Potential of integrated [18F] fluorodeoxyglucose positron-emission tomography/CT in identifying vulnerable carotid plaques.

BACKGROUND AND PURPOSE: There is a need for improved risk stratification of patients with TIA/stroke and carotid atherosclerosis. The purpose of this study was to prospectively investigate the potential of integrated (18)F-FDG PET/MDCT in identifying vulnerable carotid plaques. MATERIALS AND METHODS: Fifty patients with TIA/stroke with an ipsilateral carotid plaque causing <70% stenosis and a plaque on the contralateral asymptomatic side underwent integrated (18)F-FDG PET/MDCT within 36.1 ± 20.0 days (range, 9-95 days) of the last symptoms. Carotid plaque (18)F-FDG uptake was measured as both the mean and maximum blood-normalized SUV, known as the TBR. Using MDCT, we assessed volumes of vessel wall and individual plaque components. RESULTS: Mean TBR was only significantly larger in the ipsilateral plaques of patients who were imaged within 38 days (1.24 ± 0.04 [SE] versus 1.17 ± 0.05, P = .014). This also accounted for maximum TBR (1.53 ± 0.06 versus 1.42 ± 0.06, P = .015). MDCT-assessed vessel wall and LRNC volumes were larger in ipsilateral plaques of all patients (982.3 ± 121.3 versus 811.3 ± 106.6 mm(3), P = .016; 164.7 ± 26.1 versus 134.3 ± 35.2 mm(3), P = .026, respectively). CONCLUSIONS: In the present study, (18)F-FDG PET only detected significant differences between ipsilateral and contralateral asymptomatic plaques in patients with TIA/stroke who were imaged within 38 days, whereas MDCT detected larger vessel wall and LRNC volumes, regardless of time after symptoms. In view of the substantial overlap in measurements of both sides, it remains to be determined whether the differences we found will be clinically meaningful.

[Success of carotid endarterectomy dependent on type of atherosclerotic plaque and gender, among others]. / Succes van carotisendarteriëctomie afhankelijk van onder meer het type atherosclerotische plaque en het geslacht.

Carotid endarterectomy (CEA) reduces the risk of stroke in both symptomatic and asymptomatic patients with a high-grade stenosis of the internal carotid artery. Surgery, however, is less beneficial for women than for men. Besides gender, other factors, like degree ofstenosis and plaque morphology, influence the risk of stroke and the beneficial effect of CEA. A recent study shows that women, asymptomatic women in particular, have more stable atherosclerotic carotid plaques than men. Increasing knowledge regarding local plaque characteristics should be carried through to clinical practice. Further studies, especially prospective studies, are needed to identify subgroups of patients that will benefit most from CEA. Low surgical morbidity and mortality remain a prerequisite to perform CEA in symptomatic carotid stenosis and even more so in asymptomatic carotid stenosis.

[Differences between hospitals in outcome after a stroke are only partially explained by differences in the quality of care]. / Verschillen tussen ziekenhuizen in uitkomst na een herseninfarct vooral verklaard door patiëntkenmerken en slechts ten dele door verschillen in de kwaliteit van zorg.

OBJECTIVE: To determine the extent to which the outcome of stroke patients stroke is correlated with patient characteristics and care process parameters, and to determine whether outcome measures can be used to measure the quality of hospital care provided for these patients. DESIGN: Descriptive cohort study. METHODS: At 10 hospitals in the Netherlands, in the period October 2002-April 2003, patients with acute stroke were included in the study. Poor outcome was defined as dead or disabled at 1 year (a score on the modified Rankin scale > or = 3). Quality of the care was assessed by relating diagnostic, therapeutic and preventive procedures to indication. Multiple logistic regression models were used to compare observed numbers of patients with a poor outcome with expected numbers per hospital, after adjustment for patient characteristics and quality of care parameters. RESULTS: In total, 579 patients were included in the study, of which 271 (47%) were dead or disabled at 1 year. Poor outcome varied across the hospitals from 29 to 78%. The mean age was 70 years. There were large differences between hospitals with respect to patient characteristics and quality of care. Most of the differences in outcome between hospitals were explained by the differences in patient characteristics (Akaike's information criterion (AIC) = 134). Quality of care parameters explained just a small additional part of the variation in patient outcome (AIC = 5.5). CONCLUSIONS: Large differences between Dutch hospitals in the patient outcome after stroke could mostly be explained by differences in patient characteristics. Only a small part of the hospital variation in patient outcome was related to differences in quality of care. Therefore, outcome indicators cannot be regarded as valid performance indicators for care following a stroke.

Variation between hospitals in patient outcome after stroke is only partly explained by differences in quality of care: results from the Netherlands Stroke Survey.

BACKGROUND AND PURPOSE: Patient outcome is often used as an indicator of quality of hospital care. The aim of this study is to investigate whether there is a straightforward relationship between quality of care and outcome, and whether outcome measures could be used to assess quality of care after stroke. METHODS: In 10 centres in The Netherlands, 579 patients with acute stroke were prospectively and consecutively enrolled. Poor outcome was defined as a score on the modified Rankin scale >or=3 at 1 year. Quality of care was assessed by relating diagnostic, therapeutic and preventive procedures to indication. Multiple logistic regression models were used to compare observed proportions of patients with poor outcome with expected proportions, after adjustment for patient characteristics and quality of care parameters. RESULTS: A total of 271 (47%) patients were dead or disabled at 1 year. Poor outcome varied across the centres from 29% to 78%. Large differences between centres were also observed in clinical characteristics, prognostic factors and quality of care. For example, between hospital quartiles based on outcome, age >or=70 years varied from 50% to 65%, presence of vascular risk factors from 88% to 96%, intravenous fluids when indicated from 35% to 81%, and antihypertensive therapy when indicated from 60% to 85%. The largest part of variation in patient outcome between centres was explained by differences in patient characteristics (Akaike's Information Criterion (AIC) = 134.0). Quality of care parameters explained a small part of the variation in patient outcome (AIC = 5.5). CONCLUSIONS: Patient outcome after stroke varies largely between centres and is, for a substantial part, explained by differences in patient characteristics at time of hospital admission. Only a small part of the hospital variation in patient outcome is related to differences in quality of care. Unadjusted proportions of poor outcome after stroke are not valid as indicators of quality of care.

Long-term survival and vascular event risk after transient ischaemic attack or minor ischaemic stroke: a cohort study.

BACKGROUND: Determinants of survival and of risk of vascular events after transient ischaemic attack (TIA) or minor ischaemic stroke are not well defined in the long term. We aimed to restudy these risks in a prospective cohort of patients after TIA or minor ischaemic stroke (Rankin grade< or =3), after 10 years or more. METHODS: We assessed the survival status and occurrence of vascular events in 2473 participants of the Dutch TIA Trial (recruitment in 1986-89; arterial cause of cerebral ischaemia). We included 24 hospitals in the Netherlands that recruited at least 50 patients. Primary outcomes were all-cause mortality and the composite event of death from all vascular causes, non-fatal stroke, and non-fatal myocardial infarction. We assessed cumulative risks by Kaplan-Meier analysis and prognostic factors with Cox univariate and multivariate analysis. FINDINGS: Follow-up was complete in 2447 (99%) patients. After a mean follow-up of 10.1 years, 1489 (60%) patients had died and 1336 (54%) had had at least one vascular event. 10-year risk of death was 42.7% (95% CI 40.8-44.7). Age and sex-adjusted hazard ratios were 3.33 (2.97-3.73) for age over 65 years, 2.10 (1.79-2.48) for diabetes, 1.77 (1.45-2.15) for claudication, 1.94 (1.42-2.65) for previous peripheral vascular surgery, and 1.50 (1.31-1.71) for pathological Q waves on baseline electrocardiogram. 10-year risk of a vascular event was 44.1% (42.0-46.1). After falling in the first 3 years, yearly risk of a vascular event increased over time. Predictive factors for risk of vascular events were similar to those for risk of death. INTERPRETATION: Long-term secondary prevention in patients with cerebral ischaemia still has room for further improvement.

Stereotactic treatment of intracerebral hematoma by means of a plasminogen activator: a multicenter randomized controlled trial (SICHPA).

BACKGROUND AND PURPOSE: Treatment of intracerebral hematoma (ICH) is controversial. An advantage of neurosurgical intervention over conservative treatment of ICH has not been established. Recent reports suggest a favorable effect of stereotactic blood clot removal after liquefaction by means of a plasminogen activator. The SICHPA trial was aimed at investigating the efficacy of this treatment. METHODS: A stereotactically placed catheter was used to instill urokinase to liquefy and drain the ICH in 6-hour intervals over 48 hours. From 1996 to 1999, 13 centers entered 71 patients into the study. Patients were randomized into a surgical group (n=36) and a nonsurgical group (n=35). Admission criteria were the following: age >45 years, spontaneous supratentorial ICH, Glasgow Eye Motor score ranging from 2 to 10, ICH volume >10 cm3, and treatment within 72 hours. The primary end point was death at 6 months. As secondary end points, ICH volume reduction and overall outcome measured by the modified Rankin scale were chosen. The trial was prematurely stopped as a result of slow patient accrual. RESULTS: Seventy patients were analyzed. Overall mortality at day 180 after stroke was 57%; this included 20 of 36 patients (56%) in the surgical group and 20 of 34 patients (59%) in the nonsurgical group. A significant ICH volume reduction was achieved by the intervention (10% to 20%, P<0.05). Logistic regression analysis indicated the possibility of efficacy for surgical treatment (odds ratio, 0.23; 95% confidence interval, 0.05 to 1.20; P=0.08). The odds ratio of mortality combined with modified Rankin scale score 5 at 180 days was also not statistically significant (odds ratio, 0.52; 95% confidence interval, 1.2 to 2.3; P=0.38). CONCLUSIONS: Stereotactic aspiration can be performed safely and in a relatively uniform manner; it leads to a modest reduction of 18 mL of hematoma reduction over 7 days when compared with control, which has a 7-mL reduction, and therefore may improve prognosis.

Long-term prognosis after recovery from primary intracerebral hemorrhage.

BACKGROUND: Little is known about the long-term outcome for patients who recover from a primary intracerebral hemorrhage. The authors examined the rate of recurrence, vascular events, and death in survivors of a primary intracerebral hemorrhage and the factors related to the long-term prognosis. METHODS: All 243 patients admitted to one of three hospitals with a primary intracerebral hemorrhage who regained independence were interviewed about vascular events after the index hemorrhage. The authors used the Kaplan-Meier method to estimate the event-free survival and Cox proportional hazards regression analysis to identify predictors of recurrence, any vascular event, or death. RESULTS: During a mean follow-up of 5.5 years, the annual rates of recurrent primary intracerebral hemorrhage, vascular events, and vascular death were 2.1% (95% CI, 1.4 to 3.3%), 5.9% (95% CI, 4.5 to 7.7%), and 3.2% (95% CI, 2.2 to 4.5%). Age of 65 years or older was the only predictor of a recurrence (hazard ratio [HR], 2.8; 95% CI, 1.3 to 6.1) and vascular death (HR, 3.7; 95% CI, 2.0 to 7.0). In addition to age, male sex predicted the occurrence of vascular events (HR, 1.8; 95% CI, 1.1 to 3.0). Use of anticoagulation after the index bleeding tripled the risk of hemorrhagic events (HR, 3.0; 95% CI, 1.3 to 7.2). CONCLUSION: Patients who recovered from a primary intracerebral hemorrhage had a 2.1% to 5.9% annual rate of recurrence, vascular death, or vascular events. Age of 65 years or older more than doubled the risk of recurrence, vascular event, or death. The risk of vascular events in men was increased twofold.

[Subacute combined degeneration of the spinal cord: easy diagnosis, effective treatment]. / Gecombineerde strengziekte door vitamine-B12-deficiëntie: eenvoudige diagnose, effectieve therapie.

Four patients, three women aged 49, 47 and 74 years, and a man aged 64 years, presented with progressive sensory deficit, pyramidal tract symptoms and postural instability. Tests revealed megaloblastic anaemia and low vitamin B12 levels. Two of the female patients had undergone gynaecological surgery with nitrous oxide anaesthesia, and the male patient had undergone a gastric resection. Subacute combined degeneration of the spinal cord is a neurological disease based on vitamin B12 deficiency. It involves the posterior and lateral columns of the spinal cord, and sometimes the peripheral nerves, the optic nerve or the brain. An MRI scan of the cervical cord revealed abnormalities for three of the four patients. Following parenteral supplementation of vitamin B12, the symptoms and the MRI abnormalities either disappeared or significantly improved. Vitamin B12 deficiency can cause subacute combined degeneration of the cord by interfering with myelin synthesis. As vitamin B12 deficiency is caused by malabsorption in the gastrointestinal tract, oral supplementation is insufficient. It is essential to recognise this treatable disease at an early stage, and not to reject the possible diagnosis if the MRI findings are abnormal. Simple blood tests can lead to the diagnosis and to effective treatment.

[Thrombolytic therapy of brain infarct: the end of beginning]. / Trombolyse voor het herseninfarct: het einde van het begin.

Thrombolysis by intravenous application of thrombolytic drugs may improve the outcome of patients with a brain infarct, but it also entails risks. The effect of recombinant tissue plasminogen activator (rtPA) was compared with placebo in three medium-sized randomized controlled clinical trials. One study, performed in North America, showed a clear benefit of rtPA administered within 3 hours after the onset of symptoms. Two European trials showed a less strong effect, but the number of patients who were independent after 3 months' follow-up was also larger after treatment with rtPA within 6 hours. A meta-analysis of all three trials demonstrates a significant advantage of rtPA over placebo for all the usual outcome measures, without significant excess mortality in the rtPA group. The chance of being able to live independently increases by about 8% after treatment with rtPA. In conclusion there is now sufficient evidence to start with thrombolytic treatment for cerebral infarcts in hospitals with a stroke unit, if a number of additional quality standards for the acute diagnosis and treatment of stroke patients are met.

The significance of routine chest X-ray in acute stroke.

We retrospectively evaluated the significance of making a chest X-ray in the acute stage of a stroke. Forty percent of the chest X-rays were of suboptimal quality. Abnormal chest X-rays were, in part, the reason for consultation of chest specialists in 5%. A chest X-ray in patients with acute stroke should only be performed if there is clinical suspicion of pulmonary or cardiac pathology, not as a routine.

Clomethiazole acute stroke study (CLASS): results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients.

BACKGROUND AND PURPOSE: The efficacy and safety of the neuroprotective drug clomethiazole was tested in a double blind placebo controlled trial in patients with a clinical diagnosis of acute hemispheric stroke. METHODS: Patients with symptom onset of /=60 points on the Barthel Index) at 90 days. RESULTS: A total of 1360 patients were included. In the main efficacy analysis (n=1353), 56.1% of patients taking clomethiazole and 54.8% of placebo patients reached relative functional independence. The difference was not statistically significant. An analysis of the effect of time since onset of symptoms showed no difference between the treatment groups. Clomethiazole was generally well tolerated and appeared safe in the population studied. Sedation was the most common adverse event, leading to treatment withdrawal that occurred in 15.6% of clomethiazole-treated patients compared with 4.2% of placebo-treated patients. In a subgroup classified before randomization as having total anterior circulation syndrome (TACS) (n=545, or 40% of all randomized patients), the percentage of those reaching relative functional independence was 40.8% on clomethiazole and 29.8% on placebo, a difference of approximately 11 percentage units. TACS patients have clinical symptoms suggesting a "large" stroke. CONCLUSIONS: Clomethiazole had no adverse or beneficial effect on long-term outcome for all patients but produced sedation. The hypothesis that clomethiazole is effective in patients with large strokes will be tested in a further study.

Silent intracerebral microhemorrhages in patients with ischemic stroke. Amsterdam Vascular Medicine Group.

We compared the frequencies of signs of old intracerebral hemorrhages on brain magnetic resonance imaging scans in 66 patients with ischemic stroke, 69 with myocardial infarction, and 86 with peripheral arterial disease (a total of 221 patients). Magnetic resonance imaging scans were independently assessed by two investigators without knowledge of clinical or laboratory data. In 31 patients (14%) we found local cerebral hemosiderin deposits. In 24 patients they were clinically silent. Hemosiderin deposits were significantly more frequent in patients with ischemic stroke (26%) than in patients with myocardial infarction (4%) or peripheral arterial disease (13%). Hemosiderin deposits were associated with cerebral white matter lesions (odds ratio, 5.3; 95% confidence interval, 2.5-12.4). The odds ratios were higher in patients with severe cerebral white matter lesions. Our findings support the hypothesis that cerebral vessels of patients with ischemic stroke are more prone to rupture than those of patients with other manifestations of atherosclerotic disease, which may explain the higher incidence of intracerebral hemorrhages when these patients are treated with oral anticoagulants. The microhemorrhages were associated with cerebral white matter lesions, which suggests that they are another manifestation of cerebral small-vessel disease.

Prophylactic treatment of migraine with bisoprolol: a placebo-controlled study.

The objective of the present study was to assess the efficacy of bisoprolol in migraine prophylaxis. A double-blind placebo-controlled study was conducted in 226 patients with migraine with or without aura, a migraine history of at least 2 years at least 3 documented attacks during the 28 days run-in period. The duration of treatment was 12 weeks following an initial 28 days' run-in period. Patients reported the number of attacks and their severity in a diary. Treatment with bisoprolol 5 mg resulted in a significant reduction in the frequency of migraine attacks (39% vs 22%) compared to placebo treatment (p < 0.05). Treatment had no effect on the duration and severity of the attacks. Bisoprolol was well tolerated.

Safety and pharmacokinetics of the neuroprotective drug lubeluzole in patients with ischemic stroke.

A total of 22 patients with acute ischemic stroke participated in two randomized, single-masked, placebo-controlled studies that evaluated the safety and pharmacokinetics of single escalating intravenous doses of lubeluzole. The first dose of study medication in all patients was given within 6 hours of the first sign of stroke onset. In the first study, 6 patients received a single 1-hour intravenous infusion of 5 mg of lubeluzole; 4 of these patients received an additional 10-mg dose 3 to 4 days later. Two additional patients received placebo. In the second study, 4 patients received a single 1-hour infusion of 10 mg of lubeluzole, and 2 patients received placebo. After a safety evaluation of the second study, 6 additional patients received 15 mg of lubeluzole, and 2 other patients received placebo. Lubeluzole had no clinically relevant effects on any cardiovascular variable compared with placebo. The majority of adverse experiences were mild to moderate and resolved during treatment. No unexpected electroencephalogram abnormalities were observed, and no evidence of epileptiform discharges was found in any of the patients. At the end of the infusion, plasma lubeluzole concentrations decayed biphasically, with mean distribution half-lives of 46.3 to 101.0 minutes and mean terminal half-lives of 20.8 to 27.7 hours. Comparisons of the dose-normalized value of the individual plasma concentrations at the end of the infusion and the total area under the curve from time 0 to infinity suggested that lubeluzole exhibited linear kinetics over the dose range evaluated in patients with ischemic stroke. In the small number of patients studied, lubeluzole's favorable safety profile was demonstrated by the lack of clinically relevant effects on cardiovascular variables and by neurologic examination and clinical laboratory findings.

Acute whiplash injury: is there a role for MR imaging?--a prospective study of 100 patients.

PURPOSE: To evaluate the findings from magnetic resonance (MR) imaging of the cervical spine and brain after acute whiplash injury. MATERIALS AND METHODS: Within 3 weeks of trauma, 100 patients underwent MR imaging for evaluation of the cervical spine and the brain. In addition, plain radiographs were obtained, including functional images of the cervical spine. RESULTS: Only one patient had an abnormality on the MR image that was related to trauma (ie, prevertebral edema). In 17 patients, functional images showed a kyphotic angle, but no evidence of soft-tissue injury was seen on MR images. CONCLUSION: There is no role for MR imaging in the routine work-up of patients with acute whiplash injury who have normal plain radiographic findings and no evidence of a neurologic deficit. A kyphotic angle seen on functional images of the cervical spine should not be assumed to indicate soft-tissue injury and is most likely attributable to a compensating mechanism of hypermobility at a level of the spine above that at which hypomobility occurs, which is probably the result of a muscle spasm.

Flunarizine in stroke treatment (FIST): a double-blind, placebo-controlled trial in Scandinavia and the Netherlands.

INTRODUCTION: An international, multicenter trial was conducted in 331 patients to determine the effect of a large dose of flunarizine (a calcium entry blocker) in the treatment of acute ischemic stroke in the territory of the Middle cerebral artery. METHODS: The administration of the trial medication should start within 24 h after the initial symptoms of stroke. According to a random schedule, the patients were assigned to a 4-weeks double-blind treatment with either flunarizine (n = 166) or placebo (n = 165): one week intravenous administration (50 mg daily), followed by 3 weeks oral treatment (week 2, 21 mg daily; week 3-4, 7 mg daily). All patients had to be investigated by computerized tomography (CT) within 7 days after stroke onset; 36 patients were secundarily excluded because the CT showed another pathology. During the treatment period, other "stroke therapies" were not allowed. Patients were followed up for 24 weeks. RESULTS: After the 24 weeks trial period, the percentage of patients who were dead or pendent (modified Rankin score 3-5) was similar in both treatment groups (flunarizine 67%, placebo 65%). During the trial, the scores for handicap severity (modified Rankin scale), neurological status (Orgogozo) and activities of daily living (modified Barthel index) strongly improved in both treatment groups, but no differences were found between the treatment groups. In this trial, the administration of trial treatment started relatively late after stroke onset (flunarizine group: mean time interval 13.5 h; placebo 12.3 h). A subgroup of patients received trial medication within 6 h after stroke onset (flunarizine n = 31; placebo n = 29). Also in this subgroup, no differences were found between the flunarizine and placebo group. CONCLUSION: Flunarizine did not improve neurologic and functional outcome in patients with acute ischemic stroke.