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Sydenham's chorea (SC) is the most common form of acquired chorea during childhood (1), and is present in ∼30% of patients with rheumatic fever (RF) (2–4). Clinically, SC is characterized by motor manifestations such as involuntary movements of the extremities, muscular hypotonia, dysarthria, gait disturbance, and tics (5, 6), as well as behavioral manifestations, such as obsessive-compulsive symptoms, attention deficit disorder, and emotional lability (7, 8).
Some studies suggest that its etiopathogenesis is related to immunologic dysfunction located at the basal ganglia, mediated by antibodies that cross-react against antigens in these structures after a group A streptococcus pharyngitis infection (9, 10). Autopsy findings (11) and studies of anatomic (12, 13) and functional (14) neuroimaging show involvement of the basal ganglia and their different frontostriatal circuits.
The basal ganglia are subcortical structures that are related to the brain cortex through the frontostriatal circuits. The motor and oculomotor circuits are responsible for the production of somatic and eye movements, respectively. The orbitofrontal circuit plays an important role in the suppression of inappropriate behavior, the anterior cingulate circuit mediates motivated behavior, and finally, the dorsolateral circuit is involved in the construction of cognitive functions, particularly attention, working memory, and executive functions (15). One can hypothesize that the selective involvement of the different frontostriatal circuits provides evidence of the variability of neuropsychiatric manifestations in SC patients (16). Teixeira et al developed and validated a rating scale for clinical evaluation of SC patients and observed a poor correlation between behavior, activities of daily living, and motor function items, suggesting the selective involvement of the different circuits (16).
The few studies regarding cognitive functions in patients with SC were developed during the acute phase of the disease and showed cognitive deficits in abilities such as attention, executive functions, and phonemic verbal fluency (17–19). Therefore, there is insufficient evidence on the repercussion of cognitive impairment associated with SC in adulthood. The purpose of the current study was to evaluate the neuropsychological profile and health-related quality of life (HRQOL) of adult patients who had SC during childhood or adolescence and now are asymptomatic. A battery of standardized neuropsychological tests and specific questionnaires were applied in order to investigate possible cognitive damage resulting from this involvement.
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In this study, we evaluated the neuropsychological profile and HRQOL of adults who had RF, with and without SC, during childhood. The 2 groups of patients (SC and RF) and the CT group were homogeneous with regard to sex, age, schooling, socioeconomic status, IQ, and a specific questionnaire for anxiety and depression, which allowed us to conclude that possible cognitive deficits cannot be explained by these factors. Our results showed that patients from the SC group presented, after an average time period of 14.8 years since the first episode of chorea, weaker performance in tests that evaluate attention (Digit Span Forward and Corsi Block Forward), speeded information processing (Trail Making A and Symbol Search), and executive functions and working memory (Corsi Block Backward) when compared with RF and CT groups, suggesting a possible dysfunction at the basal ganglia circuits, specifically the dorsolateral circuit.
There are insufficient published studies about cognitive functions in patients with SC both in the acute phase as well as in the remission phase of chorea. However, in other disorders associated with the basal ganglia, cognitive deficits resulting from dysfunction of the frontostriatal circuits have been demonstrated. Neuropsychological studies in individuals with Parkinson's disease (33), Huntington's chorea (34, 35), and obsessive-compulsive disorder (36) reported similar deficits in cognitive functions such as attention, working memory, and executive functions. Therefore, independently of the etiopathogenesis of basal ganglia dysfunction, these patients presented with similar neuropsychiatric manifestations and cognitive impairment.
With regard to the studies conducted with RF and SC, all of them have been concerned with the acute phase. Sacks and colleagues evaluated, through neuropsychological tests, patients with RF and SC with and without disease activity and patients with RF without SC and without disease activity, and they did not observe significant differences with regard to IQ (37). In the same way, we also have not found this involvement, corroborating that SC seems to not compromise patients' IQ.
We observed that patients from the SC group presented lower scores when compared with the patients from the RF and CT groups in the Symbol Search and Corsi Block Forward tests, which require visuospatial tracking of information. Bird et al, although having used the Bender gestalt test (which predominantly evaluates organic involvement), also observed alteration in the visuomotor function in patients with SC after an average followup time of 8 years, in comparison with controls (38).
It is interesting to observe that studies conducted during the acute phase of SC revealed attention (response inhibition and divided attention) (17) and executive function impairment, evaluated through Tower of Hanoi problem solving (18). Although these studies used different tests from the ones used in the present study, their results suggest that patients with SC can present impairment in executive functions and in attention during the acute phase of the disease, which, according to our results, can persist into adult life in some individuals.
On the other hand, in another study conducted during the acute phase of SC that evaluated semantic and phonemic verbal fluency in 20 children, the authors observed a significant reduction in phonemic fluency in these patients when compared with the control group, without correlation with dysarthria and chorea severity. However, no difference in semantic fluency was observed between the groups (19). In the current study, we did not observe a difference between patients and controls in either semantic or phonemic fluency, which might suggest that some of the alterations found in the acute phase may not persist during the disease course.
Besides the cognitive alterations, the patients from the SC group also presented a higher frequency of symptoms that suggest ADHD through the ASRS questionnaire in comparison with the CT group. As for hyperactivity, although we have not found a statistically significant difference between the 3 groups, there was a tendency in the SC and RF groups to present higher scores when compared with the CT group. Maia et al demonstrated that ADHD is more frequent in patients with SC when compared with controls and patients with RF without SC (8). Although the objective of our study was only a screening of ADHD symptoms by means of the ASRS (28), which takes as reference the A criteria of DSM-IV for ADHD (29) and not the clinical diagnosis of ADHD, we found results similar to the ones found by Maia et al (8). Moreover, such subjective indicators corroborated the performance in objective measures in the attention tests of our protocol.
With regard to the occupational aspects, our findings did not show a higher rate of unemployment in RF patients, with or without SC, when compared with controls. Schooling and socioeconomic status were also similar for all of the groups. This suggests that cognitive changes and attention deficit symptoms found in our patients who had SC during childhood have not impacted, up to the present time, their professional performance during adult life in a significant way.
Concerning the HRQOL, although we found a statistically significant difference only in the general health domain of the SF-36 between the RF group and the CT group (P = 0.030), a detailed analysis of our results (Table 3) shows that patients with SC presented a tendency to have worse scores in other SF-36 domains, such as physical aspects, vitality, emotional aspects, and mental health. We suppose that patients with RF presented lower scores in general health (SF-36) probably because they grew up with frequent medical visits and continuous medication due to their condition. In view of our small sample size, it is possible that we did not find statistical significance in the other SF-36 domains. In summary, adult patients who had SC during childhood presented a worse self-evaluation of quality of life than the patients with RF without SC and the controls in the CT group.
The current study has some limitations, such as the difficulty in recruiting patients because they were no longer being treated in our outpatient clinic, with many of them no longer living in the same city and others having moved to another address. Typically, the majority of patients with RF are discharged or discontinue treatment, especially in the cases with no cardiac sequel. Therefore, the sample size was reduced. Another limitation of our study is that it was not a prospective investigation; that is, we built on the observations of other studies that showed cognitive changes during the acute phase of SC and verified with our results that these changes persist throughout adult life. However, the present result is important because it shows the need for a longitudinal followup of children who have SC, taking into consideration the risk for cognitive and behavioral deficits that can persist into adult life.
In summary, adult patients who had SC during childhood or adolescence can present lower results in tests that evaluate working memory, attention, and executive functions. These findings are probably a result of a dorsolateral circuit dysfunction and are not related to sex, age, education, socioeconomic status, mood disorder, and IQ.
Although prospective studies with a larger number of patients tracked from the acute phase of SC until their adult life are necessary, our results permit us to conclude that patients with SC should be assessed by a neuropsychologist in the acute phase of the disease and in the followup in order to determine the existence of cognitive and behavioral changes and to offer appropriate treatment, if necessary. We must consider that the neuropsychological rehabilitation that is conducted early on can minimize this impairment and reduce the difficulties that some patients might possibly have during adolescence or adulthood.