Putaminal diffusion tensor imaging measures predict disease severity across human prion diseases

Therapeutic trials of disease-modifying agents in neurodegenerative disease typically require several hundred participants and long durations for clinical endpoints. Trials of this size are not feasible for prion diseases, rare dementia disorders associated with misfolding of prion protein. In this situation, biomarkers are particularly helpful. On diagnostic imaging, prion diseases demonstrate characteristic brain signal abnormalities on diffusion-weighted MRI. The aim of this study was to determine whether cerebral water diffusivity could be a quantitative imaging biomarker of disease severity. We hypothesized that the basal ganglia were most likely to demonstrate functionally relevant changes in diffusivity. Seventy-one subjects (37 patients and 34 controls) of whom 47 underwent serial scanning (23 patients and 24 controls) were recruited as part of the UK National Prion Monitoring Cohort. All patients underwent neurological assessment with the Medical Research Council Scale, a functionally orientated measure of prion disease severity, and diffusion tensor imaging. Voxel-based morphometry, voxel-based analysis of diffusion tensor imaging and regions of interest analyses were performed. A significant voxel-wise correlation of decreased Medical Research Council Scale score and decreased mean, radial and axial diffusivities in the putamen bilaterally was observed (P < 0.01). Significant decrease in putamen mean, radial and axial diffusivities over time was observed for patients compared with controls (P = 0.01), and there was a significant correlation between monthly decrease in putamen mean, radial and axial diffusivities and monthly decrease in Medical Research Council Scale (P < 0.001). Step-wise linear regression analysis, with dependent variable decline in Medical Research Council Scale, and covariates age and disease duration, showed the rate of decrease in putamen radial diffusivity to be the strongest predictor of rate of decrease in Medical Research Council Scale (P < 0.001). Sample size calculations estimated that, for an intervention study, 83 randomized patients would be required to provide 80% power to detect a 75% amelioration of decline in putamen radial diffusivity. Putamen radial diffusivity has potential as a secondary outcome measure biomarker in future therapeutic trials in human prion diseases.

Depression and Anxiety in Traumatic Brachial Plexus Injury Patients Are Associated With Reduced Motor Outcome After Surgical Intervention for Restoration of Elbow Flexion

BACKGROUND: Depression has been associated with poor outcomes in neurosurgical patients, including increased pain, poorer functional recovery, delayed return to work, and decreased patient satisfaction. No reports exist regarding an association of psychiatric diagnoses with outcomes after brachial plexus reconstruction. As outcomes and patient satisfaction become increasingly important to payers and physician reimbursement, assessing modifiable preoperative risk factors for their association with poor outcome and patient satisfaction is imperative. OBJECTIVE: To analyze patients undergoing brachial plexus reconstruction to assess the relationship of depression/anxiety with functional outcome. METHODS: Data were collected retrospectively on all patients who underwent brachial plexus reconstruction to restore elbow flexion between 2005 and 2013. Elbow flexion, graded via the Medical Research Council scale, was assessed at latest follow-up. Multiple variables, including the presence of Axis I psychiatric diagnoses, were assessed for their association with the dichotomous outcome of Medical Research Council scale score ≥3 (antigravity) vs <3 elbow flexion. Standard statistical methods were used. RESULTS: Thirty-seven patients met inclusion criteria. The median postsurgical follow-up time was 21 months. Operations included neurolysis (n = 3), nerve graft repair (n = 6), and nerve transfer (n = 28). Depression was present in 10 of 37 patients (27%). Of variables tested, only depression was associated with poor elbow flexion outcome (odds ratio: 6.038; P = .04). CONCLUSION: Preoperative depression is common after brachial plexus injury. The presence of depression is associated with reduced elbow flexion recovery after reconstruction. Our data suggest assessment and treatment of preoperative mental health is important in designing a comprehensive postoperative management plan to optimize outcomes and patient satisfaction.