"IH has long been considered a rare disease, believed to be 10 times less frequent than narcolepsy. The prevalence of narcolepsy (with cataplexy) is estimated between 1/3,300 and 1/5,000. Although the true prevalence of IH is unknown, it is estimated at 1/10,000 to 1/25,000 for the long sleep form and 1/11,000 to 1/100,000 without long sleep. A more precise estimate "is complicated by a lack of clear biologic markers" and a lack of "unambiguous diagnostic criteria. "Because of the rarity of IH, research into the condition is limited "Patients are rare, researchers and scientists involved in the field are few and research findings are therefore scarce." "In Europe and in North America there is now a public health concern about helping patients and families affected by these rare diseases. Due to the complexity of the disease, they often experience difficulties to be diagnosed and often face social and professional consequences." Research
GABA-directed medications
There is ongoing research into the efficacy of gamma aminobutyric acid A (GABAA) receptor antagonists for the treatment of IH. Research findings suggest that the GABA neurotransmitter system plays a significant role in the etiology of primary hypersomnias, such as IH and Narcolepsy Type 2. Given the possible role of hyperactive GABAA receptors in IH, medications that could counteract this activity are being studied to test their potential to improve sleepiness. These currently include clarithromycin and flumazenil.Flumazenil, a GABAA receptor antagonist is approved by the FDA for use in anesthesia reversal and benzodiazepine overdose.
As of 2012, researchers have identified a few abnormalities associated with IH, which with further study may help to clarify the etiology.Destruction of noradrenergic neurons has produced hypersomnia in experimental animal studies, and injury to adrenergic neurons has also been shown to lead to hypersomnia. IH has also been associated with a malfunction of the norepinephrine system and decreased cerebrospinal fluid (CSF) histamine levels.Researchers have recently found an abnormal hypersensitivity to GABA (the major brain chemical responsible for sedation) in a subset of patients with central hypersomnia i.e. : IH, narcolepsy without cataplexy and long sleepers. They have identified a small (500 to 3000 daltons) naturally occurring bioactive substance (most likely a peptide as it is trypsin-sensitive) in the CSF of affected patients. Although this substance requires further identification of its chemical structure, it is currently referred to as a "somnogen" because it has been shown to cause hyper-reactivity of GABAA receptors, which leads to increased sedation or somnolence. In essence, it is as though these patients are chronically sedated with a benzodiazepine (medication which acts through the GABA system) such as Versed or Xanax, even though they do not take these medications. Diagnosis
Idiopathic hypersomnia lacks a clearly defining biological marker like HLA-DQB1*0602 genotype in narcolepsy. Doctors can more carefully exclude these causes of EDS in order to more correctly diagnose IH.