Faculty Bibliography

Objective: Report initial results from the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) project. Background: The Learning Health System (LHS) concept involves collecting standardized clinical and imaging data during the course of patient care. The data would then serve two purposes simultaneously: data-driven clinical care decisions and systematic learning. Design/Methods: MS PATHS was designed around the LHS concept, through collaborative meetings in 2015-2016. MS PATHS participants self-administer the Multiple Sclerosis Performance Test (MSPT) at routine clinical visits. MSPT is an iPad-based medical device designed and validated for MS. MSPT includes components of the MSFC-4, NeuroQoL, and a standardized MS history. For imaging data, brain MRIs are acquired on 3T Siemens scanners using identical image acquisition parameters, to allow generation of highly standardized MRI-metrics. Participants may also elect to contribute to a biorepository. Results: As of Oct 19, 2016, seven US centers were participating in MS PATHS in collaboration with Biogen, under guidance of a steering committee of 3 neurologists and 1 neuroradiologist from participating centers and a Biogen representative. From May 17, 2016 through October 19, 2016, 1507 patients with MS were enrolled in MS PATHS, 317 with two or more visits. Data from 1127 MSPT assessments are currently available in the LHS database, 342 with brain MRIs. Opt-in rate for data sharing has exceeded 90%, suggesting the study will yield a representative population from participating centers. Across patients currently enrolled (mean+- SD): age=52+/-12 years, Walking Speed Test = 8.46 +/- 5.54 sec, and Dominant Hand Manual Dexterity Test = 28.3 +/- 7.7 sec. Updated results and lessons learned will be presented. Conclusions: MS PATHS is the first LHS established in MS. Enrollment has been rapid, and patient acceptance high. Standardized, comprehensive clinical and imaging data collection will accelerate collaborative research efforts and support data-driven patient management

Objective: To design and implement a strategy to enable high quality, standardized MRI acquisitions across a network of participating healthcare institutions (MS PATHS). Background: Although imaging guidelines for MS patients have been recommended and MRI protocols are specified for clinical trials, there remains a high degree of variability in acquisition parameters that limit the reliability of quantitative measurements. As part of MS PATHS, we are collaborating with a network of MS centers to standardize the acquisition of MRI images for quantitative analysis. Our goal is to test the feasibility and clinical utility of collecting research-quality MRI data during routine clinical care. Design/Methods: A standardized MRI protocol was designed by healthcare institution neuroradiologists and imaging scientists at Biogen and Siemens to be feasible for routine use for multicenter imaging of any MS patient referred for MRI, and optimized for automated quantitative analysis of brain volume and MS lesions. Incorporation of these agreed-upon sequences into the routine MS-MRI protocol was part of the MS PATHS start-up process. Results: The MS PATHS brain imaging protocol includes two 1mm isotropic product sequences optimized for Siemens 3T scanners: a pre-contrast 3D MPRAGE and 3D SPACE FLAIR with a total scan time of 11.42 minutes. Currently, the highly standardized sequences have been implemented as standard of care in 8 institutions. Within the first 2 weeks since activation, 383 retrospective MRI studies from 342 unique patients were received from the first institution and 98.5% of these scans passed automated QA/QC, demonstrating the initial feasibility of this approach. Conclusions: To our knowledge this is the first implementation of a rigorously standardized MRI protocol across MS centers to generate research quality imaging metrics in clinical practice. Integration into a learning health system will improve clinical care and research

While cerebral amyloid angiopathy is a common cause of lobar hemorrhage, rarely it may be associated with an inflammatory response, thought to be incited by amyloid deposits. We report a 73-year-old woman with an extensive cancer history who presented with tumor-like lesions and symptoms of homonymous hemianopia and prosopagnosia. Found to have cerebral amyloid angiopathy-related inflammation proven by brain biopsy, she was treated successfully with immunosuppression.

Saccades rapidly direct the line of sight to targets of interest to make use of the high acuity foveal region of the retina. These fast eye movements are instrumental for scanning visual scenes, foveating targets, and, ultimately, serve to guide manual motor control, including eye-hand coordination. Cerebral injury has long been known to impair ocular motor control. Recently, it has been suggested that alterations in control may be useful as a marker for recovery. We measured eye movement control in a saccade task in subjects with chronic middle cerebral artery stroke with both cortical and substantial basal ganglia involvement and in healthy controls. Saccade latency distributions were bimodal, with an early peak at 60 ms (anticipatory saccades) and a later peak at 250 ms (regular saccades). Although the latencies corresponding to these peaks were the same in the two groups, there were clear differences in the size of the peaks. Classifying saccade latencies relative to the saccade "go signal" into anticipatory (latencies up to 80 ms), "early" (latencies between 80 and 160 ms), and "regular" types (latencies longer than 160 ms), stroke subjects displayed a disproportionate number of anticipatory saccades, whereas control subjects produced the majority of their saccades in the regular range. We suggest that this increase in the number of anticipatory saccade events may result from a disinhibition phenomenon that manifests as an impairment in the endogenous control of ocular motor events (saccades) and interleaved fixations. These preliminary findings may help shed light on the ocular motor deficits of neurodegenerative conditions, results that may be subclinical to an examiner, but clinically significant secondary to their functional implications.

BACKGROUND AND PURPOSE: Obtaining high-resolution brain MR imaging in patients with a previously implanted deep brain stimulator has been challenging and avoided by many centers due to safety concerns relating to implantable devices. We present our experience with a practical clinical protocol at 1.5T by using 2 magnet systems capable of achieving presurgical quality imaging in patients undergoing bilateral, staged deep brain stimulator insertion. MATERIALS AND METHODS: Protocol optimization was performed to minimize the specific absorption rate while providing image quality necessary for adequate surgical planning of the second electrode placement. We reviewed MR imaging studies performed with a minimal specific absorption rate protocol in patients with a deep brain stimulator in place at our institution between February 1, 2012, and August 1, 2015. Images were reviewed by a neuroradiologist and a functional neurosurgeon. Image quality was qualitatively graded, and the presence of artifacts was noted. RESULTS: Twenty-nine patients (22 with Parkinson disease, 6 with dystonia, 1 with essential tremor) were imaged with at least 1 neuromodulation implant in situ. All patients were imaged under general anesthesia. There were 25 subthalamic and 4 globus pallidus implants. Nineteen patients were preoperative for the second stage of bilateral deep brain stimulator placement; 10 patients had bilateral electrodes in situ and were being imaged for other neurologic indications, including lead positioning. No adverse events occurred during or after imaging. Mild device-related local susceptibility artifacts were present in all studies, but they were not judged to affect overall image quality. Minimal aliasing artifacts were seen in 7, and moderate motion, in 4 cases on T1WI only. All preoperative studies were adequate for guidance of a second deep brain stimulator placement. CONCLUSIONS: An optimized MR imaging protocol that minimizes the specific absorption rate can be used to safely obtain high-quality images in patients with previously implanted deep brain stimulators, and these images are adequate for surgical guidance.

Research Objectives: Processing speed (PS) deficits are among the most common neuropsychological (NP) deficits following traumatic brain injury (TBI). These objective deficits may lead to subjective feelings of being flooded and overwhelmed or that things happen too quickly that one can no longer keep up with cognitive demands made by external events. This subjective experience of slowed PS has been proposed to underlie symptoms of emotional reactivity (ER), such as, tension, frustration, and irritability, which in turn may exacerbate cognitive complaints. The aim of this study was to evaluate the role of objective PS deficits in ER and cognitive/somatic postconcussive symptoms (PCS) following mild TBI (mTBI). Design: Correlational/regression analyses examining objective PS measures, ER, and somatic/cognitive PCS. Setting: Large academic medical center. Participants: Adults with mTBI (n = 31), 52% female, primarily White (74%), average age of 35.8, with 16.1 years of education. Interventions: N/A. Main Outcome Measure(s): Standard TBI outcome battery, 6,7 addressing (a) objective NP impairments, (b) psychological status, and (c) PCS. ER was assessed using z-score composite of relevant self-report items. Results: Objective PS measures were significantly related to ER. ER explained a significant 33% of variance in somatic/cognitive PCS, Beta = -.62, t (29) = -3.15, p =.004, over and above variance explained directly by PS, Beta = -.07, t (29) = -.38, ns. Conclusions: ER is directly related to objective PS deficits. In addition, ER is a significant predictor of somatic/cognitive PCS, whereas objective PS measures are not directly related to PCS. Emotional reactions to the experience of objective cognitive slowing warrant further investigation as a predictor of those at risk for prolonged PCS. Further examination of ER as a predictor of PCS may lead to more accurate assessment/prognosis following mTBI

Mild traumatic brain injury (mTBI), also commonly referred to as concussion, affects millions of Americans annually. Although computed tomography is the first-line imaging technique for all traumatic brain injury, it is incapable of providing long-term prognostic information in mTBI. In the past decade, the amount of research related to magnetic resonance (MR) imaging of mTBI has grown exponentially, partly due to development of novel analytical methods, which are applied to a variety of MR techniques. Here, evidence of subtle brain changes in mTBI as revealed by these techniques, which are not demonstrable by conventional imaging, will be reviewed. These changes can be considered in three main categories of brain structure, function, and metabolism. Macrostructural and microstructural changes have been revealed with three-dimensional MR imaging, susceptibility-weighted imaging, diffusion-weighted imaging, and higher order diffusion imaging. Functional abnormalities have been described with both task-mediated and resting-state blood oxygen level-dependent functional MR imaging. Metabolic changes suggesting neuronal injury have been demonstrated with MR spectroscopy. These findings improve understanding of the true impact of mTBI and its pathogenesis. Further investigation may eventually lead to improved diagnosis, prognosis, and management of this common and costly condition. ((c)) RSNA, 2016.