Excessive Daytime Sleepiness and Epilepsy: A Systematic Review

Giorelli, Andre S.; Passos, Pâmela; Carnaval, Thiago; Gomes, Marleide da Mota

doi:10.1155/2013/629469

Cited by 31 publications

(21 citation statements)

References 44 publications

(75 reference statements)

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“…Also, sleep deprivation is generally considered to trigger or worsen seizures in patients with epilepsy [ 4 , 5 ]. On the other hand, seizures often influence the quality and quantity of sleep, causing irregular sleep patterns or circadian disruption in epileptic patients [ 6 , 7 ]. Furthermore, antiepileptic drugs commonly affect sleep [ 8 ], making the interactions between sleep and seizures even more complex.…”

Section: Introductionmentioning

confidence: 99%

Exaggerated Nighttime Sleep and Defective Sleep Homeostasis in a Drosophila Knock-In Model of Human Epilepsy

2015

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Despite an established link between epilepsy and sleep behavior, it remains unclear how specific epileptogenic mutations affect sleep and subsequently influence seizure susceptibility. Recently, Sun et al. (2012) created a fly knock-in model of human generalized epilepsy with febrile seizures plus (GEFS+), a wide-spectrum disorder characterized by fever-associated seizing in childhood and lifelong affliction. GEFS+ flies carry a disease-causing mutation in their voltage-gated sodium channel (VGSC) gene and display semidominant heat-induced seizing, likely due to reduced GABAergic inhibitory activity at high temperature. Here, we show that at room temperature the GEFS+ mutation dominantly modifies sleep, with mutants exhibiting rapid sleep onset at dusk and increased nighttime sleep as compared to controls. These characteristics of GEFS+ sleep were observed regardless of sex, mating status, and genetic background. GEFS+ mutant sleep phenotypes were more resistant to pharmacologic reduction of GABA transmission by carbamazepine (CBZ) than controls, and were mitigated by reducing GABAA receptor expression specifically in wake-promoting pigment dispersing factor (PDF) neurons. These findings are consistent with increased GABAergic transmission to PDF neurons being mainly responsible for the enhanced nighttime sleep of GEFS+ mutants. Additionally, analyses under other light conditions suggested that the GEFS+ mutation led to reduced buffering of behavioral responses to light on and off stimuli, which contributed to characteristic GEFS+ sleep phenotypes. We further found that GEFS+ mutants had normal circadian rhythms in free-running dark conditions. Interestingly, the mutants lacked a homeostatic rebound following mechanical sleep deprivation, and whereas deprivation treatment increased heat-induced seizure susceptibility in control flies, it unexpectedly reduced seizure activity in GEFS+ mutants. Our study has revealed the sleep architecture of a Drosophila VGSC mutant that harbors a human GEFS+ mutation, and provided unique insight into the relationship between sleep and epilepsy.

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Section: Introductionmentioning

confidence: 99%

Exaggerated Nighttime Sleep and Defective Sleep Homeostasis in a Drosophila Knock-In Model of Human Epilepsy

2015

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“…In addition, dopaminergic rescue of Rogdi mutant sleep revealed a novel sleep-regulatory mechanism that functionally links a specific subset of sleep-promoting GABAergic neurons to a wake-promoting dopaminergic pathway. Since epilepsy, a well penetrated phenotype in KTS patients, implicates GABAergic transmission 10 – 12 and sleep disorders 13 – 16 , our findings provide an important genetic clue to understanding the molecular and neural pathogenesis of KTS.…”

Section: Introductionmentioning

confidence: 78%

“…GABA has long been implicated in many aspects of neural dysfunction including seizures 10 – 12 , a well-penetrated neurological phenotype in KTS patients. Moreover, sleep deficits frequently accompany epilepsy 13 – 16 , and their severity is positively correlated in human epileptic patients and animal models 44 – 46 . In fact, sleep deprivation can cause or even aggravate epileptic seizures 46 – 48 .…”

Section: Resultsmentioning

confidence: 99%

Rogdi Defines GABAergic Control of a Wake-promoting Dopaminergic Pathway to Sustain Sleep in Drosophila

Kim

Jang

Yoo

et al. 2017

Sci Rep

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Kohlschutter-Tönz syndrome (KTS) is a rare genetic disorder with neurological dysfunctions including seizure and intellectual impairment. Mutations at the Rogdi locus have been linked to development of KTS, yet the underlying mechanisms remain elusive. Here we demonstrate that a Drosophila homolog of Rogdi acts as a novel sleep-promoting factor by supporting a specific subset of gamma-aminobutyric acid (GABA) transmission. Rogdi mutant flies displayed insomnia-like behaviors accompanied by sleep fragmentation and delay in sleep initiation. The sleep suppression phenotypes were rescued by sustaining GABAergic transmission primarily via metabotropic GABA receptors or by blocking wake-promoting dopaminergic pathways. Transgenic rescue further mapped GABAergic neurons as a cell-autonomous locus important for Rogdi-dependent sleep, implying metabotropic GABA transmission upstream of the dopaminergic inhibition of sleep. Consistently, an agonist specific to metabotropic but not ionotropic GABA receptors titrated the wake-promoting effects of dopaminergic neuron excitation. Taken together, these data provide the first genetic evidence that implicates Rogdi in sleep regulation via GABAergic control of dopaminergic signaling. Given the strong relevance of GABA to epilepsy, we propose that similar mechanisms might underlie the neural pathogenesis of Rogdi-associated KTS.

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“…We found an EDS prevalence of 25.2% in the patient group, and found no differences between the patient and control groups. In a recent literature review, 23 the prevalence of EDS in epilepsy was found to vary from 10 to 48%. In general, this prevalence was higher than 11.6% in the general population.…”

Section: Discussionmentioning

confidence: 99%

Subjective Sleep Disturbance in People with Epilepsy: Prevalence and Impact on Health-Related Quality of Life

Lee

et al. 2015

Sleep Med Res

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Background and ObjectiveaaIt is not well known whether sleep disturbances affect quality of life (QoL) independent of mood disturbance in people with epilepsy. The aim of this study was to investigate the prevalence of sleep disturbances and the impact on QoL in people with epilepsy. MethodsaaThis was a cross-sectional study involving adults with epilepsy and controls. Sleep disturbances, depression, anxiety, and QoL were assessed using several questionnaires. The direct effect of sleep disturbance on QoL was assessed using multiple linear regression analysis, and a mediational model designed with the assumption that sleep disturbances affect QoL through a mediator was tested. ResultsaaA total of 168 people with epilepsy and 56 controls were enrolled. Difficulty maintaining sleep (16.1%) and waking up too early in the morning (13.1%) were more common in patients than controls (p < 0.05). There were no differences in daytime sleepiness, sleep apnea, and restless legs syndrome between the groups. Patients had more sleep problems in the Medical Outcomes Study-Sleep Scale than controls. The effect of sleep disturbance on Quality of Life in Epilepsy 10 (QOLIE-10) lost its statistical significance (β = -0.021, p = 0.769) after controlling for Hospital Anxiety and Depression Scale (HADS). The Sobel test confirmed that the effect of sleep disturbance on QOLIE-10 was significantly mediated by both HADS-depression (β = -0.195, p < 0.001) and HADS-anxiety (β = -0.265, p < 0.001). ConclusionsaaSleep disturbances, especially insomnia, were more common in people with epilepsy. Although sleep disturbance seems to have no direct effects on QoL, it appears to have an indirect effect on QoL through depression and anxiety in people with epilepsy. Sleep Med Res 2015;6(1):16-23

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Excessive Daytime Sleepiness and Epilepsy: A Systematic Review

Cited by 31 publications

References 44 publications

Exaggerated Nighttime Sleep and Defective Sleep Homeostasis in a Drosophila Knock-In Model of Human Epilepsy

Exaggerated Nighttime Sleep and Defective Sleep Homeostasis in a Drosophila Knock-In Model of Human Epilepsy

Rogdi Defines GABAergic Control of a Wake-promoting Dopaminergic Pathway to Sustain Sleep in Drosophila

Subjective Sleep Disturbance in People with Epilepsy: Prevalence and Impact on Health-Related Quality of Life

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