Giuseppe Lanzino

Critical Care Management of Patients Following Aneurysmal Subarachnoid Hemorrhage: Recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference

Subarachnoid hemorrhage (SAH) is an acute cerebrovascular event which can have devastating effects on the central nervous system as well as a profound impact on several other organs. SAH patients are routinely admitted to an intensive care unit and are cared for by a multidisciplinary team. A lack of high quality data has led to numerous approaches to management and limited guidance on choosing among them. Existing guidelines emphasize risk factors, prevention, natural history, and prevention of rebleeding, but provide limited discussion of the complex critical care issues involved in the care of SAH patients. The Neurocritical Care Society organized an international, multidisciplinary consensus conference on the critical care management of SAH to address this need. Experts from neurocritical care, neurosurgery, neurology, interventional neuroradiology, and neuroanesthesiology from Europe and North America were recruited based on their publications and expertise. A jury of four experienced neurointensivists was selected for their experience in clinical investigations and development of practice guidelines. Recommendations were developed based on literature review using the GRADE system, discussion integrating the literature with the collective experience of the participants and critical review by an impartial jury. Recommendations were developed using the GRADE system. Emphasis was placed on the principle that recommendations should be based not only on the quality of the data but also tradeoffs and translation into practice. Strong consideration was given to providing guidance and recommendations for all issues faced in the daily management of SAH patients, even in the absence of high quality data.

Pipeline for Uncoilable or Failed Aneurysms: Results from a Multicenter Clinical Trial

PURPOSE To evaluate the safety and effectiveness of the Pipeline Embolization Device (PED; ev3/Covidien, Irvine, Calif) in the treatment of complex intracranial aneurysms. MATERIALS AND METHODS The Pipeline for Uncoilable or Failed Aneurysms is a multicenter, prospective, interventional, single-arm trial of PED for the treatment of uncoilable or failed aneurysms of the internal carotid artery. Institutional review board approval of the HIPAA-compliant study protocol was obtained from each center. After providing informed consent, 108 patients with recently unruptured large and giant wide-necked aneurysms were enrolled in the study. The primary effectiveness endpoint was angiographic evaluation that demonstrated complete aneurysm occlusion and absence of major stenosis at 180 days. The primary safety endpoint was occurrence of major ipsilateral stroke or neurologic death at 180 days. RESULTS PED placement was technically successful in 107 of 108 patients (99.1%). Mean aneurysm size was 18.2 mm; 22 aneurysms (20.4%) were giant (>25 mm). Of the 106 aneurysms, 78 met the studys primary effectiveness endpoint (73.6%; 95% posterior probability interval: 64.4%-81.0%). Six of the 107 patients in the safety cohort experienced a major ipsilateral stroke or neurologic death (5.6%; 95% posterior probability interval: 2.6%-11.7%). CONCLUSION PED offers a reasonably safe and effective treatment of large or giant intracranial internal carotid artery aneurysms, demonstrated by high rates of complete aneurysm occlusion and low rates of adverse neurologic events; even in aneurysms failing previous alternative treatments.

Endovascular Treatment of Intracranial Aneurysms With Flow Diverters: A Meta-Analysis

Background and Purpose— Flow diverters are important tools in the treatment of intracranial aneurysms. However, their impact on aneurysmal occlusion rates, morbidity, mortality, and complication rates is not fully examined. Methods— We conducted a systematic review of the literature searching multiple databases for reports on the treatment of intracranial aneurysms with flow-diverter devices. Random effects meta-analysis was used to pool outcomes of aneurysmal occlusion rates at 6 months, and procedure-related morbidity, mortality, and complications across studies. Results— A total of 29 studies were included in this analysis, including 1451 patients with 1654 aneurysms. Aneurysmal complete occlusion rate was 76% (95% confidence interval [CI], 70%–81%). Procedure-related morbidity and mortality were 5% (95% CI, 4%–7%) and 4% (95% CI, 3%–6%), respectively. The rate of postoperative subarachnoid hemorrhage was 3% (95% CI, 2%–4%). Intraparenchymal hemorrhage rate was 3% (95% CI, 2%–4%). Perforator infarction rate was 3% (95% CI, 1%–5%), with significantly lower odds of perforator infarction among patients with anterior circulation aneurysms compared with those with posterior circulation aneurysms (odds ratio, 0.01; 95% CI, 0.00–0.08; P<0.0001). Ischemic stroke rate was 6% (95% CI, 4%–9%), with significantly lower odds of perforator infarction among patients with anterior circulation aneurysms compared with those with posterior circulation aneurysms (odds ratio, 0.15; 95% CI, 0.08–0.27; P<0.0001). Conclusions— This meta-analysis suggests that treatment of intracranial aneurysms with flow-diverter devices is feasible and effective with high complete occlusion rates. However, the risk of procedure-related morbidity and mortality is not negligible. Patients with posterior circulation aneurysms are at higher risk of ischemic stroke, particularly perforator infarction. These findings should be considered when considering the best therapeutic option for intracranial aneurysms.

Stenting and secondary coiling of intracranial internal carotid artery aneurysm: technical case report.

OBJECTIVE AND IMPORTANCE Endovascular stents have been successfully used in the treatment of fusiform and dissecting aneurysms of the peripheral circulation and extracranial carotid and vertebral arteries. Technical limitations related to the inability to navigate the stent and the delivery system through tortuous vascular segments has limited their application with intracranial lesions. Availability of new flexible and pliable stent systems might overcome these difficulties. CLINICAL PRESENTATION A 49-year-old woman presented with a dissecting pseudoaneurysm of the horizontal portion of the petrous internal carotid artery that increased in size, as revealed by serial angiographic studies. INTERVENTION The aneurysm was treated by deploying a new flexible stent across the aneurysm neck and by then packing the aneurysm sac with Guglielmi detachable coils that were delivered by a microcatheter positioned through the stent struts into the aneurysm lumen. CONCLUSION New flexible stents can be used to treat intracranial internal carotid artery aneurysms in difficult-to-access areas, such as the horizontal petrous segment. The stent may disrupt the aneurysm inflow tract, thereby inducing stasis and facilitating intra-aneurysmal thrombosis. In addition, the stent acts as an endoluminal scaffold to prevent coil herniation into the parent artery, which allows tight packing of even wide-necked and irregularly shaped aneurysms. The stent may also serve as a matrix for endothelial growth. We think this new generation of flexible stents and the use of this described technique will usher in the next era of endovascular management of intracranial aneurysms.

International Retrospective Study of the Pipeline Embolization Device: A Multicenter Aneurysm Treatment Study

BACKGROUND AND PURPOSE: Flow diverters are increasingly used in the endovascular treatment of intracranial aneurysms. Our aim was to determine neurologic complication rates following Pipeline Embolization Device placement for intracranial aneurysm treatment in a real-world setting. MATERIALS AND METHODS: We retrospectively evaluated all patients with intracranial aneurysms treated with the Pipeline Embolization Device between July 2008 and February 2013 in 17 centers worldwide. We defined 4 subgroups: internal carotid artery aneurysms of ≥10 mm, ICA aneurysms of <10 mm, other anterior circulation aneurysms, and posterior circulation aneurysms. Neurologic complications included spontaneous rupture, intracranial hemorrhage, ischemic stroke, permanent cranial neuropathy, and mortality. Comparisons were made with t tests or ANOVAs for continuous variables and the Pearson χ2 or Fisher exact test for categoric variables. RESULTS: In total, 793 patients with 906 aneurysms were included. The neurologic morbidity and mortality rate was 8.4% (67/793), highest in the posterior circulation group (16.4%, 9/55) and lowest in the ICA <10-mm group (4.8%, 14/294) (P = .01). The spontaneous rupture rate was 0.6% (5/793). The intracranial hemorrhage rate was 2.4% (19/793). Ischemic stroke rates were 4.7% (37/793), highest in patients with posterior circulation aneurysms (7.3%, 4/55) and lowest in the ICA <10-mm group (2.7%, 8/294) (P = .16). Neurologic mortality was 3.8% (30/793), highest in the posterior circulation group (10.9%, 6/55) and lowest in the anterior circulation ICA <10-mm group (1.4%, 4/294) (P < .01). CONCLUSIONS: Aneurysm treatment with the Pipeline Embolization Device is associated with the lowest complication rates when used to treat small ICA aneurysms. Procedure-related morbidity and mortality are higher in the treatment of posterior circulation and giant aneurysms.

Neuroprotection with a calpain inhibitor in a model of focal cerebral ischemia.

Background and Purpose Excessive elevation of intracellular calcium and uncontrolled activation of calcium-sensitive events are believed to play a central role in ischemic neuronal damage. Calcium-activated proteolysis by calpain is a candi- date to participate in this form of pathology because it is activated under ischemic conditions and its activation results in the degradation of crucial cytoskeletal and regulatory proteins. The present studies examined the effects of a cell- penetrating inhibitor of calpain on the pathological outcome after transient focal ischemia in the brain. Methods Twenty-five male Sprague-Dawley rats were divided into four groups: a saline-treated group, a vehicle- treated group, and two calpain inhibitor-treated groups (Cbz- Val-Phe-H; 30-mg/kg and 60-mg/kg cumulative doses). Ischemia was induced by occluding the left middle cerebral artery and both common carotid arteries for 3 hours followed by reperfusion. Animals were killed 72 hours after surgery, and quantitative measurements of infarction volumes were performed using histological techniques. Eight additional rats were killed 30 minutes after ischemia and examined for the extent of proteolysis using immunoblot techniques. A final group of 12 animals was decapitated after injection of vehicle or calpain inhibitor, and the proteolytic response was measured after 60 minutes of total ischemia. Results Rats treated with Cbz-Val-Phe-H exhibited significantly smaller volumes of cerebral infarction than saline- treated or vehicle-treated control animals. Intravenous injections of cumulative doses of 30 mg/kg or 60 mg/kg of Cbz-Val- Phe-H were effective in reducing infarction, edema, and calcium-activated proteolysis. The proteolytic response to postdecapitation ischemia was also reduced by the calpain inhibitor. Conclusions These results demonstrate the neuroprotective effect of a cell-penetrating calpain inhibitor when administered systemically. The findings suggest that targeting intra- cellular, calcium-activated mechanisms, such as proteolysis, represents a viable therapeutic strategy for limiting neurological damage after ischemia.

Flow Diversion for Intracranial Aneurysms A Review

The introduction of flow diverters for treatment of intracranial aneurysms represents a major paradigm shift in the treatment of these lesions. The theoretical hallmark of flow diverters is the treatment of the diseased segment harboring the aneurysm instead of treating the aneurysm itself. Flow diverters are designed to induce disruption of flow near the aneurysm neck while preserving flow into parent vessel and adjacent branches. After flow diversion, intra-aneurysmal thrombosis occurs, followed by shrinkage of the aneurysmal sac as the thrombus organizes and retracts. Preliminary clinical series document effective treatment of wide-neck and/or large and giant aneurysms with acceptable complication rates. However, several questions remain unanswered related to the incidence and mechanisms of aneurysm rupture after treatment with flow diverters, fate of small perforating vessels, and long-term patency rates.

Microvascular Decompression for Glossopharyngeal Neuralgia

Glossopharyngeal neuralgia is an uncommon cause of facial pain with a relative frequency of 0.2 to 1.3% when compared with trigeminal neuralgia. It is characterized by intermittent, lancinating pain involving the posterior tongue and pharynx, often with radiation to deep ear structures. Since its first description in 1910 by Weisenburg, a variety of destructive procedures have been performed to provide relief in patients whose pain was refractory to medical treatment. These procedures all necessitated the sacrifice of the glossopharyngeal nerve and, in most cases, also involved the destruction of at least part of the vagus nerve as well. In 1977, Laha and Jannetta reported good results in four patients who underwent microvascular decompression of the glossopharyngeal and vagus nerves for glossopharyngeal neuralgia. Since 1971, 40 patients have undergone microvascular decompression of the glossopharyngeal and vagus nerves for treatment of typical glossopharyngeal neuralgia. This procedure provided excellent immediate results (complete or > 95% relief of pain) in 79%, with an additional 10% having a substantial (> 50%) reduction in pain. Long-term follow-up (mean, 48 mo; range, 6-170 mo) reveals excellent results (complete or > 95% reduction in pain without any medication) in 76% of the patients and substantial improvement in an additional 16%. There were two deaths at surgery (5%) both occurring early in the series as the result of hemodynamic lability causing intracranial hemorrhage. Three patients (8%) suffered permanent 9th nerve palsy. (ABSTRACT TRUNCATED AT 250 WORDS)

Multidisciplinary management and emerging therapeutic strategies in aneurysmal subarachnoid haemorrhage.

The management of patients with aneurysmal subarachnoid haemorrhage demands expertise to anticipate, recognise, and promptly treat the many neurological and systemic complications. For this reason, these patients are best cared for in high-volume medical centres with multidisciplinary teams and should preferably be treated in a specialised intensive care unit. Endovascular occlusion and surgical clipping provide complementary alternatives for the treatment of aneurysms. Perfusion scans are redefining the way we detect delayed ischaemia as a growing body of evidence indicates that monitoring vessel diameter is insufficient to prevent cerebral infarctions. Statins, endothelin antagonists, and magnesium sulfate infusion are among the novel strategies being tested for neuroprotection and attenuation of vasospasm. The effectiveness of these treatments is supported by strong experimental data and they represent a new generation of therapeutic options developed from the understanding that vasospasm is primarily caused by endothelial dysfunction.

Identification of Patients at Risk for Periprocedural Neurological Deficits Associated With Carotid Angioplasty and Stenting

BACKGROUND AND PURPOSE Transient or permanent neurological deficits can occur in the periprocedural period following carotid angioplasty and stenting (CAS), presumably due to distal embolization and/or hemodynamic compromise. We performed this study to identify predictors of neurological deficits associated with carotid angioplasty and stent placement. METHODS We reviewed medical records and angiograms in a consecutive series of patients who underwent CAS for symptomatic or asymptomatic cervical internal carotid artery stenosis from June 1996 through December 1998. Using logistic regression analysis, we evaluated the effect of demographic, clinical, intraprocedural, and angiographic risk factors on subsequent development of periprocedural neurological deficits. Periprocedural neurological deficits were defined as new or worsening transient or permanent neurological deficits that occurred during or within 48 hours of the procedure. RESULTS A total of 111 patients (mean age 68.2+/-9.1 years) who underwent CAS for asymptomatic (n=54) or symptomatic (n=57) stenoses were included in this study. A total of 14 periprocedural neurological deficits (13%) were observed either during (n=4) or after (n=10) the procedure. Three identified variables were independently associated with periprocedural neurological deficits: symptomatic lesion (OR 8.3, 95% CI 1.6 to 42.6), length of stenotic segment >/=11.2 mm (OR 5.2, 95% CI 1.2 to 22.5), and absence of hypercholesterolemia (OR 5.4, 95% CI 1.4 to 20.9). Other variables, including age and degree of stenosis (defined by NASCET criteria), were not associated with periprocedural neurological deficits. CONCLUSIONS A combination of clinical and angiographic variables can be used to identify patients at risk for periprocedural neurological deficits after CAS. Such identification may help in selection of patients who may benefit from novel pharmacological and mechanical preventive approaches.