Visual performance testing in children with attention deficit hyperactivity disorder

Poster Presentation at American Academy of Neurology 2015 Annual Meeting

Background: 
ADHD is the most prevalent pediatric neurodevelopment disorder. In the United States, it is estimated that 5.4 million children 6 and 17 years of age (or 9.5% of U.S. children) have received an ADHD diagnosis. The King-Devick (K-D) test is a vision-based test of rapid number naming that requires saccades and visual processing. In sideline studies of youth and collegiate athletes with concussion, the K-D test consistently demonstrates higher (worse) time scores post-injury compared to pre-season baseline scores. There is growing evidence that, like concussion and mild traumatic brain injury, ADHD may be associated with visual pathway dysfunction.

Purpose:
Using the King-Devick (K-D) test, a vision-based test of rapid number naming that requires saccades and visual processing. We investigated whether children with ADHD has worse scores compared to similar aged controls.

Methods: 

Prospective study of children with ADHD (diagnosed by Conners Scale and NYU pediatric neurologist) and age-matched controls. Participants: Patients diagnosed with ADHD (5-21 years of age) seeking care from the NYU Neurology Faculty Group Practice and Child Study Center. Analyses compared K-D scores of patients with ADHD to those of pre-season baseline scores for student-athletes controls category matched for age and gender. King-Devick Test: a vision-based measure of rapid number naming that varies the spacing between numbers on successive cards.

Results: 
Among 134 participants in this study, ADHD vs. control status was significantly associated with higher K-D test time scores (p<0.001, logistic regression models, accounting for age). K-D showed a greater capacity to distinguish ADHD vs. control groups in youths older than 11 years of age (ROC curve areas from logistic regression models was, 0.55 for youths ≤11 years of age and 0.79 for youths ≥11 years of age). Patients with ADHD took an average of 14 seconds longer to complete the K-D test, compared to control youth (p<0.001, two-sample t-test). Use of stimulant medications was not associated with differences in K-D time scores within the cohort of patients with ADHD (p > 0.05, best KD trial of ADHD on Rx vs. best KD trial of ADHD off Rx).

Conclusions: 
Visual pathways may perform or be utilized differently in youths with ADHD compared to controls. This alteration in visual performance on the K-D test in youths with ADHD is likely due to the widespread distribution of brain pathways devoted to vision (approximately 50% of the brain’s circuits). The limited capacity of the K-D to distinguish ADHD in youths younger than 11 years of age may be due to variations in reading ability in this age group. Use of stimulant medication was not associated with altered K-D test performance.

Validation of strategies to streamline high and low contrast acuity testing in ALS subjects

Poster Presentation at American Academy of Neurology 2015 Annual Meeting

Background: 
Afferent visual system disorders are included in the phenotypic spectrum Amyotrophic Lateral Sclerosis (ALS). High and low contrast visual acuity (HCVA and LCVA) are potential quantitative clinical markers of this dysfunction. Gold standard clinical research protocols for HCVA and LCVA measurements are difficult to implement in a neurology clinic. Pinhole is a possible substitute for refraction, which is time consuming requiring specialized equipment and personnel. Charts presented on tablets are a potential substitute for retro-illuminated charts, which are bulky and less readily available. The purpose of this study is to evaluate the effect of substituting pinhole for refraction and tablet charts for retro-illuminated charts on HCVA and LCVA in ALS patients.

Methods: 

Monocular HCVA and 2.5% LCVA were measured at 2m in 8 ALS subjects using two chart conditions (retro-illuminated Sloan charts, iPad presented charts) and two correction conditions (spherical refraction, pinhole). Number of letters correctly identified was compared between chart condition and between correction conditions. Differences less than 5 letters (1 line) were considered comparable.

Results: 
HCVA was comparable between correction conditions and between chart conditions for 6/8 (75%) and 8/7 (88%) subjects respectively. LCVA was comparable between correction conditions and between chart conditions for 3/8 (38%) and 6/8 (75%) respectively. In comparable values favored pinhole for HCVA and spherical refraction for LCVA.

Conclusions: 
In this pilot study, we find that HCVA and LCVA tablet presented charts produce comparable measurements to gold standard retro-illuminated charts in greater than 75% of ALS subjects. Pinhole correction is comparable to spherical refraction for measurements of HCVA but not LCVA. HCVA measurements with pinhole and tablet charts are less burdensome for ALS patients and research staff without sacrificing accuracy. Pinhole is not a suitable modification for LCVA measurements.

Abnormal Visual Contrast Acuity in Parkinson’s Disease

Background:
Low-contrast vision is thought to be reduced in Parkinson’s disease (PD). This may have a direct impact on quality of life such as driving, using tools, finding objects, and mobility in low-light condition. Low-contrast letter acuity testing has been successful in assessing low-contrast vision in multiple sclerosis. We report the use of a new iPad application to measure low-contrast acuity in patients with PD.

Objective: 

To evaluate low- and high-contrast letter acuity in PD patients and controls using a variable contrast acuity eye chart developed for the Apple iPad.

Methods: 
Thirty-two PD and 71 control subjects were studied. Subjects viewed the Variable Contrast Acuity Chart on an iPad with both eyes open at two distances (40 cm and 2m) and at high contrast (black and white visual acuity) and 2.5% low contrast.
Acuity scores for the two groups were compared.

Results: 
PD patients had significantly lower scores (indicating worse vision) for 2.5% low contrast at both distances and for high contrast at 2m (p < 0.003) compared to controls. No significant difference was found between the two groups for high contrast at 40 cm (p = 0.12).

Conclusions: 
PD patients had significantly lower scores (indicating worse vision) for 2.5% low contrast at both distances and for high contrast at 2m (p < 0.003) compared to controls. No significant difference was found between the two groups for high contrast at 40 cm (p = 0.12).

Further Reading
Read the whole study at Journal of Parkinson’s Disease.

Vision and vision-related outcome measures in multiple sclerosis

Objective: 
Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the
structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis.

“The King-Devick Test, a brief rapid number-naming test new to the multiple sclerosis field, is a potential quantitative bedside performance measure of efferent visual dysfunction (Moster et al., 2014). This test takes 52 min to complete and is sensitive to dysfunction of saccadic and other eye movements; time scores are higher (worse) among patients with multiple sclerosis compared to disease-free controls. Further studies of this and other efferent visual function tests in multiple sclerosis are needed to bring assessment of this aspect of vision to the level of afferent system investigation.”

Further Reading
Read the whole study at Brain – A Journal of Neurology.

Assessment of prefrontal cortex activity in amyotrophic lateral sclerosis patients with functional near infrared spectroscopy

Background: 
Cognitive impairment in amyotrophic lateral sclerosis (ALS) is associated with cortical changes beyond the motor cortex. The overall goal of this project is to determine if task induced hemodynamic changes detected by functional near infrared (fNIR) spectroscopy from the anterior prefrontal cortex (PFC) has discriminant validity across ALS (n = 17) patients and matching healthy (n = 17) controls. The experimental protocol was composed of the King-Devick Test, the Number Interference Test and a Continuous Performance Test targeting a range of cognitive domains including sustained attention and executive function. Results indicate that
fNIR measures provided significant differences between ALS and healthy controls in all three tasks providing an additional metric for the assessment of cognitive decline. Although this is a pilot study, given the safe, wearable and real world validity of fNIR, these results may set the foundation for the use of fNIR as a clinical tool in monitoring progression of neurocognitive decline in a simple, less invasive and objective manner than allowed by current imaging technology.

Further Reading
Read the whole study at Journal of Neuroscience and Neurolengineering

Early Detection of Hypoxia-Induced Cognitive Impairment Using the King-Devick Test

Introduction: 
Visual performance impairment after hypoxia is well recognized in military and civilian aviation. The aims of this study were: 1) to assess oculometric features such as blink metrics, pupillary dynamics, fixations, and saccades as cognitive indicators of early signs of hypoxia; and 2) to analyze the impact of different hypoxic conditions [ “ hypoxic hypoxia” (HH) and “isocapnic hypoxia” (IH)] on specified oculometrics during mental workloads.

Methods:
Oculometric data were collected on 25 subjects under 3 conditions: normoxia, HH (8% O 2 + balance N 2 ), and IH (7% O 2 + 5% CO 2 + balance N 2 ). The mental workload task consisted of reading aloud linear arrays of numbers after exposure to gas mixtures.

Results: 
Blink rates were significantly increased under hypoxic conditions (by +100.7% in HH and by +92.8% in IH compared to normoxia). A faster recovery of blink rate was observed in transitioning from IH (23.6% vs. 76.3%) to normoxia. The percentage change in pupil size fluctuation was increased under HH more than under IH (29% vs. 4.4%). Under HH average fixation time and target area size were significantly higher than under IH. Total saccadic times under hypoxic conditions were significantly increased compared with normoxia.

Conclusions: 
These results suggest that oculometric changes are indicators of hypoxia, which can be monitored using compact, portable, noninvasive eye-tracking devices in a cockpit analogous environment to detect hypoxia-induced physiological changes in aircrew. Comparative results between HH and IH support the potential role of carbon dioxide in augmenting cerebral perfusion and hence improved tissue oxygen delivery.

Further Reading
Read the whole study at Aviation, Space, and Environmental Medicine.

The King-Devick (K-D) test of rapid eye movements: a bedside correlate of disability and quality of life in MS

Journal of Neurological Sciences. 2014 Aug 15;343(1-2):105-9. 

Objective: 
We investigated the King-Devick (K-D) test of rapid number naming as a visual performance measure in a cohort of patients with multiple sclerosis (MS).

Methods: 
In this cross-sectional study, 81 patients with MS and 20 disease-free controls from an ongoing study of visual outcomes underwent K-D testing. A test of rapid number naming, K-D requirers saccadic eye movements as well as intact vision, attention and concentration. To perform the K-D test, participants are asked to read numbers aloud as quickly as possible from three test cards; the sum of the three test card times in seconds constitutes the summary score. High-contrast visual acuity (VA), low-contrast letter acuity (1.25% and 2.5% levels), retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT), MS Functional Composite (MSFC) and vision-specific quality of life (QOL) measures (250Item NEI Visual Functioning Questionnaire [NEI-VFQ-25] and 10-Item Neuro-Ophthalmic Supplement) were also assessed.

Results: 
K-D time scores in the MS cohort (total time to read the three cards) were significantly higher (worse) compared to those for disease-free controls (P=0.003, linear regression, accounting for age). Within the MS cohort, high K-D scores were associated with worse scores for the NEI-VFQ-25 composite (P<0.001), 10-Item Neuro-Ophthalmic Supplement (P<0.001), binocular low-contrast acuity (2.5%, 1.25%, P<0.001, and high-contrast VA (P=0.003). Monocular low-contrast vision scores (P=0.001-0.009) and RNFL thickness (P=0.001) were also reduced in eyes of patients with worse K-D scores (GEE models accounting for age and within-patient, inter-eye correlations). Patients with a history of optic neuritis (ON) had increased (worse) K-D scores. Patients who classified their work disability status as disabled (receiving disability pension) did worse on K-D testing compared to those working full-time (P=0.001, accounting for age).

Conclusions: 
The K-D test, a <2 minute bedside test of rapid number naming, is associated with visual dysfunction, neurologic impairment, and reduced vision-specific QOL in patients with MS. Scores reflect work disability as well as structural changes as measured by OCT imaging. History of ON and abnormal binocular acuities were associated with worse K-D scores, suggesting that abnormalities detected by K-D may go along with afferent dysfunction in MS patients. A brief test that requires saccadic eye movements, K-D should be considered for future MS trials as a rapid visual performance measure.

Further Reading
Read the whole study at Journal of the Neurological Sciences.

The effect of saccadic training on early reading fluency

Background: 
Eye movements are necessary for the physical act of reading and have been shown to relate to underlying cognitive and visuoattentional processes during reading. The purpose of this study was to determine the effect of saccadic training using the King-Devick remediation software on reading fluency.

Methods: 
In this prospective, single-blinded, randomized, crossover trial, a cohort of elementary students received standardized reading fluency testing pre- and post treatment. Treatment consisted of in-school training 20 minutes per day, 3 days per week for 6 weeks.

Results: 
The treatment group had significantly higher reading fluency scores after treatment (P < .001), and post treatment scores were significantly higher than the control group (P < .005).

Conclusions: 
Saccadic training can significantly improve reading fluency. We hypothesize that this improvement in reading fluency is a result of rigorous practice of eye movements and shifting visuospatial attention, which are vital to the act of reading.

Further Reading
Read the whole study at Clinical Pediatrics

Slowing of Number Naming Speed by King-Devick Test in Parkinson’s Disease

Parkinsonism & Related Disorders. 2013; ePub Oct 18 2013. 

Background: 
The King-Devick (KD) test measures the speed of rapid number naming, and is postulated to require fast eye movements, attention, language, and possibly other aspects of cognitive functions. While used in multiple sports concussion studies, it has not been applied to the field of movement disorders.

Methods: 
Forty-five Parkinson’s disease (PD), 23 essential tremor (ET), and 65 control subjects were studied. Subjects performed two trials of reading out loud single-digit numbers separated by varying spacing on three test cards that were of different formats. The sum time of the faster trial was designated the KD score and compared across the three groups.

Results: 
PD patients had higher (worse) KD scores, with longer reading times compared to ET and control subjects (66 seconds vs. 49 sec. vs. 52 sec., p < 0.001, adjusting for age and gender). No significant difference was found between ET and control (Δ = -3 seconds, 95% CI: -10 to 4).

Conclusions: 
This is the first study of the King-Devick Test in Parkinson’s disease. PD patients were found to have a slower rapid number naming speed compared to controls. This test may be a simple and rapid bedside tool for quantifying correlates of visual and cognitive function in Parkinson’s disease.

Further Reading
Read the whole study at Parkinsonism & Related Disorders.

Early Detection of Hypoxia-Induced Cognitive Impairment Using the King-Devick Test

Aviat Space Environ Med. 2013; 84:1017-22.

Introduction: 
Hypoxic incapacitation continues to be a significant threat to safety and operations at high altitude. Noninvasive neurocognitive performance testing is desirable to identify pre-symptomatic cognitive impairment, affording operators at altitude a tool to quantify their performance and safety.

Methods:
There were 25 subjects enrolled in this study. Cognitive performance was assessed by using the King-Devick (K-D) test. The performance of the subjects on the K-D test was measured in normoxia followed by hypoxia (8% O2 equivalent to 7101 m) and then again in normoxia.

Results: 
K-D test completion time in hypoxia for 3 min was significantly longer than the Baseline Test (54.5 ± 12.4 s hypoxic vs. 46.3 ± 10.4 s baseline). Upon returning to normoxia the completion time was significantly shorter than in hypoxia (47.6 ± 10.6 s post-test vs. 54.5 ± 12.4 s hypoxic). There was no statistically significant difference between baseline test and post-test times, indicating that all subjects returned to their normoxic baseline levels. SpO2 decreased from 98 ± 0.9% to 80 ± 7.8% after 3 min on hypoxic gas. During the hypoxic K-D test, SpO2 decreased further to 75.8 ± 8.3%.

Conclusions: 
In this study the K-D test has been shown to be an effective neurocognitive test to detect hypoxic impairment at early pre-symptomatic stages. The K-D test may also be used to afford a reassessment of traditional measures used to determine hypoxic reserve time.

Further Reading
Read the whole study at Aviation, Space, and Environmental Medicine.

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