Objective
This study was undertaken to quantify epilepsy‐related costs of illness (COI) in Germany and identify cost‐driving factors.
Methods
COI were calculated among adults with epilepsy of ...different etiologies and severities. Multiple regression analysis was applied to determine any epilepsy‐related and sociodemographic factors that serve as cost‐driving factors.
Results
In total, 486 patients were included, with a mean age of 40.5 ± 15.5 years (range = 18–83 years, 58.2% women). Mean 3‐month COI were estimated at €4911, €2782, and €2598 for focal, genetic generalized, and unclassified epilepsy, respectively. The mean COI for patients with drug‐refractory epilepsy (DRE; €7850) were higher than those for patients with non‐DRE (€4720), patients with occasional seizures (€3596), or patients with seizures in remission for >1 year (€2409). Identified cost‐driving factors for total COI included relevant disability (unstandardized regression coefficient b = €2218), poorer education (b = €2114), living alone (b = €2612), DRE (b = €1831), and frequent seizures (b = €2385). Younger age groups of 18–24 years (b = −€2945) and 25–34 years (b = −€1418) were found to have lower overall expenditures. A relevant disability (b = €441), DRE (b = €1253), frequent seizures (b = €735), and the need for specialized daycare (b = €749) were associated with higher direct COI, and poorer education (b = €1969), living alone (b = €2612), the presence of a relevant disability (b = €1809), DRE (b = €1831), and frequent seizures (b = €2385) were associated with higher indirect COI.
Significance
This analysis provides up‐to‐date COI data for use in further health economics analyses, highlighting the high economic impacts associated with disease severity, disability, and disease‐related loss of productivity among adult patients with epilepsy. The identified cost drivers could be used as therapeutic and socioeconomic targets for future cost‐containment strategies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective
This study was undertaken to evaluate the long‐term efficacy, retention, and tolerability of add‐on brivaracetam (BRV) in clinical practice.
Methods
A multicenter, retrospective cohort ...study recruited all patients who initiated BRV between February and November 2016, with observation until February 2021.
Results
Long‐term data for 262 patients (mean age = 40 years, range = 5–81 years, 129 men) were analyzed, including 227 (87%) diagnosed with focal epilepsy, 19 (7%) with genetic generalized epilepsy, and 16 (6%) with other or unclassified epilepsy syndromes. Only 26 (10%) patients had never received levetiracetam (LEV), whereas 133 (50.8%) were switched from LEV. The length of BRV exposure ranged from 1 day to 5 years, with a median retention time of 1.6 years, resulting in a total BRV exposure time of 6829 months (569 years). The retention rate was 61.1% at 12 months, with a reported efficacy of 33.1% (79/239; 50% responder rate, 23 patients lost‐to‐follow‐up), including 10.9% reported as seizure‐free. The retention rate for the entire study period was 50.8%, and at last follow‐up, 133 patients were receiving BRV at a mean dose of 222 ± 104 mg (median = 200, range = 25–400), including 52 (39.1%) who exceeded the recommended upper dose of 200 mg. Fewer concomitant antiseizure medications and switching from LEV to BRV correlated with better short‐term responses, but no investigated parameters correlated with positive long‐term outcomes. BRV was discontinued in 63 (24%) patients due to insufficient efficacy, in 29 (11%) for psychobehavioral adverse events, in 25 (10%) for other adverse events, and in 24 (9%) for other reasons.
Significance
BRV showed a clinically useful 50% responder rate of 33% at 12 months and overall retention of >50%, despite 90% of included patients having previous LEV exposure. BRV was well tolerated; however, psychobehavioral adverse events occurred in one out of 10 patients. Although we identified short‐term response and retention predictors, we could not identify significant predictors for long‐term outcomes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Objective
The objective of this study was to evaluate effectiveness, retention, and tolerability of brivaracetam (BRV) in genetic generalized epilepsies (GGE) in clinical practice.
Methods
A ...multicenter, retrospective cohort study recruiting all patients that started BRV in 2016 and 2017.
Results
A total of 61 patients (mean age = 29.8, range = 9‐90 years, 41 female 67%) were treated with BRV. They were difficult to control, with 2.4 failed antiepileptic drugs (AEDs) in the past, taking 1.9 AEDs on average at baseline. The length of exposure to BRV ranged from 7 days to 24 months, with a mean retention time of 7.9 months, resulting in a total exposure time to BRV of 483 months. The retention rate was 82% at 3 months and 69% at 6 months. Efficacy at 3 months was 36% (50% responder rate), with 25% seizure‐free for 3 months. Patients with juvenile myoclonic epilepsy showed a responder rate of 60%, with 40% being free of any seizures. Long‐term 50% responder rate was present in 17 patients (28%; 11 seizure‐free 18%) for >6 months and in 14 patients (23%; 10 seizure‐free 16%) for >12 months. Treatment‐emergent adverse events were observed in 26% of the patients, with the most common being somnolence, ataxia, and psychobehavioral adverse events. Use of intravenous BRV with bolus injection of 200‐300 mg in two females with absence status epilepticus was well tolerated, but did not result in cessation of status epilepticus.
Significance
Use of BRV in GGE is well tolerated, and 50% responder rates are similar to those observed in the regulatory trials for focal epilepsies. An immediate switch from levetiracetam (LEV) to BRV at a ratio of 15:1 is feasible. The occurrence of psychobehavioral adverse events seems less prominent than under LEV, and a switch to BRV can be considered in patients with LEV‐induced adverse events.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective
Despite increased awareness of the serious epilepsy complication sudden unexpected death in epilepsy (SUDEP), a substantial population of people with epilepsy (PWE) remain poorly informed. ...Physicians indicate concern that SUDEP information may adversely affect patients' health and quality of life. We examined SUDEP awareness and the immediate and long‐term effects of providing SUDEP information to PWE.
Methods
Baseline knowledge and behaviors among PWE and behavioral adjustments following the provision of SUDEP information were evaluated in a prospective, multicenter survey using the following validated scales: Neurological Disorders Depression Inventory for Epilepsy for depression symptoms, the EuroQoL five‐dimension scale for health‐related quality of life (HRQoL), a visual analog scale for overall health, the revised Epilepsy Stigma Scale for perceived stigma, and the Seizure Worry Scale for seizure‐related worries. The prospective study collected data through semiquantitative interviews before (baseline), immediately after, and 3 months after the provision of SUDEP information.
Results
In total, 236 participants (mean age = 39.3 years, range = 18–77 years, 51.7% women) were enrolled, and 205 (86.9%) completed long‐term, 3‐month follow‐up. One patient died from SUDEP before follow‐up. No worsening symptoms from baseline to 3‐month follow‐up were observed on any scale. At baseline, 27.5% of participants were aware of SUDEP. More than 85% of participants were satisfied with receiving SUDEP information. Three quarters of participants were not concerned by the information, and >80% of participants recommended the provision of SUDEP information to all PWE. Although most patients reported no behavioral adjustments, 24.8% reported strong behavioral adjustments at 3‐month follow‐up.
Significance
The provision of SUDEP information has no adverse effects on overall health, HRQoL, depressive symptoms, stigma, or seizure worry among PWE, who appreciate receiving information. SUDEP information provision might improve compliance among PWE and reduce but not eliminate the increased mortality risk.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Objective
To evaluate factors predicting efficacy, retention, and tolerability of add‐on brivaracetam (BRV) in clinical practice.
Methods
A multicenter, retrospective cohort study recruiting ...all patients who started BRV between February and November 2016 with observation time between 3 and 12 months.
Results
Of a total of 262 patients (mean age 40, range 5–81 years, 129 male) treated with BRV, 227 (87%) were diagnosed to have focal, 19 (7%) idiopathic generalized and 8 (3%) symptomatic generalized epilepsy, whereas 8 (3%) were unclassified. The length of exposure to BRV ranged from 1 day to 12 months, with a median retention time of 6.1 months, resulting in a total exposure time to BRV of 1,504 months. The retention rate was 79.4% at 3 months and 75.8% at 6 months. Efficacy at 3 months was 41.2% (50% responder rate) with 14.9% seizure‐free for 3 months and, at 6 months, 40.5% with 15.3% seizure‐free. Treatment‐emergent adverse events were observed in 37.8% of the patients, with the most common being somnolence, dizziness, and behavioral adverse events (BAEs). BAE that presented under previous levetiracetam (LEV) treatment improved upon switch to BRV in 57.1% (20/35) and LEV‐induced somnolence improved in 70.8% (17/24). Patients with BAE on LEV were more likely to develop BAE on BRV (odds ratio OR 3.48, 95% confidence interval CI 1.53–7.95).
Significance
BRV in broad clinical postmarketing use is a well‐tolerated anticonvulsant drug with 50% responder rates, similar to those observed in the regulatory trials, even though 90% of the patients included had previously been exposed to LEV. An immediate switch from LEV to BRV at a ratio of 10:1 to 15:1 is feasible. The only independent significant predictor of efficacy was the start of BRV in patients not currently taking LEV. The occurrence of BAE during previous LEV exposure predicted poor psychobehavioral tolerability of BRV treatment. A switch to BRV can be considered in patients with LEV‐induced BAE.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Multiple sclerosis (MS) is accompanied by an increased risk of epileptic seizures, but data with a detailed description of the competing causes are lacking.
Methods
We aimed to describe a ...cohort of patients with both MS and epileptic seizures in a retrospective, population-based study.
Results
We included 59 out of 2285 MS patients who had at least one epileptic seizure. Out of them, 22 had seizures before the diagnosis of MS, whereas epileptic seizures occurred after MS diagnosis in 37 patients, resulting in a total prevalence of epileptic seizures in MS of 2.6%. Competing causes could be found in 50.8% (30/59) of all patients, with 40.9% (9/22) compared to 56.8% (21/37) of the MS patients with seizures before vs after MS diagnosis. The main alternative causes were traumatic brain injury and cerebral ischemia accounting for more than 30% of the patients, with no difference between the subgroups. 33.3% and 55.6% of MS patients with seizures before/after MS diagnosis had documented pathological EEG alterations.
Conclusion
A remarkable percentage of MS patients with epileptic seizures do have alternative competing causes at the time of the first seizure. A detailed diagnostic setup including patient history, EEG and MRI is recommended in the evaluation and choice for the best treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Objective
To provide first data on inpatient costs and cost‐driving factors due to nonrefractory status epilepticus (NSE), refractory status epilepticus (RSE), and super‐refractory status ...epilepticus (SRSE).
Methods
In 2013 and 2014, all adult patients treated due to status epilepticus (SE) at the university hospitals in Frankfurt, Greifswald, and Marburg were analyzed for healthcare utilization.
Results
We evaluated 341 admissions in 316 patients (65.7 ± standard deviation18.2 years; 135 male) treated for SE. Mean costs of hospital treatment were €14,946 (median €5,278, range €776–€152,911, €787 per treatment day) per patient per admission, with a mean length of stay (LOS) of 19.0 days (median 14.0, range 1–118). Course of SE had a significant impact on mean costs, with €8,314 in NSE (n = 137, median €4,597, €687 per treatment day, 22.3% of total inpatient costs due to SE), €13,399 in RSE (n = 171, median €7,203, €638/day, 45.0% of total costs, p < 0.001), and €50,488 in SRSE (n = 33, median €46,223, €1,365/day, 32.7% of total costs, p < 0.001). Independent cost‐driving factors were SRSE, ventilation, and LOS of >14 days. Overall mortality at discharge was 14.4% and significantly higher in RSE/SRSE (20.1%) than in NSE (5.8%).
Significance
Acute treatment of SE, and particularly SRSE and ventilation, are associated with high hospital costs and prolonged LOS. Extrapolation to the whole of Germany indicates that SE causes hospital costs of >€200 million per year. Along with the demographic change, incidence of SE will increase and costs for hospital treatment and sequelae of SE will rise.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
There is a lack of data concerning socioeconomic outcome and quality of life (QoL) in patients after status epilepticus (SE) in Germany.
Adult patients treated between 2011 and 2015 due to SE at the ...university hospitals in Frankfurt, Greifswald, and Marburg were asked to fill out a questionnaire regarding long-term outcome of at least 3 months after discharge. The SE cohort consisted of 25.9% patients with an acute symptomatic, 42% with a remote symptomatic and previous epilepsy, 22.2% with a new-onset remote symptomatic, and 9.9% with other or unknown etiology. A matched case-control analysis was applied for comparison with patients with drug refractory epilepsy and seizure remission, both not previously affected by SE.
A total of 81 patients (mean age: 58.7 ± 18.0 years; 58% female) participated. A non-refractory course was present in 59.3%, while 27.2% had a refractory SE (RSE) and 13.6% had a superrefractory SE (SRSE). Before admission, a favorable modified Rankin Scale (mRS) of 0-3 was found in 82.7% (67/81), deteriorating to 38.3% (31/81) (
= 0.003) at discharge. The majority returned home 51.9% (42/81), 32.1% entered a rehabilitation facility, while 12.3% were transferred to a nursing home and 3.7% to another hospital. The overall mRS at follow-up did not change; 61.8% (45/74) reached an mRS of 0-3. In RSE and SRSE, the proportion with a favorable mRS increased from 45.5% at discharge to 70% at follow-up, while QoL was comparable to a non-refractory SE course. Matched epilepsy controls in seizure remission were treated with a lower mean number of anticonvulsants (1.3 ± 0.7) compared to controls with drug refractory epilepsy (1.9 ± 0.8;
< 0.001) or SE (1.9 ± 1.1;
< 0.001). A major depression was found in 32.8% of patients with SE and in 36.8% of drug refractory epilepsy, but only in 20.3% of patients in seizure remission. QoL was reduced in all categories (QOLIE-31) in SE patients in comparison with patients in seizure remission, but was comparable to patients with drug refractory epilepsy.
Patients after SE show substantial impairments in their QoL and daily life activities. However, in the long term, patients with RSE and SRSE had a relatively favorable outcome comparable to that of patients with a non-refractory SE course. This underlines the need for efficient therapeutic options in SE.
Background:
Epilepsy development during the course of multiple sclerosis (MS) is considered to be the result of cortical pathology. However, no long-term data exist on whether epilepsy in MS also ...leads to increasing disability over time.
Objective:
To examine if epilepsy leads to more rapid disease progression.
Methods:
We analyzed the data of 31,052 patients on the German Multiple Sclerosis Register in a case–control study.
Results:
Secondary progressive disease course (odds ratio (OR) = 2.23), age (OR = 1.12 per 10 years), and disability (OR = 1.29 per Expanded Disability Status Scale (EDSS) point) were associated with the 5-year prevalence of epilepsy. Patients who developed epilepsy during the course of the disease had a higher EDSS score at disease onset compared to matched control patients (EDSS 2.0 vs 1.5), progressed faster in each dimension, and consequently showed higher disability (EDSS 4.4 vs 3.4) and lower employment status (40% vs 65%) at final follow-up. After 15 years of MS, 64% of patients without compared to 54% of patients with epilepsy were not severely limited in walking distance.
Conclusion:
This work highlights the association of epilepsy on disability progression in MS, and the need for additional data to further clarify the underlying mechanisms.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Summary
Objective
The increasing incidence of new‐onset seizures with age is well known. Often, the etiology cannot be clarified. In the present study, patients with unprovoked late‐onset seizures ...and without known neoplasm, who might have had paraneoplastic encephalitis, were investigated for a potentially underlying autoimmunity.
Methods
Sixty‐six consecutive patients (36 women; aged ≥55 years) after having at least one seizure or seizures for ≤6 months were prospectively identified over a period of 4.75 years. All patients were tested for serum and cerebrospinal fluid (CSF) antibodies (Abs) to both neural cell‐surface and intracellular antigens. Forty‐five (68%) underwent brain magnetic resonance imaging (MRI). Follow‐up in Ab‐positive cases was ≥6 months.
Results
Two patients had high titers of anti‐CASPR2 (contactin‐associated protein‐like 2) Abs in serum and CSF and fulfilled the diagnostic criteria of definite limbic encephalitis. Another two patients had bilateral encephalitic temporal MRI abnormalities. They also satisfied the criteria of definite limbic encephalitis, even though they had no Abs in serum or CSF. All four were in the age range of 55–70 years. They received immunotherapy and/or antiepileptic drug treatment and became seizure‐free.
Significance
Our findings suggest that autoimmunity should be considered an important etiology in patients with late‐onset seizures. Testing for neural antibodies and brain MRI may be worthwhile in this patient group.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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