Safety and feasibility of collateral blood flow augmentation after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Collateral flow augmentation using partial aortic occlusion may improve cerebral perfusion in acute stroke. We assessed the safety and feasibility of partial aortic occlusion immediately after intravenous tissue plasminogen activator. METHODS: We conducted an open-label pilot study of partial aortic occlusion after thrombolysis. The primary end point was all serious adverse events within 30 days of treatment. RESULTS: None of the 22 patients enrolled developed symptomatic parenchymal hemorrhages. Asymptomatic hemorrhagic transformation occurred in 9 patients. Procedure-related adverse events were limited to groin complications (n=13). Seventy-seven percent of patients experienced neurological improvement (≥4-point improvement of the National Institutes of Health Stroke Scale score). CONCLUSIONS: Partial aortic occlusion as an adjunct to thrombolysis in the treatment of acute stroke appears safe. Studies aimed at determining the efficacy of this therapeutic approach are warranted. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01006993.

Serial electrocardiographic assessments significantly improve detection of atrial fibrillation 2.6-fold in patients with acute stroke.

BACKGROUND AND PURPOSE: Previous studies have reported a low, approximately 1% to 3%, rate of detection of occult atrial fibrillation (AF) with Holter monitor in patients with acute stroke. Furthermore, at least one study has reported that Holter monitoring could not always corroborate initial electrocardiographic (ECG) detection of AF suggesting underestimation of AF by Holter. We compare the detection of new-onset AF by serial ECG assessments and Holter after acute ischemic stroke. METHODS: One hundred forty-four patients with ischemic stroke admitted to a stroke unit were studied. The number of ECGs conducted within the first 3 days up to the detection of AF as well as the time interval for Holter "hookup" and subsequent reporting of AF was documented. RESULTS: ECGs were performed in 143 patients with a baseline of 10 (7%) patients having a history of AF. Serial ECGs detected 15 new AF cases in <2 days of admission, thereby increasing the total number of known AF cases to 25 (17.5%), a 2.6-fold increased realization of AF (P=0.011). Holter was also completed in 12 of 15 new cases of AF but surprisingly identified AF in only 50% (6 of 12). Holter monitoring was performed in 126 cases and in this subgroup, there was no statistically significant difference in the rate of AF detection with ECG or Holter. CONCLUSIONS: Serial ECG assessments within the first 72 hours of an acute stroke significantly improve detection of AF. The discordance regarding the corroboration of AF by Holter in ECG-positive patients with AF supports previous observations and suggests a high incidence of paroxysmal AF as a cause of ischemic stroke.

Inhibition of adenine nucleotide translocator pore function and protection against apoptosis in vivo by an HIV protease inhibitor.

Inhibitors of HIV protease have been shown to have antiapoptotic effects in vitro, yet whether these effects are seen in vivo remains controversial. In this study, we have evaluated the impact of the HIV protease inhibitor (PI) nelfinavir, boosted with ritonavir, in models of nonviral disease associated with excessive apoptosis. In mice with Fas-induced fatal hepatitis, Staphylococcal enterotoxin B-induced shock, and middle cerebral artery occlusion-induced stroke, we demonstrate that PIs significantly reduce apoptosis and improve histology, function, and/or behavioral recovery in each of these models. Further, we demonstrate that both in vitro and in vivo, PIs block apoptosis through the preservation of mitochondrial integrity and that in vitro PIs act to prevent pore function of the adenine nucleotide translocator (ANT) subunit of the mitochondrial permeability transition pore complex.

Thrombus detection by echocardiography in patients with acute ischemic stroke and chronic or new-onset atrial fibrillation.

INTRODUCTION: Recent articles have promoted anticoagulation for potential sources of embolism detected on echocardiography, despite lack of data regarding risk/benefit ratio for anticoagulating many of these abnormalities. Conversely, we have found echocardiography use in ambulatory stroke care to be of low yield. However, direct visualization of a thrombus might be considered a reasonable indication for anticoagulation. The current study assesses the use of transthoracic echocardiography (TTE) in thrombus detection in atrial fibrillation (AF) associated with acute stroke, which should present a good substrate for thrombus detection. METHODS: We conducted a chart review of patients admitted to our stroke department during a 6-month period, identifying and analyzing those with associated AF who were also submitted to TTE. RESULTS: In all, 31 patients with AF (12 chronic and 19 new onset) were studied. TTE was conducted within approximately 60 +/- 41 hours. Thrombus was detected in only one patient with severe left ventricular dysfunction. Moderate to severe left ventricular function was detected in two additional patients with history of myocardial infarction. There were no other pertinent findings in 28 of 31 patients. All patients were anticoagulated on the basis of AF detection. Two died in hospital from stroke-related complications and 26 of 31 were discharged home or to rehabilitation. CONCLUSIONS: TTE has a low yield of thrombus detection in patients with acute cardioembolic (AF-associated) stroke and has no impact on antithrombotic therapy in this patient population.

Titrated initiation of acetylsalicylic acid-dipyridamole therapy reduces adverse effects and improves tolerance in patients with stroke.

BACKGROUND: Standard aspirin (acetylsalicylic acid [ASA])-dipyridamole therapy twice daily is associated with high rates of discontinuation in large part because of headache and gastrointestinal side effects. Attempts to address dipyridamole-induced headache through reduced dose initiation have produced variable results. Moreover, it has been suggested that migraineurs are more likely to have a dipyridamole-induced headache. OBJECTIVE: We sought to evaluate whether titrated initiation of ASA-dipyridamole in patients with stroke/transient ischemic attack (TIA) improves tolerance and to assess the appearance of headache in those with pre-existing history of headaches. METHODS: ASA-dipyridamole (25/200 mg) once daily together with ASA (81 mg) daily was started in 130 patients given the diagnosis of stroke/TIA with instructions to increase ASA-dipyridamole to twice daily after 7 days and discontinue ASA (81 mg). Patients received a telephone call on days 7 and 14 to assess for adverse events, discontinuation, and recurrent stroke/TIA. RESULTS: Two patients were lost to follow-up. After 2 weeks, 113 patients were using the medication without any major complications. Fifteen patients were off therapy; 10 (8%) patients stopped because of headache and/or gastrointestinal symptoms, whereas 4 patients were switched to other antiplatelet agents by their primary care physician as a matter of choice rather than ASA-dipyridamole side effects. One patient had recurrent stroke because of intracranial dissection and was switched to anticoagulation. Only 4 of 27 (14%) patients with a history of headache discontinued therapy. CONCLUSIONS: Titrated initiation of ASA-dipyridamole (25/200 mg) appears to have low discontinuation rate and approximately 90% tolerance after 2 weeks. History of migraine or tension headaches was not directly associated with discontinuation because of headaches.

Usefulness of cardiovascular investigations in stroke management: clinical relevance and economic implications.

BACKGROUND AND PURPOSE: There are no prospective randomized studies assessing the clinical relevance of routine cardiovascular investigations in stroke patients. The objective of this study was to evaluate the utilization, relevance, and economics of cardiovascular investigations in an ambulatory stroke clinic. METHODS: The outcome of cardiovascular investigations in 200 patients with stroke/transient ischemic attack diagnosed in a stroke prevention clinic was assessed. Transthoracic echocardiography (TTE) was assessed for detection of thrombus or mass, poor left ventricle function, and other structural abnormalities. ECG and Holter monitor were felt to be relevant if they showed atrial fibrillation/flutter. Investigations were deemed to be clinically pertinent if they brought about a shift treatment paradigm. RESULTS: TTE and Holter were performed in >70% of cases and accounted for approximately 94% of total cardiovascular cost. Relevant TTE findings were identified in 6 (4%) patients, which did not alter antithrombotic therapy. Only 2 new cases of atrial fibrillation were identified by both ECG and Holter. CONCLUSIONS: TTE and Holter appear to be costly low-yield procedures in this clinical setting. Prospective analyses may help to provide cost effective criteria for selection of appropriate cardiovascular studies in stroke management.

Saving costs using an ounce of prevention: introduction of a regional stroke prevention clinic.

Trillium Health Centre (THC) is one of Canada's largest community hospitals and a regional provider of tertiary-level cardiac, neuroscience, and orthopedic care. In 2001, it was named one of nine Regional Stroke Centres in Ontario, with a mandate to coordinate stroke services across the continuum of care in keeping with best practices in the west Greater Toronto Area (GTA). Within its role as a Regional Stroke Centre, THC has successfully implemented an innovative approach to the delivery of stroke prevention services in its regional catchment area. Building on best practices, it has introduced a specialized and interdisciplinary team to provide timely and effective primary and secondary prevention services. The rapid growth in utilization to more than 2000 patients in the last fiscal year (2004-2005), suggests that the clinic is meeting a real need in the community for stroke prevention services. Many of these patients now benefit from appropriate medical management, stroke awareness education, lifestyle counselling, and expedited referrals to other specialists. The Regional Stroke Prevention Clinic (RSPC) may be the first step in preventing a stroke, thus avoiding the social costs to people with strokes and their families, and the financial burden on the health care system.

Severe amnesia associated with human herpesvirus 6 encephalitis after bone marrow transplantation.

BACKGROUND: Human herpesvirus 6 (HHV-6) appears to have a predilection for immunocompromised patients and has been implicated as a cause of posttransplant encephalitis. However, the pathogenesis, as well as the appropriate means of diagnosis and treatment of HHV-6 encephalitis is unclear. METHOD: We describe a case of a 20-year-old male university student with anemia who presented with an acute, severe amnesia 1 month after bone marrow transplantation. His illness was subsequently attributed to HHV-6 encephalitis. RESULTS: Cerebrospinal fluid analysis was consistent with encephalitis and polymerase chain reaction confirmed the presence of HHV-6 DNA in both cerebrospinal fluid and serum. No other herpes virus particles were detected. MRI showed bilateral hippocampal involvement. Treatment with acyclovir resulted in a decrease in serum HHV-6 DNA to undetectable levels, coincident with improvement of both memory and lesions on MRI. CONCLUSIONS: This case provides strong clinical and radiological evidence of the reversibility of this disease process and supports the recommendations for empiric treatment of post transplant patients with laboratory evidence of HHV-6 infection, culture or polymerase chain reaction, plus clinical symptoms compatible with HHV-6 infection.

Blood pressure management in acute stroke: comparison of current guidelines with prescribing patterns.

OBJECTIVE: Current recommendations for treating elevated blood pressure (BP) in the acute stroke are based largely on expert opinion and vary with regard to treatment thresholds and choice of antihypertensive agents. In this study we investigate the influence of these recommendations by comparing the management of hypertension in acute stroke at a tertiary care hospital with current guidelines. METHOD: Retrospective chart review of patients admitted with acute stroke at The Ottawa Hospital-General Campus over six consecutive months. The use of antihypertensive medications (type, dose, routes of administration, BP recordings) in the first seven days after admission was noted. RESULTS: Transdermal nitroglycerin paste was the most commonly used antihypertensive agent. In contrast to the 15% reduction in BP over 24 hours recommended for lowering BP in hypertensive patients with ischemic stroke, nitroglycerin caused a >15% reduction of BP over the first 24 hours on 60% of the occasions used. Furthermore, despite concerns about sublingual nifedipine, this was the second most commonly prescribed agent. Surprisingly, the mean time to first BP measurement following initiation of antihypertensive therapy was 117 +/- 43 minutes in ischemic stroke and 88 +/- 89 minutes in hemorrhagic strokes. CONCLUSIONS: The current guidelines for management of acute poststroke hypertension appear to have little influence on prescribing patterns, leading to considerable variations in practice. Such variations, likely due to uncertainty caused by lack of evidence from randomised controlled trials, are intolerable as patients maybe submitted to nonstandardised, potentially harmful care such as inappropriate choice of antihypertensives and inadequate BP monitoring as observed in this study.