Diffusion-weighted imaging in acute demyelinating myelopathy

Diffusion-weighted imaging (DWI) has become a reference MRI technique for the evaluation of neurological disorders. Few publications have investigated the application of DWI for inflammatory demyelinating lesions. The purpose of the study was to describe diffusion-weighted imaging characteristics of acute, spinal demyelinating lesions.

Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein

The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target cells. Strikingly, CDV transmission to remote cells could occur in less than 6 h, suggesting that a complete viral cycle with production of extracellular free particles was not essential in enabling CDV to spread in glial cells. Titration experiments and electron microscopy confirmed a very low CDV particle production despite higher titers of membrane-associated viruses. Interestingly, confocal laser microscopy and lentivirus transduction indicated expression and functionality of the viral fusion machinery, consisting of the viral fusion (F) and attachment (H) glycoproteins, at the cell surface. Importantly, using a single-cycle infectious recombinant H-knockout, H-complemented virus, we demonstrated that H, and thus potentially the viral fusion complex, was necessary to enable CDV spread. Furthermore, since we could not detect CD150/SLAM expression in brain cells, the presence of a yet non-identified glial receptor for CDV was suggested. Altogether, our findings indicate that persistence in CDV infection results from intracellular cell-to-cell transmission requiring the CDV-H protein. Viral transfer, happening selectively at the tip of astrocytic processes, may help the virus to cover long distances in the astroglial network, "outrunning" the host's immune response in demyelinating plaques, thus continuously eliciting new lesions.

Workshop report from the National Institutes of Health Taskforce on the Research Needs of Eosinophil-Associated Diseases (TREAD)

Eosinophils are blood cells that are often found in high numbers in the tissues of allergic conditions and helminthic parasite infections. The pathophysiologic roles that eosinophils may serve in other human "eosinophil-associated" diseases remain obscure.

Systematic review of clinical outcomes in hybrid procedures for aortic arch dissections and other arch diseases

Available data on clinical outcomes of hybrid aortic arch repair are limited, especially for patients with aortic dissection. The objective of this review was to provide pooled analysis of periprocedural mortality and neurologic outcomes in hybrid procedures involving the aortic arch for dissection and other aortic diseases.

Hospital for joint diseases participates in international spine registry Spine Tango after successful pilot study

Spine Tango is currently the only international spine registry in existence. It was developed under the auspices of Eurospine, the Spine Society of Europe, and is hosted at the University of Bern, Switzerland. The HJD Spine Center successfully tested Spine Tango during a 3-month pilot study and has since expanded documentation activities to more surgeons. Workflow integration and dedicated research staff are key factors for such an endeavor. Participation enables benchmarking against national and international peers and outcome research and quality assurance of surgical and non-surgical treatments.

Tumefactive demyelinating lesions during etanercept treatment requiring decompressive hemicraniectomy

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory and immunoregulatory cytokine involved in the pathogenesis of several autoimmune disorders. Etanercept, a TNF-α antagonist (anti-TNF-α) acting as a soluble TNF-α receptor, has been associated with neurological demyelinating disorders. This paper aims to report an unusual case showing tumefactive central nervous system (CNS) inflammatory demyelination in a patient in the course of TNF -α antagonist therapy, requiring decompressive hemicraniectomy. This report is based on magnetic resonance imaging (MRI) findings and histology. A biopsy confirmed the inflammatory demyelinating nature of the lesions. The clinical presentation is unusual due to the severity of the disease process, requiring decompressive hemicraniotomy with a clinically favorable outcome.

Tolerance of intravenous methylprednisolone for relapse treatment in demyelinating CNS disease

In Switzerland, the first course of intravenous steroids for treatment of episodes of demyelinating CNS disease is usually administered in an inpatient setting. We prospectively evaluated short term tolerance of treatment with special emphasis on sleep quality.

NADPH P450 oxidoreductase: structure, function, and pathology of diseases

Cytochrome P450 oxidoreductase (POR) is an enzyme that is essential for multiple metabolic processes, chiefly among them are reactions catalyzed by cytochrome P450 proteins for metabolism of steroid hormones, drugs and xenobiotics. Mutations in POR cause a complex set of disorders that often resemble defects in steroid metabolizing enzymes 17α-hydroxylase, 21-hydroxylase and aromatase. Since our initial reports of POR mutations in 2004, more than 200 different mutations and polymorphisms in POR gene have been identified. Several missense variations in POR have been tested for their effect on activities of multiple steroid and drug metabolizing P450 proteins. Mutations in POR may have variable effects on different P450 partner proteins depending on the location of the mutation. The POR mutations that disrupt the binding of co-factors have negative impact on all partner proteins, while mutations causing subtle structural changes may lead to altered interaction with specific partner proteins and the overall effect may be different for each partner. This review summarizes the recent discoveries related to mutations and polymorphisms in POR and discusses these mutations in the context of historical developments in the discovery and characterization of POR as an electron transfer protein. The review is focused on the structural, enzymatic and clinical implications of the mutations linked to newly identified disorders in humans, now categorized as POR deficiency.