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Masamitsu Nakazato - One of the best experts on this subject based on the ideXlab platform.
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Spinal Cord anteroposterior Atrophy in ham tsp magnetic resonance imaging and neuropathological analyses
Journal of the Neurological Sciences, 2017Co-Authors: Akitoshi Taniguchi, Hitoshi Mochizuki, Atsushi Yamashita, Kazutaka Shiomi, Yujiro Asada, Masamitsu NakazatoAbstract:Abstract To evaluate the Spinal Cord Atrophy that occurs in HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP), we conducted magnetic resonance imaging (MRI) and pathological analyses. In the MRI study, 15 patients with HAM/TSP and 20 age-matched normal control subjects were enrolled. Anteroposterior and transverse distances and cross-sectional areas were measured and calculated at the C2, C4, C6, T2, and T6 vertebral levels. In the pathological study, Spinal Cord autopsy specimens were compared between a HAM/TSP case and an adult T cell leukemia/lymphoma case. In both the MRI and pathological studies, HAM/TSP Spinal Cords demonstrated more severe Atrophy in the anteroposterior direction than those of controls. The Spinal Cord Atrophy and pathological changes in HAM/TSP occurred predominantly in the white matter, especially in the lateral columns. This is the first report indicating Spinal Cord Atrophy in the anteroposterior direction using MRI. In pathological analysis, Atrophy and pathological changes were prominent in areas of the Spinal Cord with slow blood flow. Hemodynamic and anatomical factors are speculated to be among the main mechanisms of Atrophy in the anteroposterior direction.
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Spinal Cord anteroposterior Atrophy in HAM/TSP: Magnetic resonance imaging and neuropathological analyses.
Journal of the neurological sciences, 2017Co-Authors: Akitoshi Taniguchi, Hitoshi Mochizuki, Atsushi Yamashita, Kazutaka Shiomi, Yujiro Asada, Masamitsu NakazatoAbstract:Abstract To evaluate the Spinal Cord Atrophy that occurs in HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP), we conducted magnetic resonance imaging (MRI) and pathological analyses. In the MRI study, 15 patients with HAM/TSP and 20 age-matched normal control subjects were enrolled. Anteroposterior and transverse distances and cross-sectional areas were measured and calculated at the C2, C4, C6, T2, and T6 vertebral levels. In the pathological study, Spinal Cord autopsy specimens were compared between a HAM/TSP case and an adult T cell leukemia/lymphoma case. In both the MRI and pathological studies, HAM/TSP Spinal Cords demonstrated more severe Atrophy in the anteroposterior direction than those of controls. The Spinal Cord Atrophy and pathological changes in HAM/TSP occurred predominantly in the white matter, especially in the lateral columns. This is the first report indicating Spinal Cord Atrophy in the anteroposterior direction using MRI. In pathological analysis, Atrophy and pathological changes were prominent in areas of the Spinal Cord with slow blood flow. Hemodynamic and anatomical factors are speculated to be among the main mechanisms of Atrophy in the anteroposterior direction.
Steven Jacobson - One of the best experts on this subject based on the ideXlab platform.
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patterns of Spinal Cord Atrophy in neuroinflammatory diseases p6 117
Neurology, 2016Co-Authors: Shila Azodi, Emily Charlip, Winston Liu, Bridgette Jeanne Billioux, Ashley Vellucci, Joan Ohayon, Govind Nair, Steven JacobsonAbstract:OBJECTIVE: Develop a Spinal Cord imaging biomarker for neuroinflammatory diseases. BACKGROUND: Multiple sclerosis (MS) and human T-cell lymphotropic virus-1 (HTLV1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) are examples of diseases with progressive myelitis. In HTLV1 infection, there is a correlation between serum proviral load and development of HAM/TSP. Using a fast and robust semiautomatic quantification program analyzing MRI Spinal Cord images, Spinal Cord cross sectional area (SCCSA) has been characterized for healthy volunteers (HV), HAM/TSP, asymptomatic HTLV1 carriers (AC) and MS at single time points. DESIGN/METHOD: MRI of the cervical and thoracic Cord was obtained in 13 HV, 38 HAM/TSP, 13 AC, 7 progressive MS, and 30 relapsing remitting MS. A subset of HAM/TSP patients had multiple MRIs. HAM/TSP patients also had HTLV1 proviral load in serum and cerebroSpinal fluid (CSF) measured. RESULTS: SCCSA in HAM/TSP patients and progressive MS show similar patterns of Spinal Cord Atrophy with both cervical and thoracic Cord Atrophy. Relapsing remitting MS patients develop cervical Cord Atrophy with longer duration of disease. Asymptomatic HTLV1 carriers had no difference in SCCSA compared to healthy volunteers. HAM/TSP patients showed a correlation between thoracic Cord CSA and CSF proviral load (p<0.05). Longitudinal HAM/TSP Spinal Cord imaging showed thoracic Cord Atrophy with short duration of disease that progressed to involve cervical Cord with time. CONCLUSION: In addition to extending the spectrum of Spinal Cord Atrophy longitudinally to support the unique patterns of Spinal Cord Atrophy in neuroinflammatory diseases, the study findings suggest the use of SCCSA may be used as a marker for disease progression. Disclosure: Dr. Azodi has nothing to disclose. Dr. Charlip has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Billioux has nothing to disclose. Dr. Vellucci has nothing to disclose. Dr. Ohayon has nothing to disclose. Dr. Nair has nothing to disclose. Dr. Jacobson has nothing to disclose.
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Patterns of Spinal Cord Atrophy in Neuroinflammatory Diseases (P6.117)
Neurology, 2016Co-Authors: Shila Azodi, Emily Charlip, Winston Liu, Bridgette Jeanne Billioux, Ashley Vellucci, Joan Ohayon, Govind Nair, Steven JacobsonAbstract:OBJECTIVE: Develop a Spinal Cord imaging biomarker for neuroinflammatory diseases. BACKGROUND: Multiple sclerosis (MS) and human T-cell lymphotropic virus-1 (HTLV1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) are examples of diseases with progressive myelitis. In HTLV1 infection, there is a correlation between serum proviral load and development of HAM/TSP. Using a fast and robust semiautomatic quantification program analyzing MRI Spinal Cord images, Spinal Cord cross sectional area (SCCSA) has been characterized for healthy volunteers (HV), HAM/TSP, asymptomatic HTLV1 carriers (AC) and MS at single time points. DESIGN/METHOD: MRI of the cervical and thoracic Cord was obtained in 13 HV, 38 HAM/TSP, 13 AC, 7 progressive MS, and 30 relapsing remitting MS. A subset of HAM/TSP patients had multiple MRIs. HAM/TSP patients also had HTLV1 proviral load in serum and cerebroSpinal fluid (CSF) measured. RESULTS: SCCSA in HAM/TSP patients and progressive MS show similar patterns of Spinal Cord Atrophy with both cervical and thoracic Cord Atrophy. Relapsing remitting MS patients develop cervical Cord Atrophy with longer duration of disease. Asymptomatic HTLV1 carriers had no difference in SCCSA compared to healthy volunteers. HAM/TSP patients showed a correlation between thoracic Cord CSA and CSF proviral load (p
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patterns of Spinal Cord Atrophy in htlv 1 associated myelopathy tropical spastic paraparesis ham tsp
Retrovirology, 2015Co-Authors: Emily Charlip, Winston Liu, Joan Ohayon, Govind Nair, Raya Massoud, Jeanne Billioux, Breanna Caruso, Steven JacobsonAbstract: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.
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in vivo imaging of Spinal Cord Atrophy in neuroinflammatory diseases
Annals of Neurology, 2014Co-Authors: Winston Liu, Govind Nair, Luisa Vuolo, Anshika Bakshi, Raya Massoud, Daniel S. Reich, Steven JacobsonAbstract:Objective Spinal Cord Atrophy is prominent in chronic progressive neurologic diseases such as human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). Here we compared the Spinal Cord cross-sectional area (SCCSA) in HAM/TSP and MS patients to that of healthy volunteers (HVs). Methods SCCSA and clinical disability scores were measured in 18 HAM/TSP patients, 4 asymptomatic carriers (ACs) of HTLV-1, 18 MS patients, and 10 HVs from a 3T magnetic resonance imaging. SCCSA measured in patients and ACs were compared to that of HVs and correlated with disability scores. Results The entire Spinal Cord in HAM/TSP patients was thin compared to HVs, whereas only the cervical Cord in MS patients was thinner than in HVs (p < 0.0001). In HAM/TSP patients, SCCSA extensively correlated with Ambulation Index, whereas only the cervical Cord correlated with disease duration (p < 0.05). In MS patients, the SCCSA extensively correlated with Scripps Neurologic Rating Score and the Expanded Disability Status Scale (p < 0.05). One of the 4 ACs showed Atrophy in a pattern similar to HAM/TSP. Interpretation These results are in acCordance with the findings that whereas over half of all lesions in an MS Cord are seen in the upper cervical Cord, most of the pathology in HAM/TSP is seen in the thoracolumbar Cord, which in turn may be responsible for the more extensive Cord Atrophy seen in HAM/TSP. An imaging marker such as SCCSA might serve as a surrogate endpoint in clinical trials, especially to assess the neuroprotective impact of various therapies. Ann Neurol 2014;76:370–378
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In-Vivo Imaging of Spinal Cord Atrophy in Neuroinflammatory Diseases
Annals of neurology, 2014Co-Authors: Winston Liu, Govind Nair, Luisa Vuolo, Anshika Bakshi, Raya Massoud, Daniel S. Reich, Steven JacobsonAbstract:Objective Spinal Cord Atrophy is prominent in chronic progressive neurologic diseases such as human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). Here we compared the Spinal Cord cross-sectional area (SCCSA) in HAM/TSP and MS patients to that of healthy volunteers (HVs). Methods SCCSA and clinical disability scores were measured in 18 HAM/TSP patients, 4 asymptomatic carriers (ACs) of HTLV-1, 18 MS patients, and 10 HVs from a 3T magnetic resonance imaging. SCCSA measured in patients and ACs were compared to that of HVs and correlated with disability scores. Results The entire Spinal Cord in HAM/TSP patients was thin compared to HVs, whereas only the cervical Cord in MS patients was thinner than in HVs (p
Maria A. Rocca - One of the best experts on this subject based on the ideXlab platform.
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Spinal Cord Atrophy in Neuromyelitis Optica Spectrum Disorders Is Spatially Related to Cord Lesions and Disability
Radiology, 2020Co-Authors: Laura Cacciaguerra, Massimo Filippi, Paola Valsasina, Sarlota Mesaros, Vittorio Martinelli, Jelena Drulovic, Maria A. RoccaAbstract: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 ± standard deviation, 44 years ± 15; 45 women) and 28 age-matched healthy control participants (mean age, 44 years ± 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 -0.53 to -0.40; P < .001) and sensitive subscore (r ranging from -0.48 to -0.46; 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 Online supplemental material is available for this article.
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MAGNIMS consensus recommendations on the use of brain and Spinal Cord Atrophy measures in clinical practice
Nature reviews. Neurology, 2020Co-Authors: Jaume Sastre-garriga, Olga Ciccarelli, Frederik Barkhof, Deborah Pareto, Marco Battaglini, Maria A. Rocca, Christian Enzinger, Jens Wuerfel, Maria Pia Sormani, Tarek A. YousryAbstract:Early evaluation of treatment response and prediction of disease evolution are key issues in the management of people with multiple sclerosis (MS). In the past 20 years, MRI has become the most useful paraclinical tool in both situations and is used clinically to assess the inflammatory component of the disease, particularly the presence and evolution of focal lesions - the pathological hallmark of MS. However, diffuse neurodegenerative processes that are at least partly independent of inflammatory mechanisms can develop early in people with MS and are closely related to disability. The effects of these neurodegenerative processes at a macroscopic level can be quantified by estimation of brain and Spinal Cord Atrophy with MRI. MRI measurements of Atrophy in MS have also been proposed as a complementary approach to lesion assessment to facilitate the prediction of clinical outcomes and to assess treatment responses. In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group critically review the application of brain and Spinal Cord Atrophy in clinical practice in the management of MS, considering the role of Atrophy measures in prognosis and treatment monitoring and the barriers to clinical use of these measures. On the basis of this review, the group makes consensus statements and recommendations for future research.
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longitudinal Spinal Cord Atrophy in multiple sclerosis using the generalized boundary shift integral
Annals of Neurology, 2019Co-Authors: Marcello Moccia, Ferran Prados, Massimo Filippi, Maria A. Rocca, Paola Valsasina, Wallace J Brownlee, Chiara Zecca, Antonio Gallo, Alex Rovira, Achim GassAbstract:OBJECTIVE Spinal Cord Atrophy is a clinically relevant feature of multiple sclerosis (MS), but longitudinal assessments on magnetic resonance imaging using segmentation-based methods suffer from measurement variability, especially in multicenter studies. We compared the generalized boundary shift integral (GBSI), a registration-based method, with a standard segmentation-based method. METHODS Baseline and 1-year Spinal Cord 3-dimensional T1-weighted images (1mm isotropic) were obtained from 282 patients (52 clinically isolated syndrome [CIS], 196 relapsing-remitting MS [RRMS], 34 progressive MS [PMS]), and 82 controls from 8 MAGNIMS (Magnetic Resonance Imaging in Multiple Sclerosis) sites on multimanufacturer and multi-field-strength scans. Spinal Cord Toolbox was used for C2-5 segmentation and cross-sectional area (CSA) calculation. After Cord straightening and registration, GBSI measured Atrophy based on the probabilistic boundary-shift region of interest. CSA and GBSI percentage annual volume change was calculated. RESULTS GBSI provided similar rates of Atrophy, but reduced measurement variability compared to CSA in all MS subtypes (CIS: -0.95 ± 2.11% vs -1.19 ± 3.67%; RRMS: -1.74 ± 2.57% vs -1.74 ± 4.02%; PMS: -2.29 ± 2.40% vs -1.29 ± 3.20%) and healthy controls (0.02 ± 2.39% vs -0.56 ± 3.77%). GBSI performed better than CSA in differentiating healthy controls from CIS (area under the curve [AUC] = 0.66 vs 0.53; p = 0.03), RRMS (AUC = 0.73 vs 0.59; p < 0.001), PMS (AUC = 0.77 vs 0.53; p < 0.001), and patients with disability progression from patients without progression (AUC = 0.59 vs 0.50; p = 0.04). Sample size to detect 60% treatment effect on Spinal Cord Atrophy over 1 year was lower for GBSI than CSA (CIS: 106 vs 830; RRMS: 95 vs 335; PMS: 44 vs 215; power = 80%; alpha = 5%). INTERPRETATION The registration-based method (GBSI) allowed better separation between MS patients and healthy controls and improved statistical power, when compared with a conventional segmentation-based method (CSA), although it is still far from perfect. ANN NEUROL 2019 ANN NEUROL 2019;86:704-713.
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Longitudinal Spinal Cord Atrophy in multiple sclerosis using the generalized boundary shift integral.
Annals of neurology, 2019Co-Authors: Marcello Moccia, Ferran Prados, Massimo Filippi, Maria A. Rocca, Paola Valsasina, Wallace J Brownlee, Chiara Zecca, Antonio Gallo, Alex Rovira, Achim GassAbstract:OBJECTIVE Spinal Cord Atrophy is a clinically relevant feature of multiple sclerosis (MS), but longitudinal assessments on magnetic resonance imaging using segmentation-based methods suffer from measurement variability, especially in multicenter studies. We compared the generalized boundary shift integral (GBSI), a registration-based method, with a standard segmentation-based method. METHODS Baseline and 1-year Spinal Cord 3-dimensional T1-weighted images (1mm isotropic) were obtained from 282 patients (52 clinically isolated syndrome [CIS], 196 relapsing-remitting MS [RRMS], 34 progressive MS [PMS]), and 82 controls from 8 MAGNIMS (Magnetic Resonance Imaging in Multiple Sclerosis) sites on multimanufacturer and multi-field-strength scans. Spinal Cord Toolbox was used for C2-5 segmentation and cross-sectional area (CSA) calculation. After Cord straightening and registration, GBSI measured Atrophy based on the probabilistic boundary-shift region of interest. CSA and GBSI percentage annual volume change was calculated. RESULTS GBSI provided similar rates of Atrophy, but reduced measurement variability compared to CSA in all MS subtypes (CIS: -0.95 ± 2.11% vs -1.19 ± 3.67%; RRMS: -1.74 ± 2.57% vs -1.74 ± 4.02%; PMS: -2.29 ± 2.40% vs -1.29 ± 3.20%) and healthy controls (0.02 ± 2.39% vs -0.56 ± 3.77%). GBSI performed better than CSA in differentiating healthy controls from CIS (area under the curve [AUC] = 0.66 vs 0.53; p = 0.03), RRMS (AUC = 0.73 vs 0.59; p
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Regional Cervical Cord Atrophy and Disability in Multiple Sclerosis: A Voxel-based Analysis
Radiology, 2012Co-Authors: Paola Valsasina, Mark A. Horsfield, Maria A. Rocca, Martina Absinta, Roberta Messina, Domenico Caputo, Giancarlo Comi, Massimo FilippiAbstract:An accurate assessment of Spinal Cord Atrophy helps improve our understanding of the major clinical manifestations of multiple sclerosis (eg, locomotor impairment) and might be useful for future longitudinal studies monitoring disease evolution.
Akitoshi Taniguchi - One of the best experts on this subject based on the ideXlab platform.
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Spinal Cord anteroposterior Atrophy in ham tsp magnetic resonance imaging and neuropathological analyses
Journal of the Neurological Sciences, 2017Co-Authors: Akitoshi Taniguchi, Hitoshi Mochizuki, Atsushi Yamashita, Kazutaka Shiomi, Yujiro Asada, Masamitsu NakazatoAbstract:Abstract To evaluate the Spinal Cord Atrophy that occurs in HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP), we conducted magnetic resonance imaging (MRI) and pathological analyses. In the MRI study, 15 patients with HAM/TSP and 20 age-matched normal control subjects were enrolled. Anteroposterior and transverse distances and cross-sectional areas were measured and calculated at the C2, C4, C6, T2, and T6 vertebral levels. In the pathological study, Spinal Cord autopsy specimens were compared between a HAM/TSP case and an adult T cell leukemia/lymphoma case. In both the MRI and pathological studies, HAM/TSP Spinal Cords demonstrated more severe Atrophy in the anteroposterior direction than those of controls. The Spinal Cord Atrophy and pathological changes in HAM/TSP occurred predominantly in the white matter, especially in the lateral columns. This is the first report indicating Spinal Cord Atrophy in the anteroposterior direction using MRI. In pathological analysis, Atrophy and pathological changes were prominent in areas of the Spinal Cord with slow blood flow. Hemodynamic and anatomical factors are speculated to be among the main mechanisms of Atrophy in the anteroposterior direction.
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Spinal Cord anteroposterior Atrophy in HAM/TSP: Magnetic resonance imaging and neuropathological analyses.
Journal of the neurological sciences, 2017Co-Authors: Akitoshi Taniguchi, Hitoshi Mochizuki, Atsushi Yamashita, Kazutaka Shiomi, Yujiro Asada, Masamitsu NakazatoAbstract:Abstract To evaluate the Spinal Cord Atrophy that occurs in HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP), we conducted magnetic resonance imaging (MRI) and pathological analyses. In the MRI study, 15 patients with HAM/TSP and 20 age-matched normal control subjects were enrolled. Anteroposterior and transverse distances and cross-sectional areas were measured and calculated at the C2, C4, C6, T2, and T6 vertebral levels. In the pathological study, Spinal Cord autopsy specimens were compared between a HAM/TSP case and an adult T cell leukemia/lymphoma case. In both the MRI and pathological studies, HAM/TSP Spinal Cords demonstrated more severe Atrophy in the anteroposterior direction than those of controls. The Spinal Cord Atrophy and pathological changes in HAM/TSP occurred predominantly in the white matter, especially in the lateral columns. This is the first report indicating Spinal Cord Atrophy in the anteroposterior direction using MRI. In pathological analysis, Atrophy and pathological changes were prominent in areas of the Spinal Cord with slow blood flow. Hemodynamic and anatomical factors are speculated to be among the main mechanisms of Atrophy in the anteroposterior direction.
Govind Nair - One of the best experts on this subject based on the ideXlab platform.
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Imaging Spinal Cord Atrophy in progressive myelopathies: HTLV-I-associated neurological disease (HAM/TSP) and multiple sclerosis (MS).
Annals of neurology, 2017Co-Authors: Shila Azodi, Emily Charlip, Ashley Vellucci, Govind Nair, Yoshimi Enose-akahata, Irene Cortese, Jenifer Dwyer, B Jeanne Billioux, Chevaz Thomas, Joan OhayonAbstract:Objective 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. Methods 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. Results 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. Interpretation 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.
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imaging Spinal Cord Atrophy in progressive myelopathies htlv i associated neurological disease ham tsp and multiple sclerosis ms
Annals of Neurology, 2017Co-Authors: Shila Azodi, Emily Charlip, Ashley Vellucci, Govind Nair, Irene Cortese, Jenifer Dwyer, Chevaz Thomas, Yoshimi Enoseakahata, Jeanne B Billioux, Joan OhayonAbstract:Objective 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. Methods 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. Results 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. Interpretation 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.
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patterns of Spinal Cord Atrophy in neuroinflammatory diseases p6 117
Neurology, 2016Co-Authors: Shila Azodi, Emily Charlip, Winston Liu, Bridgette Jeanne Billioux, Ashley Vellucci, Joan Ohayon, Govind Nair, Steven JacobsonAbstract:OBJECTIVE: Develop a Spinal Cord imaging biomarker for neuroinflammatory diseases. BACKGROUND: Multiple sclerosis (MS) and human T-cell lymphotropic virus-1 (HTLV1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) are examples of diseases with progressive myelitis. In HTLV1 infection, there is a correlation between serum proviral load and development of HAM/TSP. Using a fast and robust semiautomatic quantification program analyzing MRI Spinal Cord images, Spinal Cord cross sectional area (SCCSA) has been characterized for healthy volunteers (HV), HAM/TSP, asymptomatic HTLV1 carriers (AC) and MS at single time points. DESIGN/METHOD: MRI of the cervical and thoracic Cord was obtained in 13 HV, 38 HAM/TSP, 13 AC, 7 progressive MS, and 30 relapsing remitting MS. A subset of HAM/TSP patients had multiple MRIs. HAM/TSP patients also had HTLV1 proviral load in serum and cerebroSpinal fluid (CSF) measured. RESULTS: SCCSA in HAM/TSP patients and progressive MS show similar patterns of Spinal Cord Atrophy with both cervical and thoracic Cord Atrophy. Relapsing remitting MS patients develop cervical Cord Atrophy with longer duration of disease. Asymptomatic HTLV1 carriers had no difference in SCCSA compared to healthy volunteers. HAM/TSP patients showed a correlation between thoracic Cord CSA and CSF proviral load (p<0.05). Longitudinal HAM/TSP Spinal Cord imaging showed thoracic Cord Atrophy with short duration of disease that progressed to involve cervical Cord with time. CONCLUSION: In addition to extending the spectrum of Spinal Cord Atrophy longitudinally to support the unique patterns of Spinal Cord Atrophy in neuroinflammatory diseases, the study findings suggest the use of SCCSA may be used as a marker for disease progression. Disclosure: Dr. Azodi has nothing to disclose. Dr. Charlip has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Billioux has nothing to disclose. Dr. Vellucci has nothing to disclose. Dr. Ohayon has nothing to disclose. Dr. Nair has nothing to disclose. Dr. Jacobson has nothing to disclose.
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Patterns of Spinal Cord Atrophy in Neuroinflammatory Diseases (P6.117)
Neurology, 2016Co-Authors: Shila Azodi, Emily Charlip, Winston Liu, Bridgette Jeanne Billioux, Ashley Vellucci, Joan Ohayon, Govind Nair, Steven JacobsonAbstract:OBJECTIVE: Develop a Spinal Cord imaging biomarker for neuroinflammatory diseases. BACKGROUND: Multiple sclerosis (MS) and human T-cell lymphotropic virus-1 (HTLV1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) are examples of diseases with progressive myelitis. In HTLV1 infection, there is a correlation between serum proviral load and development of HAM/TSP. Using a fast and robust semiautomatic quantification program analyzing MRI Spinal Cord images, Spinal Cord cross sectional area (SCCSA) has been characterized for healthy volunteers (HV), HAM/TSP, asymptomatic HTLV1 carriers (AC) and MS at single time points. DESIGN/METHOD: MRI of the cervical and thoracic Cord was obtained in 13 HV, 38 HAM/TSP, 13 AC, 7 progressive MS, and 30 relapsing remitting MS. A subset of HAM/TSP patients had multiple MRIs. HAM/TSP patients also had HTLV1 proviral load in serum and cerebroSpinal fluid (CSF) measured. RESULTS: SCCSA in HAM/TSP patients and progressive MS show similar patterns of Spinal Cord Atrophy with both cervical and thoracic Cord Atrophy. Relapsing remitting MS patients develop cervical Cord Atrophy with longer duration of disease. Asymptomatic HTLV1 carriers had no difference in SCCSA compared to healthy volunteers. HAM/TSP patients showed a correlation between thoracic Cord CSA and CSF proviral load (p
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patterns of Spinal Cord Atrophy in htlv 1 associated myelopathy tropical spastic paraparesis ham tsp
Retrovirology, 2015Co-Authors: Emily Charlip, Winston Liu, Joan Ohayon, Govind Nair, Raya Massoud, Jeanne Billioux, Breanna Caruso, Steven JacobsonAbstract: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.