Diagnóstico de neurocisticercosis en pacientes con epilepsia residentes en el suroeste de la República Dominicana / Diagnosis of neurocysticercosis in patients with epilepsy living in the south-western Dominican Republic

Introducción La neurocisticercosis (NCC), una posible causa de epilepsia con datos epidemiológicos limitados en la República Dominicana, es endémica en cuatro provincias de la región suroeste. El objetivo de este estudio fue determinar la asociación entre la NCC y la epilepsia en personas que viven en estas regiones endémicas, así como obtener datos preliminares sobre la prevalencia de NCC en estas provincias. Sujetos y métodos Se utilizó un diseño de casos y controles compuesto por 111 pacientes con epilepsia de causa desconocida y 60 controles sin epilepsia ni NCC. El diagnóstico de NCC se basó en la tomografía computarizada y la resonancia magnética del cráneo, así como en el inmunotransferencia de Western para anticuerpos séricos contra Taenia solium, siguiendo los criterios de Del Brutto et al. Resultados Se encontró NCC en el 27% de los pacientes con epilepsia (n = 30/111) y en el 5% de los controles (n = 3/60); los casos de epilepsia tenían siete veces más probabilidades de tener NCC que los controles (odds ratio = 7,04, intervalo de confianza al 95%: 2,04-24,18; p < 0,001). Las características sociodemográficas de los participantes, como la edad, el sexo, el nivel de escolaridad, la ocupación y la provincia de residencia no mostraron significación estadística en cuanto a la asociación con NCC. Conclusiones Este estudio sugiere que la NCC está fuertemente asociada con la epilepsia en la región suroeste de la República Dominicana, y destaca la necesidad de medidas de salud pública para mejorar la prevención, el diagnóstico y el tratamiento de ambas enfermedades. (AU)

INTRODUCTION Neurocysticercosis (NCC), a possible cause of epilepsy with limited epidemiological data in the Dominican Republic, is endemic in four provinces in the country’s south-western region. This study aimed to determine the association between NCC and epilepsy among people living in these endemic regions, and to obtain preliminary data on the prevalence of NCC in these provinces. PATIENTS AND METHODS A case-control design was used, consisting of 111 patients with epilepsy with unknown causes, and 60 controls without epilepsy or NCC. The diagnosis of NCC was based on computed tomography and magnetic resonance imaging of the skull, as well as Western immunoblotting for serum antibodies using Taenia solium, following the criteria of Del Brutto et al. RESULTS NCC was found in 27% of the epileptic patients (n = 30/111) and in 5% of the controls (n = 3/60); the probability of the epileptic patients having NCC was seven times higher than the controls (odds ratio = 7.04, 95% confidence interval: 2.04-24.18; p < 0.001). The participants’ sociodemographic characteristics, including their age, sex, level of education, occupation, and province of residence presented no statistical significance in terms of their association with NCC. CONCLUSIONS This study suggests that NCC is strongly associated with epilepsy in the south-western region of the Dominican Republic, and highlights the need for public health measures to improve the prevention, diagnosis and treatment of both diseases. (AU)

Superparamagnetic iron oxide nanoparticles-based detection of neuronal activity.

Precise detection of brain regions harboring heightened electrical activity plays a central role in the understanding and treatment of diseases such as epilepsy. Superparamagnetic iron oxide nanoparticles (SPIONs) react to magnetic fields by aggregating and represent interesting candidates as new sensors for neuronal magnetic activity. We hypothesized that SPIONs in aqueous solution close to active brain tissue would aggregate proportionally to neuronal activity. We tested this hypothesis using an in vitro model of rat brain slice with different levels of activity. Aggregation was assessed with dynamic light scattering (DLS) and magnetic resonance imaging (MRI). We found that increasing brain slice activity was associated with higher levels of aggregation as measured by DLS and MRI, suggesting that the magnetic fields from neuronal tissue could induce aggregation in nearby SPIONs in solution. MRI signal change induced by SPIONs aggregation could serve as a powerful new tool for detection of brain electrical activity.

Feasibility of implantable iron oxide nanoparticles in detecting brain activity-proof of concept in a rat model.

BACKGROUND: Precise detection of zones of increased brain activity is a crucial aspect in the delineation of the cortical region responsible for epilepsy (epileptic focus). When possible, removal of this area can lead to improved control of epilepsy or even its cure. This study explores a new method of detection of electrical brain activity based on the surgical implantation of iron oxide superparamagnetic nanoparticles (SPIONs). By their magnetic nature, SPIONs tend to aggregate in the presence of magnetic fields. This study aims to demonstrate if brain's magnetic fields could change the aggregation status of SPIONs in a rat model. METHODS: Plastic containers (capsules) containing SPIONs in aqueous suspension were implanted over the cortex of either rats rendered epileptic or naive rats (sham). A model of focal epilepsy using cortical penicillin injection was used for the epileptic rats. Capsules not implanted in rats served as control. Using magnetic resonance imaging (MRI), the aggregation status of SPIONs contained in the capsules was assessed via measurement of the T2 relaxivity time of the solutions. RESULTS: Eight Rats were used for the experiments, with 4 rats in each group (epileptic and sham). One Rat in the sham group died immediately after surgery and 3 rats failed to demonstrate the expected behavior after intervention (2 rats in epileptic group with limited observable seizures and 1 rat in the sham group having repeated seizures). T2 of the control capsules were significantly lower than those implanted in rats (146 ms vs 7.6 ms, p < 0.001), suggesting a higher degree of SPIONs aggregation in the implanted capsules. No significant difference in T2 could be demonstrated between epileptic and sham rats. CONCLUSIONS: SPIONs implanted over the cortex of active brain showed an increased aggregation status, confirming their potential as a new marker for brain activity. One of the main advantages of SPIONs is that their aggregation status can be measured at a distance with MRI, taking advantage of its high spatial resolution and imaging capacities. The current model was suboptimal to confirm if epileptic activity can be differentiated from normal brain activity using SPIONs.

Gross Motor Development of Children with Congenital Heart Disease Receiving Early Systematic Surveillance and Individualized Intervention: Brief Report.

Purpose: This retrospective study aims to describe the gross motor development of children aged 4 to 24 months with congenital heart disease (CHD) enrolled in a systematic developmental follow-up program and to describe the frequency of physical therapy sessions they received between 4 and 8 months of age. Methods: Twenty-nine infants with CHD underwent motor evaluations using the AIMS at 4 months, and the Bayley-III at 12 and 24 months. Results: Based on AIMS, 79% of 4-month-old infants had a gross motor delay and required physical therapy. Among these, 56.5% received one to two physical therapy sessions, and 43.5% received three to six sessions. Infants who benefited from regular interventions tended to show a better improvement in motor scores from 12 to 24 months. Conclusion: This study highlights the importance of early motor screening in infants with CHD and suggests a potential benefit of early physical therapy in at-risk children. Abbreviations: CHD: Congenital heart disease; AIMS: Alberta Infant Motor Scales; Bayley-III: Bayley Scales of Infant and Toddler Development, Third edition; Bayley-III/GM: Gross Motor section of the Bayley Scales of Infant and Toddler Development, Third edition.

Seizures in Pediatric Patients With Primary Brain Tumors.

BACKGROUND: Seizures are one of the most common symptoms of pediatric brain tumors. The purpose of this study was to define seizures related to primary central nervous system tumors and to identify risk factors predictive of seizure occurrence and recurrence. METHODS: We reviewed the records of children treated from January 1, 2004, to January 1, 2018 and collected data including age, gender, tumor location, histology, extent of initial resection, seizure characteristics, treatment modalities, recurrence, and seizure control. A binomial logistic regression was performed to determine the risk factors of seizure occurrence. RESULTS: During the observation period, 348 children were diagnosed with a primary brain tumor. The median age at diagnosis was 7.8 years, and the median follow-up interval was 3.9 years. There were 196 boys (56.3%). In our cohort, a total of 70 children (20.1%) experienced seizures. Most of them (64.3%) had cortical tumors. All patients with dysembryoplastic neuroepithelial tumors and 81.8% of patients with glioneuronal tumors presented seizures. Risk factors associated with an increased risk for seizures included cortical location, tumor recurrence, and age at diagnosis. Thirty-nine (86.7%) patients with seizures at diagnosis were seizure free at last follow-up (Engel 1). Significantly more patients (69.6%) with a gross total resection were withdrawn from their antiepileptic drugs when compared with those with subtotal resection (27.3%, P = 0.007). CONCLUSIONS: Our study is the largest cohort in children with tumor-related seizures and brings new insight in terms of seizure risk according to tumor types and evolution following treatment.

Language development in children with congenital heart disease aged 12-24 months.

This longitudinal study aims to describe the trajectory of language development in children with CHD aged 12-24 months assessed through an early monitoring and individualized intervention program. We also sought to determine whether early language performances, at 12 months of age, predict 24-month language abilities. We conducted developmental assessments of 49 children with CHD using the Bayley Scales of Infant and Toddler Developmental, third edition (Bayley-III) at 12 and 24 months, and the MacArthur-Bates Communicative Development Inventories (MBCDI) at 12, 18 and 24 months. Compared to normative populations, CHD patients showed significantly lower mean scores in both receptive and expressive language scales of the Bayley-III and the MBCDI at 12 months, whereas at 18 and 24 months only expressive language scores were reduced. No differences were found in the cognitive scale. Communicative gestures at 12 months were significantly predictive of language skills at 24 months of age. Our findings indicate specific vulnerability of language outcome, especially in expressive skills, rather than a global cognitive impairment in our patients with CHD. We recommend using communicative gestures as an early marker of language development to improve our ability to detect language delays in this population.

Mutations in ACTL6B Cause Neurodevelopmental Deficits and Epilepsy and Lead to Loss of Dendrites in Human Neurons.

We identified individuals with variations in ACTL6B, a component of the chromatin remodeling machinery including the BAF complex. Ten individuals harbored bi-allelic mutations and presented with global developmental delay, epileptic encephalopathy, and spasticity, and ten individuals with de novo heterozygous mutations displayed intellectual disability, ambulation deficits, severe language impairment, hypotonia, Rett-like stereotypies, and minor facial dysmorphisms (wide mouth, diastema, bulbous nose). Nine of these ten unrelated individuals had the identical de novo c.1027G>A (p.Gly343Arg) mutation. Human-derived neurons were generated that recaptured ACTL6B expression patterns in development from progenitor cell to post-mitotic neuron, validating the use of this model. Engineered knock-out of ACTL6B in wild-type human neurons resulted in profound deficits in dendrite development, a result recapitulated in two individuals with different bi-allelic mutations, and reversed on clonal genetic repair or exogenous expression of ACTL6B. Whole-transcriptome analyses and whole-genomic profiling of the BAF complex in wild-type and bi-allelic mutant ACTL6B neural progenitor cells and neurons revealed increased genomic binding of the BAF complex in ACTL6B mutants, with corresponding transcriptional changes in several genes including TPPP and FSCN1, suggesting that altered regulation of some cytoskeletal genes contribute to altered dendrite development. Assessment of bi-alleic and heterozygous ACTL6B mutations on an ACTL6B knock-out human background demonstrated that bi-allelic mutations mimic engineered deletion deficits while heterozygous mutations do not, suggesting that the former are loss of function and the latter are gain of function. These results reveal a role for ACTL6B in neurodevelopment and implicate another component of chromatin remodeling machinery in brain disease.

Epilepsy and seizures in children with congenital heart disease: A prospective study.

PURPOSE: Children with complex congenital heart disease (CHD) experience high incidence of perioperative seizures. Population-based studies also report high epilepsy co-morbidity in CHD. Given the increasing survival of patients with CHD and the interference of seizures and epilepsy with the long-term outcomes, characterizing them in this population is of high relevance. This study investigated the incidence and risk factors of perioperative clinical seizures (CS) and epilepsy in a prospective cohort of children with complex CHD who underwent cardiac surgery. METHODS: We included 128 consecutive children with CHD, followed for at least two years at the neurocardiac clinic of Montreal's Sainte-Justine University Hospital Center. We collected perinatal, surgical, critical care and clinical follow-up information and performed logistic regression to reveal risk factors of CS and epilepsy. RESULTS: Ten patients (7.8%) experienced perioperative CS. Four of them (40%) developed epilepsy. The incidence of epilepsy was therefore 3.1%. Higher surgical complexity scores, delayed sternal closure, extracorporeal membrane oxygenation (ECMO) use, longer intensive care and hospital stay were associated with CS. ECMO use and hospital stay were also associated with epilepsy. Nine (90%) patients with CS had brain injuries: five strokes, one white matter and three hypoxic-ischemic injury (HII). All patients with HII developed epilepsy, which became intractable in one of them. CONCLUSION: Our study reports high incidence, surgical risk factors and brain injury patterns underlying CS and epilepsy in CHD. Further studies are needed to investigate how epilepsy interferes with neurodevelopment and quality of life in CHD.

Diagnostic and Therapeutic Misconception: Parental Expectations and Perspectives Regarding Genetic Testing for Developmental Disorders.

Parents' understanding/expectations regarding genetic testing for children with developmental disorders were explored. Within a month of testing, interviews were conducted with 57 parents. Many (74%) could not recall the nature of testing. Parents expected genetic testing to have positive impacts for the child (93%) and the family (98%), mainly to find the etiology and/or an intervention. Many parents (40%) reported not knowing their child's clinical diagnosis. They expected genetic testing would establish the diagnosis. Parents anticipated potential negative impacts of testing for children (78%) and families (87%), mainly finding another illness or not finding potential interventions. Abnormal results explaining the disorder were found in 9% of children. In summary, genetic results for developmental disorders are unlikely to meet parental expectations.

Surgical outcomes for medically intractable epilepsy in low- and middle-income countries: a systematic review and meta-analysis.

OBJECTIVEThe aim of this study was to describe the current state of epilepsy surgery and establish estimates of seizure outcomes following surgery for medically intractable epilepsy (MIE) in low- and middle-income countries (LMICs).METHODSThe MEDLINE and Embase databases were searched without publication date restriction. This search was supplemented by a manual screen of key epilepsy and neurosurgical journals (January 2005 to December 2016). Studies that reported outcomes for at least 10 patients of any age undergoing surgery for MIE in LMICs over a defined follow-up period were included. A meta-analysis with a random-effects model was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. Pooled estimates of seizure freedom and favorable seizure outcomes following anterior temporal lobectomy with or without amygdalohippocampectomy (ATL ± AH) were reported.RESULTSTwenty studies were selected, of which 16 were from Asian centers. The average age at surgery in all studies was less than 30 years, and the average preoperative duration of epilepsy ranged from 3 to 16.1 years. Mesial temporal sclerosis accounted for 437 of 951 described pathologies, and 1294 of the 1773 procedures were ATL ± AH. Based on 7 studies (646 patients) the pooled seizure freedom estimate following ATL ± AH was 68% (95% CI 55%-82%). Based on 8 studies (1096 patients), the pooled estimate for favorable seizure outcomes was 79% (95% CI 74%-85%).CONCLUSIONSSurgery for MIE in LMICs shows a high percentage of seizure freedom and favorable outcomes. These findings call for a concerted global effort to improve timely access to surgery for MIE patients in these regions, including investments aimed at refining existing and establishing additional centers.

Systematic review of the screening, diagnosis, and management of ADHD in children with epilepsy. Consensus paper of the Task Force on Comorbidities of the ILAE Pediatric Commission.

Attention-deficit/hyperactivity disorder (ADHD) is a common and challenging comorbidity affecting many children with epilepsy. A working group under the International League Against Epilepsy (ILAE) Pediatric Commission identified key questions on the identification and management of ADHD in children with epilepsy. Systematic reviews of the evidence to support approaches to these questions were collated and graded using criteria from the American Academy of Neurology Practice Parameter. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements were followed, with PROSPERO registration (CRD42018094617). No increased risk of ADHD in boys with epilepsy compared to girls with epilepsy was found (Level A). Valproate use in pregnancy is associated with inattentiveness and hyperactivity in offspring (1 class I study), and children with intellectual and developmental disabilities are at increased risk of ADHD (Level A). Impact of early seizure onset on development of ADHD was unclear (Level U), but more evident with poor seizure control (Level B). ADHD screening should be performed from 6 years of age, or at diagnosis, and repeated annually (Level U) and reevaluated after change of antiepileptic drug (AED) (Level U). Diagnosis should involve health practitioners with expert training in ADHD (Level U). Use of the Strength and Difficulties Questionnaire screening tool is supported (Level B). Formal cognitive testing is strongly recommended in children with epilepsy who are struggling at school (Level U). Behavioral problems are more likely with polytherapy than monotherapy (Level C). Valproate can exacerbate attentional issues in children with childhood absence epilepsy (Level A). Methylphenidate is tolerated and effective in children with epilepsy (Level B). Limited evidence supports that atomoxetine is tolerated (Level C). Multidisciplinary involvement in transition and adult ADHD clinics is essential (Level U). In conclusion, although recommendations could be proposed for some of the study questions, this systematic review highlighted the need for more comprehensive and targeted large-population prospective studies.

KCC2 Regulates Dendritic Spine Formation in a Brain-Region Specific and BDNF Dependent Manner.

KCC2 is the major chloride extruder in neurons. The spatiotemporal regulation of KCC2 expression orchestrates the developmental shift towards inhibitory GABAergic drive and the formation of glutamatergic synapses. Whether KCC2's role in synapse formation is similar in different brain regions is unknown. First, we found that KCC2 subcellular localization, but not overall KCC2 expression levels, differed between cortex and hippocampus during the first postnatal week. We performed site-specific in utero electroporation of KCC2 cDNA to target either hippocampal CA1 or somatosensory cortical pyramidal neurons. We found that a premature expression of KCC2 significantly decreased spine density in CA1 neurons, while it had the opposite effect in cortical neurons. These effects were cell autonomous, because single-cell biolistic overexpression of KCC2 in hippocampal and cortical organotypic cultures also induced a reduction and an increase of dendritic spine density, respectively. In addition, we found that the effects of its premature expression on spine density were dependent on BDNF levels. Finally, we showed that the effects of KCC2 on dendritic spine were dependent on its chloride transporter function in the hippocampus, contrary to what was observed in cortex. Altogether, these results demonstrate that KCC2 regulation of dendritic spine development, and its underlying mechanisms, are brain-region specific.

Superior Performance in Prone in Infants With Congenital Heart Disease Predicts an Earlier Onset of Walking.

Infants with congenital heart disease are at risk of impaired neurodevelopment, which frequently manifests as motor delay during their first years of life. This delay is multifactorial in origin and environmental factors, such as a limited experience in prone, may play a role. In this study, we evaluated the motor development of a prospective cohort of 71 infants (37 males) with congenital heart disease at 4 months of age using the Alberta Infant Motor Scales (AIMS). We used regression analyses to determine whether the 4-month AIMS scores predict the ability to walk by 18 months. The influence of demographic and clinical variables was also assessed. Fifty-one infants (71.8%) were able to maintain the prone prop position (AIMS score of ≥3 in prone) at 4 months. Of those, 47 (92.2%) were able to walk by 18 months compared to only 12/20 (60%) of those who did not maintain the position. Higher AIMS scores were predictive of a greater likelihood of walking by 18 months ( P < .001), with the scores in prone having a higher predictive ability compared to those in other positions (Exp(B) 15.2 vs 4.0). Shorter hospital stays and female gender were also associated with an earlier onset of walking. In conclusion, our study demonstrates that early ventral performance in infants with congenital heart disease impacts the age of acquisition of walking and could be used to guide referral to rehabilitation.

The protocol for the Cannabidiol in children with refractory epileptic encephalopathy (CARE-E) study: a phase 1 dosage escalation study.

BACKGROUND: Initial studies suggest pharmaceutical grade cannabidiol (CBD) can reduce the frequency of convulsive seizures and lead to improvements in quality of life in children affected by epileptic encephalopathies. With limited access to pharmaceutical CBD, Cannabis extracts in oil are becoming increasingly available. Physicians show reluctance to recommend Cannabis extracts given the lack of high quality safety data especially regarding the potential for harm caused by other cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC). The primary aims of the study presented in this protocol are (i) To determine whether CBD enriched Cannabis extract is safe and well-tolerated for pediatric patients with refractory epilepsy, (ii) To monitor the effects of CBD-enriched Cannabis extract on the frequency and duration of seizure types and on quality of life. METHODS: Twenty-eight children with treatment resistant epileptic encephalopathy ranging in age from 1 to 10 years will be recruited in four Canadian cities into an open-label, dose-escalation phase 1 trial. The primary objectives for the study are (i) To determine if the CBD-enriched Cannabis herbal extract is safe and well-tolerated for pediatric patients with treatment resistant epileptic encephalopathy and (ii) To determine the effect of CBD-enriched Cannabis herbal extract on the frequency and duration of seizures. Secondary objectives include (i) To determine if CBD-enriched Cannabis herbal extracts alter steady-state levels of co-administered anticonvulsant medications. (ii) To assess the relation between dose escalation and quality of life measures, (iii) To determine the relation between dose escalation and steady state trough levels of bioactive cannabinoids. (iv) To determine the relation between dose escalation and incidence of adverse effects. DISCUSSION: This paper describes the study design of a phase 1 trial of CBD-enriched Cannabis herbal extract in children with treatment-resistant epileptic encephalopathy. This study will provide the first high quality analysis of safety of CBD-enriched Cannabis herbal extract in pediatric patients in relation to dosage and pharmacokinetics of the active cannabinoids. TRIAL REGISTRATION: http://clinicaltrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2016 Dec 16. Identifier NCT03024827, Cannabidiol in Children with Refractory Epileptic Encephalopathy: CARE-E; 2017 Jan 19 [cited 2017 Oct]; Available from: http://clinicaltrials.gov/ct2/show/NCT03024827.

Humanized mouse model of Rasmussen's encephalitis supports the immune-mediated hypothesis.

Rasmussen's encephalitis (RE) is a chronic inflammatory brain disorder that causes frequent seizures and unilateral hemispheric atrophy with progressive neurological deficits. Hemispherectomy remains the only treatment that leads to seizure freedom for this refractory epileptic syndrome. The absence of an animal model of disease has been a major obstacle hampering the development of effective therapies. Here, we describe an experimental mouse model that shares several clinical and pathological features with the human disease. Immunodeficient mice injected with peripheral blood mononuclear cells from RE patients and monitored by video electroencephalography developed severe seizures of cortical origin and showed intense astrogliosis and accumulation of human IFN-γ- and granzyme B-expressing T lymphocytes in the brain compared with mice injected with immune cells from control subjects. We also provide evidence for the efficacy of α4 integrin blockade, an approved therapy for the treatment of multiple sclerosis and Crohn's disease, in reducing inflammatory markers associated with RE in the CNS. This model holds promise as a valuable tool for understanding the pathology of RE and for developing patient-tailored experimental therapeutics.

Favorable adverse effect profile of brivaracetam vs levetiracetam in a preclinical model.

Levetiracetam (LEV), and its newer selective analog brivaracetam (BRV), are two seizure medications that share an innovative mechanism of action targeting the Synaptic Vesicle Protein 2A (SV2A), altering neurotransmitter release and decreasing seizure frequency. Behavioral changes are the most significant adverse effects reported by patients taking LEV. We hypothesize that BRV, the more potent SV2A analog, could exert less behavioral side effects, as it requires lower doses than LEV. Using Kainic Acid (KA)-treated and control rats, we measured adverse behavioral effect profiles of LEV, BRV, or Saline, on social and nonsocial behaviors. Our data indicate that both tested drugs had no effect on locomotion, anxiety levels, fear learning, depression-like behavior, and memory retention in rats. However, when considering social interactions, we first confirmed the epilepsy-induced strong increase in aggressive behaviors and specific hippocampal neuronal loss. We furthermore observed, in Sham rats, that LEV-treated animals were 2 times faster to attack at first encounter, had 5 times more aggressive behaviors, and had significantly less social behaviors than control rats. In all circumstances, BRV rats behaved like Saline rats, suggesting that BRV treatment in rats leads to significantly less aggressive behaviors than LEV treatment at the doses used, while there are limited differential effects between these two drugs on other types of behaviors. Since increased aggressiveness has been reported in patients well controlled on LEV, this study indicates based on our findings, that BRV could represent an effective alternative to LEV to limit aggressiveness problems due to this antiepileptic drug (AED) therapy.

Paediatricians' expectations and perspectives regarding genetic testing for children with developmental disorders.

AIM: To investigate paediatricians' expectations and perspectives of genetic testing for children with developmental disorders. METHODS: Paediatricians working in a developmental clinic were surveyed each time they ordered a chromosomal microarray (CMA) for a child with developmental disorders. Clinical charts were reviewed. Results were analysed using mixed methodology. RESULTS: Ninety-seven % (73/76) of surveys were completed. Paediatricians reported that 36% of parents had difficulties understanding genetic testing and that 40% seemed anxious. The majority expected testing to have positive impacts on children/families. The themes raised were (i) clarifying the diagnosis (56%), (ii) understanding the aetiology of the condition (55%), (iii) enabling prenatal diagnosis/counselling (43%), (iv) improving medical care for the child (15%) and (v) decreasing parental guilt/anxiety (8%). Less than half anticipated negative impacts; 74% expected that the most helpful result for their patient would be an abnormal result explaining the disorder. Among the 73 children for whom CMA was ordered, 81% got tested: 66% of the results were normal, 19% were abnormal and contributed to explain the condition and 12% were abnormal but of unknown significance. CONCLUSION: Paediatricians generally expect many positive and less negative impacts of genetic testing for children with developmental disorders. Parental perspectives are needed.

Orbitofrontal epilepsy: Case series and review of literature.

BACKGROUND: Orbitofrontal epilepsy (OFE) is less known and is poorly characterized in comparison with temporal lobe epilepsy, partly because it is rare and possibly because it is unrecognized and therefore underestimated. OBJECTIVE: This paper aimed to better characterize seizure semiology, presurgical findings, and surgical outcomes in patients with OFE. METHODS: We retrospectively reviewed all confidently established OFE cases from six Canadian epilepsy monitoring units between 1988 and 2014, and in the literature between 1972 and 2017. Inclusion criteria were identification of an epileptogenic lesion localized in the OFC or if the patient was seizure-free after surgical removal of the OFC in nonlesional cases. RESULTS: Sixteen cases were identified from our databases. Fifty percent had predominantly sleep-related seizures; 56% had no aura (the remaining had nonspecific or vegetative auras), and 62.5% featured hypermotor (mostly hyperkinetic) behaviors. Interictal epileptiform discharges over frontal and temporal derivations always allowed lateralization. Magnetic resonance imaging (MRI) identified an orbitofrontal lesion in 8/16, positron emission tomography (PET) identified a hypometabolism extending outside the orbital cortex in 4/9, ictal single-photon emission computed tomography (SPECT) identified an orbital hyperperfusion in 1/5, magnetoencephalography (MEG) identified lateral orbital sources in 2/4, and intracranial electroencephalography (EEG) identified an orbitofrontal onset in 9/10. Fourteen patients underwent surgery, all reaching a favorable outcome (71.4% Engel 1; 28.6% Engel 2; mean FU=5.6years). Pre- and postoperative neuropsychological assessments revealed heterogeneous findings. Our review of literature identified 71 possible cases of OFE, 32 with confident focus localization. Extracted data from these cumulated cases supported observations made from our case series. CONCLUSIONS: Orbitofrontal epilepsy should be suspected with sleep-related, hyperkinetic seizures with no specific aura, and frontotemporal interictal discharges. Several patients have nonmotor seizures with or without auras which may resemble temporal lobe seizures. Postoperative seizure outcome was favorable, but there is inherent bias as we only included patients with a seizure-free outcome if the MRI was negative. A larger study is required to address identified gaps in knowledge such as identifying discriminative features between medial and lateral OFE, evaluating the value of more recent diagnostic tools, and assessing the neuropsychological outcome of orbital epilepsy surgery.

Age at first febrile seizure correlates with perinatal maternal emotional symptoms.

OBJECTIVE: Prenatal exposure to stress and fever are factors lowering seizure threshold in animal models. The fever effect on seizure threshold is well documented in human infants, however the associations between maternal perinatal stress and infants' susceptibility to seizures is unknown. This is the first study in humans to investigate longitudinally, whether in humans, the effect of maternal perinatal emotional symptoms such as stress, anxiety and depression that may trigger a biological stress response on age at first seizure occurrence. METHOD: The study sample is a subgroup drawn from a longitudinal follow up cohort (3D cohort study: Design, Develop, Discover, N=2366 mother-infant dyads). Twenty-nine otherwise healthy infants who had a febrile seizure (FS) episode before the last follow-up visit (around 24 months of age) were studied. Mothers completed questionnaires regarding their emotional health at each pregnancy trimester and at three months postpartum. The link between maternal emotional symptoms and infant age at first FS was assessed through correlations and multiple regressions. RESULTS: We found that maternal anxiety symptoms during the second trimester of pregnancy are linked to the age at first FS (r(23)=-0.459, p=0.021) and explain 21.1% of its variance. Postnatal maternal depression symptoms at 3 months postpartum were also associated with the age at first FS (r(23)=-0.587, p=0.002) and explained an additional 17.6% of variance. Together, the variables explained 38.7% of the variance in age at first FS. Maternal perceived stress symptoms at 3 months postpartum were also linked to the age at first FS (r(23)=-0.418, p=0.038), however, stress did not significantly contribute to the variance of age at first FS.. SIGNIFICANCE: Our results suggest a link between increased perinatal maternal emotional symptoms and the age at first FS. An earlier age at first FS may be the manifestation of a lower seizure threshold. Early first seizure occurrence is a risk factor for compromised neurological and cognitive development. Further studies should address the mechanisms by which perinatal maternal emotional symptoms may have an impact on seizure threshold in humans.

Periictal activity in cooled asphyxiated neonates with seizures.

PURPOSE: Seizures are common in critically ill neonates. Both seizures and antiepileptic treatments may lead to short term complications and worsen the outcomes. Predicting the risks of seizure reoccurrence could enable individual treatment regimens and better outcomes. We aimed to identify EEG signatures of seizure reoccurrence by investigating periictal electrographic features and spectral power characteristics in hypothermic neonates with hypoxic-ischemic encephalopathy (HIE) with or without reoccurrence of seizures on rewarming. METHODS: We recruited five consecutive HIE neonates, submitted to continuous EEG monitoring, with high seizure burden (>20% per hour) while undergoing therapeutic hypothermia. Two of them had reoccurrence of seizures on rewarming. We performed quantitative analysis of fifteen artifact-free consecutive seizures to appreciate spectral power changes between the interictal, preictal and ictal periods, separately for each patient. Visual analysis allowed description of electrographic features associated with ictal events. RESULTS: Every patient demonstrated a significant increase in overall spectral power from the interictal to preictal and ictal periods (p<0.01). Alpha power increase was more pronounced in the two patients with reoccurrence of seizures on rewarming and significant when comparing both interictal-to-preictal and interictal-to-ictal periods. This alpha activity increase could be also appreciated using visual analysis and distinguished neonates with and without seizure reoccurrence. CONCLUSION: This distinct alpha activity preceding ictal onset could represent a biomarker of propensity for seizure reoccurrence in neonates. Future studies should be performed to confirm whether quantitative periictal characteristics and electrographic features allow predicting the risks of seizure reoccurrence in HIE neonates and other critically ill patients.