Preliminary design and validation of the "6-K-scale" for bulbar symptoms evaluation in SBMA.

BACKGROUND: Spinal and bulbar muscular atrophy (SBMA) is a late onset, X-linked neuromuscular disease. Bulbar symptoms are a main characteristic of the disease but a tool for their clinical evaluation still does not exist. The aim of this study was to design and test a new scale (6-K-scale) for evaluation of bulbar function in SBMA. METHODS: We considered 60 genetically confirmed SBMA patients and built a scale to evaluate the V, VII, IX, X, and XII cranial nerves (CN) and the ansa cervicalis. Functional status was evaluated through the Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS), 6-min-walk-test (6MWT), Adult Myopathy Assessment Tool (AMAT) scale, and FVC%. Twenty patients underwent a re-test after 3 weeks, while 31 were tested longitudinally after 6 months. Validation of the scale included reliability assessment and factorial analysis. To evaluate convergent validity, correlations between the 6-K-scale and functional parameters were performed. RESULTS: Internal consistency as measured by Cronbach's alpha was high (0.85) as was test-retest reliability. Principal component analysis yielded a six-factor solution accounting for 71.7% of the variance. The scale score was strongly correlated with the functional parameters. CONCLUSION: In conclusion, we designed and validated a new scale for bulbar evaluation in SBMA patients. This scale will be a useful tool in the clinical practice as well as a possible outcome measure in clinical trials.

Comparison of muscle ultrastructure in myasthenia gravis with anti-MuSK and anti-AChR antibodies.

Patients with myasthenia gravis (MG) with antibodies to muscle-specific receptor tyrosine kinase (MuSK) differ from acetylcholine receptor (AChR)-positive MG patients, as they frequently present with severe oculobulbar muscle weakness or with neck, shoulder, and respiratory muscle involvement. The neuromuscular junction (NMJ) has been confirmed to be the main target of both AChR- and MuSK-MG. However, histopathological investigation disclosed that muscle fiber atrophy was prevalent in AChR-MG, whereas mild myopathic changes and mitochondrial abnormalities were more frequently observed in MuSK-MG. As the pathogenetic mechanism in MuSK-MG remains unclear, this study investigated the submicroscopic pattern of muscle histopathology to establish a possible correlation between clinical involvement and subcellular morphological findings. Muscle biopsies from seven MuSK-MG patients and from seven patients with AChR-MG were analyzed by transmission electron microscopy. Myopathic and mitochondrial abnormalities were more prominent in MuSK-MG and show giant, swollen, and degenerated mitochondria with fragmented cristae. The most common changes in AChR-MG muscles were fiber atrophy, myofibrillar disarray, and Z-line streaming, consistent with mild neurogenic abnormalities. A different pathogenetic mechanism is emerging in MuSK-MG compared to AChR-MG. Mitochondrial abnormalities seem to be more prominent in MuSK-MG, whereas neurogenic atrophy is observed in AChR-MG.