Objective:To describe the clinical, genetic, and epidemiologic features of hereditary spastic paraplegia (HSP) in Canada and to determine which clinical, radiologic, and genetic factors determine functional outcomes for patients with HSP.Methods:We conducted a multicenter observational study of patients who met clinical criteria for the diagnosis of HSP in the provinces of Alberta, Ontario, and Quebec from 2012 to 2015. Characteristics of the participants were analyzed using descriptive statistics. The main outcome measure for a subset of the cohort (n = 48) was the Spastic Paraplegia Rating Scale. We also used the SPATAX-EUROSPA disability stage (disability score) to assess disability (n = 65).Results:A total of 526 patients were identified with HSP across the country, and 150 patients had a confirmed genetic diagnosis. Mutations were identified in 15 different genes; the most common were SPAST (SPG4, 48%), ATL1 (SPG3A, 16%), SPG11 (8%), SPG7 (7%), and KIAA0196 (SPG8, 5%). The diagnosis of SPG4 was associated with older age at symptom onset (p = 0.0017). SPG4 and SPG3A were less associated with learning disabilities compared to other subtypes of HSP, and SPG11 was strongly associated with progressive cognitive deficits (odds ratio 87.75, 95% confidence interval 14.04–548.24, p < 0.0001). SPG3A was associated with better functional outcomes compared to other HSP subtypes (p = 0.04) on multivariate analysis. The strongest predictor of significant disability was abnormal brain MRI (p = 0.014).Conclusions:The most important predictors of disability in our HSP cohort were SPG11 mutations and abnormal brain MRI. Accurate molecular characterization of well-phenotyped cohorts and international collaboration are essential to establish the natural history of these rare neurodegenerative disorders.

The social impairments of autism spectrum disorder (ASD) have a major impact on quality of life, yet there are no medications that effectively treat these core social behavior deficits. Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. Using a double-blind, randomized, placebo-controlled, parallel study design, we tested the efficacy and tolerability of a 4-week intranasal AVP daily treatment in 30 children with ASD. AVP-treated participants aged 6 to 9.5 years received the maximum daily target dose of 24 International Units (IU); participants aged 9.6 to 12.9 years received the maximum daily target dose of 32 IU. Intranasal AVP treatment compared to placebo enhanced social abilities as assessed by change from baseline in this phase 2 trial’s primary outcome measure, the Social Responsiveness Scale, 2nd Edition total score (SRS-2 T score; F1,20 = 9.853; P = 0.0052; ηp2 = 33.0%; Cohen’s d = 1.40). AVP treatment also diminished anxiety symptoms and some repetitive behaviors. Most of these findings were more pronounced when we accounted for pretreatment AVP concentrations in blood. AVP was well tolerated with minimal side effects. No AVP-treated participants dropped out of the trial, and there were no differences in the rate of adverse events reported between treatment conditions. Last, no changes from baseline were observed in vital signs, electrocardiogram tracings, height and body weight, or clinical chemistry measurements after 4 weeks of AVP treatment. These preliminary findings suggest that AVP has potential for treating social impairments in children with ASD.

Merkel cell carcinoma is a rare neuroendocrine carcinoma that typically appears in sun-exposed areas of the elderly. It has a poor prognosis and with its incidence projected to increase, it is vital for dermatologists to remain up to date with recent updates in this malignancy's pathogenesis and treatment. In the past few decades Merkel cell carcinoma's pathogenesis, more specifically its relation to the Merkel cell polyomavirus, has sparked further interest in the study of this carcinoma. Most cases are attributed to malignant transformation secondary to the Merkel cell polyomavirus, with a minority derived from DNA damage resulting from ultraviolet radiation.Investigators have also determined that there are immunologic influences in the development and prognosis of Merkel cell carcinoma, as individuals with HIV, solid organ transplants, and lymphoproliferative malignancies are at a greater risk of developing this carcinoma. In addition, this immunologic link carries treatment value, as immunologic therapies are currently being investigated. This article provides a comprehensive review of the epidemiology and pathogenesis of Merkel cell carcinoma as well as the current treatments available and clinical trials underway. We also touch upon the updated National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology in respect to its diagnosis and recommended treatment modalities.

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Acne affects approximately 9% of people worldwide and is the most common skin condition in the USA. There are abundant topical and oral treatment options available for patients with acne. First-line agents include topical retinoids, azelaic acid, benzoyl peroxide, and combinations of these agents. For recalcitrant or more severe acne, oral medications, including oral antibiotics, isotretinoin, or hormonal therapy, may be considered. This review will also discuss the many advances being made in the treatment of acne vulgaris, from the development of microencapsulated medications to targeted treatments.