Sleep-wake disturbances in Parkinson's disease: current evidence regarding diagnostic and therapeutic decisions

Sleep disorders have been frequently reported in patients with Parkinson's disease (PD). However, there is insufficient evidence to guide precise recommendations on some diagnostic and treatment strategies. Here, we review clinical studies dealing with sleep abnormalities in PD and present clinical recommendations. Previous studies describing insomnia, excessive daytime sleepiness, narcolepsy-like episodes, circadian changes, sleep-disordered breathing, rapid eye movement sleep behavior disorder, vivid dreams and restless legs syndrome are evaluated. Longitudinal studies associating sleep disorders with PD onset or clinical deterioration are rare: only one longitudinal study associated daytime sleepiness with PD onset. Evidence suggests that clinical investigations must include direct questioning about depressive symptoms, nocturnal cramps, pain, nocturia and nighttime off periods. A patient interview must be conducted regarding sleep symptoms, including nightmares, abnormal behavior during sleep, snoring, restless legs syndrome and daytime sleepiness. Initial evidence indicates that light therapy improves motor function and depression. Advice on sleep hygiene, the treatment of concomitant depression and the careful use of dopaminergic drugs and hypnosedative agents should be considered. To date, very few controlled studies are available to make a recommendation for the management of sleep-wake disturbances in PD.     

Association of acanthosis nigricans and skin tags with insulin resistance

Insulin resistance is a metabolic disorder in which target cells fail to respond to normal levels of circulating insulin. Insulin resistance has been associated with presence of acanthosis nigricans and acrochordons. It is known that early diagnosis and early initial treatment are of paramount importance to prevent a series of future complications. These dermatoses may represent an easily identifiable sign of insulin resistance and non-insulin-dependent diabetes.     

Autoimmune hepatitis, HLA and extended haplotypes

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease. Characteristic liver-infiltrating immune cells in portal and periportal areas, hypergammaglobulinemia and typical autoantibodies indicate an ongoing autoimmune reaction against liver self antigens, which lead to irreversible cellular damage and ultimately to severe hepatic failure. A significant part of adult, but not pediatric AIH patients, exhibit concurrent autoimmune diseases, further strengthening the immunological etiology of the disease. Genetic susceptibility to autoimmune hepatitis is strongly associated with HLA-DRB1 alleles. In Caucasian European and North American patients, AIH-1 is associated with the presence of DRB1*0301, DRB3*0101 and DRB1*0401 alleles, while AIH-2 is associated with DRB1*0301 or DRB1*07. In Brazil, the primary susceptibility allele for AIH-1 is DRB1*1301, but a secondary association with DRB1*0301 has also been identified. We looked for additional susceptibility factors in the extended MHC region. We genotyped 107 AIH-1 children and up to 326 healthy subjects for TNFA G-308A, TNFA G-238A, LTA A+252G, LTA A+80C, NFKBIL1 T-63A, BAT1 C-348T, BAT1 G-22C, MICA, and HLA-B polymorphisms. The TNFA-308 A allele was significantly increased in AIH-1 when compared with healthy controls, confirming data from other studies. Linkage disequilibrium analysis was carried out. The ancestral haplotype comprising TNFA-308A, TNFA-238G, LTA+252G, LTA+80C, NFKBIL1-63A, BAT1-348C, BAT1-22C, HLA-B*08, MICA*08 was more common in DRB1*03 positive patients than in controls (40% vs. 14%), showing a seven-fold increased risk for the disease [OR=7.8 (95%CI 2.04-29.9.2, p=0.0021). In contrast, the remaining patients carrying DRB1*03 exhibited varied haplotypes. Finally, a variety of class III haplotypes was also present in HLA-DRB1*13 patients, without a predominant pattern. The most common of the 98 haplotypes present in patients were completely absent in controls. The extended haplotype analysis in this sample of AIH-1 patients highlights not only the genetic diversity present in the Brazilian population, but is also in accordance with the previously documented microdiversity within the MHC region. The present knowledge of AIH suggests that the same or a very similar disease can be induced by yet unknown, but different, triggers followed by presentation on different HLA-DR molecules of the epitopes derived from the corresponding autoantigens, characterizing a much more complex disease than previously thought.     

COVID-19 and dengue coinfection in Brazil

The case we present here is a man who lives in a dengue-endemic area. Initially, the patient was diagnosed with dengue fever by clinical evaluation and laboratorial confirmation. Subsequently, he presented respiratory symptoms, and a concomitant severe acute respiratory syndrome coronavirus 2 infection was confirmed. He was hospitalized for 17 d and had a satisfactory recovery.