Irene Katzan

Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations.

Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline.

The aim of this new statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches for the implementation of guidelines and their use in high-risk populations.

Update to the AHA/ASA Recommendations for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack

The American Heart Association/American Stroke Association (AHA/ASA) Writing Committee for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack (TIA) has reviewed the results of recent trials that were published after our previous recommendations were issued.1 Our intention in the present statement is to provide a brief review of the new data, to update specific recommendations, and to provide the reasons for any modifications. The 2 areas in which major new clinical trials have been published are (1) the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA and (2) the use of statins in the prevention of recurrent stroke. Recently published trials have added to the evidence of the benefit of the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA. The secondary prevention guidelines1 have been updated to reflect this new evidence. ### Addition of Clopidogrel to Aspirin for Prevention of Vascular Events The Clopidogrel and Aspirin Versus Aspirin Alone for the Prevention of Atherothrombotic Events (CHARISMA) trial2 was a double-blinded study that randomized 15 603 subjects with cardiovascular disease or multiple risk factors for cardiovascular disease to either clopidogrel 75 mg plus low-dose aspirin (75 to 162 mg) or placebo plus aspirin (75 to 162 mg). Roughly 35% of subjects (n=4320) qualified on the basis of the presence of cerebrovascular disease within 5 years of enrollment; approximately a third experienced TIA. The median follow-up was 28 months. No significant differences were seen in the rates of nonfatal ischemic stroke between the 2 groups (1.7% versus 2.1%, P =0.07). The placebo plus aspirin group showed a higher rate of nonfatal stroke than did the clopidogrel group (1.9% versus 2.4%, P =0.03). The 2 groups experienced no differences in the rate of intracerebral hemorrhage …

Cooling for Acute Ischemic Brain Damage (COOL AID) An Open Pilot Study of Induced Hypothermia in Acute Ischemic Stroke

Background and Purpose— Hypothermia is effective in improving outcome in experimental models of brain infarction. We studied the feasibility and safety of hypothermia in patients with acute ischemic stroke treated with thrombolysis. Methods— An open study design was used. All patients presented with major ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score >15) within 6 hours of onset. After informed consent, patients with a persistent NIHSS score of >8 were treated with hypothermia to 32±1°C for 12 to 72 hours depending on vessel patency. All patients were monitored in the neurocritical care unit for complications. A modified Rankin Scale was measured at 90 days and compared with concurrent controls. Results— Ten patients with a mean age of 71.1±14.3 years and an NIHSS score of 19.8±3.3 were treated with hypothermia. Nine patients served as concurrent controls. The mean time from symptom onset to thrombolysis was 3.1±1.4 hours and from symptom onset to initiation of hypothermia was 6.2±1.3 hours. The mean duration of hypothermia was 47.4±20.4 hours. Target temperature was achieved in 3.5±1.5 hours. Noncritical complications in hypothermia patients included bradycardia (n=5), ventricular ectopy (n=3), hypotension (n=3), melena (n=2), fever after rewarming (n=3), and infections (n=4). Four patients with chronic atrial fibrillation developed rapid ventricular rate, which was noncritical in 2 and critical in 2 patients. Three patients had myocardial infarctions without sequelae. There were 3 deaths in patients undergoing hypothermia. The mean modified Rankin Scale score at 3 months in hypothermia patients was 3.1±2.3. Conclusion— Induced hypothermia appears feasible and safe in patients with acute ischemic stroke even after thrombolysis. Refinements of the cooling process, optimal target temperature, duration of therapy, and, most important, clinical efficacy, require further study.

The effect of pneumonia on mortality among patients hospitalized for acute stroke

Objective: To determine the effect of pneumonia on 30-day mortality in patients hospitalized for acute stroke. Methods: Subjects in the initial cohort were 14,293 Medicare patients admitted for stroke to 29 greater Cleveland hospitals between 1991 and 1997. The relative risk (RR) of pneumonia for 30-day mortality was determined in a final cohort (n = 11,286) that excluded patients dying or having a do not resuscitate order within 3 days of admission. Clinical data were obtained from chart abstraction and were merged with Medicare Provider Analysis and Review files to obtain deaths within 30 days. A predicted-mortality model (c-statistic = 0.78) and propensity score for pneumonia (c-statistic = 0.83) were used for risk adjustment in logistic regression analyses. Results: Pneumonia was identified in 6.9% (n = 985) of all patients and in 5.6% (n = 635) of the final cohort. The rates of pneumonia were higher in patients with greater stroke severity and features indicating general frailty. Unadjusted 30-day mortality rates were six times higher for patients with pneumonia than for those without (26.9% vs 4.4%, p < 0.001). After adjusting for admission severity and propensity for pneumonia, RR of pneumonia for 30-day death was 2.99 (95% CI 2.44 to 3.66), and population attributable risk was 10.0%. Conclusion: In this large community-wide study of stroke outcomes, pneumonia conferred a threefold increased risk of 30-day death, adding impetus to efforts to identify and reduce the risk of pneumonia in patients with stroke.

The varicella zoster virus vasculopathies: Clinical, CSF, imaging, and virologic features

Background: Varicella zoster virus (VZV) vasculopathy produces stroke secondary to viral infection of cerebral arteries. Not all patients have rash before cerebral ischemia or stroke. Furthermore, other vasculitides produce similar clinical features and comparable imaging, angiographic, and CSF abnormalities. Methods: We review our 23 published cases and 7 unpublished cases of VZV vasculopathy. All CSFs were tested for VZV DNA by PCR and anti-VZV IgG antibody and were positive for either or both. Results: Among 30 patients, rash occurred in 19 (63%), CSF pleocytosis in 20 (67%), and imaging abnormalities in 29 (97%). Angiography in 23 patients revealed abnormalities in 16 (70%). Large and small arteries were involved in 15 (50%), small arteries in 11 (37%), and large arteries in only 4 (13%) of 30 patients. Average time from rash to neurologic symptoms and signs was 4.1 months, and from neurologic symptoms and signs to CSF virologic analysis was 4.2 months. CSF of 9 (30%) patients contained VZV DNA while 28 (93%) had anti-VZV IgG antibody in CSF; in each of these patients, reduced serum/CSF ratio of VZV IgG confirmed intrathecal synthesis. Conclusions: Rash or CSF pleocytosis is not required to diagnose varicella zoster virus (VZV) vasculopathy, whereas MRI/CT abnormalities are seen in almost all patients. Most patients had mixed large and small artery involvement. Detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). Determination of optimal antiviral treatment and benefit of concurrent steroid therapy awaits studies with larger case numbers. GLOSSARY: EIA = enzyme immunoabsorbent assay; VZV = varicella zoster virus.

Quality improvement and tissue-type plasminogen activator for acute ischemic stroke a cleveland update

Background and Purpose— A systematic audit of intravenous tissue-type plasminogen activator (tPA) use and stroke outcomes in Cleveland, Ohio, during 1997–1998 demonstrated higher rates of symptomatic intracranial hemorrhage (ICH) than reported in the National Institute of Neurological Disorders and Stroke (NINDS) trial. We now report updated results of intravenous tPA use in the Cleveland Clinic Health System (CCHS). Methods— A stroke quality improvement program was initiated in the 9-hospital CCHS in 1999. A retrospective chart review for all stroke patients with primary International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes 434 and 436 admitted to the 9 hospitals from June 1999 to June 2000 was used to determine outcomes of patients treated with intravenous tPA. Results— Intravenous tPA was given to 18.8% of patients arriving within 3 hours of symptom onset. Protocol deviations occurred in 19.1% of patients given intravenous tPA. The symptomatic ICH rate was 6.4%. Conclusions— Since 1997, intravenous tPA use has increased, while the rates of symptomatic ICH and protocol deviations have decreased in the CCHS. The CCHS symptomatic ICH rate is now similar to that reported in the NINDS trial. These improvements occurred after initiation of a stroke quality improvement program.

The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy

Background: Factors that may obscure the diagnosis of varicella zoster virus (VZV) vasculopathy include the absence of rash before TIAs or stroke as well as similar clinical features and imaging, angiographic, and CSF abnormalities to those of other vasculopathies. Diagnosis relies on virologic confirmation that detects VZV DNA, anti-VZV IgG antibody, or both in the CSF. Methods: We reviewed our current 14 cases of patients diagnosed with VZV vasculopathy based on combined clinical, imaging, angiographic, or CSF abnormalities. All CSFs must have been tested for VZV DNA by PCR and for anti-VZV IgG antibody by enzyme immunoassay and found to be positive for either or both. Of the 14 subjects, 8 had a history of recent zoster, whereas 6 had no history of zoster rash before developing vasculopathy. Results: All 14 subjects (100%) had anti-VZV IgG antibody in their CSF, whereas only 4 (28%) had VZV DNA. The detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). Conclusions: In varicella zoster virus (VZV) vasculopathy, the diagnostic value of detecting anti-VZV IgG antibody in CSF is greater than that of detecting VZV DNA. Although a positive PCR for VZV DNA in CSF is helpful, a negative PCR does not exclude the diagnosis of VZV vasculopathy. Only when the CSF is negative for both VZV DNA and anti-VZV IgG antibody can the diagnosis of VZV vasculopathy be excluded.

Safety of Intra-Arterial Thrombolysis in the Postoperative Period

Background and Purpose— Limited systemic fibrinolysis and reduced dosage are features of intra-arterial thrombolyis (IAT) that may be advantageous in the treatment of postoperative strokes. However, IAT may increase the risk of surgical bleeding. We sought to determine the safety of postoperative IAT. Methods— This was a retrospective case series from 6 university hospitals. All cases of IAT within 2 weeks of surgery were identified. Demographics, stroke mechanism, stroke severity, imaging and angiographic findings, time between surgery and lysis, thrombolytic agent used, surgical site bleeding, intracranial bleeding, and mortality rates were determined. Death or complications directly related to IAT were determined. Results— Thirty-six patients (median age, 71.5 years; range, 45 to 85) were identified. Median time from surgery to stroke was 21.5 hours (range, 1 to 120). Open heart surgery was done in 18 (50%), carotid endarterectomy in 6 (17%), craniotomy in 3 (8%), ophthalmologic-ear, nose and throat surgery in 2 (6%), urologic-gynecologic surgery in 4 (11%), orthopedic surgery in 2 (6%), and plastic surgery in 1 (3%). The stroke causes were cardioembolism in 24 (67%), large-vessel atherosclerosis in 4 (11%), dissection in 3 (8%), postendarterectomy occlusion in 4 (11%), and radiation arteriopathy in 1 (3%). Median time to angiogram was 2.5 hours (0.1 to 5.5). Occlusion sites were M1 in 19 (53%), M2 in 9 (25%), internal carotid artery in 5 (14%), basilar artery in 2 (6%), and posterior communicating artery in 1 (3%). Thrombolysis was completed at a median of 4.5 hours (range, 1 to 8.0). Tissue plasminogen activator was used in 19 (53%) and urokinase in 17 (47%). Nine (26%) patients died. Surgical site bleeding occurred in 9 (25%) cases (minor in 6, major in 3). The major surgical bleeds were 2 post-craniotomy intracranial hemorrhages and 1 hemopericardium after coronary artery bypass grafting; all were fatal. Six deaths were non-IAT related: 3 caused by cerebral edema and 3 by systemic causes. Major bleeding complications were significantly more common among patients with craniotomy (P <0.02). Conclusions— Postoperative IAT carries a risk of bleeding in up to 25% of patients but is usually minor surgical site bleeding. Avoiding IAT in intracranial surgery patients may reduce complications. Mortality rate in this series was similar to that reported in prior IAT trials. IAT remains a viable therapeutic option for postoperative strokes.

The cost of pneumonia after acute stroke

Objective: To determine the incremental costs of pneumonia occurring during hospitalization for stroke. Methods: We reviewed hospital records of all Medicare patients admitted for ischemic or hemorrhagic stroke to 29 hospitals in a large metropolitan area, 1991 through 1997, excluding those who died or had do not resuscitate orders written within 3 days of admission. Hospital costs of patients with stroke were determined using Medicare Provider Analysis and Review data after adjustment for baseline factors affecting cost and propensity for pneumonia. Secondary analyses examined the risk-adjusted relationship of pneumonia to discharge disposition. Results: Pneumonia occurred in 5.6% (635/11,286) of patients with stroke, and was more common among patients admitted from nursing homes and those with greater severity of illness (p < 0.001). Mean adjusted costs of hospitalization for patients with stroke with pneumonia were