Ocular Myasthenia Gravis Associated With Thymic Amyloidosis

Cilioretinal artery territory infarction can occur in isolation or in association with other vascular compromise of the retinal circulation. Our patient, an 18-year-old woman with neurofibromatosis type 2, developed a cilioretinal artery territory infarction in the setting of papilledema. Our case, together with one previous report, suggests that cilioretinal artery territory infarction in the context of papilledema, although rare, is a real entity.

Clinical Observation Ocular Myasthenia Gravis Associated With Thymic Amyloidosis Kristin O. Chapman, MD, Debra M. Beneck, MD, Marc J. Dinkin, MD Abstract: A 45-year-old woman with ptosis and diplopia was found to have myasthenia gravis (MG) associated with amyloidosis of the thymus gland. Systemic MG is frequently associated with thymomas or thymic hyperplasia but has only once previously been reported in association with amyloidosis of the thymus. This case demonstrates that isolated ocular MG rarely may also be associated with amyloidosis of the thymus. Journal of Neuro-Ophthalmology 2016;36:50-52 doi: 10.1097/WNO.0000000000000241 © 2015 by North American Neuro-Ophthalmology Society T he association of myasthenia gravis (MG) with thymic tumors is well established, as 10%-20% of patients with MG are found to have a thymoma (1,2), and in one series of patients with thymomas, there was a 55% prevalence of MG (3). Thymectomy has been associated with improvement and even resolution of myasthenic symptoms in patients with thymoma, and there is evidence of symptomatic improvement with resection of thymic hyperplasia without neoplasm (4). We present a case of ocular myasthenia with positive acetylcholine receptor antibody serologies associated with a thymic mass containing amyloid. Although rare, this association may offer new insights into the pathophysiology of MG. CASE REPORT A 45-year-old woman with a medical history of hypertension reported a 2-week history of progressive left upper eyelid ptosis. Eleven months before presentation, her left eye began deviating outward intermittently, especially at the Departments of Ophthalmology (KOC), Pathology (DMB), and Neurology (MJD), Weill Cornell Medical Center, New York, New York. The authors report no conflicts of interest. Address correspondence to Marc J. Dinkin, MD, Department of Ophthalmology, Weill Cornell Medical College, 1305 York Avenue, New York, NY 10021; E-mail: [e-mail] 50 end of a long workday. This was soon followed by intermittent binocular vertical diplopia, worse in downgaze. She was diagnosed as having congenital strabismus and offered corrective surgery. She opted instead to patch one eye and seek another opinion. On examination, visual acuity was 20/15 in right eye and 20/20 in left eye. Pupils, intraocular pressures, confrontational visual fields and funduscopy were unremarkable. Extraocular movements were full, but cross cover testing demonstrated an incomitant exotropia worse in upgaze and left gaze. There was left ptosis and no evidence of proptosis. Cogan lid twitch sign was not detected, but there was significant fatigability with worsening of left ptosis after 1 minute of upgaze. Enhanced ptosis (curtaining) was present bilaterally. The remaining general neurological examination was normal including testing for fatigability of the deltoids and ability to count to 30 in one breath. After 20 minutes of rest, the palpebral fissure and marginal reflex distance became equal at 10 and 5 mm, respectively, in both eyes (Fig. 1). Laboratory testing revealed elevated binding, blocking, and modulating acetylcholine receptor antibodies (68.0 nmol/L [normal: ,0.05 nmol/L], 45% and 83%, respectively). Magnetic resonance imaging of the chest demonstrated a minimally enhancing soft tissue mass of the thymus measuring 8.4 · 3.5 cm. Computed tomography revealed calcification of the mass (Fig. 2). A robotic thymectomy was performed, and the mediastinal mass contained both thymic tissue and amyloid (Figs. 3, 4). Immunohistochemical analysis was inconclusive for kappa and lambda light chain, as well as amyloid A. Transthyretin (TTR) amyloidosis DNA sequencing was negative for DNA sequence alteration in the coding region of the TTR gene, indicating a low likelihood of primary amyloidosis. The patient was treated with oral steroids for 3 months and experienced complete resolution of ptosis and diplopia. Chapman et al: J Neuro-Ophthalmol 2016; 36: 50-52 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Observation FIG. 1. Appearance of patient at baseline (A) and after 20 minutes of rest (B). Systemic workup including cardiac and renal evaluations failed to demonstrate amyloidosis in other organs. DISCUSSION Thymic amyloidosis in patients with MG is extremely rare. Thymomas and thymic hyperplasia may be the source of acetylcholine receptor antibodies (1,2). Imaging of the chest is recommended in patients with MG to evaluate for thymomas, and removal of the mass can often lead to improvement or even resolution of symptoms (4). Amyloidosis can occur in either a localized or systemic form and is associated with immunoglobulin dysregulation. As either a primary or secondary form, this disorder causes deposition of amyloid fibrils in tissue injuring affected organs (5). Although 11 cases of amyloid deposition in the mediastinum have been reported, we were able to find only 3 previous cases of amyloid deposition in the thymus in the English literature (6-8). In one case, there was a history of rheumatoid arthritis (6), and in the second, Son et al (8) described a 46-year-old woman with systemic MG who developed myasthenic crisis and was found to have primary amyloid deposition in her thymus gland. Removal of her FIG. 2. Computed tomography of the chest reveals calcification of the mediastinal mass (arrows) with adjacent calcified perivascular lymph nodes. Chapman et al: J Neuro-Ophthalmol 2016; 36: 50-52 thymic tumor resulted in resolution of all symptoms. The authors proposed that the deposition of misfolded light chains derived from acetylcholine receptor antibodies resulted in amyloid formation. In both, our patient and that of Son et al (8), it is difficult to know whether or not the removal of the thymic amyloid tumor contributed to clinical improvement, since both patients received systemic corticosteroids. Neither our case nor the previously reported case was associated with multiple myeloma or systemic amyloidosis. Thymic calcifications were present both in our case and the previous case of thymic amyloidosis with MG. These calcifications are more commonly seen in invasive thymomas and thymic carcinomas (up to 54% and 61%, respectively) than in noninvasive thymomas (10%-21%), but their presence does not appear to offer a reliable means of distinguishing these subtypes (9). Although thymic amyloid tumor has been reported once before in a patient with systemic MG, our report demonstrates that this also may FIG. 3. Gross view of resected thymus mass. Fatty tissue (arrow) represents residual normal thymic tissue. 51 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Observation FIG. 4. Pathology of thymic mass. A. Thymic tissue (arrows) is surrounded by pink-staining amyloid (hematoxylin & eosin, ·100). B. Island of residual thymic tissue is surrounded by congophilic amyloid (Congo red, ·100). C. Amyloid tumor viewed with polarized light shows "apple green" birefringence (Congo red, ·400). occur in patients with pure ocular MG. The significance of this rare finding to the pathogenesis of MG remains to be elucidated. 3. 4. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: K. O. Chapman, M. J. Dinkin, and D. M. Beneck; b. Acquisition of data: K. O. Chapman, M. J. Dinkin, and D. M. Beneck; c. Analysis and interpretation of data: K. O. Chapman, M. J. Dinkin, and D. M. Beneck; Category 2: a. Drafting the manuscript: K. O. Chapman, M. J. Dinkin, and D. M. Beneck; b. Revising it for intellectual content: K. O. Chapman, M. J. Dinkin, and D. M. Beneck; Category 3: a. Final approval of the completed manuscript: K. O. Chapman, M. J. Dinkin, and D. M. Beneck. 5. 6. 7. 8. REFERENCES 1. Berrih-Aknin S, Le Panse R. Myasthenia gravis: a comprehensive review of immune dysregulation and etiological mechanisms. J Autoimmun. 2013;52:1-11. 2. Berrih-Aknin S, Morel E, Raimond F, Safar D, Gaud C, Binet JP, et al. The role of the thymus in myasthenia gravis: 52 9. immunohistological and immunological studies in 115 cases. Ann N Y Acad Sci. 1987;505:50-70. Weiss JM, Cufi P, Le Panse R. The thymus in autoimmune myasthenia gravis: paradigm for a tertiary lymphoid organ. Rev Neurol (Paris). 2013;169:640-649. Wong SH, Huda S, Vincent A, Plant GT. Ocular myasthenia gravis: controversies and updates. Curr Neurol Neurosci Rep. 2014;14:421-431. Merlini G, Seldin DC, Gertz MA. 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