Clinicopathologic Features of Oculopharyngodistal Myopathy With LRP12 CGG Repeat Expansions Compared With Other Oculopharyngodistal Myopathy Subtypes.

Importance: Repeat expansion of CGG in LRP12 has been identified as the causative variation of oculopharyngodistal myopathy (OPDM). However, to our knowledge, the clinicopathologic features of OPDM with CGG repeat expansion in LRP12 (hereafter referred to as OPDM_LRP12) remain unknown. Objective: To identify and characterize the clinicopathologic features of patients with OPDM_LRP12. Design, Setting, and Participants: This case series included 208 patients with a clinical or clinicopathologic diagnosis of oculopharyngeal muscular dystrophy (OPDM) from January 1, 1978, to December 31, 2020. Patients with GCN repeat expansions in PABPN1 were excluded from the study. Repeat expansions of CGG in LRP12 were screened by repeat primed polymerase chain reaction and/or Southern blot. Main Outcomes and Measures: Clinical information, muscle imaging data obtained by either computed tomography or magnetic resonance imaging, and muscle pathologic characteristics. Results: Sixty-five Japanese patients with OPDM (40 men [62%]; mean [SD] age at onset, 41.0 [10.1] years) from 59 families with CGG repeat expansions in LRP12 were identified. This represents the most common OPDM subtype among all patients in Japan with genetically diagnosed OPDM. The expansions ranged from 85 to 289 repeats. A negative correlation was observed between the repeat size and the age at onset (r2 = 0.188, P = .001). The most common initial symptoms were ptosis and muscle weakness, present in 24 patients (37%). Limb muscle weakness was predominantly distal in 53 of 64 patients (83%), but 2 of 64 patients (3%) had predominantly proximal muscle weakness. Ptosis was observed in 62 of 64 patients (97%), and dysphagia or dysarthria was observed in 63 of 64 patients (98%). A total of 21 of 64 patients (33%) had asymmetric muscle weakness. Aspiration pneumonia was seen in 11 of 64 patients (17%), and 5 of 64 patients (8%) required mechanical ventilation. Seven of 64 patients (11%) developed cardiac abnormalities, and 5 of 64 patients (8%) developed neurologic abnormalities. Asymmetric muscle involvement was detected on computed tomography scans in 6 of 27 patients (22%) and on magnetic resonance imaging scans in 4 of 15 patients (27%), with the soleus and the medial head of the gastrocnemius being the worst affected. All 42 muscle biopsy samples showed rimmed vacuoles. Intranuclear tubulofilamentous inclusions were observed in only 1 of 5 patients. Conclusions and Relevance: This study suggests that OPDM_LRP12 is the most frequent OPDM subtype in Japan and is characterized by oculopharyngeal weakness, distal myopathy that especially affects the soleus and gastrocnemius muscles, and rimmed vacuoles in muscle biopsy.

ELectron microscopic abnormality and therapeutic efficacy in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin155 immunoglobulin G4 antibody.

INTRODUCTION: Neurofascin155 (NF155) is a target antigen for autoantibodies in a subset of chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: We report the cases of 4 patients with anti-NF155 immunoglobulin G4 (IgG4) antibody-positive CIDP who underwent sural nerve biopsies. RESULTS: All patients were relatively young at onset. Three patients experienced tremors, and 2 patients had severe ataxia. Although the response to intravenous immunoglobulin was poor in all patients, plasma exchange and corticosteroids were at least partially effective. Immunoadsorption plasmapheresis was performed in 1 patient but was ineffective. Electron microscopic examination of sural nerve biopsies revealed loss of paranodal transverse bands in all patients. DISCUSSION: Anti-NF155 IgG4 antibody-positive CIDP shows distinctive clinicopathological features, indicating that the IgG4 antibody is directly associated with the pathogenic mechanisms of anti-NF155 IgG4 antibody-positive CIDP. Muscle Nerve 57: 498-502, 2018.

Time Course of Radiological Imaging and Variable Interindividual Symptoms in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Associated with p.Arg487His Mutation in the VCP Gene.

To our knowledge, this is the first study to report the time course of radiological imaging of 3 patients from 2 families with VCP-related amyotrophic lateral sclerosis (ALS) and dementia. Both families shared the same p.Arg487His mutation in the VCP gene encoding valosin-containing protein. The first patient started to have a typical form of ALS, followed by dementia 7 years later. The second patient, a brother of the first one, had frontotemporal dementia and parkinsonism. The third patient had simultaneous ALS and dementia. All patients seemed to have progressive brain atrophy as their clinical symptoms progressed. The common and characteristic finding was atrophy of the temporal lobes including the hippocampi. The relation between imaging findings and symptoms varied considerably among the 3 patients.