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      Radiological Characteristics of Extraocular Muscles in Myasthenia Gravis Patients with Ocular Manifestations: A Case–Control Study

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          Abstract

          Purpose

          To analyze radiological characteristics of the extraocular muscles (EOMs) in myasthenia gravis (MG) patients with ocular manifestations.

          Patients and Methods

          This retrospective case–control study included all MG cases with ocular manifestations, who attended a neuro-ophthalmology clinic at a university hospital, Bangkok, from April 2009 to June 2018. They experienced double vision and ophthalmoplegia. Control participants had normal eye movements. Orbital scans were thoroughly reviewed. We measured muscle thickness (MT) of the superior rectus, inferior rectus, medial rectus and lateral rectus muscles in both eyes using magnetic resonance imaging or computed tomography scan. The sum of the muscle thickness at all sites was calculated (MTsum). Comparisons of the mean MT of each muscle type and the mean MTsum between the MG and control groups were performed by using Student’s t-test. MRI signal intensities of the EOMs were also recorded.

          Results

          Twenty MG cases and 20 controls were included in the study. The mean MTsum was 23.7 (standard deviation 4.8) mm in the MG group and 32.6 (3.5) mm in the controls. There were statistically significant differences between the two groups with respect to the mean MT and mean MTsum (p <0.001). In the MG group, there was a negative correlation between the MTsum and disease duration (p= 0.03). By using coronal T2-weighted orbital MRI with fat suppression (T2W/FS), the most frequent finding was isointensity with central hypointensity of the EOMs in the MG group.

          Conclusion

          Atrophic EOMs were frequently found in the MG group, particularly in chronic cases. Isointensity with central hypointensity of EOMs on T2W/FS was also common in the MG group. These findings highlight the importance of muscle involvement in MG and may be helpful for clinical decision-making.

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          Most cited references15

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          STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

          Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies.
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            MRI and clinical studies of facial and bulbar muscle involvement in MuSK antibody-associated myasthenia gravis.

            A proportion of patients with myasthenia gravis (MG) without acetylcholine receptor (AChR) antibodies have antibodies to muscle-specific kinase (MuSK). MG with MuSK antibodies (MuSK-MG) is often associated with persistent bulbar involvement, including marked facial weakness and tongue muscle wasting. The extent of muscle wasting in MuSK-MG, and whether it is also found in the few acetylcholine receptor (AChR-MG) patients who have persistent bulbar involvement, is not clear. We studied 12 MuSK-MG patients and recruited 14 AChR-MG patients matched broadly for age, sex ratio, duration of disease and degree of ocular, bulbar and facial weakness. We used coronal and sagittal T1-weighted (T1W) and T2-weighted (T2W) magnetic resonance imaging (MRI) to assess muscle wasting in facial and tongue muscles. Hyperintense signal on T1W MRI and comparison of axial T1W sequences with cUTE sequences were used to assess fibrous/fatty tissue in the tongue. We compared the results with those of four patients with myotonic dystrophy and 12 healthy individuals. We correlated the changes with clinical and treatment histories, and established a new ocular-bulbar-facial-respiratory (OBFR) score. At the time of study, none of the clinical measures, including the OBFR score, differed between the two MG groups. MRI demonstrated thinning of the buccinator, orbicularis oris (O.oris) and orbicularis oculi (O.oculi) muscles in MuSK-MG patients compared with healthy controls, whereas thinning of these muscles was not significant in AChR-MG. Tongue areas with T1W high signal were increased in MuSK-MG patients and the intensity of the signal on axial T1W sequences was greater in MuSK-MG than in controls. To look for possible correlations between imaging and clinical findings, we pooled results from all MG patients. The duration of treatment with prednisolone at >40 mg on alternate days (AD) correlated positively with the percentage of tongue area with high signal (P = 0.006) and negatively with MRI measurements of individual muscles and with the mean muscle dimensions (P = 0.001). The new OBFR score correlated positively with current Myasthenia Gravis Foundation of America grades and with the percentage of high signal (P = 0.004) and negatively with the mean muscle dimensions (P 40 mg AD), may be an additional factor.
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              Muscle histopathology in myasthenia gravis with antibodies against MuSK and AChR.

              We compared myopathological features in myasthenia gravis (MG) patients with antibodies against AChR (seropositive) and muscle-specific tyrosin-kinase (MuSK). While the immunopathogenesis of seropositive MG is well known, there is a lack of pathological studies in anti-MuSK antibody-positive (MuSK+) MG. We analysed skeletal muscle biopsy features of 13 MG patients: 6 MuSK+ (all women) and 7 anti-AchR antibody-positive (AChR+) (2 women and 5 men). In our histopathological examination, we quantified the atrophy factor of both fibre types, and the extent of minicores, myofibrillar disarray, cytochrome c oxidase (COX)-negative fibres, mitochondrial aggregates and fibre type grouping. Mean muscle fibre atrophy factor was higher in AChR+ MG than MuSK+ MG, both in type I fibres (494 vs. 210) and particularly in type II fibres (1023 vs. 300). Fibre type grouping was observed in AChR+ MG whereas COX-negative fibres were common in MuSK+ MG. Bulbar muscles were more severely affected in MuSK+ MG and the disease was more severe: the onset was usually earlier (39 years) with Myasthenia Gravis Foundation of America score III in MuSK+ MG, and score II was found in AChR+ MG (62 years). Muscle biopsies of MuSK+ MG show myopathic signs with prominent mitochondrial abnormalities, whereas neurogenic features and atrophy are more frequently found in AChR+ MG. The mitochondrial impairment could explain the oculo-bulbar involvement in MuSK+ MG.
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                Author and article information

                Journal
                Clin Ophthalmol
                Clin Ophthalmol
                opth
                clinop
                Clinical Ophthalmology (Auckland, N.Z.)
                Dove
                1177-5467
                1177-5483
                01 June 2021
                2021
                : 15
                : 2279-2285
                Affiliations
                [1 ]Department of Ophthalmology, Faculty of Medicine Ramathibodi Hospital, Mahidol University , Bangkok, Thailand
                [2 ]Department of Diagnostic and Therapeutic Radiology, Faculty of Medicine Ramathibodi Hospital, Mahidol University , Bangkok, Thailand
                [3 ]Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University , Bangkok, Thailand
                [4 ]Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University , Bangkok, 10400, Thailand
                Author notes
                Correspondence: Panitha Jindahra Division of Neurology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University , 270 Rama VI Road, Thung Phayathai, Ratchatewi, Bangkok, 10400, ThailandTel +6622011386 Email panitha.jin@mahidol.ac.th
                Author information
                http://orcid.org/0000-0002-5840-6172
                http://orcid.org/0000-0002-1857-8463
                http://orcid.org/0000-0003-0175-7438
                Article
                280508
                10.2147/OPTH.S280508
                8180303
                93489c3c-bebd-4724-9ddb-67f150e6ff1d
                © 2021 Lueangaram et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 01 February 2021
                : 21 April 2021
                Page count
                Figures: 3, Tables: 3, References: 15, Pages: 7
                Funding
                Funded by: Ramathibodi Hospital, Mahidol University;
                The study was supported by Division of Neurology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University.
                Categories
                Original Research

                Ophthalmology & Optometry
                myasthenia gravis,acetylcholine receptor antibodies,extraocular muscles,extraocular muscle atrophy,central hypodensity

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