Spinal Cord Cross-sectional Area Research Articles

Spinal cord involvement by atrophy and associations with disability are different between multiple sclerosis and neuromyelitis optica spectrum disorder.

The cervical and thoracic cross-sectional spinal cord area (CS-SCA) in multiple sclerosis (MS) correlates with disability, whilst such a correlation remains to be established in neuromyelitis optica spectrum disorder (NMOSD). Our aim was to clarify differences between MS and NMOSD in spinal cord segments where CS-SCA is associated with disability. The CS-SCA at C2/C3, C3/C4, T8/T9 and T9/T10 vertebral disc levels was measured in 140 MS patients (111 with relapsing-remitting MS and 29 with progressive MS) and 42 NMOSD patients with anti-aquaporin-4 immunoglobulin G. Disability was evaluated by Expanded Disability Status Scale (EDSS) scores. Multivariate associations between CS-SCA and disability were assessed by stepwise forward multiple linear regression. Thoracic CS-SCA was significantly smaller in NMOSD patients than in MS patients even after adjusting for age, sex and disease duration (P=0.002 at T8/T9), whilst there was no difference in cervical CS-SCA between the two diseases. Cervical and thoracic CS-SCA had a negative correlation with EDSS scores in MS patients (P<0.0001 at C3/C4 and P=0.0002 at T8/T9) whereas only thoracic CS-SCA correlated with EDSS scores in NMOSD patients (P=0.0006 at T8/T9). By multiple regression analyses, predictive factors for disability in MS were smaller cervical CS-SCA, progressive course, older age and a higher number of relapses, whilst those in NMOSD were smaller thoracic CS-SCA and older age. Thoracic CS-SCA is a useful predictive marker for disability in patients with NMOSD whilst cervical CS-SCA is associated with disability in patients with MS.

Mid-term clinical outcomes and radiological results of anterior cervical surgery for Hirayama disease

Objective To evaluate the effect of anterior cervical fusion or non-fusion surgery for the treatment of Hirayama disease. Methods The patients with Hirayama disease who underwent anterior cervical surgery in our hospital from July 2008 to December 2015 were retrospectively enrolled in this study. These cases were divided into two groups: fusion group (11 cases) and non-fusion group (12 cases). In fusion group, there were 9 males and 2 females, with an average age of 17.92±0.61 years (range, 15-29). In the non-fusion group, there were 10 males and 1 female, with an average age of 19.18±1.14 years (range, 15-23). Muscle strength, muscular atrophy, and the Michigan score for hand function were compared between the two groups preoperatively and postoperatively. The indexes such as arc cervical physiological curvature index, the maximum flexion angle, the maximal range of motion (ROM), flexion ROM of adjacent segments of lower cervical vertebra were measured from the X-ray of the two groups, and the cross-sectional area of spinal cord was measured and compared on neutral position MRI. Results There were no significant differences between the two groups in grip strength, preoperative hand function Michigan score, cervical physiological curvature index, the maximum flexion angle, the maximal ROM, flexion ROM of adjacent segments of lower cervical vertebra, and cross-sectional area of spinal cord on neutral position MRI (P>0.05). Patients in fusion group were followed up for 38-103 months with an average of 59.73±5.57 months, while patients in non-fusion group were followed up for 40-95 months with an average of 56.25±4.57 months. Clinical outcomes: At the last follow-up, the finger tremor and cold paralysis were alleviated in all patients, but the symptoms in fusion group and non-fusion group were not completely disappeared in 2 and 3 cases, respectively. The grip strength of fusion group (preoperative 17.14±6.09, postoperative 17.47±5.64) and the non-fusion group (preoperative 17.75±5.49, postoperative 17.40±4.58) were not significantly improved compared with preoperative (P>0.05). The Michigan score for hand function of fusion group (preoperative 10.27±0.41, postoperative 6.64±0.24) and the non-fusion group (preoperative 9.25± 0.35, postoperative 6.83±0.24) were significantly improved compared with preoperative (P 0.05). Radiological outcomes: The cervical physiological curvature index and cross-sectional area of the spinal cord of the two groups increased after operation, while the maximum flexion angle, the maximal ROM decreased. There was no significant difference in these indexes between the two groups postoperatively (P>0.05). The spinal cord had no compression on flexion MRI. The cross-sectional area of C4-C7 spinal cord in Neutral MRI were significantly increased at C6 and C7 levels in both groups. There was no significant difference in the cross-sectional area of C4-C7 spinal cord between the two groups postoperatively (P>0.05). Two cases of internal fixation loosening occurred in non-fusion group 3 years after the operation, while there were no cases of loosening in the fusion group. Conclusion Anterior cervical fusion or non-fusion surgery can limit excessive cervical kyphosis in patients with Hirayama disease, reduce atrophy of compressed cervical spinal cord, and alleviate the disease progress of muscular atrophy of the distal upper limb. It can be selected as a treatment method for Hirayama disease. However, there is a risk of internal fixation loosening in non-fusion cases, and also a risk of adjacent segment degeneration in fusion cases. The appropriate cases should be selected carefully for surgery. Key words: Cervical vertebrae; Spinal cord compression; Upper extremity; Muscular atrophy; Spinal fusion

Preoperative Clinical and Radiographic Variables Predict Postoperative C5 Palsy

Postoperative C5 palsy affects 8% of patients undergoing posterior cervical decompression. It is associated with a period functional disability that may exceed 12 months and increase direct care costs > $2000. All patients undergoing posterior cervical decompression at a single tertiary-care facility for degenerative conditions were evaluated for preoperative imaging, clinical presentation, surgical operation, and postoperative course. We sought to identify those variables predictive of postoperative C5 palsy. Of 221 included patients (mean age, 63 years; 54% male), 12.2% experienced C5 palsy. On univariate analysis, C5 palsy was associated with foraminal diameter (P= 0.0005), spinal cord cross-sectional area (P= 0.11), number of levels undergoing laminectomy (P= 0.14), and clinical presentation of dropping objects (P= 0.07), hand clumsiness (P= 0.13), or paresthesias in the upper extremities (P= 0.08). Foraminal diameter (odds ratio, 0.31 per mm increase; 95% confidence interval, 0.16-0.60; P < 0.001) and patient report of gait disturbance (odds ratio, 0.53; 95% confidence interval, 0.33-0.85; P= 0.008) were the only significant predictors on multivariate analysis. A foraminal diameter <2 mm had 2-fold greater odds of postoperative C5 palsy. A receiver operating curve for the multivariate logistic model had an associated C-statistic of 0.7818. The absolute error of this model was 9.3% on internal validation. Foraminal stenosis most strongly predicted postoperative C5 palsy. A proof-of-concept model incorporating foramen size, as well as clinical complaints of paresthesias, hand clumsiness, and gait abnormality, successfully predicts the occurrence of postoperative palsy with an overall accuracy of 78%.

Magnetic resonance imaging correlates of neuro-axonal pathology in the MS spinal cord.

In people with multiple sclerosis (MS), the spinal cord is the structure most commonly affected by clinically detectable pathology at presentation, and a key part of the central nervous system involved in chronic disease deterioration. Indices, such as the spinal cord cross-sectional area at the level C2 have been developed as tools to predict future disability, and-by inference-axonal loss. However, this and other histo-pathological correlates of spinal cord magnetic resonance imaging (MRI) changes in MS remain incompletely understood. In recent years, there has been a surge of interest in developing quantitative MRI tools to measure specific tissue features, including axonal density, myelin content, neurite density, and orientation, among others, with an emphasis on the spinal cord. Quantitative MRI techniques including T1 and T2 , magnetization transfer and a number of diffusion-derived indices have all been applied to MS spinal cord. Particularly diffusion-based MRI techniques combined with microscopic resolution achievable using high magnetic field scanners enable a new level of anatomical detail and quantification of indices that are clinically meaningful.

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.

Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters: P109. Effect of cervical deformity correction on stenosis, spinal canal and cord compression utilizing magnetic resonance and computed tomography imaging modalities

BACKGROUND CONTEXT Cervical deformity (CD), often degenerative in etiology, is typically accompanied by the onset of symptomatic spinal stenosis. It is hypothesized that causation of spinal canal and cord compressive forces is multifactorial, with reduction of compressive forces being a key driver of symptom alleviation. PURPOSE To quantify and assess the relationship between postoperative changes to sagittal alignment, canal or cord decompression, and symptom alleviation. STUDY DESIGN/SETTING Retrospective review of a prospective CD database. PATIENT SAMPLE Twenty-seven CD patients. OUTCOME MEASURES Stenotic Levels, Pavlov Ratio, Spinal Canal Cross-Sectional Area, Spinal Cord Cross-Sectional Area, mJOA scores, NSR Neck Pain scores. METHODS ConsecutiveCD patients (C2–C7 Cobb>10°, CL>10°, cSVA>4 cm, or CBVA>25°) undergoing multilevel fusion. Those with pre-operative magnetic resonance imagings (MRIs) and 1-year post-operative cervical MRI or CT scans were assessed for spinal canal and cord cross-sectional area, using dedicated imaging software at each interspace and body from C2–C7, and the apex of deformity[apex]. Stenotic vertebral levels were measured using Pavlov's method from C2 to C7: a ratio of canal to vertebral body RESULTS A total of 27 patients were included (61±10 years, 64.2%F, BMI: 29.6±8.0, CCI: 0.81±1.1). BL radiographic assessment: TS-CL: 34.0±17.2; Cervical Lordosis: −1.6±15.7; cSVA: 36.3±18.5; PI-LL: 0.12±19.3; Pelvic Tilt: 20.1±11.6; SVA: 0.94±71.6. Ames classification deformity descriptors: C: 57.7%, CT: 30.8%, T: 7.7%, S: 3.8%. Surgical approach included 7.4% anterior, 51.9% posterior, 40.7% combined; 23(79%) patients had decompression procedures, all patients had an osteotomy, and mean fusion length was 8.6±4.2 levels. Following surgical intervention, mean canal cross-sectional area (267.5 mm2 vs. 320.5 mm2, p=.025), apex canal cross-sectional area (240 mm2 vs. 301.3 mm2, p=.039), and apex cord cross-sectional area (60.6 mm2 vs. 70.1 mm2, p=.019) all increased (regardless of decompression procedure status). Decreased stenotic levels (4.11vs. 2.97, p=.003) and improved apex pavlov ratios (0.76vs. 0.91, p=.032) were also observed. Cervical kyphosis correction correlated with Δ in stenotic levels (rs: 0.664, p=.001), Δ in mean C2–C7 pavlov ratio (rs: 0.601, p=.004), and Δ in apex canal area (rs: 0.562, p=.024). TS-CL correction correlated with Δ in stenotic levels (rs: 0.751, p CONCLUSIONS Sagittal realignment was associated with reduction of symptomatic stenosis and cord compressive forces, regardless of decompression status. Stenotic level reduction was associated with improved mJOA scores, while alleviation of dynamic radial compressive forces at the apex of deformity significantly reduced patient neck pain.

Compression of Thoracic Spinal Cord with Decreased Cerebrospinal Fluid Space After Implantation of Paddle Lead Spinal Cord Stimulation at T9: A Three-Dimensional Myelographic Computed Tomography Study

To investigate the extent of spinal cord compression and cerebrospinal fluid (CSF) space after T9 paddle lead spinal cord stimulation (SCS) using three-dimensional myelographic computed tomography scans. Preoperative and postoperative three-dimensional myelographic computed tomography scans were performed in 15 patients with paddle lead SCS at T9 for neuropathic back and leg pain. Four axial levels between each row of the electrodes were selected and the cross-sectional areas of thecal sac and spinal cord, the width of anterior and posterior CSF space, and contact angle of the lead within T9 spinal canal were measured with 12-month pain relief assessment. The cross-sectional areas of thecal sac and spinal cord under each contact of paddle leads decreased significantly (23.89 ± 11.48% and 9.45 ± 4.80%; P < 0.05, respectively). The width of posterior CSF space decreased by 38.65 ± 20.97% and that of anterior CSF space showed a greater reduction by 59.09 ± 18.39% (P < 0.05). We achieved a mean pain relief of 45.49 ± 13.73% at 12-month follow-up and found a significant correlation with percentage reduction in the area of the spinal cord. Significant reduction in the cross-sectional area of spinal cord and anterior CSF space as well as thecal sac and posterior CSF space resulted in deformation of the spinal cord under paddle leads at T9 within 7 postoperative days. Close approximation to the dorsal column and the mass effect of paddle leads may determine the clinical outcome of paddle lead SCS and also raise safety concerns.

Does MR spectroscopy of normal-appearing cervical spinal cord in patients with multiple sclerosis have diagnostic value in assessing disease progression? A prospective comparative analysis

To clarify the role of magnetic resonance spectroscopy (MRS) in examining the normal-appearing cervical spinal cord of patients with multiple sclerosis (MS) to detect metabolite abnormalities in this disease and to assess its progression. Thirty-six patients with MS and 30 healthy controls were enrolled. Each patient was submitted to MRS performed using a 1.5 T magnetic resonance imaging (MRI) scanner. The spectra of total N-acetyl-aspartate (tNAA), choline (Cho), creatine (Cr), and myoinositol (M-Ins), as well as the metabolite ratios of tNAA/Cr, tNAA/Cho, Cho/Cr, and M-Ins/Cr of the two groups were measured and compared. The correlations between the metabolite concentrations, disease duration, and clinical disability (expanded disability status scale, EDSS) were further explored. Significantly lower tNAA and higher M-Ins were observed in MS patients than in health controls. The tNAA/Cr and tNAA/Cho ratios were significantly lower in MS patients than in healthy controls. In MS patients, the EDSS was correlated with the tNAA/Cr ratio. The spinal cord cross-sectional area was significantly smaller in MS patients than in healthy controls. Reduced tNAA and increased M-Ins are important, sensitive indices for differentiating between MS patients and healthy controls. In MS patients, before lesions appear, MRS of the spinal cord may provide crucial information for assessing disease progression.

Quantitative spinal cord MRI in radiologically isolated syndrome.

ObjectivesTo assess whether quantitative spinal cord MRI (SC-MRI) measures, including atrophy, and diffusion tensor imaging (DTI) and magnetization transfer imaging metrics were different in radiologically isolated syndrome (RIS) vs healthy controls (HCs).MethodsTwenty-four participants with RIS and 14 HCs underwent cervical SC-MRI on a 3T magnet. Manually segmented regions of interest circumscribing the spinal cord cross-sectional area (SC-CSA) between C3 and C4 were used to extract SC-CSA, fractional anisotropy, mean, perpendicular, and parallel diffusivity (MD, λ⊥, and λ||) and magnetization transfer ratio (MTR). Spinal cord (SC) lesions, SC gray matter (GM), and SC white matter (WM) areas were also manually segmented. Multivariable linear regression was performed to evaluate differences in SC-MRI measures in RIS vs HCs, while controlling for age and sex.ResultsIn this cross-sectional study of participants with RIS, 71% had lesions in the cervical SC. Of quantitative SC-MRI metrics, spinal cord MTR showed a trend toward being lower in RIS vs HCs (p = 0.06), and there was already evidence of brain atrophy (p = 0.05). There were no significant differences in SC-DTI metrics, GM, WM, or CSA between RIS and HCs.ConclusionThe SC demonstrates minimal microstructural changes suggestive of demyelination and inflammation in RIS. These findings are in contrast to established MS and raise the possibility that the SC may play an important role in triggering clinical symptomatology in MS. Prospective follow-up of this cohort will provide additional insights into the role the SC plays in the complex sequence of events related to MS disease initiation and progression.

Imaging spinal cord atrophy in progressive myelopathies: HTLV-I-associated neurological disease (HAM/TSP) and multiple sclerosis (MS).

Previous work measures spinal cord thinning in chronic progressive myelopathies, including human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). Quantitative measurements of spinal cord atrophy are important in fully characterizing these and other spinal cord diseases. We aimed to investigate patterns of spinal cord atrophy and correlations with clinical markers. Spinal cord cross-sectional area was measured in individuals (24 healthy controls [HCs], 17 asymptomatic carriers of HTLV-1 (AC), 47 HAM/TSP, 74 relapsing-remitting MS [RRMS], 17 secondary progressive MS [SPMS], and 40 primary progressive MS [PPMS]) from C1 to T10. Clinical disability scores, viral markers, and immunological parameters were obtained for patients and correlated with representative spinal cord cross-sectional area regions at the C2 to C3, C4 to C5, and T4 to T9 levels. In 2 HAM/TSP patients, spinal cord cross-sectional area was measured over 3 years. All spinal cord regions are thinner in HAM/TSP (56 mm2 [standard deviation, 10], 59 [10], 23 [5]) than in HC (76 [7], 83 [8], 38 [4]) and AC (71 [7], 78 [9], 36 [7]). SPMS (62 [9], 66 [9], 32 [6]) and PPMS (65 [11], 68 [10], 35 [7]) have thinner cervical cords than HC and RRMS (73 [9], 77 [10], 37 [6]). Clinical disability scores (Expanded Disability Status Scale [p = 0.009] and Instituto de Pesquisas de Cananeia [p = 0.03]) and CD8+ T-cell frequency (p = 0.04) correlate with T4 to T9 spinal cord cross-sectional area in HAM/TSP. Higher cerebrospinal fluid HTLV-1 proviral load (p = 0.01) was associated with thinner spinal cord cross-sectional area. Both HAM/TSP patients followed longitudinally showed thoracic thinning followed by cervical thinning. Group average spinal cord cross-sectional area in HAM/TSP and progressive MS show spinal cord atrophy. We further hypothesize in HAM/TSP that is possible that neuroglial loss from a thoracic inflammatory process results in anterograde and retrograde degeneration of axons, leading to the temporal progression of thoracic to cervical atrophy described here. Ann Neurol 2017;82:719-728.

Spinal cord atrophy as a primary outcome measure in phase II trials of progressive multiple sclerosis

Objectives: To measure the development of spinal cord (SC) atrophy over 1 year in patients with progressive multiple sclerosis (PMS) and determine the sample sizes required to demonstrate a reduction in spinal cord cross-sectional area (SC-CSA) as an outcome measure in clinical trials. Methods: In total, 44 PMS patients (26 primary progressive multiple sclerosis (PPMS), 18 secondary progressive multiple sclerosis (SPMS)) and 29 healthy controls (HCs) were studied at baseline and 12 months. SC-CSA was measured using the three-dimensional (3D) fast field echo sequences acquired at 3T and the active surface model. Multiple linear regressions were used to investigate changes in imaging measurements. Results: PPMS patients had shorter disease duration, lower Expanded Disability Status Scale (EDSS) and larger SC-CSA than SPMS patients. All patients together showed a significantly greater decrease in percentage SC-CSA change than HCs, which was driven by the PPMS. All patients deteriorated over 1 year, but no association was found between percentage SC-CSA change and clinical changes. The sample size per arm required to detect a 50% treatment effect over 1 year, at 80% power, was 57 for PPMS and 546 for SPMS. Conclusion: SC-CSA may become an outcome measure in trials of PPMS patients, when they are at an early stage of the disease, have moderate disability and modest SC atrophy.

Axonal loss in the multiple sclerosis spinal cord revisited.

Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss is considered a key substrate of disability. Clinically, chronic multiple sclerosis often presents as progressive myelopathy. Spinal cord cross‐sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed as an indirect index of axonal degeneration. However, the association between CSA and axonal loss, and their correlation with demyelination, have never been systematically investigated using human post mortem tissue. We extensively sampled spinal cords of seven women and six men with multiple sclerosis (mean disease duration= 29 years) and five healthy controls to quantify axonal density and its association with demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno‐stained for myelin basic protein and phosphorylated neurofilaments. Measurements included total CSA, areas of (i) lateral cortico‐spinal tracts, (ii) gray matter, (iii) white matter, (iv) demyelination, and the number of axons within the lateral cortico‐spinal tracts. Linear mixed models were used to analyze relationships. In multiple sclerosis CSA reduction at cervical, thoracic and lumbar levels ranged between 19 and 24% with white (19–24%) and gray (17–21%) matter atrophy contributing equally across levels. Axonal density in multiple sclerosis was lower by 57–62% across all levels and affected all fibers regardless of diameter. Demyelination affected 24–48% of the gray matter, most extensively at the thoracic level, and 11–13% of the white matter, with no significant differences across levels. Disease duration was associated with reduced axonal density, however not with any area index. Significant association was detected between focal demyelination and decreased axonal density. In conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord. Spinal cord cross sectional area, reduced by about 20%, appears to be a poor predictor of axonal density.

Ultrasonographic assessment of the atlanto-occipital space in healthy Thoroughbred foals and Thoroughbred foals with neonatal maladjustment syndrome

Ultrasonography of the atlanto-occipital (AO) space may be useful as a non-invasive diagnostic tool in neonatal foals. The aims of the study were establish a range of values for ultrasonographic measurements of the AO space in healthy Thoroughbred foals and to compare these variables in healthy foals with foals diagnosed with neonatal maladjustment syndrome (NMS). Ultrasonography of the AO space was performed on 38 healthy Thoroughbred foals and 28 Thoroughbred foals with NMS≤4days of age. Transverse image spinal cord height (P=0.001), width (P<0.001) and spinal cord cross sectional area (P<0.001), and longitudinal image dorsoventral diameter of the ventral spinal artery, were significantly smaller in foals with NMS than in healthy foals. Ratios of spinal canal to cord width and cross sectional area were significantly smaller in healthy foals than in foals with NMS (P<0.001). Spinal canal variables were not significantly different between groups. Several ultrasonographic measurements of the AO space were significantly different between healthy foals and foals with NMS. Further investigation is warranted to investigate the clinical application of this technique.

MRI Signal Intensity Classification in Cervical Ossification of the Posterior Longitudinal Ligament: Predictor of Surgical Outcomes.

Prospective cohort study. To investigate whether classification of increased signal intensity (ISI) on magnetic resonance imaging (MRI) of spinal cord in patients with cervical ossification of the posterior longitudinal ligament (C-OPLL) reflects severity of myelopathy and surgical outcome. The relationship between classification of ISI on C-OPLL and severity is unknown. The 119 consecutive patients (91 men, 28 women) with C-OPLL who underwent surgery were enrolled. T2-weighted MRI was performed before surgery and ISI was classified into three groups as follows, Grade 0, none; Grade 1, light (obscure); and Grade 2, intense (bright). The severity of myelopathy and surgical outcome were evaluated by the Japanese Orthopedic Association score. To determine factors that influence ISI, the change of the spinal cord cross-sectional area (SCA) during flexion and extension was calculated by computed tomography after myelography. The preoperative MRI showed 55 patients in Grade 0, 46 patients in Grade 1, and 18 patients in Grade 2. The preoperative Japanese Orthopedic Association score (Grade 0, 11.2; Grade 1, 10.3; Grade 2, 9.6 points) and surgical outcome got worsened with increasing ISI grade. The patients in Grade 2 had a longer duration of disease, while those in Grade 1 and Grade 2 had a larger change of SCA during flexion and extension (Grade 0, 4.8 mm; Grade 1, 7.3 mm; Grade 2, 7.8 mm). However age, alignment of the cervical spine, range of motion, and occupying ratio of the ossification were not different in the three grades. Grade of ISI correlated with preoperative severity of myelopathy and surgical outcome in patients with C-OPLL. Increased signal intensity of the spinal cord on MRI was associated with a larger change in SCA and longer duration of disease. 3.

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.

MRI Atlas-Based Measurement of Spinal Cord Injury Predicts Outcome in Acute Flaccid Myelitis.

Recent advances in spinal cord imaging analysis have led to the development of a robust anatomic template and atlas incorporated into an open-source platform referred to as the Spinal Cord Toolbox. Using the Spinal Cord Toolbox, we sought to correlate measures of GM, WM, and cross-sectional area pathology on T2 MR imaging with motor disability in patients with acute flaccid myelitis. Spinal cord imaging for 9 patients with acute flaccid myelitis was analyzed by using the Spinal Cord Toolbox. A semiautomated pipeline using the Spinal Cord Toolbox measured lesion involvement in GM, WM, and total spinal cord cross-sectional area. Proportions of GM, WM, and cross-sectional area affected by T2 hyperintensity were calculated across 3 ROIs: 1) center axial section of lesion; 2) full lesion segment; and 3) full cord atlas volume. Spearman rank order correlation was calculated to compare MR metrics with clinical measures of disability. Proportion of GM metrics at the center axial section significantly correlated with measures of motor impairment upon admission (r [9] = -0.78; P = .014) and at 3-month follow-up (r [9] = -0.66; P = .05). Further, proportion of GM extracted across the full lesion segment significantly correlated with initial motor impairment (r [9] = -0.74, P = .024). No significant correlation was found for proportion of WM or proportion of cross-sectional area with clinical disability. Atlas-based measures of proportion of GM T2 signal abnormality measured on a single axial MR imaging section and across the full lesion segment correlate with motor impairment and outcome in patients with acute flaccid myelitis. This is the first atlas-based study to correlate clinical outcomes with segmented measures of T2 signal abnormality in the spinal cord.

Motor recovery at 6 months after admission is related to structural and functional reorganization of the spine and brain in patients with spinal cord injury.

This study aimed to explore structural and functional reorganization of the brain in the early stages of spinal cord injury (SCI) and identify brain areas that contribute to motor recovery. We studied 25 patients with SCI, including 10 with good motor recovery and 15 with poor motor recovery, along with 25 matched healthy controls. The mean period post-SCI was 9.2 ± 3.5 weeks in good recoverers and 8.8 ± 2.6 weeks in poor recoverers. All participants underwent structural and functional MRI on a 3-T magnetic resonance system. We evaluated differences in cross-sectional spinal cord area at the C2/C3 level, brain cortical thickness, white matter microstructure, and functional connectivity during the resting state among the three groups. We also evaluated associations between structural and functional reorganization and the rate of motor recovery. After SCI, compared with good recoverers, poor recoverers had a significantly decreased cross-sectional spinal cord area, cortical thickness in the right supplementary motor area and premotor cortex, and fractional anisotropy (FA) in the right primary motor cortex and posterior limb of the internal capsule. Meanwhile, poor recoverers showed decreased functional connectivity between the primary motor cortex and higher order motor areas (supplementary motor area and premotor cortex), while good recoverers showed increased functional connectivity among these regions. The structural and functional reorganization of the spine and brain was associated with motor recovery rate in all SCI patients. In conclusion, structural and functional reorganization of the spine and brain directly affected the motor recovery of SCI. Less structural atrophy and enhanced functional connectivity are associated with good motor recovery in patients with SCI. Multimodal imaging has the potential to predict motor recovery in the early stage of SCI. Hum Brain Mapp 37:2195-2209, 2016. © 2016 Wiley Periodicals, Inc.

Fully automated segmentation of the cervical cord from T1-weighted MRI using PropSeg: Application to multiple sclerosis.

Spinal cord (SC) atrophy, i.e. a reduction in the SC cross-sectional area (CSA) over time, can be measured by means of image segmentation using magnetic resonance imaging (MRI). However, segmentation methods have been limited by factors relating to reproducibility or sensitivity to change. The purpose of this study was to evaluate a fully automated SC segmentation method (PropSeg), and compare this to a semi-automated active surface (AS) method, in healthy controls (HC) and people with multiple sclerosis (MS). MRI data from 120 people were retrospectively analysed; 26 HC, 21 with clinically isolated syndrome, 26 relapsing remitting MS, 26 primary and 21 secondary progressive MS. MRI data from 40 people returning after one year were also analysed. CSA measurements were obtained within the cervical SC. Reproducibility of the measurements was assessed using the intraclass correlation coefficient (ICC). A comparison between mean CSA changes obtained with the two methods over time was performed using multivariate structural equation regression models. Associations between CSA measures and clinical scores were investigated using linear regression models. Compared to the AS method, the reproducibility of CSA measurements obtained with PropSeg was high, both in patients and in HC, with ICC > 0.98 in all cases. There was no significant difference between PropSeg and AS in terms of detecting change over time. Furthermore, PropSeg provided measures that correlated with physical disability, similar to the AS method. PropSeg is a time-efficient and reliable segmentation method, which requires no manual intervention, and may facilitate large multi-centre neuroprotective trials in progressive MS.

Patterns of spinal cord atrophy in HTLV-1 associated myelopathy/ tropical spastic paraparesis (HAM/TSP)

Spinal cord inflammation and atrophy contribute to debilitating symptoms in HAM/TSP. We have developed a robust and fast algorithm to determine average cross-sectional area in cervical (c-spine) and thoracic (t-spine) spinal cords by tracing contours perpendicular to the edge in T1-weighted MRI images. The cross-sectional areas in the c- and t-spines were determined in 25 HAM/TSP, 10 asymptomatic carriers (AC) and 10 healthy volunteer (HV) subjects. To date, we have followed 8 of the HAM/TSP patients longitudinally over a two-year period. When compared to the HV data, the HAM/TSP spinal cord profiles fell into four general categories: atrophic entire spine (48%), atrophic t-spine (32%), atrophic c-spine (8%), and normal (12%). The majority of ACs had similar spinal cord profiles to those in the HV group, however, 3 ACs showed a pattern similar to HAM/TSP. As a group, both HAM/TSP c- and t-spines were significantly lower than those of HV (p<0.01). In the 8 patients with follow-up scans, spinal cord size showed an overall decreasing trend over time. In a rapidly progressing patient with the shortest disease duration, we could estimate spinal cord atrophy at a rate of 11% a year in the thoracic cord. In addition, change in proviral load negatively correlated with change in both c- and t-spine cross-sectional area (p<0.05) for patients with shorter disease duration and increasing proviral loads (i.e. an increase in proviral load was associated with a more atrophic cord). These results suggest that the pattern of spinal cord tissue damage is specific to the underlying inflammatory disease, a finding that has direct implications for the use of average cross-sectional spinal cord area as a surrogate end point for clinical trials.