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

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.

TITLE: Diagnóstico de neurocisticercosis en pacientes con epilepsia residentes en el suroeste de la República Dominicana.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.

TLR3 preconditioning induces anti-inflammatory and anti-ictogenic effects in mice mediated by the IRF3/IFN-ß axis.

Activation of Toll-like receptor 3 (TLR3) was previously shown to contribute to the generation of epileptic seizures in rodents by evoking a proinflammatory response in the forebrain. This suggests that TLR3 blockade may provide therapeutic effects in epilepsy. We report that brain activation of TLR3 using the synthetic receptor ligand Poly I:C may also result in remarkable dose- and time-dependent inhibitory effects on acute seizures in mice without inducing inflammation. These inhibitory effects are associated with reduced neuronal excitability in the hippocampus as shown by a decrease in the population spike amplitude of CA1 pyramidal neurons following Schaffer collaterals stimulation. TLR3 activation which results in seizure inhibition does not evoke NF-kB-dependent inflammatory molecules or morphological activation of glia, however, it induces the alternative interferon (IFN) regulatory factor (IRF)-3/IFN-ß signaling pathway. IFN-ß reproduced the inhibitory effects of Poly I:C on neuronal excitability in hippocampal slices. Seizure inhibition attained with activation the TLR3-IRF3/IFN-ß axis should be carefully considered when TLR3 are targeted for therapeutic purposes.

fMRI brain response during sentence reading comprehension in children with benign epilepsy with centro-temporal spikes.

INTRODUCTION: Children with benign epilepsy with centro-temporal spikes (BECTS) often have language problems. Abnormal epileptic activity is found in central and temporal brain regions, which are involved in reading and semantic and syntactic comprehension. Using functional magnetic resonance imaging (fMRI), we examined reading networks in BECTS children with a new sentence reading comprehension task involving semantic and syntactic processing. METHOD: Fifteen children with BECTS (age=11y 1m ± 16 m; 12 boys) and 18 healthy controls (age=11 y 8m ± 20 m; 11 boys) performed an fMRI reading comprehension task in which they read a pair of syntactically complex sentences and decided whether the target sentence (the second sentence in the pair) was true or false with respect to the first sentence. All children also underwent an exhaustive neuropsychological assessment. RESULTS: We demonstrated weaknesses in several cognitive domains in BECTS children. During the sentence reading fMRI task, left inferior frontal regions and bilateral temporal areas were activated in BECTS children and healthy controls. However, additional brain regions such as the left hippocampus and precuneus were activated in BECTS children. Moreover, specific activation was found in the left caudate and putamen in BECTS children but not in healthy controls. Cognitive results and accuracy during the fMRI task were associated with specific brain activation patterns. CONCLUSION: BECTS children recruited a wider network to perform the fMRI sentence reading comprehension task, with specific activation in the left dorsal striatum. BECTS cognitive performance differently predicted functional activation in frontal and temporal regions compared to controls, suggesting differences in brain network organisation that contribute to reading comprehension.

Enhanced EEG connectivity in children with febrile seizures.

BACKGROUND: Epilepsy is currently conceptualized as a disturbance of neuronal networks with altered connectivity that persists into the interictal phase. Febrile seizures are sometimes a precursor in childhood of lifelong epilepsy. We investigated whether studying functional connectivity in children with febrile seizures could help understand the mechanisms underlying their long-term seizure susceptibility. METHODS: EEG was recorded during rest and intermittent photic stimulation (IPS) in 12 FS patients, 5 siblings and 15 control children between 6 and 36 months of age. Original EEG data were transformed into source space using a multiple regional source model. Source coherence values were calculated for the interfrontal, interoccipital and occipito-frontal connections for the delta, theta, alpha, beta and gamma frequency bands. RESULTS: Our results suggest enhanced delta and theta frequency EEG source coherence in patients with FSs compared to siblings and control children, both under resting conditions and during IPS, more consistent for the theta band and the occipito-frontal connections. CONCLUSIONS: Enhanced connectivity in patients with FSs could indicate a seizure-prone state and interfere with the maturation of cerebral networks. Further prospective studies are needed to assess whether hyperconnectivity is a risk factor for epileptogenesis and neurodevelopmental disorders.

A recurrent mutation in DEPDC5 predisposes to focal epilepsies in the French-Canadian population.

Familial focal epilepsy with variable foci (FFEVF) is a heterogeneous epilepsy syndrome originally described in the French-Canadian (FC) population. Mutations in DEPDC5 have recently been identified in multiple cases of FFEVF as well as in a wide spectrum of other familial focal epilepsies. In this study, we aimed to determine the frequency of mutation of this gene in our large cohort of FC individuals with FFEVF, as well as familial and sporadic cases with focal epilepsy. We report a recurrent p.R843X protein-truncating mutation segregating in one large FFEVF and two small focal epilepsy FC families. Fine genotyping suggests an ancestral allele. A new p.T864M variant, predicted to be disease-causing, was also identified in a small FC family. Overall, we identified DEPDC5 mutations in 5% of our familial and sporadic focal epilepsy cases (4/79). Our results support the view that mutations in the DEPDC5 gene are an important cause of autosomal dominant focal epilepsies in the FC population, including a founder mutation that is specific to this population. These findings may facilitate molecular diagnosis in clinical practice.

Febrile and other occasional seizures.

Seizures with fever that result from encephalitis or meningitis usually occur late in the course of febrile illness, and are focal and prolonged. Febrile seizures are by far the most common affecting 5% of the population, followed by posttraumatic seizures and those observed in the setting of a toxic, infectious, or metabolic encephalopathy. This chapter reviews the clinical presentation of the three most common forms, due to fever, trauma, and intoxication. Febrile seizures carry no cognitive or mortality risk. Recurrence risk is increased by young age, namely before 1 year of age. Febrile seizures that persist after the age of 6 years are usually part of the syndrome of Generalized epilepsy febrile seizures plus. These febrile seizures have a strong link with epilepsy since non-febrile seizures may occur later in the same patient and in other members of the same family with an autosomal dominant transmission. Complex febrile seizures, i.e., with focal or prolonged manifestations or followed by focal defect, are related to later mesial temporal epilepsy with hippocampal sclerosis; risk factors are seizure duration and brain malformation. Prophylactic treatment is usually not required in febrile seizures. Early onset of complex seizures is the main indication for AED prophylaxis. Early posttraumatic seizures, i.e., within the first week, are often focal and indicate brain trauma: contusion, hematoma, 24 hours amnesia, and depressed skull fracture are major factors of posttraumatic epilepsy. Prophylaxis with antiepileptic drugs is not effective. Various psychotropic drugs, including antiepileptics, may cause seizures.

Children with a history of atypical febrile seizures show abnormal steady state visual evoked potential brain responses.

Atypical febrile seizures (FSs) are considered a risk factor for the onset of epilepsy in later life as well as for potential cognitive impairment. However, distinctive characteristics defining the group of children at risk for negative outcomes are not well established. In the following study, children from 6 to 59 months with a history of atypical FSs were investigated using steady state visual evoked potentials (ssVEP), a brain response known to increase with age. Abnormally, low theta and alpha ssVEP brain responses were found in children with a history of atypical FSs.

Vigabatrin therapy for infantile spasms: review of major trials in Europe, Canada, and the United States; and recommendations for dosing.

Infantile spasms (IS) are a unique and severe form of epilepsy associated with poor neurologic and developmental outcomes. The refractory spasms and abnormal electroencephalogram (EEG) patterns associated with the condition are believed to have a progressively detrimental impact. Therefore, rapid and complete control of spasms is the primary goal of treatment. Well-controlled clinical trials in Europe, Canada, and the United States have demonstrated that vigabatrin is efficacious and generally well-tolerated as monotherapy for IS. Several key studies, including pivotal trials that led to United States approval of vigabatrin in 2009, as well as comparative trials of vigabatrin and hormonal treatment, are the focus of this review. All studies assessed spasm cessation - usually as the primary endpoint - and adverse events. Vigabatrin dosages generally ranging from 100 to 150 mg/kg/day demonstrated efficacy to decrease or eradicate spasms and eliminate hypsarrhythmic EEG in patients with newly diagnosed IS. Several studies demonstrated long-term sustainability of spasm freedom with no negative impact on developmental outcomes. Vigabatrin was generally well-tolerated with few severe adverse events. Visual field defects cannot be adequately assessed in infants and young children, so this potential adverse effect was not evaluated in children with spasms. Notably, the time to response with vigabatrin was very rapid, generally occurring within 2 weeks of initial treatment. This allows for early treatment modification as needed. For infants who respond well to vigabatrin, treatment duration up to 6 months appears to be appropriate for realizing spasm freedom while limiting potential risks of adverse events and recurrences.

Effects of hyperthermic seizures on the developing primary visual cortex of the rat.

Febrile seizures occurring during childhood have been shown to interfere with the development of cognitive functions. However, an alteration of the developing sensory systems might also result from febrile seizures. In order to test this hypothesis, seizures were induced by hyperthermia in Long Evans rats on postnatal day 10. Extracellular single neuron recordings were carried out from postnatal days 15 to 30 and at adulthood. The response of neurons in the primary visual cortex to drifting sinusoidal gratings was recorded in anaesthetized rats. As soon as postnatal day 15, the neurons of rats having experienced a hyperthermic seizure showed significantly lower optimal spatial frequencies (SF), broader directional and temporal bandwidths, as well as higher contrast thresholds than did neurons recorded in normal rats. At adulthood, significantly broader spatial bandwidths and lower optimal temporal frequencies (TF) were obtained from neurons of rats subjected to hyperthermia. These results suggest that febrile seizures during infancy could affect the development of spatio-temporal receptive field properties of neurons in primary visual cortex. Such alterations of a sensory system might contribute to the cognitive deficits associated with early-onset febrile seizures.

Peri-insular hemispherotomy in children: a single institution experience.

The objective of this paper is to evaluate our experience in performing peri-insular hemispherotomy in refractory epileptic children. First, we address the history of hemispheric surgeries for epilepsy and then we compare our results to the medical literature in term of seizure control and complications. Between 1993 and 2007, 14 children who suffered from refractory hemispheric epilepsy underwent a peri-insular hemispherotomy. All children's charts were reviewed in a retrospective manner. Age at onset of epilepsy, imaging studies, cause of refractory epilepsy, electroencephalography findings, type of epileptic seizure, number of antiepileptic drugs (AED), preoperative neuropsychological evaluation and surgical outcome with regard to the children's seizure activity were analyzed. Nine boys and 5 girls were enrolled in this study. The mean age at onset of epilepsy was 16 months (range birth-5 years). All the children presented complex partiel seizures. Seizure frequency varied from 5 to 100 a day. The average delay prior to the hemispherotomy was 83 months (range 12-226 months). Mean age at the time of the surgery was 8.4 years (range 1.7-18 years). We performed 9 peri-insular hemispherotomies on the right side and 5 on the left. There were no reported surgical complications in this series. 10 children are seizure free (72%). Peri-insular hemispherotomy must be considered as a safe and very efficient therapeutic approach for children suffering from hemispheric refractory epilepsy. Peri-insular hemispherotomies are procedures where pathology and surgical technique interact narrowly. Acquired pathologies had better results than developmental ones.

Vagus nerve stimulation in pediatric epileptic syndromes.

Vagal nerve stimulation (VNS) has shown promising results in various cohorts of non-surgical refractory epilepsy in adults and children. However studies report a significant delay between implantation and clinical response. We describe a cohort of 28 children and adolescents prospectively followed, classified by epileptic syndromes and treated with VNS using a 6-week rapid ramping protocol between January 2000 and March 2005. Our cohort showed favorable outcome within 6 months which was sustained at 24 months: 68% (19/28) showing >or=50% reduction in seizure frequency, including 14% (4/28) who became seizure-free. VNS was particularly efficacious in children with cryptogenic generalized and partial epilepsies. Although adverse events occurred in 68% (19/28) of patients, most were transient. In conclusion, rapid ramping is associated with an early and lasting response in most children but with a slightly higher side-effect rate.

Interaction between the flash evoked SSVEPs and the spontaneous EEG activity in children and adults.

OBJECTIVE: To evaluate the interaction between the steady-state visual evoked potentials (SSVEPs) recorded during the intermittent photic stimulation (IPS) and the spontaneous EEG activities both in children and adults. METHODS: EEG was recorded during the rest and under 5, 7.5, 10 and 12.5 Hz IPS in 41 children between 3 and 16 years and 10 adults. We distinguished between the spontaneous resting EEG spectra, SSVEPs (1st harmonic) and undriven (ongoing) EEG spectra recorded during the IPS. RESULTS: We show that IPS influences spontaneous EEG activity by specifically suppressing or desynchronizing individual posterior dominant resting EEG frequencies (DF) in both children and adults. Further, this highly significant and consistent suppressing effect positively correlates with the SSVEPs amplitude. CONCLUSIONS: Our data suggest that the desynchronization of the spontaneous EEG activity under IPS and the SSVEPs are related to each other. SIGNIFICANCE: These relationships could be interesting to study in pathological conditions where the neural synchronization and the responses to IPS have been shown to be affected, such as epilepsy and schizophrenia.

Impact of childhood epilepsy on reading and phonological processing abilities.

Although children with epilepsy tend to exhibit more reading difficulties than their classmates, no systematic studies have investigated the relationship between these difficulties and epilepsy. As functional neuroimaging studies have implicated both temporal and frontal lobes in the phonological aspect of reading [K.R. Pugh, B.A. Shaywitz, S.E. Shaywitz, et al. Brain 1996;119:1221-38], seizure activity originating in either region could interfere with phonological processing, whereas generalized seizures would not disturb this function as much. To explore this hypothesis, we compared the metaphonological skills of school-aged children with either temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), or generalized absence seizures (ABS) with those of healthy controls. While the reading ability of all epileptic children was close to 2 years behind expectations, children with TLE did not differ from the controls on phonological tasks. In contrast, children with FLE exhibited significant deficits, whereas children with ABS showed difficulties restricted to phonemic segmentation. The results suggest that FLE and, to a lesser extent, generalized seizures may interfere with phonological processing, whereas TLE may affect other aspects of reading.

A motor resonance mechanism in children? Evidence from subdural electrodes in a 36-month-old child.

The presence of a neural mechanism matching execution and observation of actions in the adult human brain is well established. In children, however, description of a resonance motor mechanism is still preliminary. In the present study, we recorded electroencephalographic signals from a subdural 64-contact grid electrode in a 36-month-old child with epilepsy. Spectral analysis was performed on sequences where the child drew with her right hand, watched an experimenter drawing with his right hand or was at rest. Contact sites corresponding to sensorimotor areas were discovered where absolute power was decreased during both observation and execution of hand/arm actions. These data suggest the presence of a mirror neuron system early in the developing brain.

Clinical significance of isolated hippocampal volume asymmetry in childhood epilepsy.

This study defines the clinical characteristics and evolution of 16 epileptic children with hippocampal asymmetry (HA) without sclerosis on MRI. The association of a positive family history of epilepsy (11/16), low incidence of febrile seizures (2/16), and benign prognosis (seizure control in monotherapy in 11/16, mean follow-up = 4.3 years, range 1 to 10) suggest a different clinical presentation than patients with mesial temporal sclerosis. Genetic studies of these mostly French Canadian families should help confirm the existence of a distinct syndrome.

The pathological basis of temporal lobe epilepsy in childhood.

OBJECTIVE: To characterize the pathologic findings of temporal lobe epilepsy (TLE) in children undergoing temporal lobectomy for refractory seizures and to correlate these findings with clinical presentation. METHODS: The authors reviewed the charts of all children who underwent anterior temporal lobectomy for refractory TLE from 1979 through 1999. A new neuropathologic analysis was performed blinded to clinical features and outcome. RESULTS: Twenty-two children met inclusion criteria. Mean age at onset of epilepsy was 3 years, 7 months (range 1 month to 10 years). Mean age at surgery was 10 years, 11 months (range 1 to 18 years). All patients had complex partial seizures, 48% with secondary generalization. Most had daily seizures. Auras were reported in 45% of patients. Post-resection follow-up averaged 5 years, 2 months (range 2 to 19 years). Seizure-free status was achieved in 41% of patients, and 14% had residual auras only. The most frequent neuropathologic abnormalities were cortical dysplasia (CD) of the temporal neocortex (14 of 22) and mesial temporal sclerosis (MTS) (12 of the 15 children with available hippocampal tissue). These two findings coexisted in seven children. MTS was associated with extra-hippocampal pathology in 8 of 12 (67%) of the cases. CONCLUSIONS: MTS occurs frequently in association with CD in this population of children. The high incidence of dual pathology could explain the early age of seizure onset and high seizure frequency rate observed. TLE in childhood may constitute a different entity than in adults, from both the clinical and neuropathologic perspectives.

The carbohydrate and caloric content of concomitant medications for children with epilepsy on the ketogenic diet.

BACKGROUND: The ketogenic diet for children with refractory epilepsy requires a strict control of the amount of ingested carbohydrates. This can be altered by medication prescribed for the epileptic syndrome or for intercurrent illnesses. The goal of this paper is to compile the carbohydrate and caloric content of commonly used medications in this population. METHODS: We compiled a list of frequently used medications with the help of Canadian manufacturers and the Compendium of Pharmaceuticals and Specialties. We also tested a worst case scenario calculation based on the weight of the tablet. RESULTS: We list the carbohydrate and caloric content of 790 medications studied. Our worst case scenario gives an over-estimate in all cases, making adjustments based on this calculation in an emergency setting safe. CONCLUSION: We propose this list as a tool for physicians, dietitians, nurses and pharmacists. The list can easily be adjusted, based on local practices and reviewed periodically.

Immature rat convulsions and long-term effects on hippocampal cholinergic neurotransmission.

Generalized tonic-clonic convulsions were induced on 2 consecutive days by pentylenetetrazol (PTZ) in immature rats (postnatal days 10 and 20), and hippocampal slices were prepared at different intervals post-injection. The anticholinesterase eserine provoked interictal-like discharges in the CA3 area of PTZ-injected rats (19/33), but not in controls (0/15), an effect mimicked by carbachol and reversed by atropine. This enhanced response to eserine was recorded in slices from 25-100% of the PTZ-injected rats, the percentage varying with the age at injection and post-injection interval. These results suggest that seizures in immature brain may have long-term consequences in cholinergic neurotransmission, converting a rise in endogenous ACh into an epileptogenic stimulus, which in turn would presumably facilitate the recurrence of seizures.

Stroke in children: the coexistence of multiple risk factors predicts poor outcome.

OBJECTIVE: To characterize the risk factors for stroke in children and their relationship to outcomes. METHODS: We reviewed charts of children with ischemic and hemorrhagic stroke seen at Hopital Sainte-Justine, Montreal between 1991 and 1997. RESULTS: We found 51 ischemic strokes: 46 arterial and 5 sinovenous thromboses. Risk factors were variable and multiple in 12 (24%) of the 51 ischemic strokes. Ischemic stroke recurred in 3 (8%) patients with a single or no identified risk factor and in 5 (42%) of 12 patients with multiple risk factors (p = 0.01). We also found 21 hemorrhagic strokes, 14 (67%) of which were caused by vascular abnormalities. No patient with hemorrhagic stroke had multiple risk factors. Hemorrhagic stroke recurred in two patients (10%). Outcome in all 72 stroke patients was as follows: asymptomatic, 36%; symptomatic epilepsy or persistent neurologic deficit, 45%; and death, 20%. Death occurred more frequently in patients with recurrent stroke (40%) than in those with nonrecurrent stroke (16%). CONCLUSIONS: Multiple risk factors are found in many ischemic strokes and may predict stroke recurrence. Recurrent stroke tends to increase rate of mortality. Because of the high prevalence and importance of multiple risk factors, a complete investigation, including hematologic and metabolic studies and angiography, should be considered in every child with ischemic stroke, even when a cause is known.