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Recurrent Seizures (recurrent + seizures)
Selected AbstractsPentylenetetrazol-induced Recurrent Seizures in Rat Pups: Time Course on Spatial Learning and Long-term EffectsEPILEPSIA, Issue 6 2002Li-Tung Huang Summary: ,Purpose: Recurrent seizures in infants are associated with a high incidence of neurocognitive deficits. Animal models have suggested that the immature brain is less vulnerable to seizure-induced injury than is that in adult animals. We studied the effects of recurrent neonatal seizures on cognitive tasks performed when the animals were in adolescence and adulthood. Methods: Seizures were induced by intraperitoneal injection of pentylenetetrazol (PTZ) for 5 consecutive days, starting from postnatal day 10 (P10). At P35 and P60, rats were tested for spatial memory by using the Morris water maze task. In adulthood, motor performance was examined by the Rotarod test, and activity level was assessed by the open field test. Seizure threshold was examined by inhalant flurothyl. To assess presence or absence of spontaneous seizures, rats were video recorded for 4 h/day for 10 consecutive days for the detection of spontaneous seizures. Finally, brains were examined for histologic evidence of injury with cresyl violet stain and Timm staining in the supragranular zone and CA3 pyramidal cell layers of the hippocampus. Results: PTZ-treated rats showed significant spatial deficits in the Morris water maze at both P35 and P60. There were no differences in seizure threshold, motor balance, or activity level during the open field test. Spontaneous seizures were not recorded in any rat. The cresyl violet stain showed no cell loss in either the control or experimental rats. PTZ-treated rats exhibited more Timm staining in the CA3 subfield. However, the control and experimental rats showed similar Timm staining within the supragranular zone. Conclusions: Our findings indicate that recurrent PTZ-induced seizures result in long-term cognitive deficits and morphologic changes in the developing brain. Furthermore, these cognitive deficits could be detected during pubescence. [source] Role of cortical dysplasia in epileptogenesis following prolonged febrile seizureEPILEPSIA, Issue 9 2010Kyung-Il Park Summary Purpose:, Hippocampal sclerosis, characterized by prominent neuronal loss and reactive gliosis, is the most common pathology in human temporal lobe epilepsy (TLE). Although prolonged febrile convulsion (FC) is a risk factor of TLE, it is not clear whether FC provokes hippocampal sclerosis and subsequent TLE. Given that underlying brain lesions, such as cortical dysplasia (CD), in the immature brain predispose patients to FC, CD may link FC and TLE. However, the role of CD in epileptogenesis after FC is also unclear. Here, we investigated whether inborn CD increases the risk of later epilepsy induced by prolonged FC using a rat model. Methods:, Experimental CD was induced by in utero exposure of methylazoxymethanol (MAM). Rat pups from MAM-treated or control rats were then subjected to prolonged FC. We examined morphologic changes in the hippocampi with respect to neuronal loss, reactive gliosis, and synaptogenesis, and evaluated spontaneous recurrent seizures (SRS) by long-term video-EEG (electroencephalography). Results:, The MAM+FC group had a significantly lower hippocampal neuronal density in the CA1 and dentate hilus than other control groups. A robust increase in glial cells and synaptic reorganization was also detected in the MAM+FC groups. Furthermore, later SRS occurred in all rats in the MAM+FC group and in 50% and 25% of the rats in the FC-only and MAM-only group, respectively. The frequency and total duration of SRS was highest in the MAM+FC group. Discussion:, Our results suggest that preexisting CD in the immature brain augments the proepileptogenic effects of prolonged FC, leading to TLE. [source] High seizure frequency prior to antiepileptic treatment is a predictor of pharmacoresistant epilepsy in a rat model of temporal lobe epilepsyEPILEPSIA, Issue 1 2010Wolfgang Löscher Summary Purpose:, Progress in the management of patients with medically intractable epilepsy is impeded because we do not fully understand why pharmacoresistance happens and how it can be predicted. The presence of multiple seizures prior to medical treatment has been suggested as a potential predictor of poor outcome. In the present study, we used an animal model of temporal lobe epilepsy to investigate whether pharmacoresistant rats differ in seizure frequency from pharmacoresponsive animals. Methods:, Epilepsy with spontaneous recurrent seizures (SRS) was induced by status epilepticus. Frequency of SRS was determined by video/EEG (electroencephalography) monitoring in a total of 33 epileptic rats before onset of treatment with phenobarbital (PB). Results:, Thirteen (39%) rats did not respond to treatment with PB. Before treatment with PB, average seizure frequency in PB nonresponders was significantly higher than seizure frequency in responders, which, however, was due to six nonresponders that exhibited > 3 seizures per day. Such high seizure frequency was not observed in responders, demonstrating that high seizure frequency predicts pharmacoresistance in this model, but does not occur in all nonresponders. Discussion:, The data from this study are in line with clinical experience that the frequency of seizures in the early phase of epilepsy is a dominant risk factor that predicts refractoriness. However, resistance to treatment also occurred in rats that did not differ in seizure frequency from responders, indicating that disease severity alone is not sufficient to explain antiepileptic drug (AED) resistance. These data provide further evidence that epilepsy models are useful in the search for predictors and mechanisms of pharmacoresistance. [source] Prevalence of epilepsy and seizures in the Navajo Nation 1998,2002EPILEPSIA, Issue 10 2009Karen Parko Summary Purpose:, To determine the prevalence of epilepsy and seizures in the Navajo. Methods:, We studied 226,496 Navajo residing in the Navajo Reservation who had at least one medical encounter between October 1, 1998 and September 30, 2002. We ascertained and confirmed cases in two phases. First, we identified patients with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes signifying epilepsy or seizures using Indian Health Service (IHS) administrative data. Second, we reviewed medical charts of a geographic subpopulation of identified patients to confirm diagnoses and assess the positive predictive value of the ICD-9-CM codes in identifying patients with active epilepsy. Results:, Two percent of Navajo receiving IHS care were found to have an ICD-9-CM code consistent with epilepsy or seizures. Based on confirmed cases, the crude prevalence for the occurrence of any seizure (including febrile seizures and recurrent seizures that may have been provoked) in the geographic subpopulation was 13.5 per 1,000 and the crude prevalence of active epilepsy was 9.2 per 1,000. Prevalence was higher among males, children under 5 years of age, and older adults. Discussion:, The estimated prevalence of active epilepsy in the Navajo Nation is above the upper limit of the range of reported estimates from other comparable studies of U.S. communities. [source] Predictors of pharmacoresistant epilepsy: Pharmacoresistant rats differ from pharmacoresponsive rats in behavioral and cognitive abnormalities associated with experimentally induced epilepsyEPILEPSIA, Issue 10 2008Alexandra M. Gastens Summary Purpose:, Patients with intractable temporal lobe epilepsy (TLE) exhibit an increased risk of psychiatric comorbidity, including depression, anxiety, psychosis, and learning disorders. Furthermore, a history of psychiatric comorbidity has been suggested as a predictor of lack of response to therapy with antiepileptic drugs (AEDs) in patients with epilepsy. However, clinical studies on predictors of pharmacoresistant epilepsy are affected by several confounding variables, which may complicate conclusions. In the present study, we evaluated whether behavioral alterations in epileptic rats are different in AED nonresponders versus responders. Methods:, For this purpose, we used an animal model of TLE in which AED responders and nonresponders can be selected by prolonged treatment of epileptic rats with phenobarbital (PB). Behavioral and cognitive abnormalities were compared between responders and nonresponders as well as between epileptic rats and nonepileptic controls in a battery of tests. Results:, Fifteen epileptic rats with spontaneous recurrent seizures (SRS) either responding (11 rats) or not responding (4 rats) to PB were used for this study. The nonresponders differed markedly in behavioral and cognitive abnormalities from responders and nonepileptic controls in tests of anxiety (open field, elevated-plus maze test), behavioral hyperexcitability (approach-response, touch-response, pick-up tests), and learning and memory (Morris water maze). Discussion:, Our hypothesis that AED-resistant rats will show more severe behavioral and cognitive changes than AED-responsive rats was confirmed by the present experiments. The data substantiate that rodent models of TLE are useful to delineate predictors of pharmacoresistant epilepsy. [source] One-Year Postoperative Autobiographical Memory Following Unilateral Temporal Lobectomy for Control of Intractable EpilepsyEPILEPSIA, Issue 3 2007Virginie Voltzenlogel Summary:,Purpose: To examine the effects of temporal lobectomy (TL), particularly concerning its lateralization. Methods: Patients completed autobiographical memory tests, preoperatively and 1-year postoperatively. Results: (a) right TL (RTL) patients recalled significantly more memories from the year after surgery than from the year before TL; (b) their pre to postoperative improvement on autobiographical memory scores was positively correlated to improvement of delayed story recall scores; and (c) 1 year after surgery, performance on recent personal memory recall was normalized for RTL patients only. Conclusion: We suggest that, in the absence of recurrent seizures, the relative integrity of the left hemisphere together with residual right hemisphere structures sustains postoperative autobiographical memory consolidation, at least 1 year postoperatively. [source] Cardiac Autonomic Control in Patients with Refractory Epilepsy before and during Vagus Nerve Stimulation Treatment: A One-Year Follow-up StudyEPILEPSIA, Issue 3 2006Eija Ronkainen Summary:,Purpose: To elucidate possible effect of vagus nerve stimulation (VNS) therapy on interictal heart rate (HR) variability in patients with refractory epilepsy before and after 1-year VNS treatment. Methods: A 24-hour electrocardiogram (ECG) was recorded at the baseline and after 12 months of VNS treatment in 14 patients with refractory epilepsy, and once in 28 healthy age- and sex-matched control subjects. Time and frequency domain measures, along with fractal and complexity measures of HR variability, were analyzed from the ECG recordings. Results: The mean value of the RR interval (p = 0.008), standard deviation of N-N intervals (SDNN) (p < 0.001), very-low frequency (VLF) (p < 0.001), low-frequency (LF) (p = 0.001), and high-frequency (HF) (p = 0.002) spectral components of HR variability, and the Poincaré components SD1 (p = 0.005) and SD2 (p < 0.001) of the patients with refractory epilepsy were significantly lower than those of the control subjects before VNS implantation. The nocturnal increase in HR variability usually seen in the normal population was absent in patients with refractory epilepsy. VNS had no significant effects on any of the HR-variability indexes despite a significant reduction in the frequency of seizures. Conclusions: HR variability was reduced, and the nocturnal increase in HR variability was not present in patients with refractory epilepsy. One-year treatment with VNS did not have a marked effect on HR variability, suggesting that impaired cardiovascular autonomic regulation is associated with the epileptic process itself rather than with recurrent seizures. [source] Antiepileptic Drug Withdrawal after Successful Surgery for Intractable Temporal Lobe EpilepsyEPILEPSIA, Issue 2 2005Young Dae Kim Summary:,Purpose: To investigate the prognosis related to antiepileptic drug (AED) discontinuation after successful surgery for intractable temporal lobe epilepsy. Methods: The clinical courses after temporal lobectomies (TLs) were retrospectively analyzed in 88 consecutive patients. All the patients had TLs as the only surgical procedure, and they had been followed up for longer than 3 years. AED discontinuation was attempted if the patient had been seizure free without aura for ,1 year during the follow-up period. Results: Sixty-six (75%) patients achieved complete seizure freedom for ,1 year; 28 patients were seizure free immediately after surgery (immediate success); and 38 patients became seizure free after some period of recurrent seizures (delayed success). AED discontinuation was attempted in 60 (91%) of 66 patients with a successful outcome. In 13 (22%) patients, seizure relapse developed during AED reduction (n = 60), and in seven (12%) patients after discontinuation of AEDs (n = 38). The seizure recurrence rate was not different between the immediate- and delayed-success groups. Among 20 patients with seizure relapse related to AED tapering, nine (45%) of them regained seizure freedom after reinstitution of AED treatment, and AEDs were eventually discontinued in six of them. Seizures that recurred after complete AED discontinuation had a better prognosis than did the seizures that recurred during AED reduction (seizure freedom in 86% vs. 23%). At the final assessment, 54 (61%) patients had been seizure free ,1 year; 37 without AEDs and 17 with AEDs. The successful discontinuation of AEDs was more frequent for patients with a younger age at the time of surgery and for those patients with shorter disease duration. Conclusions: Our results suggest that seizure freedom without aura at ,1 year is a reasonable indication for the attempt at AED discontinuation. The subsequent control of recurrent seizures was excellent, especially if seizures relapsed after the complete discontinuation of AEDs. Younger age at the time of surgery and a shorter disease duration seem to affect successful AED discontinuation for a long-term period. [source] High-frequency Oscillations after Status Epilepticus: Epileptogenesis and Seizure GenesisEPILEPSIA, Issue 9 2004Anatol Bragin Summary:,Purpose: To investigate the temporal relation between high-frequency oscillations (HFOs) in the dentate gyrus and recurrent spontaneous seizures after intrahippocampal kainite-induced status epilepticus. Methods: Recording microelectrodes were implanted bilaterally in different regions of hippocampus and entorhinal cortex. A guide cannula for microinjection of kainic acid (KA) was implanted above the right posterior CA3 area of hippocampus. After recording baseline electrical activity, KA (0.4 ,g/0.2 ,l) was injected. Beginning on the next day, electrographic activity was recorded with video monitoring for seizures every day for 8 h/day for ,30 days. Results: Of the 26 rats studied, 19 revealed the appearance of sharp-wave activity and HFOs in the frequency range of 80 to 500 Hz in the dentate gyrus ipsilateral to the KA injection. In the remaining seven rats, no appreciable activity was noted in this frequency range. In some rats with recurrent seizures, HFOs were in the ripple frequency range (100,200 Hz); in others, HFOs were in the fast ripple frequency range (200,500 Hz), or a mixture of both oscillation frequencies was found. The time of detection of the first HFOs after status epilepticus varied between 1 and 30 days, with a mean of 6.3 ± 2.0 (SEM). Of the 19 rats in which HFO activity appeared, all later developed recurrent spontaneous seizures, whereas none of the rats without HFOs developed seizures. The sooner HFO activity was detected after status epilepticus, the sooner the first spontaneous seizure occurred. A significant inverse relation was found between the time to the first HFO detection and the subsequent rate of spontaneous seizures. Conclusions: A strong correlation was found between a decreased time to detection of HFOs and an increased rate of spontaneous seizures, as well as with a decrease in the duration of the latent period between KA injection and the detection of spontaneous seizures. Two types of HFOs were found after KA injection, one in the frequency range of 100 to 200 Hz, and the other, in the frequency range of 200 to 500 Hz, and both should be considered pathological, suggesting that both are epileptogenic. [source] Is the Cell Death in Mesial Temporal Sclerosis Apoptotic?EPILEPSIA, Issue 6 2003Hilmi Uysal Summary: Purpose: Mesial temporal sclerosis (MTS) is characterized by neuronal loss in the hippocampus. Studies on experimental models and patients with intractable epilepsy suggest that apoptosis may be involved in neuronal death induced by recurrent seizures. Methods: We searched evidence for apoptotic cell death in temporal lobes resected from drug-resistant epilepsy patients with MTS by using the terminal deoxynucleotidyl transferase (TdT) and digoxigenin-11-dUTP (TUNEL) method and immunohistochemistry for Bcl-2, Bax, and caspase-cleaved actin fragment, fractin. The temporal lobe specimens were obtained from 15 patients (six women and nine men; mean age, 29 ± 8 years). Results: Unlike that in normal adult brain, we observed Bcl-2 immunoreactivity in some of the remaining neurons dispersed throughout the hippocampus proper as well as in most of the reactive astroglia. Bax immunopositivity was increased in almost all neurons. Fractin immunostaining, an indicator of caspase activity, was detected in ,10% of these neurons. Des pite increased Bax expression and activation of caspases, we could not find evidence for DNA fragmentation by TUNEL staining. We also could not detect typical apoptotic changes in nuclear morphology by Hoechst-33258 or hematoxylin counterstaining. Conclusions: These data suggest that either apoptosis is not involved in cell loss in MTS, or a very slow rate of cell demise may have precluded detecting TUNEL-positive neurons dying through apoptosis. Increased Bax expression and activation of caspases support the latter possibility. [source] Increased Expression of the Neuronal Glutamate Transporter (EAAT3/EAAC1) in Hippocampal and Neocortical EpilepsyEPILEPSIA, Issue 3 2002Peter B. Crino Summary: ,Purpose: To define the changes in gene and protein expression of the neuronal glutamate transporter (EAAT3/EAAC1) in a rat model of temporal lobe epilepsy as well as in human hippocampal and neocortical epilepsy. Methods: The expression of EAAT3/EAAC1 mRNA was measured by reverse Northern blotting in single dissociated hippocampal dentate granule cells from rats with pilocarpine-induced temporal lobe epilepsy (TLE) and age-matched controls, in dentate granule cells from hippocampal surgical specimens from patients with TLE, and in dysplastic neurons microdissected from human focal cortical dysplasia specimens. Immunolabeling of rat and human hippocampi and cortical dysplasia tissue with EAAT3/EAAC1 antibodies served to corroborate the mRNA expression analysis. Results: The expression of EAAT3/EAAC1 mRNA was increased by nearly threefold in dentate granule cells from rats with spontaneous seizures compared with dentate granule cells from control rats. EAAT3/EAAC1 mRNA levels also were high in human dentate granule cells from patients with TLE and were significantly elevated in dysplastic neurons in cortical dysplasia compared with nondysplastic neurons from postmortem control tissue. No difference in expression of another glutamate transporter, EAAT2/GLT-1, was observed. Immunolabeling demonstrated that EAAT3/EAAC1 protein expression was enhanced in dentate granule cells from both rats and humans with TLE as well as in dysplastic neurons from human cortical dysplasia tissue. Conclusions: Elevations of EAAT3/EAAC1 mRNA and protein levels are present in neurons from hippocampus and neocortex in both rats and humans with epilepsy. Upregulation of EAAT3/EAAC1 in hippocampal and neocortical epilepsy may be an important modulator of extracellular glutamate concentrations and may occur as a response to recurrent seizures in these cell types. [source] N -methyl- d -aspartate, hyperpolarization-activated cation current (Ih) and ,-aminobutyric acid conductances govern the risk of epileptogenesis following febrile seizures in rat hippocampusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2010Mohamed Ouardouz Abstract Febrile seizures are the most common types of seizure in children, and are generally considered to be benign. However, febrile seizures in children with dysgenesis have been associated with the development of temporal lobe epilepsy. We have previously shown in a rat model of dysgenesis (cortical freeze lesion) and hyperthermia-induced seizures that 86% of these animals developed recurrent seizures in adulthood. The cellular changes underlying the increased risk of epileptogenesis in this model are not known. Using whole cell patch-clamp recordings from CA1 hippocampal pyramidal cells, we found a more pronounced increase in excitability in rats with both hyperthermic seizures and dysgenesis than in rats with hyperthermic seizures alone or dysgenesis alone. The change was found to be secondary to an increase in N -methyl- d -aspartate (NMDA) receptor-mediated excitatory postsynaptic currents (EPSCs). Inversely, hyperpolarization-activated cation current was more pronounced in naïve rats with hyperthermic seizures than in rats with dysgenesis and hyperthermic seizures or with dysgenesis alone. The increase in GABAA -mediated inhibition observed was comparable in rats with or without dysgenesis after hyperthermic seizures, whereas no changes were observed in rats with dysgenesis alone. Our work indicates that in this two-hit model, changes in NMDA receptor-mediated EPSCs may facilitate epileptogenesis following febrile seizures. Changes in the hyperpolarization-activated cation currents may represent a protective reaction and act by damping the NMDA receptor-mediated hyperexcitability, rather than converting inhibition into excitation. These findings provide a new hypothesis of cellular changes following hyperthermic seizures in predisposed individuals, and may help in the design of therapeutic strategies to prevent epileptogenesis following prolonged febrile seizures. [source] Rapid and long-term alterations of hippocampal GABAB receptors in a mouse model of temporal lobe epilepsyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2003Andrea Straessle Abstract Alterations of ,-aminobutyric acid (GABA)B receptor expression have been reported in human temporal lobe epilepsy (TLE). Here, changes in regional and cellular expression of the GABAB receptor subunits R1 (GBR1) and R2 (GBR2) were investigated in a mouse model that replicates major functional and histopathological features of TLE. Adult mice received a single, unilateral injection of kainic acid (KA) into the dorsal hippocampus, and GABAB receptor immunoreactivity was analysed between 1 day and 3 months thereafter. In control mice, GBR1 and GBR2 were distributed uniformly across the dendritic layers of CA1,CA3 and dentate gyrus. In addition, some interneurons were labelled selectively for GBR1. At 1 day post-KA, staining for both GBR1 and GBR2 was profoundly reduced in CA1, CA3c and the hilus, and no interneurons were visible anymore. At later stages, the loss of GABAB receptors persisted in CA1 and CA3, whereas staining increased gradually in dentate gyrus granule cells, which become dispersed in this model. Most strikingly, a subpopulation of strongly labelled interneurons reappeared, mainly in the hilus and CA3 starting at 1 week post-KA. In double-staining experiments, these cells were selectively labelled for neuropeptide Y. The number of GBR1-positive interneurons also increased contralaterally in the hilus. The rapid KA-induced loss of GABAB receptors might contribute to epileptogenesis because of a reduction in both presynaptic control of transmitter release and postsynaptic inhibition. In turn, the long-term increase in GABAB receptors in granule cells and specific subtypes of interneurons may represent a compensatory response to recurrent seizures. [source] Clinical Characteristics as Predictors of Recurrent Alcohol-related SeizuresACADEMIC EMERGENCY MEDICINE, Issue 8 2000Niels K. Rathlev MD Abstract. Objective: To determine whether clinical data available in the emergency department can accurately predict a subset of patients at low risk of developing recurrent seizures following one or more initial alcohol-related seizures in the out-of-hospital arena. Methods: This was a retrospective secondary analysis of data obtained from the placebo arms of two prospective, randomized trials of drug treatments for the prevention of recurrent alcohol-related seizures. Subjects with and without one or more recurrent alcohol-related seizures during the study period were compared according to the following characteristics: 1) age, 2) gender, 3) daily ethanol consumption, 4) years of ethanol abuse, 5) previous alcohol-related seizure, 6) previous seizure of other etiology, 7) temperature, 8) heart rate, 9) systolic blood pressure, 10) diastolic blood pressure, 11) respiratory rate, and 12) ethanol level. Data were analyzed with t-tests and chi-square where appropriate. Results: One hundred five placebo-treated patients were analyzed and 31 (30%) developed recurrent alcohol-related seizures. None of the listed characteristics were statistically different between the two groups except for the initial ethanol level. Subjects with an ethanol level higher than 100 mg/dL were less likely (0%) to develop recurrent seizures than patients with a level equal to or below 100 mg/dL (36%) (p < 0.01). Conclusions: An initial ethanol level higher than 100 mg/dL was significantly associated with a low risk for recurrent alcohol-related seizures during the observation period. No other low-risk clinical characteristics could be identified. [source] Isoform- and subcellular fraction-specific differences in hippocampal 14-3-3 levels following experimentally evoked seizures and in human temporal lobe epilepsyJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Clara K. Schindler Abstract 14-3-3 proteins are a family of signaling molecules involved in diverse cellular functions, which can mediate anti-apoptotic effects. Seizure-induced neuronal death may involve programmed (apoptotic) cell death pathways and is associated with a decline in brain 14-3-3 levels. Presently, we investigated the subcellular localization and effects of seizures on isoforms of 14-3-3 in rat hippocampus, and contrasted these to findings in human temporal lobe epilepsy (TLE). All brain isoforms of 14-3-3 were detected in the cytoplasmic compartment of rat hippocampus, while 14-3-3, and -, were also present in mitochondrial and microsome-enriched fractions. Focally evoked seizures in rats significantly reduced 14-3-3, levels within the microsome-enriched compartment at 4 h, with similar responses for 14-3-3,, while cytoplasm-localized 14-3-3,, -, and -, remained unchanged. Analysis of human autopsy control hippocampus revealed similar 14-3-3 isoform expression profiles. In TLE samples, the microsome-enriched fraction also showed differences, but here 14-3-3, and -, levels were higher than controls. TLE sample 14-3-3 isoform abundance within the cytoplasmic fraction was not different to controls. This study defines the subcellular localization of 14-3-3 isoforms in rat and human hippocampus and identifies the microsome-enriched fraction as the main site of altered 14-3-3 levels in response to acute prolonged and chronic recurrent seizures. [source] Drug treatment of neonatal seizures by neonatologists and paediatric neurologistsJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 7 2005Kathryn Browning Carmo Objective:, To survey anti-epileptic drug (AED) treatment of early-onset neonatal seizures by neonatologists and paediatric neurologists. Methods:, A self-administered questionnaire was posted to Australian and New Zealand neonatologists and paediatric neurologists. Participants were given the hypothetical case of a full-term infant with early-onset seizures following perinatal asphyxia and asked to nominate their preferred AED for treatment of three seizure episodes during the first 24 h. Results:, One hundred and seven (57%) of 187 individuals answered the questionnaire: neonatologists responded more often than neurologists (,2 (1,187) = 7.18, P = 0.007). Phenobarbitone was used by 95% of the respondents to treat the first episode of seizures and 75% of them used an appropriate loading dose (20 mg/kg). Phenobarbitone was used by 84 and 40% of the respondents to treat the second- and third-seizure episodes, respectively. Neonatologists used phenobarbitone, phenytoin and a benzodiazepine with equal frequency to treat a third episode of seizures, whereas neurologists rarely used a benzodiazepine. Neonatologists used significantly larger total doses of phenobarbitone than neurologists. Very few respondents used pyridoxine to treat recurrent seizures that were historically linked to perinatal asphyxia and hypoxic,ischaemic encephalopathy. Neonatologists were more likely than neurologists to discontinue AED within a few days of seizure cessation (,2 (1,106) = 11.60, P = 0.0006). Conclusions:, Australian and New Zealand neonatologists and paediatric neurologists generally use phenobarbitone to treat neonatal seizures presumed to be owing to hypoxic,ischaemic encephalopathy, though they do not always use appropriate doses. Neonatologists use phenobarbitone, phenytoin or a benzodiazepine for second and third episodes of seizures, whereas neurologists tend not to use benzodiazepines. Neonatologists use larger total doses of phenobarbitone than neurologists in pursuit of seizure control. Neonatologists discontinue AED earlier than neurologists. [source] Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsyANNALS OF NEUROLOGY, Issue 1 2006Jack M. Parent MD Neurogenesis in the hippocampal dentate gyrus persists throughout life and is increased by seizures. The dentate granule cell (DGC) layer is often abnormal in human and experimental temporal lobe epilepsy, with dispersion of the layer and the appearance of ectopic granule neurons in the hilus. We tested the hypothesis that these abnormalities result from aberrant DGC neurogenesis after seizure-induced injury. Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model. We also examined dentate gyri from epileptic human hippocampal surgical specimens. Prox-1 immunohistochemistry and pulse-chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat. Neuroblast marker expression indicated the delayed appearance of chainlike progenitor cell formations extending into the hilus and molecular layer, suggesting that seizures alter migratory behavior of DGC precursors. Ectopic putative DGCs also were found in the hilus and molecular layer of epileptic human dentate gyrus. These findings indicate that seizure-induced abnormalities of neuroblast migration lead to abnormal integration of newborn DGCs in the epileptic adult hippocampus, and implicate aberrant neurogenesis in the development or progression of recurrent seizures. Ann Neurol 2005 [source] | |||||||||||||