COVID-19’s dangerous impact on the brain, smartphones hindering drug response, good news in epilepsy, stroke and more
With the worsening of the COVID-19 pandemic, all eyes are on the ramifications of the virus. Even in the neurological field, researchers have uncovered a link between COVID-19 and CNS damage. But there’s much more in neuro to be discovered this week. For example, smartphone use—we’re all guilty—may be linked to headaches that just won’t go away. And researchers have discovered a new, experimental agent that just may be the ticket to treating TBI and other brain injuries. Read on to find out the details of all these and more research happenings in this week’s NeuroBrief!
In 1837—nearly 200 years ago—Jan Evangelista Purkynĕ, a Czech anatomist and physiologist, discovered Purkinje cells, large neurons found in the cerebellum. Also called Purkinje neurons, these cells are located in all vertebrate animals in the cerebellar cortex. Their cell bodies are flask-like in shape, with many fingerlike extensions—dendrites—emerging from them. The dendrites receive impulses from other neurons. Purkinje cells release the neurotransmitter GABA, which can inhibit neuronal action and reduce the transmission of nerve impulses. In this way, Purkinje cells regulate and coordinate motor movements. (For more on Purkinje cells, see “In the News.”)
In the News
COVID-19 and the CNS. It seems that coronavirus (COVID-19) keeps getting more dangerous, or rather, we keep discovering just how dangerous it really is. Recently, doctors in China discovered that infection can damage the CNS. The doctors presented the case of a 56-year-old male with severe symptoms who failed to respond to regular treatment. In the ICU, the patient developed symptoms associated with decreased consciousness, despite having no abnormal CT signs. The medical staff performed gene sequencing on CSF samples, confirmed the presence of COVID-19, and diagnosed encephalitis in the patient. Upon receiving treatment for viral encephalitis, the patient’s neurological symptoms gradually dissipated. Director of the ICU at Beijing Ditan Hospital, Xinhua, and attending doctor, Lin Kungyuan, advised that once patients have presented with symptoms of impaired consciousness, the possibility of nervous system infections should be considered, and CSF testing performed. The results were published on XinhuaNET.
Ready. Aim. Fire. Researchers have discovered that deep brain stimulation (DBS) delivered to the cerebellum may be more effective for the treatment of tremor, a common muscle disorder associated with neurological diseases such as Parkinson disease, ataxia, and dystonia. This breakthrough was made thanks to the discovery that Purkinje cells (located in the cerebellum) may trigger and produce tremor signals.
Previous research suggested that defective Purkinje cells may contribute to the generation of tremor. In this study, researchers genetically deleted the ability of Purkinje cells to communicate with other cells in mouse models, expecting tremors to occur. But, to their delight, no tremors occurred. This means that that Purkinje cell activity, instead of its loss, is important in causing tremor. They also found that, at normal state, Purkinje cell signaling to other cells was pretty regular. But, during tremors, the signals came out in bursts. They realized that these signal bursts triggered tremors. To test this theory, the researchers used optogenetics (using bursts of light to control brain activity), to generate signals in bursts. And voila—tremors!
So, they concluded that the cerebellum could be involved in many different types of tremor disorders. These days, DBS is used in patients with tremors that don’t respond to drugs, and it’s usually directed to the thalamus. With this discovery, the researchers have found a new target.
Stroke stats. Although no news is good news, as the saying goes, there is some good news for stroke patients. In the past 15 years, the risk of death after stroke has fallen significantly—by 24%. Researchers looked at data from patients in south London who suffered ischemic stroke. One-year mortality rates fell from 32.6% in 2000 to 20.15% in 2015. Similarly, the risk of disability after stroke fell by 23%, from 34.7% in 2000 to 26.7% in 2015.
The researchers noted that improved care and treatment are to thank for these drops. Specifically, researchers pointed to higher hospital admission rates, more CT and MRI scans, and increased use of thrombolytic and anticoagulative treatment in the acute phase of stroke. Improved public health could’ve also played a role, they said. Whatever the cause, the outcomes are positive!
To the rescue. B cells may be more important to recovery after stroke than we thought. In fact, researchers have found out that these little guys—that play such an important role in the immune system—actually have a broader reach in the brain, especially in helping it recover after a stroke.
After an ischemic stroke, B cells—which produce neurotrophins that regulate the development and growth of neurons—are dispatched to the site of the stroke to help with repairs. But, researchers just found—in mouse models—that B cells may also be sent out to many other areas of the brain, including those that support motor and cognitive recovery. They also saw that in mice with depleted B cells, recovery in these areas was reduced. Their results could lead to a better understanding of the immune processes that help with stroke recovery, and maybe even new therapeutic targets.
How many pain receptors are in the brain?
Zero. Zip. Zilch. Nada. None. That’s why brain surgery can be done without the brain technically feeling any pain. The meninges, the periosteum, the scalp, and the accompanying vasculature all have pain receptors. But—once you get past those—the brain becomes a pain-free zone! Hard to believe, but true!
Hey, helmet head! Easier brain scanning? Let’s have it. Researchers have come up with a way to make magnetoencephalography (MEG)—try saying that ten times without getting tongue tied—even easier by developing it into a wearable device. MEG—already noninvasive, if a little cumbersome—is typically used to locate sources of epilepsy and to study brain development, Alzheimer disease, and stroke. But, it’s not the most convenient testing around. Patients have to sit under a rigid, helmet-like dome for long periods. To help with this, the NIH has just given Sandia National laboratories a grant to build a prototype of their MEG device that would be more comfortable, more accessible, and perhaps even more accurate. The new system, according to Sandia representatives, will come in the form of a wearable device that will give patients the freedom to relax and move into comfortable positions during testing. Even better: It’s expected to be more accurate, especially in children, because it will fit closer to the head. They’re eliminating the need for liquid helium and, instead, will be using alternative sensor technology that works at room temps. Buh-bye, rigid helmet.
The new system, based on a type of quantum sensor, is called an optically pumped magnetometer (OPM), and can pinpoint brain signals with the same accuracy as the traditional superconducted-based MEGs. The OPM sensors zap rubidium gas with a laser, turning it into atomic magnets, which spin in a magnetic field. There’s a second laser that measures the changes in these spinning clouds of atomic magnets to locate magnetic fields outside of the head that are made by electrical currents in the brain. Pretty amazing, and hopefully, much more convenient for patients.
A better biomarker. It turns out that CSF phospho-tau isoform pT217 trumps pT181 as a biomarker for the differential diagnosis of Alzheimer disease (AD). Using quantitative mass spectrometry, researchers analyzed both pT217 and pT181 in a cohort of patients with probable AD, other neurologic disorders, and normal controls. Results were checked against a second cohort of cognitively normal participants, patients with mild cognitive impairments, and those with AD, classified according to amyloid status based on PiB-PET imaging. Increased CSF pT217 levels were highly specific in identifying both preclinical and advanced AD, more so than pT181. They were also correlated with PiB-PET data. Thus, researchers concluded that pT217 may be a great help in improving the diagnosis of AD and could be a potential target for future therapies.
Head-to-head fight. Two treatment options for multiple sclerosis (MS) were compared for the first time. Researchers of an observational study (the GATE study) compared fingolimod with natalizumab as second-line therapy for patients with relapsing-remitting multiple sclerosis (RRMS). Fingolimod is an immunomodulating agent, used primarily for treating MS. Natalizumab is a humanized monoclonal antibody used to treat MS and Crohn disease. This is the first head-to-head comparison of the two, and fingolimod seems to have won. After 12 months of treatment in 388 patients with RRMS, researchers found that while both fingolimod and natalizumab reduced annualized relapse rates, reductions with fingolimod were significantly higher. Adherence to treatment with fingolimod was also higher. And the winner is—fingolimod!
Too bad, TBI. Researchers may have stumbled upon a potential new treatment for traumatic brain injury (TBI) and possibly other brain injuries. Previous researchers have shown that after moderate or severe TBI, microglia activation increases and may be correlated with neurologic deficits in these patients. In fact, overactive microglia have been shown to cause neurotoxic inflammation.
Based on this, researchers conducted a new proof-of-concept study. One month after mice suffered TBI, researchers gave them an experimental drug (a CSF-1R inhibitor) for 1 week. The drug depleted over 95% of microglia. What’s exciting is that this was all done a pretty long time after the injury occurred. Within several weeks, the overactive microglia regenerated and became more like normal microglia, with fewer inflammatory features. Mice treated with the experimental drug also recovered significantly better than controls, with less tissue and neuronal loss, and significantly better motor and cognitive performance. Talk about killing two birds with one stone: Not only did they find a potential new therapeutic option, they also found evidence to suggest that inflammation plays a vital role in chronic debilitation caused by brain injury.
New Tx for Dravet syndrome. Adjunctive treatment with fenfluramine may be an effective new treatment option for patients with Dravet syndrome who have frequent seizures despite treatment with a regimen that includes stiripentol. In a double-blind, placebo-controlled, parallel-group randomized study, researchers found that adding oral fenfluramine (0.4 mg/kg/d, to a maximum of 17 mg/d) reduced mean monthly convulsive seizures by 54.0% more than placebo alone in these patients. What’s more, patients treated with fenfluramine had clinically meaningful (≥ 50%) and profound (≥ 75%) reductions in monthly convulsive seizure frequency than patients treated with placebo. The most common adverse events included decreased appetite, pyrexia, fatigue, and diarrhea. Even better? No patients developed valvular heart disease or pulmonary hypertension.
New in Patient Management
Slow going. Bad news for patients with sports-related concussions. After 2 weeks, most will not have recovered completely. Researchers, in fact, have found that recovery from sports-related mild traumatic brain injuries (mTBIs) may be slower than what current guidelines state, and that < 50% of patients have recovered 2 weeks later.
Current perceptions are that most people with sports-related mTBIs recover within 10 to 14 days. To test this, researchers analyzed recovery time in 594 patients (average age: 20 years; 77% male) with sports-related mTBI over 2 years. They saw patients, on average, 8 days after injury, and re-evaluated them at 14 days and then every 2 weeks until clinical recovery—which was defined by symptom scores, resolution of abnormalities, and exercise tolerance. At 14 days, symptoms resolved in only 45% of patients. Hold the bus because this is in direct contrast to current guidelines from the Concussion in Sport Group (CISG) consensus statement, which state that 80% to 90% of sports-related concussions resolve within 7 to 10 days.
At 4 weeks, the clinical recovery rate jumped to 77%, and at 8 weeks, to 96%. Time to recovery was similar across age groups, also in contrast to CISG and other statements that symptoms take longer to resolve in kids. Longer recovery times were seen in female athletes, patients with a history of migraine or mental health issues, and those who waited longer before their initial clinic visit. All in all, it’s something to keep in mind when your sports-playing patients present with concussions.
Such a headache! Headache is the most common symptom linked with smartphone use. But, is there an association between using your smartphone and having a bad headache that just won’t go away? Researchers sure seem to think so. They found that people with headaches who use smartphones take more pain meds and get less relief compared with those who don’t use smartphones. Coincidence? Probably not.
This might seem like a small issue, but there’s no doubt that constant headaches can be debilitating and at times may even interfere with day-to-day activities. What’s more, chronic use of pain relievers, such as NSAIDs, can also cause adverse effects, including renal function impairment, increased risk of bleeding, stomach upset, and worsening of gastric ulcers.
For their study, researchers included 400 people with migraines, tension, and other headache types who were divided in their use or non-use of smartphones (206 users, 194 non-users). Frequency of headaches, severity, and duration did not differ between the groups. But smartphone users were more likely to take pain meds for their headaches compared with non-users (96% vs 81%, respectively), and they also took more pills—an average of eight pills per month vs five pills per month in non-users. Despite taking more pills, smartphone users had less response (84% achieving moderate or complete relief of headache pain vs 94%, respectively). Why this happens is not yet clear, but could be anything, noted the researchers—like neck position, phone lighting, eye strain, or the stress of always being connected. No one yet knows, but researchers are concerned enough to have further studies planned. In the meantime, take a break from your phone, especially if you have a headache!
Antidiabetics and ALS. Does treatment with antidiabetics or statins lower the risk of amyotrophic lateral sclerosis (ALS)? A recent study suggests that it may be antidiabetics. There is the suspicion that medications used to treat metabolic disorders may be associated with ALS. So, researchers did a population-based, nested case-control study in 2,475 Swedish participants with ALS. They analyzed data on filled prescriptions for antidiabetics and statins in patients in the years before ALS diagnosis and found an inverse association between antidiabetic use and ALS. Patients with ALS were less likely to have been prescribed an antidiabetic compared with controls. Researchers didn’t find an association between statin use and ALS risk overall, although there was a positive association in women. They say that this may be because patients with ALS were more likely to receive a first prescription of statins in the year before their ALS diagnosis compared with controls. So, can antidiabetics lower ALS risks? More studies are needed, but the results look promising.
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Upcoming Medical Meetings
Please note that, in the interests of containing the current COVID-19 pandemic, the following meetings 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.
The following conference will be held as scheduled:
The 24th Annual Children’s Neuroscience Symposium, in Phoenix, AZ, March 20-21, 2020, has not yet been cancelled. Please check website for up-to-the-minute information.