Optics: eye examining – vision testing and correcting – Eye examining or testing instrument – Methods of use
Reexamination Certificate
2000-12-21
2001-11-13
Manuel, George (Department: 3737)
Optics: eye examining, vision testing and correcting
Eye examining or testing instrument
Methods of use
C600S558000
Reexamination Certificate
active
06315414
ABSTRACT:
TECHNICAL FIELD
This invention concerns the detection of neural damage to the optic nerve, optic radiations and white matter of the visual brain indicative of various neurological disorders but with particular application to multiple sclerosis.
BACKGROUND ART
Diseases such as multiple sclerosis reduce the effectiveness of neural transmission. A common diagnostic technique in these diseases is to measure electrical potentials evoked in response to various forms of stimulation of peripheral sensory nerves: abnormally long neural conduction times being equated with neural disease. Neurones concerned with conducting neural signals over longer distances are typically assisted in their conduction by a sheath of insulative material known as myelin. Diseases such as multiple sclerosis disrupt the myelin sheath and thereby impair the speed of neural conduction. Such changes in nerve conduction latency and other changes in the time-course of the evoked potential can be observed in a variety of other disorders such as optic neuritis, various optic atrophies, toxic amblyopia, papilledema, Parkinson's, tumours, migraine, various ataxias, compression of the visual nerves, spinocerebellar degenerations and Vitamin B
12
deficiency as described in the paper by S. Sokol, entitled “The visually evoked cortical potential in the optic nerve and visual pathway disorders”, which was published in
Electrophysiological testing in diseases of the retina, ootic nerve, and visual pathway
, edited by G. A. Fishman, published by the American Academy of Ophthalmology, of San Francisco, in 1990, Volume 2, Pages 105-141.
The evoked potentials (EPs) conventionally measured reflect the activity of large bundles of neurones contained within a nerve. Thus the EP represents a gross sum of many cells' activity. Such a gross sum would tend to mask the effects of small focal lesions to smaller subsets of neurones within the nerve, such as those found in multiple sclerosis, since responses from neurones with damaged and intact myelin are summed together. Therefore it would be desirable to obtain different EP responses produced by different component parts of a nerve in order to highlight focal neural damage.
In more recent times Magnetic Resonance Imaging has provided a method to obtain images at least of the larger focal lesions found in multiple sclerosis. Studies comparing the relative sensitivities and specificities of MRI with a variety of Evoked Potential (EP) methods, including Visual (VEP), Auditory (AEP) and Somatosensory (SEP) methods, reveal that MRI is superior to the EP methods in diagnosing MS as described in the paper by T. Sand and I.A. Sulg, entitled “Evoked potentials and CSF-immunoglobulins in MS: relationship to disease duration, disability, and functional status”, which was published in
Acta Neural Scand
, Volume 82, Pages 217-21, and the paper by HI.A van Diemen, P. Lanting, J.C. Koetsier, R.L. Strijers, H.K van Walbeek and C.H. Pornan, entitled “Evaluation of the visual system in multiple sclerosis, a comparative study of diagnostic tests”, which was published in
Clin Neurol Neurosurge
, Volume 94, Pages 191-5. Of these various EP methods the VEP comes closest to matching the performance of MRI
1
, VEP sensitivity rarely lagging MRI by more than 10% as described in the paper by M. Ravnborg, R. Liguori, P. Christiansen, H. Larsson and P.S. Sorensen, entitled “The diagnostic reliability of magnetically evoked motor potentials in multiple sclerosis”, which was published in
Neurology
. Volume 42, Pages 1296-301. As pointed out above part of the failing of the EP methods is undoubtedly that the measured potentials commonly represent a sum over the whole of whichever particular sensory pathway is stimulated. In the case of the VEP some differential measurement is often attempted by using stimuli consisting of checker-board patterns of different scales, the idea being that finer patterns bias the VEP somewhat towards measurements from the central retina and visual field as described in the paper by M.R. Harter, entitled “Evoked cortical responses to checkerboard patterns; effect of check-size as a function of retinal eccentricity”, which was published in
Vision Res
, Volume 10, Pages 1365-76. Attempts have been made to characterise responses from each hemifield separately and to try to achieve some separation of hemispheric responses by use of widely displaced pairs of electrodes as reported in the paper by L.D. Blumhardt, G. Barrett, A.M. Halliday and A. Kriss, entitled “The effect of experimental ‘scotomata’on the ipsilateral and contralateral responses to pattern-reversal in one half-field”, which was published in
Clin. Neurophvsiol
., Volume 45, Pages 376-392. Inadequate isolation of these responses, in conjunction with different recording electronics and different recording times for the compared responses contribute to less than satisfactory results. Nevertheless, given the close concordance between VEP and MRI
1
, an improved VEP, provides the best promise of performance comparable to MRI that could be done in the average neurologist's surgery as often as desired and at lower cost.
DISCLOSURE OF THE INVENTION
The prime objective of the present invention is the provision of a simultaneous, rapid, reliable test for damage to nerve conduction in component parts of the optic nerve, optic radiations and visual cortex. This objective is achieved by presenting visual stimuli, to parts of the visual field such that component parts of the optic nerve, optic radiations and visual cortex are roughly separately stimulated and with the temporal structure of the stimuli applied to each visual field region being sufficiently complex in their temporal characteristics to permit estimation of linear and nonlinear weighting functions such as Wiener or Volterra kernels to characterise the linear (first order) and nonlinear (second order) responses of each component part of the optic nerve, optic radiations and visual cortex.
In broad form the present invention provides a method of simultaneously assessing the presence of damage to component parts of the optic nerve, optic radiations and visual cortex, the method including the steps of.
(a) dividing the visual field of view of each eye into a plurality of zones so as to roughly isolate confluent streams within the optic nerve, optic radiations and visual cortex due to their retinotopic arrangement;
(b) presenting to the two eyes stimuli having different temporal modulation of the appearance of each of the zones of the visual field of each eye, the stimuli being different for each of the corresponding zones within the visual field of view of each eye,
(c) making the temporal content of the variations of the appearance of the time varying stimuli sufficiently complex as to permit estimation of linear and nonlinear weighting functions characterising measured responses to each stimulus region and for each eye;
(d) estimating some or all of the coefficients of the linear and nonlinear functions, for each stimulus zone, and binocular interaction, from the measured responses to said stimuli, to isolate separate contributions from component parts of the optic nerve, optic radiations and the left and right halves of the visual brain simultaneously.
Preferably, the linear and nonlinear weighting functions are Weiner or Volterra kernels.
As will be apparent the test involves measuring kernels which characterise the linear and nonlinear responses of component parts of the optic nerve, optic radiations and visual cortex in response to simultaneous stimulation of different parts of the visual field. The invention provides for the measurement of nerve conduction information, such as the conduction delay to the peak measured kernel response, for both first and second order responding nerve components and computation of binocular interaction kernels to isolate simultaneously generated kernel responses to dichoptic stimulation of the two eyes with different temporal sequences of light flashes whose temporal structure is sufficiently complex to permit calculation
James Andrew Charles
Maddess Teddy Lee
Australian National University
Manuel George
Nixon & Peabody LLP
Studebaker Donald R.
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