Low CSF hypocretin-1/orexin-A associated with hypersomnia secondary to hypothalamic lesion in a case of multiple sclerosis

Abstract

Sirs: Hypocretins/orexins are hypothalamic neuropeptides that are related to sleep-wake regulation [1,10]. It has been reported that cerebrospinal fluid (CSF) hypocretin-1/orexin-A level is dramatically decreased in narcolepsy-cataplexy [4,8,9,11]. Narcolepsy is also known to occur secondary to hypothalamic lesions caused by tumors, stroke, multiple sclerosis (MS) or acute disseminated encephalomyelitis, and the CSF hypocretin-1 level is decreased in some of them [5][6][7]12]. However, it remains unclear whether CSF hypocretin level correlates with the severity of hypersomnia and the REM pathology.We reported the MRI finding of bilateral hypothalamic lesions in a case of MS presenting with hypersomnia [3]. We further examined details of sleep investigations and correlated them with CSF hypocretin-1 level and the MRI findings.A 22-year-old woman was admitted to our hospital one week after the acute onset of hypersomnia. She had developed diplopia as an initial symptom of MS one year before the onset of hypersomnia. She also complained of numbness of the lower extremities and polyuria. She did not experience any narcolepsy-related symptoms such as cataplexy, sleep paralysis and hypnagogic hallucination. MRI revealed bilateral FLAIR hyperintensity in the hypothalamus [3].

Sleep Disorders and Multiple Sclerosis: A Clinical and Polysomnography Study

“…As in our study, in a prospective study of 70 MS patients, none fulfilled the polysomnographic criteria of narcolepsy despite several patients suffered from symptoms suggestive of narcolepsy, including a high frequency of sleep attacks, cataplexy, and sleep paralysis [2]. The lesions are often localized to the hypothalamus and cerebrospinal fluid hypocretin-1 levels are low, but may be reversible [37,39,43]. Both diseases have common genetic links since 95% of narcoleptics and 50–60% of MS patients demonstrate positivity to the DR haplotype DR2 [44].…”

Narcolepsy as an initial manifestation of neuromyelitis optica with antiaquaporin-4 antibody

“…The lack of episodes of cataplexy and HLA negativity in our patient may suggest that the disease did not occur primarily. Although a similar sleep abnormality was observed in a case of MS with hypothalamic lesions [9], the absence of anti-AQP4 antibody had been proven (personal communication).…”

“…The symptoms of narcolepsy are also known to occur secondary to hypothalamic lesions of various neurological conditions, such as brain tumors [6] and multiple sclerosis (MS) [2,9].…”

Autonomic dysfunction in multiple sclerosis

“…Involvement of hypothalamus on MRI is associated with increased fatigue [65]. There has been a report of hypersomnia and low orexin-1 level due to a demyelinating lesion in the hypothalamus [66]. However, studies in larger groups of patients with relapsing remitting MS have found cerebrospinal fluid levels of hypocretin-1 to be normal, and they didn't observe a correlation with hypersomnolence [67].…”