ObjectiveSince the introduction of diffusion tensor imaging, white matter abnormalities in epilepsy have been studied extensively. However, the affected areas reported, the extent of abnormalities and the association with relevant clinical parameters are highly variable. We aimed to obtain a more consistent estimate of white matter abnormalities and their association with clinical parameters in different epilepsy types.MethodsWe systematically searched for differences in white matter fractional anisotropy and mean diffusivity, at regional and voxel level, between people with epilepsy and healthy controls. Meta-analyses were used to quantify the directionality and extent of these differences. Correlations between white matter differences and age of epilepsy onset, duration of epilepsy and sex were assessed with meta-regressions.ResultsForty-two studies, with 1027 people with epilepsy and 1122 controls, were included with regional data. Sixteen voxel-based studies were also included. People with temporal or frontal lobe epilepsy had significantly decreased fractional anisotropy (Δ –0.021, 95% confidence interval –0.026 to –0.016) and increased mean diffusivity (Δ0.026 × 10–3 mm2/s, 0.012 to 0.039) in the commissural, association and projection white matter fibers. White matter was much less affected in generalized epilepsy. White matter changes in people with focal epilepsy correlated with age at onset, epilepsy duration and sex.SignificanceThis study provides a better estimation of white matter changes in different epilepsies. Effects are particularly found in people with focal epilepsy. Correlations with the duration of focal epilepsy support the hypothesis that these changes are, at least partly, a consequence of seizures and may warrant early surgery. Future studies need to guarantee adequate group sizes, as white matter differences in epilepsy are small.
Background For the two-thirds of patients with epilepsy who achieve seizure remission on antiseizure medications (ASMs), patients and clinicians must weigh the pros and cons of long-term ASM treatment. However, little work has evaluated how often ASM discontinuation occurs in practice. We describe the incidence of and predictors for sustained ASM fill gaps to measure discontinuation in individuals potentially eligible for ASM withdrawal. Methods This was a retrospective cohort of Medicare beneficiaries. We included patients with epilepsy by requiring International Classification of Diseases codes for epilepsy/convulsions plus at least one ASM prescription each year 2014–2016, and no acute visit for epilepsy 2014–2015 (i.e., potentially eligible for ASM discontinuation). The main outcome was the first day of a gap in ASM supply (30, 90, 180, or 360 days with no pills) in 2016–2018. We displayed cumulative incidence functions and identified predictors using Cox regressions. Results Among 21,819 beneficiaries, 5191 (24%) had a 30-day gap, 1753 (8%) had a 90-day gap, 803 (4%) had a 180-day gap, and 381 (2%) had a 360-day gap. Predictors increasing the chance of a 180-day gap included number of unique medications in 2015 (hazard ratio [HR] 1.03 per medication, 95% confidence interval [CI] 1.01–1.05) and epileptologist prescribing physician (≥25% of that physician’s visits for epilepsy; HR 2.37, 95% CI 1.39–4.03). Predictors decreasing the chance of a 180-day gap included Medicaid dual eligibility (HR 0.75, 95% CI 0.60–0.95), number of unique ASMs in 2015 (e.g., 2 versus 1: HR 0.37, 95% CI 0.30–0.45), and greater baseline adherence (> 80% versus ≤80% of days in 2015 with ASM pill supply: HR 0.38, 95% CI 0.32–0.44). Conclusions Sustained ASM gaps were rarer than current guidelines may suggest. Future work should further explore barriers and enablers of ASM discontinuation to understand the optimal discontinuation rate.
The 1991 Medical Research Council (MRC) Study compared seizure relapse for seizure-free patients randomized to withdraw vs continue of antiseizure medications (ASMs). We re-analyzed this trial to account for crossover between arms using contamination-adjusted intention to treat (CA ITT) methods, to explore dose-response curves, and to validate predictions against external data.ITT assesses the effect of being randomized to withdraw, as-treated analysis assesses the confounded effect of withdrawing, but CA ITT assesses the unconfounded effect of actually withdrawing.
Objective Guidelines suggest considering antiseizure medication (ASM) discontinuation in patients with epilepsy who become seizure‐free. Little is known about how discontinuation decisions are being made in practice. We measured the frequency of, and factors associated with, discussions and decisions surrounding ASM discontinuation. Methods We performed a multicenter retrospective cohort study at the University of Michigan (UM) and two Dutch centers: Wilhelmina Children's Hospital (WCH) and Stichting Epilepsie Instellingen Nederland (SEIN). We screened all children and adults with outpatient epilepsy visits in January 2015 and included those with at least one visit during the subsequent 2 years where they were seizure‐free for at least one year. We recorded whether charts documented (1) a discussion with the patient about possible ASM discontinuation and (2) any planned attempt to discontinue at least one ASM. We conducted multilevel logistic regressions to determine factors associated with each outcome. Results We included 1058 visits from 463 patients. Of all patients who were seizure‐free at least one year, 248/463 (53%) had documentation of any discussion and 98/463 (21%) planned to discontinue at least one ASM. Corresponding frequencies for patients who were seizure‐free at least 2 years were 184/285 (65%) and 74/285 (26%). The probability of discussing or discontinuing increased with longer duration of seizure freedom. Still, even for patients who were 10 years seizure‐free, our models predicated that in only 49% of visits was a discontinuation discussion documented, and in only 16% of visits was it decided to discontinue all ASMs. Provider‐to‐provider variation explained 18% of variation in whether patients discontinued any ASM. Significance Only approximately half of patients with prolonged seizure freedom had a documented discussion about ASM discontinuation. Discontinuation was fairly rare even among low‐risk patients. Future work should further explore barriers to and facilitators of counseling and discontinuation attempts.
Purpose Cervical spine injury after blunt trauma in children is rare but can have severe consequences. Clear protocols for diagnostic workup are, therefore, needed, but currently not available. As a step in developing such a protocol, we determined the incidence of cervical spine injury and the degree of protocol adherence at our level 2 trauma centre. Methods We analysed data from all patients aged < 16 years suspected of cervical spine injury after blunt trauma who had presented to our hospital during two periods: January 2010 to June 2012, and January 2017 to June 2019. In the intervening period, the imaging protocol for diagnostic workup was updated. Outcomes were the incidence of cervical spine injury and protocol adherence in terms of the indication for imaging and the type of imaging. Results We included 170 children in the first study period and 83 in the second. One patient was diagnosed with cervical spine injury. Protocol adherence regarding the indication for imaging was > 80% in both periods. Adherence regarding the imaging type decreased over time, with 45.8% of the patients receiving a primary CT scan in the second study period versus 2.9% in the first. Conclusion Radiographic imaging is frequently performed when clearing the paediatric cervical spine, although cervical spine injury is rare. Particularly CT scan usage has wrongly been emerging over time. Stricter adherence to current protocols could limit overuse of radiographic imaging, but ultimately there is a need for an accurate rule predicting which children really are at risk of injury.
Background and ObjectivesTo describe neurologist practice patterns, challenges, and decision support needs pertaining to withdrawal of antiseizure medications (ASMs) in patients with well-controlled epilepsy.MethodsWe sent an electronic survey to (1) US and (2) European physician members of the American Academy of Neurology and (3) members of EpiCARE, a European Reference Network for rare and complex epilepsies. Analyses included frequencies and percentages, and we showed distributions through histograms and violin plots.ResultsWe sent the survey to 4,923 individuals; 463 consented, 411 passed eligibility questions, and 287 responded to at least 1 of these questions. Most respondents indicated that they might ever consider ASM withdrawal, with respondents treating mostly children being more likely ever to consider withdrawal (e.g., medical monotherapy: children 96% vs adults 81%;p< 0.05). The most important factors when making decisions included seizure probability (83%), consequences of seizures (73%), and driving (74%). The top challenges when making decisions included unclear seizure probability (81%), inadequate guidelines (50%), and difficulty communicating probabilities (45%). Respondents would consider withdrawal after a median of 2-year seizure freedom, but also responded that they would begin withdrawal on average only when the postwithdrawal seizure relapse risk in the coming 2 years was less than 15%–30%. Wide variation existed in the use of words or numbers in respondents' counsel methods, for example, percentages vs frequencies or probability of seizure freedom vs seizure. The most highly rated point-of-care methods to inform providers of calculated risk were Kaplan-Meier curves and showing percentages only, rather than pictographs or text recommendations alone.DiscussionMost surveyed neurologists would consider withdrawing ASMs in seizure-free individuals. Seizure probability was the largest factor driving decisions, yet estimating seizure probabilities was the greatest challenge. Respondents on average indicated that they may withdraw ASM after a minimum seizure-free duration of 2 years, yet also on average were willing to withdraw when seizure risk decreased below 15%–30%, which is lower than most patients' postwithdrawal risk at 2-year seizure freedom and lower than the equivalent even of a first seizure of life. These findings will inform future efforts at developing decision support tools aimed at optimizing ASM withdrawal decisions.
Background: For the two-thirds of patients with epilepsy who achieve seizure remission on antiseizure medications (ASMs), patients and clinicians must weigh the pros and cons of long-term ASM treatment. However, little work has evaluated how often ASM discontinuation occurs in practice. We describe the incidence of and predictors for sustained ASM fill gaps to measure discontinuation in individuals potentially eligible for ASM withdrawal.Methods: This was a retrospective cohort of Medicare beneficiaries. We included patients with epilepsy by requiring International Classification of Diseases codes for epilepsy/convulsions plus at least one ASM prescription each year 2014-2016, and no acute visit for epilepsy 2014-2015 (i.e., potentially eligible for ASM discontinuation). The main outcome was the first day of a gap in ASM supply (30, 90, 180, or 360 days with no pills) in 2016-2018. We displayed cumulative incidence functions and identified predictors using Cox regressions.Results: Among 21,819 beneficiaries, 5,191 (24%) had a 30-day gap, 1,753 (8%) had a 90-day gap, 803 (4%) had a 180-day gap, and 381 (2%) had a 360-day gap. Predictors increasing the chance of a 180-day gap included number of unique medications in 2015 (hazard ratio [HR] 1.03 per medication, 95% confidence interval [CI] 1.02-1.05) and epileptologist prescribing physician (≥25% of that physician’s visits for epilepsy; HR 2.38, 95% CI 1.42-4.00). Predictors decreasing the chance of a 180-day gap included Medicaid dual eligibility (HR 0.74, 95% CI 0.59-0.93), number of unique ASMs in 2015 (e.g., 2 versus 1: HR 0.37, 95% CI 0.30-0.45), and greater baseline adherence (>80% versus ≤80% of days in 2015 with ASM pill supply: HR 0.38, 95% CI 0.32-0.44).Conclusions: Sustained ASM gaps were rarer than current guidelines may suggest. Future work should further explore barriers and enablers of ASM discontinuation to understand the optimal discontinuation rate.
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