Extraocular Muscle Atrophy Research Articles

Extraocular Muscle Atrophy in Myasthenia Gravis.

Extraocular Muscle Atrophy in Myasthenia Gravis.

MRI evidence of extraocular muscle atrophy and fatty replacement in myasthenia gravis.

The aim of the study was to evaluate extraocular muscle (EOM) atrophy and fatty replacement in ocular myasthenia gravis (OMG) and generalized myasthenia gravis (GMG) patients with chronic and untreated ocular symptoms or with inadequate response to immunotherapy and unprovoked ocular exacerbations despite chronic immunotherapy. Nineteen patients with either OMG or GMG and 19 healthy age-matched controls underwent an orbital MRI. Visually obvious muscle atrophy and muscle fatty replacement were evaluated by two raters independently. Maximum thickness of EOM was measured. Measurements of the muscles of each participant were added up, in order to calculate the total thickness. Eleven patients suffered from AChR-positive GMG, and 8 patients from OMG. All patients had chronic ocular symptoms or inadequate response to corticosteroids and unprovoked ocular exacerbations in spite of immunotherapy. Fatty replacement was reported in 6/19 (31.6%) patients and 0/19 (0%) controls (p = 0.02). Obvious atrophy in at least one muscle was reported in 8/19 (42.1%) patients and 1/19 (5.3%) controls (p = 0.019). Statistically significant differences between the two groups were also found in the mean total thickness, as well as in the thickness of superior recti, levator palpebrae, inferior recti, and superior oblique muscles. EOM atrophy and fatty replacement were seen frequently in our series of MG patients with treatment difficulties and frequent relapses of ocular involvement.

A rare association of congenital fibrosis of extraocular muscles with keratoconus and bilateral sensorineural hearing loss: A co-incidence or some syndrome?

Congenital fibrosis of extraocular muscles (CFEOM) is an inherited restrictive ocular motility disorder characterized by unilateral or bilateral horizontal and/or vertical gaze impairment with ptosis. Keratoconus is a bilateral asymmetrical corneal ecstatic disease with multifactorial etiology, including complex interaction of both genetic and environmental factors. We report a case of a 29-year-old female who presented with chief complaints of bilateral diminution of vision and drooping of eyelids since early childhood with a history of seizures for 1 year. Visual acuity at presentation was hand movement close to face with accurate projection of rays in both the eyes. Contrast-enhanced magnetic resonance imaging of the brain and orbit revealed partially empty sella, neurocysticercosis, and bilateral atrophy of extraocular muscles. On detailed examination, she was found to have CFEOM type 1A (CFEOM1A, autosomal dominant inheritance) with bilateral advanced keratoconus, bilateral sensorineural hearing loss, bilateral presenile cataract, and neurocysticercosis. The association of CFEOM1A, keratoconus, and sensorineural hearing loss is not reported in the literature to date. Whether this association is co-incidental or part of some new syndrome needs to be evaluated further.

Magnetic Resonance Imaging in 14 Patients with Congenital Oculomotor Nerve Palsy

To elucidate the imaging findings of congenital oculomotor nerve palsy by evaluating the oculomotor nerve and extraocular muscles on magnetic resonance (MR) imaging in arelatively large series of 14patients with congenital oculomotor nerve palsy. Ophthalmologic examination of 14consecutive patients diagnosed with congenital oculomotor nerve palsy, and MR imaging of the orbit and oculomotor nerves were performed. Of the 14patients with congenital oculomotor nerve palsy, 13patients (93%) were unilateral and 12patients (86%) had incomplete palsy. On MR imaging, 5patients (36%) had hypoplasia or aplasia of the oculomotor nerve with variable degrees of extraocular muscle atrophy on the affected side. Of the 14patients, nine (64%) had normal-sized oculomotor nerves with or without muscle atrophy. The most frequently involved muscles were the inferior rectus (64%) and medial rectus (50%), followed by the superior rectus (29%) and inferior oblique muscles (14%). None of the 14patients showed an abnormal abducens nerve. Congenital oculomotor nerve palsy was mostly incomplete and hypoplasia or aplasia of the oculomotor nerve was apparent in one third of patients showing variable degrees of extraocular muscle atrophy, mostly of the medial rectus and inferior rectus muscles.

A Case of Mitochondrial Disease First Diagnosed Over 30 Years After Onset

Mitochondrial disease is induced by mutations in both mitochondrial DNA and DNA of nuclear genes that encode mitochondrial proteins, and there is a general lack of genotype-phenotype correlation in many mitochondrial disorders, which makes the diagnosis of mitochondrial disease difficult. We treated a 37-year-old woman with congenital cataract, bilateral sensory deafness, severe bilateral ptosis, oculomotor disorder in all directions and systemic muscular atrophy and weakness. These clinical characteristics made us perform further examinations, and we found ischemic change in brain and remarkable atrophy of extraocular muscles by magnetic resonance imaging (MRI), optic atrophy by fundus examination and high levels of serum lactate and lactate/pyruvate ratio, which confirmed the diagnosis of mitochondrial disease. Finally, she was diagnosed with having mitochondrial disease for over 30 years after onset. J Endocrinol Metab. 2018;8(6):149-152 doi: https://doi.org/10.14740/jem542

A Case of Mitochondrial Disease First Diagnosed Over 30 Years After Onset

Mitochondrial disease is induced by mutations in both mitochondrial DNA and DNA of nuclear genes that encode mitochondrial proteins, and there is a general lack of genotype-phenotype correlation in many mitochondrial disorders, which makes the diagnosis of mitochondrial disease difficult. We treated a 37-year-old woman with congenital cataract, bilateral sensory deafness, severe bilateral ptosis, oculomotor disorder in all directions and systemic muscular atrophy and weakness. These clinical characteristics made us perform further examinations, and we found ischemic change in brain and remarkable atrophy of extraocular muscles by magnetic resonance imaging (MRI), optic atrophy by fundus examination and high levels of serum lactate and lactate/pyruvate ratio, which confirmed the diagnosis of mitochondrial disease. Finally, she was diagnosed with having mitochondrial disease for over 30 years after onset. J Endocrinol Metab. 2018;8(6):149-152 doi: https://doi.org/10.14740/jem542

Histopathological changes of fibrosis in human extra-ocular muscle caused by botulinum toxin A

We report the histopathological findings in 3 patients where injections of botulinum toxin were used prior to strabismus surgery. In all cases we found evidence of permanent extraocular muscle atrophy and fibrosis.

MRI Evidence of Cerebellar and Extraocular Muscle Atrophy Differently Contributing to Eye Movement Abnormalities in SCA2 and SCA28 Diseases.

Spinocerebellar ataxias type 2 and 28 (SCA2, SCA28) are autosomal dominant disorders characterized by progressive cerebellar and oculomotor abnormalities. We aimed to investigate cerebellar, brainstem, and extraocular muscle involvement in the mitochondrial SCA28 disease compared with SCA2. We obtained orbital and brain 1.5 T-magnetic resonance images (MRI) in eight SCA28 subjects, nine SCA2, and nine age-matched healthy subjects. Automated segmentation of cerebellum and frontal lobe was performed using Freesurfer software. Manual segmentations for midbrain, pons, and extraocular muscles were performed using OsiriX. Eye movement abnormalities in SCA2 subjects were characterized by slow horizontal saccades. Subjects with SCA28 variably presented hypometric saccades, saccadic horizontal pursuit, impaired horizontal gaze holding, and superior eyelid ptosis. Quantitative brain MRI demonstrated that cerebellar and pons volumes were significantly reduced in both SCA2 and SCA28 subjects compared with controls (P < 0.03), and in SCA2 subjects compared with SCA28 (P < 0.01). Midbrain and frontal lobe volumes were also significantly reduced in SCA2 compared to controls (P < 0.03), whereas these volumes did not differ between SCA2 and SCA28 and between SCA28 and control subjects. The extraocular muscle areas were 37% to 48% smaller in SCA28 subjects compared with controls (P < 0.002), and 14% to 36% smaller compared with SCA2 subjects (P < 0.03). Extraocular muscle areas did not differ between SCA2 and controls. Our MRI findings support the hypothesis of different cerebellar and extraocular myopathic contributions in the eye movement abnormalities in SCA2 and SCA28 diseases. In SCA28, a myopathic defect selectively involving the extraocular muscles supports a specific impairment of mitochondrial energy metabolism.

Ocular Findings of Myotonic Dystrophy Type 1 in the Korean Population

To investigate ocular findings in a Korean population with myotonic dystrophy type 1 (DM1). A total of 24 Korean patients with DM1, ranging in age from 4 to 71years, were examined over a period from June 2004 to May 2014. Ophthalmologic examinations including visual acuity assessment, slit-lamp biomicroscopy, ocular motility, cycloplegic refraction, and fundus examination were performed in all patients, and brain magnetic resonance (MR) imaging was performed in 15 patients. The ocular findings, in order of decreasing prevalence, were as follows: cataract (17 patients, 71%), myopia (22 eyes, 59%), hyperopia (13 eyes, 35%), ptosis (6 patients, 25%), epiretinal membrane (5 patients, 21%), exotropia (4 patients, 17%), ocular motility limitations (4 patients, 17%), blepharitis (2 patients, 8%), pigmentary retinopathy (2 patients, 8%), lid lag (1 patient, 4%), esotropia (1 patient, 4%), and myelinated nerve fiber layer (1 patient, 4%). Five of eight patients (63%) with CTG repeats ≥ 700 underwent cataract extraction, as did one of 13 patients (8%) with CTG repeats < 700 (P = 0.014). All four patients who showed limited ocular motility had CTG repeats ≥ 1000. Brain MR imaging showed periventricular white matter lesions in three patients, diffuse brain atrophy in two patients, and extraocular muscle atrophy in two patients. Korean patients with DM1 showed a high incidence of exotropia in comparison to Caucasian patients with DM1. Our study suggests a possible correlation between the severity of cataract and ocular motility limitation and the size of CTG repeats.

Extra-ocular muscle MRI in genetically-defined mitochondrial disease.

ObjectivesConventional and quantitative MRI was performed in patients with chronic progressive external ophthalmoplegia (CPEO), a common manifestation of mitochondrial disease, to characterise MRI findings in the extra-ocular muscles (EOMs) and investigate whether quantitative MRI provides clinically relevant measures of disease.MethodsPatients with CPEO due to single mitochondrial DNA deletions were compared with controls. Range of eye movement (ROEM) measurements, peri-orbital 3 T MRI T1-weighted (T1w) and short-tau-inversion-recovery (STIR) images, and T2 relaxation time maps were obtained. Blinded observers graded muscle atrophy and T1w/STIR hyperintensity. Cross-sectional areas and EOM mean T2s were recorded and correlated with clinical parameters.ResultsNine patients and nine healthy controls were examined. Patients had reduced ROEM (patients 13.3°, controls 49.3°, p < 0.001), greater mean atrophy score and increased T1w hyperintensities. EOM mean cross-sectional area was 43 % of controls and mean T2s were prolonged (patients 75.6 ± 7.0 ms, controls 55.2 ± 4.1 ms, p < 0.001). ROEM correlated negatively with EOM T2 (rho = −0.89, p < 0.01), whilst cross-sectional area failed to correlate with any clinical measures.ConclusionsMRI demonstrates EOM atrophy, characteristic signal changes and prolonged T2 in CPEO. Correlation between elevated EOM T2 and ROEM impairment represents a potential measure of disease severity that warrants further evaluation.Key Points• Chronic progressive external ophthalmoplegia is a common clinical manifestation of mitochondrial disease.• Existing extra-ocular muscle MRI data in CPEO reports variable radiological findings.• MRI confirmed EOM atrophy and characteristic signal changes in CPEO.• EOM T2 was significantly elevated in CPEO and correlated negatively with ocular movements.• EOM T2 represents a potential quantitative measure of disease severity in CPEO.

Atrophy and Fibrosis of Extra-Ocular Muscles in Anti-Acetylcholine Receptor Antibody Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune disorder involving the neuromuscular junction that frequently affects the extra-ocular muscles (EOMs). It has been described as a very rare cause of bilateral EOM atrophy, but histological analysis of such cases is lacking. A 66-year-old man presented with two months of right eyelid drooping and vertical diplopia. Examination showed bilateral ophthalmoparesis and complete right ptosis. The remainder of his exam was normal, and an MRI showed small EOMs. Acetylcholine receptor antibodies were elevated, establishing the diagnosis of MG. Oral corticosteroids and pyridostigmine followed by azathioprine improved his ptosis, but not his ophthalmoparesis. One year later he had surgical correction of his diplopia, and the resected superior rectus muscle showed complete replacement of EOM by connective tissue. MG can rarely cause bilateral EOM atrophy, which is characterized histologically by fibrosis in the muscle itself. Atrophy in the EOMs of a myasthenic patient may indicate a poor response to medical management alone.

Extraocular Muscle Atrophy and Central Nervous System Involvement in Chronic Progressive External Ophthalmoplegia

BackgroundChronic progressive external ophthalmoplegia (CPEO) is a classical mitochondrial ocular disorder characterised by bilateral progressive ptosis and ophthalmoplegia. These ocular features can develop either in isolation or in association with other prominent neurological deficits (CPEO+). Molecularly, CPEO can be classified into two distinct genetic subgroups depending on whether patients harbour single, large-scale mitochondrial DNA (mtDNA) deletions or multiple mtDNA deletions secondary to a nuclear mutation disrupting mtDNA replication or repair. The aim of this magnetic resonance imaging (MRI) study was to investigate whether the ophthalmoplegia in CPEO is primarily myopathic in origin or whether there is evidence of contributory supranuclear pathway dysfunction.MethodsTen age-matched normal controls and twenty patients with CPEO were recruited nine patients with single, large-scale mtDNA deletions and eleven patients with multiple mtDNA deletions secondary to mutations in POLG, PEO1, OPA1, and RRM2B. All subjects underwent a standardised brain and orbital MRI protocol, together with proton magnetic resonance spectroscopy in two voxels located within the parietal white matter and the brainstem.ResultsThere was evidence of significant extraocular muscle atrophy in patients with single or multiple mtDNA deletions compared with controls. There was no significant difference in metabolite concentrations between the patient and control groups in both the parietal white matter and brainstem voxels. Volumetric brain measurements revealed marked cortical and cerebellar atrophy among patients with CPEO+ phenotypes.ConclusionThe results of this study support a primary myopathic aetiology for the progressive limitation of eye movements that develops in CPEO.

P.17.16 Enophthalmos and MELAS

A female patient with genetically confirmed MELAS was seen when 32 old for headache of two types: daily diffuse headache and occasional right-sight migrainous.She also complained of memory loss, asthenia, episodes of dizziness resulting sometimes in falls. She never presented any seizure. Her examination revealed a right-sight sensory-motor weakness and an intellectual impairment on formal psychological testing. A CT scan showed a left temporo-sylvian arachnoid cyst with ipsilateral frontal sulcal effacement and ventricular mass effect. Cystoperitoneal shunting resulted in disappearance of right-sight headache episodes, but did not change the other symptoms, which progressively worsened. In addition, a conspicuous bilateral orbital deepening appeared within 2 months following surgery. Post-operative CT scan and brain magnetic resonance imaging revealed only temporal cyst and “ enophthalmos ”. The diagnosis of mitochondrial disease was suspected because of the familial history. A large spectrum of causes generates enophthalmos. Either the orbital volume increases or the volume of soft tissues in the orbit decreases. Few articles report enophtalmos secondary to ventriculoperitoneal shunt. The mechanism of enophthalmos in these cases has never been elucidated, but theories have included fat atrophy and expansion of the bony orbit. In our patient, neither valve pressure nor valve position were abnormal, RMI did not find any usual sign of intracranial hypotension: no thickening of the meninges; lateral ventricles and basal cisterns were present and brain did not collapse. A reduction of orbital content was discovered, due to a bilateral ocular fat atrophy and extra ocular muscles atrophy. The relation between enophthalmia and mitochondriopathies has not been reported in the literature. Fat tissue is not used to be a target-tissue of mitochondriopathies except their implication in diffuse fat atrophy in HIV patient treated with specific treatment.

Melkersson–Rosenthal syndrome associated with multiple cranial nerve palsies and progressive atrophy of facial and extraocular muscles

Melkersson–Rosenthal syndrome associated with multiple cranial nerve palsies and progressive atrophy of facial and extraocular muscles

Orbital Floor Fracture Reconstruction Using Conchal Auricular Cartilage Graft

Orbital Floor Fracture Reconstruction Using Conchal Auricular Cartilage Graft

Orbital Floor Fracture Reconstruction using Conchal Auricular Cartilage Graft

Orbital Floor Fracture Reconstruction using Conchal Auricular Cartilage Graft

Evidence of an Asymmetrical Endophenotype in Congenital Fibrosis of Extraocular Muscles Type 3 Resulting fromTUBB3Mutations

Orbital magnetic resonance imaging (MRI) was used to investigate the structural basis of motility abnormalities in congenital fibrosis of the extraocular muscles type 3 (CFEOM3), a disorder resulting from missense mutations in TUBB3, which encodes neuron-specific beta-tubulin isotype III. Ophthalmic examinations in 13 volunteers from four CFEOM3 pedigrees and normal control subjects, were correlated with TUBB3 mutation and MRI findings that demonstrated extraocular muscle (EOM) size, location, contractility, and innervation. Volunteers included clinically affected and clinically unaffected carriers of R262C and D417N TUBB3 amino acid substitutions and one unaffected, mutation-negative family member. Subjects with CFEOM3 frequently had asymmetrical blepharoptosis, limited vertical duction, variable ophthalmoplegia, exotropia, and paradoxical abduction in infraduction. MRI demonstrated variable, asymmetrical levator palpebrae superioris and superior rectus EOM atrophy that correlated with blepharoptosis, deficient supraduction, and small orbital motor nerves. Additional EOMs exhibited variable hypoplasia that correlated with duction deficit, but the superior oblique muscle was spared. Ophthalmoplegia occurred only when the subarachnoid width of CN3 was <1.9 mm. A-pattern exotropia was frequent, correlating with apparent lateral rectus (LR) muscle misinnervation by CN3. Optic nerve (ON) cross sections were subnormal, but rectus pulley locations were normal. CFEOM3 caused by TUBB3 R262C and D417N amino acid substitutions features abnormalities of EOM innervation and function that correlate with subarachnoid CN3 hypoplasia, occasional abducens nerve hypoplasia, and subclinical ON hypoplasia that can resemble CFEOM1. Clinical and MRI findings in CFEOM3 are more variable than those in CFEOM1 and are often asymmetrical. Apparent LR innervation by the inferior rectus motor nerve is an overlapping feature of Duane retraction syndrome and CFEOM1. These findings suggest that CFEOM3 is an asymmetrical, variably penetrant, congenital cranial dysinnervation disorder leading to secondary EOM atrophy.

The Changes in Extraocular Muscles in Horner's Syndrome of Rats

Purpose: The aim of this study was to understand the pathogenesis of the enophthalmos of Horner's syndrome. Methods: We performed right cervical sympathectomy in 10 Sprague-Dawley rats weighing 200300 grams at 8 weeks of age. We obtained bilateral extraocular muscle and fat from all 10 rats. These tissues were observed under light and electron microscopy. Results: After 8 weeks, ptosis and enophthalmos were seen in the right eye in all rats. We found no change bilateral fat, but the right extraocular muscle fibers had smaller diameters than the left. The right intermuscular distance was longer than the left upon light microscopy and the right extraocular muscle contained fewer and smaller mitochondria than the left extraocular muscle upon electron microscopy. Conclusions: Based on these results, it is believed that enophthalmos resulted from extraocular muscle atrophy that resulted from decreasing metabolism of mitochondria in Horner's syndrome. However, enophthalmos in Horner's syndrome requires more intensive study.

High-resolution magnetic resonance imaging demonstrates reduced inferior oblique muscle size in isolated inferior oblique palsy

The diagnosis of isolated inferior oblique muscle palsy is controversial for 2 reasons: first, clinical findings seem inconsistent with our current understanding of oculomotor neuroanatomy and, second, similar findings can occur with other causes. Because denervated extraocular muscles atrophy, we used high-resolution magnetic resonance imaging (MRI) to assess inferior oblique muscle size in patients with clinically suspected inferior oblique muscle palsy. A diagnosis of inferior oblique muscle palsy in 6 patients (4 unilateral, 2 bilateral) was made clinically. High-resolution coronal and sagittal orbital MRI were obtained in subjects with clinical inferior oblique muscle palsy and in 30 age-matched control subjects. Cross sections of the inferior oblique, inferior rectus (IR), and medial rectus muscles were determined together because each is innervated by the common inferior division of the oculomotor nerve. No subject had pupillary abnormalities or other extraocular muscle weakness or restriction. Mean cross-sectional area of the affected inferior oblique muscle (n = 8) at the midpoint of the inferior rectus muscle was 10.2 +/- 1.05 mm(2), which was significantly smaller than the value of 18.8 +/- 3.6 mm(2) for control subjects (n = 58, p < 0.00001). Unilaterally affected inferior oblique muscles were significantly smaller than unaffected inferior oblique muscles (p < 0.05). Mean medial rectus muscle cross section (n = 8) ipsilateral to the affected inferior oblique muscle was 36.8 +/- 2.4 mm(2), which was not significantly different from the 35.1 +/- 3.7 mm(2) value for the medial rectus muscles of control subjects (n = 61, p > 0.1). Mean inferior rectus muscle cross section (n = 8) ipsilateral to the affected inferior oblique muscle was 32.5 +/- 2.3 mm(2), which was significantly greater than the 29.9 +/- 3.3 mm(2) measurement for the control subjects (n = 61, p < 0.01). We used MRI to demonstrate reduced inferior oblique muscle size in patients with clinically diagnosed inferior oblique muscle palsy, supporting the concept of isolated inferior oblique muscle weakness.

High-Resolution Magnetic Resonance Imaging of the Extraocular Muscles and Nerves Demonstrates Various Etiologies of Third Nerve Palsy

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. Prospective, noncomparative, observational case series in an academic referral setting. 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. 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. 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.