Extraocular muscles have fundamentally distinct properties that make them selectively vulnerable to certain disorders.
ABSTRACT While skeletal muscles generally perform specific limited roles, extraocular muscles (EOMs) have to be responsive over a wider dynamic range. As a result, EOMs have fundamentally distinct structural, functional, biochemical and immunological properties compared to other skeletal muscles. While these properties enable high fatigue resistance and the rapid and precise control of extraocular motility, they might also explain why EOMs are selectively involved in certain disorders, such as chronic progressive external ophthalmoplegia (CPEO), myasthenia gravis and Graves' ophthalmopathy. This review first gives an overview of the novel myofibre classification in EOMs and then focuses on those properties that might explain why ophthalmoplegia should be so prominent in these disorders.
Article: Comparison of muscle ultrastructure in myasthenia gravis with anti-MuSK and anti-AChR antibodies.[show abstract] [hide abstract]
ABSTRACT: Patients with myasthenia gravis (MG) with antibodies to muscle-specific receptor tyrosine kinase (MuSK) differ from acetylcholine receptor (AChR)-positive MG patients, as they frequently present with severe oculobulbar muscle weakness or with neck, shoulder, and respiratory muscle involvement. The neuromuscular junction (NMJ) has been confirmed to be the main target of both AChR- and MuSK-MG. However, histopathological investigation disclosed that muscle fiber atrophy was prevalent in AChR-MG, whereas mild myopathic changes and mitochondrial abnormalities were more frequently observed in MuSK-MG. As the pathogenetic mechanism in MuSK-MG remains unclear, this study investigated the submicroscopic pattern of muscle histopathology to establish a possible correlation between clinical involvement and subcellular morphological findings. Muscle biopsies from seven MuSK-MG patients and from seven patients with AChR-MG were analyzed by transmission electron microscopy. Myopathic and mitochondrial abnormalities were more prominent in MuSK-MG and show giant, swollen, and degenerated mitochondria with fragmented cristae. The most common changes in AChR-MG muscles were fiber atrophy, myofibrillar disarray, and Z-line streaming, consistent with mild neurogenic abnormalities. A different pathogenetic mechanism is emerging in MuSK-MG compared to AChR-MG. Mitochondrial abnormalities seem to be more prominent in MuSK-MG, whereas neurogenic atrophy is observed in AChR-MG.Journal of Neurology 11/2010; 258(5):746-52. · 3.47 Impact Factor
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ABSTRACT: Smoking adversely affects the course and severity of Graves' orbitopathy (GO). Cigarette smoke enhances adipogenesis in cultured human orbital fibroblasts. The present study tested our hypothesis that smoking is associated with increased orbital fat in GO patients. This was an observational case series study. In 95 consecutive patients with untreated GO, the ratios of fat volume/orbital volume (FV/OV) and muscle volume/OV (MV/OV) were calculated with validated software. The most affected orbit of each patient was chosen for analysis. Patients were divided into two groups based on smoking behavior. One group was current smokers (Sm+) and the other were those who never smoked or those who had not smoked for at least 1 year (Sm-). Patients were grouped in tertiles of FV/OV and MV/OV and contrast in OVs between the Sm+ and Sm- group. The main characteristics of GO were analyzed using Jonckheere-Terpstra trend analysis and Mann-Whitney U-test. The proportion of current smokers was not different in GO patients when divided in tertiles according to their FV/OV. In contrast, analysis of MV/OV tertiles showed a trend to a higher prevalence of current smokers in patients with larger MVs. Smoking did not influence FV, but the Sm+ group had significantly larger MVs than the Sm- group. Smoking is associated with an increase in extraocular MV in untreated patients with GO and not with an increase in FV.Thyroid: official journal of the American Thyroid Association 02/2011; 21(2):177-81. · 2.60 Impact Factor
Article: Development of extraocular muscles requires early signals from periocular neural crest and the developing eye.[show abstract] [hide abstract]
ABSTRACT: To identify and explain morphologic changes of the extraocular muscles (EOMs) in anophthalmic patients. Retrospective medical record review of patients with congenital anophthalmia, using magnetic resonance imaging and intraoperative findings to characterize EOM morphology. We then used molecular biology techniques in zebrafish and chick embryos to determine the relationships among the developing eye, periocular neural crest, and EOMs. In 3 human patients with bilateral congenital anophthalmia and preoperative orbital imaging, we observed a spectrum of EOM morphologies ranging from indiscernible muscle tissue to well-formed, organized EOMs. Timing of eye loss in zebrafish and chick embryos correlated with the morphology of EOM organization in the orbit (eye socket). In congenitally eyeless Rx3 zebrafish mutants, or following genetic ablation of the cranial neural crest cells, EOMs failed to organize, which was independent of other craniofacial muscle development. Orbital development is dependent on interactions between the eye, neural crest, and developing EOMs. Timing of the ocular insult in relation to neural crest migration and EOM development is a key determinant of aberrant EOM organization. Additional research will be required to study patients with unilateral and syndromic anophthalmia and assess for possible differences in clinical outcomes of patients with varied EOM morphology. The presence and organization of EOMs in anophthalmic eye sockets may serve as a markers for the timing of genetic or teratogenic insults, improving genetic counseling, and assisting with surgical reconstruction and family counseling efforts.Archives of ophthalmology 04/2011; 129(8):1030-41. · 3.86 Impact Factor