Ricardo J. Komotar

Guidelines for the surgical treatment of unruptured intracranial aneurysms: the first annual J. Lawrence pool memorial research symposium--controversies in the management of cerebral aneurysms.

THE MANAGEMENT OF unruptured cerebral aneurysms remains one of the most controversial topics in neurosurgery. To this end, we discuss the diagnosis and estimated prevalence of these lesions as well as review the literature regarding the rate of rupture for cerebral aneurysms and risks of operative intervention. Our interpretation of the literature concludes that aneurysms are present in approximately 1% of the adult population, varying between less than 1% in young adults to 4% in the elderly. The yearly risk of subarachnoid hemorrhage for an unruptured intracranial aneurysm is approximately 1% for lesions 7 to 10 mm in diameter. Based on these assumptions, we recommend that 1) with rare exceptions, all symptomatic unruptured aneurysms should be treated; 2) small, incidental aneurysms less than 5 mm in diameter should be managed conservatively in virtually all cases; 3) aneurysms larger than 5 mm in patients younger than 60 years of age should be seriously considered for treatment; 4) large, incidental aneurysms larger than 10 mm should be treated in nearly all patients younger than 70 years of age; and 5) microsurgical clipping rather than endovascular coiling should be the first treatment choice in low-risk cases. Critical to our guidelines is collaboration by a highly experienced cerebrovascular team of microneurosurgeons and endovascular neurosurgeons working at a tertiary medical center with a high case volume and using a decision-making paradigm designed to offer only low-risk treatments. In certain patients for whom both treatment and natural history carry high risks, such as those with giant aneurysms, nonoperative management is typically elected.

Complement component C3 mediates inflammatory injury following focal cerebral ischemia.

The complement cascade has been implicated in ischemia/reperfusion injury, and recent studies have shown that complement inhibition is a promising treatment option for acute stroke. The development of clinically useful therapies has been hindered, however, by insufficient understanding of which complement subcomponents contribute to post-ischemic injury. To address this issue, we subjected mice deficient in selected complement proteins (C1q, C3, C5) to transient focal cerebral ischemia. Of the strains investigated, only C3−/− mice were protected, as demonstrated by 34% reductions in both infarct volume (P<0.01) and neurological deficit score (P<0.05). C3-deficient mice also manifested decreased granulocyte infiltration (P<0.02) and reduced oxidative stress (P<0.05). Finally, administration of a C3a-receptor antagonist resulted in commensurate neurological improvement and stroke volume reduction (P<0.05). Together, these results establish C3 activation as the key constituent in complement-related inflammatory tissue injury following stroke and suggest a C3a anaphylatoxin-mediated mechanism.

Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas.

OBJECTIVEPilocytic astrocytoma (PA) is a common type of pediatric brain tumor that can arise within the hypothalamic/chiasmatic region and typically has an excellent outcome. We identified a group of tumors, previously classified as PAs, with unique histological features and aggressive behavior. This article describes the clinicopathological features of these unusual neoplasms, which are currently known as pilomyxoid astrocytomas (PMAs), to better differentiate them from typical PAs. METHODSMedical information and surgical specimens were obtained for 42 PA cases and 21 PMA cases. Patient demographic features, treatment modalities, progression-free survival (PFS) times, overall survival (OS) times, and outcomes were compared between the groups with nonparametric tests. RESULTSThe PMA group included 12 male and 9 female patients. The PA group included 27 male and 15 female patients. The mean ages at diagnosis for the PMA and PA groups were 18 months (range, 2–84 mo) and 58 months (range, 4–189 mo), respectively (P < 0.01). The mean PFS times for the PMA and PA groups were 26 and 147 months, respectively (P < 0.001). The mean OS times for the PMA and PA groups were 63 and 213 months, respectively (P < 0.001). Sixteen patients with PMAs (76%) experienced local recurrence, and three of those patients demonstrated evidence of cerebrospinal fluid dissemination. Twenty-one patients with PAs (50%) experienced local recurrence, none with evidence of cerebrospinal fluid dissemination. Within the follow-up period, seven patients with PMAs (33%) and seven patients with PAs (17%) died as a result of their disease. In an age-matched set, the mean PFS times for the PMA and PA groups were 25 and 163 months, respectively (P < 0.01), and the mean OS times for the PMA and PA groups were 60 and 233 months, respectively (P < 0.001). CONCLUSIONHypothalamic/chiasmatic PMAs occurred in a significantly younger population and were associated with substantially shorter PFS and OS times than were typical PAs. Increased recognition of these lesions could affect the prognosis and treatment of pediatric astrocytomas.

Resuscitation and critical care of poor-grade subarachnoid hemorrhage.

As outcomes have improved for patients with aneurysmal subarachnoid hemorrhage, most mortality and morbidity that occur today are the result of severe diffuse brain injury in poor-grade patients. The premise of this review is that aggressive emergency cardiopulmonary and neurological resuscitation, coupled with early aneurysm repair and advanced multimodality monitoring in a specialized neurocritical care unit, offers the best approach for achieving further improvements in subarachnoid hemorrhage outcomes. Emergency care should focus on control of elevated intracranial pressure, optimization of cerebral perfusion and oxygenation, and medical and surgical therapy to prevent rebleeding. In the postoperative period, advanced monitoring techniques such as continuous electroencephalography, brain tissue oxygen monitoring, and microdialysis can detect harmful secondary insults, and may eventually be used as end points for goal-directed therapy, with the aim of creating an optimal physiological environment for the comatose injured brain. As part of this paradigm shift, it is essential that aggressive surgical and medical support be linked to compassionate end-of-life care. As neurosurgeons become confident that comfort care can be implemented in a straightforward fashion after a failed trial of early maximal intervention, the usual justification for withholding treatment (survival with neurological devastation) becomes less relevant, and lives may be saved as more patients recover beyond expectations.

Preoperative prediction of long-term outcome in poor-grade aneurysmal subarachnoid hemorrhage

OBJECTIVE:To evaluate which presentation indices, demographics, and clinical information predict 12-month outcome in poor-grade aneurysmal subarachnoid hemorrhage (SAH), and to provide a preoperative index of prognosis. METHODS:Data were obtained on all patients with poor-grade (Hunt and Hess Grades IV and V) aneurysmal SAH from a prospectively maintained SAH database and health outcomes project. Demographics, medical history, presenting clinical condition, and health outcomes were analyzed. Survival analysis was performed and Kaplan-Meier curves were generated. Multivariable logistic regression analysis was used to identify significant predictors of poor outcome at 12 months after hemorrhage, as measured by the modified Rankin disability scale. RESULTS:Survival curves for open surgery and endovascular treatment did not differ significantly. Overall, 40% of the 98 definitively treated patients had a favorable outcome at 12 months. Multivariable analysis identified patient age older than 65 years (P < 0.001), hyperglycemia (P < 0.03), worst preoperative Hunt and Hess Grade V (P < 0.0001), and aneurysm size of at least 13 mm (P < 0.002) as significant predictors of poor outcome. These variables were weighted and used to compute a poor-grade aneurysmal SAH Prognosis Score (hereafter, Prognosis Score) for each patient. A Prognosis Score of 0 was associated with a 90% favorable outcome; Prognosis Score of 1 with 83%; Prognosis Score of 2 with 43%; Prognosis Score of 3 with 8%; Prognosis Score of 4 with 7%; and a Prognosis Score of 5 with 0%. CONCLUSION:Outcome in poor-grade aneurysmal SAH is strongly predicted by patient age, worst preoperative Hunt and Hess clinical grade, and aneurysm size. Hyperglycemia on admission after poor-grade aneurysmal SAH increases the likelihood of poor outcome, and is a potentially modifiable risk factor. The Prognosis Score is a useful tool for preoperatively assessing the likelihood of a favorable outcome for poor-grade aneurysmal SAH patients.

Impact of a Protocol for Acute Antifibrinolytic Therapy on Aneurysm Rebleeding After Subarachnoid Hemorrhage

Background and Purpose— ϵ-Aminocaproic acid (EACA) is an antifibrinolytic agent used to prevent rebleeding in aneurysmal subarachnoid hemorrhage. Although studies have found that a decrease in rebleeding with long-term antifibrinolytic therapy is offset by an increase in ischemic deficits, more recent studies have indicated that early, short-term therapy may be beneficial. Methods— We instituted a protocol for acute EACA administration starting at diagnosis and continued for a maximum duration of 72 hours after subarachnoid hemorrhage onset. We compared 73 patients treated with EACA with 175 non-EACA-treated patients. We sought to identify differences in the occurrence of rebleeding, side effects, and outcome. Results— Baseline characteristics were similar in the 2 groups. There was a significant decrease in rebleeding in EACA-treated patients (2.7%) versus non-EACA patients (11.4%). There was no difference in ischemic complications between cohorts. There was a significant 8-fold increase in deep venous thrombosis in the EACA group but no increase in pulmonary embolism. There was a nonsignificant 76% reduction in mortality attributable to rebleeding, a 13.3% increase in favorable outcome in good-grade EACA-treated patients, and a 6.8% increase in poor-grade patients. Conclusions— When used acutely, short-term EACA treatment resulted in decreased rebleeding without an increase in serious side effects in our selected group of patients. Randomized placebo-controlled trials are needed to determine whether acute antifibrinolytic therapy should be accepted as the standard of care in all patients.

Clinical features, surgical treatment, and long-term outcome in adult patients with moyamoya disease. Clinical article.

Object To report the clinical features, surgical treatment, and long-term outcomes of adults with moyamoya phenomenon treated at a single institution in the United States.

A mouse model of intracerebral hemorrhage using autologous blood infusion

The development of controllable and reproducible animal models of intracerebral hemorrhage (ICH) is essential for the systematic study of the pathophysiology and treatment of hemorrhagic stroke. In recent years, we have used a modified version of a murine ICH model to inject blood into mouse basal ganglia. According to our protocol, autologous blood is stereotactically infused in two stages into the right striatum to mimic the natural events of hemorrhagic stroke. Following ICH induction, animals demonstrate reproducible hematomas, brain edema formation and marked neurological deficits. Our technique has proven to be a reliable and reproducible means of creating ICH in mice in a number of acute and chronic studies. We believe that our model will serve as an ideal paradigm for investigating the complex pathophysiology of hemorrhagic stroke. The protocol for establishing this model takes about 2 h.

Predictors of neurocognitive decline after carotid endarterectomy

OBJECTIVE:Although the incidence of stroke after carotid endarterectomy (CEA) is low (1–3%), approximately 25% of patients experience subtle declines in postoperative neuropsychometric function. No studies have investigated the risk factors for this neurocognitive change. We sought to identify predictors of postoperative neurocognitive dysfunction. METHODS:We enrolled 186 CEA patients, with both symptomatic and asymptomatic stenosis, to undergo a battery of neuropsychometric tests preoperatively and on postoperative Days 1 and 30. Neurocognitive dysfunction was defined as a two standard deviation decline in performance compared with a similarly aged control group of lumbar laminectomy patients. Univariate logistic regression was performed for age, sex, obesity, smoking, symptomatology, diabetes mellitus, hypertension, hypercholesterolemia, use of statin medication, previous myocardial infarction, previous CEA, operative side, duration of surgery, duration of carotid cross-clamp, and weight-adjusted doses of midazolam and fentanyl. Variables achieving univariate P < 0.10 were included in a multivariate analysis. Data is presented as (odds ratio, 95% confidence interval, P-value). RESULTS:Eighteen and 9% of CEA patients were injured on postoperative Days 1 and 30, respectively. Advanced age predicted neurocognitive dysfunction on Days 1 and 30 (1.93 per decade, 1.15–3.25, 0.01; and 2.57 per decade, 1.01–6.51, 0.049, respectively). Additionally, diabetes independently predicted injury on Day 30 (4.26, 1.15–15.79, 0.03). CONCLUSIONS:Advanced age and diabetes predispose to neurocognitive dysfunction after CEA. These results are consistent with risk factors for neurocognitive dysfunction after coronary bypass and major stroke after CEA, supporting an underlying ischemic pathophysiology. Further work is necessary to determine the role these neurocognitive deficits may play in appropriately selecting patients for CEA.

Adjuvant Embolization With N-Butyl Cyanoacrylate in the Treatment of Cerebral Arteriovenous Malformations Outcomes, Complications, and Predictors of Neurologic Deficits

Background and Purpose— The purpose of this study was to assess the frequency, severity, and predictors of neurological deficits after adjuvant embolization for cerebral arteriovenous malformations. Methods— From 1997 to 2006, 202 of 275 patients with arteriovenous malformation received embolization before microsurgery (n=176) or radiosurgery (n=26). Patients were examined before and after endovascular embolization and at clinical follow-up (mean, 43.4±34.6 months). Outcome was classified according to the modified Rankin Scale. New neurological deficits after embolization were defined as minimal (no change in overall modified Rankin Scale), moderate (modified Rankin Scale ≤2), or significant (modified Rankin Scale >2). Results— Two hundred two patients were treated in 377 embolization procedures. There were a total of 29 new clinical deficits after embolization (8% of procedures; 14% of patients), of which 19 were moderate or significant. Postembolization deficits resolved in a significant number of patients over time (P<0.0001). Five patients had persistent neurological deficits due to embolization (1.3% of procedures; 2.5% of patients). In multivariate analysis, the following variables significantly predicted new neurological deficit after embolization: complex arteriovenous malformation with treatment plan specifying more than one embolization procedure (OR, 2.7; 95% CI, 1.4 to 8.6), diameter <3 cm (OR, 3.2; 95% CI, 1.2 to 9.1), diameter >6 cm (OR, 6.2; 95% CI, 1.0 to 57.0), deep venous drainage (OR, 2.7; 95% CI, 1.1 to 6.9), or eloquent location (OR, 2.4; 95% CI, 1.0 to 5.7). These variables were weighted and used to compute an arteriovenous malformation Embolization Prognostic Risk Score for each patient. A score of 0 predicted no new deficits, a score of 1 predicted a new deficit rate of 6%, a score of 2 predicted a new deficit rate of 15%, a score of 3 predicted a new deficit rate of 21%, and a score of 4 predicted a new deficit rate of 50% (P<0.0001). Conclusions— Small and large size, eloquent location, deep venous drainage, and complex vascular anatomy requiring multiple embolization procedures are risk factors for the development of immediate postembolization neurological deficits. Nevertheless, a significant number of patients with treatment-related neurological deficits improve over time. The low incidence of permanent neurological deficits underscores the usefulness of this technique in carefully selected patients.