Meiqian Ma

All Publications

• Cerebrospinal fluid characteristics of patients presenting for evaluation of pediatric acute-neuropsychiatric syndrome. Frontiers in behavioral neuroscience Pooni, R., Zheng, W., Ma, M., Silverman, M., Xie, Y., Farhadian, B., Thienemann, M., Mellins, E., Frankovich, J. 2024; 18: 1342486

  Abstract

  This study characterizes cerebral spinal fluid (CSF) indices including total protein, the albumin quotient, IgG index and oligoclonal bands in patients followed at a single center for pediatric acute-neuropsychiatric syndrome (PANS) and other psychiatric/behavioral deteriorations.In a retrospective chart review of 471 consecutive subjects evaluated for PANS at a single center, navigational keyword search of the electronic medical record was used to identify patients who underwent lumbar puncture (LP) as part of the evaluation of a severe or atypical psychiatric deterioration. Psychiatric symptom data was ascertained from parent questionnaires and clinical psychiatric evaluations. Inclusion criteria required that subjects presented with psychiatric deterioration at the time of first clinical visit and had a lumbar puncture completed as part of their evaluation. Subjects were categorized into three subgroups based on diagnosis: PANS (acute-onset of severe obsessive compulsive disorder (OCD) and/or eating restriction plus two other neuropsychiatric symptoms), autoimmune encephalitis (AE), and "other neuropsychiatric deterioration" (subacute onset of severe OCD, eating restriction, behavioral regression, psychosis, etc; not meeting criteria for PANS or AE).71/471 (15.0 %) of patients underwent LP. At least one CSF abnormality was seen in 29% of patients with PANS, 45% of patients with "other neuropsychiatric deterioration", and 40% of patients who met criteria for autoimmune encephalitis. The most common findings included elevated CSF protein and/or albumin quotient. Elevated IgG index and IgG oligoclonal bands were rare in all three groups.Elevation of CSF protein and albumin quotient were found in pediatric patients undergoing LP for evaluation of severe psychiatric deteriorations (PANS, AE, and other neuropsychiatric deteriorations). Further studies are warranted to investigate blood brain barrier integrity at the onset of the neuropsychiatric deterioration and explore inflammatory mechanisms.

  View details for DOI 10.3389/fnbeh.2024.1342486

  View details for PubMedID 39224487

  View details for PubMedCentralID PMC11367679

• Prevalence of Neurological Soft Signs at Presentation in Pediatric Acute-Onset Neuropsychiatric Syndrome. medRxiv : the preprint server for health sciences Zebrack, J. E., Gao, J., Verhey, B., Tian, L., Stave, C., Farhadian, B., Ma, M., Silverman, M., Xie, Y., Tran, P., Thienemann, M., Wilson, J. L., Frankovich, J. 2024

  Abstract

  Importance: Studies of brain imaging and movements during REM sleep indicate basal ganglia involvement in pediatric acute-onset neuropsychiatric syndrome (PANS). Characterizing neurological findings commonly present in patients with PANS could improve diagnostic accuracy.Objective: To determine the prevalence of neurological soft signs which may reflect basal ganglia dysfunction (NSS-BG) in youth presenting with PANS and whether clinical characteristics of PANS correlate with NSS-BG. Design, Setting, and Participants: 135 new patients who were evaluated at the Stanford Children's Immune Behavioral Health Clinic between November 1, 2014 and March 1, 2020 and met strict PANS criteria were retrospectively reviewed for study inclusion. 16 patients were excluded because they had no neurological exam within the first three visits and within three months of clinical presentation.Main Outcomes and Measures: The following NSS-BG were recorded from medical record review: 1) glabellar tap reflex, 2) tongue movements, 3) milkmaid's grip, 4) choreiform movements, 5) spooning, and 6) overflow movements. We included data from prospectively collected symptoms and impairment scales.Results: The study included 119 patients: mean age at PANS onset was 8.2 years, mean age at initial presentation was 10.4 years, 55.5% were male, and 73.9% were non-Hispanic White. At least one NSS-BG was observed in 95/119 patients (79.8%). Patients had 2.1 NSS-BG on average. Patients with 4 or more NSS-BG had higher scores of global impairment (p=0.052) and more symptoms (p=0.008) than patients with 0 NSS-BG. There was no significant difference in age at visit or reported caregiver burden. On Poisson and linear regression, the number of NSS-BG was associated with global impairment (2.857, 95% CI: 0.092-5.622, p=0.045) and the number of symptoms (1.049, 95% CI: 1.018-1.082, p=0.002), but not age or duration of PANS at presentation.Conclusions and Relevance: We found a high prevalence of NSS-BG in patients with PANS and an association between NSS-BG and disease severity that is not attributable to younger age. PANS may have a unique NSS-BG profile, suggesting that targeted neurological exams may support PANS diagnosis.Key Points: Question: Do patients with pediatric acute-onset neuropsychiatric syndrome present with neurological soft signs reflective of basal ganglia dysfunction, and are these examination findings associated with disease severity?Findings: In this cohort study of 119 patients with pediatric acute-onset neuropsychiatric syndrome, most patients presented with at least one neurological soft sign pertaining to the basal ganglia. The number of signs was associated with global impairment and the number of PANS symptoms. These findings are consistent with basal ganglia pathology in pediatric acute-onset neuropsychiatric syndrome.Meaning: Targeted neurological exams may help support the diagnosis of pediatric acute-onset neuropsychiatric syndrome.

  View details for DOI 10.1101/2024.04.26.24306193

  View details for PubMedID 38746142

• Psychometric Properties of the PANS 31-Item Symptom Rating Scale. Journal of child and adolescent psychopharmacology Bernstein, G. A., Khan, M. H., Freese, R. L., Manko, C., Silverman, M., Ahmed, S., Farhadian, B., Ma, M., Thienemann, M., Murphy, T. K., Frankovich, J. 2024

  Abstract

  Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by sudden onset of obsessive-compulsive disorder and/or eating restriction with associated neuropsychiatric symptoms from at least two of seven categories. The PANS 31-Item Symptom Rating Scale (PANS Rating Scale) was developed to identify and measure the severity of PANS symptoms. The objective of this study was to define the psychometric properties of the PANS Rating Scale. Methods: Children with PANS (N = 135) and their parents participated. Parents completed the PANS Rating Scale and other scales on Research Electronic Data Capture. The PANS Rating Scale includes 31 items that are rated on a Likert scale from 0 = none to 4 = extreme. Pearson's correlations were run between the PANS Total score and scores on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS), Modified Overt Aggression Scale (MOAS), Columbia Impairment Scale (CIS), PANS Global Impairment Score (GIS), and Children's Global Assessment Scale (CGAS). Results: Convergent validity was supported by significant correlations between the PANS Total and scores on the CY-BOCS, YGTSS, MOAS, CIS, GIS, and CGAS. The largest correlations were with measures of functional impairment: PANS Total and CIS (r = 0.81) and PANS Total and GIS (r = 0.74). Cronbach's alpha was 0.89 which demonstrates strong internal consistency of the 31 items. PANS Total score was significantly higher in children in a flare of their neuropsychiatric symptoms compared to children who were not in a flare. Conclusions: This study provides preliminary support for the PANS Rating Scale as a valid research instrument with good internal consistency. The PANS Rating Scale appears to be a useful measure for assessing children with PANS.

  View details for DOI 10.1089/cap.2023.0088

  View details for PubMedID 38536004

• Development of Autoimmune Diseases Among Children With Pediatric Acute-Onset Neuropsychiatric Syndrome JAMA network open Ma, M., Masterson, E. E., Gao, J., Karpel, H., Chan, A., Pooni, R., Sandberg, J., Rubesova, E., Farhadian, B., Willet, T., Xie, Y., Tran, P., Silverman, M., Thienemann, M., Mellins, E., Frankovich, J. 2024; 7 (7)

  View details for DOI 10.1001/jamanetworkopen.2024.21688

• PANS: MARKERS OF INFLAMMATION/AUTOIMMUNITY AT CLINICAL PRESENTATION AND EVENTUAL DEVELOPMENT OF ARTHRITIS AND OTHER AUTOIMMUNE DISEASES Ma, M., Masterson, E., Frankovich, J. ELSEVIER SCIENCE INC. 2023: S275

  View details for DOI 10.1016/j.jaac.2023.09.376

  View details for Web of Science ID 001098830401228

• 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