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Biomedical subjects

S Shinnar

Publications and source records attributed to S Shinnar.

At least 73 records · Page 4Linked to original sources

In whom does status epilepticus occur: age-related differences in children.

PURPOSE: Status epilepticus (SE) is an uncommon but potentially life-threatening seizure. It is most common in children. Little is known about the differences within the pediatric age group in terms of the type of patient seen with SE. METHODS: We analyzed the records of 394 children aged 1 month to 16 years who were part of two large studies of pediatric SE conducted in Bronx, New York, and Richmond, Virginia. The 394 children had a mean age of 4.4 years and included 349 (89%) with an initial episode of SE. RESULTS: Status epilepticus was most common in younger children with >40% of cases occurring in those younger than 2 years. The distribution of causes was highly age dependent. More than 80% of children younger than 2 years had SE of febrile or acute symptomatic origin, whereas cryptogenic and remote symptomatic causes were most common in older children (p < 0.001). One hundred fifty-eight (40%) of the cases were known to be previously neurologically abnormal, including 35 (21%) of 169 younger than age 2 years and 123 (55%) of 225 older than 2 years (p < 0.001). One hundred seventy-seven (45%) children had a history of seizures including 142 (41%) of the 349 children with a first episode of SE. A history of seizures was present in 34 (20%) of those younger than 2 years and 143 (64%) of those older than 2 years (p < 0.001). The effect of age remained significant even when the analysis was limited to those with SE of cryptogenic or remote symptomatic origin. CONCLUSIONS: There is a strong effect of age on the frequency and etiology of SE, as well as on the type of child who has SE. In young children, SE occurs primarily in children who are neurologically normal and with no history of unprovoked seizures. In older children, SE occurs primarily in those who are known to have prior unprovoked seizures and who are often also neurologically abnormal.

Adolescent↗

Seizure lateralization during EEG monitoring in patients with bilateral foci: the cluster effect.

PURPOSE: To determine whether seizures that occur in clusters are more likely to reflect activity of the same focus than are seizures that are widely separated in time. METHODS: EEG monitoring data from 14 patients with bilateral independent seizure onsets were analyzed. Twelve of the 14 patients had surface recordings only, and two had implanted electrodes. Interseizure intervals (ISIs) for 151 seizure pairs were measured. Seizure onsets were classified as right hemispheric, left hemispheric, or indeterminate. Seizure pairs were classified as concordant for hemisphere of onset, discordant, or indeterminate. The relation between seizure-pair concordance and ISI was examined by using univariate analysis and analysis of variance (ANOVA). RESULTS: Both seizures originated from the same hemisphere in 61 (75%) of 81 seizure pairs with ISIs <8 h, compared with 28 (55%) of 51 seizure pairs with ISIs >8 h (p < 0.015). The cluster effect was not more pronounced for ISIs <2 h. ANOVA demonstrated that the relation between ISI and seizure concordance was not a result of the variability in seizure rates among patients. In three patients, the presence of bilateral foci was not demonstrated until more than five seizures were recorded. CONCLUSIONS: Seizures that occur after an ISI of <8 h are more likely to come from the same side as the previous seizure than are those with longer ISIs. Thus clustered seizures should not be given the same weight as seizures widely separated in time. In addition, more than five seizures may sometimes be needed to adequately assess patients being evaluated for epilepsy surgery.

Analysis of Variance↗

Surface mapping of spike potential fields: experienced EEGers vs. computerized analysis.

An EEG epileptiform spike focus recorded with scalp electrodes is clinically localized by visual estimation of the point of maximal voltage and the distribution of its surrounding voltages. We compared such estimated voltage maps, drawn by experienced electroencephalographers (EEGers), with a computerized spline interpolation technique employed in the commercially available software package FOCUS. Twenty-two spikes were recorded from 15 patients during long-term continuous EEG monitoring. Maps of voltage distribution from the 28 electrodes surrounding the points of maximum change in slope (the spike maximum) were constructed by the EEGer. The same points of maximum spike and voltage distributions at the 29 electrodes were mapped by computerized spline interpolation and a comparison between the two methods was made. The findings indicate that the computerized spline mapping techniques employed in FOCUS construct voltage maps with similar maxima and distributions as the maps created by experienced EEGers. The dynamics of spike activity, including correlations, are better visualized using the computerized technique than by manual interpretation alone. Its use as a technique for spike localization is accurate and adds information of potential clinical value.

Action Potentials↗

The epidemiology of epilepsy. Past, present, and future.

Much has been learned from epidemiologic studies about the frequency, causes, natural history, and prognosis of epilepsy and other seizure disorders. This knowledge has resulted in significant changes in the clinical management of individuals who have seizures and epilepsy. Recent changes in the known causal factors and diagnostic technologic advances, among other factors, will affect the epidemiology and prognosis of epilepsy. Continued epidemiologic monitoring of this common neurologic condition is necessary to ensure an accurate understanding of the current forms of the disorder.

Adolescent↗

Longitudinal examination of the behavioral, language, and social changes in a population of adolescents and young adults with autistic disorder.

This follow-up study evaluates the behavioral, language, and social outcomes in a population of autistic patients initially examined in childhood. We evaluated 102 (63%) of the 163 eligible subjects, including 54 adolescents (12-17 years of age) and 45 adults (> or = 18 years of age). Three patients had died in the interim. Behavior difficulties continued to be a problem in 69% of adolescents and adults. Thirty-five percent of adolescents and 49% of adults engaged in self-injurious behavior, and slightly more than 50% of adolescents and adults exhibited some stereotypic behaviors. Over 90% of both adolescents and adults had persisting social deficits. Language improved with age, although only 35% achieved normal or near-normal fluency. Comprehension also improved, although only 29% of subjects had achieved normal or near-normal comprehension of oral language. At the time of last follow-up, 28% of all patients and 53% of adults were living in residential placement. Only 11% of adults were employed on the open market, all in menial jobs; an additional 16% were employed in sheltered workshops. The social, behavioral, and language deficits identified in early life in autistic children tend to persist into adolescence and young adulthood.

Adolescent↗

Clinical characteristics of children referred to a child development center for evaluation of speech, language, and communication disorders.

Speech, language, and communication disorders are prominent reasons for referrals to a child development center. From 1984 to 1988, 1,090 preschool children were referred to our child development center, which serves the Tel Aviv metropolitan area. Of all referrals, 432 (41%) were primarily due to speech, language, and communication problems. After exclusion of those with IQ < 50 and those with non-language-related disabilities, 323 children remained. The children were classified into different subtypes of developmental language disorders and autistic spectrum disorders. The main developmental language disorder subtypes were combined expressive-receptive (49%) and expressive (44%). Central processing deficits were less common, occurring in 20 (7%) of the children. Parents of children with developmental language disorders had educational levels similar to those of parents of children referred to the child development center for other causes. However, parents of children with infantile autism had higher educational levels than parents of children with developmental language disorder or parents of children referred for other causes (P < .001). Our results reflect the distribution of language and related problems in an unselected population of preschool children referred to a child development center.

Autistic Disorder↗

Complex febrile seizures.

In the context of a prospective cohort study, we examined the associations between individual complex features of both first (n = 428) and recurrent (n = 240) febrile seizures and factors shown to predict outcome in children with febrile seizures. Thirty-five percent of first and 33% of recurrent febrile seizures had one or more complex features (focal onset, duration > or = 10 min, or multiple seizures during the illness episode). There were strong correlations between focality and prolonged duration for both first and recurrent febrile seizures. A low fever at the time of the seizure was marginally associated with prolonged duration. Most factors associated with either recurrent febrile seizures or subsequent unprovoked seizures were not associated with either the initial seizure being complex or the likelihood that a recurrence would be complex. However, the children with recurrent febrile seizures, complex features tended to repeat. This factor was statistically significant and particularly striking for prolonged duration. Genetic or other constitutional factors may explain why the prolonged feature recurs. Eleven (2.5%) children had three or four risk factors for recurrent febrile seizure that was prolonged. This very small group of children may be candidates for abortive therapy to be administered at the onset of a recurrent seizure.

Child↗

Predictors of intractable epilepsy in childhood: a case-control study.

Little is known about what factors predict intractable epilepsy at the time of initial diagnosis. We performed a case-control study to identify early predictors of medically intractable epilepsy in children. Cases were children who had an average of one seizure or more a month over a 2-year period and who, during that time, had failed trials of at least three different antiepileptic drugs (AEDs). Controls were children who had epilepsy, who had been seizure-free for > or = 2 years, and who had never, before becoming seizure-free, met the definition for intractable epilepsy. Strong univariate associations were noted between intractability and several factors: infantile spasms (IS) remote symptomatic epilepsy, a history of status epilepticus (SE) before the diagnosis of epilepsy, neonatal seizures, and microcephaly. Cases were significantly younger than controls at onset (1.8 vs. 5.8 years); this was not due solely to cases with onset during the first year of life but was an association apparent throughout the age range studied. With multiple logistic regression, independent predictors of intractability were IS, odds ratio (OR) = 10.42, p = 0.03; age at onset with a decreasing risk with increasing age, OR = 0.77 per year, p less than 0.0001; remote symptomatic epilepsy, OR = 2.24, p = 0.04; and SE, OR = 3.30, p = 0.04. These findings complement those of recent cohort studies of remission of epilepsy and provide useful leads for future prospective studies of intractable epilepsy.

Adolescent↗

Unprovoked seizures in children with febrile seizures: short-term outcome.

BACKGROUND: Febrile seizures affect 2 to 4% of children, and 2 to 10% develop subsequent unprovoked seizures. Secondary analyses of two large cohorts identified neurodevelopmental abnormalities, complex febrile seizures, and a family history of epilepsy as predictors of unprovoked seizures. We present an analysis of children prospectively followed from their first febrile seizure to reassess these three factors, examine factors of equivocal importance, and assess the importance of some new factors that we identified as predictors of recurrent febrile seizures. METHODS: Children (N = 428) were prospectively identified for a first febrile seizure through pediatric emergency departments of four hospitals. Information was collected from medical records and interviews with parents. Children were followed for 2 years or more. RESULTS: Unprovoked seizures occurred in 26 (6%). Neurodevelopmental abnormalities, complex febrile seizures, and a family history of epilepsy were associated with an increased risk of unprovoked seizures. Recurrent febrile seizures and brief duration of fever before the initial febrile seizure were also risk factors. A family history of febrile seizures, temperature and age at the initial febrile seizure, sex, and race were not associated with unprovoked seizures. CONCLUSIONS: We confirmed the increased risk associated with traditionally accepted predictors of epilepsy following febrile seizures. Also, the risk clearly increased with recurrent febrile seizures. In general, predictors of subsequent unprovoked seizures differ from predictors of recurrent febrile seizures. One notable exception, brief duration of fever before the initial febrile seizure, predicts both types of outcome and may be a marker for an increased susceptibility to seizures.

Body Temperature↗

Association of HLA class II alleles in patients with juvenile myoclonic epilepsy compared with patients with other forms of adolescent-onset generalized epilepsy.

Reports have suggested an association of juvenile myoclonic epilepsy (JME) with an HLA-DR allele. We examined the HLA-DR and DQ frequencies in two populations of epilepsy patients: (1) JME patients and (2) patients with other forms of adolescent-onset, idiopathic generalized epilepsy (IGE). We did DNA-based HLA typing on 24 JME patients and 24 patients with non-JME forms of adolescent-onset IGE, forms that are clinically similar to JME. In typing the HLA region, we paid particular attention to the alleles contributing to the HLA-DR13 type and also to the DQB1 locus alleles that are in linkage disequilibrium with the alleles that comprise the DR13 type. We also examined the HLA-AP locus, which is centromeric to the DR locus. The frequency of DR13 was significantly higher in JME compared with the non-JME patients. Nine JME patients, compared with two non-JME patients, carried that type (chi 2 = 5.78 [p < 0.017, 1 df]). The odds ratio was 6.6. Furthermore, the DQB1 alleles in linkage disequilibrium with the alleles contributing to the DR13 type were also more frequent in JME than in non-JME epilepsy patients. The chi 2 is highly significant (8.1, p < 0.005) with an odds ratio of 13.8. These results confirm that JME is an HLA-associated form of epilepsy. They also show that the JME locus probably lies within the HLA region, most likely between the HLA-DP and HLA-B loci. The association studies also confirm linkage results showing that JME is genetically different from some other IGEs and emphasize that careful diagnosis is critical to genetic studies of the epilepsies.

Adolescent↗

The risk of seizure recurrence after a first unprovoked afebrile seizure in childhood: an extended follow-up.

OBJECTIVE: To assess the long-term recurrence risks after a first unprovoked seizure in childhood. METHODS: In a prospective study, 407 children who presented with a first unprovoked seizure were then followed for a mean of 6.3 years from the time of first seizure. RESULTS: One hundred seventy-one children (42%) experienced subsequent seizures. The cumulative risk of seizure recurrence was 29%, 37%, 42%, and 44% at 1, 2, 5, and 8 years, respectively. The median time to recurrence was 5.7 months, with 53% of recurrences occurring within 6 months, 69% within 1 year, and 88% within 2 years. Only 5 recurrences (3%) occurred after 5 years. On multivariable analysis, risk factors for seizure recurrence included a remote symptomatic etiology, an abnormal electroencephalogram (EEG), a seizure occurring while asleep, a history of prior febrile seizures, and Todd's paresis. In cryptogenic cases, the risk factors were an abnormal EEG and an initial seizure during sleep. In remote symptomatic cases, risk factors were a history of prior febrile seizures and age of onset younger than 3 years. Risk factors for late recurrences (after 2 years) were etiology, an abnormal EEG, and prior febrile seizures in the overall group and an abnormal EEG in the cryptogenic group. These are similar to the risk factors for early recurrence. CONCLUSIONS: The majority of children with a first unprovoked seizure will not have recurrences. Children with cryptogenic first seizures and a normal EEG whose initial seizure occurs while awake have a particularly favorable prognosis, with a 5-year recurrence risk of only 21%. Late recurrences do occur but are uncommon.

Child↗

Unprovoked seizures and developmental disabilities: clinical characteristics of children referred to a child development center.

Few data are available on the risk of seizures in young children with developmental problems. A retrospective evaluation of 1,946 children 0-5 years of age referred to the Tel Aviv Child Development Center (CDC) between 1981 and 1990 was performed. The study was undertaken to determine the cumulative risk of unprovoked seizures in children referred to a CDC and to assess the risk factors associated with seizures in these children. The center serves the Tel Aviv area for a variety of developmental disabilities. Cumulative risk of seizures and risk factors were assessed using Kaplan-Meier methodology. Unprovoked seizures occurred in 58 patients (3%), including 10 with a single seizure and 48 with two or more seizures. Risk factors for seizures included cerebral palsy (CP) (relative risk [RR] = 28.7), neonatal seizures (RR = 15.2), mental retardation (MR) (RR = 7.8), febrile seizures (RR = 7.7), autism (RR = 3.2), and prematurity (RR = 2.7). The cumulative risk of seizures by age 5 years in children with MR, CP, and MR plus CP was 8%, 47%, and 68%, respectively, compared with 1% in those without MR or CP. On multivariate analysis, CP, MR, prior febrile seizures, and prematurity were associated with an increased risk of seizures. The risk of experiencing unprovoked seizures by age 5 in children with developmental disabilities is 3%, which is fourfold greater than that of the general population. Much of this increased risk is limited to selected subgroups with major disabilities. However, if neither MR nor CP is present, the 1% risk of developing unprovoked seizures by age 5 in children with other developmental problems is not substantially different from that expected in the general population.

Cerebral Palsy↗

Withdrawal of antiepileptic drugs.

Recent literature on withdrawing antiepileptic drug therapy in patients who are seizure free on antiepileptic drugs is reviewed. The average recurrence risk across studies is 29% at 2 years. Factors such as age of onset, etiology of seizures, the electroencephalogram and the epileptic syndrome influence outcome. Factors that need to be considered by the clinician include not just the statistical risk of recurrence but also the consequences of a recurrence, which will be a function of age and sex.

Adolescent↗

Protocol for ACTH administration in refractory childhood seizures: educational strategies.

Adrenocorticotropic hormone (ACTH) in gel form is increasingly being used in the treatment of a variety of childhood seizure disorders. The therapy involves intramuscular injections and can be associated with significant morbidity. A teaching/learning plan for parents or caregivers based on Knowles' theory of adult learning was developed and incorporated into the ACTH protocol presented here. Twenty-nine families completed this protocol. Despite a wide range of educational levels and support systems, all caregivers proved capable of administering the medication. Few complications were encountered. In interviews with the caregivers regarding the teaching-learning process, caregivers believed it contributed to their ability to complete the therapeutic program.

Adrenocorticotropic Hormone↗

Effects of MK-801 and phenytoin on flurothyl-induced seizures during development.

We determined the effects of the N-methyl-D-aspartate (NMDA) receptor blocker MK-801 (0.05, 0.1, and 0.5 mg/kg intraperitoneally, i.p.) and phenytoin (PHT, 5, 10, and 20 mg/kg i.p.) on flurothyl-induced clonic and tonic-clonic seizures in 9-, 15-, 30-, and 60-day-old male rats. Both agents had seizure-, age-, and dose-specific effects. The highest dose of MK-801 was anticonvulsant against clonic flurothyl-induced seizures only in 9- and 60-day-old rats, but suppressed tonic-clonic seizures in all ages. The lowest dose of MK-801 (0.05 mg/kg) produced significant anticonvulsant effects only in 15 day old rats. PHT did not have any effect on clonic seizures throughout development. Both doses of PHT (10 and 20 mg/kg) were anticonvulsant against tonic-clonic seizures in adult rats but not in any other age group. The results indicate that NMDA receptors play an important role in tonic-clonic flurothyl-induced seizures throughout development (especially in 15-day-old rats) and that the anticonvulsant effects of PHT may vary at different stages of brain development.

Age Factors↗

Risk factors for a first febrile seizure: a matched case-control study.

We conducted a matched case-control study to identify risk factors for first febrile seizures, with special emphasis on characteristics of the acute illness episode. Cases were identified through hospital emergency departments; controls were identified through outpatient clinics and emergency departments. Sixty-nine children with first febrile seizures and no history of previous unprovoked seizures were matched for age (+/- 6 months), site of routine pediatric care, and date of visit (+/- 2 weeks) with 1 or 2 febrile controls who had no history of previous febrile or unprovoked seizures. Medical records for the index visit were reviewed, and parents were interviewed by telephone. Illness characteristics examined included height of temperature, type of underlying illness, contact with a physician during the illness but before the index visit, and use of acetaminophen or decongestants. Family history of febrile and of unprovoked seizures, sociodemographic characteristics, daycare use, and selected pre- and perinatal variables were also studied. On multivariable analysis, significant independent risk factors were height of temperature, history of febrile seizures in a first- or in a higher degree relative. Gastroenteritis as the underlying illness had a significant inverse (i.e., protective) association with febrile seizures. Maternal smoking during pregnancy was a marginally significant predictor of febrile seizures.

Acetaminophen↗

Age-dependent effects of gamma-aminobutyric acid agents on flurothyl seizures.

Behavioral characteristics of seizures have age-dependent features, which suggests that effective treatment of seizures may be age-specific as well. In experiments that used the flurothyl seizure model, we examined the effects of several drugs that affect GABAergic neurotransmission in rats of various ages. Systemic administration of phenobarbital (PB, a drug that enhances GABAA receptor-mediated inhibition) was anticonvulsant in most age groups. In contrast, gamma-vinyl GABA (VGB, a drug that increases endogenous GABA levels and enhances both GABAA and GABAB receptor transmission) did not have anticonvulsant effects. Baclofen (a GABAB receptor agonist) was proconvulsant in 9-day-old rat pups, and anticonvulsant in 15-30-day-old rats and lost its anticonvulsant activity in 60-day-old rats. CGP 35348 (a GABAB receptor antagonist) was proconvulsant in developing rats but not in 60-day-old rats. A novel GABAB receptor antagonist, CGP 36742, was proconvulsant in 9- and 15-day-old rats but had no effects in 30- and 60-day-old rats. These results indicate that the effects of presumed GABAergic agents are not uniform across the age span. The differences may reflect age-dependent maturational changes of GABA receptor subtypes, differential action of the drugs on pre- and postsynaptic sites and possible non-GABAergic effects.

Age Factors↗