Journal of Neuro-Ophthalmology, March 2015, Volume 35, Issue 1

Autoimmune Acquired Rippling Muscle Disease and Myasthenia Gravis

REFERENCES 1. Parker SE, Gujrati M, Pula JH, Zallek SN, Kattah JC. The heidenhain variant of Creutzfeldt-Jakob disease-a case series. J Neuroophthalmol. 2014;34:4-9. 2. McGuire LI, Peden AH, Orrú CD, Wilham JM, Appleford NE, Mallinson G, Andrews M, Head MW, Caughey B, Will RG, Knight RS, Green AJ. Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease. Ann Neurol. 2012;72:278-285. 3. Caobelli F, Cobelli M, Pizzocaro C, Pavia M, Magnaldi S, Guerra UP. The role of neuroimaging in evaluating patients affected by Creutzfeldt-Jakob disease: a systematic review of the literature. J Neuroimaging. [published ahead of print March 5, 2014] doi: 10.1111/jon.12098. 4. Young GS, Geschwind MD, Fischbein NJ, Martindale JL, Henry RG, Liu S, Lu Y, Wong S, Liu H, Miller BL, Dillon WP. Diffusion-weighted and fluid-attenuated inversion recovery imaging in Creutzfeldt-Jakob disease: high sensitivity and specificity for diagnosis. Am J Neuroradiol. 2005;26:1551-1562. 5. Carswell C, Thompson A, Lukic A, Stevens J, Rudge P, Mead S, Collinge J, Hyare H. MRI findings are often missed in the diagnosis of Creutzfeldt-Jakob disease. BMC Neurol. 2012;12:153. Autoimmune Acquired Rippling Muscle Disease and Myasthenia Gravis We present an intriguing postscript to a case published by Kosmorsky et al (1) in this journal in 1995. It con-cerned a 58-year-old man with intermittent diplopia, arm, and leg weakness, dysarthria, and muscle rippling. Examination demonstrated intermittent esotropia triggered by prolonged convergence. Creatine phosphokinase (CPK) was mildly ele-vated at 676 IU (normal range 293-378 IU). Electromyogra-phy (EMG) showed electrically silent percussion-induced muscle rippling. Muscle biopsy showed a nonspecific myopa-thy consisting of rare interstitial and perivascular lymphocytic infiltrates, scattered atrophic type I and II muscle fibers, and electron microscopic subsarcolemmal honeycomb structures. The authors interpreted these findings as consistent with rip-pling muscle disease (RMD). The patient was treated with calcium channel blocking agents without response. The same patient was reported the next year by Ansevin and Agamanolis (2), who had examined him 16 months before and 3 years after he was examined by Kosmorsky. The patient's first visit had been prompted by painful muscle rippling and cramping. Examination disclosed percussion-induced muscle rippling and mild proximal extremity weakness. EMG did not reveal myotonia. CPK was elevated. At the patient's second visit 5 years later, the muscle rippling had mostly resolved, his principal complaints now being bilateral ptosis, diplopia, dysphagia, and weakness. Examination revealed fatigable neck and proximal extremity weakness. Rest and edrophonium tests suggested myasthenia gravis (MG). EMG showed a decremental response on re-petitive stimulation without improvement with exercise and no myotonia. Acetylcholine receptor antibody was elevated at 64 nmol/L (normal ,0.02 nmol/L), and skeletal muscle antibody titer was elevated at 1:320 (normal ,1:60). Chest computed tomography revealed a thymic mass, and muscle biopsy showed a nonspecific myopathy, exactly as described by Kosmorsky. Ansevin and Agamanolis did not diagnose RMD but rather MG with muscle rippling. Thymectomy and treatment with pyridostigmine and plasmapheresis im-proved the clinical manifestations. Therefore, the same patient evaluated by 2 physicians at different times with similar EMG, and muscle biopsy findings was assigned completely different diagnoses. Which diagnosis is correct? We encountered a similar patient recently who led us to believe that both diagnoses are probably correct. Our patient was a 52-year-old former Olympic-level athlete who presented with cramping and stiffness of arms, legs, and chest for 4 years without weakness. He had been evaluated extensively by rheumatologists, the only abnormal laboratory test being a mildly elevated CPK. Our examination disclosed percussion-induced muscle rippling of the chest, arms, and thighs (See Supplemental Digital Content, Video 1, http://links.lww.com/WNO/A116). A paraneoplas-tic panel revealed an elevated striated muscle antibody titer of 1:61,440 (normal ,1:60) and an elevated acetylcholine receptor binding antibody at 4.35 nmol/L (normal ,0.02 nmol/L). EMG showed non-electrically silent muscle rippling without myotonia. There was no decrement on repetitive stimulation or clinical evidence of MG. We diagnosed RMD. Five months later, he developed binocular diplopia. Examination disclosed an exodeviation on right gaze, fatigable right upper lid ptosis, persistent muscle rippling, but no extremity or bulbar weakness (See Supplemental Digital Content, Video 2, http://links.lww.com/WNO/A117). CAV3 testing was negative. Now, we diagnosed a combina-tion of RMD and MG. Treatment with pyridostigmine was unhelpful, but ptosis, diplopia, and muscle rippling resolved after several weeks' treatment with mycophenolate 2000 mg/ d and prednisone 20 mg/d. There are now 14 reported cases of concurrent RMD and MG (1-7). The classic form of RMD is an autosomal dominant caveolinopathy associated with a CAV3 mutation (8). Other CAV3-related caveolinopathies include limb gir-dle muscular dystrophy-1C, distal myopathy, idiopathic creatine phosphokinase elevation, and familial hypertrophic cardiomyopathy (9). In the acquired autoimmune form, there is no family history of RMD, and CAV3 testing is negative. Clinical manifestations develop after the second decade of life, later than in hereditary RMD (10). Muscle rippling may not be electrically silent on EMG (5). Muscle biopsy discloses nonspecific myopathic findings and rare areas of inflammation (7), abnormalities that are not found in hereditary RMD or in MG. 98 Letters to the Editor: J Neuro-Ophthalmol 2015; 35: 94-105 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. The clinical importance of recognizing concurrent RMD and MG is that muscle rippling in this condition improves after immunosuppression (6,7) but worsens af-ter treatment with conventional doses of acetylcholines-terase inhibitors, which likely unmask the muscle hyperexcitability of RMD. As in patients with MG and thymoma, antibodies are directed at the muscle protein titin but at a different site. This case also further high-lights the very low true false-positive rate of acetylcholine receptor antibodies (0.05%) (1), such that even in the absence of clinical symptoms or electrophysiologic find-ings, the presence of these antibodies may anticipate the later development of MG. Dane A. Breker, MD Department of Ophthalmology and Visual Sciences University of Michigan Ann Arbor, MI Ann A. Little, MD Department of Neurology University of Michigan Ann Arbor, MI Jonathan D. Trobe, MD Department of Ophthalmology and Visual Sciences University of Michigan Ann Arbor, MI Department of Neurology University of Michigan Ann Arbor, MI The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (www.jneuro-ophthalmology.com). REFERENCES 1. Kosmorsky GS, Mehta N, Mitsumoto H, Prayson R. Intermittent esotropia associated with rippling muscle disease. J Neuroophthalmol. 1995;15:147-151. 2. Ansevin CF, Agamanolis DP. Rippling muscles and myasthenia gravis with rippling muscles. Arch Neurol. 1996;53:197-199. 3. Vernino S, Auger RG, Emslie-Smith AM, Harper CM, Lennon VA. Myasthenia, thymoma, presynaptic antibodies, and a continuum of neuromuscular hyperexcitability. Neurology. 1999;53:1233-1239. 4. Vernino S, Lennon VA. Ion channel and striational antibodies define a continuum of autoimmune neuromuscular hyperexcitability. Muscle Nerve. 2002;26:702-707. 5. Greenberg SA. Acquired rippling muscle disease with myasthenia gravis. Muscle Nerve. 2004;29:143-146. 6. Müller-Felber W, Ansevin CF, Ricker K, Müller-Jenssen A, Töpfer M, Goebel HH, Pongratz DE. Immunosuppressive treatment of rippling muscle disease in patients with myasthenia gravis. Neuromuscul Disord. 1999;9:604-607. 7. Schoser B, Jacob S, Hilton-Jones D, Müller-Felber W, Kubisch C, Claus D, Goebel HH, Vita G, Vincent A, Toscano A, Van den Bergh P. Immune-mediated rippling muscle disease with myasthenia gravis: a report of seven patients with long-term follow-up in two. Neuromuscul Disord. 2009;19:223-238. 8. Torbergsen T. A family with dominant hereditary myotonia, muscular hypertrophy, and increased muscular irritability, distinct from myotonia congenita thomsen. Acta Neurol Scand. 1975;51:225-232. 9. Gazzerro E, Sotgia F, Bruno C, Lisanti MP, Minetti C. Caveolinopathies: from the biology of caveolin-3 to human diseases. Eur J Hum Genet. 2010;18:137-145. 10. Torbergsen T. Rippling muscle disease: a review. Muscle Nerve Suppl. 2002;11:S103-S107. Bitemporal Hemianopia Secondary to Nasal Staphylomata The interesting article by Wang et al (1) seeks to explain the mechanism of bitemporal hemianopia due to chias-mal compression. Our case is a reminder that bitemporal hemianopia may be secondary to refractive optical effects and mechanical effects on the optic chiasm. A 68-year-old woman with an 18-month history of a generalized headache was noted to have a bitemporal visual field defect by her optometrist and was referred FIG. 1. Both optic discs are tilted with less pigmentation of the nasal retina bilaterally. Letters to the Editor: J Neuro-Ophthalmol 2015; 35: 94-105 99 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.