CONTEXT Despite reported success, surgery for pharmacoresistant seizures is often seen as a last resort. Patients are typically referred for surgery after 20 years of seizures, often too late to ...avoid significant disability and premature death. OBJECTIVE We sought to determine whether surgery soon after failure of 2 antiepileptic drug (AED) trials is superior to continued medical management in controlling seizures and improving quality of life (QOL). DESIGN, SETTING, AND PARTICIPANTS The Early Randomized Surgical Epilepsy Trial (ERSET) is a multicenter, controlled, parallel-group clinical trial performed at 16 US epilepsy surgery centers. The 38 participants (18 men and 20 women; aged ≥12 years) had mesial temporal lobe epilepsy (MTLE) and disabling seizues for no more than 2 consecutive years following adequate trials of 2 brand-name AEDs. Eligibility for anteromesial temporal resection (AMTR) was based on a standardized presurgical evaluation protocol. Participants were randomized to continued AED treatment or AMTR 2003-2007, and observed for 2 years. Planned enrollment was 200, but the trial was halted prematurely due to slow accrual. INTERVENTION Receipt of continued AED treatment (n = 23) or a standardized AMTR plus AED treatment (n = 15). In the medical group, 7 participants underwent AMTR prior to the end of follow-up and 1 participant in the surgical group never received surgery. MAIN OUTCOME MEASURES The primary outcome variable was freedom from disabling seizures during year 2 of follow-up. Secondary outcome variables were health-related QOL (measured primarily by the 2-year change in the Quality of Life in Epilepsy 89 QOLIE-89 overall T-score), cognitive function, and social adaptation. RESULTS Zero of 23 participants in the medical group and 11 of 15 in the surgical group were seizure free during year 2 of follow-up (odds ratio = ∞; 95% CI, 11.8 to ∞; P < .001). In an intention-to-treat analysis, the mean improvement in QOLIE-89 overall T-score was higher in the surgical group than in the medical group but this difference was not statistically significant (12.6 vs 4.0 points; treatment effect = 8.5; 95% CI, −1.0 to 18.1; P = .08). When data obtained after surgery from participants in the medical group were excluded, the effect of surgery on QOL was significant (12.8 vs 2.8 points; treatment effect = 9.9; 95% CI, 2.2 to 17.7; P = .01). Memory decline (assessed using the Rey Auditory Verbal Learning Test) occurred in 4 participants (36%) after surgery, consistent with rates seen in the literature; but the sample was too small to permit definitive conclusions about treatment group differences in cognitive outcomes. Adverse events included a transient neurologic deficit attributed to a magnetic resonance imaging–identified postoperative stroke in a participant who had surgery and 3 cases of status epilepticus in the medical group. CONCLUSIONS Among patients with newly intractable disabling MTLE, resective surgery plus AED treatment resulted in a lower probability of seizures during year 2 of follow-up than continued AED treatment alone. Given the premature termination of the trial, the results should be interpreted with appropriate caution. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00040326
Despite recent advances in treatment and prevention, the prevalence of cerebral malaria (CM) remains high globally, especially in children under 5 years old. As treatment improves, more children will ...survive episodes of CM with lasting neurodisabilities, such as social and behavioural issues. Behaviour problems in children who survive CM are poorly characterized, and the impact of caring for a child with post-CM behaviour issues has not been well-explored. Caregivers' perceptions of and experiences with their child's post-CM behaviour problems are reported here.
Semi-structured interviews were conducted with 29 primary caregivers of children who survived CM with reported behaviour issues in Blantyre, Malawi. Interviews were conducted in Chicheŵa, audio-recorded, transcribed, and translated into English. Data were coded manually, utilizing inductive and deductive approaches. Identified codes were thematically analysed.
Post-CM behaviours reported include externalizing, aggressive behaviours and learning difficulties. Variable timescales for behaviour change onset were noted, and most caregivers reported some evolution of their child's behaviour over time. Caregivers experienced a variety of emotions connected to their child's behaviour and to reactions of family and community members. Caregivers who experienced discrimination were more likely to describe negative emotions tied to their child's behaviour changes, compared to caregivers who experienced support.
Caregiver perceptions of behaviour changes in post-CM survivors are variable, and caregiver experience is strongly impacted by family and community member responses. Future educational, rehabilitation, and support-based programmes should focus on the specific types of behaviour problems identified and the difficulties faced by caregivers and their communities.
Abstract Recent ILAE revisions to the definition and classification of the epilepsies have highlighted cognitive–behavioral comorbidities (CBCs). Integrating a CBC dimension within a formal ...classification scheme would more fully account for the burden of epilepsy. This would be technically challenging, because we use fundamentally different methods to conceptualize, define, and diagnose CBCs that require additional expertise. In low resource settings such as sub-Saharan Africa (SSA), CBC burden is high. Existing classification systems are inevitably simplified in practice, because complex classifications require training and technologies that rarely exist in these settings. This makes low-resource settings a good place to develop simple methods to integrate CBCs into existing classifications so that they ultimately will communicate the full burden of epilepsy. This article is part of a Special Issue entitled “The new approach to classification: Rethinking cognition and behavior in epilepsy”.
: media-1vid110.1542/5972295739001PEDS-VA_2018-1026
BACKGROUND AND OBJECTIVES: Cerebral malaria (CM) causes significant mortality and morbidity in sub-Saharan African children. Reliable morbidity ...estimates are scarce because of methodological variability across studies. We describe the incidence, course, and severity of neurodevelopmental impairments in survivors of CM and the associated patient characteristics to inform epidemiologic estimates of malaria morbidity rates and prevention and treatment efforts.
We conducted an exposure-control study of 85 survivors of CM and 100 age-matched patients in a control group who were enrolled at hospital discharge and assessed after 1, 6, and 12 months using caregiver interviews and standardized developmental, cognitive, and behavioral measures.
Developmental or cognitive impairment (<10th percentile of the control distribution) and/or new onset of caregiver-reported behavior problems occurred in 53% of case patients compared with 20% of the patients in the control group (odds ratio 4.5; 95% CI: 2.4 to 8.6;
< .001). In case patients, developmental or cognitive impairment at the 12-month assessment was associated with HIV-positive status and short stature at presentation, more prolonged fever and coma during admission, and severe atrophy or multifocal abnormalities being found on MRI at the 1-month assessment.
One-half of survivors of CM were neurodevelopmentally impaired at the 1-year assessment. With these results, we support prevention trials of acute, neuroprotective interventions and the allocation of resources to evaluation, education, and rehabilitation efforts to reduce the significant long-term burden of CM-associated impairments on families and their communities.
Summary
Purpose: To determine the frequency and determinants of subnormal global cognitive function in a representative, community‐based sample of children prospectively identified at the time of ...initial diagnosis of epilepsy.
Methods: In children enrolled with newly diagnosed epilepsy and followed a median of 10.5 years, level of cognitive function (within normal, borderline, mild, moderate to severe mental retardation (MR), neurologically devastated, and impaired but not further classified (NFC)) was determined based upon neurologists' and school records, repeated parental interviews, and, in over half the participants, standardized neuropsychological testing. For multivariable analyses, subnormal cognitive function was designated as consistent with a full scale IQ < 80.
Results: Global cognitive function was considered within normal, N = 451 (73.6%), borderline, N = 31 (5.1%), mild MR, N = 21 (3.4%), more severe MR, N = 45 (7.3%), devastated, N = 29 (4.7%), and impaired‐NFC, N = 36 (5.9%). Age at onset <5 years, symptomatic etiology, epileptic encephalopathy, remission status and current AED treatment were each strongly associated with level of cognitive function (all p‐values <0.0001). In a multivariable logistic regression model, all variables except remission status independently contributed to subnormal global cognitive function.
Discussion: Evidence of subnormal global cognitive function is apparent in approximately one of four children with epilepsy. Young age at onset, symptomatic cause, epileptic encephalopathy, and continued treatment, despite their strong intercorrelations, are independently associated with this outcome.
Summary
Objective
To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE).
Methods
This ...randomized, single‐blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36‐month follow‐up.
Results
A total of 58 patients (31 in SRS, 27 in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved seizure remission (difference between ATL and SRS = 26%, upper 1‐sided 95% confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean VM changes from baseline for 21 English‐speaking, dominant‐hemisphere patients did not differ between groups; consistent worsening occurred in 36% of SRS and 57% of ATL patients. QOL improved with seizure remission. Adverse events were anticipated cerebral edema and related symptoms for some SRS patients, and cerebritis, subdural hematoma, and others for ATL patients.
Significance
These data suggest that ATL has an advantage over SRS in terms of proportion of seizure remission, and both SRS and ATL appear to have effectiveness and reasonable safety as treatments for MTLE. SRS is an alternative to ATL for patients with contraindications for or with reluctance to undergo open surgery.
Purpose: Multiple studies have examined predictors of seizure outcomes after epilepsy surgery. Most are single‐center series with limited sample size. Little information is available about the ...selection process for surgery and, in particular, the proportion of patients who ultimately have surgery and the characteristics that identify those who do versus those who do not. Such information is necessary for providing the epidemiologic and clinical context in which epilepsy surgery is currently performed in the United States and in other developed countries.
Methods: An observational cohort of 565 surgical candidates was prospectively recruited from June 1996 through January 2001 at six Northeastern and one Midwestern surgical centers. Standardized eligibility criteria and protocol for presurgical evaluations were used at all seven sites.
Results: Three hundred ninety‐six (70%) study subjects had resective surgery. Clinical factors such as a well‐localized magnetic resonance imaging (MRI) abnormality and consistently localized EEG findings were most strongly associated with having surgery. Of those who underwent intracranial monitoring (189, 34%), 85% went on to have surgery. Race/ethnicity and marital status were marginally associated with having surgery. Age, education, and employment status were not. Demographic factors had little influence over the surgical decision. More than half of the patients had intractable epilepsy for ≥10 years and five or more drugs had failed by the time they initiated their surgical evaluation. During the recruitment period, eight new antiepileptic drugs were approved by the Food and Drug Administration for use in the United States and came into increasing use in this study's surgical candidates. Despite the increased availability of new therapeutic options, the proportion that had surgery each year did not fluctuate significantly from year to year. This suggests that, in this group of patients, the new drugs did not provide a substantial therapeutic benefit.
Conclusions: Up to 30% of patients who undergo presurgical evaluations for resective epilepsy surgery ultimately do not have this form of surgery. This is a group whose needs are not currently met by available therapies and procedures. Lack of clear localizing evidence appears to be the main reason for not having surgery. To the extent that these data can address the question, they suggest that repeated attempts to control intractable epilepsy with new drugs will not result in sustained seizure control, and eligible patients will proceed to surgery eventually. This is consistent with recent arguments to consider surgery earlier rather than later in the course of epilepsy. Postsurgical follow‐up of this group will permit a detailed analysis of presurgical factors that predict the best and worst seizure outcomes.
Naming decline after left temporal lobe epilepsy (TLE) surgery is common and difficult to predict. Preoperative language fMRI may predict naming decline, but this application is still lacking ...evidence. We performed a large multicenter cohort study of the effectiveness of fMRI in predicting naming deficits after left TLE surgery.
At 10 US epilepsy centers, 81 patients with left TLE were prospectively recruited and given the Boston Naming Test (BNT) before and ≈7 months after anterior temporal lobectomy. An fMRI language laterality index (LI) was measured with an auditory semantic decision-tone decision task contrast. Correlations and a multiple regression model were built with a priori chosen predictors.
Naming decline occurred in 56% of patients and correlated with fMRI LI (
= -0.41,
< 0.001), age at epilepsy onset (
-0.30,
= 0.006), age at surgery (
= -0.23,
= 0.039), and years of education (
= 0.24,
= 0.032). Preoperative BNT score and duration of epilepsy were not correlated with naming decline. The regression model explained 31% of the variance, with fMRI contributing 14%, with a 96% sensitivity and 44% specificity for predicting meaningful naming decline. Cross-validation resulted in an average prediction error of 6 points.
An fMRI-based regression model predicted naming outcome after left TLE surgery in a large, prospective multicenter sample, with fMRI as the strongest predictor. These results provide evidence supporting the use of preoperative language fMRI to predict language outcome in patients undergoing left TLE surgery.
This study provides Class I evidence that fMRI language lateralization can help in predicting naming decline after left TLE surgery.
Removal of the anterior temporal lobe (ATL) is an effective surgical treatment for intractable temporal lobe epilepsy but carries a risk of language and verbal memory deficits. Preoperative ...localization of functional zones in the ATL might help reduce these risks, yet fMRI protocols in current widespread use produce very little activation in this region. Based on recent evidence suggesting a role for the ATL in semantic integration, we designed an fMRI protocol comparing comprehension of brief narratives (Story task) with a semantically shallow control task involving serial arithmetic (Math task). The Story > Math contrast elicited strong activation throughout the ATL, lateral temporal lobe, and medial temporal lobe bilaterally in an initial cohort of 18 healthy participants. The task protocol was then implemented at 6 other imaging centers using identical methods. Data from a second cohort of participants scanned at these centers closely replicated the results from the initial cohort. The Story–Math protocol provides a reliable method for activation of surgical regions of interest in the ATL. The bilateral activation supports previous claims that conceptual processing involves both temporal lobes. Used in combination with language lateralization measures, reliable ATL activation maps may be useful for predicting cognitive outcome in ATL surgery, though the validity of this approach needs to be established in a prospective surgical series.
► An fMRI protocol emphasizing semantic integration activates the anterior temporal lobe. ► ATL activation was consistently observed in individual participants. ► The results were successfully replicated at 6 other imaging centers. ► The methods provide a valuable tool for studying cognitive effects of ATL resection.
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