Seizure Cycles under Pharmacotherapy.

OBJECTIVE: This study was undertaken to determine the effects of antiseizure medications (ASMs) on multidien (multiday) cycles of interictal epileptiform activity (IEA) and seizures and evaluate their potential clinical significance. METHODS: We retrospectively analyzed up to 10 years of data from 88 of the 256 total adults with pharmacoresistant focal epilepsy who participated in the clinical trials of the RNS System, an intracranial device that keeps records of IEA counts. Following adjunctive ASM trials, we evaluated changes over months in (1) rates of self-reported disabling seizures and (2) multidien IEA cycle strength (spectral power for periodicity between 4 and 40 days). We used a survival analysis and the receiver operating characteristics to assess changes in IEA as a predictor of seizure control. RESULTS: Among 56 (33.3%) of the 168 adjunctive ASM trials suitable for analysis, ASM introduction was followed by an average 50 to 70% decrease in multidien IEA cycle strength and a concomitant 50 to 70% decrease in relative seizure rate for up to 12 months. Individuals with a ≥50% decrease in IEA cycle strength in the first 3 months of an ASM trial had a higher probability of remaining seizure responders (≥50% seizure rate reduction, p < 10-7) or super-responders (≥90%, p < 10-8) over the next 12 months. INTERPRETATION: In this large cohort, a decrease in multidien IEA cycle strength following initiation of an adjunctive ASM correlated with seizure control for up to 12 months, suggesting that fluctuations in IEA mirror "disease activity" in pharmacoresistant focal epilepsy and may have clinical utility as a biomarker to predict treatment response. ANN NEUROL 2024;95:743-753.

Triggered Seizures for Ictal SPECT Imaging: A Case Series and Feasibility Study.

Ictal SPECT is an informative seizure imaging technique to tailor epilepsy surgery. However, capturing the onset of unpredictable seizures is a medical and logistic challenge. Here, we sought to image planned seizures triggered by direct stimulation of epileptic networks via stereotactic electroencephalography (sEEG) electrodes. Methods: In this case series of 3 adult participants with left temporal epilepsy, we identified and stimulated sEEG contacts able to trigger patient-typical seizures. We administered 99mTc-HMPAO within 12 s of ictal onset and acquired SPECT images within 40 min without any adverse events. Results: Ictal hyperperfusion maps partially overlapped concomitant sEEG seizure activity. In both participants known for periictal aphasia, SPECT imaging revealed hyperperfusion in the speech cortex lacking sEEG coverage. Conclusion: Triggering of seizures for ictal SPECT complements discrete sEEG sampling with spatially complete images of early seizure propagation. This readily implementable method revives interest in seizure imaging to guide resective epilepsy surgery.

Feasibility, Safety, and Performance of Full-Head Subscalp EEG Using Minimally Invasive Electrode Implantation.

BACKGROUND AND OBJECTIVES: Current practice in clinical neurophysiology is limited to short recordings with conventional EEG (days) that fail to capture a range of brain (dys)functions at longer timescales (months). The future ability to optimally manage chronic brain disorders, such as epilepsy, hinges upon finding methods to monitor electrical brain activity in daily life. We developed a device for full-head subscalp EEG (Epios) and tested here the feasibility to safely insert the electrode leads beneath the scalp by a minimally invasive technique (primary outcome). As secondary outcome, we verified the noninferiority of subscalp EEG in measuring physiologic brain oscillations and pathologic discharges compared with scalp EEG, the established standard of care. METHODS: Eight participants with pharmacoresistant epilepsy undergoing intracranial EEG received in the same surgery subscalp electrodes tunneled between the scalp and the skull with custom-made tools. Postoperative safety was monitored on an inpatient ward for up to 9 days. Sleep-wake, ictal, and interictal EEG signals from subscalp, scalp, and intracranial electrodes were compared quantitatively using windowed multitaper transforms and spectral coherence. Noninferiority was tested for pairs of neighboring subscalp and scalp electrodes with a Bland-Altman analysis for measurement bias and calculation of the interclass correlation coefficient (ICC). RESULTS: As primary outcome, up to 28 subscalp electrodes could be safely placed over the entire head through 1-cm scalp incisions in a ∼1-hour procedure. Five of 10 observed perioperative adverse events were linked to the investigational procedure, but none were serious, and all resolved. As a secondary outcome, subscalp electrodes advantageously recorded EEG percutaneously without requiring any maintenance and were noninferior to scalp electrodes for measuring (1) variably strong, stage-specific brain oscillations (alpha in wake, delta, sigma, and beta in sleep) and (2) interictal spikes peak-potentials and ictal signals coherent with seizure propagation in different brain regions (ICC >0.8 and absence of bias). DISCUSSION: Recording full-head subscalp EEG for localization and monitoring purposes is feasible up to 9 days in humans using minimally invasive techniques and noninferior to the current standard of care. A longer prospective ambulatory study of the full system will be necessary to establish the safety and utility of this innovative approach. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov/study/NCT04796597.

Dynamic spatiotemporal patterns of brain connectivity reorganize across development.

Late human development is characterized by the maturation of high-level functional processes, which rely on reshaping of white matter connections, as well as synaptic density. However, the relationship between the whole-brain dynamics and the underlying white matter networks in neurodevelopment is largely unknown. In this study, we focused on how the structural connectome shapes the emerging dynamics of cerebral development between the ages of 6 and 33 years, using functional and diffusion magnetic resonance imaging combined into a spatiotemporal connectivity framework. We defined two new measures of brain dynamics, namely the system diversity and the spatiotemporal diversity, which quantify the level of integration/segregation between functional systems and the level of temporal self-similarity of the functional patterns of brain dynamics, respectively. We observed a global increase in system diversity and a global decrease and local refinement in spatiotemporal diversity values with age. In support of these findings, we further found an increase in the usage of long-range and inter-system white matter connectivity and a decrease in the usage of short-range connectivity with age. These findings suggest that dynamic functional patterns in the brain progressively become more integrative and temporally self-similar with age. These functional changes are supported by a greater involvement of long-range and inter-system axonal pathways.

Exploring the role of white matter connectivity in cortex maturation.

The maturation of the cortical gray matter (GM) and white matter (WM) are described as sequential processes following multiple, but distinct rules. However, neither the mechanisms driving brain maturation processes, nor the relationship between GM and WM maturation are well understood. Here we use connectomics and two MRI measures reflecting maturation related changes in cerebral microstructure, namely the Apparent Diffusion Coefficient (ADC) and the T1 relaxation time (T1), to study brain development. We report that the advancement of GM and WM maturation are inter-related and depend on the underlying brain connectivity architecture. Particularly, GM regions and their incident WM connections show corresponding maturation levels, which is also observed for GM regions connected through a WM tract. Based on these observations, we propose a simple computational model supporting a key role for the connectome in propagating maturation signals sequentially from external stimuli, through primary sensory structures to higher order functional cortices.