New study upends understanding of the blood–brain barrier. Plus, new imaging differentiates dementias, and waking the comatose with brain stimulation

New study upends understanding of the blood–brain barrier. Plus, using imaging to differentiate dementias, and waking the comatose with brain stimulation

Since 2012, researchers have used an in vitro model to study the blood–brain barrier. But this week, we bring news of a study that points to a critical flaw in this model that raises questions over much of this work. We also have an optimistic study that sheds new light on stroke prevalence in the elderly, genetic scoring that can accurately predict a future schizophrenia diagnosis in the prenatal period, a study that suggests two popular vitamins could protect against dementia, and more.

Neuro Flashback

Over the past few decades, deep brain stimulation (DBS) has revolutionized the treatment of movement disorders, obsessive-compulsive disorder, and Tourette’s syndrome. Ongoing research suggests that it could also prove beneficial for patients with depression and schizophrenia. So how did this incredible therapy originate? Accidentally, of course. Modern DBS is widely attributed to Alim-Louis Benabid and Mahlon DeLong, who discovered that applying electrical stimulation to the basal ganglia improved symptoms of Parkinson’s disease. In 1987, the pair was creating a routine radiofrequency lesion in the thalamic ventralis intermedius to treat a patient with essential tremor, when they stumbled upon a crucial finding. While testing for adverse effects in the thalamus (like dysesthesia or muscular contractions) prior to making a lesion, the researchers observed that the patient’s tremor—although unaltered when electrically stimulated between 30 and 50 Hz—could be abruptly and reversibly stopped when stimulated at 100 Hz. This was subsequently reproduced in other patients, and it was the first step down the road of developing modern DBS as an important neurological treatment.

In the News

Misbehaving cells shed doubt on years of bloodbrain barrier research. Studies on the human blood–brain barrier (BBB) have typically involved an in vitro human BBB model, which means the experiments are conducted in cells in a lab. A new study, however, may have found a critical flaw in these models of the human BBB, which has thrown nearly a decade’s worth of research into question.

The current model, developed in 2012, manipulates cells to behave like embryonic stem cells. These stem cells can then be transformed into almost any type of mature cells—including the kind of endothelial cell that lines blood vessels in the brain and spinal cord. These cells form the BBB, which stops dangerous substances, antibodies, and immune cells from crossing from the bloodstream into the brain. But the new study, published in Proceedings of the National Academy of Sciences, found that these induced cells don’t behave the same way that normal endothelial cells do in the brain. To arrive at their findings, researchers performed bulk- and single-cell RNA sequencing, and found that the induced cells were missing several key proteins found in the natural cells. The team also identified three genes that, when activated within induced pluripotent cells, led to the creation of endothelial cells that behave more like the real thing. Keep an eye on these pioneering scientists—they didn’t just burn down the barn, they built an entirely new one.

Polluted air could lead to a clouded brain. Until recently, it’s been tricky to explore the effects of air pollution exposure on the brain. Why? Because routine monitoring of polluted air didn’t begin until the 1990s. Now that data is available, a new study has found that exposure to air pollution in childhood is linked to cognitive decline in later life.

The study, published in the Journal of Alzheimer’s Disease, tested the general intelligence of more than 500 people around 70 years of age against a test they had all completed at age 11. Researchers used a record of where each person had lived throughout their life and a model to determine levels of exposure to air pollution during their early years. They found that greater levels of pollutant exposure early in life was associated with a detrimental effect on participants’ cognitive skills up to 60 years later. The study represents a real step forward in understanding the various ways that air pollution affects us.

Fewer strokes for elderly folks. Stroke is still one of the leading causes of death and disability around the globe, but the findings of a new study suggest that the future looks a bit brighter. According to the data, people aged 70 years and older are having fewer strokes, and fewer people of all ages are dying from stroke.

The study, published in Neurology, used national health care registries in Denmark to identify people in the country hospitalized with a first-time stroke between 2005 and 2018. The cohort included 8,680 younger adults aged 18-49 years who had suffered a stroke during that period, as well as 105,240 adults aged 50 years and older. Researchers found that the incidence rate of stroke in those younger than 50 neither increased nor decreased over the study period. For those 50 years and older, rates of stroke declined over the course of the study, from 372 cases per 100,000 person-years at the start, to 311 cases by the end. Researchers believe that the decline may be associated with improved treatment of stroke risk factors, like hypertension and atrial fibrillation, as well as falling rates of smoking.

Childhood trauma can lead to adult brain changes. Childhood trauma is a well-established risk factor for the development of mental health conditions like major depressive disorder in adulthood. But a new study is the first to show that traumatic or stressful events during youth may lead to tiny changes in key brain structures that can still be identified decades later.

The study, published in Psychology & Neuroscience, looked at a cohort of 35 individuals with major depressive disorder, along with 35 healthy controls, matched by age, sex, and education. By comparing high-resolution MRI scans, researchers were able to identify small changes in specific subregions of the amygdala and the hippocampus. The researchers believe that once these changes occur, the brain can’t function as well, which may increase the risk of mental health disorders during times of stress in adulthood. Now that the specific regions of change have been identified, the study’s authors hope that further research can focus on ways to mitigate or even reverse these changes.

Neuro Trivia

Question: If you lined up all your nerve cells, how far would they stretch?

Answer: 45 miles—about half the distance from New York City to Philadelphia. Although we advise against trying it out yourself.

Novel Diagnostics

Differentiating dementia. Dementia with Lewy bodies (DLB) is often misdiagnosed as either Alzheimer’s disease or Parkinson’s-related dementia (which is present in up to 80% of Parkinson’s patients). This can lead to patient mismanagement, because patients with DLB can be markedly sensitive to certain medications. But a new study may have solved this issue. Researchers found that the imaging of a living brain can help clearly distinguish between DLB and Alzheimer’s disease.

For years, researchers have hypothesized that an imaging technique called single-photon emission computed tomography, combined with the intravenous radioactive compound [123I]FP-CIT, would allow the differentiation of DLB from Alzheimer’s disease. This is because [123I]FP-CIT binds to dopamine transporters, and the striatal dopamine-producing neurons are depleted in DLB but not in Alzheimer’s disease. The new study, published in Journal of Neurology, Neurosurgery and Psychiatry, looked at brain imaging from 36 patients and found that the technique yielded a very high degree of accuracy in not only differentiating between DLB from Alzheimer’s, but also between DLB from Parkinson’s disease. 

Risks for schizophrenia may begin prenatally. For decades, evidence has been mounting that risks for schizophrenia—which is typically first diagnosed in early adult life—begin much earlier in life, possibly even while we’re still in the womb. Now, a new study suggests that the genetic scoring of schizophrenia-related genes in the placenta can predict the size of a baby’s brain at birth and its rate of cognitive development, which may help diagnose schizophrenia later in life.

The study, published in Proceedings of the National Academy of Sciences, analyzed data from MRI scans of newborns and compared them with measures of their cognitive development over the first 2 years of life. The researchers found that schizophrenia’s placental gene-expression loci were negatively associated with the size of the baby’s brain at birth, and with cognitive development over their first year. These findings were most significant in males. The researchers concluded that higher placental genomic risk for schizophrenia may alter early brain growth and function. The findings represent the establishment of a potentially reversible neurodevelopmental path of risk that may be unique to schizophrenia.

The eyes are the window to an MS diagnosis. Multiple sclerosis diagnosis is a game of process of elimination that boils down to ruling out other conditions that produce similar symptoms. But a new tool may help with this. The device, which aims to diagnose MS via tracking eye movement, has recently earned a $2.5 million funding boost.

  1. Light Technologies announced that it raised $2.5 million in seed funding to further develop its noninvasive device, which the company hopes will diagnose a range of neurological diseases through measurements made in a matter of seconds. The device works by mapping fixational eye motion, which refers to involuntary eye movements that happen while holding the eye stable. These movements occur to ensure that vision does not fade when gaze is fixed. In MS patients, however, these movements are altered in a way that evidence indicates is associated with greater disability. The firm announced that part of the money raised will go to advance the prototype into a market-ready product.

For a dementia prognosis, look to the brain waves. When it comes to Alzheimer’s research, early detection and prevention is the Holy Grail. Now, research has established a new method that uses direct measures of brain signatures to predict individual risk of cognitive decline.

The research, published in the Journal of Alzheimer’s Disease, sought to test the hypothesis that older individuals diagnosed with incident amnestic mild cognitive impairment (aMCI) likely already have aMCI-like brain signatures years before diagnosis. Using electroencephalography to monitor brain waves, the researchers found that those who developed aMCI had significantly different baseline memory-related brain waves than those who remained healthy. They also found that a differentiation pattern of left frontal memory-related responses was associated with an increased risk of aMCI. The findings pave the way for less invasive and more sensitive and accurate predictors of memory decline than current standard behavioral testing.

Novel Treatments

Could brain stimulation help patients slip out of a coma? It’s estimated that roughly 50 to 150 per 1 million comatose patients stay in a vegetative state beyond a few months. But new research offers hope for these patients (and their loved ones). Researchers have tested brain stimulation as a means to awaken coma patients, and their preliminary results show promise.

The findings, published in Brain Stimulation, focused on testing thalamic MR-guided low intensity focused ultrasound as an intervention on three comatose patients with minimal levels of consciousness. They found that the treatment is feasible and appears to be well-tolerated and safe, with no changes to vital parameters like blood pressure, heart rate, or blood oxygen levels. What’s more, two of the three patients exhibited measurable behavioral responses. After 1 week of exposure, one of the patients was able, for the first time, to respond to two distinct commands and provide a highly accurate rate of response to autobiographical questions. Following a second exposure, the patient was able to functionally use two different objects and functionally communicate. While these results are encouraging, the patient had regressed to their prior neurological state after a 6-month follow-up. Further research may prove brain stimulation as a viable way to improve conditions for those in a coma.

Possible treatment for rare genetic condition found in sperm. Researchers recently discovered a new and rare genetic condition that is caused by faulty protein synthesis and results in delayed development and learning difficulties. The condition is so new that it has yet to be named, and it’s not yet known how many people are affected by it. However, researchers may have found a solution: a compound originally isolated from human sperm.

Their study, published in Nature Communications, was conducted after a research team identified changes in a gene called eIF5A in several children with delayed development and learning difficulties. EIF5A helps ribosomes make “tricky” proteins, and researchers observed that the changes to the gene left the ribosomes with reduced capabilities. By conducting tests on yeast cells and zebrafish, however, they found that the disease could be potentially treated with a nutritional supplement called spermidine, which was originally isolated from human sperm. The compound is also found in foods like old cheese, mushrooms, soy products, legumes, corn, and whole grains.

FDA gives thumbs up to migraine neurostimulation tech. On the long road to finding effective treatment for migraines, NYC-based firm ShiraTronics may have taken a leap forward after receiving a Breakthrough Device designation from the FDA for its neurostimulation therapy for treating migraine headaches.

ShiraTronics, a spinout of Minneapolis-based medical-device maker NuXcel, aims to commercialize novel neuromodulation technologies—and the firm has had a good few years. It secured one of 2019’s largest venture capital raises in a $33 million Series A round, led by US Venture Partners, Amzak Health, and Strategic HealthCare Investment Partners. In 2020, the company raised an additional $3 million from Breakout Ventures. Now, with the help of the Breakthrough Device designation, the firm may be able to bring its vision to the marketplace post-haste. The new designation brings with it collaboration with the FDA. It can help certain products that treat life-threatening or disabling conditions progress through the approval process more quickly. ShiraTronics is moving swiftly—keep an eye out for the FDA’s final word on their tech.

Easy peasy neurostimulation tech for Parkinson’s. One of the rarely discussed side effects of Parkinson’s disease is neurogenic bladder, which includes symptoms like nocturia, increased frequency and urgency with or without incontinence, and a general decrease in bladder control. New research, however, may have found a way to alleviate some of these symptoms: percutaneous posterior tibial nerve stimulation (PTNS).

The study, published in Urology, examined the therapeutic effects of PTNS in the treatment of neurogenic lower urinary tract symptoms in patients with Parkinson’s disease. With a cohort of 76 patients, researchers looked at the effects of nerve stimulation administered at 14-day intervals for 3 months, 21-day intervals for 3 months, and 28-day intervals through 24 months. They found that daytime frequency decreased by 4.6 voids daily, urge incontinence decreased by 4.2 episodes daily, urgency episodes decreased by 6.2 episodes daily, nocturia decreased by 2.4 voids, and voided volume improved by a mean of 71.4 mL. The findings indicate that “touching a nerve” leads to significant improvements for both voiding and urodynamic parameters.

New in Patient Management

Country life comes with higher rates of stroke recurrence. The stroke mortality rate has declined thanks to improvements in intervention and better control over risk factors. But it’s not all good news, according to new research—particularly for those living outside of cities. A new study has found that stroke recurrence in rural American stroke patients increased significantly between 2014-2018.

The study, published in the Journal of Neurological Sciences, involved building a comprehensive stroke database called Geisinger NeuroScience Ischemic Stroke (GNSIS), which used clinical data from multiple sources, including electronic health records. With a cohort of 8,561 consecutive ischemic stroke patients, researchers found that despite a significant decrease in 1-year mortality rates over the past 15 years, there’s been an increasing trend in 1-year stroke recurrence. Significantly, this is most prevalent in those who live in rural areas, who have seen both higher mortality and a higher rate of stroke recurrence than those who live in cities. The research indicates that this is likely due to a higher prevalence of risk factors like diabetes and hyperlipidemia, which may be explained by the fact that people in rural areas are less likely to be screened for diabetes and less likely to achieve diabetes control. 

Dementia patients are more vulnerable to COVID-19. You might assume that those with dementia are more vulnerable during a pandemic, but recent research has uncovered just how serious their risk really is. The new study found that people with dementia are twice as likely to get COVID-19 and are far more likely to be hospitalized and die from it.

The study, published in Alzheimer’s and Dementia, used data from the electronic health records of 61.9 million people aged 18 years and older in the United States from February to August 2020. These data came from 360 hospitals and 317,000 health-care providers across all 50 states and represent roughly one-fifth of the American population. Researchers found that 810 out of 15,770 COVID-19 patients also had dementia. After adjusting for general demographic factors (age, sex and race) and risk factors specific to COVID-19 (ie, underlying conditions), they found that those with dementia were twice as likely to have contracted the disease compared with healthy individuals. Furthermore, the findings show that Black dementia patients are three times as likely to contract COVID-19, reflecting the already established racial disparity of who’s harmed the most during the pandemic. While it remains unclear specifically what it is about dementia that causes this increased risk, the researchers noted that their findings highlight the need to protect dementia patients while the pandemic rages on. 

Vitamins C and E consumption touted as a Parkinson’s disease prevention measure. We’re always toldt we should get more vitamins and minerals in our diet. Now, a new study has found a singular and compelling reason to ensure that your intake of vitamins C and E is up to par. Consumption of these vitamins may lower the risk of developing Parkinson’s disease.

The study, published in Neurology, sought to determine whether high-baseline dietary antioxidants and total nonenzymatic antioxidant capacity are associated with a lower risk of Parkinson’s disease. Using data from National Health Registries from 1997-2016, researchers looked at the vitamin and mineral intake of a cohort of 43,865 individuals aged 18-94 years. After an average follow-up time of 17.6 years, they detected 465 incident cases of Parkinson’s. They found that vitamins C and E appeared to be inversely associated with the risk of developing the disease. So now you have another reason to make sure citrus fruits and sunflower seeds make their way into your diet.

Epileptic kids need to brush up on their sleep hygiene. For growing children, a lack of sleep can result in negative impacts on mental health and general behavior. This bodes especially poorly for children with epilepsy, who are more likely to experience sleep disruptions like night terrors, sleepwalking, or sleep disordered breathing, according to a new review. 

The study, published in Sleep Medicine Reviews, was conducted by a team of researchers at the University of Birmingham Centre for Human Brain Health in the United Kingdom. Using 19 studies on sleep and epilepsy in children and adolescents, researchers compared 901 patients with epilepsy to 1,470 healthy children. They found that epileptic children slept an average of 34 fewer minutes per night. The findings also suggest that children with drug-resistant epilepsy are most vulnerable to sleep disturbances, although further research is necessary to determine whether this is linked to medication use or recurrent seizures. Because getting less sleep can increase the likelihood of seizures, researchers concluded that physicians should integrate sleep hygiene into epilepsy diagnosis and management.

Latest in Journal Summaries

Ticagrelor added to aspirin in acute ischemic stroke or TIA in prevention of disabling stroke.

New insight into protein structures that could treat Huntington’s disease.

Asymmetry in cortical and subcortical structures of the brain in children and adolescents with ADHD.

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Upcoming Medical Meetings

The following meeting is entirely virtual:

Atrium Health Sleep Symposium. March 3, 2021.

The following meeting is scheduled to have an in-person and virtual component:

American Academy of Neurology 73rd Annual Meeting (AAN 2021). San Francisco, CA. April 17-23, 2021.

The following meeting is scheduled to be entirely in-person:

2021 Congress of Neurological Surgeons (CNS) Annual Meeting. Austin, TX. October 16-20, 2021.

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