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Brain-Immune Alterations and Mitochondrial Dysfunctions in a Mouse Model of Paediatric Autoimmune Disorder Associated with Streptococcus: Exacerbation by Chronic Psychosocial Stress

Ajmone-Cat MA, Spinello C, Valenti D, Franchi F, Macrì S, Vacca RA, Laviola G. Journal of Clinical Medicine. 2019; 8(10):1514. DOI: 10.3390/jcm8101514

  • Adverse psychosocial experiences have been shown to modulate individual responses to immune challenges and affect mitochondrial functions.
  • Results show chronic psychosocial stress altered the expression of neuroinflammatory markers in the hippocampal and hypothalamic regions, exacerbated the neuroinflammatory alterations induced by experimental GAS exposures in the same areas.
  • Psychosocial stress exacerbated individual response to GAS administrations whereby mice exposed to both treatments exhibited altered cytokine and immune-related enzyme expression in the hippocampus and hypothalamus.
  • Showed impaired mitochondrial respiratory chain complexes IV and V, and reduced adenosine triphosphate (ATP) production by mitochondria and ATP content.
  • These brain abnormalities, observed in GAS-Stress mice, were associated with blunted titers of plasma corticosterone.
  • Present data support the hypothesis that challenging environmental conditions, in terms of chronic psychosocial stress, may exacerbate the long-term consequences of exposure to GAS processes through the promotion of central immunomodulatory and oxidative stress.
Eye movement desensitisation and reprocessing (EMDR) treatment associated with parent management training (PMT) for the acute symptoms in a patient with PANDAS syndrome: a case report
Guido CA, Zicari AM, Duse M, Spalice A. Eye movement desensitisation and reprocessing (EMDR) treatment associated with parent management training (PMT) for the acute symptoms in a patient with PANDAS syndrome: a case report. Ital J Pediatr. 2019 Jun 26;45(1):74. doi: 10.1186/s13052-019-0667-1. PMID: 31242942; PMCID: PMC6595549.
Conclusions: Following eight sessions of EMDR, preceded by training sessions with the parents, the child showed a significant reduction in symptoms and disappearance of the exacerbation. These results indicate the possibility of improving the treatment outcomes of patients with PANDAS by a combined approach using both antibiotic and EMDR therapies.
Family Quality of Life When Raising a Child with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS)
Barbara B. Demchick, Julia Ehler, Shelly Marramar, Alison Mills & Amanda Nuneviller (2019) Family Quality of Life When Raising a Child with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS), Journal of Occupational Therapy, Schools, & Early Intervention, 12:2, 182-199, DOI: 10.1080/19411243.2019.1592052

“PANDAS is characterized by rapid onset of Obsessive Compulsive Disorder and/or tics following streptococcal infection in a previously healthy child. PANDAS is frequently misdiagnosed and misunderstood, which affects family quality of life (FQOL). A qualitative phenomenological design was used to examine FQOL in six families with a child with PANDAS. Data were collected through an audiotaped semi-structured interview and a phone interview to confirm findings. After rigorous data analysis, five themes emerged: Life Suddenly Turned Upside Down, My Child is Not Crazy, Emotional Distress within the Family, Major Life Alteration, and School Drastically Influences FQOL. Findings suggest that occupational performance and FQOL are severely restricted when a child has PANDAS. Implications for occupational therapy are discussed.”

PANDAS and anorexia nervosa-a spotters’ guide: Suggestions for medical assessment
Vincenzi B, O’Toole J, Lask B. PANDAS and anorexia nervosa–a spotters’ guide: suggestions for medical assessment. Eur Eat Disord Rev. 2010 Mar;18(2):116-23. doi: 10.1002/erv.977. PMID: 20148396.
Conclusion: Given the current state of knowledge, diagnosingPANDAS is extraordinarily difficult. However, extrapolating from knowledge aboutSydenham’s choreaandPANDAS–OCD and PANDAS–tics/TS, a heightened index of suspicion for the existence of an auto-immune reaction in the brain response to environmental infectious agents culminating in ‘anorexia nervosa’ should be maintained.
The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness
Hornig M. The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness. Curr Opin Rheumatol. 2013 Jul;25(4):488-795. doi: 10.1097/BOR.0b013e32836208de. PMID: 23656715.

Summary: Microbes, both pathogenic and commensal, can induce autoantibodies that bind to brain and affect behavior in susceptible hosts. Interventions that correct the microbial balance or diminish autoantibody binding may be effective in diverse neuropsychiatric conditions mediated by autoimmunity.

Immune-mediated animal models of Tourette syndrome
Hornig M, Lipkin WI. Immune-mediated animal models of Tourette syndrome. Neurosci Biobehav Rev. 2013 Jul;37(6):1120-38. doi: 10.1016/j.neubiorev.2013.01.007.
“Demonstration of the ability to recreate these abnormalities through passive transfer of serum IgG from GAS-immunized mice into naïve mice and abrogation of this activity through depletion of IgG has provided compelling evidence in support of the autoimmune hypothesis. Immunologically-based animal models of TS are a potent tool for dissecting the pathogenesis of this serious neuropsychiatric syndrome.”
Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection
Yaddanapudi K, Hornig M, Serge R, De Miranda J, Baghban A, Villar G, Lipkin WI. Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Mol Psychiatry. 2010 Jul;15(7):712-26. doi: 10.1038/mp.2009.77.
Executive and Attention Functioning Among Children in the PANDAS Subgroup
Matthew E. Hirschtritt, Christopher J. Hammond, David Luckenbaugh, Jason Buhle, Audrey E. Thurm, B. J. Casey & Susan E. Swedo (2009) Executive and Attention Functioning Among Children in the PANDAS Subgroup, Child Neuropsychology, 15:2, 179-194, DOI: 10.1080/09297040802186899

Evidence from past studies indicates that adults and children with Obsessive-Compulsive Disorder (OCD) and Tourette syndrome (TS) experience subtle neuropsychological deficits. Less is known about neuropsychological functioning of children and adolescents with a symptom course consistent with the PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection) subgroup of OCD and tics. T

  • Administered three tests of attention control and two of executive function to 67 children and adolescents (ages 5–16) diagnosed with OCD and/or tics and a symptom course consistent with the PANDAS subgroup and 98 healthy volunteers (HV) matched by age, sex, and IQ.
  • The PANDAS subjects were less accurate than HV in a test of response suppression.
  • In a two-step linear regression analysis of the PANDAS group in which clinical variables were added stepwise into the model and in the second step matching variables (age, sex, and IQ) were added, IQ emerged as a predictor of performance on this task.
  • ADHD diagnosis and age emerged as predictors of response time in a continuous performance task.
  • Subdividing the PANDAS group by primary psychiatric diagnosis revealed that subjects with TS or OCD with tics exhibited a longer response time compared to controls than subjects with OCD only
  • Children with PANDAS exhibit neuropsychological profiles similar to those of their primary psychiatric diagnosis.