Inflammatory response to intraventricular hemorrhage: Time course, magnitude and effect of t-PA

Hallevi, Hen; Walker, Kyle C.; Kasam, Mallikarjunarao; Bornstein, Natan M.; Grotta, James C.; Savitz, Sean I

doi:10.1016/j.jns.2011.11.019

Cited by 33 publications

(35 citation statements)

References 14 publications

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“…It is most likely that part of the process of both END and LND is driven by obstruction of the cerebrovascular fluid circulation and other harmful processes related to IVH. 7 30 31 We encountered two phenomena not described in great detail in the literature-delayed IVH and expansion of the IVH volume. Both of these have previously been described as independent predictors of poor outcome-to the best of our knowledge never before in relation to ND, 32 33 though intuitively correlated.…”

Section: Discussionmentioning

confidence: 96%

“…Further, little is known about late ND (LND), even though the existence of LND is well established among clinicians. 4 6 Evidence indicates that structural damage as well as secondary space-occupying lesions in the brain occurs predominantly during the very first days of illness [7][8][9][10][11][12] ( provoking END and LND). Assuming minimisation of complications by means of adequate stroke unit care (including aspiration pneumonia,…”

Section: Introductionmentioning

confidence: 99%

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Prediction and prognostication of neurological deterioration in patients with acute ICH: a hospital-based cohort study

et al. 2015

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ObjectivePatients with intracerebral haemorrhage (ICH) are at high risk of neurological deterioration (ND). We aimed at establishing predictors of early ND (END) as well as late ND (LND) and at exploring the impact of neurological stability during the first week on long-term prognosis.DesignWe conducted this study as a retrospective cohort study. ND was evaluated based on the consciousness and severity of neurological symptoms. ND during the first 24 h after admission was defined as early ND and from 24 h to 7 days as LND. Patients were followed up until February 2015.ParticipantsWe included 300 patients with acute ICH (≤4.5 h from symptom onset) who were admitted to our institution from March 2009 to January 2015.SettingSection of Acute Neurology, Department of Neurology, Bispebjerg Hospital is a specialised referral centre receiving patients with acute stroke from the entire capital region of Denmark.ResultsWe found that a spot sign on CT angiography (OR 10.7 CI 4.79 to 24.3) and extensive degree of interventricular haemorrhage (IVH) (OR 8.73 CI 2.87 to 26.5) were independent predictors of END, whereas a degree of comorbidity (Charlton Index), admission stroke severity and degree of IVH predicted LND. On follow-up imaging, haematoma expansion was independently associated with END (OR 6.1 CI 2.2 to 17.3), and expansion of IVH was independently associated with both END (OR 1.7 CI 1.2 to 2.3 per point increase) and LND (OR 2.3 CI 1.3 to 4.2 per point increase). ND during the first week was associated with a 1-year mortality of 60.5%, compared with 9.2% among the patients who remained stable.ConclusionsThese results suggest that stability during the first week entails an optimistic prognosis. A relatively easy and effective risk stratification of END and LND is possible on admission based on the spot sign, IVH and clinical parameters.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Prediction and prognostication of neurological deterioration in patients with acute ICH: a hospital-based cohort study

et al. 2015

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“…Clinically, IVH results in changes in CSF protein concentrations (e.g. [29–33]). While changes in blood-CSF barrier function are one parameter that can affect those concentrations, assessing barrier function from such data is very difficult, particularly in the setting of IVH.…”

Section: Choroid Plexus As a Site Of Injurymentioning

confidence: 99%

The choroid plexus as a site of damage in hemorrhagic and ischemic stroke and its role in responding to injury

Xiang

Routhe

Wilkinson

et al. 2017

Fluids Barriers CNS

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While the impact of hemorrhagic and ischemic strokes on the blood–brain barrier has been extensively studied, the impact of these types of stroke on the choroid plexus, site of the blood-CSF barrier, has received much less attention. The purpose of this review is to examine evidence of choroid plexus injury in clinical and preclinical studies of intraventricular hemorrhage, subarachnoid hemorrhage, intracerebral hemorrhage and ischemic stroke. It then discusses evidence that the choroid plexuses are important in the response to brain injury, with potential roles in limiting damage. The overall aim of the review is to highlight deficiencies in our knowledge on the impact of hemorrhagic and ischemic strokes on the choroid plexus, particularly with reference to intraventricular hemorrhage, and to suggest that a greater understanding of the response of the choroid plexus to stroke may open new avenues for brain protection.

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“…[17][18][19][20][21] Observational human studies have reached conflicting conclusions, with some suggesting that intraventricular TPA induces sterile meningitis and increases perihematomal edema, and others reporting that it has no such effect and may, by removing blood, actually reduce inflammation. [22][23][24][25] If intraventricular TPA does have toxic effects, it could attenuate any therapeutic benefit derived from more rapid clearance of blood. Concentrations of cytokines are known to be elevated in the cerebrospinal fluid (CSF) of patients with SAH, particularly among those with a higher clinical grade, and to be associated with a greater risk of complications and poor neurologic outcomes.…”

Section: Introductionmentioning

confidence: 99%

Intraventricular Fibrinolysis with Tissue Plasminogen Activator is Associated with Transient Cerebrospinal Fluid Inflammation: A Randomized Controlled Trial

Kramer

Jenne

Zygun

et al. 2015

J Cereb Blood Flow Metab

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Locally administered tissue plasminogen activator (TPA) accelerates clearance of intraventricular hemorrhage (IVH), but its impact on neurologic outcomes remains unclear and preclinical research suggests it may have pro-inflammatory effects. We randomly allocated patients with ruptured cerebral aneurysms and IVH, treated with endovascular coiling and ventricular drainage, to receive either 2-mg intraventricular TPA or placebo every 12 hours. Cerebrospinal fluid (CSF) and serum cytokine and white blood cell (WBC) concentrations were measured before drug administration and daily for 72 hours. Cerebrospinal fluid D-dimer levels were assessed 6 and 12 hours after administration to quantify fibrinolysis. Six patients were randomized to each group. Patients treated with TPA developed higher CSF cytokine concentrations compared with placebo-treated patients ( P < 0.05 for tumor necrosis factor- α, interferon- γ, interleukin (IL)-1 α, IL-1 β, IL-2, IL-4, and IL-6), as well as higher CSF WBC counts ( P = 0.03). Differences were greatest after 24 hours and decreased over 48 to 72 hours. The magnitude of the inflammatory response was significantly associated with peak CSF D-dimer concentration and extent of IVH clearance. We conclude that intraventricular TPA administration produces a transient local inflammatory response, the severity of which is strongly associated with the degree of fibrinolysis, suggesting it may be induced by release of hematoma breakdown products, rather than the drug itself.

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Inflammatory response to intraventricular hemorrhage: Time course, magnitude and effect of t-PA

Cited by 33 publications

References 14 publications

Prediction and prognostication of neurological deterioration in patients with acute ICH: a hospital-based cohort study

Prediction and prognostication of neurological deterioration in patients with acute ICH: a hospital-based cohort study

The choroid plexus as a site of damage in hemorrhagic and ischemic stroke and its role in responding to injury

Intraventricular Fibrinolysis with Tissue Plasminogen Activator is Associated with Transient Cerebrospinal Fluid Inflammation: A Randomized Controlled Trial

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