Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections Research Articles

Comparison of Clinical Characteristics of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections and Childhood Obsessive-Compulsive Disorder

The objectives of this study were to identify unique clinical characteristics of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) compared with a control group of children with non-PANDAS obsessive-compulsive disorder (OCD) with respect to ancillary symptoms, types of obsessions and compulsions, symptom severity, and co-morbid DSM-IV diagnoses. Classification of PANDAS was based on review of pediatric and psychiatric records using the criteria developed by Swedo and colleagues. Children aged 6-14 with PANDAS (n = 21) and non-PANDAS OCD (n = 18) were assessed by blind independent evaluators using the PANDAS Questionnaire, Children's Yale-Brown Obsessive Compulsive Scale, Yale Global Tic Severity Scale, and Anxiety Disorders Interview Schedule for DSM-IV. PANDAS children were significantly more likely to present with separation anxiety, urinary urgency, hyperactivity, impulsivity, deterioration in handwriting, and decline in school performance during their initial episode of neuropsychiatric illness compared with children with OCD. Total tics and vocal tics were more severe in PANDAS children. Separation anxiety disorder and social phobia were more prevalent in non-PANDAS OCD children. Children with non-PANDAS OCD were significantly more likely to include others in their rituals. There were no significant differences between groups on demographics or severity of OCD. Distinguishing clinical characteristics in PANDAS, which included urinary urgency, hyperactivity, impulsivity, and deterioration in handwriting, are linked to basal ganglia functions. These clinical characteristics will aid in the differentiation of PANDAS children for research and clinical purposes and ultimately advance our understanding and treatment of this disorder.

STREPTOCOCCAL INFECTION, TOURETTE SYNDROME, AND OCD: IS THERE A CONNECTION? PANDAS: HORSE OR ZEBRA?

Schrag et al.1 found “insufficient supportive evidence for a causal relationship between PANDAS and group A SI” (streptococcal infections), which led Gilbert and Kurlan2 to equate pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) to a “rare, unmarked horse” that escapes both detection and description. Neither conclusion is justified by the study design or its results, as the 5 clinical criteria that define PANDAS3 were not used to select the subjects for the investigation. Of the criteria, the sole one met was the presence of OCD or tic disorder; by contrast, unmet criteria were prepubertal onset, episodic course, association with group A streptococcal (GAS) infection, and associated neurologic abnormalities. This sample cannot provide useful information about the PANDAS cohort. Inappropriate ages and clinical presentations were included, and the 2- and 5-year intervals used were too long to allow an etiologic association. The diagnostic codes used to identify SI (see table e-1) included healthy children and individuals with diagnoses specifically known not to be GAS infections. Furthermore, GAS infections were not confirmed for any of the subjects because “too few patient records had supporting diagnostic evidence from throat swabs (n = 67) and ASO titers (n = 6).”1 This fatal flaw should have precluded further analysis, since GAS can be distinguished from other etiologies only by throat culture. In addition, interpretations and significance were based on faulty assumptions. The authors wrote, “finding increased numbers of SIs not treated with antibiotics” among the subjects with obsessive-compulsive disorder (OCD) or tics was “in the opposite direction of predicted.” An increase in untreated GAS infections is the expected result, as cross-reactive antibodies are produced only when the bacteria persist without treatment for 3–5 days or longer.4 In PANDAS, as in the model disorder Sydenham chorea (SC), prompt recognition …

A Case of PANDAS Treated With Tetrabenazine and Tonsillectomy

PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) is a rare clinical syndrome characterized by the presence of tics, Tourette syndrome, obsessive-compulsive disorder, or chorea in the context of an immediately precedent streptococcal infection. In this report, we describe the case of an 11-year-old boy who developed PANDAS with severe choreic movements. The criteria for PANDAS diagnosis were met. Moreover, serum antibrain antibodies were present. The patient was initially treated with tetrabenazine 12.5 mg twice daily with remission of the neurological symptoms. Subsequently, the patient underwent tonsillectomy and has been asymptomatic since, with antistreptolysin O titer levels in range.

Narcolepsy and Streptococcal Infections

WE READ WITH KEEN INTEREST THE PAPER BY ARAN AND COLLEAGUES READDRESSING THE ROLE OF STREPTOCOCCAL INFECTIONS IN THE ETIOLOGY OF narcolepsy.1 Prior studies have, perhaps not surprisingly, yielded mixed results for antibody testing, given the lag between infection and neurologic symptom onset for some poststreptococcal complications, such as Sydenham chorea. Antibody titer levels drop after a streptococcal infection and can be normal by the time of diagnosis. Aran and colleagues showed that the association of narcolepsy with antibody titer levels was stronger the closer that the titer levels were determined in relationship to disease onset. In a population-based case-control study of narcolepsy in King County, Washington,2 we found that 90.9% of 45 patients who were DQB1*0602 positive reported having had a strep throat infection, versus an estimated 75.9% of DQB1*0602-positive control subjects (n = 95). After adjustment for race and family income, the risk of narcolepsy in a person with a history of a physician-diagnosed strep throat before age 21 years was estimated to be 5.4-fold higher (95% confidence interval = 1.5, 19.1) than in individuals without such a history.3 In contrast, little or no association was found between narcolepsy and other childhood infectious diseases, such as mononucleosis, pneumonia, or hepatitis, or with vaccinations. These findings fit well with the observation from the same study that an increased risk of narcolepsy was associated with having lived with 2 or more household smokers before age 21 years (odds ratio =5.1; 95% confidence interval = 1.6, 12.1).4 In children, exposure to environmental tobacco smoke through passive smoking is associated with serious bacterial infections and with altered immunity.4 In addition, neurologic disorders with a hypothesized autoimmune etiology have been known to follow streptococcal infections, specifically, Sydenham chorea and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).1,3,5 Finally, people with HLA DQB1*0602 handle streptococcal infections differently than do those without HLA DQB1*0602.1,3 HLA DQB1*0602 is strongly associated with narcolepsy, and the associations mentioned previously were seen in cases and control subjects who were all positive for HLA DQB1*0602. These results support the hypothesis that genetically susceptible individuals develop narcolepsy as a complication of a streptococcal infection, which they are more likely to develop because of exposure to environmental tobacco smoke through passive smoking. The streptococcal infection may then trigger an autoimmune response with selective destruction of the hypocretin (orexin) cells in the hypothalamus. Narcolepsy ensues, with the severity reflecting the degree of hypocretin (orexin) cell loss.6 We hope that future studies will address and refine this hypothesis about narcolepsy and streptococcal infections. Such studies should involve ascertainment of HLA DQB1*0602 status in both cases and control subjects so that comparisons can be made between genetically predisposed individuals. Establishing an etiology would be the essential first step in preventing this chronic and disabling disease.

Neuropsychiatric Disorders Appear in Some Kids After Strep Infection

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessNeuropsychiatric Disorders Appear in Some Kids After Strep InfectionJun YanJun YanSearch for more papers by this authorPublished Online:7 Nov 2008https://doi.org/10.1176/pn.43.21.0018aScientists have found new evidence to support a connection between streptococcus infection and neuropsychiatric disorders in children, a study in the October Journal of the American Academy of Child and Adolescent Psychiatry reported.A connection between streptococcal infection and obsessive-compulsive disorder (OCD), Tourette syndrome (TS), and tic disorder was originally proposed by Susan Swedo, M.D., a senior investigator at the National Institute of Mental Health, and colleagues. They systematically collected a series of 50 pediatric cases and published their observations in the February 1998 American Journal of Psychiatry.Swedo and colleagues believe that there is a unique group of young patients (aged 6 to 7, on average) who develop acute, episodic neuropsychiatric symptoms following an infection with group A β-hemolytic streptococcus, possibly mediated by autoimmune response that attacks neurons in the basal ganglia. These authors termed it “pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).”Several previous studies have generated evidence to support this phenomenon, but controversies remain over the validity and pathogenesis of the PANDAS diagnosis. In the new study, Douglas Leslie, Ph.D., of the Department of Health Administration and Policy at the Medical University of South Carolina, and colleagues conducted a retrospective case-control study and found a significant association between streptococcal infection and subsequent emergence of several neuropsychiatric disorders including not only OCD, TS, and tic disorder, but also attention deficit/hyperactivity disorder (ADHD) and major depression.The authors extracted 742 cases of newly diagnosed OCD, TS, and tic disorder in children aged 4 to 13 from a national database of aggregate health care claims from 60 private insurance companies from January 1998 through December 2004.They also constructed two additional, separate cohorts of children in the same age range: those who were newly diagnosed with ADHD (n=3,650) and those newly diagnosed with major depressive disorder (n=342). Each of the three cohorts was compared with a random sample of controls matched for date of insurance enrollment, birth year, sex, and ZIP code. The size of each control group was at least five times that of the case cohort.Because ADHD is a common comorbidity for OCD, TS, and tic disorder, the cohort for ADHD and the combined cohort for OCD, TS, and tic disorder were designed to be mutually exclusive, meaning that children with diagnoses of ADHD and OCD, TS, or tic disorder were not included in either cohort.Children with newly diagnosed OCD, TS, or tic disorder were 50 percent more likely than their matched controls to have had a diagnosis of streptococcal infection in the previous year, which was statistically significant (odds ratio 1.54, 95 percent confidence interval 1.29 to 2.15). In addition, children with ADHD or depression were also significantly more likely than their controls to have had streptococcal infection in the previous year (odds ratios 1.20 and 1.63, respectively).“I was very surprised to see the significant [association] with depression,” said Leslie in an interview with Psychiatric News. He explained that the reason for extracting data on depression had originally been to get a sense of the specificity of the connection between streptococcal infection and neuropsychiatric symptoms. They had not expected to see a significant association in all three case cohorts.The pathophysiology of this possible link between pediatric neuropsychiatric disorders and streptococcal infection, which seems to affect only a subset of patients, is far from being understood. There are also no evidence-based guidelines for treatment, such as using antibiotics or immunotherapy, for children with neuropsychiatric symptoms who are suspected of having PANDAS.The study was supported in part by grants from the National Institutes of Health.An abstract of “Neuropsychiatric Disorders Associated With Streptococcal Infection: A Case Control Study Among Privately Insured Children” is posted at<www.jaacap.com/pt/re/jaacap/abstract.00004583-200810000-00011.htm>.▪ ISSUES NewArchived

The Role of Group A β-Hemolytic Streptococcal Infection in Neuropsychiatric Disorders: In Reply

We appreciate the compliments from Alvarenga et al about our recently published article on the topic of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).1 We, in turn, want to acknowledge their group for leadership in the investigation of a possible link between rheumatic fever (RF) and obsessive-compulsive disorder (OCD). In discussing a possible etiologic role of group A β-hemolytic streptococcus (GABHS) for OCD or tics, we think that it is critical to not mix information about the RF-related condition and PANDAS, because they may well be very different conditions. PANDAS has been specifically presented as a nonrheumatological entity, with patients having no history of RF and no evidence of the sequelae of RF such as cardiac valvular abnormalities.2 It is PANDAS that our study addressed.We are unable to fully disagree with the conclusion of Alvarenga et al that “GABHS may still have a major role in PANDAS,” because as we pointed out, our study was designed to examine the relationship between acute GABHS infection and exacerbations of PANDAS but not the onset of PANDAS. Our results strongly indicate that GABHS infection does not have a major role in exacerbations. The fact that our findings contradict one of the major constructs of the PANDAS hypothesis raises the possibility that GABHS has no etiologic role, but we did not investigate its possible role in onset. We noted that Perrin et al3 followed a large number of children presenting with sore throat in a community pediatrics practice and found no evidence that those whose cultures were positive for GABHS were more likely to develop tics or OCD over the next few months. These findings cast doubt on an etiologic role of GABHS in PANDAS onset.We agree that further research on the relationship between RF and development of OCD or tics is rational. However, it may not be relevant to the controversy surrounding the veracity of the PANDAS hypothesis.

Tics, OCD and Streptococcal Infection (PANDAS)

Forty matched pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) case-control pairs were prospectively evaluated clinically and with testing for group A b-hemolytic streptococcus for an average of 2 years, in a study at University of Rochester School of Medicine, New York; and WHO Streptococcal Reference Laboratory, Minneapolis, MN.

Mycoplasma pneumoniae Infection and Obsessive-Compulsive Disease: A Case Report

It has been demonstrated that obsessive-compulsive disease and/or tic syndromes in children may be triggered by an antecedent infection especially with group A beta-hemolytic streptococci, and this subgroup of children has been designated by the acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections). Other infectious agents such as viruses and bacteria have also been reported to be associated with the acute onset or dramatic exacerbation of obsessive-compulsive disease or Tourette syndrome, and another acronym, PITAND (pediatric infection-triggered autoimmune neuropsychiatric disorder) has appeared in the literature. The involvement of other infectious agents such as Mycoplasma pneumoniae has been described in single case reports. We describe a case of a 5.5-year-old boy who suddenly developed obsessive-compulsive disease symptoms during a M. pneumoniae pneumonia. After treatment with oral clarithromycin, all his obsessive-compulsive disease symptoms disappeared. To our knowledge, this is the first report that shows the association between Mycoplasma pneumoniae infection and obsessive-compulsive disease.

Spasmodic dysphonia in an adolescent patient with an autoimmune neurologic disorder

Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) has been primarily described in the neurology and psychiatry literature. The symptoms of this syndrome typically are a range of obsessive compulsive disorders and neuromuscular tics. The otolaryngologist occasionally becomes involved with these children when it is deemed that chronic tonsil infections are the source. We report here on a child diagnosed with PANDAS who presented with severe ventricular hyperfunction and adductor spasmodic dysphonia. She was treated with botulinum toxin, which resulted in a significant improvement in subjective voice as well as reduced jitter and shimmer on objective voice measurements.

Resolution of PANDAS Like Symptoms by IVIG in a Patient with Specific Antibody Deficiency against Polysaccharide Antigens

RATIONALE: PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) is a clinical entity with diagnostic criteria of prepubertal onset of symptoms, sudden onset or episodic course of symptoms, and temporal association of neuropsychiatric symptoms (tics, OCD, anxiety) with Group B Streptococcal infection. The pathogenesis of PANDAS remains controversial. We present a case of specific antibody deficiency to Str. Pneumoniae, with IgG2/IgG4 deficiency, whose clinical features include PANDAS like symptoms temporally associated with sinopulmonary infections.CASE HISTORY: 10 yo male developed neuropsychiatric symptoms (facial tic, psychogenic cough) after having Pneumonia in January, 2002, and was suspected of having PANDAS based on his clinical features and elevated ASO/anti-DNAse B Antibody titers in 2003. Despite antibiosis (Azithromycin and Amoxicillin-Clavulanate), the patient had recurrent sinopulmonary infections that correlated to the frequency and severity of behavioral symptoms.RESULTS: Conventional immune workup revealed low IgG2/IgG4 levels, suboptimal response to Pneumovax, and rapid decline of Pneumococcal Antibody titers. His peripheral blood mononuclear cells and peripheral blood derived macrophages produced low levels of proinflammatory cytokines (TNF-α, IL-6, IL1-β, and IL-12p40) in response to lipopolysaccharide, without TLR4 polymorphisms (Asp299Gly and Thr399lle). IVIG (0.6 g/kg/dose q3weeks) was started and there was nearly complete resolution of sinopulmonary infections and PANDAS like symptoms. Behavioral symptoms often reappear two to five days prior to next IVIG infusion.CONCLUSIONS: PANDAS symptoms may not be solely associated with Streptococcal infections, but could be related to other microbial infection in the presence of dysregulated inflammatory/immune responses and, in such conditions, IVIG may reveal superior therapeutic effects over antibiosis. RATIONALE: PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) is a clinical entity with diagnostic criteria of prepubertal onset of symptoms, sudden onset or episodic course of symptoms, and temporal association of neuropsychiatric symptoms (tics, OCD, anxiety) with Group B Streptococcal infection. The pathogenesis of PANDAS remains controversial. We present a case of specific antibody deficiency to Str. Pneumoniae, with IgG2/IgG4 deficiency, whose clinical features include PANDAS like symptoms temporally associated with sinopulmonary infections. CASE HISTORY: 10 yo male developed neuropsychiatric symptoms (facial tic, psychogenic cough) after having Pneumonia in January, 2002, and was suspected of having PANDAS based on his clinical features and elevated ASO/anti-DNAse B Antibody titers in 2003. Despite antibiosis (Azithromycin and Amoxicillin-Clavulanate), the patient had recurrent sinopulmonary infections that correlated to the frequency and severity of behavioral symptoms. RESULTS: Conventional immune workup revealed low IgG2/IgG4 levels, suboptimal response to Pneumovax, and rapid decline of Pneumococcal Antibody titers. His peripheral blood mononuclear cells and peripheral blood derived macrophages produced low levels of proinflammatory cytokines (TNF-α, IL-6, IL1-β, and IL-12p40) in response to lipopolysaccharide, without TLR4 polymorphisms (Asp299Gly and Thr399lle). IVIG (0.6 g/kg/dose q3weeks) was started and there was nearly complete resolution of sinopulmonary infections and PANDAS like symptoms. Behavioral symptoms often reappear two to five days prior to next IVIG infusion. CONCLUSIONS: PANDAS symptoms may not be solely associated with Streptococcal infections, but could be related to other microbial infection in the presence of dysregulated inflammatory/immune responses and, in such conditions, IVIG may reveal superior therapeutic effects over antibiosis.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections – anesthetic implications and literature review

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are rare neurobehavioral disorders in children. Affected children may have a diverse array of perioperative manifestations including compulsive behavior, agitation, and abnormal movements. Perioperative management might be more challenging for anesthesiologists. Series of therapeutic plasmapheresis in these children may complicate their anesthesia management. We describe the first case of a patient with PANDAS and its anesthesia implications.

Soluble adhesion molecules in Gilles de la Tourette's syndrome

To investigate the immune-mediated response in TS, and its relationship with streptococcal infection, we measured serum levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in patients with TS, compared to healthy and diseased controls. Soluble VCAM-1 and sE-selectin were significantly elevated in children and adults with TS, and sVCAM-1 was higher among anti-basal ganglia antibodies (ABGA)-positive adults with TS. No correlation of adhesion molecule levels to clinical severity or anti-streptococcal antibodies was observed. Children with Sydenham's chorea and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) showed an increased level of sICAM-1, but not sVCAM-1 and sE-selectin. These results provide initial evidence for a role of adhesion molecules and systemic inflammation in TS, and support the hypothesis of an ongoing immune-mediated process in this condition.

Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders

The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) describes a subgroup of children with obsessive-compulsive disorder and/or tic disorder that experience symptom exacerbations following streptococcal infections. We hypothesized that the prevention of streptococcal infections among children in the PANDAS subgroup would decrease neuropsychiatric symptom exacerbations. Twenty-three subjects with PANDAS were enrolled in a double blind, randomized controlled trial. Antibiotic prophylaxis with penicillin or azithromycin was administered for 12 months. Rates of streptococcal infections and neuropsychiatric symptom exacerbations were compared between the study year and the baseline year prior to entry. Significant decreases in streptococcal infections during the study year were found with a mean of .1 (.3 SD) per subject, compared to the baseline year with 1.9 (1.2 SD) in the penicillin group and 2.4 (1.1 SD) in the azithromycin group [p<.01]. Significant decreases in neuropsychiatric exacerbations during the study year were also found with a mean of .5 (.5 SD) per subject in the penicillin group and .8 (.6 SD) in the azithromycin group, compared to the baseline year with 2.0 (.9 SD) in the penicillin group and 1.8 (.6 SD) in the azithromycin group [p<.01]. Penicillin and azithromycin prophylaxis were found to be effective in decreasing streptococcal infections and neuropsychiatric symptom exacerbations among children in the PANDAS subgroup.

Echocardiographic Findings in the PANDAS Subgroup

Sydenham's chorea is the neurologic manifestation of rheumatic fever and is a diagnosis of exclusion requiring only the presence of frank chorea in the absence of another neurologic disorder. Two thirds of children with Sydenham's chorea also have rheumatic carditis (pathologic mitral valve regurgitation). Although there are similar neuropsychiatric symptoms and preceding group A beta-hemolytic streptococcal infection associated with both Sydenham's chorea and the PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) subgroup, it is unknown whether patients in the PANDAS subgroup have any cardiac involvement. Sixty children meeting the criteria for PANDAS were entered into protocols at National Institute of Mental Health between 1993 and 2002. Doppler and 2-dimensional echocardiograms were performed on these subjects to assess valvular heart disease. Of these 60 children, no echocardiographic evidence of significant mitral or aortic valve regurgitation was found. One patient was found to have mild mitral regurgitation, and all patients had normal left atrial size and normal left ventricular size and function. Follow-up echocardiograms on 20 children showed no significant valvular regurgitation. The evidence of a clear lack of rheumatic carditis in these children supports the hypothesis that PANDAS is a distinct neuropsychiatric diagnosis separate from Sydenham's chorea.

A Possible Association of Recurrent Streptococcal Infections and Acute Onset of Obsessive-Compulsive Disorder

Rheumatic fever is an immunologically mediated disease that follows infection by group A β-hemolytic Streptococcus (GABHS). In rheumatic fever, antibodies generated against GABHS cross-react with the heart, joints, skin, and other sites, inducing an inflammatory, multisystem disease. Brain tissue-specific antibodies have been demonstrated in a subset of children with Sydenham chorea (a component of the Jones criteria for the diagnosis of rheumatic fever), and most Sydenham chorea patients manifest obsessive-compulsive symptoms very similar to those in traditional obsessive-compulsive disorder. The parallels drawn from the paradigm of Sydenham's chorea to Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is an area of active controversy. Newly emerging information on the role of GABHS superantigens in the pathogenesis of rheumatic fever is of particular interest. In this article, we review the microbial characteristics of GABHS and the subsequent immune responses to GABHS as a possible etiology of PANDAS.

A possible association of recurrent streptococcal infections and acute onset of obsessive-compulsive disorder.

Rheumatic fever is an immunologically mediated disease that follows infection by group A beta-hemolytic Streptococcus (GABHS). In rheumatic fever, antibodies generated against GABHS cross-react with the heart, joints, skin, and other sites, inducing an inflammatory, multisystem disease. Brain tissue-specific antibodies have been demonstrated in a subset of children with Sydenham chorea (a component of the Jones criteria for the diagnosis of rheumatic fever), and most Sydenham chorea patients manifest obsessive-compulsive symptoms very similar to those in traditional obsessive-compulsive disorder. The parallels drawn from the paradigm of Sydenham's chorea to Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is an area of active controversy. Newly emerging information on the role of GABHS superantigens in the pathogenesis of rheumatic fever is of particular interest. In this article, we review the microbial characteristics of GABHS and the subsequent immune responses to GABHS as a possible etiology of PANDAS.

PANDAS: current status and directions for research.

The recognition of the five criteria for PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) by Swedo et al established a homogenous subgroup of children with childhood onset obsessive-compulsive disorder (OCD) and/or tic disorders. The five clinical characteristics that define the PANDAS subgroup are the presence of OCD and/or tic disorder, prepubertal age of onset, abrupt onset and relapsing-remitting symptom course, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and a temporal association between symptom exacerbations and a Group-A beta-hemolytic streptococcal (GAS) infection. These five criteria have been used for the purpose of systematic research on the phenomenology and unique therapies for the PANDAS subgroup as well as studies of the pathophysiology of post-streptococcal OCD and tic disorders. The etiology of OCD and tics in the PANDAS subgroup is unknown, but is theorized to occur as a result of post-streptococcal autoimmunity in a manner similar to that of Sydenham's chorea. The working hypothesis for the pathophysiology begins with a GAS infection in a susceptible host that incites the production of antibodies to GAS that crossreact with the cellular components of the basal ganglia, particularly in the caudate nucleus and putamen. The obsessions, compulsions, tics, and other neuropsychiatric symptoms seen in these children are postulated to arise from an interaction of these antibodies with neurons of the basal ganglia.

Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric disorder with a strong genetic component, and may involve autoimmune processes. Support for this latter hypothesis comes from the identification of a subgroup of children, described by the term pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), with onset of OCD symptoms following streptococcal infections. Genes involved in immune response therefore represent possible candidate genes for OCD, including the myelin oligodendrocyte glycoprotein (MOG) gene, which plays an important role in mediating the complement cascade in the immune system. Four polymorphisms in the MOG gene, a dinucleotide CA repeat (MOG2), a tetranucleotide TAAA repeat (MOG4), and 2 intronic single nucleotide polymorphisms, C1334T and C10991T, were investigated for the possibility of association with OCD using 160 nuclear families with an OCD proband. We examined the transmission of alleles of these four polymorphisms with the transmission disequilibrium test (TDT). A biased transmission of the 459-bp allele (allele 2: chi2 = 5.255, P = 0.022) of MOG4 was detected, while MOG2, C1334T, and C10991T showed no statistically significant bias in the transmission of alleles. The transmission of the C1334T.MOG2.C10991T.MOG4 haplotype 1.13.2.2 (chi2 = 6.426, P = 0.011) was also significant. Quantitative analysis using the family-based association test (FBAT) was significant for MOG4 in total Yale-Brown Obsessive-Compulsive Scale severity score (allele 2: z = 2.334, P = 0.020). Further investigations combining genetic, pathological, and pharmacological strategies, are warranted.

PANDAS tras amigdalectomía

PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) is the denomination for the disorder shown by a subgroup of patients with obsessive symptoms and/or tics that appear in relation to infections by group A beta-hemolytic streptococci. The clinical case that we present corresponds to a girl of 5 years who developed a compulsive-obsessive disorder in temporal relation to an amygdalectomy. This patient fulfilled the diagnostic criteria and the longitudinal evolution corresponding to this type of disorder.

Infections with group A β-hemolytic streptococci and poststreptococcal sequelae

Zusammenfassungβ-hämolysierende Streptokokken der Gruppe A (GABS) zählen zu den häufigsten bakteriellen Infektionen im Kindesalter.Neben bekannten Lokalinfektionen, Scharlach und Sepsis werden zunehmend Streptokokkentoxisches-Schocksyndrom (STSS) und nekrotisierende Fasziitis (NF) beschrieben.Auch bei Kindern kann durch superinfizierte Varizellen eine NF induziert werden, die mit einer hohen Letalität einhergeht.Auslöser sind erregerspezifischeKapselproteine,Virulenzfaktoren und Toxine als Superantigene.Immunologische Schnelltests zeigen eine hohe Treffsicherheit, die PCR erlaubt Typen- und Toxinanalysen. Zudem können typenspezifische Streptokokkenfolgekrankheiten durch Cstreptokokken ausgelöst werden.Rheumatisches Fieber ist in den Industrieländern eher selten,Herzbeteiligung viel häufiger als bisher angenommen.Chorea korreliert offensichtlich ebenso wie Zwangsstörungen – “pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)” – mit neuronalen Antikörpern, dabei sind auch streptokokkenassoziierte Fallserien von ADEM (akute disseminierte Enzephalomyelitis) berichtet.Es existiert keine Penizillinresistenz, jedoch ist Erregerpersistenz ein Problem.Ein 26-M-valenter Impfstoff ist in klinischer Erprobung, seine Effektivität wird noch kontrovers diskutiert.