Marcos T. Mercadante

SYDENHAM'S CHOREA

Sydenhams chorea (SC) is a disorder of the central nervous system (CNS) characterized by sudden, involuntary, arrhythmic, clonic, and purposeless movements. SC appears to provide a model for understanding various neuropsychiatric dysfunctions. Its relationship with attentional deficits, obsessive-compulsive symptoms (OCS) as well as movement disorders provides support for the hypothesis of the involvement of the corticostriatal loops in the pathophysiology of the disorder.

Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette’s syndrome, Sydenham’s chorea, and autoimmune disorders

BACKGROUND Some cases of Tourettes syndrome (TS) are hypothesized to be caused by autoantibodies that develop in response to a preceding group A beta hemolytic streptococcal infection. METHODS To test this hypothesis, we looked for the presence ot total and IgG antibodies against neural, nuclear, cytoskeletal and streptococcal epitopes using indirect immunofluorescent assays and Western blot techniques in three patient groups: TS (n = 81), SC (n = 27), and a group of autoimmune disorders (n = 52) and in normal controls (n = 67). Subjects were ranked after titrations of autoantibodies from 0 to 227 according to their level of immunoreactivity. RESULTS TS patients had a significantly higher mean rank for total antineural and antinuclear antibodies, as well as antistreptolysin O titers. However, among children and adolescents, only the total antinuclear antibodies were increased in TS patients compared to age matched controls. Compared to SC patients, TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, significantly lower IgG class anticytoskeletal antibodies, and a significantly higher rank for total antinuclear antibodies. Compared to a mixed group of autoimmune disorders, the TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, total and IgG class antinuclear antibodies, IgG class anticytoskeletal antibodies, and a significantly higher rank for antistreptococcal antibodies. CONCLUSIONS TS patients had significantly higher levels of total antineural and antinuclear antibodies than did controls. Their relation to IgG class antineural and antinuclear antibodies, markers for prior streptococcal infection, and other clinical characteristics, especially chronological age, was equivocal.

Obsessive-Compulsive Spectrum Disorders and Rheumatic Fever: A Family Study

BACKGROUND Obsessive-compulsive spectrum disorders (OCSDs) are more frequent in patients with active or prior rheumatic fever (RF), suggesting that OCSD and RF may share underlying etiologic mechanisms. Our objective was to estimate the frequency of OCSD in first-degree relatives (FDRs) of RF patients and controls to determine whether there is a familial relationship between OCSD and RF. METHODS This is a case-control family study. Of the 98 probands included in this study, 31 had RF without Sydenhams chorea (SC) and had 131 relatives, 28 had RF with SC and had 120 relatives, and 39 were controls without RF. All probands, 87.9% of the RF FDRs and 93.7% of the control FDRs were assessed directly with structured psychiatric interviews and best-estimate diagnoses were assigned. Odds ratios of morbid risks were estimated using logistic regression by the generalized estimating equations (GEE) method and compared between groups. RESULTS The rate of OCSDs was significantly higher among FDRs of RF probands than among FDRs of controls (n=37; 14.7% vs. n=10; 7.3%, i=.0279). A diagnosis of OCSDs in an RF proband was associated with a higher rate of OCSDs among FDRs when compared to control FDRs (p-GEE=.02). There was a trend for a higher rate of OCSDs among FDRs of RF probands presenting no OCSD, although the difference was not significant (p-GEE=.09). CONCLUSION The results are consistent with the hypothesis that a familial relationship exists between OCSD and RF, since an OCSD in the RF proband was found to increase the risk of OCSDs among FDRs. Additional neuroimmunological and genetic studies involving larger samples are needed to further elucidate this apparent familial relationship between RF and OCSD.

Buspirone in Rett syndrome respiratory dysfunction

This study details a case of Rett Syndrome where the patients respiratory dysfunction was improved after buspirone was administered. Polygraphic studies in the waking state, before and after treatment with 5 mg of buspirone twice a day, were obtained. Breathing movements, oxygen saturation and end-tidal carbon were monitored. Average oxygen saturation increased from 86.9 to 91%, and the period of saturation below 90% was reduced by 42.2%. The oxygen saturation improvement observed in this case suggests that buspirone might be useful in treating respiratory dysfunction associated with Rett Syndrome. Controlled clinical trials are needed to provide more evidence.

Perspectives of intellectual disability in Latin American countries: epidemiology, policy, and services for children and adults.

Purpose of review The prevalence of intellectual disability is an estimated 1–4% worldwide. Etiological factors such as malnutrition, lack of perinatal care, and exposure to toxic and infectious agents, which are more common in low-income and middle-income (LAMI) countries, may contribute to a higher prevalence of intellectual disability in Latin America. This review summarizes the data on intellectual disability coming from Latin America, which is published in scientific journals and is available from official websites and discusses potential health policy and services implications of these studies. Recent findings Methodologically rigorous studies on intellectual disability in Latin America are lacking. This paucity of basic epidemiological information is a barrier to policy and services development and evaluation around intellectual disability. Only two studies, one from Chile and another from Jamaica, allow for adequate population estimates of intellectual disability. Interestingly, the countries with the highest scientific production in Latin America, Brazil and Mexico, did not produce the most informative research in epidemiology, policy or services related to intellectual disability. Summary The main conclusion of this review is that a lack of scientific evidence makes it difficult to properly characterize the context of intellectual disability in Latin America. Insufficient data is also a barrier to policy and services development for governments in Latin America. Although recently there have been efforts to develop government programs to meet the needs of the intellectual disability population in Latin America, the effectiveness of these programs is questionable without proper evaluation. There is a need for studies that characterize the needs of people with intellectual disability specifically in Latin America, and future research in this area should emphasize how it can inform current and future policies and services for people with intellectual disability.

Autism and the pervasive developmental disorders

The Intemational Association of Child and Adolescent Psychiatry and Allied Professions (IACAPAP) is the intemational organization of national societies committed to child and adolescent psychiatry, psychology and allied professions. For more than sixty years, IACAPAP has been an intemational advocate for children and families and for the professions that serve them. Major goals are to facilitate the provision of preventive and treatment services, to enhance the training and the work of mental health professionals, and to promote the advancement of knowledge and the sharing of information across nations to improve the quality of care and treatment that is available. Autism and pervasive developmental disorders (PDD) are the most serious child psychiatric disorders. Autism affects one child in every 1,500 and associated pervasive developmental disorders affect one child in every 200 or 300. Individuals with autism and PDD are found in every nation, in all ethnic groups, in all types of families, and in every social class. Arising during the first years of life, autism and pervasive developmental disorders affect the vital areas of psychological and behavioral development, generally through the life span. Children and autism and associated disorders are impaired in the development of their social relations, communication, and emotional functioning, and are burdened in their adaptation to life in the family, in school, and in the community. They suffer from serious behavioral and emotional symptoms including over-activity, stereotypy, repetitive and restricted range of activities, anxiety, and self-injurious behavior. Most individuals with autism, although not all, are also intellectually disabled (mentally retarded) and many are non-verbal (mute). Social disturbances, however, exceed intellectual difficulties and social, emotional, and behavioral problems of autistic individuals cannot be explained solely as a result of intellectual disability.

Saccadic movements using eye-tracking technology in individuals with autism spectrum disorders: pilot study

OBJECTIVE To verify differences in the visual scanning strategies between pervasive developmental disorders (PDD) and controls when they are observing social and non-social pictures. METHOD PDD group (PDDG) comprised by 10 non-retarded subjects (age from 4 to 41) and age-matched control group (CG). Nine social pictures with human beings (including two pictures of cat mask), and 3 nonsocial pictures of objects were presented for 5 seconds. Saccadic movements and fixation were recorded with equipment EyeGaze (LC Technologies Inc.). RESULTS PDDG (mean=292.73, SE=67.62) presented longer duration of saccadic movements for social pictures compared to CG (mean=136.06, SE=14.01) (p=0.04). The CG showed a higher number of fixations in the picture 7 (a women using a cat mask, with the eyes erased) (CG: mean=3.40; PDDG: mean=1.80; p=0.007). CONCLUSION The results suggest differences in strategies that PDD explore human picture. Moreover, these strategies seem not to be affected by the lack of expected part of the face (the eyes).

As bases neurobiológicas do transtorno obsessivo-compulsivo e da síndrome de Tourette

OBJECTIVE: To describe and discuss evidence-based articles on the neurobiology of obsessive-compulsive disorder and Tourette syndrome. SOURCES OF DATA: A review of the most relevant papers on the phenomenology, neuroanatomy, neuroimaging, genetic and immunological aspects of these two disorders was performed. SUMMARY OF THE FINDINGS: Ritualistic behaviors and repetitive thoughts have been extensively studied in the last years. The definitions of obsessive-compulsive disorder and Tourette syndrome emphasize the existence of a continuum of symptoms, with high prevalence in the general population. Neurobiological findings have implicated genetic and immunological factors in the etiology of these two disorders. CONCLUSIONS: Advances in neuroscience triggered genetic and immunological research studies, allowing new perspectives on the treatment of obsessive-compulsive disorder and Tourette syndrome patients.

Transtorno obsessivo-compulsivo

Introdução O transtorno obsessivo-compulsivo (TOC) é caracterizado pela presença de obsessões e/ou de compulsões. A relativa simplicidade do diagnóstico categorial sugeriria tanto uma precisa delimitação nosográfica, quanto uma homogeneidade do quadro. No entanto, resultados de pesquisas recentes têm enfatizado dois conceitos. O primeiro refere-se à heterogeneidade do quadro. O segundo refere-se à concepção de que o TOC poderia ser estudado a partir de uma visão dimensional e contínua, ou seja, dentro de um espectro obsessivo-compulsivo. Sendo assim, para o aprofundamento do conhecimento do TOC é necessário buscar-se subgrupos mais homogêneos de pacientes. As peculiaridades da apresentação do TOC na infância e adolescência sugerem que o início precoce dos sintomas delimitaria um subtipo de pacientes. As prevalências de estudos epidemiológicos em adolescentes revelaram taxas entre 1,9% e 3,0% nos Estados Unidos e entre 2,3% e 4,1% em outros países. A distribuição entre os sexos parece variar de acordo com as diversas faixas etárias, sendo que em crianças há uma preponderância de meninos. No presente artigo, procurou-se desenvolver os aspectos mais importantes e atuais na avaliação de crianças e adolescentes com TOC.

Autism spectrum disorder in Down syndrome: definition of the cutoff point for the autism screening questionnaire screening instrument.

To the Editor: Recently, an article on the prevalence of autism spectrum disorder (ASD) in Down Syndrome (DS)1 has been published. The aforementioned work discusses the sensitivity and specificity of 2 instruments used for the screening of ASD in a population with mental retardation, particularly DS, and suggests that the instruments currently available for diagnosis of ASD have low specificity. Our research group (Lowenthal et al) had already evaluated a sample of 228 individuals with DS in the city of Curitiba, capital of the state of Paraná, in the south of Brazil and had found increased prevalence of ASD (14.5% in our study vs 18.2% in the study by DiGuiseppi et al) being 4.9% for autism (6.4% in the study by DiGiuseppi et al). In a more recent study, DiGiuseppi et al1 discuss the implications of the higher sensitivity of the instruments at the expense of specificity. In this sense, we have decided to reexamine the Brazilian DS cohort,2 looking into new possibilities with respect to the specificity of one of the instruments used, the Autism Screening Questionnaire (ASQ). The preliminary validation study of the Brazilian version of the ASQ had suggested the same cutoff points as those of the original study (without ASD [ 15], with ASD [ 15 and 21], and autism [ 22])3 in a cohort of 120 participants (40 ASD, 40 DS, and 40 other psychiatric disorders).4 First, we decided to verify the sensitivity and specificity of the cutoff point 15 applied to our sample. A sensitivity of 88.2% and a specificity of 53.3%, with good ability to recognize ASD cases (p 0.021), were found. To search for new cutoff points for this DS/ASD population, a classification analysis by decision tree test confirmed by receiver operator characteristic curve was accomplished, which furnished a cutoff point of 18, in which sensitivity and specificity were 76.5% and 93.3%, respectively (area below the curve 0.884). Despite the decreased sensitivity, this increase in the cutoff point allowed for higher specificity, which should provide this screening instrument with improved psychometric property. Many of the symptoms that are part of the ASD screening instruments are very common in subjects with intellectual disability, which can cause individuals with DS to present with isolated symptoms, thereby justifying the elevation of the ASQ cutoff point during screening of ASD cases. For this reason, an instrument with higher specificity should avoid problems with identification of false positives, which have financial implications and result in burden for the families,1 especially in investigations involving large cohorts of patients. The increased frequency of ASD in DS suggests that large epidemiologic studies should be performed on this population. As in the case of studies on other associations between low-frequency pathologies, such large studies on ASD/DS would probably facilitate the search for genes and polymorphisms associated with ASD, thus aiding better understanding of the development of the social brain in individuals with DS. Finally, screening instruments adapted for investigations on specific populations are mandatory.