Cortical Excitability Changes in Patients with Sleep-Wake Disturbances after Traumatic Brain Injury

Abstract

Although chronic sleepiness is common after head trauma, the cause remains unclear. Transcranial magnetic stimulation (TMS) represents a useful complementary approach in the study of sleep pathophysiology. We aimed to determine in this study whether post-traumatic sleep-wake disturbances (SWD) are associated with changes in excitability of the cerebral cortex. TMS was performed 3 months after mild to moderate traumatic brain injury (TBI) in 11 patients with subjective excessive daytime sleepiness (EDS; defined by the Epworth Sleepiness Scale ≥10), 12 patients with objective EDS (as defined by mean sleep latency <5 on multiple sleep latency tests), 11 patients with fatigue (defined by daytime tiredness without signs of subjective or objective EDS), 10 patients with post-traumatic hypersomnia "sensu strictu," and 14 control subjects. Measures of cortical excitability included central motor conduction time, resting motor threshold (RMT), short-latency intracortical inhibition (SICI), and intracortical facilitation to paired-TMS. RMT was higher and SICI was more pronounced in the patients with objective EDS than in the control subjects. In the other patients all TMS parameters did not differ significantly from the controls. Similarly to that reported in patients with narcolepsy, the cortical hypoexcitability may reflect the deficiency of the excitatory hypocretin/orexin-neurotransmitter system. These observations may provide new insights into the causes of chronic sleepiness in patients with TBI. A better understanding of the pathophysiology of post-traumatic SWD may also lead to better therapeutic strategies in these patients.

Sleep Disturbances in Traumatic Brain Injury: A Meta-Analysis

“…9,18,24,29 Two authors were unable to provide data for all measures of interest, 10,20 but these studies were able to be included in some analyses. Two authors were unable to provide objective data and these studies were excluded, 28,30 as the data were inadequately reported. The later study 30 was also excluded as part of a control sample featured in a previous publication already included in the current meta-analysis.…”

A systematic review of fatigue in patients with traumatic brain injury: The course, predictors and consequences

“…Excessive daytime sleepiness may be an indicator of central nervous system (CNS) pathology due to brain injury (i.e. hypocretin/orexin deficiency), as well as related to quantity and quality of sleep (Mollayeva et al, 2013b;Baumann, 2012;Nardone et al, 2011;Mathias and Alvaro, 2012;Siebern and Guilleminault, 2012). While Kempf et al (2010) studied and did not uncover a relationship between fatigue and sleep duration, quality of sleep was not investigated.…”

“…sleep-related breathing disorder, periodic leg movement disorder, etc.) highly prevalent post-TBI (Nardone et al, 2011;Mollayeva et al, 2013c) are characterized by frequent arousals, which generally result in fragmented sleep, which can produce daytime sleepiness (Stepanski, 2002). Bushnik et al (2008a) suggests assessment of sleep quality as a valuable measure when studying TBI patients with fatigue complaints.…”

Study of Sleep Patterns Might Advance Our Knowledge on Alertness in Traumatic Brain Injury

“…Nardone and colleagues recently studied cortical excitability in patients affected by different sleep-wake disturbances after TBI to determine whether changes in cortical excitability are associated with the development of post-traumatic excessive daytime sleepiness [20]. They reported that, similar to that in patients with narcolepsy [21,22], cortical hypo excitability in patients with TBI might reflect deficiency in the excitatory hypocretin/orexin-neurotransmitter system [20].Though not experimentally tested yet in the TBI population, the pre-existing level of alertness should be factored into the conclusions. This is highly relevant to the study of alertness in the TBI population, when taking into account symptom overlap between impaired alertness and daytime sleepiness; nearly half of patients with excessive sleepiness report automobile accidents, with half reporting occupational accidents and other life threatening situations [23] which can result in a TBI outcome.…”

“…Hypocretins play an essential role in promoting wakefulness. Nardone and colleagues recently studied cortical excitability in patients affected by different sleep-wake disturbances after TBI to determine whether changes in cortical excitability are associated with the development of post-traumatic excessive daytime sleepiness [20]. They reported that, similar to that in patients with narcolepsy [21,22], cortical hypo excitability in patients with TBI might reflect deficiency in the excitatory hypocretin/orexin-neurotransmitter system [20].Though not experimentally tested yet in the TBI population, the pre-existing level of alertness should be factored into the conclusions.…”