Robert S. Fisher

In 2005, the Epilepsy Foundation published an expert consensus ( Epilepsia 2005; 46:1423–1425) on actions to minimize risks of visually‐provoked (photosensitive) seizures (VPS). Since then, technology, scientific information, and experience have greatly expanded. An international expert panel convened by the Epilepsy Foundation collated literature, information, and opinions regarding VPS. Consensus guidelines are divided into advice for: patients and families, clinicians, designers of video games, architects, and regulatory agencies. No attempt was made to develop a formal systematic review. Patients are advised about symptoms and epilepsy syndromes that relate to VPS. Commonly used medications and useful behavioral modifications are reviewed. Clinicians are advised on an approach to events that are concerning for VPS, including how to use history and electroencephalography (EEG) to assess whether an event was a seizure (vs another neurologic symptom) and what visual stimuli (light or patterns) provoked it. The utility of magnetic resonance imaging (MRI) to assess for an epileptogenic lesion, routine blood tests, and genetic studies is discussed. Media designers of video games, movies, TV productions, web videos, and artificial or virtual reality images are advised to avoid bright flashing patterns in the 10–20 Hz range, repetitive color flashes, and oscillating or static stripes of ~1–8 cycles per visual degree. Signal analysis or trained human inspectors can identify provocative visual patterns. Architects and designers of public spaces should be aware that some striped patterns can provoke seizures. Government and regulatory agencies require screening of potentially provocative media in some nations. VPS are both an individual and public health problem. The Epilepsy Foundation encourages further research and efforts to minimize risks of seizures provoked by visual stimuli.

Objective. Clinical adoption of innovative EEG technology is contingent on the non-inferiority of the new devices relative to conventional ones. We present the four key results from testing the signal quality of Zeto’s WR 19 EEG system against a conventional EEG system conducted on patients in a clinical setting. Methods. We performed 30 min simultaneous recordings using the Zeto WR 19 (zEEG) and a conventional clinical EEG system (cEEG) in a cohort of 15 patients. We compared the signal quality between the two EEG systems by computing time domain statistics, waveform correlation, spectral density, signal-to-noise ratio and signal stability. Results. All statistical comparisons resulted in signal quality non-inferior relative to cEEG. (i) Time domain statistics, including the Hjorth parameters, showed equivalence between the two systems, except for a significant reduction of sensitivity to electric noise in zEEG relative to cEEG. (ii) The point-by-point waveform correlation between the two systems was acceptable (r > 0.6; P < 0.001). (iii) Each of the 15 datasets showed a high spectral correlation (r > 0.99; P < 0.001) and overlapping spectral density across all electrode positions, indicating no systematic signal distortion. (iv) The mean signal-to-noise ratio (SNR) of the zEEG system exceeded that of the cEEG by 4.82 dB, equivalent to a 16% improvement. (v) The signal stability was maintained through the recordings. Conclusion. In terms of signal quality, the zEEG system is non-inferior to conventional clinical EEG systems with respect to all relevant technical parameters that determine EEG readability and interpretability. Zeto’s WR 19 wireless dry electrode system has signal quality in the clinical EEG space at least equivalent to traditional cEEG recordings.

Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) has been shown to be effective in treating some patients with medically refractory epilepsy. However, it remains unknown how seizures spread through the ANT relative to other thalamic nuclei. This study aimed to investigate, through simultaneous recordings from both ANT and pulvinar (PLV) nucleus, their roles in seizure propagation. Our goal was to determine whether the ANT is the primary site of seizure propagation in the human thalamus, especially for focal seizure originating in the medial temporal lobe. In a retrospective design, we studied EEGs and clinical notes of patients with refractory epilepsy who were implanted with stereo-EEG (sEEG) electrodes across cortical regions, some of which were extended to reach various sites of the thalamus (i.e., multisite thalamic recordings). We selected patients from the Stanford Comprehensive Epilepsy Center with both ANT and PLV electrodes and collected information about the timing and anatomy of seizure activity in the seizure onset zones, usually temporal, and the 2 thalamic sites. We recruited 17 (5 female, mean age 32 years) adult patients with simultaneous ipsilateral ANT and PLV recordings. In all patients, the procedure was safe without any complications. In 100% of patients, the thalamus was involved during seizures (in 88% both ANT and PLV and in 82% first the PLV). In patients with confirmed hippocampal or amygdalar onset seizures, 62% had initial involvement and 100% had subsequent involvement of the PLV nucleus. Only 31% showed initial propagation to ANT. All focal-to-bilateral tonic-clonic seizures and most of the focal impaired awareness seizures had early involvement of both ANT and PLV, with rapid spread to the contralateral nuclei. sEEG of thalamic nuclei simultaneously provides an opportunity to understand propagation patterns of seizures with respect to each thalamic subdivision at the individual level. The patterns of seizure propagation, as we report here, provide insights about the prominent involvement of the PLV nucleus during seizure propagation. This may motivate future prospective work in larger cohorts of patients to understand how thalamic propagation may predict response to resective/ablative surgery or whether personalization of DBS (for instance, PLV instead of, or together with, ANT) could improve clinical outcomes.

Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in a subset of patients with refractory focal epilepsy. One important uncertainty is to what extent thalamic subregions other than the ANT could be recruited more prominently in the propagation of focal onset seizures. We designed the current study to simultaneously monitor the engagement of the ANT, mediodorsal (MD) and pulvinar (PUL) nuclei during seizures in patients who could be candidates for thalamic neuromodulation. We studied 11 patients with clinical manifestations of presumed temporal lobe epilepsy (TLE) undergoing invasive stereo-encephalography (sEEG) monitoring to confirm the source of their seizures. We extended cortical electrodes to reach the ANT, MD and PUL nuclei of the thalamus. More than one thalamic subdivision was simultaneously interrogated in nine patients. We recorded seizures with implanted electrodes across various regions of the brain and documented seizure onset zones (SOZ) in each recorded seizure. We visually identified the first thalamic subregion to be involved in seizure propagation. Additionally, in eight patients, we applied repeated single pulse electrical stimulation in each SOZ and recorded the time and prominence of evoked responses across the implanted thalamic regions. Our approach for multisite thalamic sampling was safe and caused no adverse events. Intracranial EEG recordings confirmed SOZ in medial temporal lobe, insula, orbitofrontal and temporal neocortical sites, highlighting the importance of invasive monitoring for accurate localization of SOZs. In all patients, seizures with the same propagation network and originating from the same SOZ involved the same thalamic subregion, with a stereotyped thalamic EEG signature. Qualitative visual reviews of ictal EEGs were largely consistent with the quantitative analysis of the corticothalamic evoked potentials, and both documented that thalamic nuclei other than ANT could have the earliest participation in seizure propagation. Specifically, pulvinar nuclei were involved earlier and more prominently than ANT in more than half of the patients. However, which specific thalamic subregion first demonstrated ictal activity could not be reliably predicted based on clinical semiology or lobar localization of SOZs. Our findings document the feasibility and safety of bilateral multisite sampling from the human thalamus. This may allow more personalized thalamic targets to be identified for neuromodulation. Future studies are needed to determine if a personalized thalamic neuromodulation leads to greater improvements in clinical outcome.

Objective: Focused ultrasound ablation (FUSA) is an emerging treatment for neurological and psychiatric diseases. We describe the initial experience from a pilot, open‐label, single‐center clinical trial of unilateral anterior nucleus of the thalamus (ANT) FUSA in patients with treatment‐refractory epilepsy.Methods: Two adult subjects with treatment‐refractory, focal onset epilepsy were recruited. The subjects received ANT FUSA using the Exablate Neuro (Insightec) system. We determined the safety and feasibility (primary outcomes), and changes in seizure frequency (secondary outcome) at 3, 6, and 12 months. Safety was assessed by the absence of side effects, that is, new onset neurological deficits or performance deterioration on neuropsychological testing. Feasibility was defined as the ability to create a lesion within the anterior nucleus. The monthly seizure frequency was compared between baseline and postthalamotomy.Results: The patients tolerated the procedure well, without neurological deficits or serious adverse events. One patient experienced a decline in verbal fluency, attention/working memory, and immediate verbal memory. Seizure frequency reduced significantly in both patients; one patient was seizure‐free at 12 months, and in the second patient, the frequency reduced from 90–100 seizures per month to 3–6 seizures per month.Significance: This is the first known clinical trial to assess the safety, feasibility, and preliminary efficacy of ANT FUSA in adult patients with treatment‐refractory focal onset epilepsy.

Objective: Transcranial direct current stimulation (tDCS) has been advocated for various neurological conditions, including epilepsy. A 1–4‐mA cathodal current applied to the scalp over a seizure focus can reduce spikes and seizures. This series of four patients with focal status epilepticus is among the first case series to demonstrate benefit of tDCS in the critical care setting.Methods: Patients in the intensive care unit were referred for tDCS treatment when focal status epilepticus or clinically relevant lateralized periodic discharges did not resolve with conventional antiseizure medications and anesthetics. Battery‐powered direct cathodal current at 2 mA was delivered by an ActivaDose (Caputron) tDCS device via a saline‐soaked sponge on the scalp over the seizure focus. Anode was on the contralateral forehead or shoulder. Treatment was for 30 min, repeated twice in a day, then again 1–4 times more over the next few days.Results: Three females and one male, aged 34–68 years, were treated. Etiologies of status epilepticus were posterior reversible encephalopathy syndrome in association with immunosuppressants for a liver transplant, perinatal hypoxic–ischemic injury, a prior cardioembolic parietal stroke, and central nervous system lupus. tDCS led to significant reduction of interictal spikes (.78 to .38/s, p < .0001) in three cases and electrographic seizures (3.83/h to 0/h, p < .001) in two cases. Medication reductions were enabled in all cases subsequent to tDCS. The only side effect of tDCS was transient erythema under the sponge in one case. Two patients died of causes unrelated to tDCS, one was discharged to a nursing home, and one became fully responsive as seizures were controlled with tDCS.Significance: Spikes and electrographic seizure frequency significantly improved within 1 day of tDCS. Results are potentially confounded by multiple ongoing changes in medications and treatments. These results might encourage further investigation of tDCS in the critical care setting, but verification by controlled studies will be required.