Identification of an oculomotor biomarker of preclinical Huntington disease

Golding, Charlotte; Danchaivijitr, Chotipat; Hodgson, Timothy L.; Tabrizi, Sarah J.; Kennard, Christopher

doi:10.1212/01.wnl.0000218215.43328.88

Cited by 86 publications

(78 citation statements)

References 9 publications

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“…Initiation deficits of voluntary guided saccades, saccadic slowing, and delayed reflexive saccades were present. [84][85][86] When compared with controls, premanifest individuals also show impairment in the antisaccadic and memoryguided tasks and longer latencies, especially during the latter. 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.…”

Section: Clinical Ocular Motor Findingsmentioning

confidence: 97%

“…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%

“…Volitional saccades are also often hypometric. 84,93,94 In addition, saccadic hypometria has been documented in mildly affected HD patients. 78,[91][92][93][95][96][97][98][99] Later on in the disease, manifest patients usually begin to show more prominent slowing of saccades, as well as smooth pursuit deficits.…”

Section: Clinical Ocular Motor Findingsmentioning

confidence: 99%

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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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Section: Clinical Ocular Motor Findingsmentioning

confidence: 97%

Section: Clinical Ocular Motor Findingsmentioning

confidence: 99%

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Ocular motor abnormalities in neurodegenerative disorders

Antoniades

Kennard

2014

Eye

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“…[2][3][4][5][6][7] In addition, subtle oculomotor and other movement peculiarities and neuropsychiatric changes have been reported in some mutation-positive individuals prior to the onset of clinical signs and symptoms sufficient for diagnosis. [8][9][10][11][12] However, the search for presymptomatic changes in cognition among those with the huntingtin mutation has met with mixed results. Several investigations reported no significant differences in neuropsychological functioning between those with and those without the Huntington's disease mutation.…”

Section: Introductionmentioning

confidence: 99%

Neuropsychological Deficits in Huntington's Disease Gene Carriers and Correlates of Early "Conversion"

Brandt¹,

Inscore²,

Ward³

et al. 2008

Journal of Neuropsychiatry

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The authors examined whether the baseline cognitive functioning of 21 clinically normal huntingtin mutation carriers who developed manifest Huntington's disease on follow-up differed from that of 49 mutation carriers who remain asymptomatic over the same period in a longitudinal study. One hundred thirty-four gene-negative offspring of Huntington's disease patients were studied as well. Overall, there were no differences in cognitive test performance among the three groups. However, "converters" who developed signs of Huntington's disease within 8.6 years demonstrated poorer performance on the Wisconsin Card Sorting Test at baseline. People with the Huntington's disease mutation who are carefully examined neurologically and found to be asymptomatic have, at most, very minimal problem-solving impairment, and only if they are within a few years of clinical onset.Since the discovery of the genetic mutation responsible for Huntington's disease, 1 there have been many attempts to determine whether people who carry the mutation, but who are not yet clinically ill, can be distinguished from those without the mutation. Brain imaging studies have often demonstrated structural and/or functional abnormalities in the striatum in presymptomatic individuals. [2][3][4][5][6][7] In addition, subtle oculomotor and other movement peculiarities and neuropsychiatric changes have been reported in some mutation-positive individuals prior to the onset of clinical signs and symptoms sufficient for diagnosis. [8][9][10][11][12] However, the search for presymptomatic changes in cognition among those with the huntingtin mutation has met with mixed results. Several investigations reported no significant differences in neuropsychological functioning between those with and those without the Huntington's disease mutation. [13][14][15][16][17] Others, however, have found such differences. [8][9][10]18 Deficits in reaction time, psychomotor and processing speed, 10,18,[20][21][22] executive functioning, 23-25 spatial analysis and constructional praxis, 26 verbal fluency, 23 verbal memory, [26][27][28] and mental arithmetic 9,10 have all been reported among mutation carriers, albeit inconsistently.The discrepant findings among studies are due, in large part, to methodological differences. First, studies have varied in the degree of neurologic abnormality tolerated in the "asymptomatic" mutation-positive group. 29 While some researchers enrolled only persons with no, or very minimal, nonspecific neurological signs, 22,27 others included subjects with "major signs consistent with Huntington's disease." 8,9,20,28 In addition, some studies were of young mutation carriers who were almost certainly many years from disease onset, whereas others were of older subjects nearing the age of likely clinical onset. In those studies where NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript proximity to clinical onset was explicitly addressed, time to disease onset ("conversion") was most often estimated. 10,[15][16][17]28 The pre...

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“…1 A commonly used measure of cognitive inhibition is the antisaccade (AS) task, which requires suppression of a visually guided saccade toward a target and generation of voluntary saccade in the opposite direction. 2,3 The percentage of correct AS responses is sensitive to frontal lobe dysfunction in aging, 4 schizophrenia, [5][6][7][8] Huntington disease (HD), 9,10 and a variety of neurodegenerative dementias. [11][12][13] Despite the potential clinical utility of the AS task in evaluating neurologic function, current methods of evaluation are limited to informal bedside evaluation or the use of expensive eye-tracking equipment.…”

mentioning

confidence: 99%

Multicenter validation of a bedside antisaccade task as a measure of executive function

Hellmuth¹,

Mirsky²,

Heuer³

et al. 2012

Neurology

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Objective: To create and validate a simple, standardized version of the antisaccade (AS) task that requires no specialized equipment for use as a measure of executive function in multicenter clinical studies. Methods:The bedside AS (BAS) task consisted of 40 pseudorandomized AS trials presented on a laptop computer. BAS performance was compared with AS performance measured using an infrared eye tracker in normal elders (NE) and individuals with mild cognitive impairment (MCI) or dementia (n ϭ 33). The neuropsychological domain specificity of the BAS was then determined in a cohort of NE, MCI, and dementia (n ϭ 103) at UCSF, and the BAS was validated as a measure of executive function in a 6-center cohort (n ϭ 397) of normal adults and patients with a variety of brain diseases.

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Identification of an oculomotor biomarker of preclinical Huntington disease

Cited by 86 publications

References 9 publications

Ocular motor abnormalities in neurodegenerative disorders

Ocular motor abnormalities in neurodegenerative disorders

Neuropsychological Deficits in Huntington's Disease Gene Carriers and Correlates of Early "Conversion"

Multicenter validation of a bedside antisaccade task as a measure of executive function

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