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Biomedical subjects

Joseph L Demer

Publications and source records attributed to Joseph L Demer.

At least 19 recordsLinked to original sources
PubMed2007

Two pedigrees segregating Duane's retraction syndrome as a dominant trait map to the DURS2 genetic locus.

PURPOSE: The genetic bases of Duane's retraction syndrome (DRS) were investigated to determine its molecular etiologies. In prior studies, the transcription factors SALL4 and HOXA1 were identified as the genes mutated in DRS with radial anomalies, and in DRS with deafness, vascular anomalies, and cognitive deficits, respectively. Less is known, however, about the genetic etiology of DRS when it occurs in isolation, and only one genetic locus for isolated DRS, the DURS2 locus on chromosome 2, has been mapped to date. Toward the goal of identifying the DURS2 gene, two pedigrees have been ascertained that segregate DRS as a dominant trait. METHODS: Members of two large dominant DRS pedigrees were enrolled in an ongoing study of the genetic basis of the congenital cranial dysinnervation disorders, and linkage analysis was conducted to determine whether their DRS phenotype maps to the DURS2 locus. RESULTS: By haplotype analysis, the DRS phenotype in each family cosegregates with markers spanning the DURS2 region. Linkage analysis reveals maximum lod scores >2, establishing that the DRS phenotype in these two pedigrees maps to the DURS2 locus. CONCLUSIONS: These two pedigrees double the published pedigrees known to map to the DURS2 locus and can thus contribute toward the search for the DURS2 gene. The affected members represent a genetically defined population of DURS2-linked DRS individuals, and hence studies of their clinical and structural features can enhance understanding of the DURS2 phenotype, as described in the companion paper.

Chromosome Mapping↗
PubMed2007

Magnetic resonance imaging evidence for widespread orbital dysinnervation in dominant Duane's retraction syndrome linked to the DURS2 locus.

PURPOSE: High-resolution, multipositional magnetic resonance imaging (MRI) was used to demonstrate extraocular muscles (EOMs) and associated motor nerves in Duane retraction syndrome (DRS) linked to the DURS2 locus on chromosome 2. METHODS: Five male and three female affected members of two autosomal dominant DURS2 pedigrees were enrolled in the study. Coronal T(1)-weighted MRI of the orbits was obtained in multiple gaze positions, as well as with heavy T(2) weighting in the plane of the cranial nerves. MRI findings were correlated with motility. RESULTS: All subjects had unilateral or bilateral limitation of abduction, or of both abduction and adduction, with palpebral fissure narrowing and globe retraction in adduction. Orbital motor nerves were typically small, with the abducens nerve (cranial nerve [CN]6) often nondetectable. Lateral rectus (LR) muscles were structurally abnormal in seven subjects, with structural and motility evidence of oculomotor nerve (CN3) innervation from vertical rectus EOMs leading to A or V patterns of strabismus in three cases. Four cases had superior oblique, two cases superior rectus, and one case levator EOM hypoplasia. Only the medial and inferior rectus and inferior oblique EOMs were spared. Two cases had small CN3s. CONCLUSIONS: DRS linked to the DURS2 locus is associated with bilateral abnormalities of many orbital motor nerves, and structural abnormalities of all EOMs except those innervated by the inferior division of CN3. The LR may be coinnervated by CN3 branches normally destined for any other rectus EOMs. Therefore, DURS2-linked DRS is a diffuse congenital cranial dysinnervation disorder involving but not limited to CN6.

Abducens Nerve Diseases↗
PubMed2006

High-resolution magnetic resonance imaging of the extraocular muscles and nerves demonstrates various etiologies of third nerve palsy.

PURPOSE: The etiology of third nerve palsy is usually diagnosed by history, motility examination, and presence of lid and pupil involvement, as well as cranial and vascular imaging. We used high-resolution magnetic resonance imaging (hrMRI) of the oculomotor nerve and affected extraocular muscles (EOMs) to investigate oculomotor palsy. DESIGN: Prospective, noncomparative, observational case series in an academic referral setting. METHODS: Twelve patients with nonaneurysmal oculomotor palsy of 0.75 to 252 months' duration were studied. In the orbit and along the intracranial oculomotor nerve, hrMRI at 1- to 2-mm thickness was performed. Coronal plane images of each orbit were obtained in multiple, controlled gaze positions. Structural abnormalities of the oculomotor nerve and associated changes in EOM volume and contractility were evaluated. RESULTS: Cases were categorized as tumor related, congenital, diabetic, traumatic, and idiopathic according to clinical characteristics and hrMRI findings. Reduction of volume and contractility of affected EOMs were noted in six patients; however, there was no marked EOMs atrophy in two cases of diabetic oculomotor palsy, and there were four cases of aberrant regeneration. hrMRI demonstrated the oculomotor nerve at the midbrain and at EOMs in all cases, and in two cases with previous normal neuroimaging elsewhere that demonstrated contrast-enhancing tumors on the oculomotor nerve. One patient with apparently unilateral congenital inferior division oculomotor palsy had no detectable ipsilateral and a hypoplastic contralateral oculomotor nerve exiting the midbrain. CONCLUSIONS: hrMRI provides valuable information in patients with oculomotor palsy, such as structural abnormalities of the orbit and oculomotor nerve, and atrophy and diminished contractility of innervated EOMs. This information could be helpful in diagnosis and management of oculomotor palsy.

Adult↗
PubMed2006

Temporal dynamics of semicircular canal and otolith function following acute unilateral vestibular deafferentation in humans.

Dynamic changes of deficits in canal and otolith vestibulo-ocular reflexes (VORs) to high acceleration, eccentric yaw rotations were investigated in five subjects aged 25-65 years before and at frequent intervals 3-451 days following unilateral vestibular deafferentation (UVD) due to labyrinthectomy or vestibular neurectomy. Eye and head movements were recorded using magnetic search coils during transients of directionally random, whole-body rotation in darkness at peak acceleration 2,800 degrees/s2. Canal VORs were characterized during rotation about a mid-otolith axis, viewing a target 500 cm distant until rotation onset in darkness. Otolith VOR responses were characterized by the increase in VOR gain during identical rotation about an axis 13 cm posterior to the otoliths, initially viewing a target 15 cm distant. Pre-UVD canal gain was directionally symmetrical, averaging 0.87 +/- 0.02 (+/-SEM). Contralesional canal gain declined from pre-UVD by an average of 22% in the first 3-5 days post-UVD, before recovering to an asymptote of close 90% of pre-UVD level at 1-3 months. This recovery corresponded to resolution of spontaneous nystagmus. Ipsilesional gain declined to 59%, and showed no consistent recovery afterwards. Pre-UVD otolith gain was directionally symmetrical, averaging 0.56 +/- 0.02. Immediately after UVD, the contralesional otolith gain declined to 0.30 +/- 0.02, and did not recover. Ipsilesional otolith gain declined profoundly to 0.08 +/- 0.03 (P < 0.01), and never recovered. In contrast to the modest and directionally symmetrical effect of UVD on the human otolith VOR during pure translational acceleration, otolith gain during eccentric yaw rotation exhibited a profound and lasting deficit that might be diagnostically useful in lateralizing otolith pathology. Most recovery of the human canal gain to high acceleration transients following UVD is for contralesional head rotation, occurring within 3 months as spontaneous nystagmus resolves.

Acceleration↗
PubMed2006

Comparison of orbital magnetic resonance imaging in duane syndrome and abducens palsy.

PURPOSE: To help resolve the clinical ambiguity between Duane syndrome with severe abduction deficit and abducens palsy, we performed orbital magnetic resonance imaging (MRI) to qualify abnormalities of the lateral rectus (LR) muscle in these entities. DESIGN: Prospective observational case series. METHODS: Orbital MRI was performed in 13 subjects with Duane syndrome (19 eyes), 10 subjects with chronic abducens palsy (10 eyes), and 10 orthotropic control subjects (18 eyes). High-resolution, surface coil, T(1)-weighted MRI was used to obtain contiguous, 2-mm thick quasi-coronal images of the orbits in central gaze. Digital image analysis was used to quantify cross-sectional area of the ipsilesional and contralesional LR to provide comparison with control measurements. RESULTS: Mean maximum LR cross-sectional area in Duane syndrome was statistically similar to control (P = .454) and contralesional LR cross-sectional area (P = .227). However, in chronic abducens palsy, mean maximum ipsilesional LR cross-sectional area was markedly smaller than contralesional (P = .003) and control cross-sectional areas (P < .0001), as well as smaller than the LR in Duane syndrome (P= .0017). CONCLUSIONS: The LR muscle in abducens palsy exhibits profound atrophy. The sparing of the LR in Duane syndrome from denervation atrophy despite absence of normal abducens innervation suggests existence of alternative LR innervation. High-resolution MRI can noninvasively demonstrate LR muscle size and distinguish Duane syndrome from chronic abducens palsy in uncertain cases.

Abducens Nerve Diseases↗
PubMed2006

Effect of unilateral vestibular deafferentation on the initial human vestibulo-ocular reflex to surge translation.

Transient whole-body surge (fore-aft) translation at 0.5 G peak acceleration was administered to six subjects with unilateral vestibular deafferentation (UVD), and eight age-matched controls. Subjects viewed eccentric targets to determine if linear vestibulo-ocular reflex (LVOR) asymmetry might lateralize otolith deficits. Eye rotation was measured using magnetic search coils. Immediately before surge, subjects viewed a luminous target 50 cm away, centered or displaced 10 degrees horizontally or vertically. The target was extinguished during randomly directed surges. LVOR gain relative to ideal velocity in subjects with UVD for the contralesional horizontally eccentric target (0.59 +/- 0.08, mean +/- SEM) did not differ significantly from normal (0.50 +/- 0.04), but gain for the ipsilesional eccentric target (0.35 +/- 0.02) was significantly less than normal (0.48 +/- 0.03, P < 0.05). Normal subjects had mean gain asymmetry for horizontally eccentric targets of 0.17 +/- 0.03, but asymmetry in UVD was significantly increased to 0.35 +/- 0.05 (P < 0.05). Four of six subjects with UVD had maximum gain asymmetry outside normal 95% confidence limits. Asymmetry did not correlate with UVD duration. Gain for 10 degrees vertically eccentric targets averaged 0.38 +/- 0.14 for subjects with UVD, insignificantly lower than the normal value of 0.75 +/- 0.15 (P > 0.05). Surge LVOR latency was symmetrical in UVD, and did not differ significantly from normal. There was no significant difference in response between dark and visible target conditions until 200 ms after surge onset. Chronic human UVD, on average, significantly impairs the surge LVOR for horizontally eccentric targets placed ipsilesionally, but this asymmetry is small relative to interindividual variation.

Acceleration↗
PubMed2006

Inferior rectus muscle transection: a cause of diplopia after non-penetrating orbital trauma.

BACKGROUND: Vertical diplopia after blow out fracture repair is not uncommon; we report an unusual case of inferior rectus muscle (IR) transection presenting as a persistent infra-duction deficit after uncomplicated blow out fracture repair. METHODS: We used multi-positional MRI to diagnose a transected IR with a contracted and posteriorly displaced muscle belly. RESULTS: Infra-duction improved after surgical repair of the transected IR. CONCLUSION: Multipositional MRI is a novel technology that can be used to assist in the decisive management of persistent post-operative infra-duction deficits and avoid prolonged periods of observation.

Adolescent↗
PubMed2006

High-resolution magnetic resonance imaging demonstrates abnormalities of motor nerves and extraocular muscles in patients with neuropathic strabismus.

INTRODUCTION: Although the ocular motility examination has been used traditionally in the diagnosis of strabismus that is a result of cranial nerve (CN) abnormalities, magnetic resonance imaging (MRI) now permits the direct imaging of lesions in CN palsies. METHODS: Prospectively, nerves to extraocular muscles (EOMs) were imaged with T1 weighting in orbits of 83 orthotropic volunteers and 96 strabismic patients in quasicoronal planes using surface coils. Intraorbital resolution was 234-312 microns within 1.5- to 2.0-mm thick planes. CNs were imaged at the brainstem using head coils and T2 weighting, yielding 195 micron resolution in planes 1.0-mm thick in 6 normal volunteers and 22 patients who had oculomotor (CN3), trochlear (CN4), or abducens (CN6) palsies and Duane syndrome. RESULTS: Oculomotor (CN3) and abducens (CN6) but not trochlear (CN4) nerves were demonstrable in the orbit and skull base in all normal subjects. Patients with congenital CN3 palsies had hypoplastic CN3s both in orbit and skull base, with hypoplasia of involved EOMs. Patients with chronic CN6 and CN4 palsies exhibited atrophy of involved EOMs. Patients with Duane syndrome exhibited absence or hypoplasia of CN6 in both orbit and brainstem regions, often with mild hypoplasia and apparent misdirection of CN3 to the lateral rectus muscle. Unlike CN6 palsy, patients with Duane syndrome exhibited no EOM hypoplasia. Patients with congenital fibrosis exhibited severe hypoplasia of CN3, moderate hypoplasia of CN6, and EOM hypoplasia, particularly severe for the superior rectus and levator muscles. CONCLUSION: High-resolution MRI can directly demonstrate pathology of CN3 and CN6 and affected EOM atrophy in strabismus caused by CN palsies. Direct imaging of CNs and EOMs by MRI is feasible and useful in differential diagnosis of complex strabismus.

Abducens Nerve Diseases↗
PubMed2006

Orbital magnetic resonance imaging of extraocular muscles in chronic progressive external ophthalmoplegia: specific diagnostic findings.

INTRODUCTION: Chronic progressive external ophthalmoplegia (CPEO) is characterized by slowly progressive bilateral ophthalmoplegia and blepharoptosis. Molecular diagnosis is problematic because sporadic mitochondrial DNA deletions can be causative. We sought findings using magnetic resonance imaging (MRI) that might support the diagnosis of CPEO. METHODS: Two men (ages 31 and 47 years) and 3 women (ages 40-49 years) with CPEO and symptom durations of 8 months to 28 years underwent high-resolution (2-mm slice thickness, 312 micron pixels), surface coil, T1-weighted orbital MRI in coronal planes. Images were analyzed quantitatively to determine extraocular muscle (EOM) sizes and were compared with 10 age- and gender-matched normal volunteers, one subject with myasthenia gravis, and with 30 subjects having EOM paralysis caused by oculomotor, trochlear,0 and abducens neuropathies. RESULTS: EOM function was clinically diminished in CPEO, most markedly for the superior rectus (SR) and levator muscles. All EOMs in CPEO exhibited unusual qualitative T1 MRI signal abnormalities. Unlike the profound EOM atrophy typical of neurogenic paralysis, anterior volumes of medial rectus, lateral rectus, and inferior rectus muscles in CPEO were not smaller than normal (p>0.003). Anterior volumes of the SR muscle-levator complex and superior oblique were significantly reduced (p<0.003). Denervated EOMs exhibited statistically significant volume reduction when compared with normal and CPEO groups. Volume of the SR muscle-levator complex was the same in subjects with CPEO and oculomotor palsies. CONCLUSIONS: CPEO is associated with minimal EOM volume reduction despite clinically severe weakness. This combination of findings may be specific for CPEO and could resolve the diagnostic dilemma in difficult cases.

Abducens Nerve Diseases↗
PubMed2006

Current concepts of mechanical and neural factors in ocular motility.

PURPOSE OF REVIEW: The oculomotor periphery was classically regarded as a simple mechanism executing complex behaviors specified explicitly by neural commands. A competing view has emerged that many important aspects of ocular motility are properties of the extraocular muscles and their associated connective tissue pulleys. This review considers current concepts regarding aspects of ocular motility that are mechanically determined versus those that are specified explicitly as innervation. RECENT FINDINGS: While it was established several years ago that the rectus extraocular muscles have connective tissue pulleys, recent functional imaging and histology has suggested that the rectus pulley array constitutes an inner mechanism, analogous to a gimbal, that is rotated torsionally around the orbital axis by an outer mechanism driven by the oblique extraocular muscles. This arrangement may account mechanically for several commutative aspects of ocular motor control, including Listing's Law, yet permits implementation of non-commutative motility. Recent human behavioral studies, as well as neurophysiology in monkeys, are consistent with implementation of Listing's Law in the oculomotor periphery, rather than centrally. SUMMARY: Varied evidence now strongly supports the conclusion that Listing's Law and other important ocular kinematics are mechanically determined. This finding implies more limited possibilities for neural adaptation to some ocular motor pathologies, but indicates possibilities for surgical treatments.

Animals↗
PubMed2006

Gillies Lecture: ocular motility in a time of paradigm shift.

Abstract Recent progress in understanding of the structure and function of extraocular muscles, and our ability to image them clinically, allows prediction of revolutionary progress in diagnosis and treatment of strabismus in the coming decades. This perspective memorializes a lecture given in honour of Dr William Gillies, who has for decades been the paternal leader of strabismology in southern Australia.

Australia↗
PubMed2006

Vestibulo-ocular reflex to transient surge translation: complex geometric response ablated by normal aging.

The linear vestibulo-ocular reflex (LVOR) to surge (fore-aft) translation has complex kinematics varying with target eccentricity and distance. To determine normal responses and aging changes, 9 younger [age, 28 +/- 2 (SE) yr] and 11 older subjects (age, 69 +/- 2 yr) underwent 0.5 g whole body surge transients while wearing binocular scleral search coils. Linear chair position and head acceleration were measured with a potentiometer and accelerometer. Subjects viewed centered and 10 degrees horizontally and vertically eccentric targets 50, 25, or 15 cm distant before unpredictable onset of randomly directed surge in darkness (LVOR) and light (V-LVOR). Response directions were kinematically appropriate to eccentricity in all subjects, but there were significantly more measurable LVOR and V-LVOR responses (63-79%) in younger than older subjects (38-44%, P < 0.01). Minimal LVOR latency averaged 48 +/- 4 ms for younger and significantly longer at 70 +/- 6 ms for older subjects. In the interval 200-300 ms after surge onset, horizontal LVOR gain (relative to ideal velocity) of younger subjects averaged over all target distances was 0.55 +/- 0.04 and was significantly reduced in older subjects to 0.33 +/- 0.04. Horizontal V-LVOR gain was 0.58 +/- 0.04 in younger and significantly lower at 0.35 +/- 0.06 in older subjects. Vertical gains did not differ significantly between groups. Target visibility had no effect in either group during the initial 200 ms. The LVOR and V-LVOR were augmented by saccades in younger more than older subjects. Aging thus decreases LVOR velocity gain, response rate, and saccade augmentation, but prolongs latency.

Adult↗
PubMed2006

Temporal dynamics of ocular position dependence of the initial human vestibulo-ocular reflex.

PURPOSE: While an ideal vestibulo-ocular reflex (VOR) generates ocular rotations compensatory for head motion, during visually guided movements, Listing's Law (LL) constrains the eye to rotational axes lying in Listing's Plane (LP). The present study was conducted to explore the recent proposal that the VOR's rotational axis is not collinear with the head's, but rather follows a time-dependent strategy intermediate between LL and an ideal VOR. METHODS: Binocular LPs were defined during visual fixation in eight normal humans. The VOR was evoked by a highly repeatable transient whole-body yaw rotation in darkness at a peak acceleration of 2800 deg/s2. Immediately before rotation, subjects regarded targets 15 or 500 cm distant located at eye level, 20 degrees up, or 20 degrees down. Eye and head responses were compared with LL predictions in the position and velocity domains. RESULTS: LP orientation varied both among subjects and between individual subject's eyes, and rotated temporally with convergence by 5 +/- 5 degrees (+/-SEM). In the position domain, the eye compensated for head displacement even when the head rotated out of LP. Even within the first 20 ms from onset of head rotation, the ocular velocity axis tilted relative to the head axis by 30% +/- 8% of vertical gaze position. Saccades increased this tilt. Regardless of vertical gaze position, the ocular rotation axis tilted backward 4 degrees farther in abduction than in adduction. There was also a binocular vertical eye velocity transient and lateral tilt of the ocular axis. CONCLUSIONS: These disconjugate, short-latency axis perturbations appear intrinsic to the VOR and may have neural or mechanical origins.

Adult↗
PubMed2006

Magnetic resonance imaging of the effects of horizontal rectus extraocular muscle surgery on pulley and globe positions and stability.

PURPOSE: Magnetic resonance imaging (MRI) was used to determine the effect of recessions and resections on horizontal extraocular muscle (EOM) paths and globe position. METHODS: Four adults with horizontal strabismus underwent contrast-enhanced, surface-coil MRI in central, secondary, and tertiary gazes, before and after horizontal EOM recessions and/or resections. EOM paths were determined from 2-mm thickness, quasicoronal MRI by analysis of cross-sectional area centroids in a normalized, oculocentric coordinate system. Globe displacement was determined by measuring the apparent shift of the bony orbit in eccentric gaze. RESULTS: In all subjects, the anteroposterior positions of the horizontal rectus pulleys shifted by less than 2 mm after surgery, indistinguishable from zero within measurement precision. In three subjects who underwent medial rectus (MR) recession or resection, postoperative globe position was similar in central gaze, but globe translation during vertical gaze shift changed markedly. There was no effect on globe translation in the subject who underwent only lateral rectus (LR) resection. CONCLUSIONS: Recessions and resections of horizontal EOMs have minimal effect on anteroposterior EOM pulley positions. Because the pulley does not shift appreciably despite large alterations in the EOM insertion, the proximity of a recessed EOM to its pulley would be expected to introduce torsional and vertical actions in tertiary gazes. Connective tissue dissection during MR surgery may destabilize the globe's vertical translational stability within the orbit, potentially changing the effective pulling directions of the rectus EOMs in vertical gazes. These changes may mimic oblique muscle dysfunction. LR surgery may avoid globe destabilization.

Adult↗
PubMed2005

Magnetic resonance imaging of human extraocular muscles during static ocular counter-rolling.

The rectus extraocular muscle (EOM) pulleys constrain EOM paths. During visual fixation with head immobile, actively controlled pulleys are known to maintain positions causing EOM pulling directions to change by one-half the change in eye position. This pulley behavior is consistent with Listing's law (LL) of ocular torsion as observed during fixation, saccades, and pursuit. However, pulley behavior during the vestibulo-ocular reflex (VOR) has been unstudied. This experiment studied ocular counter-rolling (OCR), a static torsional VOR that violates LL but can be evoked during MRI. Tri-planar MRI was performed in 10 adult humans during central target fixation while positioned in right and left side down positions known to evoke static OCR. EOM cross-sections and paths were determined from area centroids. Paths were used to locate pulleys in three dimensions. Significant (P < 0.025) counter-rotational repositioning of the rectus pulley arrays of both orbits was observed in the coronal plane averaging 4.1 degrees (maximum, 8.7 degrees ) from right to left side down positions for the inferior, medial, and superior rectus pulleys. There was a trend for the lateral rectus averaging 1.4 degrees . Torsional shift of the rectus pulley array was associated with significant contractile cross-section changes in the superior and inferior oblique muscles. Torsional rectus pulley shift during OCR, which changes pulling directions of the rectus EOMs, correlates with known insertions of the oblique EOM orbital layers on rectus pulleys. The amount of pulley reconfiguration is roughly one-half of published values of ocular torsion during static OCR, an arrangement that would cause rectus pulling directions to change by less than one-half the amount of ocular torsion.

Adult↗
PubMed2005

Superior oblique muscle involvement in thyroid ophthalmopathy.

BACKGROUND: Rectus muscle involvement in thyroid ophthalmopathy is well documented. The inferior rectus is the most frequently involved, followed by the medial, superior, and infrequently the lateral rectus. This study reports involvement of the superior oblique muscle as a contributory cause of restrictive strabismus in patients with thyroid ophthalmopathy. METHODS: This is a retrospective review of four patients with known thyroid ophthalmopathy who presented with incomitant vertical strabismus, A-pattern, overdepression in adduction, underelevation in adduction, and incyclotorsion. All patients underwent preoperative orbital imaging. Two of the four patients had previous orbital decompressions. All patients underwent surgery on the SO muscle. RESULTS: Preoperative scans showed enlargement of one or both SO muscles in all patients and intraoperative forced duction testing revealed restriction to elevation in adduction in all cases. Preoperative A-pattern ranged from to 6 to 22 prism diopters. All subjects had preoperative incyclotorsion, ranging from 2 and 14 degrees. Improvement of the versions, hypertropia, and cyclotorsion followed surgical weakening procedures on the SO muscle. CONCLUSION: Thyroid ophthalmopathy may involve the SO muscle. Clinical manifestations include preoperative A-pattern strabismus, incyclotorsion, and restrictive limitation to elevation in adduction. Orbital imaging documents SO muscle enlargement. Awareness of SO involvement in thyroid ophthalmopathy assists the surgeon to develop a more precise surgical strategy to correct the hypotropia.

Eye Movements↗