Neurosarcoidosis and Neurologic Complications of Sarcoidosis Treatment.

Sarcoidosis is an immune-mediated multisystem granulomatous disorder. Neurosarcoidosis (NS) accounts for 5% to 35% of cases. The diagnostic evaluation of NS can be a clinical challenge. Gadolinium-enhanced magnetic resonance imaging (MRI) is the gold standard to evaluate central nervous system NS. In almost all cases treatment is warranted. Although glucocorticoids remain the first-line therapy in patients with sarcoidosis, in NS timely initiation of second- or third-line treatment is strongly recommended. Of these, tumor necrosis factor-alpha inhibitors are the most promising. However, the treatment itself may be responsible for/associated with developing neurologic symptoms mimicking NS. Thus, it is important to consider the possibility of drug-induced neurologic symptoms in sarcoidosis.

Clinical features and diagnosis of neurosarcoidosis - review article.

Neurosarcoidosis affects 5-26% of patients with systemic sarcoidosis and can be the first or only manifestation of the disease. Neurosarcoidosis can affect any part of the nervous system with heterogeneous clinical manifestations and imaging appearances that overlap with many infectious, inflammatory, and neoplastic disorders, making its diagnosis challenging. In the absence of a reliable biomarker to confirm neurosarcoidosis, the diagnosis is based on identifying a compatible clinical and imaging profile and identifying pathological evidence of non-caseating granulomas by biopsy of other organs or, if needed, in the nervous system, with the exclusion of other causes of granulomatous disease and possible neuroinfectious and neuroinflammatory disorder mimics. This review focuses on the clinical features of neurosarcoidosis with an emphasis on the recognition of the main presentation phenotypes and the initial diagnostic approach and differential diagnosis of neurosarcoidosis.

Risk Factors for Infection and Health Impacts of the Coronavirus Disease 2019 (COVID-19) Pandemic in People With Autoimmune Diseases.

BACKGROUND: People with autoimmune or inflammatory conditions taking immunomodulatory/suppressive medications may have higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. METHODS: We included participants with autoimmune or inflammatory conditions followed by specialists at Johns Hopkins. Participants completed periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. We assessed whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterized pandemic-associated changes to care and mental health. RESULTS: In total, 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medications) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in models incorporating behavior and other potential confounders (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95% CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95% CI: 1.24, 2.28), and kidney disease (OR: 1.76; 95% CI: 1.04, 2.97) were associated with higher odds of COVID-19. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions therein, which disproportionately affected individuals experiencing changes to employment or income. CONCLUSIONS: Glucocorticoid exposure may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.

Approach to Facial Weakness.

Facial palsy is a common neurologic concern and is the most common cranial neuropathy. The facial nerve contains motor, parasympathetic, and special sensory functions. The most common form of facial palsy is idiopathic (Bell's palsy). A classic presentation requires no further diagnostic measures, and generally improves with a course of corticosteroid and antiviral therapy. If the presentation is atypical, or concerning features are present, additional studies such as brain imaging and cerebrospinal fluid analysis may be indicated. Many conditions may present with facial weakness, either in isolation or with other neurologic signs (e.g., multiple cranial neuropathies). The most important ones to recognize include infections (Ramsay-Hunt syndrome associated with herpes zoster oticus, Lyme neuroborreliosis, and complications of otitis media and mastoiditis), inflammatory (demyelination, sarcoidosis, Miller-Fisher variant of Guillain-Barré syndrome), and neoplastic. No matter the cause, individuals may be at risk for corneal injury, and, if so, should have appropriate eye protection. Synkinesis may be a bothersome residual phenomenon in some individuals, but it has a variety of treatment options including neuromuscular re-education and rehabilitation, botulinum toxin chemodenervation, and surgical intervention.

RISK FACTORS FOR INFECTION AND HEALTH IMPACTS OF THE COVID-19 PANDEMIC IN PEOPLE WITH AUTOIMMUNE DISEASES.

Background: People with autoimmune or inflammatory conditions who take immunomodulatory/suppressive medications may have a higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. Objective: Assess whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterize pandemic-associated changes to care. Design: Longitudinal registry study. Participants: 4666 individuals with autoimmune or inflammatory conditions followed by specialists in neurology, rheumatology, cardiology, pulmonology or gastroenterology at Johns Hopkins. Measurements: Periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. Results: A total of 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medication exposure) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in multivariable models incorporating behavior and other potential confounders (OR: 1.43; 95%CI: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95%CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95%CI: 1.24, 2.28), and chronic kidney disease (OR: 1.76; 95%CI: 1.04, 2.97) were each associated with higher odds of COVID-19. Pandemic-related disruption to care was common. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions. Individuals experiencing changes to employment or income were at highest odds of care disruption. Limitations: Results may not be generalizable to all patients with autoimmune or inflammatory conditions. Information was self-reported. Conclusions: Exposure to glucocorticoids may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.

The Burden of Neurosarcoidosis: Essential Approaches to Early Diagnosis and Treatment.

Neurosarcoidosis (NS) is an often severe, destructive manifestation with a likely under-reported prevalence of 5 to 15% of sarcoidosis cases, and in its active phase demands timely treatment intervention. Clinical signs and symptoms of NS are variable and wide-ranging, depending on anatomical involvement. Cranial nerve dysfunction, cerebrospinal parenchymal disease, aseptic meningitis, and leptomeningeal disease are the most commonly recognized manifestations. However, non-organ-specific potentially neurologically driven symptoms, such as fatigue, cognitive dysfunction, and small fiber neuropathy, appear frequently.Heterogeneous clinical presentations and absence of any single conclusive test or biomarker render NS, and sarcoidosis itself, a challenging definitive diagnosis. Clinical suspicion of NS warrants a thorough systemic and neurologic evaluation hopefully resulting in supportive extraneural physical exam and/or tissue findings. Treatment targets the severity of the manifestation, with careful discernment of whether NS reflects active potentially reversible inflammatory granulomatous disease versus inactive postinflammatory damage whereby functional impairment is unlikely to be pharmacologically responsive. Non-organ-specific symptoms are poorly understood, challenging in deciphering reversibility and often identified too late to respond to conventional immunosuppressive/pharmacological treatment. Physical therapy, coping strategies, and stress reduction may benefit patients with all disease activity levels of NS.This publication provides an approach to screening, diagnosis, disease activity discernment, and pharmacological as well as nonpharmacological treatment interventions to reduce disability and protect health-related quality of life in NS.

Current state of educational compensation in academic neurology: Results of a US national survey.

In the current medical climate, medical education is at risk of being de-emphasized, leading to less financial support and compensation for faculty. A rise in compensation plans that reward clinical or research productivity fails to incentivize and threatens to erode the educational missions of our academic institutions. Aligning compensation with the all-encompassing mission of academic centers can lead to increased faculty well-being, clinical productivity, and scholarship. An anonymous survey developed by members of the A.B. Baker Section on Neurologic Education was sent to the 133 chairs of neurology to assess the type of compensation faculty receive for teaching efforts. Seventy responses were received, with 59 being from chairs. Key results include the following: 36% of departments offered direct compensation; 36% did not; residency program directors received the most salary support at 36.5% full-time equivalent; and administrative roles had greatest weight in determining academic compensation. We believe a more effective, transparent system of recording and rewarding faculty for their educational efforts would encourage faculty to teach, streamline promotions for clinical educators, and strengthen undergraduate and graduate education in neurology.

Definition and Consensus Diagnostic Criteria for Neurosarcoidosis: From the Neurosarcoidosis Consortium Consensus Group.

Importance: The Neurosarcoidosis Consortium Consensus Group, an expert panel of physicians experienced in the management of patients with sarcoidosis and neurosarcoidosis, engaged in an iterative process to define neurosarcoidosis and develop a practical diagnostic approach to patients with suspected neurosarcoidosis. This panel aimed to develop a consensus clinical definition of neurosarcoidosis to enhance the clinical care of patients with suspected neurosarcoidosis and to encourage standardization of research initiatives that address this disease. Observations: The work of this collaboration included a review of the manifestations of neurosarcoidosis and the establishment of an approach to the diagnosis of this disorder. The proposed consensus diagnostic criteria, which reflect current knowledge, provide definitions for possible, probable, and definite central and peripheral nervous system sarcoidosis. The definitions emphasize the need to evaluate patients with findings suggestive of neurosarcoidosis for alternate causal factors, including infection and malignant neoplasm. Also emphasized is the need for biopsy, whenever feasible and advisable according to clinical context and affected anatomy, of nonneural tissue to document the presence of systemic sarcoidosis and support a diagnosis of probable neurosarcoidosis or of neural tissue to support a diagnosis of definite neurosarcoidosis. Conclusions and Relevance: Diverse disease presentations and lack of specificity of relevant diagnostic tests contribute to diagnostic uncertainty. This uncertainty is compounded by the absence of a pathognomonic histologic tissue examination. The diagnostic criteria we propose are designed to focus investigations on NS as accurately as possible, recognizing that multiple pathophysiologic pathways may lead to the clinical manifestations we currently term NS. Research recognizing the clinical heterogeneity of this diagnosis may open the door to identifying meaningful biologic factors that may ultimately contribute to better treatments.

High-Risk Sarcoidosis. Current Concepts and Research Imperatives.

Sarcoidosis is a disease with heterogeneous manifestations and outcomes, varying in part on the basis of organ involvement. Specifically, patients with sarcoidosis at risk for poor outcomes include individuals with treatment-resistant pulmonary sarcoidosis, including fibrotic pulmonary disease and pulmonary hypertension, as well as those with cardiac, neurologic, and multiorgan disease. The limited but available data relating to these patients with high-risk sarcoidosis, defined as those patients with presentations requiring medical intervention to avoid progressive disability or premature death, was evaluated as part of the National Heart, Lung, and Blood Institute's workshop to improve understanding of these disease manifestations. In particular, knowledge gaps that preclude a greater understanding of the pathogenesis and management of these severe sarcoidosis clinical phenotypes were identified in the workshop. Research strategies are proposed to address critical knowledge gaps that would further our understanding of these disease manifestations and enhance the care of these patients.

Infliximab for the treatment of CNS sarcoidosis: A multi-institutional series.

OBJECTIVE: To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor-α. METHODS: Investigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes. RESULTS: Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.5 years, the mean age was 47.5 years at infliximab initiation (SD 11.7, range 24-71 years); 56.1% were female; 62.1% were white, 37.0% African American, and 3% Hispanic. Sarcoidosis was isolated to the CNS in 19.7%. Using infliximab doses ranging from 3 to 7 mg/kg every 4-8 weeks, MRI evidence of a favorable treatment response was observed in 82.1% of patients with imaging follow-up (n = 56), with complete remission of active disease in 51.8% and partial MRI improvement in 30.1%; MRI worsened in 1 patient (1.8%). There was clinical improvement in 77.3% of patients, with complete neurologic recovery in 28.8%, partial improvement in 48.5%, clinical stability in 18.2%, worsening in 3%, and 1 lost to follow-up. In 16 patients in remission when infliximab was discontinued, the disease recurred in 9 (56%), typically in the same neuroanatomic location. CONCLUSIONS: Most patients with CNS sarcoidosis treated with infliximab exhibit favorable imaging and clinical treatment responses, including some previously refractory to other immunosuppressive treatments. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with CNS sarcoidosis infliximab is associated with favorable imaging and clinical responses.

Cocaine Use and Risk of Ischemic Stroke in Young Adults.

BACKGROUND AND PURPOSE: Although case reports have long identified a temporal association between cocaine use and ischemic stroke (IS), few epidemiological studies have examined the association of cocaine use with IS in young adults, by timing, route, and frequency of use. METHODS: A population-based case-control study design with 1090 cases and 1154 controls was used to investigate the relationship of cocaine use and young-onset IS. Stroke cases were between the ages of 15 and 49 years. Logistic regression analysis was used to evaluate the association between cocaine use and IS with and without adjustment for potential confounders. RESULTS: Ever use of cocaine was not associated with stroke with 28% of cases and 26% of controls reporting ever use. In contrast, acute cocaine use in the previous 24 hours was strongly associated with increased risk of stroke (age-sex-race adjusted odds ratio, 6.4; 95% confidence interval, 2.2-18.6). Among acute users, the smoking route had an adjusted odds ratio of 7.9 (95% confidence interval, 1.8-35.0), whereas the inhalation route had an adjusted odds ratio of 3.5 (95% confidence interval, 0.7-16.9). After additional adjustment for current alcohol, smoking use, and hypertension, the odds ratio for acute cocaine use by any route was 5.7 (95% confidence interval, 1.7-19.7). Of the 26 patients with cocaine use within 24 hours of their stroke, 14 reported use within 6 hours of their event. CONCLUSIONS: Our data are consistent with a causal association between acute cocaine use and risk of early-onset IS.

Neurosarcoidosis.

Neurosarcoidosis is known as the great mimicker and may appear similar to lymphoma, multiple sclerosis, and other diseases affecting the nervous system. Although definitive diagnosis requires histologic confirmation of the affected neural tissue, characteristic clinical manifestations, gadolinium-enhanced MRI patterns and specific cerebrospinal fluid findings can help support the diagnosis in the absence of neural biopsy. An understanding of the common clinical presentations and diagnostic findings is central to the evaluation and management of neurosarcoidosis.

Neurosarcoidosis: diagnosis, therapy and biomarkers.

Sarcoidosis is a multi-organ immune-mediated disease, which manifests as neurosarcoidosis (NS) in approximately 10% of all affected patients. The diagnosis of NS requires a high degree of suspicion as well as histological confirmation. Neurological symptoms in patients with systemic sarcoidosis should not be assumed to be due to NS unless proven true. The etiopathogenesis of NS is not yet fully elucidated and a reliable biomarker assessing disease progression is missing. As a probable result, there is no definitive cure for NS. The goals of available treatments include: halting inflammation, prevention of disease worsening and restoring neurological functions whenever possible. With immunosuppression, clinical remission of NS occurs in the majority of patients. However, in some others, the disease may still progress, as no permanent cure is yet available.

Neurosarcoidosis.

Sarcoidosis is an idiopathic multisystem granulomatous disorder. Neurologic manifestations in sarcoidosis are varied and making a diagnosis of neurosarcoidosis can be difficult as it mimics various other neurologic diseases. Knowledge of the syndromes associated with neurosarcoidosis can help guide the diagnostic evaluation. Definitive diagnosis requires neurologic tissue evidence of noncaseating granuloma, but in practice probable diagnosis is often made through nonneurologic biopsy and a characteristic syndrome and imaging. Treatment remains empiric, but new advances in immunologic therapy hold promise for effective and less-toxic regimens.

Relationship of thrombus length to number of stent retrievals, revascularization, and outcomes in acute ischemic stroke.

PURPOSE: To study the relationship between intracranial thrombus length and number of stent retrievals, revascularization rates, and functional outcomes in stroke. MATERIALS AND METHODS: Retrospective data were collected from consecutive cases of stroke treated with endovascular procedures at a single institution from April 2012-September 2013. Thrombus length was measured in the anterior cerebral circulation. Demographic and clinical details; involved vessels; and procedural details, including the number of devices used and number of retrievals used for each device, were recorded. Revascularization rates and 90-day functional outcomes were recorded. RESULTS: Data regarding the length of thrombus in the anterior cerebral circulation were available for 28 patients. There was no significant association between thrombus length and number of stent retrievals (P = .3780), final thrombolysis in cerebral infarction (TICI) score (P = .4835), or 90-day modified Rankin Scale score (P = .4146). There was a significant difference (P = .0280) between number of retrievals and final TICI score, with lower number of retrieval passes corresponding to higher final TICI scores. CONCLUSIONS: The data suggest no relationship between thrombus length and number of stent retrievals, final TICI score, or functional neurologic outcomes at 90 days in stent retrieval thrombectomy for acute ischemic stroke. These results do not support a predictive value for thrombus length quantification in the evaluation of stroke.

Neurosarcoidosis.

PURPOSE OF REVIEW: This article provides an update on the evaluation and treatment of neurosarcoidosis. RECENT FINDINGS: The broad range of clinical manifestations of neurosarcoidosis has recently expanded to include painful small fiber neuropathy. Although definitive diagnosis remains a challenge, fluorodeoxyglucose positron emission tomographic (FDG-PET) scan and high-resolution CT allow for improved detection of systemic sarcoidosis. In addition, endobronchial ultrasound-guided transbronchial needle aspiration provides a less invasive means of tissue confirmation of systemic sarcoidosis than mediastinoscopy. Although not standardized, treatment strategies for neurosarcoidosis now commonly include tumor necrosis factor-α antagonists in combination with corticosteroids and other cytotoxic agents for patients with severe disease. SUMMARY: Advances in the diagnosis and management of neurosarcoidosis may benefit the patient and clinician faced with this multifaceted disease.

Exploratory analysis of glyburide as a novel therapy for preventing brain swelling.

BACKGROUND: Malignant infarction is characterized by the formation of cerebral edema, and medical treatment is limited. Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema. We previously reported feasibility of the GAMES-Pilot study, a two-center prospective, open label, phase IIa trial of 10 subjects at high risk for malignant infarction based on diffusion weighted imaging (DWI) threshold of 82 cm(3) treated with RP-1127 (glyburide for injection). In this secondary analysis, we tested the hypothesis that RP-1127 may be efficacious in preventing poor outcome when compared to controls. METHODS: Controls suffering large hemispheric infarction were obtained from the EPITHET and MMI-MRI studies. We first screened subjects for controls with the same DWI threshold used for enrollment into GAMES-Pilot, 82 cm(3). Next, to address imbalances, we applied a weighted Euclidean matching. Ninety day mRS 0-4, rate of decompressive craniectomy, and mortality were the primary clinical outcomes of interest. RESULTS: The mean age of the GAMES cohort was 51 years and initial DWI volume was 102 ± 23 cm(3). After Euclidean matching, GAMES subjects showed similar NIHSS, higher DWI volume, younger age and had mRS 0-4-90% versus 50% in controls p = 0.049; with a similar trend in mRS 0-3 (40 vs. 25%; p = 0.43) and trend toward lower mortality (10 vs. 35%; p = 0.21). CONCLUSIONS: In this pilot study, RP-1127-treated subjects showed better clinical outcomes when compared to historical controls. An adequately powered and randomized phase II trial of patients at risk for malignant infarction is needed to evaluate the potential efficacy of RP-1127.

Prothrombin G20210A mutation is associated with young-onset stroke: the genetics of early-onset stroke study and meta-analysis.

BACKGROUND AND PURPOSE: Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a white case-control population and additionally performed a meta-analysis. METHODS: From the population-based Genetics of Early Onset Stroke (GEOS) study, we identified 397 individuals of European ancestry aged 15 to 49 years with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios (ORs) in the entire population and for subgroups stratified by sex, age, oral contraceptive use, migraine, and smoking status. A meta-analysis of 17 case-control studies (n=2305 cases <55 years) was also performed with and without GEOS data. RESULTS: Within GEOS, the association of the prothrombin G20210A mutation with ischemic stroke did not achieve statistical significance (OR=2.5; 95% confidence interval [CI]=0.9-6.5; P=0.07). However, among adults aged 15 to 42 years (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9; 95% CI=1.2-28.1; P=0.03), whereas adults aged 42 to 49 years were not (OR=1.4; 95% CI=0.4-5.1; P=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults ≤55 years (OR=1.4; 95% CI=1.1-1.9; P=0.02), with significance increasing with addition of the GEOS results (OR=1.5; 95% CI=1.1-2.0; P=0.005). CONCLUSIONS: The prothrombin G20210A mutation is associated with ischemic stroke in young adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger young adult population requires replication.

Intracranial stenosis: impact of randomized trials on treatment preferences of US neurologists and neurointerventionists.

BACKGROUND AND PURPOSE: Medical and endovascular treatment options for stroke prevention in patients with symptomatic intracranial stenosis have evolved over the past several decades, but the impact of 2 major multicenter randomized stroke prevention trials on physician practices has not been studied. We sought to determine changes in US physician treatment choices for patients with intracranial atherosclerotic stenosis (ICAS) following 2 NIH-funded clinical trials that studied medical therapies (antithrombotic agents and risk factor control) and percutaneous transluminal angioplasty and stenting (PTAS). METHODS: Anonymous surveys on treatment practices in patients with ICAS were sent to physicians at 3 time points: before publication of the NIH-funded Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial (pre-WASID survey, 2004), 1 year after WASID publication (post-WASID survey, 2006) and 1 year after the publication of the NIH-funded Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial (post-SAMMPRIS survey, 2012). Neurologists were invited to participate in the pre-WASID survey (n=525). Neurologists and neurointerventionists were invited to participate in the post-WASID (n=598) and post-SAMMPRIS (n=2,080) surveys. The 3 surveys were conducted using web-based survey tools delivered by E-mail, and a fax-based response form delivered by E-mail and conventional mail. Data were analyzed using the χ2 test. RESULTS: Before WASID, there was equipoise between warfarin and aspirin for stroke prevention in patients with ICAS. The number of respondents who recommended antiplatelet treatment for ICAS increased across all 3 surveys for both anterior circulation (pre-WASID=44%, post-WASID=85%, post-SAMMPRIS=94%) and posterior circulation (pre-WASID=36%, post-WASID=74%, post-SAMMPRIS=83%). The antiplatelet agent most commonly recommended after WASID was aspirin, but after SAMMPRIS it was the combination of aspirin and clopidogrel. The percentage of neurologists who recommended PTAS in >25% of ICAS patients increased slightly from pre-WASID (8%) to post-WASID surveys (12%), but then decreased again after SAMMPRIS (6%). The percentage of neurointerventionists who recommended PTAS in >25% of ICAS patients decreased from post-WASID (49%) to post-SAMMPRIS surveys (17%). CONCLUSIONS: The surveyed US physicians' recommended treatments for ICAS differed over the 3 survey periods, reflecting the results of the 2 NIH-funded clinical trials of ICAS and suggesting that these clinical trials changed practice in the USA.