Piepgras, David G.

Introduction: The long term effectiveness of preventive intracranial treatment of unruptured aneurysms for hemorrhage and aneurysm-related morbidity and mortality has been hypothesized. No randomized trial has been done. Propensity adjusted comparison within The International Study of Unruptured Intracranial Aneurysms was undertaken to compare long-term effectiveness. Hypothesis: The purpose of this analysis was to compare the long-term outcome in the treatment cohorts (surgery and endovascular) with those of the untreated subgroup. Methods: Patients were subdivided into the initial treatment and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort, 471 were in the endovascular cohort and 1917 patients were in the surgical cohort. The cohorts were followed for a median follow-up of 9.2 years. Outcomes were determined prospectively and with central review. The data were grouped together and analyzed to determine treatment decisions. Comparison of outcomes was done using covariate adjustment and using propensity analysis where equivalent probability groups were constructed. Similar main predictors of treatment and outcome were observed. Analysis of hemorrhage, mortality and short-term and long-term morbidity and mortality were assessed. Risk-benefit ratios were also calculated. Results: Significant differences in baseline variables between treatment and observed patients were aneurysm size, symptoms, age, prior SAH or not group, geographical region, family history, hypertension and myocardial infarction history. The results show comparability of groups using the patient propensity-based score subset. Using the propensity score method, the results showed a benefit in prevention of hemorrhage by surgery and endovascular treatment versus observation (p<.01). No difference was found between endovascular versus surgery. However when procedure-related outcomes are included, no significant difference at 1 year, 5 years or 10 years in the combined aneurysm or procedure related endpoint was evident between cohorts. Conclusions: Propensity score matching to achieve comparability resulted in balanced groups. Comparison of long-term results showed that intervention demonstrated a benefit in reducing hemorrhage risk. However, peri-procedural risk negates any short-term benefit for 10 years.

Introduction: Mortality in patients with unruptured intracranial aneurysm (UIA) is significantly higher than the general population. However a minority of the deaths are due to subarachnoid hemorrhage. Hypothesis: There are differential characteristics of patients that might predict specific causes of death that would be informative in counseling patients about aneurysm risk. Methods: 4059 patients with UIA who were enrolled prospectively between 1991 and 1998 were followed by 61 medical centers in North America, Canada, and Europe. Patients have at least one UIA, which may or may not be symptomatic. Patients were Rankin grade 1 or 2 at enrollment. Patients were followed annually from enrollment to 2007. For patients who died a death certificate search was done and information was requested from local physicians and other contacts. A National Death Index search in 2008 determined cases who died and cause of death. Foreign centers also did a national search where possible. Patients who died before 30 days post treatment or lost to follow up before 30 days post enrollment were excluded. Results: Twenty-five percent of patients died during follow-up. The life expectancy was significantly less than age-, sex-, and country-matched expected estimates. Among the total of 4004 patients with UIA who survived 30 days after enrollment, 2331 were treated and 1673 were not. There were 965 deaths after 30 days after treatment, of which 320 died from vascular disease (252 died from non-SAH vascular disease), 114 died from respiratory tract disease, 255 died from cancer, and the rest died of other or unknown reasons. Predictors of SAH death were aneurysm size, site, age and convulsive disorders at enrollment. Factors related to vascular death were UIA treatment, age, gender, race, hypertension, Rankin at discharge and diminishing influence of aneurysm characteristics over time. Respiratory deaths were related to treatment, race, smoking, age, initial Rankin and presentation with convulsive disorder. Cancer deaths were related to gender, race, smoking and age. Conclusions: In patients with UIA, an assessment of risk for death underscores the importance of age, race and gender and several modifiable risk factors. Patient management should include not only aneurysm rupture prevention but also modification of smoking and hypertension.

Introduction: Quality of life changes can occur following procedural interventions and subarachnoid hemorrhage in unruptured intracranial aneurysms (UIA). The International Study of Unruptured Intracranial Aneurysms conducted quality of life assessment using the Mini-Mental State Exam, Rankin Score, and Barthel Index at baseline and the Telephone Interview Cognitive Status Exam (TICS), Rankin Score, and Barthel Index at follow-up. Hypothesis: The purpose of this analysis was to compare the 1 year and 5 year outcome in the treatment cohorts (surgery and endovascular) with those of the untreated subgroup. Methods: Patients were subdivided into the initial treated and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort and 2388 in the treated cohort. The cohorts were followed annually with measures of neurological status, Rankin Scale, Barthel Index and cognition (TICS). Outcomes were determined prospectively. Comparison of outcomes was done using continuous and categorical data. Covariate adjustment was done using general linear models. Stratified analysis was done by Rankin Score at the time of follow-up. Results: The percent of patients with a Barthel Index score of less than 60 at 1 year in the cohort was 9.4% (treated patients, 9.7%; untreated patients, 9.2%). The percent of patients at year 1 with a score of greater than 90 was 87.6%, 87.4% for treated patients and 87.8% for untreated patients. The percent of patients with a Barthel Index score of less than 60 at 5 years in the cohort was 41.4% (treated patients, 41.4%; untreated patients, 41.4%). The percent of patients at year 5 with a score of greater than 90 was 56.3%, 56.1% for treated patients and 56.5% for untreated patients. TICS and Barthel Index scores were significantly associated with each other for patients with Rankin Scores 0-2 (P<0.0001). This was seen at both year 1 and year 5 follow-up, but not for patients with Rankin Score 3-5. At both 1 year and 5 year follow-up, after controlling for Rankin Score, the distribution of Barthel Index scores of untreated patients and treated patients did not significantly differ. At both the 1 year follow-up, baseline Rankin Score, TICS and follow-up Rankin Score were significant predictors of Barthel Score (P<0.0001). At 5 years, only the follow-up Rankin Score was associated with Barthel Score (P<0.0001). Conclusions: Barthel Index Score decreased over time, but does not differ with treatment. The Rankin Score was the main predictor at follow-up of Barthel Index Score distribution.

INTRODUCTION: The decision regarding whether to perform an interventional procedure as a strategy to prevent hemorrhage of an unruptured intracranial aneurysm (UIA) requires careful consideration of procedural risk and the UIA natural history. No randomized trial data are available. The International Study of Unruptured Intracranial Aneurysms (ISUIA) included a prospective cohort, examining hemorrhage risk and treatment risk. Hypothesis: The purpose of this analysis was to compare the factors related to treatment selection and determination of the number of hemorrhages prevented. Methods: Patients were allocated into the initial treatment and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort, 471 were in the endovascular cohort and 1917 patients were in the surgical cohort. The cohorts were followed for a median follow-up of 9.2 years. Outcomes were determined prospectively and with central review. The data were grouped together and analyzed to determine treatment decisions. A Cox proportional hazards model predicting hemorrhage developed in the observation cohort and was applied to the surgery and endovascular cohorts across the follow-up period. Results: Significant baseline variable differences between treated and observed patients were aneurysm size, symptoms, age, prior SAH group, geographical region, treatment percentage, aneurysm daughter sacs or multiple lobes, and history of hypertension, smoking and myocardial infarction. Aneurysm site and family history were not significant. Site, size, and aspirin use were significant predictors of hemorrhage. Long-term the predicted hemorrhage rates were 6.7% at 5 years and 8.0% at 10 years in the surgery group and 8.1% and 9.6% for the endovascular group, respectively. For comparison the rates in the observed cohort were 4.1% and 4.8%, respectively. Conclusions: Decisions for treatment are influenced by patient characteristics such as age and medical history, aneurysm characteristics such as size and morphology and center and regional practices. Patients in the treated cohorts were at moderately increased risk for hemorrhage compared to those in the observed cohort.

INTRODUCTION: Cognitive changes can occur following procedural interventions and subarachnoid hemorrhage in unruptured intracranial aneurysms (UIA). The International Study of Unruptured Intracranial Aneurysms conducted cognitive assessment using the Mini-Mental State Exam at baseline and the Telephone Interview Cognitive Status Exam (TICS) at follow-up. Hypothesis: The purpose of this analysis was to compare the 1 year and 5 year outcome in the treatment cohorts (surgery and endovascular) with those of the untreated subgroup. Methods: Patients were subdivided into the initial treatment and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort and 2388 in the treated cohort. The cohorts were followed annually with measures of neurological status, Rankin Scale and cognition (TICS). Outcomes were determined prospectively. Comparison of outcomes was done using continuous data and by categories. Covariate adjustment was done using general linear models. Stratified analysis was done by Rankin Score at the time of follow-up. Results: The mean TICS score at 1 year in the cohort was 33.4 with a median of 34 (maximum is 40). In the treated patients the mean was 33.5 and in the untreated patients it was 33.3 (P=0.644). However, Rankin Score at 1 year was significant with a higher percentage of 3-5 scores in the treated group (P=0.003) Categorical analysis of the TICS Score when stratified by Rankin Score at 1 year showed small but significant differences, P=0.03 for Rankin 0-2, and P=0.07 for Rankin 3-5. However after adjustment for baseline variables treatment TICS Score was no longer significant.. The 5 year results showed that the untreated patients did worse than the treated group in TICS. However after adjustment no differences were apparent. Conclusions: Cognitive changes associated with treatment may be minor source of disability post-treatment compared to observation and patient outcomes may be worse in the observation group over time. Differences in outcome also were better explained through the Rankin Score at follow-up than by cognitive deficits.

Introduction: There is ongoing debate regarding the rupture risk of an unruptured intracranial aneurysm (UIA), and the predictors of rupture. Hypothesis: There are aneurysm morphology characteristics which predict rupture in patients with an UIA. The purpose of this analysis was to assess for such characteristics utilizing the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort. Methods: Patients were entered prospectively at 61 centers. Patients must have had at least one UIA, which may or may not have been symptomatic. Patients were followed for a median of 9 years and all potential hemorrhages were carefully adjudicated. A case-control design was used. The cases were 57 patients with aneurysmal rupture during followup for whom detailed radiology data were available from arteriography. Controls were 198 size- (+/- 2 mm maximum diameter) and location- (parent artery) matched patients without rupture during followup. Numerous aneurysm morphology characteristics were assessed on arteriogram review. Multivariable condition logistic regression modeling was performed. Results: A total of 57 cases and 198 controls were included. Most (76%) of the 255 cases were women, and 20% had a prior history of SAH from some other aneurysm. There were no differences between cases and controls in aneurysm maximum diameter, aneurysm location, patient age, gender, reason for presentation, or prior medical history. Multivariate analysis identified that only perpendicular height of the aneurysm--the measurement of the aneurysm height at a perpendicular to the center of the aneurysm neck to the aneurysm dome-was an independent predictor of aneurysm rupture. Aspect ratio, size ratio, parent vessel diameter, presence of daughter sac, and aneurysm angle were not independent predictors of rupture. Conclusions: After controlling for aneurysm size and location, the aneurysm perpendicular height remained a predictor of UIA rupture during long-term followup. The assessment of perpendicular height may be helpful in clinical practice, in addition to the other key predictors of UIA rupture, aneurysm maximum diameter and location. Further investigation into the use of perpendicular height as a predictor of rupture in patients with UIA is indicated.

Introduction: Giant intracranial aneurysms are uncommon, have a high risk for rupture and are difficult to treat. The International Study of Unruptured Intracranial Aneurysms (ISUIA) prospective cohort included 187 patients with maximal diameter of 25 mm or greater. This analysis was to determine the long-term prognosis of these aneurysms both treated and untreated. Methods: Patients were enrolled into ISUIA at 61 centers from 1991-1998. A prospective cohort included the managed with observation, surgery or endovascular treatment. Patients were followed for a median of 9.2 years. Aneurysms were measured using a central reading of bi-planar cerebral angiography. Outcomes were determined prospectively and with central review. Results: 187 patients with a maximum diameter of 25 mm were followed. The mean size was 30.3 mm, ranging from 25 to 63 mm. 39% of the aneurysms were surgically treated at baseline, 27% were endovascularly treated, and 32% were managed conservatively;3% had subsequent endovascular treatment and 5% surgical treatment. Patients with giant aneurysms were predominantly women (83%), had a baseline Rankin Score of in 93%, were located predominantly in the anterior circulation (internal carotid 44%, cavernous ICA 28%, middle cerebral 12%). 80% of the patients were symptomatic with cranial nerve deficit in 47% (III and VI nerves), mass effect in 16%, headaches in 44%, orbital pain in 21%, and vision loss in 25%. Smoking history was present in 67%, hypertension in 44%, vascular headaches in 29% and family history in 10%. 70 patients (39%) died during follow-up however 59% were still Rankin 1 or 2. Both surgical and endovascular treated patients had 60-64% good outcome and 34-36% mortality. Untreated patients had a 57% mortality. Subarachnoid hemorrhage occurred in 11 untreated patients and 12 treated patients with most occurring in the first year. Conclusions: Giant intracranial aneurysms are typically symptomatic, and have a high risk of rupture early after diagnosis. Outcome was similar with surgical and endovascular treatment but post-procedure hemorrhage did occur.

Abstract BACKGROUND AND IMPORTANCE Progressive episodic spells of altered levels of consciousness, often advancing to include paroxysmal autonomic instability, may be indicative of a diencephalic dysfunction underlying spontaneous intracranial hypotension (SIH). A rare, and often indolent, etiology may be spinal cerebrospinal fluid (CSF) leak—an elusive diagnosis, especially in cases of CSF-venous fistula (CVF) that are often missed on routine computed tomography (CT) myelography and magnetic resonance imaging (MRI). CLINICAL PRESENTATION We report an unusual case of a 50-yr-old woman who presented with rapidly progressive cyclical, self-resolving episodes of altered mentation and decreased arousal later in the day. Scrutiny of serial brain MRIs led to a diagnosis of SIH, with severe downward diencephalic and brain stem displacement—resulting in cerebral aqueduct occlusion with obstructive hydrocephalus. Initial clinical improvement occurred with CSF diversion, but the patient quickly deteriorated—developing diencephalic spells, including extensor posturing and severely depressed levels of consciousness. Clinical improvement was seen with stopping CSF diversion and Trendelenburg-positioning. After intensive spinal imaging, dynamic CT myelography identified a left T10 nerve root diverticula and CSF-venous fistula. Surgical obliteration resulted in rapid, profound neurological improvement, and ultimately full neurological recovery by 1 yr. CONCLUSION In our patient, worsening episodes of confusion, postural headaches, and autonomic instability developed due to SIH, which induced profound downward displacement and compression of the diencephalon and brain stem, and accompanied by subsequent obstructive hydrocephalus. Diagnostic persistence identified the CVF, which had caused the complex multifold pathophysiology and clinical presentation. If suspicion remains high for CVF, persistent spinal imaging, particularly with dynamic myelography, may be crucial.

Background and objective Epidural blood patch (EBP) is a safe and effective treatment for spontaneous intracranial hypotension (SIH), but clinical and procedural variables that predict EBP efficacy remain nebulous. Methods This study is an institutional review board-approved retrospective case series with dichotomized EBP efficacy defined at 3 months. The study included 202 patients receiving 604 EBPs; iatrogenic cerebrospinal fluid leaks were excluded. Results Of the EBPs, 473 (78%) were single-level, 349 (58%) lumbar, 75 (12%) bilevel, and 56 (9%) multilevel (≥3 levels). Higher volume (OR 1.64; p<0.0001), bilevel (3.17, 1.91–5.27; p<0.0001), and multilevel (117.3, 28.04–490.67; p<0.0001) EBP strategies predicted greater efficacy. Only volume (1.64, 1.47–1.87; p<0.0001) remained significant in multivariate analysis. Site-directed patches were more effective than non-targeted patches (8.35, 0.97–72.1; p=0.033). Lower thoracic plus lumbar was the most successful bilevel strategy, lasting for a median of 74 (3–187) days. Conclusions In this large cohort of EBP in SIH, volume, number of spinal levels injected, and site-directed strategies significantly correlated with greater likelihood of first EBP efficacy. Volume and leak site coverage likely explain the increased efficacy with bilevel and multilevel patches. In patients with cryptogenic leak site, and either moderate disability, negative prognostic brain MRI findings for successful EBP, or failed previous lumbar EBP, a low thoracic plus lumbar bilevel EBP strategy is recommended. Multilevel EBP incorporating transforaminal administration and fibrin glue should be considered in patients refractory to bilevel EBP. An algorithmic approach to treating SIH is proposed.

Abstract Dr Albert L. Rhoton Jr became the focal point of neurosurgery's evolution in understanding the intricate and complex microanatomy of the human brain over the last 4 decades. His pioneering work on cadaveric specimens proved to be a pivotal endeavor in the pursuit to better understand the complex microsurgical anatomy of cranial surgery. This paper details his early career at the Mayo Clinic in Rochester, Minnesota. A comprehensive review and synthesis of data acquired from the institutional historical archives including the Annual Reports to the Executive Committee, the Reports to the Board of Directors, the MAYOVOX Newsletter, the illustration archives of the Mayo Clinic Division of Creative Media, staff biographies, curriculum vitae, personal interviews, as well as full-text journal articles, and book publications was performed. Dr Rhoton was engaged in a busy clinical practice as a young staff at the Mayo Clinic. Records show he focused on tackling complex intracranial pathologies along with numerous basic research and neuroanatomy projects that became a major part of his life's work and passion. He was a great teacher and friend to countless individuals and his work will continue to impact and improve the care provided to neurosurgery patients for generations to come.