Secondary Intracranial Hemorrhage Research Articles

Pharmacologic Venous Thromboembolism Prophylaxis in Patients with Nontraumatic Subarachnoid Hemorrhage Requiring an External Ventricular Drain.

Optimal pharmacologic thromboprophylaxis dosing is not well described in patients with subarachnoid hemorrhage (SAH) with an external ventricular drain (EVD). Our patients with SAH with an EVD who receive prophylactic enoxaparin are routinely monitored using timed anti-Xa levels. Our primary study goal was to determine the frequency of venous thromboembolism (VTE) and secondary intracranial hemorrhage (ICH) for this population of patients who received pharmacologic prophylaxis with enoxaparin or unfractionated heparin (UFH). A retrospective chart review was performed for all patients with SAH admitted to the neurocritical care unit at Emory University Hospital between 2012 and 2017. All patients with SAH who required an EVD were included. Of 1,351 patients screened, 868 required an EVD. Of these 868 patients, 627 received enoxaparin, 114 received UFH, and 127 did not receive pharmacologic prophylaxis. VTE occurred in 7.5% of patients in the enoxaparin group, 4.4% in the UFH group (p = 0.32), and 3.2% in the no VTE prophylaxis group (p = 0.08). Secondary ICH occurred in 3.83% of patients in the enoxaparin group, 3.51% in the UFH group (p = 1), and 3.94% in the no VTE prophylaxis group (p = 0.53). As steady-state anti-Xa levels increased from 0.1 units/mL to > 0.3 units/mL, there was a trend toward a lower incidence of VTE. However, no correlation was noted between rising anti-Xa levels and an increased incidence of secondary ICH. When compared, neither enoxaparin nor UFH use was associated with a significantly reduced incidence of VTE or an increased incidence of ICH. In this retrospective study of patients with nontraumatic SAH with an EVD who received enoxaparin or UFH VTE prophylaxis or no VTE prophylaxis, there was no statistically significant difference in the incidence of VTE or secondary ICH. For patients receiving prophylactic enoxaparin, achieving higher steady-state target anti-Xa levels may be associated with a lower incidence of VTE without increasing the risk of secondary ICH.

Machine learning-based CT radiomics model to discriminate the primary and secondary intracranial hemorrhage

It is challenging to distinguish between primary and secondary intracranial hemorrhage (ICH) purely by imaging data, and the two forms of ICHs are treated differently. This study aims to evaluate the potential of CT-based machine learning to identify the etiology of ICHs and compare the effectiveness of two regions of interest (ROI) sketching methods. A total of 1702 radiomic features were extracted from the CT brain images of 238 patients with acute ICH. We used the Select K Best method, least absolute shrinkage, and selection operator logistic regression to select the most discriminable features with a support vector machine to build a classifier model. Then, a ten-fold cross-validation strategy was employed to evaluate the performance of the classifier. From all quantitative CT-based imaging features obtained by two sketch methods, eighteen features were selected respectively. The radiomics model outperformed radiologists in distinguishing between primary and secondary ICH in both the volume of interest and the three-layer ROI sketches. As a result, a machine learning-based CT radiomics model can improve the accuracy of identifying primary and secondary ICH. A three-layer ROI sketch can identify primary versus secondary ICH based on the CT radiomics method.

Diagnosis and Management of Cerebral Venous Sinus Thrombosis With Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Diagnosis and Management of Cerebral Venous Sinus Thrombosis With Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Abstract P414: Outcomes of Incident Hemorrhage From Cranial Dural Arteriovenous Fistulae: Analysis of the Multi-Center International Condor Registry

Introduction: Dural artertiovenous fistulae (dAVF) are rare causes of secondary intracranial hemorrhage (ICH) and there remains a paucity of knowledge regarding their natural history. To date our knowledge comes from small case series. CONDOR, (Consortium for Dural Arteriovenous Fistula Outcomes Research), a large multi-institutional retrospective registry, provides a unique opportunity to evaluate the outcomes of patients presenting with dAVF related hemorrhages. Methods: We performed a retrospective review of 1077 dAVF patients from the CONDOR registry and selected those patients who presented with hemorrhage secondary to the dAVF. Patient characteristics, clinical presentation/follow-up, and radiographic details were analyzed for associations with patient outcomes. An outcome of mRS 0-2 was categorized as a “good” outcome and 3-6 as “poor”. Statistics were performed in SAS 9.4 with chi square, fisher’s exact test, and stepwise select variable multivariate analysis; P<.05 was marked as the level for statistical significance. Results: Evaluation of the CONDOR dataset yielded 267 patients who presented with hemorrhage. The mean age of the population was 59 ±13y.o, 30% were female, 40% had a history of smoking and 93% were not on anticoagulants. The median follow-up was 1.4 years. The mortality was 4.0 % at follow-up, and 83% of patients had a good outcome (mRS 0-2). Univariate analysis found age (p=0.001), anticoagulant use (p=0.006), and presentation mRS (p=0.03) were associated with poor outcome at follow-up. Subtype of hemorrhage (parenchymal hemorrhage or subarachnoid hemorrhage), smoking, and cortical venous shunting of the lesion, (i.e. Cognard grade IIb and greater) did not reach statistical significance. On multivariate analysis age (p=0.023) and mRS (p=0.035) at presentation but not anti-coagulant use (p=0.11) was associated with follow-up mRS. Conclusion: Within the largest individual patient series to date, we found that dAVF presenting with hemorrhage was associated with a relatively low risk of mortality. Age and mRS at presentation were most strongly predictive of outcome. Our results suggest that dAVF hemorrhage may be associated with a less morbid outcome than other forms of secondary hemorrhage.

Perioperative Blood Pressure Control in Carotid Artery Stenosis Patients With Carotid Angioplasty Stenting: A Retrospective Analysis of 173 Cases.

Background: Carotid angioplasty stenting (CAS) is a currently widely used surgical treatment of carotid artery stenosis. However, the influences of the perioperative blood pressure (BP) on patients' prognosis remain unclear.Objective: The present study was designed to explore the effects of different perioperative BP control strategies on CAS patients' prognosis.Methods: One hundred seventy-three consecutive patients admitted between January 2016 and April 2019 were reviewed retrospectively. The outcomes of patients with different systolic BP (<120, 120–130, and >130 mmHg) before CAS and within 24 h after CAS were compared. The primary outcomes were the incidence of secondary cerebral infarction (CI) and intracranial hemorrhage (ICH) after CAS. The secondary outcome was the incidence of unfavorable discharge and in-hospital death. The unfavorable discharge was defined as modified Rankin Scale (mRS) score 3–5 at discharge.Results: There was no significant difference between the incidences of ICH (P = 0.803) and CI (P = 0.410) in patients with different BP before CAS. The patients with post-CAS BP values of >130 mmHg had a 37.67-fold increased risk (95% CI: 6.79–209.01) of ICH compared with others, while no significant difference was observed on the incidence of CI (P = 0.174) among patients with different post-CAS BP values. The patients with post-CAS BP values of >130 mmHg also had a significantly higher incidence of unfavorable discharge (P = 0.002) and in-hospital death (P = 0.001) compared with others.Conclusion: High BP (>130 mmHg) within 24 h after CAS significantly increases the risks of secondary cerebral hemorrhage, unfavorable discharge, and in-hospital death. Thus, the BP should be controlled below 130 mmHg in the first 24 h after CAS.

Intracranial Pseudoaneurysm Caused by Cerebral Paragonimiasis in Pediatric Patients

BackgroundWe investigated the proportion of pediatric patients with cerebral paragonimiasis and intracranial hemorrhage who have intracranial pseudoaneurysms. MethodsImages of 17 pediatric patients with cerebral paragonimiasis that first manifested as secondary intracranial hemorrhage were evaluated. All patients underwent computed tomographic angiography before surgery. A diagnosis of cerebral paragonimiasis was confirmed based on a positive Paragonimus-specific antibody test in serum samples from all 17 patients. Cerebral paragonimiasis in five of the 17 patients was further confirmed by histopathological examination of surgical specimens. ResultsComputed tomographic angiographic images for six of the 17 patients (35.3%) showed the presence of intracranial pseudoaneurysms. Follow-up computed tomographic angiographic scans two years later showed that two of the six patients had persistent pseudoaneurysms and underwent aneurysmectomy. The diagnosis of pseudoaneurysm was confirmed by histopathological examination postsurgery. In another two of the six patients, the pseudoaneurysm lesions were absorbed and could no longer be seen on three- to six-month follow-up scans. The final two patients with pseudoaneurysms are still under follow-up. Intracranial pseudoaneurysms with various degrees of surrounding hemorrhage were frequently observed at first manifestation. ConclusionsThe rupture of intracranial pseudoaneurysms is a common characteristic feature of secondary intracranial hemorrhage caused by cerebral paragonimiasis in pediatric patients.

A case of metastatic brain tumor mimicking an expanding thalamic hematoma.

Background:Brain tumor are a major etiology of secondary intracranial hemorrhage (ICH) because ICH in patients with cancer often occurs from an intratumoral hemorrhage. However, it is sometimes difficult to detect a tumor when it is tiny and buried, especially during initial examination.Case Description:A 65-year-old woman who was diagnosed with pulmonary small cell carcinoma 6 months previously developed sudden-onset consciousness disturbance and left hemiparesis. Head computed tomography (CT) showed a round, high-density lesion with a diameter of 31 mm in the right thalamus. There was no enhancement with administration of contrast agent. Five days later, CT revealed significant progression of the hematoma in the thalamus with perifocal edema. She underwent total removal of the hematoma. Histopathological examination revealed a tiny cluster of metastatic cancer tissue within the hematoma.Conclusions:When cerebral hemorrhage occurs in a cancer patient, we must consider the possibility of hemorrhage due to a brain metastasis.

Symptomatic Hemorrhagic Complications in Clot Lysis: Evaluation of Accelerated Resolution of Intraventricular Hemorrhage Phase III Clinical Trial (CLEAR III): A Posthoc Root-Cause Analysis.

As intraventricular thrombolysis for intraventricular hemorrhage (IVH) has developed over the last 2 decades, hemorrhagic complications have remained a concern despite general validation of its safety in controlled trials in the Clot Lysis: Evaluation of Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR-IVH) program. To analyze factors associated with symptomatic bleeding following IVH with and without thrombolysis in conjunction with the recently completed CLEAR III trial. We reviewed safety reports on symptomatic bleeding events reported during the first year after randomization among subjects enrolled in the CLEAR III trial. Clinical and imaging data were retrieved through the trial database as part of ongoing quality and safety monitoring. A posthoc root-cause analysis was performed to identify potential factors predisposing to rebleeding in each case. Cases were classified according to onset of rebleeding (during dosing, early after dosing and delayed), the pattern of bleeding, and treatment rendered (alteplase vs saline). Twenty subjects developed a secondary symptomatic intracranial hemorrhage constituting 4% of subjects. Symptomatic rebleeding events occurred during the dosing protocol (n=9, 67% alteplase), early after the protocol (n=5, 40% alteplase), and late (n=6, 0% alteplase). Catheter-related hemorrhages were the most common (n=7, 35%) followed by expansion or new intraventricular (n=6, 30%) and intracerebral (n=5, 25%) hemorrhages. Symptomatic hemorrhages during therapy resulted from a combination of treatment- and patient-related factors and were at most partially attributable to alteplase. Rebleeding after the dosing protocol primarily reflected patients' risk factors. Intraventricular thrombolysis marginally increases the overall risk of symptomatic hemorrhagic complications after IVH, and only during the treatment phase.

Transfusion Practice Following Intracranial Hemorrhage in Acute Leukemia: An Institutional Review

▪Background: Intracranial hemorrhage (ICH) is a common complication in acute leukemia that is associated with significant morbidity and mortality. While evidence supports prophylactic platelet transfusions at a threshold < 10 x 109/L to reduce the risk of bleeding in acute leukemia, there is little data to guide platelet transfusion practice in patients following ICH. The objectives of this study were to characterize the clinical features and outcomes of acute leukemia patients with ICH and to understand current platelet transfusion practice following ICH.Methods: This was a retrospective study conducted at a large, quaternary, academic cancer centre. We included all adult patients with a diagnosis of acute leukemia who had a documented ICH at our centre between January 1, 2009 and December 31, 2016. We assessed demographics, medications, infection and bleeding history in the week preceding ICH, characteristics of ICH including site of bleed, acute management, transfusion practice in the first 90 days, and clinical outcomes. Radiologic scans were re-assessed by neuroradiology to determine if the ICH was stable or if new or progressive bleeding had developed. Transfusion practice following the ICH was compared between the two groups with longitudinal data analysis using platelet counts as outcome. Kaplan-Meier product limit method was used to estimate overall survival (OS) rates as well as to obtain median survival; log-rank test was used to compare OS among those without new or progressive ICH vs. those with progression.Results: During the study period, of 2576 patients diagnosed with acute leukemia, 101 suffered from ICH and were included in the study. Most patients (94) had AML, of which 9 had APL, 6 had ALL, and 1 had MPAL. At the time of ICH, 61 patients were newly diagnosed or receiving induction chemotherapy, 33 had relapsed disease and 7 were in complete remission. Spontaneous ICH occurred in 76 patients. Within the week preceding ICH, 7 patients were on medications known to increase bleeding risk and 39 were on tranexamic acid. Sixty-four patients had clinical evidence of bleeding elsewhere and 22 had evidence of infection.On the day of ICH, the median platelet count was 16 x 109/L (range 0- 433 x109/L). Thirty-one patients had a platelet count < 10 x 109/L and 10 of these patients received a platelet transfusion prior to the bleed. Seventy patients had a platelet count ≥10 x109/L and 17 of these received a platelet transfusion prior to the bleed. Six patients (6%) exhibited evidence of platelet transfusion refractoriness.In the 90 days following ICH, 21% of platelet transfusions were given for a platelet count < 10 x 109/L, 55% were given with a platelet count between 10-29 x109/L, and 24% were given with a platelet count ≥ 30 x 109/L. New or progressive ICH occurred in 28 patients. The median platelet transfusion threshold was 19 x 109/L (range 0-114 x 109/L) for those without new or progressive ICH and 21 x 109/L (range 0-93 x 109/L) for those with progression (p=0.04; Figure 1). Of the 101 study patients, 79 have died. Median OS was 5.6 months for those without new or progressive ICH and 2.9 months for those with progression (p=0.002) (Figure 2). Cause of death was attributed to non-ICH causes in the majority of patients 65/79 (82%).Conclusions: In this retrospective study, we evaluated the outcomes of 101 patients with acute leukemia and ICH. At the time of the bleed, the majority of patients had active disease and more than two thirds had platelet counts of 10 x 109/L or higher. During 90 days of follow-up, nearly one third of patients developed new or progressive ICH. Platelet transfusion practice was variable and the median threshold was, in fact, higher in those who subsequently developed new or progressive bleeding. The reasons for this were unclear from our chart review, but we hypothesize that these patients may have had additional risk factors, e.g. fever, infection. The outcomes of patients with acute leukemia and ICH are poor. Factors other than platelet transfusion threshold likely contribute to secondary ICH events and the overall poor prognosis. DisclosuresMaze:Novartis: Consultancy, Honoraria.

The progress of nimodipine in the prevention and treatment of cerebral vasospasm after intracranial hemorrhage in children

One of the majority reasons for mortality and morbidity in children is cerebral vasospasm secondary to intracranial hemorrhage(CVSIH). CVSIH prevented and treated by nimodipine in adult patients have been widely reported in China and abroad, but only limited reports in children.We aimed to describe the mechanism and diagnosis of CVSIH in children, and also the mechanism, efficacy and safety of nimodipine. Key words: Nimodipine; Intracranial hemorrhage; Cerebral vasospasm; Children

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

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.

Traumatic middle meningeal artery pseudoaneurysms

Intracranial pseudoaneurysms are rare and mostly associated with a history of head trauma. Only little is known about their natural development. They are characterized by an unpredictable course with a possibility of causing secondary intracranial hemorrhage with significant morbidity and mortality. We present two cases of traumatic pseudoaneurysms of the middle meningeal artery (MMA) treated via endovascular coil occlusion and review of literature. Pseudoaneurysms of the middle meningeal artery carry a potential risk of rupture. They can be detected via a computed tomography angiogram (CT-A). An endovascular embolization followed by catheter angiography may represent a safe treatment of traumatic middle meningeal artery pseudoaneurysms. Considering the risk of secondary rupture and the potentially catastrophic consequences, we recommend a CT-A in all patients with skull base fractures and intracranial hemorrhage.

Intra‐Arterial Tenecteplase for Treatment of Acute Ischemic Stroke: Feasibility and Comparative Outcomes

Tenecteplase (TNK) is a third-generation thrombolytic agent. We evaluated the safety and feasibility of intra-arterial (IA) administration of TNK in patients with acute ischemic stroke. Patients who received endovascular treatment for acute ischemic stroke were identified from prospectively collected databases at three university hospitals. We compared clinical and radiological outcomes of patients treated with TNK to those treated with other IA thrombolytics or mechanical thrombectomy alone. Primary outcome measures were favorable functional outcome at 30 days (modified Rankin Scale score of 0-2), and rate of intracranial hemorrhage (ICH). Early neurological improvement, angiographic recanalization, time to recanalization, and mortality at 30 days were additional outcome measures. We identified 114 patients (mean age 67 ± 15 years, 54 were women). Thirty-three patients received IA TNK, 48 received alteplase (n = 11) or reteplase (n = 37), and 33 patients had mechanical thrombectomy alone. Stroke severity was similar among the three groups. No difference between the groups was found in the secondary outcome measures and ICH. Borderline statistical significance was seen toward favorable functional outcome at 1 month in the TNK-treated patients [odds ratio (OR) = 2.8; 95% confidence interval (CI) .96-8.1, P = .063 vs. other thrombolytics, and OR = 3.0, 95% CI .97-9.5, P = .06 vs. mechanical thrombectomy alone]. Our study demonstrates that administration of IA TNK in acute stroke is safe and results in rates of favorable outcomes that are comparable to those observed with currently used drugs. Additional studies are needed to further determine the safety and efficacy of IA TNK in acute stroke treatment.

Analysis of cause of Secondary intracranial hemorrhage during craniotomy for intracranial tumor

Objective To explore the reasons and the treatment counter-measures for secondary intracranial hemorrhage happens in the intracranial tumor craniotomy. Methods Retrospectively analyzed the clinical data of 15 patients with intracranial tumor who suffered secondary intracranial hemorrhage intraoperation. Summarized the tumor characteristics and the situation of corresponding vessels confined by second operation. Results In these 15 cases,the rank of course of disease was 6.5 months to 2 years, mean 1.2 years. The size of the tumor was big with diameter 4.62 ～5. 82cm,mean 5. 12cm,and the tumor was deep surrounding by large range edema,which led to intracranial hypertension. The emissary vein,bridging vein and cortical draining vein were considered as the corresponding vessels for ' secondary intracranial hemorrhage during the second operation carried out for all 15 cases. There wsa no death cases in this research and all patients recovered the nomal ability for self-caring after 3 months following up. Conclusion Sudden drawdown of intracranial pressure and perfusion pressure breakthrough of local vessels had relationship with secondary intracranial hemorrhage during craniotomy for intracranial tumor. Accurate judgement for the occurrence of secondary intracranial hemorrhage intra-operation and quickly taking the effective corresponding measures was the important strategy for prognosis improving for these patients. Key words: Intracranial tumor; Intracranial hemorrhage

Secondary Intracranial Hemorrhage After Mild Head Injury in Patients With Low-Dose Acetylsalicylate Acid Prophylaxis

Low-dose acetylsalicylate acid (LDA) therapy is accepted as a major risk factor for intracranial hemorrhages (ICH) in head injuries. Coincidentally, patient admissions that might be indicated for in hospital observation of neurologic function causes increased health care costs. In the literature, there is no evidence concerning the incidence of secondary intracranial hemorrhagic events (SIHE) in patients with LDA prophylaxis that had negative primary computed tomography (CT)-scan of the head. In this prospective study, we enrolled 100 consecutive trauma patients older than 65 years presenting in a Level I urban trauma center after a mild head injury (Glasgow Coma Scale score of 15) who had LDA prophylaxis. Patients included had a negative primary head CT-scan concerning ICH. For analysis of the incidence of SIHEs patients had routine repeat head CT (RRHCT) after 12 hours to 24 hours. Sixty-one patients were women and 39 men. Mean age was 81 years +/- 10 years. Injury mechanism was a level fall in 84 cases and others in 16. In four patients (4%) an SIHE was detected in the RRHCT (p < 0.00001). In two patients (2%) major secondary ICH had occurred without neurologic deterioration at the time of RRHCT with fatal outcome in one patient and neurosurgical intervention in another. The remaining two patients (2%) had minor SIHE with an uneventful clinical course. The incidence of SIHE has been neglected until now. The current study revealed that patients with LDA prophylaxis after mild head injury with negative primary head CT should be subjected to RRHCT within 12 hours to 24 hours to accurately identify SIHE. Alternatively to RRHCT, patients should be subjected to a prolonged in-hospital observation for at least 48 hours.

Risk of Thrombolysis-Related Hemorrhage Associated With Microbleed Presence

To the Editor: We appreciate the article by Fiehler and colleagues regarding thrombolysis-associated bleeding risk in stroke patients.1 This is the largest prospective study to date that investigated the relation between presence of cerebral microbleeds on MRI and the risk of secondary thrombolysis-associated intracranial hemorrhage (ICH) in ischemic stroke patients. However, we respectfully disagree with the authors that on the basis of these data one can conclude that the risk of hemorrhage associated with microbleed presence is negligible. First, the prevalence of microbleeds in their study is 15%. This is much lower than expected based on previous studies that reported microbleed prevalence in ischemic stroke patients up to …

B leeding R isk A nalysis in S troke I maging Before Thrombo L ysis (BRASIL)

There has been speculation that the risk of secondary symptomatic intracranial hemorrhage (SICH) may be increased after thrombolytic therapy in ischemic stroke patients who have cerebral microbleeds (CMBs) on T2*-weighted magnetic resonance imaging. Because of this concern, some centers withhold potentially beneficial thrombolytic therapy from these patients. We analyzed magnetic resonance imaging data acquired within 6 hours after symptom onset from 570 ischemic stroke patients treated with intravenous tissue plasminogen activator in 13 centers in Europe, North America, and Asia. Baseline T2*-weighted magnetic resonance images were evaluated for the presence of CMBs. The primary end point was SICH, defined as clinical deterioration with an increase in the National Institutes of Health Stroke Scale score by >or=4 points, temporally related to a parenchymal hematoma on follow-up-imaging. A total of 242 CMBs were detected in 86 of 570 patients (15.1%). The number of CMBs ranged from 1 to 77 in the individual patient, with >or=5 CMBs in 6 of 570 patients (1.1%). Proportions of patients with SICH were 5.8% (95% CI, 1.9 to 13.0) in the presence of CMBs and 2.7% (95% CI, 1.4 to 4.5) in patients without CMBs (P=0.170, Fisher's exact test), resulting in no significant absolute increase in the risk of SICH of 3.1% (95% CI, -2.0 to 8.3). The data suggest that if there is any increased risk of SICH attributable to CMBs, it is likely to be small and unlikely to exceed the benefits of thrombolytic therapy. No reliable conclusion regarding risk in the rare patient with multiple CMBs can be reached.

Mortality of stroke patients treated with thrombolysis: Analysis of nationwide inpatient sample

The authors performed a retrospective cohort comparison using the Nationwide Inpatient Sample for 1999 through 2002 of acute ischemic stroke admissions. Mortality was compared based on the use of thrombolysis. Hospital mortality was significantly greater for the thrombolysis cohort (10.1% vs 5.8%) as was the rate of secondary intracranial hemorrhage (4.2% vs 0.4%). US community experience in the use of thrombolysis has higher rates of complications and mortality than in controlled clinical trials.

Factors Influencing Varicella-Zoster Virus (VZV) Infection after Allogeneic Peripheral Blood Stem Cell Transplantation: Low-Dose Acyclovir Prophylaxis and Pre-Transplant Diagnosis of Lymphoproliferative Disorders.

Introduction: Varicella-zoster virus (VZV) is a frequent opportunistic infection among long-term survivors after allogeneic stem cell transplantation with relatively high incidence of around 30 to 50%. A recent study reported that the cumulative incidence of VZV infection at 5 year reaches up to 63% after allogeneic bone marrow transplantation (Koc, BBMT 2000). It has been suggested that peripheral blood stem cell transplantation (PBSCT) may facilitate immune reconstitution compared to BMT. However, no data has been reported on VZV infection after allogeneic PBSCT. The current study attempted 1) to estimate the incidence of VZV infection, 2) to identify the risk factor for VZV infection, and 3) to analyze the clinical relevance of lymphocyte recovery on VZV infection after allogeneic PBSCT.Patients and methods: We report a retrospective analysis of VZV infection in 192 recipients of allogeneic PBSCT at Princess Margaret Hospital, Toronto, Canada transplanted between June 2001 and December 2005. The median duration of follow up among survivors was 26 months (2 to 60 months). The pre-transplant diagnoses included AML (77, 40%), ALL (18, 9%), CLL (20, 10%), CML (23, 12%), HD (2, 1%), MDS (15, 8%), myelofibrosis (10, 5%), MM (3, 2%), NHL (22, 12%), and renal cell carcinoma (2, 1%). Twenty-seven patients (14%) received long-term courses of low dose acyclovir prophyaxis (200mg bid po for more than 3 months) for recurrent oral (n=21) or genital HSV infection (n=5) after PBSCT or previous history of recurrent VZV infection before PBSCT (n=1).Results: Of 192 recipients, 42 patients (22%) developed VZV infection including localized (n=37) and disseminated infections (n=5). The cumulative incidence of VZV infection at 1, 2 and 3 years was 19.3±3.3, 27.0±4.1 and 36.8±5.2%, respectively. Eighteen patients (43%) developed post-herpetic neuralgia for 2 months' duration (1–21 months). Other complications included secondary bacterial infections (n=3) and intracranial hemorrhage complicated with visceral VZV infection (n=1). One risk factor was identified: pre-translpant diagnosis of a lymphoproliferative disorder (LPD; CLL, HD or NHL) (p=0.021, 52.5±11.7% in LPD group vs 32.6±5.7% in non-LPD group). The use of low dose acyclovir prophylaxis (p=0.007, 0.0% in acyclovir group vs 41.6±6.0% in non-acyclovir group) was found to be protective. While no VZV infection episode were noted in the patients on long-term acyclovir prophyaxis, 3 episodes of VZV infection were noted after cessation of acyclovir. Time-dependent Cox regression analysis confirmed these 2 factors as independent risk factors: 1) diagnosis of LPD (p=0.039, HR 1.965, 95% C.I. 1.033–3.731) and 2) the use of low dose acyclovir prophylaxis (p=0.048, HR 0.305 95% C.I. 0.094–0.991). However, no difference was noted between the group with and without VZV infection in serial lymphocyte counts which has been done before and 3,6,9,and 12 months after transplantation.Conclusion: The incidence of VZV infection after allogeneic PBSCT still remained quite high on 36.8% at 3 years with patients transplanted for LPDs at higher risk. The use of low dose acyclovir (200mg bid po) seemed to be protective from VZV infection, even though it may not completely prevent late VZV infection. The quantitative serial measurement of lymphocyte count could not predict the risk of VZV infection after allogeneic PBSCT.

Mortality of stroke patients treated with thrombolysis: Analysis of nationwide inpatient sample

The authors performed a retrospective cohort comparison using the Nationwide Inpatient Sample for 1999 through 2002 of acute ischemic stroke admissions. Mortality was compared based on the use of thrombolysis. Hospital mortality was significantly greater for the thrombolysis cohort (10.1% vs 5.8%) as was the rate of secondary intracranial hemorrhage (4.2% vs 0.4%). US community experience in the use of thrombolysis has higher rates of complications and mortality than in controlled clinical trials.