Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3

Background and objective: Proximal spinal muscular atrophy (SMA) is caused by deficiency of the ubiquitously expressed survival motor neuron protein. Although primarily a hereditary lower motor neuron disease, it is probably also characterized by abnormalities in other organs. Brain abnormalities an...

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Main Authors: Marloes Stam, Harold H.G. Tan, Ruben Schmidt, Martijn P. van den Heuvel, Leonard H. van den Berg, Renske I. Wadman, W. Ludo van der Pol
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:NeuroImage: Clinical
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213158224001499
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author Marloes Stam
Harold H.G. Tan
Ruben Schmidt
Martijn P. van den Heuvel
Leonard H. van den Berg
Renske I. Wadman
W. Ludo van der Pol
author_facet Marloes Stam
Harold H.G. Tan
Ruben Schmidt
Martijn P. van den Heuvel
Leonard H. van den Berg
Renske I. Wadman
W. Ludo van der Pol
author_sort Marloes Stam
collection DOAJ
description Background and objective: Proximal spinal muscular atrophy (SMA) is caused by deficiency of the ubiquitously expressed survival motor neuron protein. Although primarily a hereditary lower motor neuron disease, it is probably also characterized by abnormalities in other organs. Brain abnormalities and cognitive impairment have been reported in severe SMA. We aimed to systematically investigate brain structure in SMA using MRI. Methods: We acquired high-resolution T1-weighted images of treatment-naive patients with SMA, age- and sex-matched healthy and disease controls with other neuromuscular diseases, on a 3 T MRI scanner. We performed vertex-wise whole brain analysis and region of interest analysis of cortical thickness (CT), and volumetric analysis of the thalamus and compared findings in patients and controls using multiple linear regression models and Wald test. We correlated structural abnormalities with motor function as assessed by the Hammersmith Functional Motor Scale Expanded (HFMSE) and SMA Functional Rating Scale (SMA-FRS). Results: We included 30 patients, 12–70 years old, with SMA type 2 and 3, 30 age- and sex-matched healthy controls and 17 disease controls (with distal SMA, hereditary motor and sensory neuropathy, multifocal motor neuropathy, progressive muscular atrophy and segmental SMA). We found a reduced CT in patients with SMA compared to healthy controls at the precentral, postcentral and medial orbitofrontal gyri and at the temporal pole (mean differences −0.059(p = 0.04); −0.055(p = 0.04), −0.06(p = 0.04); −0.17 mm(p = 0.001)). Differences at the precentral gyrus and temporal pole were most pronounced in SMA type 2 (mean differences −0.07(p = 0.045); −0.26 mm(p < 0.001)) and were also present compared to disease controls (mean differences −0.08(p = 0.048); −0.19 mm(p = 0.003)). There was a positive correlation between CT at the temporal pole with motor function. Compared to healthy controls, we found a reduced volume of the whole thalamus (mean difference −325 mm3(p = 0.03)) and of the anterior, ventral and intralaminar thalamic nuclei (mean differences −9.9(p = 0.02); −157(p = 0.01); −24.2 mm3(p = 0.02) in patients with SMA and a positive correlation between these volumes and motor function. Conclusion: MRI shows structural changes in motor and non-motor regions of the cortex and the thalamus of patients with SMA type 2 and 3, indicating that SMA pathology is not confined to motor neurons.
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spelling doaj-art-ddfcd25692d4473da1c79723fe1c08902025-08-20T01:54:12ZengElsevierNeuroImage: Clinical2213-15822024-01-014410370810.1016/j.nicl.2024.103708Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3Marloes Stam0Harold H.G. Tan1Ruben Schmidt2Martijn P. van den Heuvel3Leonard H. van den Berg4Renske I. Wadman5W. Ludo van der Pol6UMC Utrecht Brain Center, Department of Neurology, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsUMC Utrecht Brain Center, Department of Neurology, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsUMC Utrecht Brain Center, Department of Neurology, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsConnectome Lab, Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Child Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, the NetherlandsUMC Utrecht Brain Center, Department of Neurology, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsUMC Utrecht Brain Center, Department of Neurology, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsUMC Utrecht Brain Center, Department of Neurology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Corresponding author at: UMC Utrecht Brain Center, Department of Neurology F02.230, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands.Background and objective: Proximal spinal muscular atrophy (SMA) is caused by deficiency of the ubiquitously expressed survival motor neuron protein. Although primarily a hereditary lower motor neuron disease, it is probably also characterized by abnormalities in other organs. Brain abnormalities and cognitive impairment have been reported in severe SMA. We aimed to systematically investigate brain structure in SMA using MRI. Methods: We acquired high-resolution T1-weighted images of treatment-naive patients with SMA, age- and sex-matched healthy and disease controls with other neuromuscular diseases, on a 3 T MRI scanner. We performed vertex-wise whole brain analysis and region of interest analysis of cortical thickness (CT), and volumetric analysis of the thalamus and compared findings in patients and controls using multiple linear regression models and Wald test. We correlated structural abnormalities with motor function as assessed by the Hammersmith Functional Motor Scale Expanded (HFMSE) and SMA Functional Rating Scale (SMA-FRS). Results: We included 30 patients, 12–70 years old, with SMA type 2 and 3, 30 age- and sex-matched healthy controls and 17 disease controls (with distal SMA, hereditary motor and sensory neuropathy, multifocal motor neuropathy, progressive muscular atrophy and segmental SMA). We found a reduced CT in patients with SMA compared to healthy controls at the precentral, postcentral and medial orbitofrontal gyri and at the temporal pole (mean differences −0.059(p = 0.04); −0.055(p = 0.04), −0.06(p = 0.04); −0.17 mm(p = 0.001)). Differences at the precentral gyrus and temporal pole were most pronounced in SMA type 2 (mean differences −0.07(p = 0.045); −0.26 mm(p < 0.001)) and were also present compared to disease controls (mean differences −0.08(p = 0.048); −0.19 mm(p = 0.003)). There was a positive correlation between CT at the temporal pole with motor function. Compared to healthy controls, we found a reduced volume of the whole thalamus (mean difference −325 mm3(p = 0.03)) and of the anterior, ventral and intralaminar thalamic nuclei (mean differences −9.9(p = 0.02); −157(p = 0.01); −24.2 mm3(p = 0.02) in patients with SMA and a positive correlation between these volumes and motor function. Conclusion: MRI shows structural changes in motor and non-motor regions of the cortex and the thalamus of patients with SMA type 2 and 3, indicating that SMA pathology is not confined to motor neurons.http://www.sciencedirect.com/science/article/pii/S2213158224001499Spinal muscular atrophySMAMRIBrainCortical thicknessThalamus
spellingShingle Marloes Stam
Harold H.G. Tan
Ruben Schmidt
Martijn P. van den Heuvel
Leonard H. van den Berg
Renske I. Wadman
W. Ludo van der Pol
Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3
NeuroImage: Clinical
Spinal muscular atrophy
SMA
MRI
Brain
Cortical thickness
Thalamus
title Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3
title_full Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3
title_fullStr Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3
title_full_unstemmed Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3
title_short Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3
title_sort brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3
topic Spinal muscular atrophy
SMA
MRI
Brain
Cortical thickness
Thalamus
url http://www.sciencedirect.com/science/article/pii/S2213158224001499
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