Extraocular muscles have fundamentally distinct properties that make them selectively vulnerable to certain disorders

Yu‐Wai‐Man, Cynthia; Chinnery, Patrick F.; Griffiths, Philip G.

doi:10.1016/j.nmd.2004.10.002

Cited by 96 publications

(61 citation statements)

References 42 publications

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“…High muscle density in GO is unlikely to be due to edema (in which case one would expect the density to be lower than in controls), but might be caused by muscle fibrosis or muscle fiber degeneration. Hypoxia may also play a role as extraocular muscles are extremely sensitive to hypoxia in view of their large amount of mitochondria and high oxygen need [24]. A previous study noted an inverse relation between duration of GO and rectus muscle density [25].…”

Section: Orbital Volumetry In Gomentioning

confidence: 99%

Differential Involvement of Orbital Fat and Extraocular Muscles in Graves' Ophthalmopathy

2013

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Graves' ophthalmopathy (GO) is characterized by swelling of orbital fat and extraocular muscles, but little attention has been given to differential involvement of fat and muscles. Advancements in imaging allow rather accurate measurements of orbital bony cavity volume (OV), fat volume (FV) and muscle volume (MV), and are the topics of this review. Ratios of FV/OV and MV/OV neutralize gender differences. In adult Caucasian controls, mean values ± SD of FV/OV are 0.56 ± 0.11 and of MV/OV are 0.15 ± 0.02. FV increases substantially and MV decreases slightly with advancing age, requiring age-specific reference ranges. In 95 consecutive untreated Caucasian GO patients, both FV and MV were within normal limits in 25%, increased FV but normal MV was present in 5%, normal FV but increased MV was detected in 61%, and both increased FV and MV was evident in 9%. Increased FV was associated with more proptosis and longer GO duration. Increased MV was associated with older age, more severe GO (more proptosis and diplopia, worse eye muscle ductions), higher TBII and current smoking. At the cellular and molecular level differential involvement of fat and muscles might be related to differences between fibroblast phenotypes and cytokine profiles in each compartment, to different orbital T cell subsets during the course of the disease and to peroxisome proliferator activator receptor-γ polymorphisms and modulation of 11β-hydroxysteroid dehydrogenase-1. Enlarged muscles are apparently a rather early phenomenon in GO, whereas increases in fat mass occur relatively late. Why a minor subset of GO patients presents with an increase of only fat remains poorly understood.

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Section: Orbital Volumetry In Gomentioning

confidence: 99%

Differential Involvement of Orbital Fat and Extraocular Muscles in Graves' Ophthalmopathy

2013

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“…Indeed, they should be resistant to fatigue with high blood flow, mitochondria content and metabolic rate. [15] However, the motor unit sizes are small and the firing frequencies are high, and some of the muscle fibers have multiple NMJs in which the EPPs, rather than action potentials, are directly responsible for activating the contractile apparatus. This means that any reduction in the EPP could have a direct effect on the strength of muscle contraction.…”

Section: Ocular Myasthenia Gravismentioning

confidence: 99%

Autoimmune disorders of the neuromuscular junction

Lang

Vincent

2009

Current Opinion in Pharmacology

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The neuromuscular junction (NMJ) is a prototypic synapse although its structure is rather different from those of the central nervous system (CNS). The unmyelinated motor nerve terminals are separated from the postsynaptic membrane by a cleft that contains a basal lamina. This includes many proteins such as collagens, laminins, fibronectin and perlecan which help anchor some of the key elements involved in NMJ The neuromuscular junction (NMJ) is a specialized synapse with a complex structural and functional organization. It is a target for a variety of immunological disorders and these diseases usually respond well to immunotherapies. The understanding of the immunological basis of myasthenia gravis, the most common neuromuscular junction disorder, has improved in the recent years. Most patients have antibodies to the acetylcholine receptor (AChR), but around 10% have AChR antibodies that are only identified by novel methods, and up to 5% have muscle-speciÞ c kinase antibodies which deÞ ne a different subgroup of myasthenia. The spectrum of antibodies and their pathophysiological aspects are being elucidated. Even though less common, Lambert Eaton myasthenic syndrome (LEMS) is important to recognize. The abnormality in LEMS is a presynaptic failure to release enough packets of ACh, caused by antibodies to the presynaptic voltage-gated calcium channels. More than half these patients have a small cell carcinoma of lung. Acquired neuromyotonia (NMT) is a condition associated with muscle hyperactivity. Clinical features include muscle stiffness, cramps, myokymia, pseudomyotonia and weakness. The immune mechanisms of acquired NMT relate to loss of voltage-gated potassium channel function. This review will focus on the important recent developments in the immunemediated disorders of the NMJ.Key words: Gravis, Lambert Eaton myasthenic syndrome, neuromyotonia, neuromuscular junction, autoimmunity, acetylcholine receptor, voltage-gated channel development and function; for instance acetylcholine esterase (AChE) is localized via ColQ, a collagen-like molecule, to the basal lamina. Agrin and neuregulins, secreted from the nerve terminal, are bound by the basal lamina and interact with their receptors, playing an important role in the location of postsynaptic membrane proteins, voltage-gated calcium channels and the dystroglycans. The postsynaptic membrane at the NMJ forms a series of deep folds. The acetylcholine receptors (AChRs) are found at the top one-third of these folds, whereas the voltage-gated sodium channels are anchored at the bottom of the folds. The development of the NMJ is a fascinating area of research [1] and many of the proteins involved are relevant to disease ([ Figure 1] for a simple representation).The nerve action potential opens voltage-gated calcium channels (VGCCs) that are located in the motor nerve terminal [ Figure 1]. The resulting influx of calcium leads to the release of about 30 (in human muscle) individual packets of acetylcholine (ACh). Some of the ACh is hydrolysed by AChE but about 65%...

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“…Extra-ocular muscles have fundamentally distinct properties that make them selectively vulnerable to certain disorders [12]. Kloprogge and Busuttil [13] succeeded in finding TSH receptor protein selectively in the extra-ocular eye muscles but not in other striated muscles.…”

Section: Discussionmentioning

confidence: 99%

Pure Eye Muscle Involvement in Endocrine Orbitopathy

Gerlach

Ferbert²

2008

Eur Neurol

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We present a long-term follow-up examination concerning patients with isolated extra-ocular muscle involvement in thyroid-related orbitopathy. Within the previous 13 years we observed 7 patients with endocrine orbitopathy and marked myopathy of the extra-ocular muscles. Five of these patients had no detectable proptosis, 2 of them showed a minimal unilateral proptosis. Five patients showed elevated thyroid-stimulating hormone (TSH) receptor auto-antibodies and 6 patients a marked swelling of the extra-ocular eye muscles on CT or MRI scans. One patient had elevated antibodies against thyroid peroxidase and against thyroglobulin and normal TSH receptor auto-antibodies. Four of 7 patients underwent clinical and radiological follow-up examination 1–9 years later. In 3 of these 4 patients, the clinical syndrome had completely resolved. None of the patients had developed any proptosis. The swelling of the eye muscles on radiological imaging had at least partially resolved. We conclude from our results that apart from the frequent subtype of endocrine orbitopathy with predominant proptosis there is a separate subtype in which proptosis neither exists initially nor develops in the further course. Probably these subtypes have a specific immunological antibody profile although they do not differ concerning the thyroid-stimulating antibodies.

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Extraocular muscles have fundamentally distinct properties that make them selectively vulnerable to certain disorders

Cited by 96 publications

References 42 publications

Differential Involvement of Orbital Fat and Extraocular Muscles in Graves' Ophthalmopathy

Differential Involvement of Orbital Fat and Extraocular Muscles in Graves' Ophthalmopathy

Autoimmune disorders of the neuromuscular junction

Pure Eye Muscle Involvement in Endocrine Orbitopathy

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