Prospective Study of 'PANDAS'

PANDAS（与链球菌相关的儿童自身免疫性神经精神疾病）的存在仍然受到质疑。证实这种假定的强迫症（OCD）和图雷特综合症（TS）亚型与先前的a群链球菌（GAS）之间的关系具有相当大的实际意义，因为它对治疗和预防干预的影响与使用精神药物（如SRIs或抗精神病药）来缓解症状的标准做法截然不同。特别是，一项显示血浆置换和静脉注射免疫球蛋白治疗PANDAS疗效的研究引起了公众和专业人士的争论，一些家长要求对他们的孩子进行这些干预，而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。需要进行一系列的研究，以测试病原体触发的自身免疫假说的特定方面。本研究的主要目的是评估强迫症或TS儿童的强迫症发作或加重或抽动症状是否与先前的GAS感染显著相关，这反映在血清抗体滴度升高中。79名患有强迫症、TS或慢性多发性抽动障碍（CMT）的儿童（年龄4 - 12岁）将参加本研究，随访约两年半（28个月），每隔一个月进行一次神经精神症状的临床评分和GAS感染（ASO和AntiDNAse B）的血清学检测。这项研究将在佛罗里达大学（University of Florida）和美国国家心理健康研究所（National Institute of Mental Health）这两家机构进行，采用相同的设计和程序。为了确定一个表现出预期症状加重/消退模式的队列，并考虑到损耗，我们估计在为期五年的研究中，大约需要入组180名患者。每次就诊时将采集血液样本进行GAS抗体检测和探索性免疫学研究。如果出现咽炎的临床症状，将要求进行喉咙培养，如果气体检测呈阳性，将进行适当的抗生素治疗。这些病例，估计n = 45，可能提供有用的信息，抗生素的作用，以减轻恶化或影响OC/tic症状的过程。在这个患有临床GAS咽炎的队列中，治疗后6个月的恶化率将与治疗前的相应时期进行比较。拟议的纵向研究将为PANDAS概念的有效性提供所需的数据，并有助于制定可靠的操作标准，以识别有气体引发的OC或抽动症状风险的病例。结果将有助于确定抗菌干预是否有必要在某些亚型的儿科强迫症或TS。

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.