Radiologic case study. Diagnosis: hypertrophic abductor hallucis muscle (causing tarsal tunnel syndrome).
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Adult↗
Biomedical subjects
M P Grant
Publications and source records attributed to M P Grant.
Strategies for the treatment of enophthalmos.
The surgical correction of post-traumatic enophthalmos is among the most challenging problems for the surgeon. A thorough understanding of orbital anatomy and the purposed mechanisms of enophthalmos is crucial to the ultimate success or failure of the procedures. The successful orbital reconstruction begins with a careful physical examination of the patient that is attentive to ocular function, soft-tissue position, and visible or palpable defects of the facial skeleton. The physical examination combined with thin section CT scanning in the axial and coronal planes provides the basis of the operative plan. The anatomy of the deformity should dictate the anatomy and shape in the surgical correction. In many cases, multiple surgical incisions will be required; therefore, care must be taken to maximize exposure and minimize the cosmetic problems associated with large incisions. We advocate a step-wise approach consisting of mobilization of the soft tissues in the area of the fracture, repositioning of the anterior and middle sections of the bony orbit, and reattachment of the soft tissue to the bone at the proper location. The approach to reconstruction of the bony orbit that we advocate is to first sequentially reposition each segment of the rim, carefully examining each articulation. Once rim reconstruction is complete, reconstruction of the internal wall is performed. Recall that the largest source of error is in inadequate reduction of the orbital rim, owing to the fact that this error is "squared" (according to the model) in the computation of the orbital volume. Through the application of these principles, the cosmetic and functional sequelae of post-traumatic enophthalmos can be improved greatly with minimal complications.
Adult↗
The contribution of the vertical semicircular canals to high-velocity horizontal vestibulo-ocular reflex (VOR) in normal subjects and patients with unilateral vestibular nerve section.
We have examined to what extent the vertical semicircular canals contribute to the nonlinearity of the horizontal VOR imposed by the driving of primary vestibular afferents into inhibitory cutoff at high velocities of head rotation (Ewald's second law). The gain (eye velocity/head velocity) of the horizontal component of the VOR with the head pitched down 30 degrees and pitched up 30 degrees was examined during constant-velocity rotations in normal subjects and patients following unilateral vestibular nerve section. In normal subjects, VOR gain decreases as chair velocity increases from 60-300 degrees/s when the head is pitched up, but VOR gain remains constant when the head is pitched down. This finding implies that the mechanism by which the gain of the horizontal VOR gain remains constant at all velocities of rotation depends upon the pattern of labyrinthine stimulation. Following unilateral nerve section, we found that the directional preponderance (DP) in horizontal VOR depends upon whether the head is pitched up 30 (mean asymmetry = 5%) or pitched down 30 degrees (mean asymmetry = 20%). This is what is expected based on the degree to which the lateral and vertical semicircular canals sense horizontal head acceleration with the head in different degrees of pitch. Hence, following unilateral vestibular lesions, the DP of horizontal VOR gain is most easily elicited at high velocities of head rotation and with the head pitched down 30 degrees. Evidence for DP at the bedside using the "head-shaking nystagmus" technique may be optimally elicited with the head pitched down 30 degrees.
Acceleration↗
The role of acetylcholine in regulating secretory responsiveness in rat sweat glands.
While retrograde regulation of neuronal development by target-derived factors in the autonomic nervous system is well established, the importance of anterograde influences on target development is unclear. Previous studies suggest that sympathetic innervation of sweat glands plays a critical role in the acquisition and maintenance of their secretory function. To define the signal(s) responsible, we disrupted muscarinic cholinergic transmission in developing and adult rats. Treatment of young rats with the nonselective antagonist, atropine, or an antagonist selective for the glandular muscarinic subtype, 4-DAMP, delayed the development of secretory responsiveness. Treatment of adult animals with atropine caused its loss. Further, following denervation, treatment with the muscarinic agonist, pilocarpine, largely preserved responsiveness while untreated animals lost function. Thus, acetylcholine, whose presence in sweat gland innervation is retrogradely specified by developmental interactions with the target tissue, in turn plays an important role in inducing and maintaining target tissue responsiveness through muscarinic receptor activation.
Acetylcholine↗
Dynamic properties of the human vestibulo-ocular reflex during head rotations in roll.
We investigated the dynamic properties of the human vestibulo-ocular reflex (VOR) during roll head rotations in three human subjects using the magnetic search coil technique. In the first of two experiments, we quantify the behavior of the ocular motor plant in the torsional plane. The subject's eye was mechanically displaced into intorsion, extorsion or abduction, and the dynamic course of return of the eye to its resting position was measured. The mean predominant time constants of return were 210 msec from intorsion, 83 msec from extorsion, and 217 msec from abduction, although there was considerable variability of results from different trials and subjects. In the second experiment, we quantify the efficacy of velocity-to-position integration of the vestibular signal. Position-step stimuli were used to test the torsional or horizontal VOR, being applied with subjects heads erect or supine. After a torsional position-step, the eye drifted back to its resting position, but after a horizontal position-step the eye held its new horizontal position. To interpret these responses we used a simple model of the VOR with parameters of the ocular motor plant set to values determined during Exp 1. The time constant of the velocity-to-position neural integrator was smaller (typically 2 sec) in the torsional plane than in the horizontal plane (> 20 sec). No disconjugacy of torsional eye movements was observed. Thus, the dynamic properties of the VOR in roll differ significantly from those of the VOR in yaw, reflecting different visual demands placed on this reflex in these two planes.
Adult↗
Abnormal eye movements in Creutzfeldt-Jakob disease.
We report 3 patients with autopsy-proven Creutzfeldt-Jakob disease who, early in their course, developed abnormal eye movements that included periodic alternating nystagmus and slow vertical saccades. These findings suggested involvement of the cerebellar nodulus and uvula, and the brainstem reticular formation, respectively. Cerebellar ataxia was also an early manifestation and, in 1 patient, a frontal lobe brain biopsy was normal at a time when ocular motor and cerebellar signs were conspicuous. As the disease progressed, all saccades and quick phases of nystagmus were lost, but periodic alternating gaze deviation persisted. At autopsy, 2 of the 3 patients had pronounced involvement of the cerebellum, especially of the midline structures. Creutzfeldt-Jakob disease should be considered in patients with subacute progressive neurological disease when cognitive changes are overshadowed by ocular motor findings or ataxia.
Aged↗
Loss of ipsidirectional quick phases of torsional nystagmus with a unilateral midbrain lesion.
We report a patient with a long-standing, unilateral lesion of the midbrain who showed ipsidirectional loss of torsional quick phases, impairment of all vertical eye movements and normal horizontal eye movements. The findings are consistent with recent reports of the effects of experimental lesions, in monkeys, of the rostral interstitial nucleus of the medial longitudinal fasciculus and the interstitial nucleus of Cajal.
Aged↗
High-frequency vestibuloocular reflex as a diagnostic tool.
During locomotion, the head is subject to rotational perturbations with fundamental frequencies in the range 0.5-5.0 Hz, and significant harmonics up to 20 Hz. Patients who have lost labyrinthine function complain of oscillopsia and visual impairment during locomotion. Measurements of head movements during walking and running in place in such patients indicate that head stability is similar to that in normal subjects. Therefore, head stability is mainly guaranteed by mechanical, not neurogenic, factors. On the other hand, the visual symptoms of such patients can be ascribed to instability of gaze. Thus, it seems that other mechanisms such as visual following, the cervicoocular reflex, or anticipatory eye movements cannot compensate for loss of the VOR during locomotion (though they may do so for lower-frequency or active head rotations). The indispensable role of the VOR during locomotion is probably a reflection of its short latency (16 mseconds or less in the horizontal and vertical planes), which guarantees short phase lags during high-frequency head rotations. Our results indicate that laboratory testing of patients with vestibular symptoms should employ stimuli that correspond to those occurring during locomotion.
Aged↗
Effectiveness of botulinum toxin administered to abolish acquired nystagmus.
We injected botulinum toxin into the horizontal rectus muscles of the right eyes of 2 patients who had acquired pendular nystagmus with horizontal, vertical, and torsional components. This treatment successfully abolished the horizontal component of the nystagmus in the injected eye in both patients for approximately 2 months. Both patients showed a small but measurable improvement of vision in the injected eye that may have been limited by coexistent disease of the visual pathways. The vertical and torsional components of the nystagmus persisted in both patients. In 1 patient, the horizontal component of nystagmus in the noninjected eye increased; we ascribe this finding to plastic-adaptive changes in response to paresis caused by the botulinum toxin. Such plastic-adaptive changes and direct side effects of the injections--such as diplopia and ptosis--may limit the effectiveness of botulinum toxin in the treatment of acquired nystagmus. Neither patient elected to repeat the botulinum treatment.
Adult↗
Comparison of predictable smooth ocular and combined eye-head tracking behaviour in patients with lesions affecting the brainstem and cerebellum.
We compared the ability of eight normal subjects and 15 patients with brainstem or cerebellar disease to follow a moving visual stimulus smoothly with either the eyes alone or with combined eye-head tracking. The visual stimulus was either a laser spot (horizontal and vertical planes) or a large rotating disc (torsional plane), which moved at one sinusoidal frequency for each subject. The visually enhanced vestibulo-ocular reflex (VOR) was also measured in each plane. In the horizontal and vertical planes, we found that if tracking gain (gaze velocity/target velocity) for smooth pursuit was close to 1, the gain of combined eye-hand tracking was similar. If the tracking gain during smooth pursuit was less than about 0.7, combined eye-head tracking was usually superior. Most patients, irrespective of diagnosis, showed combined eye-head tracking that was superior to smooth pursuit; only two patients showed the converse. In the torsional plane, in which optokinetic responses were weak, combined eye-head tracking was much superior, and this was the case in both subjects and patients. We found that a linear model, in which an internal ocular tracking signal cancelled the VOR, could account for our findings in most normal subjects in the horizontal and vertical planes, but not in the torsional plane. The model failed to account for tracking behaviour in most patients in any plane, and suggested that the brain may use additional mechanisms to reduce the internal gain of the VOR during combined eye-head tracking. Our results confirm that certain patients who show impairment of smooth-pursuit eye movements preserve their ability to smoothly track a moving target with combined eye-head tracking.
Adult↗
Unexpected plasticity at autonomic junctions. Environmental regulation of neurotransmitter phenotype and receptor expression.
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Animals↗
The molecular and pharmacological properties of muscarinic cholinergic receptors expressed by rat sweat glands are unaltered by denervation.
Previous studies have indicated that denervation of adult rodent sweat glands results in the loss of secretory responsiveness to muscarinic agonists. To elucidate the molecular basis of this loss, we have characterized the muscarinic cholinergic receptor present in adult rat sweat glands and examined the effects of cholinergic denervation on its properties and expression. When homogenates of gland-rich tissue from adult animals were assayed with [N-methyl-3H]-scopolamine, a high-affinity muscarinic antagonist, the concentration of muscarinic receptors was 301 fmol/mg protein and the affinity was 131 pM. Autoradiographic analysis demonstrated that ligand binding sites were detectable only on glands. In competition studies with well-characterized muscarinic agents, the receptor exhibited typical muscarinic pharmacology. Further investigation with the selective muscarinic antagonists 4-diphenylacetoxy-N-methylpiperidine methiodide, pirenzepine, and AF DX-116 revealed that the sweat gland receptor belongs to the M2 glandular pharmacological subtype. In situ hybridization histochemistry with receptor subtype-specific oligonucleotide probes indicated that rat sweat glands express the m3 molecular receptor subtype. Seven days after sciatic nerve transection, when denervated glands were compared to those on the contralateral unoperated side, there was no significant difference either in the concentration or affinity of muscarinic binding sites or in receptor density or distribution. Furthermore, the molecular subtype and the level of its expression were unchanged. Thus, it appears that muscarinic binding sites and m3 receptor mRNA are present in denervated sweat glands that are unresponsive to muscarinic stimulation. These results suggest that the regulation of responsiveness occurs at a point distal to the expression of muscarinic receptors.
Animals↗
Developmental expression of muscarinic cholinergic receptors and coupling to phospholipase C in rat sweat glands are independent of innervation.
During development, the innervation of rat sweat glands undergoes a striking change from noradrenergic to cholinergic function. The acquisition of secretory responsiveness by the glands is temporally correlated with the appearance of cholinergic properties. In addition, responsiveness fails to appear in the absence of innervation. To investigate the basis of the onset of functional transmission and secretory responsiveness and its possible relationship to innervation, we analyzed the development of muscarinic cholinergic receptors in sweat glands, examined their expression in the glands of adult rats sympathectomized at birth, and assayed the ability of muscarinic agonists to increase phosphoinositide (PI) turnover. Autoradiographic and in situ hybridization analysis revealed that muscarinic ligand binding sites were first detectable as glands begin to form on postnatal day 4 (P4). Between P4 and P14, receptor concentration increased in parallel with mRNA for the m3 receptor subtype. On P14, the concentration of ligand binding sites approached adult levels, although only a small proportion of glands at this age secrete in response to nerve stimulation or cholinergic agonists. When the pharmacological properties of muscarinic receptors in sweat glands of adult rats sympathectomized at birth were compared to those of normal glands, the concentration and affinity determined with [N-methyl-3H]-scopolamine and the Ki values determined with the subtype-selective muscarinic antagonists 4-DAMP, pirenzepine, and AF DX-116 were similar. In addition, the molecular subtype was unchanged as was the level of m3 message. Studies of PI turnover in response to muscarinic stimulation indicated that the receptors expressed in sweat glands isolated from sympathectomized and acutely denervated, as well as control, rats were functionally coupled to phospholipase C. The absence of sympathetic innervation therefore does not appear to influence either the development of muscarinic receptors or their coupling to PI turnover. Our results suggest that functional sympathetic cholinergic innervation plays a central role in the development and maintenance of secretory function at a step distal to signal transduction across the cell membrane.
Animals↗
Glimpses into the past. Extracts from Louis Pasteur.
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Famous Persons↗