Biomedical subjects

S L Moshe

Publications and source records attributed to S L Moshe.

At least 19 recordsLinked to original sources

PubMed2005

[Neurodevelopmental disorders and epilepsy].

INTRODUCTION AND DEVELOPMENT: Neurodevelopmental disorders and the epilepsies share common etiologies and pathologies. The severity of impairment and the variety of symptoms associated with neurodevelopmental disorders or with particular epilepsy syndromes reflect focal or global, structural or functional dysfunction of neuronal networks. The complex relationship between neurodevelopmental disorders and epilepsy is secondary to common factors that include genetics, cognition, motor and language function. The epileptic encephalopathies are associated with regression or slowing of cognitive, language or behavior and the accepted working hypothesis is that this is a direct consequence of the seizures or of the interictal epileptiform activity, as opposed to the associated medical condition. The evidence that recurrent seizures or abnormal electrical activity can cause specific cognitive, language or behavioral abnormalities even in accepted epileptic encephalopathies is still controversial. Data from animal studies and the clinical experience from epileptic encephalopathies of early life imply that there are developmental time windows crucial to the type of epilepsy syndrome and to cognitive and behavioral outcome. CONCLUSION: The management of children in whom a neurodevelopmental disorder coexists with epilepsy is a difficult problem that requires a multidisciplinary approach that addresses both the epilepsy and the specific cognitive or behavioral problem and is tailored to the needs of the individual child.

Epilepsy↗

PubMed2001

Neuroimaging abnormalities in children with an apparent first unprovoked seizure.

OBJECTIVE: To determine the incidence and type of neuroimaging abnormalities in children presenting with a first seizure. METHODS: In a prospective observational study, 411 children with a first afebrile seizure were seen between 1983 and 1992. Imaging studies were performed in 218 (53%). For this analysis we examined the most sensitive neuroimaging study performed which included 159 computed tomography scans and 59 magnetic resonance imagings (MRI). RESULTS: Four children were found to have lesions requiring intervention (brain tumor in two, neurocysticercosis in two). The remaining 407 were enrolled in a follow-up study of children with a first unprovoked seizure. After a mean follow-up of >10 years, none have developed clinical evidence of a tumor. In these 411 children, 45 (21%) of 218 imaging studies were abnormal. The most common abnormalities were focal encephalomalacia (n=16) and cerebral dysgenesis (n=11). Although children with partial seizures were more likely to be imaged (64%) than children with generalized seizures (43%) (P<0.001), the fraction of abnormal imaging studies was similar in both groups. Six children with a normal neurological examination who were initially classified as cryptogenic were subsequently found to have errors of cerebral migration on MRI. The incidence of lesions requiring acute intervention in children presenting with a first seizure is low. A significant proportion will have neuroimaging abnormalities particularly on MRI. CONCLUSIONS: Neuroimaging should be considered in any child with a first seizure who does not have an idiopathic form of epilepsy.

Adolescent↗

PubMed2001

Short-term outcomes of children with febrile status epilepticus.

Febrile status epilepticus (SE) represents the extreme end of the complex febrile seizure spectrum. If there are significant sequelae to febrile seizures, they should be more common in this group. We have prospectively identified 180 children aged 1 month to 10 years who presented with febrile SE over a 10-year period in Bronx, New York, and Richmond, Virginia. They were compared with 244 children who presented with their first febrile seizure (not SE) in a prospective study done in the Bronx. The mean age of the children with febrile SE was 1.92 years, and of the comparison group, 1.85 years. Duration of SE was 30-59 min in 103 (58%), 60-119 min in 43 (24%), and > or =120 min in 34 (18%). Focal features were present in 64 (35%) of cases. There were no deaths and no cases of new cognitive or motor handicap. Children with febrile SE were more likely to be neurologically abnormal (20% vs. 5%; p < 0.001), to have a history of neonatal seizures (3% vs. 0; p = 0.006) and a family history of epilepsy (11% vs. 5%; p = 0.05) and less likely to have a family history of febrile seizures (15% vs. 27%; p = 0.01) than were children in the comparison group. The short-term morbidity and mortality of febrile SE are low. There are differences in the types of children who have febrile SE compared with those who experience briefer febrile seizures. Long-term follow-up of this cohort may provide insight into the relationship of prolonged febrile seizures and subsequent mesial temporal sclerosis.

Age Distribution↗

PubMed2001

Reasons for failure of the ketogenic diet.

This study examined reasons why patients discontinue the ketogenic diet. A total of 46 children placed on the ketogenic diet between November 1994 and August 1996 were followed prospectively. Reasons for discontinuing the diet prior to 6 months were analyzed. Nineteen (41%) children discontinued the diet for either medical or nonmedical reasons. Nonmedical reasons were caregiver issues and patients' unwillingness to follow the diet. Noncompliance was more common in older children. The ketogenic diet, while effective, is a very stringent diet. Nonmedical reasons for discontinuation are as common as the traditional medical reasons of lack of efficacy or complications.

Adolescent↗

PubMed2001

Genome scan of idiopathic generalized epilepsy: evidence for major susceptibility gene and modifying genes influencing the seizure type.

Idiopathic generalized epilepsy (IGE) is a common, complex disease with an almost exclusively genetic etiology but with variable phenotypes. Clinically, IGE can be divided into different syndromes. Varying lines of evidence point to the involvement of several interacting genes in the etiology of IGE. We performed a genome scan in 91 families ascertained through a proband with adolescent-onset IGE. The IGEs included juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic clonic seizures (EGTCS). Our linkage results support an oligogenic model for IGE, with strong evidence for a locus common to most IGEs on chromosome 18 (lod score 4.4/5.2 multipoint/two-point) and other loci that may influence specific seizure phenotypes for different IGEs: a previously identified locus on chromosome 6 for JME (lod score 2.5/4.2), a locus on chromosome 8 influencing non-JME forms of IGE (lod score 3.8/2.5), and, more tentatively, two newly discovered loci for absence seizures on chromosome 5 (lod scores 3.8/2.8 and 3.4/1.9). Our data also suggest that the genetic classification of different forms of IGE is likely to cut across the clinical classification of these subforms of IGE. We hypothesize that interactions of different combinations of these loci produce the related heterogeneous phenotypes seen in IGE families.

Adolescent↗

PubMed2001

How long do new-onset seizures in children last?

Although there are data on the duration of seizures in patients with refractory epilepsy, little is known about the duration of seizures in nonrefractory epilepsy populations. In a prospective study, seizure duration was determined in 407 children with a first unprovoked seizure using a structured interview and review of medical and ambulance records. Analysis focused on the distribution of seizure duration and on the conditional probability that a seizure would stop once it had already lasted for a specified time. Seizures lasted > or = 5 minutes in 50% of cases, > or = 10 minutes in 29%, > or = 20 minutes in 16%, and > or = 30 minutes in 12%. Seizure duration data were best fit as the sum of two exponential distributions, one with a mean of 3.6 minutes accounting for 76% of cases and the other with a mean of 31 minutes accounting for 24% of cases. The longer a seizure lasted, the less likely it was to stop within the next few minutes. In the 182 children with 2 or more seizures, the durations of the first and second seizures were highly correlated (r = 0.395, p < 0.0001). We conclude that the distribution of seizure duration in children with a first unprovoked seizure differs markedly from that observed in patients with refractory epilepsy. A subgroup of patients are predisposed to prolonged seizures. The data suggest that, once a seizure lasts for more than 5-10 minutes, it is unlikely to stop spontaneously within the next few minutes, and intervention is therefore indicated. These findings also support the continued use of the current definition of status epilepticus as a seizure lasting for 30 minutes or longer for epidemiologic studies.

Adolescent↗

PubMed2000

No evidence for a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q.

Juvenile myoclonic epilepsy (JME) is a distinct epileptic syndrome with a complex mode of inheritance. Several studies found evidence for a locus involved in JME on chromosome 6 near the HLA region. Recently, Elmslie et al. [1997] reported evidence of linkage in JME to chromosome 15q14 assuming a recessive mode of inheritance with 50% penetrance and 65% linked families. The area on chromosome 15q14 encompasses the location of the gene for the alpha-7 subunit of the nicotinic acetylcholine receptor. This could fit the hypothesis that there are two interacting loci, one on chromosome 6 and on chromosome 15 or that there is genetic heterogeneity in JME. In an independent dataset of JME families, we tested for linkage to chromosome 15 but found little evidence for linkage. Moreover, families with more than one family member affected with JME provide a lodscore of 3.4 for the HLA-DR/DQ haplotype on chromosome 6. The lodscore for these same families on chromosome 15q14 is <-2 assuming homogeneity and the maximum lodscore is 0.2 assuming alpha =.25. Only one of these families has a negative lodscore on chromosome 6 and a positive lodscore of 0.5 on chromosome 15q14. Our results indicate that this possible gene on chromosome 15 plays at most a minor role in our JME families. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:49-52, 2000.

Chromosome Mapping↗

PubMed2000

Reproducibility and complications in gene searches: linkage on chromosome 6, heterogeneity, association, and maternal inheritance in juvenile myoclonic epilepsy.

Evidence for genetic influences in epilepsy is strong, but reports identifying specific chromosomal origins of those influences conflict. One early study reported that human leukocyte antigen (HLA) markers were genetically linked to juvenile myoclonic epilepsy (JME); this was confirmed in a later study. Other reports did not find linkage to HLA markers. One found evidence of linkage to markers on chromosome 15, another to markers on chromosome 6, centromeric to HLA. We identified families through a patient with JME and genotyped markers throughout chromosome 6. Linkage analysis assuming equal male-female recombination probabilities showed evidence for linkage (LOD score 2.5), but at a high recombination fraction (theta), suggesting heterogeneity. When linkage analysis was redone to allow independent male-female thetas, the LOD score was significantly higher (4.2) at a male-female theta of.5,.01. Although the overall pattern of LOD scores with respect to male-female theta could not be explained solely by heterogeneity, the presence of heterogeneity and predominantly maternal inheritance of JME might explain it. By analyzing loci between HLA-DP and HLA-DR and stratifying the families on the basis of evidence for or against linkage, we were able to show evidence of heterogeneity within JME and to propose a marker associated with the linked form. These data also suggest that JME may be predominantly maternally inherited and that the HLA-linked form is more likely to occur in families of European origin.

Alleles↗

PubMed2000

Predictors of multiple seizures in a cohort of children prospectively followed from the time of their first unprovoked seizure.

The objective of this study was to assess the risk of multiple recurrences after an initial seizure recurrence in childhood. In a prospective study, 407 children were followed for a mean of 9.6 years from the time of their first unprovoked seizure. Data regarding each seizure recurrence were obtained and analyzed using statistical methods for survival analysis. The cumulative risk of a second seizure was 29%, 37%, 43%, and 46% at 1, 2, 5, and 10 years, respectively. Of the 182 children who experienced a second seizure, 131 (72%) experienced a third seizure, 105 (58%) have had 4 or more seizures, and 52 (29%) have experienced 10 or more seizures. The cumulative risk of a third seizure was 57%, 63%, and 71% at 1, 2, and 5 years, respectively, after the second seizure. After a third seizure, the cumulative risk of another seizure was 69%, 72%, and 81% at 1, 2, and 5 years, respectively. After a second seizure, factors associated with an increased risk of additional recurrences included a remote symptomatic etiology (rate ratio = 1.7) and the occurrence of a second seizure within 6 months of the first seizure (rate ratio = 1.7). After a second seizure, the risk of subsequent seizures was greater than 50% even in the lowest risk group. With the exception of etiology, factors associated with an increased risk of multiple recurrences after the initial seizure were different than those associated with multiple recurrences after a second seizure. Factors associated with multiple recurrent seizures may be different than those associated with an initial recurrence. As most patients who experience a second seizure experience further seizures, these data suggest that two seizures are a sufficient epidemiological criterion for the definition of epilepsy.

Adolescent↗

PubMed1999

Evidence for linkage of adolescent-onset idiopathic generalized epilepsies to chromosome 8-and genetic heterogeneity.

Several loci and candidate genes for epilepsies or epileptic syndromes map or have been suggested to map to chromosome 8. We investigated families with adolescent-onset idiopathic generalized epilepsy (IGE), for linkage to markers spanning chromosome 8. The IGEs that we studied included juvenile myoclonic epilepsy (JME), epilepsy with only generalized tonic-clonic seizures occurring either randomly during the day (random grand mal) or on awakening (awakening grand mal), and juvenile absence epilepsy (JAE). We looked for a gene common to all these IGEs, but we also investigated linkage to specific subforms of IGE. We found evidence for linkage to chromosome 8 in adolescent-onset IGE families in which JME was not present. The maximum multipoint LOD score was 3.24 when family members with IGE or generalized spike-and-waves (SW) were considered affected. The LOD score remained very similar (3.18) when clinically normal family members with SW were not considered to be affected. Families with either pure grand mal epilepsy or absence epilepsy contributed equally to the positive LOD score. The area where the LOD score reaches the maximum encompasses the location of the gene for the beta3-subunit of the nicotinic acetylcholine receptor (CHRNB3), thus making this gene a possible candidate for these specific forms of adolescent-onset IGE. The data excluded linkage of JME to this region. These results indicate genetic heterogeneity within IGE and provide no evidence, on chromosome 8, for a gene common to all IGEs.

Adolescent↗

PubMed1998

Issues related to caring for infants to adults on an integrated epilepsy unit.

We integrated the care of patients of all ages (ranging thus far from 4 weeks to 73 years) in our dedicated 8-bed Epilepsy Unit. Administrative issues pertaining to admission and discharge criteria, unit policies and procedures and an interdisciplinary quality assurance plan were examined in relation to the impact of combining both pediatric and adult patients. Clinical considerations included the diversified abilities needed to care for pediatric and adult patients both in relation to the technical skills as well as psychosocial skills required. The advantages of integrating patients of all ages on one unit include having a staff highly trained in assessment and intervention skills for a particular disorder. The psychosocial issues that arise in these patients, regardless of age, tend to encompass the entire family; therefore a holistic approach is appropriate for both children and adults. An autonomous nursing practice was established with the development of critical pathways and patient care protocols. Our experience suggests that integrated specialized units can enhance the care of patients with intractable seizures.

Adolescent↗

PubMed1996

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↗

PubMed1995

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↗

PubMed1994

Chronic neonatal phencyclidine treatment produces age-related changes in pentylenetetrazol-induced seizures.

Although excitatory amino acids are known to play a critical role in the plasticity of developing brain, the behavioral effects of blocking the N-methyl-D-aspartate (NMDA) receptor-gated ion channel during development are not clear. Here we report the effects of chronic postnatal administration of 1-phenylcyclohexylpiperidine (phencyclidine or PCP), a NMDA channel blocker, on seizure susceptibility. To study the short-term effects of chronic PCP administration on pentylenetetrazol (PTZ)-induced seizures, rats were treated with PCP (5 mg/kg, i.p.) for 11 days from postnatal days 5-15, 24-34 or 44-54 and tested in the PTZ-induced seizure paradigm on postnatal days 21, 40 and 60, respectively. Administration of PCP in 5-15-day-old rats resulted in increased seizure susceptibility at day 21, while administration of PCP in postweanling rats (days 24-34) markedly attenuated their susceptibility to seizures at day 40. PCP injection had little effect on the seizure susceptibility of older rats. To study the long-term effects of postnatal PCP treatment, rats were injected with PCP (5 mg/kg from postnatal day 5-15, i.p.) and were tested for PTZ-induced seizures on postnatal days 40 and 60; each rat was tested only once. When tested for PTZ-induced seizure on day 40, PCP-treated rats did not differ from saline-treated controls. When tested on day 60, PCP-treated rats had a lower incidence of seizures and in the rats that did have seizures their latencies were significantly prolonged compared to controls. Together, our data suggest that chronic PCP administration alters PTZ-induced seizure susceptibility in an age-dependent manner and chronic PCP administration in postnatal rats produces long-term changes that persist into adulthood.

Aging↗

PubMed1992

Recurrent status epilepticus in children.

Status epilepticus is an uncommon but life-threatening seizure. Little is known about the risk of recurrent status epilepticus in patients who present with an initial episode. To determine the risk of recurrent status epilepticus in children, we prospectively followed 95 children, identified at the time of their first episode of status epilepticus, for a mean of 29.0 months (range, 4-60 months). The patients' ages ranged from 1 month to 18 years (mean, 4.6 years). The cause of the status epilepticus was classified as idiopathic (n = 24), remote symptomatic (n = 18), febrile (n = 29), acute symptomatic (n = 18), or progressive neurological disorder (n = 6). Sixteen children (17%) had at least 2 episodes of status epilepticus. The risk of recurrent status was 4% (n = 1) in the idiopathic group, 44% (n = 8) in the remote symptomatic group, 3% (n = 1) in the febrile group, 11% (n = 2) in the acute symptomatic group, and 67% (n = 4) in those with progressive neurological disease. Recurrent status epilepticus occurred primarily in neurologically abnormal children. While neurologically abnormal children accounted for 34% (n = 32) of all children with status epilepticus, they comprised 88% (n = 14) of the children with recurrent status epilepticus (p less than 0.001) and all 5 of the children with multiple (greater than or equal to 3) episodes of status (p less than 0.001). Fifteen of 16 children with recurrent status epilepticus were being treated with antiepileptic drugs at the time of recurrence. The morbidity and mortality of status epilepticus were low.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticonvulsants↗

PubMed1987

The coexistence of myasthenia gravis and myotonic dystrophy in one family.

We are reporting the unique coexistence of two distinct neuromuscular diseases, myotonic dystrophy and the juvenile form of myasthenia gravis, occurring in one family. A 16-month-old previously healthy female presented with a two month history of bilateral varying drooping of both eyelids and bilateral external ophthalmoparesis. The acetylcholine receptor antibodies were elevated, and there was a dramatic response to edrophonium confirming the clinical impression of myasthenia gravis. Spontaneous remission of the ptosis was noted after six months with no specific treatment. Many other family members were examined; none of them had clinical or laboratory evidence of myasthenia gravis. The clinical examination of the mother and the maternal grandmother, neither of whom had any complaints, resulted in a definite diagnosis of myotonic dystrophy. The proband's father and a 3-year-old sister were examined and found to be normal. We studied the HLA antigens of all of the available family members; none were found to have the HLA antigens most commonly associated with myasthenia gravis. Secretor gene studies were not helpful in providing additional genetic identification. The question generated by the coexistence of these two uncommon disorders in one family is if there is a genetic or other relationship between them or if this was merely a coincidental occurrence. At this point in time the question remains unanswered and must await demonstration of additional similar circumstances.

Female↗

PubMed1986

Age-related substantia nigra-mediated seizure facilitation.

We investigated the role of the GABAergic system of the substantia nigra in seizures of rat pups. Rat pups had bilateral cannulae implanted chronically either in the substantia nigra or 1.5 mm dorsal to it. At age 16 to 17 days, seizures were induced in the cannulated rats and naive (intact) controls by exposure to flurothyl following pretreatment with the GABA agonist, muscimol, or vehicle. Naive rats were the most resistant to flurothyl seizures. Bilateral nigral infusions of muscimol markedly facilitated the development of flurothyl seizures in a dose-response manner and differed significantly from the vehicle controls or rats infused with muscimol dorsally to the substantia nigra. In contrast, bilateral nigral muscimol infusions protected adult rats against the development of flurothyl seizures. Our data indicate that the effects of nigral GABA agonist infusions on seizures are age-dependent; the altered responsivity of the GABAergic nigral system in immature rats may be responsible in part for the increased seizure susceptibility of the developing central nervous system.

Animals↗

PubMed1986

Computed tomographic demonstration of cerebral edema in a child with galactosemia.

An eight-day-old male infant with galactosemia presented with signs of increased intracranial pressure and no evidence of intracranial infection or hemorrhage. Computed tomographic scans demonstrated the presence of diffuse cerebral edema. With treatment, the edema gradually resolved, although it persisted longer within the white matter and was associated with transient bilateral pyramidal tract signs.

Brain Edema↗