Meiqian Ma

All Publications

• Post-infectious inflammation, autoimmunity, and OCD: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS), and Pediatric Acute-onset Neuropsychiatric Disorder (PANS) DEVELOPMENTAL NEUROSCIENCE Vreeland, A., Calaprice, D., Or-Geva, N., Frye, R. E., Agalliu, D., Lachman, H. M., Pittenger, C., Pallanti, S., Williams, K., Ma, M., Thienemann, M., Gagliano, A., Mellins, E., Frankovich, J. 2023

  Abstract

  Post-infectious neuroinflammation has been implicated in multiple models of acute onset obsessive-compulsive disorder (OCD) including Sydenham's chorea (SC), pediatric acute-onset neuropsychiatric syndrome (PANS), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). These conditions are associated with a range of autoantibodies which are thought to be triggered by an infections, most notably group A streptococci (GAS). Based on animal models using huma sera, these autoantibodies are thought to cross-react with neural antigens in the basal ganglia and modulate neuronal activity and behavior. As is true for many childhood neuroinflammatory diseases and rheumatological diseases, SC, PANS, and PANDAS lack clinically available, rigorous diagnostic biomarkers and randomized clinical trials. In this review article, we outline the accumulating evidence supporting the role neuroinflammation plays in these disorders. We describe work with animal models including patient-derived anti-neuronal autoantibodies, and we outline imaging studies that show alterations in the basal ganglia. In addition, we present research on metabolites, which are helpful in deciphering functional phenotypes, and on the implication of sleep in these disorders. Finally, we encourage future researchers to collaborate across medical specialties (e.g., pediatrics, psychiatry, rheumatology, immunology, and infectious disease) in order to further research on clinical syndromes presenting with neuropsychiatric manifestations.

  View details for DOI 10.1159/000534261

  View details for Web of Science ID 001076907900001

  View details for PubMedID 37742615

• Evaluation of C4 gene copy number in Pediatric Acute Neuropsychiatric Syndrome DEVELOPMENTAL NEUROSCIENCE Kalinowski, A., Tian, L., Pattni, R., Ollila, H., Khan, M., Manko, C., Silverman, M., Ma, M., Columbo, L., Farhadian, B., Swedo, S., Murphy, T., Johnson, M., Fernell, E., Gillberg, C., Thienemann, M., Mellins, E. D., Levinson, D. F., Urban, A. E., Frankovich, J. 2023

  Abstract

  Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is an abrupt-onset neuropsychiatric disorder. PANS patients have an increased prevalence of co-morbid autoimmune illness, most commonly arthritis. In addition, an estimated one-third of PANS patients present with low serum C4 protein, suggesting decreased production or increased consumption of C4 protein. To test the possibility that copy number (CN) variation contributes to risk of PANS illness, we compared mean total C4A and total C4B CN in ethnically-matched subjects from PANS DNA samples and controls (192 cases and 182 controls). Longitudinal data from the Stanford PANS cohort (n = 121) was used to assess whether the time to Juvenile Idiopathic Arthritis (JIA) or Autoimmune Disease (AI) onset was a function of total C4A or C4B. Lastly, we performed several hypothesis-generating analyses to explore the correlation between individual C4 gene variants, sex, specific genotypes and age of PANS onset. Although the mean total C4A or C4B CN did not differ in PANS compared to controls, PANS patients with low C4B CN were at increased risk for subsequent JIA diagnosis (Hazard Ratio = 27, p-value = 0004). We also observed a possible increase in risk for AI in PANS patients and a possible correlation between lower C4B and PANS age of onset. An association between rheumatoid arthritis and low C4B CN has been reported previously. However, patients with PANS develop different types of JIA: enthesitis-related arthritis, spondyloarthritis and psoriatic arthritis. This suggests that C4B plays a role that spans these arthritis types.

  View details for DOI 10.1159/000531707

  View details for Web of Science ID 001018232500001

  View details for PubMedID 37379808

• Arthritis in Children with Psychiatric Deteriorations: A Case Series DEVELOPMENTAL NEUROSCIENCE Ma, M., Sandberg, J., Farhadian, B., Silverman, M., Xie, Y., Thienemann, M., Frankovich, J. 2023: 1

  Abstract

  Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS), Sydenham chorea and other post-infectious psychiatric deteriorations are thought to be caused by inflammatory/autoimmune mechanisms, likely involving the basal ganglia based on imaging studies. Patients have a relapsing-remitting course and some develop severe refractory psychiatric disease. We found that 55/193 (28%) of consecutive patients meeting PANS criteria developed chronic arthritis and 25/121 (21%) of those with related psychiatric deteriorations developed chronic arthritis. Here we describe 7 of these patients in detail and one sibling. Many of our patients often have "dry" arthritis (no effusions found on physical exam), but subtle effusions detected by imaging and features of spondyloarthritis, enthesitis, and synovitis. Joint capsule thickening, not previously reported in children, is a common finding in the presented cases and in psoriatic arthritis in adults. Due to the severity of psychiatric symptoms in some cases, which often overshadow joint symptoms, and concomitant sensory dysregulation (making the physical exam unreliable in the absence of effusions), we rely on imaging to improve sensitivity and specificity of the arthritis classification. We also report the immunomodulatory treatments of these 7 patients (initially non-steroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs with escalation to biologic medications) and note any coincidental changes to their arthritis and psychiatric symptoms while on immunomodulation. Conclusion: Patients with overlapping psychiatric syndromes and arthritis may have a unifying cause and pose unique challenges; a multi-disciplinary team can utilize imaging to tailor and coordinate treatment for this patient population.

  View details for DOI 10.1159/000530854

  View details for Web of Science ID 001008111700001

  View details for PubMedID 37231875