Neuro symptoms mask COVID-19, a red wine ingredient lowers dementia risk, and a mysterious new neurological disorder makes headlines
As COVID-19 moves through the country and quarantine orders ramp up, it may seem like there’s not much to look forward to. But, there is some positive news coming out of the world of neuroscience: researchers are making breakthrough discoveries and developing new treatments and diagnostics at a quick pace.
Only 4 years ago, in 2016, the WHO published its updated classification of brain tumors. For the first time, brain tumor types were defined according to their integrated histological and molecular parameters. This was a break with the century-old principle of diagnosis based entirely on microscopy. In their update, the WHO noted: “It is hoped that this additional objectivity will yield more biologically homogeneous and narrowly defined diagnostic entities than in prior classifications, which in turn should lead to greater diagnostic accuracy as well as improved patient management and more accurate determinations of prognosis and treatment response.”
In the News
A neuro-COVID-19 link? “Look for poorly-defined neurologic conditions in patients with coronavirus,” Italian researchers from University of Brescia warned. Due to the large number of acute neurology patients testing positive for COVID-19 at the university, they’ve opened a new neuro-COVID-19 unit to separate those with acute neurologic events in whom signs of coronavirus are absent, according to an article in NeurologyToday.
Patients battling the virus who also present with stroke, delirium, epileptic seizures, and non-specific neurologic syndromes that resemble encephalitis are being treated there. But, clinicians are not sure whether these neurologic syndromes are directly caused by COVID-19 entering the CNS or whether they’re an indirect response to the “viral storm” caused by COVID-19. So, they’re warning neurologists to watch for any acute neurologic complaints in patients presenting with symptoms of COVID-19. .
Brescia’s Alessandro Pezzini, MD, associate professor of neurology, warns that there are changes in presentation in the neurologic patients they are treating: they observed that there have been dramatic increases in vascular events, ischemic strokes, and thrombosis. This may be due to COVID-19 affecting coagulating mechanisms within the body. He urged investigation of the link between COVID-19 and neurological symptoms, especially in light of the fact that any added burden to the CNS leads to worse outcomes.
Strange bedfellows. Is there a connection between age-related macular degeneration (AMD) and Alzheimer disease (AD) and Parkinson disease (PD)? Results from a retrospective study conducted in Korea show that there is. Researchers studied over 300,000 patients aged ≥ 50 years from the Korean National Health Insurance Service Cohort. They found that, compared with patients without AMD, those with it had a ~48% increased risk of developing AD and a ~46% increased risk of developing PD. What’s surprising was that the association of AMD with AD and PD was higher in those who were younger than 70 years old. Researchers are working on finding out what the possible shared underlying pathophysiology may be.
New Neuro disorder. How new is it? This new brain disorder is so new that it hasn’t even been named yet. A team of investigators, led by Australian researchers from the Murdoch Children’s Research Institute, found a gene variation they described as a “severe infantile-onset neurodegenerative condition with intracranial calcification.” The infants all experienced normal or mild developmental delays, with an onset of seizures during their first year of life. After the seizures, all children underwent severe, progressive developmental regression.
Researchers performed genomic testing in six children with a similar degenerative condition, all of whom were from four families with a particular gene variant: NRROS, a protein coding gene.
To manifest, the as-yet-unnamed disorder requires two copies of the defective gene. What this means is that—for the child to inherit the disorder—each parent had to be a carrier of one altered copy of NNROS. And lo and behold, researchers identified the same gene variant in three children of the same ethnic background. The families were not directly related, but were perhaps distantly related, with common ancestors from the same town.
Food for thought? Good news for healthy eaters: Flavonoids can reduce white matter hyperintensity volumes, a marker that’s strongly associated with Alzheimer disease (AD) and related dementias. The more flavonoids you eat, the lower your risk!
To get to this conclusion, researchers assessed brain health via several MRI parameters—including total brain tissue volume, white matter hyperintensities volume, and hippocampal volume—in relation to dietary flavonoid intake in stroke-free participants from the Framingham Heart Study Offspring Cohort. Those in the highest quartile of flavonoid intake had significantly smaller white matter hyperintensity volumes than those in the lowest quartile. Less lesions equals better brain health!
Researchers also found similar trends for the intake of flavan-3-ols and flavonoid polymers. Some good sources of flavonoids are citrus fruits and their juices, berries, red wine, apples, legumes, and tea. More evidence that a glass of red wine with dinner is good for you! And so is that apple with lunch! Bon appétit!
What is agnosia?
Agnosia is the inability to identify an object using one of more of the senses. Although agnosia can involve all of the senses, it usually affects only one. It’s caused by damage to, or degeneration of, the areas of the brain that integrate perception, memory, and identification. This damage can be caused by trauma, tumors, infracts, or abscesses, while degeneration may be caused by neurological conditions like Alzheimer or Parkinson diseases. The diagnosis is clinical and can include neuropsychological testing, with brain imaging with CT or MRI to identify the cause.
Myocardial marker multitasking? Could high-sensitivity cardiac troponin be a risk marker for stroke? It seems it may, according to results from a new meta-analysis. Silver lining: This biomarker is already highly sensitive for showing myocardial injury, and testing is already readily available (and used) in most hospitals.
Researchers analyzed 17 studies with nearly 100,000 participants and found that high-sensitivity cardiac troponin is a risk marker for incident stroke in various subgroups. In the general population, high levels of high-sensitivity cardiac troponin had a 1.25 HR for the risk of incident stroke compared with low levels over an average follow-up of 1 to 20 years. This increased to 1.58 when categorical data were used. And, in patients with atrial fibrillation, the pooled adjusted HR for incident stroke was even higher—1.95 for high vs low levels. Unfortunately, researchers couldn’t determine the risk in patients with previous stroke due to lack of data. Although more studies are needed, it’s encouraging to know that such an easy-to-assess marker may help us predict the risks of incident strokes.
It’s not all in your head. Could acupuncture be a viable option for patients with migraine? According to the results of a recent study, it may very well be. People who have frequent migraines don’t have a lot of preventive options, and many don’t respond well to the ones they do have.
To that end, researchers in China compared the efficacy of manual acupuncture with placebo or usual care in 147 patients (mean age: 37 years) with a history of migraine without aura. Over 8 weeks, patients were randomized to either 20 sessions of manual acupuncture at true acupuncture points, 20 sessions of non-penetrating placebo acupuncture at non-acupuncture points, or usual care (lifestyle and self-management advice). At weeks 13–20, patients who had manual acupuncture had a bigger reduction in migraine days and in migraine attacks compared with placebo. And, all without any severe adverse effects. This added up to 1.4 fewer migraine days at weeks 13–16 and week 21. But—oddly enough—compared with the usual care group, those in the “fake” acupuncture group (placebo) also had fewer migraine days and migraine attacks.
Although the effects were modest, this is encouraging for the nearly 90% of migraineurs who have no options for effective prophylactic treatments. Researchers called for longer studies but concluded that acupuncture “can be recommended as a prophylactic treatment” and that physicians should give patients information about acupuncture when discussing prophylactic treatments. They believe that their results take acupuncture from an unproven complementary medicine option to an “acceptable evidence-based treatment.”
As safe as aspirin. For the first time, researchers have evaluated the safety of the novel oral anticoagulant dabigatran for acute stroke. In DATAS II—a phase 2, prospective, randomized, open-label, blinded endpoint trial—they randomized 305 patients with noncardioembolic stroke or transient ischemic attack (TIA) to treatment with either dabigatran or aspirin within 42 hours of symptom onset. MRIs were performed at baseline and again at day 30, and the primary endpoint of the study was symptomatic hemorrhagic transformation (HT) within 37 days. None of the patients developed symptomatic HT, but 7.8% of patients treated with dabigatran developed asymptomatic petechial HT compared with 3.5% of those treated with aspirin.
The good news is that, upon MRI at day 30, researchers found incident covert infarct in only 6.3% of patients treated with dabigatran and 9.8% of those treated with aspirin.. They also found that patients’ baseline infarct volumes were predictive of incident HT. So, the safety of dabigatran after ischemic stroke or TIA is comparable to that of aspirin. A little peace of mind for clinicians who might be weighing the risk/benefit ratios of continuing anticoagulative treatment after stroke.
New hope for the smallest patients. There’s good news for those helping children with neurofibromatosis type 1 (NF1): easing outcomes and improving life for these kids may now be possible with selumetinib. This drug—which received FDA break-through designation in 2019—blocks the MEK protein, which is part of the RAS signaling pathway—which is in overdrive in patients with NF1 and leads to tumor growth. According to results of this phase 2 study, selumetinib shrank inoperable plexiform neurofibromas in pediatric patients with NF1. Not only that, it also reduced pain and improved patients’ functioning and quality of life.
Researchers from the NIH’s Center for Cancer Research at the National Cancer Institute studied 50 children (3-17 years old) who took selumetinib twice daily in 28-day cycles continuously. They assessed the patients at least every four cycles, using a very different approach tailored to each child’s specific tumor-related symptoms. Results were spectacular, with 70% of participants having a confirmed partial response (20% or more volumetric tumor shrinkage). Most maintained the response for over 1 year. Even better, after 1 year of treatment, it was reported that the children had lower pain levels and clinically meaningful improvements in their daily function, overall quality of life, strength, and range of motion.
To researchers, this was the most exciting result—they happily found that some patients who had been living with chronic debilitating pain could even stop taking pain meds! But, five participants stopped treatment due to side effects, and six had disease progression. These patients have no effective medical treatment options, and while selumetinib is not a cure, it effectively shrank tumors and provided the children with better quality of life. Check, check, and check!
New in Patient Management
Myelin breakthrough. Take everything you ever knew about myelin and throw it out the window! Traditionally, myelin was believed to be metabolically inert. But, researchers from the University of Texas MD Anderson Cancer Center found that myelin is actually dynamic. This is due to its lipid components. They found that mature myelin lipids undergo rapid turnover and need quaking, an RNA-binding protein, to perform normally. In mouse models, depletion of quaking causes rapid demyelination and gradual neurologic deficits.
So, here’s where it gets even more exciting. They discovered that quaking works with PPAR-beta and RXR-alpha—both nuclear receptors—to modulate the transcription of lipid metabolism genes. (Nuclear receptors have a vital role in embryonic development and adult homeostasis.) And voila! A new approach to treating demyelination is born.
Treating mice with quaking depletions with PPAR-beta or RXR-alpha agonists mitigated neurologic disability and extended survival. Plus, in further studies, the researchers found that some lesions from patients with primary progressive multiple sclerosis were characterized by the downregulation of activities needed for proper lipid metabolism that were associated with quaking and PPAR-beta/RXR-alpha. Ergo, continuous production of lipid is vital for maintaining mature myelin.
Low-dose aspirin falls short. For once, aspirin does not come to the rescue. Researchers found that an aspirin a day does not reduce the risk of symptoms caused by mild cognitive impairment or Alzheimer disease (AD) and does not slow rates of cognitive decline. Previously, researchers hypothesized that, because aspirin has heart benefits, it also may have brain benefits and may reduce the risk of dementia by reducing inflammation, minimizing small clots, or preventing atherosclerotic narrowing the blood vessels in the brain.
So, a group of Australian researchers studied nearly 20,000 people without dementia or heart disease, most of whom were aged 70 years or older. In their randomized, placebo-controlled trial, patients were randomized to treatment with low-dose aspirin (100 mg/d) or placebo and received treatment for 4.7 years. Researchers found no differences in the risk of developing mild cognitive impairment, dementia, or probable AD between patients in the aspirin and placebo groups. They also found no differences in the rate of cognitive changes over time. Maybe, they said, their subjects were too healthy, and maybe follow-up just wasn’t long enough to show the benefits of aspirin. The researchers plan to continue following these patients.
A new way to monitor MS. There aren’t a lot of options to monitor patients with multiple sclerosis (MS), so accurately assessing the extent of MS-disability and disease progression has always been hard. Right now, clinicians monitor disease progression in these patients with clinical exams, done periodically. But, a new device may offer a “smarter,” easier approach. An international team of scientists have come up with a new tool that can gather all sorts of data on subtle movement changes to give a better picture of MS progression.
Made of all sorts of doodads and gadgets, this device combines sensors like accelerometers, gyroscopes, and surface electromyography that’ve been repurposed from their commercial uses. These multisensors gather lots of data, all from a small band worn on the forearm or calf. Patients with MS simply have to do 20 finger taps on each hand, and 20 foot taps on each foot (this should take no longer than 5 minutes), and the data are collected and wirelessly downloaded to a computer in real-time. Not only is this a quick process, even better is that the device can be used by anyone—not just clinicians, but by medical assistants or research coordinators, too.
Better time to thrombectomy. Time is of the essence in stroke, so it is discouraging to know that less than 20% of Americans have quick and easy access to endovascular thrombectomy (EVT), according to researchers from the University of Texas Health Science Center at Houston. This is vital because stroke is a leading cause of death and long-term disabilities. In their study, they found that only 19.8% of American have access to an EVT-capable stroke center within 15 minutes of them by ambulance. And, only 30% have access to a such a center within 30 minutes.
Researchers also evaluated two different strategies to optimize access to EVT: the flipping and the bypassing models. The flipping model would convert a certain percentage of hospitals within a geographic area with the capacity to perform EVT, while the bypassing model took patients straight to EVT-capable hospitals, passing hospitals that can’t. The bypassing model was easier and more cost-effective, and improved patient access by 16.7%, giving about 51.7 million more Americans access.
This is the first time researchers have done a comprehensive assessment of patient access to thrombectomy. A few states have already implemented legislation for bypassing hospitals without EVT capability. The researchers noted that more trained neuro-interventionalists and hospitals capable of thrombectomy would also help increase access.
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Upcoming Medical Meetings
Please note that, in the interests of containing the current COVID-19 pandemic, the following conferences have been cancelled. Please contact these organizations for details and specifics on refunds and rescheduling:
World of Neurosurgery: American Association of Neurological Surgeons (AANS) 2020 Annual Scientific Meeting, in Boston, MA, April 25-29, 2020.
American Academy of Neurology 71st Annual Meeting (AAN 2020), in Toronto, ON, Canada, April 25-May 1, 2020.
Headache Medicine Symposium, in Wauwatosa, WI, April 17, 2020.