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PANDAS is an acronym for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections, a hypothetical disease in which a subset of children are thought to exhibit a rapid onset of obsessive-compulsive disorder (OCD) or tic disorders symptoms following group A beta-hemolytic streptococcal (GABHS) infections. The proposed link between infection and these disorders is that an initial autoimmune reaction to a GABHS infection gives rise to the body's production of autoantibodies directed against the basal ganglia cells. It has been proposed that this autoimmune response can result in a broad range of neuropsychiatric symptoms.

The PANDAS hypothesis was based on observations in clinical case studies at the US National Institute of Health and in subsequent clinical trials where children appeared to have dramatic and sudden OCD exacerbations and tic disorders following infections. There is supportive evidence for the link between streptococcus infection and onset in some cases of OCD and tics, but proof of causality has remained elusive. The PANDAS hypothesis is controversial; whether it is a distinct entity differing from other cases of Tourette syndrome (TS)/OCD is debated.

PANDAS has not been validated as a disease entity; it is not listed as a diagnosis by the International Statistical Classification of Diseases and Related Health Problems (ICD) or the Diagnostic and Statistical Manual of Mental Disorders (DSM). Pediatric acute-onset neuropsychiatric syndrome (PANS) is a 2012 proposal describing another subset of acute-onset OCD cases including "not only disorders potentially associated with a preceding infection, but also acute-onset neuropsychiatric disorders without an apparent environmental precipitant or immune dysfunction".

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 require (1) that there be 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.

Characteristics

In addition to an OCD or tic disorder diagnosis, children may have other symptoms associated with exacerbations such as emotional lability, enuresis, anxiety, and deterioration in handwriting. In the PANDAS model, this abrupt onset is thought to be preceded by a strep throat infection. As the clinical spectrum of PANDAS appears to resemble that of Tourette's syndrome, some researchers hypothesized that PANDAS and Tourette's may be associated; this idea is controversial and a focus for current research.

Proposed mechanism

The PANDAS diagnosis and the hypothesis that symptoms in this subgroup of patients are caused by infection are controversial.

Whether the group of patients diagnosed with PANDAS have developed tics and OCD through a different mechanism (pathophysiology) than seen in other people diagnosed with Tourette syndrome is unclear. Researchers are pursuing the hypothesis that the mechanism is similar to that of rheumatic fever, an autoimmune disorder triggered by streptococcal infections, where antibodies attack the brain and cause neuropsychiatric conditions.

The molecular mimicry hypothesis is a proposed mechanism for PANDAS: this hypothesis is that antigens on the cell wall of the streptococcal bacteria are similar in some way to the proteins of the heart valve, joints, or brain. Because the antibodies set off an immune reaction which damages those tissues, the child with rheumatic fever can get heart disease (especially mitral valve regurgitation), arthritis, and/or abnormal movements known as Sydenham's chorea or "St. Vitus' Dance". In a typical bacterial infection, the body produces antibodies against the invading bacteria, and the antibodies help eliminate the bacteria from the body. In some rheumatic fever patients, autoantibodies may attack heart tissue, leading to carditis, or cross-react with joints, leading to arthritis. In PANDAS, it is believed that tics and OCD are produced in a similar manner. One part of the brain that may be affected in PANDAS is the basal ganglia, which is believed to be responsible for movement and behavior. It is thought that similar to Sydenham's chorea, the antibodies cross-react with neuronal brain tissue in the basal ganglia to cause the tics and OCD that characterize PANDAS. Studies neither disprove nor support this hypothesis: the strongest supportive evidence comes from a controlled study of 144 children (Mell et al, 2005), but prospective longitudinal studies have not produced conclusive results.

Diagnosis

According to Lombroso and Scahill, 2008, "(f)ive diagnostic criteria were proposed for PANDAS: (1) the presence of a tic disorder and/or OCD consistent with DSM-IV; (2) prepubertal onset of neuropsychiatric symptoms; (3) a history of a sudden onset of symptoms and/or an episodic course with abrupt symptom exacerbation interspersed with periods of partial or complete remission; (4) evidence of a temporal association between onset or exacerbation of symptoms and a prior streptococcal infection; and (5) adventitious movements (e.g., motoric hyperactivity and choreiform movements) during symptom exacerbation". The children, originally described by Swedo et al in 1998, usually have dramatic, "overnight" onset of symptoms, including motor or vocal tics, obsessions, and/or compulsions. Some studies have supported acute exacerbations associated with streptococcal infections among clinically defined PANDAS subjects (Murphy and Pichichero, 2002; Giulino et al, 2002); others have not (Luo et al, 2004; Perrin et al, 2004).

Concerns have been raised that PANDAS may be overdiagnosed, as a significant number of patients diagnosed with PANDAS by community physicians did not meet the criteria when examined by specialists, suggesting that the PANDAS diagnosis is conferred by community physicians without conclusive evidence.

Treatment

Treatment for children suspected of PANDAS is generally the same as the standard treatments for TS and OCD. These include cognitive behavioral therapy and medications to treat OCD such as selective serotonin reuptake inhibitors (SSRIs); and "conventional therapy for tics".

A controlled study (Garvey, Perlmutter, et al, 1999) of prophylactic antibiotic treatment of 37 children found that penicillin V did not prevent GABHS infections or exacerbation of other symptoms; however, compliance was an issue in this study. A later study (Snider, Lougee, et al, 2005) found that penicillin and azithromycin decreased infections and symptom exacerbation. The sample size, controls, and methodology of that study were criticized. Murphy, Kurlan and Leckman (2010) say, "The use of prophylactic antibiotics to treat PANDAS has become widespread in the community, although the evidence supporting their use is equivocal. The safety and efficacy of antibiotic therapy for patients meeting the PANDAS criteria needs to be determined in carefully designed trials"; de Oliveira and Pelajo (2009) say that because most studies to date have "methodologic issues, including small sample size, retrospective reports of the baseline year, and lack of an adequate placebo arm ... it is recommended to treat these patients only with conventional therapy".

There is insufficient evidence to determine if tonsillectomy is effective.

Experimental treatments

Prophylactic antibiotic treatments for tics and OCD are experimental and controversial; overdiagnosis of PANDAS may have led to overuse of antibiotics to treat tics or OCD in the absence of active infection.

A single study of PANDAS patients showed efficacy of immunomodulatory therapy (intravenous immunoglobulin (IVIG) or plasma exchange) to symptoms, but these results are unreplicated by independent studies as of 2010. Kalra and Swedo wrote in 2009, "Because IVIG and plasma exchange both carry a substantial risk of adverse effects, use of these modalities should be reserved for children with particularly severe symptoms and a clear-cut PANDAS presentation. The US National Institutes of Health and American Academy of Neurology 2011 guidelines say there is "inadequate data to determine the efficacy of plasmapheresis in the treatment of acute OCD and tic symptoms in the setting of PANDAS" and "insufficient evidence to support or refute the use of plasmapheresis in the treatment of acute OCD and tic symptoms in the setting of PANDAS", adding that the investigators in the only study of plasmapherisis were not blinded to the results. The Medical Advisory Board of the Tourette Syndrome Association said in 2006 that experimental treatments based on the autoimmune theory such as IVIG or plasma exchange should not be undertaken outside of formal clinical trials. The American Heart Association's 2009 guidelines state that, as PANDAS is an unproven hypothesis and well-controlled studies are not yet available, they do "not recommend routine laboratory testing for GAS to diagnose, long-term antistreptococcal prophylaxis to prevent, or immunoregulatory therapy (e.g., intravenous immunoglobulin, plasma exchange) to treat exacerbations of this disorder".

pandas were discovered On October 20,2014 in Idaho, Garden valley

See also

• Neurobiological brain disorder

References

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2. ^ de Oliveira SK, Pelajo CF (March 2010). "Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS): a Controversial Diagnosis". Curr Infect Dis Rep. 12 (2): 103–9. doi:10.1007/s11908-010-0082-7. PMID 21308506.
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External links

• National Institute of Mental Health
• International OCD Foundation
• International PANDAS Foundation
• PANDAS Resource Network
• A Feverish Debate by Alison Motluk at The Walrus

• Childhood psychiatric disorders
• Neurological disorders