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. 2021 Mar:231:102775.
doi: 10.1016/j.autneu.2021.102775. Epub 2021 Feb 5.

Autonomic dysregulation as an early pathologic feature of Huntington Disease

Jordan L Schultz  1 , Lyndsay A Harshman  2 , John A Kamholz  3 , Peg C Nopoulos  4
Affiliations

Autonomic dysregulation as an early pathologic feature of Huntington Disease

Jordan L Schultz et al. Auton Neurosci. 2021 Mar.

Abstract

Objective: Autonomic nervous system (ANS) dysfunction has been described in adults with motor-manifest Huntington's Disease (HD) or those who are near their predicted motor onset. It is unclear if ANS dysfunction is present years prior to the onset of motor symptoms of HD. To bridge this gap in knowledge, we compared crude markers of ANS function between children with the gene-expansion that causes HD (GE group) who were decades from their predicted motor onset and gene-non-expanded children (GNE group).

Methods: We included participants from the Kids-HD study who were <18 years old. Linear mixed effects regression models were constructed that controlled for sex, age, and BMI, and included a random effect per participant and per family. We compared resting heart rate (rHR), core body temperature (CBT), systolic blood pressure (SBP), and diastolic blood pressure (DBP) between the GE (n = 84) and GNE (n = 238) groups. We then grouped participants from the GE group based on their predicted years to onset (YTO) and compared their vital signs to the GNE group.

Results: The GE group had higher rHR (∆ = 3.83, p = 0.0064), SBP (∆ = 2.38, p = 0.032), and CBT (∆ = 0.16, t = 2.92, p = 0.007). The mean rHR and CBT became significantly elevated compared to the GNE group in participants who had 15-25 YTO and those who had <15 YTO. The mean SBP of participants who had 25-35 YTO was significantly elevated compared to the GNE group.

Conclusion: ANS dysfunction in HD seems to occur approximately 20 years prior to the predicted onset of motor symptoms of HD.

Keywords: Autonomic nervous system; Blood pressure; Heart rate; Huntington Disease; Temperature.

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Conflict of interest statement

Conflicts of Interest:

Dr. Schultz reports no disclosures.

Dr. Harshman reports no disclosures.

Dr. Kamholz reports no disclosures

Dr. Nopoulos reports no disclosures.

Figures

Figure 1:
Figure 1:
There was a positive, statistically significant relationship between CAG repeat length and A) rHR and B) SBP amongst participants in the GE group. This relationship was not significant when evaluating CBT (C). Abbreviations: Bpm, beats per minute; CAG, Cytosine-Adenine-Guanine; CBT, Core Body Temperature; GE, Gene-Expanded; mmHg, Millimeters of mercury; rHR, Resting Heart Rate; SBP, Systolic blood pressure
Figure 2:
Figure 2:
The GNE group has similar rHR and CBT compared to participants in the >35 YTO and 25-35 YTO groups. However, participants in the 15-25 YTO group have a significantly elevated rHR and CBT compared to the GNE group. The participants in the <15 YTO group have an even higher mean-adjusted rHR and CBT compared to the GNE group (A-B). Similarly, mean SBP is similar amongst participants in the >35 YTO group and the GNE group; however, the participants in the 25-35 YTO group and the <15 YTO group have significantly elevated mean SBP compared to the GNE group. The 15-25 YTO group has a higher mean SBP compared to the GNE group, but the difference is not statistically significant (C). DBP increases in participants in the GE group as they near their predicted motor onset, but the difference from the GNE group never reaches statistical significance (D). Dots represent the adjusted group means and lines represent the standard error for each group. Abbreviations: *, p<0.05; **, p<0.01;***, p<0.001; Bpm, beats per minute; CAG, Cytosine-Adenine-Guanine; CBT, Core Body Temperature; DBP, Diastolic Blood Pressure; GE, Gene-Expanded; mmHg, Millimeters of mercury; rHR, Resting Heart Rate; SBP, Systolic blood pressure; YTO, years to onset
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