Mycoplasma pneumoniae infection and Tourette's syndrome
Introduction
Tourette's syndrome (TS) is characterized by childhood and adolescent onset of simple or complex motor and vocal tics including echolalia and echopraxia (American Psychiatric Association, 1994, Müller et al., 1997a). The pathophysiological mechanisms underlying the disease are still unknown. However, there is no doubt that dopaminergic neurotransmission and genetic factors play a role (Pauls and Leckman, 1996, Hebebrand et al., 1997, Müller et al., 2002) and that a functional defect in the basal ganglia is involved (Kurlan, 1992, Peterson et al., 1993).
Recent reports suggest that an infectious or postinfectious process may be an important environmental factor in the pathogenesis of at least a subgroup of TS patients. In the meantime, the PANDAS syndrome for children and adolescents (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections) (Swedo et al., 1997) has been proposed, and successful experimental immune therapies have been described (Müller et al., 1997b, Perlmutter et al., 1999), although methodological and conceptual shortcomings of the PANDAS concept are still under discussion (Hoekstra et al., 2002). Similar associations between infection, postinfectious phenomena, and tics as in children/adolescents, however, have also been observed in adult TS patients (Greenberg et al., 1998, Müller et al., 2000a, Müller et al., 2001).
Streptococci are not the only infectious agents that may play a role in TS (Riedel et al., 1998). After observing that infection with M. pneumoniae worsened the clinical symptoms of TS patients (Müller et al., 2000b), we determined antibody titers against M. pneumoniae in TS patients and compared them with those of controls. M. pneumoniae is a common cause of upper and lower respiratory tract infection (Clyde, 1993) and also affects other organ systems. M. pneumoniae is known to cause extrapulmonary affections including central nervous system (CNS) manifestations in up to 10% of infected persons. The CNS complications are often seen without preceding or associated pulmonary symptoms (Hagelskjaer and Hansen, 1993). Reports of successful cultivation and the positive PCR from CSF indicate that M. pneumoniae is able to penetrate the blood–CSF barrier. One of the most common extrapulmonary manifestations is a disorder of the central or peripheral nervous system (Pfausler et al., 2002, Socan et al., 2001). In particular, involvement of the basal ganglia has been described repeatedly, resulting in motor symptoms such as dystonia or parkinsonism (Al-Mateen et al., 1988, Saitoh et al., 1993, Kim et al., 1995, Brandel et al., 1996, Larsen and Crisp, 1996, Zambrino et al., 2000, Green and Riley, 2002).
The aim of this study was to examine whether patients with TS had higher serum antibody titers against M. pneumoniae than the comparison group.
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Patients
Twenty-nine outpatients with TS (7 females/22 males) ranging from 6 to 60 years of age (mean 21.6±13.3 years) entered the study, which was performed between August and December of 1 year. TS patients and controls came from the region of upper Bavaria and Swabia. The broad age range reflects the fact that TS starts in childhood/adolescence but often persists during adulthood.
All patients fulfilled the diagnostic criteria for TS according to DSM-IV (American Psychiatric Association, 1994). The
Results
Table 1 presents results of the different M. pneumoniae antibody tests in TS patients and controls. Eight of the TS patients showed titers of ≥1:160, and seven presented titers of 1:80. In contrast, none of the controls exhibited titers ≥1:160, and only one had titers of 1:80. The statistical analysis revealed that the number of persons showing suspected positive or positive titers estimated by the MAG assay was significantly higher in the patient group (likelihood ratio: 23,182; df=1; P
Discussion
The results of this study show significant differences in antibody tests for M. pneumoniae among patients with TS and the comparison group. Determined by the MAG assay, 59% of the TS patients but only 3% of the controls had positive or suspected positive antibody titers against M. pneumoniae. The results of the immunoblot technique demonstrated significantly more IgA-antibody positive results among TS patients than in the controls (31 vs. 3%), whereas the distributions of IgM and IgG antibody
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