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.

Pediatric Chronic Inflammatory Response Syndrome

Book Nutrition and Integrative Medicine for Clinicians. ByScott W. McMahon

Edition 1st Edition. First Published 2023. Imprint CRC Press

Pages 22 eBook ISBN 9781003365839

While the same symptoms and objective laboratory tests are used to diagnose CIRS (chronic inflammatory response syndrome) in adults and children, there are differences in the diagnostic criteria used. The pathophysiology is thought to be the same at all age groups, and treatments differ slightly, but faster and more complete recovery is expected in children. Cytokine storms are seen in CIRS, in sepsis and COVID-19, and in their sequelae of post-sepsis syndrome and post-COVID syndrome. Transcriptomic changes in the latter group are similar to those of untreated CIRS patients. Overlaps are also seen in chronic fatigue syndrome, pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) patients. The prevalence of pediatric CIRS patients has been reported to be at least 7.01% and 7.6%, and it is likely higher in both children and adults. CIRS should be high on the differential for children with chronic headaches and/or abdominal issues. Fetal intrauterine exposure in water-damaged buildings may adversely affect brain development and may contribute to autism spectrum diagnoses. Pediatric CIRS is a preventable disorder, and even a preventable epidemic of medically unexplained symptoms; efforts should be made to protect children from this illness. Such measures will benefit the health of adults downstream.

Case report: Varicella associated neuropsychiatric syndrome (VANS) in two pediatric cases
Dahiya D, Matos CM, Lim M, Madureira I, Duarte S, Byrne S, Rossor T. Case report: Varicella associated neuropsychiatric syndrome (VANS) in two pediatric cases. Brain Behav Immun Health. 2023 Feb 11;28:100602. doi: 10.1016/j.bbih.2023.100602. PMID: 36860280; PMCID: PMC9969201.

Conclusion: Psychiatric syndromes with evidence of intrathecal inflammation temporally related to VZV infections that are responsive to immune modulation have not been described before. Here we report two cases demonstrating neuro-psychiatric symptoms following VZV infection, with evidence of persistent CNS inflammation following the resolution of infection, and response to immune modulation.

Chapter 24 – Obsessive-compulsive disorder and body dysmorphic disorder: Pediatric manifestation and treatment

M Jacofsky, M Fitzpatrick, F Neziroglu. Chapter 24 – Obsessive-compulsive disorder and body dysmorphic disorder: Pediatric manifestation and treatment. Bio Behavioral Institute.  https://doi.org/10.1016/B978-0-323-85757-4.00008-0

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal
infection In several cases of pediatric OCD, its onset may be triggered by a
streptococcal infection either in the child or in the mother while the child is in utero 

Rituximab as an adjunctive treatment for schizophrenia spectrum disorder or obsessive-compulsive disorder: Two open-label pilot studies on treatment-resistant patients

Susanne Bejerot, Sofia Sigra Stein, Elisabet Welin, Daniel Eklund, Ulrika Hylén, Mats B. Humble, Rituximab as an adjunctive treatment for schizophrenia spectrum disorder or obsessive-compulsive disorder: Two open-label pilot studies on treatment-resistant patients. Journal of Psychiatric Research. Volume 158, 2023, Pages 319-329, https://doi.org/10.1016/j.jpsychires.2022.12.0

  • Treatment-resistant schizophrenia benefitted from add-on treatment with rituximab.

  • Patients with schizophrenia, but not those with OCD, were much improved.

  • A ≥ 40% decrease of symptoms was seen in 7/9 patients with schizophrenia week 12.

  • Disability was diminished by 64% in patients with schizophrenia week 12.

  • Rituximab was well tolerated, and antipsychotic-related side effects decreased.

Association of Primary Immunodeficiencies in Parents With Psychiatric Disorders and Suicidal Behavior in Their Offspring

Isung J, Isomura K, Williams K, et al. Association of Primary Immunodeficiencies in Parents With Psychiatric Disorders and Suicidal Behavior in Their Offspring. JAMA Psychiatry. 2023;80(4):323–330. doi:10.1001/jamapsychiatry.2022.4786

  • Cohort study (4,294,169 offspring) revealed increased psychiatric disorder and suicidal behavior risk in offspring of mothers (not fathers) with PIDs.
  • Risk persisted after adjusting for parental psychopathology and autoimmune diseases, even when excluding offspring with PIDs and autoimmune diseases.
  • Maternal PIDs are associated with an elevated risk of psychiatric disorders and suicidal behavior in offspring, aligning with the maternal immune activation (MIA) hypothesis.
  • While supporting the MIA hypothesis, the precise mechanisms necessitate further investigation, particularly concerning the heightened risk when co-occurring with autoimmune diseases.