[Conditions regulating organogenesis and growth of muscles; research on the extrinsic muscles of the chick eye].
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Animals↗
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Rapid eye movements, muscle twitches and sawtooth waves in the sleep of narcoleptic patients and controls.
Seventeen unmedicated patients with narcolepsy-cataplexy and 17 age- and sex-matched controls were recorded polygraphically for 3 consecutive nights. Rapid eye movements (REMs), m. mentalis twitches and sawtooth waves in the EEG were visually scored. REM and twitch densities during REM sleep were significantly higher in the patients than in the controls. The distribution pattern of REMs and twitches was altered in the patients: twitch density peaked in the first REM period and density of REMs showed an even distribution across all the REM periods of the night. In the controls both REM and twitch density increased from the first to the second REM period. We therefore assume that in the narcoleptics phasic activity of REM sleep is disinhibited. Densities of REMs, twitches and sawtooth waves did not correlate with one another in patients and controls. They appear to be independently regulated. The REM periods of the patients contained 3 times as many waking epochs as those of the controls. This suggests that in narcolepsy the transition REM/waking is selectively facilitated. The REM/NREM ratio of twitch and sawtooth wave densities was the same in patients and controls.
Adult↗
Randomized double-blind trial of prednisone versus radiotherapy in Graves' ophthalmopathy.
Corticosteroids are usually given for management of Graves' ophthalmopathy, but they have many and serious side-effects. By comparison, retrobulbar irradiation is well tolerated, although its efficacy has been evaluated only in uncontrolled studies. Therefore, we did a double-blind randomised trial, in which 28 patients with moderately severe Graves' ophthalmopathy were treated with a 3-month course of oral prednisone and sham irradiation, and 28 received retrobulbar irradiation (20 Gy) and placebo capsules. Therapeutic outcome, assessed twenty-four weeks after the start of treatment, was determined by the change in the highest NOSPECS class. A successful outcome was observed in 14 prednisone-treated and in 13 irradiated patients. Responders to treatment (but not nonresponders) in both groups showed improvements in total and subjective eye score and a decrease in eye-muscle volume. Response to either treatment was due largely to changes in soft-tissue involvement and eye-muscle motility. Mean elevation in responders to radiotherapy increased from 18.5 degrees (95% CI 14.8-22.2) at baseline to 21.8 degrees (18.6-25.0) at week twenty-four (p = 0.003), but did not change in prednisone responders. Side-effects were more frequent and severe during prednisone than during radiotherapy. Radiotherapy and oral prednisone appear to be equally effective as initial treatment in patients with moderately severe Graves' ophthalmopathy. In view of its better tolerability, radiotherapy should be considered the treatment of first choice.
Administration, Oral↗
Elasmobranch oculomotor organization: anatomical and theoretical aspects of the phylogenetic development of vestibulo-oculomotor connectivity.
The oculomotor organization of two elasmobranch species, smooth dogfish (Mustelus canis) and little skate (Raja erinacea), was studied by investigating the extraocular muscle apparatus and the oculomotor motoneuron distribution. The macroscopic appearance of the eye muscles was similar to any lateral-eyed vertebrate species (e.g., goldfish, rabbit). The size of extraocular muscles was expressed by counting single muscle fibers and comparing cross-sectional areas of the extraocular muscles. There were significant differences in the number of fibers in the six extraocular muscles in dogfish, but not in skate. Fiber sizes varied considerably; thus, the number of fibers did not relate to cross-sectional areas. In the dogfish, no one pair of agonist-antagonist extraocular muscles was larger than the others, suggesting that there was no preference for eye movements in a particular plane of space. However, the lateral rectus was more than twice the size of most of the other muscles. In the skate, cross-sectional areas of the horizontal eye muscles were smaller than those of the vertical eye movers. This may indicate a reduced utilization of horizontal eye muscles, which may reflect the bottom-dwelling habitat and mode of locomotion of the skate. The distribution of the extraocular motoneurons was determined by injecting horseradish peroxidase (HRP) into single eye muscles. Medial rectus, superior rectus, and superior oblique motoneuron populations were located contralateral to their respective muscles. Lateral rectus, inferior rectus, and inferior oblique motoneurons were located ipsilateral to their muscles. This distribution is in contrast to almost all other vertebrates studied thus far, where medial rectus motoneurons are located ipsilateral to the muscle which they innervate. The oculomotor arrangement in elasmobranchs is likely to have consequences for the circuitry responsible for the production of conjugate compensatory eye movements in the horizontal plane. We hypothesize that, in contrast to other vertebrates, the basic elasmobranch vestibulo-ocular reflex pathway consists of three identically structured three-neuron-arcs connecting the three semicircular canals to their respective extraocular muscles. This innervation pattern may constitute a special feature of the elasmobranch brain or a phylogenetically older arrangement of eye movement pathways.
Animals↗
[Is there a typical motility disturbance in orbital wall fractures (author's transl)].
In case of motility disturbances due to orbital fractures generally a vertical diplopia -- that means a vertical restriction of the motility of the globe -- is found. The classification into four types according to Friemel allows a differentiation between mechanical motility disturbances and those of other origin; furthermore a prediction can be made about the extent of the field of diplopia and about the involved position of gaze. In addition the urgency of a primary reconstruction of the orbit and the prognosis of a late eye muscle surgery can be estimated by this classification. It is of differential diagnostic importance that isolated injuries of the eye muscles and the check ligaments, an intraorbital haemorrhage and a subtotal paresis of the oculomotor nerve can show a similar clinical picture as usually found with orbital fractures. The early diagnosis of ocular motility disturbances caused by orbital trauma is of essential importance for the proper treatment and the recovery of binocular single vision.
Diplopia↗
Orbital cobalt radiotherapy and systemic or retrobulbar corticosteroids for Graves' ophthalmopathy.
Orbital radiotherapy and corticosteroids are two well-established medical treatments for severe Graves' ophthalmopathy. In this report we analyze the results obtained by the combination of orbital radiotherapy and systemic or retrobulbar corticosteroids in patients with severe Graves' ophthalmopathy. Orbital cobalt radiotherapy was carried out by a cobalt unit, delivering a total of 2,000 rads to each eye in 10 daily doses. Systemic corticosteroid treatment was started with 70-80 mg methylprednisolone/day for 2-3 weeks with subsequent progressive reduction of the dose until discontinuation of the drug after 5-6 months. Retrobulbar corticosteroid therapy was performed by 14 bilateral injections of 40 mg methylprednisolone acetate at 20- to 30-day intervals. Results were evaluated both on clinical grounds and by numerical scoring (ophthalmopathy index, OI). Excellent or good responses were obtained in the majority of 72 patients by combined treatment with orbital cobalt radiotherapy and systemic corticosteroids. Soft tissue changes, newly developed eye muscle dysfunction and optic neuropathy showed the most beneficial effects from treatment, whereas proptosis, corneal lesions and long-standing eye muscle abnormalities responded to a lesser extent. The results of a controlled clinical trial showed that the combined treatment was more effective than the administration of systemic methylprednisolone alone. Because relevant side effects of systemic corticosteroid therapy were observed in 4 cases, the clinical validity of retrobulbar corticosteroids in substitution for systemic corticosteroids was evaluated in 44 patients. Excellent or good responses were observed in 25% of these patients, slight responses being obtained in 55% and no change in 20%.(ABSTRACT TRUNCATED AT 250 WORDS)
Combined Modality Therapy↗
Vestibular influence on the binocular control of vertical-torsional nystagmus after lesions in the interstitial nucleus of Cajal.
The interstitial nucleus of Cajal (iC) is a center of the velocity-to-position integration for vertical and torsional eye movements. In addition, iC has projections to and from the vestibular nuclei. Therefore the vestibular influence on the binocular alignment of vertical-torsional nystagmus after unilateral reversible iC inactivations was investigated in the alert monkey using 3D binocular search-coil recordings. The nystagmus was compared with the eye muscle rotation axes, which were corrected for the tonic ocular torsion elicited by the iC inactivation. Rotation axes of nystagmus were different for both eyes and revealed a co-activation of eye muscles similar to the effects of electrical stimulation of the anterior canal nerve. This suggests that, in addition to the deficient neural integrator, a vestibular imbalance contributes to the vertical-torsional nystagmus after iC inactivations.
Animals↗
Thyroid binding antibodies and other immunological abnormalities in patients with Graves' ophthalmopathy: effect of treatment with cyclophosphamide.
Patients with Graves' ophthalmopathy were studied for a possible role of thyroid binding antibodies (TBAb) as measured by a radioreceptor assay, and for in vitro evidence of immunoreactivity to orbital antigens. The effect of cyclophosphamide (CY) treatment on the immunological parameters and the clinical course of the eye disease was also studied. The mean TBAb index for all patients with eye disease was significantly less than that for the normal and for patients with Graves hyperthyroidism who lacked eye disease. The mean TBAb index for patients with ophthalmopathy and past or present hyperthyroidism was significantly less than for those patients with eye disease but no associated hyperthyroidism ('euthyroid Graves' disease'). TBAb levels did not correlate with the severity of duration of the eye disease and did not change during treatment with CY. Significant titres of serum antibodies against human eye muscle extract or subcellular fractions, or macrophage inhibitory factor (MIF) production in response to human orbital tissue extract were not detected in patients with eye disease. The congestive changes improved in all patients treated with CY, although the degree of proptosis and eye muscle involvement improved in only 3 of 24 and 11 of 20 patients respectively with these abnormalities. TBAb are unlikely to play a role in the pathogenesis of Graves' ophthalmopathy and the hyperthyroidism and eye disease should be considered separate autoimmune disorders. The apparently anomalous finding of a higher mean TBAb index in patients with eye disease and hyperthyroidism than in those with hyperthyroidiam alone may reflect a more severe defect of suppressor T cell function in the former group. Because evidence for specific immunoreactivity against orbital antigens was not found in this study other approaches to defining the underlying immunological mechanisms will have to be sought.
Adult↗
[Strabismus surgery under subconjunctival anesthesia: technique and evaluation by patient and his surgeon].
BACKGROUND: In adults, eye muscle surgery can be performed under local anesthesia without retrobulbar injection. We wanted to know how patients and surgeons perceive this procedure. PATIENTS AND METHODS: 50 patients and 3 surgeons were interviewed with a questionnaire after operation on one or two straight eye muscles, including revisions in 11 cases. The patients were sedated with benzodiazepines. The conjunctiva was anesthetized with tetracaine eye drops. During the operation, mepivacaine was irrigated under the muscle insertion using a blunt needle. RESULTS: The patients perceived little or no pain during the operation. This corresponded to the surgeon's judgement. 96% of the patients would prefer local over general anesthesia in case of a second operation. CONCLUSION: The technique can be recommended for surgery of rectus muscles in adults, even in the case of revision.
Adult↗
Measuring disease activity to predict therapeutic outcome in Graves' ophthalmopathy.
OBJECTIVE: The concept of disease activity in Graves' ophthalmopathy (GO) might explain why as many as one-third of patients do not respond to immunosuppressive treatment, because only patients in the active stage of disease are expected to respond. The hypothesis was adopted that a parameter used to measure disease activity should be able to predict a response to immunosuppressive treatment. The aim of this study was to develop a multivariate prediction model in which all previous tested activity parameters are integrated. DESIGN AND PATIENTS: We included 66 consecutive patients with untreated moderately severe GO who had been euthyroid for at least 2 months. All patients were treated with radiotherapy. Measurements Treatment efficacy after 6 months follow-up was used as the primary outcome measure. Disease severity and 15 different disease activity parameters were assessed before treatment. Univariate and multivariate logistic regression models were used to predict response (model 1) or no change (model 2). RESULTS: In multivariate analyses, we found that duration of GO, soft tissue involvement, elevation, soluble interleukin-2 receptor (sIL-2R), soluble CD30 (sCD30), eye muscle reflectivity and octreotide uptake ratio were significant predictors of a response to radiotherapy. Gender, duration of GO, soft tissue involvement, eye muscle reflectivity, IL-6 and urinary glycosaminoglycan (GAG) excretion were significant predictors of no change upon radiotherapy. Prognostic score charts were developed for use in clinical practice to calculate the probability of response (model 1) and the probability of no change (model 2) for each new patient. Finally we used a combination of both models to define a recommended treatment modality for each individual patient, based on both the predicted probabilities of response and no change. We were able to identify the correct treatment (based on a comparison with the observed response) in 89% of the patients. CONCLUSIONS: Although we strongly recommend that our results should be confirmed in other studies, our findings are the first evidence for the idea that disease (in)activity should determine which kind of treatment should be used.
Acute Disease↗
Antibodies to orbital tissues in thyroid-associated ophthalmopathy.
Thyroid-associated ophthalmopathy is thought to be an autoimmune disease affecting the orbit. The precise pathogenetic mechanisms are not known, but extraocular muscle and/or orbital fibroblasts are the likely targets of the autoimmune attack. Sera from 41 normal controls, 79 patients with thyroid-associated ophthalmopathy and 72 patients with other autoimmune diseases were examined for antibodies to cultured orbital fibroblasts and extraocular muscle by enzyme-linked immunosorbent assay. Orbital fibroblast antibody levels varied widely in all subject groups studied, and failed to distinguish patients with thyroid-associated ophthalmopathy from patients with other autoimmune diseases or controls. Eye-muscle binding antibody levels were higher amongst patients with ophthalmopathy compared to normal controls and patients with Graves' hyperthyroidism without clinical evidence of ophthalmopathy. Furthermore, eye-muscle binding antibody levels were found to be particularly high in patients with ophthalmopathy and concurrent dermopathy, and in patients with ophthalmic (euthyroid) Graves' disease.
Adult↗
[Immunomodulatory effect of pentoxifylline in Graves ophthalmopathy].
In the pathomechanism of the thyroid associated ophthalmopathy (TAO) the inflammatory cytokines produced by infiltrating lymphocytes of the retroorbital tissues are involved. The activated lymphocytes have been shown to secrete a number of cytokines including tumour necrosis factor-alpha, interleukin-1 and interferon-gamma. The widely used immunosuppressive therapies have potential serious side effects. The pentoxifylline (Ptx) is known to have effect on production of cytokines. The aim of this study was to investigate the effect of Ptx on expression of HLA-DR molecules and production of glycosaminoglycan of human retroorbital tissue cultures and potential efficacy in patients with TAO. It was found that pentoxifylline (Ptx) was able to inhibit significantly the HLA-DR expression and glycosaminoglycan synthesis induced by inflammatory cytokines including TNF-alpha, IFN-gamma and IL-1. Ten patients with untreated moderate severe ophthalmopathy (8 female and 2 male) were excluded from steroid treatment due diabetes mellitus and psychiatric disease. Classification of eye changes was made by NOSPECS categories and total eye score. All patients were euthyroid during the study and was no remarkable difference in thyroid function and eye symptoms. Before and during Ptx therapy the laboratory parameters were also determined including glycosaminoglycan. TNF-alpha, anti-TSH-receptor, anti-eye muscle, anti-thyroglobulin and anti-thyroid peroxidase antibodies in the patients'sera. It was found a remarkable improvement in the eye symptoms in eight of ten patients. The levels of glycosaminoglycan (uronic acid) and TNF-alpha gradually decreased in eight patients who considered to be responders. The levels of uronic acid in plasma of the responders were found to be significantly lower after Ptx treatment. Before Ptx therapy the TNF-alpha in the sera was not different remarkably in non-responders and responders. After 4 weeks Ptx treatment the TNF-alpha decreased significantly in responders compared to non-responders (20.9 +/- 4.8 pg/ml v. s. 28.3 +/- 6.1 pg/ml) (p < 0.01). The titre of anti-eye muscle antibodies were found to be lower at the end of observation, however, the anti-thyroid antibodies were not changed remarkably. It was concluded that Ptx in the majority of patients (8/10) has a beneficial effect on inflammatory symptoms of TAO and laboratory parameters and suggested to use as an additive therapy, however, further comparative studies are required for final evaluation of Ptx in the treatment of TAO.
Adjuvants, Immunologic↗
[Measurements of ultrasound reflectivity of oculomotor muscles in endocrine orbitopathy].
BACKGROUND: In the course of Graves' disease (GD) the extraocular muscles become fibrotic after an acute inflammatory stage. Differentiation of these two stages is important for therapy. MATERIALS AND METHODS: First, we examined the eye muscles of 30 healthy volunteers with the 10 MHz-B probe (Ultrascan) Digital B 2000) and then those of 20 patients with GD. The thickness was measured in the longitudinal displayed muscle always with the same gain. The amplitude of the highest inner muscle spikes expressed as a percentage of amplitude of retina-sclera spike provided the internal reflectivity. The stage of GD was determined by clinical signs. RESULTS: In GD, thickness of inferior and medial rectus was significantly enhanced in both the inflammatory and fibrotic stages, while internal reflectivity was only significantly higher in the latter stage. CONCLUSIONS: Ultrasound discriminates the acute from chronic course of GD in eye muscles and thus provides a very useful tool for making therapeutic decisions.
Adult↗
Neurotrophic factor regulation of developing avian oculomotor neurons: differential effects of BDNF and GDNF.
Neurotrophic factors support the development of motoneurons by several possible mechanisms. Neurotrophins may act as target-derived factors or as afferent factors derived from the central nervous system (CNS) or sensory ganglia. We tested whether brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), neurotrophin 4 (NT-4), and glial cell line-derived neurotrophic factor (GDNF) may be target-derived factors for neurons in the oculomotor (MIII) or trochlear (MIV) nucleus in chick embryos. Radio-iodinated BDNF, NT-3, NT-4, and GDNF accumulated in oculomotor neurons via retrograde axonal transport when the trophic factors were applied to the target. Systemic GDNF rescued oculomotor neurons from developmental cell death, while BDNF and NT-3 had no effect. BDNF enhanced neurite outgrowth from explants of MIII and MIV nuclei (identified by retrograde labeling in ovo with the fluorescent tracer DiI), while GDNF, NT-3, and NT-4 had no effect. The oculomotor neurons were immunoreactive for BDNF and the BDNF receptors p75(NTR) and trkB. To determine whether BDNF may be derived from its target or may act as an autocrine or paracrine factor, in situ hybridization and deprivation studies were performed. BDNF mRNA expression was detected in eye muscles, but not in CNS sources of afferent innervation to MIII, or the oculomotor complex itself. Injection of trkB fusion proteins in the eye muscle reduced BDNF immunoreactivity in the innervating motoneurons. These data indicate that BDNF trophic support for the oculomotor neurons was derived from their target.
Animals↗
Oculomotor corollary discharge in the cat pretectum.
Unit activity bursting after the onset of spontaneous eye movements made in total darkness has been recorded from the nucleus of the optic tract (NOT) of the cat pretectum. The present experiments are aimed at determining the functional significance of these neuronal reactions, namely whether the NOT discharge results from an afferent input arising from eye muscle proprioceptors or from a central signal (corollary discharge or efference copy). The results point to a central, rather than a peripheral, origin for NOT discharge. After both eyes have been paralysed, and therefore after eye-muscle proprioceptive input has been removed, NOT activity remained time-locked with increased activity in motoneurons of the III nerve nucleus.
Animals↗
[Cyclotropia and surgical treatment after macular translocation].
PURPOSE: Macular translocation is a new surgical treatment method successfully performed in recent years in cases of age-related macula degeneration. Cyclotropia and associated orthoptic problems may occur after macular translocations. The aim of our study was to present the application and results of various external eye muscle surgery techniques to eliminate cyclodeviation after macular translocation. METHODS: Between January 2001 and April 2001, 15 patients underwent macular translocation. After an average of 47 days counterrotation was applied to these patients to eliminate incyclotropia formed due to macular translocation. In 8 cases, superior and inferior oblique muscle surgery was combined with opposite vertical transpositions of the horizontal recti. In 5 cases, full tendon transposition of the superior oblique muscle to the nasal part of the globe was combined with the anterior margin advancement of the inferior oblique muscle. In 2 cases, only combined surgery of superior and inferior oblique muscles was performed. The degree of cyclodeviation was measured by both objective and subjective methods before and after counterrotation. Mean follow-up period was 53.9 days. RESULTS: The average objective cyclodeviation formed after macular translocation was 29.6 degrees. Combined surgery of superior and inferior oblique muscles led to a mean excyclorotation of 15 degrees whereas combined oblique muscle surgery performed with vertical transposition of horizontal recti provided a mean excylorotation of 20.8 degrees. The most effective method was the combination of total nasal transposition of superior oblique muscle with the anterior margin advancement of the inferior oblique muscle resulting in an improvement by 33 degrees. CONCLUSIONS: Macular translocations cause cyclodeviation. The ensuing cyclotropia can be eliminated by various surgical techniques of external eye muscles according to the degree of cyclotropia.
Aged↗
[Diagnosis of myasthenic eye signs. Clinical signs and electronystagmographical findings of saccadic eye movements (author's transl)].
The clinical eye signs of 31 myasthenic patients are presented and those signs important for an early diagnosis are then discussed: lid symptoms caused by fatigue (Simpson-test), characteristic lid twitches as well as alternating asymmetrical eye muscle pareses. The importance of an investigation with the tangent scale in the course of which tensilon is injected is pointed out. False diagnosis and differential diagnostic signs are then considered (disseminated sclerosis, aneeurysm, encephalitis, pseudopulbarparalysis). - Our electronystagmographical investigations of saccadic eye movements showed hypometric, alternating saccades with occasional nystagmuslike jerks. After Tensilon injection hypermetric saccades (overshoots) were observed which depended on a disproportion of the supranuclear oculomotor centers and the eye muscles. The "muscleparetic" nystagmus is a pathologically increased endposition nystagmus. The hypometric nystagmuslike jerks during a saccadic eye movement are caused by insufficient phasic innervation.
Adolescent↗
The anatomical substrate for cat extraocular muscle proprioception.
The localization of cell bodies and of the central terminal projections of extraocular muscle afferent neurons was examined in adult cats using transport of horseradish peroxidase. The results confirm that primary afferent cell somata subserving extraocular muscle proprioception are located within the medial portion of the ipsilateral trigeminal ganglion. Occasional labeling of cell bodies in the mesencephalic nucleus of the trigeminal nerve occurred only in association with evidence of spread of tracer beyond the eye muscles. These results, taken together with work of others, make it unlikely that the trigeminal mesencephalic nucleus participates significantly in eye muscle proprioception. The central projections of extraocular muscle afferent neurons were found consistently in a restricted area in the ventral portion of the pars interpolaris of the spinal trigeminal nucleus. This corresponds exactly with their site of termination in the monkey [Porter (1986) J. comp. Neurol. 247, 133-143]. Terminal labeling was restricted to this area in cases in which there was no evidence of spread of the tracer beyond the extraocular muscles. In contrast to previous findings in the monkey, the cat did not exhibit a second muscle afferent representation in the cuneate nucleus. Though it is known that extraocular muscle afferent signals interact with both retinal and vestibular signals, and thus probably are involved in both visual processing and oculomotor control, the details of their roles in these processes are not yet clear.(ABSTRACT TRUNCATED AT 250 WORDS)
Afferent Pathways↗