International controlled study of revascularization and outcomes following COVID-positive mechanical thrombectomy.

BACKGROUND AND PURPOSE: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. METHODS: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted. RESULTS: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p < 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates.

Influence of the COVID-19 Pandemic on Treatment Times for Acute Ischemic Stroke: The Society of Vascular and Interventional Neurology Multicenter Collaboration.

BACKGROUND AND PURPOSE: The pandemic caused by the novel coronavirus disease 2019 (COVID-19) has led to an unprecedented paradigm shift in medical care. We sought to evaluate whether the COVID-19 pandemic may have contributed to delays in acute stroke management at comprehensive stroke centers. METHODS: Pooled clinical data of consecutive adult stroke patients from 14 US comprehensive stroke centers (January 1, 2019, to July 31, 2020) were queried. The rate of thrombolysis for nontransferred patients within the Target: Stroke goal of 60 minutes was compared between patients admitted from March 1, 2019, and July 31, 2019 (pre-COVID-19), and March 1, 2020, to July 31, 2020 (COVID-19). The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed. RESULTS: Of the 2955 patients who met inclusion criteria, 1491 were admitted during the pre-COVID-19 period and 1464 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis. Patients treated during COVID-19 were at lower odds of receiving thrombolysis within 60 minutes of arrival (odds ratio, 0.61 [95% CI, 0.38-0.98]; P=0.04), with a median delay in door-to-needle time of 4 minutes (P=0.03). The lower odds of achieving treatment in the Target: Stroke goal persisted after adjustment for all variables associated with earlier treatment (adjusted odds ratio, 0.55 [95% CI, 0.35-0.85]; P<0.01). The delay in thrombolysis appeared driven by the longer delay from imaging to bolus (median, 29 [interquartile range, 18-41] versus 22 [interquartile range, 13-37] minutes; P=0.02). There was no significant delay in door-to-groin puncture for patients who underwent thrombectomy (median, 83 [interquartile range, 63-133] versus 90 [interquartile range, 73-129] minutes; P=0.30). Delays in thrombolysis were observed in the months of June and July. CONCLUSIONS: Evaluation for acute ischemic stroke during the COVID-19 period was associated with a small but significant delay in intravenous thrombolysis but no significant delay in thrombectomy time metrics. Taking steps to reduce delays from imaging to bolus time has the potential to attenuate this collateral effect of the pandemic.

Emergency Medicine Physicians Accurately Select Acute Stroke Patients for Tissue-Type Plasminogen Activator Treatment Using a Checklist.

Background and Purpose- There is uncertainty among many emergency medicine physicians about the decision to give intravenous tPA (tissue-type plasminogen activator), which limits its use. A checklist approach has been suggested as a solution. We compared agreement on tPA treatment in suspected acute ischemic stroke patients between emergency medicine residents (EMRs) using a checklist and vascular neurology fellows (VNFs). Methods- Every suspected acute stroke patient brought to our comprehensive stroke center emergency room within 4.5 hours from symptom onset was prospectively evaluated simultaneously and independently by VNFs and EMRs. The latter used a tPA screening checklist, which included guideline exclusion criteria to help with their treatment decision. Agreement was determined using kappa (k) statistics. Results- Over 6 months, 60 patients were enrolled; 10% large vessel atherosclerosis, 18% cardioembolism, 12% small vessel, 12% cryptogenic, and 47% mimic. Forty-two percent were deemed tPA eligible by the EMR, 30% by the VNF, and 37% by the vascular neurology faculty. There were no complications in any tPA-treated patients. Agreement was substantial between EMR and VNF (κ=0.68 [95% CI, 0.49-0.87]) and between EMR and vascular neurology faculty (κ=0.69 [95% CI, 0.50-0.87]). Stroke mimics were the main cause of disagreement between EMR and VNF (κ=0.24 [95% CI, -0.15 to 0.63]) and between EMR and vascular neurology faculty (κ=0.35 [95% CI, -0.08 to 0.78]). Conclusions- Our data suggest that with the aid of a checklist, EMRs can accurately treat stroke patients with tPA. Areas for improvement include recognition of stroke mimics. Further studies are warranted to evaluate checklist-enhanced tPA treatment to allay emergency medicine physician uncertainty and expand the use of tPA.

Prior Cannabis Use Is Associated with Outcome after Intracerebral Hemorrhage.

OBJECTIVE: Recent evidence suggests that a potential harmful relationship exists between cannabis use and ischemic stroke. The purpose of this study was to determine the implications of cannabis use in intracerebral hemorrhage (ICH) patients. METHODS: An analysis of an international, multicenter, observational database of consecutive patients with spontaneous ICH was conducted. We extracted the following characteristics on presentation: demographics, risk factors, antiplatelet or anticoagulant use, Glasgow Coma Scale, ICH score, neuroimaging parameters, and urine toxicology screen (UTS) results. Modified Rankin Scale (mRS) score was utilized for determination of outcome at discharge. Adjusted logistic ordinal regression was used as shift analysis to assess the impact of cannabis use on mRS score at discharge. The adjusted common OR measured the likelihood that cannabis use would lead to lower mRS scores. RESULTS: Within a cohort of 725 spontaneous ICH patients, UTS was positive for cannabinoids in 8.6%. Cannabinoids-positive (CB+) patients were more frequently Caucasian (p < 0.001), younger (p < 0.001), and had lower median ICH scores on admission (p = 0.017) than those who were cannabinoids-negative. CB+ patients also showed a shift toward better outcome in the distribution of mRS categories, with an adjusted common OR of 0.544 (95% CI 0.330-0.895, p = 0.017). CONCLUSION: In this multinational cohort, cannabis use was discovered in nearly 10% of patients with spontaneous ICH. Although there was no relationship between cannabis use and specific ICH characteristics, CB+ patients had milder ICH presentation and less disability at discharge.

Recommendations for management of large hemispheric infarction.

PURPOSE OF REVIEW: Large hemispheric infarction is a devastating disease that continues to be associated with significant mortality and morbidity. Most often these patients are admitted to the ICU requiring significant physician and nursing resources. This review will address some of the ICU management issues and review the evidence supporting medical and surgical management of malignant cerebral edema. RECENT FINDINGS: The most recent changes in management of large hemispheric infarct include the American Heart Association and Neurocritical Care Guidelines. These guidelines address airway management and mechanical ventilation, blood pressure control, fluid management, and glucose and temperature control. In addition, they addressed the indication for surgical management of cerebral edema. We review the recent guidelines updates and trials of surgical management of large hemispheric infarcts. SUMMARY: Large hemispheric infarcts continue to have significant morbidity and mortality. Recent guidelines have provided an excellent framework to help intensivists manage these complicated patients. Recent surgical data continue to support early hemicraniectomy even in elderly patients.

Prevention of Stroke in Rheumatoid Arthritis.

The risk of cerebrovascular disease is increased among rheumatoid arthritis (RA) patients and remains an underserved area of medical need. Only a minor proportion of RA patients achieve suitable stroke prevention. Classical cardiovascular risk factors appear to be under-diagnosed and undertreated among patients with RA. Reducing the inflammatory burden is also necessary to lower the cardiovascular risk. An adequate control of disease activity and cerebrovascular risk assessment using national guidelines should be recommended for all patients with RA. For patients with a documented history of cerebrovascular or cardiovascular risk factors, smoking cessation and corticosteroids and non-steroidal anti-inflammatory drugs at the lowest dose possible are crucial. Risk score models should be adapted for patients with RA by introducing a 1.5 multiplication factor, and their results interpreted to appropriately direct clinical care. Statins, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers are preferred treatment options. Biologic and non-biologic disease-modifying anti-rheumatic drugs should be initiated early to mitigate the necessity of symptom control drugs and to achieve early alleviation of the inflammatory state. Early control can improve vascular compliance, decrease atherosclerosis, improve overall lipid and metabolic profiles, and reduce the incidence of heart disease that may lead to atrial fibrillation. In patients with significant cervical spine involvement, early intervention and improved disease control are necessary and may prevent further mechanical vascular injury.

Inpatient Teleneurology Follow-up Has Comparable Outcomes to In-Person Neurology Follow-up.

Background and Objectives: Community emergency departments often transfer patients for lack of neurology coverage, potentially burdening patients and accepting facilities. Telestroke improves access to acute stroke care, but there is a lack of data on inpatient teleneurology and telestroke care. Methods: From our prospective telestroke registry, we retrospectively reviewed 3702 consecutive patients who were seen via telestroke between September 2015 and December 2018. Patients who required transfer after initial telestroke evaluation or who were kept at hospitals without consistent neurology coverage were excluded from analysis. We compared baseline demographics, clinical characteristics, and hospital outcomes in patients who were subsequently followed remotely by a teleneurology neurohospitalist and those followed in person by a neurohospitalist. Results: There were 447 (23%) patients followed by a teleneurology neurohospitalist and 1459 (77%) patients followed in person by a neurohospitalist. Both groups presented with similar stroke severity. In multivariate analysis, there were no significant differences in discharge disposition, stroke readmission rates, or 90-day modified Rankin Scale (mRS) scores. Length of stay was shorter with teleneurology follow-up. In the subgroup of patients who received tissue plasminogen activator, patients showed no differences in outcomes and had similar complication rates. Teleneurology follow-up resulted in a 3% transfer rate for higher level of care after admission. There remained no difference in outcomes in a subanalysis without Comprehensive Stroke Centers. A higher proportion of non-Hispanic Black patients and a lower proportion of Hispanic patients in the teleneurology follow-up group were possibly due to spoke location demographics. Discussion: Teleneurology follow-up resulted in comparable outcomes to in-person neurology follow-up, with few transfers after admission. For select neurology and ischemic stroke patients, teleneurology follow-up provides an alternative to transfer for hospitals lacking neurology coverage.

Non-contrast head CT-based thrombolysis for wake-up/unknown onset stroke is safe: A single-center study and meta-analysis.

BACKGROUND: Recent studies have shown that tPA can be safely administered past the standard 4.5 h window with good outcomes when selected with multi-model imaging, which is often lacking outside of comprehensive stroke centers. AIM: We aim to analyze the safety and outcomes of wake up/unknown onset (WUS/UNK) patients treated based on non-contrast head CT (NCCT) at our institution and in the literature. METHODS: Suspected stroke patients from January 2015 to December 2018 receiving tPA within 4.5 h (standard window-SW) and with WUS/UNK based on NCCT and clinical-imaging mismatch were identified. We compared baseline characteristics, tPA metrics, and outcome data, with primary outcome as symptomatic intracerebral hemorrhage (sICH). A meta-analysis was performed evaluating NCCT-based treatment of WUS/UNK patients. RESULTS: Of 1827 patients treated at our hub or through telestroke, 93 underwent WUS/UNK-based treatment. There was no statistical difference in sICH between WUS/UNK and SW: 1% vs. 4% (OR 0.3; 95% confidence interval 0.0-1.9). 90-day modified Rankin scale outcomes were similar between SW and WUS/UNK-treated patients. Seven studies encompassing 485 WUS/UNK patients were included in a pooled analysis with a 2.1% incidence of sICH. In our meta-analysis, three studies compared NCCT-based treated WUS/UNK patients with SW patients with no difference in rate of hemorrhage: 2.1% vs 3.4% (OR 1.01; 95% confidence interval 0.45-2.28). INTERPRETATION: Our single-center analysis and meta-analysis suggest that tPA can be safely administered based on NCCT with comparable rates of sICH for select WUS/UNK stroke patients.

Delays in thrombolysis during COVID-19 are associated with worse neurological outcomes: the Society of Vascular and Interventional Neurology Multicenter Collaboration.

INTRODUCTION: We have demonstrated in a multicenter cohort that the COVID-19 pandemic has led to a delay in intravenous thrombolysis (IVT) among stroke patients. Whether this delay contributes to meaningful short-term outcome differences in these patients warranted further exploration. METHODS: We conducted a nested observational cohort study of adult acute ischemic stroke patients receiving IVT from 9 comprehensive stroke centers across 7 U.S states. Patients admitted prior to the COVID-19 pandemic (1/1/2019-02/29/2020) were compared to patients admitted during the early pandemic (3/1/2020-7/31/2020). Multivariable logistic regression was used to estimate the effect of IVT delay on discharge to hospice or death, with treatment delay on admission during COVID-19 included as an interaction term. RESULTS: Of the 676 thrombolysed patients, the median age was 70 (IQR 58-81) years, 313 were female (46.3%), and the median NIHSS was 8 (IQR 4-16). Longer treatment delays were observed during COVID-19 (median 46 vs 38 min, p = 0.01) and were associated with higher in-hospital death/hospice discharge irrespective of admission period (OR per hour 1.08, 95% CI 1.01-1.17, p = 0.03). This effect was strengthened after multivariable adjustment (aOR 1.15, 95% CI 1.07-1.24, p < 0.001). There was no interaction of treatment delay on admission during COVID-19 (pinteraction = 0.65). Every one-hour delay in IVT was also associated with 7% lower odds of being discharged to home or acute inpatient rehabilitation facility (aOR 0.93, 95% CI 0.89-0.97, p < 0.001). CONCLUSION: Treatment delays observed during the COVID-19 pandemic led to greater early mortality and hospice care, with a lower probability of discharge to home/rehabilitation facility. There was no effect modification of treatment delay on admission during the pandemic, indicating that treatment delay at any time contributes similarly to these short-term outcomes.

Endovascular thrombectomy time metrics in the era of COVID-19: observations from the Society of Vascular and Interventional Neurology Multicenter Collaboration.

BACKGROUND: Unprecedented workflow shifts during the coronavirus disease 2019 (COVID-19) pandemic have contributed to delays in acute care delivery, but whether it adversely affected endovascular thrombectomy metrics in acute large vessel occlusion (LVO) is unknown. METHODS: We performed a retrospective review of observational data from 14 comprehensive stroke centers in nine US states with acute LVO. EVT metrics were compared between March to July 2019 against March to July 2020 (primary analysis), and between state-specific pre-peak and peak COVID-19 months (secondary analysis), with multivariable adjustment. RESULTS: Of the 1364 patients included in the primary analysis (51% female, median NIHSS 14 [IQR 7-21], and 74% of whom underwent EVT), there was no difference in the primary outcome of door-to-puncture (DTP) time between the 2019 control period and the COVID-19 period (median 71 vs 67 min, P=0.10). After adjustment for variables associated with faster DTP, and clustering by site, there remained a trend toward shorter DTP during the pandemic (ßadj=-73.2, 95% CI -153.8-7.4, Pp=0.07). There was no difference in DTP times according to local COVID-19 peaks vs pre-peak months in unadjusted or adjusted multivariable regression (ßadj=-3.85, 95% CI -36.9-29.2, P=0.80). In this final multivariable model (secondary analysis), faster DTP times were significantly associated with transfer from an outside institution (ßadj=-46.44, 95% CI -62.8 to - -30.0, P<0.01) and higher NIHSS (ßadj=-2.15, 95% CI -4.2to - -0.1, P=0.05). CONCLUSIONS: In this multi-center study, there was no delay in EVT among patients treated for intracranial occlusion during the COVID-19 era compared with the pre-COVID era.

Characteristics of a COVID-19 Cohort With Large Vessel Occlusion: A Multicenter International Study.

BACKGROUND: The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke. OBJECTIVE: To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort. METHODS: We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020. RESULTS: The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry.

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. AIM: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. METHODS: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020-16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). RESULTS: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970-1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920-1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130-280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4-60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63-15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07-2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34-0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. CONCLUSIONS: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes.

Training in Neurology: Adoption of resident teleneurology training in the wake of COVID-19: Telemedicine crash course.

The coronavirus disease 2019 pandemic has changed the way we engage patient care, with a move toward telemedicine-based health care encounters. Teleneurology is now being rapidly embraced by neurologists in clinics and hospitals nationwide but for many, this paradigm of care is unfamiliar. Exposure to telemedicine in neurology training programs is scarce despite previous calls to expand teleneurology education. Programs that provide a teleneurology curriculum have demonstrated increased proficiency, accuracy, and post-training utilization among their trainees. With the current changes in health care, broad incorporation of teleneurology education in resident and fellow training after this pandemic dissipates will only serve to improve trainee preparedness for independent practice.

Macrophage migration inhibitory factor (MIF) is essential for inflammatory and neuropathic pain and enhances pain in response to stress.

Stress and glucocorticoids exacerbate pain via undefined mechanisms. Macrophage migration inhibitory factor (MIF) is a constitutively expressed protein that is secreted to maintain immune function when glucocorticoids are elevated by trauma or stress. Here we show that MIF is essential for the development of neuropathic and inflammatory pain, and for stress-induced enhancement of neuropathic pain. Mif null mutant mice fail to develop pain-like behaviors in response to inflammatory stimuli or nerve injury. Pharmacological inhibition of MIF attenuates pain-like behaviors caused by nerve injury and prevents sensitization of these behaviors by stress. Conversely, injection of recombinant MIF into naïve mice produces dose-dependent mechanical sensitivity that is exacerbated by stress. MIF elicits pro-inflammatory signaling in microglia and activates sensory neurons, mechanisms that underlie pain. These data implicate MIF as a key regulator of pain and provide a mechanism whereby stressors exacerbate pain. MIF inhibitors warrant clinical investigation for the treatment of chronic pain.

Androgen deficiency: association with increased anxiety and depression symptom severity in anorexia nervosa.

OBJECTIVE: Anorexia nervosa is associated with a high prevalence of psychiatric comorbidities, including anxiety and depression, and with endocrine dysfunction, including relative androgen deficiency compared with healthy young women. Because androgens are known to affect mood and behavior, we hypothesized that low endogenous androgen production in anorexia nervosa would predict anxiety and depression severity. METHOD: Serum androgen levels and severity of depression (Hamilton Rating Scale for Depression) and anxiety (Hamilton Rating Scale for Anxiety) were measured in 43 community-dwelling women with DSM-IV-defined anorexia nervosa from May 2004 to July 2006. RESULTS: Strong inverse associations were observed between both total and free testosterone and anxiety and depression severity, independent of weight. Free testosterone was also inversely associated with 4 eating-disordered thinking and behavior subscales of the Eating Disorder Inventory 2 (EDI-2). Mean free testosterone blood levels were lower in women with clinically significant anxiety and in women with clinically significant depression, compared with those without. In stepwise regression models, free testosterone was an important predictor of anxiety and depression severity. EDI-2 ineffectiveness, perfectionism, interpersonal distress, and social insecurity scores were also inversely associated with androgen levels, independent of weight. CONCLUSIONS: Our data suggest that low androgen levels may contribute to anxiety, depression, and eating-disordered thinking and behavior in women with anorexia nervosa and form the basis for future studies to investigate the effectiveness of androgen replacement therapy. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00089843.