Quantifying Muscle Degeneration in Late-Onset Tay-Sachs and Sandhoff Disease

Background and/or Objectives: Quantify muscle degeneration in patients with Late-Onset Tay-Sachs and Sandhoff Disease (LOTS-SD). Determine if the extensors are more affected than flexors and if lower limb is more affected than upper limb, as postulated in the literature.

Design: Case-control study

Setting : Outpatient Clinic, Research Hospital

Participants : 20 patients (M/F 10/10, age=43.8±4.6, BMI=25.3±3.78) matched with controls (M/F 10/10, age=42.3±14.0, BMI=24.7±3.8).

Interventions: N/A

Main Outcome Measures: Difference between cohorts in stiffness, thickness, and echogenicity in the triceps, biceps, rectus femoris (RF), and semimembranosus (SM).The extensor/flexor and lower/upper limb ratios (Triceps/Biceps, RF/SM, and RF/Triceps) of each measure. Measures were acquired using B-mode and shear wave elastography musculoskeletal ultrasound (MSK-US) with a LA2-14 transducer.

Results: All muscles, besides biceps, demonstrated reduced muscle thickness (atrophy, p< 0.001), and the extensors demonstrated increased echogenicity (RF, triceps p< 0.001, p=0.006), relative to controls. Only the RF exhibited increased stiffness (p=0.021). The thickness and echogenicity ratios for the triceps/biceps (p < 0.001, p=0.035) and RF/SM (p=0.016, p=0.003) were smaller in the patient cohort. The RF-to-triceps ratio of these measures showed no difference between cohorts. The RF/triceps stiffness ratio was greater in our patient cohort (p=0.016).

Conclusions: The power of MSK-US in evaluating patients with LOTS-SD rests both in the spectrum of reliable, quantitative measures it provides and its clinical availability. Our ratio analyses support the notion that the extensors are more affected (greater atrophy with higher fibrofatty infiltration) than the flexors in LOTS-SD. However, this is not the case for the upper versus lower limb. Only RF stiffness is increased, relative to the triceps. Based on earlier work in Duchenne’s (Desguerre, 2009), this increased RF stiffness likely indicates reduced force generating capacity. Thus, our ability to provide quantitative measures of muscle integrity in our patients demonstrates the utility of MSK US in evaluating disease progression and, possibly, as a tool to differentiate LOTS-SD from other neurodegenerative diseases.