Antineuronal antibodies have been implicated in tic and obsessive compulsive disorders (OCD) associated with group A streptococcal infections. cells. Youth and young adults with chronic tics Etomoxir and OCD may have underlying infectious/immunologic etiology. Introduction In the last few decades there has been a growing interest in the association of infections autoimmunity and behavioral changes and their impact on the genesis of neuropsychiatric disorders (Murphy et al. 2012). In 1998 a link between obsessive-compulsive disorder (OCD) and group A streptococcal infections was identified by Swedo at the National Institute for Mental Health (NIMH) (Swedo et al. 1998). These disorders may be identified as pediatric autoimmune neuropsychiatric disorder associated with streptococci (PANDAS) (Swedo et al. 1998) or pediatric acute-onset neuropsychiatric syndrome (PANS) in the presence of other causes including infections (Swedo et al. 2012). This discovery was a result of two parallel studies conducted at the NIMH including investigation of children Etomoxir with OCD and tics and investigation of children with Sydenham chorea (SC) the major neurological manifestation of acute rheumatic fever (ARF) which presents with involuntary movements and neuropsychiatric disturbances including obsessive-compulsive symptoms hyperactivity and emotional lability (Marques-Dias et al. 1997). Swedo and coworkers identified a cohort of patients who experienced a sudden acute onset of obsessions and compulsions that followed a relapsing-remitting symptom course. Five diagnostic criteria emerged from careful observation of these patients: 1) Presence of OCD (by IV criteria) or a tic disorder 2 symptom onset between 3 years of age and puberty 3 episodic course of illness with abrupt and substantial symptom exacerbations 4 symptom onset and exacerbations associated temporally with group A streptococcal infections and 5) presence of neurological abnormalities including choreiform movements during symptom exacerbations (Swedo et al. 1998). Murphy also describes neurological symptoms in acute onset OCD/tic patients including severe hyperactivity loss of fine motor skills (handwriting deterioration) or adventitious movements such as choreiform Rabbit Polyclonal to FZD1. movements (Murphy et al. 2012). Psychiatric symptoms as described by Murphy et al. included irritability frequent mood changes separation anxiety hyperactivity late-onset attention problems personality change oppositional behaviors sleep disturbances and deterioration in mathematical skills. Although Etomoxir streptococcal infections have been closely associated with a Etomoxir PANDAS onset there is debate in the literature whether group A streptococcal infections are coincidental or causal. Historical accounts from the first 50 cases of PANDAS indicate that at least some cases of PANDAS occurred immediately following or during a group A streptococcal infection (Swedo et al. 1998). Whether PANDAS is a variant of ARF is still debated (Kurlan et al. 2008). Although there is still discussion as to the exact mechanism of PANDAS current PANDAS criteria cite that a history of RF is exclusionary for a PANDAS diagnosis. However controversy does exist among some neurologists regarding the validity of PANDAS as a subset of OCD/tics versus its being a of RF (SC). In SC neuropsychiatric Etomoxir symptoms predate choreoathetoid movements. PANDAS is described as including choreiform piano-playing movements of the fingers and toes (Swedo et al. 1998). Since the initial identification of the PANDAS subgroup it has been proposed that the disorder may develop as a result of postinfectious autoimmune processes (Swedo et al. 1998; Kirvan et al. 2006b). We hypothesize that antistreptococcal antibodies produced in response to group A streptococcal infection cross-react with neuronal targets of susceptible hosts through the process of molecular mimicry (Kirvan et al. 2003). We suggest that the pathogenesis of PANDAS could be similar to that of SC which was delineated by studying human monoclonal antibodies (mAbs) derived from an SC patient. Three human mAbs reacted with the surface of neuronal cells and demonstrated antibody cross-reactivity Etomoxir with the group A carbohydrate epitope 4th ed. (DSM IV) diagnosis of a tic disorder Tourette syndrome OCD or attention-deficit/hyperactivity disorder (ADHD); and had ASO titers.