Artificial Neural Networks Analysis of polysomnographic and clinical features in Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): from sleep alteration to “Brain Fog”

Abstract

Study Objectives PANS (pediatric acute onset neuropsychiatric syndrome) is thought to be the result of several mechanisms and multiple etiologies, ranging from endocrine/metabolic causes to postinfectious autoimmune and neuroinflammatory disorders. Sleep disorders represent one of the most frequent manifestations of PANS, involving around 80% of patients. The present study describes the clinical and polysomnographic features in a group of PANS children identifying the relationships between sleep disorders and other PANS symptoms. Methods All participants underwent a clinical evaluation including comprehensive sleep history, polysomnography, cognitive assessment and blood chemistry examination. A data mining approach with fourth-generation artificial neural networks has been used in order to discover subtle trends and associations among variables. Results Polysomnography showed abnormality in 17 out of 23 recruited subjects (73.9%). In particular, 8/17 children (47%) had ineffective sleep, 10/17 (58.8%) fragmented sleep, 8/17 (47.1%) periodic limb movement disorder (PLMD) and 11/17 (64.7%) REM-sleep without atonia (RSWA). Most subjects presented more than one sleep disturbances. Notably, among the 19/23 patients diagnosed with Tic/Tourette disorder, 8/19 (42.1%) show PLMD and 10/19 (52.6%) RSWA. Artificial neural network methodology and the auto-contractive map exploited the links among the full spectrum of variables revealing the simultaneous connections among them, facing the complexity of PANS phenotype. Conclusion Disordered sleep represents, for prevalence and impact on quality of life, a cardinal symptom in patients with PANS. Thus, considering the weight of sleep disturbances on diagnosis and prognosis of PANS, we could consider the possibility of including them among the major diagnostic criteria.

Commentary on the Paper by Gagliano et al: Artificial Neural Networks Analysis of Polysomnographic and Clinical Features in Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): From Sleep Alteration to “Brain Fog” [Letter]

“…A recent article by Gagliano et al emphasized the presence of sleep alterations in pediatric acute-onset neuropsychiatric syndrome (PANS), pointing out a symptomatic overlap with other sleep disorders of well-known immune-mediated pathogenesis, such as narcolepsy and Kleine-Levin syndrome. 1 While reading the article, I considered the potential role of orexin/hypocretin-system dysfunctionality in sleep disturbances for patients with PANS, alongside the development of other symptoms as part of this syndrome. Importantly, narcolepsy with cataplexy is caused by a loss of orexin-producing neurons in the hypothalamus, and orexin dysregulation has also been suggested to play a role in Kleine-Levin syndrome’s pathophysiology.…”

“… 4–8 In particular, obsessions and compulsive behaviors might be linked to the orexinergic system and its interactions with the dopaminergic system, 8 while the presence of orexin cells in the lateral hypothalamus, which is a key site of food intake regulation, 4 may relate to food restriction among patients with PANS. Considering Gagliano et al’s presentation of a putative dysfunctional model that explains the co-occurrence of sleep, cognitive, and motor symptoms in patients with PANS, 1 the orexin system’s role could be emphasized within this symptom’s framework.…”

“…Increased arousal, meanwhile, may cause hypervigilance/insomnia, cognitive dysfunction (overstimulation), panic/fear, and hallucinations/psychosis. 5 Thus, the “brain fog” that Gagliano et al 1 described might indicate a dysfunction of the orexin system that could manifest with symptoms across the arousal spectrum, affecting such domains as cognitive function, attention, alertness, and vigilance.…”

“… 2 At the same time, it might also explain the observation by Gagliano et al regarding the high prevalence of periodic limb movement disorder (a hypo-dopaminergic condition) among patients with PANS who also exhibited motor and vocal tics (a hyper-dopaminergic condition). 1 …”

“…Most, if not all, PANS symptoms could be proposed to stem from orexin-system dysfunctionality, alongside the sleep alterations that Gagliano et al described. Therefore, within the conceptual framework useful for future empirical research, 1 the orexin system could also be considered.…”