Pathophysiology of Sleep Disorder in TBI
The physical mechanisms of injury in TBI are different in direct and secondary (indirect) brain injuries.Direct brain injury occurs via diffuse degeneration of the white matter, also known as diffuse axonal injury. Shearing forces damage brain matter by inertial loading of the head with resultant damage to the septum pellucidum, corpus callosum, deep gray matter, dorso-lateral pons, and midbrain.[4,25] These areas are closely related to sleep-wake mechanisms. Postulated biochemical mechanisms for the development of neuronal injury in those with TBI include neuronal excitotoxicity, inflammation, free radical formation/eicosanoids, hyperglycolysis, hyperglycemia, and ApoE 4 protein synthesis, particularly in those with more mild injury. Indirect brain injuries can result from epidural, subdural, and intraparenchymal hematoma, as well as contusions involving the cerebral parenchyma or brainstem. These can produce mechanical distortion and/or compression of surrounding structures and may compromise sleep-wake centers. This type of injury is likely a factor in those with moderate-to-severe head injuries.
At a biochemical level, TBI may result in hypothalamic-pituitary axis injury, which reduces levels of wake-promoting neurotransmitters such as hypocretin (orexin-A) and histamine. Cerebrospinal fluid (CSF) levels of both hypocretin and histamine have been shown to be depressed in patients with pathologic causes of central hypersomnia and in those with TBIs.[7,30,31] Baumann and colleagues found that patients with acute TBI have reduced CSF levels of hypocretin. Levels of hypocretin increase in most patients in the 6 months post-injury, but may remain lower in those with persistent daytime somnolence. Following their injuries, it is postulated that these individuals have an insufficiency of the hypothalamic-pituitary axis. However, this has not been well-defined.[13,31] Similarly, depressed CSF levels of histamine have also been reported in patients with both central hypersomnias (such as idiopathic hypersomnia and narcolepsy) and TBIs.[30,32]
O'Hara and colleagues assessed the role of apolipoprotein epsilon 4 allele (APOE Ɛ4) in patients with TBI and sleep disruptions. The presence of this allele has been associated with cognitive decline and the development of dementia, and APOE Ɛ4 carriers may be more prone to the adverse effects of sleep apnea on cognition. This may have significant implications for similar genetically predisposed patients in whom TBI develops. The clinical implications of this finding, however, are unclear.
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Cite this: Jacob F. Collen, Christopher J. Lettieri. Sleep Disorders in Traumatic Brain Injury - Medscape - May 24, 2011.