Intraventricular Tissue Plasminogen Activator Research Articles

Intraventricular Tissue Plasminogen Activator and Shunt Dependency in Aneurysmal Subarachnoid Hemorrhage Patients With Cast Ventricles.

Patients with intraventricular hemorrhage (IVH) are at higher risk of hydrocephalus requiring an external ventricular drain and long-term ventriculoperitoneal shunt placement. To investigate whether intraventricular tissue plasminogen activator (tPA) administration in patients with ventricular casting due to IVH reduces shunt dependence. Patients from the Post-Barrow Ruptured Aneurysm Trial (PBRAT) database treated for aneurysmal subarachnoid hemorrhage (aSAH) from August 1, 2010, to July 31, 2019, were retrospectively reviewed. Patients with and without IVH were compared. A second analysis compared IVH patients with and without ventricular casting. A third analysis compared patients with ventricular casting with and without intraventricular tPA treatment. The primary outcome was chronic hydrocephalus requiring permanent shunt placement. Of 806 patients hospitalized with aSAH, 561 (69.6%) had IVH. IVH was associated with a higher incidence of shunt placement (25.7%vs 4.1%, P <.001). In multivariable logistic regression analysis, IVH was independently associated with increased likelihood of shunt placement (odds ratio [OR]: 7.8, 95% CI: 3.8-16.2, P <.001). Generalized ventricular casting was present in 80 (14.3%) patients with IVH. In a propensity-score adjusted analysis, generalized ventricular casting was an independent predictor of shunt placement (OR: 3.0, 95% CI: 1.8-4.9, P <.001) in patients with IVH. Twenty-one patients with ventricular casting received intraventricular tPA. These patients were significantly less likely to require a shunt (OR: 0.30, 95% CI: 0.010-0.93, P=.04). Ventricular casting in aSAH patients was associated with an increased risk of chronic hydrocephalus and shunt dependency. However, this risk decreased with the administration of intraventricular tPA.

Intraventricular haemorrhage due to re-ruptured arteriovenous malformation cleared with tissue plasminogen activator administered through a pre-existing ventriculoperitoneal shunt

In the context in intraventricular haemorrhage (IVH), intrathecal thrombolytic agents administered in conjunction with extraventricular drainage have been demonstrated to clear larger volumes of blood and reduce mortality rates. However, patients with arteriovenous malformations (AVM) have been mostly excluded from clinical trials. We describe a patient with hydrocephalus secondary to a ruptured AVM who was treated via external ventriculostomy, which was subsequently converted to a ventriculoperitoneal shunt (VPS). Eight months later, the AVM re-ruptured, causing IVH and rendering the patient comatose. Taking into consideration the patient’s poor outlook, a single dose of intraventricular tissue plasminogen activator (t-PA) was administered through the shunt reservoir. The shunt maintained its function and the patient's condition ultimately improved. This impressive case demonstrates the utility of t-PA administered through an existing VPS in the setting of IVH due to ruptured AVM, highlighting its lifesaving potential in the appropriate patient and overall decrease in the cost of care by mitigating the need for shunt revision.

Abstract TP376: Infections in Patients With Spontaneous Intraventricular Hemorrhage- Results From the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III Trial

Introduction: Intraventricular hemorrhage (IVH) occurs in about 40% of patients with intracerebral hemorrhage (ICH) and is associated with higher mortality and worse outcomes than ICH patients without IVH. Infections are common in ICH patients but data in IVH patients are limited. Methods: Prospective analysis of adjudicated adverse event infection reporting during first 180 days in 500 patients enrolled in the CLEAR III trial, a multicenter, double-blind, randomized study comparing external ventricular drain (EVD) + intraventricular recombinant tissue plasminogen activator (rtPA) vs. EVD + placebo for treatment of obstructive IVH and intracerebral hemorrhage (ICH) volume &lt;30cc. Primary outcome measures were 90-day and 180-day mortality. Secondary outcome measures were hospital length of stay (LOS). We constructed binary logistic and linear regression models for multivariable analysis. Results: Infection was reported in 269 patients (53.8%). Pneumonia was the most common infection (33%), followed by UTI (16%), and bacterial ventriculitis (4.4%). Overall 180-day mortality was 20%. Patients with infection were more likely to have older age (p=0.012), lower admission GCS (p=0.007), higher ICH volume (8.8 vs 6.7ml, p=0.001), and higher ICH+IVH volume (37.7 vs 31.7 ml, p=0.002). In the regression model, IVH volume was associated with higher odds of 90-day or 180-day mortality, but presence of any infection was not a significant predictor of mortality. Infection was however associated with longer length of stay (26 vs 22 days, p&lt;0.001). Subgroup analysis of individual infections, showed only bacterial ventriculitis to be associated with 90-day (OR: 3.84, CI: 1.36-10.82), and 180-day mortality (OR: 2.9, CI: 1.05-8.06), while pneumonia and UTI were not. Conclusion: Patients with IVH have a high incidence of infections, which is associated with longer hospitalization but does not appear to influence mortality. Of the infections, bacterial ventriculitis is a significant predictor of mortality in our 7-factor model. IVH volume did not predict infections but predicted mortality.These results form a basis for future correlation of infectious complications with treatment rendered (thrombolysis versus placebo), with upcoming unblinding of the trial.

Abstract 215: Evaluation of Intracranial Pressure and Cerebral Perfusion Pressure in the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Trial (CLEAR III)

Background: Elevated intracranial pressure (ICP) and inadequate cerebral perfusion pressure (CPP) are mechanisms causing poor outcomes in spontaneous intraventricular hemorrhage (IVH). We characterized intracranial hypertension in severe IVH requiring extraventricular drainage (EVD). Methods: Prospective analysis of ICP in all 500 patients enrolled in the CLEAR III trial, a multicenter, double-blind, randomized study comparing EVD + intraventricular recombinant tissue plasminogen activator (rtPA) vs. EVD + placebo for treatment of obstructive IVH and intracerebral hemorrhage (ICH) volume &lt;30cc. Maximum and minimum ICP/CPP were recorded every 4 hours until 7 days post randomization (rand), analyzed at pre-defined thresholds and compared by clinical and radiological variables. Results: of 23,406 ICP readings, maximum ICP ranged from 0-97 mmHg (median, IQR; 11,8); 90.7% (21,223) were ≤20mmHg, 1.8% &gt;30, 0.5% &gt;40, and 0.2% &gt; 50mm Hg. Proportion of threshold events &gt;20mmHg were more frequent with persistent closure of the lower ventricular system after day 3 (p=0.02), and was correlated with initial and end of treatment (72 hours post rand) ICH volumes (p=0.01, p=0.04, respectively). ICP elevation &gt;20mmHg occurred during a required 1 hr EVD closure interval after 566/3712 (15.3%) study agent injections. Early re-opening of the EVD occurred in 3.9%. Shunting for hydrocephalus occurred in 18.6% over 1 year follow-up and was associated with % of high ICP events &gt;20 and 30 mmHg (p=0.01 for both). After adjustment for ICH severity factors and IVH volume, % of ICP readings&gt;20 mmHg was significantly associated with 30 and 180 day mortality (p=0.01; p=0.03 respectively), and borderline with modified Rankin Scale (mRS4-6) (p=0.09; p=0.11 respectively). Proportion of CPP readings &lt;70mmHg was associated with day 30 poor mRS (p=0.02), with a weaker association for day 180 mRS (p=0.07). Conclusions: Elevated ICP and inadequate CPP are not infrequent during monitoring and EVD drainage in severe IVH and predict higher short and long-term mortality. Early opening of the lower ventricular system may reduce high ICP events. These results permit future correlation of ICP and CPP with treatment rendered (thrombolysis vs placebo), with upcoming unblinding of the trial.

Abstract 217: Venous Thromboembolism in Patients With Spontaneous Intraventricular Hemorrhage- Results From the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III Trial

Introduction: Intraventricular hemorrhage (IVH) occurs in about 40% of patients with intracerebral hemorrhage (ICH) and is associated with higher mortality and worse outcomes than ICH patients without IVH. Venous thromboembolism (VTE) is common in ICH patients but data in IVH patients are limited. Methods: Prospective analysis of adjudicated adverse event reporting of VTE (deep venous thrombosis (DVT) and pulmonary embolism (PE)) during first 180 days in 500 patients enrolled in the CLEAR III trial, a multicenter, double-blind, randomized study comparing external ventricular drain (EVD) + intraventricular recombinant tissue plasminogen activator (rtPA) vs EVD + placebo for treatment of obstructive IVH and intracerebral hemorrhage (ICH) volume &lt;30cc. Outcome measures were 90-day and 180-day mortality, ICU and hospital length of stay (LOS), catheter tract hemorrhage as well as predictors of VTE. Results: VTE was reported in 63 patients (13%); 46 (9%), 11 (2%) and 6 (1%) patients had DVT, PE or both, respectively. VTE occurred between 4 and 209 days from ICH onset. VTE pharmacologic prophylaxis was initiated in 404 (81%) patients, at median of 4 days [range:1-48] from ICH onset. Unfractionated and low molecular weight heparin were used in 71% and 29% patients, respectively. These patients had similar rates of VTE but showed a trend towards higher catheter tract hemorrhages (25 vs 15%, p=0.056) as compared to those who did not receive VTE prophylaxis. Patients who developed VTE had similar 90-d and 180-d mortality and ICU LOS but had prolonged hospital LOS (p=0.012) as compared to those who did not develop VTE. On multivariable analysis, ICH volume was a significant predictor of development of VTE (OR 1.04, 95% CI: 1.01-1.07, p=0.024). Conclusions: The association of IVH with VTE is important but complex, in spite of consideration of early VTE prophylaxis. There was trend towards higher catheter tract hemorrhages in patients receiving VTE prophylaxis. ICH volume was a significant predictor of VTE development. However, mortality and ICU LOS were not affected by VTE development. These results form a basis for future correlation of VTE complications with treatment rendered (thrombolysis versus placebo), with upcoming unblinding of the trial.

Abstract WMP86: Evaluation of Cerebrospinal Fluid Dynamics and External Ventricular Drain Management in the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage trial (CLEAR III)

Background: Acute obstructive hydrocephalus secondary to spontaneous intracerebral/intraventricular hemorrhage (ICH/IVH) requires early cerebrospinal fluid (CSF) drainage to reduce intracranial pressure (ICP). Extensive CSF drainage may reduce IVH clot burden. We characterize CSF dynamics, strategies and impact on end of treatment (EOT) IVH volume (72 hours post randomization [Rand]) in the CLEAR III trial. Methods: Prospective analysis of CSF output in all 500 patients enrolled in the CLEAR III trial, a multicenter, double-blind, randomized study comparing EVD + intraventricular recombinant tissue plasminogen activator (rtPA) vs. EVD + placebo for treatment of obstructive IVH and intracerebral hemorrhage (ICH) volume &lt;30cc. CSF output was recorded every 4 hours until 7 days post Rand, and compared by clinical and radiological variables. Results: Daily median CSF output in the first week was 188cc (IQR: 125, 252). Maximum daily EVD drip settings were &lt;10mmHg in 27.8%, =10 in 44.1% and &gt;10 in 28.1%. Independent predictors of higher daily CSF output after adjustment for initial IVH volume (p=0.04) were lower drip setting (p&lt;0.001), lower age (p&lt;0.001), male sex (p=0.03), dual EVD (p=0.005), CSF protein (p&lt;0.001) and ICP&gt;20mmHg (P=0.007). Both EOT IVH volume and change in IVH volume (ChgIVH) (over 1 st week) were independently associated with total CSF output (P=0.004/&lt;0.001, respectively), and initial IVH volume (P&lt;0.001/&lt;0.001)). Early opening of 3 rd and 4 th ventricle (P=0.03) was associated with lower EOT volumes, while CSF protein (P=0.02), and side of EVD ipsilateral to largest IVH (P=0.04) were associated with ChgIVH. Shunting for hydrocephalus was performed in 18.6% over 1 year follow-up and was associated with higher total CSF output over first week (P&lt;0.001). Conclusions: CSF circulation in severe IVH can be assessed by CSF output which is associated with EVD drip management and other clinical variables. EOT IVH volume and IVH volume reduction are important surrogate endpoints which are related to CSF dynamics. VP shunt requirement in spontaneous IVH is associated with early CSF output levels. These results permit future correlation of CSF output with treatment rendered (thrombolysis versus placebo) with upcoming unblinding of the trial.

Abstract WMP96: Incidence of Ischemic Strokes in the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) Phase III Clinical Trial

Background: Concomitant acute ischemic lesions are detected in 0-39% of patients with spontaneous intracerebral hemorrhage (ICH). Etiology and impact on functional outcomes are poorly understood nor is it known if intraventricular recombinant tissue plasminogen activator (rtPA) impacts incidence. Methods: Prospective analysis of incidence and etiology of ischemic lesions in all 500 patients enrolled in the CLEAR III trial, a multicenter, double-blind, randomized study comparing EVD + intraventricular rtPA vs. EVD + placebo for treatment of obstructive intraventricular hemorrhage (IVH) and ICH volume &lt;30cc. Two independent stroke neurologists (WZ and LR) evaluated clinical ischemic events reported during acute hospitalization. Results: Ischemic strokes occurred in 19/500 (3.8%) at median [iqr] 10[5,19] days after ICH onset. Mean age was 57.3±10.5 years. Median NIHSS was 18[12.5-37]. ICH locations were basal ganglia (15/19), frontal lobe (1); 3/19 had primary IVH. All strokes but one were distant from the ICH (7 contralateral, 6 bilateral, 3 ipsilateral,1 infratentorial). Compared to patients without strokes, patients with strokes had similar ICH (8.1[12.5] vs. 7.7[10.9]cc) and IVH volumes (23.2[30.1] vs. 24.6[25.3]cc), non-significantly higher admission systolic (201[43] vs. 193[53]mmHg) and diastolic (111[22] vs. 107[35]mmHg) blood pressure (BP), and larger decrease in SBP from admission to randomization (54.5[38] vs. 48[54]mmHg, p=0.13). Mortality was significantly higher in patients with strokes at 30 (26.3% vs. 8.5%, p=0.008) and at 180 days (33.3% vs. 13.7%, p=0.02). Mortality was significantly associated with ischemic stroke after adjustment for ICH and IVH volumes, age and Glasgow Coma Scale (p=0.03 for both day 30 and 180). There were no significant differences in comorbidities between the two groups. Conclusions: Incidence of ischemic strokes in the CLEAR III trial was low but significantly associated with increased early and late mortality. Mass effect and stroke risk factors did not appear to contribute. Acute phase BP reduction may be a predisposing factor. These results permit future correlation of ischemic complications with treatment rendered (thrombolysis versus placebo), with upcoming unblinding of the trial.

Pharmacokinetics and Pharmacodynamics of Tissue Plasminogen Activator Administered Through an External Ventricular Drain.

Intraventricular hemorrhage (IVH) frequently complicates spontaneous intracerebral or subarachnoid hemorrhage (SAH). Administration of intraventricular tissue plasminogen activator (TPA) accelerates blood clearance, but optimal dosing has not been clarified. Using a standardized TPA dose, we assessed peak cerebrospinal fluid (CSF) TPA concentrations, the rate at which TPA clears, and the relationship between TPA concentration and biological activity. Twelve patients with aneurysmal SAH and IVH, treated with endovascular coiling and ventricular drainage, were randomized to receive either 2mg intraventricular TPA or placebo every 12h (five doses). CT scans were performed 12, 48, and 72h after initial administration, and blood was quantified using the SAH Sum and IVH Scores. CSF TPA and fibrin degradation product (D-dimer) concentrations were measured at baseline and 1, 6, and 12h after the first dose using ELISA assays. Median CSF TPA concentrations in seven TPA-treated patients were 525 (IQR 352-2129), 323 (233-413), and 47 (29-283) ng/ml, respectively, at 1, 6, and 12h after drug administration. Peak concentrations varied markedly (401-8398ng/ml). Two patients still had slightly elevated levels (283-285ng/ml) when the second dose was due after 12h. There was no significant correlation between the magnitude of CSF TPA elevation and the rate of blood clearance or degree of D-dimer elevation. D-dimer peaked at 6h, had declined by 12h, and correlated strongly with radiographic IVH clearance (r=0.82, p=0.02). The pharmacokinetics of intraventricular TPA administration varies between individual patients. TPA dose does not need to exceed 2mg. The optimal administration interval is every 8-12h.

Abstract T P316: Occurrence of Intracranial Hypertension in the First 400 Patients Enrolled in the Clot Lysis: Evaluation of Accelerated Resolution of Intraventricular Hemorrhage Trial (CLEAR III)

Background: Elevated intracranial pressure (ICP) is one proposed mechanism leading to poor outcomes in patients with spontaneous intraventricular hemorrhage (IVH). We characterized occurrence and significance of intracranial hypertension in severe IVH requiring extraventricular drainage (EVD). Methods: Prospective analysis of ICP in the first 400 patients enrolled in the CLEAR III trial, a multicenter, double-blind, randomized study comparing EVD plus intraventricular recombinant tissue plasminogen activator (rtPA) vs. EVD plus placebo for treatment of IVH in patients with obstructive IVH and intracerebral hemorrhage (ICH) volume &lt;30cc. Maximum and minimum ICP was recorded every 4 hours in all patients until 7 days post randomization. ICP readings were analyzed at pre-defined thresholds and proportion of high ICP events compared by clinical/radiological variables. Impact on 30 day mortality was assessed. Results: of 17,593 ICP readings, maximum ICP ranged from -4 to 115 mm Hg (median, interquartile range; 11,8); 90.2% (15,861) were ≤ 20 mm Hg, 2.0% were &gt;30, 0.5% were &gt;40, and 0.2% were &gt; 50 mm Hg. Proportion of threshold events &gt; 20 and &gt; 30 mm Hg were more frequent in patients with persistent closure of the lower ventricular system after day 3 (p=0.047 and p=0.04, respectively), but were not correlated with initial or end of treatment (72 hours after last dose of study agent) ICH or IVH volumes. ICP elevation &gt; 20 mm Hg occurred during a required 1 hr EVD closure time after study agent injection in 507/3364 (15.1%) injections although early re-opening of EVDs occurred in only 3.9%. Shunting for hydrocephalus was required in 18% of patients over 1 yr follow-up and was not associated with high ICP events. Percentage of ICP readings per patient &gt; 30 mmHg and ICH/IVH volumes were independent predictors of 30 day mortality after adjustment for other outcome predictors (p=0.01; p=0.04; p&lt;0.001, respectively). Conclusions: ICP is not frequently elevated during monitoring and drainage with an EVD in patients with severe IVH. ICP &gt; 30 mm Hg predicts higher short-term mortality. Early opening of the lower ventricular system may reduce frequency of high ICP events. Injection of thrombolytics can be performed without additional ICP management in the majority of patients.

Intraventricular Tissue Plasminogen Activator in Subarachnoid Hemorrhage Patients: A Prospective, Randomized, Placebo-Controlled Pilot Trial

The quantity of subarachnoid (SAH) and intraventricular hemorrhage (IVH) occurring in the setting of a ruptured cerebral aneurysm is strongly associated with subsequent complications and poor outcomes. We randomly allocated aneurysmal SAH patients with a modified Fisher score of 4, who had been treated with endovascular coil embolization and ventricular drainage, to receive either 2 mg intraventricular tissue plasminogen activator (TPA) every 12 h (maximum 10 mg) or placebo. Computed tomography scans were performed 12, 48, and 72 h after administration. Primary outcomes included feasibility (enrollment and consent rates), safety (assessed by prospectively screening for complications), and rate of intracranial blood clearance (measured using sequential IVH, modified Graeb, and SAH sum scores). Secondary outcomes included angiographic vasospasm, delayed cerebral ischemia, need for ventriculoperitoneal shunting, and 6-month neurological outcomes. Seventy-seven patients were screened, 17 were eligible, and 12 were randomized. The consent rate was 87 %. There were no cases of new intracranial hemorrhage complicating use of TPA. Models fit using generalized estimating equations demonstrated more rapid reduction in IVH volume (p = 0.009), modified Graeb score (p < 0.001), and SAH sum score (p < 0.001) among patients treated with TPA. SAH clearance at 48 h was enhanced by earlier drug administration (p = 0.02). There were no differences in secondary outcomes. Intraventricular TPA accelerates clearance of SAH and IVH, especially when administered early. A larger-scale clinical trial of intraventricular TPA is feasible, will need to be conducted at multiple centers, and is required to determine whether this practice reduces complications and improves outcomes.

Intraventricular tissue plasminogen activator for intraventricular hemorrhage caused by an arteriovenous malformation

The use of thrombolytics delivered through an external ventricular drain has improved outcomes in intraventricular hemorrhage, a disease with a poor prognosis; however, presence of an arteriovenous malformation is generally considered a contraindication to thrombolytic use. Due do the high mortality with the current standard of care, thrombolytics should be considered as an acceptable treatment option despite the presence of an arteriovenous malformation in certain clinical situations. We review the available literature and present an additional patient to make the case for the use of thrombolytics for intraventricular hemorrhage from an arteriovenous malformation.

Increased ventriculostomy infection rate with use of intraventricular tissue plasminogen activator: A single-center observation

ObjectiveIntraventricular tissue plasminogen activator (alteplase) has been advocated for prevention of vasospasm in aneurysmal subarachnoid hemorrhage and treatment of traumatic or spontaneous intraventricular hemorrhage. External ventricular drain (EVD) insertion is often performed to manage increased intracranial pressure and hydrocephalus associated with these disease states. EVD-related ventriculitis is a serious infection with an up to 50% mortality rate. MethodsWe assessed the EVD infection rate in patients receiving intraventricular alteplase over a 12-month period. Patients were divided into intraventricular alteplase and non-intraventricular alteplase groups; ventriculitis rates were compared. ResultsEVDs were placed in 93 patients. Six of 7 (86%) patients who received intraventricular alteplase developed ventriculitis versus 4 of 86 (5%) patients in the non-intraventricular alteplase group (p<0.0001). ConclusionIntraventricular alteplase use may increase ventriculitis risk. Currently, we reserve intraventricular alteplase for patients with EVDs obstructed by hematoma accompanied by increased intracranial pressure.

E-006 Endovascular strategies in the management of giants rupture basilar artery aneurysm with massive intraventricular haemorrhage-a case series

BackgroundBasilar artery bifurcation aneurysm (BABA) is primarily repaired by endovascular approach due the poor outcomes associated with surgical clipping. However, there are no clear strategies in the treatment of ruptured...

Successful Treatment of Early Thrombosis of HeartWare Left Ventricular Assist Device With Intraventricular Thrombolytics

In the last few years, left ventricular assist devices (LVADs) have moved to the forefront in the management of patients with advanced heart failure. Pumps have gradually become smaller and more efficient and have clearly demonstrated survival benefits and improvement in functional status and quality of life in patients with advanced heart failure. Despite impressive advances in device technology, risk of severe complications remains, such as device thrombosis. A 62-year-old man who underwent HeartWare LVAD implantation as a bridge to cardiac transplant was admitted 18 days after device implantation with severe shortness of breath, fatigue and lethargy; he was found to have increased pump flows with high power demands and evidence of cardiogenic shock. An echocardiogram showed an echo density at the inflow cannula that was suggestive of thrombosis. Laboratory data showed evidence of hemolysis. He was treated successfully with intraventricular tissue plasminogen activator with rapid resolution of his symptoms and return of LVAD flow and power consumption to baseline. The patient was discharged with no complications or recurrence of thrombosis and received a successful transplant 1 month later.

Emergent, Controlled Lumbar Drainage for Intracranial Pressure Monitoring During Orthotopic Liver Transplantation

Measurement of intracranial pressure (ICP) is recommended in comatose acute liver failure (ALF) patients due to risk of rapid global cerebral edema. External ventricular drains (EVD) can be placed to drain cerebrospinal fluid and monitor ICP simultaneously although this remains controversial in the neurosurgical community given the risk of hemorrhagic complications. We describe a patient with ALF and global cerebral edema whose EVD failed immediately before orthotopic liver transplantation (OLT) in which a lumbar drain (LD) was used temporarily to monitor ICP. We describe a 36 year old patient with ALF and brain edema from acetaminophen overdose who had an EVD placed for ICP monitoring and management. The EVD failed repeatedly (i.e., lost CSF drainage and ICP waveform) despite several saline irrigations and three doses intraventricular tissue plasminogen activator (1 mg) in the hours that immediately preceded her planned emergency OLT. An LD was placed emergently and controlled cerebrospinal fluid (CSF) drainage and ICP measurement was performed by setting the LD at 20 mmHg and leveling at the ear level (foramen of Monro). The LD was removed once the EVD flow was re-established post-OLT. The EVD and LD ICP measurements were reported to be the same just prior to removing the LD. Controlled CSF drainage using a lumbar drain can be used to monitor ICP when leveled at the foramen of Monro if EVD failure occurs perioperatively. The LD can temporarily guide ICP management until the EVD flow can be re-established after OLT.

Intraventricular Hemorrhage Secondary to Intranidal Aneurysm Rupture—Successful Management by Arteriovenous Malformation Embolization Followed by Intraventricular Tissue Plasminogen Activator: Case Report

Intraventricular hemorrhage related to arteriovenous malformation (AVM) rupture is associated with significant morbidity and mortality. Intraventricular tissue plasminogen activator (tPA) has been used to treat spontaneous intraventricular hemorrhage. We demonstrate the successful application of endovascular occlusion to seal the rupture site of an AVM followed by intraventricular tPA. A 32-year-old woman presented with a right frontoparietal parasagittal AVM abutting the motor cortex. The AVM was diagnosed when the patient was 13 years old, and she initially underwent conservative management. At the age of 30, the patient suffered an intracranial hemorrhage, leaving her with left hemiparesis. After rehabilitation, the patient regained ambulation; however, she remained spastic and hyperreflexic on the left side. Two years after her major hemorrhage, she presented for elective treatment of her AVM. The patient was advised to undergo staged embolization before surgical resection of her AVM. The initial embolization was uneventful. A second embolization was complicated by intraventricular hemorrhage and coma. The patient was treated with placement of an external ventricular drain followed by embolization of intranidal aneurysm. After embolization of the intranidal aneurysm the ruptured, the patient was treated with intraventricular tPA. The patient had rapid clearance of the intraventricular hemorrhage and significant improvement in her neurological examination, following commands 24 hours later and returning almost to baseline. This case demonstrates the feasibility of treating AVM-related intraventricular hemorrhage with tPA if the rupture source can be confidently sealed interventionally. This strategy can be lifesaving but needs further study to ensure its safety.

Intraventricular Tissue Plasminogen Activator for the Prevention of Vasospasm and Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage

The sequelae of aneurysmal subarachnoid hemorrhage (SAH) include vasospasm and hydrocephalus. To assess whether intraventricular tissue plasminogen activator (tPA) results in less vasospasm, fewer angioplasties, or fewer cerebrospinal fluid shunting procedures. 41 patients (tPA group, Hunt and Hess 3, 4, 5) from 2007 to 2008 received intraventricular tPA and lumbar drainage for a minimum of 5 days (range 5-7 days) and were compared to a matched group of 35 patients from 2006 to 2007 (Control, HH 3, 4, 5). Statistical comparison was done by t test analysis or Fisher exact tests and data are expressed as average+/-standard error of the mean. There were no significant differences in demographic data, although the tPA group had a trend toward more surgical patients. The tPA group of patients had a significantly higher modified Fisher grade than controls (P<.001) and had a significantly better Hunt and Hess grade than controls (P<.03). The angioplasty rate was significantly lower among the tPA patients (15.0%+/-5.6) than controls (40.0%+/-8.5, P=.019). The number of days spent in severe vasospasm normalized over the 14-day monitoring period by transcranial Doppler was significantly lower in the tPA group (0.09+/-0.02) than controls (0.17+/-0.03). The shunt rate was significantly lower among tPA patients (17.5%+/-6.0) than controls (42.8%+/-8.6). There were 2 clinically silent tract hemorrhages in the tPA group (4.8%). Intraventricular tPA is a safe and effective treatment for reducing both angioplasty and shunting rates in patients with SAH H&H Grades 3 to 5. A randomized trial is indicated.

016 Intraventricular tissue plasminogen activator for the prevention of vasospasm and hydrocephalus after aneurysmal subarachnoid hemorrhage

Introduction: Among the sequelae of aneurysmal SAH are vasospasm and hydrocephalus. This study aims to assess whether intraventricular tissue plasminogen activator (tPA) results in fewer angioplasties and/or CSF shunting procedures....

Ruptured saccular aneurysm of distal vertebral artery fenestration managed with Guglielmi detachable coils and intraventricular tissue plasminogen activator

Background Aneurysms associated with vertebrobasilar fenestrations are uncommon. We report on an unusual presentation of such aneurysm with a dedicated arterial pedicle, manifesting with significant intraventricular hemorrhage. Equally important, the aneurysm was managed in a multidisciplinary fashion, which, we think, greatly contributed to a good outcome. Case Description A 55-year-old man presented in good condition after subarachnoid and massive intraventricular hemorrhage. The aneurysm location and the extent of intraventricular hemorrhage both presented concerns regarding treatment approach. The aneurysm was first treated with transarterial coil obliteration, and intraventricular tissue plasminogen activator (tPA) infusion was given, with rapid resolution of evolving hydrocephalus. The patient had an excellent outcome. Conclusion To our knowledge, this is the first report of a vertebrobasilar fenestration saccular aneurysm with a dedicated pedicle projecting toward the foramen of Magendie with significant intraventricular hemorrhage. In addition, this patient was successfully managed with endovascular obliteration and intraventricular tPA infusion.

Intraventricular Hemorrhage after Aneurysmal Subarachnoid Hemorrhage: Pilot Study of Treatment with Intraventricular Tissue Plasminogen Activator

Intraventricular (IVen) hemorrhage is considered a predictor of poor outcome after subarachnoid hemorrhage (SAH). This prospective study examines the feasibility and outcome of administration of IVen tissue plasminogen activator (tPA) after aneurysmal SAH. Ten patients with SAH who received IVen tPA after the aneurysm had been secured were compared with 10 age-, sex-, and Glasgow Coma Scale score-matched control patients. The primary end point was third and fourth ventricle clot resolution. IVen blood was quantified by use of the Graeb and Le Roux scales on admission and at an additional time (equal or longer for the control group) after the injection was terminated. Six men and four women with a mean age of 52 years in each group were evaluated. On average, 3.5 mg tPA was injected 68 +/- 51 hours after admission without ensuing complications. Although the treated group had significantly more IVen blood on admission than control subjects (mean Le Roux scale +/- standard deviation, 11 +/- 3 versus 7.6 +/- 4.2, P = 0.055, and mean Graeb scale +/- standard deviation, 8.5 +/- 2.3 in tPA versus 5.3 +/- 3, P < 0.02), it also had a significant decrease in the amount of IVen blood (mean Le Roux and Graeb scale decrease +/- standard deviation, 6.7 +/- 3.3 and 4.8 +/- 2 in tPA patients versus 0.9 +/- 3.2 and 0.5 +/- 2.6 in control subjects, P = 0.002). The tPA group had a non-statistically significantly shorter length of stay, decreased mortality, and better Glasgow Outcome Scale and modified Rankin Scale scores at discharge. Treated survivors showed a decreased need for shunt placement (2 [22%] of 9 patients versus 5 [83%] of 6 control subjects, P = 0.04). This pilot study shows that IVen tPA administration is feasible without complications after SAH and may be associated with better outcomes. These results warrant a randomized clinical trial.