Prenatal diagnosis of major malformations: quality control of routine ultrasound examinations based on a five-year study of 20,248 newborn fetuses and infants

Event-related potentials (ERPs) were recorded during a continuous recognition memory paradigm in patients with left-sided (LTLE; n = 8) or right-sided temporal lobe epilepsy (RTLE; n = 6), and in healthy control subjects (n = 24). Control subjects and both patient groups exhibited consistent OLD/NEW ERP-differences from 200-600 ms after stimulus onset. ERPs did not differ significantly between LTLE and RTLE patients, with respect to OLD/NEW distinction or the type of presented material (verbal vs. non-verbal). However, ERP topography showed significant differences between LTLE and RTLE patients: in lateral fronto-temporal recordings, patients showed larger negativities contralateral to the seizure focus, whereas we found larger negativities ipsilateral to the seizure focus in parietal recordings. Differences between the groups were significant from 300 to 600 ms post-stimulus. As a consequence, the amplitude gradient from fronto-temporal to parietal recordings was higher on the right side in LTLE patients and on the left side in RTLE patients. Again, differences between LTLE and RTLE patients were highly significant. We assume that ERPs reflect disturbances of a cortico-cortical network dependent on the side of the seizure focus in temporal lobe epilepsy. Furthermore, scalp-recorded ERPs might be a useful tool in the prediction of the side of the seizure focus in patients with temporal lobe epilepsy.     

Benefits of a clinical pharmacokinetic service in optimising phenytoin use in the western Cape

OBJECTIVES: To study the benefits of a clinical pharmacokinetic service in optimising phenytoin use in the Western Cape. DESIGN: Assessment of the response to treatment was based on the number of seizures during the 3 months before entering the study (first baseline period), 3 months after entering the study (second baseline period) and 3 months before the termination of the study (test period). Patients kept a seizure diary throughout the study. The Michaelis-Menten model was used to calculate doses and predict steady-state serum concentrations. SETTING: Nine epilepsy clinics. SUBJECTS: One hundred and ninety-five (113 black and 82 coloured) compliant people with epilepsy receiving generic phenytoin monotherapy. OUTCOME MEASURES: Reduction in seizure frequency and adverse effects. RESULTS: A reduction in seizure frequency (64.8% compared with pre-optimisation) was experienced by 64.9% of patients. Mean seizure frequency was reduced from 3.39 to 1.18 per month. Reductions in seizure frequency of 100% and more than 50% were reported by 39.2% and 58.7% of patients, respectively. Adverse effects of phenytoin were reduced from 20.5% at the first visit to 3.2% at the last visit. CONCLUSION: The clinical pharmacokinetic dosing service for phenytoin applied in this study contributed significantly to the success of epilepsy management.     

Sex difference in force generation capacity during repeated maximal knee extensions

PURPOSE: To define the risk of seizure recurrence (RSR) that families and physicians would accept before discontinuing antiepileptic drugs (AEDs) for children with controlled epilepsy. METHODS: A questionnaire was completed by families of 76 children with epilepsy > or = 3 months seizure-free and by their attending epilepsy specialist (n = 4). RESULTS: Forty-two percent of families were unwilling to discontinue AEDs with an RSR of 25%. In contrast, 20% were willing to accept a > 75% RSR. Several factors differentiated the risk acceptable to families: previous seizure frequency (risk adverse with intermediate frequency), multiple seizure types (risk taking), grade or grades repeated in school (risk adverse), and the family's strategy of playing lotteries. Although families and physicians were prepared to accept similar median RSR (35 and 40%, respectively), individual answers did not correlate (r2 = -0.07). Physicians were unable to predict the families response (r2 = 0.09). CONCLUSIONS: Our current practice is to discontinue AEDs after 2 years of seizure-free results in seizure recurrence of 30-40%. This risk may seem excessive to more than half of families, whereas other families will risk stopping AEDs at higher risks of recurrence. Physicians are poor judges of the degree of risk that is acceptable to a particular family, which may account in part for the anxiety manifested by families at AED discontinuation.     

Residential care for elderly people: the prevalence of cognitive impairment and behavioural problems

AIMS: to investigate the prevalence of and interrelationship between cognitive impairment and behavioural problems in older people in residential care. SUBJECTS: all those aged 65 years and over resident on one night in any type of residential care within the Leicestershire District Health Authority. METHODS: an assessment form for each resident was completed by care staff. The assessment included demographic information and functioning (both mental and physical) during the previous week. Cognitive impairment was measured by the confusion sub-scale of the Crichton Royal Behavioural Rating Scale. RESULTS: 6079 people were enumerated in 241 establishments, including hospitals, homes and hostels provided by the National Health Service (NHS), local authority social services and private and voluntary agencies. Thirty-eight percent (2219) were moderately or severely cognitively impaired and behavioural problems were present in 11.5%, most being associated with the presence of cognitive impairment. Compared with elderly people in private residential homes, residents in local authority (part III) homes had significantly higher odds of demonstrating offensive behaviour of 1.40 (95% confidence interval 1.11-1.78) after adjustment for age, sex and cognitive impairment. No significant association between number of patients in the home and the proportion exhibiting offensive behaviour was found in any of the non-NHS facilities. CONCLUSIONS: this survey of old people in institutional care found that most of those with behavioural problems were cognitively impaired. This has implications for staff training in the management of behavioural problems in demented people.     

Predictors of epilepsy in children who have experienced febrile seizures

We examined the frequency of development of afebrile seizures in 1706 children who had experienced at least one febrile seizure and were followed to the age of seven years. Epilepsy developed by seven years of age in 20 per 1000 (2 per cent), and another 10 per 1000 had at least one afebrile seizure that did not meet our definition of epilepsy. In children whose neurologic or developmental status was suspect or abnormal before any seizure and whose first seizure was complex (longer than 15 minutes, multiple or focal) epilepsy developed at a rate 18 times higher than in children with no febrile seizures (92 vs. 5 per 1000; P less than 0.001). In the largest group with febrile seizures, those previously normal with noncomplex first febrile seizures, epilepsy developed in 11 per 1000; this rate, although moderate, was greater than that for children with no febrile seizures (P = 0.027). Prior neurologic and developmental status and characteristics of the first febrile seizure are important predictors of epilepsy after febrile seizures.     

Altered platelet magnesium and plasma and urinary soluble form of intercellular adhesion molecule I (sICAM-1) concentrations in insulin dependent diabetes mellitus (IDDM) patients with microalbuminuria

To examine the association between anticardiolipin (aCL) antibodies and epilepsy, we investigated the serum titers of aCL antibodies in a total 252 systemic lupus erythematosus (SLE) patients recruited in a prospective study. Twenty-one cases with epilepsy which were not attributable to any causes other than SLE were identified after being followed-up for five years. The clinical manifestations were recorded and blood samples were tested for the presence of aCL antibodies (IgG, IgM and IgA isotypes). Among 21 patients with epilepsy, 12 (57.1%), 2 (9.5%) and 2 (9.5%), respectively, had elevated baseline serum levels of IgG, IgM and IgA aCL antibodies. There was a dose-response relationship between risk of seizure and the baseline serum level of aCL antibodies (P < 0.01). The odds ratio of developing seizure were 3.7 for those who had a high level of aCL antibodies compared with those without a detectable level of aCL antibodies as the referent. Our results indicate that epilepsy as a primary neuropsychiatric event among lupus patients is associated with a high titer of aCL antibodies.     

Relationship between seizure frequency and costs and quality of life of outpatients with partial epilepsy in France, Germany, and the United Kingdom

PURPOSE: The relationship between seizure frequency and both health care costs and quality of life (QOL) was investigated in a retrospective, cross-sectional, multicenter study in France, Germany, and the United Kingdom. METHODS: Three hundred outpatients with stable partial epilepsy were approximately evenly distributed among five seizure-frequency groups, ranging from seizure-free in the last 3 months (group 1) to daily seizures (group 5). Economic data, obtained through patient interviews and record abstraction, comprised direct medical costs, direct nonmedical costs, and indirect costs for the preceding 3 months. Total societal costs in the three countries were pooled and converted to United States dollar equivalents. QOL was assessed through a self-administered questionnaire, the Functional Status Questionnaire (FSQ). RESULTS: Mean total costs increased from $780 in group 1 to $2,171 in group 5 (p = 0.0001), with significant increases in each cost category as seizure frequency increased. Greater seizure frequency also significantly (p = 0.0270) correlated with lower employment rates, which ranged from 57% in group 1 to 30% in group 5. QOL declined as seizure frequency increased. Particularly affected were basic and intermediate activities of daily living (ADL), mental health, social activity, and feeling about health. CONCLUSIONS: The study results show that higher seizure frequencies are associated with higher direct and indirect costs and with reduced QOL for patients with epilepsy.     

Bilateral reductions in hippocampal volume in adults with epilepsy and a history of febrile seizures

OBJECTIVES: To examine the degree and frequency of reductions in hippocampal volume in patients with temporal lobe epilepsy with and without a history of febrile seizures. METHODS: In vivo measures of hippocampal volume were computed from three dimensional gradient echo (FLASH) images in 44 patients undergoing comprehensive evaluations for epilepsy surgery. Twenty one patients (48%) reported a history of febrile seizures. The volumes from these patients were compared with those from 23 patients without a history of febrile seizures and 34 healthy controls. RESULTS: The febrile seizure group had significant reductions in volume, both ipsilateral (30% decrease) and contralateral (15% decrease), to the EEG seizure focus. Twelve of 18 patients with febrile seizures exhibited clinically significant ipsilateral volume reductions, defined as volumes falling 2 SD below the mean obtained from the control sample. Only four of 19 patients without febrile seizures exhibited this degree of reduction. No significant correlations were found between seizure variables (for example, duration of epilepsy, seizure frequency) and ipsilateral reductions in volume. However, a significant inverse correlation (r=-0.45, P<0.05) between seizure frequency and the volume of the hippocampus contralateral to the seizure focus was found in the febrile seizure group. CONCLUSION: These results suggest that a history of febrile seizures is associated with the finding of a smaller hippocampus on the side ipsilateral to the subsequent temporal lobe focus whereas chronic factors seem to be be related to pathology contralateral to the seizure focus.     

Resident behaviors and characteristics as determinants of quality of residential care: an observational study

The effects of resident behaviors and resident characteristics on the quantity and quality of care they receive from direct-care staff was examined. Four hundred and fifty-two residents with severe and profound mental retardation and 416 direct care staff members were involved. Naturalistic observations were conducted on direct-care staff behavior, that is, staff-resident initiatives, staff affection, staff communicative behavior, on resident behaviors (i.e., maladaptive, stereotypic, and adaptive behavior, position, attending, and communicative behavior), and on resident characteristics (i.e., gender, age, ambulancy, sensory handicaps, and seizure disorder). By importance, residents' ambulancy/motoric skills, their communicative behavior, and attending behavior accounted for the greatest differences in the quality and quantity of the care they receive from direct-care staff. Given that certain resident characteristics can be ameliorated through training, residents themselves may control, to a certain extent, the care they receive from direct-care staff in residential facilities.     

Epileptic seizures can be anticipated by non-linear analysis

Epileptic seizures are a principal brain dysfunction with important public health implications, as they affect 0.8% of humans. Many of these patients (20%) are resistant to treatment with drugs. The ability to anticipate the onset of seizures in such cases would permit clinical interventions. The view of chronic focal epilepsy now is that abnormally discharging neurons act as pacemakers to recruit and entrain other normal neurons by loss of inhibition and synchronization into a critical mass. Thus, preictal changes should be detectable during the stages of recruitment. Traditional signal analyses, such as the count of focal spike density, the frequency coherence or spectral analyses are not reliable predictors. Non-linear indicators may undergo consistent changes around seizure onset. Our objective was to follow the transition into seizure by reconstructing intracranial recordings in implanted patients as trajectories in a phase space and then introduce non-linear indicators to characterize them. These indicators take into account the extended spatio-temporal nature of the epileptic recruitment processes and the corresponding physiological events governed by short-term causalities in the time series. We demonstrate that in most cases (17 of 19), seizure onset could be anticipated well in advance (between 2-6 minutes beforehand), and that all subjects seemed to share a similar 'route' towards seizure.     

Surgical treatment for epilepsy: a retrospective Swedish multicenter study

The characteristics of patients suffering from drug resistant epilepsy, including the results of the preoperative evaluation and epilepsy surgery were retrospectively analyzed in a Swedish multicenter 10-year cohort of children and adults. Altogether 152 patients (65 children and 87 adults) treated during the period 1980-1990 in three epilepsy centers were included and followed-up 2 years after surgery. Median age at onset of seizures was 4 years for the children and 12 years for the adults. A localization related epilepsy was present in 85% of the children and in 95% of the adults. The mean number of seizure types in the children was 1.7 (range 1-4) and in the adults 1.8 (range 1-4). The median monthly seizure frequency was 52 and 15 for children and adults respectively. Resective surgery was performed in 143 cases (94 temporal, 31 extratemporal, 9 multilobar and 9 major resection procedures) and palliative procedures in 16 cases (13 callosotomies and 3 stereotactic amygdalotomies). Postoperative neurological deficits were detected in 9% of the patients after temporal lobe resections and in 15% of the patients after extratemporal and multilobar resection procedures. Two years after resective surgery 53% of the children and 49% of the adults were seizure free. Another 25% of the patients had a more than 50% reduction of seizure frequency. In the postoperative non seizure free group of patients there was a negative correlation between decrease in weighted seizure severity and decrease in seizure frequency. This finding stresses the need for including other parameters than seizure frequency when evaluating the outcome of epilepsy surgery.     

Dynamic cerebral autoregulation during sevoflurane anesthesia: a comparison with isoflurane

OBJECTIVE: To study the incidence and pattern of epilepsy in patients with periventricular leukomalacia (PVLM) in two specialty clinic settings. BACKGROUND: Motor and cognitive deficit as well as epilepsy are common in patients with PVLM. With modern imaging techniques, PVLM is now easily recognized. METHODS: Epileptic seizures and syndromes as well as motor and cognitive deficits were correlated with MRI findings. Two patient populations were studied: Group A-children with cerebral palsy and PVLM presenting to a center for children with motor disability (n = 19); and Group B-epileptic patients with PVLM presenting to a tertiary epilepsy center (n = 12). A single patient with PVLM and epilepsy who underwent extensive investigations, including intracranial EEG telemetry, is reported. RESULTS: In Group A, 47% of patients had epilepsy (9/19). PVLM was found in 1.27% of patients investigated for epilepsy at a tertiary epilepsy center (12/942). The majority of patients in both groups had multiple seizure types, with complex partial seizures being most common. Of patients with seizures (Groups A and B), 85.7% had intractable epilepsy (18/21). Intracranial EEG in the illustrative case demonstrated a multifocal epileptic process with occipitotemporal predominance. CONCLUSIONS: PVLM was an uncommon underlying cause in patients presenting with epilepsy (Group A); however, patients presenting with motor disability and PVLM (Group B) had a high incidence of seizures. PVLM in epileptic patients is associated with multiple seizure types and medically refractory disease.     

Dynorphin and the kappa 1 ligand [3H]U69,593 binding in the human epileptogenic hippocampus

The distribution of dynorphin (DYN), one of its binding sites (kappa 1 receptor) and their relationship to neuronal loss and granule cell hyperexcitability was examined in hippocampi from patients with temporal lobe epilepsy (TLE). In hippocampi that were not the seizure focus (mass associated temporal lobe epilepsy, MaTLE; and paradoxical temporal lobe epilepsy, PTLE) DYN-like immunoreactivity was localized in the dentate granule cells and their mossy fiber terminals within the hilus and area CA3. In hippocampi that were the seizure focus (MTLE), 89% showed an additional band of immunoreactivity confined to the inner molecular layer (IML) of the dentate gyrus, representing recurrent mossy fiber collaterals. In 11% of MTLE patients no staining was found in the IML (MTLE/DYN-). The MTLE/DYN- hippocampi were also characterized by a significantly lower degree of cell loss than in MTLE hippocampi in the dentate granule cell layer, the hilus and CA3. Both MTLE and MTLE/DYN- hippocampi showed evoked epileptiform bursting in granule cells while MTLE showed greater polysynaptic EPSPs and spontaneous excitatory activity. Thus granule cell recurrent collateral sprouting may account for only some aspects of hyperexcitability. In 30% of the MTLE group, hilar neurons of a variety of morphological types expressed DYN immunoreactivity in their somata and dendrites. The density of [3H]U69,593 binding sites in MaTLE and PTLE patients was highest in areas CA1 and the subiculum-regions having little or no DYN-staining. In the dentate molecular layer, hilus and CA3--regions with the most DYN immunoreactivity--there was a low density of ligand binding. The significance of this transmitter/receptor mismatch is yet unknown.     

The relationship between staff burnout/distress and interactions with residents in two residential homes for older people

OBJECTIVE: The main hypothesis was that staff burnout/distress would be negatively associated with the quantity and quality of social interactions between staff and residents. The subsidiary hypothesis hypothesis was that 'perceived involvement in decision-making' among staff would be positively associated with the quantity and quality of staff-resident interactions. DESIGN: Cross-sectional and within-group. Standardized self-report questionnaires completed by staff; and non-participant, time-sampling observation and coding of staff-resident interactions. SETTING. Two independent (not-for-profit) residential care homes for older people in the UK. PARTICIPANTS: 18 out of 24 residential workers completed questionnaires. MEASURES: The 12-item General Health Questionnaire (GHQ-12); the Maslach Burnout Inventory (MBI); the Perceived Involvement Personal Questionnaire (PIPQ); and the Quality of Interactions Schedule (QUIS). RESULTS: Staff who reported higher levels of personal accomplishment (ie lower levels of burnout on the personal accomplishment subscale) exhibited significantly more staff-resident interactions; and staff who perceived more involvement in decisions relating to their work showed significantly fewer negative staff-resident interactions. Staff distress, emotional exhaustion and depersonalization were not found to be significantly related to the quantity or quality of staff resident interactions. CONCLUSIONS: The results provide some support for the hypotheses. It appears that levels of personal accomplishment and perceived involvement in decision-making among staff may significantly influence the quantity and quality of staff-resident interactions in residential settings. However, the causal relationships are uncertain, and replication of these findings is required in other contexts.     

Effects of intracerebroventricular injection of histamine on memory deficits induced by hippocampal lesions in rats

This review was conducted to evaluate the long-term prognosis of children responding to vigabatrin by examining the incidence of increased seizure frequency, loss of efficacy, and appearance of new seizures in a cohort of 196 children (mean age, 68.2 months; range, 2 months to 19 years) with drug-resistant epilepsy, who had received vigabatrin as add-on treatment in clinical trials. The results indicate that an increase in seizure frequency was uncommon, occurring in only 10% of children with highly drug-resistant epilepsy and that it usually appears shortly after the initiation of treatment. It was clearly not dose-dependent and most often occurred in patients with nonprogressive myoclonic epilepsy. No specific seizure type was specially involved and usually the problem reversed on discontinuing vigabatrin. Loss of efficacy was also uncommon (12% of patients), and again no specific seizure type was found to be associated. Epilepsy syndrome does seem to be a better predictor of loss of efficacy because it occurred most often in symptomatic generalized epilepsies and cryptogenic infantile spasms. A total of 21 patients (11%) developed genuinely new types of seizures. Fifteen of these patients developed new partial seizures that had little impact on the patients' overall clinical improvement. The new partial seizures were better tolerated than the initial seizure type which in most cases had disappeared. Approximately 3% of patients experienced new generalized seizures that aggravated their initial condition. These occurred most often in patients with nonprogressive myoclonic epilepsy; therefore vigabatrin should be used with particular caution in such patients.     

Vascular determinants of epilepsy: the Rotterdam Study

PURPOSE: To investigate the relation between vascular determinants and epilepsy in an elderly population. METHODS: This is a cross-sectional, community-based, case-control study. The total study population was comprised of 4,944 subjects, 65 of whom had epilepsy which conformed to International League Against Epilepsy (ILAE) criteria. Vascular determinants that were evaluated included a history of stroke or myocardial infarction, peripheral vascular disease, hypertension, serum total cholesterol and left ventricular hypertrophy. Multivariate logistic regression analysis was used to calculate prevalence odds ratios (OR), adjusted for age and gender, as a measure of the strength of the associations. RESULTS: A history of stroke was strongly associated with lifetime epilepsy (OR 3.3; 95% CI [Confidence Interval] 1.3-8.5), as well as with late-onset epilepsy (OR 3.1; 95% CI 0.9-10.6). All vascular determinants were associated with lifetime epilepsy and late-onset epilepsy, with odds ratios >1. When stroke patients were excluded, the odds ratios were statistically significant for the relationships between total cholesterol and late-onset epilepsy (OR 1.3, 95% CI 1.0-1.6) and left ventricular hypertrophy and late-onset epilepsy (OR 2.9, 95% CI 1.0-8.6). Furthermore, presence of any of these vascular indicators was twice as common among subjects with late-onset epilepsy as compared with subjects without epilepsy (OR 2.0, 95% CI 0.9-4.2), and this was statistically significant when stroke patients were excluded (OR 2.1, 95% CI 1.0-4.7). CONCLUSIONS: These results suggest that there may be a relationship between vascular factors and the risk of late-onset epilepsy, apart from the relationship that exists through clinically overt stroke.     

The postictal state. A clinically oriented observation of patients with epilepsy

Epileptic seizures are followed by dynamic alterations in neurologic function in the postictal period which have received little attention by clinicians over a long period of time. We therefore retrospectively studied videotapes of 160 patients with focal epilepsy who underwent presurgical evaluation, for the occurrence of postictal symptoms to determine whether these phenomena have any localizing or lateralizing value in defining the seizure onset zone. Results: (1) We found postictal paresis in 22 of 160 patients (18.8%) in each case contralateral to the hemisphere of seizure onset. (2) 'Perservative' automatisms which start during the ictus and continue in the postictal period occurred in 25.2% of 135 patients with temporal lobe epilepsy but not in patients with frontal lobe epilepsy. (3) Sexual automatisms defined as manipulations of the genitals were found exclusively in patients with temporal lobe epilepsy (in 5.9% of 135 patients). (4) Postictal 'Nose-wiping' was evident in 51.3% of 76 temporal lobe epilepsy patients but only in 12.0% of 25 extratemporal lobe epilepsy patients and was performed with the hand ipsilateral to the hemisphere of seizure onset in 86.5% of all temporal lobe seizures. (5) Postictal language disturbances were observed only in patients with temporal lobe epilepsy (34% of 97 patients) and pointed to a seizure onset in the dominant hemisphere in 80.8%. We conclude that postictal phenomena can provide reliable information for the localization of the seizure onset zone in patients with complex partial seizures. Thus, more attention should be given to the postictal state during presurgical epilepsy monitoring.     

Functional MRI lateralization of memory in temporal lobe epilepsy

OBJECTIVE: To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). BACKGROUND: Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. METHODS: fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. RESULTS: Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. CONCLUSIONS: fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery.     

Serum levels of cytokeratin 19 fragments in cervical cancer

The objective of this study was to compare the efficacy and tolerability of two new antiepileptic drugs, lamotrigine (LTG) and vigabatrin (GVG) in everyday clinical practice. A comprehensive retrospective survey of a computerized data base and hospital case notes was carried out at the Mersey Regional Epilepsy Clinic (MREC), Liverpool, which services a population of 3 million in the North West of England. The study comprised 333 out-patients with refractory epilepsy exposed to LTG and GVG forming a subset in a total population of 2250 patients with epilepsy held on a comprehensive database. The main outcome measures were duration of treatment with each drug described by a Kaplan-Meier survival curve, seizure control determined by a 50% decrease in seizure frequency and freedom from seizures, and incidence of adverse drug effects leading to discontinuation. The Kaplan-Meier curve indicated a 57% probability of patients continuing to take LTG and 43% GVG after 40 months. A 50% improvement in seizure control followed the addition of LTG in 45% of patients, with 10% seizure free, compared with 32% and 6%, respectively after the addition of GVG. LTG was discontinued because of adverse events (most frequently skin rash) in 15% of patients compared to GVG in 25% (particularly because of personality disturbance and psychiatric disorder). Both LTG and GVG are effective new AEDs in patients with refractory epilepsy, treated in a tertiary referral out-patient setting. LTG has a broader spectrum of antiepileptic efficacy for patients with both partial and idiopathic generalized seizures, whereas GVG should be reserved for patients with partial seizures at low risk of psychiatric disorder.     

Landscape ecology and epidemiology of vector-borne diseases: tools for spatial analysis

We studied twins to examine the genetics of epilepsy syndromes. We ascertained 358 twin pairs in whom one or both reported seizures. After evaluation, 253 of 358 (71%) had seizure disorders and 105 pairs were false positives. Among the monozygous (MZ) pairs, more were concordant for seizures (48 of 108; casewise concordance = 0.62 +/- 0.05) than among the dizygous (DZ) pairs (14 of 145; casewise concordance = 0.18 +/- 0.04). In 94% of concordant MZ pairs, and 71% of concordant DZ pairs, both twins had the same major epilepsy syndrome. When analyzed according to major epilepsy syndrome, the casewise concordances for generalized epilepsies (MZ = 0.82; DZ = 0.26), both idiopathic (MZ = 0.76; DZ = 0.33) and symptomatic (MZ = 0.83; DZ = 0), were greater than those for partial epilepsies (MZ = 0.36; DZ = 0.05), with intermediate values seen for febrile seizures (MZ = 0.58; DZ = 0.14) and unclassified epilepsies (MZ = 0.53; DZ = 0.18). We conclude that genetic factors are particularly important in the generalized epilepsies but also play a role in the partial epilepsies. The high frequency of concordant MZ pairs with the same major syndrome strongly suggests there are syndrome-specific genetic determinants rather than a broad genetic predisposition to seizures.