Faculty Bibliography

The epidemiology of vasculitis has witnessed extraordinary advances in the past decade influenced by the worldwide increased recognition and accurate classification and diagnosis of the vasculitides, and insights brought by genome-wide association studies and online genetic biological repositories that permit researchers to freely access a wide array of genetic and clinical resources that contribute to the understanding of the heritable factors of the systemic vasculitides. This article reviews the current knowledge of the epidemiology of vasculitides in different global regions.

Background and Aims: Contemplating the use of N-acetylcysteine as a neuroprotectant, with dextran as an antithrombotic for patients with NIHSS less than or equal to 5, we quantified treatment-relevant clinical characteristics of a sample of this patient population at a single stroke center over one year.
Method(s): Patients with NIHSSResult(s): One-hundred twenty-eight of 310 (41%) patients with ischemic stroke had NIHSSConclusion(s): Minor stroke symptoms may not be captured by the current NIHSS. This population rarely had renal or hepatic failure, making them good candidates for combination N-acetylcysteine and dextran

Rare pain-insensitive individuals offer unique insights into how pain circuits function and have led to the development of new strategies for pain control. We investigated pain sensitivity in humans with WAGR (Wilms tumor, aniridia, genitourinary anomaly, and range of intellectual disabilities) syndrome, who have variably sized heterozygous deletion of the 11p13 region. The deletion region can be inclusive or exclusive of the brain-derived neurotrophic factor (BDNF) gene, a crucial trophic factor for nociceptive afferents. Nociceptive responses assessed by quantitative sensory testing demonstrated reduced pain sensitivity only in the WAGR subjects whose deletion boundaries included the BDNF gene. Corresponding behavioral assessments were made in heterozygous Bdnf knockout rats to examine the specific role of Bdnf. These analogous experiments revealed impairment of Aδ- and C-fiber-mediated heat nociception, determined by acute nociceptive thermal stimuli, and in aversive behaviors evoked when the rats were placed on a hot plate. Similar results were obtained for C-fiber-mediated cold responses and cold avoidance on a cold-plate device. Together, these results suggested a blunted responsiveness to aversive stimuli. Our parallel observations in humans and rats show that hemizygous deletion of the BDNF gene reduces pain sensitivity and establishes BDNF as a determinant of nociceptive sensitivity.

Several pathogens have the propensity to involve blood vessels during central nervous system infection, which can lead to cerebrovascular complications. Infection is a recognized cause of secondary central nervous system vasculitis. It is important not to miss the diagnosis of infection-related central nervous system vasculitis because specific antimicrobial therapy may be necessary; this article reviews the major implicated organisms.

The systemic vasculitides are heterogeneous clinicopathologic disorders that share the common feature of vascular inflammation. The resulting disorder can vary depending on involvement of specific organs, caliber of blood vessels, the underlying inflammatory process, and individual host factors. The cumulative result is diminished blood flow, vascular alterations, and eventual occlusion with variable ischemia, necrosis, and tissue damage. An international revised nomenclature system provides the necessary nosology and findings relevant to classify each of the vasculitides. This article is an introduction and overview of the clinical presentation, differential diagnosis, laboratory evaluation, and treatment of systemic and nervous system vasculitides.

Illicit drug abuse is a common differential diagnosis of acquired central nervous system vasculitis even though there are only a handful of histopathologically confirmed patients in the literature from among the many potential classes of abused drugs traditionally implicated in this disease. This article considers the major classes of illicit drugs in those with and without human immunodeficiency virus type-1 infection and acquired immune deficiency syndrome.

Granulomatous inflammation, the prototypical histopathology of adult and childhood vasculitis, is characterized by inflammation of blood vessels accompanied by giant cells and epithelioid cells in the walls of cerebral vessels ranging from small leptomeningeal veins to large named cerebral arteries. Headache, hemiparesis, mental changes, abnormal cerebrospinal fluid protein content, and pleocytosis are suggestive features that warrant brain and leptomeningeal biopsy to make the diagnosis certain and begin cytotoxic therapy to improve outcome.

Visual performance depends on polar angle, even when eccentricity is held constant; on many psychophysical tasks observers perform best when stimuli are presented on the horizontal meridian, worst on the upper vertical, and intermediate on the lower vertical meridian. This variation in performance 'around' the visual field can be as pronounced as that of doubling the stimulus eccentricity. The causes of these asymmetries in performance are largely unknown. Some factors in the eye, e.g. cone density, are positively correlated with the reported variations in visual performance with polar angle. However, the question remains whether these correlations can quantitatively explain the perceptual differences observed 'around' the visual field. To investigate the extent to which the earliest stages of vision-optical quality and cone density-contribute to performance differences with polar angle, we created a computational observer model. The model uses the open-source software package ISETBIO to simulate an orientation discrimination task for which visual performance differs with polar angle. The model starts from the photons emitted by a display, which pass through simulated human optics with fixational eye movements, followed by cone isomerizations in the retina. Finally, we classify stimulus orientation using a support vector machine to learn a linear classifier on the photon absorptions. To account for the 30% increase in contrast thresholds for upper vertical compared to horizontal meridian, as observed psychophysically on the same task, our computational observer model would require either an increase of ~7 diopters of defocus or a reduction of 500% in cone density. These values far exceed the actual variations as a function of polar angle observed in human eyes. Therefore, we conclude that these factors in the eye only account for a small fraction of differences in visual performance with polar angle. Substantial additional asymmetries must arise in later retinal and/or cortical processing.

Vasculitis is defined as inflammation of blood vessel walls for at least some time during the course of the disease, and affects arteries and veins of varying caliber. Two Chapel Hill Consensus Conferences, in 1994 and 2012, provide consensus on nosology and definitions for the commonest forms of vasculitis. The category of single-organ vasculitis, suggesting the limited expression of a systemic vasculitis, includes primary central nervous system vasculitis and nonsystemic peripheral nervous system vasculitis. The historical aspects of systemic and limited forms of vasculitis are reviewed in 11 relevant themes.