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Progressive Spinal Cord Degeneration in Friedreich's Ataxia: Results from ENIGMA‐Ataxia
Author(s) -
Rezende Thiago J.R.,
Adanyeguh Isaac M.,
Arrigoni Filippo,
Bender Benjamin,
Cendes Fernando,
Corben Louise A.,
Deistung Andreas,
Delatycki Martin,
Dogan Imis,
Egan Gary F.,
Göricke Sophia L.,
GeorgiouKaristianis Nellie,
Henry PierreGilles,
Hutter Diane,
Jahanshad Neda,
Joers James M.,
Lenglet Christophe,
Lindig Tobias,
Martinez Alberto R.M.,
Martinuzzi Andrea,
Paparella Gabriella,
Peruzzo Denis,
Reetz Kathrin,
Romanzetti Sandro,
Schöls Ludger,
Schulz Jörg B.,
Synofzik Matthis,
Thomopoulos Sophia I.,
Thompson Paul M.,
Timmann Dagmar,
Harding Ian H.,
França Marcondes C.
Publication year - 2023
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.29261
Subject(s) - ataxia , cohort , spinal cord , medicine , central nervous system disease , magnetic resonance imaging , degenerative disease , pathology , neuroscience , psychology , radiology
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. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.