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L Nashef

Publications and source records attributed to L Nashef.

At least 19 recordsLinked to original sources
PubMed2005

Case-control study of SUDEP.

OBJECTIVE: To examine the influence of various factors on the risk of sudden unexpected death in epilepsy (SUDEP). METHODS: The authors investigated 154 cases in which a postmortem examination was performed. Each case had four controls with epilepsy from the community, matched for age and geographic location. Backward stepwise conditional logistic regression analysis was performed and odds ratios for risk and protection were determined. RESULTS: The risk of SUDEP was increased with a history of generalized tonic-clonic seizures in the previous 3 months (odds ratio [OR]: 13.8, 95% CI: 6.6 to 29.1). The presence of supervision at night was found to be protective (OR: 0.4, 95% CI: 0.2 to 0.8) when a supervising individual shared the same bedroom or when special precautions such as a listening device were employed (OR: 0.1, 95% CI: 0.0 to 0.3). CONCLUSION: This work lends support to the view that SUDEP is a seizure-related phenomenon and that control of tonic-clonic seizures is important in its prevention. Nocturnal supervision seems to protect against SUDEP.

Adolescent↗
PubMed2004

Epilepsy in the United Kingdom: seizure frequency and severity, anti-epileptic drug utilization and impact on life in 1652 people with epilepsy.

OBJECTIVES: To describe the clinical characteristics of epilepsy in a representative sample of the UK population, including seizure frequency and severity; overall severity of epilepsy; patterns of anti-epileptic drug (AED) use; and the impact of epilepsy on patients' lives. Secondly, to determine if these characteristics differ according to age. METHOD: A large, geographically comprehensive survey of people with epilepsy by means of a postal questionnaire distributed by general practitioners to 3455 unselected patients receiving AEDs for epilepsy, regardless of age or type of epilepsy and including all regions of the UK. Data were collected on age and gender; age of onset of seizures; seizure frequency and severity; AED use and adverse effect levels; and impact on life of epilepsy. Sub-analyses were performed with stratification by epilepsy severity and age-group. RESULTS: There were 1652 completed replies. The mean age was 44.2 years; there were 47.2% males, 48.5% females (4.4% not recorded). The mean age at first seizure, 25.1 years, and the mean duration of epilepsy, 19.7 years, were comparable with previous studies. In the preceding one year, 51.7% of patients had no seizures; 7.9% one seizure, 17.2% 2-9 seizures and 23.2% 10 or more. Sixty-four percent of patients had epilepsy classified as mild and 32% severe. There was a marked and significant decrement of seizure frequency with increasing age. The most commonly used AEDs were carbamazepine (37.4%), valproate (35.7%), phenytoin (29.4%), phenobarbitone or primidone (14.2%) and lamotrigine (10.3%). Monotherapy was used in 68% of patients. Patients taking multiple AEDs reported significantly higher levels of adverse effects and worse seizure control. The major impacts of epilepsy on life were work and school difficulties, driving prohibition, psychological and social life. The impacts listed varied with the epilepsy severity and age. CONCLUSIONS: Seizures remain uncontrolled in up to half of all people with epilepsy in the UK with significant impact on work, family and social life. Previously, there has been a deficiency of data on the characteristics of epilepsy in older people, although it is recognized that the condition is of increasing epidemiological importance in this age group. We have found clear differences in the clinical characteristics of epilepsy in older people, particularly that seizure frequency appears to decline with increasing age.

Adult↗
PubMed2002

Association of mu-opioid receptor subunit gene and idiopathic generalized epilepsy.

OBJECTIVE: To replicate and extend the previously reported association between the opioid receptor mu subunit gene (OPRM1) and idiopathic absence epilepsy (IAE), using a sample of 230 probands with idiopathic generalized epilepsy (IGE). BACKGROUND: In humans and in animal models, several lines of evidence implicate opioid receptors with seizures. The G118 allele of OPRM1 was associated with IAE (p = 0.019). METHODS: Three single nucleotide polymorphisms (SNP) of OPRM1 were investigated by association studies with IGE using a case/control design, one of which also used a within-family design. RESULTS: Association was found for G118 with IGE (p = 0.00027, odds ratio [OR] = 1.86), replicating the previous association. Within-family tests of linkage and association (haplotype-based haplotype relative risk and transmission disequilibrium test) confirmed this result. Further evidence for involvement of OPRM1 in IGE was provided by an association with G-172T, located in the 5' untranslated region (p = 0.0015, OR = 2.36). Haplotypes of the two SNPs were associated with IGE with a greater level of significance (p = 0.000087) suggesting that both SNPs might be in linkage disequilibrium with a single functional variant. Analysis of the results by subgroups of IGE showed association with all subgroups tested. CONCLUSIONS: These results confirm the previous association and support the hypothesis of a role for OPRM1 in IGE, including absence syndromes. However, the authors found no evidence for a specific association between OPRM1 and idiopathic absence epilepsy. The data suggest that the functional variant predisposing to IGE is located within 60kb of exon 1.

Adult↗
PubMed2002

Information recalled by women taking anti-epileptic drugs for epilepsy: a questionnaire study.

Women with epilepsy have different needs from men, particularly associated with childbearing. Despite clinical guidelines, the care of women with epilepsy remains suboptimal. The aim of this study was to establish whether women with epilepsy recall being given information on topics relating to childbearing. Design of study and methods included a postal questionnaire study of 795 women with epilepsy and of childbearing age. The respondents were identified through both general practices and hospital clinics as part of the Clinical Standards Advisory Group study into Epilepsy Services. Of those women who considered the questions personally relevant, 38-48% recalled receiving information about contraception, pre-pregnancy planning, folic acid and teratogenicity, with lower overall proportions among adolescent women. The proportions that recalled receiving information about vitamin K, safety in child-care and breast-feeding were lower at 12, 24 and 24%, respectively. While it is recognised that information provided may not be recalled, our results suggest that further measures are required to improve the effectiveness of information provision in the UK in relation to women of childbearing age with epilepsy.

Adolescent↗
PubMed2002

Suggestive evidence for association of two potassium channel genes with different idiopathic generalised epilepsy syndromes.

Several potassium channel genes have been implicated in epilepsy. We have investigated three such genes, KCNJ3, KCNJ6 and KCNQ2, by association studies using a broad sample of idiopathic generalised epilepsy (IGE) unselected by syndrome. One of the two single nucleotide polymorphisms (SNPs) examined in one of the inward rectifying potassium channel genes, KCNJ3, was associated with IGE by genotype (P=0.0097), while its association by allele was of borderline significance (P=0.051). Analysis of the different clinical subgroups within the IGE sample showed more significant association with the presence of absence seizures (P=0.0041) and which is still significant after correction for multiple testing. Neither SNP in the other rectifying potassium channel gene, KCNJ6, was associated with IGE or any subgroup. None of the three SNPs in the voltage-gated potassium channel gene, KCNQ2, was associated with IGE. However, one SNP was associated with epilepsy with generalised tonic clonic seizures only (P=0.016), as was an SNP approximately 56 kb distant in the closely linked nicotinic acetylcholine gene CHRNA4 (P=0.014). These two SNPs were not in linkage disequilibrium with each other, suggesting that if they are not true associations they have independently occurred by chance. Neither association remains significant after correcting for multiple testing.

3' Untranslated Regions↗
PubMed2002

Certification of deaths attributable to epilepsy.

OBJECTIVE: To estimate the number of sudden unexpected epilepsy deaths occurring annually in England and Wales in those 16-50 years of age. METHODS: All 1997 death entries mentioning epilepsy as a cause of death in those 16-50 years were examined and classified as sudden unexpected death in epilepsy (SUDEP), other epilepsy related deaths, or non-epilepsy deaths. RESULTS: 612 death entries were obtained with postmortem examination having been performed in 498 cases. Forty four deaths were certified as being attributable to SUDEP and a further 292 deaths were considered to be probable SUDEP cases. CONCLUSION: It is estimated that between 350 and 400 cases of SUDEP occurred in England and Wales in 1997 in those 16-50 years. SUDEP is the commonest category of epilepsy related death and accurate certification of such deaths is vital for the monitoring of trends in mortality.

Adolescent↗
PubMed2001

Sudden withdrawal of carbamazepine increases cardiac sympathetic activity in sleep.

OBJECTIVE: To evaluate the cardiac autonomic effects of abrupt withdrawal of carbamazepine (CBZ) during sleep in patients with epilepsy. BACKGROUND: The pathophysiology of sudden unexpected death in epilepsy (SUDEP) is uncertain, with ictal or peri-ictal cardiorespiratory compromise appearing probable. Risk factors for SUDEP include multiple antiepileptic drugs (AED), poor compliance, and abrupt AED withdrawal. The spectral analysis of the beat-to-beat heart rate variability (HRV) displays two main components: low frequency (LF), representing sympathetic and parasympathetic influence and high frequency (HF), representing parasympathetic influence. The LF/HF ratio is commonly regarded as an indicator of sympathovagal balance. METHOD: Twelve patients with medically intractable seizures underwent abrupt withdrawal of CBZ to facilitate seizure recording during controlled circuit TV-EEG monitoring. Continuous EKG recording was begun 24 hours before CBZ reduction. Spectral analysis of the HRV was performed during selected samples of non-REM sleep before and after CBZ reduction. Analyses were made at least 6 hours after from (complex) partial and 12 hours from generalized seizures. RESULTS: The mean LF/HF ratio before withdrawal of CBZ was 2.15 compared with a ratio of 2.65 on day 4 after withdrawal, an increase of 19% (geometric mean; 95% CI, 2% to 34%; Wilcoxon test, z = 2.36; p = 0.018). The ratio increased in 10 patients compared with a decrease in only one patient. CONCLUSION: Abrupt withdrawal of CBZ leads to enhanced sympathetic activity in sleep as evidenced by increased LF/HF ratios. Increased sympathetic activity in the setting of seizure-induced hypoxia could predispose to SUDEP.

Adolescent↗
PubMed2001

Polymorphism analysis of JRK/JH8, the human homologue of mouse jerky, and description of a rare mutation in a case of CAE evolving to JME.

Disruption of the function of the mouse jerky gene by transgene insertion causes generalized recurrent seizures reminiscent of human idiopathic generalized epilepsy (IGE). A human homologue, JRK/JH8, has been cloned, which maps to 8q24, a chromosomal region associated with several forms of IGE. JRK/JH8 is, therefore, a candidate locus for at least some forms of IGE. We report corrected cDNA sequences and extended open reading frames for the mouse jerky and human JRK/JH8 genes, which add 48 amino acids to the N-terminus of the Jerky protein and which extends the region of homology with the N-terminal DNA-binding domain of the centromere-binding protein, CENP-B. Systematic sequencing of the coding region of the extended JRK/JH8 gene identified single nucleotide polymorphisms that define three haplotypes, which were used for association studies in patients with idiopathic generalized epilepsy. We report one subject with childhood absence epilepsy (CAE) that evolved to juvenile myoclonic epilepsy (JME) that has a unique de novo mutation that results in a non-conservative amino acid change at a potential protein glycosylation site. Familial analysis supports a causal role for this mutation in the disease.

Alleles↗
PubMed2000

Failure to replicate association between the gene for the neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) and IGE.

The gene for the neuronal nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) was identified as a gene underlying a rare idiopathic partial epilepsy syndrome in humans, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In a recent study, one of four silent polymorphisms (594 C/T) in CHRNA4 showed association with the common subtypes of idiopathic generalised epilepsy (IGE). In the present study, three of these polymorphisms were investigated for association in 182 Caucasian patients with IGE, but not categorised by subtype. They were compared with 178 controls in a case/control study. Further analyses were performed using a family-based design. None of the three polymorphisms exhibited any association with IGE. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:814-816, 2000.

Adult↗
PubMed2000

No association found between polymorphisms in genes encoding mGluR7 and mGluR8 and idiopathic generalised epilepsy in a case control study.

The genes of two group III metabotropic glutamate receptors, mGluR7 and 8, are candidate susceptibility genes for epilepsy. The Tyr433Phe polymorphism of mGluR7 and a novel polymorphism in the mGluR8 gene located 29 bp after the termination codon (2756C/T) were investigated in case control association studies performed on DNA from more than 100 patients with idiopathic generalised epilepsy (IGE). No significant association was found with IGE for either polymorphism.

Alleles↗
PubMed2000

Patients' perspectives on services for epilepsy: a survey of patient satisfaction, preferences and information provision in 2394 people with epilepsy.

The objectives of this study were to provide a comprehensive survey of satisfaction with care, care preferences and information provision for patients with epilepsy, and to formulate recommendations for the development of epilepsy services based on the findings. A questionnaire was distributed to 4620 patients who were currently receiving antiepileptic drugs for epilepsy, regardless of aetiology, duration or severity. Two different samples of patients with epilepsy were questioned: the first an unselected sample drawn from primary care, and the second consisting of consecutive patients drawn from hospital clinics. There were 2394 responses to the questionnaire. Satisfaction with primary and hospital care was high, both overall and for specific aspects. However, two major shortcomings were identified. First, few respondents felt that their care was shared between hospital and GP. Secondly, provision of information about epilepsy was perceived to be poor, particularly by the elderly. Younger patients and patients with severe epilepsy had a higher satisfaction with and preference for hospital care, whereas older age groups were more satisfied with and preferred primary care. Patients' main reasons for preferring primary care were that it was more personal and the GP was more familiar with them, and secondary care was preferred because the hospital doctor knew more about epilepsy. In conclusion, we have conducted the largest representative UK survey of patients' perceptions and views of the care available for epilepsy. Although patient satisfaction was high, information provision is poor and the shared care model is not operating effectively. We recommend that an emphasis be placed on methods for improving the interface between primary and secondary care. The setting up of hospital epilepsy centres, as recommended by the recently published Clinical Standards Advisory Group report on epilepsy, would provide a focus for these efforts and for information provision.

Adolescent↗
PubMed2000

NHS services for epilepsy from the patient's perspective: a survey of primary, secondary and tertiary care access throughout the UK.

The aims of this study were to estimate the proportion of patients with epilepsy who made primary care and/or hospital outpatient medical consultations within 1 year; to formulate a model of the explanatory variables that influence whether patients consult or not; and to estimate the frequency of referral to, and waiting time for, hospital outpatient clinics in patients with new-onset seizures. Suggestions are offered for improvement of epilepsy services based on the findings. A questionnaire was distributed to 3455 unselected patients identified at population level from primary care practices in all NHS regions of the UK. There were 1652 respondents with epilepsy of all types, irrespective of aetiology, duration or severity. Fifty-two per cent of the whole sample made at least one medical consultation of any type specifically for epilepsy (42.0% primary care, 30.5% hospital, 20.4% both). Most patients with controlled epilepsy (74.5%) had no consultations. Of patients with severe epilepsy, 27.5% made no primary care consultations, 43.4% no hospital consultations and 14.1% no consultations of either type. Gender did not influence the likelihood of either GP or hospital consultations in patients with either controlled or active epilepsy. Increasing seizure frequency was associated with a greater likelihood of one or more hospital consultations for epilepsy, whereas increasing duration of epilepsy was associated with a decreased likelihood of either type of consultation. Age affected consultation rates: of those patients over the age of 65 years, only 29.9% made a medical consultation for epilepsy, compared to 53.8% of young adults. Patients under the age of 17 years were less likely to have consulted a GP and more likely to have consulted a hospital doctor. Ninety percent of new-onset patients had been referred to a hospital doctor, and the mean wait was 6.5 weeks. In conclusion, many patients with epilepsy, including severe epilepsy, are not receiving specialist input, and a significant proportion are receiving no medical supervision. The elderly are over-represented in this group. Care tends to be polarized between hospital or primary care, falling short of the ideal of shared care. It will be important to address the influences on consultation seeking in epilepsy, particularly for those patients currently under no medical supervision.

Adolescent↗
PubMed2000

Women and epilepsy

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

Sudden unexpected death in epilepsy: a series of witnessed deaths.

OBJECTIVES: Sudden unexpected death in epilepsy (SUDEP) represents a significant category of mortality in the population with chronic epilepsy. A consistent feature is that most of these deaths are unwitnessed. The aim was to identify witnessed deaths, examine the circumstances, and relate these findings to the proposed mechanisms for SUDEP. METHODS: During the course of case ascertainment for a control study on SUDEP, witnessed deaths were identified and the circumstances examined in detail. Cases were notified by coroners, neurologists, and bereaved families. The findings were related to the proposed mechanisms for SUDEP which include central and obstructive apnoea and cardiac arrhythmia. RESULTS: One hundred and thirty five SUDEP cases have been identified to date, of which 15 were witnessed deaths. Twelve deaths were associated with convulsive seizures, one collapse occurred 5 minutes after a generalised seizure, another collapse occurred after an aura and one patient died while in a probable post ictal state. Witnesses reported that 12 of the 15 cases experienced respiratory difficulty. CONCLUSIONS: Most sudden epilepsy deaths are unwitnessed. Where witnessed most occur in association with a seizure and respiratory compromise is a prominent feature. Positioning or stimulation of respiration may be important in the prevention of these deaths.

Adolescent↗
PubMed1999

A study of mortality after temporal lobe epilepsy surgery.

OBJECTIVE: To determine early and late mortality in a cohort of 305 consecutive patients who had temporal lobe epilepsy (TLE) surgery over a 20-year period. METHODS: Survival status, cause of death, and postoperative clinical details of those who died were ascertained in a cohort of 305 patients who had TLE surgery. Mortality was related to postoperative seizure status, operative pathology, and side of resection. RESULTS: The survival status of 299 patients was established. Twenty deaths occurred. Mortality was 1 per 136 person-years, with a standardized mortality ratio (SMR) of 4.5 (95% confidence interval [CI], 3.2 to 6.6). Six deaths were sudden and unexpected (SUDEP). The SUDEP rate was 1 per 455 person-years. The overall death and SUDEP rates were lower than those reported for similar patient populations with chronic epilepsy. Mortality in patients who had right-sided resections for mesial temporal sclerosis (MTS) remained considerably elevated with a mortality rate of 1 per 54 person-years, an SMR of 32.0 (95% CI, 24.7 to 40.5), and a SUDEP rate of 1 per 134 person-years. These patients had significantly lower seizure remission rates than left-sided patients, but the excess mortality was not simply explained by those patients whose partial seizures were uninfluenced by surgery. Patients who died had more severe or convulsive seizures despite an overall reduction in seizure frequency. CONCLUSIONS: The present findings confirm previous reports that TLE surgery lowers but does not normalize the overall mortality associated with chronic epilepsy. In patients with right-sided MTS, however, the postoperative mortality has remained similar to other groups with medically intractable seizures.

Adolescent↗