Neurocardiovascular pathology in pre‐manifest and early‐stage Huntington's disease

Abstract

These results suggest that higher cardiovascular risks and target-organ damage are present even in pre-manifest patients. Although larger studies are needed to confirm these findings, clinicians should consider these results in the cardiovascular management of patients with HD.

Cardiac mTORC1 Dysregulation Impacts Stress Adaptation and Survival in Huntington’s Disease

“…Epidemiological studies report a higher incidence of heart failure in HD patients compared to unaffected age-matched controls ( Abildtrup and Shattock, 2013 ; CDC, 1994 ), and HD patient heart size is decreased at autopsy ( Myers et al, 1998 ). A recent study specifically looking for cardiovascular disease risk factors found increased risk even in premanifest HD gene carriers ( Bellosta Diago et al, 2018 ). However, the pathogenic mechanisms underlying these phenotypes have remained elusive and may include autonomic circuit degeneration within the CNS, intrinsic cardiac mHTT toxicity, and other systemic abnormalities.…”

Heart rate variability and falls in Huntington’s disease

“…However, additional research should test this hypothesis A relevant result of the study was the demonstration of the association between the decreases in parasympathetic prevalence measured by HRV and be a recurrent faller independently of orthostatic phenomena. A possible explanation of the association would be a state of reactivity (hyperarousal), due to a well-determined early hyper-sympathetic state in HD [15][16][17], which in turn would be associated with having a greater awareness of the motor disability in tasks that challenge balance and potentially translate as fear of falling (FoF) [48]. Within this framework, another hypothesis states that the activity of the autonomic nervous system is a major component of the emotional response to stress, with large differences ranging from undifferentiated excitation to the recognition of a highly specific response for certain stressful emotions such as the fear [49].…”

“…ANS dysfunctions in HD population have been previously identified [10][11]. Most reports showed early sympathetic hyperactivity in the HD population [10,[12][13][14][15][16]. The most likely mechanism underlying these findings is an apoptosis-induced structural defect in the central autonomic network, such as the limbic system, the brainstem, or the hypothalamus [17][18].…”

Evidence of cardiac electrical remodeling in patients with Huntington disease

“…Nocturnal dipping is part of this normal circadian pattern, and its absence is associated with more severe end‐organ damage and increased risk of cardiovascular events. Recently, Bellosta Diago and coworkers published a study demonstrating PHD and EHD subjects to be more likely nondippers than their healthy controls (Bellosta Diago et al, 2018). Nocturnal dipping is a phenomenon describing a normal blood pressure decrease during sleep.…”