Baseline Characteristics of Patients With Cavernous Angiomas With Symptomatic Hemorrhage in Multisite Trial Readiness Project.

BACKGROUND AND PURPOSE: Brain cavernous angiomas with symptomatic hemorrhage (CASH) have a high risk of neurological disability from recurrent bleeding. Systematic assessment of baseline features and multisite validation of novel magnetic resonance imaging biomarkers are needed to optimize clinical trial design aimed at novel pharmacotherapies in CASH. METHODS: This prospective, multicenter, observational cohort study included adults with unresected, adjudicated brain CASH within the prior year. Six US sites screened and enrolled patients starting August 2018. Baseline demographics, clinical and imaging features, functional status (modified Rankin Scale and National Institutes of Health Stroke Scale), and patient quality of life outcomes (Patient-Reported Outcomes Measurement Information System-29 and EuroQol-5D) were summarized using descriptive statistics. Patient-Reported Outcomes Measurement Information System-29 scores were standardized against a reference population (mean 50, SD 10), and one-sample t test was performed for each domain. A subgroup underwent harmonized magnetic resonance imaging assessment of lesional iron content with quantitative susceptibility mapping and vascular permeability with dynamic contrast-enhanced quantitative perfusion. RESULTS: As of May 2020, 849 patients were screened and 110 CASH cases enrolled (13% prevalence of trial eligible cases). The average age at consent was 46±16 years, 53% were female, 41% were familial, and 43% were brainstem lesions. At enrollment, ≥90% of the cohort had independent functional outcome (modified Rankin Scale score ≤2 and National Institutes of Health Stroke Scale score <5). However, perceived health problems affecting quality of life were reported in >30% of patients (EuroQol-5D). Patients had significantly worse Patient-Reported Outcomes Measurement Information System-29 scores for anxiety (P=0.007), but better depression (P=0.002) and social satisfaction scores (P=0.012) compared with the general reference population. Mean baseline quantitative susceptibility mapping and permeability of CASH lesion were 0.45±0.17 ppm and 0.39±0.31 mL/100 g per minute, respectively, which were similar to historical CASH cases and consistent across sites. CONCLUSIONS: These baseline features will aid investigators in patient stratification and determining the most appropriate outcome measures for clinical trials of emerging pharmacotherapies in CASH.

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.

Association of Angiotensin-Converting Enzyme Inhibitors with Increased Mortality Among Patients with Isolated Severe Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is associated with one-third of all deaths from trauma. Preinjury exposure to cardiovascular drugs may affect TBI outcomes. Angiotensin-converting enzyme inhibitors (ACEIs) exacerbate brain cell damage and worsen functional outcomes in the laboratory setting. ß-blockers (BBs), however, appear to be associated with reduced mortality among patients with isolated TBI. OBJECTIVE: Examine the association between preinjury ACEI and BB use and clinical outcome among patients with isolated TBI. METHODS: A retrospective cohort study of patients age ≥ 40 years admitted to an academic level 1 trauma center with isolated TBI between January 2010 and December 2014 was performed. Isolated TBI was defined as a head Abbreviated Injury Scale (AIS) score ≥ 3, with chest, abdomen, and extremity AIS scores ≤ 2. Preinjury medication use was determined through chart review. All patients with concurrent BB use were initially excluded. In-hospital mortality was the primary measured outcome. RESULTS: Over the 5-year study period, 600 patients were identified with isolated TBI who were naive to BB use. There was significantly higher mortality (P = .04) among patients who received ACEI before injury (10 of 96; 10%) than among those who did not (25 of 504; 5%). A multivariate stepwise logistic regression analysis revealed a threefold increased risk of mortality in the ACEI cohort (P < .001), which was even greater than the twofold increased risk of mortality associated with an Injury Severity Score ≥ 16. A second analysis that included patients who received preinjury BBs (n = 98) demonstrated slightly reduced mortality in the ACEI cohort with only a twofold increased risk in multivariate analysis (P = .05). CONCLUSIONS: Preinjury exposure to ACEIs is associated with an increase in mortality among patients with isolated TBI. This effect is ameliorated in patients who receive BBs, which provides evidence that this class of medications may provide a protective benefit.

Developmental venous anomaly, capillary telangiectasia, cavernous malformation, and arteriovenous malformation: spectrum of a common pathological entity?

Vascular malformations of the central nervous system are thought to originate from abnormal developmental processes during embryogenesis. Reports have cited the dynamic nature of these lesions and their "maturation" into other types of malformations. Herein we report on three patients with vascular malformations who exhibited dynamic alterations with stepwise progression of their lesions. These cases lend support to the hypothesis that these malformations may constitute the spectrum of a single disease caused by alterations in a common developmental program and that accumulating injury (e.g., by radiation) may allow one malformation type to mature into another. This concept warrants further investigation.

The Insertion and Management of External Ventricular Drains: An Evidence-Based Consensus Statement : A Statement for Healthcare Professionals from the Neurocritical Care Society.

External ventricular drains (EVDs) are commonly placed to monitor intracranial pressure and manage acute hydrocephalus in patients with a variety of intracranial pathologies. The indications for EVD insertion and their efficacy in the management of these various conditions have been previously addressed in guidelines published by the Brain Trauma Foundation, American Heart Association and combined committees of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. While it is well recognized that placement of an EVD may be a lifesaving intervention, the benefits can be offset by procedural and catheter-related complications, such as hemorrhage along the catheter tract, catheter malposition, and CSF infection. Despite their widespread use, there are a lack of high-quality data regarding the best methods for placement and management of EVDs to minimize these risks. Existing recommendations are frequently based on observational data from a single center and may be biased to the authors' view. To address the need for a comprehensive set of evidence-based guidelines for EVD management, the Neurocritical Care Society organized a committee of experts in the fields of neurosurgery, neurology, neuroinfectious disease, critical care, pharmacotherapy, and nursing. The Committee generated clinical questions relevant to EVD placement and management. They developed recommendations based on a thorough literature review using the Grading of Recommendations Assessment, Development, and Evaluation system, with emphasis placed not only on the quality of the evidence, but also on the balance of benefits versus risks, patient values and preferences, and resource considerations.

Surgical clipping of a ruptured posterior inferior cerebellar artery aneurysm.

Posterior circulation aneurysms are commonly treated with endovascular techniques. In select cases, microsurgery remains an essential tool for treating these lesions. We present a case of a ruptured posterior inferior cerebellar artery (PICA) aneurysm approached via a craniotomy. Given the labyrinth of neurovascular bundles present in the posterior fossa, surgical exposure of PICA aneurysms can be challenging. This video demonstrates the steps of the craniotomy, subarachnoid dissection, mobilization of the vertebral artery and lower cranial nerves, and clipping of the aneurysm. The video can be found here: http://youtu.be/fQSxQj7oL0U .

Surgical clipping of a large left middle cerebral artery aneurysm.

Middle cerebral artery aneurysms, especially those with complex morphology, are considered excellent aneurysms for surgical clipping, given the challenges that exist with current endovascular techniques. We present a case of a large, complex, left middle cerebral artery aneurysm treated with microsurgical clipping. This video highlights critical steps in obtaining proximal and distal control as well as subarachnoid dissection necessary to prepare the aneurysm for final clipping. The video can be found here: http://youtu.be/RlKH2Km9z5Y .

Microsurgical clipping of an unruptured basilar apex aneurysm.

Unruptured posterior circulation aneurysms pose a treatment challenge. Although data supports the use of endovascular technique for select ruptured cases, in unruptured cases, there may be clinical equipoise. Furthermore, wide-necked basilar apex aneurysms commonly require the use of stents and placement of patients on dual therapy. We present a case of a healthy 50-year-old woman with an incidental basilar tip aneurysm treated via an orbitozygomatic craniotomy. This video highlights the steps of dynamic retraction, which is retraction without placement of permanent rigid retraction system, and the added maneuverability afforded by the use of the mouthpiece on the microscope. The video can be found here: http://youtu.be/jVfC6CCXdZY .

Repair of intraoperative aneurysm neck tear utilizing the cotton-clipping technique.

Intraoperative rupture of an intracranial aneurysm is a potentially devastating but controllable complication. The authors have successfully used the previously described cotton-clip technique to repair tears at the necks of aneurysms. (1-4) A tear on the neck of the aneurysm is covered with a piece of cotton and held in place with a suction device. The cotton is then clipped onto the tear with an aneurysm clip, using the cotton as a bolster. This simple, effective method has been useful in repairing a partial avulsion of the neck of an aneurysm. (1 , 3) The video can be found here: http://youtu.be/nT86RYVQWpc .

Intracranial Hemorrhage Rate and Lesion Burden in Patients With Familial Cerebral Cavernous Malformation.

Background Familial cerebral cavernous alformation (CCM) is an autosomal dominant disease caused by mutations in KRIT1, CCM2, or PDCD10. Cases typically present with multiple lesions, strong family history, and neurological symptoms, including seizures, headaches, or other deficits. Intracranial hemorrhage (ICH) is a severe manifestation of CCM, which can lead to death or long-term neurological deficits. Few studies have reported ICH rates and risk factors in familial CCM. We report ICH rates and assess whether CCM lesion burden, a disease severity marker, is associated with risk of symptomatic ICH during follow-up in a well-characterized cohort of familial CCM cases. Methods and Results We studied 386 patients with familial CCM with follow-up data enrolled in the Brain Vascular Malformation Consortium CCM Project. We estimated symptomatic ICH rates overall and stratified by history of ICH before enrollment. CCM lesion burden (total lesion count and large lesion size) assessed at baseline enrollment was tested for association with increased risk of subsequent ICH during follow-up using Cox regression models adjusted for history of ICH before enrollment, age, sex, and family structure and stratified on recruitment site. The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (P=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], P=0.006). The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (P=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], P=0.006). Conclusions Patients with familial CCM with prior history of an ICH event are at higher risk for rehemorrhage during follow-up. In addition, total CCM lesion burden is significantly associated with increased risk of subsequent symptomatic ICH; hence lesion burden may be an important predictor of patient outcome and aid patient risk stratification.

Safety and patterns of survivorship in recurrent GBM following resection and surgically targeted radiation therapy: Results from a prospective trial.

BACKGROUND: Treatment of recurrent glioblastoma (GBM) remains problematic with survival after additional therapy typically less than 12 months. We prospectively evaluated whether outcomes might be improved with resection plus permanent implantation of a novel radiation device utilizing the gamma-emitting isotope Cs-131 embedded within bioresorbable collagen tiles. METHODS: Recurrent histologic GBM were treated in a single-arm trial. Following radiation, the surgical bed was lined with the tiles. Subsequent treatments were at the treating physician's discretion. RESULTS: 28 patients were treated (20 at first recurrence, range 1-3). Median age was 58 years, KPS was 80, female:male ratio was 10:18. Methylguanine methyltransferase (MGMT) was methylated in 11%, unmethylated in 18%, and unknown in 71%. Post implant, 17 patients (61%) received ≥1 course of systemic therapy. For all patients, Kaplan-Meier estimates of median time to local failure were 12.1 months, post-implant survival was 10.7 months for all patients and 15.1 months for patients who received systemic therapy; for all patients, median overall survival from diagnosis was 25.0 months (range 9.1-143.1). Sex, age, and number of prior progressions were not statistically significant. Local control was continuously maintained in 46% of patients. Two deaths within 30 days occurred, one from intracranial hemorrhage and one after persistent coma. Three symptomatic adverse events occurred: one wound infection requiring surgery and two late radiation brain injury, resolved non-surgically. CONCLUSION: This pre-commercial trial demonstrated acceptable safety and favorable post-treatment local control and survival. The device has received FDA clearance for use in newly diagnosed malignant and all recurrent intracranial neoplasms.

Cost Comparison of Microsurgery vs Endovascular Treatment for Ruptured Intracranial Aneurysms: A Propensity-Adjusted Analysis.

BACKGROUND: In specialized neurosurgical centers, open microsurgery is routinely performed for aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE: To compare the cost of endovascular vs microsurgical treatment for aSAH at a single quaternary center. METHODS: All patients undergoing aSAH treatment from July 1, 2014, to July 31, 2019, were retrospectively reviewed. Patients were grouped based on primary treatment (microsurgery vs endovascular treatment). The primary outcome was the difference in total cost (including hospital, discharge facility, and all follow-up) using a propensity-adjusted analysis. RESULTS: Of 384 patients treated for an aSAH, 234 (61%) were microsurgically treated and 150 (39%) were endovascularly treated. The mean cost of index hospitalization for these patients was marginally higher ($9504) for endovascularly treated patients ($103 980) than for microsurgically treated patients ($94 476) ( P = .047). For the subset of patients with follow-up data available, the mean total cost was $45 040 higher for endovascularly treated patients ($159 406, n = 59) than that for microsurgically treated patients ($114 366, n = 105) ( P < .001). After propensity scoring (adjusted for age, sex, comorbidities, Glasgow Coma Scale score, Hunt and Hess grade, Fisher grade, aneurysms, and type/size/location), linear regression analysis of patients with follow-up data available revealed that microsurgery was independently associated with healthcare costs that were $37 244 less than endovascular treatment costs ( P < .001). An itemized cost analysis suggested that this discrepancy was due to differences in the rates of aneurysm retreatment and long-term surveillance. CONCLUSION: Microsurgical treatment for aSAH is associated with lower total healthcare costs than endovascular therapy. Aneurysm surveillance after endovascular treatments, retreatment, and device costs warrants attention in future studies.

The Times They Are a-Changin': Increasing Complexity of Aneurysmal Subarachnoid Hemorrhages in Patients Treated from 2004 to 2018.

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

Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis.

Cerebral cavernous malformations (CCMs) are vascular anomalies of the central nervous system, comprising dilated blood-filled capillaries lacking structural support. The lesions are prone to rupture, resulting in seizures or hemorrhagic stroke. CCM can occur sporadically, manifesting as solitary lesions, but also in families, where multiple lesions generally occur. Familial cases follow autosomal-dominant inheritance due to mutations in one of three genes, CCM1/KRIT1, CCM2/malcavernin or CCM3/PDCD10. The difference in lesion burden between familial and sporadic CCM, combined with limited molecular data, suggests that CCM pathogenesis may follow a two-hit molecular mechanism, similar to that seen for tumor suppressor genes. In this study, we investigate the two-hit hypothesis for CCM pathogenesis. Through repeated cycles of amplification, subcloning and sequencing of multiple clones per amplicon, we identify somatic mutations that are otherwise invisible by direct sequencing of the bulk amplicon. Biallelic germline and somatic mutations were identified in CCM lesions from all three forms of inherited CCMs. The somatic mutations are found only in a subset of the endothelial cells lining the cavernous vessels and not in interstitial lesion cells. These data suggest that CCM lesion genesis requires complete loss of function for one of the CCM genes. Although widely expressed in the different cell types of the brain, these data also suggest a unique role for the CCM proteins in endothelial cell biology.

Seizure Incidence Rates in Children and Adults With Familial Cerebral Cavernous Malformations.

BACKGROUND AND OBJECTIVES: Seizure incidence rates related to Familial Cerebral Cavernous Malformation (FCCM) are not well described, especially for children. To measure the seizure incidence rate, examine seizure predictors and characterize epilepsy severity, we studied a cohort of children and adults with FCCM enrolled in the Brain Vascular Malformation Consortium (BVMC). METHODS: Seizure data were collected from participants with FCCM in the BVMC at enrollment and during follow-up. We estimated seizure probability by age, and tested whether cerebral cavernous malformation (CCM) counts or genotype were associated with earlier seizure onset. RESULTS: The study cohort included 479 FCCM cases. Median age at enrollment was 42.5 years (Interquartile Range [IQR] 22.5-55.0) and 19% were children (<18 years old). Median large CCM count was 3 (IQR: 1-5). Among 393 with genotyping, mutations were: CCM1-Common Hispanic Mutations (88%), another CCM1 mutation (5%), CCM2 mutations (5%), and CCM3 mutations (2%). Prior to or during the study, 202 (42%) had a seizure. The cumulative incidence of a childhood seizure was 20.3% (95% CI 17.0 - 23.4) and by age 80 years was 60.4% (95% CI 54.2-65.7). More total CCMs (Hazard Ratio [HR] 1.24 per SD unit increase, 95% CI 1.1 - 1.4) or more large CCMs (HR=1.5 per SD unit increase, 95% CI 1.2-1.9) than expected for age and sex increased seizure risk. A CCM3 mutation also increased risk compared to other mutations (HR 3.11, 95% CI 1.15-8.45). Individuals with a seizure prior to enrollment had increased hospitalization rates during follow-up (Incidence Rate Ratio 10.9, 95% CI 2.41 - 49.32) compared to patients without a seizure history. DISCUSSION: Individuals with FCCM have a high seizure incidence, and those with more CCMs or CCM3 genotype are at greater risk. Seizures increase health care utilization in FCCM.

Decompressive Craniectomy and Risk of Wound Infection After Microsurgical Treatment of Ruptured Aneurysms.

BACKGROUND: Owing to prolonged hospitalization and the complexity of care required for patients with aneurysmal subarachnoid hemorrhage (aSAH), these patients have a high risk of complications. The risk for wound infection after microsurgical treatment for aSAH was analyzed. METHODS: All patients who underwent microsurgical treatment for aSAH between August 1, 2007, and July 31, 2019, and were recorded in the Post-Barrow Ruptured Aneurysm Trial database were retrospectively reviewed. The patients were analyzed for risk factors for wound infection after treatment. RESULTS: Of 594 patients who underwent microsurgical treatment for aSAH, 23 (3.9%) had wound infections. There was no significant difference in age between patients with wound infection and patients without infection (mean, 52.6 ± 12.2 years vs. 54.2 ± 4.0 years; P = 0.45). The presence of multiple comorbidities (including diabetes, tobacco use, and obesity), external ventricular drain, ventriculoperitoneal shunt, pneumonia, or urinary tract infection was not associated with an increased risk for wound infection. Furthermore, there was no significant difference in mean operative time between patients with wound infection and those without infection (280 ± 112 minutes vs. 260 ± 92 minutes; P = 0.38). Patients who required decompressive craniectomy (DC) were at increased risk of wound infection (odds ratio, 5.0; 95% confidence interval, 1.8-14.1; P = 0.002). Among the 23 total infections, 9 were diagnosed following cranioplasty after DC. CONCLUSIONS: Microsurgical treatment for aSAH is associated with a relatively low risk of wound infection. However, patients undergoing DC may be at an increased risk for infection. Additional attention and comprehensive wound care are warranted for these patients.

Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation.

BACKGROUND: To investigate whether common variants in EPHB4 and RASA1 are associated with cerebral cavernous malformation (CCM) disease severity phenotypes, including intracranial hemorrhage (ICH), total and large lesion counts. METHODS: Familial CCM cases enrolled in the Brain Vascular Malformation Consortium were included (n = 338). Total lesions and large lesions (≥5 mm) were counted on MRI; clinical history of ICH at enrollment was assessed by medical records. Samples were genotyped on the Affymetrix Axiom Genome-Wide LAT1 Human Array. We tested the association of seven common variants (three in EPHB4 and four in RASA1) using multivariable logistic regression for ICH (odds ratio, OR) and multivariable linear regression for total and large lesion counts (proportional increase, PI), adjusting for age, sex, and three principal components. Significance was based on Bonferroni adjustment for multiple comparisons (0.05/7 variants = 0.007). RESULTS: EPHB4 variants were not significantly associated with CCM severity phenotypes. One RASA1 intronic variant (rs72783711 A>C) was significantly associated with ICH (OR = 1.82, 95% CI = 1.21-2.37, p = 0.004) and nominally associated with large lesion count (PI = 1.17, 95% CI = 1.03-1.32, p = 0.02). CONCLUSION: A common RASA1 variant may be associated with ICH and large lesion count in familial CCM. EPHB4 variants were not associated with any of the three CCM severity phenotypes.

Nancy Davis Reagan, First Lady with a Neurosurgical Legacy.

Various well-known people associated with the history of the presidency of the United States have experienced neurologic disease or injury, especially trauma to the head or spine. Nancy Reagan, however, as the wife of President Ronald Reagan and First Lady, would leave a significant and lasting mark on the progress of neurosurgical science and education. Recognized for endeavors against drug abuse, Alzheimer disease, and polio, her interest in neurosurgical research is less well known. Nancy's father Loyal Davis was a remarkable neurosurgeon and educator of extraordinary influence. When Barrow Neurological Institute (BNI) founder John Green experienced complications after an illness, Davis served as BNI director during 1966 - 1967. After Davis's death in 1982, Robert Spetzler, who had been a student of Davis at Northwestern University Medical School and was then BNI director, convinced Green, despite his misgivings, to support a neurosurgical laboratory recognizing Davis. In 1988, Nancy Reagan, then First Lady, dedicated the Loyal and Edith Davis Neurosurgical Research Laboratory. At the dedication, she remarked on her years growing up in the home of a pioneering neurosurgeon and remarked that "my father believed deeply in the importance of research to develop new methods for treating patients." Green and Spetzler's unified efforts honored the extraordinary career of Davis in a manner he would have appreciated, were supported by a First Lady with deep involvement in politics and philanthropy dedicated to promoting advances in medicine, and are part of neurosurgery's unique heritage.