Faculty Bibliography

INTRODUCTION:There is little data on the cost of treating brain arteriovenous malformations (AVMs). The goal of this study then is to identify cost determinants in multimodal management of brain AVMs. METHODS:One hundred forty patients with brain AVMs prospectively enrolled in the UCSF brain AVM registry and treated between 2012 and 2015 were included in the study. Patient and AVM characteristics, treatment type, and length of stay and radiographic evidence of obliteration were collected from the registry. We then calculated the cost of all inpatient and outpatient encounters, interventions, and imaging attributable to the AVM. We used generalized linear models to test whether there was an association between patient and AVM characteristics, treatment type, and cost and length of stay. We tested whether the proportion of patients with radiographic evidence of obliteration differed between treatment modalities using Fisher's exact test. RESULTS:The overall median cost of treatment and interquartile range was $77,865 (49,566-107,448). Surgery with preoperative embolization was the costliest treatment at $91,948 (79,914-140,600), while radiosurgery was the least at $20,917 (13,915-35,583). In multi-predictor analyses, hemorrhage, Spetzler-Martin grade, and treatment type were significant predictors of cost. Patients who had surgery had significantly higher rates of obliteration compared with radiosurgery patients. CONCLUSIONS:Hemorrhage, AVM grade, and treatment modality are significant cost determinants in AVM management. Surgery with preoperative embolization was the costliest treatment and radiosurgery the least; however, surgical cases had significantly higher rates of obliteration.

Background:Action observation (AO) relies on the mirror neuron system (MNS) and has been proposed as a rehabilitation tool in Parkinson's disease (PD), in particular for gait disorder such as freezing of gait (FOG). In this study, we aimed to explore the brain functional correlates of the observation of human gait in PD patients with (FOG+) and without (FOG-) FOG and to investigate a possible relationship between AO-induced brain activation and gait performance. Methods:Fifty-four participants were enrolled in the study (15 PD FOG+; 18 PD FOG-; 21 healthy subjects (HS)) which consisted of two tasks in two separate days: (i) gait assessment and (ii) task-fMRI during AO of gait. Differences between patients with PD (FOG+ and FOG-) and HS were assessed at the level of behavioral and functional analysis. Results:. Patients with PD present a reduced functional activity during AO of gait, especially if FOG+. A baseline knowledge of the neural correlates of AO of gait in the clinical routine "on" status would help for the design of future AO rehabilitative interventions.

Objective: To describe sociodemographic differences between individuals with advanced Parkinson's Disease (PD) still receiving care in an outpatient clinic vs. those enrolled in an interdisciplinary home visit study.
Background(s): Individuals with PD from underrepresented minority backgrounds face disparities in access to expert neurologic care. Such disparities also persist in PD research participation, sometimes attributed to mistrust and stigma. As minority patients become homebound, they are further estranged from care and research representation. We launched an interdisciplinary home visit study to extend continuity of care to homebound individuals with advanced PD. Here, we seek to identify sociodemographic differences between home visit (HV) participants and the outpatient (OP) clinic population from which they were recruited to determine whether disparities in care and research enrollment among minority patients persist with this patient-centered, care-focused intervention. Design/Methods: Cross-sectional study comparing individuals with advanced PD-Hoehn & Yahr stage >3-drawn from a single movement disorders center between 2017- 2019. We conducted a chart review for demographic information and used t-tests or Wilcoxon signed-rank tests as appropriate to assess population differences.
Result(s): The HV population is significantly older (n = 58 HV, 1015 OP; mean age 78.4 (SD 7.5) vs. 75.0 (SD 9.2), respectively, p = 0.002) and includes nearly twice the percentage of minority patients (26.3% non-Caucasian vs. 14.7% non-Caucasian in OP, p = 0.02). As expected, HV had worse PD severity, with 62.1% stage 4 and 17.2% stage 5, vs. 28.6% and 11.0% of OP, respectively (p <0.0001).
Conclusion(s): The proportion of minority patients with advanced PD enrolled in a home-based study is significantly greater than that receiving care in the OP setting from which they originated. This suggests that social determinants of health may contribute to advanced PD patients from underrepresented minorities becoming lost to follow-up earlier than white patients. We are actively comparing our homebound population with matched controls from a longitudinal national registry to determine the generalizability of this finding. Our results suggest that despite their advanced age, disease, and homebound status, this population is amenable to research participation. Ultimately, continued access to care poses a large but surmountable hurdle to research participation for minority patients

Introduction: The FOCUS study of fremanezumab, a fullyhumanized monoclonal antibody (IgG2DELTAa) that selectively targets calcitonin gene-related peptide (CGRP), was the first and largest study of a migraine preventive treatment in adults with both chronic and episodic migraine (CM and EM) and documented inadequate response to 2-4 classes of migraine preventive medications. Efficacy in a subgroup of patients with medication overuse (use of any acute medication on >=15 days/month or triptans/ergots/combination medications on >=10 days/month) at baseline was evaluated.
Method(s): Patients were randomized (1:1:1) to quarterly fremanezumab (Month 1: 675mg; Month 2 and 3: placebo), monthly fremanezumab (Month 1: CM, 675mg; EM, 225mg; Month 2 and 3: 225mg), or matched monthly placebo for 12 weeks. Changes from baseline in monthly migraine days and headache days of at least moderate severity at 4 weeks and during 12 weeks of treatment were compared using a mixed-effect model for repeated measures.
Result(s): Of 838 randomized patients, 427 had medication overuse. Treatment with quarterly and monthly fremanezumab versus placebo resulted in significantly greater reductions from baseline in the monthly average number of migraine days at 4 weeks (least-squares mean [SE] change from baseline, -3.7 [0.62] and -4.5 [0.57] vs -0.0 [0.62]; P<0.0001) and over 12 weeks (-3.3 [0.62] and -4.5 [0.57] vs -0.5 (0.62); P<0.0001). With quarterly and monthly fremanezumab versus placebo, significant reductions from baseline were also observed in the monthly average number of headache days of at least moderate severity at 4 weeks (-4.3 [0.62] and -5.1 [0.56] vs -0.2 [0.62]; P<0.0001) and over 12 weeks (-4.0 [0.62] and -5.0 [0.56] vs -0.8 [0.62]; P<0.0001).
Conclusion(s): Quarterly and monthly fremanezumab provided early and sustained reductions in migraine and headache days vs placebo in patients with medication overuse and documented inadequate response to 2-4 classes of migraine preventive medications

Purpose Patients who overuse acute medicationsfor migraine generally experience more migraine days, greater disability, and more severe pain intensity. The FOCUS study of fremanezumab, a fully-humanized monoclonal antibody (IgG2DELTAa) that selectively targets calcitonin gene-related peptide (CGRP), was the first and largest study of a migraine preventive treatment in adults with both chronic migraine (CM) and episodic migraine (EM) and documented inadequate response to 2 to 4 classes of migraine preventive medications.This subgroup analysis of the FOCUS study evaluated the efficacy of fremanezumab in patients with baseline medication overuse (use of any acute medication on >=15 days/month or use of triptans, ergots, or combination medications on >=10 days/month). Methods In the randomized, double-blind, placebo-controlled period of the phase 3b FOCUS study, patients were randomized (1:1:1) to quarterly fremanezumab (month 1: 675 mg; months 2 and 3: placebo), monthly fremanezumab (month 1: CM, 675 mg; EM, 225 mg; months 2 and 3: 225 mg), or matched monthly placebo for 12 weeks. Changes from baseline in the monthly average number of migraine days and monthly average number of headache days of at least moderate severity at 4 weeks and during 12 weeks of treatment were compared using a mixed-effect model for repeated measures. Results Of 838 randomized patients, 435 had baseline medication overuse. Reductions from baseline in the monthly averagenumber of migraine days were significantly greater with quarterly fremanezumab (least-squares mean [standard error (SE)] change, -3.3 [0.61]) and monthly fremanezumab (-4.6 [0.55]) versus placebo (-0.5 [0.62]; both P <= 0.0001) during 12 weeks of treatment. Reductions from baseline in the monthly average number of headache days of at least moderate severity were also significantly greater with quarterly fremanezumab (least-squares mean [SE] change, -4.0 [0.61]) and monthly fremanezumab (-5.1 [0.54]) versus placebo (-0.8, [0.61]; both P < 0.0001) during 12 weeks of treatment. At 4 weeks of double-blind treatment, changes from baseline in the monthly average number of migraine days and monthly average number of headache days of at least moderate severity were also significantly greater with both dosing regimens of fremanezumab versus placebo (all P < 0.0001). Conclusions Quarterly and monthly fremanezumab provided early and sustained reductions in monthly migraine and monthly headache days of at least moderate severity versus placebo in migraine patients with medication overuse and documented inadequate response to 2 to 4 classes of migraine preventive medications

Patients suffering from COVID-19 experience a wide range of symptoms and sequelae, including increasingly recognized neurological problems. A concerted effort is necessary to identify and characterize these issues, whether newly appearing as a result of COVID-19 disease or exacerbations of underlying conditions. A national resource to collect information and/or biospecimens regarding neurological complications of COVID-19 offers an opportunity for broad representation, harmonization, and rapid learning, all while ensuring robust protection of confidential information through the use of global unique identifiers to protect patient privacy.

It is a commonplace that evolution proceeds by selection of the fittest with elimination of organisms less well adapted to the environment. Along with this, the appearance of novel form arises from preliminary stages in growth, not as additions to the endpoints of prior specialization. The mechanisms of evolutionary change, from earlier form-building layers and specification by elimination, have been described in morphogenesis as prolongation of pre-terminal stages in development and winnowing of redundancy to achieve specific-ity. In earlier writings, these trends in evolutionary and developmental growth were the basis of an account of the nature of the symptom (error) with focal brain lesion. This paper extends the argument from pathology to subjective experience, namely that patterns in evolutionary and fetal growth that are carried over into adult cognition can explain the emergence of intrapersonal phenomena in human mind conceived as a kind of organism, with activity in the mental (mind/brain) state interpreted as a dynamic process of growth.

Objective: Test the null hypothesis that Level III support measures do not differ between Chinese and Caucasian nulliparous women with normal support.
Method(s): Pelvic floor 3D MRIs at rest were analyzed (Image J, 3D slicer v. 4.10.1) from Chinese and Caucasian nulliparous women with no prolapse at/below the hymen. Urogenital hiatus (UGH), levator hiatus (LH), and levator bowl volume (LBV) were measured and levator plate (LP) was traced (Figure 1A-D). Perineal body (PB) location was measured relative to Pelvic Inclination Correction System (PICS) line, 34degree below the SCIPP line. Muscle fiber directions were traced for the pubococcygeus (PCM), puborectalis (PR), and external anal sphincter muscles (EAS) in parasagittal slides (Figure1E-F). LP shape was analyzed using principal component analysis (PCA) (Figure 2C-D). Student's t-test was used to compare measurements between groups.
Result(s): Eleven Chinese and 10 Caucasian women were included with average ages of 28+/-3 and 23+/-2 years, respectively (P<.001). BMI was lower in Chinese women (21.5+/-2.5kg/m2 vs 25.6+/-5.6kg/m2, P=.04) and height was similar (1.63 +/-0.06m vs 1.65+/-0.12m, P=.56). Chinese women had 18% smaller UGH, 10% smaller LH and 33% smaller LBV compared to Caucasian women at rest (Figure 2A). PB position was higher in Chinese versus Caucasian women (-2mm vs-12mm, P<.001). PCM fiber direction was more horizontal in Chinese women compared to Caucasian women (16+/-12degree vs 25+/-5degree, P=.047), while the direction of PR (-21+/-5degree vs-20+/-5degree, P=.91) and EAS (-49+/-9degree vs-51 +/-10degree, P=.80) are similar (Figure 2B). PCA showed the LP is significantly more horizontal in Chinese than Caucasian women (PC1 score for Chinese-6.5 vs Caucasian 7.1, P=.020).
Conclusion(s): We reject our null hypothesis. In nulliparas with normal support, Chinese women have a smaller hiatus size and LBV than Caucasian women and their PCM fiber direction and LP shape are oriented more horizontally. Comment: This analysis is consistent with the hypothesis that PCM fiber direction varies with LP shape and bowl volume. These baseline differences in anatomy may influence birth injury, mechanism of prolapse, and treatment outcomes

Introduction/UNASSIGNED:The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods/UNASSIGNED:Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results/UNASSIGNED:A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Discussion/UNASSIGNED:our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions/UNASSIGNED:Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.