More neuro effects of COVID-19, a diet for your brain, and the dangers of a common drug
Although the COVID-19 pandemic has monopolized medical and national news for months, there’s also a lot of neurological news to catch up on. There’s so much researchers are finding out about the brain itself—the lifestyle and environmental factors that affect it, the diagnostics that shed light on its more mysterious functions, and the treatments that are most effective.
A tale of two personalities. Nearly 175 years ago, Phineas Gage had an accident that would make him one of the most famous names in neuroscience. Gage, a foreman for the Rutland and Burlington Railroad, was working to clear black rock near Cavendish, VT, where he would sprinkle gunpowder into blasting holes, tamping it down—gently—with an iron rod. The gunpowder would then be covered with sand or clay to confine the blast to a small space. On September 13, 1848, Gage was distracted while tamping gunpowder with his specially made iron rod—which weighed 13.25 lb, measured 3’7”, and had a diameter of 1.25 inches. A spark flew, ignited the gunpowder, and sent the tamping iron into Gage’s skull, point first. It struck below his left cheekbone, passed behind his left eye, ripped into his brain’s left frontal lobe, and blew through the top of his skull, before exiting near the midline behind the hairline.
Miraculously, Gage survived. Unfortunately, he transformed from a conscientious, clean-cut foreman into a “dirty, scary, sociopathic drifter.” His case brought a greater understanding of the brain to both the scientific and general communities, as it was the first to suggest a link between trauma to the brain and changes in personality.
In the News
The neurology–COVID-19 link. Clinicians are discovering that COVID-19 has definite effects on the brain, with as many as one-third of patients hospitalized with COVID-19 manifesting neurologic symptoms. Researchers in China did a retrospective study involving 214 consecutive hospitalized patients (mean age: 52.7 years; 40.7% male) with SARS-CoV-2 infection. Of these, 126 had non-severe infection and 88 had severe infection. Overall, 36.4% of patients had neurologic manifestations, which increased to 45.5% among those with severe infection. What’s more, these symptoms were more common in patients with severe disease, and included acute cerebrovascular diseases (5.7%), impaired consciousness (14.8%), and skeletal muscle injury (19.3%). Their findings led the authors to conclude: “During the epidemic period of COVID-19, when seeing patients with these neurologic manifestations, clinicians should consider SARS-CoV-2 infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and prevention of transmission.” Something to consider when treating patients.
Changing your mind? Apparently, being in space for a long time changes your brain, which is very bad news for astronauts. Researchers did MRI scans of 11 astronauts the day after they returned from an extended visit in space. They found significant changes in brain volume in the form of more white-matter volume, and also observed changes to cerebrospinal fluid (CSF) flow, in elevated CSF velocities through the cerebral aqueduct. What’s worse, these changes persisted up to 1 year into recovery, which suggests, according to the researchers, that the astronauts’ brains were permanently changed. As if that weren’t bad enough, the pituitary glands of these astronauts were also significantly smaller.
Previous research has shown optical abnormalities in the eyes and brains of astronauts. Plus, astronauts can also have narrowing of CSF spaces and the central sulcus, loss of gray-matter volume, and prolonged changes in CSF circulation. A possible explanation could be that, when in microgravity, bodily fluids no longer pool towards the lower extremities but towards the head. This might explain some of the ocular and neurologic changes researchers are documenting.
But, it’s not all bad. These changes, however disturbing they sound, are not considered problematic in normal, healthy adults. Researchers hope that better understanding of the effects of microgravity and why it causes the ventricles to enlarge in astronauts will lead to more effective treatment options for patients with normal pressure hydrocephalus and related conditions. Until then, there’s something to be said for gravity!
Better food, better brain. Yeah, we all know how healthy the Mediterranean diet is. But, did we know that it can help you think? In results that solidify the Mediterranean diet as one of the best diets in the world, researchers have found that it is associated with higher cognitive function. Using data from two large ophthalmology studies, the Age-Related Eye Disease Study (AREDS) and AREDS2, researchers explored the effects of nine components of the Mediterranean diet on cognition in roughly 8,000 participants. In AREDS, they tested cognitive function at 5 years, and in AREDS2, at 2, 4, and 10 years. And guess what? Those who had the highest adherence to a Mediterranean diet had the lowest risk of cognitive impairment, and diets high in fish and vegetables gave the greatest protection. At 10 years, AREDS2 participants with the highest fish consumption demonstrated the slowest rates of cognitive decline. Their results seem to say—you are what you eat! Remember: Good food, good brain.
Right brain vs left brain. Researchers have been studying brain asymmetry for decades, trying to figure out what causes it. They may have finally gotten their answer: epigenetic differences. Let’s see how. Through epigenetic regulation, the brain can switch certain genes on the left and right sides of the brain either “on” or “off.” And while each brain cell has the same genes, each side of the brain is epigenetically different. And, researchers found, it’s these differences that cause differences in gene activity inside each of these cells. Cells can be “off” in the left hemisphere or “on” in the right hemisphere. For example, epigenetic abnormalities or differences on one side of the brain could make the cells on that side more susceptible to the apoptosis typical in Parkinson disease (PD). So, one side of the brain has more cell death and displays the hallmark symptoms of PD—like tremor—first. This may explain why neurological disorders like PD often affect one side of the body first. So, now we know: Both sides of the brain were not created equal!
On the front lines of COVID-19. Front-line healthcare workers battling COVID-19 are developing de novo headaches associated with personal protective equipment (PPE) and/or worsening of any pre-existing headache disorders. For this cross-sectional study, researchers in Singapore enrolled 158 healthcare professionals working in high-risk hospital areas during COVID-19. It’s almost unbelievable that a full 81.0% of them reported de novo PPE-associated headaches. And, de novo PPE-associated headaches were independently associated with a pre-existing primary headache diagnosis (present in almost one-third of patients) and combined PPE use for more than 4 hours per day. Researchers also found that workers based in the emergency department had a higher average daily duration of combined PPE exposure compared with those who worked in isolation wards. So, how did these headaches impact these individuals? Healthcare professionals reported that they experienced slightly decreased work performance due to these headaches. The frequency and severity of these headaches and how they affect work performance could worsen if the COVID-19 outbreak continues. Researchers suggested that shorter duty shifts and shorter duration of PPE use help keep healthcare professionals at their best.
How much blood flows through the brain per minute?
Every minute of every day, 750-1,000 mL of blood—equivalent to the volume of 3 full soda cans—flow through the brain. Somehow, this is not surprising, considering that the brain needs about 20% of the body’s oxygen—and that about 20% of the blood flowing from the heart is pumped to the brain. The brain needs this heavy, constant blood flow to keep up with the demands of its neurons. How else could neurologists churn out all of these studies?
Ultra-fast SCAPE microscopy. A new, ultra-fast, 3D imaging technique—Swept Confocally Aligned Planar Excitation (SCAPE) microscopy—allows for better visualization of the nervous system by monitoring thousands of single neurons in real time. SCAPE microscopy was developed through the NIH’s Brain Research through Advancing Innovative Technologies (BRAIN) Initiative, and it allows for high-volume tissue viewing in a way that doesn’t damage surrounding cells, with high speed visualization in 3-D.
Using SCAPE microscopy, researchers were able to see, for the first time, how the mouse olfactory epithelium responds to complex odors. They discovered that these nerve cells could play a bigger role in interpreting smells than previously thought. The loss of smell is an early symptom of several neurological disorders, including Alzheimer disease and Parkinson disease, as well as other systemic diseases and even COVID-19. Understanding changes that lead to these losses may help in the early diagnosis of these disease, before they go on to cause more debilitating symptoms. Here’s to faster and better imaging!
AI diagnostics. Researchers have developed an AI-based system that mimics how radiologists interpret images from brain MRI exams. It can give readings comparable to those from neuroradiologists in the diagnosis of 19 common and rare diseases.
Here’s how: The AI system uses a combo of approaches—deep learning-based detection of brain lesions, analysis of clinical and quantitative features of the image, and Bayesian networks for a differential diagnosis. The system is made up of a convolutional neural network that detects lesions based on abnormal FLAIR signals from the MRI scans and image processing techniques that generate a human-interpretable quantitative image and lesion features. When researchers tested it, the system consistently outperformed general radiologists and trainees, and achieved results comparable to those of neuroradiologists. The system is still a long way away from being available, and more analysis is needed. But, it’s potential in helping radiologists and neurologists diagnose a multitude of diseases is undeniable.
Open sesame! Could ultrasound help deliver disease-targeting drugs to patients with Alzheimer disease (AD)? You bet it can!Researchers, for the first time, studied the use of focused ultrasound plus microbubble treatment in brain cells derived from patients with AD.
Until now, studies of this technique—developed by researchers at the Queensland Brain Institute—were limited to preclinical models. Now, in a study involving human cells, researchers found that this ultrasound/microbubble combination creates openings in the blood-brain barrier (BBB), which has long been an unsurmountable hurdle in delivering some drugs and therapies that target brain diseases. Here’s how they did it: Lipid microbubbles were injected in the brain endothelial cells from people with a family history of AD. The cells were targeted with ultrasound, which caused them to contract and expand, disrupting the cellular connections and opening the BBB. Ta-da! What the treatment did was actually weaken the connections between the actual BBB cells themselves, which may allow brain tissue to absorb drug treatments. Amazing what a few bubbles can do, no?
Preserving the brain. An investigational drug—1-[(4-Nitrophenyl)sulfonyl]-4-phenylpiperazine (NSPP)—may decrease cognitive decline in patients who undergo partial or whole brain irradiation, all without promoting the growth of tumors. Scientists at the UCLA Center for Medical Countermeasures Against Radiation identified NSPP in 2019, and it’s already been shown to prevent acute radiation syndrome in mice. In this recent study in a mouse model of glioblastoma, researchers found that NSPP lessened the normal tissue toxicity caused by radiation, thereby increasing the number of neural stem and progenitor cells when given 24 hours after exposure to a dose of radiation. NSPP also inhibited the activation of microglia and interleukin-6 expression. And, even better, upon behavioral testing of the mice, they found that NSPP also mitigated radiation-induced declines in memory function. More positives: NSPP was not toxic to normal cells and did not lessen the effects of radiation on the growth of tumor cells. Wouldn’t it be great to have this neuroprotective drug in your holster for your glioblastoma patients?
Pulsed relief. Although their study was small, researchers found that over 50% of patients with refractory chronic cluster headache responded to treatment with pulsed radiofrequency (PRF) of the sphenopalatine ganglion. What is PRF, you ask? It’s the use of short bursts of radiofrequency current, delivered twice per second, followed by a quiet phase with no current. It’s different than non-pulsed or continuous radiofrequency ablation and has been used as an alternative to it for the treatment of some chronic pain syndromes. And, it seems that the higher the dose, the better. Most patients treated with ˃ 45 V responded compared with those treated with only 45 V (63.6% vs 33.3%, respectively). Strangely, 35.7% of patients experienced post-procedural side effects. Larger studies are needed, but here’s to hoping that PRF becomes a safe, minimally invasive and effective strategy in these patients.
New in Patient Management
Botulinum toxin B better for sialorrhea? RimabotulinumtoxinB—in doses of 2,500 and 3,500 U—is effective and safe, according to results from a recent study. Sialorrhea affects up to 74% of patients with Parkinson disease, and is considered one of the most bothersome nonmotor symptoms of the disease. It can also affect up to 50% of patients with amyotrophic lateral sclerosis, and is common in stroke survivors as well. Sialorrhea is now typically treated with oral antimuscarinic drugs, but these are problematic and can cause dry mouth and systemic anticholinergic effects.
For the phase 3, randomized, parallel, double-blind, placebo-controlled MYSTICOL study, researchers included 176 patients with a minimum unstimulated salivary flow rate (USFR) of 0.2 g/min and a minimum Drooling Frequency and Severity Scale score of 4. By the fourth week, both doses of rimabotulinumtoxinB significantly reduced USFR compared with placebo and improved Clinical Global Impression of Change scores. What’s more, benefits occurred as early as 1 week after injection and were maintained over approximately 13 weeks. Also good news is that the injections were well tolerated, and the most common side effects were self-limited mild-to-moderate dry mouth, dysphagia, and dental caries.
Hold the heartburn meds. The news about using proton pump inhibitors (PPIs) continues to get worse. In this analysis of the risk of death associated with PPI use in patients with dementia, researchers included 28,428 patients with dementia and two sex-, age-, and residence-matched controls for each. They determined the cumulative defined daily doses of PPIs for each. What they found was not good—a PPI exposure of 100 defined daily doses in the 12 months before study initiation was associated with an increased mortality in both dementia patients and matched controls. Although the risk was significantly lower in dementia patients, it was still significantly increased. What’s more, the mortality risk was highest in both dementia patients and controls in the first 2 years after the index date of the study. Just something to think about before prescribing PPIs to your patients.
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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 meeting has been changed to a virtual workshop:
14th Annual Drug Discovery for Neurodegeneration Workshop , in Philadelphia, PA, April 26-28, 2020, has been changed to a virtual workshop that will be hosted online.
The following meeting has been rescheduled:
American Spinal Injury Association (ASIA) 2020 Annual Scientific Meeting, to be held in in New Orleans, LA, May 3-7, 2020, has now been rescheduled for October 4-7, 2020, and will remain in New Orleans, LA.