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  • Hippocampal MRS and subfield volumetry at 7T detects dysfunction not specific to seizure focus.

    21 May 2018

    Ultra high-field 7T MRI offers sensitivity to localize hippocampal pathology in temporal lobe epilepsy (TLE), but has rarely been evaluated in patients with normal-appearing clinical MRI. We applied multimodal 7T MRI to assess if focal subfield atrophy and deviations in brain metabolites characterize epileptic hippocampi. Twelve pre-surgical TLE patients (7 MRI-negative) and age-matched healthy volunteers were scanned at 7T. Hippocampal subfields were manually segmented from 600μm isotropic resolution susceptibility-weighted images. Hippocampal metabolite spectra were acquired to determine absolute concentrations of glutamate, glutamine, myo-inositol, NAA, creatine and choline. We performed case-controls analyses, using permutation testing, to identify abnormalities in hippocampal imaging measures in individual patients, for evaluation against clinical evidence of seizure lateralisation and neuropsychological memory test scores. Volume analyses identified hippocampal subfield atrophy in 9/12 patients (75%), commonly affecting CA3. 7/8 patients had altered metabolite concentrations, most showing reduced glutamine levels (62.5%). However, neither volume nor metabolite deviations consistently lateralized the epileptogenic hippocampus. Rather, lower subiculum volumes and glutamine concentrations correlated with impaired verbal memory performance. Hippocampal subfield and metabolic abnormalities detected at 7T appear to reflect pathophysiological processes beyond epileptogenesis. Despite limited diagnostic contributions, these markers show promise to help elucidate mnemonic processing in TLE.

  • Spatiotemporal characterization of breathing-induced B0 field fluctuations in the cervical spinal cord at 7T.

    26 April 2018

    Magnetic resonance imaging and spectroscopy of the spinal cord stand to benefit greatly from the increased signal-to-noise ratio of ultra-high field. However, ultra-high field also poses considerable technical challenges, especially related to static and dynamic B0 fields. Breathing causes the field to fluctuate with the respiratory cycle, giving rise to artifacts such as ghosting and apparent motion in images. We here investigated the spatial and temporal characteristics of breathing-induced B0 fields in the cervical spinal cord at 7T. We analyzed the magnitude and spatial profile of breathing-induced fields during breath-holds in an expired and inspired breathing state. We also measured the temporal field evolution during free breathing by acquiring a time series of fast phase images, and a principal component analysis was performed on the measured field evolution. In all subjects, the field shift was largest around the vertebral level of C7 and lowest at the top of the spinal cord. At C7, we measured peak-to-peak field fluctuations of 36 Hz on average during normal free breathing; increasing to on average 113 Hz during deep breathing. The first principal component could explain more than 90% of the field variations along the foot-head axis inside the spinal cord in all subjects. We further implemented a proof-of-principle shim correction, demonstrating the feasibility of using the shim system to compensate for the breathing-induced fields inside the spinal cord. Effective correction strategies will be crucial to unlock the full potential of ultra-high field for spinal cord imaging.

  • Fibrin(ogen) and neurodegeneration in the progressive multiple sclerosis cortex.

    15 May 2018

    OBJECTIVE: Neuronal loss, a key substrate of irreversible disability in multiple sclerosis (MS), is a recognized feature of MS cortical pathology of which the cause remains unknown. Fibrin(ogen) deposition is neurotoxic in animal models of MS, but has not been evaluated in human progressive MS cortex. The aim of this study was to investigate the extent and distribution of fibrin(ogen) in progressive MS cortex and elucidate its relationship with neurodegeneration. METHODS: A postmortem cohort of pathologically confirmed MS (n = 47) and control (n = 10) cases was used. The extent and distribution of fibrin(ogen) was assessed and related to measures of demyelination, inflammation, and neuronal density. In a subset of cases (MS, n = 20; control, n = 10), expression of plasminogen activator inhibitor 1 (PAI-1), a key enzyme in the fibrinolytic cascade, was assessed and related to the extent of fibrin(ogen). RESULTS: Motor cortical fibrin(ogen) deposition was significantly over-represented in MS compared to control cases in all compartments studied (ie, extracellular [p = 0.001], cell body [p = 0.003], and neuritic/glial-processes [p = 0.004]). MS cases with high levels of extracellular fibrin(ogen) had significantly upregulated PAI-1 expression in all cortical layers assessed (p < 0.05) and reduced neuronal density (p = 0.017), including in the functionally-relevant layer 5 (p = 0.001). INTERPRETATION: For the first time, we provide unequivocal evidence that fibrin(ogen) is extensively deposited in progressive MS motor cortex, where regulation of fibrinolysis appears perturbed. Progressive MS cases with severe fibrin(ogen) deposition have significantly reduced neuronal density. Future studies are needed to elucidate the provenance and putative neurotoxicity of fibrin(ogen), and its potential impact on clinical disability. Ann Neurol 2017;82:259-270.

  • Cultivating the multiple sclerosis workforce of the future

    15 May 2018

    © 2017 Consortium of Multiple Sclerosis Centers. Multiple sclerosis (MS) is a complex neurologic disorder that affects people with ever-changing needs. The MS health-care field has entered an era of exponential knowledge growth in which better understanding of the immunologic dysregulation of the disease has translated into an expanding array of treatment options. It is estimated that, if it has not already, within the next decade the demands of a growing MS patient population will outstrip the number of professionals dedicated to the management of this chronic, lifelong disease. Therefore, there is a pressing need to attract and retain clinicians in this dynamic field. In response to this need, the Foundation of the Consortium of Multiple Sclerosis Centers organized a 2-day colloquium, a Mentorship Forum, on January 23-24, 2015, bringing together talented internal medicine and neurology trainees from across North America with an interest in MS and neuroimmunology. This article highlights the rationale for the MS Mentorship Forum, its structure and content, and its outcomes. We believe that the stage has been set to interest young, promising clinicians in learning more about MS and to encourage them to consider a career in this field. In so doing, we hope to contribute to the development of the next generation of MS experts to make a palpable difference in the lives of those affected by MS.

  • Effects of dopamine on reinforcement learning and consolidation in Parkinson's disease.

    10 May 2018

    Emerging evidence suggests that dopamine may modulate learning and memory with important implications for understanding the neurobiology of memory and future therapeutic targeting. An influential hypothesis posits that dopamine biases reinforcement learning. More recent data also suggest an influence during both consolidation and retrieval. Eighteen Parkinson's disease patients learned through feedback ON or OFF medication, with memory tested 24 hr later ON or OFF medication (4 conditions, within-subjects design with matched healthy control group). Patients OFF medication during learning decreased in memory accuracy over the following 24 hr. In contrast to previous studies, however, dopaminergic medication during learning and testing did not affect expression of positive or negative reinforcement. Two further experiments were run without the 24 hr delay, but they too failed to reproduce effects of dopaminergic medication on reinforcement learning. While supportive of a dopaminergic role in consolidation, this study failed to replicate previous findings on reinforcement learning.

  • Changes in health-related quality of life (HRQoL) after discharge from intensive care unit: a protocol for a systematic review.

    26 April 2018

    INTRODUCTION: Treatment on an intensive care unit (ICU) imposes a high treatment burden on patients, as well as an economic burden for the healthcare provider. Many studies have recorded health-related quality of life (HRQoL) in patients after treatment on an ICU. We propose a systematic review of these studies. METHODS: We will search the National Library of Medicine's PubMed electronic database (PubMed), the Cochrane database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science and Open Grey to identify papers reporting quality of life after discharge from ICU. We will include papers including validated quality of life measures. We will examine three categories: populations of patients treated on general ICUs, patients with severe infections and patients with respiratory dysfunction. We will extract HRQoL data. We will assess papers for risk of bias using the QUADAS-2 tool. The strength of our conclusions will depend on the quality and number of papers showing uniform results. ETHICS AND DISSEMINATION: This review will use published literature and contains no primary data; so we do not need ethical approval. We will submit the outcome of the systematic review to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015024700.