TY - JOUR
T1 - Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3
AU - Stam, Marloes
AU - Tan, Harold H.G.
AU - Schmidt, Ruben
AU - van den Heuvel, Martijn P.
AU - van den Berg, Leonard H.
AU - Wadman, Renske I.
AU - van der Pol, W. Ludo
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Brain
KW - Cortical thickness
KW - MRI
KW - SMA
KW - Spinal muscular atrophy
KW - Thalamus
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U2 - 10.1016/j.nicl.2024.103708
DO - 10.1016/j.nicl.2024.103708
M3 - Article
AN - SCOPUS:85209553321
SN - 2213-1582
VL - 44
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 103708
ER -