Safety of Thrombolysis in Patients With Acute Ischemic Stroke and Cerebral Cavernous Malformations

Erdur, Hebun; Scheitz, Jan F.; Tütüncü, Serdar; Fiebach, Jochen B.; Endres, Matthias; Werring, David J.; Nolte, Christian H.

doi:10.1161/strokeaha.113.004559

Cited by 10 publications

(8 citation statements)

References 8 publications

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“…Our data are therefore in line with previously published observations of either intra-arterial or systemic thrombolysis for ischemic stroke 3 – 6 , 12 – 14 or myocardial infarction 7 , 8 in patients with benign intracranial tumor, and also contribute to the positive safety results reported in patients with cavernoma. 15 , 17 However, we did observe independent intracranial hemorrhage following thrombolysis in one of the two patients with malignant intracranial neoplasm. This reflects the results of an increased bleeding risk in malignant brain tumor-associated stroke yielded by population-based analysis, 14 as well as by previous case reports that reported secondary intracranial hemorrhage in two of seven patients with malignant intracranial neoplasm (including this report).…”

Section: Discussionmentioning

confidence: 63%

“… 14 Treatment of these patients, however, is beyond the approval of the Food and Drug Administration. Likewise, evidence on the use of IV tissue plasminogen activator (t-PA) in patients with cavernoma is sparse, with 11 individual cases in two case reports 15 , 16 and a single systematic analysis 17 that yielded conflicting results. The aim of this study was to comprehend the risk of IV t-PA treatment in patients with intracranial tumor and cavernoma, in order to facilitate the clinician’s burden of taking the decision in this common but insufficiently respected constellation.…”

Section: Introductionmentioning

confidence: 99%

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Off-label use of IV t-PA in patients with intracranial neoplasm and cavernoma

Schwarzbach

Ebert

Hennerici

et al. 2018

Ther Adv Neurol Disord

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Background:The safety of systemic thrombolysis in patients with intracranial tumor and cavernoma are unknown. So far evidence is limited to a number of case reports and few case series or unspecified data based on population-based analysis. Our aim was to comprehend the risk of systemic thrombolysis in these patients.Methods:Patients with additional evidence of intracranial tumor or cavernoma who received IV tissue plasminogen activator (t-PA) treatment at our comprehensive stroke center over a period of 7 years were identified in our stroke database and compared to the same number of matched control subjects without any evidence of intracranial tumor and cavernoma. Clinical history and imaging patterns before and after t-PA therapy were individually reviewed for each patient.Results:Thirty-four patients with additional evidence of meningioma (19/34), cavernoma (13/34) or malignant intracranial neoplasm (2/34) were identified. The incidence of secondary intracranial hemorrhage observed showed no difference between control subjects (9/34, 26%) and patients (6/34, 18%; p = 0.56). Symptomatic hemorrhage in patients with meningioma or cavernoma could not be observed. Likewise, the prevalence of stroke mimics showed no difference between patients (8/34, 24%) and control subjects (5/34, 15%; p = 0.54). However, both patients with malignant intracranial neoplasm presented with a stroke mimic and intracranial hemorrhage was observed in one of them.Conclusions:In compliance with existing evidence, treatment in patients with meningioma and cavernoma appears to be safe and reasonable, while the therapy should be avoided in patients with malignant intracranial neoplasm with blood–brain barrier disruption.

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Off-label use of IV t-PA in patients with intracranial neoplasm and cavernoma

Schwarzbach

Ebert

Hennerici

et al. 2018

Ther Adv Neurol Disord

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“… 132 We must caution that these studies were uncontrolled, with less likely treatment of patients with recent hemorrhage. Erdur and colleagues 133 report no significant difference in symptomatic ICH and parenchymal hemorrhage rate when comparing 9 patients with CCM compared to 341 patients without CCM undergoing thrombolysis for expected cerebral ischemia. The safety of other medications including estrogens, NSAIDs, triptans, other potential blood-thinning agents (novel anticoagulants, vitamin E, fish oil, selective serotonin reuptake inhibitors) has not been studied or sufficiently studied in patients with CCM to make recommendations.…”

Section: Neurological Considerationsmentioning

confidence: 97%

Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel

et al. 2017

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BACKGROUND: Despite many publications about cerebral cavernous malformations (CCMs), controversy remains regarding diagnostic and management strategies. OBJECTIVE: To develop guidelines for CCM management. METHODS: The Angioma Alliance (www.angioma.org), the patient support group in the United States advocating on behalf of patients and research in CCM, convened a multidisciplinary writing group comprising expert CCM clinicians to help summarize the existing literature related to the clinical care of CCM, focusing on 5 topics: (1) epidemiology and natural history, (2) genetic testing and counseling, (3) diagnostic criteria and radiology standards, (4) neurosurgical considerations, and (5) neurological considerations. The group reviewed literature, rated evidence, developed recommendations, and established consensus, controversies, and knowledge gaps according to a prespecified protocol. RESULTS: Of 1270 publications published between January 1, 1983 and September 31, 2014, we selected 98 based on methodological criteria, and identified 38 additional recent or relevant publications. Topic authors used these publications to summarize current knowledge and arrive at 23 consensus management recommendations, which we rated by class (size of effect) and level (estimate of certainty) according to the American Heart Association/American Stroke Association criteria. No recommendation was level A (because of the absence of randomized controlled trials), 11 (48%) were level B, and 12 (52%) were level C. Recommendations were class I in 8 (35%), class II in 10 (43%), and class III in 5 (22%). CONCLUSION: Current evidence supports recommendations for the management of CCM, but their generally low levels and classes mandate further research to better inform clinical practice and update these recommendations. The complete recommendations document, including the criteria for selecting reference citations, a more detailed justification of the respective recommendations, and a summary of controversies and knowledge gaps, was similarly peer reviewed and is available on line www.angioma.org/CCMGuidelines.

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“…15 In one study of 350 patients undergoing thrombolysis with recombinant tissue-type plasminogen activator for acute stroke, there was no significant difference in rates of symptomatic intracranial hemorrhage and parenchymal hemorrhage among patients harboring cerebral CMs as compared with those who did not. 13 None of our reviewed studies evaluated the impact of prior radiation on risk of CM hemorrhage. In one subgroup report of 32 patients with radiation-induced CMs, the median latency from radiation treatment to CM diagnosis was 12.0 years.…”

Section: Hemorrhage Risk Factorsmentioning

confidence: 99%

Hemorrhage from cerebral cavernous malformations: a systematic pooled analysis

Gross

2017

JNS

116

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OBJECTIVE The aim of this paper is to define an overall cavernous malformation (CM) hemorrhage rate and risk factors for hemorrhage. METHODS The authors performed a systematic, pooled analysis via the PubMed database through October 2015 using the terms "cavernoma," "cavernous malformation," "natural history," "bleeding," and "hemorrhage." English-language studies providing annual rates and/or risk factors for CM hemorrhage were included. Data extraction, performed independently by the authors, included demographic data, hemorrhage rates, and hemorrhage risk factors. RESULTS Across 12 natural history studies with 1610 patients, the mean age at presentation was 42.7 years old and 52% of patients (95% CI 49%-55%) were female. Presentation modality was seizure in 30% (95% CI 25%-35%), hemorrhage in 26% (95% CI 17%-37%), incidental in 17% (95% CI 9%-31%), and focal deficits only in 16% of cases (95% CI 11%-23%). CM location was lobar in 66% (95% CI 61%-70%), brainstem in 18% (95% CI 13%-24%), deep supratentorial in 8% (95% CI 6%-10%), and cerebellar in 8% (95% CI 5%-11%). Pooling 7 studies that did not assume CM presence since birth, the annual hemorrhage rate was 2.5% per patient-year over 5081.2 patient-years of follow-up (95% CI 1.3%-5.1%). Pooling hazard ratios across 5 studies that evaluated hemorrhage risk factors, prior CM hemorrhage was a significant risk factor for hemorrhage (HR 3.73, 95% CI 1.26-11.1; p = 0.02) while younger age, female sex, deep location, size, multiplicity, and associated developmental venous anomalies (DVAs) were not. CONCLUSIONS Although limited by the heterogeneity of incorporated reports and selection bias, this study found prior hemorrhage to be a significant risk factor for CM bleeding, while age, sex, CM location, size, multiplicity, and associated DVAs were not. Future natural history studies should compound annual hemorrhage rate with prospective seizure and nonhemorrhagic neurological deficit rates.

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Safety of Thrombolysis in Patients With Acute Ischemic Stroke and Cerebral Cavernous Malformations

Cited by 10 publications

References 8 publications

Off-label use of IV t-PA in patients with intracranial neoplasm and cavernoma

Off-label use of IV t-PA in patients with intracranial neoplasm and cavernoma

Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel

Hemorrhage from cerebral cavernous malformations: a systematic pooled analysis

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