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Biomedical subjects

Shlomo Shinnar

Publications and source records attributed to Shlomo Shinnar.

At least 19 recordsLinked to original sources
PubMed2006

Felbamate: consensus of current clinical experience.

An expert panel convened to evaluate data and review current clinical practices regarding the novel antiepileptic drug (AED) felbamate. Felbamate has demonstrated efficacy against a variety of refractory seizures types, including seizures associated with Lennox-Gastaut syndrome, but postmarketing experience revealed serious idiosyncratic adverse effects that were not observed during clinical trials. Although felbamate is not indicated as first-line antiepileptic therapy, its utility in treating seizures that are refractory to other AEDs is undisputed, as shown by the number of patients who continue to use it. New exposures to felbamate number approximately 3200-4200 patients annually, and it is estimated that over the past 10 years, approximately 35,000 new starts have occurred. Recommendations by the American Academy of Neurology and a review of felbamate literature were evaluated in conjunction with the clinical experience of the expert panel to determine current medical opinion and practice regarding felbamate. The past 10 years of clinical experience have demonstrated that when used in accordance with existing recommendations and close clinical monitoring, felbamate is an effective treatment for some patients with seizures refractory to other AEDs. This review of clinical data and discussion of the current understanding of the risk:benefit of felbamate therapy supports its use as an important therapeutic option for some patients with refractory epilepsy.

Anticonvulsants↗
PubMed2006

Temporal changes in the incidence of epilepsy in Finland: nationwide study.

PURPOSE: To examine possible changes over time in the incidence of epilepsy in different age groups. METHODS: Based on the nationwide full-refundable antiepileptic drug register and population register, incidence of newly diagnosed epilepsy was measured by granted full-refundable antiepileptic drugs for epilepsy. RESULTS: The incidence was throughout all age groups higher in men than in women. The incidence in the total population had significantly declined in 1986-2002, from 71.6/100,000 to 52.9/100,000. The incidence significantly decreased in children (0.77; 0.71-0.84, p<0.0001) and adults (0.83; 0.77-0.89, p<0.0001) but increased in the elderly (1.18; 1.10-1.26, p<0.0001). The increased incidence in the elderly over the time period was primarily seen in women. CONCLUSION: The incidence of epilepsy has significantly declined in both children and adults with a concurrent increase in the incidence among the elderly. Further studies are needed to elucidate the precise cause of these temporal changes.

Adult↗
PubMed2006

Are early myoclonic encephalopathy (EME) and the Ohtahara syndrome (EIEE) independent of each other?

BACKGROUND: Early myoclonic encephalopathy (EME) and the Ohtahara syndrome are currently listed as two separate syndromes in the classification of epilepsies. The most prominent differentiating points are the observations that patients with Ohtahara syndrome experience predominantly tonic seizures; their seizures evolve to infantile spasms and the prognosis is often worse than patients with EME. SUMMARY POINTS: We performed a literature review of published cases. Although syndromes may have distinct courses, the differentiation early on may be impossible as both myoclonus and tonic seizures may coexist. There is also an overlap in the etiologies. Tonic seizures are considered a manifestation of brainstem dysfunction and it is possible that this is more prominent in Ohtahara syndrome. To date, there are 17 autopsy cases (12 presumed to be Ohtahara cases and 5 EME). Evidence of hindbrain pathology was present in all. Tonic seizures or tonic posturing was a feature of all cases. We suggest that the two syndromes may represent a continuum and that the prominence of tonic seizures in the Ohtahara syndrome may be an indication of brainstem dysfunction which may play an important role in the subsequent transition to infantile spasms.

Age of Onset↗
PubMed2006

Complex inheritance and parent-of-origin effect in juvenile myoclonic epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epilepsy (IGE) with complex inheritance. Previous studies have suggested maternal inheritance and female excess in IGEs but have not been specific for JME. We investigated evidence for maternal inheritance, female excess and patterns of familial seizure risk in a well-characterized sample of JME families. METHODS: We ascertained 89 families through a JME proband and 50 families through a non-JME IGE proband. JME families were divided into those with and without evidence of linkage to the EJM1 susceptibility locus on chromosome 6. We analyzed transmission in 43 multigenerational families, calculated the adjusted sex ratio for JME, and looked for evidence of seizure specific risk in 806 family members. RESULTS: We found evidence for preferential maternal transmission in both EJM1-linked and unlinked families (2.7:1), evidence even more marked when potential selection factors were excluded. The adjusted female: male risk ratio was very high in JME (RR=12.5; 95% CI: 1.9-83.7). Absence seizures in JME probands increased the overall risk of seizures in first degree relatives (15.8% vs. 7.0%, P=0.011), as well as first-degree relatives' specific risk of absence seizures (6% vs. 1.6%, P=0.01), but not myoclonic seizures. CONCLUSIONS: We have confirmed the finding of maternal inheritance in JME, which is not restricted to JME families linked to the EJM1 locus. The striking female excess in JME may relate to anatomical and/or endocrine sexual dimorphism in the brain. Evidence for independent inheritance of absence and myoclonic seizures in JME families reinforces a model in which combinations of loci confer susceptibility to the component seizure types of IGE.

Chromosomes, Human, Pair 6↗
PubMed2006

How long does it take for epilepsy to become intractable? A prospective investigation.

OBJECTIVE: To determine prospectively when in the course of epilepsy intractability becomes apparent. METHODS: Data are from a prospective cohort of 613 children followed for a median of 9.7 years. Epilepsy syndromes were grouped: focal, idiopathic, catastrophic, and other. Intractability was defined in two ways: (1) 2 drugs failed, 1 seizure/month, on average, for 18 months (stringent), and (2) failure of 2 drugs. Delayed intractability was defined as 3 or more years after epilepsy diagnosis. RESULTS: Eighty-three children (13.8%) met the stringent and 142 (23.2%) met the two-drug definition. Intractability depended on syndrome (p < 0.0001): 26 (31.3%) children meeting stringent and 39 (27.5%) meeting the 2-drug definition had delayed intractability. Intractability was delayed more often in focal than catastrophic epilepsy (stringent: 46.2 vs 14.3%, p = 0.003; two-drug: 40.3 vs 2.2%, p <or= 0.0001). Early remission periods preceded delayed intractability in 65.4 to 74.3% of cases. After becoming intractable, 20.5% subsequently entered remission and 13.3% were seizure free at last contact. INTERPRETATION: Intractable epilepsy may be delayed, especially in focal epilepsy. It often is preceded by a quiescent period, followed by further remissions. These findings help explain why surgically treatable epilepsies may take 20 years or longer before referral to surgery.

Adolescent↗
PubMed2006

Neurocognitive outcomes in children with chronic kidney disease: Current findings and contemporary endeavors.

Given the rise in chronic kidney disease (CKD) in both children and adults, CKD has recently been targeted as a public health priority. Childhood onset kidney disease is generally a noncurable and progressive condition that leads to kidney failure by early adulthood. Fortunately, improved identification of kidney problems allows for early intervention, which is thought to slow progression toward end-stage renal disease. In addition, medical interventions for pediatric end-stage renal disease have also improved, allowing children to take advantage of lifesaving renal replacement treatments such as dialysis and kidney transplantation. In spite of improvements in identification and treatment, CKD causes both direct and indirect insults to a variety of organ systems. This paper reviews recently published studies pertaining to the neurocognitive and psychosocial impact of CKD on children of various ages and at various stages of kidney failure. Specific attention is focused on summarizing peer reviewed research that describes associations between kidney functioning and cognitive functioning, language acquisition, visual spatial abilities, memory, and executive functioning. In addition, peer reviewed research describing psychosocial outcomes associated with CKD related to academic achievement, social-behavioral functioning, and quality of life are summarized. The authors also identified disease-specific factors that likely mediate neurocognitive outcomes (e.g., anemia, hypertension, cardiovascular) and endorse the importance of continued interdisciplinary research collaborations that will provide a better understanding of the mechanisms responsible for improved neurocognitive functioning after transplantation. The authors conclude this review by describing a multicenter, prospective, longitudinal, National Institutes of Health funded study that is currently examining the developmental outcomes of children with mild to moderate CKD. The authors speculate that the Chronic Kidney Disease in Children Prospective Cohort Study (CKiD) findings will provide additional evidence-based guidance for clinicians and researchers working with children and adolescents with deteriorating kidney function to improve medical and developmental outcomes.

Adolescent↗
PubMed2006

Sturge-Weber syndrome: deep venous occlusion and the radiologic spectrum.

Sturge-Weber syndrome is a neurocutaneous syndrome with a facial port-wine nevus and neurologic features, typically including seizures and hemiparesis. Glaucoma may also occur. MRI features include leptomeningeal angiomatosis, cortical and pial calcifications, and angiomatous change of the choroid plexus. We reviewed a subset of patients with Sturge-Weber syndrome with the rare finding of deep venous occlusion, and present such a case, unusual by comparison to previously reported cases of Sturge-Weber syndrome with deep venous occlusion. Six previously reported cases were reviewed. All cases presented with seizures; five of six had evidence of leptomeningeal angiomatosis; half had cerebral hemiatrophy. This report presents a unique case lacking clinical seizures, but with a port-wine stain and congenital glaucoma. This patient lacked the radiologic findings of leptomeningeal angiomatosis and hemicerebral atrophy, but demonstrated deep venous occlusion with frontal venous collaterals. There is a wide spectrum of findings in Sturge-Weber syndrome. The lack of seizures and angiomatosis in this case are likely "true-true" and related. The case illustrates the unusual finding of deep venous occlusion in Sturge-Weber syndrome occurring without leptomeningeal angiomatosis. Additionally, it demonstrates that although the initial evaluation is normal, patients may later manifest clinical characteristics of Sturge-Weber syndrome.

Cerebral Veins↗
PubMed2006

Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease.

This is a cross-sectional study that compares lifetime prevalence of gastrointestinal (GI) symptoms in children with autistic spectrum disorders (ASDs) and children with typical development and with other developmental disabilities (DDs) and examines the association of GI symptoms with a family history of autoimmune disease. A structured interview was performed in 50 children with ASD and 2 control groups matched for age, sex, and ethnicity-50 with typical development and 50 with other DDs. Seventy-four percent were boys with a mean age of 7.6 years (SD, +/-3.6). A history of GI symptoms was elicited in 70% of children with ASD compared with 28% of children with typical development (p <.001) and 42% of children with DD (p =.03). Abnormal stool pattern was more common in children with ASD (18%) than controls (typical development: 4%, p =.039; DD: 2%, p =.021). Food selectivity was also higher in children with ASD (60%) compared with those with typical development (22%, p =.001) and DD (36%, p =.023). Family history of autoimmune disease was reported in 38% of the ASD group and 34% of controls and was not associated with a differential rate of GI symptoms. In the multivariate analysis, autism (adjusted odds ratio (OR), 3.8; 95% confidence interval (CI), 1.7-11.2) and food selectivity (adjusted OR, 4.1; 95% CI, 1.8-9.1) were associated with GI symptoms. Children with ASD have a higher rate of GI symptoms than children with either typical development or other DDs. In this study, there was no association between a family history of autoimmune disease and GI symptoms in children with ASD.

Adolescent↗
PubMed2006

Reduction of AEDs in postsurgical patients who attain remission.

PURPOSE: Little evidence guides practice regarding the reduction of antiepileptic drugs (AEDs) in individuals who achieve significant periods of remission after resective surgery. METHODS: In a prospective study of 396 individuals who underwent resective surgery for intractable seizures, the impact of reducing AEDs on relapse and predictors of relapse were examined. RESULTS: Of 301 study subjects who attained a 1-year seizure remission after surgery, 129 reduced from two to one or from one to no AEDs after achieving remission, and 162 did not reduce drugs. Ten patients who stopped all AEDs before attaining remission were excluded from analysis. In all, 114 (39%) patients relapsed: 73 (45%) of 162 in the nonreduction group and 41 (32%) of 129 in the reduction group (p = 0.02). Patients who reduced drugs were more likely to have remitted immediately after hospital discharge (p<0.0001). After adjustment for this factor, little or no apparent impact of drug reduction on the rate of relapse was noted [rate ratio (RR), 1.1; 95% CI, 0.72-1.71; p=0.64 for reducing from two to one AED, and RR, 0.85; 95% CI, 0.50-1.45; p=0.56 for reducing from one to no AEDs]. Within the 129 patients who reduced AEDs, only delayed remission after hospital discharge was significantly associated with an increased rate of relapse (RR, 2.26; 95% CI, 1.15- 4.48; p=0.02). Continued auras had a marginally significant association with relapse (RR, 2.06; p=0.07) CONCLUSIONS: Although many relapses in this cohort of postsurgical patients who achieved remission occurred in the context of reducing or completely eliminating AEDs, the risk was no higher than in those who continued AEDs. Randomized studies are needed to test the impact of drug reduction in seizure-free postsurgical patients.

Adult↗
PubMed2005

Respiratory adverse events associated with diazepam rectal gel.

The authors reviewed respiratory adverse events and deaths spontaneously reported to Xcel Pharmaceuticals associated with diazepam rectal gel. Over 2 million doses have been prescribed. The authors identified nine respiratory adverse events and three deaths. The respiratory events associated with prolonged seizures had a good outcome. The deaths occurred in the context of a prolonged seizure and respiratory depression was not the main symptom. When used as recommended, diazepam rectal gel has a low rate of serious morbidity or mortality.

Administration, Rectal↗
PubMed2005

Mortality following a first unprovoked seizure in children: a prospective study.

In a prospective study, 407 children with a first unprovoked seizure were followed for a mean of 14.2 years. To date, nine have died. Death was unrelated to seizures in four subjects who had no further seizures and were on no medications. The remaining five subjects all had multiple seizures and were on medications. Treatment following the first seizure would not have altered mortality in any of the nine cases.

Adolescent↗
PubMed2005

Obtaining a driver's license and seizure relapse in patients with childhood-onset epilepsy.

OBJECTIVE: To examine factors influencing obtaining a driver's license and subsequent prognosis among people with epilepsy vs control subjects. METHODS: Eighty-one patients from a population-based cohort with childhood-onset epilepsy, followed prospectively for 45 years, and 96 general population control subjects were compared with regard to driving licensing, seizure relapses, and accidents. RESULTS: By the end of the follow-up period, all 81 subjects had achieved at least one 2-year seizure-free interval in adulthood and were eligible for a driver's license. Of these, 64 vs 90% of control subjects had obtained a license (p < 0.0001). On multivariable analysis, factors associated with not obtaining a driver's license among subjects were female gender (relative risk [RR] 2.4, 95% CI 1.0 to 5.5, p = 0.02), nonidiopathic etiology (RR 2.0, 95% CI 1.1 to 3.8, p = 0.02), and presence of learning disabilities (RR 2.0, 95% CI 1.2 to 3.2, p = 0.02). Having a driver's license was associated with a higher rate of employment (RR 1.9, 95% CI 1.2 to 3.0, p = 0.0002). Relapses of seizures had occurred in 37% of the 81 patients theoretically eligible for a license but only in 25% of the 52 subjects who actually obtained one (p = 0.003). Shortening the eligibility period from 2 to 1 year would not significantly alter the relapse rate in this population. The accident rate was not increased among patients vs control subjects. CONCLUSIONS: During a long-term follow-up, differences in driving licensing between patients with uncomplicated epilepsy and healthy control subjects persist despite legal eligibility. The lower actual relapse rates among those with epilepsy who obtain a license than in those who are eligible suggest that those at higher risk of relapse are less likely to obtain a license.

Accidents↗
PubMed2005

Rectal diazepam gel in the home management of seizures in children.

This study assessed the utility of rectal diazepam gel in the home management of prolonged or repetitive seizures in children. Thirty-eight children being prescribed rectal diazepam gel by their clinician were prospectively recruited. Seizures, rectal diazepam use, emergency department visits, and quality of life data before and after study entry were recorded. The 38 children included 14 (37%) with complex febrile seizures, and 24 with epilepsy (n = 22) or a single seizure (n = 2). There were 23 (61%) children with prolonged seizures and 15 (39%) with repetitive seizures. During the 6-month follow-up period, 12 children experienced 26 seizures which met the criteria for rectal diazepam administration. Rectal diazepam gel was administered to 8 children on 19 occasions. In 16 (84%) of these episodes, seizures stopped and no emergency department visit was required. Parental stress was decreased between baseline and 6 months in both the overall group and in all the subgroups. Home use of rectal diazepam gel is effective in aborting seizure activity, often avoiding an emergency department visit. Its use reduces morbidity and costs associated with hospital visits and provides parents a treatment option for home management of prolonged or repetitive seizures.

Administration, Rectal↗
PubMed2005

Special education needs of children with newly diagnosed epilepsy.

Children with epilepsy often experience poor social and educational outcomes. This study aimed to determine the timing of services with respect to the onset of seizures. It also aimed to identify the aspects of childhood epilepsy (type of epilepsy, etiology, seizure control, and treatment) that are associated with the use of special education services. As part of a prospective community-based study, 613 children were recruited when first diagnosed with epilepsy. Mean age at first seizure was 5 years 11 months (SD 4, range 1mo to 15y 8mo). Parents were interviewed 5 years after children were first diagnosed with epilepsy (n=542; 276 [51%] males). Children's mean age at time of interview was 11 years 10 months (SD 4y 1mo, range 5y 8mo to 21y 8mo). Etiology was classified as idiopathic (n=181, 33.4%), cryptogenic (n=261, 48.2%), and remote symptomatic (n=100, 18.5%). Service use was reported in 315 (58%) children. Compared with neurologically intact children (i.e. cryptogenic and idiopathic etiology; n=415, 77%), children with a remote symptomatic etiology and/or an epileptic encephalopathy (n=127, 23%) received services more frequently (88% vs 49%, p<0.001). In the former group, services were initiated for 66 (15%) children before their first seizure; according to age at onset, services were initiated before the first seizures in 12/164 (7.3%) if <5 years, 34/171 (19.9%) if 5-9 years, and 20/80 (25%) if >10 years. A large proportion of children with epilepsy, even if neurologically otherwise normal, receive special education services. Initiation of services often precedes onset of seizures even in neurologically intact children. This suggests that behavioral and cognitive abnormalities may predate the onset of epilepsy and are not necessarily the direct consequences of epilepsy.

Adolescent↗
PubMed2005

Seizure clustering: risks and outcomes.

PURPOSE: Patients with epilepsy often experience seizures in clusters. In this preliminary study, we examined the prevalence of self-reported clustering and identified potential risk factors and outcomes associated with reported clustering for further analysis in an ongoing prospective diary study. METHODS: Detailed intake questionnaires were administered. Subjects reporting their typical seizure pattern to be three or more seizures within a 24-h period were classified as clusterers. Magnetic resonance imaging (MRI) and EEG data were obtained, and epilepsy was classified by International League Against Epilepsy (ILAE) criteria. All subjects completed Beck Anxiety and Depression Inventories, and Quality of Life in Epilepsy testing. RESULTS: Overall, 29% of subjects reported typical seizure clustering. Extratemporal lobe epilepsy [p = 0.02; OR, 3.0 (1.1-7.8)] was significantly associated with reported seizure clustering. Remote symptomatic epilepsy was associated with clustering [p = 0.03; OR, 2.3 (1.1-4.3)], particularly in association with a history of head trauma with loss of consciousness before epilepsy onset [p = 0.003; OR, 4.2 (1.6-11.1)], although this analysis was limited. Reported clustering was significantly associated with a history of convulsive status epilepticus (SE) [p = 0.029; OR, 3.0 (1.1-8.3)], other seizure-related hospitalization [p = 0.006; OR, 5.3 (1.5-17.6)], and worse seizure control (p = 0.004). Quality-of-life measures were not significantly associated with reported clustering. CONCLUSIONS: These preliminary results identify extratemporal epilepsy and possibly head trauma as potential risk factors for reported seizure clustering and indicate a significant association between reported clustering and convulsive SE. Additionally, seizure clustering appears to be a marker for more intractable epilepsy. The ongoing diary study will refine the definition of seizure clustering and further evaluate specific predictors of poor and favorable outcomes of clustering.

Adult↗
PubMed2005

Genetic epidemiology of epilepsy or what do we tell families?

Over the past few decades, epidemiologic and molecular research has transformed the field of epilepsy genetics. In this review, we discuss the ways in which accumulating evidence on the genetics of epilepsy and febrile seizures can inform health care practitioners advising patients and families with epilepsy. We will review the epidemiologic data from twin and family studies, and illustrate how it can be used to guide genetic counseling. Although there have been many exciting advances in the last few decades-both molecular and epidemiologic-what we have learned has not appreciably changed what we tell families, and what we tell them can remain reassuring.

Adolescent↗