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Biomedical subjects

J L Demer

Publications and source records attributed to J L Demer.

At least 19 recordsLinked to original sources

The edrophonium-Hess screen test in the diagnosis of ocular myasthenia gravis.

The interpretation of the edrophonium (Tensilon) test in the diagnosis of acquired strabismus caused by myasthenia gravis has been problematic because of poorly defined endpoints and unknown sensitivity and specificity. We evaluated the endpoint criteria, dynamics, sensitivity, and specificity of binocular alignment in response to edrophonium by using the Hess screen test in ten normal control subjects, 12 nonmyasthenic patients with acquired strabismus, and in ten patients with acquired strabismus caused by ocular myasthenia gravis. A positive response to the edrophonium-Hess screen test was defined as a 50% or greater reduction in the strabismic deviation at the fixation point associated with maximum deviation within one minute of edrophonium infusion. All myasthenic patients had a 50% or greater reduction in the initial deviation within one minute of edrophonium infusion. Myasthenic patients had a statistically significant reduction in the average deviation up to 150 seconds after edrophonium infusion (P < .05 for all time periods). In contrast, with or without edrophonium infusion, control subjects had a purely horizontal fluctuation in binocular alignment of less than or equal to 2 degrees for the entire four-minute period after edrophonium infusion. None of the 12 nonmyasthenic patients tested positive to the edrophonium-Hess screen test. According to the criterion of positive response as was defined in this study, the test had a high sensitivity and specificity in this sample. These results suggest that clearly defined endpoint criteria make the edrophonium-Hess screen test a sensitive and specific quantitative study for the diagnosis of acquired strabismus caused by myasthenia gravis.

Adult

Ocular motility anomalies in developmental misdirection of the optic chiasm.

A 35-year-old normally pigmented man underwent monocular hemifield visual-evoked potential examinations that indicated a lack of normal decussation of nasal paramacular retinogeniculate fibers in the optic chiasm. We studied effects of this anomaly on ocular motility using electro-oculography and the magnetic search-coil technique. The patient exhibited horizontal congenital nystagmus with a predominantly positive exponential waveform. Horizontal smooth pursuit and optokinetic nystagmus were consistently reversed, independent of eye position in the orbit. Vertical tracking was uniformly normal. Horizontal vestibulo-ocular reflexes recorded in the dark during passive rotation exhibited normal gain and phase, whereas rotation recorded in the light reduced gain. Although active head movements reversed horizontal vestibulo-ocular reflexes, vertical vestibulo-ocular reflexes in light and darkness were normal. Our study suggested an association between a lack of normal decussation of retinal fibers in the optic chiasm, and reversed visual tracking and congenital nystagmus.

Adult

Mechanisms of human vertical visual-vestibular interaction.

1. The purpose of this study was to infer the properties of the mechanisms contributing to visual-vestibular interaction (VVI) of human beings during vertical motion. Predictable trains of single-frequency sinusoids; poorly predictable sums of sinusoidal harmonics; and unpredictable random impulses of passive, whole-body rotation about a horizontal, interaural axis were produced by the use of a servo-driven chair at frequencies from 0.4 to 3.2 Hz. The vestibuloocular reflex (VOR) was studied in darkness with the use of the magnetic search coil technique to record eye movements during head rotation. Telescopic spectacles of varying magnifications and visual field areas were used as a challenging stimulus to induce substantial gain enhancement by VVI. Real and imagined targets moving with the head were used to induce gain reduction. VVI was compared with vertical smooth pursuit and small field optokinetic nystagmus (OKN) for similar stimulus motion. 2. The vertical VOR and visually enhanced VOR (VVOR) were directionally symmetrical. Viewing with telescopic spectacles of powers from x1.9-4 was associated with significantly increased gain at frequencies up to 2.0 Hz as compared with the VOR (P < 0.01). Gain enhancement was not strongly influenced by stimulus velocity for either predictable or poorly predictable head motion, and there was a trend toward greater VVOR gain at higher head velocities. Phase was compensatory at all frequencies for predictable sinusoids. For poorly predictable and unpredictable head motion, gain enhancement with telescopic spectacles was significantly less than during predictable head motion. During poorly predictable head motion, phase lags were observed that increased with frequency and telescopic spectacle power. 3. The perseverance of VVI during disappearance of the visual environment was evaluated by blanking it during various proportions of the cycle of predictable head rotation at frequencies from 0.8 to 2.4 Hz. Below 2.0 Hz, a trend toward gain enhancement was observed with x1.9 telescopic spectacles when the visual environment was present for as little as 6% of the sinusoidal cycle. This effect was statistically significant (P < 0.01) at 0.8 and 1.2 Hz when the visual environment was present for 50% of the cycle. 4. Suppression of the VOR was evaluated for visual fixation of real and imaginary head-fixed targets during predictable, poorly predictable, and unpredictable rotations. Fixation of a real target was most effective at low frequencies of predictable rotation and was significantly effective in reducing gain relative to the VOR at frequencies of < or = 2.4 Hz.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Two-dimensional optokinetic nystagmus induced by moving plaids and texture boundaries. Evidence for multiple visual pathways.

Horizontal and vertical components of optokinetic nystagmus (OKN) were measured using the magnetic search coil technique in normal human adults during presentation of simple and complex moving patterns. Simple patterns were gratings moving horizontally and obliquely. Complex moving patterns consisted of plaids formed by superimposed oblique motion of two sets of gratings or of illusory contours formed by offset discontinuities in gratings. Slow-phase OKN gains (eye velocity divided by stimulus velocity) induced by high-contrast type I and type II plaids were comparable with those generated by one-dimensional moving gratings. The axis of OKN for high-contrast plaids was along the resultant direction determined by the intersection-of-constraints rule and not along any component. With low-contrast presentations, OKN induced by type I patterns remained in the resultant direction, but the OKN direction induced by type II patterns was biased toward the components' directions. The OKN generated by texture boundaries embedded in real pattern motion was measured for motion of illusory contours having systematically varying directions. The gain of OKN induced by real motion was independent of the direction of illusory contour motion, but the gain to illusory contour motion decreased with increasing contour angles. All these results suggest that input signals for driving the optokinetic system come from visual areas extracting higher order two-dimensional motion information.

Form Perception

Validation of physiologic predictors of successful telescopic spectacle use in low vision.

A group of 32 patients with low vision who were considered clinically appropriate candidates for visual rehabilitation with telescopic spectacles were prospectively studied before the first attempted use of these visual aids. Laboratory measurements were made of: (1) rotational head stability in pitch and yaw during quiet standing; (2) sensitivity of visual acuity with telescopic spectacles to imposed yaw head motion; and (3) ocular stabilization reflexes during passive, whole-body rotation in the horizontal plane. Predicted likelihood of successful use of telescopic spectacles was prospectively computed for each patient using the measurement of head stability in the pitch axis and the sensitivity of visual acuity with telescopic spectacles to head motion using a previously described statistical method. Patients were then given telescopic spectacles, and functional success was evaluated in the field at least 6 weeks later by independent masked observers. Although corrected visual acuities did not differ in the 24 patients in whom rehabilitation was successful or in the 8 patients in whom it was not, successful patients had statistically significantly less (P less than 0.05) angular head instability in pitch and yaw, as well as less impairment of visual acuity with telescopic spectacles during head motion. This finding was confirmed in a more clinically homogeneous subgroup of 16 patients who had low vision due to maculopathy. Gains of the 0.1 Hz horizontal vestibulo-ocular reflex (VOR) and visual-vestibulo-ocular reflex (VVOR) with 4X telescopic spectacles did not differ between patients in whom rehabilitation was successful and those in whom it was not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Ocular movements in essential blepharospasm.

In essential blepharospasm histopathologic and electrophysiologic evidence supports the existence of lesions in proximity to brainstem nuclei controlling ocular movements. We studied horizontal ocular movements in eight patients who had been treated previously with surgery or botulinum toxin injection to control essential blepharospasm (mean age, 58 years) and compared these with seven control subjects who did not have blepharospasm (mean age, 68 years). We examined fixation stability, saccades, the vestibulo-ocular reflex, visual enhancement and suppression of the vestibulo-ocular reflex, optokinetic nystagmus, and pursuit by using digitally sampled, direct current electro-oculography. Patients with blepharospasm exhibited no ocular movement abnormalities. Since quantitative aspects of ocular movements are sensitive to nonspecific brainstem lesions, the absence of abnormal ocular movements suggests that the lesion in blepharospasm is specifically limited to neurons regulating the facial muscles.

Adult

Eye movements in cocaine abusers.

Using electro-oculography, we quantitatively investigated eye movements in nine heavy cocaine abusers and three groups of controls. Plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabolite of brain norepinephrine, in cocaine abusers were reduced to an average of 53% of normal. Cocaine abusers had normal smooth pursuit, optokinetic nystagmus, vestibulo-ocular reflex, visual suppression of the vestibulo-ocular reflex, and caloric nystagmus. Data were suggestive of a significant reduction in the degree of immediate enhancement of visual-vestibulo-ocular reflex gain by magnified vision in the cocaine abusers. However, adaptive plasticity of the vestibulo-ocular reflex was normal in the cocaine abusers. These results suggest that, despite animal data linking vestibulo-ocular reflex plasticity to central norepinephrine, this neurotransmitter may not be important to plasticity in human beings.

Adult

Cortical areas involved in OKN and VOR in cats: cortical lesions.

Eye movements evoked by optokinetic and vestibular stimulation were measured by scleral search coil before and up to 8 weeks after unilateral cortical lesions in 11 cats. During both monocular and binocular viewing conditions, several deficits in the velocity-storage component of optokinetic nystagmus (OKN) were found. At low target velocities, the final steady-state slow-phase eye velocity and the peak value of optokinetic afternystagmus (OKAN) were reduced for slow phases towards the side of the lesion. At high target velocities OKN and OKAN were no longer elicited. The time constant of OKAN was also reduced for slow phases towards the side of the lesion. These deficits in OKN and OKAN were quantitatively similar in cats with large cortical (LC) lesions involving all known visual areas and in cats with suprasylvian (SS) lesions involving areas 21a, 21b, PMLS, and VLS. Ablation of areas 17 and 18 alone had no effect, but when combined with section of the corpus callosum (17/18+CC) resulted in a qualitatively similar but less severe deficit as the LC and SS lesions. By 3 weeks postoperatively, OKN recovered to near preoperative values in cats with SS lesions. Vestibular adaptive capabilities were impaired during the duration of the study in cats with LC, SS, and 17/18+CC lesions. Cats with these lesions could not normally increase VOR gain for slow phases directed ipsilateral to the lesion, and following vestibular adaptation most of these cats developed persistent asymmetries in VOR gain and VOR time constants. These results can be better conceptualized using a mathematical model of the vestibulo-ocular and optokinetic system adapted from Robinson (1977). This model contains a single positive-feedback velocity storage loop common to the VOR and OKN systems and a retinal-slip velocity nonlinearity. Our results suggest that SS cortex improves the retinal-slip nonlinearity feeding into the velocity-storage system by extending its range and increasing its gain. The SS cortex depends in part upon areas 17 and 18 either directly, or indirectly via the corpus callosum, for processing of high retinal-slip velocities. Cerebral cortex is also involved in increasing the gain of the velocity-storage loop during vestibular adaptation for ipsilaterally directed slow phases.

Adaptation, Physiological

Predictors of functional success in telescopic spectacle use by low vision patients.

Telescopic spectacles can theoretically improve function of low vision patients by enlarging retinal images. However, unintended head movement may produce sufficient instability of enlarged retinal images to negate the visual benefit. We investigated this phenomenon as a cause of failure in 38 low vision patients who had previously attempted use of telescopic spectacles. Patients underwent evaluation of the vestibulo-ocular reflex, visual-vestibulo-ocular reflex, head stability in the pitch and yaw axes, and sensitivity of magnified visual acuity to head motion. Although it was impossible to distinguish successful from unsuccessful telescopic spectacle users by means of clinical or historical data, multiple logistic regression analysis was used to derive a useful predictive function based on measurements of sensitivity of magnified vision to head motion, and head instability in the pitch axis. Predictive performance was found to be superior to conventional clinical judgement. These findings support the hypothesis that retinal image stability is important to functional vision, and suggest that head-stabilizing strategies may improve function with telescopic spectacles in certain low vision patients.

Adult

Adaptation to telescopic spectacles: vestibulo-ocular reflex plasticity.

The vestibulo-ocular reflex (VOR) is a mechanism for the production of rapid compensatory eye movements during head movements. To investigate the adaptation of this reflex to spectacle magnifiers, the effect on the VOR of a brief period of wearing telescopic spectacles during head rotation was studied in normal subjects. VOR gain, as measured in darkness, was defined to be the ratio of compensatory slow phase eye velocity to head velocity. Initial VOR gain as measured for vertical axis sinusoidal head rotation at 0.1 Hz, amplitude 60 degrees/sec, was about 0.7. After 15 min adaptation by sinusoidal rotation during the viewing of a remote video display through X2, X4, or X6 binocular telescopic spectacles, 47-70% of subjects exhibited significant VOR gain increases of 7-46%. These increases were measured with occlusion of the unmagnified visual field peripheral to the telescopes during adaptation. There was considerable interindividual variability in adaptation to telescopic spectacles. Telescopic spectacle power had little or no effect on the amount of VOR change after adaptation, although all telescope powers produced a greater VOR gain change than did adaptation without telescopes. Testing of VOR gain at multiple frequencies indicated that adaptation to telescopic spectacles by rotation at a single sinusoidal frequency induces VOR gain changes across a broad spectrum of frequencies of head rotation. When the unmagnified peripheral visual field was unobstructed during adaptation, VOR gain increases were significantly less than when the unmagnified peripheral visual field was occluded, and were similar to those observed during adaptation without the wearing of telescopic spectacles at all. VOR gain adaptation was associated with amerlioration of symptoms of oscillopsia and motion discomfort initially experienced by about 20% of subjects wearing telescopic spectacles.

Adaptation, Physiological

Imaging of cerebral blood flow and metabolism in amblyopia by positron emission tomography.

We used positron emission tomography to study monocular visual activation of various brain regions in four amblyopic and two normally sighted adults. Imaging of relative cerebral blood flow using the tracer H2(15)O showed reduced activation of primary visual cortex by the amblyopic as compared with the sound eye. Imaging of relative cerebral glucose metabolism using the tracer [18F]-2-deoxyglucose showed equal activation of primary visual cortex by either eye in the control subject, but reduced activation of primary and accessory visual cortex by the amblyopic as compared with the sound eye in two amblyopic subjects. Relative glucose metabolism was consistently higher in the frontal and temporal lobes contralateral to the viewing eye, both in normal and amblyopic subjects.

Amblyopia

Dynamic visual acuity with telescopic spectacles: improvement with adaptation.

Telescopic spectacles are used as aids for the visually impaired in order to increase effective visual acuity. Because ocular stabilization reflexes are not fully compensatory when telescopic spectacles are worn, head motion would be expected to produce retinal image motion which could decrease visual acuity. Using 1.0 Hz sinusoids of vertical axis head rotation, we investigated the effect of head velocity and telescopic spectacle magnification on binocular dynamic visual acuity (DVA), the acuity during head motion, in 34 normally sighted subjects. The visual field peripheral to the telescopes was masked. Up to a head velocity amplitude of 30 degrees/sec, DVA was insensitive to head velocity for X2 telescopic spectacles. For X4 and, to a greater degree, X6 telescopic spectacles, DVA decreased progressively as head velocity increased. DVA measurements were repeated after a 15 min adaptation period, during which a distant video monitor was viewed using telescopic spectacles. For X4 telescopic spectacles, DVA increased significantly after adaptation. With an unobstructed peripheral visual field, initial DVA with X4 telescopic spectacles was equal to adapted DVA with peripheral vision occluded, but adaptation produced no further improvement in DVA with the peripheral field unobstructed. These data indicate that the visual acuity obtained with telescopic spectacles is substantially reduced under conditions where head motion occurs, potentially reducing the functional value of these devices in low vision rehabilitation. The adverse effect of head motion on DVA may be reduced by adaptation.

Adaptation, Physiological

Vestibulo-ocular reflex during magnified vision: adaptation to reduce visual-vestibular conflict.

This report describes the short-term effect of 2.2X telescopic spectacles on the vestibulo-ocular reflex (VOR) in seven volunteers. VOR gain was initially measured in darkness and light during passive sinusoidal rotations. Subjects were then rotated in light for 15 min while wearing telescopic spectacles. Dynamic visual acuity (DVA), vision during head rotation, was measured with telescopic spectacles. Initial VOR gain in darkness was 0.74 +/- 0.10 (mean +/- S.D.); VOR gain with unmagnified vision was 1.07 +/- 0.04. Initial VOR gain with magnified vision was 1.37 +/- 0.53. DVA was poorer than static acuity in three of four subjects. After adaptation, VOR gain in darkness increased to 0.83 +/- 0.12, with six of seven subjects exhibiting a gain increase of 7-23% (p less than 0.05 for 5). Adapted VOR gain with magnified vision was 1.54 +/- 0.25. Adapted performance was more consistent and oscillopsia was reduced. Adapted DVA improved 30-100% in four subjects. These changes indicate VOR adaptation to telescopic spectacles decreases visual-vestibular conflict.

Adaptation, Physiological

Persistent elevation in intraocular pressure after Nd:YAG laser treatment.

A bilaterally pseudophakic patient, who had no previous evidence of glaucoma, underwent Nd:YAG laser posterior capsulotomy and dispersal of vitreous syneresis opacities of his left eye. The eye developed persistent intraocular pressure elevation and visual field loss, requiring medical therapy and argon laser trabeculoplasty. His fellow eye remained normotensive after Nd:YAG laser posterior capsulotomy. Nd:YAG laser treatment can result in chronic intraocular pressure elevation and glaucomatous visual field loss.

Cataract Extraction

Effects of electrical stimulation and reversible lesions of the olivocerebellar pathway on Purkinje cell activity in the flocculus of the cat.

The activity of Purkinje cells (P-cells) in the flocculus of 8 lightly anesthetized cats and one alert cat was recorded for periods of up to several hours each. The resting simple spike (SS) rate in the anesthetized cats was 37 +/- 21 Hz (mean +/- standard deviation), similar to that observed in the alert cat. Complex spikes (CSs) were evoked by an electrode placed in the climbing fiber (CF) decussation or inferior olive (IO). For each P-cell, SS activity was suppressed completely at or above a cut-off frequency of evoked CSs; median cut-off rate was 5 Hz (range 1-10 Hz, 15 cells). Reversible lesions of the CF pathway were made by microinjection of 1-10 microliter of saturated lidocaine into the IO or CF decussation. This abolished spontaneous CS activity and produced two reversible effects on SS discharge: (1) an increase in mean SS rate of 98%, from 23 +/- 13 to 40 +/- 18 Hz (11 cells); and (2) a decrease of 50% in the variability of SS firing rate. Similar effects were observed in two P-cells whose CF axons were lesioned mechanically. These results show that electrical stimulation and reversible lesions in areas previously shown to alter the gain of the vestibulo-ocular reflex (VOR) also alter CF input to the flocculus, suggesting that the gain changes were caused by changes in CS rate. This study confirms and extends the observation that a reciprocal relationship exists between CS rate and SS background rate, and therefore further suggests that the changes in the gain of the VOR might be due to changes in SS background rate.

Animals

Vestibulo-ocular and optokinetic deficits in albinos with congenital nystagmus.

Vestibular and optokinetic responses were recorded in three albino subjects with congenital nystagmus. Although an ice-water caloric stimulus did not elicit nystagmus, all patients showed a response to rotational stimuli containing high frequency components. Vestibular responses to a constant velocity rotation decremented with abnormally short time constants of 1-2 sec (normal 15-20 sec). For sinusoidal oscillation, in one subject, the cut-off frequency (where the amplitude of the response was 70% of maximum) was increased to 0.8 Hz (normal about 0.01 Hz). Full-field optokinetic stimulation generated no nystagmus response. These abnormalities may be due to defects in networks that act as mathematical integrators : either the final common neural gaze-holding network that converts velocity into position information for the ocular motor neurons or the "velocity-storage" mechanism that normally combines sensory inputs from both the labyrinths and visual system to generate appropriate (per-rotatory) nystagmus during rotation and to suppress inappropriate (post-rotatory) nystagmus after rotation.

Adult