Diagnostic Value of Intermittent Photic Stimulation Among Adult Patients in a Tertiary Referral Epilepsy Center: A Retrospective Study.

PURPOSE: Photosensitivity is a phenomenon that may be elicited by standardized intermittent photic stimulation during EEG recording and is detected more frequently in children and adolescents. Nevertheless, at our Epilepsy Center, we routinely assess photosensitivity in all newly referred adult patients. In this investigation, we sought to address the diagnostic yield under the prerequisites described. METHODS: We reanalyzed all routine EEG recordings among referrals to the department of adults during the first six months of 2019, including a simultaneous video that is always coregistered in our center. The prevalence of abnormal findings during photic stimulation was assessed. RESULTS: Intermittent photic stimulation was performed on 344 patients. Photoparoxysmal response were detected in five subjects (1.5%). All patients were female. Four patients were diagnosed with idiopathic generalized epilepsy, and one with Doose syndrome. Photomyogenic responses were recorded in 1.1% and only in patients with psychogenic nonepileptic seizures. In two subjects with psychogenic nonepileptic seizures, the typical seizure was provoked by intermittent photic stimulation (8.7% of all subjects with psychogenic nonepileptic seizures in this cohort). Photoparoxysmal response was not detected in any subject with focal epilepsy, syncope, or other nonepileptic paroxysmal events. In every case of photoparoxysmal responses, increased photosensitivity had already been reported before recording. CONCLUSIONS: In our study, photoparoxysmal responses was a rare phenomenon among adults with a preponderance of females and idiopathic generalized epilepsies. Intermittent photic stimulation may be helpful in provoking typical psychogenic nonepileptic seizures and thus abbreviate the diagnostic process. Provided a careful history, routine intermittent photic stimulation in adults with epilepsy does not appear to be mandatory.

Everolimus in adult tuberous sclerosis complex patients with epilepsy: Too late for success? A retrospective study.

OBJECTIVE: There is evidence that everolimus (EVE) significantly reduces seizure frequency in epilepsy patients with tuberous sclerosis complex (TSC). Given that TSC-related proliferative processes are more dynamic during brain development, seizure outcomes of patients treated with EVE may be age-related and may be less convincing in adult patients. The aim of this study was to assess the effectiveness and the safety profile of EVE in adults in clinical practice. METHODS: We performed a multicenter retrospective chart review of TSC subjects with active epilepsy who started EVE in adulthood (≥18 years of age) at seven German epilepsy centers. The primary endpoint was the retention rate after 6 months. RESULTS: A total of 45 subjects with a mean age of 31.6 ± 11.1 years at EVE start fulfilled the inclusion criteria. Retention rate after 6 months was 98% (43/44 evaluable subjects). Response rate (seizure reduction ≥ 50%) was 33% (14/43 evaluable subjects; four completely seizure-free). We did not find a significant relationship between epilepsy outcome parameters and patient age at EVE start. Adverse events were reported in 19 subjects and were judged to be serious in six patients. Three patients died during the observation period. SIGNIFICANCE: Evidence suggests that EVE is an effective add-on treatment for epilepsy in adult TSC patients, surprisingly without any age limit to individual benefit. A strong age-dependent effect within the period of adulthood seems unlikely. Even if there was no proof of a causal relationship between deaths and EVE intake, patients with EVE should be carefully monitored, especially for infections and stomatitis.

Clinical experience of abrupt discontinuation of perampanel: a case series.

With an elimination half-life of 105 hours, perampanel (PER) allows a once-daily dosing regimen. In pivotal trials, when PER was tapered, it was therefore usually discontinued abruptly. Thus, in our hospital we have always practiced abrupt cessation. In this case series, we investigated how long PER serum concentrations still remain measurable after abrupt discontinuation of PER and whether withdrawal symptoms, such as an increase in seizures or status epilepticus, occur. PER serum levels and the clinical course of 15 adult in-patients were monitored for three weeks based on a retrospective study design following abrupt discontinuation of PER. After one week, PER was still detected in 13 of 15 patients, after two weeks in 10, and after three weeks in three. Neither a severe increase in seizure frequency nor status epilepticus occurred. However, modifications of the concomitant antiseizure drugs were necessary. The abrupt discontinuation of PER leads to a slow decrease in plasma concentration, thus resembling self-evident gradual discontinuation of PER. In some cases, PER may still be measurable and thus clinically active even weeks after its discontinuation. Efficacy and safety of other antiseizure drugs can be estimated appropriately only thereafter.

Visual illustration supporting patient-physician communication in epilepsy: A validation and reliability study of seizure images.

Seizure manifestations may be difficult to describe in words alone. Thus, initially, 24 seizure images were developed to support communication and gain assistance during obtaining the patient's history. Before being used in clinical practice, these seizure images must be investigated for validity and reliability. We tested the images with untrained participants including patients with epilepsy, persons who had witnessed seizures, and participants who had neither had nor witnessed epileptic seizures. The participants filled in a questionnaire evaluating the images twice within 3 days. The participants were asked to choose one of the 2 written descriptions that best matched each seizure image. The validity was assessed using one-proportion z-test. The reliability was assessed by Gwet's AC1. The first analysis showed that the proportion of correctly identified seizure images was higher than 70%, except for 2 images representing dystonia and myoclonus. The dystonia image was modified, and the myoclonus image was removed. In the final evaluation, the seizure images were identified with an overall correctness ratio of 96%. The final AC1 of the seizure images was classified as very high. The final 23 seizure images are proved to be valid and have a high agreement that can be used in clinical practice.

Is brivaracetam-induced elevation of carbamazepine-epoxide levels common and clinically relevant? - A case series.

Brivaracetam (BRV) was recently introduced for the treatment of patients with focal epilepsy. BRV undergoes relatively few interactions, but one of them leads to the elevation of carbamazepine (CBZ)-10,11-CBZ-epoxide (CBZ-E) if BRV is co-administered with CBZ. This interaction has been considered to be clinically negligible. We present a case series of nine patients. In eight of them, levetiracetam (LEV) was switched to BRV. In the remaining case, oxcarbazepine was replaced by CBZ and added to a stable BRV dose. A marked increase of CBZ-E occurred in every case and was associated with clinically relevant symptoms including blurred vision, diplopia, dizziness, or fatigue in three of them. However, in the remaining six, the elevated CBZ-E levels were not associated with any tolerability problems. The importance of CBZ-E for adverse events under CBZ may have been overemphasized in the past and is not clinically impairing in most cases treated with the combination of BRV and CBZ.

Antiepileptic drugs-induced hyponatremia: Review and analysis of 560 hospitalized patients.

Recent evidence suggests that eslicarbazepine acetate (ESL) might be an appropriate alternative to carbamazepine (CBZ) and oxcarbazepine (OXC) due to its better safety profile. Hyponatremia may be one of the limiting safety problems in CBZ and OXC whereas it has been indicated that ESL is less sensitive for the adverse event. Since our clinical experience is different we investigated the incidence of hyponatremia in 560 consecutive adult inpatients treated at our center in 2015 by reviewing their medical records. Only CBZ, OXC and ESL were associated with hyponatremia. The incidence of hyponatremia induced by ESL was not statistically different from that induced by OXC (43% of patients with OXC and 33% with ESL, p > 0.05). Both were associated with hyponatremia more often than CBZ (16%). OXC-induced hyponatremia was dose-related, ESL-induced hyponatremia was not. Furthermore, both OXC- and ESL-induced hyponatremia occurred particularly often in elderly epilepsy patients. Thus, for elderly patients, both OXC and ESL should be considered with caution.

Real-life experience with brivaracetam in 101 patients with difficult-to-treat epilepsy-A monocenter survey.

PURPOSE: To assess the efficiency of brivaracetam under real-world conditions in a tertiary referral epilepsy center. METHODS: We consecutively collected patients treated at our center with brivaracetam (BRV). After a minimum observation period of six months we retrospectively analyzed the efficiency of BRV. RESULTS: Data of 101 patients (mean age 42 years, range 18-81 years, 54 females,) were analyzed. The median number of antiepileptic drugs (AEDs) used prior to BRV was 10 (range 2-18). The initial dose of BRV was at least 50mg per day, the mean maintenance dose at cut-off was 168.6mg (median 200mg, range 50-400mg). Efficacy data were assessed for the last three months or at the time of the last observation carried forward if BRV had been discontinued prematurely. Responder rate was 27.8% (n=28) with 7% seizure-free patients. Adverse events (AEs) occurred in 37 patients (37%). Most frequent AEs were dizziness (16%) and somnolence (11%). Psychiatric adverse events comprised irritability, aggression, depression and psychosis in single cases. Retention rate after six months was 51.5%. Main reason for discontinuation was a lack of efficacy. In 43 cases LEV and BRV were switched. The switch was performed abruptly without complications. In 26 cases (60%) BRV was discontinued and re-switched to LEV within weeks, mainly due to a lack of better efficacy. After the switch from LEV to BRV we even saw an aggravation both of seizure frequency and severity in 5 cases. Retention rate in patients who had not been on LEV was 57%. CONCLUSION: In our hands BRV appeared to be well tolerated and easy to handle. The retention rate was influenced by patients who were switched from LEV and re-switched because BRV was not more efficient. Switching from and re-switching to LEV was easy.

Volume excess in chronic haemodialysis patients--effects of treatment frequency and treatment spacing.

BACKGROUND: The main objective of this study was to theoretically quantify the fluctuations of fluid volume excess for different modes of intermittent ultrafiltration schedules and to compare the prediction for the typical and asymmetric thrice-weekly schedule to clinical, physiological and biophysical markers of volume expansion in a group of stable haemodialysis patients. METHODS: Overall volume excess (V(OVE)) was described as the sum of a time-independent (V(0)) and a time-dependent component (V). An exact relationship was developed to relate V to variable treatment frequency, treatment spacing and net volume accumulation rate. In a single-centre haemodialysis population, body mass profiling was combined with volume state evaluation by bioimpedance analysis, N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels, clinical signs, a volume questionnaire and blood pressure levels. RESULTS: In 23 patients following the typical thrice-weekly schedule, the time-averaged volume excess (V) during the whole week (1.1 ± 0.5 L) was significantly larger than that during the midweek interval (0.9 ± 0.4 L) (P < 0.002) by a factor comparable to that of 1.21 obtained from the theoretical analysis. V(OVE) was 1.3 ± 1.7 L and significantly related to pre- (P < 0.001) and post-dialysis levels of NT-pro BNP (P < 0.001). CONCLUSION: Asymmetric treatment spacing such as with the typical thrice-weekly treatment schedule leads to a significant increase in time-averaged volume excess. The theoretical analysis allows for comparison of time-averaged volume excess in treatments varying with regard to treatment frequency and regularity and could be helpful to prescribe post-treatment volume (target weight) for such variable treatment modes.

Bioimpedance-based volume at clinical target weight is contracted in hemodialysis patients with a high body mass index.

OBJECTIVE: To compare volume overload in stable hemodialysis (HD) patients assessed by standard clinical judgment with data obtained from bioimpedance analysis. METHODS: Ultrafiltration volume (VU) was delivered as prescribed by standard clinical practice. Independently, a measure for volume overload was assessed by a clinical score (SW). The Body Composition Monitor (BCM, Fresenius Medical Care, Bad Homburg, Germany) was used to derive values for extracellular volume (VE) and volume overload (VO) before HD. Arterial pressures (P0, P1) and serum levels of NT-pro-BNP (B0, B1) were evaluated before and after HD. RESULTS: In 28 patients (11 women, age: 51.3 ± 13.3 y, body mass index (BMI) 18.5 - 40.9 kg/m2; VE: 17.91 ± 3.45 l) delivered VU was 2.41 ± 1.03 l and not different from VO of 2.08 ± 1.49 l derived from bioimpedance analysis. There was no correlation between VO and VU (r = -0.15, p = 0.46) but a negative correlation between the difference VO - VU (i.e., the volume overload at treatment end) and BMI (r = -0.49, p < 0.01). Positive correlations were observed between B0 and the relative volume overload (= VO/VE) (r = 0.58, p < 0.001). CONCLUSION: The well recognized relationship between cardiac natriuretic peptides and volume expansion was confirmed. The volume overload at treatment end (VO - VU) was negligible for the whole group of patients but more negative with increasing BMI. It therefore appears that in comparison to bioimpedance-based evaluation the clinical judgment overestimates volume overload in obese patients which leads to the delivery of high ultrafiltration volumes and to volume contraction at the end of a dialysis session in this group of patients.