Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Since the Centers for Disease Control and Prevention (CDC) confirmed the first US case of novel coronavirus infection on January 20, much of the clinical focus has naturally centered on the virus' prodromal symptoms and severe respiratory effects.

However, US neurologists are now reporting that COVID-19 symptoms may also could include encephalopathy, ataxia, and other neurologic signs.

"I am hearing about strokes, ataxia, myelitis, etc," Stephan Mayer, MD, a neurointensivist in Troy, Michigan, posted on Twitter on March 26.

Other possible signs and symptoms include subtle neurologic deficits, severe fatigue, trigeminal neuralgia, complete/severe anosmia, and myalgia as reported by clinicians who responded to the tweet.

Last week, as reported by by Medscape Medical News, the first presumptive case of encephalitis linked to COVID-19 was documented in a 58-year-old woman treated at Henry Ford Health System in Detroit.

Physicians who reported the acute necrotizing hemorrhagic encephalopathy case in the journal Radiology counseled neurologists to suspect the virus in patients presenting with altered levels of consciousness.

Researchers in China also reported the first presumptive case of Guillain-Barre syndrome associated with COVID-19. A 61-year-old woman initially presented with signs of the autoimmune neuropathy GBS, including leg weakness, and severe fatigue after returning from Wuhan, China. She did not initially present with the common COVID-19 symptoms of fever, cough, or chest pain.

Her muscle weakness and distal areflexia progressed over time. On day 8, the patient developed more characteristic COVID-19 signs, including 'ground glass' lung opacities, dry cough, and fever. She was treated with antivirals, immunoglobulins, and supportive care, recovering slowly until discharge on day 30.

"Our single-case reportonly suggests a possible associationbetween GBS andSARS-CoV-2 infection. It may or may not havecausal relationship. More caseswith epidemiological data are necessary," senior author Sheng Chen, MD, PhD, told Medscape Medical News.

However, "we still suggest physicians who encounter acute GBS patients from pandemic areas protect themselves carefully and test for the virus on admission. If the results are positive, the patient needs to be isolated," added Chen, a neurologist at Shanghai Ruijin Hospital and Shanghai Jiao Tong University School of Medicine in China.

Neurologic presentations ofCOVID-19 "are not common, but could happen," Chen added. Headache, muscle weakness and myalgias have been documented in other patients in China, he said.

We know almost nothing about the potential interactions between COVID-19 and the nervous system. Dr Robert Stevens, Johns Hopkins School of Medicine, Baltimore

Despite this growing number of anecdotal reports and observational data documenting neurologic effects, the majority of patients with COVID-19 do not present with such symptoms.

"Most COVID-19 patients we have seen have a normal neurological presentation. Abnormal neurological findings we have seen include loss of smell and taste sensation, and states of altered mental status including confusion, lethargy, and coma," Robert Stevens, MD, who focuses on neuroscience critical care at the Johns Hopkins School of Medicine in Baltimore, Maryland, told Medscape Medical News.

Other groups are reporting seizures, spinal cord disease, and brain stem disease. It has been suggested that brain stem dysfunction may account for the loss of hypoxic respiratory drive seen in a subset of patients with severe COVID-19 disease, he added.

However, Stevens, who plans to track neurologic outcomes in COVID-19 patients, also cautioned that it's still early and these case reports are preliminary.

"An important caveat is that our knowledge of the different neurological presentations reported in association with COVID-19 is purely descriptive. We know almost nothing about the potential interactions between COVID-19 and the nervous system," he noted.

He added it's likely that some of the neurologic phenomena in COVID-19 are not causally related to the virus.

"This is why we have decided to establish a multisite neuro-COVID-19 data registry, so that we can gain epidemiological and mechanistic insight on these phenomena," he said.

Nevertheless, in an online report February 27 in the Journal of Medical Virology, Yan-Chao Li, MD, and colleagues write that "increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system, inducing neurological diseases."

Li is affiliated with the Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine, Jilin University, Changchun, China.

Scientists observed SARS-CoV in the brains of infected people and animals, particularly the brainstem, they note. Given the similarity of SARS-CoV to SARS-CoV2, also known as COVID-19, the researchers suggest a similar invasive mechanism could be occurring in some patients.

Although it hasn't been proven, Li and colleagues suggest COVID-19 could act beyond receptors in the lungs, traveling via "a synapseconnected route to the medullary cardiorespiratory center" in the brain. This action, in turn, could add to the acute respiratory failure observed in many people with COVID-19.

Other neurologists tracking and monitoring case reports of neurologic symptoms potentially related to COVID-19 include Mayer and Amelia Boehme, PhD, MSPH, an epidemiologist at Columbia University specializing in stroke and cardiovascular disease.

Boehme suggested on Twitter that the neurology community conduct a multicenter study to examine the relationship between the virus and neurologic symptoms/sequelae.

Medscape Medical News interviewed Michel Dib, MD, a neurologist at the Piti Salptrire hospital in Paris, who said primary neurologic presentations of COVID-19 occur rarely and primarily in older adults. As other clinicians note, these include confusion and disorientation. He also reports cases of encephalitis and one patient who initially presented with epilepsy.

Initial reports also came from neurologists in countries where COVID-19 struck first. For example, stroke, delirium, epileptic seizures and more are being treated by neurologists at the University of Brescia in Italy in a dedicated unit designed to treat both COVID-19 and neurologic syndromes, Alessandro Pezzini, MD, reported in Neurology Today, a publication of the American Academy of Neurology.

Pezzini notes that the mechanisms behind the observed increase in vascular complications warrant further investigation. He and colleagues are planning a multicenter study in Italy to dive deeper into the central nervous system effects of COVID-19 infection.

Clinicians in China also report neurologic symptoms in some patients. A study of 221 consecutive COVID-19 patients in Wuhan revealed 11 patients developed acute ischemic stroke, one experienced cerebral venous sinus thrombosis, and another experienced cerebral hemorrhage.

Older age and more severe disease were associated with a greater likelihood for cerebrovascular disease, the authors report.

Chen and Li have disclosed no relevant financial relationships.

Follow Damian McNamara on Twitter: @MedReporter. For more Medscape Neurology news, join us on Facebook and Twitter.

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Article In Brief

The article revisits the controversy around policies at some academic medical centers that require older neurologists to undergo cognitive testing for recredentialing.

Aging is known to be associated with cognitive decline. Is that reason enough to test more senior neurologists and other physicians for potential cognitive deficits that might cause a patient-care problem?

A growing number of health systems say yes and are implementing policies that require cognitive and other screenings when physicians reach a certain age. But the policies are controversial: One state passed legislation prohibiting the practice, although the ban was reversed the next year; most recently, the Equal Employment Opportunity Commission (EEOC) filed a lawsuit that argues one health system's mandatory-examination policy is illegal.

Physician demographics suggest the controversy will not go away soon. There are currently about 150,000 practicing physicians age 65 and older in the US, up from about 95,000 in 2013, according to the American Medical Association.

Proponents of age-based screenings say evidence shows they are needed. At Yale New Haven Hospital, the teaching hospital for Yale School of Medicine, physicians age 70 or older must complete a neuropsychological assessment; of the first 141 to undergo the assessment, nearly 13 percent demonstrated cognitive deficits that were likely to impair their ability to practice independently, according to a January 14 report in JAMA.

Meanwhile, about 70 older physicians from across the country have undergone a late-career health screening through the University of California-San Diego (UCSD) Physician Assessment and Clinical Education program and roughly 20 percent have been referred for further evaluation, said David Bazzo, MD, director of the UCSD Fitness for Duty program.

Opponents disagree with the idea of age-based screening. Scott E. Hirsch, MD, a neuropsychiatristboard-certified in neurology and psychiatryat NYU Langone Health, who evaluates physicians on behalf of the New York State Office of Professional Medical Conduct, is one of them. Dr. Hirsch pointed out that maintenance of certification exams require physicians to demonstrate mastery of the knowledge needed to practice.

The tests are fairly challenging and I don't think you can do well on them if you have an underlying cognitive problem, he said. We are already doing so much to stay credentialed. I don't see how cognitive screening adds anything.

A number of neurology leaders contacted for this story declined to be interviewed, but those who did agree to be interviewed had mixed opinions about mandated cognitive screening.

Policies mandating routine age-based screening started emerging about a decade ago, Dr. Bazzo said. In 2011, his UCSD program and the Coalition for Physician Enhancement convened a range of professionalsphysician-evaluators conducting assessments on behalf of state medical boards investigating complaints; geriatricians; administrative law judges who preside over physicians' disciplinary hearings; and prosecutors and defense attorneys involved in physician disciplinary casesto discuss the aging physician workforce.

In addition to educational sessions and a review of age-based physician screening commonly conducted in Canada, conference participants were surveyed on the issue. The majority favored age-based screening for physicians, starting at age 70, that includes assessments of physical and mental health and a cognitive screen, according to a report in the Journal of Medical Regulation.

That sort of started the ball rolling, Dr. Bazzo said.

Since then, many organizationsranging from huge systems like Scripps Health to community hospitals like Sinai Hospital in Baltimorehave implemented age-based screening policies. In 2014, the University of Pittsburgh Medical Center (UPMC) became one of the first to implement a policy to assess physical and cognitive abilities, said Donald M. Yealy, MD, senior medical director of the system's health services division.

Dr. Yealy and colleagues drafted the policy for two reasons. First, they recognized that some other fieldscommercial aviation, for examplehave age-related thresholds that trigger a professional re-evaluation or practice change to optimize safety.

At the same time, we also realized that we had some reported safety concerns in which we wondered, but were never certain, if a more scheduled and proactive approach might have helped us avert a patient care issue, Dr. Yealy said.

The UPMC policy applies to advanced practice providers as well as physicians. The UPMC medical staff accepted the policy, which follows steps similar to those used with other physicians when a concern arises, without much controversy.

We learned that having a set policy creates a natural and non-threatening opportunity for any physician to personally re-evaluate, he said. We have had many who, at their 70th birthday, have altered what privileges they request or shifted into a different type of practice.

By contrast, Intermountain Healthcare, a large system based in Utah, had a very different experience. That system had a mandatory retirement age of 72 for medical staff in 2013, when neuropsychologist Kelly Garrett, PhD, was asked to help plan a late-career physician program.

Our credentialing committees were giving exemptions, allowing physicians to practice beyond age 72, but they felt that they did not have enough data in order to be able to grant these extensions with much degree of confidence, Dr. Garrett said.

In 2014, Intermountain's medical staff approved a policy that required late-career physicians to complete a history and physical, including sensory and cognitive screenings. Four years later, the Utah State Legislature prohibited mandatory age-based screenings for physicians. In 2019, the ban was reversed but the new law dictates some principles that must be followed.

Intermountain has been reticent to return to business as usual and is now exploring reorganizing the program such that at least the cognitive screening part would be a voluntary program available to physicians regardless of age, Dr. Garrett said.

In February, the EEOC filed suit against Yale New Haven Hospital saying its policy requiring neuropsychological and eye examinations before physicians can obtain or renew staff privileges violates the Age Discrimination in Employment Act.

For some neurology leaders, age-based screening smacks of ageism. The idea of screening to make sure a physician's cognitive skills are adequate for the job does not alarm S. Andrew Josephson, MD, FAAN, professor and chair of neurology at the UCSF Weill Institute for Neurosciences. But age-based screening bothers him.

I would worry that, if we set some arbitrary age cutoff, we are not really focusing on the problem we should be concerned about, which is identifying physicians who have cognitive impairment from a variety of issues, whether it be a neurodegenerative process, substance abuse issues, or some other problem, he said.

Richard P. Mayeux, MD, MSc, FAAN, professor of neurology, psychiatry and epidemiology and chair of neurology at Columbia University College of Physicians and Surgeons, also gives age-based screening a thumbs-down.

It's illegal to do it as part of job credentialing based on age, said Dr. Mayeux, co-director of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center. Our strategy is to single out and test only people who have demonstrated some impairment of some sort. Impaired physicians, I have no problem evaluatingbut evaluating people simply because they're old, I think is inappropriate.

Neil A. Busis, MD, FAAN, associate chair for technology and innovation in the neurology department at New York University Grossman School of Medicine, said it's important to balance the twin goals of maintaining a robust neurology workforce and protecting patients. Screening for potential impairment might be a way of striking that balance, he said. Commercial airline pilots older than 40 years must have a first-class medical certificate renewed every six months.

I think well thought-out processes from other industries can be applicable to medicine, he said. Certain kinds of health screening seem like a reasonable thing to do.

That said, if protecting patient safety is the reason for screening, singling out physicians might not be justified. If you're going to mandate screening for physicians, how about nurses and everybody else who works at the hospital? Dr. Busis said.

There is no standard approach to age-based screening or assessment programs, which vary considerably on at least three variables.

There is no cut-off score that determines that a provider is competent to practice independently, Dr. Bazzo said. Rather, neuropsychologist (and AAN member) William Perry, PhD, vice chair of the UCSD department of psychiatry, reviews and interprets each neurocognitive screening report to determine whether more in-depth testing for diagnostic purposes is recommended.

At UPMC, by contrast, physicians and advanced practice practitioners covered by the age-based screening policy must notify the credentialing committee who will be conducting the physical examination and cognitive assessment they obtain on their own. Obviously, that would give us an opportunity to make sure that the person who is going to do any part of the assessment was qualified and did not have any conflicts, Dr. Yealy said.

The credentialing committee requires a specific tool for the cognitive assessment. The physical examination must look for physical impairment that might impact an ability to function in whatever type of physician you are, whether it's a cognitive specialty and/or procedural specialty, Dr. Yealy said.

Dr. Perry and other neuropsychologists who are most active in late-career physician screening convened last year to discuss the tools available and agreed that the MicroCog is the best option because it has been normed on physicians. Acknowledging that the instrument has some limitations, Dr. Perry said it is not used to diagnose a specific condition, but rather to determine whether a more in-depth evaluation is needed.

The idea is not to use the MicroCog to remove people from practice, he said. The idea is to catch something before it's extreme and problematic because then a physician is able to make changes to their practice.

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Article In Brief

Scores on a set of five markers of inflammation predicted the cognitive scores of patients with Parkinson's disease at 36 months. Two measures of cellular senescence likewise predicted cognitive outcomes.

Blood-derived biomarkers of senescence and inflammation look promising as predictors of cognitive decline in Parkinson's disease (PD), according to a January 13 study in the Journal of Parkinson's Disease.

At diagnosis, patients' summary scores on a set of five markers of inflammation predicted their cognitive scores at 36 months. Two measures of cellular senescence likewise predicted cognitive outcomes.

While significant, the results from the Incidence of Cognitive Impairments in Cohorts with Longitudinal Evaluation-Parkinson's Disease (ICICLE-PD) study were not strong enough to be of immediate clinical utility. They add, however, to the existing literature on risk factors observable at diagnosis that should one day enable neurologists to offer patients a reliable prognosis of cognitive outcomes, said the study's senior author and independent commentators.

The findings look robust, commented David K. Simon, MD, PhD, professor of neurology at Harvard Medical School and director of the Parkinson's Disease and Movement Disorders Center at Beth Israel Deaconess Medical Center, who was not involved with the study.

This is a very well organized, well conducted study. But we see a lot of studies about biomarkers like this, and we're not using them in the clinic yet. I'd want to see the results validated in a larger cohort before I use these biomarkers to tell a patient that they're likely to develop dementia.

The ongoing ICICLE-PD study, based in Newcastle upon Tyne and Gateshead, United Kingdom, includes154 newly diagnosed PD patients and 99 healthy, age-matched controls from the Newcastle area.

The inflammatory markers used in the study were C-reactive protein, TNF alpha, IL-6, IL-10, and IFN-gamma. For markers of senescence, the investigators used p21 and p16cell-cycle regulators known to suppress tumorsas well as telomere length in blood cells. Found at the end of every chromosome, telomeres serve as protective caps. Because their length has previously been shown to shorten with age, stress and illness, the study sought to determine if a shorter length at baseline would distinguish patients from controls and predict worse cognitive outcomes at 18 and 36 months.

As expected, the study found that PD patients as a group had shorter average telomeres in blood cells at baseline and 18 months compared to age-matched healthy controls. Shorter telomere length among the PD patients was also correlated with an increased risk of PD dementia (PDD) at 36 months.

Results from measurements of p21 and p16 were not as clear. Overall, the best predictor of cognitive score over the 36 months of the study was a summary score of the five markers of inflammation, while the development of dementia best correlated with short telomeres.

We think these different components might be related, said the senior author of the paper, Gabriele Saretzki, PhD, a lecturer in aging research at the Biosciences Institute of Newcastle University.

As more patients in the ICICLE-PD cohort progress to dementia, she said, results should strengthen.

For now we could only go to 36 months, Dr. Saretzki said. At 72 months, we should have three to four times more dementia cases, and that will allow us to make much better statistical associations.

A spate of recent studies has sought to tease out which clinical and biological markers might be predictive of PDD. Last November, another paper in the journal Movement Disorders based on the ICICLE-PD cohort reported that pro-saccades appear to be a useful non-invasive biomarker for long-term PD cognitive decline.

For the new study, Dr. Saretzki and colleagues sought to use ICICLE-PD blood and serum samples in hopes of bringing clarity to contradictory data regarding telomeres. Some prior studies had found no evidence that their length in leukocytes or other cellular chromosomes held any value for predicting PDD. Other studies had found significant effects, although one, published in PLoS One in 2014, found the opposite of the expected direction: longer, rather than shorter, telomeres were associated with increased risk of dementia progression.

The whole telomere field is very difficult, said Dr. Saretzki. I tell students, be very careful when you read papers in this area. Results can depend on not just genetics but on lifestyle factors, psychological or physical stress and inflammation. It's really complex.

After correcting for multiple comparisons, Dr. Saretzki's group found that PD subjects had significantly shorter telomere length at baseline compared with controls (p< 0.001) as well as significantly faster shortening of their telomeres over the first 18 month period (p=0.002).Even so, the telomere lengths of some PD patients overlapped with those of controls. Importantly, however, they also found shorter telomeres at baseline in those PD patients who went on to develop an early dementia.

Even so, because only 11 of the PD patients developed dementia within 36 months, as measured by the Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA), the small numbers precluded a meaningful regression analysis of the predictive power of telomere length for PDD, the paper concluded.

Contrary to expectations, PD participants displayed significantly lower levels of p21 gene expression than controls at baseline (p< 0.001), but there was no difference in change with time. For p16 expression, the differences between PD and controls at baseline or the rate of change per month of p16 expression levels did not reach statistical significance. Dr. Saretzki speculated that perhaps the gene expression measures her group conducted on p16 and p21 are less informative than the measures of protein levels previously published.

The baseline composite inflammatory score was only predictive of MoCA score (p=0.037) at 36 months, independently of age, gender, body mass index, and levodopa equivalent doses. Thus, the composite inflammatory score at baseline was best associated with cognitive score, but not with rate of change for any other clinical indicators over the follow-up period. What's more, none of the baseline biomarkers of senescence or inflammation significantly predicted motor function at 36 months or their rate of change.

Connie Marras, MD, PhD, associate professor of neurology at the University of Toronto and a neurologist at the Toronto Western Hospital Movement Disorders Centre, said that the study provides the basis for further investigations. But, she said, Because they only had 11 people who developed dementia at 36 months, we have to consider these findings quite preliminary.

Even so, she applauded the effort, given the importance to patients of a reasonably accurate prognosis of their cognitive status.

Cognitive slowing is a big deal for patients, she said. My patients ask what they can expect. It affects their planning for their lives and their careers. We need better ways to predict who will progress faster in terms of cognitive decline.

Elizabeth Bradshaw, PhD, the Adler assistant professor in neurological sciences at Columbia University's department of neurology, said she was excited to see the results on senescence. In particular, the findings regarding telomeres look straightforward and quite exciting.

But, she said, the findings for p16 and p21, as well as for the inflammatory markers, puzzled her.

The p16 and p21 didn't go in the direction you might expect based on the telomere results, Dr. Bradshaw said. But they examined total blood. If they had been able to break it out into specific cell types, like monocytes or memory T cells, perhaps that would explain what was driving the reduction of p21. If it turned out to be in a memory T population, that would be consistent with data suggesting that there is a potentially pathogenic role for memory T cells.

Dr. Simon agreed that the study's finding that increased risk of dementia was linked to lower, rather than higher, levels of p16 and p21 was the opposite of what was expected.

The authors acknowledge in the paper that some of the results were paradoxical, he said. The bottom line is I wouldn't discount their findings, but I would like to see the results replicated in other studies.

Dr. Marras has received fees for consulting for Acorda Therapeutics, serving on the advisory board of Denali Therapeutics, an honorarium for teaching from EMD Serono, and research contracts from Grey Matter Technologies.

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Working with neurology patients has inspired William Baek, MD, to write and produce songs for two albums. This lifelong musician discusses the added value music brings to his life and how that passion prevents him from feeling burnout.

William Baek, MD, is a clinical associate professor at University of California Riverside; a Fellow of the American Association of Neuromuscular and Electrodiagnostic Medicine; and diplomate of the American Board of Disability Analysts. But when he's not working as a general neurologist in private practice in Upland, CA, you can find him in a music studio, writing and recording songs.

A passionate musician since childhood, he has found inspiration for his songwriting from his patients' experiences. His first album, released in 2018, can be found on YouTube and Spotify. His second album is due out in 2020.

Dr. Baek spoke to Neurology Today about the role music-writing has played in his practice and life. His comments are edited and excerpted below.

I started playing the piano at age 10. Initially the lessons were my mom's ideashe plays the piano wellbut I loved music and really took to it. I was born in the United States, but my family moved to Seoul, Korea, when I was nine and then returned to the States when I was 26, and it was in Korea where I learned to play the piano.

As a pre-medical student, I also took up the trombone. I had always wanted to play a brass instrument, and initially I thought about the trumpet, but I found the trombone interesting because it's almost like singing. You have to have a good sense of pitch because you can play multiple notes in the same position.

I loved music so much that while I was in college, I thought that I wanted to become a singer and a rock star, but back where I come from in Korea, if you want to go into the entertainment business, you say goodbye to college. I was already a pre-med student, so I thought I should finish that. But I played lead trombone in our medical school orchestra, and while I was taking the bus home at midnight after studying in the medical school library, I would write songs.

There wasn't a lot of time for that, but I did do one fun project. My uncle was a producer with a record label, and he had a song that they wanted to be sung in many different languages. Since I'm bilingual in Korean and English, I translated the song into Korean. Translating lyrics isn't as easy as it soundsyou can't just do a direct translation. You have to make the translation work as a song. I had listened to enough Korean music that I could do that. Then one of my co-residents and I recorded the song in Korean for my uncle's label. It was a typical love song, but my uncle put a good pop-catchy spin on the arrangement that was totally amazing. I still have that CD at home.

But other than that, during my residency and fellowship my musical interests went on the back burner. I got married and we had children, and while I took a couple of voice lessons, there wasn't much time.

In 2012, I had gone into private practice and had a little more room to breathe. Recording an album of my own was my dream, but I wanted to learn how to sing more professionally first. So every Thursday at lunchtime I'd rush out of clinic, grab a sandwich, and drive to a 30-minute voice lesson. After I had been doing that for several years, all the time writing songs, one of the ICU nurses at a hospital where I work, who sings semi-professionally, introduced me to Stephan de Reine, a producer with GRA music group. Once I met him I realized that my dream could come true. I began working with himI write the melody and the lyrics, and he does all the arranging. In January 2018 I released my first album on his label.

During my rotations, I often hear very poignant stories that aren't really something I could put into scientific papers. I want other people to hear our patients' stories about their life experiences, so that maybe I can raise awareness and also maybe reach out to people who are experiencing these conditions so that they can be comforted.

Nowadays I listen to a lot of music that is a bit superficial, and I want to talk about more serious topics. The songs on my first album are about Alzheimer's and Parkinson's, there's a song about myasthenia, and a song about multiple sclerosis, Walk Again. Another song, Chained to a Dream, is about stroke. My father experienced a stroke back in 1996 and I wanted to write about what that was like. The songs don't have medical terminology or lingo, I've kept them abstract so that people who don't have these medical conditions can relate to them as well. I can't compete with Ariana Grande or Taylor Swift, but I could find my own niche, and I think this is a good niche for me.

I clearly remember when this first occurred to me. It was 2005, and I was a neuromuscular fellow at the University of California, San Diego. My mentor and I were treating patients with amyotrophic lateral sclerosis (ALS), and I thought, Maybe I could write a song that could express musically some of what they are experiencing. That song is also on my album, and it was my first song inspired by a patient.

They're always very interestedthey want to follow my YouTube channel and find out where they can get the album. Naturally, the patients gravitate toward the songs that describe their illness in particular. I recently heard from one patient and it was particularly heartwarming. She is a full-time pharmacist who has MS. She's a wonderful patient advocate and an example of how people can overcome illness. She told me, When I have a bad day, I listen to your song and it makes me feel so much better. That made me feel that I've already achieved what I wanted to do.

He's a man of few words, so it was hard for me to try to get into his brain and describe the illness. But when my mom heard it, she was like Aha! She thought it really described the struggle of the person, and their relationship to their caregiver. Some people might find it depressing, but for others, it's cathartic. I wrote the album to help heal my patients, but I think it's healed me.

The second album was completed at the end of December 2019, but there have been problems with releasing it. I went to record in France with my producer last June, but then there were strikes and some delays. It should be coming out this year, and it will include some more songs inspired by medical conditions. I see a significant pediatric population, and I wrote a song about life with ADHD called Free Wheeling. Although I don't have ADHD, I did feel a lot of stress under the school system in Korea to conform. I had to fit the norm and the social structure, but I had my ideas and my own person. The school wouldn't budge, and they wanted to treat each child uniformly in a mechanical way, which is something like the way society seems to want to control people with ADHD.

Back in 2018, I sang Walk Again at the MS Walk in Fontana, CA. That was just an amazing experience. I also sang it at a family practice conference held at Disneyland. I'm hoping to sing at another MS Walk this year, and someday I would love to share my songs at the AAN conference.

If you're always invested 100 percent of your waking time in patient care, it's exhausting and monochromatic. We need this variety and variability in our lives, in order to appreciate different things. So many of my friends who are doctors have other talents too, and they should take time for them. We see a lot of burnout, and I tell my colleagues: You were somebody before you became a doctor, and I'm sure you still have other non-medical aspects to your life. People need to explore these other sides of themselves and cultivate them in order to avoid burnout. The more involved I am in music, the happier I am.

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Researchers found in two different studies that blood tests, which indicated abnormally high levels of a tau protein closely linked to dementia due to Alzheimer's disease (AD), distinguished AD from frontotemporal lobar degeneration. In one study, it also predicted which patients who were cognitively normal or had mild cognitive impairment upon initial evaluation would later develop Alzheimer's dementia.

A blood test for Alzheimer's disease (AD) pathology appears to be as accurate as more invasive measures and equally well correlated with AD dementia, according to two studies published simultaneously in the March issue of Nature Medicine.

The studies measured plasma phosphorylated-tau-181 (p-tau181), a form of the tau protein, and found that abnormally high levels are as closely linked to dementia due to AD as are PET scans of amyloid protein and measures of p-tau181 in cerebrospinal fluid.

Not only did a high level of plasma p-tau181 distinguish AD from frontotemporal lobar degeneration, but in one of the studies it also predicted which patients who were cognitively normal or had mild cognitive impairment (MCI) upon initial evaluation would later develop Alzheimer's dementia.

While neurologists and officials at the National Institutes of Health (NIH) applauded the findings, they emphasized that the results need to be replicated and the p-tau181 test further investigated before it can be made available in the neurology clinic.

I think we are still a few years away from having this sort of test available to the general neurologist in a clinic setting or in their office, said Eliezer Masliah, MD, director of the neuroscience at NIH's National Institute on Aging. But they and their patients should know that these less expensive, less invasive tests are coming. We are hopeful that they will be approved in the near future by the FDA.

A longtime AD researcher called the findings a triumph.

I've been in this field since 1980 and having a blood test for Alzheimer's has been one of the holy grails, said Steven T. DeKosky, MD, FAAN, the Aerts-Cosper Professor of Alzheimer's Research at the University of Florida College of Medicine, and associate director of the Florida Alzheimer's Disease Research Center. This is a remarkable accomplishment. Right now, I'm sure all of us who do PET scan studies would love to be able to use this plasma test as a screen.

The principal investigator of one of the two studies told Neurology Today that his group is already working to validate plasma p-tau181 in a primary-care setting and to develop a clinical-grade test that could be used in any laboratory.

The test could be used in patients with either dementia or MCI to improve the diagnostic work-up, especially at specialized clinics and in patients where lumbar puncture or amyloid PET imaging cannot be done, said Oskar Hansson, MD, PhD, professor in the department of clinical memory research at Lund University in Sweden.

Dr. Hansson's group measured plasma p-tau181 levels in three cohorts comprising a total of 589 individuals. The first group included 64 participants who were cognitively unimpaired (with or without a positive amyloid-beta scan), 28 who had MCI, 38 who had AD dementia, and 52 with non-AD neurodegenerative disease. The second cohort, which was followed up for eight years to track conversion to AD dementia, included 219 cognitively unimpaired participants (42 percent of whom were positive for amyloid-beta), and 125 with MCI (65 percent of whom were amyloid-beta positive). A third cohort included pathology from post-mortem tests on 33 individuals:16 had confirmed AD dementia and 47 were non-AD.

The study found a clear association between plasma and CSF levels of p-tau181 in both cohorts one and two (p<0.001). In 174 participants from cohort one, plasma P-tau181 levels predicted positive tau PET scans (area under the curve (AUC) = 0.87-0.91 for different brain regions). Increased plasma p-tau181 was also associated with increased amyloid-beta PET (using a global cortical composite measure) in both cohort one and two (p< 0.001).

In the autopsy-confirmed cohort three, plasma p-tau181 distinguished AD dementia from non-AD neurodegenerative diseases as accurately as did tau PET and CSF p-tau181 (AUC = 0.94-0.98).

The results show that plasma p-tau181 may be increased early in AD, potentially even in some A+ cognitively unimpaired individuals (preclinical AD), the paper reported. Plasma p-tau181 then increased further during the symptomatic (prodromal and dementia) stages of AD. In contrast, plasma p-tau181 was not increased in non-AD. These characteristics mark out plasma p-tau181 as a promising biomarker to track disease progression in AD and to differentiate AD from non-AD conditions, with utility for patient management in clinical practice, research and trials.

In cognitively unimpaired and MCI subjects, a level of p-tau181 above 1.81 pg mL1 at baseline was associated with a dramatically increased risk of future AD dementia (p< 0.001). None of the other plasma biomarkers analyzed in the study, including total tau, amyloid-beta42/amyloid-beta 40 and neurofilament light protein, were independently related to risk of AD dementia.

The second study in Nature Medicine, part of the ongoing Advancing Research and Treatment for Frontotemporal Lobar Degeneration study, was led by Adam L. Boxer, MD, PhD, professor and director of the Alzheimer's Disease and Frontotemporal Degeneration Clinical Trials Program at the University of California, San Francisco, Memory and Aging Center. The cohort of 362 participants includes 69 healthy controls, 47 people with MCI, 56 with clinically diagnosed AD, and the remainder with various forms of frontotemporal lobar degeneration.

Dr. Boxer and colleagues found that plasma p-tau181 was increased by 3.5-fold in AD compared with controls and differentiated AD from both clinically diagnosed (AUC = 0.894) and autopsy-confirmed frontotemporal lobar degeneration (AUC = 0.878). The measure also identified individuals who were amyloid-beta positive on PET scans regardless of clinical diagnosis and correlated with cortical tau protein deposition measured by 18F-flortaucipir PET.

As promising as the results were, Dr. Boxer told Neurology Today that his group is looking at the predictive value of other variants of phosphorylated tau.

We and others think that while plasma p-tau181 seems to be very useful, it's possible there may be other epitopes that may be even slightly more accurate, he said.

Both papers credited a 2018 study published in Alzheimer's & Dementia as the first to find that plasma p-tau181 increases with AD clinical severity and is associated with tau- and amyloid-PET scans. The first author of that study said that she still wants to see the results replicated in more diverse cohorts before the test becomes available outside of research trials.

The fact that these two studies both nicely complement each other and replicate our findings is really promising, said Michelle M. Mielke, PhD, professor of epidemiology and neurology at the Mayo Clinic. But I would like to see more replication in community-based studies rather than just in studies from memory clinics.

Her 2018 study, part of the ongoing Mayo Clinic Study of Aging, is now looking not only at plasma p-tau181 but also at plasma p-tau217.

Previously there weren't the technologies available to look at [p-tau] 217, she said. Historically, p-tau181 was the first to come out, and so that tended to be the focus. Which one is more accurate is still to be determined. And other phosphorylated tau fragments are also being looked at as well.

Two studies, which were published last year, analyzed data from the Framingham Heart Study and found that total tau in serum is a biomarker not only for dementia but also for stroke risk.

We wanted to also look at phosphorylated tau in plasma but at the time the measures were not sensitive enough, said the senior author of both studies, Sudha Seshadri, MD, FAAN, professor of neurology at Boston University School of Medicine and founding director of the Glenn Biggs institute for Alzheimer's & Neurodegenerative Diseases at UT Health San Antonio.

Total tau was a very good marker in our hands for all types of dementia and stroke risk. But it does seem that total tau is sensitive but perhaps not as specific. It seems to go up with a variety of insults to the brain.

Based on the two new papers, she said, plasma P-tau181 looks to be more specific for AD dementia.

Dr. Seshadri will be measuring plasma p-tau181 in the Framingham Study to see how it compares in a community setting. I would also like to see how it works in Hispanics in south Texas, in the African-American population, and in other groups, she said.

While the new studies involved hundreds of patients, the results still need to be replicated in far larger groups, Dr. Masliah said. NIA, which supported both studies in part, will likely fund such follow-up studies in its consortium of 32 AD centers.

What we're looking into is pulling samples from all those centers so they can be tested and verified by other technologies and then followed longitudinally, Dr. Masliah said. These are very, very exciting results, very important results, something we need to follow up on. If replicated in larger, more diverse cohorts, the plasma ptau181 test could be a game changer for clinical trials, he said.

Dr. Hansson has received research support (for his institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, and Euroimmun. He has received consultancy/speaker fees from Biogen and Roche. Dr. Boxer has served as a consultant for Aeton, Abbvie, Alector, AGTC, Amgen, Arkuda, Arvinas, Asceneuron, Esai, Ionis, Lundbeck, Novartis, Passage BIO, Sangamo, Samumed, Third Rock, Toyama and UCB. He has received research support from Avid, Biogen, BMS, C2N, Cortice, Eisai, Eli Lilly, Forum, Genentech, Janssen, Novartis, Pfizer, Roche, and TauRx.

Read more here:
A Blood Test for Tau Is Consistent with PET and CSF... : Neurology Today - LWW Journals

Clinicians from Henry Ford Health System in Detroit, Michigan, have reported the first presumptive case of acute necrotizing hemorrhagic encephalopathy associated with COVID-19.

"As the number of patients with COVID-19 increases worldwide, clinicians and radiologists should be watching for this presentation among patients presenting with COVID-19 and altered mental status," the clinicians advise in a report published online March 31 in Radiology.

"This is significant for all providers to be aware of and looking out for in [COVID-19] patients who present with an altered level of consciousness. This complication is as devastating as severe lung disease," Elissa Fory, MD, a neurologist with Henry Ford who was part of the team of medical experts that made the diagnosis, said in a statement.

"We need to be thinking of how we're going to incorporate patients with severe neurological disease into our treatment paradigm," Fory added.

Brent Griffith, MD, radiologist with Henry Ford and senior author of the case report, said the case shows "the important role that imaging can play in COVID-19 cases."

The 58-year-old woman presented with a 3-day history of fever, cough, and muscle aches symptoms consistent with COVID-19. She was transported by ambulance to the emergency department and showed signs of confusion, lethargy, and disorientation.

The woman tested negative for influenza, but a rapid COVID-19 test confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) infection. She was later diagnosed with acute hemorrhagic necrotizing encephalopathy.

"The team had suspected encephalitis at the outset, but then back-to-back CT and MRI scans made the diagnosis," Fory said in the statement.

Noncontrast head CT revealed "symmetric hypoattenuation within the bilateral medial thalami with a normal CT angiogram and CT venogram," the team reports in their article. Brain MRI showed "hemorrhagic rim enhancing lesions within the bilateral thalami, medial temporal lobes, and subinsular regions."

The patient was started on intravenous immunoglobulin but not high-dose steroids, because of concern for respiratory compromise. As of April 1, the patient was hospitalized in serious condition. Henry Ford Hospital has not provided an update.

Acute necrotizing encephalopathy (ANE) is a rare complication of viral infections, but until now, it has not been known to have occurred as a result of COVID-19 infection. ANE has been associated with intracranial "cytokine storms," and a recent report in the Lancet suggested that a subgroup of patients with severe COVID-19 might develop a cytokine storm syndrome.

Commenting for Medscape Medical News, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University in St. Louis, Missoui, said, "Since this is just one report of one patient, the findings are the most preliminary we can conceive, and more research is needed to determine the extent to which COVID-19 may affect the central nervous system."

Fory, Griffith, and Raji have disclosed no relevant financial relationships.

Radiology. Published online March 31, 2020. Full text

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First Case of Encephalitis Linked to COVID-19 Reported - Medscape

Coronavirus science and news

A woman who tested positive for COVID-19 developed a rare brain disease known as acute necrotizing encephalopathy, a condition that can be triggered by viral infections like influenza and herpes.

At this point, the brain damage "has yet to be demonstrated as a result of COVID-19 infection," according to a case report published March 31 in the journal Radiology. However, as the novel coronavirus continues to spread, "clinicians and radiologists should be watching for this presentation among patients presenting with COVID-19 and altered mental status," the authors wrote.

"We need to be thinking of how were going to incorporate patients with severe neurological disease into our treatment paradigm," Dr. Elissa Fory, a Henry Ford neurologist who was part of the team of medical experts involved in making the diagnosis, said in a statement. "This complication is as devastating as severe lung disease."

The woman, a 58-year-old airline worker, checked into the Henry Ford Health System in Detroit, after having a fever, cough (known coronavirus symptoms) and "altered mental status" for three days, the report noted. At the hospital, the woman appeared confused, lethargic and disoriented, the statement noted. She tested negative for influenza, herpes, Varicella zoster virus (which causes chickenpox) and West Nile virus; and her cerebrospinal fluid, which saturates the brain and spinal cord, contained no trace of bacterial infection.

Noting her symptoms, the doctors also tested the patient for COVID-19 using a diagnostic test provided by the U.S. Centers for Disease Control and Prevention (CDC), and found that she tested positive for the disease.

Related: 10 deadly diseases that hopped across species

CT scans of the woman's brain revealed symmetrical tissue damage in the thalamus a structure buried in the center of the brain that helps relay sensory information from the body to the rest of the organ, according to BrainFacts.org. These damaged areas appeared darker on the woman's CT scan than they did in a scan of a healthy brain, meaning they were less dense than usual, according to an explanation of radiological terms from St. Vincent's University Hospital. Brain regions can become less dense when due to edema, when excess fluid floods the tissue after injury, or necrosis, when cells making up the tissue die off in large quantities, the case study authors noted.

The doctors gathered additional scans of the woman's brain using MRIs (magnetic resonance imaging) and examined them to find evidence that the patient had suffered a hemorrhage, or bleeding from a ruptured blood vessel. They again found damage in the thalamus, as well as in portions of the wrinkled cerebral cortex and in brain regions that lie just below its folds. The doctors diagnosed the woman with acute necrotizing encephalopathy, which, if left untreated, can progress to cause "coma, liver problems and neurological deficits," according to The National Institutes of Health's Genetic and Rare Disease Information Center (GARD).

"The team had suspected encephalitis at the outset, but then back-to-back CT and MRI scans made the diagnosis," Fory said.

The rare condition develops most commonly after a viral infection, such as those caused by influenza A, influenza B and the human herpes virus 6, according to GARD. These infections can trigger a so-called cytokine storm in the brain, when inflammatory substances that normally help the body fight off disease instead go haywire and damage the infected tissue, the case report authors noted. Cytokine storms break down the tissue that surrounds blood vessels in the brain, known as the blood-brain barrier, and can thus lead to hemorrhage, they wrote.

Although the doctors could not directly demonstrate that COVID-19 triggered the woman's unusual brain disease, a recent report in the journal the Lancet suggests that a subset of infected patients appear vulnerable to brain-bound cytokine storms. In addition, a case report published in the Cureus Journal of Medical Science described a 74-year-old patient with both COVID-19 and signs of encephalopathy.

It should be noted that "elderly patients with chronic conditions are at an increased risk of altered mental status in the setting of acute infections," the authors of the Cureus paper wrote. At this point, the potential neurological symptoms of COVID-19 are not well understood, but they should be further investigated in infected patients, they added. Altered mental status might even serve as an early symptom of COVID-19 in some people, they said.

"If patients with neurological conditions are not considered to have COVID-19, this may present a nationwide issue to health care team members treating patients and in turn the general public if they are discharged and further exposed to other people," the Cureus authors noted.

Originally published on Live Science.

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Woman with COVID-19 developed a rare brain condition. Doctors suspect a link. - Live Science