Longitudinal retinal changes in MOGAD

OBJECTIVE: Patients with myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro-axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON-independent retinal atrophy can be detected in MOGAD. METHODS: Eighty MOGAD patients and 139 healthy controls (HC) were included. OCT data was acquired with 1) Spectralis spectral domain OCT (MOGAD (N=66) and HC (N=103)) and 2) Cirrus HD-OCT (MOGAD (N=14) and HC (N=36)). Macular combined ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fibre layer (pRNFL) were quantified. RESULTS: At baseline, GCIPL and pRNFL were lower in MOGAD eyes with a history of ON (MOGAD-ON) compared with MOGAD eyes without a history of ON (MOGAD-NON) and HC (p12 months ago (p<0.001). The overall MOGAD cohort did not exhibit faster GCIPL thinning compared with HC. INTERPRETATION: Our study suggests the absence of attack-independent retinal damage in MOGAD. Yet, ongoing neuroaxonal damage or oedema resolution seems to occur for up to 12 months after ON, which is longer than what has been reported with other ON forms. These findings support that the pathomechanisms underlying optic nerve involvement and the evolution of OCT retinal changes after ON is distinct in MOGAD. This article is protected by copyright. All rights reserved

Clinico-genetic spectrum of limb-girdle muscular weakness in Austria: A multi-centre cohort study.

BACKGROUND: Hereditary myopathies with limb-girdle muscular weakness (LGW) are a genetically heterogeneous group of disorders, in which molecular diagnosis remains challenging. Our aim was to present a detailed clinical and genetic characterisation of a large cohort of patients with LGW. METHODS: This nationwide cohort study included patients with LGW suspected to be associated with hereditary myopathies. Parameters associated with specific genetic aetiologies were evaluated, and we further assessed how they predicted the detection of causative variants by genetic analyses. RESULTS: Molecular diagnoses were identified in 62.0% (75/121) of the cohort, with a higher proportion of patients diagnosed by next-generation sequencing (NGS) than by single gene testing (77.3% vs. 22.7% of solved cases). Median time from onset to genetic diagnosis was 8.9 years (IQR 3.7-19.9) and 17.8 years (IQR 7.9-27.8) for single gene testing and NGS, respectively. The most common diagnoses were myopathies associated with variants in CAPN3 (n = 9), FKRP (n = 9), ANO5 (n = 8), DYSF (n = 8) and SGCA (n = 5), together accounting for 32.2% of the cohort. Younger age at disease onset (p = 0.043), &gt;10x elevated CK activity levels (p = 0.024) and myopathic electromyography findings (p = 0.007) were significantly associated with the detection of causative variants. CONCLUSIONS: Our findings suggest an earlier use of NGS in patients with LGW to avoid long diagnostic delays. We further present parameters predictive of a molecular diagnosis that may help to select patients for genetic analyses, especially in centres with limited access to sequencing