The impact of cervical spinal cord atrophy on quality of life in multiple sclerosis. 
Spinal cord demyelination is common in multiple sclerosis (MS) and has been linked to increased disability and progressive clinical course.  Spinal cord atrophy shows an especially close relationship to MS-related physical disability, though the relationship between spinal cord lesions/atrophy and health-related quality of life (QOL) has not been explored.  62 patients (53 relapsing MS, 7 secondary progressive, 2 clinically isolated syndrome) from our center underwent 3 T MRI within 30 days of clinical examination and QOL assessment.  Upper cervical (C1-C3) spinal cord area (UCCA) was obtained from 3D high-resolution MPRAGE sequences (1 mm isotropic voxels).  Cervical spinal cord (C1-C7) lesion count, and cervical and brain T2 hyperintense lesion volumes were calculated.  Brain parenchymal fraction (BPF) was obtained from an automated segmentation pipeline.  Spearman correlations were assessed between MRI and clinical data.  Partial Spearman correlations adjusting for age, disease duration, and BPF assessed the independent association between MRI variables and QOL domains.  UCCA showed an inverse relationship with age (r = -0.330, p = .009), disease duration, (r = -0.444, p < .001), and nine-hole peg test (r = -0.353, p = .005).  The Upper Extremity Function QOL domain showed the strongest relationship to UCCA (r = 0.333, p = .008), with Lower Extremity Function QOL (r = 0.234, p = .067) and Satisfaction with Social Roles and Activities (r = 0.245, p = .055) correlations bordering significance.  The association between UCCA and Upper Extremity QOL remained significant after adjustment for BPF, age, and disease duration.  QOL domains reflective of psychological health (Depression, Anxiety, Emotional and Behavioral Dyscontrol, Positive Affect and Wellbeing) showed no relationship to UCCA.  Cervical and brain lesion volume related to impairment in Stigma while cervical lesion count was unrelated to NeuroQOL impairment.  Brain atrophy correlated with conventional markers of disability and cognition but did not have a significant relationship to QOL.  Cervical spinal cord volume is independently associated with impaired upper extremity-related QOL in patients with MS.  These findings suggest specific clinical relevance of MS-related spinal cord atrophy as compared to brain or cervical spinal cord lesions, or whole brain atrophy.