Monthly Archives:
March 2023

Cytokine Effects on the Basal Ganglia and Dopamine Function: the Subcortical Source of Inflammatory Malaise

Felger JC, Miller AH. Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise. Front Neuroendocrinol. 2012 Aug;33(3):315-27. doi: 10.1016/j.yfrne.2012.09.003. Epub 2012 Sep 21. PMID: 23000204; PMCID: PMC3484236.

  • Cytokines released during inflammation target the basal ganglia and dopamine
  • Cytokines can disrupt dopamine function by effects on synthesis, packaging, release, and reuptake
  • Cytokine effects on basal ganglia dopamine may cause anhedonia, fatigue, and psychomotor slowing
  • Cytokines may contribute to behavioral disorders associated with chronic inflammation
PANDAS/PANS in the COVID-19 Age: Autoimmunity and Epstein–Barr Virus Reactivation as Trigger Agents?
Pallanti S, Di Ponzio M. PANDAS/PANS in the COVID-19 Age: Autoimmunity and Epstein-Barr Virus Reactivation as Trigger Agents? Children (Basel). 2023 Mar 30;10(4):648. doi: 10.3390/children10040648. PMID: 37189896; PMCID: PMC10136983.
“Herein, we discuss the results of studies that specifically reported data about the impact of the COVID-19 pandemic or infection on children with Pediatric Acute-Onset Neuropsychiatric Disorders (PANS). Furthermore, we present the cases of five adolescents with PANS whose symptomatology increased following SARS-CoV-2 infection. What emerged from this study was that COVID-19 resulted in the exacerbation of obsessions, tics, anxiety and mood symptoms and decreased wellbeing. Moreover, new symptoms, as well as new PANS cases, are reported to have arisen after COVID-19 infection. Here, we hypothesize that the pathogenic mechanisms of silent viruses, such as the Epstein–Barr virus, are related to neuroinflammation, immune responses and reactivation, with additional roles played by social-isolation-related inflammatory processes. The discussion of PANS, which represents a model of immune-mediated neuropsychiatric manifestations, is particularly relevant, with the aim of uncovering the mechanisms that lead to neuropsychiatric Post-Acute COVID-19 Syndrome (PACS). Prospects for future studies and treatment implications are discussed.”

Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID
Vojdani A, Vojdani E, Saidara E, Maes M. Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID. Viruses. 2023 Jan 31;15(2):400. doi: 10.3390/v15020400. PMID: 36851614; PMCID: PMC9967513.
“Based on our review of the literature, in both past and recent studies, we have found clues to these mechanisms that might drive this long COVID, with the goal of identifying host or virus factors that can be intervened upon to prevent or reverse this condition. A better understanding of these immunological mechanisms in patients with severe long COVID holds great promise for designing treatment strategies to minimize viral persistence, control the reactivation of latent viruses, and to modulate a dysregulated immune system and host microbiota, which together are involved in the virus-induced inflammation and autoimmunity that are observed in patients with long COVID.”
Deep clinical phenotyping of patients with obsessive-compulsive disorder: an approach towards detection of organic causes and first results

Runge, K., Reisert, M., Feige, B. et al. Deep clinical phenotyping of patients with obsessive-compulsive disorder: an approach towards detection of organic causes and first results. Transl Psychiatry 13, 83 (2023). https://doi.org/10.1038/s41398-023-02368-8

A relevant number of organic OCD forms (in 16%) were identified, which in 5% of all patients lead to successful treatment with immunotherapies. The frequent presence of autoantibodies such as anti-TPO or ANA further support the possible influences of autoimmune processes in OCD [16]. Further findings may well have modulatory effects on the course of the disease (e.g., substitution of folic acid deficiency). In addition, these findings might have a positive influence on the disease concept and self-image of affected patients and their relatives. The establishment of diagnostic regimens such as FDP-OCD should be evaluated in larger prospective and controlled studies. This could allow for a specific treatment of a small subgroup of patients with identified organic OCD reducing treatment resistance.

Neuropsychiatric Testing Provides Objective Insight into Beneficial Effects of IVIG in Patients with PANS

PANS IVIG Neuropsych testing UofArizona

Dr. Daines and the team at the CPAE Center of Excellence (University of Arizona) recently conducted a poster presentation at the AAAAI. The study demonstrates the beneficial effects of IVIG treatments for PANS patients. 11 out of 12 PANS patients showed “significant” improvement following IVIG treatment. 

The significant presence of baseline hypogammaglobulinemia in children with PANS emphasizes the presumed role of immune dysfunction in disease pathogenesis, especially given the known connection between immunodeficiency and autoimmunity (8,9). Thus, immunomodulatory interventions are presumed to have a crucial therapeutic role.

It did not assess the benefit of IVIG for OCD or Restricted Eating as the other psychiatric, and neuropsychological manifestations can sometimes overshadow OCD (1-3). Since objective post-treatment evaluations are scarce and challenging given disease complexity (5-7), the study used standardized neuropsychiatric testing to assess how (IVIG) treatment impacts cognitive function in children with PANS.

The research, as presented in the poster session, will be submitted as a journal article.

 

Clinical manifestations of Lyme neuroborreliosis in children: a review

Bruinsma, R.A., Zomer, T.P., Skogman, B.H. et al. Clinical manifestations of Lyme neuroborreliosis in children: a review. Eur J Pediatr 182, 1965–1976 (2023). https://doi.org/10.1007/s00431-023-04811-w

Lyme neuroborreliosis (LNB) is a manifestation of Lyme disease involving the central and peripheral nervous system. It is caused by the spirochete Borrelia burgdorferi, transmitted by tick bites to a human host. Clinical signs of LNB develop after the dissemination of the pathogen to the nervous system. The infection occurs in children and adults, but the clinical manifestations differ. In adults, painful meningoradicultis is the most common manifestation of LNB, while children often present with facial nerve palsy and/or subacute meningitis. Subacute headache can be the only manifestation of LNB in children, especially during the summer months in Lyme disease-endemic regions. Non-specific symptoms, such as loss of appetite, fatigue or mood changes, may also occur, especially in young children. A high level of suspicion and early recognition of the various clinical manifestations presented by children with LNB is essential to minimize delay in diagnosis and optimize management. This review provides an overview of the spectrum of clinical manifestations, and discusses diagnosis, antibiotic treatment, and clinical outcome of LNB in children.

Neuroinflammation in Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, and Pediatric Acute Onset Neuropsychiatric Syndrome
Vreeland A, Thienemann M, Cunningham M, Muscal E, Pittenger C, Frankovich J. Neuroinflammation in Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, and Pediatric Acute Onset Neuropsychiatric Syndrome. Psychiatr Clin North Am. 2023 Mar;46(1):69-88. doi: 10.1016/j.psc.2022.11.004. PMID: 36740356.
“It is imperative to not only treat the psychiatric symptoms but to also treat active and clinically apparent infections.”

Sydenham chorea (SC), pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS) are postinfectious neuroinflammatory diseases that involve the basal ganglia and have obsessive-compulsive disorder as a major manifestation. As is true for many childhood rheumatological diseases and neuroinflammatory diseases, SC, PANDAS and PANS lack clinically available, rigorous diagnostic biomarkers and randomized clinical trials. Research on the treatment of these disorders depend on three complementary modes of intervention including: treating the symptoms, treating the source of inflammation, and treating disturbances of the immune system. Future studies should aim to integrate neuroimaging, inflammation, immunogenetic, and clinical data (noting the stage in the clinical course) to increase our understanding and treatment of SC, PANDAS, PANS, and all other postinfectious/immune-mediated behavioral disorders.