Cervical Cord Cross-sectional Area Research Articles

Association of Mean Upper Cervical Spinal Cord Cross-Sectional Area With Cerebral Small Vessel Disease: A Community-Based Cohort Study.

The purpose of this study was to investigate the association between the mean upper cervical spinal cord cross-sectional area (MUCCA) and the risk and severity of cerebral small vessel disease (CSVD). Community-dwelling residents in Lishui City, China, from the cross-sectional survey in the PRECISE cohort study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) conducted from 2017 to 2019. We included 1644 of 3067 community-dwelling adults in the PRECISE study after excluding those with incorrect, incomplete, insufficient, or missing clinical or imaging data. Total and modified total CSVD scores, as well as magnetic resonance imaging features, including white matter hyperintensity, lacunes, cerebral microbleeds, enlarged perivascular spaces, and brain atrophy, were assessed at the baseline. The Spinal Cord Toolbox was used to measure the upper cervical spinal cord cross-sectional area of the C1 to C3 segments of the spinal cord and its average value was taken as MUCCA. Participants were divided into 4 groups according to quartiles of MUCCA. Associations were analyzed using linear regression models adjusted for age, sex, current smoking and drinking, medical history, intracranial volume, and total cortical volume. The means±SD age of the participants was 61.4±6.5 years, and 635 of 1644 participants (38.6%) were men. The MUCCA was smaller in patients with CSVD than those without CSVD. Using the total CSVD score as a criterion, the MUCCA was 61.78±6.12 cm2 in 504 of 1644 participants with CSVD and 62.74±5.94 cm2 in 1140 of 1644 participants without CSVD. Using the modified total CSVD score, the MUCCA was 61.81±6.04 cm2 in 699 of 1644 participants with CSVD and 62.91±5.94 cm2 in 945 of 1644 without CSVD. There were statistical differences between the 2 groups after adjusting for covariates in 3 models. The MUCCA was negatively associated with the total and modified total CSVD scores (adjusted β value, -0.009 [95% CI, -0.01 to -0.003] and -0.007 [95% CI, -0.01 to -0.0006]) after adjustment for covariates. Furthermore, the MUCCA was negatively associated with the white matter hyperintensity burden (adjusted β value, -0.01 [95% CI, -0.02 to -0.003]), enlarged perivascular spaces in the basal ganglia (adjusted β value, -0.005 [95% CI, -0.009 to -0.001]), lacunes (adjusted β value, -0.004 [95% CI, -0.007 to -0.0007]), and brain atrophy (adjusted β value, -0.009 [95% CI, -0.01 to -0.004]). The MUCCA and CSVD were correlated. Spinal cord atrophy may serve as an imaging marker for CSVD; thus, small vessel disease may involve the spinal cord in addition to being intracranial.

MRI assessment of cervical spinal cord cross-sectional area in patients with multiple sclerosis.

Spinal cord abnormalities including cervical cord atrophy are common in multiple sclerosis (MS). This study aimed to assess the cervical spinal cord cross-sectional area (CSA) using magnetic resonance imaging (MRI) in MS patients. Sixty participants were enrolled in this study (16 male and 44 female), 30 patients with MS, diagnosed according to the revised McDonald criteria, and 30 apparently healthy individuals as the control group. CSA of the spinal cord was measured on axial T2-weighted images of the cervical MRI studies from C2 to C7 vertebral levels. There was a significant difference between MS patients and the control group in mean CSA at a different level. The mean CSA at C2, in MS cases, was significantly lower than controls (67.7 ± 9.4 mm2 vs. 81.3 ± 4.6 mm2). Similarly, the mean CSA at C7 (64.4 ± 9.9 mm2) and average C2-7 (68 ± 9.1 mm2) of MS cases were significantly lower than the control. There was a strong inverse correlation between mean cervical cord CSA and duration of the disease and disability score. The reduction in cervical cord CSA was more prominent in patients with secondary progressive MS. There was no significant difference regarding age, gender, type of treatment, or the number of cervical cord lesions. The mean CSA was significantly lower in patients with MS than in the control group and was lesser in progressive types. Patients with a longer duration of MS and a high disability score tend to have smaller CSA.

Shared imaging markers of fatigue across multiple sclerosis, aquaporin-4 antibody neuromyelitis optica spectrum disorder and MOG antibody disease.

Fatigue is frequently reported by patients with multiple sclerosis, aquaporin-4-antibody neuromyelitis optica spectrum disorder and myelin-oligodendrocyte-glycoprotein antibody disease; thus they could share a similar pathophysiological mechanism. In this cross-sectional cohort study, we assessed the association of fatigue with resting-state functional MRI, diffusion and structural imaging measures across these three disorders. Sixteen patients with multiple sclerosis, 17 with aquaporin-4-antibody neuromyelitis optica spectrum disorder and 17 with myelin-oligodendrocyte-glycoprotein antibody disease assessed, outside of relapses, at the Oxford Neuromyelitis Optica Service underwent Modified Fatigue Impact Scale, Hospital Anxiety and Depression Scale and Expanded Disability Status Scale scoring. A 3T brain and spinal cord MRI was used to derive cortical, deep grey and white matter volumetrics, lesions volume, fractional anisotropy, brain functional connectivity metrics, cervical spinal cord cross-sectional area, spinal cord magnetic transfer ratio and average functional connectivity between the ventral and the dorsal horns of the cervical cord. Linear relationships between MRI measures and total-, cognitive- and physical-fatigue scores were assessed. All analyses were adjusted for correlated clinical regressors. No significant differences in baseline clinical characteristics, fatigue, depression and anxiety questionnaires and disability measures were seen across the three diseases, except for older age in patients with aquaporin-4-antibody neuromyelitis optica spectrum disorder (P = 0.0005). In the total cohort, median total-fatigue score was 35.5 (range 3-72), and 42% of patients were clinically fatigued. A positive correlation existed between the total-fatigue score and functional connectivity of the executive/fronto-temporal network in the in left middle temporal gyrus (P = 0.033) and between the physical-fatigue score and functional connectivity of the sensory-motor network (P = 0.032) in both pre- and post-central gyri. A negative relationship was found between the total-fatigue score and functional connectivity of the salience network (P = 0.023) and of the left fronto-parietal network (P = 0.026) in the right supramarginal gyrus and left superior parietal lobe. No clear relationship between fatigue subscores and the average functional connectivity of the spinal cord was found. Cognitive-fatigue scores were positively associated with white matter lesion volume (P = 0.018) and negatively associated with white matter fractional anisotropy (P = 0.032). Structural, diffusion and functional connectivity alterations were not influenced by the disease group. Functional and structural imaging metrics associated with fatigue relate to brain rather than spinal cord abnormalities. Salience and sensory-motor networks alterations in relation to fatigue might indicate a disconnection between the perception of the interior body state and activity and the actual behavioural responses and performances (reversible or irreversible). Future research should focus on functional rehabilitative strategies.

Progressive Spinal Cord Degeneration in Friedreich's Ataxia: Results from ENIGMA-Ataxia.

Spinal cord damage is a hallmark of Friedreich's ataxia (FRDA), but its progression and clinical correlates remain unclear. The objective of this study was to perform a characterization of cervical spinal cord structural damage in a large multisite FRDA cohort. We performed a cross-sectional analysis of cervical spinal cord (C1-C4) cross-sectional area (CSA) and eccentricity using magnetic resonance imaging data from eight sites within the ENIGMA-Ataxia initiative, including 256 individuals with FRDA and 223 age- and sex-matched control subjects. Correlations and subgroup analyses within the FRDA cohort were undertaken based on disease duration, ataxia severity, and onset age. Individuals with FRDA, relative to control subjects, had significantly reduced CSA at all examined levels, with large effect sizes (d> 2.1) and significant correlations with disease severity (r< -0.4). Similarly, we found significantly increased eccentricity (d> 1.2), but without significant clinical correlations. Subgroup analyses showed that CSA and eccentricity are abnormal at all disease stages. However, although CSA appears to decrease progressively, eccentricity remains stable over time. Previous research has shown that increased eccentricity reflects dorsal column (DC) damage, while decreased CSA reflects either DC or corticospinal tract (CST) damage, or both. Hence our data support the hypothesis that damage to the DC and damage to CST follow distinct courses in FRDA: developmental abnormalities likely define the DC, while CST alterations may be both developmental and degenerative. These results provide new insights about FRDA pathogenesis and indicate that CSA of the cervical spinal cord should be investigated further as a potential biomarker of disease progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Quantification of Cervical Cord Cross-Sectional Area: Which Acquisition, Vertebra Level, and Analysis Software? A Multicenter Repeatability Study on a Traveling Healthy Volunteer.

Background: Considerable spinal cord (SC) atrophy occurs in multiple sclerosis (MS). While MRI-based techniques for SC cross-sectional area (CSA) quantification have improved over time, there is no common agreement on whether to measure at single vertebral levels or across larger regions and whether upper SC CSA can be reliably measured from brain images.Aim: To compare in a multicenter setting three CSA measurement methods in terms of repeatability at different anatomical levels. To analyze the agreement between measurements performed on the cervical cord and on brain MRI.Method: One healthy volunteer was scanned three times on the same day in six sites (three scanner vendors) using a 3T MRI protocol including sagittal 3D T1-weighted imaging of the brain (covering the upper cervical cord) and of the SC. Images were analyzed using two semiautomated methods [NeuroQLab (NQL) and the Active Surface Model (ASM)] and the fully automated Spinal Cord Toolbox (SCT) on different vertebral levels (C1–C2; C2/3) on SC and brain images and the entire cervical cord (C1–C7) on SC images only.Results: CSA estimates were significantly smaller using SCT compared to NQL and ASM (p < 0.001), regardless of the cord level. Inter-scanner repeatability was best in C1–C7: coefficients of variation for NQL, ASM, and SCT: 0.4, 0.6, and 1.0%, respectively. CSAs estimated in brain MRI were slightly lower than in SC MRI (all p ≤ 0.006 at the C1–C2 level). Despite protocol harmonization between the centers with regard to image resolution and use of high-contrast 3D T1-weighted sequences, the variability of CSA was partly scanner dependent probably due to differences in scanner geometry, coil design, and details of the MRI parameter settings.Conclusion: For CSA quantification, dedicated isotropic SC MRI should be acquired, which yielded best repeatability in the entire cervical cord. In the upper part of the cervical cord, use of brain MRI scans entailed only a minor loss of CSA repeatability compared to SC MRI. Due to systematic differences between scanners and the CSA quantification software, both should be kept constant within a study. The MRI dataset of this study is available publicly to test new analysis approaches.

Quantitative spinal cord MRI in MOG-antibody disease, neuromyelitis optica and multiple sclerosis.

Spinal cord involvement is a hallmark feature of multiple sclerosis, neuromyelitis optica with AQP4 antibodies and MOG-antibody disease. In this cross-sectional study we use quantitative spinal cord MRI to better understand these conditions, differentiate them and associate with relevant clinical outcomes. Eighty participants (20 in each disease group and 20 matched healthy volunteers) underwent spinal cord MRI (cervical cord: 3D T1, 3D T2, diffusion tensor imaging and magnetization transfer ratio; thoracic cord: 3D T2), together with disability, pain and fatigue scoring. All participants had documented spinal cord involvement and were at least 6 months post an acute event. MRI scans were analysed using publicly available software. Those with AQP4-antibody disease showed a significant reduction in cervical cord cross-sectional area (P = 0.038), thoracic cord cross-sectional area (P = 0.043), cervical cord grey matter (P = 0.011), magnetization transfer ratio (P ≤ 0.001), fractional anisotropy (P = 0.004) and increased mean diffusivity (P = 0.008). Those with multiple sclerosis showed significantly increased mean diffusivity (P = 0.001) and reduced fractional anisotropy (P = 0.013), grey matter volume (P = 0.002) and magnetization transfer ratio (P = 0.011). In AQP4-antibody disease the damage was localized to areas of the cord involved in the acute attack. In multiple sclerosis this relationship with lesions was absent. MOG-antibody disease did not show significant differences to healthy volunteers in any modality. However, when considering only areas involved at the time of the acute attack, a reduction in grey matter volume was found (P = 0.023). This suggests a predominant central grey matter component to MOG-antibody myelitis, which we hypothesize could be partially responsible for the significant residual sphincter dysfunction. Those with relapsing MOG-antibody disease showed a reduction in cord cross-sectional area compared to those with monophasic disease, even when relapses occurred elsewhere (P = 0.012). This suggests that relapsing MOG-antibody disease is a more severe phenotype. We then applied a principal component analysis, followed by an orthogonal partial least squares analysis. MOG-antibody disease was discriminated from both AQP4-antibody disease and multiple sclerosis with moderate predictive values. Finally, we assessed the clinical relevance of these metrics using a multiple regression model. Cervical cord cross-sectional area associated with disability scores (B = -0.07, P = 0.0440, R2 = 0.20) and cervical cord spinothalamic tract fractional anisotropy associated with pain scores (B = -19.57, P = 0.016, R2 = 0.55). No spinal cord metric captured fatigue. This work contributes to our understanding of myelitis in these conditions and highlights the clinical relevance of quantitative spinal cord MRI.

MRI Measurement of Upper Cervical Spinal Cord Cross-Sectional Area in Children.

Neurological and neurodegenerative diseases can affect the spinal cord (SC) of pediatric patients. Magnetic resonance imaging (MRI) allows for in vivo quantification of SC atrophy via cross-sectional area (CSA). The study of CSA values in the general population is important to disentangle disease-related changes from intersubject variability. This study aimed at providing normative values for cervical CSA in children, extending our previous work performed with adults. Seventy-eight children (age 7-17 years) were selected from a Developmental Dyslexia study. All subjects underwent a 3T brain MRI session and any incidental findings were reported on the scans. A sagittal 1 mm3 3-dimensional T1 -weighted brain acquisition extended to the upper cervical cord was used to measure CSA at C2-C3, as well as spinal canal area and skull volume (V-scale). These three metrics were linearly fitted as a function of age to extract trends and percentage annual changes. Sex differences of CSA were assessed using least squares regression analyses, adjusting for age. We tested normalization strategies proven to be effective in reducing the intersubject variability of adults' CSA. CSA changed as a function of age at a faster rate when compared with skull volume (CSA: 1.82% increase, V-scale: .60% reduction). Sex had a statistically significant effect on CSA. Normalization methods based on canal area and skull volume reduced the CSA intersubject variability up to 16.84%. We present CSA normative values in a large cohort of children, reporting on sources of intersubject variability and how to reduce them applying normalization methods previously developed.

Prospective Follow-up of Intramedullary Slitlike Cavities: A Consecutive Series of 48 Patients.

Object: Predicting whether intramedullary slitlike cavity (SC) will worsen over time or remain stable is an outstanding clinical challenge. The aim of this study was to identify early features of SC (clinical and magnetic resonance imaging [MRI] findings).Methods: We prospectively included all patients referred to our institution following the discovery of a SC and divided them in two groups: typical SC (defined as a cavity spanning fewer than three vertebrae, not enlarging the spinal cord, and located at the midline between the anterior third and posterior two-thirds of the spinal cord) or atypical SC (all others). Clinical evolution and changes in MRI features were evaluated during follow-up. In some patients, diffusion tensor imaging was performed and cervical cord cross-sectional area was analyzed.Results: A total of 48 consecutive patients were included in the study. The mean follow-up was 58 months. Of the seven patients presenting with deficits at first consultation, two worsened and five remained stable. Of the 41 patients without deficits, seven worsened and 34 remained stable. None of the patients developed severe motor deficits or experienced enlargement of the cavity; 7% of patients who presented with typical SC worsened compared with 35% with atypical SC. The negative predictive value was 0.93 (P = 0.02).Conclusion: Most patients remained stable and a subset of patients developed minor motor deficits. For clinical management, we propose surveillance of patients with a typical SC and close follow-up of those with an atypical SC and/or presenting with deficits.

Technology-enabled comprehensive characterization of multiple sclerosis in clinical practice

BackgroundObjective and longitudinal measurements of disability in patients with multiple sclerosis (MS) are desired in order to monitor disease status and response to disease-modifying and symptomatic therapies. Technology-enabled comprehensive assessment of MS patients, including neuroperformance tests (NPTs), patient-reported outcome measures (PROMs), and MRI, is incorporated into clinical care at our center. The relationships of each NPT with PROMs and MRI measures in a real-world setting are incompletely studied, particularly in larger datasets. ObjectivesTo demonstrate the utility of comprehensive neurological assessment and determine the association between NPTs, PROMs, and quantitative MRI measures in a large MS clinical cohort. MethodsNPTs (processing speed [PST], contrast sensitivity [CST], manual dexterity [MDT], and walking speed [WST]) and physical disability-related PROMs (Quality of Life in Neurological Disorders [Neuro-QoL], Patient Determined Disease Steps [PDDS], and Patient-Reported Outcomes Measurement Information System Global-10 [PROMIS-10] physical) were collected as part of routine clinical care. Fully-automated MRI analysis calculated T2-lesion volume (T2LV), whole brain fraction (WBF), thalamic volume (TV), and cervical spinal cord cross-sectional area (CA) for brain MRIs completed within 3 months of a clinic visit during which NPTs and PROMs were assessed. Spearman's rank correlation coefficients evaluated the cross-sectional associations of NPTs with PROMs and MRI measures. Linear regression was utilized to determine which combination of clinical characteristics, patient demographics, MRI measures, and PROMs best cross-sectionally explained each NPT result. Results997 unique patients (age 47.7 ± 11.4 years, 71.8% female) who underwent assessments over a 2-year period were included. Correlations among NPTs and PROMs were moderate. PST correlations were strongest for Neuro-QoL upper extremity (NQ-UE) (Spearman's rho = 0.43) and lower extremity (NQ-LE) (0.47). CST correlations were strongest for NQ-UE (0.33), NQ-LE (0.36), and PDDS (-0.31). MDT correlations were strongest for NQ-UE (-0.53), NQ-LE (-0.54), and PDDS (0.53). WST correlations were strongest for PDDS (0.64) and NQ-LE (-0.65). NPTs also had moderate correlations with MRI metrics, the strongest of which were observed with PST (with T2LV (-0.44) and WBF (0.49)). Spearman's rho for other NPT-MRI correlations ranged from 0.23 to 0.36. Linear regression identified age, disease duration, PROMIS-10 physical, NQ-UE, NQ-LE, T2LV and WBF as significant cross-sectional explanatory variables for PST (adjusted R2=0.46). For CST, significant variables included age and NQ-LE (adjusted R2 = 0.30). For MDT, significant variables included PDDS, PROMIS-10 physical, NQ-UE, NQ-LE, T2LV, and WBF (adjusted R2=0.37). For WST, significant variables included sex, PDDS, NQ-LE, T2LV, and CA (adjusted R2=0.39). ConclusionsImpaired performance on NPTs correlated with worse physical disability-related PROMs and MRI disease severity, but the strongest cross-sectional explanatory variables for each NPT component varied. This study supports the use of comprehensive, objective quantification of MS status in clinical and research settings. Future longitudinal analyses can determine predictors of treatment response and disability worsening.

Single scan quantitative gradient recalled echo MRI for evaluation of tissue damage in lesions and normal appearing gray and white matter in multiple sclerosis.

Multiple sclerosis (MS) is a chronic disease affecting the human central nervous system (CNS) and leading to neurologic disability. Although conventional MRI techniques can readily detect focal white matter (WM) lesions, it remains challenging to quantify tissue damage in normal-appearing gray matter (GM) and WM. To demonstrate that a new MRI biomarker, R2t*, can provide quantitative analysis of tissue damage across the brain in MS patients in a single scan. Prospective. Forty-four MS patients and 19 healthy controls (HC). 3T, quantitative gradient-recalled-echo (qGRE), Magnetization-prepared rapid gradient-echo, fluid-attenuated inversion recovery. Severity of tissue damage was assessed by reduced R2t*. Tissue atrophy was assessed by cortical thickness and cervical spinal cord cross-sectional area (CSA). Multiple Sclerosis Functional Composite was used for clinical assessment. R2t* in cortical GM was more sensitive to MS damage than cortical atrophy. Using more than two standard deviations (SD) reduction versus age-matched HC as the cutoff, 48% of MS patients showed lower R2t*, versus only 9% with lower cortical thickness. Significant correlations between severities of tissue injury were identified among 1) upper cervical cord and several cortical regions, including motor cortex (P < 0.001), and 2) adjacent regions of GM and subcortical WM (P < 0.001). R2t*-defined tissue cellular damage in cortical GM was greater relative to adjacent WM. Reductions in cortical R2t* correlated with cognitive impairment (P < 0.01). Motor-related clinical signs correlated most with cervical cord CSA (P < 0.001). Reductions in R2t* within cortical GM was more sensitive to tissue damage than atrophy, potentially allowing a reduced sample size in clinical trials. R2t* together with structural morphometry suggested topographic patterns of regions showing correlated tissue damage throughout the brain and the cervical spinal cord of MS patients. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:487-498.

Spinal Cord Atrophy in Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Spinal cord atrophy (SCA) is an important emerging outcome measure in multiple sclerosis (MS); however, there is limited consensus on the magnitude and rate of atrophy. The objective of this study was to synthesize the available data on measures of SCA in MS. Using published guidelines, relevant literature databases were searched between 1977 and 2017 for case-control or cohort studies reporting a quantitative measure of SCA in MS patients. Random-effects models pooled cross-sectional measures and longitudinal rates of SCA in MS and healthy controls (HCs). Student's t-test assessed differences between pooled measures in patient subgroups. Heterogeneity was assessed using DerSimonian and Laird's Q-test and the I 2 -index. A total of 1,465 studies were retrieved including 94 that met inclusion and exclusion criteria. Pooled estimates of mean cervical spinal cord (SC) cross-sectional area (CSA) in all MS patients, relapsing-remitting MS (RRMS), all progressive MS, secondary progressive MS (SPMS), primary-progressive MS (PPMS), and HC were: 73.07 mm2 (95% CI [71.52-74.62]), 78.88 mm2 (95% CI [76.92-80.85]), 69.72 mm2 (95% CI [67.96-71.48]), 68.55 mm2 (95% CI [65.43-71.66]), 70.98 mm2 (95% CI [68.78-73.19]), and 80.87 mm2 (95% C I [78.70-83.04]), respectively. Pooled SC-CSA was greater in HC versus MS (P < .001) and RRMS versus progressive MS (P < .001). SCA showed moderate correlations with global disability in cross-sectional studies (r-value with disability score range [-.75 to -.22]). In longitudinal studies, the pooled annual rate of SCA was 1.78%/year (95%CI [1.28-2.27]). The SC is atrophied in MS. The magnitude of SCA is greater in progressive versus relapsing forms and correlates with clinical disability. The pooled estimate of annual rate of SCA is greater than reported rates of brain atrophy in MS. These results demonstrate that SCA is highly relevant as an imaging outcome in MS clinical trials.

Spinal cord grey matter segmentation challenge

An important image processing step in spinal cord magnetic resonance imaging is the ability to reliably and accurately segment grey and white matter for tissue specific analysis. There are several semi- or fully-automated segmentation methods for cervical cord cross-sectional area measurement with an excellent performance close or equal to the manual segmentation. However, grey matter segmentation is still challenging due to small cross-sectional size and shape, and active research is being conducted by several groups around the world in this field. Therefore a grey matter spinal cord segmentation challenge was organised to test different capabilities of various methods using the same multi-centre and multi-vendor dataset acquired with distinct 3D gradient-echo sequences. This challenge aimed to characterize the state-of-the-art in the field as well as identifying new opportunities for future improvements. Six different spinal cord grey matter segmentation methods developed independently by various research groups across the world and their performance were compared to manual segmentation outcomes, the present gold-standard. All algorithms provided good overall results for detecting the grey matter butterfly, albeit with variable performance in certain quality-of-segmentation metrics. The data have been made publicly available and the challenge web site remains open to new submissions. No modifications were introduced to any of the presented methods as a result of this challenge for the purposes of this publication.

Longitudinal evaluation of cerebral and spinal cord damage in Amyotrophic Lateral Sclerosis.

ObjectiveTo evaluate MRI-based parameters as biomarkers of Amyotrophic Lateral Sclerosis (ALS) progression.MethodsTwenty-seven patients and 27 controls performed two clinical and MRI acquisitions 8 months apart. ALSFRS-R scale was used to quantify disease severity at both time points. Multimodal analyses of MRI included cortical thickness measurements (FreeSurfer software), analysis of white matter integrity using diffusion-tensor imaging (tract-based spatial statistics-TBSS) and measurement of cervical spinal cord cross-sectional area (SpineSeg software). All analyses were corrected for multiple comparisons. The standardized response mean (SRM = mean score change / standard deviation of score change) was calculated for all methods herein employed and used for comparison purposes.ResultsThere were 18 men and mean age at first examination was 51.9 years. Mean ALSFRS-R scores at baseline and follow-up were 34.0 and 29.0, respectively. There was no region with progressive cortical thinning, but there was significant brainstem volumetric reduction (p = 0.001). TBSS analyses revealed progressive increase of AD (axial diffusivity) and MD (mean diffusivity) at the corpus callosum (p < 0.05), whereas SpineSeg showed progressive cord area reduction (p = 0.002). Cervical spinal cord cross-sectional area reduction was the only MRI parameter that correlated with ALSFRS-R change (r = 0.309, p = 0.038). SRM for ALSFRS-R was 0.95, for cord area 0.95, for corpus callosum AD 0.62 and MD 0.65, and for brainstem volume 0.002.ConclusionsStructural MRI is able to detect short term longitudinal changes in ALS. Cervical spinal cord morphometry is a promising neuroimaging marker to assess ALS course.

Association of asymptomatic spinal cord lesions and atrophy with disability 5 years after a clinically isolated syndrome

Background: Spinal cord pathology is an important substrate for long-term disability in multiple sclerosis (MS). Objective: To investigate longitudinal changes in spinal cord lesions and atrophy in patients with a non-spinal clinically isolated syndrome (CIS), and how they relate to the development of disability. Methods: In all, 131 patients with a non-spinal CIS had brain and spinal cord imaging at the time of CIS and approximately 5 years later (median: 5.2 years, range: 3.0–7.9 years). Brain magnetic resonance imaging (MRI) measures consisted of T2-hyperintense and T1-hypointense lesion loads plus brain atrophy. Spinal cord MRI measures consisted of lesion number and the upper cervical cord cross-sectional area (UCCA). Disability was measured using the Expanded Disability Status Scale (EDSS). Multiple linear regression was used to identify independent predictors of disability after 5 years. Results: During follow-up, 93 (71%) patients were diagnosed with MS. Baseline spinal cord lesion number, change in cord lesion number and change in UCCA were independently associated with EDSS (R2 = 0.53) at follow-up. Including brain T2 lesion load and brain atrophy only modestly increased the predictive power of the model (R2 = 0.64). Conclusion: Asymptomatic spinal cord lesions and spinal cord atrophy contribute to the development of MS-related disability over the first 5 years after a non-spinal CIS.

A longitudinal MRI study of cervical cord atrophy in multiple sclerosis.

There is an urgent need of fast and accurate methods for the longitudinal quantification of cervical cord atrophy in multiple sclerosis (MS). Aim of this study was to compare a new semi-automatic method [the active surface (AS) method] with an existing cord segmentation method (the Losseff method) to measure cervical cord atrophy progression in MS patients. Using the AS and Losseff methods, normalized cervical cord cross-sectional area (CSA) was compared between 35 MS patients and 9 healthy controls (HC) at baseline and after 2.3 years of follow-up. Correlations with clinical/conventional MRI variables and a power calculation study were also performed. At follow-up, the Losseff method detected a 1 % CSA increase in HC and a 3.5 % decrease in MS patients (p = 0.01), while the AS method detected a 0.1 % decrease in HC and 3 % decrease in MS patients (p = 0.02). The AS method was more sensitive to associations with disability/conventional MRI variables and also provided lower numbers of subjects per arm compared to the Losseff method in a putative clinical trial scenario. Cord AS CSA measurements were more sensitive to longitudinal changes in MS patients than Losseff measurements. Cord AS CSA might be a valuable surrogate outcome measure for monitoring neuroprotection in MS.

Spinal cord atrophy in multiple sclerosis and relationship with disability across clinical phenotypes

BackgroundSeveral studies have shown a relationship between spinal cord atrophy and clinical disability in patients with multiple sclerosis (MS). ObjectivesWe examined the correlation between cervical cord cross-sectional area at the C2 vertebral level (CSA-C2) and the expanded disability status scale (EDSS) in patients with relapsing-remitting and progressive forms of MS. The latter included both secondary and primary progressive MS patients. MethodsA total of 150 patients with MS were recruited from the Wayne State University MS clinic. Ninety-three had relapsing-remitting MS and 57 patients had progressive MS. MRI scan of the cervical cord was obtained for each patient. Correlation studies and multivariate regression analysis was performed, blinded to clinical status. ResultsThe mean age was 41.3 year old, 64.6% were women, mean disease duration was 11.2 years, CSA-C2 was 80.2mm2 and mean EDSS was 3.8. There was significant correlation between CSA-C2 and EDSS (r −0.75, p<0.0001). Sub-group analysis showed CSA-C2 was 68.6mm2 and 87.3mm2 in the progressive and relapsing-remitting groups, respectively (p<0.0001). Multivariable regression showed that CSA-C2 was a significant predictor of disability independent of disease duration, and phenotype. ConclusionsOur study demonstrates that CSA-C2 has a strong correlation with clinical disability in both RRMS and progressive MS. Greater spinal cord atrophy was seen in patients with progressive than relapsing-remitting MS. CSA-C2, disease duration, and phenotype are independent predictors of disability.

Atrophy and structural variability of the upper cervical cord in early multiple sclerosis

Background: Despite agreement about spinal cord atrophy in progressive forms of multiple sclerosis (MS), data on clinically isolated syndrome (CIS) and relapsing–remitting MS (RRMS) are conflicting. Objective: To determine the onset of spinal cord atrophy in the disease course of MS. Methods: Structural brain magnetic resonance imaging (MRI) was acquired from 267 patients with CIS (85) or RRMS (182) and 64 healthy controls (HCs). The upper cervical cord cross-sectional area (UCCA) was determined at the level of C2/C3 by a segmentation tool and adjusted for focal MS lesions. The coefficient of variation (CV) was calculated from all measurements between C2/C3 and 13 mm above as a measure of structural variability. Results: Compared to HCs (76.1±6.9 mm2), UCCA was significantly reduced in CIS patients (73.5±5.8 mm2, p=0.018) and RRMS patients (72.4±7.0 mm2, p<0.001). Structural variability was higher in patients than in HCs, particularly but not exclusively in case of focal lesions (mean CV HCs/patients without/with lesions: 2.13%/2.55%/3.32%, all p-values<0.007). UCCA and CV correlated with Expanded Disability Status Scale (EDSS) scores (r =−0.131/0.192, p=0.044/<0.001) and disease duration (r=−0.134/0.300, p=0.039/< 0.001). CV additionally correlated with hand and arm function (r=0.180, p=0.014). Conclusion: In MS, cervical cord atrophy already occurs in CIS. In early stages, structural variability may be a more meaningful marker of spinal cord pathology than atrophy.

Cervical spinal cord volume loss is related to clinical disability progression in multiple sclerosis

ObjectiveTo examine the temporal evolution of spinal cord (SC) atrophy in multiple sclerosis (MS), and its association with clinical progression in a large MS cohort.MethodsA total of 352 patients from...

Relevance of Spinal Cord Abnormalities to Clinical Disability in Multiple Sclerosis: MR Imaging Findings in a Large Cohort of Patients

To determine whether spinal cord atrophy differs among disease subtypes in multiple sclerosis (MS) and whether it offers diagnostic and clinical correlative information beyond that provided by other magnetic resonance (MR) imaging markers. The institutional review board approved the study; all subjects gave written informed consent. Upper cervical cord cross-sectional area (UCCA), brain and spinal cord lesion loads, and brain atrophy were measured in 440 patients with MS (311 with relapsing-remitting [RR] MS, 92 with secondary-progressive [SP] MS, and 37 with primary-progressive [PP] MS) studied in two centers. Disability was scored with the Expanded Disability Status Scale (EDSS), the timed 25-foot walk test (TWT), and the nine-hole peg test. UCCA was compared between groups with the Mann-Whitney U test. Correlations were assessed with the Spearman ρ test. Multivariate associations between UCCA and clinical and other MR imaging parameters, including number of hypointense brain lesions on T1-weighted MR images, presence of diffuse abnormalities, and number of involved segments in the spinal cord, were assessed by using multiple linear regression, adjusted for study center site. The UCCA in patients with SP MS (median, 79 mm(2); interquartile range, 72.4-84.9 mm(2)) and PP MS (median, 77.3 mm(2); interquartile range, 69-82.5 mm(2)) was significantly smaller (P < .001) than that in patients with RR MS (median, 84 mm(2); interquartile range, 78.7-89.3 mm(2)). UCCA was inversely correlated with EDSS score, TWT, and nine-hole peg test findings (ρ ≤ -0.29, P < .001 for all comparisons). UCCA, number of hypointense brain lesions on T1-weighted MR images, presence of diffuse abnormalities, and number of involved segments in the spinal cord were found to be significant explanatory factors for clinical disability (R(2) = 0.564). The UCCA and the number of hypointense brain lesions on T1-weighted images were the strongest MR imaging parameters for explaining physical disability, as measured with the EDSS. Spinal cord abnormalities have a strong effect on clinical disability in MS. MR imaging-derived UCCA was found to be the most significant spinal cord parameter for explaining EDSS score.

Magnetic resonance imaging correlates of physical disability in relapse onset multiple sclerosis of long disease duration

Background: Understanding long-term disability in multiple sclerosis (MS) is a key goal of research; it is relevant to how we monitor and treat the disease. Objectives: The Magnetic Imaging in MS (MAGNIMS) collaborative group sought to determine the relationship of brain lesion load, and brain and spinal cord atrophy, with physical disability in patients with long-established MS. Methods: Patients had a magnetic resonance imaging (MRI) scan of their brain and spinal cord, from which we determined brain grey (GMF) and white matter (WMF) fractional volumes, upper cervical spinal cord cross-sectional area (UCCA) and brain T2-lesion volume (T2LV). We assessed patient disability using the Expanded Disability Status Scale (EDSS). We analysed associations between EDSS and MRI measures, using two regression models (dividing cohort by EDSS into two and four sub-groups). Results: In the binary model, UCCA (p < 0.01) and T2LV (p = 0.02) were independently associated with the requirement of a walking aid. In the four-category model UCCA (p < 0.01), T2LV (p = 0.02) and GMF (p = 0.04) were independently associated with disability. Conclusions: Long-term physical disability was independently linked with atrophy of the spinal cord and brain T2 lesion load, and less consistently, with brain grey matter atrophy. Combinations of spinal cord and brain MRI measures may be required to capture clinically-relevant information in people with MS of long disease duration.