Research

Pediatric neuropsychiatric syndromes associated with infection and microbiome alterations: clinical findings, possible role of the mucosal epithelium, and strategies for the development of new animal models
Hoffman KL, Cano-Ramírez H. Pediatric neuropsychiatric syndromes associated with infection and microbiome alterations: clinical findings, possible role of the mucosal epithelium, and strategies for the development of new animal models. Expert Opin Drug Discov. 2022 May 11. doi: 10.1080/17460441.2022.2074396. Epub ahead of print. PMID: 35543072.
“Although data from existing animal models are consistent with an important role for anti-neuronal antibodies in PANS triggered by GAS infection, we lack models for identifying pathophysiological mechanisms of PANS associated with other infectious and non-infectious triggers. The authors propose a strategy for developing such models that incorporates known vulnerability and triggering factors for PANS into the modeling process. This novel strategy should expand our understanding of the pathophysiology of PANS, as well as facilitate the development of new pharmacological treatments for PANS and related syndromes.”
Bowel and Bladder Dysfunction Is Associated with Psychiatric Comorbidities and Functional Impairment in Pediatric Obsessive-Compulsive Disorder
Clara Westwell-Roper, John R. Best, Zainab Naqqash, Kourosh Afshar, Andrew E. MacNeily, and S. Evelyn Stewart.Journal of Child and Adolescent Psychopharmacology. Published Online: 11 Apr 2022 – ahead of printhttp://doi.org/10.1089/cap.2021.0059

“Neuropsychiatric disorders are common in children with bowel and bladder dysfunction (BBD), a syndrome associated with urinary frequency, urgency, holding, incontinence, and constipation. We evaluated BBD symptom severity in children and youth attending a tertiary care obsessive-compulsive disorder (OCD) clinic….. BBD symptoms are common and associated with high OCD-related impairment and psychiatric comorbidities. Standardized assessment may facilitate identification of BBD symptoms in this population and is critical to mitigating long-term physical and mental health impacts. Further studies are required to assess the relationship between BBD and OCD treatment outcomes.”

Reader Response: Lack of Association of Group A Streptococcal Infections and Onset of Tics

Reader Response: Lack of Association of Group A Streptococcal Infections and Onset of Tics

“Schrag et al. reported that Group A streptococcal (GAS) exposure is unrelated to tics in children at risk for tic disorders.1 The critical limitations of this study are that only children with genetic risks for tics were studied and information about risk for autoimmunity, infection susceptibility, and antibiotics use are absent.1 The EMTICS home page states that many patients refused to participate when told that antibiotic use would be limited. This would introduce a negative selection bias against families who perceive themselves as high risk and patients procuring antibiotics outside the trial.2“

In response to:

Schrag AE, Martino D, Wang H, Ambler G, Benaroya-Milstein N, Buttiglione M, Cardona F, Creti R, Efstratiou A, Hedderly T, Heyman I, Huyser C, Mir P, Morer A, Moll N, Müller NE, Müller-Vahl KR, Plessen KJ, Porcelli C, Rizzo R, Roessner V, Schwarz M, Tarnok Z, Walitza S, Dietrich A, Hoekstra PJ; European Multicentre Tics in Children Study (EMTICS). Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study. Neurology. 2022 Mar 15;98(11):e1175-e1183. doi: 10.1212/WNL.0000000000013298. Epub 2022 Feb 2. PMID: 35110379.
Novel Drug Significantly Reduces Tics in Tourette’s ― Without Side Effects

An investigational drug that blocks the dopamine-1 (D1) receptor reduces tics and is safe and well tolerated in children with Tourette syndrome (TS), a new study shows.

Importantly, unlike current medications for the disorder, ecocipam does not lead to weight gain, anxiety, depression, or tardive dyskinesia compared to placebo ― a factor that may lead to better adherence.

Case Report – Pedijatrijsko autoimuno neuropsihijatrijsko oboljenje udruženo sa streptokokom

Pedijatrijsko autoimuno neuropsihijatrijsko oboljenje udruženo sa streptokokom

Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection

Jasmina Škorić1, Bojan Pavković1. 1 Dom zdravlja Dr Simo Milošević’, Beograd, Srbija

http://prevped.preventivnapedijatrija.rs/index.php/casopis/article/download/41/24

Conclusion: The patient showed signs of improvement after the intravenous administration of immunoglobulin which confirmed the underlying immunological aspect of the disease. Additionally, serologic test results that showed elevated antistreptolysin O titer and antideoxyribonuclease–B titer indicated streptococcal etiology. Precisely, these misdirected antibodies set off an inflammatory response that led to the basal ganglia damage resulting in behavioral changes, motor, cognitive and emotional disorders.

PANDAS in an Adult?: A Case Report

PANDAS in an Adult?: A Case Report. Deshmukh RP, Mane AB, Singh S.Ind J Priv Psychiatry 2022; 16 (1):44-45. DOI: 10.5005/jp-journals-10067-0104

“We report a case in order to suggest that we should be alert while assessing OCD in young patients, as it might be secondary to streptococcal infection. This has therapeutic implications. Trials of immunomodulator therapy can be given as suggested in a few kinds of literature. Although still experimental, it may have potential for the future, especially in those not responding to conventional treatment… This report might suggest that PANDAS-like syndrome may occur in adults also. We should be cautious of this syndrome during treatment.”

Neuroinflammation in a Rat Model of Tourette Syndrome

Neuroinflammation in a Rat Model of Tourette Syndrome, Zhongling Ke, Yanhui Chen, Guofeng Chen, Yanyan Liu, Neuroinflammation in a Rat Model of Tourette Syndrome, Frontiers in Behavioral Neuroscience, Vol 16, Front. Behav. Neurosci., 10 March 2022, DOI: 10.3389/fnbeh.2022.710116   

Conclusion: The 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.

Therapeutic Apheresis and Immunosuppression in Immunologic Diseases: A Review and Own Observations

Bambauer R, Schiel R. Therapeutic Apheresis and Immunosuppression in Immunologic Diseases: A Review and OwnObservations. Clin Immunol Res. 2021; 5(2): 1-36. ISSN 2639-8486

“TA should be reserved for treatment of children and adolescents

who are severely affected by PANDAS. In such patients, it

appears to be safe, well-tolerated, and beneficial treatment

option [130]. Bien et al reported in 2020, besides the first-line

interventions of steroids, IVIG, and TA as second-line treatments

cyclophosphamide or rituximab [131].”

Abnormal mTOR Activity in Pediatric Autoimmune Neuropsychiatric and MIA-Associated Autism Spectrum Disorders

Trifonova, E.A.; Mustafin, Z.S.; Lashin, S.A.; Kochetov, A.V. Abnormal mTOR Activity in Pediatric Autoimmune Neuropsychiatric and MIA-Associated Autism Spectrum Disorders. Int. J. Mol. Sci. 2022, 23, 967. https://doi.org/10.3390/ijms23020967

Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by

the early onset of communication and behavioral problems. ASD is highly heritable; however,

environmental factors also play a considerable role in this disorder. A significant part of both

syndromic and idiopathic autism cases could be attributed to disorders caused by mammalian

target of rapamycin (mTOR)-dependent translation deregulation. This narrative review analyzes both bioinformatic and experimental evidence that connects mTOR signaling to the maternal autoantibody-related (MAR) autism spectrum and autoimmune neuropsychiatric disorders simultaneously. In addition, we reconstruct a network presenting the interactions between the mTOR signaling and eight MAR ASD genes coding for ASD-specific maternal autoantibody target proteins. The research discussed in this review demonstrates novel perspectives and validates the need for a subtyping of ASD on the grounds of pathogenic mechanisms. The utter necessity of designing ELISA-based test panels to identify all antibodies related to autism-like behavior is also considered.

Discovering prescription patterns in pediatric acute-onset neuropsychiatric syndrome patients
Lopez Pineda A, Pourshafeie A, Ioannidis A, Leibold CM, Chan AL, Bustamante CD, Frankovich J, Wojcik GL. Discovering prescription patterns in pediatric acute-onset neuropsychiatric syndrome patients. J Biomed Inform. 2021 Jan;113:103664. doi: 10.1016/j.jbi.2020.103664. Epub 2020 Dec 28. PMID: 33359113.
  • PANS has an inflammatory or autoimmune etiology associated with an infection.
  • Longitudinal clustering can subset patients with polypharmacy treatments.
  • Included 43 consecutive new-onset pre-pubertal patients who had at least 3 clinic visits. “We used a cut-off age of 12 years to include only pre-pubertal children, as hormones might play a role in psychiatric symptoms and behaviors.”
  • Algorithm identified six clusters with distinct medication usage history which may represent clinician’s practice of treating PANS of different severities and etiologies i.e.,
    • two most severe groups requiring high dose intravenous steroids
    • two arthritic or inflammatory groups requiring prolonged nonsteroidal anti-inflammatory drug (NSAID)
    • two mild relapsing/remitting group treated with a short course of NSAID.
  • The psychometric scores as outcomes in each cluster generally improved within the first two years.
    Diagnostics, Differential Diagnostics And The Treatment Of Pandas Syndrome – Case Description

    Diagnostics, Differential Diagnostics And The Treatment Of Pandas Syndrome – Case Description Mukhtorjonova Khusnigul Nodirbekovna, Tukhtabayeva Kamila Abrarovna, Tashkent Padiatric Medical Institute. World Bulletin of Public Health (WBPH). Volume-6, January 2022. ISSN: 2749-3644

    This article gives a case of PANDAS syndrome in an 11-year-old boy. The
    course and clinic of the disease in the form of prolonged sneezing attacks
    made it difficult to diagnose this syndrome. Conducting biochemical blood
    tests, daily video electroencephalographic monitoring (EEG monitoring) and
    magnetic resonance imaging of the brain (MRI) allowed to determine the
    condition. The appointment of antibiotic therapy and intravenous
    administration of immunoglobulin led to remission of the disease. It is
    necessary to conduct further studies to determine the effectiveness of the
    above drugs for this syndrome.

    Read case study.

    Status Of Vitamin D In Children With Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)
    McNally JD, Menon K, Chakraborty P, Fisher L, Williams KA, Al-Dirbashi OY, Doherty DR; Canadian Critical Care Trials Group. The association of vitamin D status with pediatric critical illness. Pediatrics. 2012 Sep;130(3):429-36. doi: 10.1542/peds.2011-3059. Epub 2012 Aug 6. PMID: 22869837.
    “Numerous studies have indicated an association between vitamin D deficiency and the immune dysregulation and the pathogenesis of autoimmunity. An increased prevalence of vitamin D deficiency has been demonstrated in several pediatric autoimmune diseases, including autoimmune thyroid disease and Type-1 diabetes mellitus. This study was undertaken to determine the prevalence of vitamin D deficiency in children with PANS, an autoimmune disorder characterized by abrupt-onset neuropsychiatric symptoms.”