Objective
Astrocytes outline the perivascular space (PVS) and regulate fluid exchange through the aquaporin‐4 water channel. As neuromyelitis optica is an autoimmune astrocytopathy targeting ...aquaporin‐4, we hypothesized that it could be associatied with PVS abnormalities.
Methods
A total of 34 patients, and 46 age‐ and sex‐matched healthy controls from two independent cohorts (exploratory and validation dataset) underwent a standardized 3.0‐T magnetic resonance imaging protocol including conventional and diffusion tensor imaging. Susceptibility‐weighted imaging was also acquired in the exploratory dataset. We evaluated macroscopic and microstructural abnormalities of PVS in terms of enlargement and water diffusivity (DTI‐ALPS index). In the exploration dataset, a susceptibility‐weighted sequence was used to draw the regions of interest for the DTI‐ALPS index calculation in areas having veins perpendicular to lateral ventricles. Between‐group comparisons, correlations, and regression models were run to assess associations between PVS abnormalities, and clinical and magnetic resonance imaging variables.
Results
Patients had a higher frequency of severe PVS enlargement in the centrum semiovale (29.4% vs 8.7%), which correlated with brain atrophy, deep grey matter atrophy, and poorer cognitive performance (r‐values range: −0.44, −0.36; p values: 0.01–0.046).
In both datasets, patients had reduced DTI‐ALPS index compared with controls (p values 0.004–0.038). Lower DTI‐ALPS index, deep gray matter volume, and cortical volume could discriminate between patients and controls (R2 = 0.62), whereas lower DTI‐ALPS index, higher number of myelitis, and higher T2‐lesion volume were associated with worse disability (R2 = 0.55).
Interpretation
Patients with neuromyelitis optica spectrum disorder are characterized by abnormal enlargement and impaired water diffusion along the PVS, whose clinical implications suggest a direct correlation with disease pathogenesis and severity. ANN NEUROL 2022;92:173–183
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background:
When investigating white matter (WM) microstructure, the axonal fiber orientation should be considered. Constrained spherical deconvolution (CSD) is a diffusion-weighted imaging (DWI) ...method that estimates distribution of fibers within each imaging voxel.
Objective:
To study fiber-bundle cross-section (FC) as measured by CSD in multiple sclerosis (MS) patients versus healthy controls (HCs).
Methods:
DWI and three-dimensional (3D) T1-weighted magnetic resonance imaging (MRI) were obtained from 45 MS patients and 45 HCs. We applied fixel-based morphometry analysis to assess differences of FC in MS against HCs and voxel-based analysis of fractional anisotropy (FA).
Results:
We found a significant widespread reduction of WM FC in MS compared to HCs. The decrease in FA was less extensive, mainly located in regions with high lesion occurrence such as the periventricular WM and the corpus callosum. Progressive MS patients showed a significant FC reduction in the right anterior cingulum, bilateral cerebellum, and in several mesencephalic and diencephalic regions compared to relapsing-remitting MS patients.
Conclusion:
The CSD method can be applied in MS for a fiber-specific study of WM microstructure and quantification of FC. Fixel-based findings offered greater anatomical specificity and biological interpretability by identifying tract-specific differences and allowed substantial abnormalities to be detected.
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Objectives
To validate imaging features able to discriminate neuromyelitis optica spectrum disorders from multiple sclerosis with conventional magnetic resonance imaging (MRI).
Methods
In this ...cross‐sectional study, brain and spinal cord scans were evaluated from 116 neuromyelitis optica spectrum disorder patients (98 seropositive and 18 seronegative) in chronic disease phase and 65 age‐, sex‐, and disease duration–matched multiple sclerosis patients. To identify independent predictors of neuromyelitis optica diagnosis, after assessing the prevalence of typical/atypical findings, the original cohort was 2:1 randomized in a training sample (where a multivariate logistic regression analysis was run) and a validation sample (where the performance of the selected variables was tested and validated).
Results
Typical brain lesions occurred in 50.9% of neuromyelitis optica patients (18.1% brainstem periventricular/periaqueductal, 32.7% periependymal along lateral ventricles, 3.4% large hemispheric, 6.0% diencephalic, 4.3% corticospinal tract), 72.2% had spinal cord lesions (46.3% long transverse myelitis, 36.1% short transverse myelitis), 37.1% satisfied 2010 McDonald criteria, and none had cortical lesions. Fulfillment of at least 2 of 5 of absence of juxtacortical/cortical lesions, absence of periventricular lesions, absence of Dawson fingers, presence of long transverse myelitis, and presence of periependymal lesions along lateral ventricles discriminated neuromyelitis optica patients in both training (sensitivity = 0.92, 95% confidence interval CI = 0.84–0.97; specificity = 0.91, 95% CI = 0.78–0.97) and validation samples (sensitivity = 0.82, 95% CI = 0.66–0.92; specificity = 0.91, 95% CI = 0.71–0.99). MRI findings and criteria performance were similar irrespective of serostatus.
Interpretation
Although up to 50% of neuromyelitis optica patients have no typical lesions and a relatively high percentage of them satisfy multiple sclerosis criteria, several easily applicable imaging features can help to distinguish neuromyelitis optica from multiple sclerosis. ANN NEUROL 2019;85:371–384.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To estimate the relative contributions of baseline thalamic atrophy and abnormalities shown at magnetization transfer (MT) magnetic resonance (MR) imaging, as well as their 12-month changes, in ...predicting accumulation of disability in a relatively large sample of patients with relapse-onset multiple sclerosis (MS) during an 8-year period.
The study was conducted with approval of the institutional review board. Written informed consent was obtained from each participant. Conventional and MT MR imaging of the brain was performed at baseline and at 12-month follow-up in 13 healthy control subjects and 73 patients with relapse-onset MS; participants were monitored with clinical visits for 8 years. The following parameters were evaluated at baseline and at 12-month follow-up: volume of lesions with high signal intensity at T2-weighted imaging, volume of lesions with low signal intensity at T1-weighted imaging, mean lesion MT ratio, thalamic fraction, and thalamic MT ratio. A multivariate analysis was used to evaluate the predictors of long-term neurologic deterioration.
At 8-year follow-up, 44 patients showed worsening disability. During follow-up, reduction in thalamic fraction was more pronounced in patients with relapsing-remitting MS than in those with secondary progressive MS (P = .001); thalamic MT ratio decreased only in patients with secondary progressive MS (P = .007). In the multivariable model, baseline thalamic fraction (odds ratio = 0.62, P = .01) and mean percentage change in lesion MT ratio after 12 months (odds ratio = 0.90, P = .04) were independent predictors of worsening disability at 8 years. At baseline, thalamic fraction was correlated with lesion volumes at T2-weighted imaging (r = -0.75, P < .001) and T1-weighted imaging (r = -0.60, P < .001).
Thalamic atrophy is correlated with long-term accumulation of disability in patients with MS. White matter lesions are likely to contribute to the loss of tissue seen in the thalamus of patients with MS.
MRI plays a central role in the diagnosis of multiple sclerosis (MS) and in the monitoring of disease course and treatment response. Advanced MRI techniques have shed light on MS biology and ...facilitated the search for neuroimaging markers that may be applicable in clinical practice. MRI has led to improvements in the accuracy of MS diagnosis and a deeper understanding of disease progression. This has also resulted in a plethora of potential MRI markers, the importance and validity of which remain to be proven. Here, five recent emerging perspectives arising from the use of MRI in MS, from pathophysiology to clinical application, will be discussed. These are the feasibility of noninvasive MRI-based approaches to measure glymphatic function and its impairment; T1-weighted to T2-weighted intensity ratio to quantify myelin content; classification of MS phenotypes based on their MRI features rather than on their clinical features; clinical relevance of gray matter atrophy versus white matter atrophy; and time-varying versus static resting-state functional connectivity in evaluating brain functional organization. These topics are critically discussed, which may guide future applications in the field.
Background:
Cervical spinal cord (cSC) lesions and atrophy contribute to disability in multiple sclerosis (MS), but associations with specific sensorimotor dysfunction require further exploration.
...Objective:
To investigate the associations of brain and cSC magnetic resonance imaging (MRI) measures with sensorimotor impairment in MS.
Methods:
One hundred fifty-one MS patients and 69 healthy controls underwent 3T MRI and clinical assessments including Expanded Disability Status Scale (EDSS), 9-hole peg test (9-HPT), finger tapping test (FTT), timed 25-foot walk test (T25FWT), and vibration detection threshold (VDT). Random forest ranked brain (T2-hyperintense lesion volume (T2-LV) and normalized deep gray matter (GM), cortical and white matter (WM) volumes) and cSC (T2-LV and total, GM, and WM cross-sectional areas (CSAs) at C2/C3 level) MRI measures relevance in explaining EDSS milestones (EDSS ⩾3.0, ⩾4.0, and ⩾6.0), VDT, pyramidal and sensory functional systems (P-FS and S-FS ⩾2), and motor tests impairment.
Results:
Various combinations of brain and cSC MRI measures explained EDSS milestones (area under the curve (AUC) =0.879–0.900), VDT (R2 = 0.194), and impaired P-FS (AUC = 0.820), S-FS (AUC = 0.795), 9-HPT (AUC = 0.793), FTT (AUC = 0.740), and T25FWT (AUC = 0.825). cSC GM CSA was the most informative feature for all outcomes, except 9-HPT.
Conclusion:
cSC MRI measures, especially GM CSA, explain EDSS and sensorimotor dysfunction better than brain measures in MS.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Background:
According to the cognitive reserve (CR) theory, enriching experiences protect against cognitive decline.
Objectives:
To investigate the dynamic interaction between CR and global/regional ...measures of brain white matter (WM) and gray matter (GM) damage and their effect on cognitive performance in multiple sclerosis (MS).
Methods:
Baseline and 2 -year three-dimensional (3D) T1-weighted scans were obtained from 54 MS patients and 20 healthy controls. Patients’ cognitive functions were tested and a cognitive reserve index (CRI) was calculated. Baseline regional atrophy and longitudinal volume changes were investigated using voxel-wise methods. Structural damage and CRI effects on cognitive performance were explored with linear models.
Results:
At baseline, MS patients showed atrophy of the deep GM nuclei, GM/WM frontal–temporal–parietal–occipital regions, and left cerebellum. Controlling for atrophy, higher CRI explained significant portions of variance in verbal memory and verbal fluency (∆R2 = 0.07–0.16; p < 0.03). The interaction between thalamic volume and CRI was significant (∆R2 = 0.05; p = 0.03). Longitudinal changes in memory and attention performance were associated with local/global variations of GM/WM and T2 lesions. CRI had no effect on longitudinal cognitive changes.
Conclusion:
In MS, CR may have a protective role in preserving cognitive functions, moderating the effect of structural damage on cognitive performance. This protective role may diminish with disease progression.
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Background:
Multiple sclerosis (MS) is characterized by focal white matter damage, and when the brain is modeled as a network, lesions can be treated as disconnection events.
Objective:
To evaluate ...whether modeling disconnection caused by lesions helps explain motor and cognitive impairment in MS.
Methods:
Pathways connecting 116 cortical regions were reconstructed with magnetic resonance imaging (MRI) tractography from diffusion tensors averaged across healthy controls (HCs); maps of pathways were applied to 227 relapse-onset MS patients and 50 HCs to derive structural connectivity. Then, the likelihood of individual connections passing through lesions was used to model disconnection. Patients were grouped according to clinical phenotype (113 relapsing-remitting multiple sclerosis (RRMS), 69 secondary progressive multiple sclerosis (SPMS), 45 benign MS), and then network metrics were compared between groups (analysis of variance (ANOVA)) and correlated with motor and cognitive scores (linear regression).
Results:
Global metrics differentiated RRMS from SPMS and benign MS patients, but not benign from SPMS patients. Nodal connectivity strength replicated global results. After disconnection, few nodes were significantly different between benign MS and RRMS patients. Correlations revealed nodes pertinent to motor and cognitive dysfunctions; these became slightly stronger after disconnection.
Conclusion:
Connectivity did not change greatly after modeled disconnection, suggesting that the brain network is robust against damage caused by MS lesions.
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Background:
Hand-motor impairment affects a large proportion of multiple sclerosis (MS) patients; however, its substrates are still poorly understood.
Objectives:
To investigate the association ...between global disability, hand-motor impairment, and alterations in motor-relevant structural and functional magnetic resonance imaging (MRI) networks in MS patients with different clinical phenotypes.
Methods:
One hundred thirty-four healthy controls (HC) and 364 MS patients (250 relapsing-remitting MS (RRMS) and 114 progressive MS (PMS)) underwent Expanded Disability Status Scale (EDSS) rating, nine-hole peg test (9HPT), and electronic finger tapping rate (EFTR). Structural and resting state (RS) functional MRI scans were used to perform a source-based morphometry on gray matter (GM) components, to analyze white matter (WM) tract diffusivity indices and to perform a RS seed-based approach from the primary motor cortex involved in hand movement (hand-motor cortex). Random forest analyses identified the predictors of clinical impairment.
Result:
In RRMS, global measures of atrophy and lesions together with measures of structural damage of motor-related regions predicted EDSS (out-of-bag (OOB)-R2 = 0.19, p-range = <0.001–0.04), z9HPT (right: OOB-R2 = 0.14; left: OOB-R2 = 0.24, p-range = <0.001–0.03). No RS functional connectivity (FC) abnormalities were identified in RRMS models. In PMS, cerebellar and sensorimotor regions atrophy, cerebellar peduncles integrity and increased RS FC between left hand-motor cortex and right inferior frontal gyrus predicted EDSS (OBB-R2 = 0.16, p-range = 0.02–0.04).
Conclusion:
In RRMS, only measures of structural damage contribute to explain motor impairment, whereas both structural and functional MRI measures predict clinical disability in PMS. A multiparametric MRI approach could be relevant to investigate hand-motor impairment in different MS phenotypes.
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