Initial Response to Antiepileptic Drugs in Patients with Newly Diagnosed Epilepsy As a Predictor of Long-term Outcome.
Xia Lu,Ou Shuchun,Pan Songqing
Frontiers in neurology
OBJECTIVE:To investigate the correlation between initial response to antiepileptic drugs (AEDs) and long-term outcomes after 3 years in patients with newly diagnosed epilepsy. METHODS:This prospective study included 204 patients with newly diagnosed epilepsy, who were followed-up for at least 36 months. The long-term seizure freedom at 36 months (36MSF) was evaluated in patients with seizure freedom 6 months (6MSF) or 12 months (12MSF) after initial treatment vs those with no seizure freedom after the initial 6 months (6MNSF) or 12 months (12MNSF). Univariate analysis and a multiple logistic regression model were used to analyze the association of potential confounding variables with the initial response to AEDs. RESULTS:The number of patients with 36MSF was significantly higher for patients that had 6MSF (94/131, 71.8%) than those that had 6MNSF [16/73, 21.9%; χ = 46.862, < 0.0001, odd ratio (OR) = 9.051]. The number of patients with 36MSF was significantly higher in patients that had 12MSF (94/118 79.7%) than those that had 12MNSF (19/86, 22.1%; χ = 66.720, < 0.0001, OR = 13.811). The numbers of patients that had 36MSF were not significantly different between patients that experienced 6MSF and 12MSF or between patients that had 6MNSF and 12MNSF. Abnormalities observed in magnetic resonance imaging or computed tomography and the number of seizures before treatment correlated with poor initial 6-month response to AEDs. SIGNIFICANCE:The initial 6-month response to AEDs is a valuable predictor of long-term response in patients with newly diagnosed epilepsy. The number of seizures before treatment and brain-imaging abnormalities are two prognostic predictors of initial 6-month seizure freedom.
10.3389/fneur.2017.00658
Complete remission of childhood-onset epilepsy: stability and prediction over two decades.
Berg Anne T,Rychlik Karen,Levy Susan R,Testa Francine M
Brain : a journal of neurology
The ultimate seizure outcome of childhood epilepsy is complete resolution of all seizures without further treatment. How often this happens and how well it can be predicted early in the course of epilepsy could be valuable in helping families understand the nature of childhood epilepsy and what to expect over time. In the Connecticut study of epilepsy, a prospective cohort of 613 children with newly-diagnosed epilepsy (onset age 0-15 years), complete remission, ≥5 years both seizure-free and medication-free, was examined as a proxy of complete seizure resolution. Predictors at initial diagnosis were tested. Information about seizure outcomes within 2 years and from 2-5 years after diagnosis was sequentially added in a proportional hazards model. The predictive value of the models was determined with logistic regression. Five hundred and sixteen subjects were followed ≥10 years. Three hundred and twenty-eight (63%) achieved complete remission; 23 relapsed. The relapse rate was 8.2 per 1000 person-years and decreased over time: 10.7, 6.7, and 0 during first 5 years, the next 5 years, and then >10 years after complete remission (P=0.06 for trend). Six participants regained complete remission; 311 (60%) were in complete remission at last contact. Baseline factors predicting against complete remission at last contact included onset age≥10 years (hazard ratio=0.55, P=0.0009) and early school or developmental problems (hazard ratio=0.74, P=0.01). Factors predicting for complete remission were uncomplicated epilepsy presentation (hazard ratio=2.23, P<0.0001), focal self-limited epilepsy syndrome (hazard ratio=2.13, P<0.0001), and uncharacterized epilepsy (hazard ratio=1.61, P=0.04). Remission (hazard ratio=1.95, P<0.0001) and pharmaco-resistance (hazard ratio=0.33, P<0.0001) by 2 years respectfully predicted in favour and against complete remission. From 2 to 5 years after diagnosis, relapse (hazard ratio=0.21, P<0.0001) and late pharmaco-resistance (hazard ratio=0.21, P=0.008) decreased and late remission (hazard ratio=2.40, P<0.0001) increased chances of entering complete remission. The overall accuracy of the models increased from 72% (baseline information only), to 77% and 85% with addition of 2-year and 5-year outcomes. Relapses after complete remission are rare making this an acceptable proxy for complete seizure resolution. Complete remission after nearly 20 years is reasonably well predicted within 5 years of initial diagnosis.
10.1093/brain/awu294
Prognostic factors for time to treatment failure and time to 12 months of remission for patients with focal epilepsy: post-hoc, subgroup analyses of data from the SANAD trial.
Bonnett Laura,Smith Catrin Tudur,Smith David,Williamson Paula,Chadwick David,Marson Anthony G
The Lancet. Neurology
BACKGROUND:Epilepsy is a heterogeneous disorder, with outcomes ranging from immediate remission after taking a first antiepileptic drug to frequent unremitting seizures with multiple treatment failures. Few prognostic models enable prediction of outcome; we therefore aimed to use data from the SANAD study to predict outcome overall and for patients receiving specific treatments. METHODS:The SANAD study was a randomised controlled trial in which standard antiepileptic drugs were compared with new treatments. Arm A included patients for whom carbamazepine was considered the first-line treatment, most of whom were newly diagnosed with focal epilepsy. Patients were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Outcomes were time to treatment failure overall, because of inadequate seizure control, and because of adverse events, and time to 12 months of remission from seizures. In this post-hoc study we used regression multivariable modelling to investigate how clinical factors affect the probability of treatment failure and the probability of achieving 12 months of remission. FINDINGS:For time to treatment failure, we identified several significant risk factors: sex (male vs female, hazard ratio [HR] 0·86, 95% CI 0·75-0·99), treatment history (taking non-SANAD antiepileptic drugs [other than those listed above] vs treatment naive, 1·27, 1·05-1·53), age (eg, older than 71 years vs 10 years or younger, 0·68, 0·51-0·91), total number of seizures (eg, four to 11 seizures vs two or fewer, 1·08, 1·05-1·11), electroencephalogram results (epileptiform abnormality vs normal, 1·26, 1·07-1·50), seizure type (eg, secondary generalised vs simple or complex partial only, 0·78, 0·66-0·91), site of onset (not localised vs temporal lobe, 1·25, 1·06-1·47), and treatment (lamotrigine vs carbamazepine, 0·76, 0·61-0·95). Significant factors for time to 12 months of remission were sex (male vs female, 1·19, 1·05-1·35), treatment history (taking a non-SANAD antiepileptic drug vs treatment naive, 0·64, 0·52-0·78), age (eg, older than 71 years vs 10 years or younger, 1·60, 1·26-2·03), time from first seizure (60-239 months vs ≥2 months, 1·14, 1·01-1·29; >240 months vs ≤2 months, 1·39, 1·04-1·86), neurological insult (present vs absent, 0·75, 0·61-0·93), total number of seizures before randomisation (eg, four to 11 vs two or fewer, 0·87, 0·85-0·90), and treatment (gabapentin vs carbamazepine, 0·71, 0·59-0·86; topiramate vs carbamazepine, 0·81, 0·68-0·98). INTERPRETATION:We present a thorough investigation of prognostic factors from a large randomised controlled trial in patients starting antiepileptic monotherapy. If validated, our models could aid in individual patient risk stratification and the design and analysis of epilepsy trials. FUNDING:National Institute for Health Research (UK).
10.1016/S1474-4422(12)70018-2
Longitudinal cohort studies of the prognosis of epilepsy: contribution of the National General Practice Study of Epilepsy and other studies.
Shorvon Simon D,Goodridge David M G
Brain : a journal of neurology
Longitudinal cohort studies of prognosis in epilepsy have been carried out since the late 1970s and these have transformed our understanding of prognosis in epilepsy. This paper reviews the contribution of such studies and focuses particularly on the National General Practice Study of Epilepsy, a prospective population-based cohort study of 1195 patients that was initiated in 1983. The National General Practice Study of Epilepsy and other studies have shown that: (i) epilepsy has an often good prognosis with 65-85% of cases eventually entering long-term remission, and an even higher proportion of cases entering a short-term remission; (ii) the likelihood of long-term remission of seizures is much better in newly diagnosed cases than in patients with chronic epilepsy; (iii) the early response to treatment is a good guide to longer term prognosis (although not inevitably so, as in a minority of cases seizure remission can develop after prolonged activity); (iv) the longer is the remission (and follow-up), the less likely is subsequent recurrence; (v) the longer an epilepsy is active, the poorer is the longer term outlook; (vi) that delaying treatment, even for many years, does not worsen long-term prognosis; (vii) the 'continuous' and 'burst' patterns are more common than the 'intermittent' seizure pattern; (viii) epilepsy has a mortality that is highest in the early years after diagnosis, and in the early years is largely due to the underlying cause, however, higher mortality rates than expected are observed throughout the course of an epilepsy; (ix) the prognosis of febrile seizures is generally good, with ~6-7% developing later epilepsy; and (x) clinical factors associated with outcome have been well studied, and those consistently found to predict a worse outcome include: the presence of neurodeficit, high frequency of seizures before therapy (seizure density), poor response to initial therapy, some epilepsy syndromes.
10.1093/brain/awt223
Factors predictive of late remission in a cohort of Chinese patients with newly diagnosed epilepsy.
Shen Chunhong,Du Ye,Lu Ruyi,Zhang Yinxi,Jin Bo,Ding Yao,Yi Guo,Ding Meiping
Seizure
PURPOSE:Limited data have focused on predictive factors of late remission in patients with newly diagnosed epilepsy. We are aiming to identify prognostic predictors of late remission in a prospective cohort of Chinese patients. METHODS:Patients with newly diagnosed epilepsy were included from 2009 to September 2012 at a tertiary hospital, with follow-up of at least two years. Early remission was defined by seizure free either immediately or within six months of treatment initiation, late remission was defined by seizure free achieved after more than six months. All analyses were performed with SPSS 13.0 software. RESULTS:A total of 223 patients were included, and followed for an average of 43 months. 115 patients (51.6%) achieved early remission and 39 patients (17.5%) achieved late remission. Multivariable logistic regression analysis demonstrated more than 3 seizures prior to treatment (OR=3.12, 95% CI 1.39-7.04, p=0.006) and multiple seizure types (OR=2.49, 95% CI 1.02-6.11, p=0.046) may predict late remission. However, nonadherence was not significantly associated with late remission. CONCLUSION:Patients with a high frequency of seizures prior to treatment or multiple seizure types may achieve late remission. Particular consideration should be given to these patients.
10.1016/j.seizure.2016.02.007
Prediction for relapse and prognosis of newly diagnosed epilepsy.
Su L,Di Q,Kwan P,Yu N,Zhang Y,Hu Y,Gao L
Acta neurologica Scandinavica
OBJECTIVE:The objective of this study was to investigate the timing of therapy initiation and other clinical factors as potential predictors for relapse and prognosis of epilepsy, based on hospital-based prospective observational data in China. METHODS:One hundred and seventy-one newly diagnosed patients with one or more seizures were recruited and followed for at least 2 years. Kaplan-Meier survival analysis was used for calculating recurrence and remission rates. Univariate and multivariate analyses for risk factors were performed using Cox proportional hazards model. RESULTS:Among the 171 patients analyzed, more patients had partial (54.4%) than generalized seizures (45.6%). The range of patients' age was 6-70 years, but 70% were under 16 years of age. Multiple seizure types (HR = 2.01; 95% CI, 1.31-3.10), epileptiform electroencephalogram (EEG) abnormality (HR = 1.95; 95% CI, 1.09-3.49), and >1 seizure monthly before treatment (HR = 2.74; 95% CI, 1.69-4.51) were predictors of seizure recurrence. The best negative predictors of remission were as follows: relapse (HR = 0.13; 95% CI, 0.07-0.23) and epileptiform EEG within 1 year of treatment (HR = 0.61; 95% CI, 0.39-0.97). Delayed treatment after three or more seizures did not significantly increase the risk of recurrence (P = 0.70) or remission (P = 0.31) compared with early treatment after one or two seizures. CONCLUSIONS:Multiple seizure types, epileptiform EEG abnormality, and >1 seizure monthly before treatment predict seizure recurrence. Relapse and epileptiform EEG within 1 year of treatment predict adverse seizure outcome. Early treatment does not affect relapse or prognosis.
10.1111/j.1600-0404.2012.01711.x
Pharmacological outcomes in teenagers with newly diagnosed epilepsy: A 30-year cohort study.
Alsfouk Bshra A,Alsfouk Aisha A,Chen Zhibin,Kwan Patrick,Brodie Martin J
Epilepsia
OBJECTIVE:To evaluate the long-term pharmacological outcomes in teenagers with different epilepsies. METHOD:This study included teenagers aged 13-19 years at treatment initiation who were newly treated with antiepileptic drugs (AEDs) at the epilepsy unit of the Western Infirmary in Glasgow, Scotland, between 1 September 1982 and 30 September 2012. Patients were prospectively followed until 30 April 2016, or death, with at least a 2-year follow-up. RESULTS:A total of 332 adolescent patients (53% female; median age 16 years; 54% with generalized epilepsy) were included. At the end of the study, 221 patients (67%) were seizure-free. A higher seizure-free rate was observed in those with generalized compared to focal epilepsy (72% versus 60%, P = 0.01). During the study, 108 patients had relapses after periods of being seizure-free, most commonly due to poor adherence to AEDs (49%, n = 53/108). AED withdrawal was associated with a high risk of seizure recurrence (70%, n = 26/37), but 56% (n = 61/108) of relapsed patients became seizure-free again by the end of the study, with only 9% (n = 31/332) meeting the International League Against Epilepsy (ILAE) definition of pharmacoresistance during follow-up. Of the 221 seizure-free patients, 83% achieved this on monotherapy. There was no significant difference in efficacy rate between new and standard AED monotherapy (74% versus 77%, P = 0.66). The overall poor tolerability rate of AEDs was 21% (n = 69/332). Among the different new and standard AEDs used as initial monotherapy, lamotrigine was associated with the lowest rate of adverse effects (12%, n = 15/124), while topiramate was associated with the highest rate (56%, n = 5/9). SIGNIFICANCE:Teenagers with epilepsy showed good seizure control, particularly those with generalized epilepsy. However, relapse was common and there was high risk of seizure recurrence after treatment withdrawal. Most patients were controlled on monotherapy. As the efficacy of AEDs was comparable, tolerability can be a primary consideration for AED selection in this population.
10.1111/epi.15664
Early predictors of remission in newly diagnosed epilepsy: a systematic approach to reviewing prognostic factor studies.
Abimbola Seye,Martiniuk Alexandra L C,Hackett Maree L,Glozier Nicholas,Mohamed Armin,Anderson Craig S
Neurological research
BACKGROUND:It is necessary to select a range of consistently identified prognostic factors from exploratory studies to include in multivariate models of confirmatory studies. We illustrate a systematic approach to selecting consistently identified prognostic factors using the example of predictors of remission in newly diagnosed epilepsy. METHODS:Medline and Embase were searched for reports of cohort studies enrolling at least 100 people with epilepsy within 1 year of diagnosis, and followed up for at least 1 year. We included studies that identified predictors of remission after adjusting for confounders using multivariate regression analysis. To identify consistent predictors a chart was designed to list the variables considered for inclusion in each model and those retained in more than one model from different cohorts were deemed to be consistent. RESULTS:Remission off medication was less likely if there was more than one seizure between 6 and 12 months on medication and if there was comorbid intellectual disability in childhood onset epilepsy. The likelihood of remission on or off medication reduces with mixed seizure types at onset, intellectual disability, symptomatic aetiology, and also with increasing number of seizures before diagnosis or in the first 6 months after diagnosis. CONCLUSION:A greater number of seizures before diagnosis and early in treatment, intellectual disability, and symptomatic aetiology are consistent predictors of less likelihood of remission. This suggests that early identification, diagnosis of epilepsy, and seizure control should be the primary aim of medical intervention, and that these predictors should be included in future confirmatory studies of prognostic factors of remission in newly diagnosed epilepsy.
10.1179/1743132813Y.0000000257
Prediction of antiepileptic drug treatment outcomes of patients with newly diagnosed epilepsy by machine learning.
Yao Lijun,Cai Mengting,Chen Yang,Shen Chunhong,Shi Lei,Guo Yi
Epilepsy & behavior : E&B
OBJECTIVE:The objective of this study was to build a supervised machine learning-based classifier, which can accurately predict the outcomes of antiepileptic drug (AED) treatment of patients with newly diagnosed epilepsy. METHODS:We collected information from 287 patients with newly diagnosed epilepsy between 2009 and 2017 at the Second Affiliated Hospital of Zhejiang University. Patients were prospectively followed up for at least 3 years. A number of features, including demographic features, medical history, and auxiliary examinations (electroencephalogram [EEG] and magnetic resonance imaging [MRI]) are selected to distinguish patients with different remission outcomes. Seizure outcomes classified as remission and never remission. In addition, remission is further divided into early remission and late remission. Five classical machine learning algorithms, i.e., Decision Tree, Random Forest, Support Vector Machine, XGBoost, and Logistic Regression, are selected and trained by our dataset to get classification models. RESULTS:Our study shows that 1) compared with the other four algorithms, the XGBoost algorithm based machine learning model achieves the best prediction performance of the AED treatment outcomes between remission and never remission patients with an F1 score of 0.947 and an area under the curve (AUC) value of 0.979; 2) The best discriminative factor for remission and never remission patients is higher number of seizures before treatment (>3); 3) XGBoost-based machine learning model also offers the best prediction between early remission and later remission patients, with an F1 score of 0.836 and an AUC value of 0.918; 4) multiple seizure type has the highest dependence to the categories of early and late remission patients. SIGNIFICANCES:Our XGBoost-based machine learning classifier accurately predicts the most probable AED treatment outcome of a patient after he/she finishes all the standard examinations for the epilepsy disease. The classifier's prediction result could help disease guide counseling and eventually improve treatment strategies.
10.1016/j.yebeh.2019.04.006
A prospective cohort study of prognosis for newly diagnosed epilepsy in east China.
Zhang Yanfang,Yu Nian,Su Lingying,Di Qing
BMC neurology
BACKGROUND:Limited data are available on the outcome of antiepileptic drug treatment response in patients of Chinese Han ethnicity with newly diagnosed epilepsy. We sought to explore the prognosis with antiepileptic drug treatment and to identify the predictors of poor drug control of seizures in these patients. METHODS:For at least 2 years, we prospectively followed up a cohort of patients with newly diagnosed epilepsy and analyzed the response to each antiepileptic drug. Cumulative risk for seizure relapse after initial remission achieved was estimated. The patients were divided into two groups (poor and good control) and compared for clinical characteristics. RESULTS:A total of 180 patients were included. Early remission was reached in 125 (69.44%) patients, 19 (10.56%) patients entered late remission, while 36 (20%) patients failed to achieve remission. The relapse rates were 19.5% at 2 years and 31.9% at 3 years of the follow-up. The response rates of the first throughout the fourth treatment regimens were 60.0%, 16.1%, 2.8%, and 0.6%, respectively. Multiple seizure types and changes in seizure type during treatment were significantly (p = 0.013 and 0.047, respectively) associated with a poor control. CONCLUSIONS:The prognosis of the majority of patients with newly diagnosed epilepsy is good and the clinical pattern of epilepsy during treatment is complex. The chances of seizure control declines with each subsequent treatment regimen. The prognosis for patients with multiple seizure types and seizure type changes during treatment is unfavorable.
10.1186/1471-2377-13-116
Prognostic analysis for short- and long-term outcomes of newly diagnosed epilepsy.
Jiang Yong-Li,Yuan Fang,Yang Fang,Sun Xiao-Long,Yang Xi-Ai,Song Lu,Jiang Wen
Seizure
PURPOSE:To explore predictors for short- and long-term prognosis of newly diagnosed epilepsy. METHODS:549 consecutive patients with newly diagnosed epilepsy were reviewed, 336 were enrolled in the study. Two-year remission in the short term (5 years) and five-year remission in the long term (>5, up to 8 years) were assessed as the outcomes. Logistic regression was used to identify independent predictors for unfavorable outcomes. χ test was used to compare the retention rates of old and new antiepileptic drugs (AEDs). RESULTS:185 patients (55%) attained two-year remission in the short term, 163 (48.5%) attained terminal remission in the long term. The time interval between index seizure and AED start >12 months implied an unfavorable outcome in the short term (OR=1.9, p=0.03). Two or more seizures in the first year after AED start showed the strongest negative prognostic impact in the both short- and long-term outcomes (OR=2.3, p=0.02; OR=1.9, p=0.03). As the seizure frequency rose, the possibility for unfavorable outcome increased. The terminal retention rates of traditional and new AEDs were not significantly different (p=0.07). CONCLUSIONS:For patients with newly diagnosed epilepsy, the time interval between index seizure and AED start only influences the short-term outcome. Number of seizures in the first year after AED start is associated with both short- and long-term outcomes. It's imperative to initiate adequate, tolerated and appropriately chosen AED schedules after the definitive diagnosis of epilepsy.
10.1016/j.seizure.2017.02.018
The long-term prognosis of newly diagnosed epilepsy in Egypt: A retrospective cohort study from an epilepsy center in Greater Cairo.
Ashmawi Ayman,Hosny Hassan,Abdelalim Ahmed,Bianchi Elisa,Beghi Ettore
Seizure
PURPOSE:To investigate the long-term prognosis and prognostic patterns of epilepsy in a single practice study from a developing country. METHODS:Consecutive patients first seen in an epilepsy clinic in Cairo, Egypt between January 1994 and December 2009 with at least 4 years of follow-up were included. Demographic, clinical, EEG and imaging findings at diagnosis were recorded. At follow-up, treatment was adjusted as clinically indicated. The response to the first drug was defined as 6-month seizure remission. Outcome measures included 2-year remission (R) and 2-year sustained remission (SR). Prognostic patterns were early (ER) and late remission (LR), relapsing-remitting (RR) course, worsening course (WC) and no remission. RESULTS:Included were 287 patients aged 1-66 years and followed for 2237.0 person-years (mean 7.8 years). 244 (85%) attained 2-year R. The cumulative time dependent probability of R was 86.7% at 10 years. Only the response to the first drug predicted R. 82 (28.6%) attained 2-year SR. The probability of SR was 40.9% at 10 years. Poor treatment response and nocturnal seizures predicted lowered SR. R and SR were inversely correlated to the number of drugs. 208 patients (72.5%) entered ER, 36 (12.5%) entered LR, 138 (48.1%) had RR course. A WC was present in 24 (8.4%), 43 (15.0%) never entered remission. Prognostic patterns varied with neurological examination, MRI findings, pre-treatment seizure frequency, seizure type, number of seizure types, etiology, syndrome and response to first drug. CONCLUSIONS:The long-term prognosis of newly diagnosed epilepsy patients from a developing country is in keeping with published reports.
10.1016/j.seizure.2016.07.016