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The coronavirus disease 2019 pandemic necessitated the use of telemedicine for most medical specialties, including neurosurgery, although before the pandemic, neurosurgeons infrequently used telemedicine for outpatient visits. We conducted a patient-centric evaluation of telemedicine in our endovascular neurosurgery practice, covering a 4-month period early in the pandemic. Survey e-mails after telemedicine visits were sent to all patients who underwent an outpatient telemedicine visit between March 11, 2020, and June 22, 2020, at an endovascular neurosurgery clinic affiliated with a tertiary care center. Of 140 patients, 65 (46%) completed the e-mail survey. Of the 65 respondents, 35 (54%) agreed or strongly agreed with the statement that even before their telemedicine experience, they thought telemedicine would be a convenient way to receive a neurological consultation. After their telemedicine visit, 47 (72%) agreed or strongly agreed with this statement, and 28 (43%) agreed or strongly agreed that they would prefer telemedicine for future visits. Of the 65 respondents, 61 (94%) rated their telemedicine visit as average or better: 34 (52%) rated it excellent, 12 (18%) rated it above average, and 15 (23%) rated it average. When patients compared their telemedicine visit with a prior in-person clinic visit, only 10 of 44 patients (23%) thought the telemedicine visit was more complicated than an in-person visit, and 21 of 44 (48%) said they would prefer telemedicine for future visits. Our patients expressed satisfaction with their telemedicine visits, and telemedicine will likely play an important role in future outpatient endovascular neurosurgery consultations. [ABSTRACT FROM AUTHOR]

Stroke-induced immune suppression predisposes the host to infections and can contribute to high morbidity and mortality in stroke patients. Because ischemic stroke has a profound effect on the systemic immune response, which may explain the increased susceptibility of stroke patients to infection, an urgent need persists for a better understanding of mechanisms associated with immune suppression; new and effective treatments for stroke can then be identified. NK cells play a key role in early host defense against pathogens by killing infected cells and/or producing cytokines such as IFN-γ. Because the phenotype and function of peripheral NK cells have been widely investigated in ischemic stroke, nCounter Inflammation Gene Array Analysis was used to build immune-related gene profiles of NK cells to comprehensively analyze the molecular signature of NK cells after ischemic brain injury. We observed distinct gene expression profiles reflecting different splenic NK-cell phenotypes and functional properties across the time course of transient middle cerebral artery occlusion (MCAO). Based on gene expression and pathway-network analysis, lower expression levels of signal transducer and activator of transcription-3 (STAT3) were observed in animals with MCAO compared with sham control animals. Genetic activation of STAT3 through the introduction of STAT3 clustered regularly interspaced short palindromic repeats (CRISPR) plasmid prevented the loss of NK-cell-derived IFN-γ production after MCAO, together with reduced bacterial burden and mortality. Our data suggest that brain ischemia impairs NK-cell-mediated immune defense in the periphery, at least in part through the JAK-STAT3 pathway, which can be readdressed by modulating STAT3 activation status. [ABSTRACT FROM AUTHOR]

Background/objective Transarterial infusion of Onyx is now widely used in the treatment of arteriovenous malformations (AVMs) and dural arteriovenous fistulas (DAVFs). Transvenous Onyx embolization is rarely performed, and usually in cases of carotid cavernous fistulas. We describe a novel technique of transvenous Onyx embolization in the treatment of three high risk DAVFs and one vein of Galen (VOG) AVM. Methods Cases were evaluated with specific attention to technical caveats, clinical indications, and complications. Patients were treated during 2011-2012 by two operators (FCA and CGM). Standard transfemoral venous approaches were employed in order to obtain access into the draining venous system in all cases. Results Four female patients, aged 5 months to 68 years, were treated. Two patients, one presenting with headache and the other with a bruit, demonstrated high risk DAVFs involving the transverse-sigmoid sinuses. One patient, who was asymptomatic, manifested a high risk ethmoidal DAVF that was discovered incidentally during treatment of a basilar aneurysm. The final patient presented with symptoms of a pineal region mass and was found to have a VOG AVM. In all cases, a microcatheter was navigated through the draining venous pouch and into the ostium of an arterial feeder. A single Onyx infusion from this position filled multiple arterial feeders and resulted in cures in the first three patients and a significant reduction in AVM nidus in the fourth patient. No complications occurred. Conclusions Transvenous Onyx infusion into a single arterial feeder can produce retrograde embolization of numerous other arterial feeders supplying high risk DAVFs and complex cerebral AVMs. This technique appears to be safe and potentially curative in select cases. [ABSTRACT FROM AUTHOR]

Background Recent reports suggest that placement of a venous sinus stent improves symptoms in selected patients with idiopathic intracranial hypertension (IIH). We report our evaluation of the long-term patency of venous stents placed for IIH. Methods We retrospectively reviewed our clinical database for 30 patients (mean age 33±10 years) with IIH who underwent placement of 36 venous sinus stents between October 2006 and December 2012. Relevant clinical, demographic and radiographic data were extracted after review of these records. All patients underwent retrograde venography to confirm a >50% stenosis and a trans-stenosis pressure gradient. Follow-up catheter angiography was performed beginning 3 months after the procedure. Results Follow-up imaging was available for 23 (77%) of the 30 patients (mean 23 months). For seven patients, angiographic follow-up of >2 years (mean 45 months) was available. All stents remained patent with mild (<25%) in-stent stenosis observed in four patients. In five patients, however, we observed a narrowing of the sinus proximal to the stent. Although no patient underwent repeat stent placement for persistent or recurrent symptoms, cerebrospinal fluid diversion was performed in five cases. Conclusions Venous sinus stent placement has emerged as a promising treatment option for the subgroup of patients with IIH with a pressure gradient across a stenotic venous sinus. We observed long-term patency of all stents placed in this patient population. Further prospective investigation is necessary to improve our understanding of the phenomenon of sinus narrowing upstream of a patent stent and to establish definitively the long-term clinical efficacy of venous sinus stent placement for IIH. [ABSTRACT FROM AUTHOR]

Objective: Carotid-cavernous fistulas (CCFs) are pathologic arteriovenous shunts between the carotid artery and cavernous sinus. The resulting venous congestion within the cavernous sinus accounts for the classic ocular symptoms associated with these lesions. Endovascular treatment of CCFs has evolved over time to include a variety of transarterial and transvenous embolization techniques. The present series comprises our institutional experience with the endovascular treatment of CCF. Methods: We reviewed our prospectively maintained clinical database for patients with CCF who were evaluated between December 1995 and August 2012. Clinical and demographic data were extracted from medical records, operative notes, and radiographic reports. Cerebral angiograms were reviewed. Results: The study included 100 (42 direct CCF [dCCF], 58 indirect [iCCF]) patients. Of the 42 patients with dCCF, endovascular treatment was possible in 40 (95%), with an overall 8% morbidity and 2% mortality. Before March 2004, dCCFs were primarily treated with the use of detachable balloons. After the withdrawal of detachable balloons from the market, coil embolization emerged as the first-line treatment. It was accomplished either transarterially or transvenously and often incorporated balloon or stent protection of the parent vessel. After initial treatment, 33 patients (82%) exhibited complete obliteration of their fistula, whereas an additional four (10%) patients demonstrated fistula thrombosis on follow-up angiography. Endovascular access was achieved in 48 (83%) of the 58 patients with iCCF. In this cohort, the morbidity rate was 8%, and there were no deaths. Transvenous approaches were used to treat 88% of these patients and included both transfemoral venous access to the cavernous sinus and direct access through the ophthalmic veins. Immediate fistula occlusion was observed in 37 (77%) patients, and 1 of the 11 patients with a residual fistula progressed to thrombosis on follow-up. Transarterial embolization alone was used in six cases, and five required combined transvenous/transarterial approaches. Conclusions: For dCCF, the lack of availability of detachable balloons led to the adoption of both transarterial and transvenous coil embolization with adjunctive techniques of parent vessel protection. For iCCF, advances in techniques of venous access have facilitated treatment of lesions with restricted venous outflow. Treatment strategies for CCF continue to evolve with advances in endovascular techniques. [ABSTRACT FROM AUTHOR]

Spinal arteriovenous malformations (sAVMs) are rare vascular lesions whose natural history remains incompletely defined. Several classification schemes for sAVMs have evolved based on an improved understanding of the anatomic characteristics as well as pathophysiologic behavior of these arteriovenous shunts. Advances in endovascular technology have inspired the adoption of interventional techniques both as stand-alone treatment and as part of a multi-modality management paradigm for sAVMs. Further refinements in liquid embolic agents as well as improved microcatheter navigability will contribute to an ever-expanding role for endovascular intervention in the management of these lesions. [ABSTRACT FROM AUTHOR]

Background The Pipeline embolization device has been used successfully to treat intracranial aneurysms with difficult morphologies. However, the need for dual antiplatelet therapy has limited its use after subarachnoid hemorrhage. Case report A 42-year-old woman with a ruptured dissecting aneurysm of her dominant vertebral artery (V4) was successfully treated by Pipeline embolization with preservation of flow through a covered posterior inferior cerebellar artery. This strategy preserved endovascular access for the treatment of severe posterior circulation vasospasm. She was a non-responder to thienopyridine agents and was thus maintained on aspirin and heparin, which was transitioned to warfarin following ventricular drain removal. The aneurysm remains angiographically obliterated at 6 months. Despite a moribund presentation and an extended hospitalization, she has made a remarkable neurological recovery. Conclusions Pipeline embolization may be used to treat a ruptured dissecting aneurysm in selected cases where parent vessel preservation is paramount. [ABSTRACT FROM AUTHOR]

We report a case of a patient who developed glioblastoma in the territory of a previous infarction. Two years after an ischemic stroke, the patient presented with a cystic, necrotic, and heterogeneously enhancing mass. Open biopsy and debulking of the mass with histological analysis revealed the mass to be glioblastoma. Though several cases of posttraumatic GBM have been reported, this is the first proposed case of GBM after an ischemic stroke. From this case, we suggest that the ischemic stroke, like other forms of cortical injury, may predispose to glioblastoma formation. [ABSTRACT FROM AUTHOR]

Background and Purpose: The restoration of blood-flow following cerebral ischemia incites a series of deleterious cascades that exacerbate neuronal injury. Pharmacologic inhibition of the C3a-receptor ameliorates cerebral injury by attenuating post-ischemic inflammation. Recent reports also implicate C3a in the modulation of tissue repair, suggesting that complement may influence both injury and recovery at later post-ischemic time-points. Methods: To evaluate the effect of C3a-receptor antagonism on post-ischemic neurogenesis and neurological outcome in the subacute period of stroke, transient focal cerebral ischemia was induced in adult male C57BL/6 mice treated with multiple regimens of a C3a receptor antagonist (C3aRA). Results: Low-dose C3aRA administration during the acute phase of stroke promotes neuroblast proliferation in the subventricular zone at 7 days. Additionally, the C3a receptor is expressed on T-lymphocytes within the ischemic territory at 7 days, and this cellular infiltrate is abrogated by C3aRA administration. Finally, C3aRA treatment confers robust histologic and functional neuroprotection at this delayed time-point. Conclusions: Targeted complement inhibition through low-dose antagonism of the C3a receptor promotes post-ischemic neuroblast proliferation in the SVZ. Furthermore, C3aRA administration suppresses T-lymphocyte infiltration and improves delayed functional and histologic outcome following reperfused stroke. Post-ischemic complement activation may be pharmacologically manipulated to yield an effective therapy for stroke. [ABSTRACT FROM AUTHOR]

Chronic subdural hematoma (cSDH) is an increasingly common neurological disease process. Despite the wide prevalence of cSDH, there remains a lack of consensus regarding numerous aspects of its clinical management. We provide an overview of the epidemiology and pathophysiology of cSDH and discuss several controversial management issues, including the timing of post-operative resumption of anticoagulant medications, the effectiveness of anti-epileptic prophylaxis, protocols for mobilization following evacuation of cSDH, as well as the comparative effectiveness of the various techniques of surgical evacuation. A PubMed search was carried out through October 19, 2010 using the following keywords: 'subdural hematoma', 'craniotomy', 'burr-hole', 'management', 'anticoagulation', 'seizure prophylaxis', 'antiplatelet', 'mobilization', and 'surgical evacuation', alone and in combination. Relevant articles were identified and back-referenced to yield additional papers. A meta-analysis was then performed comparing the efficacy and complications associated with the various methods of cSDH evacuation. There is general agreement that significant coagulopathy should be reversed expeditiously in patients presenting with cSDH. Although protocols for gradual resumption of anti-coagulation for prophylaxis of venous thrombosis may be derived from guidelines for other neurosurgical procedures, further prospective study is necessary to determine the optimal time to restart full-dose anti-coagulation in the setting of recently drained cSDH. There is also conflicting evidence to support seizure prophylaxis in patients with cSDH, although the existing literature supports prophylaxis in patients who are at a higher risk for seizures. The published data regarding surgical technique for cSDH supports primary twist drill craniostomy (TDC) drainage at the bedside for patients who are high-risk surgical candidates with non-septated cSDH and craniotomy as a first-line evacuation technique for cSDH with significant membranes. Larger prospective studies addressing these aspects of cSDH management are necessary to establish definitive recommendations. [ABSTRACT FROM AUTHOR]

Despite extensive effort to elucidate the cellular and molecular bases for delayed cerebral injury after aneurysmal subarachnoid hemorrhage (aSAH), the pathophysiology of these events remains poorly understood. Recently, much work has focused on evaluating the genetic underpinnings of various diseases in an effort to delineate the contribution of specific molecular pathways as well as to uncover novel mechanisms. The majority of subarachnoid hemorrhage genetic research has focused on gene expression and linkage studies of these markers as they relate to the development of intracranial aneurysms and their subsequent rupture. Far less work has centered on the genetic determinants of cerebral vasospasm, the predisposition to delayed cerebral injury, and the determinants of ensuing functional outcome after aSAH. The suspected genes are diverse and encompass multiple functional systems including fibrinolysis, inflammation, vascular reactivity, and neuronal repair. To this end, we present a systematic review of 21 studies suggesting a genetic basis for clinical outcome after aSAH, with a special emphasis on the pathogenesis of cerebral vasospasm and delayed cerebral ischemia. In addition, we highlight potential pitfalls in the interpretation of genetic association studies, and call for uniformity of design of larger multicenter studies in the future. [ABSTRACT FROM AUTHOR]

Intracranial infectious aneurysms, or mycotic aneurysms, are rare infectious cerebrovascular lesions which arise through microbial infection of the cerebral arterial wall. Due to the rarity of these lesions, the variability in their clinical presentations, and the lack of population-based epidemiological data, there is no widely accepted management methodology. We undertook a comprehensive literature search using the OVID gateway of the MEDLINE database (1950–2009) using the following keywords (singly and in combination): “infectious,” “mycotic,” “cerebral aneurysm,” and “intracranial aneurysm.” We identified 27 published clinical series describing a total of 287 patients in the English literature that presented demographic and clinical data regarding presentation, treatment, and outcome of patients with mycotic aneurysms. We then synthesized the available data into a combined cohort to more closely estimate the true demographic and clinical characteristics of this disease. We follow by presenting a comprehensive review of mycotic aneurysms, highlighting current treatment paradigms. The literature supports the administration of antibiotics in conjunction with surgical or endovascular intervention depending on the character and location of the aneurysm, as well as the clinical status of the patient. Mycotic aneurysms comprise an important subtype of potentially life-threatening cerebrovascular lesions, and further prospective studies are warranted to define outcome following both conservative and surgical or endovascular treatment. [ABSTRACT FROM AUTHOR]

Abstract: Intracerebral hemorrhage (ICH) is the second most common and deadliest form of stroke. Currently, no pharmacologic treatment strategies exist for this devastating disease. Following the initial mechanical injury suffered at hemorrhage onset, secondary brain injury proceeds through both direct cellular injury and inflammatory cascades, which trigger infiltration of granulocytes and monocytes, activation of microglia, and disruption of the blood–brain barrier with resulting cerebral edema. The complement cascade has been shown to play a central role in the pathogenesis of secondary injury following ICH, although the specific mechanisms responsible for the proximal activation of complement remain incompletely understood. Cerebral injury following cleavage of complement component 3 (C3) proceeds through parallel but interrelated pathways of anaphylatoxin-mediated inflammation and direct toxicity secondary to membrane attack complex-driven erythrocyte lysis. Complement activation also likely plays an important physiologic role in recovery following ICH. As such, a detailed understanding of the variation in functional effects of complement activation over time is critical to exploiting this target as an exciting translational strategy for intracerebral hemorrhage. [Copyright &y& Elsevier]

The complement anaphylatoxin C3a contributes to injury after cerebral ischemia in mice. This study assesses the effect of C3a receptor antagonist (C3aRA) on leukocyte infiltration into the ischemic zone. Transient or permanent middle cerebral artery occlusion (MCAO) was induced in wild-type C57Bl/6 mice. Intraperitoneal C3aRA or vehicle was administered 45 mins before or 1 h after occlusion. Twenty-four hours after occlusion, we harvested brain tissue and purified inflammatory cells using flow cytometry. Soluble intercellular adhesion molecule (ICAM)-1 protein levels were assessed using enzyme-linked immunosorbent assays, and ICAM-1 and C3a receptor (C3aR) expression was confirmed via immunohistochemistry. In the transient MCAO model, animals receiving C3aRA showed smaller strokes, less upregulation of C3aR-positive granulocytes, and less ICAM-1 protein on endothelial cells than vehicle-treated animals; no significant differences in other inflammatory cell populations were observed. C3a receptor antagonist-treated and vehicle-treated animals showed no differences in stroke volume or inflammatory cell populations after permanent MCAO. These data suggest that blocking the binding of C3a to C3aR modulates tissue injury in reperfused stroke by inhibiting the recruitment of neutrophils to the ischemic zone. It further establishes antagonism of the C3a anaphylatoxin as a promising strategy for ameliorating injury after ischemia/reperfusion.Journal of Cerebral Blood Flow & Metabolism (2008) 28, 1048–1058; doi:10.1038/sj.jcbfm.9600608; published online 16 January 2008 [ABSTRACT FROM AUTHOR]

Background Soluble complement receptor-1 (sCR1), a potent complement inhibitor, confers neuroprotection in a murine stroke model. Additional neuroprotective benefit is achieved by sLex-glycosylation of sCR1. In an effort to translate sCR1-sLex to clinical trials, we evaluated this agent in a primate stroke model. Methods Adult male baboons randomly received either sCR1-sLex or vehicle. Stroke volume was assessed on day 3, and neurological examinations were conducted daily. Complement activity (CH50) was measured at 30 minute, 2, 6, 12 hour, 3, and 10 days post-ischemia. Results The experiment was terminated prematurely following an interim analysis. In a preliminary cohort (n = 3 per arm), infarct volume was greater in the treated animals. No difference in neurological score was found between groups. CH50 levels were significantly reduced in the sCR1sLex-treated groups. A hypotensive response was also observed in animals treated with sCR1-sLex. Conclusions Further work is necessary to explain the hypotensive response observed in primates prior to further clinical development of sCR1-sLex. [ABSTRACT FROM AUTHOR]

Examines ortho-linked polyphenols, quaterphenol and moderately hindered terphenol as novel multidentate polyaryloxide ligands for transition-metal chemistry. Synthesis of the polyphenols using ortho-metalation and metal-catalyzed cross-coupling; Synthetic routed fr facile electronic and stearic modification of the basic ligand design.

Traumatic optic neuropathy (TON) has been regarded a vision-threatening condition caused by either ocular or blunt/penetrating head trauma, which is characterized by direct or indirect TON. Injury happens during sports, vehicle accidents and mainly in military war and combat exposure. Earlier, we have demonstrated that remote ischemic post-conditioning (RIC) therapy is protective in TON, and here we report that AMPKα1 activation is crucial. AMPKα1 is the catalytic subunit of the heterotrimeric enzyme AMPK, the master regulator of cellular energetics and metabolism. The α1 isoform predominates in immune cells including macrophages (Mφs). Myeloid-specific AMPKα1 KO mice were generated by crossing AMPKα1Flox/Flox and LysMcre to carry out the study. We induced TON in mice by using a controlled impact system. Mice (mixed sex) were randomized in six experimental groups for Sham (mock); Sham (RIC); AMPKα1F/F (TON); AMPKα1F/F (TON+RIC); AMPKα1F/F LysMCre (TON); AMPKα1F/F LysMCre (TON+RIC). RIC therapy was given every day (5–7 days following TON). Data were generated by using Western blotting (pAMPKα1, ICAM1, Brn3 and GAP43), immunofluorescence (pAMPKα1, cd11b, TMEM119 and ICAM1), flow cytometry (CD11b, F4/80, CD68, CD206, IL-10 and LY6G), ELISA (TNF-α and IL-10) and transmission electron microscopy (TEM, for demyelination and axonal degeneration), and retinal oxygenation was measured by a Unisense sensor system. First, we observed retinal morphology with funduscopic images and found TON has vascular inflammation. H&E staining data suggested that TON increased retinal inflammation and RIC attenuates retinal ganglion cell death. Immunofluorescence and Western blot data showed increased microglial activation and decreased retinal ganglion cell (RGCs) marker Brn3 and axonal regeneration marker GAP43 expression in the TON [AMPKα1F/F] vs. Sham group, but TON+RIC [AMPKα1F/F] attenuated the expression level of these markers. Interestingly, higher microglia activation was observed in the myeloid AMPKα1F/F KO group following TON, and RIC therapy did not attenuate microglial expression. Flow cytometry, ELISA and retinal tissue oxygen data revealed that RIC therapy significantly reduced the pro-inflammatory signaling markers, increased anti-inflammatory macrophage polarization and improved oxygen level in the TON+RIC [AMPKα1F/F] group; however, RIC therapy did not reduce inflammatory signaling activation in the myeloid AMPKα1 KO mice. The transmission electron microscopy (TEM) data of the optic nerve showed increased demyelination and axonal degeneration in the TON [AMPKα1F/F] group, and RIC improved the myelination process in TON [AMPKα1F/F], but RIC had no significant effect in the AMPKα1 KO mice. The myeloid AMPKα1c deletion attenuated RIC induced anti-inflammatory macrophage polarization, and that suggests a molecular link between RIC and immune activation. Overall, these data suggest that RIC therapy provided protection against inflammation and neurodegeneration via myeloid AMPKα1 activation, but the deletion of myeloid AMPKα1 is not protective in TON. Further investigation of RIC and AMPKα1 signaling is warranted in TON. [ABSTRACT FROM AUTHOR]

This study assessed neurological outcomes and variables associated with favorable outcomes in aneurysmal subarachnoid hemorrhage patients with low functional status (Glasgow Coma Scale [GCS] score ≤8) on postbleed day 7 (PBD7). A retrospective analysis was conducted of all patients in the Barrow Ruptured Aneurysm Trial (January 1, 2014–July 31, 2019) treated for a ruptured aneurysm and who had a GCS score ≤8 on PBD7. The primary outcome was a favorable neurological outcome (modified Rankin Scale score ≤2) at last follow-up. Of 312 patients, 63 had low GCS scores at PBD7. These patients had a significantly greater proportion of poor Hunt and Hess scale grades (≥4) (44/63 [70%] vs. 49/249 [19.7%], P < 0.001) and poor Fisher grades (grade = 4) (58/63 [92%] vs. 174/249 [69.9%], P < 0.001) compared to patients who did not have low GCS scores on PBD7, but no differences were found in age, sex, anterior location, aneurysm size, or type of treatment. Of the 63 patients, 7 (11%) experienced a favorable neurological outcome. On univariate analysis, none of the physical examination reflexes predicted a favorable neurological outcome. The middle cerebral artery aneurysm territory was the only significant predictor of a favorable neurological outcome by multivariate analysis (odds ratio, 10.8; 95% confidence interval, 1.16–100], P = 0.04). This study yielded no significant physical examination findings that predict a favorable outcome in patients with a GCS score ≤8 on PBD7. This finding may inform the decision of whether to prolong hospital management or arrange for end-of-life care. [ABSTRACT FROM AUTHOR]

Disorders of consciousness impair early recovery after aneurysmal subarachnoid hemorrhage (aSAH). Modafinil, a wakefulness-promoting agent, is efficacious for treating fatigue in stroke survivors, but data pertaining to its use in the acute setting are scarce. This study sought to assess the effects of modafinil use on mental status after aSAH. Modafinil timing and dosage, neurological examination, intubation status, and physical and occupational therapy participation were documented. Repeated-measures paired tests were used for a before-after analysis of modafinil recipients. Propensity score matching (1:1 nearest neighbor) for modafinil and no-modafinil cohorts was used to compare outcomes. Modafinil (100–200 mg/day) was administered to 21% (88/422) of aSAH patients for a median (IQR) duration of 10.5 (4–16) days and initiated 14 (7–17) days after aSAH. Improvement in mentation (alertness, orientation, or Glasgow Coma Scale score) was documented in 87.5% (77/88) of modafinil recipients within 72 hours and 86.4% (76/88) at discharge. Of 37 intubated patients, 10 (27%) were extubated within 72 hours after modafinil initiation. Physical and occupational therapy teams noted increased alertness or participation in 47 of 56 modafinil patients (83.9%). After propensity score matching for baseline covariates, the modafinil cohort had a greater mean (SD) change in Glasgow Coma Scale score than the no-modafinil cohort at discharge (2.2 [4.0] vs. −0.2 [6.32], P = 0.003). A temporal relationship with improvement in mental status was noted for most patients administered modafinil after aSAH. These findings, a favorable adverse-effect profile, and implications for goals-of-care decisions favor a low threshold for modafinil initiation in aSAH patients in the acute-care setting. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and aneurysms, are characterized by the abnormal accumulation and aggregation of disease-causing proteins in the brain and spinal cord. Recent research suggests that proteins linked to these conditions can be secreted and transferred among cells using exosomes. The transmission of abnormal protein buildup and the gradual degeneration in the brains of impacted individuals might be supported by these exosomes. Furthermore, it has been reported that neuroprotective functions can also be attributed to exosomes in neurodegenerative diseases. The potential neuroprotective functions may play a role in preventing the formation of aggregates and abnormal accumulation of proteins associated with the disease. The present review summarizes the roles of exosomes in neurodegenerative diseases as well as elucidating their therapeutic potential in AD, PD, ALS, HD, stroke, and aneurysms. By elucidating these two aspects of exosomes, valuable insights into potential therapeutic targets for treating neurodegenerative diseases may be provided. [ABSTRACT FROM AUTHOR]

Background: Controversy remains regarding the appropriate screening for intracranial aneurysms or for the treatment of aneurysmal subarachnoid hemorrhage (aSAH) for patients without known high-risk factors for rupture. This study aimed to assess how sex affects both aSAH presentation and outcomes for aSAH treatment. Method: A retrospective cohort study was conducted of all patients treated at a single institution for an aSAH during a 12-year period (August 1, 2007–July 31, 2019). An analysis of women with and without high-risk factors was performed, including a propensity adjustment for a poor neurologic outcome (modified Rankin Scale [mRS] score > 2) at follow-up. Results: Data from 1014 patients were analyzed (69% [n = 703] women). Women were significantly older than men (mean ± SD, 56.6 ± 14.1 years vs 53.4 ± 14.2 years, p < 0.001). A significantly lower percentage of women than men had a history of tobacco use (36.6% [n = 257] vs 46% [n = 143], p = 0.005). A significantly higher percentage of women than men had no high-risk factors for aSAH (10% [n = 70] vs 5% [n = 16], p = 0.01). The percentage of women with an mRS score > 2 at the last follow-up was significantly lower among those without high-risk factors (34%, 24/70) versus those with high-risk factors (53%, 334/633) (p = 0.004). Subsequent propensity-adjusted analysis (adjusted for age, Hunt and Hess grade, and Fisher grade) found no statistically significant difference in the odds of a poor outcome for women with or without high-risk factors for aSAH (OR = 0.7, 95% CI = 0.4–1.2, p = 0.18). Conclusions: A higher percentage of women versus men with aSAH had no known high-risk factors for rupture, supporting more aggressive screening and management of women with unruptured aneurysms. [ABSTRACT FROM AUTHOR]

Background Rotational vertebral artery occlusion is a rare syndrome characterized by vertebrobasilar insufficiency secondary to position-dependent occlusion of the vertebral artery. Most cases reported in the literature have been attributed to osteophytic compression, either from the occipital condyle or within the transverse foramen. However, vertebral artery dissection secondary to motion in the setting of anomalous anatomy has not been reported. Case Description To the authors' knowledge, rotational vertebral artery occlusion and dissection secondary to anomalous entrance into the transverse foramen have never been reported. The authors describe the case of a 42-year-old male who presented with multiple posterior circulation transient ischemic attacks. Standard digital subtraction cerebral angiography demonstrated a non−flow-limiting right vertebral artery dissection, while dynamic digital subtraction cerebral angiography was remarkable for right vertebral artery stenosis that worsened with neck rotation. Computed tomography angiography of the neck revealed an anomalous course of the right vertebral artery, which entered the transverse foramen at C4 with preforaminal compression by the anterior tubercle of the C5 transverse process. The patient had no further symptomatic events after decompression of the vertebral artery by resecting the anterior C5 tubercle. Conclusions In the setting of codominant vertebral circulation and unilateral bony compression, the authors propose that neck rotation led to vertebral artery trauma, causing dissection complicated by thromboembolism. This is a novel and unusual entity that is different from Bowhunter's syndrome. [ABSTRACT FROM AUTHOR]

Background Dural arteriovenous fistulas (dAVFs) often are treated via transarterial or transvenous embolization. Incomplete penetration of the draining vein/occult residual often will become apparent on follow-up angiography, requiring repeat embolization, or at times, surgical resection. Case Description A 41-year-old woman presented with cerebellar hemorrhage from a tentorial dAVF treated with transvenous coil embolization. Follow-up angiography disclosed a residual/recurrent fistula treated with transvenous Onyx embolization. After further follow-up angiography demonstrated another occult residual/recurrence, the fistula was disconnected with the tentorial dura excised via a retrosigmoid approach. Six-month follow-up angiography demonstrated no recurrence. Conclusions Although endovascular treatment of dAVFs is generally first-line therapy, surgical disconnection of fistulas, particularly high-risk residual/recurrent fistulas, is an excellent option in well-selected cases. [ABSTRACT FROM AUTHOR]

Background: Controversy remains regarding the appropriate screening for intracranial aneurysms or for the treatment of aneurysmal subarachnoid hemorrhage (aSAH) for patients without known high-risk factors for rupture. This study aimed to assess how sex affects both aSAH presentation and outcomes for aSAH treatment. Method: A retrospective cohort study was conducted of all patients treated at a single institution for an aSAH during a 12-year period (August 1, 2007–July 31, 2019). An analysis of women with and without high-risk factors was performed, including a propensity adjustment for a poor neurologic outcome (modified Rankin Scale [mRS] score > 2) at follow-up. Results: Data from 1014 patients were analyzed (69% [n = 703] women). Women were significantly older than men (mean ± SD, 56.6 ± 14.1 years vs 53.4 ± 14.2 years, p < 0.001). A significantly lower percentage of women than men had a history of tobacco use (36.6% [n = 257] vs 46% [n = 143], p = 0.005). A significantly higher percentage of women than men had no high-risk factors for aSAH (10% [n = 70] vs 5% [n = 16], p = 0.01). The percentage of women with an mRS score > 2 at the last follow-up was significantly lower among those without high-risk factors (34%, 24/70) versus those with high-risk factors (53%, 334/633) (p = 0.004). Subsequent propensity-adjusted analysis (adjusted for age, Hunt and Hess grade, and Fisher grade) found no statistically significant difference in the odds of a poor outcome for women with or without high-risk factors for aSAH (OR = 0.7, 95% CI = 0.4–1.2, p = 0.18). Conclusions: A higher percentage of women versus men with aSAH had no known high-risk factors for rupture, supporting more aggressive screening and management of women with unruptured aneurysms. [ABSTRACT FROM AUTHOR]

A correction in author's name Kristen N. Andersen in the article "The surgical management of chronic subdural hematoma" that was published in the previous issue is presented.

Aneurysmal subarachnoid hemorrhage (aSAH) is associated with increased blood-brain barrier permeability, disrupted tight junctions, and increased cerebral edema. Sulfonylureas are associated with reduced tight-junction disturbance and edema and improved functional outcome in aSAH animal models, but human data are scant. We analyzed neurological outcomes in aSAH patients prescribed sulfonylureas for diabetes mellitus. Patients treated for aSAH at a single institution (August 1, 2007–July 31, 2019) were retrospectively reviewed. Patients with diabetes were grouped by presence or absence of sulfonylurea therapy at hospital admission. The primary outcome was favorable neurologic status at last follow-up (modified Rankin Scale score ≤2). Variables with an unadjusted P -value of <0.20 were included in a propensity-adjusted multivariable logistic regression analysis to identify predictors of favorable outcomes. Of 1013 aSAH patients analyzed, 129 (13%) had diabetes at admission, and 16 of these (12%) were receiving sulfonylureas. Fewer diabetic than nondiabetic patients had favorable outcomes (40% [52/129] vs. 51% [453/884], P = 0.03). Among diabetic patients, sulfonylurea use (OR 3.90, 95% CI 1.05–15.9, P = 0.046), Charlson Comorbidity Index <4 (OR 3.66, 95% CI 1.24–12.1, P = 0.02), and absence of delayed cerebral infarction (OR 4.09, 95% CI 1.20–15.5, P = 0.03) were associated with favorable outcomes in the multivariable analysis. Diabetes was strongly associated with unfavorable neurologic outcomes. An unfavorable outcome in this cohort was mitigated by sulfonylureas, supporting some preclinical evidence of a possible neuroprotective role for these medications in aSAH. These results warrant further study on dose, timing, and duration of administration in humans. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the use of intraaortic balloon pump (IABP) placement to counter severe cardiac dysfunction after aneurysmal subarachnoid hemorrhage (SAH). Methods: From August 2006 to October 2011, eight patients (seven women, mean age 47 years ± 5) with aneurysmal SAH underwent IABP placement. The modified Rankin scale (mRS) was used to assess outcome at discharge and long-term follow-up. Results: Most patients presented in poor Hunt & Hess grade (grade III, 25%; grade IV, 62.5%; grade V, 12.5%). Three patients underwent surgical clipping, and five patients underwent endovascular treatment. All patients had severe cardiogenic shock, with a mean ejection fraction of 21%. One patient (12.5%) experienced transient left leg ischemia attributable to the IABP. No patient deaths occurred. At discharge, one patient was moderately disabled (mRS = 3), two patients were moderately to severely disabled (mRS, 4), and five patients were severely disabled (mRS = 5). The seven patients available for long-term follow-up (mean, 11.25 months) showed substantial functional improvements. Two patients exhibited no significant disability (mRS = 1), two patients exhibited only slight disability (mRS = 2), and 3 patients exhibited moderate to severe disability (mRS = 4). Conclusions: In select patients, particularly young women with poor-grade SAH, balloon-pump counterpulsation may serve as a useful adjunct in the management of severe cardiac dysfunction after SAH. Further investigation is necessary to define the optimal patient population for this technique. [ABSTRACT FROM AUTHOR]

Background: Withholding prophylactic anticoagulation from patients with aneurysmal subarachnoid hemorrhage (aSAH) before external ventricular drain (EVD) removal or replacement remains controversial. This study analyzed whether prophylactic anticoagulation was associated with hemorrhagic complications related to EVD removal. Method: All aSAH patients treated from January 1, 2014, to July 31, 2019, with an EVD placed were retrospectively analyzed. Patients were compared based on the number of prophylactic anticoagulant doses withheld for EVD removal (> 1 vs. ≤ 1). The primary outcome analyzed was deep venous thrombosis (DVT) or pulmonary embolism (PE) after EVD removal. A propensity-adjusted logistic-regression analysis was performed for confounding variables. Results: A total of 271 patients were analyzed. For EVD removal, > 1 dose was withheld from 116 (42.8%) patients. Six (2.2%) patients had a hemorrhage associated with EVD removal, and 17 (6.3%) patients had a DVT or PE. No significant difference in EVD-related hemorrhage after EVD removal was found between patients with > 1 versus ≤ 1 dose of anticoagulant withheld (4 of 116 [3.5%] vs. 2 of 155 [1.3%]; p = 0.41) or between those with no doses withheld compared to ≥ 1 dose withheld (1 of 100 [1.0%] vs. 5 of 171 [2.9%]; p = 0.32). After adjustment, withholding > 1 dose of anticoagulant versus ≤ 1 dose was associated with the occurrence of DVT or PE (OR 4.8; 95% CI, 1.5–15.7; p = 0.009). Conclusions: In aSAH patients with EVDs, withholding > 1 dose of prophylactic anticoagulant for EVD removal was associated with an increased risk of DVT or PE and no reduction in catheter removal–associated hemorrhage. [ABSTRACT FROM AUTHOR]

Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed. [ABSTRACT FROM AUTHOR]

Sparse data exist on socioeconomic disparities among patients treated for aneurysmal subarachnoid hemorrhage (aSAH). The authors analyzed factors possibly influencing patient outcomes, including having a primary care physician (PCP) at admission, family/caregiver support, a foreign language barrier, primary payer status, and race. Socioeconomic data were abstracted for patients treated endovascularly or microsurgically for aSAH at a single center (January 1, 2014–July 31, 2019). Binary logistic regression analyses were used to identify independent predictors of an unfavorable outcome (modified Rankin Scale [mRS] score >2) and for predictive modeling. Among 422 patients, the median (interquartile range) follow-up was 2 (1–23) months. Lack of caregiver support was the only socioeconomic factor associated with an unfavorable outcome at discharge. Independent predictors of mRS score >2 at last follow-up included baseline markers of disease severity (P ≤ 0.03), nonwhite race (OR, 1.69; P = 0.047), lack of caregiver support (OR, 5.55; P = 0.007), and lack of a PCP (OR, 1.96; P = 0.007). Adjusting for follow-up mediated the effects of race and PCP, although caregiver support remained significant and PCP was associated with a lower mortality risk independent of follow-up (OR, 0.51; P = 0.047). Predischarge socioeconomic factors, alongside disease severity, predicted a follow-up mRS score >2 with excellent discrimination (area under the receiver operating curve, 0.81; 95% CI, 0.77–0.86). At a large, urban, comprehensive stroke center, patients with PCPs, caregiver support, and white race had significantly better long-term outcomes after aSAH. These results reflect disparities in access to healthcare after aSAH for vulnerable populations with extensive lifetime needs. [ABSTRACT FROM AUTHOR]

Background: Optimal definitive treatment timing for patients with aneurysmal subarachnoid hemorrhage (aSAH) remains controversial. We compared outcomes for aSAH patients with ultra-early treatment versus later treatment at a single large center. Method: Patients who received definitive open surgical or endovascular treatment for aSAH between January 1, 2014, and July 31, 2019, were included. Ultra-early treatment was defined as occurring within 24 h from aneurysm rupture. The primary outcome was poor neurologic outcome (modified Rankin Scale score > 2). Propensity adjustment was performed for age, sex, Charlson Comorbidity Index, Hunt and Hess grade, Fisher grade, aneurysm treatment type, aneurysm type, size, and anterior location. Results: Of the 1013 patients (mean [SD] age, 56 [14] years; 702 [69%] women, 311 [31%] men) included, 94 (9%) had ultra-early treatment. Compared with the non-ultra-early cohort, the ultra-early treatment cohort had a significantly lower percentage of saccular aneurysms (53 of 94 [56%] vs 746 of 919 [81%], P <0.001), greater frequency of open surgical treatment (72 of 94 [77%] vs 523 of 919 [57%], P <0.001), and greater percentage of men (38 of 94 [40%] vs 273 of 919 [30%], P =.04). After adjustment, ultra-early treatment was not associated with neurologic outcome in those with at least 180-day follow-up (OR = 0.86), the occurrence of delayed cerebral ischemia (OR = 0.87), or length of stay (exp(β), 0.13) (P ≥ 0.60). Conclusions: In a large, single-center cohort of aSAH patients, ultra-early treatment was not associated with better neurologic outcome, fewer cases of delayed cerebral ischemia, or shorter length of stay. [ABSTRACT FROM AUTHOR]

The incidence and risk factors for chronic depression after aneurysmal subarachnoid hemorrhage (aSAH) are described. Patients with aSAH treated at a single institution (January 1, 2003–December 31, 2019) and a modified Rankin Scale score ≤3 at follow-up who were evaluated for chronic depression were analyzed. Chronic depression was defined using a depression screening questionnaire as ≥5 positive answers for symptoms lasting >2 weeks. A predictive model was designed for the primary outcome of depression. Among 1419 patients with aSAH, 460 patients were analyzed; 130 (28%) had major depressive disorder. Mean follow-up was >6 years. Higher depression rates were associated with tobacco smoking (odds ratio [OR] = 2.64, P < 0.001), illicit drug use (OR = 2.35, P = 0.007), alcohol use disorder (1.92, P = 0.04), chronic obstructive pulmonary disease (COPD) (OR=2.68, P = 0.03), and vasospasm requiring angioplasty (OR=2.09, P = 0.048). The predictive model included tobacco smoking, illicit drug use, liver disease, COPD, diabetes, nonsaccular aneurysm type, anterior communicating artery or anterior cerebral artery aneurysm location, refractory spasm requiring angioplasty, and a modified Rankin Scale score at discharge of >1 (P ≤ 0.03). The model performed with appropriate goodness of fit and an area under the receiver operator curve of 0.70 for depression. Individual independent predictors of depression were tobacco smoking, COPD, diabetes, and nonsaccular aneurysm. A substantial percentage of patients had symptoms of depression on follow-up. The proposed predictive model for depression may be a useful clinical tool to identify patients at high risk for developing depression who warrant early screening and evaluation. [ABSTRACT FROM AUTHOR]

The "weekend effect" is the negative effect on disease course and treatment resulting from being admitted to the hospital during a weekend. Whether the weekend effect is associated with worse outcomes for patients treated for aneurysmal subarachnoid hemorrhage (aSAH) is unknown. We assessed neurologic outcomes of patients with aSAH admitted during the weekend versus during the week. A retrospective database was reviewed to identify all patients with aSAH who received open or endovascular treatment from August 1, 2007, to July 31, 2019, at a quaternary center. The primary outcome was a poor neurologic outcome (modified Rankin Scale score >2). Propensity adjustment included age, sex, treatment type, Hunt and Hess grade, and Charlson Comorbidity Index. A total of 1014 patients (women, 703 [69.3%]; men, 311 [30.7%]; mean age, 56 [standard deviation, 14]) met inclusion criteria; 726 (71.6%) had weekday admissions, and 288 (28.4%) had weekend admissions. There was no significant difference between patients with a weekday versus a weekend admission in mean (standard deviation) time to treatment (0.85 [1.29] vs. 0.93 [1.30] days, P = 0.10) or length of stay (19 [9] vs. 19 [9] days, P = 0.04). Total cost and rates of delayed cerebral ischemia and vasospasm were similar between the admission groups, both overall and within the open and endovascular treatment cohorts. After propensity adjustment, weekend admission was not a significant predictor of a modified Rankin Scale score greater than 2 (odds ratio [95% confidence interval]; 1.12 [0.85–1.49]; P = 0.4). No difference in neurologic outcomes was associated with weekend admission among this cohort of patients with aSAH. [ABSTRACT FROM AUTHOR]

Liver cirrhosis is associated with an increased risk of aneurysmal subarachnoid hemorrhage (aSAH). However, large studies analyzing the prognosis of cirrhotic patients after aSAH treatment are lacking. This study explores factors associated with inpatient mortality among aSAH patients with cirrhosis. All patients who underwent open or endovascular treatment for an aSAH at a large quaternary center between January 1, 2003, and July 31, 2019, were retrospectively reviewed. Patients were grouped into cirrhosis versus noncirrhosis groups. Univariate analysis determined variables associated with inpatient mortality. Variables with P < 0.20 were included in a propensity-adjusted multivariable logistic regression analysis to predict inpatient mortality. A total of 1419 patients were treated for aSAH; 17 (1.2%) had confirmed cirrhosis. Inpatient mortality was significantly higher among cirrhotic patients than noncirrhotic patients (35.3% vs. 6.8%; P < 0.001). In the univariate analysis for inpatient mortality, the variables cirrhosis, age >65 years, Charlson Comorbidity Index >4, aneurysm size ≥10 mm, Hunt and Hess grade >3, Fisher grade 4, delayed cerebral ischemia (DCI), and posterior circulation aneurysm had P < 0.20 and were included in the multivariable analysis. The propensity-adjusted stepwise multivariable logistic regression analysis showed that cirrhosis (odds ratio [OR]: 12.7, 95% confidence interval [CI]: 3.3–48.7), Hunt and Hess grade >3 (OR: 3.9, 95% CI: 2.3–6.4), Fisher grade 4 (OR: 3.7, 95% CI: 1.3–10.7), and DCI (OR: 2.4, 95% CI: 1.5–3.9) were associated with inpatient mortality (P ≤ 0.01). Cirrhosis was a predictor of inpatient mortality among aSAH patients and was a stronger predictor than DCI or a poor Hunt and Hess grade among patients in this study. [ABSTRACT FROM AUTHOR]

The additional hospital costs associated with delayed cerebral ischemia (DCI) have not been well investigated in prior literature. In this study, the total hospital cost of DCI in aneurysmal subarachnoid hemmorhage (aSAH) patients treated at a single quaternary center was analyzed. All patients in the Post-Barrow Ruptured Aneurysm Trial treated for an aSAH between January 1, 2014, and July 31, 2019, were retrospectively analyzed. DCI was defined as cerebral infarction identified on computed tomography, magnetic resonance imaging, or autopsy after exclusion of procedure-related infarctions. The primary outcome was the difference in total cost (including hospital, discharge facility, and all follow-up) using a propensity-adjusted analysis. Propensity score covariate-adjusted linear regression analysis included age, sex, open versus endovascular treatment, Hunt and Hess score, and Charlson Comorbidity Index score. Of the 391 patients included, 144 (37%) had DCI. Patients with DCI had a significantly greater cost compared to patients without DCI (mean standard deviation $112,081 [$54,022] vs. $86,159 [$38,817]; P < 0.001) and a significantly greater length of stay (21 days [11] vs. 18 days [8], P = 0.003, respectively). In propensity-adjusted linear regression analysis, both DCI (odds ratio, $13,871; 95% confidence interval, $7558–$20,185; P < 0.001) and length of stay (odds ratio, $3815 per day; 95% confidence interval, $3480–$4149 per day; P < 0.001) were found to significantly increase the cost. The significantly higher costs associated with DCI further support the evidence that adverse effects associated with DCI in aSAH pose a significant burden to the health care system. [ABSTRACT FROM AUTHOR]

Introduction Reports of the limitations and feasibility of balloon remodeling for treatment of complex anterior communicating artery (ACoA) aneurysms are scarce. Methods Ninety-nine patients were treated with balloon-assisted coil embolization for ACoA aneurysms between August 2004 and October 2012. Records were reviewed for aneurysm characteristics, balloon trajectory (vessel and side), bilateral access, treatment-related complications, and aneurysm recurrence determined by magnetic resonance angiography (MRA). Morphological outcomes following treatment were categorized into Raymond class I, II, or III. Results Fifty-three aneurysms (53.5%) were unruptured and 46 (46.4%) were ruptured. Aneurysmal occlusion (Raymond I or II) was achieved in 89 patients (89.9%); three (3.0%) were incompletely embolized and treatment was aborted in six (6.1%). Balloon trajectories were from the A1 to either the ipsilateral or contralateral A2. In 17 cases (17.2%), bilateral A1 access was used to achieve balloon protection of the contralateral A2. In four cases (4.0%), balloon remodeling was aborted due to technical difficulty. There were 15 (15.2%) treatment-related complications; five (5.1%) were intraoperative ruptures, one of which resulted in a neurological deficit and another in death. All other complications were clinically silent, producing a permanent complication rate of 2.0%. Mean radiographic follow-up was 2.5 years, and six patients (6.1%) were retreated for recurrence or known remnant. Conclusions Balloon remodeling should be considered for broad-based complex ACoA aneurysms. This technique provides a high rate of aneurysm occlusion with an acceptable complication profile, and avoids the need for dual antiplatelet therapy. The balloon trajectory will depend on aneurysm morphology and bilateral access may be useful in selected cases. [ABSTRACT FROM AUTHOR]

Background Clinical outcomes of methamphetamine users with aneurysmal subarachnoid hemorrhage (aSAH) are unknown. Objective To analyze differences in presentation, in-hospital morbidity, and outcomes between methamphetamine users and non-users. Methods All 472 patients included in the Barrow Ruptured Aneurysm Trial from 2003 to 2007 were reviewed. Patients with 1- and 3-year follow-up were included in this analysis (n=398). Methamphetamine users were identified as patients who provided a history of methamphetamine use on admission or tested positive on urine toxicology testing. Methamphetamine users were compared with non-users using univariate analysis. Outcomes were then analyzed using multivariate logistic regression models for demographic characteristics, medical comorbidities, radiographic and clinical presentation, and vasospasm. Results Thirty-one patients (7.8%) were identified as methamphetamine users in this cohort. Methamphetamine users were younger than non-users (mean age 42.8 vs 55 years, p<0.001). In multivariate logistic regression models, methamphetamine use was an independent predictor of poor Glasgow Outcome Scale score at both 1 year (OR=5.02; 95% CI 1.03 to 24.48; p<0.05) and 3 years (OR=7.18; 95% CI 1.73 to 29.87; p=0.007). Other independent predictors in this model included older age, clinical vasospasm, diabetes, and aneurysm size. Cocaine and tobacco use were not significantly associated with poor outcome in our cohort. Methamphetamine use was not significantly associated with vasospasm, higher Fisher or Hunt and Hess grade, or intraparenchymal hemorrhage/intraventricular hemorrhage. Conclusions Methamphetamine users have significantly worse outcomes at 1 and 3 years following aSAH. Further analysis is necessary to understand the pathological response associated with methamphetamine use in this setting. [ABSTRACT FROM AUTHOR]

Background: Aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to primary stroke centers are often transferred to neurosurgical and endovascular services at tertiary centers. The effect on microsurgical outcomes of the resultant delay in treatment is unknown. We evaluated microsurgical aSAH treatment > 72 h after the ictus. Methods: All aSAH patients treated at a single tertiary center between August 1, 2007, and July 31, 2019, were retrospectively reviewed. The additional inclusion criterion was the availability of treatment data relative to time of bleed. Patients were grouped based on bleed-to-treatment time as having acute treatment (on or before postbleed day [PBD] 3) or delayed treatment (on or after PBD 4). Propensity adjustments were used to correct for statistically significant confounding covariables. Results: Among 956 aSAH patients, 92 (10%) received delayed surgical treatment (delayed group), and 864 (90%) received acute endovascular or surgical treatment (acute group). Reruptures occurred in 3% (26/864) of the acute group and 1% (1/92) of the delayed group (p = 0.51). After propensity adjustments, the odds of residual aneurysm (OR = 0.09; 95% CI = 0.04–0.17; p < 0.001) or retreatment (OR = 0.14; 95% CI = 0.06–0.29; p < 0.001) was significantly lower among the delayed group. The OR was 0.50 for rerupture, after propensity adjustments, in the delayed setting (p = 0.03). Mean Glasgow Coma Scale scores at admission in the acute and delayed groups were 11.5 and 13.2, respectively (p < 0.001). Conclusions: Delayed microsurgical management of aSAH, if required for definitive treatment, appeared to be noninferior with respect to retreatment, residual, and rerupture events in our cohort after adjusting for initial disease severity and significant confounding variables. [ABSTRACT FROM AUTHOR]

Background Flow-diverting stents represent a substantial advancement in the treatment of cerebral aneurysms. They can, however, be associated with unique complications that may require management through adjunctive techniques. Objective To present a technical report of a salvage technique used to realign a prolapsed Pipeline Embolization Device (PED) during the treatment of a giant internal carotid artery (ICA) aneurysm. Methods A patient in his late 70s with an incidental giant supraclinoid ICA aneurysm presented for endovascular consideration. Treatment was planned using the PED. Following placement of the device there were two focal areas of incomplete expansion and balloon angioplasty was performed. This manipulation resulted in foreshortening of the distal aspect of the PED which caused the device to prolapse into the aneurysm. After multiple unsuccessful attempts to regain distal access, a salvage technique was attempted in which a balloon was inflated in the middle cerebral artery and, by applying traction, the PED was realigned with the parent artery. Results After the PED was realigned, direct distal catheter access was achieved and a second Pipeline device was deployed, successfully covering the aneurysm neck with resultant flow stasis. The patient had no postoperative issues and was discharged 2 days later without deficit. Conclusions The balloon-anchoring technique was successfully used to realign a PED that had prolapsed into a giant ICA aneurysm. This maneuver prevented potentially disastrous complications and allowed the satisfactory completion of the aneurysm embolization. This represents a useful salvage technique that should be considered when encountering a prolapsed stent. [ABSTRACT FROM AUTHOR]

Nationwide study results have suggested varying trends in the incidence of aneurysmal subarachnoid hemorrhage (aSAH) over time. Herein, trends over time for aSAH treated at a quaternary care center are compared with low-volume hospitals. Cases were retrospectively reviewed for patients with aSAH treated at our institution. Trend analyses were performed on the number of aSAH hospitalizations, treatment type, Charlson Comorbidity Index (CCI), Hunt and Hess grade, aneurysm location, aneurysm type, and in-hospital mortality. The National Inpatient Sample (NIS) was queried to compare the CCI scores of our patients with those of patients in low-volume hospitals (<20 aSAH/year) in our census division. Some 1248 patients (321 during 2004−2006; 927 during 2008−2018) hospitalized with aSAH were treated with endovascular therapy (489, 39%) or microsurgery (759, 61%). A significant downtrend in the annual aSAH caseload occurred (123 patients in 2004, 75 in 2018, P < 0.001). A linear uptrend was observed for the mean CCI score of patients (R 2 = 0.539, P < 0.001), with no change to in-hospital mortality (R 2 = 0.220, P = 0.24). Mean (standard deviation) CCI for small-volume hospitals treating aSAH within our division was significantly lower than that of our patient population (1.8 [1.6] vs 2.1 [2.0]) for 2012−2015. A decreasing number of patients were hospitalized with aSAH throughout the study. Compared with patients with aSAH admitted in 2004, those admitted more recently were sicker in terms of preexisting comorbidity and neurologic complexity. These trends could be attributable to the increasing availability of neurointerventional services at smaller-volume hospitals capable of treating healthier patients. [ABSTRACT FROM AUTHOR]

Although several commercially available sutureless anastomotic techniques are available, they are not routinely used in neurosurgery. We performed an in vivo flow analysis of end-to-end anastomosis using a microvascular coupler device in rats. We report our first clinical use of the microvascular anastomotic coupler. Bilateral rat common carotid arteries (CCAs) were exposed, and a microvascular coupler was used to perform 8 anastomoses. A microflow probe provided quantitative measurement of blood-flow volume. Flow augmentation was assessed with end-to-side anastomoses connecting the distal CCA to the jugular vein (JV). A patient with chronic dominant hemisphere atherosclerotic ischemic disease and progressive symptoms refractory to medical management underwent end-to-end cerebral artery bypass using the microvascular coupler. Mean preanastomosis flow in the rat CCA was 3.95 ± 0.45 mL/min; this flow was maintained at 3.99 ± 0.24 mL/min on final measurements 54–96 minutes postanastomosis. Total occlusion time for each rat CCA was 12–19 minutes. After end-to-side anastomosis, with proximal and distal JV patent, CCA flow increased 477% to 22.8 ± 3.70 mL/min (P = 0.04, proximal; P = 0.01, distal). After in vivo testing, we successfully used the coupler clinically in a superficial temporal artery–to–middle cerebral artery bypass for dominant hemisphere flow augmentation. In vivo quantitative flow analysis demonstrated no flow difference between an unaltered artery and artery with end-to-end anastomosis using a microvascular coupler in rats. A 1-mm coupled anastomosis achieved a 4-fold flow increase with low-resistance venous outflow in rats, simulating increased arterial demand. The coupler was successfully used for extracranial-to-intracranial bypass in a patient. [ABSTRACT FROM AUTHOR]

Background: Historically, the prognosis for poor grade subarachnoid hemorrhage patients has been considered dismal. As a result, many hospitals have chosen conservative management over aggressive therapy. This guarded approach, however, is based on studies that do not take into account newer, more effective, management protocols and more recent long-term evidence that significant neurological recovery occurs in the months to years following discharge. More accurate and predictive methods are needed to decide when aggressive therapy is warranted.Methods: Two hundred and twenty-six grade aneurysmal subarachnoid hemorrhage (aSAH) patients of grades IV and V were admitted to Columbia University Medical Center and enrolled in our study. Demographics, clinical information (e.g. pupillary reactivity on admission), and treatment course (operative versus non-operative) were recorded. Rankin scores at 14 days, 3 months, and 1 year were also recorded. A favorable Rankin score was defined as 0-3. Unfavorable was defined as 4-6.Results: Among all poor grade patients who received operative therapy, pupillary reactivity at admission was not predictive of a favorable Rankin score at day 14 (odds ratio = 3.3, P = 0.129). Pupillary reactivity, however, was predictive of Rankin score at 3 months (odds ratio = 4.57, P = 0.05) and 12 months (odds ratio = 6.44, P = 0.008). After constructing a Kaplan-Meiers survival curve, pupillary reactivity was a better predictor of survival at 12 months than H&H grade [Hazard ratio 3.342 (1.596-7.000) P = 0.001 versus 1.964 (1.016-3.798) P = 0.045].Conclusions: This study demonstrates that significant recovery occurs in the weeks to months after poor grade aSAH. Pupillary reactivity on admission can be used as a predictor of survival and recovery at intermediate and long-term time points, more so than Hunt and Hess grade. [ABSTRACT FROM AUTHOR]

Background: Outcomes for octogenarians and nonagenarians after an aneurysmal subarachnoid hemorrhage (aSAH) are particularly ominous, with mortality rates well above 50%. The present analysis examines the neurologic outcomes of patients ≥ 80 years of age treated for aSAH. Method: A retrospective review was performed of all aSAH patients treated at Barrow Neurological Institute from January 1, 2003, to July 31, 2019. Patients were placed in 2 groups by age, < 80 vs ≥ 80 years. The ≥ 80-year-old group of octogenarians and nonagenarians was subsequently analyzed to compare treatment modalities. Poor neurologic outcome was defined as a modified Rankin Scale (mRS) score of > 2. Results: During the study period, 1418 patients were treated for aSAH. The mean (standard deviation) age was 55.1 (13.6) years, the mean follow-up was 24.6 (40.0) months, and the rate of functional independence (mRS 0–2) at follow-up was 54% (751/1395). Logistic regression analysis found increasing age strongly associated with declining functional independence (R2 = 0.929, p < 0.001). Forty-three patients ≥ 80 years old were significantly more likely to be managed endovascularly than with open microsurgery (67% [n = 29] vs 33% [n = 14], p < 0.001). Compared with younger patients, those ≥ 80 years old had an increased risk of mortality and poor neurologic outcomes at follow-up. In the ≥ 80-year-old group, only 4 patients had good outcomes; none of the 4 had preexisting comorbidities, and all 4 were treated endovascularly. Conclusions: Age is a significant prognostic indicator of functional outcomes and mortality after aSAH. Most octogenarians and nonagenarians with aSAH will become severely disabled or die. [ABSTRACT FROM AUTHOR]