Insomnia cycling with a 42-day infradian period: Evidence for two uncoupled circadian oscillators?

Vignatelli, Luca; Masetti, Simone; Amore, Mario; Laterza, C.; Mattarozzi, Katia; Pierangeli, Giulia; Cortelli, Pietro; Vandi, Stefano; Vetrugno, Roberto; Plazzi, Giuseppe; Montagna, Pasquale

doi:10.1016/j.sleep.2009.09.006

Cited by 5 publications

(5 citation statements)

References 48 publications

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“…Further analysis of the rise and decay kinetics of IEA fluctuations may be informative with regard to underlying biological mechanisms. We speculate that the seemingly independent circadian and multidien oscillators may in fact be co-modulated by hormonal, genetic, environmental 29 , sleep-wake cycle 30 , and behavioral factors 31 . Hormonal influence on seizures occurs in catamenial epilepsy 32 , 33 , and one of the 15 female subjects had seizures related to menstrual cycles 32 , 33 with IEA cycling at 13 and 26 days.…”

Section: Discussionmentioning

confidence: 96%

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Multi-day rhythms modulate seizure risk in epilepsy

et al. 2018

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Epilepsy is defined by the seemingly random occurrence of spontaneous seizures. The ability to anticipate seizures would enable preventative treatment strategies. A central but unresolved question concerns the relationship of seizure timing to fluctuating rates of interictal epileptiform discharges (here termed interictal epileptiform activity, IEA), a marker of brain irritability observed between seizures by electroencephalography (EEG). Here, in 37 subjects with an implanted brain stimulation device that detects IEA and seizures over years, we find that IEA oscillates with circadian and subject-specific multidien (multi-day) periods. Multidien periodicities, most commonly 20–30 days in duration, are robust and relatively stable for up to 10 years in men and women. We show that seizures occur preferentially during the rising phase of multidien IEA rhythms. Combining phase information from circadian and multidien IEA rhythms provides a novel biomarker for determining relative seizure risk with a large effect size in most subjects.

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Section: Discussionmentioning

confidence: 96%

“…Multidien rhythms have been identified in mood disorders 35 , sleep patterns 30 , and cardiovascular physiology 36 , and their role in epilepsy will further fuel investigations into the underlying biological mechanisms. An endocrine basis seems likely 37 , 38 .…”

Section: Discussionmentioning

confidence: 99%

Multi-day rhythms modulate seizure risk in epilepsy

et al. 2018

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“…Following the results of (Baldin et al, 2017; van Campen et al, 2016), another explanation could be the patient’s stress level, which was higher in the first (shortly before final training examinations) than in the second stimulation week (after exams). In addition to these factors, IED frequencies may have been modulated by sleep-wake cycle (Vignatelli et al, 2010) and environmental factors (Rakers et al, 2017), which may have contributed to the strong daily IED fluctuations seen in our data (Figure 8).…”

Section: Discussionmentioning

confidence: 93%

Targeted and optimized multi-channel transcranial direct current stimulation for focal epilepsy: An N-of-1 trial

Antonakakis,

Kaiser,

Rampp

et al. 2023

Preprint

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Transcranial direct current stimulation (tDCS) has been used to noninvasively reduce epileptic activity in focal epilepsy. In this proof-of-principle N-of-1 trial in a patient with drug-resistant focal epilepsy, we propose distributed constrained maximum intensity (D-CMI) for individually targeted and optimized multi-channel (mc-)tDCS to reduce epileptic activity. Combined electro- and magnetoencephalography (EMEG) source analysis in a realistic calibrated head model defines location and orientation of the target epileptogenic source. Converging evidence for this determination is achieved by retrospective identification of a cortical malformation in magnetic resonance imaging and by successful EMEG-guided invasive EEG. We applied D-CMI in a double-blind, sham-controlled stimulation experiment. In two stimulation weeks, either D-CMI or sham stimulation with 4 mA injection current were applied twice every week-day for 20 min each, with a 20 min pause in between. EEG was recorded 1 h before and after stimulation. For D-CMI, we find a highly significant reduction in IED frequency (p < 0.0001) marked by three experts of on average 37% to 81% over the five days of stimulation (mean +- SD: 58% +- 19%), while this is not the case for sham. The proposed procedure was well-tolerated and parameterizes a group clinical trial (Study registration number: DRKS00029384).

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“…In contrast, greater durations of sleep have been associated with a lower probability of seizure in some people with epilepsy 46 . Although sleep–wake cycles operate in a circadian pattern, sleep duration and insomnia have both been reported to exhibit multi‐day variation, and variation can be unique to the individual 47,48 …”

Section: What Types Of Tools or Methods Would Be Needed To Support Fu...mentioning

confidence: 99%

“…46 Although sleep-wake cycles operate in a circadian pattern, sleep duration and insomnia have both been reported to exhibit multi-day variation, and variation can be unique to the individual. 47,48 Multi-day variation has been described for some hormones, such as sex steroids (estradiol, testosterone), aldosterone, and cortisol [49][50][51] ; as such, hormones are potentially useful biomarkers for seizure. Cortisol response to stress has been reported to be higher in people with epilepsy who are prone to stress, 52,53 and seizures and IEDs have been associated with cortisol levels in these patients.…”

Section: Triggers and Biomarkersmentioning

confidence: 99%

Future opportunities for research in rescue treatments

et al. 2022

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Clinical studies of rescue medications for seizure clusters are limited and are designed to satisfy regulatory requirements, which may not fully consider the needs of the diverse patient population that experiences seizure clusters or utilize rescue medication. The purpose of this narrative review is to examine the factors that contribute to, or may influence the quality of, seizure cluster research with a goal of improving clinical practice. We address five areas of unmet needs and provide advice for how they could enhance future trials of seizure cluster treatments. The topics addressed in this article are: (1) unaddressed end points to pursue in future studies, (2) roles for devices to enhance rescue medication clinical development programs, (3) tools to study seizure cluster prediction and prevention, (4) the value of other designs for seizure cluster studies, and (5) unique challenges of future trial paradigms for seizure clusters. By focusing on novel end points and technologies with value to patients, caregivers, and clinicians, data obtained from future studies can benefit the diverse patient population that experiences seizure clusters, providing more effective, appropriate care as well as alleviating demands on health care resources.

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Insomnia cycling with a 42-day infradian period: Evidence for two uncoupled circadian oscillators?

Cited by 5 publications

References 48 publications

Multi-day rhythms modulate seizure risk in epilepsy

Multi-day rhythms modulate seizure risk in epilepsy

Targeted and optimized multi-channel transcranial direct current stimulation for focal epilepsy: An N-of-1 trial

Future opportunities for research in rescue treatments

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