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Special Issue "Pathophysiology and Imaging Diagnosis of Demyelinating Disorders"

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A special issue of Brain Sciences (ISSN 2076-3425).

Deadline for manuscript submissions: closed (30 April 2017)

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Special Issue Editor

Guest Editor

Dr. Evanthia Bernitsas

Multiple Sclerosis Center, Wayne State University School of Medicine, Detroit, USA
Website | E-Mail
Interests: demyelinating disorders; clinical trials; therapeutic neuroimaging; OCT

Special Issue Information

Dear Colleagues,

Demyelinating disorders are chronic autoimmune disorders characterized by inflammation, demyelination, axonal degeneration, and neuronal loss. They have complex pathophysiology and diverse clinical presentations. The etiology of these disorders lies in the interaction between genetic and environmental factors. Due to the complexity in pathophysiology and presentation, diagnosis and treatment can be challenging. Advanced technology, including modern imaging techniques, as well as optical coherence tomography (OCT), enrich our understanding of the disease process, improve diagnostic accuracy, and may guide treatment decisions.

In this Special Issue, we invite and welcome manuscripts addressing, but not limited to: Genetics, etiology, pathogenesis, differential diagnosis, brain imaging, OCT, therapeutics, biomarkers related to disability progression, and critical reviews of clinical trials. Of greatest interest are articles focusing on: (1) advanced MRI imaging modalities and OCT in the differential diagnosis and treatment decisions. (2) novel agents treating symptoms, relapses, and promoting axonal/myelin repair.

We kindly invite you to contribute a manuscript to this Special Issue of Brain Sciences.

Evanthia Bernitsas, MD
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 650 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

•   demyelinating disorders
•   multiple sclerosis
•   therapeutics
•   neuroimaging
•   optical coherence tomography
•   autoimmune
•   remyelination

Published Papers (5 papers)

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Research

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Open AccessArticle Evaluation of Visual-Evoked Cerebral Metabolic Rate of Oxygen as a Diagnostic Marker in Multiple Sclerosis

by Nicholas A. Hubbard, Yoel Sanchez Araujo, Camila Caballero, Minhui Ouyang, Monroe P. Turner, Lyndahl Himes, Shawheen Faghihahmadabadi, Binu P. Thomas, John Hart, Hao Huang, Darin T. Okuda and Bart Rypma

Brain Sci. 2017, 7(6), 64; doi:10.3390/brainsci7060064

Received: 31 March 2017 / Revised: 3 June 2017 / Accepted: 5 June 2017 / Published: 11 June 2017

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A multiple sclerosis (MS) diagnosis often relies upon clinical presentation and qualitative analysis of standard, magnetic resonance brain images. However, the accuracy of MS diagnoses can be improved by utilizing advanced brain imaging methods. We assessed the accuracy of a new neuroimaging marker, visual-evoked cerebral metabolic rate of oxygen (veCMRO₂), in classifying MS patients and closely age- and sex-matched healthy control (HC) participants. MS patients and HCs underwent calibrated functional magnetic resonance imaging (cfMRI) during a visual stimulation task, diffusion tensor imaging, T₁- and T₂-weighted imaging, neuropsychological testing, and completed self-report questionnaires. Using resampling techniques to avoid bias and increase the generalizability of the results, we assessed the accuracy of veCMRO₂ in classifying MS patients and HCs. veCMRO₂ classification accuracy was also examined in the context of other evoked visuofunctional measures, white matter microstructural integrity, lesion-based measures from T₂-weighted imaging, atrophy measures from T₁-weighted imaging, neuropsychological tests, and self-report assays of clinical symptomology. veCMRO₂ was significant and within the top 16% of measures (43 total) in classifying MS status using both within-sample (82% accuracy) and out-of-sample (77% accuracy) observations. High accuracy of veCMRO₂ in classifying MS demonstrated an encouraging first step toward establishing veCMRO₂ as a neurodiagnostic marker of MS. Full article

(This article belongs to the Special Issue Pathophysiology and Imaging Diagnosis of Demyelinating Disorders)

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Review

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Open AccessReview Multiple Sclerosis: Immunopathology and Treatment Update

by Narges Dargahi, Maria Katsara, Theodore Tselios, Maria-Eleni Androutsou, Maximilian de Courten, John Matsoukas and Vasso Apostolopoulos

Brain Sci. 2017, 7(7), 78; doi:10.3390/brainsci7070078

Received: 25 June 2017 / Revised: 30 June 2017 / Accepted: 3 July 2017 / Published: 7 July 2017

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The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS. Full article

(This article belongs to the Special Issue Pathophysiology and Imaging Diagnosis of Demyelinating Disorders)

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Open AccessReview The Role of Peripheral CNS‐Directed Antibodies in Promoting Inflammatory CNS Demyelination

by Silke Kinzel and Martin S. Weber

Brain Sci. 2017, 7(7), 70; doi:10.3390/brainsci7070070

Received: 18 May 2017 / Revised: 16 June 2017 / Accepted: 17 June 2017 / Published: 22 June 2017

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In central nervous system (CNS) demyelinating disorders, such as multiple sclerosis (MS), neuromyelitis optica (NMO) and related NMO-spectrum disorders (NMO-SD), a pathogenic role for antibodies is primarily projected into enhancing ongoing CNS inflammation by directly binding to target antigens within the CNS. This scenario is supported at least in part, by antibodies in conjunction with complement activation in the majority of MS lesions and by deposition of anti-aquaporin-4 (AQP-4) antibodies in areas of astrocyte loss in patients with classical NMO. A currently emerging subgroup of AQP-4 negative NMO-SD patients expresses antibodies against myelin oligodendrocyte glycoprotein (MOG), again suggestive of their direct binding to CNS myelin. However, both known entities of anti-CNS antibodies, anti-AQP-4- as well as anti-MOG antibodies, are predominantly found in the serum, which raises the questions why and how a humoral response against CNS antigens is raised in the periphery, and in a related manner, what pathogenic role these antibodies may exert outside the CNS. In this regard, recent experimental and clinical evidence suggests that peripheral CNS-specific antibodies may indirectly activate peripheral CNS-autoreactive T cells by opsonization of otherwise unrecognized traces of CNS antigen in peripheral compartments, presumably drained from the CNS by its newly recognized lymphatic system. In this review, we will summarize all currently available data on both possible roles of antibodies in CNS demyelinating disorders, first, directly enhancing damage within the CNS, and second, promoting a peripheral immune response against the CNS. By elaborating on the latter scenario, we will develop the hypothesis that peripheral CNS-recognizing antibodies may have a powerful role in initiating acute flares of CNS demyelinating disease and that these humoral responses may represent a therapeutic target in its own right. Full article

(This article belongs to the Special Issue Pathophysiology and Imaging Diagnosis of Demyelinating Disorders)

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Open AccessReview Contribution of the Degeneration of the Neuro-Axonal Unit to the Pathogenesis of Multiple Sclerosis

by Hannah E. Salapa, Sangmin Lee, Yoojin Shin and Michael C. Levin

Brain Sci. 2017, 7(6), 69; doi:10.3390/brainsci7060069

Received: 5 May 2017 / Revised: 9 June 2017 / Accepted: 14 June 2017 / Published: 18 June 2017

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Abstract

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Multiple sclerosis (MS) is a demyelinating, autoimmune disease of the central nervous system. In recent years, it has become more evident that neurodegeneration, including neuronal damage and axonal injury, underlies permanent disability in MS. This manuscript reviews some of the mechanisms that could be responsible for neurodegeneration and axonal damage in MS and highlights the potential role that dysfunctional heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and antibodies to hnRNP A1 may play in MS pathogenesis. Full article

(This article belongs to the Special Issue Pathophysiology and Imaging Diagnosis of Demyelinating Disorders)

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Open AccessReview Is Decompressive Surgery for Cervical Spondylotic Myelopathy Effective in Patients Suffering from Concomitant Multiple Sclerosis or Parkinson’s Disease?

by Taylor E. Purvis, Daniel Lubelski and Thomas E. Mroz

Brain Sci. 2017, 7(4), 39; doi:10.3390/brainsci7040039

Received: 24 February 2017 / Revised: 29 March 2017 / Accepted: 6 April 2017 / Published: 10 April 2017

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A subset of patients with a demyelinating disease suffer from concurrent cervical spondylotic myelopathy, both of which evince similar symptomatology. Differentiating the cause of these symptoms is challenging, and little research has been done on patients with coexisting diseases. This review explores the current literature on the appropriate surgical management of patients with concurrent multiple sclerosis (MS) and cervical spondylotic myelopathy (CSM), and those with both Parkinson’s disease (PD) and CSM. MS and CSM patients may benefit from surgery to reduce pain and radiculopathy. Surgical management in PD and CSM patients has shown minimal quality-of-life improvement. Future studies are needed to better characterize demyelinating disease patients with concurrent disease and to determine ideal medical or surgical treatment. Full article

(This article belongs to the Special Issue Pathophysiology and Imaging Diagnosis of Demyelinating Disorders)

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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Pathophysiology, Differential Diagnosis and Treatment of Acute MS Presentations
Author: Regina Berkovich
Affiliation: Neurology Department, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Abstract: Exacerbation or relapse is a classic acute presentation of Multiple Sclerosis (MS), and is commonly associated with disabling symptoms. The chapter will review the pathoimmunology of MS relapse and variants of clinical presentation; specific attention will be given to pseudo-exacerbations and importance of differential diagnosis.
Adequate management of MS relapses as ways to shorten and lessen associated impairments are going to be discussed. Systemic corticosteroids have broad regulatory approval and remain the most frequently used, well established and validated treatment options for MS relapse. Adrenocotricotropic hormone (ACTH) as a second line therapy for steroid-intolerant or resistant cases will be reviewed. We will discuss clinical trials, therapeutic mechanisms and side effects of systemic steroids and ACTH. Second line options for treatment-unresponsive MS relapses will be reviewed along with proposed algorithm for MS relapse management.

Title: Aerobic Exercise to Enhance Neuroplasticity and Restore Walking Ability among People with Multiple Sclerosis—A Systematic Review of Animal and Clinical Studies
Authors: Augustine Joshua Devasahayam, Matthew B. Downer, Samantha N. Rancourt, Michelle Ploughman.
Affiliation: Recovery and Performance Laboratory, Faculty of Medicine, Memorial University of Newfoundland, L.A. Miller Centre, 100 Forest Road, St. John’s NL Canada A1A1E5.
Abstract: Introduction: Aerobic exercise has been found to regulate proteins in the blood that may reduce inflammation and promote healing in the brain among people with Multiple Sclerosis (MS). However, it is not clear if such regulatory effects of aerobic exercise will result in improvements on walking ability in people with MS. The aim of this review is to assess the effectiveness of aerobic exercise in improving walking ability while regulating serum levels of brain-derived neurotrophic factors and inflammatory cytokines among people with MS.
Methods: Five literature databases (PubMed, Cochrane Library, Embase, Physiotherapy Evidence Database [PEDro], and SCOPUS) and reference lists of relevant reviews were searched. The human trials that investigated aerobic exercise for a period of at least 3 weeks or more, having outcomes in walking ability, were included. The animal trials that investigated aerobic exercise having blood and brain tissue outcomes were included. Two reviewers independently performed title, abstract and full-text review. From a total of 1783 articles identified, 10 human trials and 7 animal trials were included in this review. A subsequent methodological assessment was performed on all the selected articles.
Results: In human trials, 5 aerobic type interventions produced significant improvements in walking ability: treadmill training, repetitive endurance activities, progressive aerobic/strength combination training, robot-assisted treadmill and leg ergometer. Out of 10 selected human trials, only two studies evaluated outcomes on both walking ability and blood markers on brain inflammation and repair (IL-6, sIL-6R, BDNF, NGF). Six out of seven selected animal trials report positive change in the levels of blood and brain tissue proteins on aerobic type intervention.
Conclusion: This systematic review suggests that aerobic exercise may improve walking ability in people with MS. Further research is needed to corroborate this finding among those with higher disability. More studies are needed to identify changes in blood profile while evaluating recovery on walking ability in people with MS. The exercise protocols investigated in animal trials cannot be translated to suit patient needs as the exercise parameters used in animal research do not simulate human MS trials.

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