Research

Wayne, Charlotte Remy. Roles of Th17 cytokines in microglial and neurovascular responses to recurrent intranasal Streptococcus pyogenes infections. 2022 Theses Doctoral. Columbia Academic Commons. https://doi.org/10.7916/62va-6330

Academic Units: Cellular, Molecular and Biomedical Studies
Thesis Advisors: Agalliu, Dritan
Degree: Ph.D., Columbia University
Published:  September 7, 2022

Autoimmune-mediated obsessive-compulsive disorder (OCD) during childhood has long been established in the context of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection. In adult psychiatry, the topic has increasingly gained interest in light of new developments regarding autoimmune encephalitis and autoimmune psychosis. Hence, diagnostic criteria for autoimmune OCD in adulthood have been proposed recently, and the first respective cases were reported. For the detection of neuroinflammatory processes, cerebrospinal fluid (CSF) analysis (besides the far more invasive brain biopsy) is considered the most sensitive diagnostic tool. Here, we present 2 paradigmatic OCD patients with inflammatory CSF signals including antinuclear antibody staining in CSF and magnetic resonance imaging (MRI)/electroencephalography (EEG) findings compatible with OCD.

Ilyas U, Umar Z, Lin D (August 26, 2022) Group A Beta-Hemolytic Streptococcus-Induced Tic-Like Movement Disorder in an Adult: A Case Report. Cureus 14(8): e28451. doi:10.7759/cureus.28451

Jaynelle Gao, Avis Chan, Theresa Willett, Bahare Farhadian, Melissa Silverman, Paula Tran, Sana Ahmed, Margo Thienemann, and Jennifer Frankovich.Sex and Aggression Characteristics in a Cohort of Patients with Pediatric Acute-Onset Neuropsychiatric Syndrome.Journal of Child and Adolescent Psychopharmacology.ahead of print http://doi.org/10.1089/cap.2021.0084

• Males had a higher median Modified Overt Aggression Scale (MOAS) score in the first year of clinic when compared with females and a higher median subscore for physical aggression.
• The median time from PANS symptom onset to first administration of immunotherapy, which did not include nonsteroidal anti-inflammatory drugs or short bursts of oral steroids, was 6.9 years for females and 3.7 years for males.
• Although the physical aggression measured by the MOAS was significantly higher in males, caregivers of males and females reported similar levels of caregiver burden.
• The two groups did not differ significantly in age of PANS onset, time from onset to clinic entry, other psychiatric symptom measures, or laboratory markers of inflammation.

Conclusion: Among patients with PANS, males exhibit more aggressive behavior when compared with females, which may advance the decision to treat with immunotherapy. Scores that capture a more global level of functioning show that despite there being a higher level of aggression in males, female patients with PANS have similar levels of overall impairment.

Della Vecchia A, Marazziti D. Back to the Future: The Role of Infections in Psychopathology. Focus on OCD. Clin Neuropsychiatry. 2022;19(4):248-263. doi:10.36131/cnfioritieditore20220407

“Several pathogens have been associated with an increased risk to develop a broad spectrum of neuropsychiatric conditions, such as schizophrenia, mood disorders, autism, attention-deficit/hyperactivity disorder, anorexia nervosa, and post-traumatic stress disorder. Some evidence supported a possible role of infections also in the pathophysiology of OCD. Infections from Herpes simplex virus 1, Borna disease virus, Group A-Beta Hemolytic Streptococcus, Borrelia spp., and Toxoplasma gondii were actually found in patients with OCD. Although different mechanisms have been hypothesized, all would converge to trigger functional/structural alterations of specific circuits or immune processes, with cascade dysfunctions of several other systems.”

Fabricius RA, Sørensen CB, Skov L, Debes NM, Cytokine profile of pediatric patients with obsessive-compulsive and/or movement disorder symptoms: A review. Frontiers in Pediatrics. Vol 10, 2022. DOI: 10.3389/fped.2022.893815 

• Cytokines modulate the immune system. Significantly altered in many neurological and psychiatric disorders, like OCD, movement disorder, and PANDAS
• Review of current literature on the cytokine profile of pediatric patients with symptoms of OCD and/or movement disorder symptoms. 19 studies were found. 12 included a healthy control group. 4 had control groups of children with other disorders, primarily neurological or psychiatric. 1 compared cytokines measurements to reference intervals. 2 had a longitudinal design.
• Many cytokines were found to have significant changes in patients with symptoms of OCD and/or movement disorders compared to both healthy controls and other control groups.
• Differences were found when comparing cytokines in periods of exacerbation with periods of remission of symptoms in study participants.
• The cytokines that most studies with healthy control groups found to be significantly altered were TNF-α, IL-1β and IL-17.
• The exact role of these cytokines in OCD and movement disorder symptoms remains unclear, but the available literature suggests a proinflammatory cytokine profile offering interesting perspectives on the pathogenesis of OCD and/or movement disorder symptoms in children
• Further research into the implications of cytokines in neuropsychiatric disorders is warranted.

U Prosell, H Norman, A Sand, A McAllister, Infection and speech: Disfluency and other speech symptoms in Pediatric Acute-onset Neuropsychiatric Syndrome, Journal of Communication Disorders, 2022, 106250, https://doi.org/10.1016/j.jcomdis.2022.106250.

Hajjari, P., Oldmark, M.H., Fernell, E. et al. Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) and intravenous immunoglobulin (IVIG): comprehensive open-label trial in ten children. BMC Psychiatry 22, 535 (2022). https://doi.org/10.1186/s12888-022-04181-x

Conclusion: Considerable and pervasive improvements in symptoms and clinical impairments were seen in these ten children after three monthly IVIG treatments. Moderate to severe transient side effects occurred in three cases.

• Considerable improvements of PANS global symptoms and impairment were seen on the PANS Scale, CGI-S, CGI-I, and improved OCD symptoms on the CY-BOCS scale, lasting at least one month after the third IVIG treatment (at Visit 3).
• All children had improved at Visit 1 (one month after the first IVIG treatment).
• At Visit 3 – 8 of 10 children had lasting improvements, but 2 showed symptom rebounds
  • 1 patient had good but transient responses lasting only 2–3 weeks after each IVIG, followed by deteriorations
  • One had a concurrent viral infection at Visit 3.
• At baseline the severe symptoms had considerable impact on the children’s school attendance
  • Marked improvements in attendance were seen post-treatment
  • School absence during 3 months before baseline was 47% of the school days/month, compared to 13% after the third IVIG treatment.
• The main side effects were of a previously well-known type, i.e. transient headache, neck pain, nausea/vomiting (mild to severe), stomach pain, mild transient anemia, and brief allergic reaction.

Hutanu A, Reddy L N, Mathew J, et al. (August 06, 2022) Pediatric Autoimmune Neuropsychiatric Disorders Associated With Group A Streptococci: Etiopathology and Diagnostic Challenges. Cureus 14(8): e27729. doi:10.7759/cureus.27729

O’Dor, S.L., Zagaroli, J., Belisle, R. et al. The COVID-19 pandemic and children with PANS/PANDAS: an evaluation of symptom severity, telehealth, and vaccination hesitancy. Child Psychiatry Hum Dev (2022). https://doi.org/10.1007/s10578-022-01401-z

• Assessed the impact of the COVID-19 pandemic on children with PANS/PANDAS
• A majority of respondents endorsed a negative impact on their child’s friendships, relationships with extended family, hobbies, and academic skills due to the pandemic
• Children with suspected or diagnosed COVID-19 experienced new or worsened psychiatric symptoms, particularly mood lability, OCD, and anxiety
• Telehealth care was the preferred treatment modality if the child had mild symptoms of PANS/PANDAS
• Caregivers experienced a high level of burn-out both before and during the pandemic, and thus this should continue to be an area of inquiry and appropriate intervention by providers
• Data suggest an overall negative impact of the COVID-19 pandemic on children with PANS/PANDAS and their caregivers.