这PANDAS Hypothesis and Causes of OCD

它可能听起来不可能是喉咙喉咙可能是一个原因obsessive-compulsive disorder。然而,第一次大规模的研究h coming out of Denmark seems to support this causal relationship.

背景

Bacteria are responsible for between 5 and 10 percent of sore throats. The most common bacterial agent responsible for sore throat is group A beta-hemolytic streptococci (GAS or “strep”).

In 1998, researchers at the National Institute of Mental Health (NIHM) observed that some children abruptly develop obsessive-compulsive disorder,tics, and other neuropsychiatric symptoms after being infected with GAS and other types of bacteria and viruses. These symptoms are rapid onset, and peak in intensity within 24 to 48 hours.

Usually, OCD begins more gradually. Furthermore, the initial presentation of OCD can be hidden for months by a child secondary to anxiety or embarrassment about irrational worries and behaviors.

在开始，NIMH选择将其初步的研究努力集中在链球菌感染与喉咙痛之间的关联。他们提出了一个题为与链球菌感染相关的儿科自身免疫性神经精神病学疾病的工作假想或PANDAS。

这PANDAS假设是有争议的，多年来，对它的支持有限，因为所有研究都在检查链球菌感染，OCD和TICS之间的关系涉及少数参与者。

However, in a May 2017 issue ofJAMA Psychiatry, Orlovska and co-authors detail a large study examining the link between GAS—as well as other types of infection—andOCD and tics。这y looked at the records of more than one million Danish children spanning 17 years.

PANDAS Diagnosis

没有实验室测试诊断熊猫。相反，熊猫的诊断基于详细的历史和体格检查。

Here are the five criteria used to diagnose PANDAS:

1. OCD，TIC疾病或两者的存在。
2. 这explosion in the onset of OCD, tics, or both that occurs abruptly and can wax and wane following subsequent streptococcal infections. Subsequent exacerbations similarly present with dramatic symptoms.
3. Onset between 3 years and 11 years (the beginning of puberty). (This criterion is arbitrary, and adolescents can rarely be diagnosed with PANDAS.)
4. 与突然发作的症状突然发作，暗示其他神经精神疾病，包括浓度困难，一般焦虑，床润湿，烦躁和发育回归。
5. 通过咽喉培养或血液试验（即，抗气体抗体滴度升高），需要建立与链球菌感染的时间相关性。

Sydenham chorea, which also results in rapid, involuntary movements resembling tics, must also be ruled out to diagnose PANDAS. Like PANDAS, Sydenham chorea and, more generally, rheumatic fever have autoimmune underpinnings and occur secondary to streptococcal infection.

熊猫怎么发生？

遗传学，发展和免疫力有助于大熊猫的发展：

• First, certain children seem susceptible to PANDAS, and these children may share genetic similarities with those who experience rheumatic fever and Sydenham chorea.
• 其次，Pandas本质上是发展的，因为它通常会影响尚未经历过青春期的儿童，峰值年龄为6或7。
• 第三，与Syndenham Chorea一样，那些有熊猫的人被假设，以开发攻击脑中神经细胞的抗体。

When GABS mimic the appearance of brain cells, antibodies to brain tissue are thought to form. These antibodies end up attacking the basal ganglia, and instead of causing Sydenham chorea, result in OCD, tics, and so forth.

平底锅诊断

Because it is often hard to pinpoint an exact temporal relationship between strep infection and OCD or tics, in 2010, clinicians and researchers expanded the classification of PANDAS so that it falls under the umbrella of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS).

Instead of explicitly tying diagnosis to only streptococcal infection, PANS is more generally described by the abrupt onset of OCD and can be associated with nonstreptococcal infection, too, including influenza and varicella (chicken pox). Specifically, here are the diagnostic criteria for PANS:

1. 突然和戏剧性onset of OCD
2. 两种额外的神经精神症状的同时存在与在熊猫中看到的症状相似
3. 症状不能更好地通过另一种神经系统或运动障碍解释，例如Sydenham Chorea，Lupus或Tourette障碍

Notably, by formulating the PANS diagnosis, these clinicians and researchers hope to facilitate the diagnosis and treatment of abrupt-onset OCD.

这relationship between PANDAS and PANS is analogous to the relationship between melanoma and cancer. In other words, just like melanoma is a subset of cancer, PANDAS is a subset of PANS. Of note, a diagnosis of PANS is also based on a detailed history and physical exam.

New Research

Orlovska and colleagues examined Danish patient records spanning 17 (1996 to 2013) years and representing 1,067,743 children (defined as fewer than 18 years old). This study is by far the highest-powered analysis of the PANDAS hypothesis to date, and results support fundamental elements of this hypothesis.

Here is a more specific breakdown of the patient records:

• 519,821 girls
• 547,922个男孩
• 638,265名儿童接受了一种链球菌测试
• 349,982 had at least one positive streptococcal test

More specifically, children with a positive strep test had an 18 percent higher risk of developing any mental disorder, a 51 percent higher risk of developing OCD, and a 35 percent higher risk of developing tic disorders.

研究人员还发现,孩子nonstreptococcal throat infection (i.e., negative streptococcal test) also were at increased risk for mental disorders, OCD, and tic disorders. However, the magnitude of this risk was lower than that for streptococcal infection.

这researchers found that, as defined by PANDAS criteria, children between age 3 and 11 had the greatest increased risk of OCD and tic disorders.

According to the researchers, the results of the study support the PANDAS hypothesis to some extent. With regards to nonstreptococcal infection, they write the following:

"Our findings that the risk of mental disorders is only slightly less elevated after a nonstreptococcal throat infection than after a streptococcal infection suggest that other, possibly viral, infectious agents are also linked with the development of OCD and tic disorders. This finding might instead support the recently proposed concept of pediatric acute-onset neuropsychiatric syndrome … Pediatric acute-onset neuropsychiatric syndrome offers an alternative to PANDAS with wider diagnostic criteria; it is primarily thought to be a postinfectious condition but without restriction to streptococcal infections."

PANDAS Treatment and Prevention

As described inFogin和Cherry的儿科疾病教科书：

"This proposed disorder [PANDAS] is currently a hypothesis, and it remains a controversial topic. Several authors believe in this disorder as a separate entity and recommend treatment and prophylaxis. Others argue that it is only a hypothesis and that further evidence withdouble-blind studiesis needed before recommending treatment and prevention for children given a diagnosis of PANDAS."

建议书

Of note, the尼姆does recommend certain treatment options for those who are thought to have the condition:

与熊猫相关的强迫症状的儿童将受益于认知行为治疗（CBT）和/或抗痴迷药物。研究表明，最佳结果是由CBT和SSRI药物的组合产生的（例如氟西汀，氟虫胺，肉甲腺嘌呤或帕罗西汀）。熊猫的孩子似乎对SSRIS和其他药物的副作用异常敏感，因此重要的是“从低头开始慢慢！”使用这些药物时。

经过starting children on low dosages of psychotropic medications, the number and severity of negative side effects are minimized. If a child ends up experiencing negative side effects while on medication, the dosage should be decreased immediately. Of note, psychotropic medications should not be stopped abruptly because doing so could be dangerous.

Antibiotics

这尼姆stresses that if the strep infection is still present, the best treatment for PANDAS is antibiotics, including amoxicillin, penicillin, azithromycin, and cephalosporins. With positive throat cultures, a single course of antibiotics should be sufficient. Other measures include replacing toothbrushes and testing family members for strep to limit the risk of re-infection.

基于免疫的疗法，包括血浆交换（即浆术）和静脉内免疫球蛋白，也被用来有效地治疗与熊猫有关的症状。

Steroids

Steroids have also been used to treat PANDAS. However, the results of steroid treatment are mixed, with only some reports of benefit and other reports of worsening tics. Furthermore, steroids should be used only for a short period of time because they can be dangerous when used long-term. Finally, patients with PANDAS who receive steroids can experience a rebound effect which results in PANDAS symptoms that are even worse than when the steroids were started. For these reasons, steroids are usually not recommended for treatment in children who have PANDAS.

注意，有时用类固醇的简要治疗可以帮助临床医生衡量，患者对血浆交换和静脉注射免疫球蛋白。

在相关说明，前面的治疗指导主要适用于Pandas而不是平底锅，因为PAN是一种更新的诊断，没有测试治疗。尽管如此，如果似乎通过传染性药剂触发平底锅，感染的治疗可能会衰减symptoms of OCDand other neuropsychiatric symptoms. Additionally, treatments that work for PANDAS, such as immune-based therapies, as well as preventive strategies, may also be useful when treating symptoms related to PANS.

In two small clinical trials, prophylactic treatment with antibiotics—or treatment before the occurrence of streptococcal throat infection and PANDAS symptoms—proved effective in preventing strep infections and reducing recurrences of PANDAS symptoms.

Analogously, treatment with prophylactic antibiotics has proven useful with other streptococcal sequelae that have autoimmune origins, such as rheumatic fever and Sydenham chorea thus providing further support for this intervention.