PMID- 35577579
OWN - NLM
STAT- MEDLINE
DCOM- 20221013
LR  - 20230220
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 99
IP  - 6
DP  - 2022 Aug 9
TI  - Prospective Natural History Study in 24 Adult Patients With LGMDR12 Over 2 Years 
      of Follow-up: Quantitative MRI and Clinical Outcome Measures.
PG  - e638-e649
LID - 10.1212/WNL.0000000000200708 [doi]
AB  - BACKGROUND AND OBJECTIVES: Limb-girdle muscular dystrophy autosomal recessive 
      type 12 (LGMDR12) is a rare hereditary muscular dystrophy for which outcome 
      measures are currently lacking. We evaluated quantitative MRI and clinical 
      outcome measures to track disease progression to determine which tests could be 
      useful in future clinical trials to evaluate potential therapies. METHODS: We 
      prospectively measured the following outcome measures in all participants at 
      baseline and after 1 and 2 years: 6-minute walk distance (6MWD), 10-meter walk 
      test (10MWT), the Medical Research Council (MRC) sum scores, Biodex isometric 
      dynamometry, serum creatine kinase, and 6-point Dixon MRI of the thighs. RESULTS: 
      We included 24 genetically confirmed, adult patients with LGMDR12 and 24 
      age-matched and sex-matched healthy controls. Patients with intermediate-stage 
      thigh muscle fat replacement at baseline (proton density fat fraction [PDFF] 
      20%-70%) already showed an increase in PDFF in 8 of the 14 evaluated thigh 
      muscles after 1 year. The standardized response mean demonstrated a high 
      responsiveness to change in PDFF for 6 individual muscles over 2 years in this 
      group. However, in patients with early-stage (<20%) or end-stage (>70%) muscle 
      fat replacement, PDFF did not increase significantly over 2 years of follow-up. 
      Biodex isometric dynamometry showed a significant decrease in muscle strength in 
      all patients in the right and left hamstrings (-6.2 Nm, p < 0.002 and -4.6 Nm, p 
      < 0.009, respectively) and right quadriceps muscles (-9 Nm, p = 0.044) after 1 
      year of follow-up, whereas the 6MWD, 10MWT, and MRC sum scores were not able to 
      detect a significant decrease in muscle function/strength even after 2 years. 
      There was a moderately strong correlation between total thigh PDFF and clinical 
      outcome measures at baseline. DISCUSSION: Thigh muscle PDFF imaging is a 
      sensitive outcome measure to track progressive muscle fat replacement in selected 
      patients with LGMDR12 even after 1 year of follow-up and correlates with clinical 
      outcome measures. Biodex isometric dynamometry can reliably capture the loss of 
      muscle strength over the course of 1 year in patients with LGMDR12 and should be 
      included as an outcome measure in future clinical trials as well.
CI  - (c) 2022 American Academy of Neurology.
FAU - De Wel, Bram
AU  - De Wel B
AD  - From the Departments of Neurology (B.D.W., A.D.H., K.G.C.) and Radiology (R.P., 
      V.G., S.G., K.B., G.P.), and Medical Imaging Research Centre (L.H., F.M.), 
      University Hospitals Leuven; Laboratories for Muscle Diseases and Neuropathies 
      (B.D.W., K.G.C.) and Cognitive Neurology (P.D.), Department of Neurosciences, and 
      Department ESAT-PSI (L.H., F.M.), KU Leuven; Leuven Brain Institute (LBI) 
      (B.D.W., K.G.C., P.D.); and Department of Neurology (J.L.D.B.), University 
      Hospital Gent, Belgium.
FAU - Huysmans, Lotte
AU  - Huysmans L
AD  - From the Departments of Neurology (B.D.W., A.D.H., K.G.C.) and Radiology (R.P., 
      V.G., S.G., K.B., G.P.), and Medical Imaging Research Centre (L.H., F.M.), 
      University Hospitals Leuven; Laboratories for Muscle Diseases and Neuropathies 
      (B.D.W., K.G.C.) and Cognitive Neurology (P.D.), Department of Neurosciences, and 
      Department ESAT-PSI (L.H., F.M.), KU Leuven; Leuven Brain Institute (LBI) 
      (B.D.W., K.G.C., P.D.); and Department of Neurology (J.L.D.B.), University 
      Hospital Gent, Belgium.
FAU - Peeters, Ronald
AU  - Peeters R
AD  - From the Departments of Neurology (B.D.W., A.D.H., K.G.C.) and Radiology (R.P., 
      V.G., S.G., K.B., G.P.), and Medical Imaging Research Centre (L.H., F.M.), 
      University Hospitals Leuven; Laboratories for Muscle Diseases and Neuropathies 
      (B.D.W., K.G.C.) and Cognitive Neurology (P.D.), Department of Neurosciences, and 
      Department ESAT-PSI (L.H., F.M.), KU Leuven; Leuven Brain Institute (LBI) 
      (B.D.W., K.G.C., P.D.); and Department of Neurology (J.L.D.B.), University 
      Hospital Gent, Belgium.
FAU - Goosens, Veerle
AU  - Goosens V
AD  - From the Departments of Neurology (B.D.W., A.D.H., K.G.C.) and Radiology (R.P., 
      V.G., S.G., K.B., G.P.), and Medical Imaging Research Centre (L.H., F.M.), 
      University Hospitals Leuven; Laboratories for Muscle Diseases and Neuropathies 
      (B.D.W., K.G.C.) and Cognitive Neurology (P.D.), Department of Neurosciences, and 
      Department ESAT-PSI (L.H., F.M.), KU Leuven; Leuven Brain Institute (LBI) 
      (B.D.W., K.G.C., P.D.); and Department of Neurology (J.L.D.B.), University 
      Hospital Gent, Belgium.
FAU - Ghysels, Stefan
AU  - Ghysels S
AD  - From the Departments of Neurology (B.D.W., A.D.H., K.G.C.) and Radiology (R.P., 
      V.G., S.G., K.B., G.P.), and Medical Imaging Research Centre (L.H., F.M.), 
      University Hospitals Leuven; Laboratories for Muscle Diseases and Neuropathies 
      (B.D.W., K.G.C.) and Cognitive Neurology (P.D.), Department of Neurosciences, and 
      Department ESAT-PSI (L.H., F.M.), KU Leuven; Leuven Brain Institute (LBI) 
      (B.D.W., K.G.C., P.D.); and Department of Neurology (J.L.D.B.), University 
      Hospital Gent, Belgium.
FAU - Byloos, Kris
AU  - Byloos K
AD  - From the Departments of Neurology (B.D.W., A.D.H., K.G.C.) and Radiology (R.P., 
      V.G., S.G., K.B., G.P.), and Medical Imaging Research Centre (L.H., F.M.), 
      University Hospitals Leuven; Laboratories for Muscle Diseases and Neuropathies 
      (B.D.W., K.G.C.) and Cognitive Neurology (P.D.), Department of Neurosciences, and 
      Department ESAT-PSI (L.H., F.M.), KU Leuven; Leuven Brain Institute (LBI) 
      (B.D.W., K.G.C., P.D.); and Department of Neurology (J.L.D.B.), University 
      Hospital Gent, Belgium.
FAU - Putzeys, Guido
AU  - Putzeys G
AD  - From the Departments of Neurology (B.D.W., A.D.H., K.G.C.) and Radiology (R.P., 
      V.G., S.G., K.B., G.P.), and Medical Imaging Research Centre (L.H., F.M.), 
      University Hospitals Leuven; Laboratories for Muscle Diseases and Neuropathies 
      (B.D.W., K.G.C.) and Cognitive Neurology (P.D.), Department of Neurosciences, and 
      Department ESAT-PSI (L.H., F.M.), KU Leuven; Leuven Brain Institute (LBI) 
      (B.D.W., K.G.C., P.D.); and Department of Neurology (J.L.D.B.), University 
      Hospital Gent, Belgium.
FAU - D'Hondt, Ann
AU  - D'Hondt A
AD  - From the Departments of Neurology (B.D.W., A.D.H., K.G.C.) and Radiology (R.P., 
      V.G., S.G., K.B., G.P.), and Medical Imaging Research Centre (L.H., F.M.), 
      University Hospitals Leuven; Laboratories for Muscle Diseases and Neuropathies 
      (B.D.W., K.G.C.) and Cognitive Neurology (P.D.), Department of Neurosciences, and 
      Department ESAT-PSI (L.H., F.M.), KU Leuven; Leuven Brain Institute (LBI) 
      (B.D.W., K.G.C., P.D.); and Department of Neurology (J.L.D.B.), University 
      Hospital Gent, Belgium.
FAU - De Bleecker, Jan L
AU  - De Bleecker JL
AD  - From the Departments of Neurology (B.D.W., A.D.H., K.G.C.) and Radiology (R.P., 
      V.G., S.G., K.B., G.P.), and Medical Imaging Research Centre (L.H., F.M.), 
      University Hospitals Leuven; Laboratories for Muscle Diseases and Neuropathies 
      (B.D.W., K.G.C.) and Cognitive Neurology (P.D.), Department of Neurosciences, and 
      Department ESAT-PSI (L.H., F.M.), KU Leuven; Leuven Brain Institute (LBI) 
      (B.D.W., K.G.C., P.D.); and Department of Neurology (J.L.D.B.), University 
      Hospital Gent, Belgium.
FAU - Dupont, Patrick
AU  - Dupont P
AD  - From the Departments of Neurology (B.D.W., A.D.H., K.G.C.) and Radiology (R.P., 
      V.G., S.G., K.B., G.P.), and Medical Imaging Research Centre (L.H., F.M.), 
      University Hospitals Leuven; Laboratories for Muscle Diseases and Neuropathies 
      (B.D.W., K.G.C.) and Cognitive Neurology (P.D.), Department of Neurosciences, and 
      Department ESAT-PSI (L.H., F.M.), KU Leuven; Leuven Brain Institute (LBI) 
      (B.D.W., K.G.C., P.D.); and Department of Neurology (J.L.D.B.), University 
      Hospital Gent, Belgium.
FAU - Maes, Frederik
AU  - Maes F
AD  - From the Departments of Neurology (B.D.W., A.D.H., K.G.C.) and Radiology (R.P., 
      V.G., S.G., K.B., G.P.), and Medical Imaging Research Centre (L.H., F.M.), 
      University Hospitals Leuven; Laboratories for Muscle Diseases and Neuropathies 
      (B.D.W., K.G.C.) and Cognitive Neurology (P.D.), Department of Neurosciences, and 
      Department ESAT-PSI (L.H., F.M.), KU Leuven; Leuven Brain Institute (LBI) 
      (B.D.W., K.G.C., P.D.); and Department of Neurology (J.L.D.B.), University 
      Hospital Gent, Belgium.
FAU - Claeys, Kristl G
AU  - Claeys KG
AD  - From the Departments of Neurology (B.D.W., A.D.H., K.G.C.) and Radiology (R.P., 
      V.G., S.G., K.B., G.P.), and Medical Imaging Research Centre (L.H., F.M.), 
      University Hospitals Leuven; Laboratories for Muscle Diseases and Neuropathies 
      (B.D.W., K.G.C.) and Cognitive Neurology (P.D.), Department of Neurosciences, and 
      Department ESAT-PSI (L.H., F.M.), KU Leuven; Leuven Brain Institute (LBI) 
      (B.D.W., K.G.C., P.D.); and Department of Neurology (J.L.D.B.), University 
      Hospital Gent, Belgium. kristl.claeys@uzleuven.be.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220516
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Protons)
RN  - EC 2.7.3.2 (Creatine Kinase)
RN  - Limb-girdle muscular dystrophy autosomal recessive
SB  - IM
CIN - Neurology. 2023 Feb 14;100(7):354. PMID: 36781287
CIN - Neurology. 2023 Feb 14;100(7):353-354. PMID: 36781292
MH  - Adult
MH  - Creatine Kinase
MH  - Humans
MH  - *Magnetic Resonance Imaging/methods
MH  - Muscle, Skeletal/diagnostic imaging
MH  - Muscular Dystrophies, Limb-Girdle
MH  - Outcome Assessment, Health Care
MH  - Prospective Studies
MH  - *Protons
EDAT- 2022/05/17 06:00
MHDA- 2022/10/14 06:00
CRDT- 2022/05/16 21:52
PHST- 2021/12/19 00:00 [received]
PHST- 2022/03/24 00:00 [accepted]
PHST- 2022/05/17 06:00 [pubmed]
PHST- 2022/10/14 06:00 [medline]
PHST- 2022/05/16 21:52 [entrez]
AID - WNL.0000000000200708 [pii]
AID - 10.1212/WNL.0000000000200708 [doi]
PST - ppublish
SO  - Neurology. 2022 Aug 9;99(6):e638-e649. doi: 10.1212/WNL.0000000000200708. Epub 
      2022 May 16.