The Molecular Diagnosis of streptococcal Infection in Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS) and Tourette Syndrome

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University College of London UK
Investigators Name
Giovannoni, Gavin, PhD

Sydenham’s chorea, PANDAS and a subset of patients with Tourette Syndrome (TS) have evidence of recent or preceding streptococcal infection usually in the form of pharyngitis and/or tonsillitis. These patients also commonly have antibodies that react with the area of the brain called the basal ganglia. These anti-basal ganglia antibodies, at least in the case of Sydenham’s chorea, cross react with proteins on the surface of the streptococcal bacteria. This suggests they are induced by a process of molecular mimicry in which antibodies produced appropriately in response to streptococcal infection cross-react inappropriately with the basal ganglia. Because basal ganglia dysfunction is implicated in both the neurological and psychiatric manifestations of these disorders, it has been suggested that these antibodies may actually initiate or be responsible for these disorders. Unfortunately, the majority of patients affected come to medical attention some time after their streptococcal infection. Therefore it is difficult to obtain culture streptococci from routine throat swabs. Recent microbiology data have demonstrated that streptococci are difficult to eradicate, and probably remain latent within cells of the pharynx for prolonged periods of time. This may explain why many patients with TS have persistent serological evidence of streptococcal infection despite the lack of clinical evidence of a recent infection. We hypothesized that despite negative throat cultures, patients with these disorders may have persistent colonization of the nasopharynx with strains of streptococci that cause the symptoms. This persistent colonization could be sufficient to maintain the over-production of cross-reactive antibodies and hence cause the disorder, be it Sydenham’s chorea, PANDAS or TS. In our first six months of the study we developed molecular or DNA-based assays to diagnose streptococcal colonization in patients with these disorders. Using these methods we have been able to culture streptococci from 3 out of the initial 15 patients enrolled in a longitudinal clinical study. In a fourth patient we detected molecular fingerprints of the streptococci, but did not isolate the organisms. These preliminary data suggest that molecular or PCR tests may be more sensitive than culture for detecting persistent nasopharyngeal colonization with streptococci. Also we have established a DNA database of streptococcal organisms isolated from patients. Therefore it appears that a proportion of patients with TS have asymptomatic infection or colonization of the nasopharynx with streptococci. As a direct result of our preliminary findings we have now started a large hospital based cross-sectional and smaller longitudinal study to investigate the significance of these preliminary findings. These studies are allowing us to further explore the link between streptococcal infection and TS symptoms in some patients. In conclusion, our preliminary results are exciting and support part of our initial hypothesis, i.e. a subset of patients with Sydenham’s chorea, PANDAS and TS have persistent, asymptomatic streptococcus infection of the nasopharynx. Whether the strains of streptococci from these patients differ from other strains of streptococci requires further investigation. Gavin Giovannoni, Ph.D., Institute of Neurology, University College, Queens Square, London, UK Award: $35,715 Tourette Association of America Inc. – Research Grant Award 2003-2004