The impact of subthalamic deep brain stimulation on polysomnographic sleep pattern in patients with Parkinson's disease – Preliminary report

Aim of the study We present the preliminary results of the study focused on the impact of subthalamic deep brain stimulation (DBS-STN) on sleep and other non-motor symptoms (NMS). Materials and methods Ten patients with advanced PD, underwent two-night polysomnography (PSG) mean 1.1 week before surgery and 6.2 months post DBS programming. NMS were assessed with a set of scales before surgery and 6 months and 12 months following DBS programming. Results Contrary to previous studies, we noted deterioration of sleep pattern in the follow-up PSG. We found a decrease in total sleep time, duration of the stage N2, with prolongation of stage N1 and wakefulness after sleep onset. We did not detect any impact of DBS-STN on subjective severity of restless legs syndrome. REM – sleep behavior disorder, however reported was not observed in any patient during PSG evaluations. We also found statistically significant correlations between severity of sleep disturbances and quality of life, as well as, between severity of motor symptoms and worse objective sleep quality. Conclusions We found that DBS-STN improved quality of life, subjective quality of sleep and sleepiness, however, contrary to the previous studies the objective parameters of sleep worsened after the surgery

Duplicated Enhancer Region Increases Expression of CTSB and Segregates with Keratolytic Winter Erythema in South African and Norwegian Families

Keratolytic winter erythema (KWE) is a rare autosomal-dominant skin disorder characterized by recurrent episodes of palmoplantar erythema and epidermal peeling. KWE was previously mapped to 8p23.1-p22 (KWE critical region) in South African families. Using targeted resequencing of the KWE critical region in five South African families and SNP array and whole-genome sequencing in two Norwegian families, we identified two overlapping tandem duplications of 7.67 kb (South Africans) and 15.93 kb (Norwegians). The duplications segregated with the disease and were located upstream of CTSB, a gene encoding cathepsin B, a cysteine protease involved in keratinocyte homeostasis. Included in the 2.62 kb overlapping region of these duplications is an enhancer element that is active in epidermal keratinocytes. The activity of this enhancer correlated with CTSB expression in normal differentiating keratinocytes and other cell lines, but not with FDFT1 or NEIL2 expression. Gene expression (qPCR) analysis and immunohistochemistry of the palmar epidermis demonstrated significantly increased expression of CTSB, as well as stronger staining of cathepsin B in the stratum granulosum of affected individuals than in that of control individuals. Analysis of higher-order chromatin structure data and RNA polymerase II ChIA-PET data from MCF-7 cells did not suggest remote effects of the enhancer. In conclusion, KWE in South African and Norwegian families is caused by tandem duplications in a non-coding genomic region containing an active enhancer element for CTSB, resulting in upregulation of this gene in affected individuals