Sleep Dysfunction in Huntington’s Disease: Perspectives from Patients

2020 ◽  
Vol 9 (4) ◽  
pp. 345-352
Author(s):  
Will K. Tanigaki ◽  
Maria A. Rossetti ◽  
Natalia P. Rocha ◽  
Erin Furr Stimming
Keyword(s):  
Cognitive Function ◽  
Sleep Quality ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Sleep Disturbances ◽  
Clinical Symptoms ◽  
Depression Symptoms ◽  
Sleep Complaints ◽  
Sleep Dysfunction ◽  
Clinical Tools

Background: Despite the abundance of clinical tools, sleep disorders are still not routinely evaluated in patients with Huntington’s disease (HD). Sleep disturbances can exacerbate cognitive impairment and mood disorders and seriously affect the life of the patients and their families. Objective: The current study was designed to investigate sleep quality and its association with clinical symptoms in HD. As an exploratory aim, we also evaluated sleep quality in caregivers of patients with HD. Methods: Twenty-nine patients with HD and 22 caregivers completed a series of self-reported questionnaires about sleep quality and pattern, cognitive function, and depression and anxiety symptoms. Spearman correlation analyses were performed to ascertain the association between sleep quality and severity of self-perceived clinical symptoms. Results: The primary sleep complaints reported by the patients were related to waking up in the middle of the night or early in the morning; and increased sleep latency. Seventeen of 29 HD patients (59%) and 12 of 22 caregivers (55%) were classified as “poor” sleepers. Worse sleep quality among HD patients was associated with greater severity of anxiety and depression symptoms. Importantly, a decline in sleep quality was associated with decreased self-perceived cognitive function for both HD patients and caregivers. Conclusion: Increasing awareness and improving our understanding of sleep dysfunction in HD is imperative for individuals with HD and indirectly, their caregivers. Regularly incorporating sleep assessments when evaluating HD patients should be considered to address this troublesome nonmotor symptom.

352 Feasibility of Hypnosis as Adjunctive Treatment for Subjective Sleep Disturbance: A Pilot Study and Proof of Concept

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A140-A141
Author(s):  
Emma Zhao ◽  
Afik Faerman ◽  
David Spiegel
Keyword(s):  
Sleep Quality ◽  
Sleep Disturbances ◽  
Positive Impact ◽  
Self Report ◽  
Adjunctive Treatment ◽  
Current Evidence ◽  
Data Set ◽  
Sleep Complaints ◽  
Subjective Sleep ◽  
Before And After

Abstract Introduction Hypnosis-based interventions have been shown to have a positive impact on several dimensions of sleep health. However, current evidence is limited as only a paucity of studies included populations with sleep complaints. Here we present a pilot data set to demonstrate the feasibility of developing a hypnosis-based adjunctive treatment for subjective sleep complaints. Methods Eleven adults (42% female; mean age 45±16.87 years) who sought treatment at the Stanford Sleep Medicine Center or Center for Integrative Medicine for subjective sleep complaints received hypnosis as adjunctive treatment. Self-report questionnaires were used to assess the weekly frequency of subjective sleep disturbances experienced before and after treatment, as well as 5-point Likert scale ratings of perceived qualitative improvement in symptom severity and overall sleep quality. Results Five participants (45%) reported a reduction in symptom frequency and severity after hypnosis treatment. All five participants attributed at least some of the improvement to hypnosis treatment. Most participants (63%) observed post-treatment improvements in their overall sleep quality. No participants reported adverse effects of hypnosis. Conclusion Results suggest hypnosis-based adjunctive treatment may be effective for alleviating subjective sleep disturbances. The findings serve as preliminary support for further randomly controlled trials in larger samples. Support (if any):

scholarly journals Investigating the Transition of Pre-Symptomatic to Symptomatic Huntington’s Disease Status Based on Omics Data

2020 ◽  
Vol 21 (19) ◽  
pp. 7414
Author(s):  
Christiana C. Christodoulou ◽  
Margarita Zachariou ◽  
Marios Tomazou ◽  
Evangelos Karatzas ◽  
Christiana A. Demetriou ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Transforming Growth Factor Beta ◽  
Kinase Activity ◽  
Transforming Growth Factor ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Binding Protein ◽  
Biological Data ◽  
Disease Stage

Huntington’s disease is a rare neurodegenerative disease caused by a cytosine–adenine–guanine (CAG) trinucleotide expansion in the Huntingtin (HTT) gene. Although Huntington’s disease (HD) is well studied, the pathophysiological mechanisms, genes and metabolites involved in HD remain poorly understood. Systems bioinformatics can reveal synergistic relationships among different omics levels and enables the integration of biological data. It allows for the overall understanding of biological mechanisms, pathways, genes and metabolites involved in HD. The purpose of this study was to identify the differentially expressed genes (DEGs), pathways and metabolites as well as observe how these biological terms differ between the pre-symptomatic and symptomatic HD stages. A publicly available dataset from the Gene Expression Omnibus (GEO) was analyzed to obtain the DEGs for each HD stage, and gene co-expression networks were obtained for each HD stage. Network rewiring, highlights the nodes that change most their connectivity with their neighbors and infers their possible implication in the transition between different states. The CACNA1I gene was the mostly highly rewired node among pre-symptomatic and symptomatic HD network. Furthermore, we identified AF198444 to be common between the rewired genes and DEGs of symptomatic HD. CNTN6, DEK, LTN1, MST4, ZFYVE16, CEP135, DCAKD, MAP4K3, NUPL1 and RBM15 between the DEGs of pre-symptomatic and DEGs of symptomatic HD and CACNA1I, DNAJB14, EPS8L3, HSDL2, SNRPD3, SOX12, ACLY, ATF2, BAG5, ERBB4, FOCAD, GRAMD1C, LIN7C, MIR22, MTHFR, NABP1, NRG2, OTC, PRAMEF12, SLC30A10, STAG2 and Y16709 between the rewired genes and DEGs of pre-symptomatic HD. The proteins encoded by these genes are involved in various biological pathways such as phosphatidylinositol-4,5-bisphosphate 3-kinase activity, cAMP response element-binding protein binding, protein tyrosine kinase activity, voltage-gated calcium channel activity, ubiquitin protein ligase activity, adenosine triphosphate (ATP) binding, and protein serine/threonine kinase. Additionally, prominent molecular pathways for each HD stage were then obtained, and metabolites related to each pathway for both disease stages were identified. The transforming growth factor beta (TGF-β) signaling (pre-symptomatic and symptomatic stages of the disease), calcium (Ca2+) signaling (pre-symptomatic), dopaminergic synapse pathway (symptomatic HD patients) and Hippo signaling (pre-symptomatic) pathways were identified. The in silico metabolites we identified include Ca2+, inositol 1,4,5-trisphosphate, sphingosine 1-phosphate, dopamine, homovanillate and L-tyrosine. The genes, pathways and metabolites identified for each HD stage can provide a better understanding of the mechanisms that become altered in each disease stage. Our results can guide the development of therapies that may target the altered genes and metabolites of the perturbed pathways, leading to an improvement in clinical symptoms and hopefully a delay in the age of onset.

Sleep disturbances and severity of Huntington's disease

Neurology ◽  
1985 ◽  
Vol 35 (11) ◽  
pp. 1672-1672 ◽  
Author(s):  
P. Hansotia ◽  
R. Wall ◽  
J. Berendes
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Sleep Disturbances

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease

2014 ◽  
Vol 44 (15) ◽  
pp. 3341-3356 ◽  
Author(s):  
R. C. Wolf ◽  
F. Sambataro ◽  
N. Vasic ◽  
M. S. Depping ◽  
P. A. Thomann ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Motor Function ◽  
Neural Activity ◽  
Resting State ◽  
Brain Atrophy ◽  
Clinical Symptoms ◽  
Resting State Fmri ◽  
Cognitive Networks ◽  
The Impact

Background.Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's ‘resting state’ could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients.Method.Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and ‘biological parametric mapping’ analyses to investigate the impact of atrophy on neural activity.Results.Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition.Conclusions.This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

scholarly journals Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Isabelle Arnoux ◽  
Michael Willam ◽  
Nadine Griesche ◽  
Jennifer Krummeich ◽  
Hirofumi Watari ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Clinical Symptoms ◽  
Activity Patterns ◽  
Disease Onset ◽  
Network Activity ◽  
Critical Window ◽  
Functional Changes ◽  
Window Of Vulnerability

Catching primal functional changes in early, ‘very far from disease onset’ (VFDO) stages of Huntington’s disease is likely to be the key to a successful therapy. Focusing on VFDO stages, we assessed neuronal microcircuits in premanifest Hdh150 knock-in mice. Employing in vivo two-photon Ca2+ imaging, we revealed an early pattern of circuit dysregulation in the visual cortex - one of the first regions affected in premanifest Huntington’s disease - characterized by an increase in activity, an enhanced synchronicity and hyperactive neurons. These findings are accompanied by aberrations in animal behavior. We furthermore show that the antidiabetic drug metformin diminishes aberrant Huntingtin protein load and fully restores both early network activity patterns and behavioral aberrations. This network-centered approach reveals a critical window of vulnerability far before clinical manifestation and establishes metformin as a promising candidate for a chronic therapy starting early in premanifest Huntington’s disease pathogenesis long before the onset of clinical symptoms.

scholarly journals Rotigotine Objectively Improves Sleep in Parkinson’s Disease: An Open-Label Pilot Study with Actigraphic Recording

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Giovanna Calandra-Buonaura ◽  
Pietro Guaraldi ◽  
Andrea Doria ◽  
Stefano Zanigni ◽  
Stefania Nassetti ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pilot Study ◽  
Motor Activity ◽  
Sleep Quality ◽  
Sleep Disturbances ◽  
Open Label ◽  
Sleep Complaints ◽  
Objective Evidence ◽  
Rotigotine Treatment

Sleep disturbances represent important predictors of poor quality of life (QoL) in Parkinson’s disease (PD). This open-label pilot study aimed to objectively assess, by means of actigraphic recording, effect of rotigotine on sleep in PD patients with self-reported sleep complaints. 15 PD patients underwent one-week actigraphic recording before (T0) and during (T1) rotigotine treatment, which was titrated to the dose subjectively improving motor symptoms (4–8 mg/24 h). Sleep disturbances, daytime sleepiness, cognitive performance, QoL, and depression were also evaluated with questionnaires. Actigraphic recordings showed a significant reduction in nocturnal motor activity and mean duration of wake episodes after sleep onset during rotigotine treatment compared to baseline. In 10 patients presenting objective evidence of poor sleep quality at T0 (sleep efficiency ≤ 85%), rotigotine also significantly improved other sleep parameters and further reduced nocturnal motor activity and mean duration of wake episodes. A significant decrease in number and duration of daytime sleep episodes was also observed at T1. Finally we confirmed that rotigotine significantly improves perceived sleep quality and QoL. Our study showed for the first time that rotigotine is associated with an objective improvement of nocturnal and diurnal sleep disturbances in PD patients with self-reported sleep complaints. This study is registered with AIFA-observational study registry number 12021.

scholarly journals Genomic architecture differences at the HTT locus underlie symptomatic and pre-symptomatic cases of Huntington’s disease.

F1000Research ◽  
2019 ◽  
Vol 7 ◽  
pp. 1757
Author(s):  
Matthew Salter ◽  
Ryan Powell ◽  
Jennifer Back ◽  
Francis Grand ◽  
Christina Koutsothanasi ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Clinical Symptoms ◽  
Disease Onset ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Healthy Controls ◽  
Chromosome Conformation ◽  
Chromatin Architecture ◽  
Patient Groups

Background:Huntington’s disease (HD) is a progressive neurodegenerative condition that causes degeneration of neurons in the brain, ultimately leading to death. The root cause of HD is an expanded trinucleotide cytosine-adenine-guanine (CAG) repeat in the “huntingtin gene” (HTT). While there is a rough correlation between the number of CAG repeats and disease onset, the development of clinical symptoms can vary by decades within individuals and little is known about this pre-symptomatic phase.Methods:Using peripheral blood samples from HD patients and healthy controls we usedEpiSwitch™, a validated high-resolution industrial platform for the detection of chromosome conformations, to assess chromatin architecture in the immediate vicinity of theHTTgene. We evaluated chromatin conformations at 20 sites across 225 kb of theHTTlocus in healthy controls, verified symptomatic HD patients (CAG, n>39) and patients with CAG expansions who had not yet manifested clinical symptoms of HD.Results:Discrete chromosome conformations were observed across the patient groups. We found two constitutive interactions (occurring in all patient groups) and seven conditional interactions which were present in HD, but not in healthy controls. Most important, we observed three conditional interactions that were present only in HD patients manifesting clinical symptoms (symptomatic cases), but not in presymptomatic cases. Of the patients in the symptomatic HD cohort, 86% (6 out of 7) demonstrated at least one of the specific chromosome conformations associated with symptomatic HD.Conclusion:Our results provide the first evidence that chromatin architecture at theHTTlocus is systemically altered in patients with HD, with conditional differences between clinical stages. Given the high clinical need in having a molecular tool to assess disease progression in HD, these results strongly suggest that the non-invasive assessment of chromosome conformation signatures can be a valuable addition to prognostic assessment of HD patients.

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