Distúrbio cognitivo e imagens neurofuncionais no lúpus eritematoso sistêmico de início na infância

Abstract

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with highly heterogeneous clinical manifestations. Juvenile SLE (JSLE) is called the disease initiated before 18 years of age. Patients with JSLE tend to have high disease activity at presentation, with an increased rate of organ involvement and long term immunosuppressive treatment during the disease. Among the neuropsychiatric manifestations associated with SLE and JSLE, one of the most frequent is cognitive impairment (CI). Which may negatively impact patients' quality of life (QOL). However, studies on the subject are still scarce in the literature. The diagnosis of neuropsychiatric manifestations of SLE (NPSLE) is challenging, and recently molecular images such as positron emission tomography (PET-CT) have been pointed out as a useful tool for this purpose. This study aimed to evaluate the frequency of cognitive impairment in young adults diagnosed with JSLE and correlate it with their perception of the quality of life, and the findings of PET-CT performed with Fluorodeoxyglucose([18F]FDG). As far as we are aware, this is the first study to correlate all these variables in this particular group of patients. Thirty-nine patients over 18 years of age and previous diagnosis of JSLE underwent extensive cognitive study encompassing the following domains: memory, executive functions, attention, psychomotor speed, problem-solving, language, and visuospatial processing. Patients were considered with cognitive impairment if the score of each test was ≥2.0 standard deviation below the normative data. The overall quality of life was assessed by WHOQOL-bref and SLEQOL. The General Scale of Activities of Daily Living (GALD) was used to evaluate the degree of independence for activities of daily living. Criterion Brazil addressed the socioeconomic status (SES) of the patients. All medical records were reviewed, the cumulated dose of prednisone was calculated, and patients classified concerning disease activity at the time of interview by SLEDAI 2K and accumulated damage related to the disease, its complications, or treatment by SLICC - ACR. The first 21 patients underwent PET-CT with [18F]FDG. The results of the images were correlated with cognitive data. The impairment of at least one cognitive domain was found in 87.2% of patients. The most compromised domains were attention (64.1%), memory (46.2%), and executive functions (38.5%). Those with cognitive impairment were older, presented more accumulated damage and worse SES. Memory impairment was correlated with the worst perception of environmental conditions and factors related to treatment. The issue of treatment was also relevant in the older patients and in those with worse SES. The initial analysis of PET-CT identified areas of hypometabolism in the cerebellum and areas of the occipital, parietal, limbic, and frontal lobe, in agreement with the previously described in the literature, suggesting hypofunction of these areas. Areas of hypermetabolism, suggestive of increased local metabolism, neuronal activity, inflammatory activity, or disinhibition of neurons after the damage of remote but interconnected regions, in the sublobar region, and temporal, frontal and limbic lobe. Memory impairment was associated with the area of hypercatation in the frontal lobe and the impairment of attention to an area of hyperuptake in the sublobar region. The scores of the tests of the executive functions correlated with areas of hypouptake in the parietal lobe. The scores of the tests for evaluation of psychomotor speed correlated with frontal lobe hypercatpation area. The scores of the tests for language evaluation correlated with hypouptake area in occipital lobe and in Brocca area. The scores of the tests for evaluation of problem solving correlated with area of hypouptake in the parietal lobe and the scores of the tests for evaluation of the visuo-spatial processing correlated with hyperuptake area in the frontal lobe. In this study, the frequency of CI was very high, but only a small impact associated with quality of life was identified. Socioeconomic status and environmental issues, closely related topics, have great weight in the perception of the quality of life in this group of patients, as well as the burden represented by the treatment of chronic disease, a fact that may be related to issues of the transition from pediatric to adult rheumatologic care. Each of the cognitive functions studied correlated with well-delimited brain areas, most often areas traditionally associated with the functions studied, indicating that PET-CT may be a biomarker of CNS involvement in lupus patients with CD, even with the brain in a resting state. Prospective, multicenter studies with a larger number of patients are necessary for the evaluation of cognitive impairment and its relationship with molecular functional images in this particular group of patients, comparing them directly with patients with other chronic diseases, including autoimmune diseases, and with healthy young people, in order to establish the real prevalence and incidence of the manifestation, in order to optimize the management design.