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Research Briefs April 2018

Stroke Patients May Have a Wider Window of Treatment Opportunity

Stroke patients may benefit from endovascular thrombectomy later than previously believed, according to findings from the Endovascular Therapy Following Imaging Evaluation for the Ischemic Stroke (DEFUSE 3) trial. Until recently, thrombectomy was approved for use only up to six hours after symptom onset; the researchers discovered that even 16 hours after symptom onset it could improve outcomes compared with standard medical therapy.

Using automated software to analyze perfusion magnetic resonance imaging or computerized tomography scans, the researchers identified patients thought to have salvageable tissue. The patients were randomly assigned to receive endovascular thrombectomy plus standard medical therapy or medical therapy alone.

In the thrombectomy group, 45% of patients achieved functional independence compared with 17% of the control group. Thrombectomy was also associated with improved survival: 14% of the treated group died within 90 days of the study compared with 26% of the control group.

DEFUSE 3 is a large study supported by StrokeNet, a network of hospitals providing research infrastructure for multisite clinical trials, in this case, at 38 centers. The study was ended early because of “overwhelming” evidence of benefit from the clot removal procedure.

“These striking results will have an immediate impact and save people from life-long disability or death,” said Walter Korshetz, MD, Director of the National Institute of Neurological Disorders and Stroke. “I really cannot overstate the size of this effect.” He adds that one in three stroke patients with at-risk brain tissue improves and some may walk out of the hospital “saved from what would otherwise have been a devastating brain injury.”

Source: National Institutes of Health, January 2018

Unprecedented Study Gathers Data on Adolescent Development

An “unparalleled dataset” is providing high-quality information on the many factors that influence brain, cognitive, social, and emotional development in children.

The Adolescent Brain Cognitive Development study, involving more than 7,500 9- and 10-year-old children and their families, is the largest long-term study of brain development and child health in the U.S. Interim results on approximately 30 terabytes of data (three times the size of the Library of Congress collection) obtained from the first 4,500 participants will allow scientists to begin analyzing and publishing novel research, said Nora Volkow, MD, Director of the National Institute on Drug Abuse.

Researchers will be able to examine many aspects of growth and development, such as the impact of sports injuries on developmental outcomes, the relationship between screen time and brain and social development, and which brain pathways are associated with the onset and progression of mental health disorders.

The study aims to enroll 11,500 children by the end of 2018. Participants will be followed for 10 years, with data collected every six and 12 months through interviews and behavioral testing. Neuroimaging data are being collected every two years.

Source: National Institutes of Health, February 2018

Treating Cancer Fatigue With Placebo

Cancer-related fatigue can linger long after treatments are ended, making daily activities harder and diminishing quality of life. But researchers from the University of Alabama and Harvard University suggest a nonpharmaceutical way to help patients feel better: placebo.

They compared an open-label placebo with treatment as usual in patients with cancer-related fatigue in a 21-day controlled trial. The patients had completed cancer treatment six months to 10 years prior to enrollment. Of 74 patients, 28 reported a moderate level of fatigue, and 46 reported a severe level. The mean fatigue scores at baseline were similar for both groups.

The participants randomly assigned to placebo took two placebo pills twice a day. At 21 days, the average difference in scores was statistically significant. The placebo group reported a 29% improvement in fatigue severity and a 39% improvement in fatigue-disrupted quality of life. Put another way, 74% of the placebo group had a change score above the mean change score of the usual-treatment group. The results were clinically meaningful, the researchers said. Moreover, there were no reported adverse events or side effects.

After that main study, the researchers also conducted a 21-day exploratory crossover extension, which began one week later. Their findings supported the main study results, with the same magnitude of improvement. The usual-treatment patients who chose to try the placebo also reported a similar magnitude of reductions in fatigue severity (23%) and fatigue-disrupted quality of life (35%).

Interestingly, the effects seemed to be sustained, the researchers said. At day 48, there was no significant change in fatigue scores compared with day 21, an “exciting” preliminary finding they say needs further exploration.

Source: Scientific Reports, February 2018

Windows to the Brain

“We were kind of astounded by this—it’s a very unrecognized phenomenon,” said Richard Leigh, MD, Assistant Clinical Investigator at the National Institute of Neurological Disorders and Stroke. He was talking about the fact that he and his co-researchers had discovered that gadolinium, used in brain scans for stroke patients, sometimes leaks into the eyes—literally highlighting abnormalities. The finding could lead to more accurate stroke treatment.

The researchers performed magnetic resonance imaging (MRI) scans on 167 stroke patients upon admission to the hospital without administering gadolinium and compared them to scans taken using gadolinium two hours and 24 hours later.

They found that, thanks to the gadolinium, some eyes glowed brightly, marking the location of brain damage. It appeared that the stroke could compromise the blood–ocular barrier. “It looks like the stroke is influencing the eye, and so the eye is reflective of what is going on in the brain,” Dr. Leigh said.

In roughly three-quarters of the patients, gadolinium leaked into the eyes on one of the scans: 66% in the two-hour scan (typically leaking in the aqueous chamber in the front of the eye) and 75% in the 24-hour scan (typically in the vitreous chamber in the back of the eye).

Older patients, those with hypertension, and those with more bright spots on their brain scans (associated with brain aging) were more likely to show gadolinium in the vitreous chamber at 24 hours. In a minority of patients, both eye chambers showed gadolinium at two hours. In those patients, stroke tended to affect a larger portion of the brain and cause more damage to the blood–brain barrier than strokes in patients with a slower pattern of gadolinium leakage or no leakage.

The researchers observed the phenomenon in both untreated patients and in those who received tissue plasminogen activator.

The findings raise the possibility that clinicians could administer a substance to patients that would collect in the eye, like gadolinium, and quickly yield information about the stroke without the need for an MRI, the researchers said. “It’s much easier for us to look inside somebody’s eye than to look into somebody’s brain,” Dr. Leigh said. “So if the eye truly is a window to the brain, we can use one to learn about the other.”

Source: National Institutes of Health, February 2018

When Your Neighborhood Is a CVD Risk Factor

Living in a neighborhood with poor access to food and poor “walkability” puts people at risk for cardiovascular disease (CVD)—and according to researchers from Morehouse School of Medicine, African-Americans have the highest risk.

In a study funded by the Centers for Disease Control and Prevention, the researchers examined the relationship between neighborhood-level food access and walkability on premature CVD mortality rates in Atlanta, using census tracts to map neighborhoods. (Atlanta is located in Fulton County, which has a food insecurity rating of nearly 20%.) Food access was defined as the percentage of no-vehicle households living beyond a 0.9-mile radius of a food outlet in 2012. Walkability was measured in relationship to amenities, population density, and road metrics.

The researchers found no significant difference in walkability scores between high-poverty and low-poverty census tracts. However, they did find significant racial differences: Census tracts with high concentrations of minority populations had higher levels of poor food access, poor walkability, and premature CVD mortality.

Of 124 census tracts, 87 contained 73% of the city’s population 35 to 64 years of age, and accounted for 1,225 deaths between 2010 and 2014, with a premature CVD mortality rate of 11 per 1,000. Black premature CVD deaths accounted for nearly 85% of the premature CVD deaths in all census tracts—a “disproportionate number,” the researchers said, because blacks make up only 52% of the city’s total population 35 to 64 years of age.

Their findings can be used to “calibrate” neighborhood interventions based on racial/ethnic or other demographic characteristics, the researchers suggested. They added that the results highlight the need to examine racially stratified health outcomes.

Source: Preventing Chronic Disease, February 2018

A Rapid Diagnostic Test for Parkinson’s Disease

Scientists from the National Institutes of Health (NIH) who developed a rapid test for early diagnosis of prion diseases have modified it to improve early diagnosis of Parkinson’s disease and dementia with Lewy bodies.

The researchers ran the assay with 60 cerebral spinal fluid samples: 12 from people with Parkinson’s disease, 17 from people with dementia with Lewy bodies, and 31 controls, including 16 people with Alzheimer’s disease. The test correctly excluded all 31 controls and diagnosed both Parkinson’s disease and dementia with Lewy bodies with 93% accuracy.

Moreover, the test results were available within two days, compared with 13 days for related assays.

Like prion diseases, Parkinson’s disease and dementia with Lewy bodies cause progressive deterioration of brain functions. The diseases typically progress for years before symptoms appear; once they do, distinguishing one from another can be difficult. The NIH says early, accurate diagnoses are essential for developing treatments and identifying patients eligible for clinical trials.

Source: NIH, February 2018