MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection

OBJECTIVE: The authors assessed selective basal ganglia involvement in a subgroup of children with obsessive-compulsive disorder (OCD) and/or tics believed to be associated with streptococcal infection. METHOD: Using computer-assisted morphometric techniques, they analyzed the cerebral magnetic resonance images of 34 children with presumed streptococcus-associated OCD and/or tics and 82 healthy comparison children who were matched for age and sex. RESULTS: The average sizes of the caudate, putamen, and globus pallidus, but not of the thalamus or total cerebrum, were significantly greater in the group of children with streptococcus-associated OCD and/or tics than in the healthy children. The differences were similar to those found previously for subjects with Sydenham's chorea compared with normal subjects. CONCLUSIONS: These results support the hypothesis that there is a distinct subgroup of subjects with OCD and/or tics who have enlarged basal ganglia. These findings are consistent with the hypothesis of an autoimmune response to streptococcal infection.     

Antistreptococcal,neuronal, and nuclear antibodies in Tourette syndrome

Previous studies have suggested associations between Tourette syndrome and attention-deficit-hyperactivity disorder and antistreptococcal antibodies and between Tourette syndrome and antinuclear antibodies. In this study, antistreptolysin O, antideoxyribonuclease B, antinuclear, and antineuronal antibodies were measured in 41 children with Tourette syndrome and 38 controls, selected without regard to history of streptococcal infection. Results revealed that mean antistreptococcal titers did not differ between diagnostic groups. In addition, multiple regression analysis was unable to predict antistreptococcal antibody titers according to age and diagnosis. The frequency of elevated antistreptolysin O titers, based on a cutoff of 1:240, was significantly higher (P = 0.04) in patients with attention-deficit-hyperactivity disorder (64%) than in the group without attention-deficit-hyperactivity disorder (34%) but not when dichotomized according to age-matched normal values. No analysis of antideoxyribonuclease B titers identified any differences between groups. Antinuclear antibody titers were at least 1:160 in three of 33 Tourette syndrome patients; only one subject manifested a homogeneous staining pattern. Multiple regression analyses were unable to predict antinuclear, antineuronal, or anti-HTB-10 antibody titers according to the combination of age, diagnosis, and antistreptococcal titer. We suggest that longitudinal rather than single-point-in-time laboratory measurements be evaluated before definitive conclusions are drawn on associations between the diagnosis of Tourette syndrome, attention-deficit-hyperactivity disorder, or obsessive-compulsive disorders and antistreptococcal or antinuclear antibody titers.     

Increased number of subcortical hyperintensities on MRI in children and adolescents with Tourette's syndrome, obsessive-compulsive disorder, and attention deficit hyperactivity disorder

OBJECTIVE: To investigate whether cerebral hyperintensities on T2-weighted magnetic resonance images (MRI) are associated with childhood neuropsychiatric disorders. METHOD: The authors compared the frequency of cortical and subcortical cerebral hyperintensities in 100 children and adolescents with Tourette's syndrome, obsessive-compulsive disorder (OCD), or attention deficit hyperactivity disorder (ADHD) and 32 healthy comparison subjects. RESULTS: The frequency of cerebral hyperintensities was significantly higher in subjects with Tourette's syndrome, OCD, or ADHD than in healthy comparison subjects; each diagnostic group seemed to contribute to this effect. Among the patient groups, the likelihood of detecting cerebral hyperintensities in the subcortex (primarily the basal ganglia and thalamus) was significantly greater than in the cortex. CONCLUSIONS: A childhood diagnosis of Tourette's syndrome, OCD, or ADHD significantly increased the likelihood of detecting cerebral hyperintensities, particularly in the subcortex, supporting the notion that subcortical injury may play a role in the pathophysiology of these conditions.     

Increased antistreptococcal antibody titers and anti-basal ganglia antibodies in patients with Tourette syndrome: controlled cross-sectional study

The association between Tourette syndrome, attention-deficit hyperactivity disorder (ADHD), and obsessive-compulsive disorder following streptococcal infections has been documented, but with conflicting reports. We thus felt it was important to investigate this association in a group of Italian patients not previously documented. We took blood on 69 patients with Tourette syndrome and 72 age- and sex-matched tic-free controls. Laboratory staff were blind to the diagnostic status of the subjects. Evidence of recent streptococcal infection was defined using antistreptolysin titers. Anti-basal ganglia antibodies were determined using human basal ganglia sections. Statistical analysis was conducted using analysis of variance and chi-square tests. Raised antistreptolysin titers were found in 41 of 69 (59%) patients with Tourette syndrome and 14 of 72 (19%) controls (P = .000). Positive anti-basal ganglia antibodies were found in 22 of 69 (32%) subjects with Tourette syndrome compared with 7 of 72 (10%) controls, which was also significant (P = .002). Raised antistreptolysin titers were detected in 18 of 22 (82%) patients with Tourette syndrome with positive anti-basal ganglia antibodies and 22 of 47 (47%) patients with negative anti-basal ganglia antibodies (P = .01). These results support the reported association between streptococcal infection and anti-basal ganglia antibodies and some patients with Tourette syndrome.     

Antineuronal antibodies in a group of children with obsessive-compulsive disorder and Tourette syndrome

An autoimmune hypothesis has been suggested for early onset obsessive-compulsive disorder and Tourette syndrome. The term: Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) has been proposed as an aetiological subtype of OCD and TS, related to a Group A beta haemolytic streptococcal (GABHS) infection that triggers an autoimmune response. Antineural antibodies have been studied and found in the sera of some patients with these disorders, and they are thought to cross-react with streptococcal and basal ganglia antigens. The present study included 32 prepubertal-onset OCD patients, 21 with TS diagnosis (some of them meeting criteria for PANDAS) and 19 normal children, all aged between 9 and 17 years. Antibodies were assayed by immunohistochemistry and immunoblot. Special attention was paid to the methodology and a high serum dilution was used to minimize non-specific binding. No anti-basal ganglia antibodies were detected by immunohistochemistry in any of the samples. Two proteins, with approximate molecular weights of 86 kDa and 55 kDa, were found in sera from 7 patients. Though the study supports the hypothesis of an autoimmune process underlying OCD or TS in some patients, further research is needed.     

Neuropsychiatric disorders associated with streptococcal infection: a case-control study among privately insured children

ObjectiveTo assess whether antecedent streptococcal infection(s) increase the risk of subsequent diagnosis of obsessive-compulsive disorder (OCD), Tourette syndrome (TS), other tic disorders, attention-deficit/hyperactivity disorder (ADHD), or major depressive disorder (MDD) in a national sample of privately insured children.MethodUsing health insurance claims data, we compared the prior year's occurrence of streptococcal infection in children ages 4 to 13 years with OCD, TS, or tic disorder newly diagnosed between January 1998 and December 2004 to that of a cohort of matched controls. Conditional logistic regression models were used to determine the association of prior streptococcal sore throat or scarlet fever with a diagnosis of OCD, TS, or tic disorder. We repeated the analyses for two other infectious diseases (otitis media and sinusitis) and one noninfectious condition (migraine). We also investigated the potential specificity of this association by performing similar analyses focused on newly diagnosed ADHD and newly diagnosed MDD.ResultsSubjects with newly diagnosed OCD, TS, or tic disorder were more likely than controls to have had a diagnosis of streptococcal infection in the previous year (odds ratio 1.54,95% confidence interval 1.29–2.15). Prior streptococcal infection was also associated with incident diagnoses of ADHD (odds ratio 1.20, 95% confidence interval 1.06–1.35) and MDD (odds ratio 1.63, 95% confidence interval 1.12–2.30).ConclusionsThese findings provide epidemiologic evidence that some pediatric-onset neuropsychiatric disorders, including OCD, tic disorders, ADHD, and MDD, may be temporally related to prior streptococcal infections. Whether this is the result of a nonspecific stress response or secondary to an activation of the immune system remains to be determined.     

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.     

Obsessive-compulsive disorder and immunocompetence

OBJECTIVE: A postinfectious, autoimmune response may be associated with the development of pediatric obsessive-compulsive disorder (OCD). According to this model, antistreptococcal antibodies cross-react with basal ganglia neurons following streptococcus infection. This autoimmune reaction disrupts a basal ganglia-thalamocortical circuit and generates obsessive-compulsive symptoms. One implication of this model is that prolonged immunologic stress may be a risk factor for OCD. That is, immunologic stress may compromise the blood-brain barrier and permit the influx of antistriatal antibodies into the central nervous system. This article explores one part of this putative relationship by investigating whether adult OCD patients, compared to members of other psychiatric groups, demonstrate a higher incidence of recurrent infections and other conditions suggestive of compromised immune function. METHOD: To test this hypothesis, we conducted a medical records review of 100 consecutive patients evaluated at a private psychiatric clinic specializing in the treatment of anxiety disorders. Sixty-five patients met diagnostic criteria for an Axis-I syndrome. Primary diagnoses included OCD, posttraumatic stress disorder, social anxiety disorder, generalized anxiety disorder, panic disorder with agoraphobia, and dysthymic disorder. Each medical record was reviewed for the presence of target syndromes or presenting symptoms suggestive of compromised immune function. RESULTS: Chart review revealed an increased rate of immune-related symptoms and syndromes among OCD patients in comparison to other anxiety and mood disorder groups. Groups did not differ significantly in the incidence of non-immune symptoms and syndromes. CONCLUSION: Adult OCD patients appear to have an increased rate of immune-related diseases above and beyond that seen in other psychiatric disorders.     

Prospective, longitudinal study of tic, obsessive-compulsive, and attention-deficit/hyperactivity disorders in an epidemiological sample

OBJECTIVE: Understanding the interrelatedness of tics, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD) has been complicated by studying only cross-sectional samples of clinically referred subjects. The authors report the cross-sectional and longitudinal associations of these disorders in an epidemiological sample of children followed prospectively into early adulthood. METHOD: Structured diagnostic interview information was acquired on 976 children, aged 1 to 10 years, who were randomly selected from families living in upstate New York in 1975. Reassessments were acquired in 776 of these subjects 8, 10, and 15 years later. Diagnostic prevalences were estimated at each time point. The associations among tics, OCD, and ADHD were assessed within and across time points, as were their associations with comorbid illnesses and demographic risk factors. RESULTS: In temporal cross-section, tics and ADHD symptoms were associated with OCD symptoms in late adolescence and early adulthood after demographic features and comorbid psychiatric symptoms were controlled. In prospective analyses, tics in childhood and early adolescence predicted an increase in OCD symptoms in late adolescence and early adulthood. ADHD symptoms in adolescence predicted more OCD symptoms in early adulthood, and OCD in adolescence predicted more ADHD symptoms in adulthood. The associations of tics with ADHD were unimpressive in temporal cross-section and were not significant in prospective analyses. Tics, OCD, and ADHD shared numerous complex associations with demographic and psychopathological risk factors. ADHD was associated with lower IQ and lower social status, whereas OCD was associated with higher IQ. CONCLUSIONS: Tics and OCD were significantly associated in this sample, as were OCD and ADHD. These findings are in general consistent with those from family studies, and they help to define the natural history, comorbid illnesses, and interrelatedness of these conditions.     

Comorbidity of obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in referred children and adolescents

OBJECTIVE: The aim of this study was to explore whether comorbid attention-deficit/hyperactivity disorder (ADHD) affects the clinical expression and outcome of obsessive-compulsive disorder (OCD) in a clinical sample. METHOD: A consecutive series of 94 children and adolescents (mean age, 13.6 +/- 2.8 years) with current diagnosis of OCD were included in the study. Twenty-four (25.5%) patients were diagnosed as having a comorbid ADHD. Subjects with OCD plus ADHD were compared with subjects with OCD but without ADHD. RESULTS: Comorbid ADHD with OCD was significantly associated with a higher rate of males, an earlier onset of OCD, a greater psychosocial impairment, and a heavier comorbidity, namely, with bipolar disorder, tic disorder, and oppositional defiant disorder/conduct disorder. Phenomenology of obsessions and compulsions and outcome were not affected by ADHD comorbidity. CONCLUSIONS: A screening for ADHD should be performed in patients with OCD, as these patients and their parents are frequently not aware that the impairment may be partly due to a comorbid ADHD.     

The effects of methylphenidate on neural systems of attention in attention deficit hyperactivity disorder

OBJECTIVE: Recent studies have suggested that attention deficit hyperactivity disorder (ADHD) is associated with abnormalities in basal ganglia and prefrontal cortical functioning. However, these studies have primarily relied upon cognitive tasks that reflect impulse control rather than attentional mechanisms. METHOD: The authors used functional magnetic resonance imaging to investigate the neural correlates of selective and divided attention in a randomized, double-blind, placebo-controlled pharmacological challenge with methylphenidate in 15 adolescents with ADHD (ages 14-17), eight adolescents with reading disorder (ages 12-17), and four adolescents with both reading disorder and ADHD (ages 14-18) who were scanned during both a methylphenidate and a placebo session. Fourteen healthy comparison subjects (ages 12-20) who were not given methylphenidate served as the primary comparison group. RESULTS: During the divided attention task, unmedicated subjects with ADHD or reading disorder recruited the left ventral basal ganglia significantly less than the healthy comparison subjects. Methylphenidate led to an increase in activation in this region but had no effect on task performance. Subjects with ADHD also recruited the middle temporal gyrus significantly less than the comparison subjects, but methylphenidate did not have a direct effect on activation in this region. CONCLUSIONS: These results suggest that ADHD is associated with abnormal processing in attentional networks, with specific dysfunction in striatal circuitry. Methylphenidate may act to normalize activity within this network.     

Progress toward analysis of D8/17 binding to B cells in children with obsessive compulsive disorder and/or chronic tic disorder

Background: Previous research has suggested that a subgroup of children with obsessive compulsive disorder (OCD) have neuropsychiatric sequelae of streptococcal pharyngitis, similar to that seen in the neurological manifestation of rheumatic fever (RF). Monoclonal antibody D8/17 demonstrates increased binding to B cells in patients with RF and in patients with neuropsychiatric disorders using immunofluorescent microscopy. Objective: The aim of this study was to determine if an earlier immunofluorescent microscopy study of monoclonal antibody D8/17 in childhood-onset OCD and/or chronic tic disorder (CTD) could be replicated using the more objective method of flow cytometric analysis. Method: D8/17 binding to B cells was determined in patients with OCD and or CTD (N=32), and healthy controls (N=12) by flow cytometric analysis. Results: Subjects with OCD/CTD showed increased mean cell binding (26.0%) of monoclonal antibody compared with healthy controls (9.1%) (p<0.001). When using the threshold of greater than 19% binding (95% upper confidence interval) as a measure of positivity, 65.6% of patients compared with 8.3% of controls showed increased antibody binding to B cells (p=0.01). Conclusions: Although this study reports positive results, many methodological issues will need to be addressed before generalized use of assay for diagnostic purposes.     

Case series: increased vulnerability to obsessive-compulsive symptoms with repeated episodes of Sydenham chorea

The association between obsessive-compulsive symptoms (OCS) and Sydenham chorea (SC) supports the hypothesis of a common neuroimmunological dysfunction in basal ganglia associated with group A beta-hemolytic streptococcal infection underlying both conditions. Four children with 2 distinct SC episodes were evaluated to assess the course of OCS. All patients developed OCS during their second episodes (3 met criteria for obsessive-compulsive disorder [OCD]), but not in their first episodes (2 developed OCS and met criteria for OCD). These data suggest that the recurrence of SC episodes may result in a cumulative effect, thus increasing the risk of appearance and intensification of OCS.     

Adaptive, emotional, and family functioning of children with obsessive-compulsive disorder and comorbid attention deficit hyperactivity disorder

OBJECTIVE: The purpose of the study was to examine adaptive, emotional, and family functioning in a well-characterized group of children and adolescents with obsessive-compulsive disorder (OCD) and to evaluate the influence of comorbid attention deficit hyperactivity disorder (ADHD) on the levels of impairment in various functional domains. METHOD: The study group included 287 children and adolescents (191 boys, 96 girls) ages 7-18 years. Fifty-six subjects had a diagnosis of OCD only, 43 had both OCD and ADHD, 95 had ADHD, and 93 were unaffected comparison children. Best estimate DSM-IV diagnoses were assigned on the basis of structured interviews and clinical ratings. The children's functioning was evaluated with a comprehensive battery of well-established, standardized measures, including the Vineland Adaptive Behavior Scales, parents' ratings of social and family functioning, and children's self-reports of emotional adjustment. RESULTS: The children with OCD only were more impaired than were unaffected comparison subjects in most areas of adaptive functioning and emotional adjustment. Children with OCD plus ADHD had additional difficulties in social functioning, school problems, and self-reported depression. Impairment in daily living skills, reduced number of activities, and self-reported anxiety were uniquely associated with the diagnosis of OCD. Family dysfunction was associated with ADHD but not with OCD. CONCLUSIONS: Children and adolescents with OCD are impaired in multiple domains of adaptive and emotional functioning. When comorbid ADHD is present, there is an additional burden on social, school, and family functioning.     

Antibasal ganglia antibodies and their relevance to movement disorders

PURPOSE OF REVIEW: Recently, autoaggressive immunological responses were included among the causative agents of basal ganglia dysfunction. Autoaggressive immune-mediated illnesses secondary to group A beta-haemolytic streptococcal infections present with motor and psychiatric symptoms, due to basal ganglia involvement. These disorders have been associated with serum antineuronal antibodies, relatively specific to human basal ganglia tissue. This review summarizes the most recent studies concerning antibasal ganglia antibodies, focusing on the associated phenotypes and the hypotheses concerning their pathogenicity. RECENT FINDINGS: The spectrum of post-streptococcal neuropsychiatric disorders associated with antibasal ganglia antibodies seems broader than previously recognized. Other than chorea, tics and obsessive-compulsive disorder, which constituted the bulk of previously described disorders associated with antibasal ganglia antibodies, post-streptococcal neuropsychiatric disturbances include a wider range of motor and behavioural abnormalities, in keeping with the multifunctional role of the basal ganglia. An encephalitis lethargica-like illness following streptococcal infection was reported, and unusual adult-onset movement disorders associated with antibasal ganglia antibodies were documented. Moreover, investigators provided preliminary evidence for a pathogenic role of autoantibodies in Sydenham's chorea, the prototypic post-streptococcal neuropsychiatric disorder. SUMMARY: Antibasal ganglia antibodies are relatively specific in identifying post-streptococcal neuropsychiatric disorders, which constitute a wider spectrum of movement disorders than previously recognized. Although their sensitivity in diagnosing Sydenham's chorea seems excellent, it is not yet possible to extrapolate this sensitivity to all the recently identified post-streptococcal neuropsychiatric disorders. The antigens targeted by these autoantibodies and their pathogenic importance are currently under investigation. Preliminary evidence suggests that antibasal ganglia antibodies may be pathogenic.     

Disproportionate increases of white matter in right frontal lobe in Tourette syndrome.

OBJECTIVE: Based on previous findings implicating abnormalities of cortico-striatal-thalamo-cortical circuitry in Tourette syndrome (TS), the authors performed a volumetric analysis of frontal and nonfrontal tissue (gray + white matter) in boys with TS, with and without attention deficit hyperactivity disorder (ADHD). METHODS: Frontal and nonfrontal gray and white matter compartment volumes, obtained by a MRI protocol, were analyzed with a 2 x 2 factorial multivariate analysis of variance approach for associations with a TS or ADHD factor in 11 boys with TS only, 14 with TS + ADHD, 12 with ADHD only, and 26 healthy boys. RESULTS: In subjects with TS, the right frontal lobe showed a larger proportion of white matter. In addition, results were consistent with previous reports of reduced frontal lobe volumes associated with ADHD. Our analyses suggested these reductions to be mainly the consequence of smaller gray matter volumes, particularly on the left. CONCLUSIONS: These findings, suggesting the volumetric composition of frontal lobe tissue to be different in TS, support the hypothesis proposing frontostriatal pathway involvement in the pathophysiology of the disorder. Differences in composition of right frontal lobe attributable to white matter do not definitively implicate the hypothesized fiber pathways; however, considered in the context of the unilateral directionality of frontal-striatal circuitry, these results suggest the white matter connections as one explanation for basal ganglia anomalies (loss of normal left > right asymmetry) in TS.     

Tourette's syndrome: a cross sectional study to examine the PANDAS hypothesis

BACKGROUND: The classical neurological disorder after group A beta haemolytic streptococcal infection is Sydenham's chorea. Recently a tic disorder occurring after group A streptococcal infection has been described and termed PANDAS (paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). It is proposed that antibodies induced after group A streptococcal infection react with basal ganglia neurones in Sydenham's chorea and PANDAS. Anti-basal ganglia antibodies (ABGA) are present in most cases of acute Sydenham's chorea, but rarely in controls. OBJECTIVE: To investigate the hypothesis that Tourette's syndrome may be associated with group A streptococcal infection and ABGA. METHODS: 100 patients with Tourette's syndrome (DSM-IV-TR) were enrolled in a cross sectional study. Children with neurological disease (n = 50) and recent uncomplicated streptococcal infection (n = 40), adults with neurological disease (n = 50), and healthy adults (n = 50) were studied as controls. Recent group A streptococcal infection was defined using antistreptolysin O titre (ASOT). ABGA were detected using western immunoblotting and indirect immunofluorescence. RESULTS: ASOT was raised in 64% of children with Tourette's syndrome compared with 15% of paediatric neurological disease controls (p < 0.0001), and in 68% of adults with Tourette's syndrome compared with 12% of adult neurological controls and 8% of adult healthy controls (p < 0.05). Western immunoblotting showed positive binding in 20% of children and 27% of adults with Tourette's syndrome, compared with 2-4% of control groups (p < 0.05). The most common basal ganglia binding was to a 60 kDa antigen, similar to the proposed antigen in Sydenham's chorea. Indirect immunofluorescence revealed autoantibody binding to basal ganglia neurones. Serological evidence of recent group A streptococcal infection, assessed by a raised ASOT, was detected in 91% (21/23) of Tourette's syndrome patients with positive ABGA compared with 57% (44/77) with negative ABGA (p < 0.01). CONCLUSIONS: The results support a role of group A streptococcal infection and basal ganglia autoimmunity in a subgroup of patients with Tourette's syndrome and suggest a pathogenic similarity between Sydenham's chorea and some patients with Tourette's syndrome.     

Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection

The objective of this study was to assess brain involvement through the presence of antineuronal antibodies in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) and in uncomplicated active Group A streptococcal infection. We compared serum antibrain antibody to human basal ganglia sections assessed by indirect tissue immunofluorescence in two groups: a PANDAS group, comprised of 22 patients (mean age 10.1 years; 20 male, 2 female) who met strict National Institutes of Mental Health diagnostic criteria for PANDAS and had clinically active tics or obsessive-compulsive disorder, or both; and a GABHS control group consisting of 22 patients (mean age 9.1 years; 15 mol/L, 7 female) with clinical evidence of active Group A beta-hemolytic streptococcal (GABHS) infection confirmed by throat culture and elevated antistreptolysin O titers but without history or clinical evidence of tics or obsessive-compulsive disorder. We observed positive anti-basal ganglia staining (defined as detectable staining at 1:10 serum dilution) in 14/22 patients in the PANDAS group (64%) but only 2/22 (9%) in the GABHS control group (P < 0.001, Fisher's exact test). These results suggest that antibrain antibodies are present in children with PANDAS that cannot be explained merely by a history of GABHS infection.     

Anti-basal ganglia antibodies in acute and persistent Sydenham's chorea

OBJECTIVE: To determine the sensitivity and specificity of methods to detect anti-basal ganglia antibodies (ABGA) in Sydenham's chorea (SC). BACKGROUND: SC is a delayed manifestation of group Abeta hemolytic streptococcal infection typically associated with rheumatic fever (RHF). SC is characterized by chorea and motor and neuropsychiatric symptoms. Patients with SC produce antibodies that cross-react with streptococcal, caudate, and subthalamic nuclei antigens detected using an immunofluorescent (IF) method with inconsistent reports of positivity. METHODS: The authors developed ELISA and Western immunoblotting (WB) methods to detect ABGA and compared these assays to IF. They investigated samples from patients with acute SC (n = 20), persistent SC (n = 16), control samples from RHF (n = 16), and healthy pediatric volunteers (n = 11). RESULTS: ABGA ELISA had a sensitivity of 95% and specificity of 93% in acute SC. Both WB and IF had a sensitivity of 100% and specificity of 93%. In the persistent SC group, ABGA sensitivity dropped to 69% using WB and to 63% using IF. Three common basal ganglia antigens were identified by WB in both acute and persistent SC (40 kDa [n = 15], 45 kDa [n = 15], and 60 kDa [n = 13]). There was no antibody reactivity to cerebellum, cerebral cortex, or myelin antigen preparations in any group. CONCLUSIONS: These results support the hypothesis that Syndenham's chorea is an autoantibody-mediated disorder. Western immunoblotting and immunofluorescence are the best methods for detecting anti-basal ganglia antibodies, and reactivity to basal ganglia antigens of 40, 45, and 60 kDa were commonly seen in both acute and persistent cases of SC.     

Transcranial sonography in obsessive–compulsive disorder

There is convergent evidence that basal ganglia structures are involved in the pathogenesis of obsessive–compulsive disorder (OCD). It has been also assumed that OCD is caused by a central serotonergic dysfunction. Transcranial sonography (TCS) has become a reliable, sensitive and non-invasive diagnostic tool concerning the evaluation of extrapyramidal movement disorders. This study used TCS to examine the alterations in different parenchymal regions, especially concerning serotonergic brainstem raphe nuclei as well as basal ganglia in OCD. Thirty-one OCD patients were compared with 31 matched healthy controls. Echogenecities were investigated according to the examination protocol for extrapyramidal disorders using a Siemens Sonoline^® Elegra system. Obsessive–compulsive disorder patients showed reduced echogenity of the serotonergic brainstem raphe nuclei (32.3%) compared with healthy controls (16.1%). In nine OCD-patients (31%), but only in 2 control subjects (6.2%), a hyperechogenicity of the caudate nucleus was found. Patients with OCD significantly more often reveal a hypoechogenic brainstem raphe possibly reflecting altered serotonergic neurons there and a hyperechogenicity of caudate nucleus indicating structural or molecular cell changes. Further research is warranted to examine, whether TCS is useful in order to classify OCD and its subtypes.