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

BACKGROUND:Cognitive deficits (CDs) in schizophrenia affect poor outcome and real-world community functioning. Because redox imbalance has been implicated, among other factors, in the pathophysiology of CDs, antioxidant compounds may have a beneficial effect in their treatment. Red yeast rice (RYR), besides its lipid-lowering effect, exhibit antioxidant and anti-inflammatory. METHODS:Thirty-five schizophrenia outpatients (age range, 18-60 years) on stable antipsychotic treatment and assessed by neuropsychological (Wisconsin Card Sorting Test [WCST], Verbal Fluency, and Stroop task) and psychodiagnostic instruments (Brief Psychiatric Rating Scale) received RYR at daily dosage of 200 mg/d (total monacolin K/capsule content, 11.88 mg) for 12 weeks. RESULTS:Red yeast rice supplementation significantly improved WCST "perseverative errors" (P = 0.015), "total errors" (P = 0.017, P = 0.001), and phonemic fluency test (P = 0.008); a trend for improvement on other WCST variables ("nonperseverative errors," "perseverative responses," and "categories") was observed. Effect sizes, according to Cohen's suggestions, were small in all explored cognitive dimensions. There were no significant change in clinical symptoms and no subject-reported adverse effects. CONCLUSIONS:Despite several limitations (open design, lack of a control group, short period of observation, small sample size, mode of controlling patients' compliance, the lack of assessment of patients' functional improvement), results suggest that RYR supplementation may be a potentially promising strategy for addressing CDs in schizophrenia; further randomized, placebo-controlled studies are needed to better evaluate the potential role of RYR for the treatment of CDs in schizophrenia.

Autoimmune encephalitis is a severe inflammatory disorder of the brain with diverse causes and a complex differential diagnosis. Recent advances in the past decade have led to the identification of new syndromes and biological markers of limbic encephalitis, the commonest presentation of autoimmune encephalitis. The successful use of serum and intrathecal antibodies to diagnose affected patients has resulted in few biopsy and postmortem examinations. In those available, there can be variable infiltrating inflammatory T cells with cytotoxic granules in close apposition to neurons, consistent with an inflammatory autoimmune basis, but true vasculitis is rarely seen. The exception is Hashimoto encephalopathy.

Familial dysautonomia (Riley-Day syndrome, hereditary sensory and autonomic neuropathy type III) is a rare autosomal recessive disease characterized by impaired development of primary sensory and autonomic neurons resulting in a severe neurological phenotype, which includes arterial baroreflex and chemoreflex failure with high frequency of sleep-disordered breathing and sudden death during sleep. Although a rare disease, familial dysautonomia represents a unique template to study the interactions between sleep-disordered breathing and abnormal chemo- and baroreflex function. In patients with familial dysautonomia, ventilatory responses to hypercapnia are reduced, and to hypoxia are almost absent. In response to hypoxia, these patients develop paradoxical hypoventilation, hypotension, bradycardia, and potentially, death. Impaired ventilatory control due to chemoreflex failure acquires special relevance during sleep when conscious control of respiration withdraws. Overall, almost all adult (85%) and pediatric (95%) patients have some degree of sleep-disordered breathing. Obstructive apnea events are more frequent in adults, whereas central apnea events are more severe and frequent in children. The annual incidence rate of sudden death during sleep in patients with familial dysautonomia is 3.4 per 1000 person-year, compared to 0.5-1 per 1000 person-year of sudden unexpected death in epilepsy. This review summarizes recent developments in the understanding of sleep-disordered breathing in patients with familial dysautonomia, the risk factors for sudden death during sleep, and the specific interventions that could prevent it.

Systemic and localized vasculitis affects the skin and subcutis, due to large vascular beds and hemodynamic factors, such as stasis in lower extremities, and environmental influences, as occur in cold exposure. Initial cutaneous manifestations of vasculitides include diverse and dynamic patterns of discoloration, swelling, hemorrhage, and necrosis. One-half of affected patients present with localized, self-limited disease to the skin without any known trigger or associated systemic disease, known as idiopathic cutaneous leukocytoclastic vasculitis. Skin biopsy and dermatopathology contribute relevant information; however, they require correlation with clinical history, physical examination, and laboratory findings to reach an accurate diagnosis.

PURPOSE/OBJECTIVE:Patients undergoing epilepsy surgery often require invasive EEG, but few studies have examined the signal characteristics of contacts on the surface of the brain (electrocorticography, ECOG) versus depth contacts, used in stereoelectroencephalography (SEEG). As SEEG and ECOG have significant differences in complication rates, it is important to determine whether both modalities produce similar signals for analysis, to ultimately guide management of medically intractable epilepsy. METHODS:Twenty-seven patients who underwent SEEG (19), ECOG (6), or both (2) were analyzed for quantitative measures of activity including spectral power and phase-amplitude coupling during approximately 1 hour of wakefulness. The position of the contacts was calculated by coregistering the postoperative computed tomography with a reconstructed preoperative MRI. Using two types of referencing schemes-local versus common average reference-the brain regions where any quantitative measure differed systematically with contact depth were established. RESULTS:Using even the most permissive statistical criterion, few quantitative measures were significantly correlated with contact depth in either ECOG or SEEG contacts. The factors that predicted changes in spectral power and phase-amplitude coupling with contact depth were failing to baseline correct spectral power measures, use of a local rather than common average reference, using baseline correction for phase-amplitude coupling measures, and proximity of other grey matter structures near the region where the contact was located. CONCLUSIONS:The signals recorded by ECOG and SEEG have very similar spectral power and phase-amplitude coupling, suggesting that both modalities are comparable from an electrodiagnostic standpoint in delineation of the epileptogenic network.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The diagnosis of primary central and peripheral nerve vasculitides should be established with certainty if suspected before commencing potent immunosuppressive therapy. The aim of induction therapy is to rapidly control the underlying inflammatory response and stabilize the blood-brain and blood-nerve barriers, followed by maintenance immunosuppression tailored to the likeliest humoral and cell-mediated autoimmune inflammatory vasculitic processes.

OBJECTIVES/OBJECTIVE:The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection. METHODS:Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD-9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)-9 scores ≥ 10. The outcome was all-cause mortality. Covariates were demographics, comorbid conditions and health behaviours. RESULTS:Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11 years. The death rate was 25.3 [95% confidence interval (CI) 25.0-25.6] deaths per 1000 person-years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI 1.01, 1.07]. This association was modified by HIV status (interaction P-value = 0.02). In HIV-stratified analyses, depression was significantly associated with mortality among HIV-uninfected veterans but not among those with HIV infection. Among those with PHQ-9 data (n = 7372), 50% had HIV infection, 22% had PHQ-9 scores ≥ 10, and 28% died over a median follow-up time of 12 years. The death rate was 27.3 (95% CI 26.1-28.5) per 1000 person-years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P-value = 0.05). In HIV-stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection. CONCLUSIONS:Depression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment.