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PubMed2005

Add-on topiramate in the treatment of refractory partial-onset epilepsy: clinical experience of outpatient epilepsy clinics from 11 general hospitals.

An open, prospective, observational study was performed to assess efficacy and adverse-event profile of topiramate as add-on therapy in epilepsy. Outpatient neurology clinics from 11 general hospitals in Greece participated in the study. In total, 211 patients with treatment resistant partial-onset seizures who met the inclusion criteria, were studied. After baseline evaluation, topiramate was given at a target dose of 200mg/day over a 1-month titration period. In the subsequent maintenance period, the topiramate dose could be varied according to the clinical results. Patients were followed for in total 6 months, with monthly visits and regular physical, neurological and laboratory examinations. Seizure frequencies decreased to 35--40% of baseline values following 3 months of treatment and remained relatively constant thereafter. The average monthly seizure frequency over the 6-month study period was 4.61, compared to 9.21 at baseline. The number of responders (patients with at least 50% reduction in seizure frequency) followed a similar pattern, i.e., increase during the first 3 months levelling off at a final 80--85% response rate. Of those completing the study, 30% had been seizure-free for at least 3 months and 12% for 5 months. Topiramate was well tolerated, no deviations in laboratory values were found. Adverse events appeared to occur less frequently, and antiepileptic effects were more pronounced in this prospective open-label study than in earlier reports from randomised controlled trials. The nature of the patient population and the application of individualised dose optimisation are proposed as contributing factors to explain the favourable results of this study.

Adolescent↗
PubMed2004

Effect of interstitial stereotactic radiosurgery on behavior and subjective handicap of epilepsy in patients with gelastic epilepsy.

Patients with symptomatic epilepsy due to hypothalamic hamartomas often are compromised not only by pharmacoresistant epileptic seizures but also by behavioral disturbances and cognitive dysfunction. We report the effect of successful treatment with stereotactic interstitial radiosurgery by intrahypothalamic implantation of 125I seeds on behavior and subjective handicap. In all patients rendered seizure-free or suffering only from auras, improvement of behavior was reported by parents and colleagues or schoolteachers. Parents' ratings according to the Child Behavior Checklist showed improvements with respect to social problems and attention. Self-ratings of quality of life by adult patients showed improvements in activities, working situation, and self-perception. These improvements were not observed in patients in whom clinically manifest seizures and interictal EEG discharges persisted after radiosurgery.

Activities of Daily Living↗
PubMed1998

Neuropsychological consequences of epilepsy surgery in frontal lobe epilepsy.

The present study investigated the effect of frontal lobe surgery on "cognitive functions", which have previously been shown to be discriminative in the evaluation of non-resected patients with frontal lobe epilepsy (FLE). The cognitive outcome was evaluated with particular consideration of the side (left/right), the site (lateral, orbital, mesial, premotor/SMA), the type of surgery (resections vs resections plus Multiple Subpial Transections), and seizure outcome. The evaluation is based on 33 patients with left (n = 17) or right (n = 16) frontal surgery. Forty-five patients who underwent successful left (n = 21) or right (n = 24) temporal lobectomy served as controls. The neuropsychological examination covered speed/attention, motor sequencing/coordination, response maintenance/inhibition, short-term memory, and language. With the exception of short term memory, the chosen tests were discriminative in determining preoperative frontal lobe dysfunctions but they did not differentiate patients with a different lateralization or localization of the frontal focus. At the three month follow-up examination, patients with temporal lobectomy had improved frontal functions, while patients with frontal lobe surgery showed a mild deterioration. Within the frontally resected group, completely seizure free patients had significantly improved short-term memory. Further consideration of the side, site and the type of the frontal resection indicated that patients with premotor/SMA surgery and patients with precentral/central MST had additional impairment after surgery. Premotor/SMA resections led to a deterioration in response maintenance/inhibition and if performed left sided also to deteriorated language functions. The latter impairment could be clearly related to transient aphasia directly after surgery. Irrespective of pareses observed immediately after surgery, patients with MST's of precentral/central areas displayed additional problems in motor coordination at the follow-up examination. In this group the seizure outcome was also less favorable. In summing up, frontal lobe surgery does not cause any considerable additional impairment in the short term follow-up. However, caution is recommended when surgery or MST affect functional relevant cortex (here the prefrontal/SMA and precentral/central area). Finally, a release of functions associated to frontal areas not affected by surgery is suggested, when seizures are successfully controlled by surgery.

Adolescent↗
PubMed2001

The ovarian hormones and absence epilepsy: a long-term EEG study and pharmacological effects in a genetic absence epilepsy model.

In the first experiment, the relationship between the phase of the estrous cycle and the number of spontaneously occurring spike-wave discharges was investigated in WAG/Rij rats, a model for generalized absence epilepsy. The electroencephalogram (EEG) was continuously recorded for 96 h in eight rats chronically equipped with cortical EEG electrodes. A circadian pattern emerged for the number of spike-wave discharges: a nadir during the first hours of the light period, and an acrophase during the first hours of the dark period. This daily maximum was increased at proestrus day compared with the other days of the cycle, when the plasma level of progesterone is enhanced specifically at these hours of this day. This suggests that progesterone enhances spike-wave discharges. There was no difference in the first few hours of the light period in the number of spike-wave discharges between proestrus and the three other days, suggesting that estradiol has no effect on spike-wave discharges. In the second study, the effects of the systemic administration of progesterone and 17 beta-estradiol on spike-wave discharges and spontaneous behavior were investigated. It was shown that progesterone (20 and 30 mg/kg) but not estradiol (0.17-1.5 mg/kg) increased the number and total duration of spike-wave discharges. On the other hand, injection of RU 38486 (10 and 30 mg/kg), an antagonist of intracellular progesterone receptors, had no effect on spike-wave discharges and did not block the stimulatory effect of progesterone. The antagonist of 17 beta-estradiol tamoxifen (1 and 3 mg/kg) did not evoke alterations in the number or duration of spike-wave discharges. Our results indicate that progesterone aggravates spike-wave discharges, but is not mediated through intracellular receptors. Since progesterone is rapidly metabolized in the brain to the positive modulator of GABA(A) receptor allopregnanolone, which increases spike-wave discharges in WAG/Rij rats, it is possible that the epileptiformic effects of progesterone are mediated through this metabolite.

Animals↗
PubMed1998

Hippocampal AMPA and NMDA mRNA levels and subunit immunoreactivity in human temporal lobe epilepsy patients and a rodent model of chronic mesial limbic epilepsy.

This study compared temporal lobe epilepsy patients, along with kindled animals and self sustained limbic status epilepticus (SSLSE) rats for parallels in hippocampal AMPA and NMDA receptor subunit expression. Hippocampal sclerosis patients (HS), non-HS cases, and autopsies were studied for: hippocampal AMPA GluR1-3 and NMDAR1&2b mRNA levels using in situ hybridization: GluR1, GluR2/3, NMDAR1, and NMDAR2(a&b) immunoreactivity (IR); and neuron densities. Similarly, spontaneously seizing rats after SSLSE, kindled rats, and control animals were studied for: fascia dentata neuron densities: GluR1 and NMDAR2(a&b) IR; and neo-Timm's staining. In HS and non-HS cases, the mRNA hybridization densities per granule cell, as well as molecular layer IR, showed increased GluR1 (relative to GluR2/3) and increased NMDAR2b (relative to NMDAR1) compared to autopsies. Likewise, the molecular layer of SSLSE rats with spontaneous seizures demonstrated more neo-Timm's staining, and higher levels of GluR1 and NMDAR2(a&b) IR compared to kindled animals and controls. These results indicate that hippocampal AMPA and NMDA receptor subunit mRNAs and their proteins are differentially increased in association with spontaneous, but not kindled, seizures. Furthermore, there appears to be parallels in fascia dentata AMPA and NMDA receptor subunit expression between HS (and non-HS) epileptic patients and SSLSE rats. This finding supports the hypothesis that spontaneous seizures in humans and SSLSE rats involve differential alterations in hippocampal ionotrophic glutamate receptor subunits. Moreover, non-HS hippocampi were more like HS cases than hippocampi from kindled animals with respect to glutamate receptors; therefore, hippocampi from kindled rats do not accurately model human non-HS cases, despite some similarities in neuron densities and mossy fiber axon sprouting.

Animals↗
PubMed1998

Epilepsy needs revisited: a revised epilepsy needs document for the UK.

We revisit epilepsy needs in the United Kingdom, and update our previous publication to take into account new epidemiological data, changes in investigation and treatment and trends in the organization of health and other caring agencies. This document attempts to define and quantify the scope, content and standards of services required, from primary care settings to specialized centres. Reference is also made to the role of other agencies.

Adult↗
PubMed1998

The Epilepsy Outcome Scale: the development of a measure for use with carers of people with epilepsy plus intellectual disability.

This paper describes the development of a new scale for the assessment of epilepsy in people with learning disabilities. The scale was developed and validated in consultation with principal carers, and reflects their concerns about seizures, their impact and their treatment. Further testing of the scale revealed high internal consistency, testretest reliability and a robust factor structure. The scale can be completed in 5-10 min and may be useful as an outcome measure both in clinical practice and in research trials.

Adaptation, Psychological↗
PubMed2001

Development and validation of the Glasgow Epilepsy Outcome Scale (GEOS): a new instrument for measuring concerns about epilepsy in people with mental retardation.

PURPOSE: To develop a measure for use with adults with epilepsy and mental retardation, capable of assessing both clinical and care concerns and of quantifying treatment outcomes. METHODS: Extensive validational and other psychometric evaluation was undertaken, comprising initial scale development work with 48 carers and 46 health practitioners, followed by formal field testing on a sample of 186 patients, using 384 respondents (160 clinicians, 141 staff, 83 family). Recognised qualitative methods were applied to identify central themes, and psychometric procedures generated data on validity, reliability, and component structure. RESULTS: A total of 1,007 items of concern was generated, which was reduced systematically to a representative set of 90 items. The GEOS-90 comprises four subscales: concerns about "seizures," "treatment," "caring," and "social impact," each explaining approximately 70% of variance. Subscales and factor scales had strong internal consistency (alpha > or = 0.82). Stepwise linear regression was applied to derive a short-form version with similar structure. Thirty-five items were retained (GEOS-35; alpha > or = 0.89). Both scales discriminated moderately on clinical variables (number of seizure types, mono- vs. polytherapy, seizure frequency; all values of p < 0.05) and demonstrated concurrent validity with interview ratings from the ELDQOL (p < 0.05). CONCLUSIONS: The GEOS scales appear valid and reliable for use with clinical populations of people with mental retardation.

Adolescent↗
PubMed1992

Occipital lobe epilepsy: electroclinical manifestations, electrocorticography, cortical stimulation and outcome in 42 patients treated between 1930 and 1991. Surgery of occipital lobe epilepsy.

Our study documents the clinical and electrographic findings in 42 patients with medically refractory occipital lobe epilepsy, who underwent surgery at the Montreal Neurological Institute between 1930 and 1991, and the evolving manner in which those patients were studied by successive generations of investigators. In more than two-thirds of the patients the clinical manifestations indicated the occipital onset of the seizures. Seventy-three percent experienced visual aurae, of which elementary hallucinations were the most common and 12 also had ictal blindness. Other occipital manifestations included: contralateral eye deviation, blinking, a sensation of eye movement and nystagmoid eye movements. Intra-operative cortical stimulation elicited a habitual aura in 37% of 29 patients. Lateralizing clinical features were seen in almost two-thirds of patients: contralateral head deviation occurred in half, 59% had visual field defects contralateral to the epileptogenic area and 64% had abnormal imaging studies ipsilateral to the side of surgery. More than one-third of patients exhibited more than one seizure type, suggesting ictal spread to temporal or frontal lobe: 50% had typical temporal lobe automatisms, and 38% exhibited focal motor seizure activity. Surface electroencephalogram (EEG) recordings showed posterior temporal-occipital epileptiform discharges in 46% of patients. Only 18% had electronegative spiking limited to 01 or 02. Large epileptogenic areas were often found on intracranial recording with depth electrodes and on electrocorticography. Pre-excision electrocorticography spiking was restricted to the occipital lobe in only 13 out of 34 patients. More often spiking also involved the posterior temporal and posterior parietal regions. Twenty-three patients underwent only occipital resections; five had only temporal resections, so as to preserve the visual fields, and the remaining 14 patients had extensive resections, which included the posterior temporal or posterior parietal regions. A follow-up period of 1 to 46 yrs (mean 17 yrs) was available for 37 patients. Forty-six percent became seizure free and 21% had a significant reduction in seizure frequency. A better outcome was observed in those patients in whom there was no post-resection electrocorticographic or surface EEG epileptiform discharge, or who exhibited an occipital lobe lesion.

Adolescent↗
PubMed2004

Differential neuroplastic changes in neocortical movement representations and dendritic morphology in epilepsy-prone and epilepsy-resistant rat strains following high-frequency stimulation.

The epileptogenic-prone (FAST) and epileptogenic-resistant (SLOW) rat strains have become a valuable tool for investigating the neurochemical and neurophysiological basis of epilepsy. This study examined the two strains with respect to their neocortical movement representations and cortical layer III pyramidal cell dendritic morphology in both control and potentiated conditions. FAST and SLOW rats received high-frequency stimulation of the corpus callosum in order to induce long-term polysynaptic potentiation of the transcallosal pathway to the sensorimotor neocortex. Baseline-evoked potentials of this pathway were recorded in the left hemisphere before stimulation, and following 5, 10, 15 and 20 days of high-frequency stimulation. All rats then underwent high-resolution intracortical microstimulation (ICMS) in order to assess functional movement representations of the left caudal forelimb area of the sensorimotor cortex. Immediately following ICMS, the brains were stained with the Golgi-Cox method, and the length, branching and spine density of frontal and occipital neocortical layer III pyramidal neurons were measured. We observed that high-frequency stimulation induced similar increases in polysynaptic potentiation in both rat strains; however, only the FAST strain showed an increase (doubling) in the size of their motor maps. We also observed decreases in dendritic length and branching in the FAST rats, and the opposite profile in the SLOW rats. The potentiated FAST rats also showed an increase in spine density. Our results suggest that differences in susceptibility to epileptogenesis may result in a differential response to stimulation-induced plasticity.

Animals↗
PubMed1983

Epilepsy and alcohol: the influence of social alcohol intake on seizures and treatment in epilepsy.

People suffering from epileptic seizures are often confronted with restrictions resulting from their attacks, such as exclusion from several professions and from some sports, not being allowed to drive a car, and prohibition of alcohol. Consultation of manuals to trace the literature studies on which this last prohibition was based was unsuccessful since there was no mention of the original research from which it appeared that alcohol was provocative of seizures. To be able to give a well-founded judgment on the influence of social alcohol intake on epilepsy, research was undertaken with epileptic patients who had never before or very sporadically used alcohol. During 16 weeks, twice a week, in a clinical setting, 1-3 glasses of an alcoholic beverage were consumed within a period of 2 h. The examination could be carried out double-blind since the drink that was chosen, vodka, is odorless and cannot be tasted when mixed with orangeade. We concluded the following. (a) No influence of social alcohol use on tonic-clonic convulsions or partial complex seizures is demonstrable. (b) Blood levels of carbamazepine, phenobarbital, and phenytoin are not influenced by alcohol intake. The valproic acid concentration is possibly slightly increased. However, this needs further examination before judgment can be made. (c) Both in frequency bands and in the amount of epileptic activity, no change is produced by alcohol use.

Adolescent↗
PubMed1998

Intracranial EEG seizure-offset termination patterns: relation to outcome of epilepsy surgery in temporal lobe epilepsy.

PURPOSE: Studies using stereo-EEG (SEEG) and electrocorticography (ECoG) should not only identify a patient's epileptogenic zone, but also should provide prognostic information for surgical outcome. In this respect, seizure-offset patterns have so far been the subject of only one study, in which they were shown to be associated with poor outcome when recorded over cortical areas outside the temporal lobe of seizure onset. To clarify whether seizure-offset patterns are reliable in predicting seizure outcome, we studied SEEG/ECoG in a similar group of patients with temporal lobe epilepsy (TLE). METHODS: SEEG/ECoG records of 44 patients with refractory TLE were analyzed. The areas of seizure termination were classified as ipsilateral or contralateral (mesial and/or lateral) temporal, (temporal and) frontal, and diffuse/bilateral. Patients were classified with respect to seizure outcome as either seizure-free (UCLA class 1a) or not seizure free (UCLA class 2-4); both groups were correlated with specific seizure-offset categories using Fisher's exact probability test and analysis of variance (ANOVA). RESULTS: Of the 44 patients, the majority (n = 36) had at least part of their seizure offsets in the ipsilateral temporal lobe, whereas 8 patients manifested no seizure offsets in this lobe. Only 9 patients (20%) showed exclusive offsets in the ipsilateral temporal lobe. No statistically significant difference was evident between patients with all seizure offsets in the ipsilateral temporal lobe and those with offsets elsewhere. Similarly, no statistically significant difference was evident between patients with a diffuse seizure offset and those with seizure offsets of a different category. CONCLUSIONS: Seizure-offset patterns in SEEG/ECoG are unreliable in predicting seizure outcome after resective activity surgery for TLE.

Adolescent↗
PubMed2003

The epilepsy, the protease inhibitor and the dodecamer: progressive myoclonus epilepsy, cystatin b and a 12-mer repeat expansion.

Progressive myoclonus epilepsy 1 (EPM1) or Unverricht-Lundborg disease is a human autosomal recessive neurodegenerative disorder caused by mutations in cystatin B (CSTB). The CSTB gene maps to human chromosome 21 and encodes an inhibitor of lysosomal cysteine proteases. Five point mutations have been found, two of which are seen in numerous unrelated patients. However, the main CSTB mutation in EPM1, even among patients of different ethnic origins, is an expansion of a dodecamer repeat (CCCCGCCCCGCG) in the 5' flanking area of CSTB. Most normal alleles contain either two or three repeats, while rarer normal alleles that are highly unstable contain between 12 and 17 repeats. Mutant expanded alleles have been reported to contain between 30 and 80 copies and are also highly unstable, particularly via parental transmission. There is no apparent correlation between mutant repeat length and disease phenotype. While the repeat expansion is outside the CSTB transcriptional unit, it results in a marked decrease in CSTB expression, at least in certain cell types in vitro. CSTB homozygous knockout mice show some parallels to the phenotype of human EPM1 including myoclonic seizures, development of ataxia and neuropathological changes associated with cell loss via apoptosis. Loss of CSTB function due to mutations is consistent with the observed neurodegenerative pathology and phenotype, but the functional link to the epileptic phenotype of EPM1 remains largely unknown.

Base Sequence↗
PubMed1988

Determining the prevalence of epilepsy in the semi-urban population of Nakuru, Kenya, comparing two independent methods not apparently used before in epilepsy studies.

Due to meagre resources in terms of trained medical personnel and financial support and the absence of accurate population-based data in most parts of the developing world, there is an urgent need to develop new epidemiological study designs that are simple, accurate and easy to use. Key informant methodology and random cluster sample survey methods were used independently (a) to determine the prevalence of epilepsy and (b) to compare the efficiency, cost effectiveness and feasibility of the two survey methods. The random cluster method proved more scientifically valid and sensitive as compared to the key informant methods, which was found to be less accurate, although simple and easy to use, for example, by nonmedical workers in identifying epileptics.

Adolescent↗
PubMedDate not supplied

Lamotrigine as add-on therapy in treatment-resistant epilepsy. Portuguese Lamotrigine as Add-on Therapy in Treatment-resistant Epilepsy Study Group.

The efficacy and safety of lamotrigine as add-on therapy in treatment-resistant epilepsy were evaluated in an open prospective study carried out at five centres in Portugal and involving 61 patients. Daily seizure diaries were kept by patients, and used by the investigators to give a rating of response to therapy. Assessments were recorded after 1, 2, 3, 6, 9, 12, 18 and 24 months. Overall, seizure control was improved in 57% of patients, remained unchanged in 34% and deteriorated in 9%. There were some indications that efficacy was greatest in patients with generalized seizures and in those taking concomitant valproate. Efficacy was maintained throughout the 2-year study. It was possible to reduce the dose of concomitant antiepileptic drug in 56% of patients, and seven patients no longer needed a concomitant antiepileptic drug. Although 75% of patients reported an adverse experience, most of these were mild or moderate in intensity, did not require treatment and were not judged to be serious. A total of 13 patients withdrew from the study (four due to adverse events, four due to lack of efficacy and five for other reasons).

Administration, Oral↗
PubMed1994

The role of epilepsy centers in delivering care to patients with intractable epilepsy.

Epilepsy is a disorder that can profoundly influence people's ability to participate fully in society. To ameliorate the effects of the disorder, the health care system should provide mechanisms that explicitly facilitate consultations among primary-, secondary-, and tertiary-level health care providers. Second, it should develop schedules for compensating for both the less and the more technologically intensive methods of diagnosis and treatment. These should allow improved or complete seizure control in a significant portion of patients with intractable seizures. Although there are costs for such changes, the costs of not making them may be higher.

Delivery of Health Care↗
PubMed2000

Successful epilepsy surgery in catastrophic postencephalitic epilepsy.

The authors studied prognostic factors for surgical treatment in 22 patients with intractable postencephalitic epilepsy. A small subgroup of patients (9/22) had a positive outcome after resective surgery. They had a higher functional level after encephalitis as measured by Glasgow Outcome Score, a longer time interval between encephalitis and onset of seizures, and localization of ictal EEG to one temporal lobe. The other patients had devastating seizures with poor outcome after surgery.

Adolescent↗