Tag: Tissue plasminogen activator

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Surgical Performance in Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation

Neurosurgery 81:860–866, 2017

Minimally invasive thrombolytic evacuation of intracerebral hematoma is being investigated in the ongoing phase III clinical trial of Minimally Invasive Surgery plus recombinant Tissue plasminogen activator for Intracerebral hemorrhage Evacuation (MISTIE III).

OBJECTIVE: To assess the accuracy of catheter placement and efficacy of hematoma evacuation in relation to surgical approach and surgeon experience.

METHODS:We performed a trial midpoint interim assessment of 123 cases that underwent the surgical procedure. Accuracy of catheter placement was prospectively assessed by the trial Surgical Center based on prearticulated criteria. Hematoma evacuation efficacy was evaluated based on absolute volume reduction, percentage hematoma evacuation, and reaching the target end-of-treatment volume of <15 mL. One of 3 surgical trajectories was used: anterior (A), posterior (B), and lobar (C). Surgeonswere classified based on experience with the MISTIE procedure as prequalified, qualified with probation, and fully qualified.

RESULTS: The average hematoma volume was 49.7 mL (range 20.0-124), and the mean evacuation rate was 71% (range 18.4%-99.8%). First placed catheters were 58% in good position, 28% suboptimal (but suitable to dose), and 14% poor (requiring repositioning). Posterior trajectory (B) was associated with significantly higher rates of poor placement (35%, P = .01). There was no significant difference in catheter placement accuracy among surgeons of varying experience. Hematoma evacuation efficacy was not significantly different among the 3 surgical approaches or different surgeons’ experience.

CONCLUSION: Ongoing surgical education and quality monitoring in MISTIE III have resulted in consistent rates of hematoma evacuation despite technical challenges with the surgical approaches and among surgeons of varying experience.

 

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Minimally invasive treatment for intracerebral hemorrhage

Neurosurg Focus 32 (4):E3, 2012. http://thejns.org/doi/abs/10.3171/2012.1.FOCUS11362

Spontaneous intracerebral hemorrhage is a serious public health problem and is fatal in 30%–50% of all occurrences. The role of open surgical management of supratentorial intracerebral hemorrhage is still unresolved. A recent consensus conference sponsored by the National Institutes of Health suggests that minimally invasive techniques to evacuate clots appear to be a promising area and warrant further investigation. In this paper the authors review past, current, and potential future methods of treating intraparenchymal hemorrhages with minimally invasive techniques and review new data regarding the role of stereotactically placed catheters and thrombolytics.

A minimally invasive approach to evacuate ICH has been well documented to be a safe practice. Thus far, the CLEAR and MISTIE studies have supported this assertion. An increased rate of clot lysis could potentially be achieved with a combination of mechanical and pharmaceutical approaches. However, more extensive studies need to be conducted to determine whether the additional mechanical effects via ultrasound further yield beneficial long-term outcome versus pharmacological lysis alone. Currently, catheters are being redesigned for this purpose and will be evaluated in additional future clinical trials.

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Sonothrombolysis for acute ischemic stroke: a systematic review of randomized controlled trials

Neurosurg Focus 32 (1):E5, 2012. 10.3171/2011.10.FOCUS11251

Sonothrombolysis has recently been considered an emerging modality for the treatment of stroke. The purpose of the present paper was to review randomized clinical studies concerning the effects of sonothrombolysis associated with tissue plasminogen activator (tPA) on acute ischemic stroke.

METHODS

Systematic searches for literature published between January 1996 and July 2011 were performed for studies regarding sonothrombolysis combined with tPA for acute ischemic stroke. Only randomized controlled trials were included. Data extraction was based on ultrasound variables, patient characteristics, and outcome variables (rate of intracranial hemorrhages and arterial recanalization).

RESULTS

Four trials were included in this study; 2 trials evaluated the effect of transcranial Doppler (TCD) ultrasonography on sonothrombolysis, and 2 addressed transcranial color-coded duplex (TCCD) ultrasonography. The frequency of ultrasound waves varied from 1.8 to 2 MHz. The duration of thrombus exposure to ultrasound energy ranged from 60 to 120 minutes. Sample sizes were small, recanalization was evaluated at different time points (60 and 120 minutes), and inclusion criteria were heterogeneous. Sonothrombolysis combined with tPA did not lead to an increase in symptomatic intracranial hemorrhagic complications. Two studies demonstrated that patients treated with ultrasound combined with tPA had statistically significant higher rates of recanalization than patients treated with tPA alone.

CONCLUSIONS

Despite the heterogeneity and the limitations of the reviewed studies, there is evidence that sonothrombolysis associated with tPA is a safe procedure and results in an increased rate of recanalization in the setting of acute ischemic stroke when wave frequencies and energy intensities of diagnostic ultrasound systems are used.

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Minimally invasive evacuation of spontaneous intracerebral hemorrhage using sonothrombolysis

J Neurosurg 115:592–601, 2011. DOI: 10.3171/2011.5.JNS10505

Catheter-based evacuation is a novel surgical approach for the treatment of brain hemorrhage. The object of this study was to evaluate the safety and efficacy of ultrasound in combination with recombinant tissue plasminogen activator (rt-PA) delivered through a microcatheter directly into spontaneous intraventricular (IVH) or intracerebral (ICH) hemorrhage in humans.

Methods. Thirty-three patients presenting to the Swedish Medical Center in Seattle, Washington, with ICH and IVH were screened between November 21, 2008, and July 13, 2009, for entry into this study. Entry criteria included the spontaneous onset of intracranial hemorrhage ≥ 25 ml and/or IVH producing ventricular obstruction. Nine patients (6 males and 3 females, with an average age of 63 years [range 38–83 years]) who met the entry criteria consented to participate and were entered into the trial. A ventricular drainage catheter and an ultrasound microcatheter were stereotactically delivered together, directly into the IVH or ICH. Recombinant tissue plasminogen activator and 24 hours of continuous ultrasound were delivered to the clot. Gravity drainage was performed. In patients with IVHs, 3 mg of rt-PA was injected; in patients with intraparenchymal hemorrhages, 0.9 mg of rt-PA was injected. The rt-PA was delivered in 3 doses over 24 hours.

Results. All patients had significant volume reductions in the treated hemorrhage. The mean percentage volume reduction after 24 hours of therapy, as determined on CT and compared with pretreatment stability scans, was 59 ± 5% (mean ± SEM) for ICH and 45.1 ± 13% for IVH (1 patient with ICH was excluded from analysis because of catheter breakage). There were no intracranial infections and no significant episodes of rebleeding according to clinical or CT assessment. One death occurred by 30 days after admission. Clinical improvements as determined by a decrease in the National Institutes of Health Stroke Scale score were demonstrated at 30 days after treatment in 7 of 9 patients. The rate of hemorrhage lysis was compared between 8 patients who completed treatment, and patient cohorts treated for IVH and ICH using identical doses of rt-PA and catheter drainage but without the ultrasound (courtesy of the MISTIE [Minimally Invasive Surgery plus T-PA for Intracerebral Hemorrhage Evacuation] and CLEAR II [Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage II] studies). Compared with the MISTIE and CLEAR data, the authors observed a faster rate of lysis during treatment for IVH and ICH in the patients treated with sonolysis plus rt-PA versus rt-PA alone.

Conclusions. Lysis and drainage of spontaneous ICH and IVH with a reduction in mass effect can be accomplished rapidly and safely through sonothrombolysis using stereotactically delivered drainage and ultrasound catheters via a bur hole. A larger clinical trial with catheters specifically designed for brain blood clot removal is warranted.

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

Neurosurgery 67:110-117, 2010 DOI: 10.1227/01.NEU.0000370920.44359.91

The sequelae of aneurysmal subarachnoid hemorrhage (SAH) include vasospasm and hydrocephalus.

OBJECTIVE: To assess whether intraventricular tissue plasminogen activator (tPA) results in less vasospasm, fewer angioplasties, or fewer cerebrospinal fluid shunting procedures.

METHODS: 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.

RESULTS: 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%).

CONCLUSION: 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.

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Exacerbation of Perihematomal Edema and Sterile Meningitis With Intraventricular Administration of Tissue Plasminogen Activator in Patients With Intracerebral Hemorrhage

Neurosurgery 66:631-638, 2010. DOI: 10.1227/01.NEU.0000367634.89384.4B

Intraventricular hemorrhage (IVH) is associated with a poor outcome. External ventricular drainage together with clot lysis through intrathecal tissue plasminogen activator (IT-tPA) has been proposed as a promising therapy. However, recent experimental work has implicated tissue plasminogen activator (tPA) in the pathogenesis of cerebral edema.

METHODS: We reviewed the records of all patients with IVH caused by primary supratentorial intracerebral hemorrhage who underwent external ventricular drainage without surgical evacuation between January 2001 and June 2008. Of these 30 patients, we identified 13 who received IT-tPA. The remaining 17 patients served as controls. Hemorrhage, edema volume, and IVH score were determined on admission and by follow-up computed tomographic scans for 96 hours after admission. Discharge outcome was evaluated using the modified Rankin Scale.

RESULTS: There were no significant differences between the treatment and controls in terms of age, Glasgow Coma Scale score, Graeb and LeRoux IVH scores, or intracerebral hemorrhage volume on admission. IT-tPA resulted in more rapid clearance of IVH as determined by the 96-hour decrease in both the Graeb IVH score (tPA, 3.00 ± .55; control, 1.00 ± 0.57; P = .05) and the LeRoux IVH score (tPA, 6.2 ± 0.80; control, 2.25 ± 1.32; P = .05). Patients treated with IT-tPA demonstrated significantly larger peak ratios of edema to intracerebral hemorrhage volume (1.24 ± 0.14 vs 0.70 ± 0.08 in controls; P = .002). Additionally, increased rates of sterile meningitis (46% vs 12%; P = .049) and a trend toward shunt dependence (38% vs 6%; P = .06) were observed in the tPA cohort. Nevertheless, no significant differences in outcome at discharge or length of hospital stay were observed between cohorts.

CONCLUSION: Although IT-tPA hastens the resolution of IVH, it may worsen perihematomal edema formation. Larger prospective studies are required to confirm these findings and to determine whether outcome is adversely affected by IT-tPA administration.

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