Huntington’s patients see day-to-day variation in symptoms, function
Once-daily evaluations may be better than real-time reports, findings suggest
People with Huntington’s disease have greater variations in disease symptoms and physical function between days than within each day, according to a study based on patient reports and objective data collected with a wrist-worn device in the U.S.
The findings suggest “it may be sufficient and reliable to evaluate symptoms once daily rather than using multiple real-time symptom reports over the course of the day,” the researchers wrote. “This approach could decrease participant burden and improve recruitment and compliance.”
The study, “Daily variation in symptoms and functioning in Huntington disease: Feasibility and variability,” was published in Parkinsonism & Related Disorders.
Huntington’s is caused by excessive repeats of a small section of the HTT gene that contains three DNA building blocks, called C, A, and G. While a healthy HTT gene has 10 to 35 CAG repeats, the region may be repeated 36 to more than 120 times in Huntington’s. The disease’s symptoms include chorea, or involuntary movements that can interfere with swallowing, speech, and walking, along with cognitive and psychiatric problems.
“Traditionally, clinical care and research rely on intermittent in-person assessments under constrained conditions in clinical or laboratory spaces,” the researchers wrote. “Such assessments offer a single snapshot of functioning, garnered under optimal conditions and may not accurately depict abilities in the home environment.”
Collecting clinical data from patients in their homes could offer a better picture of their state and be used as future outcome measures in clinical trials. However, “the day-to-day experience of symptoms and functioning are largely understudied in people with Huntington’s,” the researchers wrote.
Comparing symptoms, function evaluations
Here, researchers at the University of Michigan examined the day-to-day and within-a-day variability of symptoms and physical functioning in 52 adults with Huntington’s as part of a weeklong study.
Most patients (69.2%) had manifest disease, meaning they were already having symptoms, while the remaining 30.8% had pre-manifest Huntington’s, meaning they weren’t yet showing symptoms.
During the study, the participants wore the PRO-Diary wrist-worn device to passively collect objective physical activity and sleep data, and completed real-time symptom reports on chorea, sleep, fatigue, and anxiety three times a day. They also completed daily diaries each night regarding these symptoms, plus anger and depression, along with overall functioning, including physical activity, speech/swallowing, and social participation.
Completion rates ranged from 48% to 77% for the real-time symptom report and from 65% to 81% for the daily diaries. Compliance with the PRO-Diary device ranged between 64% and 78%. The device “offers a small screen and small buttons that require multiple presses to toggle a response,” wrote the researchers, who noted it’s possible “the higher rates of missing data among those with manifest [Huntington’s disease] may be in part due to chorea and dexterity loss.” Most participants had a low degree of missing data, while 11 (21.2%) “missed most of their assessments.”
The rates of missing data were generally higher among those with worse self-reported health-related quality of life and those with manifest relative to pre-manifest Huntington’s.
The variability of each participant’s symptoms in the real-time daily reports was higher between days (median of 1.9 to 4.4 standard deviations) than within each day (median of 0 to 2 standard deviations). Standard deviation measures how much a single measure deviates from the mean. For instance, the standard deviation for chorea was 1.89 between days and 0 within a day, with similar effects seen for anxiety (3.38 vs. 0) and fatigue (3.36 vs. 2.19).
“These findings argue against the reliability of (and need for) multiple within-day symptom probes in future [Huntington’s disease] studies,” the researchers wrote.
Worse chorea, fatigue, and anxiety reported in daily diaries were each associated with worse health-related quality of life for all survey measures. Worse chorea was also linked to less physical activity as assessed by the PRO-Diary device, while more anxiety and fatigue were associated with more social participation.
“In addition, on days when participants report worse-than-average fatigue and anxiety, they also report worse-than-average same-day sleep-related impairment,” the researchers wrote.
The pattern of self-reported chorea, anxiety, and fatigue weren’t consistent with objective and subjective assessments of physical activity and sleep, indicating the “inclusion of both types of estimates (subjective and objective) have value toward a comprehensive assessment,” they wrote. “Understanding the real-world challenges of using these technologies and intensive study designs in a disease such as [Huntington’s disease], with its physical and motor problems, will position us to successfully use them in personalized clinical care and research.”
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