Classification
PANDAS is hypothesized to be an autoimmune disorder that results in a variable combination of tics, obsessions, compulsions, and other symptoms that may be severe enough to qualify for diagnoses such as chronic tic disorder, OCD, and Tourette syndrome (TS or TD). The cause is thought to be akin to that of Sydenham's chorea, which is known to result from childhood Group A streptococcal (GAS) infection leading to the autoimmune disorder acute rheumatic fever of which Sydenham's is one manifestation. Like Sydenham's, PANDAS is thought to involve autoimmunity to the brain's basal ganglia. Unlike Sydenham's, PANDAS is not associated with other manifestations of acute rheumatic fever, such as inflammation of the heart. Pichechero notes that PANDAS has not been validated as a disease classification, for several reasons. Its proposed age of onset and clinical features reflect a particular group of patients chosen for research studies, with no systematic studies of the possible relationship of GAS to other neurologic symptoms. There is controversy over whether its symptom of choreiform movements is distinct from the similar movements of Sydenham's. It is not known whether the pattern of abrupt onset is specific to PANDAS. Finally, there is controversy over whether there is a temporal relationship between GAS infections and PANDAS symptoms.
To establish that a disorder is an autoimmune disorder, Witebsky criteria requires that there be (1) a self-reactive antibody, (2) that a particular target for the antibody is identified (autoantigen) (3) that the disorder can be caused in animals and (4) that transferring antibodies from one animal to another triggers the disorder (passive transfer). In addition, to show that a microorganism causes the disorder, the Koch postulates would require one show that the organism is present in all cases of the disorder, that the organism can be extracted from those with the disorder and be cultured, that transferring the organism into healthy subjects causes the disorder, and the organism can be reisolated from the infected party. Giovanonni notes that the Koch postulates cannot be used in the case of post-infection disorders (such as PANDAS and SC) because the organism may no longer be present when symptoms emerge, multiple organisms may cause the symptoms, and that the symptoms may be a rare reaction to a common pathogen.
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