Ophthalmoparesis as an Unusual Manifestation of Anti-HMGCR Antibody-related Myopathies
Brendan Putko1, Gregory Van Stavern2, Alan Pestronk3, Cecile Phan4, Grayson Beecher4, Teerin Liewluck1
1Department of Neurology, Mayo Clinic, 2Department of Ophthalmology, Washington University in St. Louis, 3Department of Neurology, Washington University in St. Louis, 4Department of Neurology, University of Alberta
Objective:
To describe two patients with anti-HMGCR antibodies, who developed limb-girdle and bulbar weakness, and ophthalmoparesis.
Background:
Ophthalmoparesis due to orbital myopathy is common in thyroid orbitopathy, mitochondrial myopathy, brachiocervical inflammatory myopathy (BCIM) and immune checkpoint inhibitor myopathy, but is not described in anti-HMGCR antibody-related myopathies.
Design/Methods:
Review of clinicoradiological and laboratory findings.
Results:
Patient 1 was a 53-year-old male who developed progressive proximal limb weakness, dysphagia, ptosis and diplopia over 6 weeks and creatine kinase (CK) of 3,512 units/L. Patient 2 was a 55-year-old female who had progressive proximal weakness, dysarthria, ptosis, diplopia and dyspnea over 2 weeks and CK of 31,998 units/L. Both patients had normal TSH and repetitive nerve stimulation, and myopathic motor unit potentials with fibrillation potentials in proximal and axial musculature. Patient 1 had normal single fiber EMG. Brain and/or orbit MRI displayed T2 hyperintensity in extraocular muscles in patient 1 and abnormal enhancement of extraocular muscles in both patients. Muscle biopsy showed rare necrotic and regenerating myofibers and a perimysial mononuclear cell collection, resembling cell foci described in BCIM, in patient 1 (deltoid), and scattered necrotic and regenerating myofibers without inflammation in patient 2 (quadriceps). Mitochondrial pathology was absent in both patients. Anti-HMGCR antibodies were present in both patients, who were on statins for several years. Anti-PM/Scl antibodies were borderline positive in patient 1 and negative in patient 2. Comprehensive cancer screening in both patients identified oropharyngeal squamous cell carcinoma in patient 1 only. Aggressive immunomodulatory therapies in both patients led to resolution of oculobulbar weakness and normalization of CK levels. Limb weakness resolved completely in patient 1 and partially in patient 2.
Conclusions:
Our patients expand the phenotypic spectrum of anti-HMGCR antibody-associated myopathies. A syndrome of subacute ophthalmoparesis with limb-girdle weakness and severe hyperCKemia should not preclude a diagnosis of anti-HMGCR antibody-related myopathies.