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OBJECTIVE: Epilepsy is a common and often highly stigmatized disorder. Several international organizations indicate a need to assess the stigma that exists and to develop and evaluate interventions to dispel myths about epilepsy. METHODS: A stratified cluster randomized controlled trial evaluated whether an epilepsy education program (intervention) increases knowledge of and positive attitudes about epilepsy in Grade 5 students (ages 9-11). The study also investigated characteristics of the individuals (gender, language spoken at home, familiarity with epilepsy) and schools (Catholic vs public, size of school, and school level socioeconomic status) that affect epilepsy knowledge and attitudes. We assessed epilepsy knowledge and attitudes at baseline and 1 month following the program using a 33-item questionnaire. RESULTS: In total, 24 schools (783 individuals) were cluster randomized. Those in the intervention group had an average 11.8-point increase (95% confidence interval (CI)=11.4-12.5) in knowledge 1 month following the program, compared with the control group increase of 2.2 points (95% CI=1.8-2.6) out of a total of 57 points. For attitudes, the intervention group had a mean increase of 8.15 points (95% CI=4.70-11.60), compared with the control group increase of 1.64 points (95% CI=-0.84-4.42) out of a total of 50 points. The intervention was responsible for 63% of the variation in postprogram epilepsy knowledge and 28% of the variation in postprogram attitudes about epilepsy. CONCLUSIONS: The epilepsy education program was associated with a significant increase in epilepsy knowledge and positive attitudes in the intervention group 1 month later compared with the control group.  相似文献   

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Summary: Some investigators argue that treating epilepsy with several antiepileptic drugs (AEDs) simultaneously (polytherapy) may give rise to more adverse effects than monotherapy, but this argument lacks supporting quantitative data. To reexamine this issue, we recruited a cohort of patients from the outpatients of the Special Centres for Epilepsy in The Netherlands and from the outpatients of the Department of Neurology, Nijmegen University, The Netherlands. Two tools were used for analysis. All daily doses of antiepileptic drugs (AEDs) were standardized by the ratio of prescribed daily dose to defined daily dose (PDD/DDD). The DDD is the assumed average effective daily dose for a drug used for its main indication in adults. The assignment of DDD Values is the task of the World Health Organization (WHO) Collaborating Centre for Drugs Statistics Methodology and Nordic Council on Medicines, which regularly publishes Guidelines for Defined Daily Doses. The severity of adverse effects (AE) was assessed by using the Neurotoxicity Index and the Systemic Toxicity Index as developed by the VA Cooperative Study Group for their recent studies comparing the efficacy and tolerability of AEDs. One hundred sixty-one patients received monotherapy; all had a PDD/DDD ratio ≤2/day; 128 of 262 patients receiving polytherapy also had ≤2 PDD/DDD ratios/day. The mono- and polytherapy groups were stratified according to the PDD/DDD ratio. The prevalence of neurological AE for patients with similar PDD/DDD ratios was 50–80% for monotherapy patients and 50–80% for polytherapy patients. The difference between the mono- and polytherapy groups was not significant. The prevalence of neurological AE for patients receiving polytherapy with a PDD/DDD ratio >2.0 was 71–100%, whereas all patients with a PDD/DDD ratio >4.0 had neurological AE. This difference between patients with a PDD/DDD ratio ≤2.0 and those with >2.0 was statistically significant; p < 0.05. The severity of neurological AE also increased with dose, but appeared to peak at ~3.5 PDD/DDD ratio. Our study underscores the usefulness of applying quantitative methods to the analysis of drug AE. Comparison of monotherapy and polytherapy showed no difference for equipotent doses. Because distribution of the AED doses was uneven between the groups receiving mono- and polytherapy, our study permits only a tentative statement that the frequency and severity of AE is independent of the use of either. In addition, frequency and intensity of AE apparently are not very sensitive to changes in dose. An experimental prospective study is planned to verify or refute the conclusions of this observational pilot study.  相似文献   

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Summary: Purpose: We reviewed the literature to determine whether an analysis of published data could clarify the relationship between antiepileptic drug (AED) polytherapy and adverse affects (AE). We highlight the problems encountered. Methods: We made a Medline-search for articles published between 1974 and 1994 reporting the number of AE and doses or serum levels of every AED, per patient or treatment group, and used the PDD/DDD ratio to calculate AED load per patient from doses or the OSL/AToxL ratio to do so from serum levels of individual drugs. The PDD/DDD is the sum of ratios of the actual prescribed daily doses divided by the published average therapeutic dose of each drug. The OSL/AToxL is the sum of each observed serum level divided by its average toxic level. Results: We retrieved 118 trial reports. Most had to be excluded because of incomplete reporting of concomitant medication or AE. The data of the 15 articles selected for further analysis indicate a relationship between drug load and number of AE. We noted no relationship between the number of AEDs administered and AE. In add-on studies, the difference in neurotoxicity between the active and placebo arm may be obscured if the relative increase in drug load is small, as exemplified by the study of McGuire et al. (35). Conclusions: Articles reporting add-on trials of new AEDs generally do not provide detailed information about the basic medication to which the new AED is added, which makes calculation of total drug load impossible. Furthermore, often only frequency of AE is reported, not severity or development of tolerance, making it difficult to judge the impact of AE. However, despite the paucity of available information, we present some evidence that toxicity in AED polytherapy may be related to total drug load, rather than to the number of drugs administered. Therefore, the present trend to reject polytherapy for fear of increased toxicity is not warranted, which removes one of the objections to initiating specific research to prove or disprove the value of AED combinations as long as the drug load is appropriate.  相似文献   

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The importance of drug interactions in epilepsy therapy   总被引:16,自引:8,他引:16  
Long-term antiepileptic drug (AED) therapy is the reality for the majority of patients diagnosed with epilepsy. One AED will usually be sufficient to control seizures effectively, but a significant proportion of patients will need to receive a multiple AED regimen. Furthermore, polytherapy may be necessary for the treatment of concomitant disease. The fact that over-the-counter drugs and nutritional supplements are increasingly being self-administered by patients also must be considered. Therefore the probability of patients with epilepsy experiencing drug interactions is high, particularly with the traditional AEDs, which are highly prone to drug interactions. Physicians prescribing AEDs to patients with epilepsy must, therefore, be aware of the potential for drug interactions and the effects (pharmacokinetic and pharmacodynamic) that can occur both during combination therapy and on drug discontinuation. Although pharmacokinetic interactions are numerous and well described, pharmacodynamic interactions are few and usually concluded by default. Perhaps the most clinically significant pharmacodynamic interaction is that of lamotrigine (LTG) and valproic acid (VPA); these drugs exhibit synergistic efficacy when coadministered in patients with refractory partial and generalised seizures. Hepatic metabolism is often the target for pharmacokinetic drug interactions, and enzyme-inducing drugs such as phenytoin (PHT), phenobarbitone (PB), and carbamazepine (CBZ) will readily enhance the metabolism of other AEDs [e.g., LTG, topiramate (TPM), and tiagabine (TGB)]. The enzyme-inducing AEDs also enhance the metabolism of many other drugs (e.g., oral contraceptives, antidepressants, and warfarin) so that therapeutic efficacy of coadministered drugs is lost unless the dosage is increased. VPA inhibits the metabolism of PB and LTG, resulting in an elevation in the plasma concentrations of the inhibited drugs and consequently an increased risk of toxicity. The inhibition of the metabolism of CBZ by VPA results in an elevation of the metabolite CBZ-epoxide, which also increases the risk of toxicity. Other examples include the inhibition of PHT and CBZ metabolism by cimetidine and CBZ metabolism by erythromycin. In recent years, a more rational approach has been taken with regard to metabolic drug interactions because of our enhanced understanding of the cytochrome P450 system that is responsible for the metabolism of many drugs, including AEDs. The review briefly discusses the mechanisms of drug interactions and then proceeds to highlight some of the more clinically relevant drug interactions between AEDs and between AEDs and non-AEDs. Understanding the fundamental principles that contribute to a drug interaction may help the physician to better anticipate a drug interaction and allow a graded and planned therapeutic response and, therefore, help to enhance the management of patients with epilepsy who may require treatment with polytherapy regimens.  相似文献   

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ObjectivesWe analyzed changes in sleep profile and architecture of patients with drug-resistant TLE-HS using three validated sleep questionnaires- Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), NIMHANS Comprehensive Sleep Disorders, and polysomnography (PSG). We studied the effect of epilepsy surgery in a subset of patients.MethodsIn this prospective observational cohort study, sleep profile of 40 patients with drug-resistant TLE-HS was compared to 40 healthy matched controls. Sleep architecture of 22 patients was studied by overnight PSG and compared to 22 matched controls. Sleep profile was reassessed in 20 patients after a minimum period of three months after epilepsy surgery.ResultsThe mean PSQI was higher among patients compared to controls(P=0.0004) while mean ESS showed no difference. NCSDQ showed fewer patients feeling refreshed after a night's sleep compared to controls (p=0.006). PSG revealed a higher time in bed (p=0.0001), longer total sleep time (p=0.006) and more time spent in NREM stage 1 (p=0.001) and stage 2 (p=0.005) while spending less time in stage 3 (p=0.039) among TLE patients. Sleep efficiency was worse in patients on ≥3 ASMs compared to those on 2 ASMs (p-0.044). There was no change in mean ESS (p=0.48) or PSQI (p=0.105) after surgery.ConclusionsPatients with drug-resistant TLE-HS have an altered sleep profile and architecture. Patients on ≥3 ASMs have a lower sleep efficiency. Reassessment at short intervals after epilepsy surgery did not reveal significant changes in sleep profile.  相似文献   

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PURPOSE: Previous reports have suggested that hormone replacement therapy (HRT) could increase seizure activity in women with epilepsy. We sought to determine whether adding HRT to the medication regimen of postmenopausal women with epilepsy was associated with an increase in seizure frequency. METHODS: This was a randomized, double-blind, placebo-controlled trial of the effect of HRT on seizure frequency in postmenopausal women with epilepsy, taking stable doses of antiepileptic drugs (AEDs), and within 10 years of their last menses. After a 3-month prospective baseline, subjects were randomized to placebo, Prempro (0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate or CEE/MPA) daily, or double-dose CEE/MPA daily for a 3-month treatment period. RESULTS: Twenty-one subjects were randomized after completing baseline. The subjects' ages ranged from 45 to 62 years (mean, 53 years; SD, +/-5), and the number of AEDs used ranged from none to three (median, one). Five (71%) of seven subjects taking double-dose CEE/MPA had a worsening seizure frequency of at least one seizure type, compared with four (50%) of eight taking single-dose CEE/MPA and one (17%) of six taking placebo (p = 0.05). An increase in seizure frequency of the subject's most severe seizure type was associated with increasing CEE/MPA dose (p = 0.008). An increase in complex partial seizure frequency also was associated with increasing CEE/MPA dose (p = 0.05). Two subjects taking lamotrigine had a decrease in lamotrigine levels of 25-30% while taking CEE/MPA. CONCLUSIONS: CEE/MPA is associated with a dose-related increase in seizure frequency in postmenopausal women with epilepsy. CEE/MPA may decrease lamotrigine levels.  相似文献   

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PURPOSE: This randomised, double-blind study compared the newer antiepileptic drugs (AEDs) gabapentin (GBP) and lamotrigine (LTG) as monotherapy in newly diagnosed epilepsy. METHODS: Patients with partial seizures with and/or without secondary generalization or primary generalized tonic-clonic seizures were randomized to either GBP or LTG. During 2- and 6-week titration periods, respectively, GBP dosage reached 1,800 mg/day, and LTG, 150 mg/day. In the subsequent 24-week maintenance phase, the dose could be adjusted based on seizure control or adverse events between 1,200 and 3,600 mg/day for GBP and 100 and 300 mg/day for LTG. The primary end point was time to exit, a composite of efficacy and tolerability. Evaluable patients were used for the primary efficacy analysis, whereas tolerability was examined on an intent-to-treat basis. RESULTS: A total of 309 patients was randomized, and 291 (148 GBP, 143 LTG) were included in the evaluable population. Nineteen patients in each group had an exit event. The median time to exit was 69 days for GBP and 48 days for LTG. The hazard ratio was estimated as 1.043 (90% confidence intervals, 0.602-1.809). Overall, 106 (71.6% of the evaluable population) GBP-treated and 96 (67.1%) LTG-treated patients completed the study. Of those, 80 (75.5%) patients taking GBP and 73 (76.0%) taking LTG remained seizure free during the final 12 weeks of treatment. Only 14 (8.9%) GBP-treated patients and 15 (9.9%) LTG-treated patients withdrew because of study drug-related adverse events. CONCLUSIONS: GBP and LTG monotherapy were similarly effective and well tolerated in patients with newly diagnosed epilepsy.  相似文献   

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"Classic" and "newer" antiepileptic drugs (AEDs) were compared in an epidemiological survey regarding patient's acceptance of AEDs, quality of life (QoL), and employment. Data from 907 outpatients, 45.9% female (mean age: 44.8 ± 17.9 years), were evaluated by 90 neurologists in private practices, who were also involved in a non-interventional study by Sanofi-Aventis Deutschland GmbH, regarding medication, seizure type, illness duration, employment, patients' acceptance of AEDs (4-point scale where 1=very good), and QoL (6-point scale where 1=very good). Among the patients, 69.7% were on monotherapy, 25.4% were taking two AEDs, and 4.9% were taking more than two AEDs. Patient's acceptance of AEDs (mean ± SD=1.65 ± 0.62) and QoL (2.34 ± 0.89) were "good." Among patients aged 18-65 years, 68.6% were employed. QoL and acceptance were lower with polytherapy. Older age and polytherapy were associated with lower probability of employment. No differences emerged between "classic" and "newer" AED monotherapy. Polytherapy-associated lower QoL could be due to severity of illness or adverse effects of treatment.  相似文献   

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The aim of this study is to describe aggressiveness in the epilepsy population and to identify possible relationships between this type of behavior and clinical and sociodemographic variables. Aggressive responses were measured by the Aggression Questionnaire (AQ), a standardized and validated instrument, which was administered to 503 patients from nine Italian centers for the care of epilepsy. Aggressive behavior in patients with epilepsy was different from that in the normal Italian population. After adjustment for age and sex, when appropriate, the following variables significantly affected aggressiveness: presence of compromised intellectual functioning, psychiatric disturbances, disability status, number of medications, geographic distribution, education, chronologic age, and disease duration. Our study offers a starting point for further investigations aimed at better understanding the mechanisms connecting aggression and epilepsy.  相似文献   

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PURPOSE: To evaluate the effect of low-dose clonazepam (CZP) on the amount of epileptiform activity in children with focal and generalized epilepsy. METHODS: In a single-blind pilot study, followed by a double-blind, placebo-controlled, randomized, crossover study, 15 children with epilepsy were evaluated by using 24-h long-term EEG recordings during baseline days and days after injections of placebo and CZP. The drug was given as a single i.m. injection of 0.02 mg/kg BW. Blood samples were obtained regularly for analysis of plasma concentrations of CZP. The number of epileptiform discharges was determined during corresponding periods with the individual child in the same state of alertness, the same real time of day, and with concomitant antiepileptic drugs (AEDs) unchanged. RESULTS: In the double-blind study, low-dose CZP produced a highly significant (p = 0.0015) decrease in the amount of epileptiform activity (mean, -69% vs. placebo, -2%) obtained during periods when median plasma concentrations ranged from 18 to <14 nM. The maximal plasma level (median, 24 nM) was reached before the start of the analysis periods. The pilot study showed reductions of epileptiform discharges within the same range as the double-blind study. In the children with daily seizures, a parallel decrease in seizures and the number of epileptiform discharges was seen after the administration of CZP. CONCLUSIONS: Our data demonstrate a significant reduction of epileptiform discharges on long-term EEGs after a single low dose of CZP with concomitant low plasma levels, which were considerably lower than the doses and plasma levels usually recommended. A concomitant reduction of seizures also was seen.  相似文献   

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Twenty therapy-resistant epileptic patients entered a double-blind, randomized, two-period, cross-over trial comparing progabide (19.3-36 mg/kg/day) and placebo as add-on drugs to standard therapy. Each period lasted 6 weeks with a gradual crossover during 4 days. Five patients were dropped because of reasons unrelated to treatment. Among the 15 patients who completed the study, seven had partial, six primary generalized, and two secondary generalized epilepsies. Preexisting antiepileptic drugs (AEDs) ranging from one to three per patient (mean 2.2 AEDs/patient) were maintained unchanged during the trial. Efficacy was assessed biweekly by means of total seizure counts, counts of each seizure type, and global clinical judgment. At the same time intervals, safety was assessed by means of reports of adverse events, clinical and neurological examination, laboratory tests, and measurement of plasma concentrations of progabide and associated AEDs. According to the clinical global judgment, eight patients were considered improved during progabide treatment. Seizures were reduced in 14 of 15 patients during the progabide as compared with the placebo period. During the progabide period, the reduction of the total seizure count was 45 and 58% in two patients and 88-97% in six patients. A significant reduction of the total seizure number was observed in the progabide period as compared with the placebo period, both in the whole patient group (p less than 0.01) and in the two subgroups of patients with generalized (p less than 0.01) and partial (p less than 0.05) epilepsies.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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PURPOSE: Although complex idiopathic generalized epilepsies (IGEs) are recognized to have a significant genetic component, as yet there are no known common susceptibility variants. It has recently been suggested that variation in the BRD2 gene confers increased risk of juvenile myoclonic epilepsy (JME), which accounts for around a quarter of all IGE. Here we examine the association between the candidate causal SNP (the promoter variant rs3918149) and JME in five independent cohorts comprising in total 531 JME cases and 1,390 healthy controls. METHODS: The strongest candidate causal variant from the original report (rs3918149) was genotyped across all five cohorts. In an effort to identify novel candidate causal polymorphisms, previously unscreened regions of UTR were resequenced. RESULTS: We observed a significant effect in a small sample recruited in Britain (genotype p = 0.001, allele p = 0.001), a borderline significant effect in a sample recruited in Ireland and no association in larger samples of German, Australian, and Indian populations. There was no association with other common forms of epilepsy or any other clear candidate casual variants in or near the BRD2 region. CONCLUSIONS: The replication of an effect in the British cohort and suggestive evidence from that recruited in Ireland but lack of replication from the larger German, Australian, and Indian cohorts is surprising and difficult to explain. Further replication in carefully matched populations is required. Results presented here do not, however, support a strong effect for susceptibility to JME across populations of European descent.  相似文献   

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The objective of this study is to assess patients’ satisfaction with migraine treatment with frovatriptan (F) or zolmitriptan (Z), by preference questionnaire. 133 subjects with a history of migraine with or without aura (IHS criteria) were randomized to F 2.5 mg or Z 2.5 mg. The study had a multicenter, randomized, double-blind, cross-over design, with each of the two treatment periods lasting no more than 3 months. At the end of the study, patients were asked to assign preference to one of the treatments (primary endpoint). The number of pain-free (PF) and pain-relief (PR) episodes at 2 h, and number of recurrent and sustained pain-free (SPF) episodes within 48 h were the secondary study endpoints. Seventy-seven percent of patients expressed a preference. Average score of preference was 2.9 ± 1.3 (F) versus 3.0 ± 1.3 (Z; p = NS). Rate of PF episodes at 2 h was 26% with F and 31% with Z (p = NS). PR episodes at 2 h were 57% for F and 58% for Z (p = NS). Rate of recurrence was 21 (F) and 24% (Z; p = NS). Time to recurrence within 48 h was better for F especially between 4 and 16 h (p < 0.05). SPF episodes were 18 (F) versus 22% (Z; p = NS). Drug-related adverse events were significantly (p < 0.05) less under F (3 vs. 10). In conclusion, our study suggests that F has a similar efficacy of Z, with some advantage as regards tolerability and recurrence.  相似文献   

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PURPOSE: This article is the first prospective documentation of the efficacy and safety of gamma knife surgery (GKS) in the treatment of drug-resistant epilepsies of mesial temporal lobe origin. METHODS: From July 1996 to March 2000, three European centers selected 21 patients with mesial temporal lobe epilepsy (MTLE) for a temporal lobectomy. The preoperative investigations included video-EEG with foramen ovale electrodes, magnetic resonance imaging, neuropsychological testing, and the ESI-55 quality-of-life questionnaire. In place of a cortectomy, radiosurgical treatment was performed by using the Leksell Gamma Knife (LGK) at a dose of 24 +/- 1 Gy at the margin. The target included the anterior parahippocampal cortex and the basal and lateral part of the amygdala and anterior hippocampus (head and body). One patient (a heavy smoker) died of a myocardial infarction. Twenty patients were available for prospective evaluation. A minimum 2-year follow-up period included clinical, neuropsychological, and radiologic evaluations. RESULTS: At each 6-month follow-up evaluation, the frequency of seizures was significantly smaller than that at the previous visit. The median seizure frequency of 6.16 the month before treatment was reduced to 0.33 at 2 years after treatment. At 2 years, 65% of the patients (13 of 20) were seizure free. Five patients had transient side effects, including depression, headache, nausea, vomiting, and imbalance. There was no permanent neurological deficit reported except nine visual field deficits. No neuropsychological deterioration was observed 2 years after treatment. The quality of life was significantly better than that before surgery. CONCLUSIONS: The safety and efficacy of the radiosurgical treatment of MTLEs appears good in this group of patient over short-to-middle term. Delay of the seizure cessation was the major disadvantage of GKS. A longer follow-up period is required for confirmation of these results.  相似文献   

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PURPOSE: To assess the comparative effectiveness, efficacy, and tolerability of lamotrigine (LTG) and sustained-release carbamazepine (CBZ) in the treatment of newly diagnosed epilepsy in the elderly. METHODS: Patients aged 65 years or older, who had experienced at least two unprovoked partial and/or generalized tonic-clonic seizures, were randomized to receive LTG (n=93) or CBZ (n=92) according to a multicenter double-blind, parallel-group design. Trial duration was 40 weeks and included a 4-week dose escalation followed by a maintenance phase during which dosages could be adjusted according to response. Initial, maintenance and maximum dosages were 25 mg, 100 mg, and 500 mg per day for LTG, and 100 mg, 400 mg, and 2,000 mg per day for CBZ, respectively. The primary end point was retention in the trial. RESULTS: In the LTG group, 68 patients (73%) completed the 40-week study period compared with 61 (67%) in the CBZ group, a nonsignificant difference. Time to withdrawal from any cause did not differ between groups (p=0.34). The number of subjects who completed the 40-week period and were seizure free in the last 20 weeks was 48 (52%) in the LTG group and 52 (57%) in the CBZ group. Adverse events leading to withdrawal occurred in 13 (14%) subjects in the LTG group and 23 (25%) subjects in the CBZ group. CONCLUSION: LTG and CBZ showed comparable effectiveness, with a trend for higher seizure-free rates for CBZ and better tolerability for LTG. Differences in outcome compared with previous trials may be related to different dosing rates and use of a sustained-release formulation for CBZ.  相似文献   

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Purpose: To assess outcomes of language, verbal memory, cognitive efficiency and mental flexibility, mood, and quality of life (QOL) in a prospective, multicenter pilot study of Gamma Knife radiosurgery (RS) for mesial temporal lobe epilepsy (MTLE). Methods: RS, randomized to 20 Gy or 24 Gy comprising 5.5–7.5 ml at the 50% isodose volume, was performed on mesial temporal structures of patients with unilateral MTLE. Neuropsychological evaluations were performed at preoperative baseline, and mean change scores were described at 12 and 24 months postoperatively. QOL data were also available at 36 months. Key Findings: Thirty patients were treated and 26 were available for the final 24‐month neuropsychological evaluation. Language (Boston Naming Test), verbal memory (California Verbal Learning Test and Logical Memory subtest of the Wechsler Memory Scale‐Revised), cognitive efficiency and mental flexibility (Trail Making Test), and mood (Beck Depression Inventory) did not differ from baseline. QOL scores improved at 24 and 36 months, with those patients attaining seizure remission by month 24s accounting for the majority of the improvement. Significance: The serial changes in cognitive outcomes, mood, and QOL are unremarkable following RS for MTLE. RS may provide an alternative to open surgery, especially in those patients at risk of cognitive impairment or who desire a noninvasive alternative to open surgery.  相似文献   

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