Intracerebral haemorrhage in patients with brain metastases receiving therapeutic anticoagulation.

BACKGROUND: Venous thromboembolism is common in patients with solid malignancies and brain metastases. Whether to anticoagulate such patients is controversial given the possibility of intracerebral haemorrhage (ICH). We evaluated the added risk of ICH in patients with brain metastases receiving therapeutic anticoagulation. METHODS: We performed a matched, retrospective cohort study of 291 patients (100 receiving therapeutic anticoagulation vs 191 controls) with brain metastases managed at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 1998 and 2015. For each patient, all MRI studies of the brain were reviewed to identify ICH. Propensity score matching and multivariable Cox regression were used to mitigate confounding. RESULTS: The risk of ICH was comparable in patients receiving anticoagulation versus controls preanticoagulation. Postanticoagulation, we observed significant or borderline-significant associations between anticoagulation and development of any ICH (HR 1.31, 95% CI 0.96 to 1.79, p=0.09), ICH as identified by gradient echo/susceptibility-weighted imaging (HR 1.46, 95% CI 1.06 to 2.01, p=0.02), symptomatic ICH (HR 1.80, 95% CI 1.01 to 3.22, p=0.05), extralesional ICH (HR 5.82, 95% CI 1.56 to 21.7, p=0.009) and fatal ICH (HR 5.68, 95% CI 0.60 to 54.2, p=0.13). Anticoagulation was associated with differentially higher ICH risk in patients with prior ICH versus no prior ICH (HR 2.20 vs 0.68, respectively, p interaction <0.001) and symptomatic ICH risk in melanoma versus other primary malignancies (HR 6.46 vs 1.36, respectively, p interaction=0.02). CONCLUSIONS: Anticoagulation is associated with clinically significant ICH in patients with brain metastases, especially those with melanoma or prior ICH. The indication for anticoagulation and risk of intracerebral bleeding should be considered on an individual basis among such patients.

Imaging Considerations in Spinal Cord Evaluation.

Multiple diverse pathologies result in the clinical presentation of myelopathy. The preferred way to image the spinal cord depends on clinical history, anatomic site of interest, and patient issues limiting certain imaging modalities. This radiology-focused article discusses pertinent physiological considerations, reviews basic and newer imaging techniques, and examines several distinct disease entities in order to highlight the key role of imaging in the work-up of myelopathy.

Racial and Ethnic Disparities in Postcardiac Arrest Targeted Temperature Management Outcomes.

OBJECTIVES: To evaluate racial and ethnic disparities in postcardiac arrest outcomes in patients undergoing targeted temperature management. DESIGN: Retrospective study. SETTING: ICUs in a single tertiary care hospital. PATIENTS: Three-hundred sixty-seven patients undergoing postcardiac arrest targeted temperature management, including continuous electroencephalogram monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical variables examined in our clinical cohort included race/ethnicity, age, time to return of spontaneous circulation, cardiac rhythm at time of arrest, insurance status, Charlson Comorbidity Index, and time to withdrawal of life-sustaining therapy. CT at admission and continuous electroencephalogram monitoring during the first 24 hours were used as markers of early injury. Outcome was assessed as good (Cerebral Performance Category 1-2) versus poor (Cerebral Performance Category 3-5) at hospital discharge. White non-Hispanic ("White") patients were more likely to have good outcomes than white Hispanic/nonwhite ("Non-white") patients (34.4 vs 21.7%; p = 0.015). In a multivariate model that included age, time to return of spontaneous circulation, initial rhythm, combined electroencephalogram/CT findings, Charlson Comorbidity Index, and insurance status, race/ethnicity was still independently associated with poor outcome (odds ratio, 3.32; p = 0.003). Comorbidities were lower in white patients but did not fully explain outcomes differences. Nonwhite patients were more likely to exhibit signs of early severe anoxic changes on CT or electroencephalogram, higher creatinine levels and receive dialysis, but had longer duration to withdrawal of lifesustaining therapy. There was no significant difference in catheterizations or MRI scans. Subgroup analysis performed with patients without early electroencephalogram or CT changes still revealed better outcome in white patients. CONCLUSIONS: Racial/ethnic disparity in outcome persists despite a strictly protocoled targeted temperature management. Nonwhite patients are more likely to arrive with more severe anoxic brain injury, but this does not account for all the disparity.

Brachytherapy with surgical resection as salvage treatment for recurrent high-grade meningiomas: a matched cohort study.

PURPOSE: To evaluate surgical resection with brachytherapy placement as a salvage treatment in patients with recurrent high-grade meningioma who exhausted prior external beam treatment options. METHODS: Single-center retrospective review of our institutional experience of brachytherapy implantation from 2012 to 2018. The primary outcome of the study was progression free survival (PFS). Secondary outcomes included overall survival (OS) and complications. A matched cohort of patients not treated with brachytherapy over the same time period was evaluated as a control group. All patients had received prior radiation treatment and underwent planned gross total resection (GTR) surgery. RESULTS: A total of 27 cases were evaluated. Compared with prior treatment, brachytherapy implantation demonstrated a statistically significant improvement in tumor control [HR 0.316 (0.101 - 0.991), p = 0.034]. PFS-6 and PFS-12 were 92.3% and 84.6%, respectively. Compared with the matched control cohort, brachytherapy treatment demonstrated improved PFS [HR 0.310 (0.103 - 0.933), p = 0.030]. Overall survival was not statistically significantly different between groups [HR 0.381 (0.073 - 1.982), p = 0.227]. Overall postoperative complications were comparable between groups, although there was a higher incidence of radiation necrosis in the brachytherapy cohort. CONCLUSION: Brachytherapy with planned GTR improved PFS in recurrent high-grade meningioma patients who exhausted prior external beam radiation treatment options. Future improvement of brachytherapy dose delivery methods and techniques may continue to prolong control rates and improve outcomes for this challenging group of patients.

Emerging Cases of Powassan Virus Encephalitis in New England: Clinical Presentation, Imaging, and Review of the Literature.

BACKGROUND: Powassan virus (POWV) is a rarely diagnosed cause of encephalitis in the United States. In the Northeast, it is transmitted by Ixodes scapularis, the same vector that transmits Lyme disease. The prevalence of POWV among animal hosts and vectors has been increasing. We present 8 cases of POWV encephalitis from Massachusetts and New Hampshire in 2013-2015. METHODS: We abstracted clinical and epidemiological information for patients with POWV encephalitis diagnosed at 2 hospitals in Massachusetts from 2013 to 2015. We compared their brain imaging with those in published findings from Powassan and other viral encephalitides. RESULTS: The patients ranged in age from 21 to 82 years, were, for the most part, previously healthy, and presented with syndromes of fever, headache, and altered consciousness. Infections occurred from May to September and were often associated with known tick exposures. In all patients, cerebrospinal fluid analyses showed pleocytosis with elevated protein. In 7 of 8 patients, brain magnetic resonance imaging demonstrated deep foci of increased T2/fluid-attenuation inversion recovery signal intensity. CONCLUSIONS: We describe 8 cases of POWV encephalitis in Massachusetts and New Hampshire in 2013-2015. Prior to this, there had been only 2 cases of POWV encephalitis identified in Massachusetts. These cases may represent emergence of this virus in a region where its vector, I. scapularis, is known to be prevalent or may represent the emerging diagnosis of an underappreciated pathogen. We recommend testing for POWV in patients who present with encephalitis in the spring to fall in New England.

Discrimination faced by radiology residents: an analysis of experiences and mitigation strategies.

RATIONALE AND OBJECTIVES: Literature shows that discrimination has been pervasive in the field of medicine. The aim of this study was to collect experiences related to discrimination among US radiology residents, including type and source, as well as the residents' perception on lectures about discrimination and harassment. We also explored the barriers to reporting, and suggested strategies to overcome them. MATERIAL AND METHODS: Following Institutional Review Board (IRB) approval, an online survey was sent to program directors and coordinators across the US, who were asked to forward the link to their radiology residents. A reminder email was sent over a period of 4 months. The participants were reassured the survey was confidential and anonymous. RESULTS: Among the respondents, the most reported types of discrimination were based in gender, race and nationality, the majority of which not being reported. The most common perpetrators were attending radiologists, co-residents, technologists, and patients. The main barriers for reporting were fear of retaliation, confidentiality concerns, and skepticism about a positive outcome. CONCLUSION: Our study examines some experiences of discrimination shared by residents during their training, with gender and race being the most common causes. This sheds light into a hidden and unspoken issue and highlights the need for more active discussions in radiology on microaggressions and implicit bias. Our data can guide future studies as well as residency programs to build effective strategies to address discrimination, aiming for sustainable changes.

Durable responses in patients with HER2+ breast cancer and leptomeningeal metastases treated with trastuzumab deruxtecan.

Leptomeningeal metastases (LM) are a devastating complication of HER2 + metastatic breast cancer (MBC), with no effective treatments. In a case series of 8 patients with heavily pretreated HER2 + MBC and progressing LM, all 8 patients (100%) derived clinical benefit from Trastuzumab deruxtecan (TDXd), and 4 patients (50%) had an objective partial response based on formal neuroradiology MRI reads using the EORTC/RANO-LM Revised-Scorecard. T-DXd warrants further study in LM in HER2 + MBC and solid tumors where T-DXd may be active.

Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases.

PURPOSE: Brain metastases can occur in up to 50% of patients with metastatic HER2-positive breast cancer. Because patients with active brain metastases were excluded from previous pivotal clinical trials, the central nervous system (CNS) activity of the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) is not well characterized. EXPERIMENTAL DESIGN: We studied how T-DXd affects growth and overall survival in orthotopic patient-derived xenografts (PDX) of HER2-positive and HER2-low breast cancer brain metastases (BCBM). Separately, we evaluated the effects of T-DXd in a retrospective cohort study of 17 patients with stable or active brain metastases. RESULTS: T-DXd inhibited tumor growth and prolonged survival in orthotopic PDX models of HER2-positive (IHC 3+) and HER2-low (IHC 2+/FISH ratio < 2) BCBMs. T-DXd reduced tumor size and prolonged survival in a T-DM1-resistant HER2-positive BCBM PDX model. In a retrospective multi-institutional cohort study of 17 patients with predominantly HER2-positive BCBMs, the CNS objective response rate (ORR) was 73% (11/15) while extracranial response rate was 45% (5/11). In the subset of patients with untreated or progressive BCBM at baseline, the CNS ORR was 70% (7/10). The median time on treatment with T-DXd was 8.9 (1.3-16.2) months, with 42% (7/17) remaining on treatment at data cutoff. CONCLUSIONS: T-DXd demonstrates evidence of CNS activity in HER2-positive and HER2-low PDX models of BCBM and preliminary evidence of clinical efficacy in a multi-institution case series of patients with BCBM. Prospective clinical trials to further evaluate CNS activity of T-DXd in patients with active brain metastases are warranted. See related commentary by Soffietti and Pellerino, p. 8.

Salvage brachytherapy for multiply recurrent metastatic brain tumors: A matched case analysis.

Background: Patients with recurrent brain metastases who have exhausted external radiation options pose a treatment challenge in the setting of advances in systemic disease control which have improved quality of life and survival. Brachytherapy holds promise as salvage therapy given its ability to enforce surgical cytoreduction and minimize regional toxicity. This study investigates the role of salvage brachytherapy in maintaining local control for recurrent metastatic lesions. Methods: We retrospectively reviewed our institution's experience with brachytherapy in patients with multiply recurrent cerebral metastases who have exhausted external radiation treatment options (14 cases). The primary outcome of the study was freedom from local recurrence (FFLR). To capture the nuances of tumor biology, we compared FFLR achieved by brachytherapy to the preceding treatment for each patient. We further compared the response to brachytherapy in patients with lung cancer (8 cases) against a matched cohort of maximally radiated lung brain metastases (10 cases). Results: Brachytherapy treatment conferred significantly longer FFLR compared to prior treatments (median 7.39 vs 5.51 months, P = .011) for multiply recurrent brain metastases. Compared to an independent matched cohort, brachytherapy demonstrated superior FFLR (median 8.49 vs 1.61 months, P = .004) and longer median overall survival (11.07 vs 5.93 months, P = .055), with comparable side effects. Conclusion: Brachytherapy used as salvage treatment for select patients with a multiply recurrent oligometastatic brain metastasis in the setting of well-controlled systemic disease holds promise for improving local control in this challenging patient population.

Neuroimaging during pregnancy.

Pregnancy can be associated with a wide variety of neurologic problems, resulting from alterations in physiology of the pregnant state. The pregnant patient presenting with neurologic symptoms poses both diagnostic and therapeutic challenges. The physician will often require some form of neuroimaging as part of their ongoing evaluation. This review discusses potential risks to the embryo and fetus that can be caused by undergoing computed tomography (CT) and magnetic resonance imaging (MRI), including those associated with the administration of intravenous contrast. Neurologic diseases or syndromes specifically associated with pregnancy are also discussed.

Falcine chondroma: illustrative case.

BACKGROUND: Chondromas are benign cartilaginous tumors that are rarely seen in the brain. OBSERVATIONS: A 58-year-old woman had undergone routine brain imaging after a motor vehicle accident and was incidentally found to have a right falcine lesion. Contrast magnetic resonance imaging showed a mostly nonenhancing mass with discontinuous rim enhancement. She was taken to the operating room and pathology revealed a chondroma. LESSONS: Falcine intracranial chondromas are rare and typically misdiagnosed as meningiomas. Chondromas should be in the differential for patients presenting with nonenhancing falcine lesions.

CSF lipocalin-2 increases early in subarachnoid hemorrhage are associated with neuroinflammation and unfavorable outcome.

Lipocalin-2 mediates neuro-inflammation and iron homeostasis in vascular injuries of the central nervous system (CNS) and is upregulated in extra-CNS systemic inflammation. We postulate that cerebrospinal fluid (CSF) and blood lipocalin-2 levels are associated with markers of inflammation and functional outcome in subarachnoid hemorrhage (SAH). We prospectively enrolled 67 SAH subjects, serially measured CSF and plasma lipocalin-2, matrix metallopeptidase 9 (MMP-9), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) on post-SAH days 1-5 and assessed outcome by modified Rankin Scale (mRS) every 3 months. Unfavorable outcome is defined as mRS > 2. Twenty non-SAH patients undergoing lumbar drain trial were enrolled as controls. Lipocalin-2 was detectable in the CSF and significantly higher in SAH compared to controls (p < 0.0001). Higher CSF LCN2 throughout post-SAH days 1-5 was associated with unfavorable outcome at 3 (p = 0.0031) and 6 months (p = 0.014). Specifically, higher CSF lipocalin-2 on post-SAH days 3 (p = 0.036) and 5 (p = 0.016) were associated with unfavorable 3-month outcome. CSF lipocalin-2 levels positively correlated with CSF IL-6, TNF-α and MMP-9 levels. Higher plasma lipocalin-2 levels over time were associated with worse 6-month outcome. Additional studies are required to understand the role of lipocalin-2 in SAH and to validate CSF lipocalin-2 as a potential biomarker for SAH outcome.

Fulminant Acanthamoeba castellanii Encephalitis in an Ibrutinib-Treated Patient.

We report a case of fulminant Acanthamoeba castellanii encephalitis in a patient with chronic lymphocytic leukemia treated with ibrutinib. The unusually rapid neurologic decline and fatal outcome observed are probably related to alterations in immunologic function associated with inhibition of Bruton tyrosine kinase.

CerebroVis: Designing an Abstract yet Spatially Contextualized Cerebral Artery Network Visualization.

Blood circulation in the human brain is supplied through a network of cerebral arteries. If a clinician suspects a patient has a stroke or other cerebrovascular condition, they order imaging tests. Neuroradiologists visually search the resulting scans for abnormalities. Their visual search tasks correspond to the abstract network analysis tasks of browsing and path following. To assist neuroradiologists in identifying cerebral artery abnormalities, we designed CerebroVis, a novel abstract-yet spatially contextualized-cerebral artery network visualization. In this design study, we contribute a novel framing and definition of the cerebral artery system in terms of network theory and characterize neuroradiologist domain goals as abstract visualization and network analysis tasks. Through an iterative, user-centered design process we developed an abstract network layout technique which incorporates cerebral artery spatial context. The abstract visualization enables increased domain task performance over 3D geometry representations, while including spatial context helps preserve the user's mental map of the underlying geometry. We provide open source implementations of our network layout technique and prototype cerebral artery visualization tool. We demonstrate the robustness of our technique by successfully laying out 61 open source brain scans. We evaluate the effectiveness of our layout through a mixed methods study with three neuroradiologists. In a formative controlled experiment our study participants used CerebroVis and a conventional 3D visualization to examine real cerebral artery imaging data to identify a simulated intracranial artery stenosis. Participants were more accurate at identifying stenoses using CerebroVis (absolute risk difference 13%). A free copy of this paper, the evaluation stimuli and data, and source code are available at osf.io/e5sxt.

Fibrosing Inflammatory Pseudotumor Presenting as Cranial Neuropathy.

We report two cases of biopsy-corroborated "fibrosing inflammatory pseudotumor" to illustrate that the entity, rarely described in the neurological literature, should be included in the differential diagnosis of either a cranial mononeuropathy or, certainly, in the case of progressive cranial neuropathies. A broad differential diagnosis arises in certain contexts. Early steroid treatment can be effective, and perhaps later-generation immune-modulating agents may confer further options, although there is no known definitive treatment.

MRI-EEG correlation for outcome prediction in postanoxic myoclonus: A multicenter study.

OBJECTIVE: To examine the prognostic ability of the combination of EEG and MRI in identifying patients with good outcome in postanoxic myoclonus (PAM) after cardiac arrest (CA). METHODS: Adults with PAM who had an MRI within 20 days after CA were identified in 4 prospective CA registries. The primary outcome measure was coma recovery to command following by hospital discharge. Clinical examination included brainstem reflexes and motor activity. EEG was assessed for best background continuity, reactivity, presence of epileptiform activity, and burst suppression with identical bursts (BSIB). MRI was examined for presence of diffusion restriction or fluid-attenuated inversion recovery changes consistent with anoxic brain injury. A prediction model was developed using optimal combination of variables. RESULTS: Among 78 patients, 11 (14.1%) recovered at discharge and 6 (7.7%) had good outcome (Cerebral Performance Category < 3) at 3 months. Patients who followed commands were more likely to have pupillary and corneal reflexes, flexion or better motor response, EEG continuity and reactivity, no BSIB, and no anoxic injury on MRI. The combined EEG/MRI variable of continuous background and no anoxic changes on MRI was associated with coma recovery at hospital discharge with sensitivity 91% (95% confidence interval [CI], 0.59-1.00), specificity 99% (95% CI, 0.92-1.00), positive predictive value 91% (95% CI, 0.59-1.00), and negative predictive value 99% (95% CI, 0.92-1.00). CONCLUSIONS: EEG and MRI are complementary and identify both good and poor outcome in patients with PAM with high accuracy. An MRI should be considered in patients with myoclonus showing continuous or reactive EEGs.

Soluble vascular endothelial-cadherin in CSF after subarachnoid hemorrhage.

OBJECTIVE: To determine if CSF and plasma levels of soluble vascular endothelial (sVE)-cadherin are associated with functional outcome after subarachnoid hemorrhage (SAH) and to investigate sVE-cadherin effects on microglia. METHODS: Serial CSF and plasma were collected from prospectively enrolled patients with nontraumatic SAH from a ruptured aneurysm in the anterior circulation and who required an external ventricular drain for clinical indications. Patients with normal-pressure hydrocephalus without SAH served as controls. For prospective assessment of long-term outcomes at 3 and 6 months after SAH, modified Rankin Scale scores (mRS) were obtained and dichotomized into good (mRS ≤ 2) vs poor (mRS > 2) outcome groups. For SAH severity, Hunt and Hess grade was assessed. Association of CSF sVE-cadherin levels with long-term outcomes, HH grade, and CSF tumor necrosis factor (TNF)-α levels were evaluated. sVE-cadherin effects on microglia were also studied. RESULTS: sVE-cadherin levels in CSF, but not in plasma, were higher in patients with SAH and were associated with higher clinical severity and higher CSF TNF-α levels. Patients with SAH with higher CSF sVE-cadherin levels over time were more likely to develop worse functional outcome at 3 months after SAH. Incubation of cultured microglia with sVE-cadherin resulted in increased inducible nitric oxide synthase, interleukin-1ß, reactive oxygen species, cell soma size, and metabolic activity, consistent with microglia activation. Microinjection of sVE-cadherin fragments into mouse brain results in an increased number of microglia surrounding the injection site, compared to injection of denatured vascular endothelial-cadherin fragments. CONCLUSIONS: These results support the existence of a novel pathway by which sVE-cadherin, released from injured endothelium after SAH, can shift microglia into a more proinflammatory phenotype and contribute to neuroinflammation and poor outcome in SAH.

Imaging Considerations in Pregnancy.

Pregnancy is a complex physiologic state with hormonal, hemodynamic, hematologic, and immunologic changes at both global and cellular levels affecting brain, heart, pituitary, thyroid, and kidney. There are many situations in which imaging can aid in diagnosis and subsequent treatment of neurologic conditions during pregnancy.

Invasive Fungal Carotiditis: A Rare Manifestation of Cranial Invasive Fungal Disease: Case Series and Systematic Review of the Literature.

BACKGROUND: Rhinosinusitis, malignant otitis externa, and skull base osteomyelitis represent a spectrum of cranial invasive fungal disease (IFD). These syndromes have distinct characteristics, yet they may progress to involve similar structures, resulting in inflammation and invasion of the adjacent internal carotid artery (ICA). Invasive fungal carotiditis can have devastating consequences, including cerebral infarction, subarachnoid hemorrhage, and death. METHODS: We retrospectively studied all patients diagnosed with cranial IFD and carotid involvement at our institution from 2003 to 2018. We also searched Medline/PubMed for reports of Aspergillus or Mucorales cranial infections with ICA involvement. All cases with mycologic evidence of cranial IFD and radiographic or pathologic evidence of ICA involvement were included. RESULTS: We identified 78 cases of invasive fungal carotiditis between 1958 and 2018, including 4 cases at our own institution. Forty-one were caused by Aspergillus and 37 by Mucorales species. Presenting symptoms included vision changes (73%), cranial nerve palsy (69%), and headache (42%). Carotid events included occlusion, aneurysm formation, and vessel rupture. Cerebral infarcts occurred in 50% of cases. Mortality at 6 weeks, 12 weeks, and 2 years was 27%, 41%, and 71% respectively. The median time from symptom onset to death was 150 days for cases due to Aspergillus and 51 days for cases due to Mucorales species. CONCLUSIONS: Invasive fungal carotiditis is a rare but morbid manifestation of cranial IFD. Early suspicion of IFD and administration of antifungal treatment, vascular imaging, and endovascular interventions should be considered to reduce the high mortality of this disease.

Emergent Neuroimaging in the Oncologic and Immunosuppressed Patient.

Neuroimaging in the emergency department increasingly involves patients at increased risk for acute neurologic complications from malignancy and immunosuppression, including patients with organ transplantation, diabetes mellitus, treatment of chronic disease, and HIV positivity. These patients are susceptible to the same infections and emergencies as immunocompetent patients, but may present differently with common illnesses and are susceptible to a variety of other diseases. This article reviews important patient risk factors, emergent central nervous system abnormalities, and their imaging findings. Detailed knowledge of risk factors and specific complications in these complex patients is essential for optimal image acquisition, interpretation, diagnosis, and treatment.