Serena Ruggieri1, Maria Petracca2, Aaron Miller3, Stephen Krieger3, Rezwan Ghassemi4, Yadira Bencosme3, Claire Riley5, Jonathan Howard6, Fred Lublin3, Matilde Inglese7. 1. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York2Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy. 2. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York3Department of Neurosciences, Reproductive Sciences, and Odontostomatology, University of Naples Federico II, Naples, Italy. 3. Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York. 4. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York. 5. The Neurological Institute of New York, Department of Neurology, Columbia University Medical Center, New York, New York. 6. Department of Neurology, Langone Medical Center, New York University, New York, New York. 7. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York8Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York9Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New Yo.
Abstract
IMPORTANCE: The investigation of cortical gray matter (GM), deep GM nuclei, and spinal cord damage in patients with primary progressive multiple sclerosis (PP-MS) provides insights into the neurodegenerative process responsible for clinical progression of MS. OBJECTIVE: To investigate the association of magnetic resonance imaging measures of cortical, deep GM, and spinal cord damage and their effect on clinical disability. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of 26 patients with PP-MS (mean age, 50.9 years; range, 31-65 years; including 14 women) and 20 healthy control participants (mean age, 51.1 years; range, 34-63 years; including 11 women) enrolled at a single US institution. Clinical disability was measured with the Expanded Disability Status Scale, 9-Hole Peg Test, and 25-Foot Walking Test. We collected data from January 1, 2012, through December 31, 2013. Data analysis was performed from January 21 to April 10, 2015. MAIN OUTCOMES AND MEASURES: Cortical lesion burden, brain and deep GM volumes, spinal cord area and volume, and scores on the Expanded Disability Status Scale (score range, 0 to 10; higher scores indicate greater disability), 9-Hole Peg Test (measured in seconds; longer performance time indicates greater disability), and 25-Foot Walking Test (test covers 7.5 m; measured in seconds; longer performance time indicates greater disability). RESULTS: The 26 patients with PP-MS showed significantly smaller mean (SD) brain and spinal cord volumes than the 20 control group patients (normalized brain volume, 1377.81 [65.48] vs 1434.06 [53.67] cm3 [P = .003]; normalized white matter volume, 650.61 [46.38] vs 676.75 [37.02] cm3 [P = .045]; normalized gray matter volume, 727.20 [40.74] vs 757.31 [38.95] cm3 [P = .02]; normalized neocortical volume, 567.88 [85.55] vs 645.00 [42.84] cm3 [P = .001]; normalized spinal cord volume for C2-C5, 72.71 [7.89] vs 82.70 [7.83] mm3 [P < .001]; and normalized spinal cord volume for C2-C3, 64.86 [7.78] vs 72.26 [7.79] mm3 [P =.002]). The amount of damage in deep GM structures, especially with respect to the thalamus, was correlated with the number and volume of cortical lesions (mean [SD] thalamus volume, 8.89 [1.10] cm3; cortical lesion number, 12.6 [11.7]; cortical lesion volume, 0.65 [0.58] cm3; r = -0.52; P < .01). Thalamic atrophy also showed an association with cortical lesion count in the frontal cortex (mean [SD] thalamus volume, 8.89 [1.1] cm3; cortical lesion count in the frontal lobe, 5.0 [5.7]; r = -0.60; P < .01). No association was identified between magnetic resonance imaging measures of the brain and spinal cord damage. CONCLUSIONS AND RELEVANCE: In this study, the neurodegenerative process occurring in PP-MS appeared to spread across connected structures in the brain while proceeding independently in the spinal cord. These results support the relevance of anatomical connectivity for the propagation of MS damage in the PP phenotype.
IMPORTANCE: The investigation of cortical gray matter (GM), deep GM nuclei, and spinal cord damage in patients with primary progressive multiple sclerosis (PP-MS) provides insights into the neurodegenerative process responsible for clinical progression of MS. OBJECTIVE: To investigate the association of magnetic resonance imaging measures of cortical, deep GM, and spinal cord damage and their effect on clinical disability. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of 26 patients with PP-MS (mean age, 50.9 years; range, 31-65 years; including 14 women) and 20 healthy control participants (mean age, 51.1 years; range, 34-63 years; including 11 women) enrolled at a single US institution. Clinical disability was measured with the Expanded Disability Status Scale, 9-Hole Peg Test, and 25-Foot Walking Test. We collected data from January 1, 2012, through December 31, 2013. Data analysis was performed from January 21 to April 10, 2015. MAIN OUTCOMES AND MEASURES: Cortical lesion burden, brain and deep GM volumes, spinal cord area and volume, and scores on the Expanded Disability Status Scale (score range, 0 to 10; higher scores indicate greater disability), 9-Hole Peg Test (measured in seconds; longer performance time indicates greater disability), and 25-Foot Walking Test (test covers 7.5 m; measured in seconds; longer performance time indicates greater disability). RESULTS: The 26 patients with PP-MS showed significantly smaller mean (SD) brain and spinal cord volumes than the 20 control group patients (normalized brain volume, 1377.81 [65.48] vs 1434.06 [53.67] cm3 [P = .003]; normalized white matter volume, 650.61 [46.38] vs 676.75 [37.02] cm3 [P = .045]; normalized gray matter volume, 727.20 [40.74] vs 757.31 [38.95] cm3 [P = .02]; normalized neocortical volume, 567.88 [85.55] vs 645.00 [42.84] cm3 [P = .001]; normalized spinal cord volume for C2-C5, 72.71 [7.89] vs 82.70 [7.83] mm3 [P < .001]; and normalized spinal cord volume for C2-C3, 64.86 [7.78] vs 72.26 [7.79] mm3 [P =.002]). The amount of damage in deep GM structures, especially with respect to the thalamus, was correlated with the number and volume of cortical lesions (mean [SD] thalamus volume, 8.89 [1.10] cm3; cortical lesion number, 12.6 [11.7]; cortical lesion volume, 0.65 [0.58] cm3; r = -0.52; P < .01). Thalamic atrophy also showed an association with cortical lesion count in the frontal cortex (mean [SD] thalamus volume, 8.89 [1.1] cm3; cortical lesion count in the frontal lobe, 5.0 [5.7]; r = -0.60; P < .01). No association was identified between magnetic resonance imaging measures of the brain and spinal cord damage. CONCLUSIONS AND RELEVANCE: In this study, the neurodegenerative process occurring in PP-MS appeared to spread across connected structures in the brain while proceeding independently in the spinal cord. These results support the relevance of anatomical connectivity for the propagation of MS damage in the PP phenotype.
Authors: A Burgetova; P Dusek; M Vaneckova; D Horakova; C Langkammer; J Krasensky; L Sobisek; P Matras; M Masek; Z Seidl Journal: AJNR Am J Neuroradiol Date: 2017-04-27 Impact factor: 3.825
Authors: Gilles Allali; Helena M Blumen; Hervé Devanne; Elvira Pirondini; Arnaud Delval; Dimitri Van De Ville Journal: Neurophysiol Clin Date: 2018-10-25 Impact factor: 3.734
Authors: Arman Eshaghi; Razvan V Marinescu; Alexandra L Young; Nicholas C Firth; Ferran Prados; M Jorge Cardoso; Carmen Tur; Floriana De Angelis; Niamh Cawley; Wallace J Brownlee; Nicola De Stefano; M Laura Stromillo; Marco Battaglini; Serena Ruggieri; Claudio Gasperini; Massimo Filippi; Maria A Rocca; Alex Rovira; Jaume Sastre-Garriga; Jeroen J G Geurts; Hugo Vrenken; Viktor Wottschel; Cyra E Leurs; Bernard Uitdehaag; Lukas Pirpamer; Christian Enzinger; Sebastien Ourselin; Claudia A Gandini Wheeler-Kingshott; Declan Chard; Alan J Thompson; Frederik Barkhof; Daniel C Alexander; Olga Ciccarelli Journal: Brain Date: 2018-06-01 Impact factor: 13.501