Long-term treatment with everolimus in TSC-associated therapy-resistant epilepsies.

PURPOSE: To investigate the efficacy and tolerability of long-term treatment with Everolimus (EVO) in patients with tuberous sclerosis complex (TSC) and therapy-resistant epilepsy in a compassionate use trial. METHODS: After a 3-month baseline, patients were treated with EVO. Treatment was divided into treatment phases each lasting at least 9 months. Patients started with one of three target serum levels. In case of insufficient seizure control, subsequent treatment phases with other target serum levels followed. The accompanying antiseizure medication (ASM) remained stable during the baseline phase and for at least the initial three treatment phases. We evaluated changes in seizure frequency and seizure-free days compared to baseline for each patient (Cox-Stuart-test). RESULTS: Fifteen patients were followed up for up to 10 years (minimum 0.6 years, median 5.8 years). Twelve patients (80%) experienced a significant reduction in seizure frequency or an increase in seizure-free days: Six (40%) patients became seizure-free and four patients (26.7%) remained seizure free for > 7 years, of which three required no additional ASM. All participants reported at least one adverse effect, the vast majority (92.5%) of which were mild or moderate. CONCLUSION: Long-term treatment with EVO was highly efficacious, safe and well tolerated. While EVO can be a therapeutic option for therapy-resistant epilepsy in TSC, it can take a long time for seizure relief to manifest.

Epilepsy associated with tuberous sclerosis complex in childhood: Long-term outcome in children after epilepsy surgery and children non-eligible for epilepsy surgery.

OBJECTIVE: Drug-resistant epilepsy is one of the major disease burdens in patients with tuberous sclerosis complex (TSC). Epilepsy surgery has been shown to be effective in TSC, but making a decision for surgery is often more complex than in other surgically amenable epilepsy syndromes and not all patients with TSC are eligible. We investigated long-term outcomes (after ≥one year; median, 6.4 years) with a special interest in general developmental level, health-related quality of life, parental concerns due to epilepsy, impact on family, and social adaptation in children who underwent epilepsy surgery and in children who were not eligible for surgery. METHODS: Eighty-five children (median age at intervention: 3.3 years, interquartile range [IQR]: 1.8-6.3 years) with TSC-related epilepsy had a presurgical investigation, and 34 of this group underwent epilepsy surgery. At follow-up (median age: 11.5 years, IQR: 7.8-15.5 years), we assessed seizure outcome, health-related quality of life, social adaptation, parental concerns due to epilepsy, and general developmental level based on established questionnaires and a standardized interview. Generalized linear models were performed for statistical evaluation. RESULTS: At follow-up, 53% (18/34) of the operated patients were seizure free for ≥12 months and 30% (15/50) of the patients non-eligible for epilepsy surgery (p = 0.037). In the surgical group, developmental level was significantly higher in seizure-free patients, in comparison to non-seizure-free patients (p = 0.004); this was also observed in the non-surgical group, but less marked (p = 0.089). Furthermore, developmental level was significantly (p ≤ 0.001) related to quality of life, social adaptation, impact on family, and parental concerns. In both cohorts, parental concerns were less pronounced if children became seizure free (p < 0.001 and p = 0.018, respectively). SIGNIFICANCE: In children with TSC-related epilepsy, quality of life, social adaptation, and impact on family were related to general developmental level, which in turn was significantly related to seizure freedom. Consequent epilepsy management aiming at seizure freedom, including presurgical evaluation and, if indicated, epilepsy surgery in a center specifically experienced with TSC-related epilepsy, is a worthwhile effort to improve quality of life in patients with TSC and their families.

Incidence, characteristics and risk factors for perioperative cardiac arrest and 30-day-mortality in preterm infants requiring non-cardiac surgery.

STUDY OBJECTIVE: To determine 30-day-mortality, incidence and characteristics of perioperative cardiac arrest as well as the respective independent risk factors in preterm infants undergoing non-cardiac surgery. DESIGN: Retrospective observational Follow-up-study. SETTING: Bielefeld University Hospital, a German tertiary care hospital. PATIENTS: Population of 229 preterm infants (age < 37th gestational week at the time of surgery) who underwent non-cardiac surgery between 01/2008-12/2018. MEASUREMENTS: Primary endpoint was overall 30-day-mortality. Secondary endpoints were the incidence of perioperative cardiac arrest and identification of independent risk factors. We performed univariate and multivariate analyses and calculated odds ratios (OR) for risk factors associated with these endpoints. MAIN RESULTS: 30-day-mortality was 10.9% and perioperative mortality 0.9%. Univariate risk factors for 30-day-mortality were perioperative cardiac arrest (OR,12.5;95%CI,3.1 to 50.3), comorbidities of lungs (OR,3.7;95%CI,1.2 to 11.3) and gastrointestinal tract (OR,3.5;95%CI,1.3 to 9.6); sepsis (OR,3.6;95%CI,1.4 to 9.5); surgery between 22:01-7:00 (OR,7.3;95%CI,2.4 to 21.7); emergency (OR,4.5;95%CI,1.6 to 12.4); pre-existing catecholamine therapy (OR,5.0;95%CI,2.1 to 11.9). Multivariate logistic regression indicated that perioperative cardiac arrest (OR,13.9;95%CI,2.7 to 71.3), low body weight (weight < 1000 g: OR,26.0;95%CI,3.2 to 212; 1000-1499 g: OR,10.3; 95%CI,1.1 to 94.9 compared to weight > 2000 g), and time of surgery (OR,5.9;95%CI,1.6 to 21.3) for 22:01-7:00 compared to 7:01-15:00) were the major independent risk factors of mortality. Incidence of perioperative cardiac arrests was 3.9% (9 of 229;95%CI,1.8 to 7.3). Univariate risk factors were congenital anomalies of the airways (OR,4.7;95%CI,1.2 to 20.3), lungs (OR,4.7;95%CI,1.2 to 20.3) and heart (OR,8.0;95%CI,2 to 32.2), pre-existing catecholamine therapy (OR,59.5;95%CI,3.4 to 1039), specifically, continuous infusions of epinephrine (OR,432;95%CI,43.2 to 4318). CONCLUSIONS: 30-day-mortality and the incidence of perioperative cardiac arrest of preterms undergoing non-cardiac surgery were higher than previously reported. The identified independent risk factors may improve interdisciplinary perioperative risk assessment, optimal preoperative stabilization and scheduling of optimal surgical timing.

Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome.

OBJECTIVE: To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions. METHODS: Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters. RESULTS: Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6-46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-D-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention. CONCLUSIONS: This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

Operative posterior disconnection in epilepsy surgery: Experience with 29 patients.

OBJECTIVE: It has been suggested that multilobar epilepsies caused by lesions restricted to the posterior cerebral quadrant (ie, the parietal, temporal, and occipital lobes) can be treated successfully by a procedure termed posterior disconnection. The objective of the present paper was to identify determinants of the epileptological outcome following posterior disconnection surgery. METHODS: The authors retrospectively analyzed a series of 29 consecutive patients undergoing posterior disconnection surgery between 2005 and 2017 for the treatment of refractory posterior quadrantic epilepsy. Specifically, all presurgical and postoperative magnetic resonance (MR) studies were reviewed to identify cases with an incomplete disconnection, or the presence of a more widespread pathology involving the whole hemisphere rather than only its posterior quadrant. In addition, we reevaluated all presurgical video-electroencephalography (EEG) reports. RESULTS: Seizure-free (International League Against Epilepsy [ILAE] 1) after surgery were 3/3 patients with EEG findings restricted to the posterior quadrant, 0/7 patients who had propagation of epileptic activity to the contralateral frontal lobe, and 11/19 (57.9%) who showed propagation to ipsilateral frontal and/or contralateral posterior. Eleven of 13 (84.6%) patients with purely posterior quadrantic magnetic resonance imaging (MRI) findings (as retrospectively diagnosed by neuroimaging) vs 3/16 (18.8%) cases with additional subtle abnormalities outside the posterior quadrant became seizure-free (P = .001). Eleven of 16 (68.8%) patients with complete disconnections were seizure-free vs only 3/13 (23.0%) cases with leftover temporal lobe tissue with contact to the insula (P = .025, both Fisher's exact test). SIGNIFICANCE: A posterior disconnection is a technically demanding but very effective operation for posterior quadrantic epilepsy. Good epileptologic outcomes require not only that the epileptogenic lesion does not extend beyond the confines of the disconnected cerebral volume but also the absence of subtle MRI abnormalities, more widespread than the clear-cut lesion of the posterior quadrant. Hemispheric or contralateral (particularly frontal) propagation of the epileptic activity may also indicate the presence of a hemispheric rather than posterior quadrantic pathology.

Differences in pediatric and adult epilepsy surgery: A comparison at one center from 1990 to 2014.

OBJECTIVE: Surgical volumes at large epilepsy centers are decreasing. Pediatric cohorts, however, show a trend toward more resections and superior outcome. Differences in pediatric and adult epilepsy surgery were investigated in our cohort. METHODS: The Bethel database between 1990 and 2014 was retrospectively analyzed. RESULTS: A total of 1916 adults and 1300 children underwent presurgical workup. The most common etiologies were medial temporal sclerosis (35.4%) in adults, and focal cortical dysplasias (21.1%) and diffuse hemispheric pathologies (14.7%) in children. Only 1.4% of the total cohort had normal histopathology. A total of 1357 adults (70.8%) and 751 children (57.8%) underwent resections. Surgery types for children were more diverse and showed a higher proportion of extratemporal resections (32.8%) and functional hemispherectomies (20.8%). Presurgical evaluations increased in both groups; surgical numbers remained stable for children, but decreased in the adult group from 2007 on. The patients' decision against surgery in the adult nonoperated cohort increased over time (total = 44.9%, 27.4% in 1995-1998 up to 53.2% in 2011-2014; for comparison, in children, total = 22.1%, stable over time). Postsurgical follow-up data were available for 1305 adults (96.2%) and 690 children (91.9%) 24 months after surgery. The seizure freedom rate was significantly higher in children than in adults (57.8% vs 47.5%, P < 0.001) and significantly improved over time (P = 0.016). SIGNIFICANCE: Pediatric epilepsy surgery has stable surgical volumes and renders more patients seizure-free than epilepsy surgery in adults. A relative decrease in hippocampal sclerosis, the traditional substrate of epilepsy surgery, changes the focus of epilepsy surgery toward other pathologies.

Characteristics and healthcare situation of adult patients with tuberous sclerosis complex in German epilepsy centers.

OBJECTIVE: The objective of the present study was to collect systematic data on the care of adult patients with tuberous sclerosis complex (TSC) in German epilepsy centers, to describe the characteristics of patients in this age group, and to clarify whether and how the recommended interdisciplinary care is implemented. METHODS: This retrospective survey involved 12 major epilepsy centers in Germany. Aggregated data were collected based on an electronic questionnaire that addressed the sociodemographic data, characteristics of the epilepsy syndromes, and general healthcare setting of adult patients with TSC. RESULTS: The survey included 262 patients (mean age: 36.2±9.0years) with TSC, most of whom were reported to live in either a home for persons with a disability (37.0%), a residential care home (6.9%), or with their parents (31.1%). A further 13.0% were self-sustaining, and 8.8% were living with a partner. Most patients presented with focal (49.6%) or multifocal (33.2%) epilepsy, with complex partial, dialeptic, and automotor seizures in 66% of patients and generalized tonic-clonic seizures in 63%. Drug-refractory epilepsy was seen in 78.2% of patients, and 17.6% were seizure-free at the time of the survey. Of the 262 patients, presurgical diagnostics were performed in 27% and epilepsy surgery in 9%, which rendered 50% of these patients seizure-free. Renal screening had been performed in 56.1% within the last three years and was scheduled to be performed in 58.0%. Cases of renal angiomyolipoma were present in 46.9% of the patients. Dermatologic and pulmonary screenings were known to be planned for only few patients. CONCLUSION: Despite TSC being a multisystem disorder causing considerable impairment, every fifth adult patient is self-sustaining or living with a partner. In clinical practice, uncontrolled epilepsy and renal angiomyolipoma are of major importance in adult patients with TSC. Most patients suffer from focal or multifocal epilepsy, but epilepsy surgery is performed in less than 10% of these patients. Interdisciplinary TSC centers may help to optimize the management of patients with TSC regardless of age and ensure early and adequate treatment that also considers the advances in new therapeutic options.

Psychiatric lifetime diagnoses are associated with a reduced chance of seizure freedom after temporal lobe surgery.

OBJECTIVE: To examine whether psychiatric comorbidity is a predictor of long-term seizure outcome following temporal lobe epilepsy surgery. METHODS: A sample of 434 adult patients who received temporal lobe resection to treat epilepsy between 1991 and 2009 and were psychiatrically assessed before surgery were followed for 2 years to assess seizure outcome. Stepwise multivariate logistic regression analyses were used to assess the impact of psychiatric variables on complete seizure freedom (Engel class IA), and freedom from disabling seizures (Engel class I). Lifetime histories of three psychiatric syndromes (PS: psychosis; depression; other) and five personality disorders (PD: DSM-IV Clusters A, B, and C; organic personality disorder; other) were considered as predictors, complemented by age at onset, duration of epilepsy, type of lesion (mesiotemporal sclerosis vs. other), and year of surgery. RESULTS: Seizure-freedom rates were significantly higher (p < 0.001) in patients with no history of PS or PD (N = 138; Engel class IA: 61.6%; Engel class I: 87.7%) than in those with any PS or PD (N = 296; Engel class IA: 39.5%; Engel class I: 58.8%). Particularly low seizure-freedom rates were found in patients with a diagnosis of psychosis (N = 32, Engel class IA: 21.9%; Engel class I: 40.6%), organic PD (N = 48, Engel class IA: 25.0%; Engel class I: 35.4%) or a double diagnosis of PS plus PD (N = 97; Engel class IA: 27.8%; Engel class I: 45.5%). No other variables emerged as significant risk factors in multivariate logistic regression analyses. SIGNIFICANCE: Patients with and without psychiatric comorbidities can benefit from temporal lobe epilepsy surgery; however, psychiatric comorbidities are negatively associated with postoperative seizure-freedom rates. Surgical outcome is related to the type and extent of preoperative psychiatric morbidity, which underscores the prognostic value of presurgical psychiatric evaluation. The data support the argument that there are common pathogenetic mechanisms underlying both epilepsy and psychiatric conditions.

Trends in epilepsy surgery: stable surgical numbers despite increasing presurgical volumes.

INTRODUCTION: Despite the success of epilepsy surgery, recent reports suggest a decline in surgical numbers. We tested these trends in our cohort to elucidate potential reasons. PATIENTS AND METHODS: Presurgical, surgical and postsurgical data of all patients undergoing presurgical evaluation in between 1990 and 2013 were retrospectively analysed. Patients were grouped according to the underlying pathology. RESULTS: A total of 3060 patients were presurgically studied, and resective surgery was performed in 66.8% (n=2044) of them: medial temporal sclerosis (MTS): n=675, 33.0%; benign tumour (BT): n=408, 20.0%; and focal cortical dysplasia (FCD): n=284, 13.9%. Of these, 1929 patients (94.4%) had a follow-up of 2 years, and 50.8% were completely seizure free (Engel IA). Seizure freedom rate slightly improved over time. Presurgical evaluations continuously increased, whereas surgical interventions did not. Numbers for MTS, BT and temporal lobe resections decreased since 2009. The number of non-lesional patients and the need for intracranial recordings increased. More evaluated patients did not undergo surgery (more than 50% in 2010-2013) because patients were not suitable (mainly due to missing hypothesis: 4.5% in 1990-1993 up to 21.1% in 2010-2013, total 13.4%) or declined from surgery (maximum 21.0% in 2010-2013, total 10.9%). One potential reason may be that increasingly detailed information on chances and risks were given over time. CONCLUSIONS: The increasing volume of the presurgical programme largely compensates for decreasing numbers of surgically remediable syndromes and a growing rate of informed choice against epilepsy surgery. Although comprehensive diagnostic evaluation is offered to a larger group of epilepsy patients, surgical numbers remain stable.

Validation of rapid suicidality screening in epilepsy using the NDDIE.

OBJECTIVE: Standard mortality ratio for suicide in patients with epilepsy is three times higher than in the general population, and such a risk remains high even after adjusting for clinical and socioeconomic factors. It is thus important to have suitable screening instruments and to implement care pathways for suicide prevention in every epilepsy center. The aim of this study is to validate the use of the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) as a suicidality-screening instrument. METHODS: The study sample included adult patients with epilepsy assessed with the Mini International Neuropsychiatric Interview (MINI) and the NDDIE. A high suicidality risk according to the Suicidality Module of the MINI was considered the gold standard. Receiver operating characteristic analyses for NDDIE total and individual item scores were computed and subsequently compared using a nonparametric approach. The best possible cutoff was identified with the highest Youden index (J). Likelihood ratios were then computed, and specificity, sensitivity, positive, and negative predictive values calculated. RESULTS: The study sample consisted of 380 adult patients with epilepsy: 46.3% male; mean age was 39.4 ± 14.6; 76.7% had a diagnosis of focal epilepsy; mean age at onset of the epilepsy was 23.3 ± 17.5. According to the MINI, 74 patients (19.5%) fulfilled criteria for a major depressive episode and 19 (5%) presented a high suicidality risk. A score >2 (J = 0.751) for item 4 "I'd be better off dead" of the NDDIE displayed excellent psychometric properties with a good to excellent validity (area under the curve [AUC] 0.906; 95% confidence interval [CI] 0.820-0.992; p < 0.001), sensitivity 84.21% (95% CI 60.4-96.6), specificity 90.86% (95% CI 87.4-93.6), likelihood ratio+ 9.21 (95% CI 6.3-13.5), likelihood ratio- 0.17 (95% CI 0.06-0.50). SIGNIFICANCE: Item 4 of the NDDIE has shown to be an excellent suicidality screening instrument allowing the development of further care pathways for suicide prevention in epilepsy centers.

Effects of an inpatient rehabilitation program after temporal lobe epilepsy surgery and other factors on employment 2 years after epilepsy surgery.

OBJECTIVE: To evaluate the effects of a postsurgical rehabilitation program on employment status 2 years after temporal lobe epilepsy surgery in relation to other predictors. METHODS: Employment outcome 2 years after temporal lobe resection in a group of 232 adult patients with the offer of a 3-week inpatient rehabilitation program immediately after surgery ("Reha group") was compared to a group of 119 patients who had surgery before such a rehabilitation program existed. One hundred thirty-nine (59.9%) of the Reha group patients attended the rehabilitation program. Further predictors for employment outcome were analyzed using multivariate logistic regression analysis. RESULTS: Preoperatively, the groups did not differ significantly in variables relevant for employment, including employment rate. Two years after surgery, the rate of those not being employed had decreased in the Reha group from 38.4% to 27.6% (p < 0.001, McNemar test), and slightly increased in the control group (37.8-42.0%; n.s.), resulting in a difference of 14.4% in favor of the Reha group (p = 0.008). General unemployment rates during the two observation periods were similar. In addition to the offer of rehabilitation support ("Reha group") and preoperative employment, the following other variables were shown as significant predictors of employment post surgery in multivariate regression analysis: seizure outcome, diagnosis of a personality disorder preoperatively, and age at surgery (all, p < 0.01; Nagelkerkes R(2) = 0.59). SIGNIFICANCE: Independently from other factors, a 3-week inpatient rehabilitation program after temporal lobe epilepsy surgery seems to improve employment status 2 years after surgery.

Everolimus in tuberous sclerosis patients with intractable epilepsy: a treatment option?

BACKGROUND: Tuberous Sclerosis Complex (TSC) is an often severe neurodevelopmental disorder caused by overactivation of the mTOR pathway due to mutations in either the TSC1 or TSC2 genes. Seizures are the primary cause of neurologic morbidity and often refractory. The mTOR inhibitor everolimus was recently approved for the treatment of giant cell astrocytomas and renal angiomyolipomas in TSC. Whether everolimus has any direct effect on epilepsy in TSC is not known. METHODS: Within the framework of a compassionate use trial, we evaluated the safety and efficacy of everolimus in seven patients with TSC and intractable epilepsy. We evaluated seizure frequency, seizure-free days and adverse effects including standard laboratory parameters. Seizure frequency was analysed in each patient using a non-parametric test for trend and using a Generalized Estimating Equations Model in the total patient group. The observation period was continued for nine months. RESULTS: One patient discontinued the medication at the beginning of the observation period due to side effects (flushing). In the remaining 6 patients, we observed a reduction of seizures in 4/6 patients with a reduction of 25-100%. In addition, the percentage of seizure-free days increased in 3/4 of these patients. In 2/6 patients, no alteration of seizure frequency was noted. We observed an increase of mild infections and an increase of triglycerides and various liver function tests. We did not encounter life-threatening infections or other side effects of everolimus. INTERPRETATION: In some patients with TSC, everolimus may have an anticonvulsant effect with a reduction in seizure frequency and increase of seizure-free days. Everolimus was well tolerated, with adverse effects similar to those reported in previous studies.

Determinants of quality of life in patients with refractory focal epilepsy who were not eligible for surgery or who rejected surgery.

UNLABELLED: The aim of the study was to assess the determinants of quality of life (QOL) in adult patients with refractory focal epilepsy who were not eligible for surgery or who rejected surgery after presurgical evaluation. The QOLIE-31, the Hospital Anxiety and Depression Scale and PESOS questionnaire were mailed in 2009 to all adult patients who had been evaluated for suitability for epilepsy surgery between 2001 and 2007 in the Bethel Epilepsy Center and had been deemed not eligible for surgery or had decided against surgery. Questionnaires were sent by post to 359 patients: 172 (47.9%) replied, and of these, 125 patients were eligible for this study. The remaining 47 patients were excluded mainly because they did not fulfill the criteria of refractory epilepsy. Out of the included 125 patients, 106 were considered to be poor surgical candidates for medical reasons, and 19 had decided against surgery. The mean follow-up was 4.1±2.1 years. In the past 6 months, 13.9% of the patients were seizure free, 12 of them (9.6%) were seizure free for one year, 10.7% had 1-2 seizures, 11.5% had 3-5 seizures, 27.0% had one or more seizures a month, 23.0% had one or more seizures a week, and 13.9% had one or more seizures a day. Patient-perceived changes in their seizures since presurgical evaluation were rated by 15.6% of the patients as 'improved significantly', by 28.7% as 'improved', by 46.7% as 'no change', by 6.6% as 'deteriorated' and by 2.5% as 'significantly deteriorated'. Quality of life in patients with refractory epilepsy was much lower compared to operated patients from our center. Multivariate analysis of QOL showed that depression and anxiety are strong predictors but not exclusively. Furthermore, tolerability and efficacy of AEDs are significant predictors of most QOLIE-31 subscales. Employment, seizure frequency, patient-perceived change in their seizures, number of AEDs and the degree of comorbidity appeared as predictors for some aspects of QOL as well. When excluding anxiety and depression, the most important predictors of QOL were tolerability of AEDs and employment. For other aspects of QOL, efficacy of AEDs, gender, number of AEDs, degree of comorbidity and a certificate of disability were additional predictors. The results of the multivariate analysis did not essentially change when seizure-free patients were excluded. CONCLUSION: Quality of life in non-operated patients with refractory epilepsy is significantly lower than in operated patients from the same center. Besides depression and anxiety, patient-rated tolerability and efficacy of AEDs, seizure frequency and employment are the main determinants of QOL.

Retention rate of pregabalin in drug-resistant epilepsy: 1-year follow-up, single-centre observation in 105 consecutive, adult patients.

OBJECTIVES: Pregabalin (PGB) is a newer antiepileptic drug (AED) licensed as add-on treatment for partial epilepsy in adults. Efficacy and safety have been proven in several controlled clinical studies. These trials, however, only partially reflect clinical practice. Retention rate has been established as a marker for efficacy and safety of AEDs in long-term follow-up studies. METHODS: We evaluated the data of the first 105 patients treated with PGB at Bethel Epilepsy Centre, a tertiary referral centre for epilepsy. The patients were interviewed after 3, 6 and 12 months. RESULTS: 105 adult patients (aged 38+/-13 years) were treated with PGB, on average in combination with 2.1 AEDs (mean observation period 232 days). 76.2% had focal epilepsy, 19.0 multifocal epilepsy, and 3.8% epilepsy with both focal and generalised seizures. 40% continued PGB with the following outcome: 5.7% seizure-free for at least 1 month (4.8% for at least 3 months, 2.4% for at least 6 months; one of the seizure-free patients, however, had had epilepsy surgery during the observational period), 17.1% responders (> or =50% reduction of seizure frequency but not seizure-free), 13.3% with unchanged or increased seizure frequency. Reasons for withdrawal were lack of efficacy (47.6%) or side-effects (12.7%). CONCLUSIONS: PGB is a new therapeutic option as add-on therapy for patients with highly refractory focal epilepsies although the therapeutic success that can be expected in this group of patients is limited.