Browsing by Author "Rocca, Maria A. (34973365100)"

Objectives: To apply a deep-learning algorithm to brain MRIs of seronegative patients with neuromyelitis optica spectrum disorders (NMOSD) and NMOSD-like manifestations and assess whether their structural features are similar to aquaporin-4-seropositive NMOSD or multiple sclerosis (MS) patients. Patients and methods: We analyzed 228 T2- and T1-weighted brain MRIs acquired from aquaporin-4-seropositive NMOSD (n = 85), MS (n = 95), aquaporin-4-seronegative NMOSD [n = 11, three with anti-myelin oligodendrocyte glycoprotein antibodies (MOG)], and aquaporin-4-seronegative patients with NMOSD-like manifestations (idiopathic recurrent optic neuritis and myelitis, n = 37), who were recruited from February 2010 to December 2019. Seventy-three percent of aquaporin-4-seronegative patients with NMOSD-like manifestations also had a clinical follow-up (median duration of 4 years). The deep-learning neural network architecture was based on four 3D convolutional layers. It was trained and validated on MRI scans of aquaporin-4-seropositive NMOSD and MS patients and was then applied to aquaporin-4-seronegative NMOSD and NMOSD-like manifestations. Assignment of unclassified aquaporin-4-seronegative patients was compared with their clinical follow-up. Results: The final algorithm differentiated aquaporin-4-seropositive NMOSD and MS patients with an accuracy of 0.95. All aquaporin-4-seronegative NMOSD and 36/37 aquaporin-4-seronegative patients with NMOSD-like manifestations were classified as NMOSD. Anti-MOG patients had a similar probability of being NMOSD or MS. At clinical follow-up, one unclassified aquaporin-4-seronegative patient evolved to MS, three developed NMOSD, and the others did not change phenotype. Conclusions: Our findings support the inclusion of aquaporin4-seronegative patients into NMOSD and suggest a possible expansion to aquaporin-4-seronegative unclassified patients with NMOSD-like manifestations. Anti-MOG patients are likely to have intermediate brain features between NMOSD and MS. © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.

Objectives: To apply a deep-learning algorithm to brain MRIs of seronegative patients with neuromyelitis optica spectrum disorders (NMOSD) and NMOSD-like manifestations and assess whether their structural features are similar to aquaporin-4-seropositive NMOSD or multiple sclerosis (MS) patients. Patients and methods: We analyzed 228 T2- and T1-weighted brain MRIs acquired from aquaporin-4-seropositive NMOSD (n = 85), MS (n = 95), aquaporin-4-seronegative NMOSD [n = 11, three with anti-myelin oligodendrocyte glycoprotein antibodies (MOG)], and aquaporin-4-seronegative patients with NMOSD-like manifestations (idiopathic recurrent optic neuritis and myelitis, n = 37), who were recruited from February 2010 to December 2019. Seventy-three percent of aquaporin-4-seronegative patients with NMOSD-like manifestations also had a clinical follow-up (median duration of 4 years). The deep-learning neural network architecture was based on four 3D convolutional layers. It was trained and validated on MRI scans of aquaporin-4-seropositive NMOSD and MS patients and was then applied to aquaporin-4-seronegative NMOSD and NMOSD-like manifestations. Assignment of unclassified aquaporin-4-seronegative patients was compared with their clinical follow-up. Results: The final algorithm differentiated aquaporin-4-seropositive NMOSD and MS patients with an accuracy of 0.95. All aquaporin-4-seronegative NMOSD and 36/37 aquaporin-4-seronegative patients with NMOSD-like manifestations were classified as NMOSD. Anti-MOG patients had a similar probability of being NMOSD or MS. At clinical follow-up, one unclassified aquaporin-4-seronegative patient evolved to MS, three developed NMOSD, and the others did not change phenotype. Conclusions: Our findings support the inclusion of aquaporin4-seronegative patients into NMOSD and suggest a possible expansion to aquaporin-4-seronegative unclassified patients with NMOSD-like manifestations. Anti-MOG patients are likely to have intermediate brain features between NMOSD and MS. © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.

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. © 2019 American Neurological Association

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. © 2019 American Neurological Association

Objective: The brain reserve hypothesis links larger maximal lifetime brain growth (MLBG, estimated with intracranial volume [ICV]) with lower risk for cognitive decline/dementia. We examined whether larger MLBG is also linked to less physical disability progression over 5 years in a prospective sample of treatment-naive patients with multiple sclerosis (MS). Methods: Physical disability was measured with the Expanded Disability Status Scale (EDSS) at baseline and 5-year follow-up in 52 treatment-naive Serbian patients with MS. MRI measured disease burden (cerebral atrophy, T2 lesion volume) and MLBG: a genetically determined, premorbid (established during adolescence, stable thereafter) patient characteristic estimated with ICV (adjusted for sex). Logistic regression tested whether MLBG (smaller vs larger) predicts disability progression (stable vs worsened) independently of disease burden. Results: Disability progression was observed in 29 (55.8%) patients. Larger MLBG predicted lower risk for progression (odds ratio 0.13, 95% confidence interval 0.02-0.78), independently of disease burden. We also calculated absolute change in EDSS scores, and observed that patients with smaller MLBG showed worse EDSS change (0.91 ± 0.71) than patients with larger MLBG (0.42 ± 0.87). Conclusions: Larger MLBG was linked to lower risk for disability progression in patients with MS over 5 years, which is the first extension of the brain reserve hypothesis to physical disability. MLBG (ICV) represents a clinically available metric that may help gauge risk for future disability in patients with MS, which may advance the science and practice of early intervention. Potential avenues for future research are discussed. © 2016 American Academy of Neurology.

Here, we explored trajectories of sub-regional thalamic resting state (RS) functional connectivity (FC) modifications occurring in clinically isolated syndrome (CIS) patients early after their first clinical episode, and assessed their relationship with disability over 7 years. RS fMRI and clinical data were prospectively acquired from 59 CIS patients and 13 healthy controls (HC) over 2 years. A clinical re-assessment was performed in 53 (89%) patients after 7 years. Using a structural connectivity-based atlas, five thalamic sub-regions (frontal, motor, postcentral, occipital, and temporal) were used for seed-based RS FC. Thalamic RS FC abnormalities and their longitudinal changes were correlated with disability. Thirty-nine (66.1%) patients suffered a second clinical relapse, but the median EDSS remained stable over time. At baseline, CIS patients vs HC showed reduced RS FC (p < 0.001, uncorrected) with: (1) frontal cortices, for the whole thalamus, occipital, postcentral, and temporal thalamic sub-regions, (2) occipital cortices, for the occipital thalamic sub-region. In CIS, the longitudinal analysis revealed at year 2 vs baseline: (1) no significant whole-thalamic RS FC changes; (2) reduction of motor, postcentral, and temporal sub-regional RS FC with occipital cortices (p < 0.05, corrected); (3) an increase (p < 0.001, uncorrected) of postcentral and occipital sub-regional thalamic RS FC with frontal cortices, left putamen, and ipsi- and contralateral thalamus, this latter correlating with less severe clinical disability at year 7. Thalamo-cortical disconnections were present in CIS mainly in thalamic sub-regions closer to the third ventricle early after the demyelinating event, evolved in the subsequent 2 years, and were associated with long-term clinical disability. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

Here, we explored trajectories of sub-regional thalamic resting state (RS) functional connectivity (FC) modifications occurring in clinically isolated syndrome (CIS) patients early after their first clinical episode, and assessed their relationship with disability over 7 years. RS fMRI and clinical data were prospectively acquired from 59 CIS patients and 13 healthy controls (HC) over 2 years. A clinical re-assessment was performed in 53 (89%) patients after 7 years. Using a structural connectivity-based atlas, five thalamic sub-regions (frontal, motor, postcentral, occipital, and temporal) were used for seed-based RS FC. Thalamic RS FC abnormalities and their longitudinal changes were correlated with disability. Thirty-nine (66.1%) patients suffered a second clinical relapse, but the median EDSS remained stable over time. At baseline, CIS patients vs HC showed reduced RS FC (p < 0.001, uncorrected) with: (1) frontal cortices, for the whole thalamus, occipital, postcentral, and temporal thalamic sub-regions, (2) occipital cortices, for the occipital thalamic sub-region. In CIS, the longitudinal analysis revealed at year 2 vs baseline: (1) no significant whole-thalamic RS FC changes; (2) reduction of motor, postcentral, and temporal sub-regional RS FC with occipital cortices (p < 0.05, corrected); (3) an increase (p < 0.001, uncorrected) of postcentral and occipital sub-regional thalamic RS FC with frontal cortices, left putamen, and ipsi- and contralateral thalamus, this latter correlating with less severe clinical disability at year 7. Thalamo-cortical disconnections were present in CIS mainly in thalamic sub-regions closer to the third ventricle early after the demyelinating event, evolved in the subsequent 2 years, and were associated with long-term clinical disability. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

Purpose: To investigate the patterns of regional gray matter (GM) and white matter (WM) atrophy, WM microstructural tissue damage, and changes in patients with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis at 2 years from clinical onset. Materials and Methods: Institutional review board approval and written informed consent from all patients were obtained. Neurologic assessment and conventional, diffusion-tensor, and volumetric brain MR imaging sequences were performed in 37 patients with CIS within 2 months of clinical onset, and after 3, 12, and 24 months. Fourteen healthy control subjects also were studied. Longitudinal GM and WM volume changes and WM microstructural abnormalities were assessed by using voxel-based morphometry (P <.001, uncorrected) and tract-based spatial statistics (P <.05, corrected). Results: At 24 months, 33 of 37 (89%) patients had developed multiple sclerosis. At month 3, patients with CIS showed a transient volume increase in frontal, parietal, temporal, and cerebellar GM regions. At 12 months, patients with CIS developed atrophy of the thalami, caudate nuclei, cerebellum, and frontal, parietal, and temporal lobes. At 24 months GM volume of the frontal, temporal, and parietal cortical areas further decreased from that at 12 months. WM atrophy involved only a few WM regions at 2 months from clinical onset, with progressive involvement of additional WM tracts with time. A diffuse pattern of WM microstructural abnormalities was detected within 2 months of onset and had worsened at 24 months. Conclusion: After an acute inflammatory event, dynamic modifications of regional GM and WM damage occur in patients with CIS, with a progressive evolution of WM damage from disease onset and a transient, early increase in GM volume, followed by GM atrophy. Neurodegenerative processes start early in patients with multiple sclerosis. © RSNA, 2015.

Purpose: To study the concomitant use of structural and functional magnetic resonance (MR) imaging correlates to explain information processing speed (IPS) and executive function (EF) in multiple sclerosis (MS). Materials and Methods: Local ethics committee approval was obtained at all sites for this prospective, multicenter study. All subjects provided written informed consent. Twenty-six patients with relapsing-remitting MS and 32 healthy control subjects from four centers underwent structural and functional MR imaging, including a go/no-go task and neuropsychological assessment. Subtests of the Brief Repeatable Battery of Neuropsychological Tests, the Wisconsin Card Sorting Test, and the performance with the functional MR imaging paradigm were used as estimates of IPS and EF. Activation of the thalamus and the inferior frontal gyrus (pars triangularis), thalamic volume, T2 lesion load, and age were used to explain IPS and EF in regression models. Results: Compared with control subjects, patients showed increased activation in a frontoparietal network, including both thalami, during the execution of the go/no-go task. Patients had decreased thalamic volume (P , .001). Among tested variables, thalamic volume (b = 0.606, P = .001), together with thalamic activation (b = 20.410, P = .022), were the best predictors of IPS and EF and helped explain 52.7% of the variance in IPS and EF. Conclusion: This study highlights the potential of the combined use of functional and morphologic parameters to explain IPS and EF in patients with relapsing-remitting MS and confirms the central role of the thalamus as a relay station in executive functioning. © RSNA, 2016.

[No abstract available]

Purpose: To apply voxelwise analysis of diffusion-tensor (DT) magnetic resonance (MR) tractography and T2-weighted MR lesion measurements to characterize intrinsic damage to the brain white matter (WM) tracts and the relation of this damage to the presence and location of focal lesions among the main clinical phenotypes of multiple sclerosis (MS). Materials and Methods: The study was conducted with institutional review board approval. Written informed consent was obtained from each participant. Brain dual-echo and DT MR images were obtained in 172 patients with MS (22 [13%] with clinically isolated syndromes [CIS] suggestive of MS, 51 [30%] with relapsing-remitting [RR] MS, 44 [26%] with secondary progressive MS, 20 [12%] with benign MS, 35 [20%] with primary progressive MS) and 46 healthy control subjects. Probability maps of the major brain WM tracts were produced. Between-group comparisons were assessed by using analysis of covariance. Results: Compared with the healthy control subjects, the patients with CIS had significantly increased (P<.001) mean diffusivity, axial diffusivity, and radial diffusivity in the majority of WM tracts. The primary progressive MS group showed diffuse increases in mean, axial, and radial diffusivity, with fractional anisotropy (FA) damage involving the majority of WM tracts. No relevant difference in diffusivity measures was found between the CIS and RR-MS groups. Compared with the benign MS group, the RR-MS group had reduced FA values in all WM tracts and decreased axial diffusivity in the majority of tracts. The secondary progressive MS group had pronounced damage to the majority of tracts and, compared with the benign MS group, pronounced FA alteration of the tracts relevant for motor impairment. Conclusion: Voxelwise assessment of DT MR index abnormalities is a rewarding strategy for understanding the heterogeneity of clinical MS phenotypes. © RSNA, 2011.

In this longitudinal study, we investigated the regional patterns of focal lesions accumulation, and gray (GM) and white matter (WM) atrophy progression over a five-year follow-up (FU) in multiple sclerosis (MS) patients and their association with clinical and cognitive deterioration. Neurological, neuropsychological and brain MRI (dual-echo and 3D T1-weighted sequences) assessments were prospectively performed at baseline (T0) and after a median FU of 4.9 years from 66 MS patients (including relapse-onset and primary progressive MS) and 16 matched controls. Lesion probability maps were obtained. Longitudinal changes of GM and WM volumes and their association with clinical and cognitive deterioration were assessed using tensor-based morphometry and SPM12. At FU, 36/66 (54.5%) MS patients showed a significant disability worsening, 14/66 (21.2%) evolved to a worse clinical phenotype, and 18/63 (28.6%) developed cognitive deterioration. At T0, compared to controls, MS patients showed a widespread pattern of GM atrophy, involving cortex, deep GM and cerebellum, and atrophy of the majority of WM tracts, which further progressed at FU (P < 0.001, uncorrected). Compared to stable patients, those with clinical and cognitive worsening showed a left-lateralized pattern of GM and WM atrophy, involving deep GM, fronto-temporo-parieto-occipital regions, cerebellum, and several WM tracts (P < 0.001, uncorrected).GM and WM atrophy of relevant brain regions occur in MS after 5 years. A different vulnerability of the two brain hemispheres to irreversible structural damage may be among the factors contributing to clinical and cognitive worsening in these patients. Hum Brain Mapp 38:5648–5665, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

In this longitudinal study, we investigated the regional patterns of focal lesions accumulation, and gray (GM) and white matter (WM) atrophy progression over a five-year follow-up (FU) in multiple sclerosis (MS) patients and their association with clinical and cognitive deterioration. Neurological, neuropsychological and brain MRI (dual-echo and 3D T1-weighted sequences) assessments were prospectively performed at baseline (T0) and after a median FU of 4.9 years from 66 MS patients (including relapse-onset and primary progressive MS) and 16 matched controls. Lesion probability maps were obtained. Longitudinal changes of GM and WM volumes and their association with clinical and cognitive deterioration were assessed using tensor-based morphometry and SPM12. At FU, 36/66 (54.5%) MS patients showed a significant disability worsening, 14/66 (21.2%) evolved to a worse clinical phenotype, and 18/63 (28.6%) developed cognitive deterioration. At T0, compared to controls, MS patients showed a widespread pattern of GM atrophy, involving cortex, deep GM and cerebellum, and atrophy of the majority of WM tracts, which further progressed at FU (P < 0.001, uncorrected). Compared to stable patients, those with clinical and cognitive worsening showed a left-lateralized pattern of GM and WM atrophy, involving deep GM, fronto-temporo-parieto-occipital regions, cerebellum, and several WM tracts (P < 0.001, uncorrected).GM and WM atrophy of relevant brain regions occur in MS after 5 years. A different vulnerability of the two brain hemispheres to irreversible structural damage may be among the factors contributing to clinical and cognitive worsening in these patients. Hum Brain Mapp 38:5648–5665, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Purpose: To assess whether a structural disconnection between the cerebellum and the cerebral hemispheres contributes to cerebellar and brainstem symptoms in multiple sclerosis (MS). Materials and Methods: This study was approved by the local ethics committee, and written informed consent was obtained from each participant. Brain T2 lesion load, cerebellar white matter and gray matter volumes, and tract-specific measures of the middle and superior cerebellar peduncles were derived from 172 patients with MS and 46 control subjects. Predictors of clinical impairment, which was determined at ambulation and with cerebellar and brainstem functional system scores, were identified by using random forest analysis. Results: Of the 172 patients, 112 (65%) had middle cerebellar peduncle T2 lesions and 74 (43%) had superior cerebellar peduncle T2 lesions. T2 lesions in the middle and superior cerebellar peduncles were more common in clinically impaired patients than in unimpaired patients (P =.05 to <.0001). Most conventional magnetic resonance imaging metrics were more abnormal in impaired patients than in unimpaired patients (P =.03 to <.0001). Except for axial diffusivity, diffusivity abnormalities of the middle and superior cerebellar peduncles were more severe in clinically impaired patients than in unimpaired patients (P =.04 to <.0001). A minimal overlap was found between diffusivity abnormalities and T2 lesions. Compared with volumetric measures of T2 lesions or cerebellar atrophy, diffusivity measures of middle or superior cerebellar peduncle damage enabled better differentiation between clinically impaired and unimpaired patients (C statistics: 61%-70%). Conclusion: The assessment of middle and superior cerebellar peduncle damage contributes to the explanation of cerebellar and/or brainstem symptoms and ambulatory impairment in MS. © 2014 RSNA.

Background: The spinal cord is commonly involved in patients with neuromyelitis optica spectrum disorders (NMOSDs). However, the relationship between inflammation and atrophy remains unclear. Purpose: To characterize the spatial distribution of T1-hypointense lesions in the spinal cord at MRI, its association with cord atrophy, and its correlation with disability in participants with NMOSDs. Materials and Methods: This prospective study evaluated three-dimensional T1-weighted spinal cord MRI scans in seropositive participants with NMOSDs and in age-matched healthy control participants acquired between February 2010 and July 2018. Binary masks of T1-hypointense lesions and lesion probability maps were produced. Cross-sectional area of the cervical and upper thoracic cord (down to T3 level) was calculated with the active-surface method. Full factorial models were used to assess cord atrophy in participants with NMOSDs. Correlations between cord atrophy and clinical and brain MRI measures were investigated with multiple regression models. Results: A total of 52 participants with NMOSDs (mean age 6 standard deviation, 44 years 6 15; 45 women) and 28 age-matched healthy control participants (mean age, 44 years 6 13; 16 women) were evaluated. Thirty-eight of 52 (73%) participants with NMOSDs had T1-hypointense cord lesions. No cord lesions were detected in the healthy control participants. Lesion probability maps showed a predominant involvement of the upper cervical (C2–C4) and upper thoracic (T1–T3 level) cord. The greater involvement of C1–C4 survived Bonferroni correction (P value range, .007–.04), with a higher percentage lesion extent in the gray matter (P , .001). Atrophy colocalized with focal cord lesions and correlated with pyramidal subscore (r ranging from 20.53 to 20.40; P , .001) and sensitive subscore (r ranging from 20.48 to 20.46; P = .001) of the Expanded Disability Status Scale. Participants without cord lesions had no cord atrophy. Conclusion: In participants with neuromyelitis optica spectrum disorders, focal areas of spinal cord atrophy at MRI were topographically associated with lesions and correlated to motor and sensory disability. Participants without visible cord lesions had no atrophy. © RSNA, 2020.

Objective: To apply voxel-based methods to map the regional distribution of atrophy and T2 hyperintense lesions in the cervical cord of multiple sclerosis (MS) patients with different clinical phenotypes. Methods: Brain and cervical cord 3D T1-weighted and T2-weighted scans were acquired from 31 healthy controls (HC) and 77 MS patients (15 clinically isolated syndromes (CIS), 15 relapsing-remitting (RR), 19 benign (B), 15 primary progressive (PP) and 13 secondary progressive (SP) MS). Hyperintense cord lesions were outlined on T2-weighted scans. The T2- and 3D T1-weighted cord images were then analysed using an active surface method which created output images reformatted in planes perpendicular to the estimated cord centre line. These unfolded cervical cord images were co-registered into a common space; then smoothed binary cord masks and lesion masks underwent spatial statistic analysis (SPM8). Results: No cord atrophy was found in CIS patients versus HC, while PPMS had significant cord atrophy. Clusters of cord atrophy were found in BMS versus RRMS, and in SPMS versus RRMS, BMS and PPMS patients, mainly involving the posterior and lateral cord segments. Cord lesion probability maps showed a significantly greater likelihood of abnormalities in RRMS, PPMS and SPMS than in CIS and BMS patients. The spatial distributions of cord atrophy and cord lesions were not correlated. In progressive MS, regional cord atrophy was correlated with clinical disability and impairment in the pyramidal system. Conclusions: Voxel-based assessment of cervical cord damage is feasible and may contribute to a better characterisation of the clinical heterogeneity of MS patients.