Risk of Seizure Recurrence Due to Autoimmune Encephalitis With NMDAR, LGI1, CASPR2, and GABABR Antibodies: Implications for Return to Driving.

BACKGROUND AND OBJECTIVES: Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABABR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months. This would render them eligible for noncommercial driving according to driving regulations in several countries. METHODS: This retrospective multicenter cohort study analyzed follow-up data from patients aged 15 years or older with seizures resulting from NMDAR-, LGI1-, CASPR2-, or GABABR-AIE, who had been seizure-free for ≥3 months. We used Kaplan-Meier (KM) estimates for the seizure recurrence risk at 12 months for each antibody group and tested for the effects of potential covariates with regression models. RESULTS: We included 383 patients with NMDAR-, 440 with LGI1-, 114 with CASPR2-, and 44 with GABABR-AIE from 14 international centers. After being seizure-free for 3 months after an initial seizure period, we calculated the probability of remaining seizure-free for another 12 months (KM estimate) as 0.89 (95% confidence interval [CI] 0.85-0.92) for NMDAR, 0.84 (CI 0.80-0.88) for LGI1, 0.82 (CI 0.75-0.90) for CASPR2, and 0.76 (CI 0.62-0.93) for GABABR. DISCUSSION: Taking a <20% recurrence risk within 12 months as sufficient, patients with NMDAR-AIE and LGI1-AIE could be considered eligible for noncommercial driving after having been seizure-free for 3 months.

Rehabilitation in patients with newly diagnosed epilepsy: A controlled, 1-year follow-up study on a specialized inpatient rehabilitation program.

OBJECTIVES: To evaluate the efficacy of a specialized inpatient rehabilitation program in patients with newly diagnosed epilepsy (NDE), who had been referred within 1 year after diagnosis. METHODS: We performed an open, prospective, controlled study comparing a 1-year follow-up assessment of patients with NDE after completing a rehabilitation program at an epilepsy center (rehabilitation group) with a control group of patients with similar epilepsy duration, but without rehabilitation in the first year after diagnosis. Primary outcome measures comprised emotional adaptation to epilepsy, depression and anxiety; and secondary outcome measures were overall quality of life (QoL), overall health, perceived restrictions because of epilepsy, level of information about epilepsy, and employment status. RESULTS: Comparison of the admission data of 74 rehabilitation group patients (mean age and SD 47.7 ± 13.0 years) with the pre-rehabilitation assessment of 56 control patients (45.5 ± 12.1 years) revealed no significant differences concerning sociodemographic and health data. Comparison of the follow-up assessment of the rehabilitation group and the pre-rehabilitation assessment of the control group showed significantly better values for the rehabilitation group on emotional adaptation to epilepsy (p = .003), overall QoL (p = .006) and overall health (p = .011), perceived restrictions because of epilepsy, and subjective level of information about epilepsy (both p's < .001). There were no statistically significant differences concerning depression and anxiety or employment status (all p's > .50). One year after rehabilitation, patients in the rehabilitation group were more often seizure-free and less often on sickness absence than control group patients (both p's < .001). SIGNIFICANCE: Since reduced QoL shortly after diagnosis of NDE is associated with seizure recurrence, an early identification of patients with a greater need for support seems important. This epilepsy-related rehabilitation program showed lasting effects on several aspects of adaptation to epilepsy and QoL.

Efficacy of a specialized inpatient rehabilitation program in patients with early versus chronic epilepsy.

OBJECTIVE: To evaluate the efficacy of a specialized inpatient rehabilitation program in patients with early in comparison with chronic epilepsy. METHODS: We performed a prospective, open pre/post study using a parallel group design. Patients with early epilepsy (EE, treatment with anti-seizure medication [ASM] ≤ 1 year) or with chronic epilepsy (CE, ASM treatment > 5 years) completed questionnaires at the time of their admission to the rehabilitation program and at discharge. Outcome measures comprised scales from the PESOS questionnaire (PErformance, SOciodemographic aspects, Subjective estimation; e.g., emotional adaptation to epilepsy) as well as screening instruments for depression (Neurological Disorders Depression Inventory for Epilepsy, NDDI-E) and anxiety (Generalized Anxiety Disorder Scale, GAD-7). Linear mixed models (LMMs) were used to determine the effects of the program in the total group and to compare the effects between patients with EE and CE. RESULTS: The analyses included 79 patients with EE and 157 patients with CE. Baseline comparisons revealed differences in disease-related and sociodemographic variables (e.g., patients with EE were older, those with CE had a higher seizure frequency and a higher rate of unemployment; all p < .01). LMMs showed significant improvements in emotional adaptation to epilepsy, depression, anxiety, overall quality of life and overall health as well as in perceived overall restrictions because of epilepsy and the subjective level of information about epilepsy (all p < .001). Despite the different duration of epilepsy, baseline levels as well as improvements did not differ between patients with EE and CE (all p > .05) except for the perceived level of information, which was significantly lower in patients with EE at admission and improved to a higher extent in this group (both p < .001). CONCLUSION: Both patients with EE and patients with CE who are referred to a specialized comprehensive rehabilitation program benefit from the participation in this program with respect to emotional adaptation to epilepsy, aspects of quality of life, and level of information about epilepsy.

Driving eligibility: Implications of studies on seizure recurrence risk.

BACKGROUND: Driving is one of the most important issues for patients with seizures. The 2009 European directive provides a framework for evaluating standard situations in assessing the ability to drive. Such a framework may not be sufficient for individual scenarios. AIMS OF THE STUDY: To analyse current data on seizure recurrence risks (RcRs) focusing on their potential implications for car driving issues (group 1). METHODS: We evaluated current studies and meta-analyses on RcR. RESULTS: A meta-analysis of seizure-free patients who withdrew their medication (Lamberink et al Lancet Neurology 2017;16:523) created a nomogram and a web-based tool that allow estimating RcR in individual patients and thus to identify those in whom medication withdrawal is possible without the common driving ban during withdrawal. The 2-year prediction model of that meta-analysis has been recently externally tested and confirmed. A meta-analysis of patients with a first unprovoked seizure (Bonnett et al PloS ONE 2014;9:e99063) determined to which extent RcRs depend on established risk factors. The seizure-free period required to restart driving could be tailored according to the individual RcR. CONCLUSION: These current studies allow estimating individual RcR more precisely and thus modifying periods of driving bans beyond the existing guidelines.

Genetic generalized epilepsies with frontal lesions mimicking migratory disorders on the epilepsy monitoring unit.

OBJECTIVE: Some patients with genetic generalized epilepsy (GGE) may present with ambiguous and atypical findings and even focal brain abnormalities. Correct diagnosis may therefore be difficult. METHODS: We retrospectively collected six patients investigated on the epilepsy monitoring unit with MRI abnormalities mimicking focal cortical dysplasia (FCD-like) or heterotopias, but with semiology and EEG features of GGE. We compared them to four additional patients with GGE and nonmigratory abnormalities. RESULTS: All six patients presented with frontal MRI lesions: radial ("transmantle," n = 4), cortical-subcortical (n = 1), and periventricular heterotopia (n = 1). Five had positive family histories. Semiologic lateralizing signs compatible with the lesion were seen in four. Five patients had 3/s spike-wave complexes, with an asymmetric appearance in three. Regional EEG changes matched with the side of the abnormality in three patients. Invasive EEG (n = 2) or postoperative outcomes (n = 3) argued against an ictogenic role of the MRI abnormalities. Histology showed mild malformation of cortical development, but no focal cortical dysplasia. The six patients were finally diagnosed with juvenile myoclonic epilepsy (n = 2), juvenile absence epilepsy (n = 2), or GGE not further specified (nfs, n = 2). Compared to these patients, the other four (final diagnoses: childhood absence epilepsy, n = 1; perioral myoclonia with absences, n = 1; and GGE nfs, n = 2) had no lateralizing EEG findings. SIGNIFICANCE: Patients with GGE may have coincidental MRI abnormalities. These cases are challenging as frontal epilepsy and GGE can present with similar semiologies. GGE with coincidental FCD-like lesions/heterotopias is in particular difficult to diagnose as patients have more lateralizing features (in semiology and EEG) than those with tumors. A detailed noninvasive presurgical evaluation may be justified. We point out red flags that may help to distinguish GGE from frontal epilepsy, even in the presence of brain abnormalities: 3/s spike waves (even if asymmetric), changing lateralizing signs at different times, and a positive family history hinting at GGE.

Patients' perspectives on management and barriers of regular antiepileptic drug intake.

PURPOSE: The aim of our study was to assess the management of drug intake and potential barriers to adherence reported by two different patient groups. METHODS: The study was performed in cooperation with the Regional Chamber of Pharmacists of Rhineland-Palatinate and three neurologists in private practice specialized in epileptology. In total, 108 patients surveyed in 43 pharmacies (Group P) and 118 patients treated by the specialized neurologists (Group N) completed anonymously a questionnaire on intake of antiepileptic drugs (AEDs). The statistical evaluation was performed using nonparametric tests and logistic regression analyses. RESULTS: Group N more often used adherence aids, compared with Group P (68.6% vs. 46.3%, p<0.01), and the number of doses per day was significantly lower in Group N (Mann-Whitney test, p=0.046), but the percentage of patients who reported problems with the regular intake of their medication did not differ significantly between groups (Group N vs. P: 47.0% vs. 40.0%). If patients noticed that they missed a dose, 45.3% completely skipped the missed dose (Group N vs. P: 43.0% vs. 48.1%, n.s.). In a multivariate analysis, significant risk factors of problems with regular drug intake were age<25yrs. (p<0.01) and patient-reported adverse effect of AED (p<0.01), followed by the number of AED doses per day (p<0.05), while gender, intake habits, usage of adherence aids, and patient-rated efficacy of AEDs were not significant. CONCLUSION: Patients treated by neurologists specialized in epileptology did not report less problems with adherence than patients surveyed in pharmacies. Since barriers for a regular intake are diverse, the use of a short questionnaire on management of drug intake may lead to an individually tailored counseling of patients to improve adherence.

Risk factors for early disability pension in patients with epilepsy and vocational difficulties - Data from a specialized rehabilitation unit.

PURPOSE: The purpose of this study was to assess the risk factors for early disability pension (EDP) in adult patients with epilepsy in a specialized epilepsy rehabilitation setting. METHODS: In a retrospective study, 246 patients with epilepsy and employment difficulties leading to referral to an inpatient rehabilitation unit were evaluated with a questionnaire on admission and after a mean of 2.5years after discharge. Patients already receiving EDP at baseline were excluded. Epilepsy-related, demographic, and employment-related data as well as cognitive functioning and psychiatric comorbidity were assessed as risk factors for EDP at follow-up and analyzed using logistic regression models. RESULTS: Seventy-six percent of the patients had uncontrolled epilepsy, and 66.7% had psychiatric comorbidity. At follow-up, 33.7% received an EDP. According to multivariate logistic regression analysis, age>50years (odds ratio (OR) 5.44, compared to age<30years), application for an EDP prior to admission (OR 3.7), sickness absence>3months in the previous year (OR 3.30, compared to sickness absence<3months), and psychiatric comorbidity (OR 2.79) were significant risk factors for an EDP at follow-up, while epilepsy-related factors and cognitive impairment showed an effect only in the univariate analyses. CONCLUSIONS: Potential risk factors for EDP in patients with epilepsy were evaluated using multivariate analysis. Knowledge of such factors may help to develop appropriate criteria for rehabilitation candidacy and interventions to reduce the risk for EDP. This might lead to an amelioration of both psychosocial burden of patients and economic burden on society.

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.

Should patients with psychogenic nonepileptic seizures be allowed to drive? Recommendations of German experts.

In the absence of evidence-based regulations on the driving ability of patients with psychogenic nonepileptic seizures (PNES), we asked 41 German epileptologists via e-mail for their recommendations on driving with PNES. This survey was modeled on an earlier study by Benbadis et al. in the United States and was compared with it. Thirty-four (82.9%) epileptologists responded. Three responses were possible: (A) same restrictions as stipulated for patients with epilepsy, answered by 11 epileptologists (32.4%); (B) no restrictions at all, which no German expert gave as an answer (0%); (C) decision on an individual basis, answered by 23 experts (67.6%). The divergent approaches reflect the poor data on motor vehicle accidents of patients with PNES and the great variability of PNES with respect to semiology, psychiatric morbidity, and prognosis. In the study by Benbadis et al., 49% chose A, 32% B, and 19% C. The considerable national differences may be explained by differences between the two countries with respect to driving regulations and cultural aspects.

Valproic acid-induced hepatopathy: nine new fatalities in Germany from 1994 to 2003.

PURPOSE: Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for generalized and focal epilepsies. We provide an update on hepatotoxic side effects in Germany between 1994 and 2003. METHODS: We mailed a questionnaire to all members of the German Section of the International League Against Epilepsy, asking for VPA-induced side effects, especially severe side effects such as hepatopathy. RESULTS: As a result of our questionnaire, we found 31 cases of reversible hepatotoxicity and nine cases of lethal hepatopathies in Germany from 1994 to 2003. CONCLUSIONS: The outcome of patients with severe hepatotoxicity is better than that in the past. The risk of a VPA-induced hepatopathy is not limited to patients younger than 2 years, receiving polytherapy, or patients with congenital or acquired metabolic diseases.