title: Brain atrophy and physical disability in primary progressive multiple sclerosis: A volumetric study.
abstract: Grey matter atrophy has been shown in primary progressive multiple sclerosis (PPMS), but its association with physical incapacity is unclear. We submitted 19 patients with PPMS to a neurological evaluation and brain magnetic resonance imaging (MRI) with volumetric analysis using FreeSurfer. We found no relation between the Expanded Disability Status Scale or disease duration and the grey matter or white matter structures analysed. Lesion load was negatively correlated with cortical and subcortical grey matter volumes, but not with total white matter volume. We concluded that physical disability in PPMS is not directly related to brain atrophy and that focal inflammatory white matter lesions may contribute to progressive neuronal degeneration.
  
  
  BACKGROUND
  Primary progressive multiple sclerosis (PPMS) is characterized by chronic progression since onset, with predominant involvement of the spinal cord and prominent neurodegeneration. Grey matter atrophy has been shown in patients with PPMS, but its association with clinical incapacity is uncertain. We investigated the relationship between regional brain atrophy and physical disability in patients with PPMS.
  
  
  METHODS
  Patients with an established diagnosis of PPMS underwent a neurological evaluation followed by brain MRI at 1.5 T. Volumetric analysis was performed with FreeSurfer software, and evaluated the neocortex, total white matter, total subcortical grey matter, putamen, caudate, globus pallidus, thalamus, hippocampus, brainstem, corpus callosum and pre-central gyrus volumes. Clinical data obtained included physical disability as measured by the Expanded Disability Status Scale (EDSS).
  
  
  RESULTS
  Nineteen patients were included, 14 female (73.7%), mean age of 55.7 (SD 7.6) and mean disease duration of 13.0 years (SD 8.8). Median EDSS score was 6.0 (3.5-8.0). The average T1 lesion load (4.9 cm³, SD 3.4) and T2 load (10.5 cm³, SD 9.9) did not relate to disease duration. There was no significant correlation between EDSS score or disease duration and the cortical grey matter, deep grey matter or white matter structures analysed. Lesion load was negatively correlated with cortical and subcortical grey matter volumes (p < 0.05), but not with total white matter volume.
  
  
  CONCLUSIONS
  Physical disability in PPMS is not directly related to brain volume loss. Grey matter atrophy correlates with lesion load in patients with PPMS, indicating that focal inflammatory white matter lesions may contribute to progressive neuronal degeneration.
authors.affiliation: Coimbra Hospital and University Centre, Department of Neuroradiology, Coimbra, Portugal orlando.galego@gmail.com.
authors.forename: Orlando
authors.initials: O
authors.lastname: Galego
authors.affiliation: Coimbra Hospital and University Centre, Department of Neurology, Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Gouveia
authors.affiliation: Coimbra Hospital and University Centre, Department of Neurology, Coimbra, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Batista
authors.affiliation: Coimbra Hospital and University Centre, Department of Neuroradiology, Coimbra, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Moura
authors.affiliation: Coimbra Hospital and University Centre, Department of Neuroradiology, Coimbra, Portugal.
authors.forename: Egídio
authors.initials: E
authors.lastname: Machado
mesh_terms: D001284:Atrophy; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis*; D009929:Organ Size; D066127:White Matter / Q000473:pathology
keywords: FreeSurfer; MRI; Primary progressive multiple sclerosis; grey matter atrophy