In this chapter, we review the evolution of our understanding of the genetic aspects of HD, and the applications of our understanding in the management of Huntington's disease patients and families ...over the last 150 years. Important aspects of the clinical genetics and epidemiology of Huntington's disease are discussed, such as the definition of "normal" and "abnormal" numbers of CAG (cytosine-adenine-guanine) repeats in the critical spot within the huntingtin gene, meiotic instability of CAG repeat numbers, common Huntington's disease genetic haplotypes, compound heterozygosity for an abnormal gene, and somatic mosaicism for CAG repeat expansions. We touch only briefly on the creation of multiple animal models for Huntington's disease that have profoundly impacted our understanding of the disease and permitted the development of potential disease-modifying treatments, and end with what is, at the time of writing, the dawn of a new era: the advent of gene-based therapies (gene silencing, gene editing) for Huntington's disease.
To improve our understanding of sex differences in the clinical characteristics of Parkinson's Disease, we sought to examine differences in the clinical features and disease severity of men and women ...with early treated Parkinson's Disease (PD) enrolled in a large-scale clinical trial.
Analysis was performed of baseline data from the National Institutes of Health Exploratory Trials in Parkinson's Disease (NET-PD) Long-term Study-1, a randomized, multi-center, double-blind, placebo-controlled study of 10 grams of oral creatine/day in individuals with early, treated PD. We compared mean age at symptom onset, age at PD diagnosis, and age at randomization between men and women using t-test statistics. Sex differences in clinical features were evaluated, including: symptoms at diagnosis (motor) and symptoms at randomization (motor, non-motor, and daily functioning).
1,741 participants were enrolled (62.5% male). No differences were detected in mean age at PD onset, age at PD diagnosis, age at randomization, motor symptoms, or daily functioning between men and women. Differences in non-motor symptoms were observed, with women demonstrating better performance compared to men on SCOPA-COG (Z = 5.064, p<0.0001) and Symbol Digit Modality measures (Z = 5.221, p<0.0001).
Overall, men and women did not demonstrate differences in clinical motor features early in the course of PD. However, the differences observed in non-motor cognitive symptoms suggests further assessment of the influence of sex on non-motor symptoms in later stages of PD is warranted.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Death anxiety, represented by the HDQLIFE™ Concern with Death and Dying (CwDD) patient-reported outcome (PRO) questionnaire, captures a person's worry about the death and dying process. Previous work ...suggests that death anxiety remains an unremitting burden throughout all stages of Huntington disease (HD). Although palliative interventions have lessened death anxiety among people with advanced cancer, none has yet to undergo testing in the HD population. An account of how death anxiety is associated with longitudinal changes to aspects of health-related quality of life (HRQoL) would help optimize neuropalliative interventions for people with HD.
HDQLIFE collected PROs concerning physical, mental, social, and cognitive HRQoL domains and clinician-rated assessments from people with HD at baseline and 12 and 24 months. Linear mixed-effects models were created to determine how baseline death anxiety was associated with follow-up changes in HRQoL PROs after controlling for baseline death anxiety and other disease and sociodemographic covariates.
Higher baseline HDQLIFE CwDD is associated with 12- and 24-month declines in HDQLIFE Speech Difficulties, neurology quality of life (NeuroQoL) Depression, Suicidality, HDQLIFE Meaning and Purpose, and NeuroQoL Positive Affect and Well-being.
Death anxiety may be a risk factor for worsening mental health and speech difficulty. A further prospective study is required to evaluate whether interventions on death anxiety or mental health generally can reduce declines in HRQoL for people with HD over time.
Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous diseases that affect the upper motor neurons and their axonal projections. For the novel
SPG31 locus ...on chromosome 2p12, we identified six different mutations in the receptor expression–enhancing protein 1 gene (
REEP1).
REEP1 mutations occurred in 6.5% of the patients with HSP in our sample, making it the third-most common HSP gene. We show that REEP1 is widely expressed and localizes to mitochondria, which underlines the importance of mitochondrial function in neurodegenerative disease.
Huntington's disease is a slowly progressive neurodegenerative disorder with wide-ranging effects on affected individuals and their families. Until a cure is found for the disease, patients and their ...families will continue to need care over years, even generations. The ideal care for HD is provided by a team, led by a physician, with input from rehabilitation therapists, nurses, psychologists, genetic counselors, social workers, and other health care providers. The goals of care are to maximize the quality of life at all points through the course of the disease, in part by anticipating problems that are likely to arise at the next stage of the illness. We describe below an approach to comprehensive care, and introduce the concept of the "Huntington disease molecule", in which the patient, in the center, is surrounded by a shell of immediate and extended family members, with bonds extended in multiple directions to provider who can give appropriate medical care, education, crisis management, research opportunities, address family issues, maximize function, and prepare for the future.
The PD GENEration (PD GENE) study (NCT04057794) is an interventional clinical trial offering genetic testing with result disclosure and genetic counseling to individuals with Parkinson disease (PD). ...In general, experiences of those providing PD genetic testing and counseling in a research or clinical setting have not been extensively evaluated. In this study, providers' experiences when providing research result disclosure and genetic counseling to people with PD were explored with the goal of improving PD genetics services.
Qualitative semistructured interviews of all neurologists and genetic counselors who performed genetic test result disclosure and genetic counseling to at least 5 participants in the pilot portion of the PD GENE study were conducted. An inductive thematic analysis of the transcribed interviews identified core themes and subthemes for "lessons learned" and "challenges encountered."
Interviews were conducted with 14 providers (7 neurologists and 7 genetic counselors) who described multiple lessons learned while disclosing genetic test results, including the ability to adapt to participant background and needs and the value of a well-structured and supportive study that also provides training and educational materials for the provider. Of importance, responses suggested that the PD GENE study answered a real need, highlighting a strong interest in the community. Providers also voiced several shared challenges including the complexities of PD and PD genetics, unexpected confusion on provider roles within a research study, and complicated family histories/dynamics.
Providers in the pilot portion of the PD GENE study encountered enthusiasm and strong engagement from many of the participants, and they, too, voiced significant satisfaction about their roles and the mission of the study. They learned valuable lessons, and their comfort providing genetic test result disclosure and genetic counseling grew as the study progressed. Although there were challenges, they were deemed manageable. The results from this qualitative study can inform both the expanded PD GENE study and other providers offering genetic testing and counseling to their patients in a neurology setting. It will also allow for targeted PD provider education.
Huntington's disease is a complex neurodegenerative hereditary disease with symptoms in all domains of a person's functioning. It begins after a healthy start in life and leads through the relentless ...progression over many years to complete care dependency and finally death. To date, the disease is incurable. The long progressive complex nature of the disease demands multiple disciplines for treatment and care of patient and family. These health care providers need inter- and multidisciplinary collaboration to persevere and be efficacious in this devastating disease trajectory.
The position paper outlines current knowledge and experience alongside the experience and consensus of a recognised group of HD multidisciplinary experts. Additionally the patient's voice is clear and calls for health care providers with a holistic view on patient and family. Building long-term trust is a cornerstone of the network around the patient. This paper describes a managed care network comprising all the needed professionals and services. In the health care system, the role of a central coordinator or case manager is of key importance but lacks an appropriate guideline. Other disciplines currently without guidelines are general practitioners, nurses, psychologists, and social workers. Guidelines for neurologists, psychiatrists, geneticists, occupational therapists, speech and language therapists, physiotherapists, dieticians, and dentists are being discussed. Apart from all these profession-specific guidelines, distinctive inter- and multidisciplinary collaboration requirements must be met.
The complex nature of Huntington's disease demands multidisciplinary treatment and care endorsed by international regulations and the lay association. Available guidelines as reviewed in this paper should be used, made available by a central body, and updated every 3-5 years. Time needs to be invested in developing missing guidelines but the lack of this 'proof' should not prevent the 'doing' of good care.
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