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Thursday, January 29, 2015



Image via Robbie Grubbs on Flickr.


A study of former NFL players suggests that youth concussion may be especially harmful for children between the ages of 10 and 12, when the brain undergoes a crucial development period that may be stalled by repeated blows to the head.


Past research has shown that repeat concussion or traumatic brain injury (TBI) can cause thinking and memory problems, lower intelligence, and emotional and behavioral issues such as depression later in life.


For the study, published in the Jan. 28 online issue of Neurology, researchers administered tests of memory, intelligence, and executive function to 42 former NFL players aged 41 to 65; all had complained of problems with memory, thinking, and mood in the preceding six months. Half had played tackle football before age 12, while the other half started playing football in their teenage years. Players in both groups had sustained a similar overall number of concussions.


The researchers found that athletes who began playing tackle football before age 12 performed worse on the entire battery of cognitive tests, performing approximately 20 percent worse than players who were exposed to tackle football after age 12.


“Our study suggests that there may be a critical window of brain development during which repeated head impacts can lead to thinking and memory difficulties later in life,” said study author Robert A. Stern, PhD, a professor of neurology, neurosurgery and anatomy and neurobiology at Boston University School of Medicine, in a news release.


During this period, key brain structures such as the amygdala and hippocampus begin to reach their adult volume. Extra synapses are pruned away during this time, allowing for more efficient information processing. But repeated concussion or TBI may keep the brain from developing normally during this crucial period, Dr. Stern said.


“If larger studies confirm this association, there may be a need to consider safety changes in youth sports,” he added.


The researchers warned that the study results cannot be extrapolated to all children who play sports, or even to all children who play football. The athletes in this study had all played professional football and had experienced many more concussions in their lives than the average person.


“Further investigations of individuals who started in youth football but did not play beyond high school (the vast majority of players) are clearly needed,” wrote Christopher M. Filley, MD, a behavioral neurologist at the University of Colorado School of Medicine in Aurora, CO, and Charles Bernick, MD, MPH, medical director of the Lou Ruvo Center for Brain Health at the Cleveland Clinic in Ohio, in an accompanying editorial.


However, the study underscores the importance of understanding the impact of concussion and on developing brains, particularly since repeated mild TBI has been linked to chronic traumatic encephalopathy (CTE), a degenerative form of dementia, said Dr. Filley and Dr. Bernick.


Football has the highest injury rate of all team sports, and approximately 70 percent of football players in the US are under the age of 14, they noted. As such, “a better understanding of neuro-behavioral sequelae among children who play football is urgently needed.”


Look for a more in-depth discussion of the study in the Feb. 19 issue of Neurology Today. For more coverage of concussion and TBI, browse our archives here.

Wednesday, January 28, 2015



Falling is the most common cause of injury among adults age 65 and older, and can lead to lifelong impairment or even death. As many as one-third of elderly adults fall each year, and people with neurological disorders have an even higher risk; in fact, a 2013 study from British Medical Journal Open found that elderly patients with mild to moderate neurological issues have a tripled risk for falls.


Now, a new 12-year survey has found that falls are still on the rise among elderly adults.



The survey, published in the Jan. 19 online issue of JAMA Internal Medicine, looked at a nationally representative sample of middle-aged and older adults (age 50 and over) who were enrolled in the University of Michigan Health and Retirement Study — which surveys more than 26,000 American adults every two years in order to track shifting demographic patterns as people leave the work force and develop new health care needs.


For the current study, investigators analyzed data from 1998 through 2010 for a sample of adults aged 65 and older, looking at reports of falls every two years. They found that self-reported falls increased by 8 percent over the 12-year period, from about 28 percent in 1998 to 36 percent in 2010. However, these adults did not report more injuries as a result of a fall.


The investigators had expected falls to increase as the number of 80 and 90-year-old seniors continues to rise, “but we were very surprised to find that the increase in falls was not due to the changing demography,” lead author Christine Cigolle, MD, MPH, an assistant professor in the departments of Family Medicine and Internal Medicine at the University of Michigan and a research scientists at the VA Ann Arbor Healthcare System Geriatric Research, Education and Clinical Center, said in a news release.


“We saw a higher number of falls across all age groups — not just the oldest — and that was unexpected,” she said.


This increase in falls was seen at all ages, but it was surprisingly most pronounced among the youngest survey participants, those just over 65.


So, what was responsible for the uptick? “It’s possible that older adults are more aware of fall risk and may be more likely to report it now than before,” said Dr. Cigolle. “However, if the prevalence of falls is actually increasing as much as it seems to be, we need to do more work to identify possible factors and how we can address what we know to be a high risk among a vulnerable group.”


If the increase in falls is not simply a result of better reporting, it could be that an increase in fall risk factors (for example, taking medications with side effects like dizziness and drowsiness) is responsible, she said. More research will be needed to determine the cause of the upswing.


For more coverage of the prevalence of falls in various neurological illnesses, browse our archives here.

Tuesday, January 27, 2015



A new study published in the Jan. 21 issue of Neuron suggests that the blood-brain barrier, a protective layer that prevents blood-derived products, cells, and pathogens from entering the brain, becomes damaged and leaky with age. That breakdown seems to begin in the hippocampus, a region critical for learning and memory that becomes impaired early in Alzheimer’s disease.


The blood-brain barrier is essential for normal neuronal functioning and information processing. Post-mortem studies of brain tissue have shown that it becomes impaired in Alzheimer’s disease, according to the study investigators.


With the current study, the investigators sought to understand when this damage first occurs in the neurodegenerative process. They used dynamic contrast-enhanced magnetic resonance imaging (MRI) to look at the blood-brain barrier integrity of 64 adults aged 23 to 91. Of these, 21 had mild cognitive impairment (MCI) and the rest were cognitively normal.


The three components of the blood-brain barrier: the astrocyte and astrocyte end feet that encircle the capillary, the capillary basement membrane, and the tight junctions that join the overlapping capillary endothelial cells.


The researchers found that in cognitively normal older adults, the blood-brain barrier showed age-dependent signs of leakage and damage in the hippocampus. That leakage was more pronounced in the hippocampi of subjects with MCI.


To validate their findings, the researchers then looked at cerebrospinal fluid (CSF) biomarkers of blood-brain barrier breakdown in these subjects. They found that those with MCI had 30 percent more of the blood protein albumin in their CSF than age-matched cognitively normal controls, as well as a 115 percent increase in a protein related to pericyte injury — damage to the cells that surround blood vessels and help maintain the blood-brain barrier. Pericyte injury has been linked to dementia in past research, the authors noted.


Taken together, these findings suggest that people with MCI have extra damage to the blood-brain barrier, beyond what can be expected in normal aging. “Our data suggest that BBB [blood-brain barrier] breakdown is an early event in the aging human brain that begins in the hippocampus and may contribute to cognitive impairment,” the authors wrote.


“This is a significant step in understanding how the vascular system affects the health of our brains,” said lead investigator Berislav V. Zlokovic, MD, PhD, director of the Zilkha Neurogenetic Institute at the Keck School of Medicine and the Mary Hayley and Selim Zilkha Chair for Alzheimer's Disease Research at the University of Southern California in Los Angeles.


The research also implies that contrast-enhanced MRI can detect changes in blood vessels in the hippocampus before the damage that causes MCI and dementia sets in. This could lead to the development of therapies to slow or stop blood-brain barrier breakdown, Dr. Zlokovic said.


“To prevent dementias including Alzheimer's, we may need to come up with ways to reseal the blood-brain barrier and prevent the brain from being flooded with toxic chemicals in the blood,” he said. “Pericytes are the gate-keepers of the blood-brain barrier and may be an important target for prevention of dementia.”


Look for the full story in an upcoming issue of Neurology Today. For more coverage of the blood-brain barrier’s role in neurologic illness, browse our archives here.

Monday, January 26, 2015



Depression is common in people with Alzheimer’s disease and dementia, and past research has identified it as an independent risk factor for cognitive decline. Now, a new study has shown that depression and other behavioral changes can appear years before memory loss develops.


The study, published in the Jan. 14 online issue of Neurology, looked at 2,416 adults over the age of 50 who had visited one of 34 Alzheimer’s centers across the country. At their first visit, all of the subjects were cognitively normal. The researchers administered neuropsychiatric tests such as the Neuropsychiatric Inventory Questionnaire and the Geriatric Depression Scale, which assess the presence and severity of psychiatric symptoms such as depression, delusions, agitation, anxiety, apathy, irritability, and abnormal motor behavior.


After up to seven years of follow-up, 1,218 subjects developed dementia. The researchers found that subjects with dementia developed depression and other behavioral symptoms sooner than those who did not progress to dementia (p<0.001). For instance, 30 percent of people who developed dementia had symptoms of depression after four years of follow up, compared with 15 percent of those who did not develop dementia.


“While earlier studies have shown that an estimated 90 percent of people with Alzheimer’s experience behavioral or psychological symptoms such as depression, anxiety, and agitation, this study suggests that these changes begin before people even have diagnosable dementia,” study author Catherine M. Roe, PhD, a research assistant professor of neurology in the Knight Alzheimer's Disease Research Center at Washington University School of Medicine in St. Louis, said in a news release.



The researchers noted that these non-cognitive symptoms appeared in three distinct phases: first, irritability, depression, and changes in nighttime behavior; next, anxiety, apathy, agitation, and changes in appetite; and lastly, elation, hallucinations, delusions, disinhibition, and motor disturbances.


Both subjects who progressed to dementia and those who did not developed neuropsychiatric symptoms over time, albeit at different rates, suggesting that these conditions are at least in part diseases of the aging brain, the researchers said. Overall, the findings suggest that depression may be a “modest risk factor” for people with preclinical dementia, they wrote.


However, they could not determine whether these non-cognitive symptoms were a result of the same brain pathology that causes Alzheimer’s and dementia. “We still don’t know whether depression is a response to the psychological process of Alzheimer’s disease or a result of the same underlying changes in the brain,” Dr. Roe said. She added that more research is needed to identify the relationship between these two conditions.


For more coverage of the link between depression and dementia, browse our archives here.

Friday, January 23, 2015



Part of a generalized tonic–clonic seizure: The seizure begins with a generalized spike-and-wave burst (arrow) that is replaced by polyspike and wave.


Epilepsy patients who sleep on their stomachs may be at a higher risk for sudden unexpected death in epilepsy (SUDEP) than those who sleep in other positions, according to a study published in the Jan. 21 online issue of Neurology. The findings suggest that the condition may share an underlying mechanism with sudden infant death syndrome, or SIDS.


SUDEP is the main cause of death in epilepsy patients whose seizures are not adequately controlled with medication, and it usually occurs unwitnessed during sleep, study author James X. Tao, MD, PhD, an associate professor of neurology and director of the Electroencephalography (EEG) Laboratory at the University of Chicago, said in a news release.


Patients with tonic-clonic seizures are more likely to die from SUDEP than those with partial seizures. Other known risk factors for SUDEP include early onset of epilepsy, chronic resistance to medications, and nocturnal seizures.


For the study, Dr. Tao and colleagues conducted a meta-analysis of 25 studies including 253 cases of SUDEP where body position was recorded. Overall, they found that 73 percent of the patients died sleeping on their stomachs, while 27 percent died in other sleep positions. In a subgroup of 88 SUDEP cases, younger epilepsy patients were nearly four times as likely to be found on their stomachs as older patients (p=0.009); 86 percent of people under 40 who died from SUDEP were found in the prone position, compared with 60 percent of those over 40.


“We’re not sure why this was more common in younger people. It may be that they are more likely to be single and not have anyone with them during a seizure while sleeping,” Dr. Tao said.


In addition, 11 SUDEP cases occurred while the patients were being monitored with video EEG. All 11 of these patients died while in a prone position, and most had been sleeping on their stomachs before the seizure occurred. The patients also all had generalized tonic-clonic seizures and postictal generalized EEG suppression, a post-seizure EEG pattern that is nearly exclusive to tonic-clonic seizures.


The researchers suggested that these three factors — sleeping in a prone position, generalized tonic-clonic seizures, and postictal generalized EEG suppression — may play a major role in SUDEP, and recommended that all future SUDEP case reports should include information related to body position.


The mechanisms of SUDEP remain largely unknown, but its circumstances are quite similar to SIDS, the authors wrote. As in SIDS, “adults often have an impaired ability to wake up after a seizure,” which may impair their ability to auto-resuscitate when the airway is obstructed by soft bedding, Dr. Tao said.


“Discovering a possible modifiable risk factor for SUDEP, such as sleeping in the prone position, is clearly important because it implies the possibility of preventing a substantial number of deaths by having patients sleep on their back, as has been done with SIDS,” wrote Barbara Dworetzky, MD, an associate professor of neurology at Harvard Medical School, and Stephan U. Schuele, MD, MPH, an associate professor of neurology at Northwestern University Feinberg School of Medicine, in an accompanying editorial.


Dr. Dworetzky and Dr. Shuele suggested that high-risk patients should be identified and followed prospectively in order to better understand risk factors and possible preventive measures for SUDEP. “This approach would truly benefit our patients,” they said, “as current treatments still fall short in stopping all seizures.”


For more coverage of SUDEP, browse our archives here.