Letter on the article Artificial Neural Networks Analysis of polysomn


Dear editor

A recent article by Gagliano et al. emphasized the presence of sleep alterations in pediatric acute neuropsychiatric syndrome (PANS) and indicated a symptomatic overlap with other sleep disorders of the well-known immune-mediated pathogenesis such as narcolepsy and Kleine Levin syndrome.1 In reading the article, I have considered the possible role of orexin / hypocretin system dysfunction in insomnia in patients with PANS, in addition to developing other symptoms as part of this syndrome. Importantly, cataplexy narcolepsy is caused by loss of orexin-producing neurons in the hypothalamus, and orexin dysregulation has also been suggested to play a role in the pathophysiology of Kleine Levin syndrome.2.3 In addition, narcolepsy and some neuropsychiatric disorders may share features, and although precise mechanisms have yet to be identified, orexin deficiency has been suggested as the pathophysiological mechanism underlying these disorders.4th Therefore, due to the neuropsychiatric symptoms within PANS, dysfunction of the orexin system could play a plausible role in the development of this syndrome.

The orexin system is involved in the regulation of several physiological processes4th this can be important in connection with PANS. These processes include wakefulness, arousal, sleep-wake behavior, central motor control, cognitive processes, fear, reward, motivated behavior, food intake, and involvement in the micturition reflex.4-8 In particular, obsessions and compulsive behavior can be associated with the orexinergic system and its interactions with the dopaminergic system.8th while the presence of orexin cells in the lateral hypothalamus, which is a key point in regulating food intake,4th may be related to dietary restriction in patients with PANS. In view of the presentation by Gagliano et al. a putative dysfunctional model explaining the coexistence of sleep, cognitive and motor symptoms in patients with PANS,1 the role of the orexin system could be emphasized in the context of this symptom.

Given that orexin is a key component of the arousal system and takes into account the sleep-wake arousal spectrum,5 its effects on all aspects of the entire spectrum seem plausible. An optimal balance of arousal enables a person to be alert, alert, creative, and able to solve problems.5 In contrast, with decreasing arousal, a person may experience not only inattention and cognitive dysfunction (under-stimulation), but also excessive daytime sleepiness. Meanwhile, increased arousal can cause hypervigilance / insomnia, cognitive dysfunction (overstimulation), panic / anxiety, and hallucinations / psychosis.5 The “brain fog” that Gagliano et al1 may indicate a dysfunction of the orexin system, which could manifest itself with symptoms across the spectrum of arousal affecting areas such as cognitive function, attention, alertness, and alertness.

Given the pathophysiology of movement disorders, which is often observed at the onset of the disease in childhood narcolepsy with cataplexy, rapid loss of orexin neurons may likely be associated with possible involvement of secondary dopaminergic abnormalities.2 Given several motor deficits associated with the loss of orexins and the assumption that the orexin system orchestrates central motor control through homeostatic regulation,6th Motor phenomena can also be conceptualized as a spectrum in which the orexin system plays an important role. This conceptualization can help explain the “complex series of ‘negative’ (hypotension) and ‘active’ (from perioral movements to dyskinetic-dystonic movements or stereotypical movements) motor disorders” that Plazzi et al. in children with narcolepsy with cataplexy.2 At the same time, the observation by Gagliano et al. explain the high prevalence of periodic limb movement disorders (a hypodopaminergic disorder) in patients with PANS who also had motor and vocal tics (a hyperdopaminergic disorder).1

In summary, the dysfunction of the orexin system, although not fully understood, can be suggested as an important factor in the pathophysiological mechanisms underlying PANS. Most, if not all, of PANS symptoms, along with those reported by Gagliano et al. The sleep disorders described above can be attributed to a dysfunction of the orexin system. Within the conceptual framework useful for future empirical research,1 the orexin system could also be considered.


The author does not report any conflicts of interest in this release.


1. Gagliano A, Puligheddu M, Ronzano N, et al. Analysis of artificial neural networks of polysomnographic and clinical features in pediatric acute neuropsychiatric syndrome (PANS): from sleep changes to “brain fog”. Nat Sci sleep. 2021; 13: 1209-1224. doi: 10.2147 / NSS.S300818

2. Plazzi G, Pizza F, Palaia V, et al. Complex movement disorders at the onset of the disease in childhood narcolepsy with cataplexy. brain. 2011; 134 (Pt 12): 3477-3489. doi: 10.1093 / brain / awr244

3. Wang JY, Han F, Dong SX, et al. Cerebrospinal fluid orexin A levels and autonomic function in Kleine Levin syndrome. sleep. 2016; 39 (4): 855-860. doi: 10.5665 / sleep.5642

4. BaHammam AS, Alnakshabandi K, Pandi-Perumal SR. Neuropsychiatric correlates of narcolepsy. Curr Psychiatry Rep. 2020; 22 (8): 36. doi: 10.1007 / s11920-020-01159-y

5. Steel SM, Morrissette DA. Stahl’s illustrated sleep and wake disorders. Cambridge University Press; 2016.

6. Hu B, Yang N, Qiao QC, Hu ZA, Zhang J. Roles of the orexin system in the central motor control. Neurosci Biobehav Rev. 2015; 49: 43-54. doi: 10.1016 / j.neubiorev.2014.12.005

7. M. Kobayashi, M. Nomura, H. Fujihara, et al. Involvement of orexin-A in the micturition reflex in normal and cyclophosphamide-induced cystitis in rats. Peptides. 2009; 30 (12): 2348-2356. doi: 10.1016 / j.peptides.2009.07.025

8. M. Abounoori, MM Maddah, E. Akbari, G. Houshmand, M. Ardeshiri. The effect of orexin receptor antagonism on quinpirole-induced compulsive control behavior in rats. Neurotox Res. 2020; 38 (1): 18-26. doi: 10.1007 / s12640-020-00196-y


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