Dataset Information

Protocol for an observational cohort study investigating biomarkers predicting seizure recurrence following a first unprovoked seizure in adults.

ABSTRACT:

Introduction

A first unprovoked seizure is a common presentation, reliably identifying those that will have recurrent seizures is a challenge. This study will be the first to explore the combined utility of serum biomarkers, quantitative electroencephalogram (EEG) and quantitative MRI to predict seizure recurrence. This will inform patient stratification for counselling and the inclusion of high-risk patients in clinical trials of disease-modifying agents in early epilepsy.

Methods and analysis

100 patients with first unprovoked seizure will be recruited from a tertiary neuroscience centre and baseline assessments will include structural MRI, EEG and a blood sample. As part of a nested pilot study, a subset of 40 patients will have advanced MRI sequences performed that are usually reserved for patients with refractory chronic epilepsy. The remaining 60 patients will have standard clinical MRI sequences. Patients will be followed up every 6 months for a 24-month period to assess seizure recurrence. Connectivity and network-based analyses of EEG and MRI data will be carried out and examined in relation to seizure recurrence. Patient outcomes will also be investigated with respect to analysis of high-mobility group box-1 from blood serum samples.

Ethics and dissemination

This study was approved by North East-Tyne & Wear South Research Ethics Committee (20/NE/0078) and funded by an Association of British Neurologists and Guarantors of Brain clinical research training fellowship. Findings will be presented at national and international meetings published in peer-reviewed journals.

Trial registration number

NIHR Clinical Research Network's (CRN) Central Portfolio Management System (CPMS)-44976.

SUBMITTER: Adan GH

PROVIDER: S-EPMC9723849 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Protocol for an observational cohort study investigating biomarkers predicting seizure recurrence following a first unprovoked seizure in adults.

Adan Guleed H GH de Bézenac Christophe C Bonnett Laura L Pridgeon Michael M Biswas Shubhabrata S Das Kumar K Richardson Mark P MP Laiou Petroula P Keller Simon S SS Marson Tony T

BMJ open 20221205 12

<h4>Introduction</h4>A first unprovoked seizure is a common presentation, reliably identifying those that will have recurrent seizures is a challenge. This study will be the first to explore the combined utility of serum biomarkers, quantitative electroencephalogram (EEG) and quantitative MRI to predict seizure recurrence. This will inform patient stratification for counselling and the inclusion of high-risk patients in clinical trials of disease-modifying agents in early epilepsy.<h4>Methods an ...[more]

PMID: 36576179

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Project description:Venous thromboembolism (VTE) is a chronic disease, with fatal recurrences occurring in 5% to 9% of patients, yet it is also one of the best examples of preventable disease. Prognostic models that utilise multiple prognostic factors (demographic, clinical and laboratory patient characteristics) in combination to predict individual outcome risk may allow the identification of patients who would benefit from long-term anticoagulation therapy, and conversely those that would benefit from stopping such therapy due to a low risk of recurrence. The study will systematically review the evidence on potential prognostic models for the recurrence of VTE or adverse outcomes following the cessation of therapy, and synthesise and summarise each model's prognostic value. The review has been registered with PROSPERO (CRD42013003494).Articles will be sought from the Cochrane library (CENTRAL, CDSR, DARE, HTA databases), MEDLINE and EMBASE. Trial registers will be searched for ongoing studies, and conference abstracts will be sought. Reference lists and subject experts will be utilised. No restrictions on language of publications will be applied. Studies of any design will be included if they examine, in patients ceasing therapy after at least three months' treatment with an oral anticoagulant therapy, whether more than one factor in combination is associated with the risk of VTE recurrence or another adverse outcome. Study quality will be assessed using appropriate guidelines for prognostic models. Prognostic models will be summarised qualitatively and, if tested in multiple validation studies, their predictive performance will be summarised using a random-effects meta-analysis model to account for any between-study heterogeneity.The results of the review will identify prognostic models for the risk of VTE recurrence or adverse outcome following cessation of therapy for a first unprovoked VTE. These will be informative for clinicians currently treating patients for a first unprovoked VTE and considering whether to stop treatment or not for particular individuals. The conclusions of the review will also inform the potential development of new prognostic models and clinical prediction rules to identify those at high or low risk of VTE recurrence or adverse outcome following a first unprovoked VTE.

Project description:BACKGROUND:Increasing numbers of reports show the beneficial effects of listening to Mozart music in decreasing epileptiform discharges as well as seizure frequency in epileptic children. There has been no effective method to reduce seizure recurrence after the first unprovoked seizure until now. In this study, we investigated the effect of listening to Mozart K.448 in reducing the seizure recurrence rate in children with first unprovoked seizures. METHODS:Forty-eight children who experienced their first unprovoked seizure with epileptiform discharges were included in the study. They were randomly placed into treatment (n = 24) and control (n = 24) groups. Children in the treatment group listened to Mozart K.448 daily before bedtime for at least six months. Two patients in the treatment group were excluded from analysis due to discontinuation intervention. Finally, forty-six patients were analyzed. Most of these patients (89.1%) were idiopathic in etiology. Seizure recurrence rates and reduction of epileptiform discharges were compared. RESULTS:The average follow-up durations in the treatment and control groups were 18.6 ± 6.6 and 20.1 ± 5.1 months, respectively. The seizure recurrence rate was estimated to be significantly lower in the treatment group than the control group over 24 months (37.2% vs. 76.8%, p = 0.0109). Significant decreases in epileptiform discharges were also observed after 1, 2, and 6 months of listening to Mozart K.448 when compared with EEGs before listening to music. There were no significant differences in gender, mentality, seizure type, and etiology between the recurrence and non-recurrence groups. CONCLUSIONS:Although the case number was limited and control music was not performed in this study, the study revealed that listening to Mozart K.448 reduced the seizure recurrence rate and epileptiform discharges in children with first unprovoked seizures, especially of idiopathic etiology. We believe that Mozart K.448 could be a promising alternative treatment in patients with first unprovoked seizures and abnormal EEGs. Further large-scaled study should be conducted to confirm the effect. TRIAL REGISTRATION:NCT01892605, date: June-19-2013.

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Project description:ObjectiveThis study evaluates the performance of the novel MRI sequence stimulus-induced rotary saturation (SIRS) to map responses to interictal epileptic activity in the human cortex. Spin-lock pulses have been applied to indirectly detect neuronal activity through magnetic field perturbations. Following initial reports about the feasibility of the method in humans and animals with epilepsy, we aimed to investigate the diagnostic yield of spin-lock MR pulses in comparison with scalp-EEG in first seizure patients.MethodsWe employed a novel method for measurements of neuronal activity through the detection of a resonant oscillating field, stimulus-induced rotary saturation contrast (SIRS) at spin-lock frequencies of 120 and 240 Hz acquired at a single 3T MRI system. Within a prospective observational study, we conducted SIRS experiments in 55 patients within 7 days after a suspected first unprovoked epileptic seizure and 61 healthy control subjects. In this study, we report on the analysis of data from a single 3T MRI system, encompassing 35 first seizure patients and 31 controls.ResultsThe SIRS method was applicable in all patients and healthy controls at frequencies of 120 and 240 Hz. We did not observe any significant age- or sex-related differences. Specificity of SIRS at 120 Hz was 90.3% and 93.5% at 240 Hz. Sensitivity was 17.1% at 120 Hz and 40.0% at 240 Hz.SignificanceSIRS targets neuronal oscillating magnetic fields in patients with epilepsy. The coupling of presaturated spins to epilepsy-related magnetic field perturbations may serve as a-at this stage experimental-diagnostic test in first seizure patients to complement EEG findings as a standard screening test.Plain language summaryRoutine diagnostic tests carry several limitations when applied after a suspected first seizure. SIRS is a noninvasive MRI method to enable time-sensitive diagnosis of image correlates of epileptic activity with increased sensitivity compared to routine EEG.

Dataset Information

Protocol for an observational cohort study investigating biomarkers predicting seizure recurrence following a first unprovoked seizure in adults.

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

Protocol for an observational cohort study investigating biomarkers predicting seizure recurrence following a first unprovoked seizure in adults.

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