Strep-induced Movement Disorders: Should the Term 'PANDAS' Be Extinct?

Abstract & Commentary

By Melissa J. Nirenberg, MD, PhD, Assistant Professor, Neurology and Neuroscience, Weill Cornell Medical College. Dr. Nirenberg reports no financial relationships relevant to this field of study.

Synopsis: Anti-neuronal antibodies can be detected in Sydenham's chorea, but not in PANDAS or Tourette's syndrome.

Source: Brilot F, et al. Antibody binding to neuronal surface in Sydenham chorea, but not in PANDAS or Tourette Syndrome. Neurology 2011;76:1508-1513.

Sydenham's chorea (SC) is a female-predominant childhood-onset neurological disorder characterized by chorea, hypotonia, and psychiatric/behavioral changes such as emotional lability or obsessive-compulsive disorder (OCD). The symptoms of SC are acute or subacute in onset and occur in the setting of acute rheumatic fever. Tourette's syndrome (TS), in contrast, is a chronic, familial, male-predominant childhood-onset motor and vocal tic disorder with frequent psychiatric comorbidity (including OCD, anxiety disorders, and attention deficit-hyperactivity disorder).

SC is believed to be an autoimmune disorder, attributable to cross-reactivity between group A beta-hemolytic streptococcus (GABHS) and antigens expressed on basal ganglia neurons. Given the clinical similarities between SC and TS, it has been postulated that some cases of TS may have a similar underlying cause. The term PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection) has been used to describe cases in which tic disorders, OCD, or related neuropsychiatric disorders abruptly develop and/or markedly worsen after GABHS infection. Despite extensive study, however, a causal relationship between GABHS and TS/OCD has not been clearly demonstrated, and the existence of PANDAS remains controversial.

The goal of the current study was to test the hypothesis that IgG autoantibodies from patients with SC — but not those from patients with TS or PANDAS — would cross-react with neuronal cell surface antigens. Serum samples were obtained from subjects with SC (n = 11, 9 female), PANDAS (n = 12, 2 female), TS (n = 11, 2 female), healthy controls, and children with non-inflammatory neurological diseases. Flow cytometry (fluorescence-activated cell sorting) then was used to detect and quantitate antibody binding to neuronally differentiated SH-SY5Y cells.

The authors found that the mean IgG cell surface binding to SH-SY5Y cells was significantly higher in the SC group compared with all other groups (P < 0.001). In contrast, IgG cell surface binding in the PANDAS and TS groups was similar to that of controls. The findings confirm the autoimmune nature of SC, but show no evidence to support a similar underlying cause for TS or PANDAS.

Commentary

Despite compelling evidence in the literature that SC is autoimmune in nature and related to cross-reactivity with GABHS exposure, the putative relationship between GABHS childhood neuropsychiatric disorders remains unclear. The findings of the current study cast further doubt on the hypothesis that TS and PANDAS are caused by autoimmune cross-reactivity with GABHS.

The authors emphasize the benefits of using live cells with neuronal and dopaminergic features to examine antigens in their native conformational state. They also acknowledge a major study limitation — that the SH-SY5Y cells used in the study are from human-derived neuroblastoma cell lines, which may have different available epitopes than normal dopaminergic neurons. The sex distribution with subject groups was markedly skewed, representing a potential confounder; sample sizes also were relatively small, limiting the power of the study.

In summary, this study provides further support for the concept of SC as an autoimmune disorder due to cross-reactivity GABHS, but fails to show evidence to support a similar underlying mechanism for TS and PANDAS. The potential utility of antibiotic or autoimmune therapies in PANDAS and TS therefore remains unclear.