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Biomedical subjects

Helmi L Lutsep

Publications and source records attributed to Helmi L Lutsep.

15 recordsLinked to original sources
PubMed2006

MATCH results: implications for the internist.

The long-awaited results of the Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent Transient Ischemic Attack (MATCH) study, a large-scale trial undertaken to evaluate the safety and efficacy of clopidogrel + aspirin for secondary prevention of stroke, have been published. The efficacy of any antiplatelet therapy, including aspirin, is modest when it is used as monotherapy, and combination therapy with 2 antiplatelet agents has shown promise in reducing the risk for secondary stroke in patients who have had a previous transient ischemic attack (TIA) or ischemic stroke. However, unlike the Second European Stroke Prevention Study (ESPS-2), which demonstrated a significant reduction in risk for secondary stroke with aspirin + extended-release dipyridamole versus aspirin alone the results of the MATCH trial indicated that the reduction in risk achieved by adding aspirin to clopidogrel is not significantly greater than that achieved with clopidogrel alone. Furthermore, a significant increase in life-threatening bleeding complications was associated with the combination of clopidogrel + aspirin. Given these findings, clopidogrel + aspirin cannot be recommended at this time for the secondary prevention of stroke in patients who have had a previous ischemic stroke or TIA.

Aspirin↗
PubMed2006

Motor cortex stimulation for the enhancement of recovery from stroke: a prospective, multicenter safety study.

OBJECTIVE: Functional magnetic resonance imaging and transcranial magnetic stimulation studies suggest that human cortex shows evidence of neuroplasticity. Preclinical studies in rats and monkeys suggest that motor cortical stimulation can enhance plasticity and improve recovery after stroke. This study assesses the safety and preliminary efficacy of targeted subthreshold epidural cortical stimulation delivered concurrently with intensive rehabilitation therapy while using an investigational device in patients with chronic hemiparetic stroke. METHODS: This is a prospective, multicenter, and nonblinded trial randomizing patients to rehabilitation with or without cortical stimulation. Patients aged 20 to 75 years who had had an ischemic stroke at least 4 months previously causing persistent moderate weakness of the arm were included. Functional magnetic resonance imaging localized hand motor function before surgery to place an epidural cortical electrode. Both groups then underwent rehabilitation for 3 weeks after which the electrode was removed. Outcome measures were obtained at baseline, during therapy, and at 1, 4, 8, and 12 weeks postprocedure. RESULTS: Ten patients were randomized; six patients to surgery, four to the control group. No patient deaths, neurological deterioration, or seizures occurred. There were two infections from nonprotocol-related causes. Of the eight patients completing the treatment, the stimulation plus rehabilitation group improved significantly better than controls in the Upper Extremity Fugl-Meyer (P = 0.003 overall) and the hand function score of the Stroke Impact Scale (P = 0.001 overall). CONCLUSION: The technique of cortical stimulation to enhance stroke recovery is well tolerated and safe.

Adult↗
PubMed2006

Thrombolytic and newer mechanical device treatment for acute ischemic stroke.

For 8 years, only intravenous tissue plasminogen activator was approved by the US FDA for acute stroke treatment. The US FDA has now cleared the Merci Retriever (Concentric Medical, Inc.), a corkscrew-like device attached to a catheter, for the removal of clots causing ischemic strokes. Since the clearance was based on nonrandomized treatment trials, practitioners must scrutinize available data describing effects of the device on recanalization of the vessel, outcomes and important adverse events, such as symptomatic intracranial hemorrhage. This article reviews the study findings that are likely to contribute to current treatment decisions.

Acute Disease↗
PubMed2005

Plasma total homocysteine levels in stroke patients screened for the vitamin intervention for stroke prevention clinical trial in the era of folate fortification.

Folic acid fortification of grain products was mandated in the USA by January 1998 and in Canada by November 1998. It was hypothesized that screening total plasma homocysteine levels adjusted for age, sex, race and country that were drawn in stroke patients for the Vitamin Intervention for Stroke Prevention trial from 1997 to 2001 would be steady when fortification was completed. Samples were grouped by years 1997/1998, 1999 and 2000/2001, and adjusted means were calculated using a general linear regression model. In 2,612 US and 1,059 Canadian patients, levels showed no consistent trend in the USA alone, while Canadian levels declined (p = 0.06 overall, 0.0003 in the oldest age group). US levels were 0.39 micromol/l (95% CI: -0.08, 0.85) lower than in Canada. Neither fasting nor time since stroke affected the results.

Adult↗
PubMed2005

Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial.

BACKGROUND AND PURPOSE: The only Food and Drug Administration (FDA)-approved treatment for acute ischemic stroke is tissue plasminogen activator (tPA) given intravenously within 3 hours of symptom onset. An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy, especially for patients ineligible for intravenous tPA. METHODS: We investigated the safety and efficacy of a novel embolectomy device (Merci Retriever) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospective, nonrandomized, multicenter trial. All patients were ineligible for intravenous tPA. Primary outcomes were recanalization and safety, and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients. RESULTS: Recanalization was achieved in 46% (69/151) of patients on intention to treat analysis, and in 48% (68/141) of patients in whom the device was deployed. This rate is significantly higher than that expected using an historical control of 18% (P<0.0001). Clinically significant procedural complications occurred in 10 of 141 (7.1%) patients. Symptomatic intracranial hemorrhages was observed in 11 of 141 (7.8%) patients. Good neurological outcomes (modified Rankin score < or =2) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization (46% versus 10%; relative risk [RR], 4.4; 95% CI, 2.1 to 9.3; P<0.0001), and mortality was less (32% versus 54%; RR, 0.59; 95% CI, 0.39 to 0.89; P=0.01). CONCLUSIONS: A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics.

Angiography↗
PubMed2005

Use of functional MRI to guide decisions in a clinical stroke trial.

BACKGROUND AND PURPOSE: An investigational trial examined safety and efficacy of targeted subthreshold cortical stimulation in patients with chronic stroke. The anatomical location for the target, hand motor area, varies across subjects, and so was localized with functional MRI (fMRI). This report describes the experience of incorporating standardized fMRI into a multisite stroke trial. METHODS: At 3 enrollment centers, patients moved (0.25 Hz) the affected hand during fMRI. Hand motor function was localized at a fourth center guiding intervention for those randomized to stimulation. RESULTS: The fMRI results were available within 24 hours. Across 12 patients, activation site variability was substantial (12, 23, and 11 mm in x, y, and z directions), exceeding stimulating electrode dimensions. CONCLUSIONS: Use of fMRI to guide decision-making in a clinical stroke trial is feasible.

Adult↗
PubMed2005

Thrombolysis in young adults.

Obstacles to thrombolytic treatment could be unique in young stroke patients and identifying and addressing them would potentially enhance outcomes. However, it has not been well studied how age affects the time to presentation, diagnosis or treatment of acute strokes. Although studies suggest that younger patients may be more aware of stroke symptoms and signs than older ones, they may be less likely to use emergency medical services. Importantly, for strokes of similar severity, younger patients have more favorable outcomes with thrombolysis than older patients. On the other hand, young patients who experience extensive middle cerebral artery strokes are more likely to develop fatal brain edema than older patients. Current data support the use of thrombolytics for all ischemic stroke etiologies, including entities such as cervical artery dissection that are more common in young patients.

Adolescent↗
PubMed2005

Repinotan, A 5-HT1A agonist, in the treatment of acute ischemic stroke.

Serotonin agonists can reduce glutamate-induced excitotoxicity in cerebral ischemia. The potent 5-HT1A agonist BAY x 3702, or repinotan, has reduced cortical infarct volume in pre-clinical models even when given 5 hours after injury. Early clinical trials showed that the drug was safe, and displayed primarily serotonergic side effects such as nausea and vomiting. A phase IIb trial in moderate to moderately severe strokes completed enrollment in June 2004.

Acute Disease↗
PubMed2003

Increased pelvic vein thrombi in cryptogenic stroke: results of the Paradoxical Emboli from Large Veins in Ischemic Stroke (PELVIS) study.

BACKGROUND AND PURPOSE: Cryptogenic stroke is associated with an increased prevalence of patent foramen ovale. The Paradoxical Emboli From Large Veins in Ischemic Stroke (PELVIS) study hypothesized that patients with cryptogenic stroke have an increased prevalence of pelvic deep venous thrombosis (DVT). METHODS: At 5 sites, patients 18 to 60 years of age received an MRI venogram (MRV) of the pelvis within 72 hours of new symptom onset. Clinical data were then determined. Radiologists blinded to clinical data later read the scans. RESULTS: The 95 patients who met entry criteria were scanned. Their mean+/-SD age was 46+/-10 years, and time from stroke onset to pelvic MRV scan was 49+/-16 hours. Compared with those with stroke of determined origin (n=49), patients with cryptogenic stroke (n=46) were significantly younger, had a higher prevalence of patent foramen ovale (61% versus 19%), and had less atherosclerosis risk factors. Cryptogenic patients had more MRV scans with a high probability for pelvic DVT (20%) than patients with stroke of determined origin (4%, P<0.03), with most having an appearance of a chronic DVT. CONCLUSIONS: In this study of young stroke patients evaluated early after stroke, patients with cryptogenic stroke showed differences in several clinical features compared with patients with stroke of determined origin, including increased prevalence of pelvic DVT. The results require confirmation but suggest that paradoxical embolus from the pelvic veins may be the cause of stroke in a subset of patients classified as having cryptogenic stroke.

Adolescent↗
PubMed2003

Mapping individual brains to guide restorative therapy after stroke: rationale and pilot studies.

Some treatments under development to improve motor outcome after stroke require information about organization of individual subject's brain. The current study aimed to characterize normal inter-subject differences in localization of motor functions, and to consider these findings in relation to a potential treatment of motor deficits after stroke. Functional MRI (fMRI) scanning in 14 subjects examined right index finger tapping, shoulder rotation, or facial movement. The largest activation cluster in left sensorimotor cortex was identified for each task, and its center expressed in Talairach stereotaxic coordinates. Across subjects, each task showed considerable variability in activation site coordinates. For example, during finger tapping, the range for center of activation was 7 mm in the x-axis, 19 mm in the y-axis, and 11 mm in the z-axis. The mean value for center of activation was significantly different for all three coordinates for all pairwise task comparisons. However, the distribution of activation site centers for the finger task overlapped with the other two tasks in the x- and y-axes, and with the shoulder task in the z-axis. On average, the center of activation for the three motor tasks were spatially separated and somatotopically distributed. However, across the population, there was considerable overlap in the center of activation site, especially for finger and shoulder movements. Restorative therapies that aim to target specific body segments, such as the hand, in the post-stroke motor system may need to map the individual brain rather than rely on population averages. Initial details are presented of a study using this approach to evaluate such a therapy.

Aged↗
PubMed2002

GABA agonist: clomethiazole.

Neuroprotective agents inhibit reactions in the brain ischaemic injury cascade which lead to neuronal death. Gamma-aminobutyric acid (GABA) is a naturally occurring inhibitory neurotransmitter that increases chloride influx into the neuron and counteracts the toxic effects of glutamate. Clomethiazole is a GABA(A) agonist, which causes membrane hyperpolarization, counteracting depolarization and the subsequent cascade of biochemical events that result in neuronal death. Promising results in animal models resulted in clinical trials conducted in humans. However, large randomized placebo controlled trials in Europe, Canada and North America did not show the superiority of clomethiazole over placebo that was seen in animal models.

Chlormethiazole↗
PubMed2002

Intraarterial suction thrombectomy in acute stroke.

Three patients with internal carotid artery thrombus and thrombolysis in myocardial infarction (TIMI) 0-1 flow were treated by using intraarterial (IA) suction thrombectomy a mean of 4.2 hours after stroke onset. After catheterization with a 7F guide-catheter, thrombus was aspirated by using a 60-mL syringe. TIMI flow improved to 3 in all patients. The median National Institutes of Health Stroke Scale score decreased from 22 (range, 12-23) to 4 (range, 2-22) at 3 months. IA suction thrombectomy may be safe and feasible in patients with acute stroke.

Aged↗
PubMed2002

Repinotan Bayer.

Bayer is developing the aminomethylchroman derivative, repinotan, a 5-HT1A agonist, as a potential treatment for ischemic stroke and traumatic brain injury [216172]. It has completed phase III trials in Canada and the US [342562], [344747]. In June 2001, NDA filing was expected by 2004 [411649]. As of March 2002, it was undergoing phase III trials for both indications, and Bayer expected to launch the product in 2006 in Europe and the US [443846]. Repinotan was being developed initially as an i.v. formulation for the treatment of ischemic stroke and brain injury and as an oral formulation for the treatment of depression; however, development has been discontinued for the latter indication [317452]. In March 2002, Lehman Brothers predicted a launch date of 2006, estimating peak sales of US $1000 million and a 20 to 30% probability of reaching market [450456], while in April 2002, Bank Vontobel also predicted a launch in 2006 with potential sales of Euro450 million in its fifth year of sales [450454]. Bayer predicts peak sales of Euro450 million [397137].

Animals↗