Musculoskeletal Ultrasound: A Quantitative Predictor of Functional Muscle Strength in Late Onset Tay Sachs/Sandhoff's Disease

Background and/or Objectives: Expanding interest in developing pharmacotherapeutics for Late Onset Tay Sachs/Sandhoff’s Disease (LOTS-SD) has exposed a need for sensitive, reliable, and quantitative biomarkers of disease-related functional progression and interventional efficacy in these patients. To this end, we explored the relationships between musculoskeletal ultrasound (MSK-US) measurements of muscle integrity and functional strength in patients with LOTS-SD.

Design: Cross-Sectional Retrospective Analysis

Setting : Outpatient Clinic, Research Hospital

Participants : 20 patients with confirmed diagnoses of LOTS-SD (10/10 M/F, age = 43.6±14 years, time since requiring handrails = 23±13 years).

Interventions: (not applicable)

Main Outcome Measures: The biceps, triceps, rectus femoris (RF), vastus intermedius (VI) and semimembranosus were assessed. Muscle integrity was defined by muscle thickness and echogenicity (quantified using B-mode MSK-US) and muscle stiffness (quantified using shear wave elastography). Maximal isometric elbow and knee flexion and extension torque were measured via dynamometry. Spearman’s correlations between each muscle parameter and its corresponding strength measure were evaluated.

Results: Short-axis muscle thickness was positively correlated with strength in the biceps (rho=0.541, p< 0.05) and triceps (rho=0.474, p< 0.05). This relationship was not preserved in the lower extremity muscles. Inclusion of both the VI and RF in our quadriceps analysis did not improve the relationship between muscle thickness and strength. Neither echogenicity nor stiffness correlated with strength for any muscle.

Conclusions: MSK-US biceps and triceps thickness are well-suited as sensitive, reliable, quantitative, and clinically available surrogate measurements for strength in LOTS-SD. As such, they are powerful biomarkers for disease progression in patients with LOTS-SD. Since our patient population was relatively advanced in disease progression, the lower extremity muscles were likely sufficiently atrophic to exhibit a flooring effect, deteriorating the muscle thickness-strength relationship. Given the prevalence of diagnostic latency in LOTS-SD, identifying triceps and biceps muscle thickness as biomarkers of functional progression, which remains sensitive even in advanced disease stages, is particularly clinically valuable.