Value of ultra-high field MRI in patients with suspected focal epilepsy and negative 3 T MRI (EpiUltraStudy): protocol for a prospective, longitudinal therapeutic study.

PURPOSE: Resective epilepsy surgery is a well-established, evidence-based treatment option in patients with drug-resistant focal epilepsy. A major predictive factor of good surgical outcome is visualization and delineation of a potential epileptogenic lesion by MRI. However, frequently, these lesions are subtle and may escape detection by conventional MRI (≤ 3 T). METHODS: We present the EpiUltraStudy protocol to address the hypothesis that application of ultra-high field (UHF) MRI increases the rate of detection of structural lesions and functional brain aberrances in patients with drug-resistant focal epilepsy who are candidates for resective epilepsy surgery. Additionally, therapeutic gain will be addressed, testing whether increased lesion detection and tailored resections result in higher rates of seizure freedom 1 year after epilepsy surgery. Sixty patients enroll the study according to the following inclusion criteria: aged ≥ 12 years, diagnosed with drug-resistant focal epilepsy with a suspected epileptogenic focus, negative conventional 3 T MRI during pre-surgical work-up. RESULTS: All patients will be evaluated by 7 T MRI; ten patients will undergo an additional 9.4 T MRI exam. Images will be evaluated independently by two neuroradiologists and a neurologist or neurosurgeon. Clinical and UHF MRI will be discussed in the multidisciplinary epilepsy surgery conference. Demographic and epilepsy characteristics, along with postoperative seizure outcome and histopathological evaluation, will be recorded. CONCLUSION: This protocol was reviewed and approved by the local Institutional Review Board and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: www.trialregister.nl : NTR7536.

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.

[Levetiracetam: an anti-epileptic drug with interesting pharmacokinetic properties]. / Levetiracetam: een anti-epilepticum met interessante farmacokinetische eigenschappen.

Levetiracetam is a new anticonvulsant for adjunctive treatment of partial epilepsy. It is well tolerated, with no significant risks, at a dose of 1000-3000 mg/day in adults. The efficacy (> 50% reduction in attacks) in refractory partial epilepsy is 22-40%, depending on the dose. Efficacy was also seen with levetiracetam monotherapy in more than half of the positive responders. Levetiracetam does not cause induction or inhibition of the P450 enzyme system or other enzyme systems, there is no active metabolite and it exhibits almost no protein binding. These factors mean that this drug undergoes no significant interactions with other medication and appears suitable for elderly patients and for conditions requiring complex pharmacotherapy. Compared with other recently registered anti-epilepsy drugs, levetiracetam appears promising in terms of efficacy, tolerability and pharmacokinetics. The simple dosing schedule is an additional benefit.

Transcranial magnetic stimulation in patients with cervical spondylotic myelopathy: clinical and radiological correlations.

Motor evoked potentials (MEPs) were studied in 28 patients with cervical spondylotic myelopathy. MEPs after cortical stimulation were abnormal in 27 patients, the responses in the leg muscles being affected the most often. Clinically asymptomatic motor lesions were detected in 7 patients (25%). The central motor conduction time (CMCT) for the abductor digiti minimi muscles correlated significantly with the clinical disability, whereas the radiological findings did not correlate with the clinical and neurophysiological parameters. In 9 patients MEPs were also recorded in the biceps muscles. The 7 patients with an abnormal CMCT for the biceps muscles had the most severe stenosis at the C-4-C-5 level or higher. The 2 patients with normal MEPs of the biceps muscles both had a stenosis at the C-5-C-6 level. The results of this study suggest that MEPs are useful for detecting spinal cord dysfunction and for localizing the level of the lesion. Some recommendations regarding the possible use of MEPs in the clinical evaluation of patients with cervical spondylotic myelopathy are given.

Killing of bacillus spores by aqueous dissolved oxygen, ascorbic acid, and copper ions.

An approach to decontamination of biological endospores is discussed. Specifically, the performance of an aqueous modified Fenton reagent is examined. A modified Fenton reagent formulation of cupric chloride, ascorbic acid, and sodium chloride is shown to be an effective sporicide under aerobic conditions. The traditional Fenton reaction involves the conversion of hydrogen peroxide to hydroxyl radical by aqueous ionic catalysts such as the transition metal ions. Our modified Fenton reaction involves the conversion of aqueous dissolved oxygen to hydrogen peroxide by an ionic catalyst (Cu(2+)) and then subsequent conversion to hydroxyl radicals. Results are given for the modified Fenton reagent deactivating spores of Bacillus globigii. A biocidal mechanism is proposed that is consistent with our experimental results and independently derived information found in the literature. This mechanism requires diffusion of relatively benign species into the interior of the spore, where dissolved O(2) is then converted through a series of reactions which ultimately produce hydroxyl radicals that perform the killing action.