Whole-Body Muscle MRI in Non-5q Spinal Muscular Atrophy

Figures

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  Figure 1. Heat Map of Whole-Body Muscle MRI Mercuri Scores Using Side-Averaged Values per Muscle Heat map showing involvement of cranial, axial, arm, trunk, pelvic, gluteal, thigh, and leg muscles. Patients and muscles are ordered according to clustering by the gene involved. The color of each square represents the mean score of the left and right sides for a given muscle in an individual patient (see legend, bottom left). The score of a muscle in a patient is indicated by the color of the square (legend at bottom left). Gray squares indicate that data are not available. The first column (left) indicates the implicated gene; the second column, patient age (legend at bottom left). The last column (right) indicates the disease duration, time from onset of symptom to the MRI in years (legend at bottom left). L = left; R = right.

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  Figure 2. Lower Limb Muscle MRI Pattern in VRK1, DYNC1H1, VWA1, and TRPV4 Patients Severely affected muscles are shown in white, moderately affected muscles in dark gray, and spared muscles in dark. The distribution patterns observed in this cohort in patients carrying pathogenic variants in VRK1 (A), DYNC1H1 (B), VWA1 (C), and TRPV4 (D) are depicted. AL = adductor longus; AM = adductor magnus; BF = biceps femoris; EDL = extensor digitorum longus; FD = flexor digitorum; GL = gastrocnemius lateralis; GM = gastrocnemius medius; GR = gracilis; LH = long head; PE = peroneus; RF = rectus femoris; SAR = sartorius; SCM = sternocleidomastoid; SH = short head; SM = semimembranous; SOL = soleus; ST = semitendinous; TA = tibialis anterior; TP = tibialis posterior; TRAP = trapezius; VI = vastus intermedius; VL = vastus lateralis; VM = vastus medius.

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  Figure 3. Lower Limb Muscle MRI Patterns on Thigh and Leg Severely affected muscles are shown in white, moderately affected muscles in dark gray, and spared muscles in black. Representative regional patterns observed in some patients at the thigh (A) and leg (B) levels are also shown. Each circle corresponds to a regional pattern (C), and each patient is represented by a triangle. When multiple patterns are present in a given patient, the triangle is placed at the intersection of the circles corresponding to those patterns. The size of each circle is proportional to the number of patients displaying that pattern. BF = biceps femoris; EDL = extensor digitorum longus; GL = gastrocnemius lateralis; GM = gastrocnemius medius; GR = gracilis; LH = long head; PE = peroneus; RF = rectus femoris; SAR = sartorius; SH = short head; SOL = soleus; TA = tibialis anterior; TP = tibialis posterior; VI = vastus intermedius; VL = vastus lateralis; VM = vastus medius.

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  Figure 4. Comparison of DYNC1H1, VWA1 and TRPV4 MRI Patterns Described in the Literature With Muscle Involvement Observed in the Cohort, by Associated Gene The x-axis indicates the mutated gene identified in each patient or “undiagnosed” when no associated variant was found. The y-axis shows the number of muscles whose involvement status (affected or spared) differed from the previously reported DYNC1H1-associated (A and D), VWA1-associated (B), or TRPV4-associated (C) MRI pattern. Panels A, B, and C represent a qualitative assessment based on the Mercuri score and panel D represents a quantitative evaluation (DYNC1H1-associated pattern) using fat fraction measurements (muscles were considered to be involved when fat fraction exceeded 30%).

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  Figure 5. Proposed MRI-Based Approach to Guide Gene Prioritization in Non-5q SMA Flowchart illustrating how thigh and lower leg MRI patterns, combined with tibialis posterior and sternocleidomastoid involvement, can help clinicians propose likely associated genes (VWA1, DYNC1H1, BICD2, or TRPV4) prior to genetic testing. Schematic diagrams and representative axial MRI images from cohort patients are shown for illustration. SMA = spinal muscular atrophy.