Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.

Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME. Methods: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on treatment outcomes of people diagnosed with JME and available seizure outcome data after a minimum one-year follow-up. We invited authors to share standardised IPD to identify predictors of drug resistance using multivariable logistic regression. We excluded pseudo-resistant individuals. A subset who attempted to withdraw ASM was included in a multivariable proportional hazards analysis on seizure recurrence after ASM withdrawal. The study was registered at the Open Science Framework (OSF; https://osf.io/b9zjc/). Findings: Our search yielded 1641 articles; 53 were eligible, of which the authors of 24 studies agreed to collaborate by sharing IPD. Using data from 2518 people with JME, we found nine independent predictors of drug resistance: three seizure types, psychiatric comorbidities, catamenial epilepsy, epileptiform focality, ethnicity, history of CAE, family history of epilepsy, status epilepticus, and febrile seizures. Internal-external cross-validation of our multivariable model showed an area under the receiver operating characteristic curve of 0·70 (95%CI 0·68-0·72). Recurrence of seizures after ASM withdrawal (n = 368) was predicted by an earlier age at the start of withdrawal, shorter seizure-free interval and more currently used ASMs, resulting in an average internal-external cross-validation concordance-statistic of 0·70 (95%CI 0·68-0·73). Interpretation: We were able to predict and validate clinically relevant personalised treatment outcomes for people with JME. Individualised predictions are accessible as nomograms and web-based tools. Funding: MING fonds.

Do Spike Domain Analysis Interictally Correlate With the Ictal Patterns in Temporal Lobe Epilepsy?

PURPOSE: To study if one can conceptualize the scalp ictal onset pattern through analysis of interictal spike domain analysis in temporal lobe epilepsy (TLE). METHODS: Seventy-four patients with unilateral mesial temporal sclerosis (MTS) were categorized into "type A" interictal epileptiform discharges (IEDs) with negativity over infero-lateral scalp electrodes over temporal region and contralateral central region showing positivity; all IEDs other than type A were categorized as type B. The ictal electrographic patterns was termed "focal" when confined to side of MTS, was "regional" when lateralized to the ipsilateral hemisphere; "diffuse" if nonlateralized/localized; and ictal onset contralateral to MTS termed as "discordant." RESULTS: A total of 377 seizures and 5,476 spikes were studied. These were divided into four types: (1) type A IEDs ipsilateral to MTS (44 patients), (2) type A IEDs bitemporally (16 patients), (3) type A IEDs contralaterally (7 patients) and type B IEDs ipsilaterally, and (4) bilateral type B IEDs (7 patients). The ictal pattern was either focal or regional in 51 of 60 patients (85%) with type A IEDs; it was "diffuse" in 9 patients (15%). Diffuse ictal onset was seen in 12 of 14 (86%) with either ipsilateral/bitemporal type B IEDs. Ictal onset on the opposite hemisphere was noted in 2 (14%). CONCLUSIONS: Type A IEDs signify a focal ictal onset and type B IEDs suggest a diffuse ictal onset in patients with MTS on one side. SIGNIFICANCE: Interictal spike domain analysis helps predicting ictal patterns in temporal lobe epilepsy.

How does "locus of control" affect persons with epilepsy?

PURPOSE: Locus of control (LOC) is the degree to which people believe that they have control over the outcome of events in their lives. A person's locus can be internal, external, or chance. A person with internal locus of control believes that one can control one's own life. A person with external locus of control believes that his life is controlled by external factors or people over which he has no influence. A person with chance locus of control believes that fate, chance, or luck controls his own life. The aim of the current study was to determine the health locus of control, anxiety, and depression levels in persons with epilepsy (PWE) and to assess whether locus of control has relation to anxiety, depression, and seizure control. METHODS: Patients aged 18 years or older with a history of epilepsy for at least 1 year were recruited from the outpatient epilepsy clinic or from the inpatient epilepsy monitoring unit at SCTIMST, Trivandrum from January 2019 to May 2020. Patients filled the questionnaire form consisting of demographic data, age of onset of seizures, present seizure control, and the current antiepileptic drugs. The Hospital Anxiety and Depression (HAD) scale was used to estimate the level of anxiety and depression in these patients. The Form-C of the Multidimensional Health Locus of Control (MHLC) scale was used to evaluate the health locus of control. Healthy controls aged 18 years or older and free of any chronic disease or psychiatric illness were also recruited. They were asked to fill the questionnaire forms with basic demographic data. HAD scale was used to estimate the level of anxiety and depression and form-C of MHLC was used to evaluate the health locus of control in the healthy controls. The mean scores of anxiety, depression, and locus of control were compared between the two groups. RESULTS: A total of 170 participants were recruited which consisted of 100 PWE and 70 healthy controls. The mean anxiety and depression scores were 8.13(SD = 4.23) and 5.85(SD = 3.66) in the PWE group and 6.75(SD = 3.39) and 4.14(SD = 2.96) in the control group, respectively. The mean internal, external, and chance LOC scores were 24.95(SD = 10.92), 26.94(SD = 4.96), and 24.41(SD = 6.46) in the PWE group; and 29.44(SD = 5.62), 26.53(SD = 5.79), and 19.9(SD = 7.13) in the control group, respectively. Persons with epilepsy had higher chance LOC scores and lower internal LOC scores compared to controls (p = 0.00003, p < 0.00001 respectively). There were no differences in the external LOC scores between the two groups (p = 0.620). Persons with epilepsy with some level of anxiety had lower internal LOC scores compared to patients with no anxiety (p = 0.04). PWE with poor seizure control had higher external LOC score and lower internal LOC scores which however did not reach statistical significance. Persons with epilepsy with poor seizure control had higher anxiety and depression scores. CONCLUSIONS: Persons with epilepsy had low perceptions of internal and strong perceptions of chance health locus of control. This means that PWE feel that luck plays an important role in their disease control. This information is important in the counseling of persons with epilepsy.

Personality disorders in temporal lobe epilepsy: What do they signify?

OBJECTIVES: To estimate the prevalence of personality disorders in patients with temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) and compare it with general population and analyze their implications on treatment outcome. MATERIALS AND METHODS: TLE was diagnosed based on clinical history, MRI, and Video EEG data. IPDE-ICD10 screening questionnaire was applied to investigate personality disorder in 120 subjects, 60 cases, and 60 normal controls. Bear-Fedio inventory (BFI) was used to study different behavior traits in patients with TLE and controls. RESULTS: Prevalence of personality disorders was higher (71.7% in cases versus 38.3% in controls) in patients with TLE compared to controls (P < .001). Some personality traits like schizoid (P = .002), dissocial (P = .001), impulsive (P = .003), anankastic (P < .001), anxious (P < .001), and dependent (P < .001) personalities were found to have high prevalence in TLE. Personality disorder was higher among those cases who had been tried on more than two antiepileptic drugs (AEDs) (P = .033) and in those with duration of illness more than 10 years (P = .026). Cases also showed significantly higher score in BFI for all behavioral traits except for aggression. No significant difference of BFI score was seen based on laterality of epileptic focus, gender, duration of illness, or number of AEDs tried. CONCLUSION: There is a significantly higher prevalence of personality disorders in patients with TLE. Specific interventions for these disorders should be considered at the earliest pari passu with AEDs and surgery.