Metabolomic Characterization of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)

Murgia, Federica; Gagliano, Antonella; Tanca, Marcello G; Or-Geva, Noga; Hendren, Aran; Carucci, Sara; Pintor, Maura; Cera, Francesca; Cossu, Fausto; Sotgiu, Stefano; Atzori, Luigi; Zuddas, Alessandro

doi:10.3389/fnins.2021.645267

Cited by 11 publications

(16 citation statements)

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“…Recently, in the research of markers for diagnosis, an alteration of plasma metabolic profile was observed in patients with PANS compared to healthy children, with regard to the metabolite levels associated with neurotransmission (glycine, tryptophan, histamine/histidine) and neuroinflammation (glutamine, 2-hydroxybutirate) ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical Features in Patients With PANDAS/PANS and Therapeutic Approaches: A Retrospective Study

2021

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Objective: The clinical characteristics of patients with PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) and PANS (pediatric acute-onset neuropsychiatric syndrome) and the efficacy of antibiotic therapy with psychotherapy and antipsychotics were investigated to improve neurological symptoms as well as obsessive compulsive disorder (OCD).Methods: We retrospectively analyzed 62 patients with a clinical diagnosis of PANDAS/PANS enrolled from May 14, 2013 to September 15, 2020 in the Neurology Childhood Division, Department of Pediatrics at Sapienza, Rome. Clinical manifestations, neurological and psychiatric, laboratory investigations, and familiar history were collected to evaluate the differences between the two groups. The effects of various therapeutic approaches were examined. Descriptive and comparative statistical analyses were performed.Results: The mean age at onset of PANDAS/PANS symptoms was 6.2 ± 1.2 years. The most common diagnosis was PANDAS, followed by PANS. Neurological and psychiatric symptoms were mostly evident in both groups (>70% of the population), with no significant difference between them (P = 0.52 and P = 0.15, respectively). Irritability, aggressivity, and food restriction were more prevalent in children with PANS than in those with PANDAS (P = 0.024 and P = 0.0023, respectively). The levels of anti-streptolysin O and anti-DNAse B 10-fold higher in PANDAS than those in PANS (P < 0.0001). Antibiotics or psychotherapy were administered in most cases (90.3 and 53.2%, respectively), followed by antipsychotic treatments (24.2%). In the multivariate analysis, among the therapies used, psychotherapy significantly resulted in the most efficacious relief of OCD, reducing stress in patients and their parents (P = 0.042).Conclusion: Our findings confirm a clear clinical difference between the two groups, PANDAS and PANS, using different approaches. In fact, irritability, aggressivity, and food restriction were significantly more frequent in children with PANS and the levels of anti-streptolysin O and anti-DNAse B were higher in PANDAS. Another relevant finding is the efficacy of psychotherapy, especially for obsessive-compulsive disorder, and of antibiotic prophylaxis in managing acute neurological symptoms.

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Section: Discussionmentioning

confidence: 99%

Clinical Features in Patients With PANDAS/PANS and Therapeutic Approaches: A Retrospective Study

2021

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“…Considering the common and the specific metabolic features of ASD and PANS classes, we can summarize that asparagine and glycine appeared to be significantly decreased in both ASD and PANS sera and that impaired glucose metabolism appears to be a key feature of ASD, while a decreased tryptophan concentration, previously identified as a significant feature of metabolomic profile of PANS [ 18 ], was not observed in ASD subjects.…”

Section: Discussionmentioning

confidence: 74%

“…Blood samples (10 mL by venipuncture) were collected after an overnight fast (12 h) and centrifuged at 2500× g for 10 min at 4 °C. Sera, stored at −80 °C until analysis, were analysed as described in our previous study (Murgia et al, 2021) [ 18 ]. Details are reported in the Supplementary Materials .…”

Section: Methodsmentioning

confidence: 99%

“…In this scenario, metabolomics could offer the opportunity to screen new biomolecules as potential biomarkers as it allows the quantification of an array of metabolites through two sensitive and specific methodologies: nuclear magnetic resonance (NMR) [ 14 ] and mass spectrometry (MS) [ 15 ]. Attempts to identify metabolomic biomarkers in several distinct brain disorders have revealed intriguing results [ 14 , 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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1H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome

Gagliano

Murgia

Capodiferro

et al. 2022

JCM

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We recently described a unique plasma metabolite profile in subjects with pediatric acute-onset neuropsychiatric syndrome (PANS), suggesting pathogenic models involving specific patterns of neurotransmission, neuroinflammation, and oxidative stress. Here, we extend the analysis to a group of patients with autism spectrum disorder (ASD), as a consensus has recently emerged around its immune-mediated pathophysiology with a widespread involvement of brain networks. This observational case-control study enrolled patients referred for PANS and ASD from June 2019 to May 2020, as well as neurotypical age and gender-matched control subjects. Thirty-four PANS outpatients, fifteen ASD outpatients, and twenty-five neurotypical subjects underwent physical and neuropsychiatric evaluations, alongside serum metabolomic analysis with 1H-NMR. In supervised models, the metabolomic profile of ASD was significantly different from controls (p = 0.0001), with skewed concentrations of asparagine, aspartate, betaine, glycine, lactate, glucose, and pyruvate. Metabolomic separation was also observed between PANS and ASD subjects (p = 0.02), with differences in the concentrations of arginine, aspartate, betaine, choline, creatine phosphate, glycine, pyruvate, and tryptophan. We confirmed a unique serum metabolomic profile of PANS compared with both ASD and neurotypical subjects, distinguishing PANS as a pathophysiological entity per se. Tryptophan and glycine appear as neuroinflammatory fingerprints of PANS and ASD, respectively. In particular, a reduction in glycine would primarily affect NMDA-R excitatory tone, overall impairing downstream glutamatergic, dopaminergic, and GABAergic transmissions. Nonetheless, we found metabolomic similarities between PANS and ASD that suggest a putative role of N-methyl-D-aspartate receptor (NMDA-R) dysfunction in both disorders. Metabolomics-based approaches could contribute to the identification of novel ASD and PANS biomarkers.

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“…The relationship between immune activation, neuroinflammation, and behavioral symptoms had been largely studied in the past two decades, especially in the pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS)/pediatric acute-onset neuropsychiatric syndrome (PANS; Murphy et al, 2010 ; Swedo et al, 2015 , 2017 ; Zheng et al, 2020 ; Murgia et al, 2021 ). Some TS cases, considered as a putative example of such phenomenon, meet the criteria for PANDAS/PANS, suggesting that the two diseases may have similar etiological mechanisms in some specific situations ( Lamothe et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammation in a Rat Model of Tourette Syndrome

Zhang

Chen

et al. 2022

Front. Behav. Neurosci.

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ObjectiveTourette syndrome (TS) is a group of childhood-onset chronic neuropsychiatric disorders characterized by tics, i.e., repetitive, sudden, and involuntary movements or vocalizations, which is often associated with various psychopathological and/or behavioral comorbidities, including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and sleep disorders and have a worse prognosis. The mechanism of TS is still not clear. The relationship between immune activation, neuroinflammation, and neuropsychiatric disorders has attracted much attention in the past two decades. To explore the underlying mechanism in TS, the relationship between neuroinflammation and behavioral alterations in TS rats was investigated in this study.MethodsA total of 36 Sprague-Dawley male rats were divided into three groups randomly as follows: the TS, control (CON), and drug intervention groups. The TS rat group was treated with haloperidol (Hal) (the TS + Hal group). The TS rat model was established using 3,3-iminodipropionitrile (IDPN), which is a well-known animal model of TS. The behavioral syndromes, brain tissue cytokines, like interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), and microglial activation of the three groups were assessed.ResultsThe behavioral scores of rats in the TS group and the TS + Hal group were higher than those in the CON group (P < 0.05), but the scores of behavioral tests in the TS + Hal group were lower than those in the TS group (P < 0.05). The levels of IL-6 and TNF-α in the rat brain tissue were significantly higher in the TS group than in the CON group (P < 0.05), while no significant differences were found between the CON group and the TS + Hal group (P > 0.05). The microglia was significantly activated in the TS group and slightly activated in the TS + Hal group, which was considerably less than that in the TS group.ConclusionThe IDPN-induced TS rats had significant neuroinflammation in the brain, and the interaction between dopamine (DA) dysregulation and immune dysfunction may play a vital role in the pathogenic mechanisms of TS.

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Metabolomic Characterization of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)

Cited by 11 publications

References 85 publications

Clinical Features in Patients With PANDAS/PANS and Therapeutic Approaches: A Retrospective Study

Clinical Features in Patients With PANDAS/PANS and Therapeutic Approaches: A Retrospective Study

1H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome

Neuroinflammation in a Rat Model of Tourette Syndrome

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