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Biomedical subjects

James A Sharpe

Publications and source records attributed to James A Sharpe.

At least 19 recordsLinked to original sources
PubMed2006

Saccade dynamics in peripheral vs central sixth nerve palsies.

OBJECTIVE: To investigate differences between peripheral idiopathic and central sixth nerve palsies from brainstem damage by comparing peak velocities and durations of horizontal saccades. METHODS: Fourteen patients with unilateral incomplete sixth nerve palsies caused by idiopathic, presumed ischemic, peripheral damage, 5 with incomplete central (fascicular) palsy caused by brainstem lesions, and 10 controls were studied. Palsies under 1 month in duration were designated as acute and those of longer duration were chronic. Among peripheral palsies, five were acute, nine were chronic. Among central palsies, two were acute, three were chronic. Subjects made +/- 10 deg horizontal saccades while wearing search coils. Serial recordings were made in seven patients with acute palsy (five peripheral, two central). RESULTS: Centrifugal abducting saccadic velocities in the paretic eye were subnormal in both central and peripheral acute palsies, as anticipated from lateral rectus weakness. In chronic central palsies, abducting velocities in the paretic eye remained reduced. However, in chronic peripheral palsies, velocities became normal in the tested range of excursion, within 2 months of onset, despite persisting abduction deficit. CONCLUSIONS: Saccade peak velocities are reduced and their durations are prolonged in the field of action of acutely palsied peripheral and central nerves. Speeds remain reduced in chronic central (fascicular) palsies, consistent with limited regeneration within the brain. Saccade speeds are repaired in chronic peripheral palsies, probably by remyelination and axonal regeneration, and perhaps also by central monocular adaptation of innervation selectively to the paretic eye, in order to drive both eyes rapidly and simultaneously into the paretic field of motion.

Abducens Nerve↗
PubMed2006

Saccadic adaptation in Chiari type II malformation.

BACKGROUND: Saccadic adaptation corrects errors in saccadic amplitude. Experimentally-induced saccadic adaptation provides a method for studying motor learning. The cerebellum is a major participant in saccadic adaptation. Chiari type II malformation (CII) is a developmental deformity of the cerebellum and brainstem that is associated with spina bifida. We investigated the effects of CII on saccadic adaptation. METHOD: We measured eye movements using an infrared eye tracker in 21 subjects with CII (CII group) and 39 typically developing children (control group), aged 8-19 years. Saccadic adaptation was induced experimentally using targets that stepped horizontally 120 to the right and then stepped backward 3 degrees during saccades. RESULTS: Saccadic adaptation was achieved at the end of the adaptation phase in participants in each group. Saccadic amplitude gain decreased by 6.9% in the CII group and 9.3% in the control group. The groups did not differ significantly (p = 0.27). Amplitude gain reduction was significantly less in the CII participants who had multiple shunt revisions. Regression analyses revealed no effects of spinal lesion level, presence of nystagmus, or cerebellar vermis dysmorphology on saccadic adaptation. CONCLUSION: The neural circuits involved in saccadic adaptation appear to be functionally intact in CII.

Adaptation, Physiological↗
PubMed2006

Saccadic adaptation in children.

Saccades are fast-orienting eye movements. Saccadic adaptation, a form of motor learning, is a corrective change in the amplitude of saccades in response to error. The aim of the study was to ascertain whether saccadic adaptation occurs in typically developing children. We recorded saccades with an infrared eye tracker in 39 children, aged 8 to 19 years, at baseline to 12-degree horizontal target steps and after an adaptive task. During the adaptive task, a saccadic hypometric error was induced. This task consisted of 200 12-degree target steps that stepped backward 3 degrees during the initial saccade and without the participants' awareness. The initial saccade triggered the back-step. This paradigm required a corrective reduction of the amplitude of the initial saccades in response to the induced error. Saccadic adaptation was achieved in 26 participants, whose mean saccadic amplitudes decreased by 13% (P < .05). Saccadic adaptation was not influenced by age. We conclude that children as young as 8 years old have established functions of the neural circuits responsible for the motor learning required for saccadic adaptation.

Adaptation, Physiological↗
PubMed2005

Cerebellar vermis morphology in children with spina bifida and Chiari type II malformation.

OBJECTIVE: Posterior fossa size and cerebellar weight and volume are reduced in Chiari type II malformation (CII). This is assumed to affect the cerebellum uniformly. We quantified the presumed reduction in vermis size on magnetic resonance imaging (MRI). METHODS: A midsagittal brain MRI slice was selected from each of 68 participants with CII (mean age 13 years). Control participants were 28 typically developing children (mean age 14.1 years). Midsagittal surface areas occupied by the intracranial fossa, posterior fossa, vermis, and its lobules were measured. CONCLUSIONS: Mean posterior fossa area was significantly smaller (P<0.003), although mean vermis area was significantly larger (P<0.0001), in participants with CII than in control participants. This expansion involved vermis lobules I-V and VI-VII areas (P<0.0001). The midsagittal vermis was expanded and not reduced in size in participants with CII. This is attributed to compressive displacement of midline structures within the confines of a small posterior fossa.

Adolescent↗
PubMed2005

Smooth pursuit eye movements in children.

Smooth pursuit eye movements consists of slow eye movements that approximate the velocity of the eyes to that of a small moving target, so that target image is kept at or near the fovea. Little information on smooth pursuit is available in children. We used an infrared eye tracker to record smooth pursuit in 38 typically developing children, aged 8-19 years. Participants followed a visual target moving sinusoidally at +/-10 degrees amplitude, horizontally and vertically at 0.25 or 0.5 Hz. The mean horizontal smooth pursuit gains, the ratio of eye to target velocities, were 0.84 at 0.25 Hz and 0.73 at 0.5 Hz. Mean vertical smooth pursuit gains were 0.68 at 0.25 Hz and 0.45 at 0.5 Hz. Smooth pursuit gains were significantly lower for vertical in comparison to horizontal tracking, and for 0.5 Hz in comparison to 0.25 Hz tracking (P<0.0001). Smooth pursuit gains increased with age (P<0.01, Pearson's correlation tests), with horizontal gains attaining reported adult values by mid adolescence. Vertical gains had large variability among participants. The median phase, the time interval between eye and target velocities, varied between 39 and 86 ms. Phase was not influenced by age. We conclude that smooth pursuit gains are lower in children than gains reported in adults. Vertical pursuit gain is significantly lower than horizontal pursuit gain. Gains improve with age and approach adult values in mid adolescence. Children have larger phases than reported adults values indicating that prediction in the smooth pursuit system is less mature in children.

Adolescent↗
PubMed2005

Cerebellar skew deviation and the torsional vestibuloocular reflex.

BACKGROUND: Skew deviation is typically caused by brainstem damage, and has not been identified with focal cerebellar lesions. This vertical strabismus has been attributed to asymmetric disruption of vestibuloocular reflex (VOR) projections from otolithic receptors of the utricle to ocular motoneurons, but asymmetry of the utriculo-ocular counter-roll reflex has not been detected. METHODS: Lesions localized to the cerebellum were identified by MRI in five patients with vertical strabismus. Their skew deviation was measured by prism cover tests in all patients and by search coils in three patients. The angular VOR was tested in patients and 10 controls during sinusoidal +/- 10 degree torsional, vertical, and horizontal head-on-body rotations at 0.5, 1, and 2 Hz. Static torsional VOR gain was measured by the change in torsional eye position divided by change in head position during maintained head tilt. RESULTS: Static torsional VOR gains were asymmetric in each patient. Three patterns of asymmetry were identified: 1) decreased static gain in one eye in both directions; 2) decreased gains in both eyes in one direction; and 3) asymmetric gain in one direction in one eye alone. Dynamic torsional VOR gains were symmetrically reduced in both directions in both eyes in all patients. CONCLUSIONS: Focal cerebellar lesions can cause skew deviation. The static torsional vestibuloocular reflex (VOR) is linked to cerebellar control of vertical vergence. Asymmetry between the eyes or in direction of the static torsional VOR provides evidence that monocular or binocular imbalance of the utriculo-ocular reflex leads to cerebellar skew deviation.

Adult↗
PubMed2005

Saccades in children.

Saccades are necessary for optimal vision. Little is known about saccades in children. We recorded saccades using an infrared eye tracker in 39 children, aged 8-19 years. Participants made saccades to visual targets that stepped 10 degrees or 15 degrees horizontally and 5 degrees or 10 degrees vertically at unpredictable time intervals. Saccadic latency decreased significantly with increasing age, while saccadic gain and peak velocity did not vary with age. Saccadic gains and peak velocities in children are similar to reported adult values. This implies maturity of the neural circuits responsible for making saccades accurate and fast. Saccade latency decreases as the brain matures.

Adolescent↗
PubMed2005

Recovery of peripheral versus central nerves identified by saccadic velocity after abducens neuropathy.

The abducens is the motor nerve with the most substantial course, both within and outside the brain and it innervates only one muscle. Sixth nerve palsy affords an opportunity to compare recovery after central versus peripheral nerve damage by assessing the dynamics of abduction. Horizontal saccade peak velocities and durations in 14 patients with unilateral peripheral sixth nerve palsies (5 acute, 9 chronic) are compared with those in 5 patients with central sixth nerve palsies (2 acute, 3 chronic) and with those in 10 normal subjects. Acutely, abducting saccades in the paretic eye were slow in both central and peripheral palsies, as anticipated from weakness of the lateral rectus muscle. In chronic central palsies, abducting saccadic velocities remained reduced, but in chronic peripheral palsies, they increased to normal within the limited range of excursion. The chronically damaged peripheral nerve behaves like a high-pass filter in transmitting phasic velocity commands, whereas tonic position commands remain defective, accounting for limited abduction but normal velocities within the range of duction. In chronic central (fascicular) palsies, saccade velocities remain reduced. Impaired conduction from damage to central myelin or axons is more persistent in central palsies, consistent with limited regeneration within the brain. Recording of saccade velocities may aid the distinction of fascicular from peripheral palsies. Saccade speed is repaired in peripheral palsies, probably by remyelination, and perhaps also by central monocular adaptation of innervation selectively to the paretic eye in order to drive both eyes rapidly and simultaneously to a target in the paretic field of motion.

Abducens Nerve Diseases↗
PubMed2004

Progressive ataxia and palatal tremor (PAPT): clinical and MRI assessment with review of palatal tremors.

Palatal tremor has been subdivided into essential (EPT) and symptomatic palatal tremor (SPT). A subgroup of the SPT form has a syndrome of progressive ataxia and palatal tremor (PAPT). Published details of cases of PAPT are sparse and the disorder appears heterogeneous. We present clinical and MRI features of six patients with sporadic PAPT who attended The University Health Network between 1991 and 2002. Eye movements were recorded using a magnetic search coil technique. We review previously reported cases of PAPT from the English language literature and relate this disorder to EPT and SPT. PAPT may be divided into sporadic and familial forms. We identified 22 other prior reported cases of sporadic PAPT. Sporadic PAPT is a subtype of SPT in which progressive cerebellar degeneration is the most symptomatic feature. A combination of vertical nystagmus and palatal tremor was found in one of our cases. Internuclear ophthalmoplegia, a new finding, was present in two of our patients and indicated additional brainstem dysfunction. Inferior olivary high signal abnormalities were present on MRI in all of our cases. The cause of sporadic PAPT remains uncertain. In some previous reports of sporadic PAPT, the combination of brainstem or pontine atrophy, parkinsonism, autonomic dysfunction or corticospinal tract abnormalities suggests a diagnosis of multiple system atrophy, although pathological verification is lacking. Familial PAPT is associated with marked brainstem and cervical cord atrophy with corticospinal tract findings, but the typical olivary MRI abnormalities have not been reported. A substitution in the glial fibrillary acidic protein (GFAP) gene has been described in a family with PAPT, raising the possibility of Alexander's disease. One other familial syndrome of PAPT, termed 'dark dentate disease', has also been reported. PAPT is a subgroup of SPT in which ataxia progresses and is not usually the result of a monophasic illness. Eye movement abnormalities suggest a disorder of both the cerebellum and brainstem. Familial PAPT differs from sporadic PAPT in having marked atrophy of cervical cord and brainstem with corticospinal signs but without hypertrophic olivary appearance on MRI.

Adolescent↗
PubMed2004

Widespread tangential dispersion and extensive cell death during early neurogenesis in the mouse neocortex.

The development of the mammalian neocortex requires radial and tangential migration of cells. Radial migration of differentiated neurons from the ventricular zone (VZ) is well established. It is hypothesised that an earlier phase of tangential migration of mitotically active cells lays down a widespread periodically spaced set of progenitors that generate radial arrays of postmitotic neurons. We use a transgenic cell lineage marker to label and observe the behaviour of progenitors before and during the early stages of neurogenesis. Using optical projection tomography (OPT), we show that individual progenitor cells generate many radially arrayed columns of periodically spaced cells. Column positions indicate the paths taken by these progenitor cells as they migrate, often over long distances, through the proliferative zone. Clonally related cells can be distributed in both hemispheres, suggesting progenitor cells cross the midline in the anterior neural plate. We observe a dramatic and rapid decline in the number of labelled clones after E13.5, indicating that there is extensive cell death at this time.

Animals↗
PubMed2003

Adaptations and deficits in the vestibulo-ocular reflex after peripheral ocular motor palsies.

Palsy of a nerve might be expected to lower vestibulo-ocular reflex (VOR) responses in its fields of motion, but effects of peripheral neuromuscular disease were unknown. We recorded the VOR during sinusoidal head rotations in yaw, pitch, and roll at 0.5-2 Hz and static torsional gain in 43 patients with unilateral nerve palsies. Sixth nerve palsy (n = 21) reduced both abduction and adduction VOR gains in darkness. In light, horizontal visually enhanced VOR (VVOR) gains were normal in moderate and mild palsy. In severe palsy, horizontal VVOR gains remained low in the paretic eye when it was fixating, whereas gains in the nonparetic eye became higher than normal. Third nerve palsy (n = 10) decreased VOR and VVOR gains during abduction, adduction, elevation, depression, extorsion, and intorsion. Fourth nerve palsy (n = 13) reduced VOR gains of the paretic eye during intorsion, extorsion, elevation, depression, abduction, and adduction, but in light vertical and horizontal VVOR gains were normal. In the nonparetic eye, all gains were normal. Reduced VOR gains in the direction of paretic muscles and also in the direction of their antagonists, together with normal gains in the nonparetic eye, indicate a selective adjustment to the antagonists of paretic muscles. Increase of VVOR gains to normal in the paretic eye, when used for fixation, without conjugate increase in gains in the occluded nonparetic eye, provides further evidence of selective adaptation for the paretic eye. Motions of the eyes after nerve palsies indicate monocular VOR adaptation in three dimensions.

Abducens Nerve Diseases↗
PubMed2002

Adaptations and deficits in the vestibulo-ocular reflex after third nerve palsy.

OBJECTIVE: To analyze the vestibulo-ocular reflex (VOR) in patients with unilateral peripheral third nerve palsy. PARTICIPANTS AND METHODS: Ten patients and 15 healthy subjects were studied using magnetic search coils. Subjects made sinusoidal +/-10 degrees head-on-body rotations in yaw, pitch, and roll in darkness and during monocular viewing in light. RESULTS: Horizontal VOR and visually enhanced VOR (VVOR) gains of the paretic eye were decreased during both abduction and adduction. Vertical VOR and VVOR gains of the paretic eye were decreased during both elevation and depression. Dynamic and static torsional VOR and VVOR gains of the paretic eye were reduced during both excyclotorsion and incyclotorsion. Horizontal, vertical, and torsional VOR and VVOR gains were normal in the nonparetic eye. CONCLUSIONS: Adducting VOR gains were reduced as anticipated from medial rectus palsy. Abducting gains were also reduced; the reduction is attributed to an adaptive decrease in innervation to the lateral rectus to achieve symmetry of the horizontal VOR in the paretic eye. Torsional VOR gains were reduced during excyclotorsion from palsy of the inferior oblique muscle. Gains were also reduced during incyclotorsion, which can be explained by an adaptive decrease in innervation to the superior oblique to restore symmetry of the torsional VOR in the paretic eye. CLINICAL RELEVANCE: Monocular adaptation in the VOR of the paretic eye reduces asymmetrical movement of retinal images during head motion, prevents nystagmus, and reduces retinal image disparity.

Adaptation, Ocular↗
PubMed2002

The vestibulo-ocular reflex in fourth nerve palsy: deficits and adaptation.

The effects of fourth nerve palsy on the vestibulo-ocular reflex (VOR) had not been systematically investigated. We used the magnetic scleral search coil technique to study the VOR in patients with unilateral fourth nerve palsy during sinusoidal head rotations in yaw, pitch and roll at different frequencies. In darkness, VOR gains are reduced during incyclotorsion, depression and abduction of the paretic eye, as anticipated from paresis of the superior oblique muscle. VOR gains during excyclotorsion, elevation and adduction of the paretic eye are also reduced, whereas gains in the non-paretic eye remain normal, indicating a selective adjustment of innervation to the paretic eye. In light, torsional visually enhanced VOR (VVOR) gains in the paretic eye remain reduced; however, visual input increases vertical and horizontal VVOR gains to normal in the paretic eye, without a conjugate increase in VVOR gains in the non-paretic eye, providing further evidence of selective adaptation in the paretic eye. Motions of the eyes after fourth nerve palsy exemplify monocular adaptation of the VOR, in response to peripheral neuromuscular deficits.

Adaptation, Physiological↗
PubMed2002

Vertical misalignment in unilateral sixth nerve palsy.

OBJECTIVE: To detect and determine the magnitude of vertical deviation in patients with unilateral sixth nerve palsy. DESIGN: Prospective consecutive comparative case series. PARTICIPANTS: Twenty patients with unilateral peripheral sixth nerve palsy, 7 patients with central palsy caused by brainstem lesions, and 10 normal subjects. METHODS: Subjects were tested by the prism and cover test, Maddox rod and prism test, and magnetic search coil recordings in nine diagnostic eye positions. They were also tested during static lateral head tilt by the prism and cover, and Maddox rod and prism tests. MAIN OUTCOME MEASURES: The magnitudes of horizontal and vertical deviations. RESULTS: All patients had an abduction deficit and incomitant esodeviation that increased in the field of action of the paretic muscle, indicating sixth nerve palsy. Mean vertical deviations, for all positions of gaze in peripheral palsy were 0.3 +/- 0.8 prism diopters (PD) by prism and cover test, 1.3 +/- 1.6 PD by Maddox rod and prism test, and 2.0 +/- 1.4 PD by coil recordings. Mean vertical deviations in normal subjects were 0.0 +/- 0.0 PD by prism and cover test, 1.0 +/- 0.9 PD by Maddox rod and prism test, and 1.9 +/- 2.1 PD by coil recordings. Therefore, peripheral palsy did not cause abnormal vertical deviation. In central palsy, for all positions together mean vertical deviations were 0.9 +/- 1.3 PD by prism and cover test, 1.4 +/- 1.6 PD by Maddox rod and prism test, and 2.5 +/- 1.6 PD by coil recordings; they were not different from normal values. During static head roll, patients with peripheral palsy had a right hyperdeviation on right head tilt and a left hyperdeviation on left head tilt, regardless of the side of the palsy. In contrast, in central palsy, head tilt caused vertical strabismus that remained on the same side on head tilt to either side. CONCLUSIONS: Small vertical deviations in sixth nerve palsy are consistent with normal hyperphorias that become manifest in the presence of esotropia. In peripheral sixth nerve palsy, static head roll to either side induces hyperdeviation in the eye on the side of the head tilt. Hyperdeviation of the same eye induced by head tilt to either direction implicates a brainstem lesion as the cause of paretic abduction. Quantitative study of sixth nerve palsy demonstrates that if a vertical deviation falls within the normal range of hyperphoria, multiple cranial nerve palsy or skew deviation may not be responsible. Conversely, vertical deviation > 5 PD indicates skew deviation or peripheral nerve palsy in addition to abduction palsy.

Abducens Nerve Diseases↗
PubMed2002

Midbrain disorders of vertical gaze: a quantitative re-evaluation.

The mesodiencephalic junction is the site of the prenuclear control of vertical eye motion. We measured vertical saccades, smooth pursuit (SP), the vertical vestibulo-ocular reflex (VOR), and its interactions with vision during active head motion in 21 patients with midbrain lesions causing palsy of vertical saccades, upward, downward, or in both directions. Most patients with limited slow or slowed saccades in one direction on clinical examination had slowed saccades in the opposed direction. SP gain was decreased in both directions in most patients, and decreased upward or downward in few. VOR gain was subnormal in both directions in many patients, and upward only in one; phase lead of the VOR was recorded in 33% of them. Subnormal SP and VOR gains were often dissociated. Visually enhanced VOR gains were subnormal in both directions in many patients. Cancellation of the VOR was impaired in many patients, both upward and downward in most and upward in few patients. Gaze (eye plus head) tracking gain was subnormal in 29% of patients. Defective SP and defective cancellation of the VOR during head free tracking were often dissociated. We conclude that VOR and SP gains are usually subnormal in patients with paresis of vertical saccades. Impairment of pursuit and the VOR are often dissociated. Phase lead of the VOR implicates damage to velocity-to-position neural integrator for vertical eye motion. These associations and dissociations of impaired vertical eye motion signify discrete structural and functional effects of supranuclear midbrain damage that are undetected by examination of saccades.

Adult↗