Prospective Study of 'PANDAS'

熊猫(与链球菌相关的儿科自身免疫性神经精神疾病)的存在继续受到质疑。确认强迫症(OCD)和多发性抽动症(TS)亚型与前驱A组链球菌(GAS)的关系具有相当重要的实际意义，因为这对治疗和预防干预措施的影响与使用精神药物(如SRIs或抗精神病药物)以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大熊猫的有效性的研究引发了公众和专业人士的辩论，一些父母要求为他们的孩子进行这些干预，大多数临床医生兼科学家敦促谨慎。进一步研究的必要性是显而易见的，但没有一项研究能解决围绕熊猫的所有问题。将需要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儿童的强迫症或抽动症状的发作或加重是否与既往GAS感染显著相关，如血清抗体滴度升高所反映的那样。79名患有强迫症、抽动障碍或慢性多发性抽动障碍(CMT)的儿童(年龄4至12岁)将参与这项研究，并每隔28个月对大约两年半的时间进行跟踪，以进行神经精神症状的临床评级和气体感染的血清学测试(ASO和AntiDNAse B)。这项研究将在佛罗里达大学和国家心理健康研究所两个机构进行，使用相同的设计和程序。为了确定表现出理想的症状恶化/消退模式的队列，并考虑到自然减员，我们估计在这项为期五年的研究中将有大约180名患者入选。每次就诊时将采集血液样本进行GAS抗体和探索性免疫学研究。如果出现咽炎的临床症状，将要求进行咽部培养，如果GAS呈阳性，将实施适当的抗生素治疗。这些病例估计为45例，可能提供有关抗生素缓解病情恶化或影响OC/TIC症状进程的有用信息。在这个有临床气性咽炎的队列中，治疗后6个月的恶化速度将与治疗前的相应时期进行比较。拟议的纵向研究将为熊猫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，以确定有可能出现气体引发的OC或抽动症状的病例。这一结果将有助于确定是否有必要对某些亚型的儿童强迫症或TS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.