Motor Changes in Presymptomatic Huntington Disease Gene Carriers

Siemers, Eric; Foroud, Tatiana; Dj, Bill; Sorbel, J.; Ja, Norton; Me, Hodes; G, Niebler; Pm, Conneally; Jc, Christian

doi:10.1001/archneur.1996.00550060029011

Cited by 61 publications

(54 citation statements)

References 16 publications

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“…Although some studies have shown processing speed to be the hallmark of early cognitive decline in HD (Kirkwood et al, 2000;Kirkwood et al, 1999;Siemers et al, 1996), others have shown different patterns of impairment. Lawrence et al (1998) examined cognitive task performance in 54 at-risk carriers of the HD mutation and found that they performed significantly worse than noncarriers on tasks of cognitive set-shifting and fluency, deficits attributed to inhibitory control mediated by striatofrontal circuitry.…”

Section: Discussionmentioning

confidence: 99%

Modeling longitudinal change in motor and cognitive processing speed in presymptomatic Huntington's disease

Maroof

Gross

Brandt

2011

Journal of Clinical and Experimental Neuropsychology

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Persons who have the genetic mutation responsible for Huntington's disease (HD) have been shown to exhibit lower cognitive test scores years prior to manifest HD. Most studies have examined cognitive performance in presymptomatic persons by using estimated times to manifest HD based on published algorithms. We followed 19 gene-positive persons who were presymptomatic using an objective criterion (i.e., Quantified Neurological Exam score ≤ 10) at baseline for up to 21 years (median = 5 years) with periannual neuropsychological assessments until a diagnosis of manifest HD. Results showed that our tests of information- and psychomotor-processing speed that place minimal demands on cognition, worsening performance became evident 5-10 years prior to the development of manifest HD. In conclusion, cognitive decline precedes motor signs in HD and may be an important target in clinical trials and early intervention. Cognitive test scores may also improve the ability to predict disease onset among gene mutation carriers and help families to better plan for potential personal and economic hardship.

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Section: Discussionmentioning

confidence: 99%

Modeling longitudinal change in motor and cognitive processing speed in presymptomatic Huntington's disease

Maroof

Gross

Brandt

2011

Journal of Clinical and Experimental Neuropsychology

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“…Furthermore, the saccadometry research tool has proved valuable in separating premanifest, manifest, and controls who showed an increased incidence of early saccades with unusually short latencies. [84][85][86][87][88][89] Manifest patients early in the course of their disease, exhibit reduced saccadic velocity, 78,81,90 impaired initiation of saccades, an increase in the frequency of square-wave jerks, and an increase in saccadic latencies, that is greater for voluntary than reflexive saccades. They have excessive distractibility during attempted fixation, even when specifically instructed to maintain fixation on a centrally located target.…”

Section: Clinical Ocular Motor Findingsmentioning

confidence: 99%

Ocular motor abnormalities in neurodegenerative disorders

Antoniades

Kennard

2014

Eye

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Eye movements are a source of valuable information to both clinicians and scientists as abnormalities of them frequently act as clues to the localization of a disease process. Classically, they are divided into two main types: those that hold the gaze, keeping images steady on the retina (vestibulo-ocular and optokinetic reflexes) and those that shift gaze and redirect the line of sight to a new object of interest (saccades, vergence, and smooth pursuit). Here we will review some of the major ocular motor abnormalities present in neurodegenerative disorders.

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“…Firstly it seems that the impairment in voluntary movement is closely related to the functional disability experienced by patients [2,7,20,21], suggesting that a faithful marker of the movement abnormality may also reveal functional status. Secondly, motor deficits can be detected early in the disease process, even in presymptomatic gene-positive subjects [8,9,19], raising the possibility that an objective marker might be of use even in early disease. And finally, motor deficits progress in line with other clinical measures of disease stage [17,20,21], and correlate with the loss of striatal D2 binding on raclopride 11C PET [18].…”

Section: Introductionmentioning

confidence: 99%

Hand tapping: A simple, reproducible, objective marker of motor dysfunction in Huntington’s disease

Michell

Goodman

Silva³

et al. 2008

J Neurol

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Huntington's disease (HD) is a severe neurodegenerative condition in which the impairment in voluntary movement is related to functional disability. Clinical assessment of motor deficit currently relies largely on subjective rating scales without objective measurement. We have developed a quick and easy-to-use hand tapping device that enables measurement of (a) the number of taps in 30 seconds, (b) variability in tapping rhythm and (c) fatigue over the testing period. Initial cross-sectional testing of 178 consecutive HD clinic patients using an early model of the device showed that the total number of taps in 30 seconds correlated with the motor UHDRS (Spearmann's rho, r(s) = -0.81, p < 0.0001) and independence scores (r(s) = 0.78, p = 0.01). Longitudinal data from a small cohort followed over 10 years reveals a correlation between total number of taps in 30 seconds and motor UHDRS over time (rs = -0.49, p < 0.001), and suggests the technique may provide an objective measure of disease progression. Further tests on 15 HD patients and 9 controls were repeated three times in a single day using an updated device. The HD group made significantly fewer taps in 30 seconds (median HD = 79, control = 104, p = 0.009) and had greater variability of inter-tap interval (mean interdecile range HD = 148, control = 56, p = 0.016) compared to controls. Both the total number of taps and variability of inter-tap interval correlated with motor UHDRS. Of vital importance for any potential marker of disease progression is that these tapping parameters were reproducible with repeated measurement. Given that hand tapping parameters differ between HD and control populations, they correlate with motor UHDRS over time and are reproducible, we propose that assessment of hand tapping represents a useful objective adjunct to the clinical assessment of HD patients.

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Motor Changes in Presymptomatic Huntington Disease Gene Carriers

Abstract: These results suggest that subtle subclinical changes in motor function are present in presymptomatic individuals who have inherited the HD allele.

Cited by 61 publications

References 16 publications

Modeling longitudinal change in motor and cognitive processing speed in presymptomatic Huntington's disease

Modeling longitudinal change in motor and cognitive processing speed in presymptomatic Huntington's disease

Ocular motor abnormalities in neurodegenerative disorders

Hand tapping: A simple, reproducible, objective marker of motor dysfunction in Huntington’s disease

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