23 Apr Pathophysiology Idiopathic Hypersomnolence
Defined
Previously characterised by hypersomnolence with sleep drunkenness (Billiard & Sonka, 2016), the “unique symptomatology” demonstrated by IH patients combined with a lack of physiological biomarkers makes disease classification difficult, relying on the absence of specific narcoleptic symptoms rather than a display of exclusive symptoms (Nishino, 2017). Nosologic uncertainty means a unanimous definition of the disorder is yet to be attained, but frequent characterisations of IH as a central nervous system disorder has been noted manifesting into excessive daytime sleepiness, laborious awakenings from sleep, sleep drunkenness and severe sleep inertia, all of which provide some context to the polysymptomatic nature of this disorder.
Symptoms
IH symptomatology is variant on a case-by-case basis, but recurring symptoms seem to indicate the presence of severe sleep inertia, impairing the patient’s ability to transition between states of sleep and wakefulness. This transitional dysfunction manifests into excessive daytime sleepiness, frequent but long and unrefreshing naps with laborious awakenings often referred to as sleep drunkenness and more infrequently abnormally prolonged nocturnal sleep. Autonomic dysfunction in the form of temperature dysregulation and digestive problems are sometimes demonstrated by patients, as well as reports of symptomatic attention and memory deficits, mental fatigability and transient alertness in the evening (Billiard & Sonka, 2016).
Pathophysiology
Disease onset is generally insidious and most prominent during adolescence but is often seen between the ages of ten and thirty-years-old, with progressive worsening of symptoms eventually stabilising and becoming long-lasting. The origin of IH still remains unknown with varying experiences such as abrupt alterations to sleep-wake cycle, general anaesthesia, viral illness and head trauma being reported around the time of disease onset, although nil reports have been validated by research (Nishino, 2017). A strong genetic link has been discovered in previous research suggesting the likelihood of familial incidence of IH, with more robust research required to indicate the extent of this genetic factor (Billiard & Sonka, 2016).
The absence of physiological biomarkers in IH present another diagnostic barrier. With IH being well established as hypocretin non-deficient disorder, research is focussing on GABAergic mechanisms and histamine neurotransmission in the brain. Pilot research observed that IH patients presented with decreased CSF levels of histamine, a wake-active monoamine which demonstrates a central mechanism of hypersomnolence; reduced concentrations are known to impair histamine neurotransmission potentially promoting diurnal sleepiness. Treatment with GABAA receptor antagonists like Flumazenil has recently been successful in augmenting inhibitory GABA signalling and normalising vigilant states in IH, thus validating the effectiveness of decreasing GABA neurotransmission indicating its possible role in contributing to excessive sleepiness in IH patients (Nishino, 2017).
References
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental
disorders (5th ed.). Washington, DC: Author.
Billiard, & Sonka. (2016). Idiopathic hypersomnia. Sleep Medicine Reviews, 29, 23-33.
Nishino S. (2017) Narcolepsy and Idiopathic Hypersomnia. In: Chokroverty S. (eds) Sleep
Disorders Medicine. Springer, New York, NY.