Single sessions of transcranial direct current stimulation and transcranial random noise stimulation exert no effect on sleepiness in patients with narcolepsy and idiopathic hypersomnia.

Background: Hypersomnia poses major challenges to treatment providers given the limitations of available treatment options. In this context, the application of non-invasive brain stimulation techniques such as transcranial electrical stimulation (tES) may open up new avenues to effective treatment. Preliminary evidence suggests both acute and longer-lasting positive effects of transcranial direct current stimulation (tDCS) on vigilance and sleepiness in hypersomniac patients. Based on these findings, the present study sought to investigate short-term effects of single sessions of tDCS and transcranial random noise stimulation (tRNS) on sleepiness in persons suffering from hypersomnia. Methods: A sample of 29 patients suffering from narcolepsy or idiopathic hypersomnia (IH) was recruited from the Regensburg Sleep Disorder Center and underwent single sessions of tES (anodal tDCS, tRNS, sham) over the left and right dorsolateral prefrontal cortex on three consecutive days in a double-blind, sham-controlled, pseudorandomized crossover trial. The primary study endpoint was the mean reaction time measured by the Psychomotor Vigilance Task (PVT) before and directly after the daily tES sessions. Secondary endpoints were additional PVT outcome metrics as well as subjective outcome parameters (e.g., Karolinska Sleepiness Scale; KSS). Results: There were no significant treatment effects neither on objective (i.e., PVT) nor on subjective indicators of sleepiness. Conclusion: We could not demonstrate any clinically relevant effects of single sessions of tDCS or tRNS on objective or subjective measures of sleepiness in patients with hypersomnia. However, we cannot exclude that repeated sessions of tES may affect vigilance or sleepiness in hypersomniac patients.

Hypothalamo-pituitary-adrenal axis, glucose metabolism and TNF-α in narcolepsy.

Narcolepsy with cataplexy is caused by a deficiency in the production of hypocretin/orexin, which regulates sleep and wakefulness, and also influences appetite, neuroendocrine functions and metabolism. In this case-control study, 11 patients with narcolepsy with cataplexy and 11 healthy adults underwent an oral glucose tolerance test, and dexamethasone suppression/corticotropin-releasing hormone stimulation test. The average age of patients and controls was 35.1 ± 13.2 and 41.0 ± 2.9 years, respectively, body mass index was 28.1 ± 6.6 and 25.5 ± 4.7 kg m(-2) . We did not find evidence of a significantly increased prevalence of disturbed glucose tolerance in patients with narcolepsy. After hypothalamo-pituitary-adrenal axis suppression, the number of non-suppressors did not differ between the groups, indicating normal negative feedback sensitivity. The level of cortisol after dexamethasone suppression was significantly lower in patients with narcolepsy, suggesting a slight basal downregulation and/or a slightly increased negative feedback sensitivity of the major endocrine stress system in narcolepsy. Following corticotropin-releasing hormone stimulation, there were no significant differences in levels of adrenocorticotropic hormone or cortisol, and in adrenocortical responsivity to adrenocorticotropic hormone. Finally, patients with narcolepsy displayed significantly higher plasma levels of tumour necrosis factor alpha, soluble tumour necrosis factor receptor p55, soluble tumour necrosis factor receptor p75 and interleukin 6 after adjustment for body mass index. The present study confirms that narcolepsy by itself is not associated with disturbances of glucose metabolism, but goes along with a subtle dysregulation of inflammatory cytokine production. We also found that dynamic hypothalamo-pituitary-adrenal system response is not altered, whereas negative feedback to dexamethasone might be slightly enhanced.

Presynaptic dopaminergic function in patients with restless legs syndrome: are there common features with early Parkinson's disease?

The cause of restless legs syndrome (RLS) is unknown, but an involvement of the dopaminergic system and a possible relation to Parkinson's disease (PD) is suggested by the positive response to dopaminergic treatment. We imaged the striatal dopamine transporter with [(123)I] N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(chloro-phenyl) tropane ([(123)I]IPT) and single-photon emission computed tomography (SPECT) in 28 RLS patients, and compared the results with transporter binding in 29 patients with early PD and 23 age-matched controls. No difference in IPT binding was found between RLS patients and controls. IPT binding was correlated significantly with age in RLS patients and controls, whereas there was no relation with the duration of symptoms or severity of RLS. PD patients presented significant lower presynaptic IPT binding ipsi- and contralateral to the affected body side compared with RLS patients or controls. We found no common characteristics between RLS patients and patients with early PD detectable by dopamine transporter SPECT. Our results do not strengthen an identical pathophysiologic pathway between RLS and PD on the level of nigrostriatal presynaptic terminal function.