Abstract:Atrophy of specific cerebellar lobules explains different aspects of motor and cognitive disability in patients with progressive MS. Investigation of cerebellar involvement provides further insight into the pathophysiological basis of clinical disability in progressive MS.
“…In one study, cerebellar GM volume was found to be reduced in SP-MS patients compared to healthy controls [ 123 ]. In another study, atrophy of specific cerebellar lobules in PMS patients correlated with clinical disability, as assessed by means of 9-hole-peg-test and cognitive tests [ 124 ]. Fig.…”
Section: Cerebellummentioning
confidence: 99%
“…Right image: the SUIT cerebellar atlas aligned in the native subject space. Reproduced from Cocozza et al [ 124 ] …”
Section: Cerebellummentioning
confidence: 99%
“… Not a good correlation between lesion aspects and pathological findings Present Spinal cord: PMS : cervical spinal cord lesion load was higher compared to RR-MS, and related to clinical disability [ 100 ] PP-MS : the presence of spinal cord lesions predicted conversion from RIS to PP-MS [ 102 ] Post-contrast FLAIR Cortex: SP-MS : leptomengingeal infiltrates were more frequent compared to RR-MS and tended to remain stable over time [ 58 – 60 ] Absent T1W sequences Cortex: PMS : global cortical atrophy was more prominent compared to other ClPh and was related to motor and cognitive impairment [ 20 , 57 , 84 ] SP-MS : temporal cortical atrophy was accelerated [ 85 ] Need of standardized protocols including high resolution images. The need of a reproducible and reliable method to quantify atrophy Present Whole brain, GM and spinal cord atrophy have been used in clinical trials [ 30 , 87 – 89 , 116 , 117 ] Spinal cord: PMS : higher cervical and thoracic spinal cord atrophy compared to RR-MS and it correlated to clinical disability [ 100 , 111 ] PP-MS : cervical spinal cord atrophy did not correlate with brain lesion or volume [ 16 ] SP-MS : cross-sectional area at the level of C7 presented the greatest difference compared to RR-MS [ 112 ] Results of longitudinal studies were discordant (see text) Cerebellum: PP-MS : higher rate of atrophy compared to HC over 5 years, with greater volume loss in patients with disease progression [ 125 , 126 ] SP-MS: GM volume was reduced compared to HC and atrophy of specific lobules correlate with clinical disability [ 123 , 124 ] DGM: PP-MS : atrophy of the thalami was detected since the early years and ...…”
Section: Recent Advancements and Future Perspectivesmentioning
Imaging markers for monitoring disease progression in progressive multiple sclerosis (PMS) are scarce, thereby limiting the possibility to monitor disease evolution and to test effective treatments in clinical trials. Advanced imaging techniques that have the advantage of metrics with increased sensitivity to short-term tissue changes and increased specificity to the structural abnormalities characteristic of PMS have recently been applied in clinical trials of PMS. In this review, we (1) provide an overview of the pathological features of PMS, (2) summarize the findings of research and clinical trials conducted in PMS which have applied conventional and advanced magnetic resonance imaging techniques and (3) discuss recent advancements and future perspectives in monitoring PMS with imaging techniques.
“…In one study, cerebellar GM volume was found to be reduced in SP-MS patients compared to healthy controls [ 123 ]. In another study, atrophy of specific cerebellar lobules in PMS patients correlated with clinical disability, as assessed by means of 9-hole-peg-test and cognitive tests [ 124 ]. Fig.…”
Section: Cerebellummentioning
confidence: 99%
“…Right image: the SUIT cerebellar atlas aligned in the native subject space. Reproduced from Cocozza et al [ 124 ] …”
Section: Cerebellummentioning
confidence: 99%
“… Not a good correlation between lesion aspects and pathological findings Present Spinal cord: PMS : cervical spinal cord lesion load was higher compared to RR-MS, and related to clinical disability [ 100 ] PP-MS : the presence of spinal cord lesions predicted conversion from RIS to PP-MS [ 102 ] Post-contrast FLAIR Cortex: SP-MS : leptomengingeal infiltrates were more frequent compared to RR-MS and tended to remain stable over time [ 58 – 60 ] Absent T1W sequences Cortex: PMS : global cortical atrophy was more prominent compared to other ClPh and was related to motor and cognitive impairment [ 20 , 57 , 84 ] SP-MS : temporal cortical atrophy was accelerated [ 85 ] Need of standardized protocols including high resolution images. The need of a reproducible and reliable method to quantify atrophy Present Whole brain, GM and spinal cord atrophy have been used in clinical trials [ 30 , 87 – 89 , 116 , 117 ] Spinal cord: PMS : higher cervical and thoracic spinal cord atrophy compared to RR-MS and it correlated to clinical disability [ 100 , 111 ] PP-MS : cervical spinal cord atrophy did not correlate with brain lesion or volume [ 16 ] SP-MS : cross-sectional area at the level of C7 presented the greatest difference compared to RR-MS [ 112 ] Results of longitudinal studies were discordant (see text) Cerebellum: PP-MS : higher rate of atrophy compared to HC over 5 years, with greater volume loss in patients with disease progression [ 125 , 126 ] SP-MS: GM volume was reduced compared to HC and atrophy of specific lobules correlate with clinical disability [ 123 , 124 ] DGM: PP-MS : atrophy of the thalami was detected since the early years and ...…”
Section: Recent Advancements and Future Perspectivesmentioning
Imaging markers for monitoring disease progression in progressive multiple sclerosis (PMS) are scarce, thereby limiting the possibility to monitor disease evolution and to test effective treatments in clinical trials. Advanced imaging techniques that have the advantage of metrics with increased sensitivity to short-term tissue changes and increased specificity to the structural abnormalities characteristic of PMS have recently been applied in clinical trials of PMS. In this review, we (1) provide an overview of the pathological features of PMS, (2) summarize the findings of research and clinical trials conducted in PMS which have applied conventional and advanced magnetic resonance imaging techniques and (3) discuss recent advancements and future perspectives in monitoring PMS with imaging techniques.
“…A substantial number of studies have examined the relationship between magnetic resonance imaging (MRI) neuroimaging measures and walking in PwMS. Grey matter volumes of the putamen, caudate, globus pallidus and nucleus accumbens have been linked to the Timed 25‐ft Walk (T25FW) test in relapsing–remitting MS , whereas cerebellar volume has been associated with the T25FW test in primary progressive MS . Recently, an association between low left hippocampal, putamen volumes and step time variability was found in PwMS with a history of falls .…”
Background and purpose
Existing research studies have demonstrated a relationship between magnetic resonance imaging (MRI) neuroimaging measures and walking speed in people with multiple sclerosis (PwMS). However, to date there are no data as to the brain structures involved in gait coordination and control in PwMS. Therefore, the aim of our study was to investigate the association between walk ratio, an indicator of gait coordination, and related brain structures in PwMS.
Methods
A brain MRI was performed by a 3.0‐T MR scanner in conjunction with a volumetric analysis based on three‐dimensional T1‐weighted images. Regions of interest were volumes of the hippocampus, amygdala, putamen, caudate, pallidum, thalamus, cerebellum and the corpus callosum regions. Walking speed and walk ratio, defined as step length divided by step rate, was measured whilst walking on an electronic walkway.
Results
In all, 343 PwMS (41.1 ± 13.4 years, 69.1% female, median Expanded Disability Status Scale 2.5) were included in the study. A significant association was found between the left cerebellum volume and walk ratio after controlling for age, gender, total cranial volume and disability; R2 = 0.379, P = 0.002. A similar association was found between the right cerebellum volume and walk ratio, R2 = 0.364, P = 0.002. No correlations were observed between walk ratio and the thalamus, basal ganglia, hippocampus, amygdala and the corpus callosum volumes. No association was found between walking speed and all brain measures.
Conclusions
The walk ratio should be considered when evaluating and assessing PwMS presenting with ataxia. Furthermore, it is also hypothesized that a low walk ratio indicates a lower cerebellum volume in the MS population.
“…While subcortical gray matter degeneration in MS has been associated with a number of non-motor symptoms, such as fatigue, ( 8 – 10 ) memory impairment, ( 11 , 12 ) and depression, ( 13 ) these structures are difficult to evaluate qualitatively in a clinical setting. Cerebellar imaging in MS has also overwhelmingly focused on white matter metrics, even though cerebellar gray matter degeneration have been linked to motor disability, ( 14 ) impaired information processing, ( 15 ), and falls ( 16 ).…”
Background: Magnetic resonance imaging is a key diagnostic and monitoring tool in multiple Sclerosis (MS). While the substrates of motor and neuropsychological symptoms in MS have been extensively investigated, nystagmus-associated imaging signatures are relatively under studied. Accordingly, the objective of this study is the comprehensive characterisation of cortical, subcortical, and brainstem involvement in a cohort of MS patients with gaze-evoked nystagmus.Methods: Patients were recruited from a specialist MS clinic and underwent multimodal neuroimaging including high-resolution structural and diffusion tensor data acquisitions. Morphometric analyses were carried out to evaluate patterns of cortical, subcortical, brainstem, and cerebellar gray matter pathology. Volumetric analyses were also performed to further characterize subcortical gray matter degeneration. White matter integrity was evaluated using axial-, mean-, and radial diffusivity as well as fractional anisotropy.Results: Whole-brain morphometry highlighted considerable brainstem and cerebellar gray matter atrophy, and the tract-wise evaluation of white matter metrics revealed widespread pathology in frontotemporal and parietal regions. Nystagmus-associated gray matter degeneration was identified in medial cerebellar, posterior medullar, central pontine, and superior collicular regions. Volume reductions were identified in the putamen, thalamus and hippocampus.Conclusions: Multiple sclerosis is associated with widespread gray matter pathology which is not limited to cortical regions but involves striatal, thalamic, cerebellar, and hippocampal foci. The imaging signature of gaze-evoked nystagmus in MS confirms the degeneration of key structures of the neural integrator network.
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