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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
PubMed2006

Diffusion tensor MRI shows abnormal brainstem crossing fibers associated with ROBO3 mutations.

Horizontal gaze palsy with progressive scoliosis (HGPPS) is caused by mutations in the ROBO3 gene, critical for the crossing of long ascending medial lemniscal and descending corticospinal tracts in the medulla. Diffusion tensor imaging in a patient with HGGPS revealed the absence of major pontine crossing fiber tracts and no decussation of the superior cerebellar peduncles. Mutations in the ROBO3 gene lead to a widespread lack of crossing fibers throughout the brainstem.

Adult↗
PubMed2001

Dynamic visual acuity during transient and sinusoidal yaw rotation in normal and unilaterally vestibulopathic humans.

The vestibulo-ocular reflex (VOR) stabilizes gaze to permit clear vision during head movements. It has been supposed that VOR function might be inferred from dynamic visual acuity (DVA), the acuity during imposed head motion. We sought to determine effectiveness of DVA for detection and lateralization of unilateral vestibulopathy, using rigorous psychophysical methods. Seventeen normal and 11 unilaterally vestibulopathic subjects underwent measurement of optically best corrected DVA during head motion. A variable size letter "E" 6 m distant was displayed in oblique random orientations to determine binocular DVA by a computer controlled, forced choice method. Three types of whole-body yaw rotation were delivered by a servo-controlled chair synchronized with optotype presentation. Two types of motion were predictable: (1) steady-state 2.0-Hz rotation at 10-130 degrees/s peak velocity with repetitive optotype presentation only during head velocity exceeding 80% of peak; and (2) directionally predictable transients at peak accelerations of 1000, 1600 and 2800 degrees/s2 with optotype presentation for 300 ms. For neither of these predictable motions did DVA in vestibulopathic subjects significantly differ from normal, with suggestions from search coil recordings that this was due to predictive slow and saccadic eye movements. Unilaterally vestibulopathic subjects experienced a significant decrease in DVA from the static condition during ipsilesional rotation for all three peak head accelerations. Only during directionally unpredictable transients with 75 ms or 300 ms optotype presentation was the sensitivity of DVA in unilaterally vestibulopathic subjects significantly abnormal during ipsilesional rotation. The ipsilesional decrease in DVA with head motion was greater for 75 ms than 300 ms optotype presentation. Search coil recordings confirmed hypometric compensatory eye movements during DVA testing with unpredictable, ipsilesional rotation. Receiver-operator characteristic analysis indicated ideal detection and lateralization of unilateral vestibulopathy by DVA tested with a 75-ms optotype exposure for unpredictable transient rotations to a peak acceleration of 2800 degrees/s. DVA can reliably detect unilateral deafferentation only if precautions are taken to prevent compensation by predictive slow eye movements and saccades.

Adaptation, Physiological↗
PubMed2001

Impairments in the initial horizontal vestibulo-ocular reflex of older humans.

To determine age-related changes, the initial horizontal vestibulo-ocular reflex (VOR) of 11 younger normal subjects (aged 20-32 years) was compared with that of 12 older subjects (aged 58-69 years) in response to random transients of whole-body acceleration of 1,000 and 2,800 degrees/s2 delivered around eccentric vertical axes ranging from 10 cm anterior to 20 cm posterior to the eyes. Eye and head positions were sampled at 1,200 Hz using magnetic search coils. Subjects fixed targets 500 cm or 15 cm distant immediately before the unpredictable onset of rotation in darkness. For all testing conditions, younger subjects exhibited compensatory VOR slow phases with early gain (eye velocity/head velocity, interval 35-45 ms from onset of rotation) of 0.90 +/- 0.02 (mean +/- SEM) for the higher head acceleration, and 0.79 +/- 0.02 for the lower acceleration. Older subjects had significantly (P < 0.0001) lower early gain of 0.77 +/- 0.04 for the higher head acceleration and 0.70 +/- 0.02 for the lower acceleration. Late gain (125-135 ms from onset of rotation) was similar for the higher and lower head accelerations in younger subjects. Older subjects had significantly lower late gain at the higher head acceleration, but gain similar to the younger subjects at the lower acceleration. All younger subjects maintained slow-phase VOR eye velocity to values > or = 200 degrees/s throughout the 250-ms rotation, but, after an average of 120 ms rotation (mean eccentricity 13 degrees), 8 older subjects consistently had abrupt declines (ADs) in slow-phase VOR velocity to 0 degree/s or even the anticompensatory direction. These ADs were failures of the VOR slow phase rather than saccades and were more frequent with the near target at the higher acceleration. Slow-phase latencies were 14.4 +/- 0.4 ms and 16.8 +/- 0.4 ms for older subjects at the higher and lower accelerations, significantly longer than comparable latencies of 10.0 +/- 0.5 ms and 12.0 +/- 0.6 ms for younger subjects. Late VOR gain modulation with target distance was significantly attenuated in older subjects only for the higher head acceleration.

Acceleration↗
PubMed2001

Orbital wall approach with preoperative orbital imaging for identification and retrieval of lost or transected extraocular muscles.

PURPOSE: To report the results of an anterior approach along the orbital wall to recover a lost or transected extraocular muscle. METHODS: This is a retrospective review of lost or transected muscles retrieved by an anterior orbitotomy approach to the adjacent orbital wall because they were unable to be recovered by a standard conjunctival approach. Magnetic resonance imaging or computed tomography was performed on all subjects before surgery. RESULTS: Six patients underwent anterior orbitotomy via an orbital wall approach; all had undergone an attempted retrieval from a standard transconjunctival approach that failed. Five muscles had been lost from surgical or traumatic transection, and 1 muscle had been lost during strabismus surgery. The muscle location at retrieval ranged from 20 to 25 mm (mean, 23 mm) posterior to the limbus. The duration that these muscles were disinserted ranged from 7 days to 7.5 years (mean, 24 months). Preoperative deviation in primary gaze ranged from 15 to 50 PD, whereas first day postretrieval deviations all measured less than 8 PD. After a mean follow-up of 162 weeks, the mean deviation in primary gaze was 2 PD (range, orthotropia to 7 PD of esotropia). CONCLUSIONS: Anterior orbitotomy along the orbital wall with preoperative orbital imaging of extraocular muscle anatomy and function combine to create a valuable approach for retrieval of a lost or transected muscle. This technique may successfully retrieve lost or transected muscles that previously were irretrievable when using a standard transconjunctival approach.

Humans↗
PubMed2001

Otolith function in cerebellar ataxia due to mutations in the calcium channel gene CACNA1A.

The vestibulo-ocular reflexes stabilize retinal images during head movements. While there is a wealth of information about the interaction between the cerebellum and vestibulo-ocular reflexes mediated by the semicircular canals, little is known about the role of the cerebellum in the generation of the otolith-mediated linear vestibulo-ocular reflex (LVOR). By means of transient linear acceleration of the whole body along the interaural axis, we examined the LVOR in six patients with hereditary cerebellar ataxia due to mutations of the calcium channel gene CACNA1A, five with spinocerebellar ataxia type 6 (SCA6) and one with episodic ataxia type 2 (EA-2). Six age-matched normal subjects served as controls. Using a peak acceleration of 0.5 g in combination with recording by the binocular scleral magnetic search coil method, it was possible to study the latency and sensitivity of the LVOR in the first 150 ms after motion onset. The normal LVOR showed a significant dependence on viewing distance and covaried with vergence angle, and could be enhanced by the presence of a visible target. In contrast, the LVOR of ataxic patients had normal latency but significantly decreased sensitivity that was not enhanced with visible or nearer targets despite normal vergence. Substituting for the normal smooth LVOR slow phase, ataxic patients employed catch-up saccades 150-250 ms after motion onset. These findings suggest a critical role of the cerebellum in the modulation of otolith-ocular signals that is independent of motor vergence.

Adult↗
PubMed2001

New tests of vestibular function.

The vestibulo-ocular reflex (VOR) is the only drive for short-latency eye movements stabilizing the retina during externally imposed, sudden, high-head accelerations. New strategies can exploit this unique VOR feature to study it under conditions relevant to the daily lives of patients, and to exclude the contributions from confounding nonvestibular mechanisms. Testing of the yaw vestibulo-ocular reflex (VOR) during random, whole-body rotational transients at < or = 2800 degrees/s2 delivered about centered and eccentric axes enables measurement of gains and millisecond latencies of the canal and otolith VORs in humans. Repeated measurements in acute unilateral deafferentation show sequential recovery of canal and otolith VORs to contralesional rotation, but severe and permanent deficits to ipsilesional rotation. Patients with bilateral loss of caloric responses show severe bilateral loss of VORs to transient rotation, suggesting that the apparent preservation of their VORs during sinusoidal rotations at moderate frequencies may be due instead to somatosensory inputs. Since visual acuity is degraded by retinal image motion, dynamic visual acuity (DVA) measured during imposed head-on-body or whole-body transient motion can correlate closely with VOR performance only if optotypes are presented during directionally and temporally unpredictable, high-acceleration head motion. Prediction and efference copy are relentlessly employed by vestibulopathic patients to enable good DVA during predictable or low-acceleration head motion. The linear VOR to transient lateral acceleration is strongly dependent upon viewing distance. The latency of this otolith VOR is slightly longer and more variable than the canal VOR. Unlike the canal VOR, the otolith VOR does not develop a strong directional asymmetry in unilateral deafferentation. The otolith VOR is bilaterally attenuated in bilateral vestibulopathy, and loses target distance dependence in cerebellar degeneration.

Adult↗
PubMed2001

Vestibular function in severe bilateral vestibulopathy.

OBJECTIVES: To assess residual vestibular function in patients with severe bilateral vestibulopathy comparing low frequency sinusoidal rotation with the novel technique of random, high acceleration rotation of the whole body. METHODS: Eye movements were recorded by electro-oculography in darkness during passive, whole body sinusoidal yaw rotations at frequencies between 0.05 and 1.6 Hz in four patients who had absent caloric vestibular responses. These were compared with recordings using magnetic search coils during the first 100 ms after onset of whole body yaw rotation at peak accelerations of 2800 degrees /s(2). Off centre rotations added novel information about otolithic function. RESULTS: Sinusoidal yaw rotations at 0.05 Hz, peak velocity 240 degrees/s yielded minimal responses, with gain (eye velocity/head velocity)<0.02, but gain increased and phase decreased at frequencies between 0.2 and 1.6 Hz in a manner resembling the vestibulo-ocular reflex. By contrast, the patients had profoundly attenuated responses to both centred and eccentric high acceleration transients, representing virtually absent responses to this powerful vestibular stimulus. CONCLUSION: The analysis of the early ocular response to random, high acceleration rotation of the whole body disclosed a profound deficit of semicircular canal and otolith function in patients for whom higher frequency sinusoidal testing was only modestly abnormal. This suggests that the high frequency responses during sinusoidal rotation were of extravestibular origin. Contributions from the somatosensory or central predictor mechanisms, might account for the generation of these responses. Random, transient rotation is better suited than steady state rotation for quantifying vestibular function in vestibulopathic patients.

Adult↗
PubMed2001

Quantitative analysis of rectus extraocular muscle layers in monkey and humans.

PURPOSE: Rectus extraocular muscles (EOMs) consist of orbital (OL) and global (GL) layers. This study enumerated the fibers in both layers along the length of each EOM. METHODS: Four human (ages 17 months-93 years) and three monkey (ages 5-7 years) orbits were serially sectioned in the coronal plane and stained with Masson's trichrome. All fibers of the rectus EOMs were counted using light microscopy at midorbit in all specimens and regular intervals throughout the orbits for one human and one monkey. RESULTS: In the GL, human EOMs in midorbit contained 8000 to 16,400 fibers, and monkey EOMs contained 3600 to 6600 fibers, varying little among the four rectus EOMs. In humans and monkeys, the number of OL fibers in midorbit varied widely according to specific EOM, being most numerous for the medial rectus (human: 7400-14,600; monkey: 3700-7000). The GL existed over the entire extent of each EOM from origin in the orbital apex into continuity with the tendon inserting on the globe. The OL was absent in the most anterior portion of each EOM, because OL fibers inserted on the respective EOM pulley. CONCLUSIONS: Primate EOMs contain substantial numbers of OL fibers. Numerical similarity of GL fibers is consistent with similar mechanical loading on each of the four rectus EOMs, as required to rotate the globe. Numerical dissimilarity of OL fibers correlates with varying mechanical loading because of varying elasticities of connective tissues onto which these fibers insert.

Adolescent↗
PubMed2001

Structure-function correlation of laminar vascularity in human rectus extraocular muscles.

PURPOSE: Orbital and global layers of rectus extraocular muscles (EOMs) are believed to serve different functions. This study sought anatomic and functional evidence of differing blood flow in the two layers of rectus EOMs. METHODS: Four human orbits ranging in age from 17 months to 93 years were serially sectioned and stained for muscle fibers with Masson's trichrome and for vascular smooth muscle with monoclonal antibody to smooth muscle alpha-actin. Digitally assisted microscopy was used to obtain measurements of luminal cross sections and counts of muscular blood vessels, as well as measurements of muscle fiber number and cross-sectional areas of the two layers. Findings were correlated with first-pass gadodiamide contrast magnetic resonance imaging (MRI) in two living humans to demonstrate relative perfusion of EOMs. RESULTS: In all rectus EOMs, the orbital layer had significantly more vessels per unit area, more vessels per fiber, and more total vascular luminal area, than the global layer (P: < 0.05). Vascularity of EOMs was greatest in the youngest specimen. First-pass contrast MRI was consistent with perfusion of the orbital layer earlier than the global layer of living human rectus EOMs. CONCLUSIONS: Orbital layers of human rectus EOMs have significantly more muscular vessels than the global layers and stain earlier after intravenous bolus injection of paramagnetic MRI contrast. These findings suggest higher and even more rapid blood flow in the orbital layers that may correlate with greater metabolic activity. Greater blood flow is consistent with more sustained mechanical loading of the orbital than the global layer.

Adult↗
PubMed2000

Initial vestibulo-ocular reflex during transient angular and linear acceleration in human cerebellar dysfunction.

During transient, high-acceleration rotation, performance of the normal vestibulo-ocular reflex (VOR) depends on viewing distance. With near targets, gain (eye velocity/head velocity) enhancement is manifest almost immediately after ocular rotation begins. Later in the response, VOR gain depends on both head rotation and translation; gain for near targets is decreased for rotation about axes anterior to the otoliths and augmented for rotation about axes posterior to the otoliths. We sought to determine whether subjects with cerebellar dysfunction have impaired modification of the VOR with target distance. Eleven subjects of average age 48 +/- 16 years (mean +/- standard deviation, SD) with cerebellar dysfunction underwent transients of directionally unpredictable whole-body yaw rotation to a peak angular acceleration of 1000 or 2800 degrees/s2 while viewing a target either 15 cm or 500 cm distant. Immediately before onset of head rotation, the lights were extinguished and were relit only after the rotation was completed. The axis of head rotation was varied so that it was located 20 cm behind the eyes, 7 cm behind the eyes (centered between the otoliths), centered between the eyes, or 10 cm anterior to the eyes. Angular eye and head positions were measured with magnetic search coils. The VOR in subjects with cerebellar dysfunction was compared with the response from 12 normal subjects of mean age 25 +/- 4 years. In the period 35-45 ms after onset of 2800 degrees/s2 head rotation, gain was independent of rotational axis. In this period, subjects with cerebellar dysfunction had a mean VOR gain of 0.5 +/- 0.2, significantly lower than the normal range of 1.0 +/- 0.2. During a later period, 125-135 ms after head rotation about an otolith-centered axis, subjects with cerebellar dysfunction had a mean VOR gain of 0.67 +/- 0.46, significantly lower than the value of 1.06 +/- 0.14 in controls. Unlike normal subjects, those with cerebellar dysfunction did not show modification of VOR gain with target distance in the early response and only one subject showed a correct effect of target distance in the later response. The effect of target distance was quantitatively assessed by subtracting gain for a target 500 cm distant from gain for a target 15 cm distant. During the period 35-45 ms after the onset of 2800 degrees/s2 head motion, only two subjects with cerebellar loss demonstrated significant VOR gain enhancement with a near target, and both of these exhibited less than half of the mean enhancement for control subjects. During the later period 125-135 ms after the onset of head rotation, when VOR gain normally depended on both target location and otolith translation, only one subject with cerebellar dysfunction consistently demonstrated gain changes in the normal direction. These findings support a role for the cerebellum in gain modulation of both the canal and otolith VOR in response to changes in distance. The short latency of gain modification suggests that the cerebellum may normally participate in target distance-related modulation of direct VOR pathways in a manner similar to that found in plasticity induced by visual-vestibular mismatch.

Adult↗
PubMed2000

Vestibular catch-up saccades in labyrinthine deficiency.

During rapid head rotations, saccades ipsiversive with compensatory vestibulo-ocular reflex (VOR) slow phases may augment the deficient VOR and assist gaze stabilization in space. The present experiments compared these vestibular catch-up saccades (VCUSs) with visually and memory-guided saccades. To characterize VCUSs and their relationship to deficiency of the initial VOR, we delivered random, whole-body transients of 1000 and 2800 degrees/s2 peak yaw acceleration around four different eccentric vertical axes in eight unilaterally and one bilaterally vestibulopathic subjects, as well as nine age-matched normal subjects. Eye and head movements were sampled at 1200 Hz using magnetic search coils. Subjects fixed targets at either 500 or 15 cm distance immediately before unpredictable onset of rotation in darkness. Under all testing conditions, normal subjects exhibited only compensatory vestibular slow phases and occasional anticompensatory quick phases. This behavior was also typical of unilaterally vestibulopathic subjects rotated contralesionally. When rotated ipsilesionally, however, vestibulopathic subjects had deficient slow-phase VOR gain with prolonged latency, and six of the nine exhibited saccadic movements in the compensatory direction (VCUSs). Higher head accelerations preferentially evoked VCUSs, but there were no preferred combinations of target distances and eccentric rotation axes. Peak velocities and durations of VCUSs increased with saccade amplitude. The latency distribution for VCUSs peaked around 70 ms, substantially shorter than reported for either visually guided express saccades or vestibular memory contingent saccades. The latency of each VCUS was highly correlated with the gaze error prior to that VCUS. The amplitude of VCUSs was calibrated to gaze position error, such that VCUSs reduced gaze error by an average of 37%. Thus when VOR slow-phase responses cannot compensate fully for head rotation, vestibular gaze position error can nevertheless calibrate the programming of VCUSs to augment the deficient VOR, much like catch-up saccades substitute for deficient visual pursuit.

Acceleration↗
PubMed2000

Effects of vestibular and cerebellar deficits on gaze and torso stability during ambulation.

We measured gaze, head, and torso stability during ambulation to determine how vestibulo-ocular reflex dysfunction caused by unilateral vestibulopathy, bilateral vestibulopathy, and cerebellar dysfunction might affect image stabilization on the retina. Subjects were tested during standing, walking, and running on a treadmill. Gaze velocity, vestibulo-ocular reflex gain, and head velocities were calculated from angular positions of the eye and head, as well as linear positions of the head and trunk. Mean gaze velocity with a visible, distant target was below 4 degrees /second for all measurement conditions in control and vestibulopathic subjects. The performance of unilaterally vestibulopathic subjects was indistinguishable from that of control subjects except that the former had less vertical translation during walking. Bilaterally vestibulopathic subjects demonstrated less head translation than control subjects but had higher gaze velocity. In subjects with cerebellar dysfunction, gaze velocity was elevated by pathologic nystagmus, but head movements were similar to those of control subjects.

Adult↗
PubMed2000

Facial asymmetry in superior oblique muscle palsy and pulley heterotopy.

INTRODUCTION: Some observers have considered facial asymmetry as characteristic of congenital superior oblique muscle (SO) palsy. However, recent orbital imaging studies have determined that incomitant vertical strabismus resembling SO palsy can be caused by heterotopic rectus muscle pulleys. This finding suggests that facial asymmetry may predict the presence of abnormal orbital anatomy rather than be secondary to ocular torticollis. METHODS: Subjects who underwent orbital computed tomography or magnetic resonance imaging were divided into 5 groups based on clinical evaluation and previously established imaging criteria: (1) congenital SO palsy; (2) acquired SO palsy; (3) strabismus with pulley heterotopy; (4) strabismus without SO palsy or pulley heterotopy; and (5) orthotropic subjects. Frontal photographs were digitized and the following 3 facial morphometric features recorded: (1) angle of inclination of each orbit; (2) relative facial size; and (3) facial angle. RESULTS: The 79 subjects who underwent imaging were divided into the 5 groups as follows: 6 with congenital SO palsy; 7 with acquired SO palsy; 20 with pulley heterotopy; 26 with strabismus without SO palsy or pulley heterotopy; and 20 control subjects. All subjects with either congenital or acquired SO palsy had torticollis. Multivariate analysis demonstrated no significant differences in any of the 3 facial morphometric features among any of the groups. CONCLUSION: Facial asymmetry as assessed by these 3 morphometric features is not useful in distinguishing between congenital SO palsy or pulley heterotopy and other acquired forms of strabismus. This finding casts doubt on the relationship between ocular torticollis and facial asymmetry.

Adolescent↗