Posts by:
Gabriella True

The Dysfunctional Mechanisms Throwing Tics: Structural and Functional Changes in Tourette Syndrome
Lamanna J, Ferro M, Spadini S, Racchetti G, Malgaroli A. The Dysfunctional Mechanisms Throwing Tics: Structural and Functional Changes in Tourette Syndrome. Behav Sci (Basel). 2023 Aug 10;13(8):668. doi: 10.3390/bs13080668. PMID: 37622808; PMCID: PMC10451670.
“TS etiology is very complex, with strong genetic influences, repeated streptococcal infections, and also pre and perinatal phenomena [13]. There is accumulating evidence that immune dysregulation contributes to the pathophysiology of OCD, TS, and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). TS patients may, in fact, have a predisposition to autoimmune responses or impaired general immunity; recently, beta-hemolytic streptococcal infections and/or an increase in anti-basal ganglia antibodies have been found in patients with TS. “
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and pediatric acute-onset neuropsychiatric syndrome.
Hoppin, K. M., & Doran, P. R. (2023). Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and pediatric acute-onset neuropsychiatric syndrome. In M. M. Perfect, C. A. Riccio, & M. A. Bray (Eds.), Health-related disorders in children and adolescents: A guidebook for educators and service providers (pp. 185–193). American Psychological Association. https://doi.org/10.1037/0000349-022

In the mid-1990s, researchers at the National Institute of Mental Health identified a link between recent streptococcal infection and the development of neuropsychiatric symptoms such as separation anxiety, tics, behavioral regression, rage, restricted eating, and obsessive–compulsive disorder. Research has found that in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS), exposure to an infection or other agent that activates the immune system creates an immune response that goes awry, causing autoantibodies (or immune cells) to attack brain cells instead. PANDAS and PANS are complex neurological disorders, and their medical impact is significant. Educators should be aware that PANDAS and PANS may have a significant impact on a student’s attendance. This chapter discusses etiology, prevalence and incidence, symptoms, and outcomes of PANDAS and PANS. It presents the psychoeducational implications and school-based interventions organized by medical management, cognitive/academic functioning, and social–emotional and behavioral functioning. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

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Pediatric de novo movement disorders and ataxia in the context of SARS-CoV-2

Wilpert, NM., de Almeida Marcelino, A.L., Knierim, E. et al. Pediatric de novo movement disorders and ataxia in the context of SARS-CoV-2. J Neurol 270, 4593–4607 (2023). https://doi.org/10.1007/s00415-023-11853-5

Our data suggest that children with de novo movement disorders, and cerebellar inflammation can benefit from immune-modulating therapy, especially methylprednisolone, despite negative results in clinical investigations.

Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation

Salvucci F, Codella R, Coppola A, et al. Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation. Front Cardiovasc Med. 2023;10:1202696. doi:10.3389/fcvm.2023.1202696.

Mast cell activation in Long COVID (related work)

  • Observational study evaluating Long COVID patients treated with H1/H2 antihistamines.

  • Reports improvement in fatigue, cognitive symptoms, tachycardia, and other systemic complaints.

  • Supports the hypothesis that mast cell activation contributes to Long COVID symptom persistence.

  • Suggests immune dysregulation—rather than viral persistence—may drive ongoing symptoms in a subset of patients.

PANDAS – a rare but severe disorder associated with streptococcal infections; Awareness is needed, Acta Oto-Laryngologica Case Reports,
Karin Frånlund & Charbél Talani (2023) PANDAS – a rare but severe disorder associated with streptococcal infections; Awareness is needed, Acta Oto-Laryngologica Case Reports, 8:1, 104-107, DOI: 10.1080/23772484.2023.2231146
“We present a case of PANDAS with the aim of raising awareness of its diagnosis. PANDAS is a rare condition with an impact on the patient’s quality of life; thus, awareness is needed. A multidisciplinary team is needed for diagnosis and treatment. Otorhinolaryngologists may play an important role in the well-being of these patients when performing tonsillectomy.”
Autoantibodies in patients with obsessive-compulsive disorder: a systematic review
Denzel D, Runge K, Feige B, Pankratz B, Pitsch K, Schlump A, Nickel K, Voderholzer U, Tebartz van Elst L, Domschke K, Schiele MA, Endres D. Autoantibodies in patients with obsessive-compulsive disorder: a systematic review. Transl Psychiatry. 2023 Jul 3;13(1):241. doi: 10.1038/s41398-023-02545-9. PMID: 37400462; PMCID: PMC10318087.

Emerging evidence suggests that biological components, especially autoimmune processes, may be associated with some cases of OCD and treatment resistance. Therefore, this systematic literature review summarizing all case reports/case series as well as uncontrolled and controlled cross-sectional studies investigating autoantibodies in patients with OCD and obsessive-compulsive symptoms (OCS) was performed. In summary, the available case reports suggest an association between OCD and autoantibodies in rare cases, which has been supported by initial cross-sectional studies. However, scientific data is still very limited. Thus, further studies on autoantibodies investigated in patients with OCD compared with healthy controls are needed.

  • Nine case reports with autoantibody-associated OCD/OCS were identified: five patients with anti-neuronal autoantibodies (against N-methyl-D-aspartate-receptor [NMDA-R], collapsin response mediator protein [CV2], paraneoplastic antigen Ma2 [Ma2], voltage gated potassium channel complex [VGKC], and “anti-brain” structures) and four with autoantibodies associated with systemic autoimmune diseases (two with Sjögren syndrome
  • one with neuropsychiatric lupus
  • one with anti-phospholipid autoantibodies).
  • Six patients (67%) benefited from immunotherapy.
  • In addition, eleven cross-sectional studies (six with healthy controls, three with neurological/psychiatric patient controls, and two uncontrolled) were identified with inconsistent results, but in six studies an association between autoantibodies and OCD was suggested.
Evaluation of C4 gene copy number in Pediatric Acute Neuropsychiatric Syndrome

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 ED, Levinson DF, Urban AE, Frankovich J. Evaluation of C4 gene copy number in Pediatric Acute Neuropsychiatric Syndrome. Dev Neurosci. 2023 Jun 28. doi: 10.1159/000531707. Epub ahead of print. PMID: 37379808.

Pediatric acute-onset neuropsychiatric syndrome (PANS) is an abrupt-onset neuropsychiatric disorder. PANS patients have an increased prevalence of comorbid 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) were used to assess whether the time to juvenile idiopathic arthritis (JIA) or autoimmune disease (AI) onset was a function of total C4A or C4B CN. 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.

Cortical glutamate and GABA are related to compulsive behaviour in individuals with obsessive compulsive disorder and healthy controls

Biria, M., Banca, P., Healy, M.P. et al. Cortical glutamate and GABA are related to compulsive behaviour in individuals with obsessive compulsive disorder and healthy controls. Nat Commun 14, 3324 (2023). https://doi.org/10.1038/s41467-023-38695-z

A Cambridge neuroimaging study found that compulsive behavior is associated with glutamate–GABA imbalance, particularly elevated glutamate, across both individuals with OCD and healthy controls. Using ultra–high field MRS, the authors show that compulsivity maps to excitatory–inhibitory imbalance in brain regions involved in habit formation and control. These findings support a mechanism-based view of compulsive symptoms, while underscoring the need for caution when targeting glutamatergic systems clinically due to their broader downstream effects. The findings are particularly relevant given increasing clinical interest in glutamate-modulating medications, which are sometimes used off-label in OCD and neuroimmune conditions. At the same time, the study reinforces the need for caution: altering glutamatergic systems can have complex downstream effects, especially in conditions where dopamine and immune signaling may also be involved. This work strengthens the rationale for mechanism-focused research while underscoring why individualized, carefully monitored treatment remains essential.