Prospective Study of 'PANDAS'

PANDAS（与链球菌相关的小儿自身免疫性神经精神疾病）的存在仍然受到质疑。 确认这种假定的强迫症（OCD）和图雷特综合征（TS）亚型与前驱A组链球菌（GAS）的关系已获得相当大的实际意义，因为其对治疗和预防干预的影响与给予精神药物（如SRI或精神抑制剂）缓解症状的标准做法完全不同。 特别是，一项显示血浆置换和静脉注射免疫球蛋白治疗在PANDAS中的疗效的研究引发了公众和专业辩论，一些父母要求为他们的孩子进行这些干预，大多数临床科学家敦促谨慎。 进一步研究的必要性是明确的，但没有一项研究能够解决围绕PANDAS的所有问题。 需要进行一系列旨在测试病原体触发的自身免疫假说的特定方面的研究。 本研究的主要具体目的是评估强迫症或TS儿童的强迫症（OC）或抽动症状的发作或加重是否与先前的GAS感染显著相关，如血清抗体滴度升高所反映的。 79名患有强迫症、TS或慢性多发性抽动症（CMT）的儿童（年龄4 - 12岁）将参加本研究，并随访约两年半，为期28个月，每月进行一次神经精神症状的临床评级和GAS感染的血清学检测（阿索和抗DNA酶B）。 这项研究将在两个机构进行，佛罗里达大学和国家精神卫生研究所，使用相同的设计和程序。 为了确定一个表现出所需的症状加重/消退模式的队列，并考虑到损耗，我们估计在5年研究期间将招募约180例患者。 将在每次访视时采集用于GAS抗体和探索性免疫学研究的血样。 如果出现咽炎的临床症状，将安排咽喉培养，如果GAS阳性，将开始适当的抗生素治疗。 这些病例（估计n = 45）可能提供关于抗生素缓解急性加重或影响OC/抽动症状过程的作用的有用信息。 在该临床GAS咽炎队列中，将比较治疗后6个月与治疗前相应时期的加重率。 拟议的纵向研究将提供有关PANDAS概念有效性的所需数据，并有助于产生可靠的操作标准，以识别有气体触发OC或抽动症状风险的病例。 这些结果将有助于确定在某些亚型的儿童强迫症或TS中是否需要进行抗菌干预。

The existence of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) continues to be questioned. Confirmation of a relationship of this putative subtype of obsessive compulsive disorder (OCD) and Tourette's Syndrome (TS) to an antecedent Group A Streptococcal (GAS) has gained considerable practical importance because of implications for treatment and prevention interventions that are radically different from the standard practice of administering psychotropics (such as SRIs or neuroleptics) for symptomatic relief. In particular, a study showing the efficacy of plasmapheresis and intravenous immunoglobulin treatment in PANDAS has stimulated public and professional debate, with some parents demanding these interventions for their children and most clinician-scientists urging caution. The need for further research is clear, but no one study will address all the questions surrounding PANDAS. A series of studies designed to test specific aspects of the pathogen-triggered autoimmune hypothesis will be required. The primary specific aim of the present study is to evaluate whether episodes or exacerbations in obsessive-compulsive (OC) or tic symptoms in children with OCD or TS are significantly associated with antecedent GAS infection, as reflected in elevated serum antibody titers. Seventy-nine children (ages 4 to 12 years) with OCD, TS, or Chronic Multiple Tic Disorder (CMT) will participate in this study and be followed for approximately two and a half years, a 28-month period, at monthly intervals for clinical ratings of neuropsychiatric symptoms and serological testing for GAS infection (ASO and AntiDNAse B). The study will be conducted at two institutions, the University of Florida and the National Institute of Mental Health, using identical designs and procedures. In order to identify a cohort that exhibits the desired pattern of exacerbation/regression of symptoms and to allow for attrition, we estimate that approximately 180 patients will have to be enrolled over the five-year study. Blood samples will be obtained at each visit for GAS antibodies and for exploratory immunologic studies. Should clinical signs of pharyngitis develop, throat cultures will be ordered and, if positive for GAS, appropriate antibiotic treatment will be instituted. These cases, estimated at n = 45, may provide useful information on the effect of antibiotics to attenuate exacerbations or influence OC/tic symptom course. In this cohort with clinical GAS pharyngitis, the rate of exacerbations for the 6-months following treatment will be compared to the corresponding period prior to treatment. The proposed longitudinal study will furnish needed data on the validity of the PANDAS concept and help generate reliable operational criteria for identifying cases at risk of GAS-triggered OC or tic symptoms. The results will help determine if antimicrobial interventions are warranted in certain subtypes of pediatric OCD or TS.