Abstract Introduction Symptoms suggestive of autonomic nervous system (ANS) dysfunction have been previously described in patients with idiopathic hypersomnia (IH), however, objective ANS reflex testing data has not been reported. We aimed to better quantify symptoms of ANS dysfunction in a cohort of patients with IH through the use of standardized ANS reflex testing. Methods Patients diagnosed with IH based on ICSD-3 criteria using overnight video polysomnography and multiple sleep latency testing (MSLT) were consecutively enrolled in our study, regardless of ANS symptoms. All patients underwent ANS reflex testing, including measures of parasympathetic (heart rate variability with deep breathing and Valsalva ratio) and sympathetic adrenergic function (Valsalva blood pressure response and 10-minute head-up tilt at an angle of 70 degrees) with continuous blood pressure and heart rate monitoring. Eleven patients also underwent measures of sympathetic cholinergic function (quantitative sudomotor axon reflex testing). All medications that affect ANS function were held prior to ANS testing, including wake-promoting medications and sodium oxybate. Results Twenty patients with IH were enrolled. Fifty percent (10/20) were long sleepers (>11hrs). Mean sleep onset latency and number of sleep onset REM periods (SOREMs) on MSLT were 6.9 (± 3.1) mins and 0.2 (± 0.4), respectively. Mean duration of IH symptoms prior to the date of ANS testing was 6.3 (± 8.1) yrs. Eighty-five percent (17/20) of patients had abnormal ANS testing. Of these, 75% (15/20) had sympathetic adrenergic impairment, 64% (7/11) had sympathetic cholinergic impairment, and 5% (1/20) had parasympathetic impairment. Fifty-five percent (11/20) of patients were diagnosed with postural tachycardia syndrome (POTS), 45% (5/11) with small fiber neuropathy, 5% (1/20) with inappropriate sinus tachycardia and 15% (3/20) with neurally-mediated syncope. Seventy percent (14/20) of patients reported orthostatic intolerance regardless of autonomic diagnosis. Conclusion ANS dysfunction was common and severe in our cohort of IH patients, affecting all domains of ANS reflex testing, with more prominent impairment in sympathetic domains. POTS was the most common comorbid diagnosis, and most patients reported orthostatic intolerance. There was no association with IH disease duration, though our sample size was limited. Future studies will focus on ANS testing in larger cohorts of IH patients, specifically on shared pathophysiological mechanisms of hypersomnia and ANS dysfunction. Support (If Any)

Sleep-related rhythmic movements (SRRMs) are typical in infancy and childhood, where they usually occur at the wake-sleep transition. However, they have rarely been observed in adults, where they can be idiopathic or associated with other sleep disorders. We report a video case series of 5 adults with sleep-related rhythmic movement disorder (SRRMD), 4 of which had a previous history of SRRMs in childhood. All of them underwent a full-night Video-PSG. A total of 411 RMEs were recorded in our 5 subjects, 78% of them occurred during consolidated sleep, of these, 18% in REM sleep. In the great majority of the cases (81.4%), RMEs were preceded by pathological breathing events. In at least 2 cases, the duration of breathing events associated with RMEs was longer than the one of those unassociated. RMEs retreated after CPAP ventilation in one subject. Four out of five subjects reported a previous history of SRRMD during childhood. We speculate that respiratory-related arousals could drive the occurrence of motor events in predisposed subjects. We strongly recommend to investigate the sleep-related breathing pattern by means of a full video-polysomnography in adults with SRRMD, particularly in those with a new-onset disorder or a recent aggravation, as well as in those whose RMEs tend to occur in consolidated sleep. This may speak against an unsafe treatment with benzodiazepines, which can aggravate sleep apnea. When sleep apnea is confirmed, treatment with CPAP might be beneficial also for RMEs. The SAS-CARE study was supported by grants from the Swiss National Science Foundation (SNF Grant 320030_125069) and SwissHeart.

Skin biopsy and microneurography are autonomic tests directly evaluating adrenergic and cholinergic sympathetic fibers to identify selective deficiency of a specific peripheral sympathetic subdivision. We describe a patient with tomacular neuropathy due to a deletion of the PMP22 gene who complained of chronic orthostatic hypotension due to a dopamine-β-hydroxylase deficiency confirmed by genetic analysis demonstrating two novel mutations in the DβH gene. To further characterize autonomic dysfunctions the proband underwent skin biopsy and microneurography. These tests disclosed a selective peripheral adrenergic dysfunction demonstrating the possibility to ascertain DβH deficiency. In conclusion, skin biopsy and microneurography may help to increase the diagnosis of this peculiar disorder particularly when routine autonomic nervous system tests show uncertain results.