Community use of intravenous tissue plasminogen activator for acute stroke: results of the brain matters stroke management survey.

BACKGROUND AND PURPOSE: Little is known of neurologists' viewpoints regarding intravenous tPA use or institutional readiness to evaluate potential thrombolytic candidates. METHODS: Surveys were distributed at the Brain Matters Stroke Management Workshops held in 16 cities in the United States. RESULTS: Intravenous tPA was administered by 46.9% of responding neurologists. Almost 30% (29.9%) of surveyed neurologists were "very convinced" of its efficacy, whereas 61.6% were "very concerned" about the risk of intracranial hemorrhage. Only half of the respondents believed their institutions could meet all NINDS-recommended stroke-evaluation time targets. CONCLUSIONS: Neurologists' enthusiasm for the efficacy of intravenous tPA is tempered by their concern about intracranial hemorrhage. Institutional readiness for evaluating acute stroke patients is not optimized.

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 degrees 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.

Progressive vision loss. A rare manifestation of familial cavernous angiomas.

We studied four generations of a family in which the index case had progressive loss of vision secondary to a cavernous angioma of the optic nerve and chiasm. Magnetic resonance imaging of the brain revealed multiple, asymptomatic intracerebral cavernous angiomas. Brain magnetic resonance imaging scans of the family members revealed multiple cavernous angiomas in the brother and paternal grandfather, but none in the father or his siblings. Autopsy reports of the paternal great grandfather noted multiple cavernous angiomas in the brain and abdominal viscera. We believe our patient to be the sixth reported case in which a cavernous angioma involved the optic chiasm and optic nerve. Magnetic resonance imaging is a sensitive and specific method of detecting cavernous angiomas. Cavernous angiomas have an autosomal dominant pattern of inheritance with variable penetrance. Surgical intervention in patients with symptomatic cavernous angiomas depends on the location and size of the lesion and associated surgical risks.

Mechanism of stroke in patients taking aspirin.

During a 1-year period, we prospectively studied the mechanism and severity of stroke in 47 patients sustaining a cerebral infarction while taking aspirin. The mechanism of stroke was undetermined in 12 patients (26%). In the remaining 35 patients, we identified 39 potential mechanisms: large-artery atherosclerosis (19 patients, 40%), cardioembolism (15 patients, 32%), and small-vessel occlusive disease (5 patients, 11%). Of 11 patients with carotid atherosclerosis and stroke, 9 (82%) had greater than 90% carotid stenosis or occlusion; of 12 patients with stroke of undetermined mechanism, 10 (83%) had previous stroke, of which 8 were also of undetermined mechanisms. Disability after stroke was moderate or severe in 27 patients (57%). These data suggest that (1) stroke in patients taking aspirin has a variety of etiologies and frequently causes moderate or severe disability; (2) patients with carotid disease failing aspirin often have high-grade carotid stenosis or occlusion; (3) stroke of undetermined mechanism may recur more frequently than other stroke subtypes in patients taking aspirin.

Ibuprofen-induced meningitis: detection of intrathecal IgG synthesis and immune complexes.

We report a case of ibuprofen-induced meningitis in an otherwise healthy individual. This is the 1st case documenting intrathecal IgG synthesis and immune complex formation in this disorder. The immunopathogenesis remains obscure, but is suggestive of an antigen-specific process requiring the presence of or exposure to ibuprofen.

Transcranial Doppler assessment of cerebral perfusion reserve in patients with carotid occlusive disease and no evidence of cerebral infarction.

Using transcranial Doppler ultrasound (TCD), we measured bilateral middle cerebral artery mean blood flow velocities (MCAVs) before and 10 minutes after intravenous infusion of 1 gram of acetazolamide in 20 patients without cerebral infarction. Seven patients had normal carotid arteries (group 1), seven had unilateral internal carotid artery (ICA) stenosis > or = 75% (group 2), and six had unilateral ICA occlusion (group 3). Before acetazolamide infusion, side-to-side differences in MCAV were 0.06 cm/sec in group 1 (p = 0.98), 4.3 cm/sec in group 2 (p = 0.36), and 15.0 cm/sec in group 3 (p = 0.02). Bilateral MCAV increased in all three groups after acetazolamide infusion, and the side-to-side differences in MCAV were 3.2 cm/sec in group 1 (p = 0.40), 11.4 cm/sec in group 2 (p = 0.04), and 27.6 cm/sec in group 3 (p = 0.03). Patients with carotid stenosis or occlusion and ipsilateral transient ischemic attacks (TIAs) had higher side-to-side differences in MCAV before (p = 0.03) and after (p = 0.01) acetazolamide than did asymptomatic patients with carotid disease. The association of impaired cerebral perfusion reserve and TIAs suggests that the TCD-acetazolamide test may enable identification of a subgroup of patients with carotid occlusive disease who are at higher risk for stroke.

The Warfarin-Aspirin Symptomatic Intracranial Disease Study.

We conducted a retrospective, multicenter study to compare the efficacy of warfarin with aspirin for the prevention of major vascular events (ischemic stroke, myocardial infarction, or sudden death) in patients with symptomatic stenosis of a major intracranial artery. Patients with 50 to 99% stenosis of an intracranial artery (carotid; anterior, middle, or posterior cerebral; vertebral; or basilar) were identified by reviewing the results of consecutive angiograms performed at participating centers between 1985 and 1991. Only patients with TIA or stroke in the territory of the stenotic artery qualified for inclusion in the study. Patients were prescribed warfarin or aspirin according to local physician preference and were followed by chart review and personal or telephone interview. Seven centers enrolled 151 patients; 88 were treated with warfarin and 63 were treated with aspirin. Median follow-up was 14.7 months (warfarin group) and 19.3 months (aspirin group). Vascular risk factors and mean percent stenosis of the symptomatic artery were similar in the two groups, yet the rates of major vascular events were 18.1 per 100 patient-years of follow-up in the aspirin group (stroke rate, 10.4/100 patient-years; myocardial infarction or sudden death rate, 7.7/100 patient-years) compared with 8.4 per 100 patient-years of follow-up in the warfarin group (stroke rate, 3.6/100 patient-years; myocardial infarction or sudden death rate, 4.8/100 patient-years). Kaplan-Meier analysis showed a significantly higher percentage of patients free of major vascular events among patients treated with warfarin (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Intra-arterial thrombolysis for perioperative stroke after open heart surgery.

Recent major surgery is an exclusion criterion for thrombolysis. Six patients with acute ischemic stroke underwent intra-arterial thrombolysis after recent open heart surgery without clinically significant bleeding complications, although one patient developed a small, asymptomatic cerebellar hemorrhage. Intra-arterial thrombolysis may be an option for patients with cerebral embolism in the perioperative period.

Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial.

OBJECTIVE: To analyze the frequency, clinical characteristics, and predictors of symptomatic intracerebral hemorrhage (ICH) after intraarterial (IA) thrombolysis with recombinant pro-urokinase (r-proUK) in acute ischemic stroke. METHOD: The authors conducted an exploratory analysis of symptomatic ICH from a randomized, controlled clinical trial of IA thrombolysis with r-proUK for patients with angiographically documented occlusion of the middle cerebral artery within 6 hours from stroke onset. Patients (n = 180) were randomized in a ratio of 2:1 to either 9 mg IA r-proUK over 120 minutes plus IV fixed-dose heparin or IV fixed-dose heparin alone. As opposed to intention to treat, this analysis was based on "treatment received" and includes 110 patients given r-proUK and 64 who did not receive any thrombolytic agent. The remaining six patients received out-of-protocol urokinase and were excluded from analysis. The authors analyzed centrally adjudicated ICH with associated neurologic deterioration (increase in NIH Stroke Scale [NIHSS] score of > or =4 points) within 36 hours of treatment initiation. RESULTS: Symptomatic ICH occurred in 12 of 110 patients (10.9%) treated with r-proUK and in two of 64 (3.1%) receiving heparin alone. ICH symptoms in r-proUK-treated patients occurred at a mean of 10.2 +/- 7.4 hours after the start of treatment. Mortality after symptomatic ICH was 83% (10/12 patients). Only blood glucose was significantly associated with symptomatic ICH in r-proUK-treated patients based on univariate analyses of 24 variables: patients with baseline glucose >200 mg/dL experienced a 36% risk of symptomatic ICH compared with 9% for those with < or =200 mg/dL (p = 0.022; relative risk, 4.2; 95% CI, 1.04 to 11.7). CONCLUSIONS: Symptomatic ICH after IA thrombolysis with r-proUK for acute ischemic stroke occurs early after treatment and has high mortality. The risk of symptomatic ICH may be increased in patients with a blood glucose >200 mg/dL at stroke onset.

Prophylaxis and treatment of stroke. The state of the art in 1993.

The most significant impact on cerebral infarction comes from the primary prevention of the processes that lead to stroke in at-risk individuals prior to the development of symptoms. Antithrombotic therapy with warfarin or aspirin significantly reduces thromboembolic risk in non-valvular atrial fibrillation. The failure of primary preventive measures and the progression of disease is heralded by the development of cerebral or retinal ischaemic events; the majority of clinical trials investigating stroke prevention have targeted the secondary prevention of stroke in patients with ischaemic symptoms. A 25% risk reduction has been demonstrated with antiplatelet therapy. This was typically aspirin 1000 to 1300 mg/day, but more recently even lower doses have been beneficial, with lower rates of minor and major bleeding. Ticlopidine has demonstrated efficacy in the secondary prevention of stroke after transient ischaemic attacks and completed stroke, with a 2% risk of significant neutropenia. The benefits of carotid endarterectomy have been demonstrated in patients with symptomatic internal carotid artery stenosis involving 70 to 99% of the arterial diameter. Surgery is not indicated in patients with less than 30% internal carotid artery stenosis; 30 to 69% continues to be studied. When primary and secondary preventive measures have failed, strategies directed at managing acute focal cerebral ischaemia include re-establishing cerebral blood flow and limiting ischaemic neuronal injury. Advances in basic research that have identified components of the ischaemic cascade have been translated clinically into numerous clinical trials, each targeted to one or sometimes two steps in the hope of improving neuronal salvage.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug treatment of stroke. Current status and future prospects.

Despite advances in the understanding of the mechanism of cerebral injury during focal ischaemia, the best treatment of cerebral ischaemia is still prevention. The pathophysiological mechanisms that contribute to cerebral ischaemia are discussed relative to the many therapeutic interventions that have been attempted. It is our impression that the treatment of such a complex multifactor process will require multimodal therapy, as most of the unifactorial therapies used to date have proven relatively unsuccessful in improving neurological outcome and survival.

Cerebrovascular complications of rheumatic disease.

Cerebral ischemia and infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebral venous thrombosis, and cerebral vasculitis are dreaded but largely uncommon complications of most rheumatic diseases. In some conditions, however, such as the antiphospholipid syndrome or Behcet's disease, stroke may be the presenting complaint. A format for approaching the patient and localizing the cerebrovascular lesion has been presented along with a summary of the specific rheumatologic diseases implicated for each stroke subtype.

Safety and efficacy of intraarterial thrombolysis for perioperative stroke after cardiac operation.

BACKGROUND: Acute ischemic stroke after cardiac operations is a devastating complication with limited therapeutic options. As clinical trials of thrombolysis for acute ischemic stroke exclude patients with recent major surgery, the safety of intraarterial thrombolysis in this setting is unknown. METHODS: Thirteen patients with acute ischemic stroke within 12 days of cardiac operation underwent intraarterial thrombolysis within 6 hours of stroke symptom onset. The National Institutes of Health Stroke Scale was used to assess neurologic recovery. RESULTS: The mean age was 69 years (standard deviation +/-5 years) and 62% were men. Cardiac procedures included valve operations in 6 patients, coronary artery bypass grafting in 4, valve and coronary artery bypass grafting in 2, and left ventricular assist device in 1 patient. Atrial fibrillation occurred in 5 patients (38%). The mean time from operation to stroke was 4.3 days (standard deviation +/- 3 days). Thrombolysis was initiated within 3.6 hours (standard deviation +/-1.6 hours) of stroke symptom onset. Recanalization was complete in 1 patient, partial in 5, and 7 patients had low flow. Neurologic improvement occurred in 5 patients (38%). One patient needed a chest tube for hemothorax, 2 others were transfused for low hemoglobin. No operative intervention for bleeding was necessary. CONCLUSIONS: In select patients with acute ischemic stroke after recent cardiac operation, intraarterial thrombolysis appears to be reasonably safe and may lead to neurologic recovery.

Giant and multiple aneurysms of the distal posterior inferior cerebellar artery.

A case involving giant and multiple aneurysms of the distal posterior inferior cerebellar artery (PICA) is presented. Of the 130 reported cases of peripheral aneurysms of the PICA, 6 have been described as giant aneurysms and 5 have involved multiple aneurysms located on a single PICA. The occurrence of multiple aneurysms including one giant aneurysm has not been reported previously. A clinical description of our case as well as a review of the literature is presented.

Reversal of a dense, persistent, holohemispheric neurological deficit after an endarterectomy of the carotid artery: case report.

The role and timing of a carotid endarterectomy in the setting of an acute ischemic stroke-in-evolution remain controversial. Although computed tomographic (CT) scans typically show no abnormalities in the acute stage, it is generally agreed that a dense neurological deficit (hemiplegia) and/or multiple modality neurological disturbance (involving motor, sensory, gaze, and visual field impairment) represent contraindications to surgical intervention. We present a case of an acute right holohemispheric neurological deficit including dense hemiplegia, hemisensory loss, gaze disturbance, hemineglect, and impaired level of consciousness. This persisted for 4 days while serial CT scans showed no evidence of infarction. Angiography revealed pre-occlusive stenosis of the right internal carotid artery with sluggish antegrade flow. The anterior collaterals of the circle of Willis were impaired, and the right middle cerebral artery territory filled via the posterior communicating artery. Despite the dense neurological deficit persisting for 4 days, a carotid endarterectomy was performed. Gradual neurological improvement was noted within hours of the operation, and all neurological deficits resolved within the subsequent 3 days. This case is consistent with prolonged holohemispheric hemodynamic compromise below the threshold of neurological dysfunction, but above the threshold of tissue infarction ("idling neurons"). Features assisting in the recognition of this unusual scenario and the indications and risks of revascularization in this setting are discussed.

The effect of subarachnoid hemorrhage on blood and CSF atrial natriuretic factor.

Atrial natriuretic factor (ANF) is a diuretic natriuretic peptide hormone produced by both the heart and brain which has been postulated to play a role in the hemodynamic and sodium instability that frequently follows subarachnoid hemorrhage (SAH). Levels of ANF were measured in 12 patients with nontraumatic SAH and nine control patients with unruptured cerebral aneurysms. At surgery, the mean plasma ANF level (+/- standard deviation) of the SAH group was significantly higher than that of the control group (158.1 +/- 83.8 vs. 57.8 +/- 45.3 pg/ml, respectively; p = 0.01). There was no significant difference in serum sodium concentration, blood pressure, or central venous pressure between these groups. Nine patients with SAH due to aneurysm rupture had plasma ANF levels similar to those in three patients with SAH due to other causes. Four patients with moderate to severe SAH had significantly higher mean cerebrospinal fluid (CSF) ANF values (17.7 +/- 12.8 pg/ml) than five patients with minimal SAH (0.6 +/- 0.9 pg/ml) or the control group of nine patients (3.7 +/- 1.3 pg/ml) (p less than 0.05). Five patients with moderate to severe SAH had significantly higher plasma ANF values (202.6 +/- 72.2 pg/ml) than five with minimal SAH (86.8 +/- 29.2 pg/ml) or the control group (57.8 +/- 45.3 pg/ml) (p less than 0.05). Plasma ANF values were substantially higher than CSF ANF content in the SAH group (p less than 0.01) and in the control group (p = 0.05). From these data it is concluded that: 1) plasma ANF is elevated significantly after SAH; 2) this rise appears unrelated to the cause of hemorrhage, serum sodium concentration, blood pressure, or central venous pressure, but is related to the extent of the hemorrhage; 3) ANF concentrations in the CSF are significantly lower than in plasma, and are elevated after moderate to severe SAH; and 4) the source of CSF ANF is probably the plasma, and the source of plasma ANF is likely the heart.

Neurologic complications of vascular surgery.

Technological advances in the management of cardiovascular disorders have resulted in an expansion of eligibility criteria for treatment, as well as an increased demand for improved outcomes. Neurologic complications after coronary artery bypass surgery, particularly stroke and cognitive dysfunction, substantially increase mortality, strain health care resources, and reduce the clinical effectiveness of the procedure. Carotid endarterectomy can be both the optimum stroke preventative strategy as well as a cause of stroke. The trend toward minimally invasive endovascular procedures, which has provided non-surgical options for both coronary and cerebral vascular occlusive lesions, is slowly being compared to conventional surgical and medical therapies. The identification of risk factors and mechanisms of adverse cerebral outcomes of these myriad vascular procedures is essential in improving their clinical effectiveness and patient applicability.

Neurologic complications related to cardiac surgery.

Neurologic complications are a major cause of morbidity, complicating open heart surgery, cardiac catheterization, and interventional techniques. Global or focal brain ischemia related to embolism or hypoperfusion predominates. Breakthrough cerebral hemorrhage and infection can complicate cardiac transplantation. Identifying individuals at risk for cerebrovascular complications may lead to more effective preventative and treatment measures.

Carotid stenosis: current strategies for choosing between medical and surgical management.

The effectiveness of carotid revascularization depends on appropriate patient selection and balancing the expected benefits with the risks of treatment. Exceeding a rate of serious complications (strokes and deaths) of 5% for asymptomatic and 9% for symptomatic patients negates any benefit for carotid endarterectomy. Endovascular techniques such as stent-supported angioplasty will likely change the management approach for some patients with carotid occlusive disease. This paper contains the author's recommendations for choosing between medical and surgical management of carotid stenosis.

Stereotactic biopsy of non-neoplastic lesions in adults.

Stereotactic biopsy of intracranial lesions has been used primarily for the diagnosis of neoplastic lesions. A series of 158 consecutive stereotactic biopsies performed at The Cleveland Clinic Foundation resulted in 28 diagnoses of non-neoplastic disorders (18%). The majority of these were infectious, inflammatory, or demyelinating disorders. Stereotactic biopsy alone was diagnostic in 17 cases (61%), and biopsy in conjunction with clinical and laboratory data established definitive diagnoses in six cases (22%). All 23 definitive diagnoses led to modifications in patient management. Permanent neurologic morbidity occurred in only two patients (7%). We maintain that this procedure is underused. Stereotactic biopsy is safe, accurate, and useful for diagnosis of non-neoplastic neurologic disorders when the diagnosis is unclear by conventional means. In such cases, its use can lead to early diagnosis and treatment.