EEG can help ‘talk’ to unresponsive patients, women are being left out of TBI research, and a futuristic drug delivery method could break through the blood-brain barrier

It may sound like something straight out of a sci-fi novel, but we assure you this week’s news of a newly developed nanoparticle drug-delivery system is quite real. The creators suggest the innovation could be three times more effective at crossing the blood-brain barrier than conventional systems. We also have details on the efficacy of cannabidiol in treating TSC-associated seizures, the latest on how “junk DNA” may play a key role in the circadian rhythms of cells, and much more.

Neuro Flashback

In 1927, António Egas Moniz, a Portuguese neurologist, performed the first-ever cerebral arteriogram. The diagnostic test uses an x-ray of the intracranial blood vessels following the injection of radiopaque dye into the carotid artery to produce a cerebral angiogram. Physicians then use the resulting image to find blockages or other issues in the blood vessels of the head and neck, which can lead to strokes or aneurysms. While this might have been Moniz’s most useful medical contribution, he’s primarily remembered for winning the Nobel Prize in 1949 in recognition of his work introducing the prefrontal lobotomy as a treatment for certain psychoses and mental disorders.

In the News

Women fall through the research gap for traumatic brain injury. Gender and sex inequality rears its head in all kinds of areas that you wouldn’t expect, and a newly published analysis has illuminated a new one: Research on the effects of traumatic brain injury.

According to an analysis from a workshop convened by the National Institute of Neurological Disorders and Stroke in 2017, there is evidence that traumatic brain injury affects women differently than it affects men. But past studies have primarily been conducted on men, leaving gaps in the understanding of these differences. For example, there is evidence that head injuries which occur to women during the luteal phase of the menstrual cycle—when levels of progesterone are high—could be associated with worse outcomes and decreased quality of life. The authors of the analysis suggest that additional research is required to fully understand these differences, which would improve treatment options and outcomes for female patients.

Decades of research points to anticipated long-term effects of COVID-19. When facing a seemingly unprecedented situation like the ongoing COVID-19 pandemic, sometimes all you can do is look to the past and hope it offers insight into the future. In this vein, a recently published article in Alzheimer’s & Dementia cited decades of published scientific evidence to make a compelling case for SARS-CoV-2’s expected long-term effects on the brain and nervous system.

The article revisits events like the 1918 influenza pandemic, which was suspected to be the cause of subsequent cases of encephalitis lethargica and other brain disorders. Based on these historical examples—and an increasing understanding of SARS‐CoV‐2’s impact on the central nervous system—the authors conclude that there are key questions on the impact for risk of later-life cognitive decline, -Alzheimer disease, and other dementia, which should be answered as soon as possible. As such, they’ve proposed an enormous research project conducted by the Alzheimer’s Association and representatives from more than 30 countries, forming an international consortium to study the short- and long-term effects of COVID-19 on the central nervous system.

Nanoparticles could be the future of treatment delivery. In recent years, the identification of biological pathways that lead to neurodegenerative diseases has pushed scientists to develop molecular agents to target them. However, innovation has run up against a wall in the form of the blood-brain barrier (BBB). A team of bioengineers and physicians recently announced in Science Advances that they have created a nanoparticle platform that can facilitate therapeutically effective delivery of encapsulated agents in mice with a physically breached or intact BBB.

According to the team of bioengineers, physicians, and collaborators at Brigham and Women’s Hospital and Boston Children’s Hospital who created the system, it shows three times more accumulation in the brain than that of conventional methods of delivery. The system may open a world of possibilities for the treatment of various neurological disorders.

Ethnicity may dictate how we taste foods. Years ago, it was established that women tend to have a greater sensitivity to bitter flavors than men do. Now, new research suggests that ethnicity may also play a role in the extent to which a person experiences the bitter taste.

The research, published in Food Quality and Preference, looked at a cohort of roughly 150 individuals, half of whom were Chinese and half of whom were Danish. Researchers found that the majority of Chinese participants were more sensitive to bitter flavors compared to the Danish participants. The Chinese participants also tended to have more fungiform papillae, which contain taste buds and are located at the tip of the tongue, than Danish participants did, which may offer a reason why they experience tastes differently. The findings suggest that the Danish participants tended to prefer hard, chewy foods, whereas Chinese participants preferred softer foods. More research is required to discern why and how these differences arose, but researchers believe it’s related to food culture and the ways in which we learn how to eat from a young age.

Neuro Trivia

How much cerebrospinal fluid (CSF) does an adult produce?

The average adult produces about 1 pint of CSF daily.

Novel Diagnostics

MR quantitative susceptibility mapping could help to discern ALS. Several diseases can result in symptoms that mimic those of amyotrophic lateral sclerosis (ALS), making the condition tricky to diagnose. But a new study appears to have found a solution: MR quantitative susceptibility mapping.

The study, published in Clinical Imaging, compared motor cortex susceptibility along with the hand and face homunculi in ALS patients and in patients with similar clinical presentations in a blind, retrospective study of MRIs with quantitative susceptibility mapping (QSM) from 2015-2018. Fifty ALS patients, 35 mimic patients, and 70 non-motor neuron symptom patients were included in the study. Researchers found that hand and face homunculi mean susceptibility values were significantly greater in those with ALS vs the other groups. In fact, Youden’s index showed 100% specificity and 36% sensitivity for hand homunculus measurements in discriminating ALS from mimics. Researchers concluded that QSM has diagnostic potential in the assessment of suspected ALS patients, indicating very high specificity in discriminating ALS from mimic diagnoses.

Noninvasive retinal imaging as a Parkinson’s biomarker? As the old saying goes, the eyes are the window to the soul. But they also may be the window to detecting changes associated with Parkinson’s disease (PD). A new study has found that noninvasive retinal imaging parameters could be biomarkers for diagnosing Parkinson’s disease.

The study, published in JAMA Ophthalmology, sought to establish whether noninvasive retinal imaging parameters from optical coherence tomography angiography and enhanced depth imaging optical coherence tomography could be used to detect structural changes associated with PD and potentially serve as a new biomarker for the disease. After looking at the eyes of 69 participants with PD and 137 healthy control participants, researchers found that individuals with PD had decreased retinal vessel and perfusion densities, increased total choroidal area and choroid luminal area, and decreased choroidal vascularity index compared with age- and sex-matched control patients. The findings suggest that this noninvasive technique could help to quickly and comfortably determine whether a patient requires further examination for PD.

Blood in feces may indicate stroke on the horizon. Occult blood in feces is typically used as an indicator of colorectal cancer. But a new nationwide population study has found that it is also associated with an increased risk of ischemic stroke and myocardial infarction.

The study, published in The Journal of the American Heart Association, used data from the National Health Insurance database to assess the possible clinical utility of a fecal immunochemical test (FIT) for patients suffering from cardiovascular diseases — specifically ischemic stroke and myocardial infarction. Using records from more than 6 million patients, researchers found that a higher risk of ischemic stroke was observed in the FIT‐positive population, as was a raised risk of MI and increased all‐cause death. The study’s authors concluded that more clinical information may be afforded by occult blood in feces beyond its well‐known conventional role in CRC screening.

Computer simulation could help standardize ADHD diagnoses. Most mental health disorders are still diagnosed and treated based on interviews, questionnaires, and cognitive tests. But researchers at Ohio State University have found that computational models could provide an additional objective tool, which could help to assess the severity and complexity of a patient’s behavioral issues more accurately.

The researchers analyzed 50 studies that looked at cognitive tests for ADHD. Children with ADHD tended to take a longer time to make decisions while performing tasks than other children, and these tests are typically based on average response times to certain tasks. The researchers of the study concluded that neurocognitive testing lacks evidence-based standards, due to the differences in tasks and performance measures. As such, they suggested that sequential sampling models could be used as an objective tool to improve the general understanding of differences and similarities between various ADHD endophenotypes and frequently co-occurring diagnoses.

Novel Treatments

New tool could help unconscious patients “talk” to doctors. Unresponsive patients, like those who’ve suffered a severe brain injury, often present a challenge for doctors. But research conducted by a team at the University of Birmingham has shown that electroencephalography (EEG), a noninvasive technique used to record electrical signals in the brain, could be used to provide an accurate prognosis.

The research was published in Annals of Neurology. The study included 28 patients with acute traumatic brain injury, all of whom were unresponsive. Researchers played the patients’ streams of isochronous monosyllabic words that built meaningful phrases and sentences, while monitoring and recording their brain activity via electroencephalography. What they found was that, in healthy individuals, the EEG activity only synchronized with the rhythm of phrases and sentences when listeners consciously comprehended the speech. As such, the method can be used to measure residual speech comprehension, which could assist physicians in making effective treatment decisions.

CBD may help to treat TSC seizures. As research into the medicinal properties of cannabis continues, scientists are squashing—and elevating—the many claims that have cropped up around cannabis over the years. And the results of one recent study suggest that the long-held belief that cannabidiol can help treat some seizures may hold water.

The new study, published in JAMA Neurology, looked at the impact of CBD as an additional treatment for seizures associated with tuberous sclerosis complex (TSC). The randomized clinical trial saw 224 patients with TSC given either cannabidiol (in doses of either 25 or 50 mg/kg/day) or a matched placebo over the course of roughly 4 months. Researchers found that the CBD doses resulted in a roughly 50% reduction in TSC seizures, compared to a 27% reduction for the placebo. They also found that the 25-mg CBD dose led to fewer adverse events than the 50-mg dose. The results suggest that CBD could be an effective treatment for TSC-induced seizures.

“Junk DNA” plays a role in regulating circadian rhythms. For decades, scientists have been working to figure out how DNA plays a role in humans’ circadian rhythms, and how that might affect the development of certain diseases like Alzheimer, cancer, and diabetes. Now, a new study has found that a genome-wide regulatory layer made up of small chains of noncoding nucleotides known as microRNAs (miRNAs) are key to modulating circadian rhythms.

Formerly known as “junk DNA,” miRNAs affect gene expression by preventing messenger RNA from making proteins. The new research saw a team of scientists conducting the first cell-based, genome-wide screening to identify which miRNAs had an impact on the circadian rhythm cells; in the process, they discovered that 110 to 120 miRNAs did just that. Subsequently, the researchers conducted further tests on mice to see if deactivating miRNAs made any difference in behavior. One of the tests resulted in an interference with a mouse’s wheel-running behavior in the dark compared with control mice. The research also suggests that the way the miRNAs regulate the circadian clock is tissue-specific, which suggests that this could be a route to treating or preventing specific diseases.

Neuroblasts and NK cells: Key to aging. Aging leads to the deterioration and shutting down of organs, but scientists still don’t entirely understand the neural mechanisms and environmental factors that impact the speed of these processes. Recently published research, however, is beginning to shed light on how these mechanisms work

As part of a new study, published in Nature Neuroscience, researchers set out to identify the reason these immune cells accumulate in the brain during the aging process, and to what extent these cells impact tissue regeneration and cognition. Using single-cell sequencing, lineage tracing and flow cytometry techniques to measure immune cell properties, researchers found that the deterioration of neuroblasts (which are the embryonic cells from which nerve fibers originate) in aging brains prompts an increase in the toxicity of natural killer (NK) cells. NK cells are a type of blood cell that are part of the immune system. Researchers concluded that the accumulation of these toxic cells ultimately leads to impairments in neurogenesis and cognition. The research could lead to the development of more effective treatment strategies for preventing cognitive decline in the elderly.

New in Patient Management

Analysis shows opioid treatment for migraine decreasing. Treating migraines can be a tricky business, but one thing has become increasingly clear: It’s best to limit the use of addictive opioid painkillers as much as possible. Fortunately, according to a recent analysis, physicians in emergency departments (EDs) across the country are doing just that.

The analysis, which was published in The American Journal of Emergency Medicine, looked at data from the 2010 to 2017 National Hospital Ambulatory Medical Care Survey and found a number of interesting trends. Among those trends, opioid administration for migraine in EDs across the United States decreased 10% annually during the study period, which shows improved adherence to migraine guidelines recommending against opioids. However, the analysis also identified several risk factors for unnecessary opioid administration in the ED setting. These include female sex, older age, White race, higher pain score, and having Medicare or private insurance as the primary expected source of payment.

Possible new treatment for dystonic hand tremor. The symptoms of the neurological movement, disorder dystonia, can be debilitating, but a new study may have illuminated a possible new treatment for controlling tremors in the upper body: Botulinum neurotoxin injections.

The study, published in JAMA Neurology, was a placebo-controlled, parallel-group randomized clinical trial involving 30 patients with upper-extremity dystonic tremors. Participants received either electromyographically guided intramuscular injections of botulinum neurotoxin into the tremulous muscles of the upper extremity, or a placebo. They were then monitored over the course of 3 months. Researchers found that the patients receiving botulinum neurotoxin injections experienced a mean difference of 10.9 units on the Fahn-Tolosa-Marin Tremor Rating Scale, compared to the placebo group, by the end of the trial. Researchers also noted that injections did not result in any unacceptable hand weakness or other adverse effects, suggesting that botulinum neurotoxin injections may be a feasible treatment for tremors.

Research finds genetic answer to questions surrounding lithium. Lithium is often held as the gold standard for treating bipolar disorder, but 70% of patients don’t respond to it. Researchers at the Salk Institute may have discovered why: decreased activation of a gene called LEF1.

The new study, published in Molecular Psychology, indicates that a lack of activity from this particular gene disrupts normal neuronal function and promotes hyperexcitability in brain cells, which is a hallmark of bipolar disorder. Researchers looked for specific targets of lithium resistance and found that the activity of Wnt/β-catenin signaling pathway was severely affected, and the expression of LEF1 was minimal. Because lithium targets this signaling pathway, researchers hypothesized that the inactivity of LEF1 could be the cause for lithium resistance. As such, they tested valproic acid, a drug used to treat bipolar disorder, and found that it upregulated LEF1 and Wnt/β-catenin gene targets and reduced excitability in the neurons of patients. The results suggest that LEF1 could be a useful target in developing new drugs to treat bipolar disorder.

Brain health boost from keeping arteries loose. In the hunt to find more ways to prevent cognitive decline in the elderly, one group of scientists has found a new possible strategy: Prevent arterial stiffening. That posit comes after the publication of research indicating that faster rates of aortic stiffening in mid-to-late life were associated with greater levels of brain deterioration.

The study, published in PLoS Medicine, saw researchers looking at a cohort from a decades-long ongoing study. During a 4-year follow-up, 542 participants with no clinical diagnosis of dementia and no gross brain structural abnormalities received a multimodal 3T brain MRI scan and cognitive tests. Over the study period, researchers found that rates of aortic stiffening were associated with poor brain white matter microstructural integrity and reduced cerebral perfusion, leading them to conclude that strategies to prevent arterial stiffening may offer cognitive benefit in older age.

Latest in Journal Summaries

Diagnostic value of olfactory dysfunction in a population screened for COVID-19.

Dynamic prevalence of sleep disorders following stroke or TIA.

Risk factors for residual headache in CVT.

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Upcoming Medical Meetings

The following meetings are entirely virtual:

14th Annual UCLA Sleep Medicine Virtual Course. January 23, 2021.

Mayo Clinic Multiple Sclerosis and Autoimmune Neurology Update 2021 – Livestream. February 5-6, 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.

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