Objective characterization of the relative afferent pupillary defect in MS

To develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative afferent pupillary defects (RAPD) in patients with MS. Binocular infrared pupillometry was performed in 40 control subjects and 32 MS patients with RAPDs, using...

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Published in:	Journal of the neurological sciences Vol. 323; no. 1-2; pp. 193 - 200
Main Authors:	Blazek, Paul, Davis, Scott L., Greenberg, Benjamin M., Conger, Amy, Conger, Darrel, Vernino, Steven, Beh, Shin, Stuve, Olaf, Saidha, Shiv, Ratchford, John N., Green, Ari, Calabresi, Peter A., Balcer, Laura J., Frohman, Teresa C., Frohman, Elliot M.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 15.12.2012 Elsevier
Subjects:	Adult Afferent Pathways - physiopathology Anthropometry - methods Asymmetry Asymmetry ratio Biological and medical sciences Case-Control Studies Female Forecasting Humans Light Male Medical sciences Middle Aged Multiple sclerosis Multiple Sclerosis - complications Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis Neurology Optic neuritis Optic Neuritis - diagnosis Optic Neuritis - etiology Optic Neuritis - physiopathology Phase‐plane constriction area Photic Stimulation Pupil Disorders - diagnosis Pupil Disorders - etiology Reflex, Pupillary - physiology Reflex, Pupillary - radiation effects Relative afferent pupillary defect Reproducibility of Results Sensitivity and Specificity Phase‐plane constriction area Multiple sclerosis Asymmetry ratio Optic neuritis Relative afferent pupillary defect Nervous system diseases Optic nerve Phase-plane constriction area Inflammatory disease Eye disease Cranial nerve disease Visual pathway Asymmetry Optic nevritis Central nervous system disease
ISSN:	0022-510X, 1878-5883, 1878-5883
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Abstract	To develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative afferent pupillary defects (RAPD) in patients with MS. Binocular infrared pupillometry was performed in 40 control subjects and 32 MS patients with RAPDs, using two precisely defined sequences of alternating light flashes (right–left and left–right). We analyzed three distinct pupillary metrics in response to light stimulation. These included percent diameter change (DC), constriction curve area (CCA), which measures change in diameter over time, and the phase-plane curve area (PCA) which measures change in diameter with change in velocity. Direct and consensual response ratios (for each eye) were computed and analyzed for each metric in response to both the first flash (i.e. first phase) and second flash (i.e. second phase) of the ‘swinging flashlight’ test. Second flash pupillary response metric asymmetry ratios yielded the highest discriminatory power for RAPD detection. Receiver operating characteristic areas under the curve for each of the pupillary metric response asymmetry ratios were as follows: diameter change: 0.97; constriction curve area: 0.96; phase-plane curve area: 0.95 (p<0.0001 for all comparisons compared to normal subjects). The sum of these three squared ratios (SSR) yielded a combined metric with the greatest discriminatory power (receiver operator characteristic area under the curve=0.99). Second flash (i.e. the second phase of the swinging light test) pupillary metric response asymmetry ratios are highly sensitive and specific for the confirmation and characterization of an RAPD in patients with MS. This objective neurophysiologic method may be useful for studying the relationship between a stereotyped reflex, and nervous system architecture, with potential ramifications for detecting and monitoring neuroprotective and restorative effects of novel agents in MS treatment trials.
AbstractList	AbstractObjectiveTo develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative afferent pupillary defects (RAPD) in patients with MS. MethodsBinocular infrared pupillometry was performed in 40 control subjects and 32 MS patients with RAPDs, using two precisely defined sequences of alternating light flashes (right–left and left–right). We analyzed three distinct pupillary metrics in response to light stimulation. These included percent diameter change (DC), constriction curve area (CCA), which measures change in diameter over time, and the phase-plane curve area (PCA) which measures change in diameter with change in velocity. Direct and consensual response ratios (for each eye) were computed and analyzed for each metric in response to both the first flash (i.e. first phase) and second flash (i.e. second phase) of the ‘swinging flashlight’ test. ResultsSecond flash pupillary response metric asymmetry ratios yielded the highest discriminatory power for RAPD detection. Receiver operating characteristic areas under the curve for each of the pupillary metric response asymmetry ratios were as follows: diameter change: 0.97; constriction curve area: 0.96; phase-plane curve area: 0.95 (p < 0.0001 for all comparisons compared to normal subjects). The sum of these three squared ratios (SSR) yielded a combined metric with the greatest discriminatory power (receiver operator characteristic area under the curve = 0.99). ConclusionsSecond flash (i.e. the second phase of the swinging light test) pupillary metric response asymmetry ratios are highly sensitive and specific for the confirmation and characterization of an RAPD in patients with MS. This objective neurophysiologic method may be useful for studying the relationship between a stereotyped reflex, and nervous system architecture, with potential ramifications for detecting and monitoring neuroprotective and restorative effects of novel agents in MS treatment trials. To develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative afferent pupillary defects (RAPD) in patients with MS. Binocular infrared pupillometry was performed in 40 control subjects and 32 MS patients with RAPDs, using two precisely defined sequences of alternating light flashes (right–left and left–right). We analyzed three distinct pupillary metrics in response to light stimulation. These included percent diameter change (DC), constriction curve area (CCA), which measures change in diameter over time, and the phase-plane curve area (PCA) which measures change in diameter with change in velocity. Direct and consensual response ratios (for each eye) were computed and analyzed for each metric in response to both the first flash (i.e. first phase) and second flash (i.e. second phase) of the ‘swinging flashlight’ test. Second flash pupillary response metric asymmetry ratios yielded the highest discriminatory power for RAPD detection. Receiver operating characteristic areas under the curve for each of the pupillary metric response asymmetry ratios were as follows: diameter change: 0.97; constriction curve area: 0.96; phase-plane curve area: 0.95 (p<0.0001 for all comparisons compared to normal subjects). The sum of these three squared ratios (SSR) yielded a combined metric with the greatest discriminatory power (receiver operator characteristic area under the curve=0.99). Second flash (i.e. the second phase of the swinging light test) pupillary metric response asymmetry ratios are highly sensitive and specific for the confirmation and characterization of an RAPD in patients with MS. This objective neurophysiologic method may be useful for studying the relationship between a stereotyped reflex, and nervous system architecture, with potential ramifications for detecting and monitoring neuroprotective and restorative effects of novel agents in MS treatment trials. Objective: To develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative afferent pupillary defects (RAPD) in patients with MS. Methods: Binocular infrared pupillometry was performed in 40 control subjects and 32 MS patients with RAPDs, using two precisely defined sequences of alternating light flashes (rightaleft and leftaright). We analyzed three distinct pupillary metrics in response to light stimulation. These included percent diameter change (DC), constriction curve area (CCA), which measures change in diameter over time, and the phase-plane curve area (PCA) which measures change in diameter with change in velocity. Direct and consensual response ratios (for each eye) were computed and analyzed for each metric in response to both the first flash (i.e. first phase) and second flash (i.e. second phase) of the aswinging flashlighta test. Results: Second flash pupillary response metric asymmetry ratios yielded the highest discriminatory power for RAPD detection. Receiver operating characteristic areas under the curve for each of the pupillary metric response asymmetry ratios were as follows: diameter change: 0.97; constriction curve area: 0.96; phase-plane curve area: 0.95 (p < 0.0001 for all comparisons compared to normal subjects). The sum of these three squared ratios (SSR) yielded a combined metric with the greatest discriminatory power (receiver operator characteristic area under the curve = 0.99). Conclusions: Second flash (i.e. the second phase of the swinging light test) pupillary metric response asymmetry ratios are highly sensitive and specific for the confirmation and characterization of an RAPD in patients with MS. This objective neurophysiologic method may be useful for studying the relationship between a stereotyped reflex, and nervous system architecture, with potential ramifications for detecting and monitoring neuroprotective and restorative effects of novel agents in MS treatment trials. To develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative afferent pupillary defects (RAPD) in patients with MS.OBJECTIVETo develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative afferent pupillary defects (RAPD) in patients with MS.Binocular infrared pupillometry was performed in 40 control subjects and 32 MS patients with RAPDs, using two precisely defined sequences of alternating light flashes (right-left and left-right). We analyzed three distinct pupillary metrics in response to light stimulation. These included percent diameter change (DC), constriction curve area (CCA), which measures change in diameter over time, and the phase-plane curve area (PCA) which measures change in diameter with change in velocity. Direct and consensual response ratios (for each eye) were computed and analyzed for each metric in response to both the first flash (i.e. first phase) and second flash (i.e. second phase) of the 'swinging flashlight' test.METHODSBinocular infrared pupillometry was performed in 40 control subjects and 32 MS patients with RAPDs, using two precisely defined sequences of alternating light flashes (right-left and left-right). We analyzed three distinct pupillary metrics in response to light stimulation. These included percent diameter change (DC), constriction curve area (CCA), which measures change in diameter over time, and the phase-plane curve area (PCA) which measures change in diameter with change in velocity. Direct and consensual response ratios (for each eye) were computed and analyzed for each metric in response to both the first flash (i.e. first phase) and second flash (i.e. second phase) of the 'swinging flashlight' test.Second flash pupillary response metric asymmetry ratios yielded the highest discriminatory power for RAPD detection. Receiver operating characteristic areas under the curve for each of the pupillary metric response asymmetry ratios were as follows: diameter change: 0.97; constriction curve area: 0.96; phase-plane curve area: 0.95 (p<0.0001 for all comparisons compared to normal subjects). The sum of these three squared ratios (SSR) yielded a combined metric with the greatest discriminatory power (receiver operator characteristic area under the curve=0.99).RESULTSSecond flash pupillary response metric asymmetry ratios yielded the highest discriminatory power for RAPD detection. Receiver operating characteristic areas under the curve for each of the pupillary metric response asymmetry ratios were as follows: diameter change: 0.97; constriction curve area: 0.96; phase-plane curve area: 0.95 (p<0.0001 for all comparisons compared to normal subjects). The sum of these three squared ratios (SSR) yielded a combined metric with the greatest discriminatory power (receiver operator characteristic area under the curve=0.99).Second flash (i.e. the second phase of the swinging light test) pupillary metric response asymmetry ratios are highly sensitive and specific for the confirmation and characterization of an RAPD in patients with MS. This objective neurophysiologic method may be useful for studying the relationship between a stereotyped reflex, and nervous system architecture, with potential ramifications for detecting and monitoring neuroprotective and restorative effects of novel agents in MS treatment trials.CONCLUSIONSSecond flash (i.e. the second phase of the swinging light test) pupillary metric response asymmetry ratios are highly sensitive and specific for the confirmation and characterization of an RAPD in patients with MS. This objective neurophysiologic method may be useful for studying the relationship between a stereotyped reflex, and nervous system architecture, with potential ramifications for detecting and monitoring neuroprotective and restorative effects of novel agents in MS treatment trials.
Author	Stuve, Olaf Saidha, Shiv Conger, Amy Balcer, Laura J. Blazek, Paul Frohman, Teresa C. Ratchford, John N. Frohman, Elliot M. Beh, Shin Conger, Darrel Davis, Scott L. Vernino, Steven Green, Ari Greenberg, Benjamin M. Calabresi, Peter A.
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Keywords	Phase‐plane constriction area Multiple sclerosis Asymmetry ratio Optic neuritis Relative afferent pupillary defect Nervous system diseases Optic nerve Phase-plane constriction area Inflammatory disease Eye disease Cranial nerve disease Visual pathway Asymmetry Optic nevritis Central nervous system disease
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Snippet	To develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative afferent pupillary... AbstractObjectiveTo develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative... Objective: To develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative afferent...
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SubjectTerms	Adult Afferent Pathways - physiopathology Anthropometry - methods Asymmetry Asymmetry ratio Biological and medical sciences Case-Control Studies Female Forecasting Humans Light Male Medical sciences Middle Aged Multiple sclerosis Multiple Sclerosis - complications Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis Neurology Optic neuritis Optic Neuritis - diagnosis Optic Neuritis - etiology Optic Neuritis - physiopathology Phase‐plane constriction area Photic Stimulation Pupil Disorders - diagnosis Pupil Disorders - etiology Reflex, Pupillary - physiology Reflex, Pupillary - radiation effects Relative afferent pupillary defect Reproducibility of Results Sensitivity and Specificity
Title	Objective characterization of the relative afferent pupillary defect in MS
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