Publications by authors named "Janet C Rucker"

94 Publications

Exploration of Rapid Automatized Naming and Standard Visual Tests in Prodromal Alzheimer Disease Detection.

J Neuroophthalmol 2021 May 17. Epub 2021 May 17.

Departments of Neurology (SZW, RNK, NM, LH, BJ, AC, JCR, SLG, TMW, AVM, and LJB), Population Health (RNK and LJB), and Ophthalmology (SZW, JCR, SLG, and LJB), New York University Grossman School of Medicine, New York, New York.

Background: Visual tests in Alzheimer disease (AD) have been examined over the last several decades to identify a sensitive and noninvasive marker of the disease. Rapid automatized naming (RAN) tasks have shown promise for detecting prodromal AD or mild cognitive impairment (MCI). The purpose of this investigation was to determine the capacity for new rapid image and number naming tests and other measures of visual pathway structure and function to distinguish individuals with MCI due to AD from those with normal aging and cognition. The relation of these tests to vision-specific quality of life scores was also examined in this pilot study.

Methods: Participants with MCI due to AD and controls from well-characterized NYU research and clinical cohorts performed high and low-contrast letter acuity (LCLA) testing, as well as RAN using the Mobile Universal Lexicon Evaluation System (MULES) and Staggered Uneven Number test, and vision-specific quality of life scales, including the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement. Individuals also underwent optical coherence tomography scans to assess peripapillary retinal nerve fiber layer and ganglion cell/inner plexiform layer thicknesses. Hippocampal atrophy on brain MRI was also determined from the participants' Alzheimer disease research center or clinical data.

Results: Participants with MCI (n = 14) had worse binocular LCLA at 1.25% contrast compared with controls (P = 0.009) and longer (worse) MULES test times (P = 0.006) with more errors in naming images (P = 0.009) compared with controls (n = 16). These were the only significantly different visual tests between groups. MULES test times (area under the receiver operating characteristic curve [AUC] = 0.79), MULES errors (AUC = 0.78), and binocular 1.25% LCLA (AUC = 0.78) showed good diagnostic accuracy for distinguishing MCI from controls. A combination of the MULES score and 1.25% LCLA demonstrated the greatest capacity to distinguish (AUC = 0.87). These visual measures were better predictors of MCI vs control status than the presence of hippocampal atrophy on brain MRI in this cohort. A greater number of MULES test errors (rs = -0.50, P = 0.005) and worse 1.25% LCLA scores (rs = 0.39, P = 0.03) were associated with lower (worse) NEI-VFQ-25 scores.

Conclusions: Rapid image naming (MULES) and LCLA are able to distinguish MCI due to AD from normal aging and reflect vision-specific quality of life. Larger studies will determine how these easily administered tests may identify patients at risk for AD and serve as measures in disease-modifying therapy clinical trials.
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http://dx.doi.org/10.1097/WNO.0000000000001228DOI Listing
May 2021

Dysfunctional mode switching between fixation and saccades: collaborative insights into two unusual clinical disorders.

J Comput Neurosci 2021 Apr 10. Epub 2021 Apr 10.

Laboratory of Sensorimotor Research, NEI, NIH, DHHS, Bethesda, MD, USA.

Voluntary rapid eye movements (saccades) redirect the fovea toward objects of visual interest. The saccadic system can be considered as a dual-mode system: in one mode the eye is fixating, in the other it is making a saccade. In this review, we consider two examples of dysfunctional saccades, interrupted saccades in late-onset Tay-Sachs disease and gaze-position dependent opsoclonus after concussion, which fail to properly shift between fixation and saccade modes. Insights and benefits gained from bi-directional collaborative exchange between clinical and basic scientists are emphasized. In the case of interrupted saccades, existing mathematical models were sufficiently detailed to provide support for the cause of interrupted saccades. In the case of gaze-position dependent opsoclonus, existing models could not explain the behavior, but further development provided a reasonable hypothesis for the mechanism underlying the behavior. Collaboration between clinical and basic science is a rich source of progress for developing biologically plausible models and understanding neurological disease. Approaching a clinical problem with a specific hypothesis (model) in mind often prompts new experimental tests and provides insights into basic mechanisms.
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http://dx.doi.org/10.1007/s10827-021-00785-6DOI Listing
April 2021

Haploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor.

Hum Mutat 2021 Jun 15;42(6):685-693. Epub 2021 Apr 15.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

De novo, heterozygous, loss-of-function variants were identified in Pou domain, class 4, transcription factor 1 (POU4F1) via whole-exome sequencing in four independent probands presenting with ataxia, intention tremor, and hypotonia. POU4F1 is expressed in the developing nervous system, and mice homozygous for null alleles of Pou4f1 exhibit uncoordinated movements with newborns being unable to successfully right themselves to feed. Head magnetic resonance imaging of the four probands was reviewed and multiple abnormalities were noted, including significant cerebellar vermian atrophy and hypertrophic olivary degeneration in one proband. Transcriptional activation of the POU4F1 p.Gln306Arg protein was noted to be decreased when compared with wild type. These findings suggest that heterozygous, loss-of-function variants in POU4F1 are causative of a novel ataxia syndrome.
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http://dx.doi.org/10.1002/humu.24201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162891PMC
June 2021

Sleep-deprived residents and rapid picture naming performance using the Mobile Universal Lexicon Evaluation System (MULES) test.

eNeurologicalSci 2021 Mar 2;22:100323. Epub 2021 Feb 2.

Departments of Neurology, New York University Grossman School of Medicine, New York, NY, USA.

Objective: The Mobile Universal Lexicon Evaluation System (MULES) is a rapid picture naming task that captures extensive brain networks involving neurocognitive, afferent/efferent visual, and language pathways. Many of the factors captured by MULES may be abnormal in sleep-deprived residents. This study investigates the effect of sleep deprivation in post-call residents on MULES performance.

Methods: MULES, consisting of 54 color photographs, was administered to a cohort of neurology residents taking 24-hour in-hospital call ( = 18) and a group of similar-aged controls not taking call (n = 18). Differences in times between baseline and follow-up MULES scores were compared between the two groups.

Results: MULES time change in call residents was significantly worse (slower) from baseline (mean 1.2 s slower) compared to non-call controls (mean 11.2 s faster) ( < 0.001, Wilcoxon rank sum test). The change in MULES time from baseline was significantly correlated to the change in subjective level of sleepiness for call residents and to the amount of sleep obtained in the 24 h prior to follow-up testing for the entire cohort. For call residents, the duration of sleep obtained during call did not significantly correlate with change in MULES scores. There was no significant correlation between MULES change and sleep quality questionnaire score for the entire cohort.

Conclusion: The MULES is a novel test for effects of sleep deprivation on neurocognition and vision pathways. Sleep deprivation significantly worsens MULES performance. Subjective sleepiness may also affect MULES performance. MULES may serve as a useful performance assessment tool for sleep deprivation in residents.
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http://dx.doi.org/10.1016/j.ensci.2021.100323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876539PMC
March 2021

Practical Approach to the Tele-Neuro-Ophthalmology and Neuro-Otology Visits: Instructional Videos.

J Neuroophthalmol 2021 03;41(1):10-12

Department of Neurology (RC, SNG, CC, SLG, LJB, JCR), New York University Grossman School of Medicine, New York, New York; Department of Ophthalmology (NR, LS), University of California San Francisco, San Francisco, California; Departments of Ophthalmology (SLG, LJB, JCR) and Population Health (LJB), New York University Grossman School of Medicine, New York, New York.

Abstract: A collection of instructional videos that illustrate a step by step approach to tele-neuro-ophthalmology and neuro-otology visits. These videos provide instruction for patient preparation for their video visit, patient and provider interface with an electronic medical record associated video platform, digital applications to assist with vision testing, and practical advice for detailed remote neuro-ophthalmologic and neuro-otologic examinations.
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http://dx.doi.org/10.1097/WNO.0000000000001195DOI Listing
March 2021

How sandbag-able are concussion sideline assessments? A close look at eye movements to uncover strategies.

Brain Inj 2021 Mar 2;35(4):426-435. Epub 2021 Feb 2.

Department of Neurology, NYU School of Medicine, New York, NY, United States.

Sideline diagnostic tests for concussion are vulnerable to volitional poor performance ("sandbagging") on baseline assessments, motivated by desire to subvert concussion detection and potential removal from play. We investigated eye movements during sandbagging versus best effort on the King-Devick (KD) test, a rapid automatized naming (RAN) task. Participants performed KD testing during oculography following instructions to sandbag or give best effort. Twenty healthy participants without concussion history were included (mean age 27 ± 8 years). Sandbagging resulted in longer test times (89.6 ± 39.2 s vs 48.2 ± 8.5 s, < .001), longer inter-saccadic intervals (459.5 ± 125.4 ms vs 311.2 ± 79.1 ms, < .001) and greater numbers of saccades (171.4 ± 47 vs 138 ± 24.2, < .001) and reverse saccades (wrong direction for reading) (21.2% vs 11.3%, < .001). Sandbagging was detectable using a logistic model with KD times as the only predictor, though more robustly detectable using eye movement metrics. KD sandbagging results in eye movement differences that are detectable by eye movement recordings and suggest an invalid test score. Objective eye movement recording during the KD test shows promise for distinguishing between best effort and post-injury performance, as well as for identifying sandbagging red flags.
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http://dx.doi.org/10.1080/02699052.2021.1878554DOI Listing
March 2021

Neuro-Ophthalmological Findings in Early Fatal Familial Insomnia.

Ann Neurol 2021 04 11;89(4):823-827. Epub 2021 Jan 11.

Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Fatal familial insomnia (FFI) is a rare inherited prion disease characterized by sleep, autonomic, and motor disturbances. Neuro-ophthalmological abnormalities have been reported at the onset of disease, although not further characterized. We analyzed video recordings of eye movements of 6 patients with FFI from 3 unrelated kindreds, seen within 6 months from the onset of illness. Excessive saccadic intrusions were the most prominent findings. In patients with severe insomnia, striking saccadic intrusions are an early diagnostic clue for FFI. The fact that the thalamus is the first structure affected in FFI also suggests its role in the control of steady fixation. ANN NEUROL 2021;89:823-827.
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http://dx.doi.org/10.1002/ana.26008DOI Listing
April 2021

The complexity of eye-hand coordination: a perspective on cortico-cerebellar cooperation.

Cerebellum Ataxias 2020 Nov 13;7(1):14. Epub 2020 Nov 13.

Department of Rehabilitation Medicine, NYU Grossman School of Medicine, New York, NY, USA.

Background: Eye-hand coordination (EHC) is a sophisticated act that requires interconnected processes governing synchronization of ocular and manual motor systems. Precise, timely and skillful movements such as reaching for and grasping small objects depend on the acquisition of high-quality visual information about the environment and simultaneous eye and hand control. Multiple areas in the brainstem and cerebellum, as well as some frontal and parietal structures, have critical roles in the control of eye movements and their coordination with the head. Although both cortex and cerebellum contribute critical elements to normal eye-hand function, differences in these contributions suggest that there may be separable deficits following injury.

Method: As a preliminary assessment for this perspective, we compared eye and hand-movement control in a patient with cortical stroke relative to a patient with cerebellar stroke.

Result: We found the onset of eye and hand movements to be temporally decoupled, with significant decoupling variance in the patient with cerebellar stroke. In contrast, the patient with cortical stroke displayed increased hand spatial errors and less significant temporal decoupling variance. Increased decoupling variance in the patient with cerebellar stroke was primarily due to unstable timing of rapid eye movements, saccades.

Conclusion: These findings highlight a perspective in which facets of eye-hand dyscoordination are dependent on lesion location and may or may not cooperate to varying degrees. Broadly speaking, the results corroborate the general notion that the cerebellum is instrumental to the process of temporal prediction for eye and hand movements, while the cortex is instrumental to the process of spatial prediction, both of which are critical aspects of functional movement control.
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http://dx.doi.org/10.1186/s40673-020-00123-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666466PMC
November 2020

Role for OCT in detecting hemi-macular ganglion cell layer thinning in patients with multiple sclerosis and related demyelinating diseases.

J Neurol Sci 2020 Dec 28;419:117159. Epub 2020 Sep 28.

Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA; Department of Ophthalmology, New York University Grossman School of Medicine, New York, NY, USA. Electronic address:

Objective: Investigations have found associations of homonymous thinning of the macular ganglion cell/ inner-plexiform layer (GCIPL) with demyelinating lesions in the post-chiasmal visual pathway among patients with multiple sclerosis (MS). Retinal thinning may also occur through retrograde trans-synaptic degeneration, a process by which lesions in post-geniculate visual pathway structures lead to thinning of the GCIPL across thalamic synapses. The purpose of our study was to determine the frequency of homonymous hemimacular thinning that occurs in association with post-chiasmal visual pathway demyelinating lesions in patients with MS and other demyelinating diseases.

Methods: Adult patients with demyelinating diseases (MS, neuromyelitis optica spectrum disorder [NMOSD], myelin oligodendrocyte glycoprotein antibody disease (anti-MOG)) who were participants in an ongoing observational study of visual pathway structure and function were analyzed for the presence of hemimacular GCIPL thinning on OCT scans. Brain MRI scans were examined for the presence of post-geniculate visual pathway demyelinating lesions.

Results: Among 135 participants in the visual pathway study, 5 patients (3.7%) had homonymous hemimacular GCIPL thinning. Eleven patients (8.1%) had a whole+half pattern of GCIPL thinning, characterized by hemimacular thinning in one eye and circumferential macular thinning in the contralateral eye. All but one patient with homonymous hemimacular thinning had demyelinating lesions in the post-geniculate visual pathway; however, these lesions were located in both cerebral hemispheres.

Conclusion: Homonymous hemimacular thinning in the GCIPL by OCT is associated with post-chiasmal visual pathway demyelinating lesions but it appears to be a relatively uncommon contributor to GCIPL loss. Patients with this pattern of GCIPL often fail to complain of hemifield visual loss. Future studies with prospective and detailed MR imaging may be able to more closely associate demyelinating lesions in anatomically appropriate regions of the post-chiasmal visual pathways with homonymous hemimacular thinning.
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http://dx.doi.org/10.1016/j.jns.2020.117159DOI Listing
December 2020

Concerning Vision Therapy and Ocular Motor Training in Mild Traumatic Brain Injury.

Ann Neurol 2020 11 16;88(5):1053-1054. Epub 2020 Sep 16.

Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA.

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http://dx.doi.org/10.1002/ana.25875DOI Listing
November 2020

Drs. Richard John Leigh and David Zee.

J Neuroophthalmol 2020 09;40(3):e17-e26

Departments of Neurology and Ophthalmology, New York University School of Medicine, New York, New York.

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http://dx.doi.org/10.1097/WNO.0000000000001018DOI Listing
September 2020

Tele-Neuro-Ophthalmology During the Age of COVID-19.

J Neuroophthalmol 2020 09;40(3):292-304

Department of Ophthalmology (KEL), Indiana University School of Medicine, Indianapolis, Indiana; Surgical Division (KEL), Ophthalmology Service, Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana; Circle City Neuro-Ophthalmology (KEL), Indianapolis, Indiana; Midwest Eye Institute (KEL), Indianapolis, Indiana; Departments of Neurology (MWK), Ophthalmology and Neurosurgery, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana; Departments of Neurology and Ophthalmology (JCR, SLG), New York University Langone Health, New York, New York; Department of Ophthalmology (JGO, JS), New York Presbyterian/Columbia University Medical Center, New York, New York; Departments of Neurology and Ophthalmology (LDS), New York Presbyterian/Columbia University Medical Center, New York, New York; Departments of Neurology and Ophthalmology (KMW), Casey Eye Institute, Oregon Health & Science University, Portland, Oregon; Operative Care Division (KMW), Ophthalmology Eye Care Service, Veteran Affairs Portland Health Care System, Portland, Oregon; Texas A&M University College of Medicine (AG), Temple, Texas; Department of Ophthalmology (SHB, NB, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Baylor College of Medicine (SW), Houston, Texas; Departments of Neurology and Ophthalmology (MJD, AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (NR), University of California San Francisco, San Francisco, California; Department of Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; Department of Ophthalmology (AGL), University of Texas Maryland Anderson Cancer Center, Houston, Texas; Department of Ophthalmology (AGL), Texas A&M University College of Medicine, Houston, Texas; Baylor College of Medicine and the Center for Space Medicine (AGL), Houston, Texas; University of Iowa Hospitals and Clinics (AGL), Iowa City, Iowa; and University of Buffalo (AGL), Buffalo, New York.

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http://dx.doi.org/10.1097/WNO.0000000000001024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418186PMC
September 2020

The SUN test of vision: Investigation in healthy volunteers and comparison to the mobile universal lexicon evaluation system (MULES).

J Neurol Sci 2020 08 30;415:116953. Epub 2020 May 30.

Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA; Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA; Department of Ophthalmology, New York University Grossman School of Medicine, New York, NY, USA. Electronic address:

Objective: Tests of rapid automatized naming (RAN) have been used for decades to evaluate neurological conditions. RAN tests require extensive brain pathways involving visual perception, memory, eye movements and language. To the extent that different naming tasks capture varied visual pathways and related networks, we developed the Staggered Uneven Number (SUN) test of rapid number naming to complement existing RAN tests, such as the Mobile Universal Lexicon Evaluation System (MULES). The purpose of this investigation was to determine values for time scores for SUN, and to compare test characteristics between SUN and MULES.

Methods: We administered the SUN and MULES tests to healthy adult volunteers in a research office setting. MULES consists of 54 color photographs; the SUN includes 145 single- and multi-digit numbers. Participants are asked to name each number or picture aloud.

Results: Among 54 healthy participants, aged 33 ± 13 years (range 20-66), the average SUN time score was 45.2 ± 8.3 s (range 30-66). MULES test times were 37.4 ± 9.9 s (range 20-68). SUN and MULES time scores did not differ by gender, but were greater (worse) among older participants for MULES (r = 0.43, P = .001). Learning effects between first and second trials were greater for the MULES; participants improved (reduced) their time scores between trials by 5% on SUN and 16% for MULES (P < .0001, Wilcoxon signed-rank test).

Conclusion: The SUN is a new vision-based test that complements presently available picture- and number-based RAN tests. These assessments may require different brain pathways and networks for visual processing, visual memory, language and eye movements.
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http://dx.doi.org/10.1016/j.jns.2020.116953DOI Listing
August 2020

Rapid picture naming in Parkinson's disease using the Mobile Universal Lexicon Evaluation System (MULES).

J Neurol Sci 2020 Mar 9;410:116680. Epub 2020 Jan 9.

Departments of Neurology, New York University School of Medicine, New York, NY, USA; Departments of Population Health, New York University School of Medicine, New York, NY, USA; Departments of Ophthalmology, New York University School of Medicine, New York, NY, USA. Electronic address:

Objective: The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming that captures extensive brain networks, including cognitive, language and afferent/efferent visual pathways. MULES performance is slower in concussion and multiple sclerosis, conditions in which vision dysfunction is common. Visual aspects captured by the MULES may be impaired in Parkinson's disease (PD) including color discrimination, object recognition, visual processing speed, and convergence. The purpose of this study was to compare MULES time scores for a cohort of PD patients with those for a control group of participants of similar age. We also sought to examine learning effects for the MULES by comparing scores for two consecutive trials within the patient and control groups.

Methods: MULES consists of 54 colored pictures (fruits, animals, random objects). The test was administered in a cohort of PD patients and in a group of similar aged controls. Wilcoxon rank-sum tests were used to determine statistical significance for differences in MULES time scores between PD patients and controls. Spearman rank-correlation coefficients were calculated to examine the relation between MULES time scores and PD motor symptom severity (UPDRS). Learning effects were assessed using Wilcoxon rank-sum tests.

Results: Among 51 patients with PD (median age 70 years, range 52-82) and 20 disease-free control participants (median age 67 years, range 51-90), MULES scores were significantly slower (worse performance) in PD patients (median 63.2 s, range 37.3-296.3) vs. controls (median 53.9 s, range 37.5-128.6, P = .03, Wilcoxon rank-sum test). Slower MULES times were associated with increased motor symptom severity as measured by the Unified Parkinson's Disease Rating Scale, Section III (r = 0.37, P = .02). Learning effects were greater among patients with PD (median improvement of 14.8 s between two MULES trials) compared to controls (median 7.4 s, P = .004).

Conclusion: The MULES is a complex test of rapid picture naming that captures numerous brain pathways including an extensive visual network. MULES performance is slower in patients with PD and our study suggests an association with the degree of motor impairment. Future studies will determine the relation of MULES time scores to other modalities that test visual function and structure in PD.
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http://dx.doi.org/10.1016/j.jns.2020.116680DOI Listing
March 2020

Eye Movement Recordings: Practical Applications in Neurology.

Semin Neurol 2019 12 17;39(6):775-784. Epub 2019 Dec 17.

Departments of Neurology and Ophthalmology, New York University School of Medicine, New York, New York.

Accurate detection and interpretation of eye movement abnormalities often guides differential diagnosis, discussions on prognosis and disease mechanisms, and directed treatment of disabling visual symptoms and signs. A comprehensive clinical eye movement examination is high yield from a diagnostic standpoint; however, skillful recording and quantification of eye movements can increase detection of subclinical deficits, confirm clinical suspicions, guide therapeutics, and generate expansive research opportunities. This review encompasses an overview of the clinical eye movement examination, provides examples of practical diagnostic contributions from quantitative recordings of eye movements, and comments on recording equipment and related challenges.
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http://dx.doi.org/10.1055/s-0039-1698742DOI Listing
December 2019

Unraveling Concussion Impact by Impact.

Authors:
Janet C Rucker

J Eye Mov Res 2019 Nov 25;12(7). Epub 2019 Nov 25.

Langone, New York University.

Keynote at the 20th European Conference on Eye Movement Research (ECEM) in Alicante, 20.8.2019. https://vimeo.com/357889739.
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http://dx.doi.org/10.16910/jemr.12.7.5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917480PMC
November 2019

Nystagmus and Saccadic Intrusions.

Authors:
Janet C Rucker

Continuum (Minneap Minn) 2019 Oct;25(5):1376-1400

Purpose Of Review: This article provides an overview of nystagmus and saccadic intrusions with the goal of facilitating recognition and differentiation of abnormal eye movements to assist with accurate diagnosis of neurologic disease and evidence-based specific treatment of oscillopsia. Myriad advances have been made in the understanding of several types of nystagmus and saccadic intrusions, even in the past 5 to 10 years, especially regarding underlying pathophysiology, leading to pharmacologic advances rooted in physiologic principles.

Recent Findings: Specific recent advances in the study of nystagmus and saccadic intrusions include (1) improved understanding of the underlying etiologies and mechanisms of nystagmus enhanced or unmasked by provocative maneuvers such as supine position or head shaking; (2) recognition of the differences in behavior and treatment responsivity of acquired pendular nystagmus in demyelinating disease versus oculopalatal myoclonus; (3) recognition that oculopalatal myoclonus results from a dual mechanism of abnormal inferior olivary gap junction connection formation and maladaptive cerebellar learning; and (4) well-controlled clinical trials to evaluate the efficacy of pharmacologic interventions, such as memantine for acquired pendular nystagmus and 4-aminopyridine for downbeat nystagmus.

Summary: Accurate recognition of nystagmus and saccadic intrusions, including familiarity with the subtleties of examination techniques that allow such eye movements to be unmasked, is critical to proper diagnosis and ultimate alleviation of the visual impairment these patients experience.
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http://dx.doi.org/10.1212/CON.0000000000000772DOI Listing
October 2019

Case Studies in Neuroscience: Instability of the visual near triad in traumatic brain injury-evidence for a putative convergence integrator.

J Neurophysiol 2019 09 24;122(3):1254-1263. Epub 2019 Jul 24.

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York.

Deficits of convergence and accommodation are common following traumatic brain injury, including mild traumatic brain injury, although the mechanism and localization of these deficits have been unclear and supranuclear control of the near-vision response has been incompletely understood. We describe a patient who developed profound instability of the near-vision response with inability to maintain convergence and accommodation following mild traumatic brain injury, who was identified to have a structural lesion on brain MRI in the pulvinar of the caudal thalamus, the pretectum, and the rostral superior colliculus. We discuss the potential relationship between posttraumatic clinical near-vision response deficits and the MRI lesion in this patient. We further propose that the MRI lesion location, specifically the rostral superior colliculus, participates in neural integration for convergence holding, given its proven anatomic connections with the central mesencephalic reticular formation and C-group medial rectus motoneurons in the oculomotor nucleus, which project to extraocular muscle nontwitch fibers specialized for fatigue-resistant, slow, tonic activity such as vergence holding. Supranuclear control of the near-vision response has been incompletely understood to date. We propose, based on clinical and anatomic evidence, functional pathways for vergence that participate in the generation of the near triad, "slow vergence," and vergence holding.
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http://dx.doi.org/10.1152/jn.00861.2018DOI Listing
September 2019

Eye position-dependent opsoclonus in mild traumatic brain injury.

Prog Brain Res 2019 23;249:65-78. Epub 2019 May 23.

Department of Neurology, New York University School of Medicine, New York, NY, United States; Department of Ophthalmology, New York University School of Medicine, New York, NY, United States. Electronic address:

Opsoclonus consists of bursts of involuntary, multidirectional, back-to-back saccades without an intersaccadic interval. We report a 60-year-old man with post-concussive headaches and disequilibrium who had small amplitude opsoclonus in left gaze, along with larger amplitude flutter during convergence. Examination was otherwise normal and brain MRI was unremarkable. Video-oculography demonstrated opsoclonus predominantly in left gaze and during pursuit in the left hemifield, which improved as post-concussive symptoms improved. Existing theories of opsoclonus mechanisms do not account for this eye position-dependence. We discuss theoretical mechanisms of this behavior, including possible dysfunction of frontal eye field and/or cerebellar vermis neurons; review ocular oscillations in traumatic brain injury; and consider the potential relationship between the larger amplitude flutter upon convergence and post-traumatic ocular oscillations.
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http://dx.doi.org/10.1016/bs.pbr.2019.04.016DOI Listing
May 2020

Eye-hand re-coordination: A pilot investigation of gaze and reach biofeedback in chronic stroke.

Prog Brain Res 2019 6;249:361-374. Epub 2019 Jun 6.

Department of Physical Medicine & Rehabilitation, NYU School of Medicine, New York, NY, United States; Department of Neurology, NYU School of Medicine, New York, NY, United States.

Within the domain of motor performance, eye-hand coordination centers on close relationships between visuo-perceptual, ocular and appendicular motor systems. This coordination is critically dependent on a cycle of feedforward predictions and feedback-based corrective mechanisms. While intrinsic feedback harnesses naturally available movement-dependent sensory channels to modify movement errors, extrinsic feedback may be provided synthetically by a third party for further supplementation. Extrinsic feedback has been robustly explored in hand-focused, motor control studies, such as through computer-based visual displays, highlighting the spatial errors of reaches. Similar attempts have never been tested for spatial errors related to eye movements, despite the potential to alter ocular motor performance. Stroke creates motor planning deficits, resulting in the inability to generate predictions of motor performance. In this study involving visually guided pointing, we use an interactive computer display to provide extrinsic feedback of hand endpoint errors in an initial baseline experiment (pre-) and then feedback of both eye and hand errors in a second experiment (post-) to chronic stroke participants following each reach trial. We tested the hypothesis that extrinsic feedback of eye and hand would improve predictions and therefore feedforward control. We noted this improvement through gains in the spatial and temporal aspects of eye-hand coordination or an improvement in the decoupling noted as incoordination post-stroke in previous studies, returning performance toward healthy, control behavior. More specifically, results show that stroke participants, following the interventional feedback for eye and hand, improved both their accuracy and timing. This was evident through a temporal re-synchronization between eyes and hands, improving correlations between movement timing, as well as reducing the overall time interval (delay) between effectors. These experiments provide a strong indication that an extrinsic feedback intervention at appropriate therapeutic doses may improve eye-hand coordination during stroke rehabilitation.
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http://dx.doi.org/10.1016/bs.pbr.2019.04.013DOI Listing
May 2020

Modeling gaze position-dependent opsoclonus.

Prog Brain Res 2019 2;249:35-61. Epub 2019 Mar 2.

NYU School of Medicine, New York, NY, United States.

Opsoclonus/flutter (O/F) is a rare disorder of the saccadic system. Previously, we modeled O/F that developed in a patient following abuse of anabolic steroids. That model, as in all models of the saccadic system, generates commands to make a change in eye position. Recently, we saw a patient who developed a unique form of opsoclonus following a concussion. The patient had postsaccadic ocular flutter in both directions of gaze, and opsoclonus during fixation and pursuit in the left hemifield. A new model of the saccadic system is needed to account for this gaze-position dependent O/F. We started with our prior model, which contains two key elements, mutual inhibition between inhibitory burst neurons on both sides and a prolonged reactivation time of the omnipause neurons (OPNs). We included new inputs to the OPNs from the nucleus prepositus hypoglossi and the frontal eye fields, which contain position-dependent neurons. This provides a mechanism for delaying OPN reactivation, and creating a gaze-position dependence. A simplified pursuit system was also added, the output of which inhibits the OPNs, providing a mechanism for gaze-dependence during pursuit. The rest of the model continues to generate a command to change eye position.
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http://dx.doi.org/10.1016/bs.pbr.2019.01.002DOI Listing
May 2020

Binocular Diplopia Caused by an Epiretinal Membrane With Foveal Displacement.

J Neuroophthalmol 2020 03;40(1):110-111

Departments of Neurology (DMG), Ophthalmology (YSM), and Neurology and Ophthalmology (FAW, JCR), NYU Langone Health, New York, New York.

A 73-year-old woman presented with 3 years of monocular visual distortion and progressive binocular diplopia. She was found to have a comitant left hypertropia due to an epiretinal membrane causing inferior foveal drag. Displacement of the fovea from an epiretinal membrane is a likely under-recognized cause ocular cause of a comitant binocular diplopia.
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http://dx.doi.org/10.1097/WNO.0000000000000824DOI Listing
March 2020

MULES on the sidelines: A vision-based assessment tool for sports-related concussion.

J Neurol Sci 2019 Jul 28;402:52-56. Epub 2019 Apr 28.

Department of Neurology, New York University School of Medicine, New York, NY, USA; Department of Population Health, New York University School of Medicine, New York, NY, USA; Department of Ophthalmology, New York University School of Medicine, New York, NY, USA. Electronic address:

Objective: The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming under investigation. Measures of rapid automatic naming (RAN) have been used for over 50 years to capture aspects of vision and cognition. MULES was designed as a series of 54 grouped color photographs (fruits, random objects, animals) that integrates saccades, color perception and contextual object identification. We examined MULES performance in youth, collegiate and professional athletes at pre-season baseline and at the sidelines following concussion.

Methods: Our study teams administered the MULES to youth, collegiate and professional athletes during pre-season baseline testing. Sideline post-concussion time scores were compared to pre-season baseline scores among athletes with concussion to determine degrees and directions of change.

Results: Among 681 athletes (age 17 ± 4 years, range 6-37, 38% female), average test times at baseline were 41.2 ± 11.2 s. The group included 280 youth, 357 collegiate and 44 professional athletes; the most common sports were ice hockey (23%), soccer (17%) and football (11%). Age was a predictor of MULES test times, with longer times noted for younger participants (P < .001, linear regression). Consistent with other timed performance measures, significant learning effects were noted for the MULES during baseline testing with trial 1 test times (mean 49.2 ± 13.1 s) exceeding those for trial 2 (mean 41.3 ± 11.2 s, P < .0001, paired t-test). Among 17 athletes with concussion during the sports seasons captured to date (age 18 ± 3 years), all showed increases (worsening) of MULES time scores from pre-season baseline (median increase 11.2 s, range 0.6-164.2, P = .0003, Wilcoxon signed-rank test). The Symptom Severity Score from the SCAT5 Symptom Evaluation likewise worsened from pre-season baseline following injury among participants with concussion (P = .002).

Conclusions: Concussed athletes demonstrate worsening performance on the MULES test compared to their baseline time scores. This test samples a wide network of brain pathways and complements other vision-based measures for sideline concussion assessment. The MULES test demonstrates capacity to identify athletes with sports-related concussion.
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http://dx.doi.org/10.1016/j.jns.2019.04.036DOI Listing
July 2019

Efficiently Recording the Eye-Hand Coordination to Incoordination Spectrum.

J Vis Exp 2019 03 21(145). Epub 2019 Mar 21.

Dept. of Rehabilitation Med, New York University Langone Health; Dept. of Neurology, New York University Langone Health.

The objective analysis of eye movements has a significant history and has been long proven to be an important research tool in the setting of brain injury. Quantitative recordings have a strong capacity to screen diagnostically. Concurrent examinations of the eye and upper limb movements directed toward shared functional goals (e.g., eye-hand coordination) serve as an additional robust biomarker-laden path to capture and interrogate neural injury, including acquired brain injury (ABI). While quantitative dual-effector recordings in 3-D afford ample opportunities within ocular-manual motor investigations in the setting of ABI, the feasibility of such dual recordings for both eye and hand is challenging in pathological settings, particularly when approached with research-grade rigor. Here we describe the integration of an eye tracking system with a motion tracking system intended primarily for limb control research to study a natural behavior. The protocol enables the investigation of unrestricted, three-dimensional (3D) eye-hand coordination tasks. More specifically, we review a method to assess eye-hand coordination in visually guided saccade-to-reach tasks in subjects with chronic middle cerebral artery (MCA) stroke and compare them to healthy controls. Special attention is paid to the specific eye- and limb-tracking system properties in order to obtain high fidelity data from participants post-injury. Sampling rate, accuracy, permissible head movement range given anticipated tolerance and the feasibility of use were several of the critical properties considered when selecting an eye tracker and an approach. The limb tracker was selected based on a similar rubric but included the need for 3-D recording, dynamic interaction and a miniaturized physical footprint. The quantitative data provided by this method and the overall approach when executed correctly has tremendous potential to further refine our mechanistic understanding of eye-hand control and help inform feasible diagnostic and pragmatic interventions within the neurological and rehabilitative practice.
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http://dx.doi.org/10.3791/58885DOI Listing
March 2019

Clinical and Diffusion Tensor MRI Findings in Congenital Homonymous Hemianopia.

J Neuroophthalmol 2019 09;39(3):401-404

Departments of Radiology (JR, TMS); Neurology (MS, JR); Endocrinology (MS); and Ophthalmology (JR), New York University Langone Medical Center, New York, New York.

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http://dx.doi.org/10.1097/WNO.0000000000000770DOI Listing
September 2019

Neuro-ophthalmologic disorders following concussion.

Handb Clin Neurol 2018 ;158:145-152

Department of Neurology, NYU School of Medicine, New York, NY, United States; Ophthalmology, NYU School of Medicine, New York, NY, United States. Electronic address:

Visual symptoms, such as photophobia and blurred vision, are common in patients with concussion. Such symptoms may be accompanied by abnormalities of specific eye movements, such as saccades and convergence, or accommodation deficits. The high frequency of visual involvement in concussion is not surprising, since more than half of the brain's pathways are dedicated to vision and eye movement control. These areas include many that are most vulnerable to head trauma, including the frontal and temporal lobes. Vision and eye movement testing is important at the bedside and on the sidelines of athletic events, where brief performance measures that require eye movements, such as rapid number naming, are reliable and sensitive measures for concussion detection. Tests of vision and eye movements are also being explored clinically to identify and monitor patients with symptoms of both sport- and nonsport-related concussion. Evaluation of vision and eye movements can assist in making important decisions after concussion, including the prognosis for symptom recovery, and to direct further visual rehabilitation as necessary.
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http://dx.doi.org/10.1016/B978-0-444-63954-7.00015-XDOI Listing
March 2019

History and Future Directions of Vision Testing in Head Trauma.

J Neuroophthalmol 2019 03;39(1):68-81

Departments of Neurology (OA, JRR, LH, SLG, LJB), Population Health (LJB), Ophthalmology (SLG, LJB), and Physical Medicine and Rehabilitation (JRR), New York University School of Medicine, New York, New York.

Background: Concussion leads to neurophysiologic changes that may result in visual symptoms and changes in ocular motor function. Vision-based testing is used increasingly to improve detection and assess head injury. This review will focus on the historical aspects and emerging data for vision tests, emphasizing rapid automatized naming (RAN) tasks and objective recording techniques, including video-oculography (VOG), as applied to the evaluation of mild traumatic brain injury.

Methods: Searches on PubMed were performed using combinations of the following key words: "concussion," "mild traumatic brain injury," "rapid automatized naming," "King-Devick," "mobile universal lexicon evaluation system," "video-oculography," and "eye-tracking." Additional information was referenced from web sites of vendors of commercial eye-tracking systems and services.

Results: Tests of rapid number, picture, or symbol naming, termed RAN tasks, have been used in neuropsychological studies since the early 20th century. The visual system contains widely distributed networks that are readily assessed by a variety of functionally distinct RAN tasks. The King-Devick test, a rapid number naming assessment, and several picture-naming tests, such as the Mobile Universal Lexicon Evaluation System (MULES) and the modified Snodgrass and Vanderwart image set, show capacity to identify athletes with concussion. VOG has gained widespread use in eye- and gaze-tracking studies of head trauma from which objective data have shown increased saccadic latencies, saccadic dysmetria, errors in predictive target tracking, and changes in vergence in concussed subjects. Performance impairments on RAN tasks and on tasks recorded with VOG are likely related to ocular motor dysfunction and to changes in cognition, specifically to attention, memory, and executive functioning. As research studies on ocular motor function after concussion have expanded, so too have commercialized eye-tracking systems and assessments. However, these commercial services are still investigational and all vision-based markers of concussion require further validation.

Conclusions: RAN tasks and VOG assessments provide objective measures of ocular motor function. Changes in ocular motor performance after concussion reflect generalized neurophysiologic changes affecting a variety of cognitive processes. Although these tests are increasingly used in head injury assessments, further study is needed to validate them as adjunctive diagnostic aids and assessments of recovery.
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http://dx.doi.org/10.1097/WNO.0000000000000726DOI Listing
March 2019

Mobile Universal Lexicon Evaluation System (MULES) in MS: Evaluation of a new visual test of rapid picture naming.

J Neurol Sci 2018 11 23;394:1-5. Epub 2018 Aug 23.

Departments of Neurolog, New York University School of Medicine, New York, NY, USA; Population Health, New York University School of Medicine, New York, NY, USA; Ophthalmology, New York University School of Medicine, New York, NY, USA. Electronic address:

Objective: The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming that is under investigation for concussion. MULES captures an extensive visual network, including pathways for eye movements, color perception, memory and object recognition. The purpose of this study was to introduce the MULES to visual assessment of patients with MS, and to examine associations with other tests of afferent and efferent visual function.

Methods: We administered the MULES in addition to binocular measures of low-contrast letter acuity (LCLA), high-contrast visual acuity (VA) and the King-Devick (K-D) test of rapid number naming in an MS cohort and in a group of disease-free controls.

Results: Among 24 patients with MS (median age 36 years, range 20-72, 64% female) and 22 disease-free controls (median age 34 years, range 19-59, 57% female), MULES test times were greater (worse) among the patients (60.0 vs. 40.0 s). Accounting for age, MS vs. control status was a predictor of MULES test times (P = .01, logistic regression). Faster testing times were noted among patients with MS who had greater (better) performance on binocular LCLA at 2.5% contrast (P < .001, linear regression, accounting for age), binocular high-contrast VA (P < .001), and K-D testing (P < .001). Both groups demonstrated approximately 10-s improvements in MULES test times between trials 1 and 2 (P < .0001, paired t-tests).

Conclusion: The MULES test, a complex task of rapid picture naming involves an extensive visual network that captures eye movements, color perception and the characterization of objects. Color recognition, a key component of this novel assessment, is early in object processing and requires area V4 and the inferior temporal projections. MULES scores reflect performance of LCLA, a widely-used measure of visual function in MS clinical trials. These results provide evidence that the MULES test can add efficient visual screening to the assessment of patients with MS.
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http://dx.doi.org/10.1016/j.jns.2018.08.019DOI Listing
November 2018