with that administered to dogs that did not have seizures, although dosage did not differ between groups. Weight was significantly correlated with risk of seizure, and dogs that weighed > 20 kg (44 lb) had higher prevalence of seizures than dogs that weighed < 20 kg. It is preferential to administer iohexol via the L5-6 intervertebral space to minimize the risk of seizures. Higher prevalence of seizures in large dogs, compared with smaller dogs, may be caused by administration of larger total volumes of contrast agent per volume of CSF.