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Biomedical subjects

N G Wahlgren

Publications and source records attributed to N G Wahlgren.

At least 19 recordsLinked to original sources
PubMed2003

Amphetamines for improving recovery after stroke.

BACKGROUND: Experimental animal research shows that treatment with amphetamines improves recovery after focal cerebral ischaemia. If the effect were similar in humans, amphetamine treatment could have a major impact on recovery from stroke. OBJECTIVES: The objective of this review was to assess the effects of amphetamine treatment in patients with stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched November 2002). In addition, we searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 4 2002), MEDLINE (1966-September 2002), EMBASE (1980-November 2002), and Science Citation Index (1992-December 2002). The reference lists of all relevant articles and reviews were checked, and we contacted researchers in the field to identify further published and unpublished studies. SELECTION CRITERIA: Randomized unconfounded trials comparing amphetamine with placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Seven studies involving 172 patients were included. The quality of the trials varied but was generally high. Based on two trials (85 patients) there was no evidence that amphetamine treatment reduced death or dependence (Peto's odds ratio, [Peto OR] 1.54; 95% Confidence Interval [CI] 0.64 to 3.73). In these two trials, there were imbalances at baseline, with more serious strokes allocated to amphetamine. This imbalance may account for the trend for more deaths at the end of follow-up among amphetamine allocated patients (Peto OR 3.33; 95% CI 0.99 to 11.24). Based on 4 studies (95 patients) there was evidence of a better relative change in motor function according to the Fugl-Meyer motor scale (Weighted Mean Difference, [WMD] -8.17 points; 95% CI -13.58 to -2.76) and based on 1 study (21 patients) there was evidence of a better change in language function as assessed by the Porch Index of Communicative Ability score (WMD -7.51 points; 95% CI -14.42 to -0.60) in amphetamine allocated patients. REVIEWER'S CONCLUSIONS: At present, too few patients have been studied to draw any definite conclusions about the effects of amphetamine treatment on recovery from stroke. The suggested benefits on motor and language function, and the non-significant trend towards increased risk of death, could be related to imbalances in prognostic variables or other bias in studies. Further research in this area is therefore justified.

Amphetamines↗
PubMed2000

[Commission of inquiry scrutinized complications of carotid surgery. Half of the complications could be explicable by errors or dubious indications].

As carotid endarterectomy is a prophylactic procedure, it would seem particularly important to analyze complications with an aim to avoiding them. All carotid endarterectomies in Sweden are registered, and all serious complications (death and permanent neurological deficit) are analyzed in detail, classified and discussed within the profession. During the period 1994-1996 the frequency was 4.3 percent (technical causes in 17 percent, contraindications in 8 percent and dubious indications in 21 percent, but correct indication and surgery in 54 percent). Thus, even when conditions are optimal there is a certain price to pay for the prevention of ischemic stroke.

Adult↗
PubMed2000

[Multidisciplinary cooperation behind a quality registry for carotid surgery. Good coverage during the first two years].

Carotid surgery prevents recurrent stroke in patients with symptomatic tight stenosis of the carotid artery. The Swedish Carotid Surgery Monitoring Registry seeks to promote selection of patients with significant spontaneous risk for recurrent stroke, with an eye toward expediting evaluation and minimizing surgical complications. To this end, professionals at participating hospitals are informed about their own patient selection and surgery risk in comparison with those in the country as a whole and with set targets. We report the results from the first two years, during which it is estimated that more than half of all patients eligible for carotid surgery in Sweden were included in the registry. Although almost all patients had recent onset of relevant neurological symptoms, less than 60% had a documented tight (80-99% occlusion) stenosis. While the final decision to operate a patient was made within 4 weeks of onset of symptoms for only 18% of the patients the first year, this proportion increased to 33% in the following year. The total incidence of surgery related stroke, myocardial infarct and death was 7.7%, while the incidence of severe stroke, myocardial infarct and death was 3.0%.

Amaurosis Fugax↗
PubMed2000

Results in 95 hemorrhagic stroke patients included in CLASS, a controlled trial of clomethiazole versus placebo in acute stroke patients.

BACKGROUND AND PURPOSE: Clomethiazole is a neuroprotective drug that enhances gamma-aminobutyrate type A (GABA(A)) receptor activity. Its efficacy and safety were tested in the CLomethiazole Acute Stroke Study (CLASS). The protocol allowed a CT scan to be done after randomization but within 7 days of stroke onset to minimize delays before start of treatment. Ninety-five of the 1360 patients randomized were diagnosed as having intracranial hemorrhage rather than ischemic stroke. Safety results for clomethiazole compared with placebo in this group are reported. METHODS: The study included patients with a clinical diagnosis of acute hemispheric cerebral infarction. Treatment was a 24-hour intravenous infusion of 75 mg/kg clomethiazole or placebo. Patients with intracranial hemorrhage discovered on a postrandomization CT were withdrawn from study treatment if treatment was ongoing, and all patients were followed up to 90 days. RESULTS: Ninety-four patients received treatment, 47 in each group. The hemorrhage was classified as intracerebral in 89 patients (94%). Mortality at 90 days was 19.1% in the clomethiazole group and 23.4% in the placebo group. Sedation was the most common adverse event, occurring at a higher incidence in clomethiazole-treated patients (clomethiazole 53%, placebo 17%), followed by rhinitis and coughing. The incidence and pattern of serious adverse events was similar between the treatment groups. The percentage of patients reaching relative functional independence on the Barthel Index (score >/=60) at 90 days was 59.6% in the clomethiazole group and 53.2% in the placebo group. CONCLUSIONS: Clomethiazole appears safe to administer to hemorrhagic stroke patients compared with placebo. These results would obviate the need for a CT scan before therapy is initiated in acute stroke. The safety of clomethiazole in hemorrhagic stroke patients will be further evaluated in a prospective study that is under way in North America.

Acute Disease↗
PubMed2000

Effect of intravenous nimodipine on blood pressure and outcome after acute stroke.

BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.

Acute Disease↗
PubMed1999

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 </=12 hours before the start of treatment were included in the study. Clomethiazole (75 mg/kg) or placebo was given as an intravenous infusion over a 24-hour period. Patients were followed up for 90 days. The primary efficacy variable was the proportion of patients reaching relative functional independence (>/=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.

Acute Disease↗
PubMed1999

Thrombolysis in acute ischemic stroke: controlled trials and clinical experience.

Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) is approved in the United States for treatment of acute ischemic stroke. Approval was granted after a large, randomized, placebo-controlled study by the National Institute of Neurological Disorders and Stroke (NINDS) showed a significant improvement in 3-month outcomes with rtPA despite a significant risk for symptomatic hemorrhage. Two other trials, the first and second European Cooperative Acute Stroke Study (ECASS I and II), have shown comparable results, but neither was statistically positive for the predefined primary end point. An analysis of the risk/benefit profile of rtPA therapy based on the results of these three trials indicates that the treatment is effective and, when administered within 3 hours of symptom onset at a dose of 0.9 mg/kg, the benefits by far outweigh the risks for eligible patients. Even with the 6-hour time window of the two ECASS trials, a combined analysis of the three studies shows the number of disabled or dead patients to be significantly reduced. Preliminary data collected on the use of rtPA outside of clinical trials in the United States and Europe suggest that, when rtPA is used according to the trial protocol, the risks and benefits are similar to those observed in clinical trials. However, even within the United States, rtPA is underutilized. The most substantial treatment barrier is the narrow time window, which may be expanded if long-term experience shows that this is possible. Most stroke patients arrive at the hospital too late to be eligible for screening and treatment. Education of the public and physicians may help to overcome this difficulty.

Acute Disease↗
PubMed1998

[Thrombolysis changes the care of stroke].

Thrombolysis using tissue plasminogen activator (tPA) is not the leading strategy in the development of pharmacological treatments for acute ischaemic stroke. The prospect of tPA becoming routine treatment in ischaemic stroke raises several issues the magnitude of the treatment load, the requisite neurological and neuroradiological diagnostic qualifications, identification of local reperfusion effects in the brain, and the pre-hospital and hospital management of acute stroke patients. The results of large randomised trials of intravenous tPA treatment are reviewed in the article, and the current state of our knowledge about interventional thrombolysis is reported. Recruitment for the second European intravenous tPA trail, ECASS II, has recently been completed, and the study findings will be available during the latter half of 1988. In the USA, tPA is already recommended treatment for acute ischaemic stroke within three hours after the onset of symptoms. In Europe, the formulation of guidelines awaits the results of ECASS II.

Cerebral Infarction↗
PubMed1998

New concepts for drug therapy after stroke. Can we enhance recovery?

Neurologic functions improve in most patients days and weeks after onset of a stroke. This can not be explained by recovery of the early salvageable ischemia zone. The most likely mechanism is relearning, a process in which healthy brain takes over functions lost with the infarct. Experimental studies indicate that this recovery can be modulated by pharmacological agents. NMDA antagonists and GABA agonists found to reduce infarct size in stroke models may have a harmful effect on relearning and neurologic recovery. This should be considered when clinical trial protocols are designed.

Cerebrovascular Disorders↗
PubMed1996

Carotid artery blood flow and middle cerebral artery blood flow velocity during physical exercise.

Factors controlling cerebral blood flow (CBF) during exercise are complex and incompletely known. Different techniques have shown partly contradictory results of changes in regional and global cerebral perfusion during dynamic exercise in healthy subjects. To elucidate the global CBF response to supine stepwise increasing physical exercise, we measured blood flow in the left common carotid artery (QCCA) and the left internal carotid artery (QICA) simultaneously with the blood flow velocity in the ipsilateral middle cerebral artery (VMCA) using duplex ultrasonography and transcranial Doppler ultrasonography. During moderate exercise intensity (60-67% of maximal capacity), the VMCA increased 14% (P < 0.001), the QICA 17% (P < 0.01), and the QCCA 33% (P < 0.001) compared with baseline values. High physical exercise intensity (80-90% of maximal capacity) tended to reduce VMCA and QICA compared with moderate exercise, in contrast to a continued increase in QCCA. The results indicate an increased global CBF during exercise. This increase was reduced during hard exercise due to a decrease of the arterial PCO2 secondary to hyperventilation.

Adult↗
PubMed1993

Physical exercise increases middle cerebral artery blood flow velocity.

The effect on the middle cerebral artery blood flow velocity (VMCA) of moderate and hard physical exercise on an ergometer cycle was examined in 10 healthy volunteers using transcranial Doppler sonography (TCD). During exercise, the heart rate increased by 136% and the systolic blood pressure by 37% (mean values). During initial moderate exercise, VMCA increased by 51%; in a following period of maximal physical work, VMCA decreased again by 20% in 9 of 10 volunteers although the heart rate continued to increase by 10% and the systolic blood pressure by 5% (mean values). Constriction of the MCA may explain the initial increase of VMCA, suggesting a role for large cerebral arteries in autoregulation. Our data indicate that the subsequent decrease of VMCA is caused by arteriolar constriction, a likely cause of which was hyperventilation during the excessive work period.

Adult↗
PubMed1993

Minimally invasive and non-invasive diagnosis of carotid artery obstructive disease: an evaluation of supraorbital fluorescein angiography and ultrasonic duplex technique.

The carotid arteries of twenty-five patients with transient ischaemic attacks, minor stroke or amaurosis fugax were examined by conventional angiography, the ultrasonic duplex technique and supraorbital fluorescein angiography (SOFA). The results of the last two techniques (non-invasive and minimally invasive, respectively) were compared with the results of angiography. We found that the ultrasonic duplex technique is highly sensitive and specific for both high and low-grade carotid stenoses while the less costly SOFA can only identify stenoses equal to or more than 75%. However, since tight stenosis has proved to be an indication for surgical reconstruction, SOFA - or possibly the still simpler procedure with direct ocular inspection of the supraorbital fluorescence pattern without any recording - would be useful for initial screening in smaller units without access to ultrasonic duplex examination. In this way potential candidates for surgery can be identified without delay and forwarded to larger units for further supplementary examinations.

Adult↗