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Biomedical subjects

Markku Kaste

Publications and source records attributed to Markku Kaste.

At least 37 records · Page 2Linked to original sources
PubMed2004

Long-term outcome after intravenous thrombolysis of basilar artery occlusion.

CONTEXT: Basilar artery occlusion (BAO) is an infrequent disease with high morbidity and mortality. Intra-arterial thrombolysis is advocated for treatment but is limited to use at specialized centers. OBJECTIVE: To evaluate outcomes for patients with BAO treated with intravenous thrombolytic therapy. DESIGN, SETTING, AND PARTICIPANTS: During 1995 to 2003, 50 consecutive patients with angiographically proven BAO were treated according to an institutional therapy protocol based on intravenous thrombolysis with recombinant tissue plasminogen activator (alteplase). Patients were treated at an urban university teaching hospital receiving all patients with ischemic stroke who were considered for thrombolysis in a catchment area of 1.5 million inhabitants in Helsinki, Finland. INTERVENTION: Intravenous administration of alteplase (0.9 mg/kg) during a 1-hour infusion. MAIN OUTCOME MEASURES: Basilar artery recanalization determined by magnetic resonance angiography and clinical outcomes at 3 months and at 1 year or longer determined by modified Rankin Scale and Barthel Index scores. RESULTS: Recanalization was studied in 43 patients and verified in 26 (52%) of all patients. By 3 months, 20 patients (40%) had died while 11 had good outcomes (modified Rankin Scale score, 0-2); 12 (24%) reached independence in activities of daily living (Barthel Index score, 95-100), and 6 (16%) were severely disabled (Barthel Index score, 0-50). In the long term (median follow-up 2.8 years), 15 patients (30%) reached good outcomes (modified Rankin Scale score, 0-2) while 23 (46%) died. CONCLUSIONS: Intravenous administration of alteplase for patients with BAO appears to be associated with rates of survival, recanalization, and independent functional outcome comparable with those reported with endovascular approaches. These data suggest that a randomized trial is needed to compare these approaches for treatment of BAO.

Adult↗
PubMed2004

Targeting neuroprotection clinical trials to ischemic stroke patients with potential to benefit from therapy.

BACKGROUND AND PURPOSE: Clinical trials of neuroprotective drugs have had limited success. We investigated whether selecting patients according to prognostic features would improve the statistical power of a trial to identify an efficacious treatment. METHODS: Using placebo data from the Glycine Antagonist in Neuroprotection (GAIN) International and National Institute of Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator (rtPA) clinical trials, we developed and validated simple prognostic models for stroke trial end points: Barthel Index > or =95, modified Rankin Scale < or =1, National Institutes of Health Stroke Scale < or =1, and Glasgow Outcome Scale=1. Using these models, we simulated 1000 clinical trials and estimated, under several hypothetical treatment effect patterns of neuroprotection, the effect on statistical power of including only patients with moderate prognosis. We calculated the number of patients that would have to be enrolled to maintain the statistical power achieved in selecting the whole trial population. Reanalysis of actual data from the NINDS rtPA trials confirmed the results independently. RESULTS: Selecting patients with moderate prognosis (predicted probability of favorable outcome 0.2 to 0.8) enabled a sample size reduction, without loss of statistical power, of between 54.6% (51.3% to 57.6%) and 68.6% (66.0% to 71.1%), depending on the treatment effect pattern and outcome measure. These benefits were largely due to the exclusion of patients with poor prognosis. CONCLUSIONS: Targeting patients with potential to benefit enables a substantial sample size reduction without compromising statistical power or duration of recruitment. As part of a broader trial design strategy, informed use of prognostic data available acutely would help in identifying effective neuroprotective treatments.

Aged↗
PubMed2004

Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials.

BACKGROUND: Quick administration of intravenous recombinant tissue plasminogen activator (rt-PA) after stroke improved outcomes in previous trials. We aimed to analyse combined data for individual patients to confirm the importance of rapid treatment. METHODS: We pooled common data elements from six randomised placebo-controlled trials of intravenous rt-PA. Using multivariable logistic regression we assessed the relation of the interval from stroke onset to start of treatment (OTT) on favourable 3-month outcome and on the occurrence of clinically relevant parenchymal haemorrhage. FINDINGS: Treatment was started within 360 min of onset of stroke in 2775 patients randomly allocated to rt-PA or placebo. Median age was 68 years, median baseline National Institute of Health Stroke Scale (NIHSS) 11, and median OTT 243 min. Odds of a favourable 3-month outcome increased as OTT decreased (p=0.005). Odds were 2.8 (95% CI 1.8-4.5) for 0-90 min, 1.6 (1.1-2.2) for 91-180 min, 1.4 (1.1-1.9) for 181-270 min, and 1.2 (0.9-1.5) for 271-360 min in favour of the rt-PA group. The hazard ratio for death adjusted for baseline NIHSS was not different from 1.0 for the 0-90, 91-180, and 181-270 min intervals; for 271-360 min it was 1.45 (1.02-2.07). Haemorrhage was seen in 82 (5.9%) rt-PA patients and 15 (1.1%) controls (p<0.0001). Haemorrhage was not associated with OTT but was with rt-PA treatment (p=0.0001) and age (p=0.0002). INTERPRETATION: The sooner that rt-PA is given to stroke patients, the greater the benefit, especially if started within 90 min. Our results suggest a potential benefit beyond 3 h, but this potential might come with some risks.

Aged↗
PubMed2004

Management of atherothrombosis with clopidogrel in high-risk patients with recent transient ischaemic attack or ischaemic stroke (MATCH): study design and baseline data.

BACKGROUND: The CAPRIE study showed the superiority of clopidogrel over acetylsalicylic acid (ASA) for reducing the combined risk of major atherothrombotic events in patients with recent myocardial infarction (MI), recent ischaemic stroke (IS) or established peripheral arterial disease. The benefit of clopidogrel over ASA is amplified in high-risk patients. Proof of concept for the benefit of clopidogrel in addition to ASA in patients with coronary manifestations of atherothrombosis was provided by the CURE trial. METHODS: MATCH is a randomized, double-blind, placebo-controlled trial that compares clopidogrel and ASA versus clopidogrel alone in high-risk patients with recently symptomatic cerebrovascular disease. Eligible patients have experienced a transient ischaemic attack (TIA) or IS within the last 3 months and have evidence of at least 1 additional risk factor within the last 3 years (prior IS, MI, stable or unstable angina pectoris, diabetes or symptomatic peripheral arterial disease). Patients were randomized to receive ASA 75 mg once daily or placebo, with both groups receiving clopidogrel 75 mg once daily as part of standard therapy. The primary end point is the composite of IS, MI, vascular death and rehospitalization for an acute ischaemic event. The duration of treatment and follow-up is 18 months for each patient. RESULTS: Enrollment was completed in April 2002, with 7,599 patients randomized to receive the study medication. The mean age at randomization was 66 years, and the qualifying event was IS in 78.9% of patients and TIA in 21.1%. The baseline features of the study cohort indicate a population that is at a high risk for atherothrombotic recurrence. CONCLUSION: MATCH is a major ongoing trial that will provide important data on the benefit of clopidogrel and ASA compared with clopidogrel alone for reduction of vascular ischaemic events in patients with recent TIA or IS who are at high risk of atherothrombotic event recurrence.

Arteriosclerosis↗
PubMed2004

An update on thrombolytic therapy for acute stroke.

PURPOSE OF REVIEW: Stroke is the third leading cause of death after myocardial infarction and cancer, and is the leading cause of permanent disability and disability-adjusted loss of independent life-years in western countries. Thrombolysis is the treatment of choice for acute stroke within 3 h after the onset of symptoms. We present an overview of a diagnostic approach to acute stroke management that allows the individualization of patient management based on pathophysiological reasoning and not rigid time windows established by randomized controlled trials. RECENT FINDINGS: This review concentrates in the first part on giving the reader an integrated knowledge of the current status of thrombolytic therapy in stroke, and in the second part develops a treatment algorithm based on pathophysiological information rendered by a multiparametric stroke magnetic resonance imaging protocol. SUMMARY: Thrombolysis is an effective therapy for ischemic stroke, whether performed intravenously within 3 h or intra-arterially within 3-6 h. Meta-analyses have provided evidence of an effect of intravenous thrombolysis beyond the 3 h time window, especially when improved selection criteria such as modern magnetic resonance imaging protocols are applied. Sadly, thrombolysis is still underused. Positive results from studies currently underway may encourage more centers to offer this therapy to an increasing number of stroke patients, and thereby reduce the considerable socioeconomic burden of stroke.

Cerebral Infarction↗
PubMed2004

Brain metabolic alterations in patients with type 1 diabetes-hyperglycemia-induced injury.

Microangiopathic end-organ injury is common in type 1 diabetes. However, the pathophysiology of diabetic encephalopathy is poorly understood. The authors studied 10 normotensive patients with type 1 diabetes with retinopathy, autonomic neuropathy, but without nephropathy, and 10 healthy subjects. Proton magnetic resonance spectroscopy was performed at 1.5 T in the frontal cortex, thalamus, and posterior frontal white matter. There was no change in N-acetyl-containing compounds (NA), but choline-containing compounds (Cho) were increased in the white matter and in the thalamus; myo-inositol was increased in the white matter, glucose excess was found in all brain, and water intensity was increased in the cortical voxel in the patients. Calculated lifetime glycemic exposure correlated inversely with Cho and NA in white matter and with Cho in thalamus. Concentrations of soluble intercellular adhesion molecules and vascular cell adhesion molecules were increased in the patients. In conclusion, in patients with type 1 diabetes, the increase in adhesion molecules and an association between altered brain metabolites and glycemic exposure suggest the presence of a vascularly mediated, progressive metabolic disturbance in the brain.

Adult↗
PubMed2003

Auditory discrimination after left-hemisphere stroke: a mismatch negativity follow-up study.

BACKGROUND AND PURPOSE: We sought to determine the recovery of cortical auditory discrimination in aphasic, left-hemisphere-stroke patients by using an electrophysiological response called mismatch negativity (MMN) and speech-comprehension tests. METHODS: MMN in 8 left-hemisphere stroke patients was recorded in response to duration and frequency changes in a repetitive, harmonically rich tone 4 and 10 days and again 3 and 6 months after their first unilateral stroke. Eight age-matched, healthy persons served as control subjects. RESULTS: At 4 days after stroke onset, patients' sound discrimination was impaired in their left hemisphere, as suggested by attenuated MMNs, especially to right-ear stimuli. At 3 months after stroke, however, MMN to the right-ear duration change had significantly increased and was of normal size. A significant change for the frequency MMN was found for left-ear stimuli between 3 and 6 months after stroke. During the follow-up period, progressive improvement in speech-comprehension tests was also observed. Furthermore, there was a significant correlation between the change in the duration MMN amplitude and the Boston Diagnostic Aphasia Examination speech-comprehension test from 10 days to 3 months after stroke. CONCLUSIONS: These results suggest that the MMN can be used as an index of the recovery of auditory discrimination.

Acoustic Stimulation↗
PubMed2003

Cerebral hemodynamics in asymptomatic and symptomatic patients with high-grade carotid stenosis undergoing carotid endarterectomy.

BACKGROUND AND PURPOSE: Asymptomatic patients with carotid stenosis benefit less from carotid endarterectomy (CEA) than symptomatic patients because the risk of embolic events is lower, but it is not known whether the hemodynamic effect of CEA is different between the groups. We evaluated hemodynamics of symptomatic and asymptomatic patient groups before and after CEA. METHODS: Forty-six independent patients with a unilateral high-grade carotid stenosis, 23 asymptomatic and 23 symptomatic, underwent dynamic susceptibility contrast MRI (DSC-MRI) and transcranial Doppler ultrasound (TCD) evaluation before CEA and 3 and 100 days afterward. Quantitative perfusion parameters were calculated separately in selected regions of white and gray matter and watershed regions in each hemisphere, and mean transit time (MTT) maps were assessed visually by 2 independent observers. Vasomotor reactivity was determined with breath-holding index and flow impedance with pulsatility index ipsilaterally. RESULTS: In contrast to the asymptomatic carotid stenosis group, symptomatic carotid stenosis patients had preoperatively increased MTT and lower cerebral blood flow values in the ipsilateral hemisphere, more in white matter and watershed regions than in gray matter. Visually detected perfusion deficits were associated with symptomatic status. The interhemispheric asymmetries were abolished by CEA. The improving trend over time was greater in the symptomatic carotid stenosis group and was best seen in MTT. On TCD, pulsatility index was lower in symptomatic carotid stenosis patients preoperatively, with no postoperative difference, whereas the breath-holding index improved only in the symptomatic carotid stenosis group after CEA. CONCLUSIONS: Patients with asymptomatic and symptomatic carotid stenosis differ significantly by means of DSC-MRI and TCD before and in response to CEA.

Aged↗
PubMed2003

Community-based thrombolytic therapy of acute ischemic stroke in Helsinki.

BACKGROUND AND PURPOSE: Thrombolysis with alteplase is used in acute ischemic stroke within 3 hours after symptom onset in many stroke centers, but experience remains limited in Europe. METHODS: Using eligibility and management criteria similar to those published by the American Heart Association, we treated 75 consecutive patients aged 21 to 83 years (mean age, 63.6 years; median Scandinavian Stroke Scale score, 32/58) with hemispheric infarction with alteplase in 1998-2001. Their neuroradiological findings (ischemic and hemorrhagic changes) and functional outcome at 3 months were evaluated. RESULTS: Sixty-one percent of the patients had recovered functional independence (Barthel Index 95 to 100) at the 3-month follow-up. On the modified Rankin Scale (mRS), 37% (28/75) of patients had no or minimal symptoms (mRS 0 to 1), while 17% (13/75) remained dependent (mRS 4 to 5) and 5% (4/75) died. Cerebral parenchymal hematomas occurred in 8% (6/75) and hemorrhagic transformation in 8% (6/75) of the patients. Low initial diastolic blood pressure and administration of intravenous antihypertensive medication were associated with unfavorable outcome (mRS 3 to 6). CONCLUSIONS: We conclude that our management protocol for thrombolytic therapy is safe. These rates of functional outcome, case fatality, and hemorrhagic cerebral events compare favorably with those of other published series of stroke thrombolysis with similar time windows and management guidelines. Associations between blood pressure and its treatment during thrombolysis with functional outcome deserve further analysis.

Academic Medical Centers↗
PubMed2003

Recommendations for the relationship between sponsors and investigators in the design and conduct of clinical stroke trials.

BACKGROUND: As increasing numbers of clinical trials are being conducted worldwide, there has been concern about the relationship between the sponsors and investigators. Both parties need benchmarks or recommendations to act as a reference point when trials are initiated and conducted. These recommendations are designed to fulfill this role. SUMMARY OF COMMENT: A series of meetings of the International Trial Subcommittee of the International Stroke Liaison Committee, American Stroke Association, were conducted to review a series of draft recommendations that were then modified on the basis of the experience of the committee in the conduct of clinical trials. Consensus was reached on all points of the final document. The recommendations represent the opinions of the authors and do not necessarily reflect the views of the American Stroke Association. The document contains sensible recommendations concerning required sponsor company qualities, trial management structure, protocol development, trial conduct, data management, blinding, data analyses, publication, remuneration, and conflict of interest issues. CONCLUSIONS: The recommendations should provide a simple and practical benchmark for both investigators and sponsors in the conduct of clinical trials. Although designed for trials involving therapies for stroke, the framework allows generalization to other disciplines.

Clinical Trials as Topic↗
PubMed2003

Thrombolysis for acute stroke.

PURPOSE OF REVIEW: Stroke thrombolysis is in the process of moving from academic centers into community-based standard therapy in experienced centers. Recently published data on patient selection, imaging and other technical or organizational advances are reviewed in order to improve the safety and efficacy of stroke thrombolysis and identify areas in which more study is needed. RECENT FINDINGS: During the past year, several open series were published on the application of thrombolysis in community-based settings, which have mostly reproduced the outcome described in randomized, placebo-controlled recombinant tissue plasminogen activator cohorts. New information has been produced to identify the clinical parameters that are associated with good and adverse outcomes after stroke thrombolysis. Elevated blood glucose decreases the likelihood of a good outcome and increases that of cerebral hemorrhagic change, but the effect of early glucose reduction needs to be investigated. Non-contrast computed tomography still prevails as the standard imaging method in patient selection, but computed tomography angiography can be added within a reasonable time to furnish vascular diagnosis. Perfusion-weighted imaging is used to quantify the fraction of brain tissue salvaged by intravenous thrombolysis, and may be used in the future to select patients with still viable penumbral brain tissue, even beyond a 3-h time-window, if efficacy can be proved. SUMMARY: Thrombolysis with recombinant tissue plasminogen activator is well tolerated and effective within 3 h of symptoms, and new trials will determine if extension of this time-window or new target populations for thrombolysis, such as children with stroke, can be substantiated. An unfinished task remains in the education of health personnel; imperatives stemming from pathophysiology need to penetrate attitudes on acute stroke at all levels before acute therapies such as thrombolysis can have an impact on stroke outcome in general.

Cerebral Infarction↗
PubMed2003

Administration of nonionic iodinated contrast medium does not influence the outcome of patients with ischemic brain infarction.

Some reports indicate that exposure to iodinated contrast medium (CM) could worsen the outcome of patients with brain infarction. In this prospective study, we compared the outcome of 77 patients receiving and 128 not receiving nonionic iodinated CM. Stroke severity was assessed by the Scandinavian Prognostic Stroke Score, and outcome by the Rankin Scale. All radiological studies using intravenous or intra-arterial CM were registered. Two nonionic iodinated CM (iopamidol and iohexol) were used. Exposure to CM did not influence case fatality, ability to live at home, ability to walk, disability and stroke severity. Initial stroke severity and arterial hypertension were independent determinants of poor neurological recovery or death. Large infarct, age, male gender, and baseline stroke severity were independent determinants of major disability or death. CM enhancement on CT did not show any harmful effect on stroke severity or outcome. As a conclusion, intravascular administration of nonionic iodinated CM did not influence stroke severity or outcome of our patients.

Age Factors↗