IMPORTANCEThe investigation of cortical gray matter (GM), deep GM nuclei, and spinal corddamage in patients with primary progressive multiple sclerosis (PP-MS) provides insights intothe neurodegenerative process responsible for clinical progression of MS.OBJECTIVETo investigate the association of magnetic resonance imaging measures ofcortical, deep GM, and spinal cord damage and their effect on clinical disability.DESIGN, SETTING, AND PARTICIPANTSCross-sectional analysis of 26 patients with PP-MS(mean age, 50.9 years; range, 31-65 years; including 14 women) and 20 healthy controlparticipants (mean age, 51.1 years; range, 34-63 years; including 11 women) enrolled at a singleUS 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, throughDecember 31, 2013. Data analysis was performed from January 21 to April 10, 2015.MAIN OUTCOMES AND MEASURESCortical lesion burden, brain and deep GM volumes, spinalcord area and volume, and scores on the Expanded Disability Status Scale (score range, 0 to10; higher scores indicate greater disability), 9-Hole Peg Test (measured in seconds; longerperformance time indicates greater disability), and 25-Foot Walking Test (test covers 7.5 m;measured in seconds; longer performance time indicates greater disability).RESULTSThe 26 patients with PP-MS showed significantly smaller mean (SD) brain and spinalcord 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] vs676.75 [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 thethalamus, 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 withcortical lesion count in the frontal cortex (mean [SD] thalamus volume, 8.89 [1.1] cm3; corticallesion count in the frontal lobe, 5.0 [5.7];r=−0.60;P< .01). No association was identifiedbetween magnetic resonance imaging measures of the brain and spinal cord damage.CONCLUSIONS AND RELEVANCEIn this study, the neurodegenerative process occurring inPP-MS appeared to spread across connected structures in the brain while proceedingindependently in the spinal cord. These results support the relevance of anatomicalconnectivity for the propagation of MS damage in the PP phenotype.

Association of deep gray matter damage with cortical and spinal cord degeneration in primary progressive multiple sclerosis / Ruggieri, Serena; Petracca, Maria; Miller, Aaron; Krieger, Stephen; Ghassemi, Rezwan; Bencosme, Yadira; Riley, Claire; Howard, Jonathan; Lublin, Fred; Inglese, Matilde. - In: JAMA NEUROLOGY. - ISSN 2168-6149. - 72:12(2015), pp. 1466-1474. [10.1001/jamaneurol.2015.1897]

Association of deep gray matter damage with cortical and spinal cord degeneration in primary progressive multiple sclerosis

RUGGIERI, SERENA;Petracca, Maria;
2015

Abstract

IMPORTANCEThe investigation of cortical gray matter (GM), deep GM nuclei, and spinal corddamage in patients with primary progressive multiple sclerosis (PP-MS) provides insights intothe neurodegenerative process responsible for clinical progression of MS.OBJECTIVETo investigate the association of magnetic resonance imaging measures ofcortical, deep GM, and spinal cord damage and their effect on clinical disability.DESIGN, SETTING, AND PARTICIPANTSCross-sectional analysis of 26 patients with PP-MS(mean age, 50.9 years; range, 31-65 years; including 14 women) and 20 healthy controlparticipants (mean age, 51.1 years; range, 34-63 years; including 11 women) enrolled at a singleUS 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, throughDecember 31, 2013. Data analysis was performed from January 21 to April 10, 2015.MAIN OUTCOMES AND MEASURESCortical lesion burden, brain and deep GM volumes, spinalcord area and volume, and scores on the Expanded Disability Status Scale (score range, 0 to10; higher scores indicate greater disability), 9-Hole Peg Test (measured in seconds; longerperformance time indicates greater disability), and 25-Foot Walking Test (test covers 7.5 m;measured in seconds; longer performance time indicates greater disability).RESULTSThe 26 patients with PP-MS showed significantly smaller mean (SD) brain and spinalcord 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] vs676.75 [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 thethalamus, 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 withcortical lesion count in the frontal cortex (mean [SD] thalamus volume, 8.89 [1.1] cm3; corticallesion count in the frontal lobe, 5.0 [5.7];r=−0.60;P< .01). No association was identifiedbetween magnetic resonance imaging measures of the brain and spinal cord damage.CONCLUSIONS AND RELEVANCEIn this study, the neurodegenerative process occurring inPP-MS appeared to spread across connected structures in the brain while proceedingindependently in the spinal cord. These results support the relevance of anatomicalconnectivity for the propagation of MS damage in the PP phenotype.
2015
Adult; Aged; Disability Evaluation; Female; Gray Matter; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive; Spinal Cord; Spinocerebellar Degenerations; Statistics as Topic; White Matter; Neurology (clinical)
01 Pubblicazione su rivista::01a Articolo in rivista
Association of deep gray matter damage with cortical and spinal cord degeneration in primary progressive multiple sclerosis / Ruggieri, Serena; Petracca, Maria; Miller, Aaron; Krieger, Stephen; Ghassemi, Rezwan; Bencosme, Yadira; Riley, Claire; Howard, Jonathan; Lublin, Fred; Inglese, Matilde. - In: JAMA NEUROLOGY. - ISSN 2168-6149. - 72:12(2015), pp. 1466-1474. [10.1001/jamaneurol.2015.1897]
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