Perampanel for focal epilepsy: insights from early clinical experience.

Perampanel is approved for adjunctive therapy of focal epilepsy with or without secondarily generalized seizures in patients aged >12 years. This narrative review uses real-world and clinical trial data to elucidate perampanel's role in the clinic. Audit data show good tolerability with perampanel and higher freedom-from-seizure rates in elderly vs younger patients. When using perampanel in elderly patients, special attention should be given to comorbidities and co-medication to avoid potential interactions or adverse events. Slower titration is generally recommended, and seizure control should be reassessed at a dose of 4 mg before further dose increases. Perampanel efficacy is similar in adolescents and adults; however, somnolence, nasopharyngitis, and aggression are more frequent in adolescents vs the overall population. Individualized and slow-dose titration can minimize adverse events. Low serum concentrations of perampanel may occur in patients also receiving some enzyme-inducing anti-epileptic drugs; a perampanel dose increase may be required. Adverse events of importance with perampanel include dizziness; anger, aggression, and hostile behavior (particularly in adolescents); and falls (particularly in patients >65 years). An individualized approach to dosing, including slower up-titration and bedtime dosing, reduces dizziness risk. Other drugs may cause or aggravate dizziness; reducing concomitant drugs may be necessary when up-titrating perampanel. It would seem clinically appropriate to give due consideration to avoiding use in patients with a history of anger or hostile/aggressive behavior. The possibility of such behaviors should be discussed with patients before starting perampanel, with monitoring during up-titration. Slower up-titration of perampanel in older patients helps reduce fall risk.

Zonisamide: its pharmacology, efficacy and safety in clinical trials.

Zonisamide is a benzisoxazole derivative, chemically unrelated to other antiepileptic drugs, that appears to have multiple mechanisms of action, including inhibition of Na(+) channels and reduction of T-type Ca(2+) currents. It is currently licensed in Europe and the USA for adjunctive treatment of partial seizures in adults, and in Europe as monotherapy for treatment of partial seizures in adults with newly diagnosed epilepsy. Zonisamide displays predictable, dose-dependent pharmacokinetics and has a half-life of ~60 h, allowing once- or twice-daily administration. It has a low potential for interactions with other medications, including oral contraceptives. The clinical efficacy of adjunctive zonisamide therapy has been established in four pivotal, phase III, randomized, double-blind, placebo-controlled trials, which together included approximately 850 patients, aged 12-77 years, with refractory partial epilepsy. In all four trials, zonisamide 300-600 mg/day resulted in significant reductions in median total seizure rates vs placebo, and zonisamide was generally well tolerated; the most frequently reported adverse events being somnolence, dizziness and anorexia/weight loss. Subanalysis of the primary European trial indicated that zonisamide was effective when administered as first-line adjunctive treatment, and a long-term extension to the same trial demonstrated that the efficacy and safety/tolerability of adjunctive zonisamide was sustained for up to 36 months. Once-daily monotherapy with zonisamide (200-500 mg/day) has been shown to be non-inferior to, and as well tolerated as, twice-daily monotherapy with controlled-release carbamazepine (400-1200 mg/day) in adults with newly diagnosed partial epilepsy. Zonisamide has also been shown to have favourable long-term retention rates, an important indication of its overall effectiveness.

Patterns of treatment response in newly diagnosed epilepsy.

OBJECTIVE: To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy. METHODS: Patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982, and April 1, 2006, were followed up until March 31, 2008. Outcomes were categorized into 4 patterns: (A) early and sustained seizure freedom; (B) delayed but sustained seizure freedom; (C) fluctuation between periods of seizure freedom and relapse; and (D) seizure freedom never attained. Probability of seizure freedom with successive drug regimens was compared. Seizure freedom was defined as no seizures for ≥1 year. RESULTS: A total of 1,098 patients were included (median age 32 years, range 9-93). At the last clinic visit, 749 (68%) patients were seizure-free, 678 (62%) on monotherapy. Outcome pattern A was observed in 408 (37%), pattern B in 246 (22%), pattern C in 172 (16%), and pattern D in 272 (25%) patients. There was a higher probability of seizure freedom in patients receiving 1 compared to 2 drug regimens, and 2 compared to 3 regimens (p < 0.001). The difference was greater among patients with symptomatic or cryptogenic than with idiopathic epilepsy. Less than 2% of patients became seizure-free on subsequent regimens but a few did so on their sixth or seventh regimen. CONCLUSIONS: Most patients with newly diagnosed epilepsy had a constant course which could usually be predicted early. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third and among patients with localization-related epilepsies.

Adjunctive pregabalin for uncontrolled partial-onset seizures: findings from a prospective audit.

AIMS: Pregabalin (PGB) was licensed in Europe as an add-on antiepileptic drug (AED) for the treatment of partial-onset seizures in 2004. This audit assessed the response to adjunctive PGB in patients with uncontrolled seizures. METHODS: PGB was titrated in 135 patients [73 men; 62 women, aged 18-76 (median 44 years) until one of the following occurred: ≥ 6 months' seizure freedom, ≥ 50% or < 50% seizure reduction over 6 months; PGB withdrawal because of adverse effects, lack of efficacy or both. RESULTS: Of the 135 patients, 14 (10.4%) became seizure-free for ≥ 6 months (median PGB dose 300 mg/day; range 75-600 mg). A ≥ 50% seizure reduction occurred in 33 (24.4%) patients; 20 (14.8%) had < 50% reduction. PGB was withdrawn in 68 (50.4%) (40 adverse effects, seven lack of efficacy and 21 both). Commonest problems resulting in withdrawal were sedation (n = 18), weight gain (n = 14) and ataxia (n = 9). There was a positive correlation between increasing dose and weight gain (r = 0.42, P = 0.045). CONCLUSIONS: Add-on PGB benefited 50% of patients, but only 10% achieved 6 months' seizure freedom. Adverse effects, most commonly sedation, dose-related weight gain and ataxia, led to drug discontinuation by 45%. Prospective audits of novel AEDs are a useful adjunct to randomized, controlled trials in managing epilepsy.

Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy.

OBJECTIVE: This study assessed the efficacy and safety of the neuronal potassium channel opener ezogabine (US adopted name; EZG)/retigabine (international nonproprietary name; RTG) as adjunctive therapy for refractory partial-onset seizures. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial in adults with ≥4 partial-onset seizures per month receiving 1 to 3 antiepileptic drugs. EZG (RTG) or placebo, 3 times daily, was titrated to 600 or 900 mg/d over 4 weeks, and continued during a 12-week maintenance phase. Median percentage seizure reductions from baseline and responder rates (≥50% reduction in baseline seizure frequency) were assessed. RESULTS: The intention-to-treat population comprised 538 patients (placebo, n = 179; 600 mg, n = 181; 900 mg, n = 178), 471 of whom (placebo, n = 164; 600 mg, n = 158; 900 mg, n = 149) entered the maintenance phase. Median percentage seizure reductions were greater in EZG (RTG)-treated patients (600 mg, 27.9%, p = 0.007; 900 mg, 39.9%, p < 0.001) compared with placebo (15.9%). Responder rates were higher in EZG (RTG)-treated patients (600 mg, 38.6%, p < 0.001; 900 mg, 47.0%, p < 0.001) than with placebo (18.9%). Treatment discontinuations due to adverse events (AEs) were more likely with EZG (RTG) than with placebo (placebo, 8%; 600 mg, 17%, 900 mg, 26%). The most commonly reported (>10%) AEs in the placebo, EZG (RTG) 600 mg/d, and EZG (RTG) 900 mg/d groups were dizziness (7%, 17%, 26%), somnolence (10%, 14%, 26%), headache (15%, 11%, 17%), and fatigue (3%, 15%, 17%). CONCLUSIONS: In this dose-ranging, placebo-controlled trial, adjunctive EZG (RTG) was effective and generally well tolerated in adults with refractory partial-onset seizures. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that adjunctive EZG/RTG reduces the occurrence of partial-onset seizures.

Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy.

OBJECTIVE: We report the results of a prospective study of the efficacy and tolerability of levetiracetam, a new antiepileptic drug with a unique mechanism of action, in comparison with controlled-release carbamazepine as first treatment in newly diagnosed epilepsy. METHODS: Adults with > or =2 partial or generalized tonic-clonic seizures in the previous year were randomly assigned to levetiracetam (500 mg twice daily, n = 288) or controlled-release carbamazepine (200 mg twice daily, n = 291) in a multicenter, double-blind, noninferiority, parallel-group trial. If a seizure occurred within 26 weeks of stabilization, dosage was increased incrementally to a maximum of levetiracetam 1,500 mg twice daily or carbamazepine 600 mg twice daily. Patients achieving the primary endpoint (6-month seizure freedom) continued on treatment for a further 6-month maintenance period. RESULTS: At per-protocol analysis, 73.0% (56.6%) of patients randomized to levetiracetam and 72.8% (58.5%) receiving controlled-release carbamazepine were seizure free at the last evaluated dose (adjusted absolute difference 0.2%, 95% CI -7.8% to 8.2%) for > or =6 months (1 year). Of all patients achieving 6-month (1-year) remission, 80.1% (86.0%) in the levetiracetam group and 85.4% (89.3%) in the carbamazepine group did so at the lowest dose level. Withdrawal rates for adverse events were 14.4% with levetiracetam and 19.2% with carbamazepine. CONCLUSIONS: Levetiracetam and controlled-release carbamazepine produced equivalent seizure freedom rates in newly diagnosed epilepsy at optimal dosing in a setting mimicking clinical practice. This trial has confirmed in a randomized, double-blind setting previously uncontrolled observations that most people with epilepsy will respond to their first-ever antiepileptic drug at low dosage.

Outcomes of newly diagnosed idiopathic generalized epilepsy syndromes in a non-pediatric setting.

INTRODUCTION: The prognosis of idiopathic generalized epilepsy syndromes (IGES) in the adult setting may vary from that in children owing to differences in genetic, environmental and lifestyle factors. METHODS: All patients diagnosed with epilepsy at the Epilepsy Unit, Western Infirmary, Glasgow, between 1981 and 2001 were reviewed. RESULTS: Of 890 patients, 118 (13%) met the criteria for IGES. Outcomes were known for 103, 66 (64%) of whom achieved remission. The responder rate with sodium valproate was superior (66% vs 45%, P = 0.073) to that with lamotrigine (LTG) particularly in patients with juvenile myoclonic epilepsies (75% vs 39%, P = 0.014). History of febrile seizures was the only factor associated with reduced likelihood of remission (P = 0.032) CONCLUSIONS: Idiopathic generalized epilepsy syndromes constituted 13% of cases in a largely adult cohort of newly diagnosed epilepsy, most of whom achieved remission usually with a single antiepileptic drug. History of febrile seizures was associated with a poorer outcome.

Which electroencephalography (EEG) for epilepsy? The relative usefulness of different EEG protocols in patients with possible epilepsy.

BACKGROUND AND AIMS: Electroencephalography (EEG) is an essential investigative tool for use in young people with epilepsy. This study assesses the effects of different EEG protocols on the yield of EEG abnormalities in young people with possible new epilepsy. METHODS: 85 patients presenting to the unit underwent three EEGs with differing protocols: routine EEG (r-EEG), sleep-deprived EEG (SD-EEG), EEG carried out during drug-induced sleep (DI-EEG). The yield of EEG abnormalities was compared using each EEG protocol. RESULTS: 98 patients were recruited to the study. Of the 85 patients who completed the study, 33 (39%) showed no discernible abnormality on any of their EEG recordings. 36 patients (43%) showed generalised spike and wave during at least one EEG recording, whereas 15 (18%) had a focal discharge evident at some stage. SD-EEG had a sensitivity of 92% among these patients, whereas the sensitivity of DI-EEG and r-EEG was 58% and 44%, respectively. The difference between the yield from SD-EEG was significantly higher than that from other protocols (p < 0.001). Among the 15 patients showing focal discharges, SD-EEG provoked abnormalities in 11 (73%). r-EEG and DI-EEG each produced abnormalities in 40% and 27%, respectively. 7 patients (47%) had changes seen only after sleep deprivation. In 2 (13%), the only abnormalities were seen on r-EEG. In only 1 patient with focal discharges (7%) was the focal change noted solely after drug-induced sleep. These differences did not reach significance. CONCLUSION: EEG has an important role in the classification of epilepsies. SD-EEG is an easy and inexpensive way of increasing the yield of EEG abnormalities. Using this as the preferred protocol may help reduce the numbers of EEGs carried out in young patients presenting with epilepsy.

Diagnosing refractory epilepsy: response to sequential treatment schedules.

Diagnosing refractory epilepsy would facilitate referral for specialist pharmacological review and early consideration of epilepsy surgery. An outcomes study was undertaken in an unselected cohort of newly diagnosed patients to determine the number of antiepileptic drug (AED) regimens needed to be failed before the epilepsy could be designated as pharmacoresistant. Between July 1982 and May 2001, 780 adolescents and adults prescribed their first AED at the Western Infirmary in Glasgow, Scotland provided longitudinal data suitable for analysis. Overall, 504 (64.6%) patients became seizure free for at least 12 months. Of these, 462 (59.2%) remained in remission, while 42 (5.4%) relapsed and subsequently developed refractory epilepsy. The relapse rate peaked at 10.4% after 8 years of follow-up. The other 276 (35.4%) patients were uncontrolled from the outset. Prognosis appeared better in seniors (85% remission, P < 0.001) and adolescents (65% remission, P < 0.01) than in the remainder of the population (55% remission). Overall response rates with the first, second and third treatment schedules were 50.4, 10.7 and 2.7%, respectively, with only 0.8% patients responding optimally to further drug trials. Patients not tolerating at least one AED schedule did better than those failing because of lack of efficacy. These data suggest that suitable patients failing two AED regimens should be referred for epilepsy surgery. Those who do not attain long-term seizure freedom with the first three treatment schedules are likely to have refractory epilepsy.

Epileptogenesis and rational therapeutic strategies.

The understanding of neurobiological mechanisms of epileptogenesis is essential for rational approaches for a possible disease modification as well as treatment of underlying causes of the epilepsies. More effort is necessary to translate results from basic investigations into new approaches for clinical research and to better understand a relationship with findings from clinical studies. The following report is a condensed synapsis in which molecular mechanisms of epileptogenesis, pharmacological modulation of epileptogenesis, evidence based therapy, refractoriness and prediction of outcome is provided in order to stimulate further collaborative international research.

Diagnosing and predicting refractory epilepsy.

Over 30% of people with epilepsy will never achieve remission with antiepileptic drug (AED) therapy. These individuals are often severely disabled by their condition, have an unsatisfactory quality of life, and are at increased risk of sudden unexpected death. Early identification of refractory epilepsy would allow prompt referral to specialist services, where the diagnosis can be confirmed, seizures and syndromes classified, AED therapy optimized, and suitability for surgery assessed. Recent studies suggest that patients with symptomatic or cryptogenic epilepsy, those who experience multiple seizures before AED treatment initiation, and those with febrile convulsions, a family history of epilepsy, or psychiatric comorbidities are least likely to respond to drug therapy. Failure to achieve good seizure control with the first one or two AED monotherapies is usually sufficient to highlight the possibility of subsequent refractory epilepsy. For most of these individuals, combination therapy using AEDs with complementary modes of action is the recommended treatment approach.

A randomised open-label study of tiagabine given two or three times daily in refractory epilepsy.

Efficacy and tolerability of tiagabine was evaluated in patients with non-controlled partial seizures in a multicentre, open-label, parallel group study. Tiagabine was administered either two (b.i.d.) or three times daily (t.i.d.) as adjunctive therapy and titrated stepwise to a target of 40 mg/day during a 12-week, fixed-schedule titration period; this was followed by a 12-week flexible continuation period. The primary efficacy endpoint was the proportion of patients completing the fixed-schedule titration period. A total of 243 patients were randomised and received treatment, 123 to b.i.d. and 120 to t.i.d. dosing. Fewer patients in the b.i.d. (76 and 62%) than in the t.i.d. (87 and 72%) group completed the fixed-schedule titration period (OR: 0.562; 95% CI: 0.309-1.008; P=0.0532). The median percentage decrease in all types of seizure (excluding status epilepticus) during the fixed schedule titration period was 33.4% for the b.i.d. and 23.8% for the t.i.d. groups (P=0.9634; Van Elteren's test). The proportion of responders was similar for the b.i.d. and t.i.d. groups. There were no significant differences between dosage regimens in the change in median seizure rates from baseline. Adverse events were more frequent during the titration than the continuation period. Most events were mild and related to the central nervous system. Although their incidence was similar between treatment groups, severity was more frequent in the b.i.d. group. Our results suggest that during titration tiagabine is better tolerated with t.i.d. dosing, but during long-term maintenance, a t.i.d. schedule is as effective and well tolerated as b.i.d.

Peripheral retinal dysfunction in patients taking vigabatrin.

OBJECTIVE: To assess the wide-field multifocal electroretinogram (WF-mfERG) for assessment of retinal function in vigabatrin-treated patients. METHODS: Thirty-two adults who had taken vigabatrin for at least 3 years for localization-related epilepsy underwent WF-mfERG, ERG, logMar visual acuity and color vision evaluation, Humphrey visual field analysis (static perimetry), and funduscopy. The group was matched with a cohort of patients who had never received vigabatrin. Results were compared with a normative data set (120 drug-free controls) with respect to potential bilateral abnormalities in response timing. RESULTS: There were no significant differences between groups in visual acuity or color vision testing. Of the vigabatrin patients, 19 (59%) had bilateral visual field defects compared to none of the controls. Using WF-mfERG, all patients on vigabatrin with visual field defects showed abnormalities (100% sensitivity) and only 2 of the 13 patients without a field defect showed retinal abnormalities (86% specificity). CONCLUSIONS: WF-mfERG may be useful for detecting retinal pathology in patients taking vigabatrin. The majority of previous reports based on subjective testing may have underestimated the prevalence of peripheral retinal toxicity related to the drug.

Psychopathology in people with epilepsy and intellectual disability; an investigation of potential explanatory variables.

OBJECTIVES: There are few studies on epilepsy and psychopathology in people with intellectual disability (mental retardation) despite epilepsy prevalence rates that are thirty times higher than in the general population. The aims of this study, therefore, were to identify reliable, epilepsy-specific predictors of psychiatric and behavioural disorder in these patients, and to investigate reliable predictors of carer stress. METHODS: A database of 685 patients was compiled, from which 250 were randomly selected. Structured interviews were completed on 186 of these 250 patients (74%) (108 men, 78 women; mean age (SD) 35.5 (10.1)) comprising descriptive, clinical and functional components, and validated measures of psychopathology for which comparative data were available. Logistic and linear regression methods were used to identify predictors. RESULTS: One-third of patients with epilepsy and intellectual disability met criteria for possible psychiatric disorder, particularly affective/neurotic disorder; twice the comparison rates for intellectual disability alone. Behavioural problem levels, however, were lower than population norms. Regression models explaining modest amounts of variance (R(2)< or =24%) suggested certain seizure phenomena (greater seizure severity, more seizures in past month, lesser tendency to loss of consciousness during seizures) as particular risk factors for psychiatric disorder. General disability factors such as level of intellectual, sensory or motor disability and side effects of medication, however, contributed more to explaining behavioural problems. Around half of the family carers reported significant stress, and one-third exhibited clinically significant anxiety symptoms. Younger carers were more stressed, and side effects from patients' medication also contributed to carer stress. CONCLUSIONS: Although epilepsy in itself may be a risk factor for psychopathology in a minority of people with intellectual disability, some epilepsy-specific factors may predict psychiatric disorder. Behavioural problems need to be considered separately from psychiatric disorder because general factors, more closely associated with disability, are stronger predictors of their occurrence.

Topiramate, carbamazepine and valproate monotherapy: double-blind comparison in newly diagnosed epilepsy.

OBJECTIVES: To compare topiramate (TPM) with investigator's choice of carbamazepine (CBZ) or valproate (VPA) for initial treatment in patients with newly diagnosed epilepsy. MATERIAL AND METHODS: In patients with epilepsy diagnosed within previous 3 months, investigators selected CBZ (600 mg/day) or VPA (1250 mg/day) as preferred therapy based on the patient's clinical presentation. Based on investigators' treatment choice, patients (n=613) were assigned to the CBZ or VPA treatment branch. Within each branch, patients were randomized to double-blind treatment with the traditional antiepileptic drugs (CBZ or VPA), TPM 100 mg/day, or TPM 200 mg/day. Patients continued double-blind treatment until exiting the study or until 6 months after last patient randomized. RESULTS: No statistically significant differences between fixed doses of TPM and CBZ or VPA were observed in efficacy measures: time to exit, time to first seizure, and the proportion of patients seizure-free during the last 6 months of treatment. TPM 100 mg/day was associated with the fewest discontinuations due to adverse events. CONCLUSION: In patients with newly diagnosed epilepsy, an initial target dose of TPM 100 mg/day is at least as effective as therapeutic doses of CBZ and VPA.

A crossover, add-on trial of talampanel in patients with refractory partial seizures.

The authors report a double-blind, placebo-controlled, crossover study of talampanel in 49 patients with refractory partial seizures. Three doses of talampanel were investigated based on differences in patients' concomitant antiepileptic drug usage. Talampanel showed efficacy in reducing seizure frequency (p = 0.001) with a median seizure reduction of 21%. Eighty percent of patients had fewer seizures on talampanel than on placebo. Dizziness (52%) and ataxia (26%) were the only significant adverse events.

Effectiveness of first antiepileptic drug.

PURPOSE: To investigate the interaction among efficacy, tolerability, and overall effectiveness of the first antiepileptic drug (AED) in patients with newly diagnosed epilepsy. METHODS: The 470 patients were diagnosed, treated and followed up from January 1984 at a single center. Outcome was classified as seizure freedom for at least the last year or failure of initial treatment because of inadequate seizure control, adverse events, or for other reasons. RESULTS: Overall, 47% of patients became seizure-free with the first prescribed AED. A higher proportion (p = 0.025) of patients with symptomatic or cryptogenic epilepsy changed treatment because of intolerable side effects (17%), and a lower proportion (p = 0.007) became seizure-free (43.5%) compared with those with idiopathic epilepsy (8.5% and 58%, respectively). Most patients (83%) received carbamazepine (CBZ; n = 212), sodium valproate (VPA; n = 101), or lamotrigine (LTG; n = 78). The majority of seizure-free patients required only a moderate daily AED dose (93.1% with < or =800 mg CBZ, 91.3% with < or =1,500 mg VPA, 93.8% with < or =300 mg LTG), with commonest dose ranges being 400-600 mg for CBZ, 600-1,000 mg for VPA, and 125-200 mg for LTG. Most withdrawals due to poor tolerability also occurred at or below these dose levels (CBZ: 98%; VPA: 100%; LTG: 75%). Patients taking CBZ (27%) had a higher incidence of adverse events necessitating a change of treatment than did those treated with VPA (13%) or LTG (10%), resulting in fewer becoming seizure-free (CBZ vs. VPA, p = 0.02; CBZ vs. LTG, p = 0.002). CONCLUSIONS: Nearly 50% of newly diagnosed patients became seizure-free on the first-ever AED, with >90% doing so at moderate or even modest dosing. Tolerability was as important as efficacy in determining overall effectiveness.

Hormone profiles in young adults with epilepsy treated with sodium valproate or lamotrigine monotherapy.

PURPOSE: Treatment with sodium valproate (VPA) may be associated with polycystic ovarian syndrome (PCOS) in some women with epilepsy. By comparing hormone profiles in young adults taking VPA or lamotrigine (LTG) as monotherapy, this study aimed to explore whether a pharmacologic effect of VPA could be responsible for this observation. METHODS: Hormone profiles in men and women taking VPA (n = 40) or LTG (n = 36) monotherapy for epilepsy were compared. None of the women were receiving hormonal contraception or replacement. Patients gave details of seizure type and frequency, menstrual cycle, and medical and drug history. Body mass index was calculated, and fasting insulin, glucose, cholesterol, triglycerides (TG), high- and low-density lipoproteins, testosterone, dihydroepiandosterone (DHEA), androstenedione, sex hormone-binding globulin (SHBG), free androgen index (FAI), luteinising hormone (LH), follicle-stimulating hormone (FSH), and antiepileptic drug (AED) concentrations were measured. RESULTS: There were no differences between treatment groups for both sexes in age and seizure control. Only four obese VPA-treated women were hyperinsulinaemic (p = 0.05); three with abnormal menstrual cycles; one with raised testosterone. Testosterone (p = 0.02), FAI (p = 0.03), and TG (p = 0.02) levels were higher, however, in women taking the drug. Obese patients of both sexes (p = 0.01) and VPA-treated men (p = 0.03) had higher insulin concentrations. CONCLUSIONS: VPA therapy may be associated with subclinical elevation in fasting insulin levels. Testosterone and TG levels were higher in VPA-treated women compared with the levels in those taking LTG. However, only a minority of obese females exhibited biochemical characteristics suggestive of PCOS. Biochemical screening may allow women at risk of developing PCOS to avoid VPA.

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.