Dee Rapposelli

MRI-assisted thrombolysis is as good as and perhaps better than CT-assisted thrombolysis, and it may be particularly valuable for patients treated outside of the prescribed 3-hour treatment window after stroke onset.1 These findings were part of a large multicenter European study reported at the 2007 International Stroke Conference in San Francisco in February by Peter D. Schellinger, MD, PhD, a professor of neurology at the University of Erlangen in Germany.

The study, which compared standard CT-based thrombolysis (within the 3-hour treatment window) with MRI-based thrombolysis within and outside the 3-hour window, included 1210 patients from 5 stroke centers in Germany and Spain. CT-assisted thrombolysis within 3 hours of stroke onset was performed in 714 patients, MRI-assisted thrombolysis within 3 hours after stroke was performed in 322 patients, and MRI-assisted thrombolysis after 3 hours of stroke onset was performed in 174 patients. The mean onset to treatment time was 130, 136, and 279 minutes, respectively.

Despite their significantly longer treatment window and higher baseline National Institutes of Health Stroke Scale scores, patients who received MRI-assisted thrombolysis more than 3 hours after stroke onset fared just as well as or better than patients receiving CT-assisted thrombolysis within 3 hours of stroke onset. Rates of symptomatic intracranial hemorrhage (ICH) for the 3 approaches were 5.3%, 3.1%, and 4.0%, respectively. Mortality rates were 13.7%, 12.4%, and 12.1%, respectively. Favorable outcomes in terms of effectiveness and safety were seen in 35.6%, 35.7%, and 42% of patients, respectively.

Schellinger and coinvestigators from the University of Erlangen and the University of Heidelberg have been looking at the value of MRI-assisted thrombolysis for several years. The study presented at the International Stroke Conference was a recapitulation of a recently published study by Schellinger and coresearchers of 382 patients that specifically looked at the effectiveness and safety of MRI-assisted thrombolysis outside of the 3-hour treatment window after stroke onset.2

The investigators explained in the article that patients are treated at their institutions only if a perfusion-diffusion MRI mismatch (perfusion exceeding diffusion) is apparent. No cutoff for age or stroke severity is applied, but thrombolysis is contraindicated in patients with a diffusion-weighted MRI lesion covering more than 50% of the middle cerebral artery.

Seventy patients received MRI-assisted thrombolysis after 3 hours of stroke onset, 103 received it within 3 hours of stroke onset, and 209 patients received CT-assisted thrombolysis within 3 hours of stroke onset. Incidence of ICH was lower in the MRI-treated groups than in the CT-treated group, although the investigators noted that ICH was more common among older patients (mean age 75 years versus mean age 71 years) and among patients with higher stroke severity scores. Increased age and stroke severity were strong predictors of worse outcomes.

At 90 days, favorable outcomes were seen in 41% of patients receiving MRI-assisted thrombolysis outside of the 3-hour treatment window, 33% receiving MRI-assisted thrombolysis within the treatment window, and 38% receiving CT-assisted thrombolysis. Mortality also was lower among patients treated with MRI compared with those treated with CT.

The investigators came to the same conclusion as the investigators involved in the larger study, that MRI-assisted thrombolysis is at least as good as CT-assisted thrombolysis and of particular value to patients treated outside the prescribed 3-hour window. They added that a good outcome in relation to thrombolytic therapy is more dependent on patient selection than on time to treatment.

1. Schellinger PD, Thomalla G, Fiehler J, et al. MRI-based thrombolysis is at least as safe and effective as standard CT-based treatment: a multicenter study of 1210 patients. Stroke 2007;38:454.

2. Kohrmann M, Juttler E, Fiebach JB, et al. MRI versus CT-based thrombolysis treatment within and beyond the 3 h time window after stroke onset: a cohort study. Lancet Neurol 2006;5:661-667.

Articles

Delayed treatment outcomes compare with early CT thrombolysis if diffusion-perfusion mismatch is present

Thrombolysis Proves Effective Outside the 3-Hour Window

An acute diffusion lesion is evident in one third of patients who have had a transient ischemic attack,1 and those patients may be at higher risk for stroke,2 according to a pair of studies presented at the 2007 International Stroke Conference in San Francisco in February.

Those patients most likely to show evidence of brain injury on MR diffusion-weighted imaging (DWI) are patients who have motor symptoms or whose symptoms last longer (i.e., a mean 60 minutes compared with a mean 30 minutes among patients whose imaging studies are negative for brain injury).1 The findings were the work of the MRI in TIA Collaborative Group, a multi-institutional international endeavor.

The group, which included 11 academic medical centers, looked at all studies within the literature that addressed DWI findings in patients who had experienced a TIA and also looked at data from 808 patients who met traditional criteria for TIA (complete resolution of symptoms within 24 hours) from 9 of the 11 participating centers.

Patients' mean age was 69; 58% were men. Median duration of symptoms was 55 minutes. Lesions were observed on DWI in 33% of patients.

Patients with lesions typically had a longer duration of symptoms. The longer symptoms persisted, the researchers found, the more likely that brain injury would be detected on DWI. Indeed, brain injury was more likely than not to have developed in patients whose symptoms persisted for longer than 6 hours.

Brain injury was also more likely to be detected in patients who had motor symptoms. Positivity for lesions on DWI was more common among patients who had an MR scan within 24 hours of symptom resolution than among patients who had an MR scan outside the 24-hour postresolution time frame.

A study by a team from Massachusetts General Hospital demonstrated that DWI lesion positivity and a history of prior TIAs heightens stroke risk immediately following a TIA. Identifying patients who present with TIA and have these features might allow clinicians to head off an imminent stroke, according to the investigators.2

They looked at 325 consecutive patients who had experienced a TIA and underwent DWI within 72 hours of symptom onset. Age, symptom duration, blood pressure, speech disturbance, and motor symptoms were all evaluated. Risk in relation to these factors was predicted using the ABCD score (a simple scoring method derived from the Oxfordshire Community Stroke Project, a prospective study that comprehensively looked at cardiovascular disease in 105,000 persons presenting to general practitioners in Oxford, U.K.). The predictive value was then calculated for ABCD score, DWI lesion positivity, and history of TIA.

While hospitalized, 12 (3.7%) of patients experienced stroke and 21 (6.5%) experienced another TIA. The positive predictive value for stroke for ABCD score was 4.5%, compared with 8% for lesion positivity on DWI, and 8.9% for history of previous TIA. The researchers concluded that careful examination of clinical history and DWI findings-"irrespective of other clinical features"-could reliably identify patients at risk for stroke following a TIA. They suggested that proactive identification of such patients and preventive intervention could potentially make inhospital stroke care more efficient.

1. Shah SH, Saver JL, Kidwell CS, et al. A multicenter pooled, patient-level data analysis of diffusion-weighted MRI in TIA patients. Stroke 2007;38:463.

2. Ay H, Arsava EM, Koroshetz WJ, Sorensen AG. Clinical imaging predictors of in-hospital stroke risk in patients with TIA. Stroke 2007;38:459.

Evidence of brain injury is most prevalent in patients with physical symptoms and long duration of symptoms

DWI Shows Some Potential to Predict Post-TIA Stroke Risk

Shah SH, Saver JL, Kidwell CS, et al. A multicenter pooled, patient-level data analysis of diffusion-weighted MRI in TIA patients. Stroke 2007;38:463.

Ay H, Arsava EM, Koroshetz WJ, Sorensen AG. Clinical imaging predictors of in-hospital stroke risk in patients with TIA. Stroke 2007;38:459.

Schellinger PD, Thomalla G, Fiehler J, et al. MRI-based thrombolysis is at least as safe and effective as standard CT-based treatment: a multicenter study of 1210 patients. Stroke 2007;38:454.

Kohrmann M, Juttler E, Fiebach JB, et al. MRI versus CT-based thrombolysis treatment within and beyond the 3 h time window after stroke onset: a cohort study. Lancet Neurol 2006;5:661-667.

MRI-assisted thrombolysis is as good as and perhaps better than CT-assisted thrombolysis, and it may be particularly valuable for patients treated outside of the prescribed 3-hour treatment window after stroke onset.

Two different advanced MRI techniques can help clinicians choose epilepsy patients who will favorably respond to surgical intervention, according to a pair of studies published in the October 2005 issue of 

One technique uses 3T phased-array MRI to gain finer resolution, translating into detection of lesions not visible on 1.5T. The other is a 3D mapping method that uses volume differences to improve surgical prognosis. 

About 15% of patients with focal epilepsy are not adequately managed with anti-epileptic drugs and may be candidates for surgical intervention. MRI has been used to detect lesions in the epileptogenic area of the brain. 

When MRI and electroencephalogram findings are concordant, 72% of patients are more likely to be seizure-free after surgery, compared with 41% of patients whose MRI/EEG findings are not concordant.

Dr. Susanne Knake and colleagues from Massachusetts General Hospital and the University of Marburg in Germany reasoned that more sensitive MRI technology is needed. They compared 1.5T MR scans with 3T phased-array MR scans in 40 patients with medically intractable focal epilepsy (Neurology 2005;65:1026-1031). All 40 patients were considered candidates for epilepsy surgery.

Using 3T phased-array MRI, the researchers detected new lesions that had not been seen with 1.5T MRI in 15 patients. The new data changed clinical management in eight patients who had focal cortical dysplasias, lesions that are typically difficult to detect with 1.5T MRI. The 3T results also influenced the surgical procedure in four of these patients, who were seizure-free after 10 to 16 months of follow-up.

Another 15 patients had abnormal studies using both 1.5T and 3T, but the 3T images contributed additional relevant clinical information in five of these patients. A larger area of damage was identified in two of the five. Both have undergone surgery, and one has experienced a significant reduction in seizures, while the other is seizure-free after 12 months follow-up. 

In another of these 15 patients, 3T imaging revealed bilateral hippocampal sclerosis and a left hemisphere stroke. As a result, the patient was considered a poor surgical candidate. Nevertheless, a right hippocampal-amygdala resection was performed, but the patient has had no significant improvement in seizure frequency.

Of the remaining patients, two had normal 1.5T studies and indeterminate 3T studies. The 3T studies raised the suspicion of a focal cortical lesion. Neither patient has proceeded to invasive monitoring or surgical resection, and the significance of the 3T findings is unclear, according to the authors. Eight other patients had studies that were normal with both 1.5T and 3T. None has progressed to surgery. 

"The proper identification of abnormal tissue, which may otherwise be unrecognized, is crucial for identifying a potential epileptic focus and thereby increases the likelihood of a better surgical outcome," said Dr. Fernando Cendes, an associate professor of neurology in Brazil's University of Campinas, in an accompanying commentary.

In the second study, Dr. Jack J. Lin and colleagues from the University of California, Los Angeles showed that analysis of hippocampal volume differences using 3D surface meshes of MR scans can predict which patients with temporal lobe epilepsy will respond adequately to surgical intervention (Neurology 2005;65:1094-1097).

Patients with mesial temporal lobe epilepsy and hippocampal sclerosis are more likely to be helped by surgical intervention than with anti-epileptic drugs. Some patients continue to experience seizures postsurgery, however. Predictors of which patients will be seizure-free have been elusive. 

The team developed a surface modeling technique to compare hippocampal anatomy in patients free of seizures postoperatively with those who continue to have seizures. These mapping techniques were applied to isolate profiles of hippocampal deficits associated with better or poorer outcomes after surgery.

Using this technology, the researchers examined the hippocampi of 40 patients who had received surgical intervention for mesial temporal lobe epilepsy. They found that non-seizure-free patients had more diffuse atrophy in the area of the hippocampus ipsilateral to seizure activity, compared with seizure-free patients. They hypothesized that the greater atrophy could be attributed to disease progression. 

The researchers concluded that surface-based anatomic mapping can detect prognostic features of hippocampal anatomy.

In his commentary, Cendes said the two studies raise additional questions: Should general neurologists be arranging for their patients to receive these sophisticated MRI techniques? Might these tests point the way to more restricted surgical approaches, such as a lesionectomy? 

More studies are needed to answer these questions, Cendes said. 

"As our imaging becomes more refined, so will our ability to ask and answer more complex and subtle questions about the management of medically resistant partial epilepsy. This may be the greatest argument in favor of promoting newer imaging techniques," he said. 

For more information from the Diagnostic Imaging archives:

MRS gains indications, but still fights for reimbursement

MR imaging reveals signs of temporal lobe epilepsy

Intraoperative high-field MR imaging revamps neurosurgery practice

MR explores hippocampal abnormalities of epilepsy

Two different advanced MRI techniques can help clinicians choose epilepsy patients who will favorably respond to surgical intervention, according to a pair of studies published in the October 2005 issue of Neurology. 

Dee Rapposelli

Articles

Thrombolysis Proves Effective Outside the 3-Hour Window

DWI Shows Some Potential to Predict Post-TIA Stroke Risk

DWI Shows Some Potential to Predict Post-TIA Stroke Risk

Thrombolysis Proves Effective Outside the 3-Hour Window

Advanced MR imaging in epilepsy assists presurgical evaluation