scholarly journals Spontaneous Intraventricular Hemorrhage: When Should Intraventricular tPA Be Considered?

2017 ◽  
Vol 38 (06) ◽  
pp. 745-759 ◽  
Author(s):  
Peter Abdelmalik ◽  
Wendy Ziai
Keyword(s):  
Intraventricular Hemorrhage ◽  
Obstructive Hydrocephalus ◽  
External Ventricular Drain ◽  
Standard Of Care ◽  
Phase Iii ◽  
Functional Improvement ◽  
Severity Factor ◽  
Surgical Interventions ◽  
Intraventricular Fibrinolysis ◽  
Recent Phase

AbstractSpontaneous intracerebral hemorrhage (ICH) is the most common cause of intraventricular hemorrhage (IVH) in adults. Complicating approximately 40% of ICH cases, IVH adds to the morbidity and mortality of this often fatal form of stroke. It is also a severity factor that complicates subarachnoid hemorrhage and traumatic brain injury, along with other less common causes of intracranial bleeding. Medical and surgical interventions to date have focused on limiting ICH and IVH expansion, controlling intracranial pressure, and relieving obstructive hydrocephalus. The placement of an external ventricular drain (EVD) can achieve the latter two goals but has not demonstrated improvement in clinical outcomes beyond mortality reduction. More recently, intraventricular fibrinolysis, utilizing the EVD, has gained interest as a safe and potentially effective method to maintain catheter patency and facilitate hematoma removal. A recent phase III clinical trial evaluating the efficacy of intraventricular alteplase versus intraventricular saline showed a mortality benefit, but failed to meet the primary endpoint of significant functional improvement. However, planned subgroup analysis focusing on patients with IVH volume > 20 mL, and those with IVH removal > 85% suggest that significant functional benefits may be attainable with this therapy. The practice of intraventricular fibrinolysis for spontaneous IVH is not the standard of care; however, based on 20 years of experience, it meets thresholds as a safe intervention, and in those patients with a high burden of intraventricular blood, aggressive clearance may lead to improved quality of life in survivors of this morbid syndrome.

scholarly journals Using low-dose tissue plasminogen activator through external ventricular drain and Cerebrolysin for the treatment of severe intraventricular hemorrhage: A case report

2020 ◽  
Vol 8 ◽  
pp. 2050313X2098146
Author(s):  
Nguyen Hoang Ngoc ◽  
Nguyen Van Tuyen
Keyword(s):  
Arteriovenous Malformation ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Intraventricular Hemorrhage ◽  
Low Dose ◽  
Obstructive Hydrocephalus ◽  
External Ventricular Drain ◽  
Endovascular Embolization ◽  
Intraventricular Fibrinolysis ◽  
Tissue Plasminogen

Acute obstructive hydrocephalus is a complication of intraventricular hemorrhage, which requires a combination of medical and surgical treatments. We report a clinical case of intraventricular hemorrhage extension secondary to a ruptured arteriovenous malformation, successfully treated with a combination of methods: endovascular embolization of arteriovenous malformation, external ventricular drainage, intraventricular fibrinolysis with low-dose recombinant tissue plasminogen activator, and medical treatment with the neurotrophic drug Cerebrolysin in combination with neurorehabilitation.

Recombinant Tissue Plasminogen Activator in the Treatment of Intraventricular Hemorrhage Secondary to Periventricular Arteriovenous Malformation before Surgery: Case Report

Neurosurgery ◽  
2003 ◽  
Vol 52 (4) ◽  
pp. 964-969 ◽  
Author(s):  
Krishna Kumar ◽  
Denny D. Demeria ◽  
Ashok Verma
Keyword(s):  
Magnetic Resonance ◽  
Arteriovenous Malformation ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Intraventricular Hemorrhage ◽  
Surgical Intervention ◽  
Obstructive Hydrocephalus ◽  
External Ventricular Drain ◽  
Recombinant Tissue Plasminogen Activator ◽  
Tissue Plasminogen

Abstract OBJECTIVE AND IMPORTANCE Intraventricular hemorrhage (IVH) is known to cause acute obstructive hydrocephalus, refractory elevated intracranial pressures (ICPs), and lowered cerebral perfusion pressures, leading to cortical ischemia. Frequent obstruction of external ventricular drains as a result of thrombus is a recurring theme. We present a case of IVH secondary to periventricular arteriovenous malformation (AVM) that was not visible at admission angiography and was treated by intraventricular infusion of recombinant tissue plasminogen activator before surgical intervention. CLINICAL PRESENTATION An 11-year-old boy presented with acute onset of headache followed by two seizures, loss of consciousness, decerebration, right temporal hematoma, IVH, and acute obstructive hydrocephalus. INTERVENTION A right external ventricular drain was placed but functioned poorly. ICP could not be controlled by conventional methods. Five milligrams of recombinant tissue plasminogen activator was injected into the ventricular system via the external ventricular drain. This was repeated daily for 4 days. This treatment resulted in progressive improvement in ICP and clinical status. Once the clot partially cleared, magnetic resonance imaging and magnetic resonance angiography suggested the presence of a right periventricular arteriovenous malformation, which was confirmed by angiography and subsequently resected. CONCLUSION Recombinant tissue plasminogen activator is effective in resolving IVH causing obstructive hydrocephalus and uncontrollable ICP posing a life-threatening situation, secondary to ruptured arteriovenous malformation, before surgical intervention.

Time to testosterone (T) and PSA rises during first “off treatment” interval (1OFF-2ON) of intermittent androgen deprivation (IAD) as prognostic for time to castration resistance (CRPC) and prostate cancer mortality (PCM) in men with biochemical relapse (BR).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4557-4557
Author(s):  
Evan Y. Yu ◽  
Kevin F Kuo ◽  
Rachel Hunter-Merrill ◽  
Roman Gulati ◽  
Suzanne P Hall ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Prospective Trial ◽  
Local Therapy ◽  
Standard Of Care ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistance ◽  
Treatment Interval ◽  
Cox Proportional Hazards Models ◽  
Recent Phase

4557 Background: A recent phase III trial of intermittent vs. continuous AD supports IAD as standard of care for men treated with AD for BR. To identify potential prognostic factors during 1OFF, times to T and PSA rises from our prospective trial of IAD in men with BR were analyzed in relation to times to CRPC and PCM. Methods: 72 men with BR after definitive local therapy were treated with IAD, each cycle consisting of 9 months of leuprolide and flutamide followed by a variable “off treatment” interval. T and PSA were followed monthly; AD was resumed when PSA reached a pre-specified value. Cycles repeated until CRPC, defined as ≥2 PSA rises with T≤50 ng/dL. Markers of interest from 1OFF-2ON were time to first T>50, time from first T>50 to first PSA rise ≥0.1 ng/mL, time to first PSA rise ≥0.1, and PSA doubling time (PSAdt), calculated using the first 3 PSA measurements starting from first PSA ≥0.1. The associations of these markers with CRPC and PCM were evaluated using Cox proportional hazards models (or logistic regression if the Cox proportional hazards assumption was not met), controlling for age at study entry and Gleason score categorized to ≤7 or >7. Results: A 30-day increase in time to first T>50 was significantly associated with a 75% increase in the risk of PCM. A 30-day increase in time to PSA rise from 1OFF or after T>50 was significantly associated with a 23% or 72% reduction in the risk of CRPC, respectively. While neither of the associations of PSAdt with CRPC or PCM were significant, they were of moderate size: PSAdt displayed a moderate reduction in risk of CRPC by 35% and PCM by 38%. Conclusions: During the first “off treatment” interval of IAD, the time to first T>50 is prognostic for PCM. Time to first PSA rise after 1OFF and after first T>50 are both prognostic for CRPC. [Table: see text]

scholarly journals Demographic Risk Factors for Vascular Lesions as Etiology of Intraventricular Hemorrhage in Prospectively Screened Cases

2017 ◽  
Vol 43 (5-6) ◽  
pp. 223-230 ◽  
Author(s):  
Maged D. Fam ◽  
Alice Pang ◽  
Hussein A. Zeineddine ◽  
Steven Mayo ◽  
Agnieszka Stadnik ◽  
...  
Keyword(s):  
Intraventricular Hemorrhage ◽  
Clinical Characteristics ◽  
Primary Diagnosis ◽  
Vascular Lesion ◽  
Phase Iii ◽  
Vascular Lesions ◽  
Clot Lysis ◽  
Screening Process ◽  
Intraventricular Fibrinolysis ◽  
Demographic Risk

Background: Spontaneous intraventricular hemorrhage (IVH) is associated with high rates of morbidity and mortality despite critical care and other advances. An important step in clinical management is to confirm/rule out an underlying vascular lesion, which influences further treatment, potential for further bleeding, and prognosis. Our aim is to compare demographic and clinical characteristics between IVH patients with and without an underlying vascular lesion, and among cohorts with different vascular lesions. Methods: We analyzed prospectively collected data of IVH patients screened for eligibility as part of the Clot Lysis: Evaluation Accelerated Resolution of IVH Phase III (CLEAR III) clinical trial. The trial adopted a structured screening process to systematically exclude patients with an underlying vascular lesion as the etiology of IVH. We collected age, sex, ethnicity, and primary diagnosis on these cases and vascular lesions were categorized prospectively as aneurysm, vascular malformation (arteriovenous malformation, dural arteriovenous fistula, and cavernoma), Moyamoya disease, or other vascular lesion. We excluded cases <18 or >80 years of age. Baseline characteristics were compared between the CLEAR group (IVH screened without vascular lesion) and the group of IVH patients screened and excluded from CLEAR because of an identified vascular lesion. We further analyzed the differential demographic and clinical characteristics among subcohorts with different vascular lesions. Results: A total of 10,538 consecutive IVH cases were prospectively screened for the trial between 2011 and 2015. Out of these, 496 cases (4.7%) screened negative for underlying vascular lesion, met the inclusion criteria, and were enrolled in the trial (no vascular etiology group); and 1,205 cases (11.4%) were concurrently screened and excluded from the trial because of a demonstrated underlying vascular lesion (vascular etiology group). Cases with vascular lesion were less likely to be >45 years of age (OR 0.28, 95% CI 0.20-0.40), African-American (OR 0.23, 95% CI 0.18-0.31), or male gender (OR 0.48, 95% CI 0.38-0.60), and more likely to present with primary IVH (OR 1.85, 95% CI 1.37-2.51) compared to those with no vascular etiology (p < 0.001). Other demographic factors were associated with specific vascular lesion etiologies. A combination of demographic features increases the association with the absence of vascular lesion, but not with absolute reliability (OR 0.1, 95% CI 0.06-0.17, p < 0.001). Conclusion: An underlying vascular lesion as etiology of IVH cannot be excluded solely by demographic parameters in any patient. Some form of vascular imaging is necessary in screening patients before contemplating interventions like intraventricular fibrinolysis, where safety may be impacted by the presence of vascular lesion.

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)

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Wendy Ziai ◽  
Mariam Bhuiyan ◽  
Nichol McBee ◽  
Rachel Dlugash ◽  
Kevin Sheth ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Intraventricular Hemorrhage ◽  
Obstructive Hydrocephalus ◽  
External Ventricular Drain ◽  
Randomized Study ◽  
Recombinant Tissue Plasminogen Activator ◽  
Clot Lysis ◽  
Csf Dynamics ◽  
Double Blind ◽  
Csf Drainage

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 <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 <10mmHg in 27.8%, =10 in 44.1% and >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<0.001), lower age (p<0.001), male sex (p=0.03), dual EVD (p=0.005), CSF protein (p<0.001) and ICP>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/<0.001, respectively), and initial IVH volume (P<0.001/<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<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.

Influence of the Extent of Intraventricular Hemorrhage on Functional Outcome and Mortality in Intracerebral Hemorrhage

2019 ◽  
Vol 47 (5-6) ◽  
pp. 245-252 ◽  
Author(s):  
Sebastian S. Roeder ◽  
Maximilian I. Sprügel ◽  
Jochen A. Sembill ◽  
Antje Giede-Jeppe ◽  
Kosmas Macha ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Intraventricular Hemorrhage ◽  
Obstructive Hydrocephalus ◽  
External Ventricular Drain ◽  
Multivariable Analysis ◽  
Unfavorable Outcome ◽  
Unfavorable Clinical Outcome ◽  
Multivariable Analyses ◽  
The Impact

Background and Objective: Intraventricular hemorrhage (IVH) is a verified independent prognostic parameter in patients with intracerebral hemorrhage (ICH). However, the impact of the extent of IVH on clinical outcomes is unestablished. Methods: We analyzed 1,112 consecutive primary ICH patients of the UKER-ICH cohort (NCT03183167) and hypothesized that there is no difference in outcome between patients without IVH and patients with minor IVH not leading to obstructive hydrocephalus. Propensity score matching and multivariable analyses were performed to account for imbalances in baseline characteristics. Primary outcome was defined as functional outcome 3 months after ICH ­assessed using the modified Rankin Scale (mRS) dichotomized into favorable (mRS = 0–3) and unfavorable outcome (mRS = 4–6). Secondary outcomes included mortality at 3  months and a Graeb score-based threshold analysis for association of the extent of IVH with unfavorable clinical outcome. Results: Among the 461 out of 1,112 (41.5%) ICH patients with IVH, 191 out of 461 (41.4%) showed IVH without obstructive hydrocephalus and no requirement of external ventricular drain (EVD) placement. After adjusting for baseline imbalances we found no difference in functional outcome at 3 months between patients without IVH (No-IVH) and patients with IVH not requiring EVD (IVH-w/o-EVD): mRS 0–3: No-IVH 64/161 (39.8%) vs. IVH-w/o-EVD 53/170 (31.2%); p = 0.103. However, there was a trend toward a higher mortality in IVH-w/o-EVD patients (mRS 6: No IVH 40/161 [24.8%] vs. IVH-w/o-EVD 57/170 [33.5%]; p = 0.083). Multivariable analysis revealed that a Graeb score >2 was independently associated with unfavorable outcome (mRS 4–6: OR 3.16 [1.54–6.48]; p = 0.002), and higher mortality (mRS 6: OR 2.57 [1.40–4.74]; p = 0.002) in IVH patients. Conclusions: Small amounts of intraventricular blood (Graeb score ≤2) not leading to obstructive hydrocephalus are not associated with unfavorable outcome or death after ICH. Thus, IVH per se should not be considered a binary variable in outcome prediction for ICH patients.

scholarly journals Perioperative pembrolizumab therapy in muscle-invasive bladder cancer: Phase III KEYNOTE-866 and KEYNOTE-905/EV-303

2021 ◽  
Author(s):  
Matthew D Galsky ◽  
Christopher J Hoimes ◽  
Andrea Necchi ◽  
Neal Shore ◽  
J Alfred Witjes ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Standard Of Care ◽  
Phase Iii ◽  
Invasive Bladder Cancer ◽  
Efficacy And Safety ◽  
Muscle Invasive Bladder Cancer ◽  
Clinical Trial Registration ◽  
Recent Phase ◽  
Muscle Invasive ◽  
Systemic Therapies

Muscle-invasive bladder cancer (MIBC) is associated with high rates of recurrence and poor prognosis despite aggressive treatment. Neoadjuvant chemotherapy before radical cystectomy (RC) improves outcomes in cisplatin-eligible patients; however, the improvement in overall survival is modest. Standard of care for cisplatin-ineligible patients remains RC; more effective systemic therapies are needed. Recent Phase Ib/II studies suggest pembrolizumab monotherapy and combination therapy are effective neoadjuvant therapies for MIBC. The randomized Phase III KEYNOTE-866 and KEYNOTE-905/EV-303 studies are being conducted to evaluate efficacy and safety of perioperative pembrolizumab or placebo with chemotherapy in cisplatin-eligible patients with MIBC (KEYNOTE-866) and of pembrolizumab monotherapy versus pembrolizumab plus enfortumab vedotin versus RC plus pelvic lymph node dissection alone in cisplatin-ineligible patients with MIBC (KEYNOTE-905/EV-303). Clinical trial registration: NCT03924856 & NCT03924895 (ClinicalTrials.gov)

scholarly journals Early Inflammatory Cytokine Expression in Cerebrospinal Fluid of Patients with Spontaneous Intraventricular Hemorrhage

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1123
Author(s):  
Wendy C. Ziai ◽  
Adrian R. Parry-Jones ◽  
Carol B. Thompson ◽  
Lauren H. Sansing ◽  
Michael T. Mullen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Intraventricular Hemorrhage ◽  
Inflammatory Responses ◽  
Obstructive Hydrocephalus ◽  
External Ventricular Drainage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Injury Reduction ◽  
Positive Correlations ◽  
Factor Α ◽  
Perihematomal Edema

We investigated cerebrospinal fluid (CSF) expression of inflammatory cytokines and their relationship with spontaneous intracerebral and intraventricular hemorrhage (ICH, IVH) and perihematomal edema (PHE) volumes in patients with acute IVH. Twenty-eight adults with IVH requiring external ventricular drainage for obstructive hydrocephalus had cerebrospinal fluid (CSF) collected for up to 10 days and had levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), and C-C motif chemokine ligand CCL2 measured using enzyme-linked immunosorbent assay. Median [IQR] ICH and IVH volumes at baseline (T0) were 19.8 [5.8–48.8] and 14.3 [5.3–38] mL respectively. Mean levels of IL-1β, IL-6, IL-10, TNF-α, and CCL2 peaked early compared to day 9–10 (p < 0.05) and decreased across subsequent time periods. Levels of IL-1β, IL-6, IL-8, IL-10, and CCL2 had positive correlations with IVH volume at days 3–8 whereas positive correlations with ICH volume occurred earlier at day 1–2. Significant correlations were found with PHE volume for IL-6, IL-10 and CCL2 at day 1–2 and with relative PHE at days 7–8 or 9–10 for IL-1β, IL-6, IL-8, and IL-10. Time trends of CSF cytokines support experimental data suggesting association of cerebral inflammatory responses with ICH/IVH severity. Pro-inflammatory markers are potential targets for injury reduction.

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