Sleep dysfunction is highly prevalent across the spectrum of neurodegenerative conditions and is a key determinant of quality of life for both patients and their families. Mounting recent evidence also suggests that such dysfunction exacerbates cognitive and affective clinical features of neurodegeneration, as well as disease progression through acceleration of pathogenic processes. Effective assessment and treatment of sleep dysfunction in neurodegeneration is therefore of paramount importance; yet robust therapeutic guidelines are lacking, owing in part to a historical paucity of effective treatments and trials. Here, we review the common sleep abnormalities evident in neurodegenerative disease states and evaluate the latest evidence for traditional and emerging interventions, both pharmacological and nonpharmacological. Interventions considered include conservative measures, targeted treatments of specific clinical sleep pathologies, established sedating and alerting agents, melatonin, and orexin antagonists, as well as bright light therapy, behavioral measures, and slow-wave sleep augmentation techniques. We conclude by providing a suggested framework for treatment based on contemporary evidence and highlight areas that may emerge as major therapeutic advances in the near future.
Introduction
Mounting evidence supports the existence of an important feedforward cycle between sleep and neurodegeneration, wherein neurodegenerative diseases cause sleep and circadian abnormalities, which in turn exacerbate and accelerate neurodegeneration. If so, sleep therapies bear important potential to slow progression in these diseases.
Findings
This cycle is challenging to study, as its bidirectional nature renders cause difficult to disentangle from effect. Likewise, well-controlled intervention studies are often impractical in the setting of established neurodegenerative disease. It is this that makes understanding sleep and circadian abnormalities in Huntington’s disease (HD) important: as a monogenic fully penetrant neurodegenerative condition presenting in midlife, it provides a rare opportunity to study sleep and circadian abnormalities longitudinally, prior to and throughout disease manifestation, and in the absence of confounds rendered by age and comorbidities. It also provides potential to trial sleep therapies at a preclinical or early disease stage. Moreover, its monogenic nature facilitates the development of transgenic animal models through which to run parallel pre-clinical studies. HD, therefore, provides a key model condition through which to gain new insights into the sleep-neurodegeneration interface.
Conclusions
Here, we begin by summarising contemporary knowledge of sleep abnormalities in HD, and consider how well these parallel those of Alzheimer’s and Parkinson’s as more common neurodegenerative conditions. We then discuss what is currently known of the sleep-neurodegeneration cyclical relationship in HD. We conclude by outlining key directions of current and future investigation by which to advance the sleep-neurodegeneration field via studies in HD.
Bone marrow involvement is assessed in lymphoma staging/restaging following treatment/relapse by a combination of an aspirate and trephine biopsy. Of 262 consecutive cases staged by aspirate and trephine, the aspirate yielded a diagnosis when a trephine did not in only 11.8%. Trephine biopsies were positive in 34.7% cases and equivocal/insufficient in 14.9%, while aspirates were positive in 11.1% cases and equivocal/insufficient in 21%. We suggest that in the majority of cases, it may be acceptable either to store an aspirate for reporting only if the trephine is inconclusive or to take a trephine biopsy without an aspirate.
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