High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial).

INTRODUCTION: The standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up). METHODS: In this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated. DISCUSSION: This is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021.

Evaluation of MEG vs EEG after sleep deprivation in epilepsy.

OBJECTIVE: MEG and EEG after sleep deprivation (EEG-SD) are applied as diagnostic tools in the evaluation of patients with possible epilepsy. There is no gold standard to check whether the diagnosis based on these two modalities is correct. The best standard available is the long-term follow-up of patients. As follow-up of an earlier study in which the additional value of MEG vs EEG-SD diagnosis was evaluated, we investigated the long-term validity of MEG-based and EEG-SD-based diagnosis. MATERIALS AND METHODS: Data collected from 46 patients were used in a comparative study of the last known diagnosis against the original one of 8 years ago. RESULTS: Long-term (3-8 years) sensitivity of sharp phenomena (combining spikes and sharp waves) in routine MEG and in EEG-SD for the diagnosis epilepsy is 71% and 62%, respectively. When compared to the original study, this hardly changed. Over time, uncertainty on diagnosis diminishes. CONCLUSION: MEG as well as EEG-SD are robust long-term predictors for epilepsy.

Feasibility of online seizure detection with continuous EEG monitoring in the intensive care unit.

INTRODUCTION: Continuous EEG (cEEG) is of great interest in view of the reported high prevalence of non-convulsive seizures on intensive care units (ICUs). Here, we describe our experiences applying a seizure warning system using cEEG monitoring. METHODS: Fifty comatose ICU patients were included prospectively and monitored. Twenty-eight patients had post-anoxic encephalopathy (PAE) and 22 had focal brain lesions. A measure of neuronal interactions, synchronization likelihood, was calculated online over 10s EEG epochs and instances when the synchronization likelihood exceeded a threshold where marked as seizures. RESULTS: Five patients developed seizures. Our method detected seizures in three patients, in the other patients seizures were missed because of they were non-convulsive and had a focal character. The average false positive rate was 0.676/h. DISCUSSION: This is our first attempt to implement online seizure detection in the ICU. Despite problems with artifacts and that we missed focally oriented seizures, we succeeded in monitoring patients online. Given the relatively high occurrence of seizures, online seizure detection with cEEG merits further development for use in ICUs.

Inter-observer variability of the EEG diagnosis of seizures in comatose patients.

OBJECTIVE: To assess the inter-observer agreement of the electroencephalogram (EEG) diagnosis of (non-convulsive) seizures in comatose patients. DESIGN/SETTING/PATIENTS: Nine clinicians with different levels of experience in clinical neurophysiology were asked to evaluate in a strictly controlled way 90 epochs (10s each) of 30 EEG's of 23 comatose patients admitted to the intensive care unit (ICU). For each EEG clinicians had to decide whether there was an electrographic seizure or not. Furthermore, Young's EEG criteria for (non-convulsive) seizures were scored in detail for all EEG's. Agreement was determined by calculating kappa values. RESULTS: The inter-observer agreement of an EEG diagnosis of seizure was limited. The overall kappa score for the five experienced raters was 0.5, and the kappa score for less experienced raters was 0.29. Kappa values for the individual Young's criteria were highly variable, indicating discrepancies in the interpretation of specific phenomena. Especially, some types of periodic discharges gave rise to different interpretations. CONCLUSIONS: The EEG diagnosis of (non-convulsive) seizures in ICU patients is not very reliable, even when strict criteria such as proposed by Young are applied. There is a need for less ambiguous EEG criteria for (non-convulsive) seizures and status epilepticus.