Microstructural Changes in the Left Mesocorticolimbic Pathway are Associated with the Comorbid Development of Fatigue and Depression in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Lower reward responsiveness has been associated with fatigue in multiple sclerosis (MS). However, association of MS-related fatigue with damage to the mesocorticolimbic reward pathway (superolateral medial forebrain bundle [slMFB]) has not been assessed. We investigated the association of fatigue and depression with slMFB damage in MS patients stratified based on longitudinal fatigue patterns. METHODS: Patient stratification: 1. Sustained Fatigue (SF): latest two Modified Fatigue Impact Scale (MFIS) ≥ 38 (n = 26); 2. Reversible Fatigue (RF): latest MFIS < 38, and at least one previous MFIS ≥ 38 (n = 25); 3. Never Fatigued (NF): ≥ 5 consecutive MFIS < 38 (n = 42); 4. Healthy Controls (n = 6). Diffusion MRI-derived measures of fractional anisotropy (FA), axial (AD), mean (MD), and radial diffusivity (RD) of the slMFB were compared between the groups. Depression was assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D). RESULTS: Depressed (CES-D ≥ 16) SF patients showed significantly higher MD and RD than nondepressed SF and RF, and depressed RF patients, and significantly lower FA than nondepressed SF and depressed RF patients in their left slMFB. Depressed SF patients showed significantly higher left slMFB MD and AD than healthy controls. CONCLUSION: Microstructural changes to the left slMFB may play a role in the comorbid development of fatigue and depression in MS.

Identification and Characterization of Leptomeningeal Metastases Using SPINE, A Web-Based Collaborative Platform.

BACKGROUND AND PURPOSE: Leptomeningeal metastases (LMs) carry a poor prognosis. Existing LM scoring systems show limited reproducibility. We assessed the contribution of education level on the reproducibility of LM scoring using structured planning and implementation of new experiments (SPINE), a novel web-based platform. METHODS: Stringent radiological definitions of LM and a customized interactive scoring system were implemented in SPINE. Five patients with brain LM and 3 patients with spine, but no brain LM, were selected. Each patient's baseline post-contrast T1-weighted brain MRI was analyzed by three attending neuroradiologists, two neuroradiology fellows, and two radiology residents. Raters identified and characterized all LMs based on: (1) location (cerebrum, cerebellum, brainstem, ventricle, and/or cranial nerves); (2) shape (nodular and/or linear/curvilinear); (3) size (≥ or <5mm in two orthogonal diameters); (4) spatial extension (focal or diffuse). Inter-rater agreement and association of LM with patient survival were investigated. RESULTS: On average, 6.5 LMs per case were detected. Forty-nine percent of LMs were cerebral, 77.7% were nodular, 86.6% were focal, and 66% were <5 × 5 mm. Agreement on the total number of LMs and the above-mentioned common LM characteristics was higher between attendings (intra-class correlation [ICC] = 0.8-0.94) than fellows (ICC = 0.6-0.82) or residents (ICC = 0.43-0.73). Agreement on ventricular, cranial nerve, and nodular + linear LM was low even between attendings. The number of brainstem LMs showed significant correlation with survival. CONCLUSION: Structured education using SPINE may improve consistency in LM reporting. Future work should address the impact of the presented approach on the reproducibility of longitudinal analyses directly relevant to the assessment of treatment-response.

Reliability of the nitrogen washin-washout technique to assess end-expiratory lung volume at variable PEEP and tidal volumes.

BACKGROUND: End-expiratory lung volume measurement by the nitrogen washin-washout technique (EELVWI-WO) may help titrating positive end-expiratory pressure (PEEP) during acute respiratory distress syndrome (ARDS). Validation of this technique has been previously performed using computed tomography (EELVCT), but at mild PEEP levels, and relatively low fraction of inspired oxygen (FiO2), which may have insufficiently challenged the validity of this technique. The aims of this study were (1) to evaluate the reliability of EELVWI-WO measurements at different PEEP and V T during experimental ARDS and (2) to evaluate trending ability of EELVWI-WO to detect EELV changes over time. METHODS: ARDS was induced in 14 piglets by saline lavage. Optimal PEEP was selected during a decremental PEEP trial, based on best compliance, best EELVWI-WO, or a PEEP-FiO2 table. Eight V T (4 to 20 mL · kg(-1)) were finally applied at optimal PEEP. EELVWI-WO and EELVCT were determined after ARDS onset, at variable PEEP and V T. RESULTS: EELVWI-WO underestimated EELVCT with a non-constant linear bias, as it decreased with increasing EELV. Limits of agreement for bias were ±398 mL. Bias between methods was greater at high PEEP, and further increased when high PEEP was combined with low V T. Concordance rate of EELV changes between consecutive measurements was fair (79%). Diagnostic accuracy was good for detection of absolute EELV changes above 200 mL (AUC = 0.79). CONCLUSIONS: The reliability of the WI-WO technique is critically dependent on ventilatory settings, but sufficient to accurately detect EELV change greater than 200 mL.