Epilepsy, sleep, and Alzheimer's disease (AD) are tightly and potentially causally interconnected. The aim of our review was to investigate current research directions on these relationships. Our hope is that they may indicate preventive measures and new treatment options for early neurodegeneration. We included articles that assessed all three topics and were published during the last ten years. We found that this literature corroborates connections on various pathophysiological levels, including sleep-stage-related epileptiform activity in AD, the negative consequences of different sleep disorders on epilepsy and cognition, common biochemical pathways as well as network dysfunctions. Here we provide a detailed overview of these topics and we discuss promising diagnostic and therapeutic consequences.

Epilepsy is characterized by the occurrence of epileptic events, ranging from brief bursts of interictal epileptiform brain activity to their most dramatic manifestation as clinically overt bilateral tonic–clonic seizures. Epileptic events are often modulated in a patient-specific way, for example by sleep. But they also reveal temporal patterns not only on ultra- and circadian, but also on multidien scales. Thus, to accurately track the dynamics of epilepsy and to thereby enable and improve personalized diagnostics and therapies, user-friendly systems for long-term out-of-hospital recordings of electrical brain signals are needed. Here, we present two wearable devices, namely ULTEEM and ULTEEMNite, to address this unmet need. We demonstrate how the usability concerns of the patients and the signal quality requirements of the clinicians have been incorporated in the design. Upon testbench verification of the devices, ULTEEM was successfully benchmarked against a reference EEG device in a pilot clinical study. ULTEEMNite was shown to record typical macro- and micro-sleep EEG characteristics in a proof-of-concept study. We conclude by discussing how these devices can be further improved and become particularly useful for a better understanding of the relationships between sleep, epilepsy, and neurodegeneration.

Stimulation-induced sensations including the perception of flickering lights (phosphenes) and scalp tingling are commonly reported in studies on transcranial alternating current stimulation (tACS). So far, these sensations have been considered benign side-effects of stimulation that may interfere with the blinding of participants in trials. It remains unknown what shapes the susceptibility to such side-effects. We hypothesized that cortical excitability predicts their intensity. Hence, we investigated the relationship between sensations during tACS and the motor threshold measured by transcranial magnetic stimulation (TMS). Nine healthy participants aged 50 and older underwent two tACS sessions at 21 Hz and 40 Hz as part of a cross-over pilot study. The stimulation amplitude was individualized to tolerability. Sensations were assessed post-session to calculate correlation with TMS-determined motor thresholds. Stimulation sensations (a flickering light and tingling scalp sensation) correlated with brain excitability as determined by the TMS motor threshold (r = −0.51, p = 0.03, N = 9). The findings suggest a relationship between the intensity of tACS-induced sensations and cortical excitability. Tailoring tACS intensity to individual tolerability and excitability thresholds may enhance the efficacy of tACS by ensuring a more consistent and effective dose relative to endogenous cortical excitability.

Objective: Clinical trials on drug safety and efficacy are understood to be valid for all humans, but are not equally distributed worldwide. We aimed to analyze the global distribution of clinical drug trials (phase I– IV ) in epilepsy and its correlation with key demographical and epidemiological factors. Methods: We combined data on industry‐funded interventional drug trials in epilepsy from clinicaltrials.gov with epidemiological, geographical, socioeconomic, and human development data. This allowed us to analyze the distribution of trials and trial sites in relation to population, epilepsy incidence, and prevalence. Results: Among 459 trials conducted in 69 countries, a vast majority of sites were situated in high‐income regions and countries with very high Human Development Index ( HDI ). There was a striking underrepresentation of low‐income countries and those with low HDI . Specifically, we found a 40‐ to 145‐fold underrepresentation of trial sites in the WHO regions of Africa and the Eastern Mediterranean when comparing the actual number of sites to the expected number, assuming an even distribution by population, incidence, or prevalence. Significance: Our findings highlight inequalities in the distribution of epilepsy trial sites based on population size and disease burden. They underscore the need for more equitable trial placement strategies that consider both disease epidemiology and demographic diversity to ensure adequate representation of all affected populations. Plain Language Summary: This study looked at where clinical trials for epilepsy medications are being done around the world. We found that most trials take place in high‐income countries, while many areas with a high number of people living with epilepsy—especially in Africa and the Eastern Mediterranean—are left out. This shows a big gap between where the disease is most common and where research happens. Highlighting this mismatch can help guide future efforts to make clinical research more inclusive and globally relevant.

Einleitung Weltweit sind 50 Millionen Menschen von Epilepsien betroffen (Weltgesundheitsorganisation [WHO], 2019). Die weltweite Prävalenz beträgt dabei etwa 0,3 bis 1%. Die Epilepsie ist eine der häufigsten chronisch-neurologischen Erkrankungen in der Schwangerschaft (SS) (Schneider et al., 2011; Schindler et al., 2005) wobei heute generell nicht mehr von einer Schwangerschaft bei Frauen mit Epilepsie abgeraten wird (Krämer, 2018). Dennoch wirft das Thema «Mutter werden» für Frauen mit Epilepsie viele Fragen auf. In der Schweiz wurde bislang nie geklärt, ob die aktuelle Versorgung den Bedürfnissen der betroffenen Frauen und deren mitbetreuenden Fachpersonen gerecht wird. Forschungsziel Eruierung des Bedarfs nach einem spezialisierten und interprofessionellen Versorgungsangebot für Frauen mit Epilepsie in der Reproduktionsphase. Zudem soll der Bedarf und Nutzen einer spezialisierten Hebamme ins interprofessionelle Versorgungsteam, eine sogenannte «Advanced Practice Midwife» (APM), abgeklärt werden. Methode Eine qualitative, deskriptive Bedarfsanalyse wurde durchgeführt, worin Frauen mit Epilepsie und mitbetreuende Fachpersonen befragt wurden. Die Interviews wurden einer inhaltlich strukturierenden Inhaltsanalyse nach Kuckartz (2018) unterzogen und anschliessend in die Struktur des PEPPA-Rahmenmodells (Bryant-Lukosius, 2004), welches für APM-Rollenentwicklung wegweisend ist, integriert. Ergebnisse Insgesamt wurden 12 semistrukturierte Einzelinterviews durchgeführt. Es wurden fünf Frauen mit Epilepsie befragt und sieben Fachexpertinnen- und Experten. Dies waren Hebammen sowie ärztliche Fachpersonen aus dem Bereich der Gynäkologie & Geburtshilfe und Neurologie. Aus den Interviews konnten vier bislang unerfüllte Bedürfnisse identifiziert werden: a) Orientierungshilfe im Betreuungsprozess gewährleisten, b) Förderung der fachlichen Zusammenarbeit, c) Beratung zur anfallsunterdrückenden Therapie und zum Geburtsmanagement anbieten und d) postpartale Nachbetreuung gewährleisten. Eine APM-Rollenentwicklung ins interprofessionelle Team sollte bedacht werden. Diskussion Es konnte aufgezeigt werden, welchen Bedarf Frauen mit Epilepsie in der Reproduktionsphase und deren mitbetreuenden Fachpersonen haben. Ebenso konnten mögliche Arbeitsfelder einer «APM for epilepsy» umschrieben werden, die dem Bedarf nach einem kontinuierlichen und koordinierten Beratungsangebot gerecht würde. Eine APM hat das Potential das Sicherheitsgefühl der Frauen zu erhöhen und ihnen eine gute Orientierung im Betreuungsverlauf zu vermitteln. Schlussfolgerung Die verbesserte interprofessionelle Zusammenarbeit zwischen Geburtshilfe und Neurologie, könnte sich vorteilhaft auf die Betreuungskontinuität betroffener Frauen auswirken. Publication Date: 26 November 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

Spontaneous neural dynamics manifest across multiple timescales, which are intrinsic to brain areas and exhibit hierarchical organization across the cortex. In wake, a hierarchy of timescales is thought to naturally emerge from microstructural properties, gene expression, and recurrent connections. A fundamental question is timescales’ organization and changes in sleep, where physiological needs are different. Here, we describe two coexisting but distinct measures of neural timescales, obtained from broadband activity and gamma power, which display complementary properties. We leveraged intracranial electroencephalography (iEEG) data to characterize timescale changes from wake to sleep across the cortical hierarchy. We show that both broadband and gamma timescales are globally longer in sleep than in wake. While broadband timescales increase along the sensorimotor-association axis, gamma ones decrease. During sleep, slow waves can explain the increase of broadband and gamma timescales, but only broadband ones show a positive association with slow-wave density across the cortex. Finally, we characterize spatial correlations and their relationship with timescales as a proxy for spatiotemporal integration, finding high integration at long distances in wake for broadband and at short distances in sleep for gamma timescales. Our results suggest that mesoscopic neural populations possess different timescales that are shaped by anatomy and are modulated by the sleep/wake cycle. Significance statement: Understanding the organization of intrinsic neural dynamics is crucial for investigating brain functions in health and disease. A key question is: how do neural dynamics change in the sleeping brain? Here we focus on neural timescales, which measure temporal autocorrelation and are organized hierarchically across the cortex, and spatial correlations. We show that two types of timescales exist in neural populations recorded with intracranial electroencephalography in humans, corresponding to broadband (0.5-80 Hz) and gamma (40-80 Hz) frequency ranges. Both timescales increase in sleep, where slow waves have an important role, but follow opposite hierarchies: broadband timescales increase from sensory to associative areas, while gamma timescales show the reverse pattern. Finally, timescales covary with spatial correlations, suggesting higher spatiotemporal integration over long distances in wake compared to sleep.