Non-Vitamin K Antagonist Oral Anticoagulants for the Treatment of Cerebral Venous Sinus Thrombosis: a Retrospective, Matched Cohort Analysis.

BACKGROUND: The management of cerebral venous sinus thrombosis (CVT) is a common problem facing vascular neurologists. American Heart Association/American Stroke Association guidelines suggest the use of heparin followed by vitamin K antagonists (VKAs) for anticoagulation in CVT. In recent years, the evidence base has solidified for the use of non-vitamin K antagonist oral anticoagulants (NOACs) in lower extremity deep vein thrombosis. Because data supporting their use in CVT are limited, with the strongest evidence comprising one randomized controlled trial of dabigatran, we sought to review our experience with NOACs in the treatment of CVT at a tertiary care center to address efficacy and safety. METHODS: We retrospectively reviewed charts of all patients with CVT treated with an NOAC at our tertiary care facility in the years 2011-2019. We collected data on demographics, risk factors for CVT, clinical features at presentation, imaging results, anticoagulation regimen, bleeding complications, and disability at follow-up. We compared disability at follow-up and major hemorrhagic events with age-matched and sex-matched controls treated with VKAs over the same time period and with historical controls. RESULTS: We identified 29 patients with CVT treated with an NOAC, 27 of whom had follow-up within our system. NOACs that were used for treatment included apixaban (20 patients), rivaroxaban (6 patients) and dabigatran (1 patient). NOAC use was associated with stabilization of a clot or partial recanalization in 55.6% of patients and complete recanalization in 14.8% at a median follow-up time of 6 months. The median modified Rankin Score (mRS) at follow-up was 0, with one death. Three patients (11.1%) had major bleeding complications, including two with symptomatic worsening of intracranial hemorrhage. Comparisons of 27 age-matched and sex-matched controls treated with VKAs showed no significant differences in terms of partial recanalization (55.6% vs. 63.0%, p = 0.29), complete recanalization (14.8% vs. 25.9%, p = 0.73), mRS at follow-up (median 0 vs. 0, p = 0.23), or major bleeding (11.1% vs. 11.1%, p > 0.99). Comparisons with the historical International Study on Cerebral Vein and Dural Sinus Thrombosis cohort showed similar functional outcomes: 92.6% of patients treated with NOACs and 88.9% of patients treated with VKAs at the Washington University School of Medicine in St. Louis, as well as 86.2% of patients treated with VKAs in the historical study cohort, had mRS of 0-2 at follow-up (p = 0.60). Rates of major bleeding compared with this cohort were also similar (11.1% vs. 11.1% vs. 14.5%, p = 0.80). CONCLUSIONS: The safety and efficacy results of NOAC use for CVT were similar to those for age-matched and sex-matched controls treated with VKAs, as well as historical published controls. Assessment of NOAC efficacy and safety in CVT in multicenter cohort studies and randomized controlled trials is warranted.

Neurovascular trauma: Diagnosis and therapy.

Traumatic cerebrovascular injuries are common in both military and civilian populations. Whether such injuries occur in the aftermath of blunt or penetrating trauma has major implications for characteristics, classification, diagnosis, and optimal management of these lesions. Advances in screening methods, including particularly the dramatic rise of high-quality CT angiography, have facilitated early detection of these lesions. Fortunately, these diagnostic advances have occurred alongside improvements in pharmacological treatment and endovascular intervention, which now play an important role alongside surgical intervention in reducing the likelihood of adverse clinical outcomes. While the management of victims of trauma remains challenging, improved understanding of and ability to appropriately manage traumatic cerebrovascular lesions promises to yield better clinical outcomes for these vulnerable patients.

Intraprocedural Back Pain Associated with Awake Neuroendovascular Procedures.

BACKGROUND AND PURPOSE: The prevalence and characteristics of intraprocedural back pain is not well studied in awake patients undergoing neuroendovascular procedures. METHODS: We performed a prospective study as part of quality improvement initiative in which all patients who underwent neuroendovascular procedures in awake state were inquired regarding presence, severity (using a numeric rating scale score ranging from 0 [no pain] to 10 [worst pain possible]), and location (using anatomical chart) of back pain immediately after the procedure. The primary endpoint was the proportion of patients with moderate to severe pain (score of ≥3). RESULTS: A total of 100 (41.3%) of 242 patients reported intraprocedural back pain with a median severity of 5/10 (range 1-10). The mean age was 58.7 ± 16.2 years. The mean duration of the procedure was 82.3 minutes (range 15-410 minutes). The pain was classified as moderate to severe in 86 of 100 patients. The locations of pain were identified in lumbar (n = 77), thoracic (n = 6), cervical (n = 7), cervical and lumbar (n = 8), and cervical with thoracolumbar (n = 2) regions. There was a significant relationship between patients' history of the previous neck and/or back surgery and frequency of moderate to severe back pain (P = .02). No significant relationship was observed between frequency of none to mild and moderate to severe back pain among the strata by patients' age, body mass index, or duration of procedures. CONCLUSIONS: The relatively high prevalence of intraprocedural back pain in patients undergoing neuroendovascular procedures in awake state must be recognized, and strategies to reduce the occurrence need to be identified.

Lesion evolution and neurodegeneration in RVCL-S: A monogenic microvasculopathy.

OBJECTIVE: To characterize lesion evolution and neurodegeneration in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) using multimodal MRI. METHODS: We prospectively performed MRI and cognitive testing in RVCL-S and healthy control cohorts. Gray and white matter volume and disruption of white matter microstructure were quantified. Asymmetric spin echo acquisition permitted voxel-wise oxygen extraction fraction (OEF) calculation as an in vivo marker of microvascular ischemia. The RVCL-S cohort was included in a longitudinal analysis of lesion subtypes in which hyperintense lesions on fluid-attenuated inversion recovery (FLAIR), T1-postgadolinium, and diffusion-weighted imaging were delineated and quantified volumetrically. RESULTS: Twenty individuals with RVCL-S and 26 controls were enrolled. White matter volume and microstructure declined faster in those with RVCL-S compared to controls. White matter atrophy in RVCL-S was highly linear (ρ = -0.908, p < 0.0001). Normalized OEF was elevated in RVCL-S and increased with disease duration. Multiple cognitive domains, specifically those measuring working memory and processing speed, were impaired in RVCL-S. Lesion volumes, regardless of subtype, progressed/regressed with high variability as a function of age, while FLAIR lesion burden increased near time to death (p < 0.001). CONCLUSION: RVCL-S is a monogenic microvasculopathy affecting predominantly the white matter with regard to atrophy and cognitive impairment. White matter volumes in RVCL-S declined linearly, providing a potential metric against which to test the efficacy of future therapies. Progressive elevation of white matter OEF suggests that microvascular ischemia may underlie neurodegeneration in RVCL-S.

The Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis Trial: Reanalysis Using the FDA "On Label" Criteria.

BACKGROUND AND PURPOSE: Due to higher rates of 1-month stroke and death with Wingspan intracranial stent placement observed in SAMMPRIS, the Food and Drug Administration (FDA) announced a more limited indication for Wingspan stent. METHODS: We compared the results of intracranial stent placement with best medical treatment in patients recruited in SAMMPRIS who met the new "on label" criteria with those who were categorized as "off label." The primary endpoint was any stroke or death occurring within 30 days of enrollment, or an ischemic stroke in the territory of the symptomatic intracranial artery from day 31 after study entry to completion of follow-up. RESULTS: A total of 31 (7%) among 451 recruited patients met the "on label" criteria. The relative risk of primary endpoint was lower in "on label" patients treated with stent placement compared with best medical treatment (relative risk .61, 95% confidence interval .2-1.7) but higher in "off label" patients (relative risk 1.81, 95% confidence interval 1.2-2.6). Primary endpoint was seen in 20% and 23.4% of patients treated with stent placement in "on label" and "off label" patients, respectively. Primary endpoint was seen in 25% and 14.2% of patients treated with best medical treatment in "on label" and "off label" patients, respectively. CONCLUSION: The new FDA "on label" criteria may identify a small group of people, who may benefit from intracranial stent placement due to higher risk of primary endpoint in those treated with best medical treatment.

Percutaneous Fenestration of a Spinal Arachnoid Web Using an Intrathecal Catheter: Effect on Cerebrospinal Fluid Flow and Clinical Status.

BACKGROUND: Spinal arachnoid webs are a rare anatomic entity manifesting as neuropathic back pain, compressive myelopathy, radiculopathy, and hydrocephalus. Typical treatments include hemilaminectomy or full laminectomy with durotomy and microsurgical resection, which can result in secondary scarring and recurrent blockage of cerebrospinal fluid (CSF) flow perpetuating the cycle. CASE DESCRIPTION: A 66-year-old woman presented with progressively worsening gait and memory. Magnetic resonance imaging demonstrated an arachnoid web in the high thoracic region, causing CSF flow obstruction and hydrocephalus. A standard lumbar drainage catheter was introduced percutaneously into the lumbar thecal sac and advanced in a cephalad direction, across the arachnoid web, to the high thoracic region. The patient underwent continuous CSF drainage through this catheter for a total of 3 days, displaying measurable clinical improvement that persisted at the 3-month follow-up visit. Phase-contrast magnetic resonance imaging demonstrated interval reconstitution of dorsal synchronous CSF flow at the second thoracic vertebral level, both on day 3 and at the 3-month control imaging study. CONCLUSIONS: This minimally invasive approach seems useful in achieving restoration of spinal fluid flow at the thoracic region when the underlying blockage results from an arachnoid web and leads to quantifiable clinical improvement.

Central Nervous System Complications and Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Central nervous system complications (CNSC) can be the cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to determine the incidence of CNSC and its impact on survival. PATIENTS AND METHODS: This retrospective cohort study included patients with hematologic disorders who received allo-HSCT between 2002 and 2011 at the University of Nebraska Medical Center. RESULTS: Of the 351 patients identified, 45 developed CNSC (12.8%). The 100-day cumulative incidence of CNSC was 8% (95% confidence interval, 8-15). The most common CNSC included posterior reversible encephalopathy syndrome (40%), stroke or transient ischemic attack (24%), seizures (20%), and infection (9%). The 5-year overall survival was significantly lower among patients with versus without CNSC (14% vs. 44%, P = .0004). In multivariate analysis, the risk of mortality for patients with versus without CNSC was significantly higher (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36; P = .04). CONCLUSION: The occurrence of CNSC after allo-HSCT was associated with reduced survival. Identifying patients at risk, monitoring, early detection, and management of CNSC after allo-HSCT are needed to improve outcomes.