The psychiatric symptoms of rheumatic fever

OBJECTIVE: This study examined the frequency and age at onset of psychiatric disorders among children with rheumatic fever, Sydenham's chorea, or both and a comparison group. METHOD: Twenty children with rheumatic fever, 22 with Sydenham's chorea, and 20 comparison children were assessed by means of a semistructured interview and rating scales for tic disorders and obsessive-compulsive disorder. RESULTS: Obsessive-compulsive symptoms were more frequent in both the Sydenham's chorea and rheumatic fever groups than in the comparison group. The Sydenham's chorea group had a higher frequency of major depressive disorder, tic disorders, and attention deficit hyperactivity disorder (ADHD) than both the comparison and rheumatic fever groups. ADHD symptoms were associated with a higher risk of developing Sydenham's chorea. CONCLUSIONS: Both the rheumatic fever and Sydenham's chorea groups were associated with a higher risk of developing neuropsychiatric disorders than the comparison group. ADHD appears to be a risk factor for Sydenham's chorea in children with rheumatic fever.     

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.     

Immunological alterations in adult obsessive-compulsive disorder.

BACKGROUND: Some recent findings suggest the involvement of autoimmune mechanisms in childhood onset of obsessive-compulsive disorder (OCD), on the basis of a parallel drawn with Sydenham's chorea, a manifestation of rheumatic fever. A monoclonal antibody called D8/D17 characterizing a B-lymphocyte antigen, present in almost all patients with rheumatic fever, has been found also in children affected by OCD, Tourette syndrome, and chronic tics to a greater degree than in healthy control subjects. The few observations of disturbances of some immunologic parameters in adult OCD patients, prompted the authors to investigate and compare subsets of peripheral immunological cells for differences in adult patients with OCD and healthy control subjects. METHODS: Twenty patients suffering from OCD, with no comorbidity for other psychiatric disorders, were compared with a similar group of healthy control subjects. The immune subsets were measured by flow cytometry. RESULTS: The CD8+ lymphocytes were significantly increased and CD4+ lymphocytes significantly decreased in OCD patients, while the other cells did not differ between the two groups. No correlation was found between immunologic and clinical parameters. CONCLUSIONS: These data indicate that patients with adult OCD showed increased CD8+, i.e., suppressor T lymphocytes, and decreased CD4+, which identify helper T lymphocytes, as compared with a similar group of healthy control subjects. The findings appear peculiar to patients with OCD and are suggestive of an immunologic imbalance, which might be related to the stress deriving from the frustrating situation determined by the disorder itself.     

High prevalence of obsessive-compulsive symptoms in patients with Sydenham's chorea

The 20-item Leyton Obsessional Inventory--Child Version was completed by children and adolescents who had had Sydenham's chorea (N = 23) or rheumatic fever without chorea (N = 14). The Sydenham's chorea subjects had significantly more obsessive thoughts and compulsive behaviors and significantly greater interference from these behaviors. Three Sydenham's chorea patients but no rheumatic fever patients had substantial obsessional interference and met criteria for obsessive-compulsive disorder when interviewed by telephone. This suggests that obsessive-compulsive disorder, at least in some patients, may be due to basal ganglia dysfunction.     

Obsessive-compulsive disorder and immunology: a review

Interest in the possibility of an immune-mediated pathophysiology of obsessive-compulsive disorder and related disorders has increased. In the late 1980s, the National Institute of Mental Health reported an increase in obsessive-compulsive symptoms (OCS) in patients with Sydenham chorea (SC). Subsequently, a precipitating streptococcal infection in children with sudden onset of OCS but no chorea led to the coining of PANDAS (Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). This association has furthered interest in biological measures for immune and genetic susceptibility in non-PANDAS obsessive-compulsive disorder patients (OCD). Furthermore, some studies are trying to demonstrate alterations of immune parameters in OCD patients, with few positive results. In this narrative review, our objective was to describe the immunologic findings in OCD, PANDAS, and their association with SC.     

The use of antibody D8/17 to identify B cells in adults with obsessive-compulsive disorder.

Compared with healthy control subjects, individuals with childhood-onset obsessive-compulsive disorder (OCD) have been reported to have a higher percentage of B cells that react with the monoclonal antibody D8/17, a marker for rheumatic fever. This study sought to replicate these findings in adults with OCD. Double-blind analyses of blood samples from 29 consecutive adults with primary OCD and 26 healthy control subjects were conducted to determine the percentage of B cells identified by D8/17. Using a standard criterion of > or =12% labeled B cells to denote positivity, rates of D8/17 positive individuals did not significantly differ between the OCD (58.6%) and control (42.3%) groups. Early age of onset was not a predictor of D8/17 positivity in the OCD group. The percentage of B cells identified by the monoclonal antibody marker D8/17 did not distinguish adults with OCD from control subjects, nor did it distinguish a sub-group of adults with OCD who described pre-pubertal onset of their OCD symptoms.     

The link between autoimmune diseases and obsessive-compulsive and tic disorders: A systematic review

Immunological factors are increasingly recognized as being important in a range of neuropsychiatric disorders. We aimed to summarize the disperse and often conflicting literature on the potential association between autoimmune diseases (ADs) and obsessive-compulsive disorder (OCD) and tic disorders. We searched PubMed, EMBASE, and PsycINFO for original studies evaluating the relationship between ADs and OCD/tic disorders until July, 13th 2016. Seventy-four studies met inclusion criteria. Overall, the studies were of limited methodological quality. Rates of OCD were higher in rheumatic fever patients who were also affected by its neurological manifestation, Sydenham’s chorea. The literature on other ADs was scarce and the findings inconclusive. Few studies examined the association between ADs and tic disorders. A handful of family studies reported elevated rates of ADs in first-degree relatives of individuals with OCD/tic disorders, and vice versa, potentially suggesting shared genetic and/or environmental mechanisms. In conclusion, at present, there is modest evidence for a possible association and familial co-aggregation between ADs and OCD/tic disorders. We offer some suggestions for future research.     

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.     

Sydenham chorea in a 5-year-old Saudi patient

Despite improvements in socio-economic status and the standard of health care services, rheumatic fever continuous to occur in Saudi Arabia, although with decreasing frequency. The disease is most commonly observed in school-aged children, but can also occur in a younger age group. Carditis and arthritis are the major clinical symptoms on presentation of acute rheumatic fever in young children. Rheumatic chorea is infrequently reported in young children. Here, a case of Sydenham chorea, in a 5-year-old boy, is presented. Although rare, the diagnosis of Sydenham chorea should always be considered in young children with choreiform movements.Acute rheumatic fever (ARF) is most frequently seen in school-aged children. The disease and its neurological manifestation, Sydenham chorea, are considered rare in preschool aged children (<5 years of age). As the most common cause of acquired chorea, Sydenham chorea must be included in the deferential diagnosis of choreiform movements among young children. Failure to recognize this disease may increase the risk of recurrence of ARF as well as rheumatic heart disease. We present a case of Sydenham chorea in a 5-year-old boy. The objective in presenting this particular case is to highlight the need to raise awareness of the possibility of Sydenham chorea in young children.     

Obsessive-compulsive symptoms in adults with history of rheumatic fever, Sydenham's chorea and type I diabetes mellitus: preliminary results

OBJECTIVE: Rheumatic fever (RF) associated with Sydenham's chorea (a neurological variant of RF), but not RF without chorea, has been acutely related to obsessive-compulsive symptomatology/disorder (OCS/OCD). This study investigated the presence of OCS in adults who had RF with or without chorea in childhood. METHOD: The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to evaluate OCS in 38 adults with history of RF (13 with chorea; 25 without chorea) or diabetes (controls; n = 19). RESULTS: The OCS was similar in both groups, although the intensity of symptoms was not clinically relevant. Moreover, subjects with RF with or without chorea did not score differently in the Y-BOCS. CONCLUSION: The similar occurrence of OCS in patients with history of RF and diabetes suggests that the development of this symptomatology, triggered by group A beta-haemolytic streptococcus infections, is restricted to the RF acute phase, occurred during infancy, and did not seem to predispose the appearance of OCS in adulthood.     

Infection-triggered anorexia nervosa in children: clinical description of four cases

BACKGROUND: Anorexia nervosa (AN) is a serious illness with no definitive treatment. Clinical and research evidence led to the hypothesis that some children with AN may have a pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS), similar in pathogenesis to other hypothesized PANDAS disorders. METHODS: Four youngsters (ages, 11-15 years) with PANDAS AN were treated with an open trial of antibiotics, in addition to conventional treatment. They were evaluated for eating disorder and obsessive-compulsive symptoms, and for weight gain. Evidence of streptococcal infection came from clinical evaluation, throat cultures, and two serological tests: anti-deoxyribonuclease B (anti-DNase B) and anti-streptolysin O (ASO) titers. The "rheumatic" marker D8/17 was also measured. This B-cell alloantigen is associated, in several publications, with poststreptococcal autoimmunity: Rheumatic fever (RF), Sydenham's chorea (SC), and possibly PANDAS obsessive compulsive disorder (OCD) and tic disorders. RESULTS: There was clinical evidence of possible antecedent streptococcal infection in all four patients, two of whom had comorbid OCD, with possible infection-triggered AN. All four had the rheumatic marker: A percentage of D8/17-positive B cells of 28-38%, with a mean of 33% (12% or more is considered positive for the marker). The patients responded to conventional treatment plus antibiotics with weight restoration and decreased eating disorder and obsessive-compulsive symptoms. Three needed to gain weight and did so. CONCLUSIONS: There may be a link between infectious disease and some cases of AN, which raises the possibility of new treatment.     

Obsessive-compulsive symptoms among patients with Sydenham chorea.

BACKGROUND: Among patients with tic disorders, a distinctive clinical profile of obsessive-compulsive symptomatology has been described. The present investigation was designed to document the phenomenology of obsessive-compulsive symptoms (OCS) among patients with Sydenham chorea (SC), the neurologic variant of rheumatic fever. We hypothesized that OCS occurring in association with SC would be similar to those among patients with tic disorders. METHODS: The authors studied the presence of OCS in 73 patients with SC by using the Yale-Brown Obsessive-Compulsive Scale at the Pediatric Clinics of the University of Sao Paulo Medical Center in Sao Paulo, Brazil (n = 45) and at the National Institute of Mental Health in Bethesda, Maryland (n = 28). RESULTS: The most frequent symptoms observed among subjects with comorbid SC and OCS were aggressive, contamination, and somatic obsessions and checking, cleaning, and repeating compulsions. A principal component factor analysis yielded a five-factor solution (accounting for 64.5% of the total variance), with contamination and symmetry obsessions and cleaning compulsions loading highly. CONCLUSIONS: The symptoms observed among the SC patients were different from those reported by patients with tic disorders but were similar to those previously noted among samples of pediatric patients with primary obsessive-compulsive disorder.     

A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections.

BACKGROUND: Some children with obsessive-compulsive disorder (OCD) and tic disorders appear to have symptom exacerbations triggered by group A beta-hemolytic streptococcal infections in a manner that is similar to rheumatic fever and its neurologic variant, Sydenham's chorea. Because penicillin prophylaxis has proven to be effective in preventing recurrences of rheumatic fever, it was postulated that it might also prevent streptococcal-triggered neuropsychiatric symptom exacerbations in children with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). These children are identified by five clinical characteristics: presence of OCD or tic disorder, prepubertal onset, episodic symptom course, neurologic abnormalities (i.e., choreiform movements) and streptococcal-triggered symptom exacerbations. METHODS: Thirty-seven children with PANDAS were enrolled in an 8 month, double-blind, balanced cross-over study. Patients were randomized to receive either 4 months of the active compound (twice daily oral 250 mg penicillin V) followed by 4 months of placebo, or placebo followed by penicillin V. Tic, OCD, and other psychiatric symptoms were monitored monthly. Throat cultures and streptococcal antibody titers were also obtained. RESULTS: There were an equal number of infections in both the active and placebo phases of the study. There was no significant change seen in either the obsessive-compulsive or tic symptom severity between the two phases. CONCLUSIONS: Because of the failure to achieve an acceptable level of streptococcal prophylaxis, no conclusions can be drawn from this study regarding the efficacy of penicillin prophylaxis in preventing tic or OCD symptom exacerbations. Future studies should employ a more effective prophylactic agent, and include a larger sample size.     

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.     

Autism and ADHD Symptoms in Patients with OCD: Are They Associated with Specific OC Symptom Dimensions or OC Symptom Severity?

In obsessive-compulsive disorder (OCD), the relationship between autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) symptom, and obsessive-compulsive (OC) symptom dimensions and severity has scarcely been studied. Therefore, 109 adult outpatients with primary OCD were compared to 87 healthy controls on OC, ADHD and ASD symptoms. OCD patients showed increased ADHD and autism symptom frequencies, OCD + ADHD patients reporting more autism symptoms (particularly attention switching and social skills problems) than OCD − ADHD patients. Attention switching problems were most significant predictors of OC symptom dimensions (except hoarding) and of symptom severity. Hoarding was not associated with elevated autism scale scores, but with inattention. In conclusion, attention switching problems may reflect both symptom overlap and a common etiological factor underlying ASD, ADHD and OCD.     

Did Gustav Mahler have Sydenham's chorea?

Sydenham's chorea (SC), a major manifestation of acute rheumatic fever (RF), is characterized by chorea and other motor and non-motor features. Among the latter are behavioral symptoms, including obsessive-compulsive disorder. Although SC is typically a self-limited condition, up to 50% of patients may evolve with persistent chorea. There is evidence that Gustav Mahler had a movement disorder, but its nature remains undetermined. There are witnesses describing him as having facial dyskinesia and a gait disorder consistent with chorea. His conducting performance was notorious for obsessive attention to details of the staging and musical production. Mahler was diagnosed with a valvulopathy in 1907 and died of subacute bacterial endocarditis in 1911. It is possible that the composer suffered from RF in childhood with carditis and SC, which may left him with valvulopathy, obsessive-compulsive disorder, and persistent chorea.     

Aggressive behaviour in children with Tourette syndrome and comorbid attention-deficit hyperactivity disorder and obsessive-compulsive disorder.

BACKGROUND: Aggressive behaviour, defined as sudden, explosive outbursts of rage, has been reported as a clinical problem in approximately 23% to 40% of Tourette syndrome (TS) patients (1-5). Attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) are also reported in 50% to 70% of TS patients (6). OBJECTIVE: To investigate whether aggressive behaviour was associated with TS directly or found primarily in TS with comorbid ADHD or OCD. METHOD: Aggressive behaviour in 33 nonmedicated patients with TS (ages 6 to 14 years) and 6 healthy control subjects (ages 7 to 12 years) was examined by semistructured interview and multiinformant questionnaires. RESULTS: Aggression subscales on Achenbach's Child Behavior Checklist (CBCL) completed by parents and Teacher's Report Form (TRF) completed by teachers distinguished the TS-only and control groups from the group with TS + Comorbidity (P < 0.046, and P < 0.016) after adjusting for tic severity and age. The conduct disorder subscale on the Conners Parent Rating Scale (CPRS) was also significantly higher (P < 0.005) in the TS + comorbidity group than in the TS-only or control groups, with more problems reported in the older children. CONCLUSIONS: These findings provide additional evidence that aggressive behaviour observed in children with TS may be associated with comorbid ADHD or OCD (6), independent of tic severity or age. This is consistent with the clinical observation that most TS patients have only minimal symptoms, which do not interfere with their daily functioning.     

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.     

A controlled study of sensory tics in Gilles de 1a Tourette syndrome and obsessive-compulsive disorder using a structured interview.

OBJECTIVE: To determine the prevalence and characteristics of sensory tics in the Gilles de la Tourette syndrome (GTS), and a matched population of patients with obsessive-compulsive disorder (OCD) using a structured assessment. METHODS: 50 subjects each of GTS, OCD, and healthy controls were studied to determine the prevalence and phenomenology of sensory tics, and diagnose tic disorders, OCD, and affective disorders according to DSM-III-R criteria. The severity of tics and obsessive-compulsive symptoms were quantified using the Tourette syndrome global scale (TSGS) and Yale-Brown obsessive-compulsive scale (Y-BOCS) respectively. RESULTS: The GTS group (28%) had significantly-greater life-time prevalence of sensory tics than the OCD (10%) and healthy (8%) groups (P < 0.05). The sensory tics in both the GTS and OCD groups were predominantly located in rostral anatomical sites. Multiple sensory tics occurred in some patients with GTS or OCD, but not in healthy subjects. Within the OCD group, those who had sensory tics had significantly higher TSGS scores (P < 0.0001), and a higher prevalence of GTS (P < 0.005). CONCLUSIONS: Sensory tics seem to be a common and distinctive feature of GTS and that subpopulation of patients with OCD predisposed to tic disorders. Neurophysiologically, a possible explanation for sensory tics is that they represent the subjectively experienced component of neural dysfunction below the threshold for motor and vocal tic production.     

Caudate regional cerebral blood flow in obsessive-compulsive disorder, panic disorder and healthy controls on single photon emission computerised tomography

We compared regional cerebral blood flow (rCBF) in 15 patients with DSM IIIR obsessive-compulsive disorder (OCD), 15 patients with DSM IIIR panic disorder and 15 healthy controls matched for age, sex and hand preference, using uptake of technetium-99m-D,L-hexamethyl-propylene amine oxime (99mTc HMPAO), on single photon emission computerised tomography (SPECT). Caudate rCBF was significantly reduced in OCD patients compared to healthy subjects and panic disorder patients. When four patients were excluded from each group, right caudate rCBF remained significantly lower in OCD patients than in panic disorder patients or healthy subjects. The data suggest functional involvement of the right caudate nucleus is present in OCD.