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Objective: To investigate executive functions and attention with repeated EpiTrack evaluations in a group of DR patients with drug-resistant epilepsy (DRE) receiving vagus nerve stimulation (VNS) during a follow-up duration of up to 5 years., Methods: The study involved 33 patients with DRE who were assessed with EpiTrack as a part of the clinical VNS protocol. Evaluations were scheduled prior to VNS implantation and then at 6 months, 12 months, and yearly thereafter. However, the COVID-19 pandemic disrupted follow-up. Therefore, changes in EpiTrack total scores over time were analyzed using a linear mixed-effects (LMEs) model to compensate for the variation in follow-up duration when predicting EpiTrack total score changes over 5 years., Results: The median follow-up time was 29 months. During each month, the EpiTrack total score was predicted to increase by 0.07 units (95% confidence interval [CI]: 0.01-0.12, P = 0.02), corresponding to a change from a baseline score of 27.3 (severe impairment) to a score of 28.9 (mild impairment) at 2 years and a score of 31.5 (almost normal) at 5 years. In the group of patients with psychiatric comorbidities, the EpiTrack total score increased by 0.14 units per month (P = 0.003), which was 3.5-fold higher than the increase of patients without psychiatric comorbidities. For the patients taking 1-2 antiseizure medications (ASMs), the EpiTrack total score increased by 0.11 units per month (P = 0.005), which was almost quadruple the rate of patients taking 3-4 ASMs., Significance: Based on EpiTrack total scores, the LME model predicted a four-point improvement in executive functions among patients with DRE at 5 years after the initiation of VNS, representing a clinically meaningful change. DRE patients with comorbid depression seemed to experience the most cognitive benefits. In addition, better cognitive outcomes were achieved if the patient took less than three ASMs., Plain Language Summary: Executive functions and attention may improve during vagus nerve stimulation therapy in patients with drug-resistant epilepsy. Epilepsy patients who have depression or use fewer than three antiseizure medications are likely to benefit cognitively more from the treatment., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: To investigate the antiseizure medication (ASM) doses required to achieve seizure freedom and their correlation with the World Health Organization's defined daily doses (DDDs) in patients aged 16 years or older with newly diagnosed epilepsy., Methods: The study included 459 patients with a validated diagnosis of new-onset epilepsy. Patient records were retrospectively analyzed to determine the ASM doses in patients with or without seizure freedom during follow-up. The DDD of the relevant ASM was then retrieved., Results: The seizure-freedom rate with first and subsequent ASMs was 88% (404/459 patients) during the follow-up. The mean prescribed doses (PDDs) and PDD/DDD ratio of the most commonly used ASMs, ie, oxcarbazepine (OXC), carbamazepine (CBZ), and valproic acid (VPA), differed significantly between seizure-free and non-seizure-free status (992 mg and 0.99 vs 1132 mg and 1.13; 547 mg and 0.55 vs 659 mg and 0.66; and 953 mg and 0.64 vs 1260 mg and 0.84, respectively). The effect of the OXC dose as the first failed ASM on the possibility of achieving seizure freedom was significant (Fisher's exact test, p = 0.002). Thirty-four of 43 patients (79%) in which an OXC dose of ≤900 mg failed became seizure-free, as compared with 24 of 54 patients (44%) with a failed OXC dose >900 mg., Significance: The present study provides new insights into the doses of the commonly used ASMs such as OXC, CBZ, and VPA that can lead to seizure freedom as monotherapy or as combination therapy. The higher PDD/DDD ratio of OXC (0.99) than that of CBZ or VPA renders a generalized PDD/DDD comparison highly problematic., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: To investigate the interaction among the efficacy, tolerability and overall effectiveness of the first antiseizure medication in patients 16 years or older with newly diagnosed epilepsy., Materials and Methods: The study included 584 patients who were referred to the Tampere University Hospital between 1 January 1995 and 31 December 2005 and were diagnosed with epilepsy. All individuals were retrospectively followed up until 31 December 2006, until reaching at least one year of seizure freedom, or until death if before the cut-off date., Results: Overall, after thorough validation of the epilepsy diagnosis 459 patients comprised the study cohort; among these patients, 73% of males and 60% of females became seizure-free for at least one year with the first antiseizure medication. The seizure freedom rate for focal epilepsy was 67%. There was no significant difference in focal epilepsy to achieve seizure freedom between oxcarbazepine, carbamazepine or valproic acid. The seizure freedom rate among patients above 60 years of age was 67%. For patients with structural and unknown aetiology, seizure freedom rates were 61.5% and 75.3%, respectively. Additionally, epileptiform activity on EEG in patients with focal epilepsy decreased odds of seizure freedom in adjusted logistic regression models (OR 0.55, p=0.036)., Conclusions: This study provides a more positive prediction of seizure freedom compared with previous studies with the onset of epilepsy at 16 years or older with an overall estimation that two-thirds of patients with new-onset epilepsy obtain seizure freedom with the first antiseizure medication., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Women with epilepsy (WWE) are generally treated as a risk group during pregnancy, but over 90% of pregnant WWE have favorable pregnancies. However, the risk of some pregnancy and delivery complications may be increased among WWE, especially those on antiepileptic drugs., Material and Methods: This nationwide, retrospective population-based cohort study includes WWE who gave birth in Finland during 1987-2008 (n = 1737) and the reference cohort of a random sample of women without epilepsy (n = 4357). Identification of the cohorts, and information on hospitalizations and deliveries were obtained from the Finnish Health Registers and population statistics. Multivariate analyses were conducted by binomial regression., Results: WWE were more often hospitalized during pregnancy for accidents or other external causes [adjusted risk ratio (aRR) 1.74, 95% confidence interval (CI) 0.98-3.09], premature rupture of membranes (aRR 1.75, 95% CI 1.14-2.69) and premature contractions (aRR 1.75, 95% CI 1.36-2.23). Hospitalizations for infections were more frequent in WWE (1.4% vs. 0.4%, aRR 3.15, 95% CI 1.72-5.76). The risk for induction of delivery or a cesarean section was increased in WWE. There was no difference in premature deliveries between the groups, but the risk of being small for gestational age (aRR 1.57, 95% CI 1.23-2.01), admission to neonatal intensive care unit (aRR 1.66, 95% CI 1.39-1.97), and need for respiratory care (aRR 2.37, 95% CI 1.57-3.60) was clearly increased in the offspring of WWE., Conclusions: WWE are at an increased risk of complications and hospitalizations during pregnancy and delivery. However, the majority of WWE have a normal pregnancy and delivery., (© 2017 Nordic Federation of Societies of Obstetrics and Gynecology.)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We systematically quantified excess mortality in epilepsy patients by cause of death using the population-attributable fraction and epilepsy-attributable years of potential life lost (YPLL) by age 75 years at ages 15 and over. We updated and undertook a re-review of mortality studies from our previous systematic review following PRISMA guidelines to identify cohort studies of general epilepsy populations reporting a relative risk (RR) of death by cause relative to the background rates in the population. Studies on epilepsy prevalence were identified through published reviews. Country-specific mortality figures were obtained from the WHO World Mortality Database. We performed a pooled analysis with the DerSimonian-Laird random effects method. In countries with very high Human Development Indices, epilepsy contributed to 0.5-1.1 % of all deaths in the total population. Among external causes, suicides (RR 2.9, 95 % confidence interval 2.2-3.8; I(2) 52 %) were the major contributor to YPLL, corresponding to 6.7 % and 4.2 % of excess YPLL due to epilepsy in the United States (US) and in the United Kingdom (UK) in 2010, with 541 (346-792) and 44 (28-65) excess suicide cases, respectively. Fatal accidental falls were more common, with 813 (610-1064) and 95 (71-125) excess deaths in the US and in the UK, but these caused only 2.0 % of excess YPLL as they occurred in older age groups. Suicides were the most important external cause of death in epilepsy patients in terms of excess YPLL, whereas other external causes were either more common in older ages or caused less excess deaths.

Objective: We systematically synthesized the epidemiologic literature on mortality in patients with epilepsy (PWE) by epilepsy-related clinical characteristics with an aggregate data meta-analysis., Methods: We systematically searched 15 electronic databases, browsed reference lists of pertinent publications, and contacted authors in the field. We were interested in cohort studies that reported the relative risk of death in representative epilepsy populations relative to the general population, with exclusion of highly selected subpopulations of PWE, such as patients with intellectual disabilities or epilepsy surgery series. Search, data abstraction, and study quality assessment with the Newcastle-Ottawa Scale were all performed in duplicate., Results: Pooled mortality was threefold (relative risk 3.33, 95% confidence interval 2.83-3.92) in 38 epilepsy cohorts including 165,879 patients (79.6% from Nordic countries). Among incident cases, idiopathic epilepsies did not associate with materially increased mortality (1.29, 0.75-2.20; 4 studies), whereas mortality was almost twofold in cryptogenic epilepsy (1.75, 1.20-2.54; 5 studies), and highly elevated in patients with symptomatic epilepsy (4.73, 3.27-6.83; 12 studies) and especially in epilepsies due to congenital or developmental causes (10.3, 4.03-26.2; 2 studies). Newly diagnosed patients who attained seizure freedom did not have elevated mortality (0.97, 0.73-1.30; 2 studies)., Conclusion: Excess mortality was highly related to the etiology of epilepsy in all ages. In adult patients without neuroradiologic abnormalities or other identifiable cause of epilepsy, only patients with cryptogenic epilepsy exhibited excess mortality. Risk of premature death was lowest in idiopathic epilepsy and in PWE who attained seizure freedom., (© 2014 American Academy of Neurology.)

We evaluated mortality in relation to a panel of autoimmunity-related immunological serum markers in adult patients with epilepsy (PWE), seen in 1996-1997 at the Department of Neurology, Oulu University Hospital in Finland. Blood samples were drawn from 968 volunteers, and baseline measurements included serum immunoglobulins (IgG, IgA, and IgM), and the following antibodies: anticardiolipin, antinuclear, antimitochondrial, antigliadin (IgA and IgG classes), IgA tissue transglutaminase, and IgA endomysial. Hazard ratios (HR) for all-cause mortality in PWE with abnormal immunological markers relative to 413 patients with normal findings were evaluated with adjustment for confounders during a follow-up of nine years. Borderline statistically significant associations were found only for elevated IgA (HR 2.09, 95% CI 0.99-4.42) and for having two or more abnormal antibody titers (HR 1.58, 95% CI 0.98-2.56). The findings of this exploratory study suggested that elevated serum IgA might be associated with excess mortality in PWE., (Copyright © 2014 Elsevier B.V. All rights reserved.)

To estimate long-term mortality by cause of death in a nationwide, register-based cohort of newly diagnosed patients with epilepsy (PWE). All noninstitutionalized Finnish PWE aged 10-74 years (n = 10,818) eligible for reimbursement for antiepileptic medication for the first time between 1990 and 1994 were identified in the database of Social Insurance Institution of Finland. Mortality was compared against a population-based reference cohort (n = 43,894). Hazard ratios (HR) and their 95 % confidence intervals (95 % CI) during a follow-up of 18 years were estimated using proportional hazards modeling. Potential years of life lost (PYLL) and excess fraction of causes of death attributable to epilepsy were estimated. PWE contributed 137,610 person-years of observation and there were 3,558 deaths. Mortality remained elevated up to 18 years post-diagnosis (HR 3.21, 95 % CI 3.07-3.35). Ischemic heart disease mortality in PWE was two-fold (HR 2.31, 95 % CI 2.09-2.54), and remained constantly elevated during entire follow-up in both men and women. Most premature mortality in terms of PYLL was attributable to brain cancer (17 %), other cancers (15 %), ischemic heart disease (11 %), as well as cerebrovascular diseases (10 %). The percentage of deaths in PWE statistically attributable to epilepsy was 3.9 % for accidents, 3.4 % for alcohol-related diseases, and 1.6 % for suicides. PWE had substantial excess mortality from non-communicable diseases, which did not disappear by 18 years. Diseases of the circulatory system and cancers, especially brain cancer, were the most important causes of death almost regardless of the mortality indicator.

The authors evaluated the contribution of various clinical characteristics to mortality risk and underlying causes of death among all adult patients with epilepsy seen at the Department of Neurology, Oulu University Hospital in Finland during 1996 and 1997. Hazard ratios (HRs) for mortality in 1998-2006 relative to a population-based reference cohort were estimated using Cox modeling, with adjustment for age and gender. The HR for total mortality was 2.66 (95% confidence interval [CI] 2.09-3.39). Infectious etiology of epilepsy (HR 5.77, 95% CI 2.52-13.2) and a seizure frequency of ≥1 per month (HR 4.42, 95% CI 3.00-6.52) related to high risks of death. Cancer (21%), ischemic heart disease (15%), and accidents (12%) caused most of the potential years of life lost. Despite recent advances in treatment of epilepsy and improved seizure control, chronic epilepsy still carries a substantially increased risk of death., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Immune mechanisms have been implicated in the pathogenesis of epilepsy. An increased prevalence of autoantibodies, as well as changes in serum immunoglobulin concentrations, has been reported in patients with epilepsy. The presence of unspecific antimitochondrial antibodies (AMAs) and their possible associations with other immunological markers were evaluated in a cohort of 1386 adult patients with epilepsy and population-based reference subjects. Unspecific AMAs were more frequent in epilepsy patients than in the reference group. Thirty-seven epilepsy patients (3.9%) and eleven control subjects (1.9%) had unspecific AMAs (RR 2.1, CI 1.05-4.1, P=0.03). These antibodies were associated with long duration of epilepsy and old age at the onset of epilepsy among patients with epilepsy. Their presence was independent of other immunological markers, comorbidity, and epilepsy medications.

Celiac disease (CD) is a common immunologically mediated enteropathic condition manifesting in genetically predisposed individuals after exposure to wheat gluten. CD may be associated with a number of neurological disorders, and the prevalence of epilepsy is reported to be increased in patients with CD. We studied the prevalence of CD-associated antibodies in a cohort of 968 patients with epilepsy and in a population-based reference group of 584 subjects. There was no difference in the prevalence of IgA and IgG class antigliadin antibodies (AGAbA and AGAbG, respectively), endomysial antibodies (EMA), and tissue transglutaminase antibodies (tTGAbA) between patients with epilepsy and the control population. This suggests the presence of CD to be the same in patients with epilepsy and the reference population. However, AGAbA was more prevalent in patients with primary generalized epilepsy (19.6%) than in the reference population (10.6%, relative risk 1.8, 95% confidence interval 1.1-3.0, P=0.012).

Conflicting reports have been published on serum immunoglobulin (Ig) concentrations in patients with epilepsy. Serum IgA, IgG, and IgM concentrations were determined in a cohort of 958 patients and in a reference population of 581 subjects. Overall, 8.2% of patients with epilepsy and 1.9% of control subjects had low serum IgA concentrations. Low serum IgA levels were measured in 19.1% of patients currently on phenytoin therapy and in 11.9% of patients who had previously been treated with phenytoin, whereas only 3.8% of patients who had never been on phenytoin therapy had low serum IgA. In multivariate analysis low serum IgA concentrations were associated with phenytoin medication and female gender. No differences in serum IgG and IgM concentrations were observed between patients and control subjects. However, in patients with epilepsy, low serum IgG concentrations were associated with concomitant autoimmune diseases, and low IgM levels with older age at the onset of epilepsy, long duration of epilepsy, and autoimmune diseases. In conclusion, the prevalence of low serum IgA concentrations was increased in patients with epilepsy, but serum IgG and IgM concentrations were similar in patients with epilepsy and reference subjects. The low serum IgA concentrations were associated with phenytoin medication. In addition to current phenytoin medication, previous phenytoin therapy also was associated with low serum IgA concentrations. This implies that phenytoin medication may have permanent immunological effects in some patients.

Background: A prior small-scale single center study suggested an association between celiac disease (CD)-type immunity and refractory temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). The present study addresses this putative association in a large, well-characterized group of drug-resistant epilepsy (DRE) patients. These patients were grouped based on the spectrum of CD and gluten sensitivity-associated antibodies. Methods: In this cross-sectional study, 253 consecutive adult epilepsy patients (135 females, 118 males; age 16–76 years) were categorized into three groups: (i) CD-positive group with either prior diagnosis of CD or CD-specific TG2/EmA antibodies, (ii) AGA-positive group with antigliadin antibodies (AGA) but without CD, and (iii) CD/AGA-negative group without any gluten sensitivity-associated antibodies or CD. Clinical and immunological findings were then compared among the groups. Results: TLE with HS was more common in the CD-positive group compared to CD/AGA-negative group (31.8% versus 11.9%, P = 0.019). Autoimmune disorders were more common in the AGA-positive group than in the CD/AGA-negative group (P = 0.025). Considering HS lateralization; left lateralization was more common in CD-positive group compared to CD/AGA-negative group (71.4% versus 25%, P = 0.030). TG6 seropositivity did not differ among the groups (P > 0.05). Conclusions: This study provides further evidence linking TLE with HS and CD-type autoimmunity suggesting that CD-type immune response to gluten can be one potential mechanism as a disease modifier leading to DRE and HS. Understanding these immunological factors is imperative for developing immunomodulatory or dietary treatments for DRE potentially preventing HS progression. [ABSTRACT FROM AUTHOR]

Introduction: There is a paucity of clinical studies examining the long-term effects of vagus nerve stimulation (VNS) on cognition, although a recent study of patients with drug-resistant epilepsy (DRE) treated with VNS therapy demonstrated significant improvement in executive functions as measured by the EpiTrack composite score. The present study aimed to investigate performance variability in three cognitive tests assessing executive functions and working memory in a cohort of DRE patients receiving VNS therapy during a follow-up duration of up to 5 years. Methods: The study included 46 DRE patients who were assessed with the Trail Making Test (TMT) (Parts A and B) and Digit Span Backward (DB) task prior to VNS implantation, 6 months and 12 months after implantation, and yearly thereafter as a part of the clinical VNS protocol. A linear mixed-effects (LME) model was used to analyze changes in test z scores over time, accounting for variations in follow-up duration when predicting changes over 5 years. Additionally, we conducted descriptive analyses to illustrate individual changes. Results: On average, TMT-A z scores improved by 0.024 units (95% confidence interval (CI): 0.006 to 0.042, p = 0.009), TMT-B z scores by 0.034 units (95% CI: 0.012 to 0.057, p = 0.003), and DB z scores by 0.019 units per month (95% CI: 0.011 to 0.028, p < 0.001). Patients with psychiatric comorbidities achieved the greatest improvements in TMT-B and DB z scores among all groups (0.0058 units/month, p = 0.036 and 0.028 units/month, p = 0.003, respectively). TMT-A z scores improved the most in patients taking 1-2 ASMs as well as in patients with psychiatric comorbidities (0.042 units/month, p = 0.002 and p = 0.003, respectively). Conclusion: Performance in all three tests improved at the group level during the follow-up period, with the most robust improvement observed in TMT-B, which requires inhibition control and set-switching in addition to the visuoperceptual processing speed that is crucial in TMT-A and working-memory performance that is essential in DB. Moreover, the improvement in TMT-B was further enhanced if the patient had psychiatric comorbidities. [ABSTRACT FROM AUTHOR]

Objective: We evaluate the effect of distinct clinical features on anti-seizure medication (ASM) doses in seizure-free and not seizure-free patients aged ≥16 years with new-onset epilepsy. Materials and methods: This study included 459 patients with a validated diagnosis of epilepsy. The most prescribed ASMs were oxcarbazepine (OXC; n = 307), followed by valproic acid (VPA; n = 115), carbamazepine (CBZ; n = 81), and lamotrigine (LTG; n = 67). The seizure freedom rate with their first or subsequent ASM was 88.0%. A retrospective analysis of patient records was performed to determine any association between doses of ASMs and patient characteristics. Results: The median OXC dose in seizure-free patients aged >60 years was 600mg compared to 900mg in younger patients.When controlling for age but not in an unadjusted model, the median dose of OXC was lower (300mg, p = 0.018) for seizure-free patients compared to non-seizure-free patients, and the median dose of OXC was also 300mg lower among older patients aged >60 years (p < 0.001). The median OXC doses for men aged ≤60 years were 300mg higher than for women aged >60 years (900mg vs. 600mg, p = 0.021). The median dose of VPA was 400mg higher inmen than in women (p<0.001) and 400mg higher in not seizure-free patients compared to seizure-free patients only when adjusting for sex (p < 0.001). Higher median doses for CBZ were registered with FAS compared with FBTCS (difference in median doses of 200mg; p = 0.017). Conclusion: Significant OXC dose differences were detected between age groups, whereas VPA dosing was different in men and women. Moreover, CBZ doses were dependent on some seizure types. These data allow for the individualization of the initial target dosing based on key clinical characteristics. [ABSTRACT FROM AUTHOR]

Objective: There is a lack of studies using the International League Against Epilepsy (ILAE) recommendation to define drug-resistant epilepsy (DRE). This study evaluated the seizure freedom rates of substitution or add-on and subsequent antiseizure medication (ASM) therapies using different proposed definitions of DRE or ASM trials in patients with a failed first ASM. We also identified prognostic factors for 1-year seizure freedom. Methods: This study included 459 patients with epilepsy of whom 151 were not seizure-free after the first ASM. Multilevel mixed-effects logistic regression was used to examine the correlation between observations from the same patient. Results: The overall seizure freedom rate with the first and subsequent ASMs was 88.0% (404/459). The rate of DRE when defined as the failure of two ASMs for any reason was 20.0%, and according to the ILAE definition of DRE, it was 16.3%. After failing the first ASM, 63.6% of patients (96/151) became seizure free with subsequent ASMs and tried an average of 1.9 ASMs (range 1-5). Of the patients who achieved 1-year seizure freedom, 10.1% (41/404) were taking polytherapy and there was no difference between substitution and add-on. All the patients with generalized epilepsy were seizure-free. A favorable prognostic factor was age>60 years and an EEGwithout epileptiform activity. The effcacies of the different ASMs were largely similar, but drugs that enhanced GABA-mediated inhibitory neurotransmission had the lowest seizure freedom rate. Significance: In adults with newly-diagnosed epilepsy, 1-year seizure freedom was achieved for almost 90% of the patients. After failing the first ASM, two-thirds of the patients responded to subsequent ASM regimens. Our results support the feasibility and applicability of the ILAE concept of an adequate ASM trial and the failure of two ASMs as a definition of DRE. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Cell-free DNA (cf-DNA) is a marker of inflammation and cell death. The purpose of the present study was to analyze the role of cf-DNA as a putative biomarker in refractory epilepsy. Methods: Baseline concentration of cf-DNA was measured in the serum of 51 carefully evaluated refractory epilepsy patients undergoing video-EEG monitoring. Epilepsy was classified based on seizure semiology, patient history, and imaging findings. Majority of the patients (47) had focal epilepsy. The association of the concentration cf-DNA with different clinical determinants was analyzed. 250 healthy individuals served as control subjects. Results: The mean baseline concentration of cf-DNA was lower in patients with extra temporal lobe epilepsy (XTLE) compared to control subjects (0.72 μg/ml vs. 0.80 μg/ml; p = 0.001). The difference in concentration of cf-DNA between patients with temporal lobe epilepsy (TLE) and control subjects was not significant. The maximum concentration of cf-DNA after baseline measurement was significantly lower in patients with duration of epilepsy ≥ 18 years compared to those with duration of epilepsy < 18 years (0.022 μg/ml vs. 0.031 μg/ml; p = 0.044). The maximum concentration of cf-DNA was higher in patients with body mass index (BMI) ≥ 25 compared to those with BMI < 25 (0.004 μg/ml vs. 0.041 μg/ml; p = 0.006). Discussion: The difference in cf-DNA concentration between patients with XTLE and control subjects strengthens the previous observations of the importance of epilepsy type with regard of different biomarkers. [ABSTRACT FROM AUTHOR]

Highlights: [•] Cell-free-DNA (cf-DNA) is regarded a marker of inflammation, cell death and degeneration in many medical conditions. [•] Cf-DNA was measured in 167 consecutive well-evaluated patients with focal epilepsy. [•] 74.8% of the patients had increased concentrations of cf-DNA. [•] Symptomatic etiology was associated with increased concentrations of cf-DNA compared to probably symptomatic etiology supporting the inflammatory nature of symptomatic focal epilepsy. [ABSTRACT FROM AUTHOR]