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Tourette

An investigational drug that blocks the dopamine-1 (D1) receptor reduces tics and is safe and well tolerated in children with Tourette syndrome (TS), a new study shows.

Importantly, unlike current medications for the disorder, ecocipam does not lead to weight gain, anxiety, depression, or tardive dyskinesia compared to placebo ― a factor that may lead to better adherence.

Neuroinflammation in a Rat Model of Tourette Syndrome, Zhongling Ke, Yanhui Chen, Guofeng Chen, Yanyan Liu, Neuroinflammation in a Rat Model of Tourette Syndrome, Frontiers in Behavioral Neuroscience, Vol 16, Front. Behav. Neurosci., 10 March 2022, DOI: 10.3389/fnbeh.2022.710116   

Conclusion: The IDPN-induced TS rats had significant neuroinflammation in the brain, and the interaction between dopamine (DA) dysregulation and immune dysfunction may play a vital role in the pathogenic mechanisms of TS.

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November 2021, PREPRINT (Version 1) available at Research Square DOI: 10.21203/rs.3.rs-1079406/v1  This case study has not been peer-reviewed.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.

Ueda K, Black KJ. Recent progress on Tourette syndrome. Fac Rev. 2021;10:70. Published 2021 Sep 7. DOI:10.12703/r/10-70

“Recent years have seen increasing information about the relationship between tics and comorbidities and about new genetic findings. Inflammatory processes have also been a topic of continued interest.

“The prevalence and characteristics of tics in patients with encephalitis were reviewed in a systematic study, which found that sporadic cases of tics were associated with encephalitis, particularly during a post-encephalitis period, and with basal ganglia involvement⁵⁴. A case-control autopsy study (of nine individuals with TS) using basal ganglia transcriptome by RNA sequencing in the caudate and putamen found disrupted basal ganglia neuronal signaling⁵⁵. The study also found a significant increase in immune and inflammatory transcripts. These results suggest metabolic alterations and inflammatory involvement in TS pathophysiology.”

“Inflammation has been extensively discussed in tic pathophysiology. A recent review article on immunological mechanisms in the pathophysiology of tic disorders argues that innate and adaptive systemic immune pathways and neuroinflammatory mechanisms play an important role in the pathogenesis of at least some patients with TS⁵³.”

“Complementary and alternative medicines—including dietary or nutritional supplements (calcium, magnesium, coenzyme Q₁₀, fish oil, gastrodin, and vitamins B, C, D, and E), chiropractic manipulations, meditation, acupuncture, hypnosis, homeopathy, and biofeedback—have been reported for the treatment of tics^116,117; however, the evidence is limited because of a lack of randomized control studies. The efficacy and safety of a Chinese herbal medicine (5-Ling granule) in the treatment of TS were evaluated in a multicenter, double-blind randomized controlled trial, finding it as effective as tiapride in improving tic symptoms¹¹⁸.”

Mechanisms by which microglial abnormalities contribute to disease are likely to be shared across distinct etiologies and traditional diagnoses. For instance, abnormal synaptic pruning was observed both in animals inoculated with GAS (which may capture key elements of the pathophysiology of PANDAS) and in mice that develop excessive grooming after inactivation of the progranulin gene. In both cases, increased synaptic pruning cooccurs with microglia activation.

A review of clinical observations and literature reports leads to the hypothesis that, via a process analogous to Sydenham’s chorea, infections with group A β-hemolytic streptococci, among others, may trigger autoimmune responses that cause or exacerbate some cases of childhood-onset obsessive-compulsive disorder (OCD) or tic disorders (including Tourette’s syndrome).