title: Association of Deep Gray Matter Damage With Cortical and Spinal Cord Degeneration in Primary Progressive Multiple Sclerosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York2Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Ruggieri
authors.affiliation: 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.
authors.forename: Maria
authors.initials: M
authors.lastname: Petracca
authors.affiliation: Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Aaron
authors.initials: A
authors.lastname: Miller
authors.affiliation: Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Stephen
authors.initials: S
authors.lastname: Krieger
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Rezwan
authors.initials: R
authors.lastname: Ghassemi
authors.affiliation: Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Yadira
authors.initials: Y
authors.lastname: Bencosme
authors.affiliation: The Neurological Institute of New York, Department of Neurology, Columbia University Medical Center, New York, New York.
authors.forename: Claire
authors.initials: C
authors.lastname: Riley
authors.affiliation: Department of Neurology, Langone Medical Center, New York University, New York, New York.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Howard
authors.affiliation: Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Fred
authors.initials: F
authors.lastname: Lublin
authors.affiliation: 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.
authors.forename: Matilde
authors.initials: M
authors.lastname: Inglese
mesh_terms: D000328:Adult; D000368:Aged; D004185:Disability Evaluation; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000150:complications*; D013116:Spinal Cord / Q000473:pathology; D013132:Spinocerebellar Degenerations / Q000209:etiology* / Q000473:pathology*; D013223:Statistics as Topic; D066127:White Matter / Q000473:pathology