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Sabine Hazan, MD, Sheldon Jordan, MD. SARS-CoV-2 as a Trigger in the Development of Tourette’s-Like Symptoms: A Case Report, 15 November 2021, PREPRINT (Version 1) available at Research Square DOI: 10.21203/rs.3.rs-1079406/v1  This case study has not been peer-reviewed.

• Case report describe Tourette’s-like symptoms resulting from SARS-CoV-2 disrupting gut microbiota
• SARS-CoV-2 could cause significant havoc in the enteric flora, damaging intestinal barrier, disrupting communication along the GMBA, imparing immune function, leading to neuropsychiatric symptoms
• Several possible therapeutic approaches change the microbiome including prebiotics, postbiotics, synbiotics, and fecal transplantation
• Using these therapies to modulate bacterial composition and enhance microbiota diversity is a pragmatic approach for enhanced protection against the acute morbidities associated with viral illnesses including COVID-19.

Tang, A. W., Appel, H. J., Bennett, S. C., Forsyth, L. H., Glasser, S. K., Jarka, M. A., Kory, P. D., Malik, A. N., Martonoffy, A. I., Wahlin, L. K., Williams, T. T., Woodin, N. A., Woodin, L. C., Miller, I. K. T., & Miller, L. G. (2021). Treatment barriers in PANS/PANDAS: Observations from eleven health care provider families. Families, Systems, & Health. Advance online publication. DOI: 10.1037/fsh0000602

Despite published diagnostic and treatment guidelines for this condition, there are long delays in obtaining appropriate care. We sought to identify health care system barriers to timely treatment by examining cases of PANDAS/PANS occurring in children of health care professionals.

• Parents included 11 physicians, 2 mental health professionals, 2 nurses, and a PharmD.
  Nine cases (82%) had “very delayed” diagnosis and treatment (>4 weeks after onset).
• The most commonly encountered causes for treatment delay were clinician lack of awareness (82%), clinician skepticism (82%), overdependence on diagnostic testing (91%), and out-of-pocket expenses >$100 US (82%).
• Other common challenges included difficulties finding a provider to spearhead care (64%), psychological misdiagnosis (55%), and children’s suppression of behaviors during assessments (55%).

J Schnell, M Bond, N Moll, E Weidinger, B Burger, R Bond, A Dietrich, PJ. Hoekstra, A Schrag, D Martino, M Schwarz, U-X Meier, N Müller. Brain, Behavior, and Immunity. Vol 99, 2022. DOI: 10.1016/j.bbi.2021.10.012

• M. pneumoniae IgG positivity was not associated with the presence of CTD.
• M. pneumoniae IgG positivity was not associated with the first onset of tics.
• M. pneumoniae IgG positivity was significantly associated with higher tic severity.

“It is possible that M. pneumoniae infection influences tic severity in CTD or, that having more severe tics, increases the risk of infection. However, it is more likely that the association observed in this study reflects a propensity toward enhanced immune responses in people with CTD and that, rather than a causal relationship, infection and greater tic severity are indirectly linked via shared underlying immune mechanisms.”

Sizgoric MK, Kovac Sizgoric M, Miculinic A, et al. Clinical manifestations of patients with PANDAS in patients followed up at Srebrnjak children’s hospital in 5-year period. Archives of Disease in Childhood 2021;106:A169. Article

Clinical:
– 20 children, 16 (80%) male, 4 (20%) female, aged 3 to 11 years (median age 6.5)
-Elevated levels of antistreptolysin titers 19 of 20 (95%). Anti-DNAse-B levels were tested in 7 patients and was elevated in 4 (57%)
-Neuroimaging studies (N=12 or 60%) – no specific findings found
-Family history of tics and autoimmune disorders was positive in N=5
(25%)

Symptoms:
-All patients had OCD and tics with acute onset of symptoms
-Attention disorders N=17 (85%)
-Sleeping difficulties N=4 (20%)
-Speech difficulties N=5 (25%)
-Decline in school performance N=10 (71%)

Treatment:
-15 (75%) patients given first-line antibiotics. In 5 (25%) patients a full regression of symptoms was registered, 10 (50%) had partial improvement, 5 (25%) had no response.
-7 (35%) were given IVIG after initial antibiotic treatment with incomplete regression. Tics persisted in 11 patients and 4 had tics with behavioral difficulties. In 7 patients treated with IVIG we proceeded with parenteral antibiotics because of partial symptom regression and 2 were given corticosteroids (still followed).

A Krouse, H Li, JA Krenzer, WN Rose. Plasmapheresis, Rituximab, and Ceftriaxone Provided Lasting Improvement for a 27-Year-Old Adult Male with PANDAS. Dept of Pathology, University of Wisconsin Hospital. Article

• At 17 – developed sudden psychosis and confusion after GAS infection. Had elevated anti-streptolysin O (ASO) titers. Did not present with typical symptoms of PANDAS – OCD and/or tic-like symptoms were not observed. A tentative diagnosis of PANDAS was given. Treated with antipsychotics, antibiotics, tonsillectomy, and IVIG which resulted in remissions and relapses of his neuropsychiatric symptoms.
• At age 27 – received a trial of therapeutic plasma exchange (TPE), rituximab, and ceftriaxone. Eventually resulted in sustained benefit and minimal fluctuations of his clinical symptoms.

de Oliveira, K.C., Camilo, C., Gastaldi, V.D. et al. Brain areas involved with obsessive-compulsive disorder present different DNA methylation modulation. BMC Genom Data 22, 45 (2021). DOI:10.1186/s12863-021-00993-0

• Confirms involvement of previously associated genes and biological processes in OCD as well as reports differences related to specific brain areas
• Findings point to a role of cellular communication, inflammatory processes and behavior mediated by DNA methylation in OCD brain tissues.
• Findings were related to the immune system, reaffirming the current literature findings about its involvement with OCD.
• Changes in DNA methylation are involved with OCD and further studies are needed to characterize alterations in different paths in each brain area.

Dolce, J.L., LaRusso, M.D. & Abadia-Barrero, C. Disruptions and Adaptations in Family Functioning: A Study of Families’ Experiences with PANS/PANDAS. J Child Fam Stud (2021). DOI:10.1007/s10826-021-02101-3

• Examined family functioning utilizing online parent forums and nine semi-structured interviews with PANS/PANDAS families.
• Unpredictability & relapsing-remitting nature of neuropsychiatric symptoms cause significant disruptions to daily life.
• Financial strain, social isolation, and lack of support from schools and medical institutions transform family functioning.
• Parents’ frequent use of trauma metaphors to describe experience diverges from literature on other chronic illnesses.