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Background: The overall safety and efficacy of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) in frail patients is not well delineated. This systematic review aims to summarize and compare outcomes in frail and non-frail patients who underwent MT for AIS., Methods: A systematic review of the literature was performed using PubMed, Ovid Medline, and Web of Science to identify studies with outcomes-related data for frail patients with MT-treated AIS. The recanalization rate, procedural complications, and clinical outcome at 90-day follow-up were collected., Results: In the four included studies there were 642 frail patients and 499 non-frail patients. Frail patients had reduced rates of good functional outcomes (29% vs 42%; χ 2 =22, p<0.01) and increased 90-day mortality (51% vs 25%; χ 2 =38, p<0.01) compared with non-frail patients., Conclusion: MT for treatment of AIS in frail patients may be associated with worse rates of morbidity and mortality along with reduced efficacy. Given that no studies to date directly compare conservative measures with endovascular management for AIS in frail patients, more studies are required to further evaluate and identify characteristics that may improve outcomes in these patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: The treatment of brain arteriovenous malformations (AVMs) involves multiple approaches, including embolization, microsurgical resection, and radiosurgery. With the advent of new embolisates, dual-lumen balloon catheters, detachable tip microcatheters, and transvenous embolization, endovascular AVM obliteration has become more effective. Although adjuvant embolization and embolization are commonly used, the safety and effectiveness of curative embolization remain unclear., Methods: We conducted a systematic literature review using PubMed, Ovid Medline, and Web of Science to identify studies reporting outcomes in patients with AVMs who underwent primary embolization with the intention to cure. We collected data on patient characteristics, AVM features, complications, and radiographic and clinical outcomes for meta-analysis., Results: We identified 25 studies with a total of 1425 patients with 1427 AVMs who underwent curative embolization. Of these patients, 70% were low grade (pooled = 61% [39-82]), 67% were <3 cm (pooled = 78% [60-92]), and 75% were in superficial locations (pooled = 80% [72-86]). At last radiographic follow-up (mean, 16.7 ± 10.9 months), the full obliteration rate was 52% (pooled = 61% [43-77]) and retreatment rate was 25% (pooled = 17% [8.3-27]). At last clinical follow-up (mean, 24.2 ± 13.3 months), the poor clinical outcome rate was 7.9% (pooled = 4.4% [1.3-8.7]) and symptomatic complication rate was 13% (pooled = 13% [8-19]). There was no significant difference in the rate of radiographic cure, need for retreatment, and poor outcomes between ruptured and unruptured AVMs. Symptomatic complications were more common in the treatment of unruptured AVMs. The primary outcomes showed high heterogeneity (I2 = 72%-94%)., Conclusion: Curative embolization of AVM is primarily reserved for small and low-grade AVMs, with highly variable outcomes. Our findings suggest poor radiographic outcomes and increased risk of complications. Outcomes are highly dependent on patient selection and technique used. Large multicenter prospective studies are required to further guide patient selection, categorize clinical and radiographic outcomes, and identify subgroup of patients that may benefit from curative embolization., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Purpose: Non-O blood types are known to be associated with thromboembolic complications (TECs) in population-based studies. TECs are known drivers of morbidity and mortality in intracerebral hemorrhage (ICH) patients, yet the relationships of blood type on TECs in this patient population are unknown. We sought to explore the relationships between ABO blood type and TECs in ICH patients., Methods: Consecutive adult ICH patients enrolled into a prospective observational cohort study with available ABO blood type data were analyzed. Patients with cancer history, prior thromboembolism, and baseline laboratory evidence of coagulopathy were excluded. The primary exposure variable was blood type (non-O versus O). The primary outcome was composite TEC, defined as pulmonary embolism, deep venous thrombosis, ischemic stroke or myocardial infarction, during the hospital stay. Relationships between blood type, TECs and clinical outcomes were separately assessed using logistic regression models after adjusting for sex, ethnicity and ICH score., Results: Of 301 ICH patients included for analysis, 44% were non-O blood type. Non-O blood type was associated with higher admission GCS and lower ICH score on baseline comparisons. We identified TECs in 11.6% of our overall patient cohort. . Although TECs were identified in 9.9% of non-O blood type patients compared to 13.0% in O blood type patients, we did not identify a significant relationship of non-O blood type with TECs (adjusted OR=0.776, 95%CI: 0.348-1.733, p=0.537). The prevalence of specific TECs were also comparable in unadjusted and adjusted analyses between the two cohorts. In additional analyses, we identified that TECs were associated with poor 90-day mRS (adjusted OR=3.452, 95% CI: 1.001-11.903, p=0.050). We did not identify relationships between ABO blood type and poor 90-day mRS (adjusted OR=0.994, 95% CI:0.465-2.128, p=0.988)., Conclusions: We identified that TECs were associated with worse ICH outcomes. However, we did not identify relationships in ABO blood type and TECs. Further work is required to assess best diagnostic and prophylactic and treatment strategies for TECs to improve ICH outcomes., Competing Interests: Declaration of competing interest This study follows the guidelines set forth by the Strengthening the Reporting of Observational Studies in Epidemiology statement., (Copyright © 2024. Published by Elsevier Inc.)

Background: There exists a complex and ever-evolving relationship between social media and medicine. This study investigates the usage of X (formerly Twitter) among neurosurgeons and explores how virtual engagement potentially impacts this specialty., Methods: The researchers examined X posts from the top fifty influential neurosurgeons over 6 months. Demographics and practice information were collected. Posts were categorized into 9 predetermined coding definitions. Descriptive statistics were used to summarize user characteristics. χ 2 tests and two-tailed T-tests were employed to examine patterns of posting behavior., Results: Most influencers practiced in an academic setting (89%) and 43% of them were age fifty or older. Only 15% identified as female. Cerebrovascular subspecialists accounted for 39% of the cohort. Reposting was the most popular type of posting, constituting 61% of all posts. The most common postcategory observed was "Professional Events" (31%), while "Patient Education" was the least common (0.8%). Private practice and general neurosurgeons infrequently posted about "Professional Events" (5.1%, P < 0.01 and 3.2%, P < 0.01, respectively). "Personal Thoughts" constituted the second most common category, with a notable increase among users younger than 50 (25%, P < 0.01), individuals who identified as female (62%, P < 0.01), those in private practice (69%, P < 0.01), and general neurosurgeons (86%, P < 0.01)., Conclusions: Neurosurgeons of all ages use X to advance their careers and stay updated. However, the utilization of this influential platform likely varies depending on the current practice setting and individual career goals. Neurosurgeons on X appear to have the greatest influence within an academic context, particularly when promoting professional events., (Copyright © 2023. Published by Elsevier Inc.)

Background: Clival chordomas are challenging because of their proximity to critical neurovascular structures. Stereotactic radiosurgery (SRS) has been proven effective with minimal adverse effects., Objective: To compare the outcomes of histologically confirmed primary clival chordomas in adults who underwent SRS alone (SRS group) vs SRS after fractionated radiotherapy (FRT+SRS group)., Methods: We collected patient data from 10 institutions affiliated with the International Radiosurgery Research Foundation. We evaluated overall survival, tumor control, and freedom from additional treatment (FFAT)., Results: Fifty-seven (77%) patients were included in the SRS group and 17 (23%) in the FRT+SRS group. The median radiological follow-up was 48 months (IQR, 24-85) in the SRS group and 36 months (IQR, 25-41) in the FRT+SRS group. During the follow-up, 8 SRS and 2 FRT+SRS patients died ( P = .80). The groups had comparable 10-year overall survival (SRS: 76% vs FRT+SRS: 80%; logrank test, P = .75) and tumor control rates (SRS: 34% vs FRT+SRS: 45%; logrank test, P = .29). The SRS group had a superior 10-year FFAT rate (40%) compared with FRT+SRS (23%; logrank test, P = .02). This finding persisted in the multivariate analysis of the Cox proportional hazards illustrating a 2.40-fold increase in the relative risk of requiring additional treatment among the FRT+SRS group ( P = .04)., Conclusion: Adjuvant FRT with subsequent boost SRS did not provide superior overall survival or tumor control compared with patients who underwent adjuvant SRS alone. Further studies are required to refine management guidelines among adults with clival chordomas., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Flow diversion, specifically with the Pipeline embolization device (PED), represents a paradigm shift in the treatment of intracranial aneurysms. Several studies have demonstrated its efficacy and at times superiority to conventional treatment modalities for aneurysms with a fusiform morphology, giant size, or wide neck. However, there may be a nonsignificant risk of recurrence after flow diversion of these historically difficult-to-treat aneurysms, relative to aneurysms with a more favorable morphology and size (i.e., saccular, narrow necked). To date, only three papers in the literature have demonstrated the recurrence of a completely occluded aneurysm on follow-up., Observations: The authors describe a patient with a giant middle cerebral artery fusiform aneurysm treated with multiple telescoping PEDs. On the 3-month follow-up angiogram, there was complete occlusion of the aneurysm. The patient was lost to follow-up and presented 4 years later with a recurrence of the aneurysm between PED segments, requiring retreatment. The patient represented 3 years posttreatment with the need for repeat treatment of the fusiform aneurysm due to separation of the existing PEDs along with stent reconstruction. At the 20-month follow-up after the third treatment, the initial aneurysm target was found to be occluded., Lessons: This case illustrates the need for long-term follow-up, specifically for patients with giant wide-necked or fusiform aneurysms treated with overlapping PEDs.

Background: The overall safety and efficacy of mechanical thrombectomy for anterior cerebral artery strokes remain unclear., Purpose: Our aim was to summarize procedural and clinical outcomes in patients who underwent mechanical thrombectomy for treatment of anterior cerebral artery ischemic stroke., Data Sources: A systematic literature review was performed using PubMed, Ovid MEDLINE, and the Web of Science from inception until March 4, 2022., Study Selection: We identified 9 studies with a total of 168 patients with mechanical thrombectomy-treated anterior cerebral artery occlusions., Data Analysis: Recanalization, procedural data, and clinical outcome at last follow-up were collected and summarized. Categoric variables were reported as proportions. The χ 2 test of independence or the Kruskal-Wallis test was performed to assess the relationship between selected variables and the anterior cerebral artery embolus type (ie, primary isolated anterior cerebral artery, primary combined anterior cerebral artery, and secondary anterior cerebral artery occlusion) or the mechanical thrombectomy technique., Data Synthesis: For mechanical thrombectomy-treated anterior cerebral artery occlusions, recanalization modified TICI 2b/3 was achieved in 80%, postprocedural complications occurred in 17% of patients, and the 90-day mortality rate was 19%. The rate of symptomatic intracranial hemorrhage varied depending on the anterior cerebral artery embolus type (χ 2 = 8.45, P = .01)., Limitations: This analysis did not consider factors such as small-study effects that affect reliability and limit interpretation., Conclusions: Mechanical thrombectomy for the treatment of anterior cerebral artery occlusions is safe and efficacious, offering a favorable rate of recanalization and procedural complications. Mechanical thrombectomy-treated anterior cerebral artery occlusions appear to have lower rates of short-term good functional outcomes and an increased risk of symptomatic intracerebral hemorrhage compared with mechanical thrombectomy-treated MCA/ICA occlusions. Single and multicenter studies are needed to further examine the safety and efficacy of mechanical thrombectomy-treated anterior cerebral artery occlusions., (© 2022 by American Journal of Neuroradiology.)

Background: Surgical removal has been performed as the first line treatment for symptomatic or enlarging hypoglossal schwannomas (HS). Stereotactic radiosurgery (SRS) offers a minimally invasive approach that may afford long-term tumor control for patients with HS particularly those who refuse or are unfit for surgery. This study evaluates outcomes after SRS performed for both newly diagnosed and residual tumors after incomplete resection., Methods: This retrospective, multi-institutional study involved patients treated with adjuvant or primary SRS for HS. The study end-points included local tumor response, clinical outcomes, and procedure-related complications. All the patients had Gamma Knife SRS., Results: The cohort included 12 patients (five females), median age at SRS 49.5 years (range, 37-76)]. The median tumor target volume was 5.9 cm 3 (range, 0.7-27.23). At median imaging follow-up of 37 months (range, 6-153), tumor control was achieved in 11 patients. Tumor enlargement that was managed with surgical resection was noted at the 6-month follow-up in one patient. At median clinical follow-up of 30.5 months (range, 6-157), stability, or improvement of all pre-SRS signs and symptoms was noted in nine patients. Two patients experienced worsening of at least one pre-existing symptoms or sign. New-onset trapezius weakness was noted in one patient and tongue atrophy in two patients., Conclusion: Single-fraction SRS appears to be a safe and effective upfront and adjuvant treatment option for HS. SRS may be recommended as an alternative to surgery for patients presenting with HS or as an adjuvant treatment following subtotal resection and at HS recurrence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Drugs of abuse have been associated with ischemic stroke; however, the clinical presentation, outcomes, and treatment data in this population are limited. The overall safety and efficacy of thrombolytic therapy and thrombectomy in these patients remain unclear. This scoping review summarizes published complications and clinical outcomes in patients with recent abuse of cocaine, methamphetamine (MA), cannabis, decongestant, opioids, alcohol, and 3,4-methylenedioxymethamphetamine (MDMA) presenting with acute ischemic stroke., Methods: We conducted a scoping review of the primary literature that assessed outcomes data of thrombolytic therapy or thrombectomy in drug users with acute ischemic stroke. We searched PubMed, Ovid Medline, and Web of Science. Demographic and stroke characteristics, treatment, complications, and clinical outcomes at last follow-up were collected and summarized., Results: We identified 51 studies in this review. Drugs of abuse of interest were cocaine (14 studies), MDMA (one study), MA (eight studies), cannabis (23 studies), alcohol (two studies), decongestants (one study), and opioids (two studies). Clinical presentation and stroke presentation were most commonly described features. Thrombectomy outcomes were reported for four patients total (two studies), all with history of cocaine use. Thrombolysis treatment and outcomes were reported for 8851 patients (five studies) with history of cocaine, alcohol, or cannabis. Both treatments were pursued in three patients (three studies). Treatment complications included intracerebral hemorrhage, vasospasm, and cerebral edema., Conclusion: Evidence for thrombolytic and thrombectomy treatment in drug users remains limited. Controlled studies are needed to examine complication profile and outcomes following thrombolytic and thrombectomy treatment in this population., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)

Background: The overall safety and efficacy of flow diverting stents (FDSs) deployed in small caliber parent arteries (≤2.5 mm) for the treatment of intracranial aneurysms remains unclear. Recent studies have provided additional outcomes data to assess the use of FDSs for such arteries. In the present review, we have summarized the reported clinical and angiographic outcomes of FDS-treated brain aneurysms in small parent arteries., Methods: A systematic literature review was performed for outcomes data related to FDS-treated intracranial aneurysms using PubMed, Ovid Medline, and Web of Science. Procedural data, angiographic outcomes, and clinical outcomes at various time points were collected and summarized., Results: The 19 studies included 580 patients with 604 aneurysms, of which 6.1% had been acutely ruptured and 28.3% had been previously treated. The procedural complication rate and symptomatic stroke rate was 9.8% and 7.5%. The complete occlusion rate at the last radiographic follow-up (mean, 12.1 months) was 73.6%. At the last clinical follow-up (mean, 10.6 months), the FDS-associated mortality was 2.5%., Conclusions: FDSs for the treatment of intracranial aneurysms located in small caliber arteries was associated with rates of long-term complete aneurysm occlusion, mortality, and permanent neurologic deficit comparable to the rates with FDS-treated aneurysms in larger parent arteries. However, the relatively increased risk of symptomatic stroke of these FDS-treated aneurysms should not be ignored. Direct comparisons with alternative endovascular approaches are necessary to further define the optimal use of FDS for these aneurysms., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hypoglossal schwannomas (HS) are extremely rare neoplasms. Surgical resection has historically been the treatment of choice but carries a significant risk of postoperative neurological deficits and mortality. Stereotactic radiosurgery (SRS) is a minimally invasive approach that may afford long-term tumour growth. However, literature to determine the safety and effectiveness of SRS in the treatment of HS is scarce. We report on a patient who presented with progressive headache and dysphagia as well as tongue deviation to the left, due to a space-occupying lesion, consistent on brain MRI with a left HS. Primary SRS using a prescription dose of 12 Gy in a single fraction was used to treat the tumour without complications. By last follow-up, the tumour regressed, and the patient's symptoms improved. Our case shows that radiosurgery can be safe and effective for the management of HS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The object of this study was to evaluate the safety, efficacy, and long-term outcomes of stereotactic radiosurgery (SRS) in the management of intracranial chordomas., Methods: This retrospective multicenter study involved consecutive patients managed with single-session SRS for an intracranial chordoma at 10 participating centers. Radiological and neurological outcomes were assessed after SRS, and predictive factors were evaluated via statistical methodology., Results: A total of 93 patients (56 males [60.2%], mean age 44.8 years [SD 16.6]) underwent single-session SRS for intracranial chordoma. SRS was utilized as adjuvant treatment in 77 (82.8%) cases, at recurrence in 13 (14.0%) cases, and as primary treatment in 3 (3.2%) cases. The mean tumor volume was 8 cm3 (SD 7.3), and the mean prescription volume was 9.1 cm3 (SD 8.7). The mean margin and maximum radiosurgical doses utilized were 17 Gy (SD 3.6) and 34.2 Gy (SD 6.4), respectively. On multivariate analysis, treatment failure due to tumor progression (p = 0.001) was associated with an increased risk for post-SRS neurological deterioration, and a maximum dose > 29 Gy (p = 0.006) was associated with a decreased risk. A maximum dose > 29 Gy was also associated with improved local tumor control (p = 0.02), whereas the presence of neurological deficits prior to SRS (p = 0.04) and an age > 65 years at SRS (p = 0.03) were associated with worse local tumor control. The 5- and 10-year tumor progression-free survival rates were 54.7% and 34.7%, respectively. An age > 65 years at SRS (p = 0.01) was associated with decreased overall survival. The 5- and 10-year overall survival rates were 83% and 70%, respectively., Conclusions: SRS appears to be a safe and relatively effective adjuvant management option for intracranial chordomas. The best outcomes were obtained in younger patients without significant neurological deficits. Further well-designed studies are necessary to define the best timing for the use of SRS in the multidisciplinary management of intracranial chordomas.

Objective: The long-term safety and efficacy of intrasaccular flow disruption (IFD) for the treatment of brain aneurysms remain unclear. With accumulating experience and increasing use of IFD devices, recent studies have provided additional data regarding their outcomes. This review summarizes the long-term outcomes of IFD-treated brain aneurysms., Methods: A systematic literature review was performed on May 23, 2021, in PubMed, Web of Science, and Ovid MEDLINE for aneurysm treatment outcomes with IFD devices. Procedural details, including use of adjunctive devices and complications, were collected. The quality of studies was assessed using the Downs and Black checklist. Angiographic outcomes were classified as complete occlusion, residual neck, and residual aneurysm. Other outcomes included need for retreatment, permanent neurological deficit, and mortality. Pooled analyses were performed., Results: The final analysis comprised 1217 patients with 1249 aneurysms from 22 studies. The mean aneurysm diameter and neck width were 6.9 and 4.5 mm, respectively, and 27.6% of aneurysms were ruptured. The complete occlusion rates at 12 months and final follow-up (pooled mean duration 15.7 months) were 50.1% and 58.2%, respectively. Adjunctive devices were used in 6.4% of cases. The rates of hemorrhage, symptomatic infarction, permanent neurological deficit, and mortality were 1.2%, 2.8%, 1.0%, and 2.6%, respectively., Conclusions: IFD is a very safe treatment for appropriately selected brain aneurysms with low complication and neurological deterioration rates. However, complete occlusion is achieved in only half of IFD-treated aneurysms at 1 year with a modest increase beyond this time point. As the majority of the studies were single arm, the pooled data are subject to selection and reporting biases. Future device developments, increased operator experience, and direct comparisons with alternative endovascular strategies and surgical clipping may clarify the role of IFD in aneurysm management.

Background: The management of craniopharyngiomas is challenging, usually requiring multidisciplinary care. We evaluated the long-term clinical and radiologic outcomes of Gamma Knife radiosurgery (GKRS) for craniopharyngiomas., Methods: This retrospective study involved patients managed with GKRS for a craniopharyngioma during the period of 1989 to 2019. Patient clinical and radiologic data, tumor characteristics, and procedural details were analyzed., Results: Thirty-eight consecutive patients (24 males; mean patient age at GKRS = 30.82 years [SD ± 20.45 years]) were treated with GKRS for craniopharyngioma. Overall survival rates at 5 and 10 years were 84.1% and 80.1%, respectively. Progression-free survival at 5 years was 48.1%, and, at 10 years, it was 29.8%. Risk factors for post-GKRS clinical deterioration were increasing number of isocenters used (p = 0.04 (HR1.32, CI 1-1.73)), increasing margin dose [p = 0.02 (HR1.52, CI 1.31-1.84)], and maximum dose > 35 Gy [p = 0.002 (HR1.35, CI 1.11-1.63)]., Conclusion: Stereotactic radiosurgery (SRS) appears a safe and effective management option in selected craniopharyngioma patients. Increasing margin dose and maximum dose > 35 Gy are associated with an increased risk for post-SRS neurologic deficit. Further, well-designed studies are necessary to determine the optimal timing and SRS parameters and to identify which patients with craniopharyngioma will benefit the most from SRS., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Aging leads to a progressive deterioration of meningeal lymphatics and peripheral immunity, which may accelerate cognitive decline. We hypothesized that an age-related reduction in C-C chemokine receptor type 7 (CCR7)-dependent egress of immune cells through the lymphatic vasculature mediates some aspects of brain aging and potentially exacerbates cognitive decline and Alzheimer's disease-like brain β-amyloid (Aβ) pathology. We report a reduction in CCR7 expression by meningeal T cells in old mice that is linked to increased effector and regulatory T cells. Hematopoietic CCR7 deficiency mimicked the aging-associated changes in meningeal T cells and led to reduced glymphatic influx and cognitive impairment. Deletion of CCR7 in 5xFAD transgenic mice resulted in deleterious neurovascular and microglial activation, along with increased Aβ deposition in the brain. Treating old mice with anti-CD25 antibodies alleviated the exacerbated meningeal regulatory T cell response and improved cognitive function, highlighting the therapeutic potential of modulating meningeal immunity to fine-tune brain function in aging and in neurodegenerative diseases., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Alzheimer's disease (AD) is the most prevalent cause of dementia 1 . Although there is no effective treatment for AD, passive immunotherapy with monoclonal antibodies against amyloid beta (Aβ) is a promising therapeutic strategy 2,3 . Meningeal lymphatic drainage has an important role in the accumulation of Aβ in the brain 4 , but it is not known whether modulation of meningeal lymphatic function can influence the outcome of immunotherapy in AD. Here we show that ablation of meningeal lymphatic vessels in 5xFAD mice (a mouse model of amyloid deposition that expresses five mutations found in familial AD) worsened the outcome of mice treated with anti-Aβ passive immunotherapy by exacerbating the deposition of Aβ, microgliosis, neurovascular dysfunction, and behavioural deficits. By contrast, therapeutic delivery of vascular endothelial growth factor C improved clearance of Aβ by monoclonal antibodies. Notably, there was a substantial overlap between the gene signature of microglia from 5xFAD mice with impaired meningeal lymphatic function and the transcriptional profile of activated microglia from the brains of individuals with AD. Overall, our data demonstrate that impaired meningeal lymphatic drainage exacerbates the microglial inflammatory response in AD and that enhancement of meningeal lymphatic function combined with immunotherapies could lead to better clinical outcomes.

Change history: In this Article, Extended Data Fig. 9 was appearing as Fig. 2 in the HTML, and in Fig. 2, the panel labels 'n' and 'o' overlapped the figure; these errors have been corrected online.

Ageing is a major risk factor for many neurological pathologies, but its mechanisms remain unclear. Unlike other tissues, the parenchyma of the central nervous system (CNS) lacks lymphatic vasculature and waste products are removed partly through a paravascular route. (Re)discovery and characterization of meningeal lymphatic vessels has prompted an assessment of their role in waste clearance from the CNS. Here we show that meningeal lymphatic vessels drain macromolecules from the CNS (cerebrospinal and interstitial fluids) into the cervical lymph nodes in mice. Impairment of meningeal lymphatic function slows paravascular influx of macromolecules into the brain and efflux of macromolecules from the interstitial fluid, and induces cognitive impairment in mice. Treatment of aged mice with vascular endothelial growth factor C enhances meningeal lymphatic drainage of macromolecules from the cerebrospinal fluid, improving brain perfusion and learning and memory performance. Disruption of meningeal lymphatic vessels in transgenic mouse models of Alzheimer's disease promotes amyloid-β deposition in the meninges, which resembles human meningeal pathology, and aggravates parenchymal amyloid-β accumulation. Meningeal lymphatic dysfunction may be an aggravating factor in Alzheimer's disease pathology and in age-associated cognitive decline. Thus, augmentation of meningeal lymphatic function might be a promising therapeutic target for preventing or delaying age-associated neurological diseases.