TY - JOUR
T1 - Progressive Spinal Cord Degeneration in Friedreich's Ataxia
T2 - Results from ENIGMA-Ataxia
AU - Rezende, Thiago J.R.
AU - Adanyeguh, Isaac M.
AU - Arrigoni, Filippo
AU - Bender, Benjamin
AU - Cendes, Fernando
AU - Corben, Louise A.
AU - Deistung, Andreas
AU - Delatycki, Martin
AU - Dogan, Imis
AU - Egan, Gary F.
AU - Göricke, Sophia L.
AU - Georgiou-Karistianis, Nellie
AU - Henry, Pierre Gilles
AU - Hutter, Diane
AU - Jahanshad, Neda
AU - Joers, James M.
AU - Lenglet, Christophe
AU - Lindig, Tobias
AU - Martinez, Alberto R.M.
AU - Martinuzzi, Andrea
AU - Paparella, Gabriella
AU - Peruzzo, Denis
AU - Reetz, Kathrin
AU - Romanzetti, Sandro
AU - Schöls, Ludger
AU - Schulz, Jörg B.
AU - Synofzik, Matthis
AU - Thomopoulos, Sophia I.
AU - Thompson, Paul M.
AU - Timmann, Dagmar
AU - Harding, Ian H.
AU - França, Marcondes C.
N1 - Publisher Copyright:
© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PY - 2023/1
Y1 - 2023/1
N2 - Background: Spinal cord damage is a hallmark of Friedreich's ataxia (FRDA), but its progression and clinical correlates remain unclear. Objective: The objective of this study was to perform a characterization of cervical spinal cord structural damage in a large multisite FRDA cohort. Methods: We performed a cross-sectional analysis of cervical spinal cord (C1–C4) cross-sectional area (CSA) and eccentricity using magnetic resonance imaging data from eight sites within the ENIGMA-Ataxia initiative, including 256 individuals with FRDA and 223 age- and sex-matched control subjects. Correlations and subgroup analyses within the FRDA cohort were undertaken based on disease duration, ataxia severity, and onset age. Results: Individuals with FRDA, relative to control subjects, had significantly reduced CSA at all examined levels, with large effect sizes (d > 2.1) and significant correlations with disease severity (r < −0.4). Similarly, we found significantly increased eccentricity (d > 1.2), but without significant clinical correlations. Subgroup analyses showed that CSA and eccentricity are abnormal at all disease stages. However, although CSA appears to decrease progressively, eccentricity remains stable over time. Conclusions: Previous research has shown that increased eccentricity reflects dorsal column (DC) damage, while decreased CSA reflects either DC or corticospinal tract (CST) damage, or both. Hence our data support the hypothesis that damage to the DC and damage to CST follow distinct courses in FRDA: developmental abnormalities likely define the DC, while CST alterations may be both developmental and degenerative. These results provide new insights about FRDA pathogenesis and indicate that CSA of the cervical spinal cord should be investigated further as a potential biomarker of disease progression.
AB - Background: Spinal cord damage is a hallmark of Friedreich's ataxia (FRDA), but its progression and clinical correlates remain unclear. Objective: The objective of this study was to perform a characterization of cervical spinal cord structural damage in a large multisite FRDA cohort. Methods: We performed a cross-sectional analysis of cervical spinal cord (C1–C4) cross-sectional area (CSA) and eccentricity using magnetic resonance imaging data from eight sites within the ENIGMA-Ataxia initiative, including 256 individuals with FRDA and 223 age- and sex-matched control subjects. Correlations and subgroup analyses within the FRDA cohort were undertaken based on disease duration, ataxia severity, and onset age. Results: Individuals with FRDA, relative to control subjects, had significantly reduced CSA at all examined levels, with large effect sizes (d > 2.1) and significant correlations with disease severity (r < −0.4). Similarly, we found significantly increased eccentricity (d > 1.2), but without significant clinical correlations. Subgroup analyses showed that CSA and eccentricity are abnormal at all disease stages. However, although CSA appears to decrease progressively, eccentricity remains stable over time. Conclusions: Previous research has shown that increased eccentricity reflects dorsal column (DC) damage, while decreased CSA reflects either DC or corticospinal tract (CST) damage, or both. Hence our data support the hypothesis that damage to the DC and damage to CST follow distinct courses in FRDA: developmental abnormalities likely define the DC, while CST alterations may be both developmental and degenerative. These results provide new insights about FRDA pathogenesis and indicate that CSA of the cervical spinal cord should be investigated further as a potential biomarker of disease progression.
KW - ENIGMA-ataxia
KW - Friedreich's ataxia
KW - MRI
KW - SCT
KW - spinal cord
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U2 - 10.1002/mds.29261
DO - 10.1002/mds.29261
M3 - Article
C2 - 36308733
AN - SCOPUS:85141342893
SN - 0885-3185
VL - 38
SP - 45
EP - 56
JO - Movement Disorders
JF - Movement Disorders
IS - 1
ER -