Journal Article

Genotype-specific spinal cord damage in spinocerebellar ataxias: an ENIGMA-Ataxia study

Teive, Helio, Mariotti, Caterina, Göricke, Sophia L, van de Warrenburg, Bart P C, Cendes, Fernando, Öz, Gülin, Pedroso, José Luiz, Coutinho, Leo, Nigri, Anna, Lenglet, Christophe, Mochel, Fanny, Synofzik, Matthis, França, Marcondes C, Durr, Alexandra, Fernandez-Ruiz, Juan, Thomopoulos, Sophia I, Rezende, Thiago Junqueira Ribeiro, Ono, Sergio E, Massuyama, Breno K, Harding, Ian H, Grisoli, Marina, Martinez, Alberto R M, Reetz, Kathrin, Thompson, Paul M, Adanyaguh, Isaac, Nanetti, Lorenzo, van Gaalen, Judith, Dogan, Imis, Barsottini, Orlando G P, Deistung, Andreas, Bender, Benjamin, Timmann, Dagmar, Hernandez-Castillo, Carlos R

2024

Overview

BackgroundSpinal cord damage is a feature of many spinocerebellar ataxias (SCAs), but well-powered in vivo studies are lacking and links with disease severity and progression remain unclear. Here we characterise cervical spinal cord morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI dataset.MethodsUpper spinal cord (vertebrae C1–C4) cross-sectional area (CSA) and eccentricity (flattening) were assessed using MRI data from nine sites within the ENIGMA-Ataxia consortium, including 364 people with ataxic SCA, 56 individuals with preataxic SCA and 394 nonataxic controls. Correlations and subgroup analyses within the SCA cohorts were undertaken based on disease duration and ataxia severity.ResultsIndividuals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had significantly reduced CSA and increased eccentricity at all examined levels. CSA showed large effect sizes (d>2.0) and correlated with ataxia severity (r<−0.43) and disease duration (r<−0.21). Eccentricity correlated only with ataxia severity in SCA2 (r=0.28). No significant spinal cord differences were evident in SCA6. In preataxic individuals, CSA was significantly reduced in SCA2 (d=1.6) and SCA3 (d=1.7), and the SCA2 group also showed increased eccentricity (d=1.1) relative to nonataxic controls. Subgroup analyses confirmed that CSA and eccentricity are abnormal in early disease stages in SCA1, SCA2 and SCA3. CSA declined with disease progression in all, whereas eccentricity progressed only in SCA2.ConclusionsSpinal cord abnormalities are an early and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using quantitative MRI.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adult / Aged / Amyotrophic lateral sclerosis / Ataxia / Atrophy / Biomarkers / Brain research / Case-Control Studies / cerebellar ataxia / Cervical Cord - diagnostic imaging / Cervical Cord - pathology / Disease / Disease progression / Female / Gait / Genotype / Humans / image analysis / Magnetic Resonance Imaging / Male / Middle Aged / MRI / Neurogenetics / Neuropathology / Patients / Severity of Illness Index / Spinal cord / Spinal Cord - diagnostic imaging / Spinal Cord - pathology / Spinocerebellar Ataxias - diagnostic imaging / Spinocerebellar Ataxias - genetics / Spinocerebellar Ataxias - pathology / Working groups