Brain damage caused by severe sleep apnea is reversible

A neuroimaging study is the first to show that white matter damage caused by severe obstructive sleep apnea can be reversed by continuous positive airway pressure therapy. The results underscore the importance of the “Stop the Snore” campaign of the National Healthy Sleep Awareness Project, a collaboration between the Centers for Disease Control and Prevention, American Academy of Sleep Medicine, Sleep Research Society and other partners.

Results show that participants with severe, untreated sleep apnea had a significant reduction in white matter fiber integrity in multiple brain areas. This brain damage was accompanied by impairments to cognition, mood and daytime alertness. Although three months of CPAP therapy produced only limited improvements to damaged brain structures, 12 months of CPAP therapy led to an almost complete reversal of white matter abnormalities. Treatment also produced significant improvements in nearly all cognitive tests, mood, alertness and quality of life.

“Structural neural injury of the brain of obstructive sleep apnea patients is reversible with effective treatment,” said principal investigator and lead author Vincenza Castronovo, PhD, clinical psychologist at the Sleep Disorders Center at San Raffaele Hospital and Vita-Salute San Raffaele University in Milano, Italy. “Treatment with CPAP, if patients are adherent to therapy, is effective for normalizing the brain structure.”

The study results are published in the September issue of the journal Sleep.

“Obstructive sleep apnea is a destructive disease that can ruin your health and increase your risk of death,” said American Academy of Sleep Medicine President Dr. Timothy Morgenthaler, a national spokesperson for the Healthy Sleep Project. “Treatment of sleep apnea can be life-changing and potentially life-saving.”

The “Stop the Snore” campaign was launched recently to encourage people to talk to a doctor about the warning signs for sleep apnea, which afflicts at least 25 million adults in the U.S. Sleep apnea warning signs include snoring and choking, gasping or silent breathing pauses during sleep. Pledge to stop the snore at www.stopsnoringpledge.org.

The study involved 17 men with severe, untreated obstructive sleep apnea who had an average age of 43 years. They were evaluated at baseline and after both three months and 12 months of treatment with CPAP therapy. At each time point they underwent a neuropsychological evaluation and a diffusion tensor imaging examination. DTI is a form of magnetic resonance imaging that measures the flow of water through brain tissue. Participants were compared with 15 age-matched, healthy controls who were evaluated only at baseline.

A previous study by Castronovo’s research team found similar damage to gray matter volume in multiple brain regions of people with severe sleep apnea. Improvements in gray matter volume appeared after three months of CPAP therapy. According to the authors, the two studies suggest that the white matter of the brain takes longer to respond to treatment than the gray matter.

“We are seeing a consistent message that the brain can improve with treatment,” said co-principal investigator Mark Aloia, PhD, Associate Professor of Medicine at National Jewish Health in Denver, Colorado, and Senior Director of Global Clinical Research for Philips Respironics, Inc. “We know that PAP therapy keeps people breathing at night; but demonstrating effects on secondary outcomes is critical, and brain function and structure are strong secondary outcomes.”

Longitudinal study explores white matter damage, cognition after traumatic axonal injury

Traumatic Axonal Injury is a form of traumatic brain injury that can have detrimental effects on the integrity of the brain’s white matter and lead to cognitive impairments. A new study from the Center for BrainHealth at The University of Texas at Dallas investigated white matter damage in the acute and chronic stages of a traumatic axonal injury in an effort to better understand what long-term damage may result.

The study, published online July 21 in the Journal of Neurotrauma, looked at 13 patients ages 16 to 60 with mild to severe brain injuries from the intensive care unit at a Level I trauma center. This group was matched to a cohort of 10 healthy individuals resembling the age, gender, and ethnicity of the patients. White matter integrity was measured using diffusion tensor imaging (DTI) in the acute stage of injury, at day one, and again at the chronic stage, seven months post-injury. In addition, neuropsychological assessments measured cognitive performance including processing speed, attention, learning and memory at both stages after injury.

“We intended to determine whether DTI could not only identify early compromise to white matter, but also demonstrate an association with functional and neuropsychological outcomes months post-injury,” said Carlos Marquez de la Plata, Ph.D., Assistant Director of Rehabilitation Research at Pate Rehabilitation in Dallas, Texas.

The study’s findings suggest DTI may be used to detect meaningful changes in white matter as early as one day after a traumatic brain injury. White matter integrity measured at the chronic stage was also found to significantly correlate with cognitive processing speed.

“On the first day after the injury, we found white matter integrity was compromised due to swelling in the brain,“ said the study’s lead author Alison Perez. “As the swelling subsided over time and the brain began to repair itself, we found that many of the damaged neurons that were unable to repair themselves began to die off, which appears to slow the speed of cognitive processing.”

Interestingly, the degree of white matter compromise detected early after injury was associated with markers of injury severity such as the number of days in the intensive care unit and hospital, but not to outcomes months later. 

At seven months post-injury, many of the patients’ cognitive performance improved including processing speed, divided attention, and short and long-term memory. In addition, patients with better white matter integrity at the chronic stage had the fastest processing speed.

By studying the long-term effects of a traumatic axonal injury at both the acute and chronic stages, researchers hope to assist in the advancement of future assessment and treatment options after a traumatic brain injury.

Wii Balance Board Induces Changes in the Brains of MS Patients

A balance board accessory for a popular video game console can help people with multiple sclerosis (MS) reduce their risk of accidental falls, according to new research published online in the journal Radiology. Magnetic resonance imaging (MRI) scans showed that use of the Nintendo Wii Balance Board system appears to induce favorable changes in brain connections associated with balance and movement.

Balance impairment is one of the most common and disabling symptoms of MS, a disease of the central nervous system in which the body’s immune system attacks the protective sheath around nerve fibers. Physical rehabilitation is often used to preserve balance, and one of the more promising new tools is the Wii Balance Board System, a battery-powered device about the size and shape of a bathroom scale. Users stand on the board and shift their weight as they follow the action on the television screen during games like slalom skiing.

While Wii balance board rehabilitation has been reported as effective in patients with MS, little is known about the underlying physiological basis for any improvements in balance.

Researchers recently used an MRI technique called diffusion tensor imaging (DTI) to study changes in the brains of 27 MS patients who underwent a 12-week intervention using Wii balance board-based visual feedback training. DTI is a non-conventional MRI technique that allows detailed analysis of the white matter tracts that transmit nervous signals through the brain and body.

MRI scans of the MS patients showed significant effects in nerve tracts that are important in balance and movement. The changes seen on MRI correlated with improvements in balance as measured by an assessment technique called posturography.

These brain changes in MS patients are likely a manifestation of neural plasticity, or the ability of the brain to adapt and form new connections throughout life, according to lead author Luca Prosperini, M.D., Ph.D., from Sapienza University in Rome, Italy.

"The most important finding in this study is that a task-oriented and repetitive training aimed at managing a specific symptom is highly effective and induces brain plasticity," he said. "More specifically, the improvements promoted by the Wii balance board can reduce the risk of accidental falls in patients with MS, thereby reducing the risk of fall-related comorbidities like trauma and fractures."

Dr. Prosperini noted that similar plasticity has been described in persons who play video games, but the exact mechanisms behind the phenomenon are still unknown. He hypothesized that changes can occur at the cellular level within the brain and may be related to myelination, the process of building the protective sheath around the nerves.

The rehabilitation-induced improvements did not persist after the patients discontinued the training protocol, Dr. Prosperini said, most likely because certain skills related to structural changes to the brain after an injury need to be maintained through training.

"This finding should have an important impact on the rehabilitation process of patients, suggesting that they need ongoing exercises to maintain good performance in daily living activities," Dr. Prosperini said.

Abnormal White Matter Integrity in Chronic Users of Codeine-Containing Cough Syrups: A Tract-Based Spatial Statistics Study

Physically fit kids have beefier brain white matter than their less-fit peers

A new study of 9- and 10-year-olds finds that those who are more aerobically fit have more fibrous and compact white-matter tracts in the brain than their peers who are less fit. “White matter” describes the bundles of axons that carry nerve signals from one brain region to another. More compact white matter is associated with faster and more efficient nerve activity.

The team reports its findings in the open-access journal Frontiers in Human Neuroscience.

“Previous studies suggest that children with higher levels of aerobic fitness show greater brain volumes in gray-matter brain regions important for memory and learning,” said University of Illinois postdoctoral researcher Laura Chaddock-Heyman, who conducted the study with kinesiology and community health professor Charles Hillman and psychology professor and Beckman Institute director Arthur Kramer. “Now for the first time we explored how aerobic fitness relates to white matter in children’s brains.”

The team used diffusion tensor imaging (DTI, also called diffusion MRI) to look at five white-matter tracts in the brains of the 24 participants. This method analyzes water diffusion into tissues. For white matter, less water diffusion means the tissue is more fibrous and compact, both desirable traits.

The researchers controlled for several variables – such as social and economic status, the timing of puberty, IQ, or a diagnosis of ADHD or other learning disabilities – that might have contributed to the reported fitness differences in the brain.

The analysis revealed significant fitness-related differences in the integrity of several white-matter tracts in the brain: the corpus callosum, which connects the brain’s left and right hemispheres; the superior longitudinal fasciculus, a pair of structures that connect the frontal and parietal lobes; and the superior corona radiata, which connect the cerebral cortex to the brain stem.
“All of these tracts have been found to play a role in attention and memory,” Chaddock-Heyman said.

The team did not test for cognitive differences in the children in this study, but previous work has demonstrated a link between improved aerobic fitness and gains in cognitive function on specific tasks and in academic settings.

“Previous studies in our lab have reported a relationship between fitness and white-matter integrity in older adults,” Kramer said. “Therefore, it appears that fitness may have beneficial effects on white matter throughout the lifespan.”

To take the findings further, the team is now two years into a five-year randomized, controlled trial to determine whether white-matter tract integrity improves in children who begin a new physical fitness routine and maintain it over time. The researchers are looking for changes in aerobic fitness, brain structure and function, and genetic regulation.

“Prior work from our laboratories has demonstrated both short- and long-term differences in the relation of aerobic fitness to brain health and cognition,” Hillman said. “However, our current randomized, controlled trial should provide the most comprehensive assessment of this relationship to date.”

The new findings add to the evidence that aerobic exercise changes the brain in ways that improve cognitive function, Chaddock-Heyman said.

“This study extends our previous work and suggests that white-matter structure may be one additional mechanism by which higher-fit children outperform their lower-fit peers on cognitive tasks and in the classroom,” she said.

Kids with Autism, Sensory Processing Disorders Show Brain Wiring Differences

Researchers at UC San Francisco have found that children with sensory processing disorders have decreased structural brain connections in specific sensory regions different than those in autism, further establishing SPD as a clinically important neurodevelopmental disorder.

The research, published in the journal PLOS ONE, is the first study to compare structural connectivity in the brains of children with an autism diagnosis versus those with an SPD diagnosis, and with a group of typically developing boys. This new research follows UCSF’s groundbreaking study published in 2013 that was the first to find that boys affected with SPD have quantifiable regional differences in brain structure when compared to typically developing boys. This work showed a biological basis for the disease but prompted the question of how these differences compared with other neurodevelopmental disorders.

“With more than 1 percent of children in the U.S. diagnosed with an autism spectrum disorder, and reports of 5 to 16 percent of children having sensory processing difficulties, it’s essential we define the neural underpinnings of these conditions, and identify the areas they overlap and where they are very distinct,” said senior author Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging and bioengineering at UCSF.

SPD Gains Recognition as Distinct Condition

SPD can be hard to pinpoint, as more than 90 percent of children with autism also are reported to have atypical sensory behaviors, and SPD has not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists.

“One of the most striking new findings is that the children with SPD show even greater brain disconnection than the kids with a full autism diagnosis in some sensory-based tracts,” said Elysa Marco, MD, cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital San Francisco and the study’s corresponding author. “However, the children with autism, but not those with SPD, showed impairment in brain connections essential to the processing of facial emotion and memory.”

Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with emotional regulation. Furthermore, a sound that is an irritant one day can be tolerated the next. The disease can be baffling for parents and has been a source of much controversy for clinicians who debate whether it constitutes its own disorder, according to the researchers.

“These kids, however, often don’t get supportive services at school or in the community because SPD is not yet a recognized condition,” said Marco. “We are starting to catch up with what parents already knew; sensory challenges are real and can be measured both in the lab and the real world. Our next challenge is to find the reason why children have SPD and move these findings from the lab to the clinic.”

Examining White Matter Tracts in the Brain

In the study, researchers used an advanced form of MRI called diffusion tensor imaging (DTI), which measures the microscopic movement of water molecules within the brain in order to give information about the brain’s white matter tracts. The brain’s white matter forms the “wiring” that links different areas of the brain and is therefore essential for perceiving, thinking and action. DTI shows the direction of the white matter fibers and the integrity of the white matter, thereby mapping the structural connections between brain regions.

The study examined the structural connectivity of specific white matter tracts in16 boys with SPD and 15 boys with autism between the ages of 8 and 12 and compared them with 23 typically developing boys of the same age range.

The researchers found that both the SPD and autism groups showed decreased connectivity in multiple parieto-occipital tracts, the areas that handle basic sensory information in the back area of the brain. However, only the autism cohort showed impairment in the inferior fronto-occipital fasciculi (IFOF), inferior longitudinal fasciculi (ILF), fusiform-amygdala and the fusiform-hippocampus tracts – critical tracts for social-emotional processing.  

“One of the classic features of autism is decreased eye-to-eye gaze, and the decreased ability to read facial emotions,” said Marco. “The impairment in this specific brain connectivity, not only differentiates the autism group from the SPD group but reflects the difficulties patients with autism have in the real world.  In our work, the more these regions are disconnected, the more challenge they are having with social skills.”

Kids with isolated SPD showed less connectivity in the basic perception and integration tracts of the brain that serve as connections for the auditory, visual and somatosensory (tactile) systems involved in sensory processing.

“If we can start by measuring a child’s brain connectivity and seeing how it is playing out in a child’s functional ability, we can then use that measure as a metric for success in our interventions and see if the connectivities are changing based on our clinical interventions,” said Marco. “Larger studies to replicate this early work are clearly needed but we are encouraged that DTI can be a powerful clinical and research tool for understanding the basis for sensory neurodevelopmental differences.”

(Image caption: Uncinate fasiculus, an important tract with the greatest concentration of progesterone receptors, show greater injury in males than females after mild traumatic brain injury (mTBI). (a) Axial and (b) coronal images show regions of decreased fractional anisotropy in male patients with mTBI relative to female mTBI patients, involving the uncinate fasiculus (red) bilaterally.)

Gender May Contribute to Recovery Time After Concussion

A study of concussion patients using diffusion tensor imaging (DTI) found that males took longer to recover after concussion than females did. Results of the study, which show that DTI can be used as a bias-free way to predict concussion outcome, are published online in the journal Radiology.

Each year, more than 17 million Americans suffer a mild traumatic brain injury (mTBI), more commonly known as a concussion, of which approximately 15 percent suffer persistent symptoms beyond three months.

Assessing outcomes and recovery time after concussion can be very subjective. Typically, physicians must rely on patient cooperation to assess injury severity.

"MRI and CT brain images of concussion patients are often normal," said Saeed Fakhran, M.D., assistant professor of neuroradiology at the University of Pittsburgh School of Medicine. "Diffusion tensor imaging is the first imaging technique that shows abnormalities associated with concussion, because it is able to see white matter tracts at a microscopic level."

DTI is an advanced form of MRI that allows researchers to assess microscopic changes in the brain’s white matter. The brain’s white matter is composed of millions of nerve fibers called axons that act like communication cables connecting various regions of the brain. DTI produces a measurement, called fractional anisotropy (FA), of the movement of water molecules along axons. In healthy white matter, the direction of water movement is fairly uniform and measures high in FA. When water movement is more random, FA values decrease. Abnormally low FA is associated with cognitive impairment in patients with brain injuries.

The research team examined the medical records and imaging results of 69 patients diagnosed with mTBI between 2006 and 2013, including 47 males and 22 females, and 21 controls consisting of 10 males and 11 females (median age of males: 17; median age of females: 16). Of the 47 males with mTBI, 32 (68 percent) were injured while playing a sport, as were 10 of the 22 females (45 percent).

All patients underwent the same evaluation, including a computerized neurocognitive test and DTI of the brain. The DTI scans of the mTBI patients revealed abnormalities within the uncinate fasciculi (UF), a white matter tract that connects the frontal and temporal lobes of the brain. Although its exact role is controversial, the UF tract is believed to allow temporal lobe-based memory associations to modify behavior though interactions with another area of the brain.

The DTI scans revealed that compared to the female mTBI patients, the male mTBI patients had significantly decreased UF FA values.

"In the future, we would like to look at the issue of gender and concussions more in depth to determine who does better and why," Dr. Fakhran said.

A statistical analysis of the data revealed that UF FA value was a stronger predictor of recovery time than initial symptom severity based on neurocognitive testing. The most substantial risk factor for a recovery time longer than three months was decreased UF FA. Male gender also directly correlated with increased recovery time.

"The potential of DTI and UF FA to predict outcome after concussion has great clinical impact," Dr. Fakhran said. "Currently, we are heavily reliant on patient reporting, and patients may have ulterior motives, such as wanting to get back to play. But you can’t trick an MR scanner."

The average time to symptom recovery for all concussion patients was 54 days. However, compared to the female patients who recovered in an average of 26.3 days, recovery was significantly longer for the male patients (an average of 66.9 days), irrespective of initial symptom severity.

"Male gender and UF FA values are independent risk factors for persistent post-concussion symptoms after three months and stronger predictors of time to recovery than initial symptom severity or neurocognitive test results," Dr. Fakhran said.

He said results of the study indicate a potential role for UF FA values in triaging concussion patients in the future.

"There’s prognostic value in DTI for both children participating in sports as well as for professional athletes," he said. "Lower FA values in the uncinate fasciculi could offer a metric for evaluating the severity of mild traumatic brain injuries and predicting clinical outcome. We’re not at the point where DTI can provide individual prognoses yet, but that’s the hope and goal."