Evaluation and Treatment of Obsessive Compulsive and Related Disorders

强迫症（OCD）影响1-2%的儿童和青少年，从无情的强迫思想和强迫行为中造成显着的痛苦和损害。 一个独特的亚组的儿童强迫症已被确定的基础上，他们的症状发作的敏锐性。 该队列由首字母缩略词PANS确定，即儿科急性发作神经精神综合征。 该综合征的特征在于强迫症和/或进食障碍的突然发作，伴有以下七种共病中的至少两种：1）焦虑; 2）情绪不稳定和/或抑郁; 3）易怒、攻击和/或严重对立行为; 4）行为不稳定和/或焦虑; 5）情绪不稳定和/或焦虑; 6）情绪不稳定和/或焦虑; 7）情绪不稳定和/或焦虑; 8）情绪不稳定和/或焦虑; 9）情绪不稳定和/或焦虑; 10）情绪不稳定和/或焦虑。（发育）退化; 5）学校表现恶化; 6）感觉或运动异常; 7）躯体体征和症状，包括睡眠障碍、遗尿或尿频等。 有关完整描述，请参见：Swedo SE，Leckman JF，Rose NR。 从研究亚组到临床综合征：修改PANDAS标准以描述PANS（儿科急性发作性神经精神综合征）。 Pediatr Therapeut 2012，2：2 http://dx.doi.org/10.4172/2161-0665.1000113 PANS的临床描述来自于对一组急性发作强迫症儿童的研究，这些儿童的症状似乎是由于常见的儿童感染引起的，包括A组链球菌（GAS）感染（“链球菌性咽喉炎”和猩红热）。在GAS感染后症状开始或恶化的儿童可能属于由首字母缩略词PANDAS（与链球菌感染相关的儿童自身免疫性神经精神疾病）确定的神经精神疾病亚组。PANDAS亚组的假定病因是A组链球菌（GAS）的特定菌株在遗传易感个体中引起交叉反应性抗体的产生，这些抗体不仅识别GAS细胞壁上的抗原，而且识别宿主脑组织中的抗原，引起强迫症、强迫症、抽搐和其他神经精神症状。 交叉反应性抗体已被证明与其他抗链球菌抗体相关，也与神经精神症状的严重程度相关，在患有Sydenham舞蹈病或PANDAS舞蹈病的儿童中观察到最高滴度。 美国国立卫生研究院和其他地方的研究表明：PANDAS亚组有一个特定的和可识别的症状过程（最显著的特征是症状的急性、突然、过夜发作（“在不到24小时内从0到60”）;交叉反应性抗体与GABHS感染状态和神经精神症状严重程度相关;交叉反应性抗体的被动转移在动物模型中复制疾病症状;通过抗生素预防来预防GABHS感染可预防神经精神症状恶化;并且，用免疫调节疗法特别是静脉内免疫球蛋白（IVIG）或血浆除去法治疗急性病儿童可显著降低症状严重程度。 这一系列研究是不寻常的，因为它扭转了典型的“从实验室到床边”的进展，并将临床观察和经验带入实验室，以寻找有关病因机制的信息。 结果令人兴奋，因为交叉反应性抗体鉴定了CNS中的抗原靶点，这可能为治疗干预提供新的靶点。 博士Swedo博士、耶鲁大学儿童研究中心的James Leckman博士及其同事，以及俄克拉荷马州大学健康科学中心的Madeleine Cunningham博士共同获得了NIH“从实验室到临床”奖，该奖资助了一项针对PANDAS重症儿童的静脉注射免疫球蛋白（IVIG）的多中心安慰剂对照试验（方案11-M-0058，NCT 01281969）超过40名儿童（3-12岁）将入组试验，35名随机分配接受IVIG或安慰剂输注。 参与者的长期随访正在进行中，但可获得基线、6周、3个月和6个月评估的数据。 双盲和开放标签的结果正在进行分析，以评估强迫症和相关症状的严重程度，整体功能和不良反应的变化。 除了提供关于IVIG治疗PANDAS的效用的信息外，该试验还提供了由坎宁安博士、凯尔威廉姆斯博士分析的生物样本。（MGH-Harvard），Mady Hornig博士（哥伦比亚大学）和卡洛斯帕尔多博士（约翰霍普金斯），目的是进一步阐明交叉反应性抗体的病理作用，以及潜在地开发疾病活动和治疗反应的生物标志物。 有关该研究的更多信息，请访问：http://clinicalstudies.info.nih.gov/cgi/detail.cgi? B_2011-M-0058.html

Obsessive-compulsive disorder (OCD) affects 1-2% of children and adolescents, causing significant distress and impairments from the unrelenting obsessional thoughts and compulsive behaviors. A unique subgroup of children with OCD has been identified on the basis of the acuity of their symptom onset. The cohort is identified by the acronym PANS, for Pediatric Acute-onset Neuropsychiatric Syndrome. The syndrome is characterized by the foudroyant onset of OCD and/or eating disorder, accompanied by at least two of the following seven comorbidities: 1) Anxiety; 2) Emotional lability and/or depression; 3) Irritability, aggression and/or severely oppositional behaviors; 4) Behavioral (developmental) regression; 5) Deterioration in school performance; 6) Sensory or motor abnormalities; 7) Somatic signs and symptoms, including sleep disturbances, enuresis or urinary frequency and others. For full description, see: Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). Pediatr Therapeut 2012, 2:2 http://dx.doi.org/10.4172/2161-0665.1000113 The clinical description of PANS arose from investigations of a group of children with acute-onset OCD whose symptoms appeared to arise as a consequence of common childhood infections, including Group A streptococcal (GAS) infections ("strep throat" and Scarlet fever). Children whose symptoms begin or exacerbate following GAS infections may belong to a subgroup of neuropsychiatric disorders identified by the acronym PANDAS (for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). The postulated etiology for the PANDAS subgroup is that specific strains of Group A streptococci (GAS), in genetically susceptible individuals, elicit the production of cross-reactive antibodies which recognize antigens not only on the GAS cell wall, but also in the host brain tissue, eliciting obsessions, compulsions, tics and other neuropsychiatric symptoms. The cross-reactive antibodies have been shown to correlate with other anti-streptococcal antibodies and also with neuropsychiatric symptom severity, with highest titers seen in children acutely ill with Sydenham chorea or PANDAS symptomatology. Research at NIH and elsewhere has revealed that: the PANDAS subgroup has a specific and identifiable symptom course (marked most notably by the acute, abrupt, overnight onset of symptoms ("zero to sixty in less than 24 hours"); the cross-reactive antibodies correlate with both GABHS infection status and neuropsychiatric symptom severity; passive transfer of the cross-reactive antibodies replicated disease symptoms in animal models; prevention of GABHS infections through antibiotic prophylaxis results in prevention of neuropsychiatric symptom exacerbations; and, treatment of acutely ill children with immunomodulatory therapies specifically, intravenous immunoglobulin (IVIG) or plasmapheresis may produce dramatic reductions in symptom severity. This line of research is unusual, in that it reversed the typical "bench to bedside" progression and took clinical observations and experiences into the laboratory in search of information about etiopathogenic mechanisms. The results proved exciting, as the cross-reactive antibodies identified antigenic targets in the CNS which might provide new targets for therapeutic interventions. Dr. Swedo, Dr. James Leckman and colleagues at the Yale University Child Study Center, and Dr. Madeleine Cunningham of the University of Oklahoma Health Sciences Center were the joint recipients of an NIH "Bench to Bedside" award which helped fund a multi-site placebo-controlled trial of intravenous immunoglobulin (IVIG) for severely ill children with PANDAS (Protocol 11-M-0058, NCT 01281969) More than 40 children (3-12 yrs old) will be enrolled in the trial and 35 were randomly assigned to receive an infusion of IVIG or placebo. Long-term follow-up of the participants is ongoing, but data are available from baseline, 6 weeks, 3 months and 6 months evaluations. The double-blind and open-label results are being analyzed to evaluate changes in severity of OCD and related symptoms, overall functioning and adverse effects. In addition to providing information about the utility of IVIG treatment for PANDAS, the trial provided biological samples to be analyzed by Dr. Cunningham, Dr. Kyle Williams (MGH-Harvard), Dr. Mady Hornig (Columbia University) and Dr. Carlos Pardo (Johns Hopkins), with the goal of further delineating the pathologic role of the cross-reactive antibodies, as well as potentially developing biomarkers for disease activity and treatment response. More information about the study is available at: http://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2011-M-0058.html