Clinical utility of a video/audio-based epilepsy monitoring system Nelli.

OBJECTIVE: The aim of this study was to evaluate the clinical utility of a semi-automated hybrid video/audio-based epilepsy monitoring system (Nelli®) in a home setting. METHODS: In this retrospective study, 104 consecutive patients underwent Nelli-registration for an average of 29 days at their home. The seizure-related data obtained from the registration were assessed to investigate the utility of the Nelli-registration regarding clinical decision-making. RESULTS: Of 104 patients, Nelli® hybrid system was able to recognize clinically relevant events in 83 (80%) patients: epileptic seizures in 67 (65%) and nonepileptic events in 16 (15%). A total of 2767 epileptic seizures of different seizure types were captured and identified. These seizures included not only tonic-clonic seizures but also other complex or simple motor seizures. For the outcomes regarding clinical decision-making, a need for a new therapeutic intervention was recognized in 54 (51.9%) patients based on the number and severity of seizures captured by Nelli-registration. In 12 (11.5%) patients, the need to change the treatment plan was excluded because no evidence of suspected epileptic seizures was found. Nelli-registration aided in confirming the therapeutic efficacy of modifications of antiseizure medications (ASMs) or neuromodulation therapies in 13 (12.5%) patients. Nelli-registration enabled to determine the change in seizure classification and facilitated to reach clear diagnostic conclusions in 11 (10.6%) patients. In 14 (13.5%) patients, there was no change in clinical outcome, as Nelli-registration was unable to infer any clinical decision either due to inconclusive results or lack of typical events. Seizures detected during Nelli-registration aided in decision-making for therapeutic interventions in 71 (68%) patients. Altogether, 44 (42%) patients had adjustment of ASMs, and in 9 (9%) patients, Nelli-registrations led to the change in the settings of vagus nerve stimulation (VNS) or deep brain stimulation (DBS) treatment. Additionally, 18 (17%) patients were referred to presurgical evaluation or established a baseline seizure frequency before surgical implantation for neuromodulation treatment with VNS or DBS, while 33 (32%) patients had no change in therapy. Nine patients (8.7%) were referred to video-EEG monitoring (VEM), as Nelli-recorded events highlighted the need for presurgical evaluation in 6 patients or further diagnostic evaluation in 3 patients. CONCLUSION: This study confirms the clinical utility of the video/audio monitoring system Nelli® in home settings. Home monitoring with Nelli® hybrid system provides a new alternative for the assessment of frequency and type of epileptic seizures as well as for a recognition of nonepileptic events. Thus, Nelli-registration can facilitate the optimization of seizure monitoring and management in clinical practice, complementing existing methods such as VEM and ambulatory EEG recordings.

Anti-epileptic drugs and prostate cancer-specific mortality compared to non-users of anti-epileptic drugs in the Finnish Randomized Study of Screening for Prostate Cancer.

BACKGROUND: Drugs with histone deacetylase inhibitory (HDACi) properties have shown to decrease prostate cancer (PCa) cell growth in vitro. METHODS: A cohort of 9261 PCa cases from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) was used to evaluate prostate cancer-specific mortality in men using anti-epileptic drugs (AEDs). A national subscription database was used to obtain information on medication use. Cox regression with AED use as a time-dependent variable was used to analyse prostate cancer mortality in men using AEDs compared to non-users, and in men using HDACi AEDs compared to users of other AEDs. The analysis was adjusted for age, screening trial arm, PCa risk group, primary treatment of PCa, Charlson co-morbidity score and concomitant use of other drugs. RESULTS: The use of AEDs, in general, was associated with an increased risk of PCa death. The use of HDACi AEDs was not significantly associated with decreased PCa mortality compared to use of other AEDs (HR 0.61, 95% CI 0.31-1.23). CONCLUSIONS: AED usage is associated with elevated PCa mortality compared to non-users, likely reflecting the differences between men with epilepsy and those without. No benefit was observed from HDACi drugs compared to other AEDs.

Treatment outcomes in women with idiopathic generalized epilepsy.

OBJECTIVES: To evaluate the changes in prescription patterns in the treatment of idiopathic generalized epilepsy (IGE) due to updated treatment recommendations and to assess seizure outcomes of valproate compared to other antiseizure medications (ASMs), with emphasis on women with epilepsy (WWE). MATERIALS AND METHODS: Records of IGE patients treated at Tampere University Hospital between 1 January 2009 and 31 December 2018 were retrospectively inspected. Data were analysed for two subgroups based on age and sex. Seizure control with reference to the efficacy of different ASMs and their combinations was examined for each subgroup. RESULTS: The study compiled 263 subjects (166 females and 97 males). Of all patients, 72.6% remained seizure free. There was no difference in seizure control between sexes (OR 1.25, p = .48). Males used valproate more often than females while females used lamotrigine and levetiracetam more often than males. Lamotrigine and levetiracetam were used especially as monotherapy in WWE, and mostly as part of combination therapy in males. Valproate alternatives were found as effective as valproate when used in monotherapy in adults. Valproate remained the most used ASM in the paediatric subgroup. CONCLUSIONS: The use of valproate has decreased in daily clinical use with the simultaneous increased use of alternative ASMs compared to our previous study. Decreasing use of valproate in WWE did not increase the risk of seizure recurrence; therefore, valproate alternatives could be considered as first-line ASMs for WWE. Overall, IGE patients demonstrated good clinical outcomes with valproate or other broad-spectrum ASMs as monotherapy.

Antiepileptic drugs and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer.

Antiepileptic drugs (AEDs) with histone deacetylase (HDAC) inhibitor properties decrease prostate cancer (PCa) cell proliferation in vitro. A population-based cohort of 78 615 men was used to evaluate the risk of PCa among users of AEDs. Study population was linked to the Finnish national prescription database to obtain information on individual medication reimbursements in 1996 to 2015. Cox regression with antiepileptic medication use as a time-dependent variable was used to analyze PCa risk overall, and low, medium and high-risk PCa separately. The analysis was adjusted for age, screening trial arm, and other drugs in use, including statins, antidiabetic drugs, antihypertensive drugs, aspirin, and nonsteroidal anti-inflammatory drugs. Compared to the nonusers of AEDs, overall PCa risk was decreased among AED users (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.76-0.96). A similar PCa risk decrease was observed among users of HDACi AEDs (HR = 0.87, 95% CI = 0.76-1.01), but no risk difference was found when comparing HDACi AED users to users of other AEDs (HR = 0.98, 95% CI = 0.76-1.27). Our study showed a decrease in overall PCa risk among men using AEDs compared to nonusers. The risk associations were similar for HDAC inhibitors as for AEDs in general.

Chediak-Higashi syndrome: neurocognitive and behavioral data from infancy to adulthood after bone marrow transplantation.

Chediak-Higashi syndrome (CHS) is a rare autosomal disorder characterized by immunodeficiency, albinism, and progressive neurologic abnormalities. While survivors of the childhood-onset disease are known to exhibit learning disabilities and neuropsychiatric disorders followed by middle-age dementia, we lack detailed data on the progression. We present the case of a young adult with records from infancy to the first signs of deterioration. An early neuropsychological and neuropsychiatric profiling is crucial to intervention selection as children with CHS may not benefit from regular special education. Our patient never showed neuropsychiatric symptoms but high levels of socioemotional adaptability.

Impacts of Oil Spills on Arctic Marine Ecosystems: A Quantitative and Probabilistic Risk Assessment Perspective.

Oil spills resulting from maritime accidents pose a poorly understood risk to the Arctic environment. We propose a novel probabilistic method to quantitatively assess these risks. Our method accounts for spatiotemporally varying population distributions, the spreading of oil, and seasonally varying species-specific exposure potential and sensitivity to oil. It quantifies risk with explicit uncertainty estimates, enables one to compare risks over large geographic areas, and produces information on a meaningful scale for decision-making. We demonstrate the method by assessing the short-term risks oil spills pose to polar bears, ringed seals, and walrus in the Kara Sea, the western part of the Northern Sea Route. The risks differ considerably between species, spatial locations, and seasons. Our results support current aspirations to ban heavy fuel oil in the Arctic but show that we should not underestimate the risks of lighter oils either, as these oils can pollute larger areas than heavier ones. Our results also highlight the importance of spatially explicit season-specific oil spill risk assessment in the Arctic and that environmental variability and the lack of data are a major source of uncertainty related to the oil spill impacts.

Discontinuation of carbamazepine due to concerns of long-term consequences of enzyme induction.

OBJECTIVE: Treatment with carbamazepine (CBZ), a potent enzyme inducer, is known to affect the lipid profile, steroid, and vitamin D metabolism. Consequently, it has been postulated that patients on CBZ should be switched to noninducing antiepileptic drugs (AEDs). However, little is known about the seizure outcome following a CBZ switch in seizure-free patients. We aimed to address this issue using a controlled observational study design. METHODS: Fifty-eight patients taking CBZ for focal epilepsy were assessed for discontinuing CBZ treatment due to concerns of long-term adverse-effects; 34 discontinued its therapy and 24 continued with CBZ. Six-month seizure freedom was the primary end point. Furthermore, serum samples (total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, sex hormone-binding globulin (SHBG), free testosterone, and 25-hydroxyvitamin D levels from before and at least 3 months after discontinuation or continuation were obtained from all patients. RESULTS: Seizure-free patients had a 5-fold elevated odds of seizure recurrence if CBZ was discontinued (95% confidence interval [CI 0.51-49.3; p = 0.17). A significant decrease in serum levels of TC, LDL, HDL, and SHBG as well as a significant increase in that of free testosterone were found in the discontinuation group compared with those who continued CBZ. Nonsignificant changes in triglycerides and vitamin D levels were detected. SIGNIFICANCE: Discontinuation of CBZ in seizure-free patients seems to carry a moderate, but legitimate, risk of relapse. Conversely, our results indicate that CBZ might have unfavorable effects on serum levels of TC, LDL, HDL, SHBG, and free testosterone.

The production of IL-6 in acute epileptic seizure: A video-EEG study.

Experimental and clinical reports highlight the role of cytokines in pathophysiological processes in underpinning epilepsy, but the clinical data remains somewhat limited. The levels of Interleukin (IL)-6 were measured in serum from 49 patients with refractory epilepsy [temporal lobe epilepsy (TLE, n=23), extratemporal lobe epilepsy (XLE, n=22), and idiopathic generalized epilepsy (IGE, n=4)] before and after the first verified seizure (IS; index seizure) during inpatient video-electroencephalographic (VEEG) monitoring. The levels of IL-6 increased significantly at all time points between 3h and 24h after the IS compared to the baseline. IL-6 concentrations were significantly higher at the 3h and 6h time point after tonic-clonic seizures (TCS) compared to the situation with simple partial and complex partial seizures. An IS duration longer than 100s, low baseline IL-6 level and <10 seizures/month in patients with TLE were associated with an increase in IL-6 concentrations during the 24h after the IS. In patients with TLE, the maximum change in IL-6 levels after IS was significantly higher than in XLE. If the baseline level of IL-6 was low (under 5pg/ml), seizures induced a significant elevation in both absolute and relative values in TLE patients but not in XLE. In patients with ≤10 seizures per month during the last year, the maximum change was higher than in patients with >10 seizures. If the total seizure burden during registration was ≥100s, the IL-6 increase was significantly higher than if it were under 100s. The results of this study highlight the complexity of factors involved in the seizure induced production of the inflammatory cytokine, IL-6. The major factor is the epilepsy type i.e. increased production of IL-6 in TLE compared to XLE. The response to a single seizure in TLE is dependent on the previous seizure frequency and the baseline IL-6 concentration.

Clinical management of elderly patients with epilepsy; the use of lacosamide in a single center setting.

INTRODUCTION: Lacosamide (LCM) is a third-generation antiepileptic drug (AED) for which there is limited experience in the treatment of elderly patients with epilepsy. This study was performed to evaluate the use of LCM in this particular patient group, focusing on its tolerability and effectiveness. This is a retrospective, single-center study, in patients over 60years old treated with LCM between 1/2010 and 5/2015. Altogether, 233 elderly patients receiving LCM were identified; of these, 67 fulfilled the inclusion criteria, i.e., LCM administered for at least 2weeks. RESULTS: Lacosamide was initiated for acute seizure disorders (prolonged complex partial seizures, recurrent seizures, or status epilepticus) in 54 patients (81%) and for chronic epilepsy in 13 patients in an outpatient setting. The mean follow-up period for LCM treatment was 14months. The mean daily dose of LCM at the end of follow-up was 368mg (range: 100-600) for those 57 patients that continued treatment. Ten patients (15%) stopped LCM treatment but none because of lack of efficacy and only three patients (4%) because of side effects. The most frequent side effects were dizziness, fatigue, and tremor. CONCLUSIONS: Lacosamide was well tolerated even at relatively high doses and in combination therapy.

Comparative effectiveness of eight antiepileptic drugs in adults with focal refractory epilepsy: the influence of age, gender, and the sequence in which drugs were introduced onto the market.

The first objective was to determine the long-term retention rate of eight antiepileptic drugs (AEDs) commonly used as adjunctive therapy in adults with focal refractory epilepsy. Second, we assessed the effects of age and gender on retention rates. Third, we examined if the retention rate could be influenced by the sequence in which the AEDs had entered the market. Patients with focal refractory epilepsy treated with any of the eight AEDs in Tampere University Hospital were identified retrospectively (N = 507). Retention rates were evaluated with the Kaplan-Meier method. Follow-up started at the first date of treatment and each individual was followed a maximum of 36 months. We calculated the following 3-year retention rates: lacosamide 77.1% (N = 137), lamotrigine 68.3% (N = 177), levetiracetam 66.7% (N = 319), clobazam 65.6% (N = 130), topiramate 61.6% (N = 178), zonisamide 60.4% (N = 103), pregabalin 54.6% (N = 127), and gabapentin 40.2% (N = 66). Lacosamide, levetiracetam, and clobazam were the most effective AEDs in the elderly. The retention rate for pregabalin was higher in males (65%) than females (51%) whereas females had higher retention rates for both topiramate (72 vs. 58%) and zonisamide (67 vs. 57%). The retention rate was influenced by the sequence in which these AEDs entered the market. We provide important information about practical aspects of these eight AEDs, revealing that there are differences in their effectiveness as adjunctive treatment for focal refractory epilepsy. Most importantly, the retention rate appears to be influenced by the sequence in which these AEDs were introduced onto the market.

Transition from oxcarbazepine to eslicarbazepine acetate: A single center study.

OBJECTIVES: There is limited clinical evidence for comparison between oxcarbazepine (OXC) and eslicarbazepine acetate (ESL) in terms of tolerability, or how to execute the change from OXC to ESL. We report the process of transitioning patients with focal epilepsy from previous OXC treatment to ESL due to tolerability problems. The rationale for change from OXC is reported, and the outcome with respective to this rationale is analyzed in terms of tolerability and efficacy. MATERIALS AND METHODS: The subjects were transitioned overnight from OXC to ESL in a hospital inpatient setting. An evaluation of the effects of the transition was made after 1 and 3 months. All adverse events (AEs) were recorded following the transition period. Subjects were classified by outcome in terms of AEs. RESULTS: Twenty-three subjects were transitioned from OXC to ESL. Fifteen patients OXC-related AEs reduced significantly after transition. Particularly, most of (93%) the AEs presented in the morning resolved after transition to ESL. No patient had an increase in seizure frequency following the transition. The incidence of ESL-related AEs was 39% at 1 month and 13% at 3 month follow-up; however, all patients continued ESL throughout the study period. CONCLUSIONS: This study demonstrates that patients suffering from OXC-related AEs improve in terms of tolerability after a switch to ESL with maintaining seizure control. This improvement is more pronounced if the OXC-related AEs are most evident following morning dosing of OXC. Transition can be safely executed in an outpatient setting.

The effect of newer antiepileptic drugs in combination therapy.

PURPOSE: To assess the impact of the new AEDs on overall outcome for patients with epilepsy. METHODS: In 2004, the effect of combination therapy on seizure frequency in adult patients with focal epilepsy was evaluated in a cross-sectional study in our center. We repeated this analysis ten years and eight new antiepileptic drugs (AED) later. RESULTS: In 2014, a higher percentage of patients with polytherapy (117 out of 396; 30%) were seizure-free compared with the original analysis (22%) (p=0.042). Eighty three out of 218 (38%) subjects on duo-therapy were seizure-free (27% in 2004) (p=0.040); in the 151 receiving triple therapy there were 30 (20%) seizure-free subjects (10% in 2004). Four out of 27 subjects (15%) with four AEDs were seizure-free (0% in 2004). The most common pairing of 52 different combinations for duo-therapy was levetiracetam-oxcarbazepine. Eighty different AEDs regimens were being used in the patients administered three AEDs. CONCLUSION: Our combined data from these two studies indicate that some patients with focal epilepsy might benefit from newer AEDs as an adjunctive therapy in the hope they could acquire seizure freedom.

Negative symptoms and their predictors in schizophrenia within the Northern Finland 1966 Birth Cohort.

Negative symptoms are a major scientific and therapeutic challenge in schizophrenia. We report the occurrence and predicting factors of negative symptoms at two time points in a population-based birth cohort. The negative symptoms of subjects with Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R) schizophrenia (n=46) were scrutinized at the first hospitalization due to psychosis from hospital records (first-episode psychosis) and with an interview approximately 10 years later (follow-up phase). Developmental and sociodemographic predictors of negative symptoms in first-episode psychosis, follow-up phase and at both measurements were analysed. Forty-one percent of the subjects had negative symptoms at the first episode, 39% in the follow-up phase, and in 24% the symptoms persisted at both measurements. Smoking at the age of 14, definite psychosocial stressor and not being married predicted more negative symptoms whereas good school performance and using less alcohol at age 14 predicted fewer persistent negative symptoms. These findings are new. However, we were not able to identify any major premorbid phenotype or endophenotype predicting negative symptoms which support the view that negative symptoms might mainly be a specific part of the illness.