What is the role of streptococcal infections in the etiology of Tourette syndrome (TS) and other tic disorders?

Updated: May 30, 2019
  • Author: William C Robertson, Jr, MD; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP  more...
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In the late 1800s and early 1900s, chorea was widely assumed to be usually due to rheumatic fever. The link of chorea to prior streptococcal illness first was proven in the 1950s. The delay occurred partly because in many cases chorea does not follow streptococcal recurrence until several months afterward, and it often occurs without coeval arthritis, carditis, or serologic abnormality.

In the 1970s, patients with Sydenham chorea were demonstrated to have high levels of antibodies that react to human brain. These antibodies have since been shown to cross-react to certain proteins on group A beta-hemolytic streptococci (GABHS). [113]

Although tics and chorea can be differentiated clinically, the definitions were less clear in the 19th century. For instance, Charcot and Gilles de la Tourette distinguished tics and chorea primarily on grounds of course and presumed cause rather than phenomenology.

In recent years, interest has been growing in the possibility that streptococcal illness may produce not only chorea but also tics, obsessions, or compulsions. In several cases tics began suddenly after a streptococcal infection, and investigators proposed a research case definition for poststreptococcal autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). [114]

Although streptococcal infection may cause TS symptoms in a small subgroup of patients, the precise relationship between such infections, antineuronal antibodies, and TS remains unknown.

Some observations support a connection between GABHS infection and tics. [115] OCD occurs more frequently in children with Sydenham chorea than in healthy controls or those who have rheumatic fever without chorea. [116] In a large case-control study, children with OCD or a chronic tic disorder were more than twice as likely as controls to have had a documented GABHS infection in the 3 months prior to the neuropsychiatric diagnosis, and children with multiple GABHS infections in a 12-month period were 13.6 times more likely to later be diagnosed with TS. [117]

Several patients with either tics or OCD have been found to have high levels of antistreptococcal or anti-DNase antibodies. [114] This is not a nonspecific indicator of distress, since other patient populations do not have these findings. Patients with tics or OCD also have high levels of a B-cell marker (D8/17) that similarly is elevated in Sydenham chorea. [118] Finally, children with TS may have increased levels of circulating antineuronal antibodies (see the image below). [119, 120, 121, 122]

Tourette syndrome and other tic disorders. Immunol Tourette syndrome and other tic disorders. Immunologic response found in patients with Sydenham chorea is also found in patients with Tourette syndrome and obsessive-compulsive disorder. Points on the graph represent percent expression of D8/17 antigen on circulating B lymphocytes.

The results above must be tempered by several considerations. [123, 124] First, almost all humans have a GABHS infection at some time, whereas more than 95% never develop OCD or chronic tics, suggesting a substantial role for host factors.

Second, any stressor—including an acute infectious illness—can exacerbate tics. Even without a direct causal link, patients or their parents first may notice tics at a time of stress. The association of TS with immune response is not specific to GABHS (see Pathophysiology). [125]

Third, a positive laboratory result for streptococcal infection can occur without current illness. Additionally, most people with tics simply do not meet a case definition of sudden onset with infection and dramatic subsequent remission. For instance, a nationwide search for such cases for a treatment study sponsored by the National Institute of Mental Health resulted in only approximately 50 referrals. [126]

Fourth, some laboratory reports contradict the aforementioned results. [127, 128] A large study found no evidence for abnormal serum antineuronal antibodies in patients diagnosed either with PANDAS or with TS. [129]

Streptococcal involvement represents a promising lead that may result in breakthroughs in the understanding of tic pathogenesis. However, treatment based on this hypothesis is not standard care at present. A controlled study showed that, in highly selected patients, OCD can improve after intravenous immunoglobulin (IVIG) therapy. [126] However, achieving true blinding for IVIG administration is difficult, and a placebo effect cannot be excluded. Tics were not affected by treatment in the blinded condition.

Whether antibody-mediated poststreptococcal illness causes most, a few, or no cases of TS is still unknown. In the meantime, a reasonable approach in these cases is to treat acute GABHS infections or rheumatic fever with antibiotics to prevent cardiac sequelae but to avoid invasive immune therapies. A possible exception may be highly select cases of OCD that fit stringent criteria for PANDAS, which might be treated in a research protocol.

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