Brainstem and striatal volume changes are detectable in under 1 year and predict motor decline in spinocerebellar ataxia type 1

Timothy R Koscik; Lauren Sloat; Ellen van der Plas; James M Joers; Dinesh K Deelchand; Christophe Lenglet; Gülin Öz; Peggy C Nopoulos

doi:10.1093/braincomms/fcaa184

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Brainstem and striatal volume changes are detectable in under 1 year and predict motor decline in spinocerebellar ataxia type 1

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Brainstem and striatal volume changes are detectable in under 1 year and predict motor decline in spinocerebellar ataxia type 1

Timothy R Koscik, Lauren Sloat, Ellen van der Plas, James M Joers, Dinesh K Deelchand, Christophe Lenglet, Gülin Öz and Peggy C Nopoulos

Brain Communications, Vol.2(2), pp.fcaa184-fcaa184

01/01/2020

DOI: 10.1093/braincomms/fcaa184

PMCID: PMC7772094

PMID: 33409488

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Abstract

Abstract Spinocerebellar ataxia type 1 is a progressive neurodegenerative, movement disorder. With potential therapies on the horizon, it is critical to identify biomarkers that (i) differentiate between unaffected and spinocerebellar ataxia Type 1-affected individuals; (ii) track disease progression; and (iii) are directly related to clinical changes of the patient. Magnetic resonance imaging of volumetric changes in the brain may be a suitable source of biomarkers for spinocerebellar ataxia Type 1. In a previous report on a longitudinal study of patients with spinocerebellar ataxia Type 1, we evaluated the volume and magnetic resonance spectroscopy measures of the cerebellum and pons, showing pontine volume and pontine N-acetylaspartate-to-myo-inositol ratio were sensitive to change over time. As a follow-up, the current study conducts a whole brain exploration of volumetric MRI measures with the aim to identify biomarkers for spinocerebellar ataxia Type 1 progression. We adapted a joint label fusion approach using multiple, automatically generated, morphologically matched atlases to label brain regions including cerebellar sub-regions. We adjusted regional volumes by total intracranial volume allowing for linear and power-law relationships. We then utilized Bonferroni corrected linear mixed effects models to (i) determine group differences in regional brain volume and (ii) identify change within affected patients only. We then evaluated the rate of change within each brain region to identify areas that changed most rapidly. Lastly, we used a penalized, linear mixed effects model to determine the strongest brain predictors of motor outcomes. Decrease in pontine volume and accelerating decrease in putamen volume: (i) reliably differentiated spinocerebellar ataxia Type 1-affected and -unaffected individuals; (ii) were observable in affected individuals without referencing an unaffected comparison group; (iii) were detectable within ∼6–9 months; and (iv) were associated with increased disease burden. In conclusion, volumetric change in the pons and putamen may provide powerful biomarkers to track disease progression in spinocerebellar ataxia Type 1. The methods employed here are readily translatable to current clinical settings, providing a framework for study and usage of volumetric neuroimaging biomarkers for clinical trials. There is an urgent need for biomarkers that track neurodegenerative disease progression. Pontine and putamen volume decreases are specific to affected individuals, track disease progression within 6–9 months and are directly related to clinical changes in individuals affected by spinocerebellar ataxia Type 1, making them potential biomarkers for clinical trials. Graphical Abstract

volumetry

motor disorders

spinocerebellar ataxia

biomarkers

Details

Title: Subtitle: Brainstem and striatal volume changes are detectable in under 1 year and predict motor decline in spinocerebellar ataxia type 1
Creators: Timothy R Koscik - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242-1000, USA
Lauren Sloat - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242-1000, USA
Ellen van der Plas - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242-1000, USA
James M Joers - Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN 55455, USA
Dinesh K Deelchand - Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN 55455, USA
Christophe Lenglet - Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN 55455, USA
Gülin Öz - Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN 55455, USA
Peggy C Nopoulos - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242-1000, USA
Resource Type: Journal article
Publication Details: Brain Communications, Vol.2(2), pp.fcaa184-fcaa184
DOI: 10.1093/braincomms/fcaa184
PMID: 33409488
PMCID: PMC7772094
NLM abbreviation: Brain Commun
eISSN: 2632-1297
Publisher: Oxford University Press
Grant note: DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: R01 NS070815, R01 NS080816; name: Jay D. Schlueter Ataxia Research Fund; DOI: 10.13039/100000070, name: National Institute of Biomedical Imaging and Bioengineering; name: Institutional Center Cores for Advanced Neuroimaging; name: National Center for Advancing Translational Sciences of the National Institutes of Health
Language: English
Date published: 01/01/2020
Academic Unit: Neurology; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984071705302771

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