Sex differences in patients with and without high-risk factors associated with aneurysmal subarachnoid hemorrhage.

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.

Propensity-adjusted analysis of ultra-early aneurysmal subarachnoid hemorrhage treatment and patient outcomes.

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(ß), 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.

Roles of Phytoestrogen in the Pathophysiology of Intracranial Aneurysm.

Background and Purpose: The incidences of intracranial aneurysm and aneurysmal subarachnoid hemorrhage are high in postmenopausal women. Although population-based studies suggest that hormone replacement therapy is beneficial for postmenopausal women with intracranial aneurysms, estrogen replacement may no longer be recommended for the prevention of chronic diseases given its association with adverse outcomes, such as cancer and ischemic stroke. The isoflavone daidzein and its intestinal metabolite equol are bioactive phytoestrogens and potent agonists of estrogen receptors. Given their estrogenic properties, we investigated whether the isoflavones daidzein and equol are protective against the formation and rupture of intracranial aneurysms in a mouse model of the postmenopausal state. Methods: We induced intracranial aneurysms in ovariectomized adult female mice using a combination of induced systemic hypertension and a single injection of elastase into the cerebrospinal fluid. We fed the mice with an isoflavone-free diet with/without daidzein supplementation, or in a combination of intraperitoneal equol, or oral vancomycin treatment. We also used estrogen receptor beta knockout mice. Results: Both dietary daidzein and supplementation with its metabolite, equol, were protective against aneurysm formation in ovariectomized mice. The protective effects of daidzein and equol required estrogen receptor-ß. The disruption of the intestinal microbial conversion of daidzein to equol abolished daidzein's protective effect against aneurysm formation. Mice treated with equol had lower inflammatory cytokines in the cerebral arteries, suggesting that phytoestrogens modulate inflammatory processes important to intracranial aneurysm pathogenesis. Conclusions: Our study establishes that both dietary daidzein and its metabolite, equol, protect against aneurysm formation in ovariectomized female mice through the activation of estrogen receptor-ß and subsequent suppression of inflammation. Dietary daidzein's protective effect required the intestinal conversion to equol. Our results indicate the potential therapeutic value of dietary daidzein and its metabolite, equol, for the prevention of the formation of intracranial aneurysms and related subarachnoid hemorrhage.

METAP1 mutation is a novel candidate for autosomal recessive intellectual disability.

Intellectual disability (ID) is a genetic and clinically heterogeneous common disease and underlying molecular pathogenesis can frequently not be identified by whole-exome/genome testing. Here, we report four siblings born to a consanguineous union who presented with intellectual disability and discuss the METAP1 pathway as a novel etiology of ID. Genomic analyses demonstrated that patients harbor a novel homozygous nonsense mutation in the gene METAP1. METAP1 codes for methionine aminopeptidase 1 (MetAP1) which oversees the co-translational excision of the first methionine remnants in eukaryotes. The loss-of-function mutations to this gene may result in a defect in the translation of many essential proteins within a cell. Improper neuronal function resulting from this loss of essential proteins could lead to neurologic impairment and ID.

Delays in presentation and mortality among Black patients with mechanical thrombectomy after large-vessel stroke at a US hospital.

OBJECTIVE: The incidence and severity of stroke are disproportionately greater among Black patients. In this study, the authors sought to examine clinical outcomes among Black versus White patients after mechanical thrombectomy for stroke at a single US institution. METHODS: All patients who underwent mechanical thrombectomy at a single center from January 1, 2014, through March 31, 2020, were retrospectively analyzed. Patients were grouped based on race, and demographic characteristics, preexisting conditions, clinical presentation, treatment, and stroke outcomes were compared. The association of race with mortality was analyzed in multivariable logistic regression analysis adjusted for potential confounders. RESULTS: In total, 401 patients (233 males) with a reported race of Black (n = 28) or White (n = 373) underwent mechanical thrombectomy during the study period. Tobacco use was more prevalent among Black patients (43% vs 24%, p = 0.04), but there were no significant differences between the groups with respect to insurance, coronary artery disease, diabetes, illicit drug use, hypertension, or hyperlipidemia. The mean time from stroke onset to hospital presentation was significantly greater among Black patients (604.6 vs 333.4 minutes) (p = 0.007). There were no differences in fluoroscopy time, procedural success (Thrombolysis in Cerebral Infarction grade 2b or 3), hospital length of stay, or prevalence of hemicraniectomy. In multivariable analysis, Black race was strongly associated with higher mortality (32.1% vs 14.5%, p = 0.01). The disparity in mortality rates resolved after adjusting for the average time from stroke onset to presentation (p = 0.14). CONCLUSIONS: Black race was associated with an increased risk of death after mechanical thrombectomy for stroke. The increased risk may be associated with access-related factors, including delayed presentation to stroke centers.

Small intracranial aneurysms in the Barrow Ruptured Aneurysm Trial (BRAT).

BACKGROUND: Treatment of small ruptured aneurysms (SRAs) remains controversial, with literature reporting difficulty with endovascular versus microsurgical approaches. This paper analyzes outcomes after endovascular coiling and microsurgical clipping among patients with SRAs prospectively enrolled in the Barrow Ruptured Aneurysm Trial (BRAT). METHOD: All BRAT patients were included in this study. Patient demographics, aneurysm size, aneurysm characteristics, procedure-related complications, and outcomes at discharge and at 1-year and 6-year follow-up were evaluated. A modified Rankin scale (mRS) score > 2 was considered a poor outcome. RESULTS: Of 73 patients with SRAs, 40 were initially randomly assigned to endovascular coiling and 33 to microsurgical clipping. The rate of treatment crossover was significantly different between coiling and clipping; 25 patients who were assigned to coiling crossed over to clipping, and no clipping patients crossed over to coiling (P < 0.001). Among SRA patients, 15 underwent coiling and 58 underwent clipping; groups did not differ significantly in demographic characteristics or aneurysm type (P ≥ 0.11). Mean aneurysm diameter was significantly greater in the endovascular group (3.0 ± 0.3 vs 2.6 ± 0.6; P = 0.02). The incidence of procedure-related complications was similar for endovascular and microsurgical treatments (odds ratio [95% confidence interval], 1.0 [0.1-10.0], P = 0.98). Both groups had comparable overall outcome (mRS score > 2) at discharge and 1-year and 6-year follow-up (P = 0.48 and 0.73, respectively). CONCLUSIONS: Most SRA patients in the BRAT underwent surgical clipping, with a high rate of crossover from endovascular approaches. Endovascular treatment was equivalent to surgical clipping with regard to procedure-related complications and neurologic outcomes.

Treatment of octogenarians and nonagenarians with aneurysmal subarachnoid hemorrhage: a 17-year institutional analysis.

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.

Nationwide Trends in Carotid Endarterectomy and Carotid Artery Stenting in the Post-CREST Era.

Background and Purpose- The CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) demonstrated equivalent composite outcomes between carotid endarterectomy (CEA) and carotid artery stenting (CAS) for treating carotid stenosis. We investigated nationwide trends in these procedures and associated periprocedural stroke, myocardial infarction, death, cost, and readmission rates since CREST outcomes were published. Methods- We queried the Nationwide Readmissions Database to identify patients undergoing CEA and CAS for asymptomatic and symptomatic carotid stenosis from 2010 to 2015. Patients were matched based on demographics, comorbidities, and severity of illness. Results- In total, 378 354 CEA and 57 273 CAS patients were treated during this 6-year period. CEA volume decreased by an average of 2669 procedures annually (P=0.001) with stable CAS volume (P=0.225). After matching, CEA patients had a higher rate of periprocedural stroke than CAS patients, driven by increased stroke risk in symptomatic CEA patients (8.1% versus 5.6%; odds ratio, 1.47 [CI, 1.29-1.68]; P<0.001) but a lower rate of overall inpatient mortality (0.8% versus 1.4%; odds ratio, 0.57 [CI, 0.48-0.68]; P<0.001). CEA patients were less likely to be readmitted within 30 days (7.2% versus 8.0%; odds ratio, 0.90 [CI, 0.84-0.96]; P=0.018) and 90 days (12.3% versus 14.1%; odds ratio, 0.86 [CI, 0.81-0.90]; P<0.001), and mean hospital costs were lower for CEA compared with CAS ($14 433 versus $19 172; P<0.001). Conclusions- The procedural treatment of carotid stenosis has changed dramatically in the post-CREST era. When matched for characteristics and illness severity, patients undergoing CEA had a higher rate of perioperative stroke than patients undergoing CAS, primarily among symptomatic patients. These findings are in contrast to the findings of CREST, which showed nearly twice the risk of stroke in CAS patients compared with CEA patients. CEA was associated with lower procedure cost and readmission rate.

A patient with a novel homozygous missense mutation in FTO and concomitant nonsense mutation in CETP.

The fat mass and obesity associated (FTO) gene has previously been associated with a variety of diseases and conditions, notably obesity, acute coronary syndrome and metabolic syndrome. Reports describing mutations in FTO as well as in FTO animal models have further demonstrated a role for FTO in the development of the brain and other organs. Here, we describe a patient born of consanguineous union who presented with microcephaly, developmental delay, behavioral abnormalities, dysmorphic facial features, hypotonia and other various phenotypic abnormalities. Whole-exome sequencing revealed a novel homozygous missense mutation in FTO and a nonsense mutation in the cholesteryl ester transfer protein (CETP). Exome copy number variation analysis revealed no disease-causing large duplications or deletions within coding regions. Patient's, her parents' and non-related control' fibroblasts were analyzed for morphologic defects, abnormal proliferation, apoptosis and transcriptome profile. We have shown that FTO is located in the nucleus of cells from each tested sample. Western blot analysis demonstrated no changes in patient FTO. Quantitative (qPCR) analysis revealed slightly decreased levels of FTO expression in patient cells compared with controls. No morphological or proliferation differences between the patient and control fibroblasts were observed. There is still much to be learned about the molecular mechanisms by which mutations in FTO contribute to such severe phenotypes.

Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration.

Ubiquitin C-terminal hydrolase-L1 (UCHL1), a neuron-specific de-ubiquitinating enzyme, is one of the most abundant proteins in the brain. We describe three siblings from a consanguineous union with a previously unreported early-onset progressive neurodegenerative syndrome featuring childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfuction, and spasticity with upper motor neuron dysfunction. Through homozygosity mapping of the affected individuals followed by whole-exome sequencing of the index case, we identified a previously undescribed homozygous missense mutation within the ubiquitin binding domain of UCHL1 (UCHL1(GLU7ALA)), shared by all affected subjects. As demonstrated by isothermal titration calorimetry, purified UCHL1(GLU7ALA), compared with WT, exhibited at least sevenfold reduced affinity for ubiquitin. In vitro, the mutation led to a near complete loss of UCHL1 hydrolase activity. The GLU7ALA variant is predicted to interfere with the substrate binding by restricting the proper positioning of the substrate for tunneling underneath the cross-over loop spanning the catalytic cleft of UCHL1. This interference with substrate binding, combined with near complete loss of hydrolase activity, resulted in a >100-fold reduction in the efficiency of UCHL1(GLU7ALA) relative to WT. These findings demonstrate a broad requirement of UCHL1 in the maintenance of the nervous system.

Fenestrated Aneurysm Clip Trigeminal Decompression after CyberKnife Treatment Failure.

Objective This article describes a novel technique for trigeminal nerve decompression in the setting of refractory trigeminal neuralgia (TN). Design Technical note with an illustrative case example and operative video. Setting Outpatient, inpatient, and operating room of a quaternary neurosurgical referral center. Participant A woman in her early 70s who had previously undergone linear accelerator-based stereotactic radiotherapy (i.e., CyberKnife) and achieved 2 years of partial pain relief. However, facial pain, numbness, and parasympathetic dysfunction returned and became unbearable. Main Outcome Measure Durable relief of TN. Results Microvascular decompression was recommended for refractory TN. Intraoperatively, the trigeminal nerve was markedly attenuated from previous irradiation, with the superior cerebellar artery (SCA) loop embedded in the nerve at its root entry zone. The arterial loop was mobilized into a new position superior to the nerve, thus liberating it from the impingement. The tentorium was incised, and a fenestrated aneurysm clip was positioned such that the SCA loop was transmitted via the fenestration. The clip was applied across the tentorium, thus suspending the artery in a kink-free orientation that made no contact with the nerve. Conclusion This procedure provided excellent neurovascular decompression without placing mechanical strain on the nerve, relieving the patient's persistent postirradiation TN. The technique could have broader applications for other challenging or atypical microvascular decompression procedures.

Vitamin D deficiency promotes intracranial aneurysm rupture.

Intracranial aneurysm rupture causes severe disability and high mortality. Epidemiological studies show a strong association between decreased vitamin D levels and an increase in aneurysm rupture. However, the causality and mechanism remain largely unknown. In this study, we tested whether vitamin D deficiency promotes aneurysm rupture and examined the underlying mechanism for the protective role of vitamin D against the development of aneurysm rupture utilizing a mouse model of intracranial aneurysm. Mice consuming a vitamin D-deficient diet had a higher rupture rate than mice with a regular diet. Vitamin D deficiency increased proinflammatory cytokines in the cerebral arteries. Concurrently, vitamin D receptor knockout mice had a higher rupture rate than the corresponding wild-type littermates. The vitamin D receptors on endothelial and vascular smooth muscle cells, but not on hematopoietic cells, mediated the effect of aneurysm rupture. Our results establish that vitamin D protects against the development of aneurysmal rupture through the vitamin D receptors on vascular endothelial and smooth muscle cells. Vitamin D supplementation may be a viable pharmacologic therapy for preventing aneurysm rupture.

Microsurgical Resection of Brainstem Cavernous Malformations in Older Adults: A Multicenter, 30-Year Experience.

BACKGROUND AND OBJECTIVES: Microsurgical resection is the only curative intervention for symptomatic brainstem cavernous malformations (BSCMs), but the management of these lesions in older adults (≥65 years) is not well described. This study sought to address this gap by examining the safety and efficacy of BSCM resection in a cohort of older adults. METHODS: Records of patients who underwent BSCM resection over a 30-year period were reviewed retrospectively. Baseline characteristics and outcomes were compared between older (≥65 years) and younger (<65 years) patients. RESULTS: Of 550 patients with BSCM who met inclusion criteria, 41 (7.5%) were older than 65 years. Midbrain (43.9% vs 26.1%) and medullary lesions (19.5% vs 13.6%) were more common in the older cohort than in the younger cohort ( P = .01). Components of the Lawton BSCM grading system (ie, lesion size, crossing axial midpoint, developmental venous anomaly, and timing of hemorrhage) were not significantly different between cohorts ( P ≥ .11). Mean (SD) Elixhauser comorbidity score was significantly higher in older patients (1.86 [1.06]) than in younger patients (0.66 [0.95]; P < .001). Older patients were significantly more likely than younger patients to have poor outcomes at final follow-up (28.9% vs 13.8%, P = .01; mean follow-up duration, 28.7 [39.1] months). However, regarding relative neurological outcome (preoperative modified Rankin Scale to final modified Rankin Scale), rate of worsening was not significantly different between older and younger patients (23.7% vs 14.9%, P = .15). CONCLUSION: BSCMs can be safely resected in older patients, and when each patient's unique health status and life expectancy are taken into account, these patients can have outcomes similar to younger patients.

A Review of Preoperative Embolization Effectiveness in Patients With Arteriovenous Malformations.

BACKGROUND AND OBJECTIVES: Preoperative embolization of arteriovenous malformations (AVMs) remains controversial. This study sought to analyze the cost-effectiveness of preoperative embolization of AVMs. METHODS: Patients who underwent AVM resection at a single institute (January 1, 2015-December 31, 2020) were analyzed. Patients with preoperative embolization (embolization cohort) were compared with those without preoperative embolization (nonembolization cohort). Cost-effectiveness score (CE) was the primary outcome of interest and was determined by dividing the total 1-year cost by effectiveness, which was derived from a validated preoperative to last follow-up change in the modified Rankin Scale utility score. A lower CE signifies a more cost-effective treatment strategy. RESULTS: Of 188 patients, 88 (47%) underwent preoperative embolization. The mean (SD) total cost was higher in the embolization group than in the nonembolization group ($117 594 [$102 295] vs $84 348 [$82 326]; P < .001). The mean (SD) CE was higher in the embolization cohort ($336 476 [$1 303 842]) than in the nonembolization cohort ($100 237 [$246 255]; P < .001). Among patients with Spetzler-Martin (SM) grade I and II AVMs, the mean (SD) CE was higher in the embolization (n = 40) than in the nonembolization (n = 72) cohort ($164 950 [$348 286] vs $69 021 [$114 938]; P = .004). Among patients with SM grade III AVMs, the mean (SD) CE was lower in the embolization (n = 33) than in the nonembolization (n = 25) cohort ($151 577 [$219 130] vs $189 195 [$446 335]; P = .006). The mean (SD) CE was not significantly different between cohorts among patients with higher-grade AVMs (embolization cohort [n = 3] vs nonembolization cohort [n = 15]: $503 639 [$776 492] vs $2 048 419 [$4 794 758]; P = .49). The mean CE for embolized SM grade III aneurysms was nonsignificant in the ruptured group; however, for the unruptured group, CE was significantly higher in the embolization cohort (n = 26; $160 871 [$240 535]) relative to the nonembolization cohort (n = 15; $108 152 [$166 446]) ( P = .006). CONCLUSION: Preoperative embolization was cost-effective for patients with SM grade III AVMs but not for patients with lower-grade AVMs.

Early Treatment of Ruptured Cerebral Arteriovenous Malformations: Analysis of Neurological Outcomes and Health Care Costs.

BACKGROUND: The timing of surgical resection is controversial when managing ruptured arteriovenous malformations (AVMs) and varies considerably among centers. OBJECTIVE: To retrospectively analyze clinical outcomes and hospital costs associated with delayed treatment in a ruptured cerebral AVM patient cohort. METHODS: Patients undergoing surgical treatment for a ruptured cerebral AVM (January 1, 2015-December 31, 2020) were retrospectively analyzed. Patients who underwent emergent treatment of a ruptured AVM because of acute herniation were excluded, as were those treated >180 days after rupture. Patients were stratified by the timing of surgical intervention relative to AVM rupture into early (postbleed days 1-20) and delayed (postbleed days 21-180) treatment cohorts. RESULTS: Eighty-seven patients were identified. The early treatment cohort comprised 75 (86%) patients. The mean (SD) length of time between AVM rupture and surgical resection was 5 (5) days in the early cohort and 73 (60) days in the delayed cohort ( P < .001). The cohorts did not differ with respect to patient demographics, AVM size, Spetzler-Martin grade, frequency of preoperative embolization, or severity of clinical presentation ( P ≥ .15). Follow-up neurological status was equivalent between the cohorts ( P = .65). The associated mean health care costs were higher in the delayed treatment cohort ($241 597 [$99 363]) than in the early treatment cohort ($133 989 [$110 947]) ( P = .02). After adjustment for length of stay, each day of delayed treatment increased cost by a mean of $2465 (95% CI = $967-$3964, P = .002). CONCLUSION: Early treatment of ruptured AVMs was associated with significantly lower health care costs than delayed treatment, but surgical and neurological outcomes were equivalent.

Modafinil Therapy and Mental Status Following Aneurysmal Subarachnoid Hemorrhage: Comprehensive Stroke Center Analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Rapid ventricular overdrive pacing and other advanced flow-control techniques for the endovascular embolization of vein of galen malformations.

Endovascular embolization is the primary strategy in the management for vein of Galen malformations (VOGM). However, despite significant advances in endovascular embolization technologies and techniques, VOGMs remain very technically challenging lesions largely due to the high-flow arteriovenous shunts present in these malformations. A variety of advanced flow-control techniques can be implemented to mitigate the risk of venous escape and increase the safety and efficacy of endovascular treatment. These techniques include regionally targeted strategies (transvenous embolization and balloon-assisted transarterial embolization) and global flow-control methods (pharmacologic cardiac arrest and rapid ventricular overdrive pacing). Each of these strategies are associated with unique advantages and disadvantages, highlighting the importance of a patient-specific approach when treating these challenging lesions.

Thrombotic, Dolichoectatic, Distal Posterior Cerebral Artery Aneurysm Treated with Excision and P2-P2 Reanastomosis.

Posterior cerebral artery aneurysms are rare and often optimally treated with clip reconstruction.1-3 Complex cases may require aneurysm excision with in situ reanastomosis.4-6 A woman in her early 40s presented with 2 weeks of severe headache and received a diagnosis of a thrombotic, dolichoectatic, distal right P2 aneurysm. Clip reconstruction was recommended. After providing consent, the patient underwent a right subtemporal approach. The P2 aneurysm was encountered in the ambient cistern. The aneurysm and its inflow and outflow arteries were isolated, and bleeding was controlled with temporary clips. Primary clip reconstruction was aborted due to a neck configuration that precluded preservation of the outflow vessels during primary clip reconstruction. The decision was made to excise the aneurysm and perform a P2-P2 end-to-end reanastomosis.7 After completion of the initial bypass, indocyanine green videoangiography indicated bypass thrombosis, which was thought to be attributable to poor tissue quality from inadequate vessel trimming at the anastomosis site. We elected to excise the bypass, trim both P2 ends back to healthy tissue, and perform a repeat end-to-end P2-P2 reanastomosis, which ultimately resulted in successful revascularization with indocyanine green confirmation. Postoperative angiography confirmed complete obliteration of the aneurysm with stable graft patency, and the patient remained intact at her neurologic baseline through last follow-up at 6 weeks after discharge from the hospital. Video 1 demonstrates microsurgical nuances for deep end-to-end reanastomosis, as well as intraoperative troubleshooting in the setting of a complex ruptured posterior circulation aneurysm.

Resection of Quadrigeminal Midbrain Cavernous Malformation Using the Supracollicular Safe Entry Zone.

Brainstem cavernous malformations (BSCMs) are rare and challenging neurosurgical lesions that demand a sophisticated and nuanced strategy for resection. A key element of surgical planning for BSCM resection is brainstem safe entry zones, a set of neuroanatomically defined locations where a pial resection can be executed with minimal risk to the adjacent central nervous system tracts and nuclei.1-5 Quadrigeminal BSCMs are particularly unusual and can be accessed via the supra-, inter-, or infracollicular safe entry zones.2,4,5 We report a unique demonstration of the supracollicular safe entry zone for the resection of a symptomatic hemorrhagic quadrigeminal plate BSCM. A man in his early 60s presented with transient hearing loss and visual dysfunction. A right quadrigeminal midbrain cavernous malformation was identified on magnetic resonance imaging. Surgical resection was performed with the patient in the sitting position. A bipedicular suboccipital flap, torcular craniotomy, and midline supracerebellar infratentorial approach were used. The lesion itself was accessed via the supracollicular safe entry zone, where pial hemosiderin staining was also encountered, using a linear transverse incision just above the right superior colliculus. Gross total resection was achieved, and the patient recovered from surgery with no new neurologic deficits (Video 1).