Diseases › Pediatric autoimmune neuropsychiatric syndromes (PANS or PANDAS) Pediatric autoimmune neuropsychiatric syndromes (PANS or PANDAS) Suspicion of auto-antibodies as underlying cause of sudden neuropsychiatric symptoms in children and adolescents. The test package focuses on the auto-immune part of the symptoms and if the symptoms can be correlated to auto-antibodies. The test package gives no results related to if the symptoms are correlated to underlying infections. Indication Autoantibodies have been associated with OCD (obsessive compulsive disorder), ticks, Tourettes syndrome, Sydenham Chorea, PANS (Pediatric Acute-onset Neuropsychiatric syndrome), and PANDAS “Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection.” PANDAS has been described as presenting with an acute onset of obsessive-compulsive disorder (OCD) and/or motor tics in children with a recent streptococcal infection. PANS also includes other causes than the PANDAS syndrome. Symptoms include neurological symptoms that may be presented as ticks, dyskinesia, hyperactivity, obsessions and compulsions. Clinical Background In the 1990-ies, Dr. Swedo had been studying Sydenham Chorea where 70% of patients exhibit sudden onset OCD symptoms before or after this classic movement disorder. Dr. Swedo and other researchers were finding children who had sudden onset OCD symptoms without the carditis (heart inflammation) or movement disorder normally characteristic of Sydenham Chorea and acute rheumatic fever. PANDAS was defined in 1998 by Dr. Sue Swedo. Auto-antibodies were observed in the carditis of Acute Rheumatic Fever, and Dr. Swedo theorized that perhaps a related set of antibodies were mistakenly attacking the basal ganglia (part of the brain) rather than the intended streptococcal bacteria due to molecular mimicry. Auto-antibodies against antigens in the basal-ganglia would trigger the movement disorder/sudden onset of OCD. In July 2010, researchers met at the NIH to discuss the past decade of clinical findings. Of significance, the panel found that while strep throat seems to be a trigger, it may not be the only trigger. Sudden onset OCD could be triggered by other diseases, including Lyme, Mono, Mycoplasma and the flu virus (such as H1N1). Based on this and other clinical reports, the panel modified the research definition of PANDAS to PANS. One of the researchers Madeleine Cunningham developed a panel of tests called the Cunningham test panel which can be used as an aid in the diagnosis of PANS. The test package includes antibody induced CaM kinase II activity concentration (Calcium / calmodulin-dependent protein kinase, CaM KII) and auto-antibodies against lyso GM1 (lyso-ganglioside GM1 antibody), Dopamine R1 (D1A dopamine receptor antibody), Dopamine R2 (D2 dopamine receptor antibody) and beta tubulin (Tubulin beta-chain antibody). These diagnostic tests have been shown to be correlated with disease activity in Sydenhams Choera, OCD (obsessive compulsive disorder), Tourettes syndrome, PANS and PANDAS. Samples collected early after symptom outbreak may be negative. After serum-conversion, it is possible to monitor the disease progression with new tests as the symptoms often show relapse and remission patterns. It is hypothesized that recurring infections may trigger the increase of auto-antibodies and relapse of disease symptoms. The test panel only tests for auto-antibodies and cannot show if the symptoms and auto-antibodies are directly related to an infection. Currently only serum is analyzed. The time to test result on this test panel is approximately 8 weeks. Interpretation of test results The five tests that are included in the test package consist of four tests for auto-antibodies against Beta-Tubulin, Dopamine receptor 1, Dopamine receptor 2 and Lyso-GM1. The fifth test is an analysis that tests whether the patient serum can induce increased signaling activation in neuronal cells. Increased CaM KII activity indicates that factors in the serum may cause an increased stimulation of receptors on nerve cells compared to normal serum. Publications have shown that increased stimulation of CaM KII activity is associated to auto-antibodies in serum directed against structures on neurons. Dr. Cunninghams research group has published that when antibodies are removed from serum, the activity of the nerve cells returns to normal. The ELISA tests for auto-antibodies that are included in the test package (Dopamine D1 receptor, Dopamine D2L Receptor, Lysoganglioside-GM1 and Beta-Tubulin) can be negative even though the CaM KII activity is increased. This may be due to various reasons. One reason could be that yet unknown auto-antibodies can cause increased stimulation of the nerve cells. Another reason may be that other unknown factors can induce an increased stimulation of the nerve cells. Research is ongoing to find further autoantibodies (or other factors) that can be associated with neuropsychiatric symptoms and induce increased stimulation of neurons. When the CaM KII activity is confirmed by a positive auto-antibody test, this gives a high probability that the symptoms are related to autoimmunity and are associated with PANS / PANDAS. Similar to other autoimmune diseases related to autoantibodies the symptoms and autoantibodies may be treated with immune modifying therapies. Immune therapy when only CaM kinase II activity is positive may be effective in some patients. The reference values have been calculated on the results of serum for 20 healthy children and are given as mean + 2 SD. Remember that the test package gives no results related to if the symptoms are correlated to underlying infections.
Posted on: Tue, 20 Jan 2015 04:40:33 +0000
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