Dulski, Jaroslaw

Aim: The aim of this study was to evaluate the efficacy of ultrasound guidance (US) in the treatment of cervical dystonia (CD) with botulinum neurotoxin type A (BoNT-A) injections in comparison to anatomical landmarks (AL). To date, US is routinely used in many centers, but others deny its usefulness. Materials and Methods: Thirty-five patients (12 males, 23 females) with a clinical diagnosis of CD were included in the study. Intramuscular administration of BoNT-A was performed using either US guidance, or with AL, in two separate therapeutic sessions. The efficacy of BoNT-A administration was assessed with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), Tsui modified scale, Craniocervical Dystonia Questionnaire (CDQ-24) and Clinical Global Impression—Improvement scale (CGI-I). Additionally, patients at therapeutic sessions were digitally recorded and evaluated by two blinded and independent raters. Results: A significant decrease in total TWSTRS, severity subscale TWSTRS, Tsui score, and CDQ-24 was found in both the AL and US group; however, in the TWSTRS disability and pain subscales, a significant decrease was found only in the US group. Moreover, US guided treatment also resulted in a greater decrease in TWSTRS, Tsui score and CDQ-24 compared to anatomical landmarks use only. Conclusions: US guidance might be helpful in improving the results of BoNT-A injections in cervical dystonia, reducing associated pain and disability; however, more studies are needed to evaluate its clinical efficacy.

Parkinson’s disease (PD) is generally considered a sporadic disorder, but a strong genetic background is often found. The aim of this study was to identify the underlying genetic cause of PD in two affected siblings and to subsequently assess the role of mutations in Cathepsin B (CTSB) in susceptibility to PD. A typical PD family was identified and whole-exome sequencing was performed in two affected siblings. Variants of interest were validated using Sanger sequencing. CTSB p.Gly284Val was genotyped in 2077 PD patients and 615 unrelated healthy controls from the Czech Republic, Ireland, Poland, Ukraine, and the USA. The gene burden analysis was conducted for the CTSB gene in an additional 769 PD probands from Mayo Clinic Florida familial PD cohort. CTSB expression and activity in patient-derived fibroblasts and controls were evaluated by qRT-PCR, western blot, immunocytochemistry, and enzymatic assay. The CTSB p.Gly284Val candidate variant was only identified in affected family members. Functional analysis of CTSB patient-derived fibroblasts under basal conditions did not reveal overt changes in endogenous expression, subcellular localization, or enzymatic activity in the heterozygous carrier of the CTSB variant. The identification of the CTSB p.Gly284Val may support the hypothesis that the CTSB locus harbors variants with differing penetrance that can determine the disease risk.

AbstractBackground and purposePerry disease (or Perry syndrome) is an autosomal dominant neurodegenerative disorder characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, weight loss and distinct TDP‐43 pathology. It is caused by mutations of the DCTN1 gene encoding an essential component of axonal transport. The objectives were to provide the current state of knowledge on clinical, pathological and genetic aspects of Perry disease, as well as practical suggestions for the management of the disease.MethodsData on new patients from New Zealand, Poland and Colombia were collected, including autopsy report. Also all of the published papers since the original work by Perry in 1975 were gathered and analyzed.ResultsParkinsonism was symmetrical, progressed rapidly and was poorly responsive to L‐Dopa; nonetheless, a trial with high doses of L‐Dopa is warranted. Depression was severe, associated with suicidal ideations, and benefited from antidepressants and L‐Dopa. Respiratory symptoms were the leading cause of death, and artificial ventilation or a diaphragm pacemaker prolonged survival. Weight loss occurred in most patients and was of multifactorial etiology. Autonomic dysfunction was frequent but underdiagnosed. There was a clinical overlap with other neurodegenerative disorders. An autopsy showed distinctive pallidonigral degeneration with TDP‐43 pathology. Genetic testing provided evidence of a common founder for two families. There was striking phenotypic variability in DCTN1‐related disorders. It is hypothesized that oligogenic or polygenic inheritance is at play.ConclusionsPerry disease and other DCTN1‐related diseases are increasingly diagnosed worldwide. Relatively effective symptomatic treatments are available. Further studies are needed to pave the way toward curative/gene therapy.