Abstract
Background:
Anosognosia, or unawareness of illness of deficits, has been observed in Huntington’s disease (HD) in relation to motor and cognitive signs and symptoms. Most studies of awareness in HD have used self-report questionnaire methodology rather than asking patients to report on their symptoms in real-time. The two studies in which patients were asked about their chorea in real-time had small sample sizes and only examined patients early in disease progression.
Objective:
To examine awareness of chorea in real-time in HD patients across a broad range of disease progression.
Methods:
Fifty HD patients across motor and cognitive impairment severity were asked if they noticed any involuntary movements after completing a simple working memory task used to elicit chorea. A movement disorders specialist rated the presence or absence of chorea while the patients completed the task. Disagreement between the patient and movement disorders specialist’s ratings was considered to be an indicator of unawareness.
Results:
Approximately 46% of patients who exhibited chorea did not report chorea. Eighty-eight percent of participants who acknowledged chorea did not report chorea in all parts of the body that chorea was observed.
Conclusions:
HD patients demonstrate unawareness of chorea across cognitive and motor sign severity.
INTRODUCTION
Huntington’s disease (HD) is a genetic, neurodegenerative condition that impacts motor and cognitive brain systems [1]. Anosognosia, or unawareness of illness or deficits, has been observed in relation to the motor signs of HD, such as chorea [2, 3]. Chorea is a hyperkinetic movement disorder that is characterized by unpredictable, involuntary movements that occur randomly throughout the body [4]. While clinically it has been accepted that patients are unaware of chorea, there have been few empirical studies in HD examining this phenomenon. In clinical settings, unawareness in HD is associated with delay in diagnosis and access to treatment, safety concerns, and increased caregiver burden [5], thus making it an important topic to investigate.
Past research has shown that in general, HD patient self-report of involuntary movements is unrelated to objective measures of motor or cognitive functioning [2, 3]. Patients also underestimate chorea compared with informant report [6]. These studies involved asking patients to provide retrospective report of their chorea, rather than asking them about chorea in real-time. Theories of awareness suggest that differences in awareness can manifest when patients provide self-report of their current functioning versus when they are confronted with evaluating their functioning when completing a task [7], which also has been demonstrated in HD [8]. Therefore, there may be differences in awareness when HD patients are asked to provide a self-report on their history of motor functioning versus when they are asked to evaluate their motor functioning in real-time. There have only been two studies that have involved asking patients to monitor their chorea in real-time rather than relying on retrospective report. One study involved asking nine HD patients if they were aware of involuntary movement while performing motor tasks, which included standing, walking, finger-tapping, and hand pronation-supination. A negative relationship was found between awareness and motor impairment as well as disease duration. However, only two participants in the sample were aware of chorea and only those with minimal cognitive impairment were included [9]. Another study used a videotaped interview to compare early HD patient report of chorea in real-time to observer-rated chorea. Gene positive premanifest participants and healthy volunteers were interviewed in the same manner except they were asked about normal involuntary movements such as twitches and postural changes. Unawareness of involuntary movements was observed in almost all participants, including the healthy controls, suggesting that unawareness of involuntary movement may not be pathological [10].
The purpose of this study was to replicate the finding that HD patients are unaware of their chorea in real-time while completing a task used to elicit chorea in a larger sample with a larger range of cognitive and motor impairment severity than previous studies [9, 10].
MATERIALS AND METHODS
Participants
Fifty participants with a diagnosis of HD were recruited from the Huntington’s Disease Society of America’s (HDSA) Center of Excellence Clinic at the University of South Florida. The HD diagnosis was defined as having a rating of a “4” on the Unified Huntington’s Disease Rating Scale (UHDRS) Diagnostic Confidence Interval (“motor abnormalities that are unequivocal signs of HD (≥99% confidence)”) [11] and either genetic testing with a positive result for the expanded CAG repeat or a family history of HD with clinical confirmation by a movement disorder specialist. Thirty-eight individuals were genetically tested and 12 had a positive family history of HD. The 12 participants who were diagnosed through clinical confirmation were included to maximize the number of participants in the study.
Twenty-two participants were prescribed medications thought to impact motor symptoms [12] (15 on Risperidone, 1 on Tetrabenazine, 1 on Haloperidol, 3 on Olanzapine, and 2 on Pimozide). All participants were 18 years of age or older, did not have neurological diagnoses other than HD, and had the capacity to consent as determined by study staff. The study was approved and data were obtained in compliance with the regulations of the University of South Florida Institutional Review Board. See Table 1 for Participant Characteristics.
Participant Characteristics
Measures
Unified Huntington’s Disease Rating Scale (UHDRS) – Motor Scale is a 15-category neurological scale, which includes a measure of chorea, with higher ratings indicating greater motor impairment severity. High internal consistency (Cronbach’s α= 0.95) and intercorrelations between domains of the UHDRS have been found. The UHDRS has high interrater reliability (intraclass correlation coefficient = 0.94 for total motor score). Scores range from 0 to 124.
Montreal Cognitive Assessment (MoCA) [14] is a cognitive screening measure that includes tasks of visuospatial abilities/executive function, naming, memory (delayed recall), attention, language, abstraction, and orientation. It is scored on a 30-point scale, with a score of 26 or above indicating normal performance. Test-retest reliability has been reported to be r = 0.92 with adequate internal consistency (Cronbach’s α= 0.83). In this sample, internal consistency was adequate (Cronbach’s α= 0.76).
Procedures
Capacity to consent was evaluated for all patients prior to enrolling in the study. Individuals with ≥22 on the MoCA, a cut-off used in previous research [15], were considered capable of providing consent for the study. Individuals who scored <22 were assessed by a healthcare professional on the study team. These patients had to demonstrate that they understood key points of the study, the risks and benefits of the study, and express an understanding that their decision to participate in the study was voluntary.
A certified, trained movement disorders specialist administered the UHDRS motor exam. Chorea can be elicited or is worsened when patients engage in cognitively demanding tasks, such as a working memory task [10, 16]. To elicit chorea, participants were asked to close their eyes, hold out their arms in front of themselves, and count backward from 20. They were not corrected if they counted incorrectly. The task used in this current study was designed to be simple so that it can be used efficiently in both clinical and research settings. The movement disorders specialist rated chorea while the patient completed the working memory task. After completion of the task, another study staff member immediately asked the participant, “Did you notice any involuntary movement during the task?” If the participant answered yes, he or she was asked, “Where exactly? Which part of your body moved?” Patient responses were coded in concordance with the UHDRS motor exam (i.e., facial, buccal-oral-lingual (BOL), trunk, right upper extremity (RUE), left upper extremity (LUE), right lower extremity (RLE), left lower extremity (LLE)). For example, if a patient reported that their left arm moved, the response was coded as the participant being aware of left upper extremity chorea. Patient responses were compared to the movement disorder specialist ratings of chorea for each body part on the UHDRS motor exam.
RESULTS
Forty-seven out of the fifty participants exhibited chorea. The three participants without chorea demonstrated other positive motor signs (e.g., oculomotor) and were removed from further analyses. Of the remaining patients, twenty-two participants (46.8%) did not acknowledge any chorea. Twenty-six (55.33%) participants acknowledged chorea. Of the 26 participants who acknowledged chorea, 23 (88%) did not notice chorea in all parts of the body that chorea was observed, suggesting they were only partially aware of chorea. The body part associated with the largest proportion of patients who were unaware of chorea was facial chorea. Patients were most aware of left upper extremity and right upper extremity chorea. The proportion of those aware of facial chorea vs. left upper extremity chorea, χ2(1) = 6.2, p < 0.05, and right upper extremity chorea χ2(1) = 6.5, p < 0.05, were both statistically different (see Table 2).
Unawareness of Chorea by Body Part
BOL, Buccal-Oral-Lingual; RUE, right upper extremity; LUE, left upper extremity; RLE, right lower extremity; LLE, left lower extremity.
When comparing the full/partial awareness and no awareness groups, there were no differences in demographic variables, including age, t(45) = 0.05, p = 0.96, education, t(45) = 0.35, p = 0.72, age at diagnosis, t(41) = 0.04, p = 0.97, duration of illness, t(41) = 0.45, p = 0.65, UHDRS motor scores, t(45) = 0.32, p = 0.75, overall cognitive ability as measured by the MoCA scores, t(45) = 0.32, p = 0.75, or whether or not medications for chorea were prescribed, χ2(5) = 4.4, p = 0.5.
DISCUSSION
The purpose of this study was to replicate past findings that HD patients have limited awareness of chorea in real-time given the few empirical studies demonstrating this effect. The current study also included a larger sample with a larger range of disease severity than in previous studies. Patients were questioned about the presence of chorea directly after a simple working memory task that was used to elicit chorea as part of the standard neurological exam. During the task, patients were asked to close their eyes so that they did not have any visual feedback of their chorea. Half of the participants who exhibited chorea were completely unaware of any movements at all. Of those who did acknowledge chorea, most patients were not able to identify the location of the chorea in all parts of their body where chorea was present. This supports past research that has shown that patients who demonstrate motor signs of HD may not complain of motor symptoms [2, 3]. There was no difference in cognitive functioning when comparing participants with no awareness and partial/full awareness of their chorea, which is consistent with past research showing no relationship between cognitive functioning and awareness of chorea in HD [3] or awareness of dyskinesia in Parkinson’s disease [17]. While the study included participants with a broad range of cognitive and motor functioning, the majority of our sample was cognitively impaired (average MoCA score of 21) with only 7 participants performing in the normal range of cognitive functioning on the MoCA. This sample characteristic may also explain this negative finding. It is possible that prefrontal dysfunction through degeneration of frontal-striatal pathways and associated executive dysfunction plays a role in anosognosia in HD [5, 20]. However, Justo and colleagues found that healthy volunteers and individuals with premanifest HD were also unaware of involuntary movements despite performing significantly better on tasks of executive functioning compared to the early HD participants, suggesting that cognitive impairment may not be the sole reason for unawareness of chorea in HD. The authors of the study also suggested that not all unawareness of involuntary movements is pathological [10]. However, the natural unawareness of involuntary movements that do occur in healthy individuals could potentially turn pathological for persons with HD as the disease progresses if the unawareness causes problems for safety and care, which still makes this an important issue to identify in patients with HD.
For those who acknowledged chorea, most did not acknowledge movement in all parts of the body affected by chorea, suggesting they were not in denial of their involuntary movement overall; they were unable to recognize it in all parts of their body. Some suggest that there is a physiological component involved in unawareness of chorea; patients fail to acknowledge chorea because they do not have a subjective experience of it [3, 20]. One of the strengths of our study’s design is that patients did not have visual feedback of their chorea, which supports the theory that patients do not perceive the sensation of chorea. However, visual feedback in the moment may not help awareness, as past studies have allowed for visual feedback [10] and otherwise are primarily based on patient self-report of chorea that they experience day-to-day in which they do have visual feedback. Small studies have also shown that patients who are unaware of the presence of chorea or dyskinesia when asked about it in real-time acknowledge the presence of the movements when they are shown a videotape of themselves [18, 19]. Future research can explicitly examine if there are differences in perception of chorea with visual feedback.
There are some limitations of this study. Perhaps patients were unaware of their chorea because they were focused on the working memory task and were not asked to attend to involuntary movements. Patients with HD have impaired performance in dual-task paradigms because of diminished attentional resources [21]. This study may have benefited from asking patients about their chorea in real-time before the working memory task. Additionally, patients were asked about their motor functioning with an open-ended question and those who were identified as partially aware may have not have considered all of the possible options (such as facial chorea). Future studies can ask patients explicitly about each body part corresponding to the UHDRS motor exam. Finally, as mentioned above, most of the participants in this study were cognitively impaired. Future studies may benefit from including an even larger range of disease severity, with both individuals with premanifest HD and early HD with less severe cognitive impairment.
Overall, this study provides additional empirical evidence and substantiates further that HD patients across motor and cognitive severity are unaware of their chorea.
CONFLICT OF INTEREST
The authors report no conflict of interests or financial disclosures.
Footnotes
ACKNOWLEDGMENTS
We thank Kelly Elliott, RN for help with recruitment for this project.
This research was unfunded.