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- Akel, Sarah, et al.
(författare)
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Neurofilament light, glial fibrillary acidic protein, and tau in a regional epilepsy cohort: High plasma levels are rare but related to seizures
- 2023
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Ingår i: Epilepsia. - 0013-9580. ; 64:10, s. 2690-2700
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Higher levels of biochemical blood markers of brain injury have been described immediately after tonic-clonic seizures and in drug-resistant epilepsy, but the levels of such markers in epilepsy in general have not been well characterized. We analyzed neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and tau in a regional hospital-based epilepsy cohort and investigated what proportion of patients have levels suggesting brain injury, and whether certain epilepsy features are associated with high levels.Methods: Biomarker levels were measured in 204 patients with an epilepsy diagnosis participating in a prospective regional biobank study, with age and sex distribution correlating closely to that of all patients seen for epilepsy in the health care region. Absolute biomarker levels were assessed between two patient groups: patients reporting seizures within the 2 months preceding inclusion and patients who did not have seizures for more than 1 year. We also assessed the proportion of patients with above-normal levels of NfL.Results: NfL and GFAP, but not tau, increased with age. Twenty-seven patients had abnormally high levels of NfL. Factors associated with such levels were recent seizures (p = .010) and epileptogenic lesion on radiology (p = .001). Levels of NfL (p = .006) and GFAP (p = .032) were significantly higher in young patients (<65 years) with seizures & LE;2 months before inclusion compared to those who reported no seizures for >1 year. NfL and GFAP correlated weakly with the number of days since last seizure (NfL: r(s) = -.228, p = .007; GFAP: r(s) = -.167, p = .048) in young patients. NfL also correlated weakly with seizure frequency in the last 2 months (r(s) = .162, p = .047).Significance: Most patients with epilepsy do not have biochemical evidence of brain injury. The association with seizures merits further study; future studies should aim for longitudinal sampling and examine whether individual variations in NfL or GFAP levels could reflect seizure activity.
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| 4. |
- Håkansson, Samuel, 1996, et al.
(författare)
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Big data analysis of ASM retention rates and expert ASM algorithm: A comparative study
- 2022
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 63:6, s. 1553-1562
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Tidskriftsartikel (refereegranskat)abstract
- Objective Only 50% of patients with new-onset epilepsy achieve seizure freedom with their first antiseizure medication (ASM). A growing body of data illustrates the complexity of predicting ASM response and tolerability, which is influenced by age, sex, and comorbidities. Randomized data with sufficient resolution for personalized medicine are unlikely to emerge. Two potential facilitators of ASM selection are big data using real-world retention rates or algorithms based on expert opinion. We asked how these methods compare in adult-onset focal epilepsy. Methods ASM retention rates were determined by cross-referencing data from comprehensive Swedish registers for 37 643 individuals, with identified comorbidities. Eight fictive cases were created and expert advice was collected from the algorithm Epipick. We compared Epipick suggestions in representative patient subgroups, and determined whether ranking based on retention rate reflected expert advice. Results The Epipick algorithm suggested six ASM alternatives for younger patients and three ASM alternatives for older patients. In the real-world data, retention rates for the ASMs ranked as best options by Epipick were high; 65%-72% for young patients and 71%-84% for older patients. The lowest retention rate for Epipick suggestions was 42%-56% in younger cases, and 70%-80% in older cases. The ASM with the best retention rate was generally recommended by Epipick. Significance We found a large overlap between expert advice and real-world retention rates. Notably, Epipick did suggest some ASMs with more modest retention rates. Conversely, clearly inappropriate ASMs (not recommended by Epipick) had high retention rates in some cases, showing that decision systems should not rely indiscriminately on retention rates alone. In future clinical decision support systems, expert opinion and real-world retention rates could work synergistically.
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| 5. |
- Håkansson, Samuel, 1996, et al.
(författare)
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Potential for improved retention rate by personalized antiseizure medication selection: A register-based analysis
- 2021
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 62:9, s. 2123-2132
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Tidskriftsartikel (refereegranskat)abstract
- Objective The first antiseizure medication (ASM) is ineffective or intolerable in 50% of epilepsy cases. Selection between more than 25 available ASMs is guided by epilepsy factors, but also age and comorbidities. Randomized evidence for particular patient subgroups is seldom available. We asked whether register data could be used for retention rate calculations based on demographics, comorbidities, and ASM history, and quantified the potential improvement in retention rates of the first ASM in several large epilepsy cohorts. We also describe retention rates in patients with epilepsy after traumatic brain injury and dementia, patient groups with little available evidence. Methods We used medical, demographic, and drug prescription data from epilepsy cohorts from comprehensive Swedish registers, containing 6380 observations. By analyzing 381 840 prescriptions, we studied retention rates of first- and second-line ASMs for patients with epilepsy in multiple sclerosis (MS), brain infection, dementia, traumatic brain injury, or stroke. The rank of retention rates of ASMs was validated by comparison to published randomized control trials. We identified the optimal stratification for each brain disease, and quantified the potential improvement if all patients had received the optimal ASM. Results Using optimal stratification for each brain disease, the potential improvement in retention rate (percentage points) was MS, 20%; brain infection, 21%; dementia, 14%; trauma, 21%; and stroke, 14%. In epilepsy after trauma, levetiracetam had the highest retention rate at 80% (95% confidence interval [CI] = 65-89), exceeding that of the most commonly prescribed ASM, carbamazepine (p = .04). In epilepsy after dementia, lamotrigine (77%, 95% CI = 68-84) and levetiracetam (74%, 95% CI = 68-79) had higher retention rates than carbamazepine (p = .006 and p = .01, respectively). Significance We conclude that personalized ASM selection could improve retention rates and that national registers have potential as big data sources for personalized medicine in epilepsy.
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| 6. |
- Larsson, David, 1986, et al.
(författare)
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Antiseizure medication selection and retention for adult onset focal epilepsy in a Swedish health service region: A population-based cohort study
- 2023
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Ingår i: Epilepsia. - 0013-9580. ; 64:10, s. 2617-2624
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Historically, approximately half of those with newly diagnosed epilepsy have responded to and tolerated the first antiseizure medication (ASM), but there are few contemporary real-world data. Third-generation ASMs have improved tolerability and are increasingly used according to prescription data. We aimed to describe current ASM selection and retention in adult onset focal epilepsy in western Sweden. Methods: A multicenter retrospective cohort study was performed at five public neurology care providers in western Sweden (nearly complete coverage in the area). We reviewed 2607 medical charts and included patients diagnosed with nongeneralized epilepsy after January 1, 2020 who had a seizure onset after age 25 years (presumed focal onset) and were started on ASM monotherapy. Results: A total of 542 patients (median age at seizure onset = 68 years, interquartile range = 52-77) were included. Most patients received levetiracetam (62%) or lamotrigine (35%), with levetiracetam being more common among men and those with structural causes or short epilepsy duration. During follow-up (median = 471.5 days), 463 patients (85%) remained on the first ASM. Fifty-nine (18%) patients discontinued levetiracetam, and 18 (10%) ended treatment with lamotrigine (p =.010), most commonly because of side effects. In a multivariable Cox regression model, the discontinuation risk was higher for levetiracetam than lamotrigine (adjusted hazard ratio = 2.01, 95% confidence interval = 1.16-3.51). Significance: Levetiracetam and lamotrigine were the dominating first ASMs for adult onset focal epilepsy in our region, indicating good awareness of problems with enzyme induction or teratogenicity of older drugs. The most striking finding is the high retention rates, perhaps reflecting a shift toward an older epilepsy population, higher tolerability of newer ASMs, or suboptimal follow-up. The finding that treatment retention differed among patients receiving levetiracetam and lamotrigine aligns with the recent SANAD II results. It suggests lamotrigine may be underutilized in our region and that education efforts are needed to ensure it is considered the first choice more often.
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| 7. |
- Magnusson, Carl, 1976, et al.
(författare)
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High-resolution mapping of epilepsy prevalence, ambulance use, and socioeconomic deprivation in an urban area of Sweden
- 2019
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 60:10, s. 2060-2067
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Tidskriftsartikel (refereegranskat)abstract
- Objective Geographic differences in epilepsy prevalence between areas of different socioeconomic standing have been demonstrated in the United Kingdom, but knowledge from other health care systems is scarce. Our objective was to compare epilepsy prevalence and emergency medical service (EMS) assignments for seizures in areas of different socioeconomic standings in the urban area of Gothenburg. Methods Register-based study in Gothenburg (population 690 000), the second largest city in Sweden. Epilepsy cases were identified in the comprehensive national patient register in 2014-2015. EMS assignments were identified in the EMS dispatch system in 2013-2018. Socioeconomic variables were mean income and proportion of welfare recipients. Results Significant correlations were seen between epilepsy prevalence and the proportion of welfare recipients (r = .49, P = .0014) and annual income per capita (r = -.42, P = .0071). There were 7907 assignments for seizures during the study years. GPS-based analysis showed that most assignments occurred in the city center. In addition, several high-density areas correlated with areas with a high proportion of inhabitants receiving welfare. Correlation analysis showed significant associations between the number of EMS assignments per capita and the proportion of welfare recipients (r = .31, P < .0001) and income (r = -.19, P < .0001). When comparing representative areas, a greater proportion of assignments was given the highest priority in high status areas compared to low status areas, both by the dispatch center and EMS clinicians on scene. Significance Our findings that epilepsy prevalence and seizure frequency differ with socioeconomic status on a microgeographic level considerably strengthen the generalizability of previous observations across different health care systems. Differences in priority may reflect health utilization behavior or access to neurologic care.
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| 8. |
- Magnusson, Carl, 1976, et al.
(författare)
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Prehospital lactate levels in blood as a seizure biomarker : A multi-center observational study.
- 2021
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 62:2, s. 408-415
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of this study was to assess the value of prehospital measurement of lactate level in blood for diagnosis of seizures in cases of transient loss of consciousness.METHODS: Between March 2018 and September 2019, prehospital lactate was measured with a point-of-care device by the emergency medical services in an area serving a population of 900 000. A total of 383 cases of transient loss of consciousness were identified and categorized as tonic-clonic seizure (TCS), other seizure, syncope, or other cause, according to the final diagnosis in the electronic medical records system. Receiver operating characteristic curve analyses were used to identify the optimal lactate cut-off.RESULTS: A total of 383 cases were included (135 TCS, 42 other seizure, 163 syncope, and 43 other causes). The median lactate level in TCS was 7.0 mmol/L, compared to a median of 2.0 mmol/L in all other cases (P < .001). The area under the curve (AUC) of TCS vs nonepileptic causes was 0.87 (95% confidence interval [CI] 0.83-0.91). The optimal cut-off (Youden index, 67.8%) was 4.75 mmol/L, with 79% sensitivity (95% CI 71-85) and 89% specificity (95% CI 85-93) for TCS.SIGNIFICANCE: Prehospital lactate can be a valuable tool for identifying seizures in transient loss of consciousness. For acceptable specificity, a higher cut-off than that previously demonstrated for hospital-based measurements must be used when values obtained close to the time of the event are interpreted.
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