This article provides an overview and update on the current status of academic neurology based on structured insights from departmental leaders across the United States. Academic neurology, at a time when and leaders in academic medicine in general, are facing protean administrative, structural, and financial challenges that threaten all academic missions.(1,2) In 2002, the Association of University Professors of Neurology (AUPN) and American Neurologic Association (ANA) jointly surveyed US neurology department chairs on the health of US academic neurology.(1) The results showed troublesome findings related to adverse financial pressures on education, research, faculty development, and growth of new programs. In 2016, the AUPN surveyed neurology department chairs to better understand the organization and operations of neurology departments under contemporary health care reform. Results highlight that most neurology departments had fewer than 60 faculty members, a minority of whom were tenured or on a tenure track. Over a third had faculty members on a purely clinical track, with no education or research responsibilities.(2) In early 2019, the AUPN partnered with the American Academy of Neurology (AAN) to resurvey academic neurology chairs using most of the 2002 AAN/AUPN survey questions. Survey responses from 2019 were compared with the earlier findings.

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Background: Few data are available on associations of antiphospholipid (aPL) antibodies with cognitive and motor decline in aging, and cerebrovascular disease on in vivo neuroimaging and postmortem neuropathology. Methods: This longitudinal, clinical-pathologic study (aPL antibodies, brain infarcts, and cognitive and motor decline in aging), was derived from 2 ongoing community-based cohort studies. A panel of 3 aPL antibodies was assayed in serum from 956 older individuals (mean age = 81.1 years; 72% women). Serum was also tested in a subset for markers of inflammation (C-reactive protein [CRP]) and blood-brain barrier breakdown (matrix metalloproteinases, MMPs). Annual clinical evaluations documented cognitive (17 neuropsychological tests) and motor function including parkinsonism. Cerebrovascular disease data were derived from in vivo neuroimaging and postmortem neuropathologic evaluations (699 individuals). We examined associations of aPL with cognitive and motor decline, other serum markers, neuroimaging, and neuropathology. Results: Of 956 individuals, 197 (20.6%) had aPL positivity, defined as positivity on any of the assays, at the time of first measurement. During a mean follow-up of 6.6 years (SD 4), overall aPL positivity was not associated with change in global cognition (estimate = –0.005, SE 0.011; p = 0.622) or parkinsonian signs (estimate = –0.003, SE 0.017; p = 0.860). aPL were not associated with serum CRP or MMPs (both p > 0.268). aPL were not associated with in vivo brain magnetic resonance imaging white matter hyperintensities or infarcts (both p > 0.376). Among those autopsied, aPL were not associated with pathologically confirmed brain infarcts, or cerebral atherosclerosis or arteriolosclerosis (all p≥ 0.447). Conclusions: In older individuals followed longitudinally, aPL do not relate to cognitive or motor decline, inflammation, or cerebrovascular disease on in vivo neuroimaging or postmortem neuropathology.

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Evidence for the association and the increased risk of stroke with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is growing. Recent studies have reported on HIV infection as a potent risk factor for intracerebral hemorrhage (ICH). We used the pooled results from case–control studies to conduct a systematic review and a meta-analysis in order to evaluate the risk of ICH with HIV/AIDS. Our systematic review and meta-analysis was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses algorithm of all available case–control studies that reported on the risk of ICH in patients with HIV/AIDS. Five eligible studies were identified, totaling 5,310,426 person-years studied over various periods that ranged from 1985 to 2010. There were a total of 724 cases of ICH, 138 with HIV/AIDS. HIV-infected ICH patients were in average younger. Pooled crude incidence rate ratio (IRR) for ICH in HIV/AIDS patients was 3.40 (95 % confidence intervals [CI] 1.44–8.04; p = 0.005, random-effects model). Clinical AIDS was associated with a higher IRR of ICH (11.99, 95 % CI 2.84–50.53; p = 0.0007) than HIV+ status without AIDS (1.73, 95 % CI 1.39–2.16; p < 0.0001). Patients with CD4+ lymphocyte count <200 cells/mm3 were similarly at a higher risk. Antiretroviral therapy did not seem to increase the risk of ICH. The available evidence suggests that HIV/AIDS is an important risk factor for ICH, particularly in younger HIV-infected patients and those with advanced disease.

Background— There are few data on the relationship of antiphospholipid antibodies (aPLs) to pathologically proven brain infarcts. We tested the hypothesis that aPLs are associated with a higher odds of brain infarcts among older, community-dwelling individuals who came to autopsy. Methods and Results— Specimens and clinical and pathological data were derived from 607 deceased subjects (mean age at death, 89 years; 66% women) who were participating in 1 of 2 cohort studies of aging (Rush Memory and Aging Project and Religious Orders Study) and had agreed to brain autopsy. Brain infarcts were identified on gross and microscopic examinations, and severity of cerebral vessel disease (atherosclerosis, arteriolosclerosis) was graded. Four clinically used aPLs were measured longitudinally: 3 in serum (anticardiolipin antibodies, β 2- glycoprotein I, and anti–phosphatidyl-serine) and 1 in plasma (lupus anticoagulant). A quarter of subjects (142 of 607, 23%) had at least 1 aPL present at baseline (median time interval from baseline to death, 4.6 years), and three quarters of these subjects had persistently positive measures over time. In a logistic regression analysis, baseline aPL positivity did not increase the odds of brain infarcts (odds ratio=1.08; 95% confidence interval, 0.74–1.58; P =0.19) or of gross or microscopic infarcts separately. Findings were essentially unchanged when considering number of baseline aPLs, aPLs proximate to death, and persistence of aPLs. Associations did not differ among subjects with increased severity of vessel disease. Conclusion— Overall, we did not find evidence that aPLs increase the odds of pathological brain infarcts in older people.

Objective Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. Methods Information and blood samples were obtained in a cross-sectional study from patients with SLE ( n = 308) and other rheumatologic diseases ( n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. Results Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8–4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7–5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2–5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9–6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5–5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3–4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8–38.4, p < 0.01). Conclusions Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.

Background: There are very limited prospective data on the significance of persistent antiphospholipid antibodies (aPL) and recurrent thrombo-occlusive events (TOEs). We investigated the prognostic value of (1) 2 newer aPL assays, (2) an aPL portfolio and (3) persistent aPL positivity following stroke. Methods: A total of 1,770 subjects from the APASS-WARSS study underwent further aPL testing for antibodies to phosphatidylserine (aPS) and anti-β2-glycoprotein-I (anti-β2GPI) from stored sera. Follow-up aPL status was also tested in a subset of subjects. Primary analysis was based on time to any TOE (ischemic stroke, myocardial infarction, transient ischemic attack, deep vein thrombosis, pulmonary embolism or systemic arterial occlusion)/death at 2 years. Cox proportional hazard analyses assessed whether aPL independently related to outcome. Results: Persistent anti-β2GPI decreased the time to TOE/death after adjustment for potential confounders (hazards ratio (HR) 2.86, 95% CI 1.21-6.76, p = 0.017). When persistent anti-β2GPI was combined with another persistently positive aPL, time to TOE/death was also reduced (HR 3.79, 95% CI 1.18-12.14, p = 0.025). Neither persistent anticardiolipin antibodies nor persistent aPS alone nor a single positive anti-β2GPI nor aPS was associated with decreased time to TOE/death. No single positive aPL, portfolio of baseline aPL or any persistent aPL increased the rate of TOE/death. Conclusions: Rates of TOE/death were not influenced by aPL results at baseline or follow-up. Persistent anti-β2GPI alone, and with persistent second aPL, was independently associated with decreased time to TOE/death. Persistent aPL, an aPL portfolio and newer aPL in ischemic stroke patients are not helpful in predicting an increased rate of recurrent TOEs.

OBJECTIVE: In the ongoing Antiphospholipid Antibodies, Brain Infarcts, and Cognitive and Motor Decline in Aging Study (Arvanitakis Z, et al: Neuroepidemiology 2013) we tested the hypothesis that aPL are associated with an increased risk of brain infarcts (BI) at autopsy and are related to cognitive and motor decline in aging. We present the final results for cerebral infarction. BACKGROUND: Antiphospholipid antibody positivity (aPL+) has been associated with clinical ischemic stroke. DESIGN/METHODS: Baseline and follow-up stored blood assayed for aPL [anticardiolipin antibodies (aCL), lupus anticoagulant, antiphosphatidylserine antibodies, and anti-β2-glycoprotein 1 antibodies] from 2 longitudinal clinical-pathologic cohort studies based at Rush University [Rush Memory and Aging Project (MAP) and Religious Order Study (ROS)]. Standardized neuropathological protocol assessed BI (macro-/microscopic, cortical/subcortical) blinded to aPL status. We had 80% power to detect an odds ratio (OR) of 2. aPL+ was defined as positive on any one of the 4 aPL assays. Multiple logistic regression performed for independent effect of aPL+ on BI. RESULTS: aPL were assayed at baseline (n=572, mean 82±7 yrs., 30% male, 97% Caucasian) ~7yrs. prior to death. BI occurred in 279/572 (49%): macroscopic (37%: cortical 15%, subcortical 28%) and microscopic in 29%. Controlling for age and sex, aPL+ at baseline (OR 1.14, 95%CI 0.77,1.70, p = 0.50) or proximal to death (OR 0.98, (95%CI 0.65,1.48, p = 0.92) was not associated with BI. Neither macro- nor microscopic infarcts were associated with aPL+. Persistence (n= 426) of aPL+ was not associated with BI when aPL+ was defined as either any persistent aPL+ assay (OR 0.89, 95%CI 0.56, 1.41, p = 0.62) as the same aPL+ isotype (OR 0.90, 95%CI 0.55, 1.45, p = 0.66). CONCLUSIONS: Overall aPL+ at baseline, proximal to death, or persistent aPL+ are not independent risk factors for BI in the elderly. Study Supported by: NIH grants R01HL96944, R01AG040039, P30AG10161, R01AG15819, R01AG17917, R01 AG24480 Disclosure: Dr. Levine has received personal compensation in an editorial capacity for MedLink. Dr. Levine has received royalty payments as editor of a book. Dr. Arvanitakis has received personal compensation for activities with Vista Health. Dr. Arvanitakis has received research support from Ceregene, Inc. Dr. Brey has received personal compensation in an editorial capacity for Neurology Now. Dr. Rand has nothing to disclose. Dr. Schneider has received personal compensation for activities with AVID Radiopharmaceuticals, Inc., and GE Healthcare. Dr. Yu has nothing to disclose. Dr. Leurgans has nothing to disclose. Dr. Bennett has received personal compensation for activities with Danone Inc., Dr. Wilmar Schwabe GmbH & Co., KG Pharmaceuticals, and Eli Lilly & Company. Dr. Bennett has received research support from Danone, Inc.

Background and Purpose— Because of its association with atrial fibrillation and heart failure, we hypothesized that amino terminal pro–B-type natriuretic peptide (NT-proBNP) would identify a subgroup of patients from the Warfarin–Aspirin Recurrent Stroke Study, diagnosed with inferred noncardioembolic ischemic strokes, where anticoagulation would be more effective than antiplatelet agents in reducing risk of subsequent events. Methods— NT-proBNP was measured in stored serum collected at baseline from participants enrolled in Warfarin–Aspirin Recurrent Stroke Study, a previously reported randomized trial. Relative effectiveness of warfarin and aspirin in preventing recurrent ischemic stroke or death over 2 years was compared based on NT-proBNP concentrations. Results— About 95% of 1028 patients with assays had NT-proBNP below 750 pg/mL, and among them, no evidence for treatment effect modification was evident. For 49 patients with NT-proBNP >750 pg/mL, the 2-year rate of events per 100 person-years was 45.9 for the aspirin group and 16.6 for the warfarin group, whereas for 979 patients with NT-proBNP ≤750 pg/mL, rates were similar for both treatments. For those with NT-proBNP >750 pg/mL, the hazard ratio was 0.30 (95% confidence interval: 0.12–0.84; P =0.021) significantly favoring warfarin over aspirin. A formal test for interaction of NT-proBNP with treatment was significant ( P =0.01). Conclusions— For secondary stroke prevention, elevated NT-proBNP concentrations may identify a subgroup of ischemic stroke patients without known atrial fibrillation, about 5% based on the current study, who may benefit more from anticoagulants than antiplatelet agents. Clinical Trial Registration— This trial was not registered because enrollment began before 2005.

OBJECTIVE:The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE. METHODS:The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios. RESULTS:Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001). CONCLUSION:The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or anti-double-stranded DNA antibodies.

The overall goal of the Antiphospholipid Antibodies, Brain Infarcts, and Cognitive and Motor Decline in Aging study is to test the hypothesis that antiphospholipid antibodies (aPL) are associated with an increased risk of pathologically proven brain infarcts and are related to cognitive and motor decline in aging. Putative biologic mechanisms underlying the association of aPL with infarcts and the relation of aPL with clinical outcomes of cognitive and motor impairment, including vascular and other processes, will be examined. The design of this longitudinal, clinical-pathologic study involves quantifying four aPL assays, and relating these to brain infarcts, and to cognitive and motor decline. Vascular mechanisms assessed using antemortem magnetic resonance neuroimaging and postmortem neuropathology, as well as nonvascular mechanisms of inflammation and blood-brain barrier permeability alterations will be examined as plausible mediators of the relation of aPL to cognitive and motor impairment. We will take advantage of antemortem biological specimens (longitudinally collected sera and plasma from which aPL, annexins, C-reactive protein, and matrix metalloproteinases will be quantified), and clinical, neuroimaging, and postmortem neuropathologic data from about 800 elderly, community-dwelling women and men who have agreed to brain autopsy at the time of death, participating in one of two ongoing studies of aging: the Religious Orders Study and the Memory and Aging Project.

Methods TNPB, Ped-ANAM, quality of life (PedsQL), and depression scales (CDI-S) were administered by psychology associates blinded to clinical status at two research visits. Differences in mean TNPB standardized scores, PedANAM throughput scores (raw Throughput=correct responses/minute), and clinical variables between visits were compared using paired Student t-tests. Multi-variable linear regression analysis was used to assess the influence of initial test performance, aPL/LAC status, disease duration, and cumulative prednisone dosing on composite TNPB or Ped-ANAM scores at a second visit.

The antiphospholipid syndrome (APS) is defined by the presence of thrombosis and/or pregnancy morbidity in combination with the persistent presence of circulating antiphospholipid antibodies: lupus anticoagulant, anticardiolipin antibodies and/or anti-β2-glycoprotein I antibodies in medium to high titers. The management of thrombosis in patients with APS is a subject of controversy. This set of recommendations is the result of an effort to produce guidelines for therapy within a group of specialist physicians in Cardiology, Neurology, Hematology, Rheumatology and Internal Medicine, with a clinical and research focus on APS.