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.

Photosensitivity and self-induction in patients aged 50 and older.

OBJECTIVE: Photosensitivity is known to occur predominantly in children and adolescents and with a clear female predominance. Little is known on the prevalence of photosensitivity in older patients (50+) and its phenotypical appearance. METHODS: A retrospective observational study was performed investigating the prevalence of a photoparoxysmal EEG response (PPR) on at least one EEG during the period 2015-2021. Data were gathered from patients aged 50 years and older by retrieving clinical and EEG characteristics from existing medical records. Data on photosensitivity-related symptoms in daily life were gathered with telephone interviewing. RESULTS: In 248 patients a PPR had been elicited, of whom 16 patients (6.5%) were 50 years or older. In older patients, photosensitivity was a persistent feature of childhood-onset epilepsy (n = 8), of adult-onset epilepsy (n = 7), or an incidental finding (n = 1). In the 50+ group, 56% of photosensitive patients was female, whereas 72% in the total PPR-group. In six of 16 older patients, eye closure sensitivity was observed; two of these patients reported self-induction. Symptoms of photosensitivity in daily life were present in eight out of nine patients who consented in a telephone interview. For seven of these patients, wearing sunglasses was helpful. SIGNIFICANCE: Female preponderance for photosensitivity was not found in epilepsy patients of 50 years and older. In 44% of the older photosensitive patients in this series, the PPR was a feature of adult-onset epilepsy. Symptoms of photosensitivity in daily life in older patients with epilepsy seem comparable to those in younger patients, and thus worthwhile to diagnose and treat them equally.

Outcome after intracranial haemorrhage from dural arteriovenous fistulae; a systematic review and case-series.

Dural arteriovenous fistulae (DAVFs) are a rare cause of intracranial haemorrhage. We aimed to investigate outcome of patients with intracranial haemorrhage from a DAVF. We performed a systematic literature search for studies reporting outcome after intracranial haemorrhage caused by a DAVF. We used predefined selection criteria and assessed the quality of the studies. In addition, we studied outcome in all patients with DAVF who had presented with intracranial haemorrhage at two university centers in the Netherlands, between January 2007 and April 2012. We calculated case fatality and proportions of patients with poor outcome (defined as modified Rankin Scale ≥ 3 or Glasgow Outcome Scale ≤ 3) during follow-up. We investigated mean age, sex, mid-year of study and percentage of patients with parenchymal haemorrhage as determinants of case fatality and poor outcome. The literature search yielded 16 studies, all but two retrospective and all hospital-based. Combined with our cohort of 29 patients the total number of patients with DAVF-related intracranial haemorrhage was 326 (58% intracerebral haemorrhage). At a median follow-up of 12 months case fatality was 4.7% (95% CI 2.5-7.5; 17 cohorts) and the proportion of patients with poor outcome 8.3% (95% CI 3.1-15.7; nine cohorts). We found no effect of mean age, sex, mid-year of the cohorts and percentage of patients with parenchymal haemorrhage on either outcome. Hospital based case-series suggest a relatively low risk of death and poor outcome in patients with intracranial haemorrhage due to rupture of a DAVF. These risks may be underestimated because of bias.

Acute hydrocephalus and cerebral perfusion after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Acute hydrocephalus after aneurysmal subarachnoid hemorrhage (SAH) may decrease cerebral perfusion by increasing intracranial pressure. We studied cerebral perfusion in patients with and without acute hydrocephalus after SAH. MATERIALS AND METHODS: We performed noncontrast CT scans, CT perfusion (CTP), and CT angiography on admission in all patients with aneurysmal SAH. Patients were dichotomized at a relative bicaudate index of 1 for the presence or absence of hydrocephalus. Cerebral perfusion was measured in the cortex, basal ganglia, and periventricular white matter. Mean CTP parameters were compared between patients with and without acute hydrocephalus (ie, within 3 days after SAH). RESULTS: We included 138 consecutive patients with successful CTP measurements, of whom 49 (36%) had acute hydrocephalus. Mean cerebral blood flow (CBF) was lower in patients with hydrocephalus than in those without in the basal ganglia (difference of means, 6.8; 95% CI, 1.6-11.0 mL/100 g/min) and periventricular white matter (difference of means, 3.8; 95% CI, 0.9-6.8 mL/100 g/min) but not in the cortex (difference of means, 1.8; 95% CI, -2.8 to 6.4 mL/100 g/min). In all regions studied, mean transit time (MTT) and time-to-peak (TTP) were statistically significantly longer in patients with hydrocephalus, but cerebral blood volume (CBV) values were similar. CONCLUSIONS: Acute hydrocephalus after SAH reduces CBF in the deep gray matter and periventricular white matter and delays MTT and TTP in all investigated brain areas. The negative effect of acute hydrocephalus on cerebral perfusion in patients with SAH seems more pronounced in the vicinity of the ventricles than in remote sites.