Progressive external ophthalmoplegia as initial manifestation of sporadic late-onset nemaline myopathy

Abstract

Sporadic late-onset nemaline myopathy (SLONM) is a rare disease and typically presents in patients older than 40 years with slowly progressive weakness in a limb-girdle distribution and unremarkable family history [1, 2]. Serum creatine kinase is usually normal, and electromyography may show myopathic changes. Nemaline rods in affected muscle fibers are considered the histopathological hallmark of nemaline myopathy and are mainly found within the sarcoplasm, inside of myonuclei, or both [3]. Ocular involvement has never been described in a patient with SLONM. We report a patient with SLONM suffering from prominent involvement of external ocular muscles. A 60-year-old female patient was reexamined for a chronic progressive oculopharyngeal syndrome that was present for 6 years. Initial symptoms were double vision and ptosis, followed by weakness of eye-closure. Two years after the onset of symptoms, she presented an exclusive picture of external ophthalmoplegia. During the following years she was unable to open or close her eyes voluntarily, lost her ability to whistle or smile, developed a hoarse voice and swallowing difficulties. There was no diurnal variation of symptoms, or fatigability. Family history for neuromuscular diseases was unremarkable. On examination she had complete bilateral ptosis and palsy of extraocular muscles, while pupillar size and pupillar reactions to light and accommodation were normal. She had a myopathic face with atrophy of masseter and temporalis muscles, severe bilateral facial palsy, and severe dysphonia. Strength was MRC grade 4 for neck flexion, head rotation, and neck extension. Further neurological examination was normal, notably fundoscopy and proximal and distal limb strength. Laboratory examinations provided normal values for standard parameters, serum creatine kinase, a comprehensive panel of autoimmune antibodies, including antibodies against acetylcholine receptor or muscle-specific kinase, anti-HIV 1/2 antibodies, and p24 antigen. Serum ACE, soluble Interleukin-2 receptor levels, serum and urine calcium levels, and repeated imaging studies ruled out sarcoidosis. Protein electrophoresis and immunofixation did not show any paraprotein, findings that rule out an association with HIV, sarcoidosis, or monoclonal gammopathy, as described in some patients in the literature [4–7]. MRI revealed symmetric atrophy of ocular muscles and fatty degeneration of pterygoideus medialis and masseter muscles, no signs of edema or contrast enhancement. Thorough neuromuscular transmission studies as well as spinal cord and brain imaging were unremarkable. No other organs were involved. Muscle biopsy of the sternocleidomastoideus revealed numerous rods, which appeared to be O. Wengert A. Meisel Department of Neurology, Charite-Universitatsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany