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A brain-computer interface (BCI), developed by a company tied with Elon Musk, offers an innovative new technology to move the field forward. But independent experts said some of the claims about what that technology can potentially do are somewhat hyperbolic at this stage. Other efforts around BCI are also featured.

It's going to blow your mind, said Elon Musk, the billionaire founder and CEO of Tesla, SpaceX and Neuralink. Speaking via a webcast on August 28, Musk introduced the latest developments, or at least made the latest claims, regarding Neuralink's brain-computer interface (BCI), a computer-based system that measures and analyzes brain activity and then converts signals into commands that are relayed to output devices that carry out the desired action.

The US Food and Drug Administration (FDA), he announced, had given the company a Breakthrough Devices Designation, and good progress, he said, was being made toward clinical trials.

As evidence of that progress, Musk presented what he called the Little Pigs demo. Three pigs in the webcast looked equally healthy, but one of them had been implanted with a device that was wirelessly transmitting neural spikes from the snout area of its brain as it rooted around in a pen.

There's a lot of function that this device could do related to monitoring your health and warning you about a possible heart attack or stroke, and convenience features like playing music, Musk said. It's sort of like if your phone went in your brain.

He predicted that, one day, you will be able to save and replay memories...Over time we could actually give someone super vision. You could have ultraviolet or infrared, or seeing radar, and actually have superhuman vision.

Alas, none of those capabilities has ever been demonstrated by Musk's company or, for that matter, by any scientist or company. Neurologists and neuroscientists who have been laboring in the field for over a decade seek not to endow healthy humans with superpowers, but to help people with neurodegenerative diseases, strokes or traumatic injuries to regain speech and motor functions. Despite that disconnect, however, leaders in the field told Neurology Today that they are impressed by the legitimate progress Neuralink appears to have made.

The company's implantable device, they say, is doing things that none of their own devices have yet achieved: It communicates to a nearby computer wirelessly, rather than through wires; its low-powered battery, also recharges wirelessly, lasts up to a day; it bristles with over a thousand electrodes, compared to a few hundred in traditional arrays; and rather than attaching those electrodes to inflexible shanks, the Neuralink device uses flexible threads so delicate they are implanted by a robotic sewing machine.

If indeed they have made a device that can detect a thousand channels with good fidelity, and it can scan through this wireless technology, that is an important development, said Karunesh Ganguly, MD, PhD, associate professor of neurology at the University of California, San Francisco. At some point, you want to see it peer reviewed to know that what they're identifying as a neuron is actually a neuron. But they do seem to be pushing the technology ahead.

More evidence of progress in the BCI field came with a September 7 report by Dr. Ganguly's group in Nature Biotechnology. Unlike other approaches for invasive BCIs, his plug and play system based on electrocorticography (ECoG) has permitted an individual with tetraplegia to maintain control of a computer cursor without daily recalibration and retraining.

While he and other scientists in the BCI field expressed some skepticism about some of the claims made by Neurolink and Musk, they told Neurology Today they appreciate the interest that Neuralink is bringing to the field.

It will be really important, as these technologies become available, hopefully over the next few years, for neurologists to become familiar with how BCI can help the patients they see in their daily practice, said Leigh Hochberg, MD, PhD, FAAN, professor of engineering at Brown University, senior lecturer in neurology at Harvard Medical School, and director of the Center for Neurotechnology and Neurorecovery at Massachusetts General Hospital.

As a neurologist, I am completely focused on developing and testing technology that will help patients I see who have paralyzing disorders to maintain or regain their ability to move and speak.

Companies like Neuralink, he said, are essential to achieving that goal.

At the end of the day, neither universities nor academic medical centers make the final marketed and supported medical devices that become available to patients outside of clinical trials, Dr. Hochberg said. That is always done by a company. The engagement of companies in this field will ultimately benefit our patients.

Although Neuralink has not published a description of its technology in peer-reviewed scientific literature, and neither Musk nor any of the scientists working for him responded to requests for interviews, some detailed descriptions have appeared on the preprint server bioRxiv.

In March of 2019, Philip Sabes, PhD, of the University of California, San Francisco (and a founding team leader at Neuralink) was the lead author of a paper describing the sewing machine his group had developed with funding by the Defense Advanced Research Projects Agency (DARPA).

The fixed, rigid metal arrays used since the 1950s to penetrate the brain, the paper noted, disturbs the vasculature and attracts immune cells. Thinner, more flexible probes, however, would not be stiff enough to insert into the brain directly. Dr. Sabes' solution was to design a system that works like a sewing machine, with stiff needle-like injectors that implant polymer probes with the aid of a neurosurgical robot.

Each of the system's 96 polymer threads, the paper stated, holds 32 electrodes, for a total of 3,072 electrodes. We developed miniaturized custom electronics that allow us to stream full broadband electrophysiology data simultaneously from all these electrodes. We packaged this system for long-term implantation and developed custom online spike detection software that can detect action potentials with low latency.

Five months later, in August of 2019, Musk was listed as the first author of another preprint on bioRxiv that described Sabes' sewing machine as part of Neuralink's BCI platform. We have built arrays of small and flexible electrode threads, Musk's paper stated, with as many as 3,072 electrodes per array distributed across 96 threads.

As described by Musk in his webcast in August, implantation of the company's device will require removal of what he called a coin-sized piece of skull by its robot. Then the device replaces the portion of skull that we removed.

Technological advances already made and anticipated from the Neuralink effort are remarkable and will serve the neuroengineering community well, Lee E. Miller, PhD, Distinguished Professor of Neuroscience at the Feinberg School of Medicine of Northwestern University, said. This scale of private investment of financial and intellectual effort is unprecedented in our field. He added, however, that the company needs to demonstrate that its device is doing what it claims to be doing.

They showed these rasters of brain activity on the webcast, with cool bloopy sounds, he said. For peer review, I would insist on seeing the actual signals they recorded. Although there is no reason to believe it to be the case, they could be recording movement artifacts.

My hunch is that it will not be as expensive as deep brain stimulation for Parkinson's disease, which costs tens of thousands of dollars. But it's going to be more expensive than, say, LASEK surgery.

DR. LEE MILLER

When I was first approached about working on brain-machine interfaces, I thought, This is crazy. But we went farther than we could have reasonably hoped to do. That's why I'm not completely closed to the wildest claims Musk makes. It's not insane that maybe one day we can replay memories.

DR. SLIMAN BENSMAIA

Dr. Miller also took issue with Musk's prediction that a BCI device could eventually cost as little as a few thousand dollars. That's not going to happen any time soon, Dr. Miller said. My hunch is that it will not be as expensive as deep brain stimulation for Parkinson's disease, which costs tens of thousands of dollars. But it's going to be more expensive than, say, LASEK surgery.

He also disagreed with Musk's over-the-top claims about recording and replaying memories.

There's a lot of science in the realm of memory, he said, including Wilder Penfield's decades-old work that appeared to show existing memories being triggered by electrical stimulation of the brain's temporal lobes during neurosurgery.

That's a far cry, however, from suggesting it would ever be possible to record from a particular memory and play it back, Dr. Miller continued. While short-term, working memory very likely is based on reverberating neural activity and amenable to the intriguing hippocampus memory prosthesis that Ted Berger has been working on, long-term memories almost certainly require protein synthesis and structural changes to neurons that couldn't even be recorded, let alone played back. That's pure science fiction, and to suggest otherwise sets up all sorts of false expectations.

Sliman Bensmaia, PhD, the James and Karen Frank Family Professor of Organismal Biology and Anatomy at the University of Chicago, runs a laboratory there devoted to research in somatosensory neuroscience and prosthetics. Earlier this year, before COVID-19 restrictions began, he visited the Neuralink offices and gave a talk.

There's a team of really great people working there, and the device they have come up with is really remarkable, Dr. Bensmaia said. The device that I work with, that almost everyone works with, the only device that has been used in humans so far, is the Utah array, made of metal microelectrodes. It's like a mini bed of nails that you press into the brain. Of course the brain doesn't like that, and the electrodes don't last. So the fact that Neuralink has these thin, flexible fibers should cause much less damage. And they have a lot more electrical contacts. The question is how robust and stable it will be. Will it last for decades? But it's pretty cool. It's way further along now than it was just six months ago when I visited them.

Despite all that, Dr. Bensmaia added, Then there is Musk and the way he talks about it. Some of the stuff he says is outrageous. It might be possible to achieve some of the things he's talking about one day, but it won't happen for a very long time.

Even so, he said, the progress made in the field in recent years is already beyond anything he thought possible in such a short time.

I participated in DARPA's Revolutionizing Prosthetics program, he said. When I was first approached about working on brain-machine interfaces, I thought, This is crazy. But we went farther than we could have reasonably hoped to do. That's why I'm not completely closed to the wildest claims Musk makes. It's not insane that maybe one day we can replay memories.

In fact, a 2018 paper published in the Journal of Neural Engineering described a study involving epilepsy patients with surgically implanted electrodes near the hippocampus whose electrical spikes were recorded and analyzed while they performed a memorization task. When scientists stimulated the CA1 region by playing back the sequence of neural firing made when the subjects correctly remembered a preliminary set of memorizing tasks, their performance on subsequent memorization tasks improved by 35 percent.)

Dr. Hochberg leads the BrainGate consortium, which includes researchers from Massachusetts General Hospital, Brown University, the Providence VA Medical Center, Stanford University and Case Western Reserve.

Over the past few years, in our published research, the participants in our trial who had very little or no movement of their arm or hand have been able to control an unmodified tablet computer for email, for texting, for controlling their music players, Dr. Hochberg said.

I used to say it would take decades before a BCI is available to people outside of research trials that could offer a true clinical benefit. I now think we are just a few years away. Right now these systems often require the oversight or engagement of a trained technician to start the system and calibrate it at the beginning of each day. We need it to work 24 hours a day, seven days a week, in the absence of any technical oversight. On all those merits, we are on track to achieve that goal with a flexible, powerful and reliable system.

Because Mass General has a clinical research support agreement with Neuralink, Dr. Hochberg said he should not speak specifically about the company. But, he said, I'm excited by the entrants of multiple companies to the BCI field. The engagement of companies will ultimately benefit our patients who have neurological disease or injury.

As for those neurologists who remain leery of a field in which companies like Neuralink are publishing accounts of apparent gains in preprints posted without peer review, a University of Toronto fellow said, essentially, this is a sign of things to come in this burgeoning world of technology.

What we are seeing is a shift to Silicon Valley-style neurotechnology companies that attract venture capital and a lot of talent quickly, said Graeme Moffat, PhD, a former managing editor of Frontiers in Neuroscience who now also runs a company developing non-invasive brain imaging devices.

The pace of iteration in fields that adopt this approachseveral new electronics designs every year and regular software updatesis too fast for journal review cycles. We'll see papers on the long term effects of new BCIs on the brain, but the peer-reviewed scholarly literature is just unsuited to reflecting the rapid innovation in devices like those that Neuralink is building.

Dr. Ganguly has received a one-time consulting fee from Lightside Medical, a medical incubator company. Dr. Stavisky is a scientific advisor to Vorso Corporation and Broad Mind Inc. and has equity in both companies. Dr. Angle owns stock and is employed by Paradromics. Drs. Miller, Bensmaia, and Moffat had no disclosures.

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By Stephanie Cajigal October 8, 2020

Two neurologists contennd that stroke disparities are only partially explained by differences in the prevalence of traditional stroke risk factors between Black and White patients. They discuss the framework for understanding the effects of racism on stroke risk and where the field needs to go from here.

Black Americans are twice as likely to have a stroke and 40 percent more likely to die from one as compared with White Americans, according to the Centers for Disease Control and Prevention. Although decades of research have highlighted racial stroke disparities, there is a dearth of evidence on why they exist.

Now two prominent stroke neurologists are calling on the field to investigate how racism may impact vascular health. In an opinion article published online on August 21st in JAMA Neurology, Bruce Ovbiagele, MD, FAAN, and Olajide A. Williams, MD, note that stroke disparities are only partially explained by differences in the prevalence of traditional stroke risk factors between Black and White patients.

Dr. Ovbiagele, professor of neurology at the University of California San Francisco Weill Institute for Neurosciences, and Dr. Williams, professor and chief of staff of the department of neurology at the Columbia University Vagelos College of Physicians and Surgeons, recently spoke with Neurology Today about a framework for understanding the effects of racism on stroke risk and where the field needs to go from here.

Dr. Ovbiagele: While stroke disparities have been well documented, we haven't fully resolved what all the explanations or solutions are. This is an issue that has been pervasive for five decades. As you saw from the article, we can only explain about half of what seems to be contributing to Black-White disparity in terms of stroke outcomes.

Dr. Williams: I think the nation is sensitized, the world is sensitized, given the events of George Floyd in addition to the devastating disparities that were illuminated by COVID-19. Bruce and I have been working within the world of health disparities for decades, but it's amazing just how few Americans understand the severity of these disparities and how they impact all of us. I think COVID really showed the interconnectedness of all of us in society, whether you are the cleaning person going into a patient's room, or whether you are the physician walking into it, or a nurse, or a nursing aide. If one of those people in that chain has COVID, everyone is at risk. It shows we have to take care of the least among us. We thought we should take advantage of this moment by expanding the knowledge of the academic community on this topic.

Dr. Williams: Institutionalized racism is the codification of discrimination and bias into the structures of societies. These structural biases are driven by individual-level biases. For example, if I put a group of biased individuals on the governance committee of a particular organization, those individuals will translate their bias into policies and procedures. And then there is internalized racism, which is the effect of chronic racism on an individual. Chronic discrimination, chronic dehumanization, chronic marginalization causes the individual on the receiving end to ask, what is my worth? Before you know it, that individual will start internalizing the worth that society has placed on him. Once you internalize racism, it can be self-destructive.

What happens across these different levels is the systematic denial of opportunities such as access to health care. There is also the denial of diversity within health care by discriminating against people of color seeking admission into the medical field. This was highlighted by the Flexner Report [on medical education in the United States and Canada, originally published in 2010].

So structurally, you're being denied access, denied opportunities, and denied the ability to improve diversity within medicine. Personally, you're experiencing daily discrimination. Bruce and I included the Everyday Discrimination Scale in our paper to highlight the daily injustices experienced by people of color as a result of personally mediated racism. That in itself can be quite traumatic; it can generate anxiety, it can generate chronic stress responses, which in turn can lead to higher levels of inflammation, hypertension, etc. Couple that with decreased access to get these things fixed; couple that with decreased motivation to get these things addressed because you don't value yourself. Now you're dealing with a perfect storm that may lead to strokes and earlier mortality among people of color.

Dr. Ovbiagele: What we do know is that on the surface, at least, there are clearly differences in the timeliness and appropriateness of care that is delivered to Black people either at risk for stroke or who have experienced stroke. Can you categorically say that is due to racism? It is very hard to say. But that is what we are trying to call people to look into. If we don't have clear evidence pointing in one direction, it would be hard to design interventions or solutions to address it.

Dr. Williams: The 2013 Institute of Medicine report, Unequal Treatment, reviewed examples of implicit biases in medicine and showed quite tangibly that due to implicit bias, Black individuals may not receive the same level of pain treatment as White individuals. They showed that Black individuals may not get appropriate referrals for cardiac catherization compared to White individuals. We need much more rigorous research into this area in order to best determine where our resources should be focused.

Dr. Ovbiagele: Specifically, for stroke, as noted in the American Stroke Association Racial-Ethnic Disparities in Stroke Care statement in 2011. Black individuals have longer waiting times in the emergency department and are less likely to receive tPA or carotid revascularization procedures than White individuals.

Dr. Williams: I think the vascular effects of racism need to be better studied. For example, we now know the effects of rumination on blood pressure. We know that among people who are exposed to a racist eventsuch as when police pull someone over, grab him/her out of their car, and handcuff that person because he/she is Blackblood pressure surges due to the acute stress response at that moment. But these events are not isolated experiences, and so the cycle repeats itself. Moreover, the events are also replayed in your mind in the form of recurrent nightmares, the post-traumatic stress disorder of that experience. So not only is the experience continuing to happen in the real world, you're also being assaulted by the memory of the experience over and over again. All this causes vascular effects and inflammatory responses.

Dr. Ovbiagele: We need more representation of people of color but especially African-Americans in trials... I think we need to incorporate measures of discrimination and racism into trials as well. I would like to see those as endpoints in trials. I think those are the things that could be done almost immediately, and it would be wonderful to get the NIH to encourage that. I think grooming more researchers of all stripes; it doesn't have to be just people of color, who are interested in health inequities, to consider studying the issue of racism, would also be very important. We need more training programs to help people develop their careers in stroke disparities research. We need all hands-on deck if we are actually going to successfully tackle this issue.

Dr. Williams: There aren't enough Black neurologists, certainly not enough Black stroke neurologists to do the volume of work required. Because this is a societal problem, it's critically important for us to mobilize not just people of color, but allies who feel passionate about this injustice to join hands and help with the research and solutions.

Dr. Ovbiagele: Advocacy with nongovernmental organizations, professional organizations like the American Academy of Neurology, the American Neurological Association, the American Stroke Association, as well as major funders like the NIH. And, also not to just make this an American issue...this is a call to motivate a global cohort of people to address potentially racism-contributing stroke disparities in their countries.

Dr. Williams: There have been many acts of racism in medicine against the Black community, such as [the Tuskegee Study of Untreated Syphilis in the Negro Male] that have really drowned the confidence that people of color have with the health care system. They need truth and reconciliation. They need to be told that it's not in their minds; it's not in their heads. This is real, and it happened, and it is still happening. There needs to be acknowledgment before there is that recovery.

Dr. Williams: It all begins with the individual. I would say, listen, learn, and become an ally.

Dr. Ovbiagele: Undergo implicit bias and cultural sensitivity awareness training. Look at your own practice and routinely examine whether there are racial differences in care and outcomes among the stroke patients you see and address them. Lend your voice to support studies and programs aiming to eliminate this prominent and long-standing health disparity in our country. In Forecasting the Future of Stroke in the United States (Stroke. 2013;44:2361-2375), it's been projected that racial/ethnic disparities in stroke will likely worsen with time, without new concerted efforts, so there is no time like the present to strongly address this issue.

Drs. Williams and Ovbiagele reported no relevant disclosures.

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Two new research studies focus on the neurologic issues that present in patients with COVID-19: One proposes that the disease that starts in the respiratory tract brings on coagulopathy and stroke risk, while the other asserts that, so far, the neurologic effects of the virus does not appear to involve direct invasion of the central nervous system.

Two new studies attempt to bring into focus neurological issues that present in patients with COVID-19: One proposes that the disease that starts in the respiratory tract brings on coagulopathy and stroke risk, and another asserts that, so far, the virus' neurologic effects do not appear to involve direct invasion of the central nervous system (CNS).

The studies represent two of the latest publications in the expanding literature on the virus and its neurological manifestations, which reflect an updated understanding that COVID-19 is not merely a respiratory phenomenon.

In an August 10 online report in the Journal of Neuroimaging, the authors proposed a cascade of events they say could be taking place in COVID-19 patients after the virus escapes the respiratory system and gets into the bloodstream, a process they say points to the potential for specific modes of therapy tailored to different steps in the cascade.

The authorstwo of whom are associated with a company that has developed a tool that, once approved, could be used to treat the type of patients they describesay that after the virus enters the alveolus of the lung, it causes inflammation that damages the thin membrane between the alveolus and the adjacent lung capillary, or the blood-air barrier.

Then a potentially disastrous string of events begins, first with the development of endothelial dysfunction. This happens, they say, in one of two ways: Either the virus enters endothelial cells directly, or damaging angiotensin II accumulates because their usual docks, angiotensin-converting enzyme 2 (ACE2) receptors, become occupied by the virus, which has a high affinity for the receptors. The angiotensin II leads to oxidative stress and oxidation of the typically circular Beta2glycoprotein1 (B2GP1) but becomes unwound into a J shape.

At that point, the authors posit, there is an opening on B2GP1 for antiphospholipid antibody complexes, associated with thrombotic tendencies, to form. The lack of non-oxidized B2GP1 to competitively bind von Willebrand Factor leads to platelet adhesion and platelet attachment to sub-endothelial collagen, and then to platelet activation and aggregation in the setting of the thrombosis-friendly antiphospholipid antibodies. In the worst cases, the resulting clots lead to pulmonary emboli or stroke from large vessel occlusion.

Vallabh Janardhan, MD, the paper's lead author and a stroke and interventional neurologist at the Medical Center of Plano, said that a proper understanding of the process points to opportunities to intervene therapeuticallywith antiplatelet, antithrombotic, and antifibrinolytic therapy, and if necessary, with clot-removal devices.

In some cases, you don't have all day to dissolve the clothalf the brain will die, he said. So you need to go pull out the clot with clot-removal devices and initiate blood thinners, so it doesn't re-clot.

With his brother Vikram Janardhan, he co-founded Insera Therapeutics, which has developed a clot-removal system using intermittent or cyclicalrather than continuoussuction designed to be gentler on the vessel and for better removal of clots.

We believe, yes, there was a lot of attention towards ventilators early onthat's because we didn't connect the dots at that time, Vikram Janardhan said. Now that we're connecting the dots, there are other therapeutics that are a better fit in reducing mortality than an exclusive concern on the number of ventilators.

Insera's device is approved in Europe but not the United States and is not yet commercially launched.

We fully anticipate and hope the vaccines will be out and available before our therapy is ready worldwide, Vikram Janardhan said.

The other paper, which was published in the August 19 issue of Cell, conveys the broad scope of the neurological manifestations seen in COVID-19 patients.

Neurological abnormalities have been described in 30 percent of patients. But the most frequent neurological problemsespecially malaise, dizziness, and headachetend to be confined to non-specific abnormalities in patients experiencing mild COVID-19, said lead author Constantino Iadecola, MD, director of the Feil Family Brain and Mind Research Institute at Weill Cornell. Among those with more severe diseases requiring hospitalization, neurological manifestations are more severewith ischemic stroke and encephalopathy, for example, Dr. Iadecola said.

While serious neurological complications have been reported in patients with otherwise mild COVID-19, the most severe complications occur in critically ill patients and are associated with significantly higher mortality, he said.

COVID-19 is a much more aggressive disease, he said, noting that to date, no convincing evidence shows that the virus directly infiltrates neurons.

There's no evidence that this is a neurotropic virus, he said. In the case of the loss of smell, he said, some cells in the nasal cavity, such as epithelial cells, might become infected, but there is no definitive evidence that the nerves themselves are invaded.

Most of the neurological problems seen in COVID-19 patients, he said, result from systemic effects on the virus, Dr. Iadecola said.

He cautioned, though, that the data that has been published so far has mostly come from the most serious cases.

We're not going to know maybe until a year from now when you look at the population as a whole, the real mortality, the real incidence of neurological manifestations, and the most prevalent neurological manifestations, he said. Because now we know only the patient who gets very, very sick and goes to the hospital and may be intubated.

The most pressing research questions remaining, he said, include whether neurological manifestations of COVID-19 reflect brain invasion, whether the brain contributes to immune dysregulation and respiratory failure, and the long-term neurological consequences of the virus.

He urged centers treating COVID-19 patients to establish systems to track patients longitudinally.

The mortality from the COVID-19 virus may not be extremely high, he said, but a lot of people are getting infected. Evidence from other viral infections suggests that even if you have a mild infection .... there could be long-term neuropsychiatric effects that range from anxiety, PTSD, and depression, to cognitive impairment.

The message for clinicians, he said, is to be aware that the major complications that come from this are most likely due to whatever is going on elsewhere in the body, especially the hypercoagulable state and hypoxia. That's what the evidence so far suggests. They've got to pay almost more attention to what goes on outside the brain because most likely what goes on in the brain may be a reflection of that. And then pay attention to the sequelaewhatever it is going to be coming up in the next several months.

Be very attentive to the patients, he continued. Ask general questionsabout their mood, sleep pattern, appetite, social life, and whether they've gone back to work, he suggested.

As the acute phase resolves, quality of life is going to be paramount, Dr. Costantino said.

Adnan I. Qureshi, MD, FAAN, professor of clinical neurology at the University of Minnesota, who has studied COVID-19, said there are two main ways the virus can affect the CNS. One is a direct effect by the virus or inflammation affecting neuronal cells and the blood-brain barrier. These patients can get encephalitis or have demyelination, but it's unclear whether there is any treatment except for a therapy that can suppress the excessive inflammation, such as IL-6 inhibitors.

The second is through blood-clotting mechanisms, he said.

Some large studies, including one of ours, [published in July in the International Journal of Stroke], has shown that patients who develop ischemic stroke with COVID-19 are at risk due to older age and high prevalence of hypertension, diabetes mellitus, and hyperlipidemia. Therefore, these patients have other cardiovascular risk factors for ischemic stroke. COVID-19 may simply be a precipitant like other respiratory and systemic infections.

Important pending questions, Dr. Qureshi said, include how to best manage neurological patients, since focusing on neurological aspects alone might not be enough; the effect of remdesivir and convalescent serum; the role of anticoagulation in those with stroke risk; and the length of time stroke risk lasts after the infection.

Drs. Vallabh and Vikram Janardhan report receiving grants from the National Science Foundation and Insera Therapeutics. Dr. Vallabh Janardhan has also received grants from the Society of Vascular and Interventional Neurology. In addition, he and his brother, Dr. Vikram Janardhan, have 20 patents pending with the US Patent and Trademark Office and more than 65 patents in the US and worldwide issue.

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Therapy options for patients with migraines have expanded over the past couple of years, with several new drug classes specific to the disorder. Leading migraine experts discuss how they decide to choose one therapy over another.

Treatment options for migraine have expanded considerably over the past two years, with several new classes of targeted, migraine-specific drugs coming to the market.

The expansion of therapies for acute migraine and migraine prevention is welcome news for migraine sufferers, many of whom do not get adequate relief despite trying multiple treatments.

For neurologists and others who treat migraine patients, the new options may provide a clearer rationale for how to approach treatment because, until recently, most of the drugs used for migraine were developed for other conditions such as epilepsy. The newer medications are designed to target pathophysiologic pathways involved in the migraine process in the hope of achieving better pain relief with fewer side effects.

For our patients with migraine, we often have to say, I am going to give you this medicine that was originally created to help seizures (or blood pressure, or depression), and it is going to help your headache, said Rebecca E. Wells, MD, MPH, associate professor of neurology and founder and director of the Comprehensive Headache Program at Wake Forest Baptist Health.

With the new drugs, she now can tell patients how the drug is different and how it targets the pathophysiology of how migraine is working in their brain.

Among the newer class of preventive drugs generating excitement are calcitonin gene-related peptide (CRGP) inhibitors, monoclonal antibodies that block a pathway involved in the migraine process.

There are over 30 million people (in the US) with migraine, and yet only about 40 percent of them get adequate treatment, said Jessica Ailani, MD, FAAN, director of Medstar Georgetown Headache Center and professor of clinical neurology at Medstar Georgetown University Hospital.

She and other migraine experts say the newer migraine drugs aren't a panacea for all patients and don't render obsolete the older, less expensive migraine therapies that work well for many people. But they hope that a broader range of treatments will lead to more people being effectively treated and sticking with their medicines because of fewer side effects.

We are definitely seeing more patients come back to the practice we haven't seen in a while, said Dr. Ailani. Some patients come in saying, I hear there is something new.

Erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality) are humanized monoclonal antibodies that block CGRP by either binding to the CGRP receptor (erenumab) or binding to the CGRP ligand (fremanezumab and galcanezumab).

The injectables are administered every one to three months, depending on the drug. Erenumab carries a warning of possible hypersensitivity reactions, and the drug can also cause severe constipation. Galcanezumab is also approved for cluster headaches.

Epitenezumab (Vyepti), which works by binding to the CGRP ligand, is the first approved intravenous treatment for migraine prevention. It is administered via IV infusion at a clinic every three months. Because the drug was approved by the US Food and Drug Administration (FDA) in February just as the pandemic was taking off in the US, doctors say they have minimal experience in prescribing it.

The clinical trial results submitted to the FDA vary for each of the CGRP therapies, though in general, they are effective for about 50 to 60 percent of patients, Dr. Ailani said. While longer-term effects are not known with the newer migraine drugs, CGRPs come with very few side effects from what we can tell, and they are much better tolerated by patients, she said.

Ubrogepant (Ubrelvy) is the first in a class of oral medications called gepants, a small molecule CGRP receptor antagonist. Ubrogepant was approved in December 2019 for the acute treatment of migraine with or without aura. Unlike triptans, the drug works without constricting blood vessels, which means it could be an attractive alternative choice for patients with a history or risk of cardiovascular disease or stroke, Dr. Ailani said.

Rimegepant (Nurtec), another drug in the gepant classa dissolvable tabletwas approved by the FDA in February for acute treatment of migraine. Like ubrogepant, the drug does not constrict blood vessels and likewise could be useful for migraine patients with a history of high blood pressure or stroke, Dr. Ailani said.

Rimegepant has a long half-life of 11 hours and is prescribed once as needed for migraine, Dr. Ailani said. Both of the gepants are processed through the liver and have specific interactions with certain medications, so this is important to take into account when prescribing, she said.

Lasmiditan (Reyvow), the first medication in a new class of migraine drugs called ditans, is approved for the acute treatment of migraine with or without aura. Ditans do not cause vasoconstriction, so this drug can be an option for patients with vascular disease who need migraine-specific treatment, Dr. Alaini said.

The drug, which is a serotonin (5-HT)1F receptor agonist, can cause dizziness and sedation, and patients are warned not to drive or operate machinery within eight hours of taking it, even if they feel alert. The drug is a controlled substance.

Dr. Ailani said triptans are still her go-to generics for acute migraine because they are cheaper than the new drugs, and insurance companies cover them. They also have a known track record. She said that typically insurance companies require that patients fail two triptans before switching to a gepant.

Kathleen B. Digre, MD, FAAN, distinguished professor of neurology at the University of Utah, said that even with the bigger tool chest doctors now have to work with, the basic principles of migraine management should remain key to every patient encounter.

The first guiding principle is always make a right diagnosis, Dr. Digre said. That means a careful history and exam to make sure I know what the patient has. Then I look for comorbidities, things that run with migraine, like poor sleep, depression and anxiety, obesity, things that can make migraine worse, she said.

It's also essential to understand patients' expectations, she added. If I am going to talk with them about treatment options, I need to know where they are in their own minds. Are they willing to try a medication, or do they want to consider neuromodulation or do they want a healthy lifestyle approach? They are not going to take something just because you said so, Dr. Digre said.

She said many patients have tried every drug in the book, and may have mistakenly fallen into the category of being a non-responder because they were not on an effective dose of a medicine or only took it on and off as symptoms flared or subsided. Some have experienced intolerable side-effects.

They might have thrown out drugs that might have helped, just because they didn't take them long enough or at the correct dosage, she said.

Dr. Digre said she tends to start treatment with older drugs such as triptans for acute migraine and antihypertensives, tricyclics, or anticonvulsants for prevention because of their known track record and availability in inexpensive generic forms. She said her practice often faces pushback from insurers to pay for the costlier newer drugs.

I try to practice cost-effective medicine, and I am always thinking of cost to the patient and cost to the system, she said. If patients fail two or three classes of generic medications, I am going to advocate for them to get a new CGRP monoclonal therapy.

Randolph W. Evans, MD, FAAN, clinical professor of neurology at Baylor College of Medicine, said there has long been an unmet need for migraine drugs.

We are picking up many of the patients who were formally non- responders, he said, noting that the new medications are also more tolerable for many of our patients.

But even with the new lineup of drugs, there is nothing close to 100 percent for prevention. We still have people who don't respond, and that is the big mystery, he said.

Dr. Evans conducts industry-sponsored educational sessions for primary care doctors on the new migraine therapies, and he said they feel comfortable using the new medications. One limitation in explaining the pros and cons of the various drugs is that we don't have head-to-head studies (of the new migraine drugs) so many times we are driven by insurance coverage, when picking a treatment, Dr. Evans said.

Dr. Evans said the new drugs might prove effective in combined therapy for prevention, in the same way, that older medications are used in combination.

We have been combining Botox with a (CGRP) monoclonal antibody and finding additional efficacy in those who are partial responders to one, he said. There have also been favorable anecdotal reports of rimegepant used in combination with a CGRP monoclonal antibody, he said.

Dr. Wells, of Wake Forest, said that with the broader array of drugs to now choose from, patient education is more important than ever. She said it is hard to thoroughly discuss the many options during the time allotted for a clinical visit, and the similar-sounding names of drugs can be confusing for patients.

In 2018, when the CGRP medications first came on the market, she initiated separate patient education sessions to introduce patients to their possible treatment choices before their appointments. The sessions were at first held in person, but to increase access and availability, they are now available online.

Surveys before and after the sessions showed that not only were they helpful for improving patient understanding of the new medications, the online format was also as effective as the in-person sessions, Dr. Wells said. She said the separate educational sessions help improve clinic flow.

Dr. Wells said the overall message that she tries to convey to patients, no matter their ultimate treatment choice, is that migraine is a complex neurologic disease and it's not something that is just in their head.

Deborah I. Friedman, MD, MPH, FAAN, professor of neurology and ophthalmology at UT Southwestern Medical Center, said the ability to take migraine prevention medicine with a monthly or quarterly injection or instead of daily oral medication is a welcome switch for some patients.

We know the adherence rate for oral medications, both preventive and acute, is very poor, she said. Eighty percent of people who get a prescription for a migraine drug are not on it at the end of the year.

But Dr. Friedman said that one of the things she's gleaned from her clinical practice is that even though migraine therapy overall has benefited from the addition of the CGRPs, patience is still required.

When these drugs first came out, there was a mistaken impression that they would work very quickly for everyone, she said. While many patients do report a decline in headache in the first three months, as was shown in clinical testing, one of the things we've learned is that you have to give patients a five to six-month trial to make sure they have time to respond.

Dr. Digre had no relevant disclosures. Dr. Ailani has received honoraria from- Allergan/Abbvie, Biohaven, Axsome, Lundbeck, Amgen, Eli Lilly, Teva, Impel, Satsuma, and Revance. Dr. Friedman serves on the advisory board of Allergan, BioBiohaven Pharmaceuticals, Eli Lilly, Impel, Invex, Lundbeck, Merck, Revance, Teva, Theranica, and Zosano. She has received grant support from Allergan and Merck. Dr. Evans has received fees for serving on the speakers' bureau for Allergan, Amgen, Biohaven, Eli Lilly, Novartis, and Teva.

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So Many Migraine Therapies, So Many Decisions: Here's How... : Neurology Today - LWW Journals

Demetrius Demetri Maraganore, MD, is the recently appointed Herbert J. Harvey, Jr. Chair in Neurosciences and Chair of the Department of Neurology at Tulane University School of Medicine, where he runs the Healthy Brain Aging Initiative that helps patients prevent cognitive decline and dementia, including Alzheimers disease. (Photo by Paula Burch-Celentano)

More than 5 million Americans of all ages have Alzheimers. While deaths from heart disease and cancer have been declining due to treatment advances, deaths from Alzheimer's have grown significantly in the last two decades as more people live longer.

The costs are staggering. Alzheimers and other dementias will cost the nation $305 billion this year and more than triple by 2050, according to the Alzheimers Association.

This isnt inevitable and Americans must do more to protect themselves from dementia as they age, said Demetrius Demetri Maraganore, MD, the recently appointed Herbert J. Harvey, Jr. Chair in Neurosciences and Chair of the Department of Neurology at Tulane University School of Medicine.

We can prevent Alzheimers disease. There are about 20 well-defined risk factors for dementiaeach at least doubling the likelihood of Alzheimers disease.

Demetrius Demetri Maraganore, MD

We can prevent Alzheimers disease. There are about 20 well-defined risk factors for dementiaeach at least doubling the likelihood of Alzheimers disease, Maraganore said. Yet little effort is being made by health agencies or doctors to create awareness of these modifiable risks, or to identify and address related health disparities. When a disease has modifiable risk factors, it can be prevented by reducing those medical risks. There are also several protective lifestyle and behavioral interventions that can reduce the risk for Alzheimers by 50% or more. These include regular aerobic fitness, adherence to the Mediterranean diet, cognitive training and good sleep habits.

Maraganore, who joined the School of Medicine this summer, is also co-director of the Tulane Center for Clinical Neurosciences and a professor of neurology. He has launched the Tulane Healthy Brain Aging Initiative to help patients prevent cognitive decline and dementia (including Alzheimers disease) and to reduce the burden of Alzheimers disease and related disorders. The program will lead population health initiatives to identify people at greater risk for cognitive decline as well as serve as a self-referral and physician-referral destination for the evaluation and management of brain health.

Typical patients may include those with a family history of dementia or Alzheimers or a known genetic risk for late-onset Alzheimers disease. It will also serve those looking to age free of cognitive decline or dementia.

Our outpatient office evaluations include an inventory of possible modifiable risk factors for dementia, a comprehensive neurological examination to rule out cognitive impairment and the delivery of evidence-based interventions to reduce the risk for dementia, Maraganore said. We will order diagnostic studies when indicated. We will also offer genetic testing for late-onset Alzheimers disease and provide annual followup evaluations to refine our preventive care plans as needed to early detect and manage cognitive impairment.

The programs multidisciplinary team will include not only neurologists, but also physical therapy (for instruction in aerobic exercise), nutrition therapy (for instruction in the Mediterranean diet), speech therapy (for cognitive training), occupational therapy (for instruction in sleep hygiene), and also the opportunity to work with a licensed clinical social worker or health psychologist (for lifestyle coaching). Patients can opt in or out of these services as they consult with their neurologist.

Before joining Tulane, Maraganore was the BJ and Eve Wilder Professor of Alzheimers Disease at the University of Florida, and the founder and director of the University of Florida Brain Health Program. He has published more than 180 peer-reviewed studies and was the principal investigator or co-investigator for research grants totaling in excess of $20 million. His research projects have included using electronic medical record (EMR) data to predict Alzheimers and dementia risks and studying super agers who live beyond 90 years old to better understand healthy aging. Using an electronic medical records registry, he was part of a team that identified 45,000 Floridians over the age of 90 who were living independently and free of dementia-related diagnoses.

Using the EMR we computed a successful aging status in the over-90-year-olds. We are in the process of contacting those persons to confirm that the medical records estimations of successful aging are accurate, and to invite the successfully aged over-90-year-olds to mail in a saliva sample for DNA studies, he said. We hope to find in these persons genome the fountain of youth. We anticipate similar studies in the state of Louisiana, using a similar electronic medical registry that is available, and similar population health screening approaches.

A Chicago native, Maraganore received his Bachelor of Science and medical degree at Northwestern University. He then completed his internship and residency at the Mayo Clinic in Rochester, Minnesota. He was then the Honorary Clinical and Research Fellow to Professor C. David Marsden at the National Hospital for Neurology and Neurosurgery in London, England.

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Neurology chair dedicated to dementia prevention and brain health - News from Tulane

Article In Brief

The Society of Neurocritical Care has launched a new campaign to encourage research that enables clinicians to better understand not only acute coma but also disorders of consciousness broadly, including patients with altered consciousness. Efforts will also focus on better understanding the anatomical and physiological commonalities across disorders.

In response to huge gaps in the way patients in a coma with disorders of consciousness (DoC) are treated, the Scientific Advisory Council of the Neurocritical Care Society (NCS) has initiated an ambitious initiative, the Curing Coma Campaign, to identify critical areas of research and treatment protocols.

The campaign, described in an August paper in Neurocritical Care, identified three major pillarsthe identification of endotypes, development of biomarkers, and initiation of proof-of-concept trialsas essential to a grand effort that NCS leaders are likening to a moonshot. The campaign aims to jump start research but also to expand the curing coma community to ensure broad participation of clinicians, scientists, and patient advocates with the goal of developing treatments to improve the outcome of patients.

The way we treat coma and disorders of consciousness has not been sufficient, and there are huge gaps in our understanding and in the way, we are caring for patients, said J. Claude Hemphill, MD, FAAN, professor of neurology at the University of California, San Francisco, a lead author of the paper.

We know this is not going to be easy. It's a grand challenge, and it will not be quick. We have set out a ten-year scientific road map recognizing that advances will come incrementally over time.

Dr. Hemphill emphasized that the campaign is aimed at better understanding not only acute coma but also disorders of consciousness broadly, encompassing patients with altered consciousness that may be less complete than coma. And the campaign aims to move beyond the traditional focus on disease-specific DoCcardiac arrest, traumatic brain injury, brainstem stroketo better understand the anatomical and physiological commonalities across disorders.

We have had a lot of failed clinical trials in neurocritical care using a one-size-fits-all approach, Dr. Hemphill said. Instead of saying, `let's study this treatment or clinical approach for this disease-related DoC,' we need to step back and try to understand the fundamental underpinning of all DoC.

Toward that end, The Curing Coma Campaign Scientific Advisory Committee met for the first time in person during the NCS Annual Meeting in Vancouver in October 2019, where the council outlined three overarching, interrelated areas of research necessary to move the field forward: 1) endotypingdeveloping a better understanding of the different types of coma, 2) biomarkersevaluating current tools and their shortcomings in understanding coma and its prognosis, and developing new biomarkers that accurately determine DOC endotypes, and 3) proof-of-concept clinical trialsidentifying early interventional studies to evaluate new treatment protocols and inform clinical trial design.

Dr. Hemphill said the campaign grew out of a 2017 strategic planning meeting of the NCS looking at what they referred to as blue-ocean endeavorsthose research and treatment areas that are under-investigated but which are high-priority because they cut across all of the disorders treated by neurocritical care experts.

It was very clear that the biggest problem we face in neurocritical care is the care of coma and DoC, he said. We deliberately framed the campaign as a grand challenge that would galvanize people across the field to come together and participate.

Dr. Hemphill said the Curing Coma Campaign is not restricted to researchers but actively solicits the participation of the entire community of clinicians, hospitals and health systemsas well as patients and familiesinvolved in neurocritical care. He noted that in September, the National Institutes of Health and the National Institute of Neurological Disorders and Stroke sponsored a two-day virtual symposium on neurocritical care of DOC. Additionally, NCS is sponsoring World Coma Day on March 22, 2021. He urged researchers, clinicians, and families to visit the Curing Coma Campaign website: https://www.curingcoma.org/home.

The campaign is also sponsoring a survey of clinicians involved in neurocritical carehttps://www.curingcoma.org/research/come-togetherdesigned to inform the coma scientific community about current prevailing concepts of coma and assess the spectrum of practice variability.

In order for the campaign to be successful, it requires a fundamental change in the understanding of coma, and for this, we need to leverage the wider community to participate, Dr. Hemphill told Neurology Today.

He said the ambitiousness of the campaign goals reflects an urgency felt by families and clinicians when a patient with DOC is in the neurocritical care unit: Will they wake up? Can they wake up? What can be done to help them wake up?

The gaps in understating of coma result often in a self-fulfilling prophesy of poor outcomes. There is probably not a single neurocritical care provider who doesn't have a dramatic story of a patient who they thought would never wake up, but after aggressive treatment recovered and did, he said. The problem is that currently, it is very challenging to identify at the time who those patients are going to be.

Experts who reviewed the paper for Neurology Today said the campaign is extraordinary in its visionand long overdue. We are not good at neuro-prognostication, said Gunjan Parikh, MD, associate medical director of the division of neurocritical care and emergency neurology at the University of Maryland.

Care withdrawal based on inadequate data persists, he said. Diagnostic error and misclassification of coma recovery potential in the ICU phase of care remain alarmingly high. Clinical consensus by the medical team after review of imprecise testing remains the primary means by which DoC diagnosis is made.

Dr. Parikh added that the agenda of the campaign is realistic and attainable but will require NCS to partner with public and private organizations already involved in the ongoing NIH BRAIN Initiative. Mapping the brain circuitry underlying consciousness is far more complex and open-ended than mapping the genome, he said. Localized neural circuits can involve one million cells in a complex, recursive network; however, consciousness is an emergent property of a more complex, distributed network of interconnected neural circuitry.

Shraddha Mainali, MD, assistant professor of clinical neurology at Ohio State University, said she believes the goal is ambitious, but not impossible. The authors have rightly pointed out the existing barriers in advancing coma science, she said.

Existing clinical classification of disorders of consciousness does not address distinctions based on underlying biological/pathophysiological mechanisms or functional/anatomical integrity of neural pathways necessary to maintain consciousness, Dr. Mainali added.

We lack biomarkers that can accurately assess severity, functional integrity and related connectivity (or lack thereof) of neural networks. Of the available tools to detect biomarkers, several are not easily available and are difficult to administer in the acute ICU setting. Such limitations in biomarkers and endotyping of individual patients have made it difficult to develop clinical trials in the acute phase of the disease.

Dr. Mainali added that there is wide variability in management, including practice regarding the withdrawal of care of patients with DOC, which accounts for a large proportion of deaths in this population.

The lack of precise biomarkers and prognostic models has led to such variability, as individual treating teams are obligated to come up with their own best estimate of disease severity and prognosis.

Dr. Parikh said a necessary first step is more widespread adoption of validated behavioral assessments in the acute phase. Sufficient behavioral sampling with serial examination after maximal arousal and accounting for all ICU confounders is paramount for progress, he said. Collaboration between intensivists, rehab specialists and physical therapists during the acute ICU phase is key for tracking the progress of arousal potential, whether in the neuro ICU, cardiothoracic ICU or medical ICU.

What are the implications for individual clinicians? A working understanding of bedside decision-support tools leveraging computational workflows that continuously improve coma recovery prediction models, based on real-time ICU data streams in individual patients, will become routine and a part of the competency assessment of future trainees, Dr. Parikh said.

Dr. Hemphill said he is hopeful that the complete net cast by the Curing Coma Campaign will ultimately make this moonshot successful. Some of the advances are going to be from scientific advances, but others from the community coming together and thinking about how to improve care right now with this patientbeing careful about prognostication and targeting aggressive therapies. Advances will also come from educating clinicians about the ability of patients to recover and families about what is and is not possible.

Drs. Hemphill, Parikh, and Mainali had no relevant disclosures.

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A Grand Initiative to Improve Coma Care in Disorders of... : Neurology Today - LWW Journals

Young people have suffered less under the COVID-19 virus than older people medically, but experts say the gap has narrowed, and so-called superspreading among the young is a factor.

The epidemic is changing. People in their 20s, 30s and 40s are increasingly driving its spread, said Dr. Takeshi Kasai, World Health Organization regional director for the Western Pacific, in a virtual press conference Aug. 18.

Many are unaware theyre infected with very mild symptoms or none at all. This can result in them unknowingly passing on the virus to others, he added.

But on Sept. 28, a 19-year-old college student died, apparently of neurological complications related to the coronavirus.

Chad Dorrill, a sophomore at Appalachian State University in Boone, North Carolina, was diagnosed with COVID-19 in early September and suffered from later complications.

Dorrill developed additional complications even after being cleared by his doctor to return to Boone from his home county, according to an announcement from Appalachian State University Chancellor Sheri Everts.

All of us must remain vigilant with our safety behaviors wherever we are in our community. We must flatten the curve, but to do so, we must persevere, Everts said.

Research published Sept. 23 from the Centers for Disease Control and Prevention (CDC) in Atlanta reports that the COVID-19 incidence was highest in adults ages 20 to 29 years during June to August 2020 in the United States.

The report states that younger adults likely contribute to community transmission of COVID-19, and that increases in positive test results among adults ages 20 to 39 preceded increases among those 60 and older by an average of 8.7 days across the southern United States in June 2020.

As of Oct. 5, the 18-to-29 age group led all positive cases in the United States with 23.7%, or 1,269,397 cases, according to CDC data. The 50-to-64 age group followed in second with 20.6% of positive cases, or 1,000,476 cases.

Research shows that the coronavirus carries long-term health implications, even in younger adults.

A multistate telephone survey of adults who had symptoms and tested positive for COVID-19 showed 35% had not returned to their usual state of health when interviewed two to three weeks after testing, according to a report by the CDC.

Twenty percent of 18-to-34-year-olds with no chronic medical conditions reported they had not returned to their usual state of health.

A study published this month in the Journal of the American Heart Association found that pediatric patients 18 and younger with acute or prior coronavirus infection can have a broad range of cardiac findings, even though they are experiencing mild symptoms.

While data show that cases were the highest among older adults in the early stages of the pandemic, German epidemiologist Karl Lauterbach suggested in April, when the pandemic was widespread in China and Italy, that thousands of young people may have helped seed the COVID-19 pandemic since last December.

Experience maybe believes that its a severe disease for older people, Lauterbach told VOA in March. But we now know that many of the younger people also get severely ill and may sustain long-term consequences.

They get a very severe and atypical pneumonia and may end up in the [intensive care unit], Lauterbach, a scientist and member of Germanys Bundestag Parliament, said. And they have way more severe disease than we initially believed.

In December 2019, as COVID-19 was emerging in China, colleges and universities worldwide released hundreds of thousands of students home for winter break. Many of the more than 360,000 Chinese students who study in the U.S. returned to China for the holiday.

A month later, they and other international students returned to their campuses in the U.S. and around the world as COVID-19 was gaining speed.

In March, U.S. colleges and universities began their spring breaks, times when students traditionally head to warm beach destinations, such as in Florida, Texas and Mexico, to blow off steam after studying for midterms.

Dr. Sean OLeary, associate professor of pediatrics-infectious diseases at the University of Colorado Anschutz Medical Campus, told VOA that in response to the wave of COVID-19 cases in the U.S., many universities shut down their campuses, sent students home or asked them to return from spring break to clean out their rooms, and then put them on airplanes for points around the country.

From the perspective of the U.S. as a country, was that the best choice? OLeary asked. Campuses were one place where we knew there was widespread transmission.

Lauterbach said the disease is insidious in younger people because they typically show only mild or no symptoms, and scientists now believe that 80% of COVID-19 transmission occurs among those who dont seem ill.

A study by the American Academy of Pediatrics looked at more than 2,000 youths ages 18 and younger in China.

Doctors from Shanghai Childrens Medical Center and Shanghai Jiao Tong University School of Medicine wrote that where the virus first emerged, in Hubei province, 13% of confirmed cases had asymptomatic infection, a rate that almost certainly understates the true rate of asymptomatic infection, since many asymptomatic children are unlikely to be tested.

Research published Aug. 6 by JAMA Internal Medicine found that many COVID-19 patients remained asymptomatic for a prolonged period, and the viral load was similar to that of symptomatic patients.

Older children have also been shown to transmit the coronavirus as much as adults, according to a large study from South Korea.

The study, which analyzed nearly 65,000 people in South Korea, found that children younger than 10 were around half as likely to spread the virus as adults. However, young people ages 10 to 19 years old are more likely than other age groups to disperse COVID-19 into households.

Of 10,592 household contacts, 11.8% had COVID-19, with 18.6% being index patients ages 10 to 19. It was 1.9% for the 48,481 non-household contacts.

We should make it clear to younger people that if they behave in a careless fashion, that they are not only putting themselves, their peers, older people and peers [with underlying conditions] at risk, Lauterbach said, but they put themselves at risk and their best friends. So, we need to convey a message that this is a serious disease for all age groups.

It is quite clear that not many young people die from the disease, Lauterbach said.

But it is astonishing that we see very, let's say, remarkable numbers of younger people in the ICU and also often on ventilator support, he said.

Currently, we do not know whether they will fully recover their lung function or not. We definitely do not know that for certain. So, we have to take this way more seriously than we did in the past.

Kathleen Struck contributed to this report.

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Neurological, Cardiac Issues Linger in COVID-19 Youth - Voice of America

STEAMBOAT SPRINGS Opera Steamboat has announced plans to host two virtual seminars this month discussing neurological health themes from the book The Man Who Mistook His Wife for a Hat. The book was published in 1985 by neurologist Oliver Sacks and was subsequently turned into an opera the following year by composer Michael Nyman.

The seminars will introduce the content of the book and help set the stage for Opera Steamboats 2021 performance of the opera.

These seminars came as an idea to address the health issues around rural Colorado that as an organization we see on a regular basis, said Andres Cladera, general and artistic director of Opera Steamboat. Specifically, we wanted to address the neurological illnesses and mental health issues that our community are experiencing, while having difficulty getting treatment and/or support for the caregivers and families.

Cladera pointed out that up until recently, Steamboat did not have a regular neurologist on staff and patients would have to travel to Denver on a regular basis to seek treatment.

We have a lot of patrons and community members in Steamboat who have gone through neurological illnesses themselves or have taken care of a family member who has Parkinsons disease or Alzheimers, Cladera said. We want to bring awareness to the topic so that people can think about it and discuss it. Its not always easy to find treatment or care in rural Colorado.

The Man Who Mistook His Wife for a Hat describes the case histories of several of Sacks patients with the title based on one case in particular of a patient whom he refers to as Dr. P, who suffers from visual agnosia, a neurological condition that leaves him unable to recognize faces and objects.

Speakersfor the two seminars will include Dr. Ron Krall, a retired neurologist who lives in Steamboat; Dr. Samantha K. Holden, who is the assistant professor of neurology and medical director of the Memory Disorders Clinic at UCHealth, and Barbara Bronner, a retired licensed medical social worker focusing on issues of aging and caregiver support groups for the Alzheimers Association. Cladera will be a fourth speaker, discussing minimalism in the opera and how it relates to neuro illness.

Using music as a way of coping and understanding the world is a main theme, Cladera explained. When people suffer from neurological disorders, music can help them communicate and cope with their lives.

Dr. Krall, who owns Off the Beaten Path bookstore with his wife, will discuss the book.

From a literary standpoint, this is a book that is a piece of remarkable writing and reporting that makes for a wonderful education, he said. It illustrates the potential value of art in the treatment of the disease, in particular music, as it enables persons who have experienced some loss of neuro function to engage in relatively normal activities. Additionally, it teaches the importance of empathy for persons who have experienced a loss of function and support for them in obtaining care.

Those who wish to participate in the seminars can register for the two free seminars on Opera Steamboats website at operasteamboat.org/the-man-who-mistook-his-wife-for-a-hat.

The first seminar will take place at 5:30 p.m. Monday and the second at 5:30 p.m. Monday, Oct. 19. Participants will be emailed a Zoom link once they have registered.

Sophie Dingle is a contributing writer for Steamboat Pilot & Today.

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Opera Steamboat virtual seminars to tackle neurological health with discussion of 1985 book-turned-opera - Steamboat Pilot and Today

The Department of Neurology at the Wayne State University School of Medicine, partnered with Department of Psychiatry and Behavioral Sciences, has an endowment from the Albert and Goldye J. Nelson Fund to support scientific research in the detection, pathogenesis, molecular genetics, neurobiology and therapeutic development to cure Alzheimers disease and related disorders. Available funds for the coming fiscal year are between $50,000 and $100,000.

The Neurology Department is accepting proposals for FY 2021.Interested applicants must submit a proposal that consists of:

1. Specific aim (one page)

2. Research plan (six pages)

3. Human subjects if applicable (two pages)

4. Vertebral animals if applicable (two pages)

5. Biosketch (National Institutes of Health format) for all personnel involved in the study

6. Budget with budget justification

7. Resource

8. Support letters

Funds may not be used to cover the principal investigators salary. Proposals are for two to three years. Applicants must have at least a .25 FTE faculty appointment at the School of Medicine.

The deadline for submission is Jan. 31, 2021. The grant will begin Aug. 1, 2021.

Submit proposals to Carla Santiago, research administrator, WSU Department of Neurology - 8D UHC, 4201 St. Antoine, Detroit, MI 48201. E-mail:csantiago@med.wayne.edu.

Please note that the grant submissions must follow grant guidelines. Please click here for the guidelines.

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Neurology Department calls for grant proposals to support Alzheimer's disease and related research - The South End

DEVON, Pa., Oct. 08, 2020 (GLOBE NEWSWIRE) -- Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today has announced the acceptance and presentation details of two posters at the virtual Joint 49th Annual Child Neurology Society & 16th International Child Neurology Society Congress (CNS-ICNA) Meeting. The CNS-ICNA annual meeting is being held virtually from October 12th through October 23rd, 2020. A copy of the posters will be made available on the Zynerba corporate website at the time of presentation on Monday October 12th at http://zynerba.com/publications/.

Title: "ZYN002 Cannabidiol Transdermal Gel in Children and Adolescents With Fragile X Syndrome: Role of Methylation Status as a Correlate to Disease Severity and as a Prognostic Biomarker"Abstract number: 0406 0585 000889Primary keyword: Cognitive/Behavioral Disorders(including Autism) Poster number: 678

Title: "Tolerability and Efficacy of ZYN002 Cannabidiol (CBD) Transdermal Gel in Children and Adolescents With Autism Spectrum Disorder: An Open-Label Phase 2 Study [BRIGHT (ZYN2-CL-030)]Abstract number: 0406 0585 000888Primary keyword: Cognitive/Behavioral Disorders(including Autism) Poster number: 677

About Zynerba Pharmaceuticals, Inc. Zynerba Pharmaceuticals is the leader in pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome, autism spectrum disorder, 22q11.2 deletion syndrome, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies. Learn more at http://www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as predicts, believes, potential, proposed, continue, estimates, anticipates, expects, plans, intends, may, could, might, will, should or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Companys current expectations. These and other risks are described in the Companys periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available atwww.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Zynerba ContactWill Roberts, VP Investor Relations and Corporate Communications484.581.7489robertsw@zynerba.com

Media contactMolly DevlinEvoke KYNE215.928.2199Molly.Devlin@evokegroup.com

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Zynerba Pharmaceuticals Announces the Acceptance of Two Posters at the Virtual Joint 49th Annual Child Neurology Society & 16th International...

The Center for Regenerative Medicine in Miami, Florida, helps patients get back to a functional level of life and activities using Regenerative medicine and autologous therapy. Since 2000, the Center has developed non-surgical and rehabilitation techniques to treat and manage various diseases related to Neurology, Ophthalmology, and Orthopedics.

The Center for Regenerative Medicine includes a team of dedicated professionals working with cutting edge medical technology. The Center has patients from around the world including celebrities, sports legends, professional athletes, amateur athletes, dancers, and more.

The Center for Regenerative Medicines core values are as follows:

The Founder/Director of the Center for Regenerative Medicine is Alimorad Farshchian, MD. He is a medical doctor, medical author, and humanitarian. In 2005, Dr. Farshchian was the first doctor in the U.S.A. to perform an autologous biologics transplantation into an arthritic knee. Dr. Farshchian served as the TEAM USA Track & Field Orthopedic Regenerative Medicine consulting physician, for the 2012 London Olympics and the 2016 Rio Olympics.

For more information and patient testimonials, visit http://www.NeuroRegenesis.com

The Center for Regenerative Medicine in Miami, Florida concentrates on helping patients to get back to a functional level of life and their activities using Regenerative medicine.

Founded in 2000 by Dr. A.J. Farshchian, medical director of the center in order to pursue pioneering regimens in the treatment of arthritis and neurodegenerative diseases. The Center for Regenerative Medicine has over 20 years experience in Neurological diseases and more than 50,000 cases treated.

Above content provided by The Center for Regenerative Medicine.

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The Center For Regenerative Medicine Has Over 20 Years Experience In Neurological Diseases, More Than 50,000 Cases Treated - CBS Miami

Sleeping too little or too much, meaning no more than 4 hours per night or at least 10 hours per night, respectively, is associated with faster cognitive decline compared with sleeping approximately 7 hours per night, according to study results published in JAMA Network Open.

Study researchers from China sought to examine the relationship between sleep duration and cognitive decline. They achieved this by conducting an observational study, analyzing a pooled cohort of participants from waves 4 to 8 (2008-2009 to 2016-2017) of the English Longitudinal Study of Ageing and waves 1 to 3 (2011 to 2015) of the China Health and Retirement Longitudinal Study. In total, the pooled cohort included 9254 individuals from England who were at least 50 years of age (55.9% women; mean age, 64.6 years; median follow-up duration, 8 years) and 10,811 individuals living in China who were at least 45 years of age (50.2% men; mean age, 57.8 years; median follow-up duration, 4 years).

The investigators assessed face-to-face interview responses to obtain self-reported, per-night sleep duration information from participants. Sleep duration data were then correlated with global cognitive z scores, which were calculated based on the immediate and delayed recall test, animal fluency test, serial sevens test, an intersecting pentagon copying test, as well as a date orientation test.

Compared with a reference group of participants who slept for approximately 7 hours per night, global cognitive z scores declined significantly faster for those who slept no more than 4 hours per night (pooled =-0.022; 95% CI, -0.035 to -0.009; P =.001) or at least 10 hours per night (pooled =-0.033; 95% CI, -0.054 to -0.011; P =.003) in an analysis adjusted for age, body mass index, and other covariates. The investigators observed an inverted U-shaped association between sleep duration and global cognitive decline, in addition to memory in these participants.

Limitations of this study included its observational design, the reliance on self-reported data for the assessment of sleep duration, and the use of isolated tasks rather than more sensitive methods for the measurement of cognitive function.

The study researchers concluded that the inverted U-shaped association indicates that cognitive function should be monitored in middle-aged and older individuals with insufficient or excessive sleep duration.

Reference

Ma Y, Liang L, Zheng F, Shi L, Zhong B, Xie W. Association between sleep duration and cognitive decline. JAMA Netw Open. Published online September 21, 2020. doi:10.1001/jamanetworkopen.2020.13573

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Insufficient and Excessive Sleep Associated With Faster Cognitive Decline - Neurology Advisor

The 2020 Neuroscience Expo will host a morning of free online sessions with legal and financial advisers, tailored exclusively to those dealing with a neurological condition and their caregivers.

Living a happy, fulfilling life goes beyond exceptional medical care. It includes caring for the whole person and their day-to-day struggles.

This Norton Neuroscience Institute event gives individuals living with a neurological condition and their family, caregivers, support care providers and others a way to collect valuable information.

Friday, Oct. 23, 9 a.m. to 12:30 p.m.

This years Norton Neuroscience Institute conference will be livestreamed, but space is limited.

Register Today

This years track for legal and financial resources features the following sessions:

Learn how to create a life care plan for you or a loved one.

Jefferey Yussman and Gordon Homes

Living with a disability can be challenging and requires planning for future needs. Youll learn ways you can financially prepare for the future.

Jefferey Yussman and Gordon Homes

If you wanted to know about the importance of having your affairs in order, this presentation will outline the various legal documents that would ensure your peace of mind.

Victor E. Tackett Jr.

Is it time to apply for disability? Where do I begin? Learn the latest on Social Security disability applications and the process of filing a disability claim.

Sam Schad

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Free sessions on legal and financial issues for those with neurological conditions - Norton Healthcare

Las Vegas: The National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH) has awarded a grant expected to total $3.8 million to Virendra Mishra, Ph.D., associate staff at Cleveland Clinic Lou Ruvo Center for Brain Health, to identify biomarkers or disease indicators to predict dementia in patients with Parkinsons disease.

Although dementia affects approximately 50-80% of those living with Parkinsons disease within 12 years of diagnosis, currently there are no means for predicting dementia in specific individuals, said Mishra. The possibility of identifying who will develop dementia with Parkinsons disease progression has several clinical benefits, including providing individuals with greater clarity on their future and helping clinicians better manage disease progression.

The five-year grant supports the project, Towards Generating a Multimodal and Multivarate Classification Model from Imaging and Non-Imaging Measures for Accurate Diagnosis and Monitoring of Dementia in Parkinsons Disease, which will use biomarkers spanning imaging, blood, cerebrospinal fluid and genetics to develop a predictive mathematical model to identify specific individuals with Parkinsons disease who may develop dementia as their disease progresses.

Utilizing sophisticated and pathologically relevant neuroimaging measures such as diffusion-weighted MRI and resting state functional MRI with non-imaging measures, including clinical data, demographics, genetics and cerebrospinal fluid, Mishra aims to:

Through this research, Mishra plans to develop a method that can be applied in clinical care with a greater-than-chance success rate to improve patient outcomes. In addition to clinical implications, identifying pathophysiology-based biomarkers for dementia in Parkinsons disease is critical for selecting appropriate individuals for participation in clinical trials of potential new disease-modifying therapies, and better understanding of the underlining pathophysiological processes.

Additionally, the novel imaging techniques developed for this research also can be applied in other neurodegenerative diseases such as Alzheimers disease to help advance the understanding of disease-specific neuroanatomical changes indicative of dementia.

This project is supported by NIH grant award R01NS117547.

For more information about ongoing research at Cleveland Clinic Lou Ruvo Center for Brain Health, visit ClevelandClinic.org/Nevada or call 702-701-7944.

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National Institute of Neurological Disorders and Stroke Awards $3.8 Million to Cleveland Clinic Researcher to Predict Dementia in Parkinson's Disease...

Overview

This WHO report of a survey completed by 130 countries during the period June-August 2020 provides information about the extent of disruption to mental, neurological and substance use services due to COVID-19, the types of services that have been disrupted, and how countries are adapting to overcome these challenges.

The World Health Organization (WHO) has identified mental health as an integral component of the COVID-19 response. Its rapid assessment of service delivery for mental, neurological and substance use (MNS) disorders during the COVID-19 pandemic, on which this report is based, is the first attempt to measure the impact of the pandemic on such services at a global level. The data were collected through a web-based survey completed by mental health focal points at ministries of health between June and August 2020. The questionnaire covered the existence and funding of mental health and psychosocial support (MHPSS) plans, the presence and composition of MHPSS coordination platforms, the degree of continuation and causes of disruption of different MNS services, the approaches used to overcome these disruptions, and surveillance mechanisms and research on MNS data.

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The impact of COVID-19 on mental, neurological and substance use services - PAHO/WHO - Pan American Health Organization

New research from the results of a 1000-person study suggests improving blood sugar control could improve brain health for individuals with type 2 diabetes.

An analysis of data from the Look AHEAD (Action for Health In Diabetes) study, results of the study indicate improvements in glycemic control, but not weight status were linked to better subsequent cognitive performance.

"It's important to properly control your blood sugar to avoid the bad brain effects of your diabetes," saidOwen Carmichael, PhD, professor and director of Biomedical Imaging at the Louisiana State University Pennington Biomedical Research Center, in a statement. Don't think you can simply let yourself get all the way to the obese range, lose some of the weight, and everything in the brain is fine. The brain might have already turned a corner that it can't turn back from."

With an interest in how disease management might impact the cognitive function of in patients with type 2 diabetes, Carmichael and a team of colleagues hoped to design a study to describe associations between physiological markers and cognitive performance in patients with diabetes in the Look AHEAD study. A randomized controlled trial assessing the efficacy of intensive lifestyle intervention, the study provided data related to more than 5000 diabetic patients aged 45-76 years old.

Patients included in the study randomized to the intensive lifestyle intervention were prescribed to a daily calorie goal of 1200-1800 and a physical activity goal of more than 175 minutes per week with the aim of inducing weight loss to average more than 7% at 1-year and to be maintained over time.

As part of the ancillary studies, patients from the Look AHEAD study were invited to take part in cognitive assessments and 3920 participants provided at least 1 cognitive assessment between years 8-13 of follow-up. These assessments provided investigators information related to short-term memory, planning, impulse control, attention, ability to switch between tasks, verbal learning, and overall memory. For the purpose of the current analysis, investigators only included patients who provided 2 or 3 cognitive assessments, which yielded a cohort of 1089 individuals.

Of the 1089 included in the study, the mean age was 58.36.7 years, 58.8% were female, and 84.5% of patients had a BMI of 30 kg/m2 or greater. Investigators pointed out all 1089 patients underwent at least 2 cognitive assessments and a cohort of 315 patients completed all 3 cognitive assessments.

Upon analysis, results of the study suggested greater improvements in blood sugar control were associated with increased cognitive scores. Specific associations included fasting blood glucose and Rey Auditory Verbal Learning Test (P=.0148), fasting blood glucose and Digit Symbol Coding (P=.0360), and HbA1C and DSC (P=.0477).

However, investigators noted weight loss appeared to have mixed associations with cognitive scoresnoting greater BMI reduction and worse auditory verbal learning test scores overall (P=.0053) while greater BMI reduction and better digit symbol coding scores were observed among patients who were overweight but not obese (P=.010).

Results of the study also indicated apparent associations were strongest among patients who were overweight but not obese at baseline. Additionally, investigators pointed out associations appeared to also be stronger Amon those with a history of cardiovascular disease at baseline.

"The results were worse for people who had obesity at the beginning of the study. That's a 'too little, too late' type of message," added Carmichael, in the aforementioned statement. "People with diabetes who let their obesity go too far, for too long may be past the point of no return, cognition-wise."

This study, Long-term change in physiological markers and cognitive performance in type 2 diabetes: the Look AHEAD Study, was published in the Journal of Clinical Endocrinology and Metabolism.

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Blood Sugar Control Could Help Protect Neurologic Health in Patients with Diabetes - Endocrinology Network