Chapter 5. The Sensorimotor System

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By Ferris Jabr To hear more audio stories from publications like The New York Times, download Audm for iPhone or Android. On the evening of Oct. 10, 2006, Dennis DeGray’s mind was nearly severed from his body. After a day of fishing, he returned to his home in Pacific Grove, Calif., and realized he had not yet taken out the trash or recycling. It was raining fairly hard, so he decided to sprint from his doorstep to the garbage cans outside with a bag in each hand. As he was running, he slipped on a patch of black mold beneath some oak trees, landed hard on his chin, and snapped his neck between his second and third vertebrae. While recovering, DeGray, who was 53 at the time, learned from his doctors that he was permanently paralyzed from the collarbones down. With the exception of vestigial twitches, he cannot move his torso or limbs. “I’m about as hurt as you can get and not be on a ventilator,” he told me. For several years after his accident, he “simply laid there, watching the History Channel” as he struggled to accept the reality of his injury. Some time later, while at a fund-raising event for stem-cell research, he met Jaimie Henderson, a professor of neurosurgery at Stanford University. The pair got to talking about robots, a subject that had long interested DeGray, who grew up around his family’s machine shop. As DeGray remembers it, Henderson captivated him with a single question: Do you want to fly a drone? Henderson explained that he and his colleagues had been developing a brain-computer interface: an experimental connection between someone’s brain and an external device, like a computer, robotic limb or drone, which the person could control simply by thinking. DeGray was eager to participate, eventually moving to Menlo Park to be closer to Stanford as he waited for an opening in the study and the necessary permissions. In the summer of 2016, Henderson opened DeGray’s skull and exposed his cortex — the thin, wrinkled, outermost layer of the brain — into which he implanted two 4-millimeter-by-4-millimeter electrode arrays resembling miniature beds of nails. Each array had 100 tiny metal spikes that, collectively, recorded electric impulses surging along a couple of hundred neurons or so in the motor cortex, a brain region involved in voluntary movement. © 2022 The New York Times Company

Keyword: Robotics
Link ID: 28326 - Posted: 05.14.2022

By Laura Sanders Deep in the human brain, a very specific kind of cell dies during Parkinson’s disease. For the first time, researchers have sorted large numbers of human brain cells in the substantia nigra into 10 distinct types. Just one is especially vulnerable in Parkinson’s disease, the team reports May 5 in Nature Neuroscience. The result could lead to a clearer view of how Parkinson’s takes hold, and perhaps even ways to stop it. The new research “goes right to the core of the matter,” says neuroscientist Raj Awatramani of Northwestern University Feinberg School of Medicine in Chicago. Pinpointing the brain cells that seem to be especially susceptible to the devastating disease is “the strength of this paper,” says Awatramani, who was not involved in the study. Parkinson’s disease steals people’s ability to move smoothly, leaving balance problems, tremors and rigidity. In the United States, nearly 1 million people are estimated to have Parkinson’s. Scientists have known for decades that these symptoms come with the death of nerve cells in the substantia nigra. Neurons there churn out dopamine, a chemical signal involved in movement, among other jobs (SN: 9/7/17). But those dopamine-making neurons are not all equally vulnerable in Parkinson’s, it turns out. “This seemed like an opportunity to … really clarify which kinds of cells are actually dying in Parkinson’s disease,” says Evan Macosko, a psychiatrist and neuroscientist at Massachusetts General Hospital in Boston and the Broad Institute of MIT and Harvard. © Society for Science & the Public 2000–2022.

Keyword: Parkinsons
Link ID: 28320 - Posted: 05.07.2022

Perspective by Susan Berger As I faced a prophylactic double mastectomy in hopes of averting cancer, I had many questions for my surgeons — one of which was about pain. I was stunned when both my breast surgeon and plastic surgeon said that a nerve block would leave me pain-free for about three days, after which the worst of the pain would be over. Pectoralis nerve (PECS) blocks were developed to provide analgesia or pain relief for chest surgeries, including breast surgery. That is what happened. I went through the mastectomy Dec. 1 after learning I had the PALB2 gene mutation that carried a sharply elevated risk of breast cancer as well as a higher risk of ovarian and pancreatic cancers. I also had my fallopian tubes and ovaries removed in July. I had learned about the gene mutation in April 2021, when one of my daughters found out she was a carrier. As a 24-year breast cancer survivor and longtime health reporter, I was astonished that I had heard nothing about this mutation. I researched it and wrote “This Breast Cancer Gene Is Less Well Known, but Nearly as Dangerous” in August. After the double mastectomy, I also wrote about it for The Washington Post. Just as my surgeons at NorthShore University HealthSystem predicted, I was released from the hospital the same day as my surgery and remarkably pain-free. I took one Tramadol (a step down from stronger medications containing codeine) when I got home — only because it was suggested I take one pill. As I recovered, I only took Advil and Tylenol. The opioid epidemic is a major public health issue in the United States and nerve blocks could be a solution. According to a study published in the Journal of Clinical Medicine in 2021, 1 in 20 surgical patients will continue to use opioids beyond 90 days. “There is no association with magnitude of surgery, major versus minor, and the strongest predictor of continued use is surgical exposure,” the study states. © 1996-2022 The Washington Post

Keyword: Pain & Touch; Drug Abuse
Link ID: 28316 - Posted: 05.07.2022

By Jim Robbins TUCSON, Ariz. — In a small room in a building at the Arizona-Sonora Desert Museum, the invertebrate keeper, Emma Califf, lifts up a rock in a plastic box. “This is one of our desert hairies,” she said, exposing a three-inch-long scorpion, its tail arced over its back. “The largest scorpion in North America.” This captive hairy, along with a swarm of inch-long bark scorpions in another box, and two dozen rattlesnakes of varying species and sub- species across the hall, are kept here for the coin of the realm: their venom. Efforts to tease apart the vast swarm of proteins in venom — a field called venomics — have burgeoned in recent years, and the growing catalog of compounds has led to a number of drug discoveries. As the components of these natural toxins continue to be assayed by evolving technologies, the number of promising molecules is also growing. “A century ago we thought venom had three or four components, and now we know just one type of venom can have thousands,” said Leslie V. Boyer, a professor emeritus of pathology at the University of Arizona. “Things are accelerating because a small number of very good laboratories have been pumping out information that everyone else can now use to make discoveries.” She added, “There’s a pharmacopoeia out there waiting to be explored.” It is a striking case of modern-day scientific alchemy: The most highly evolved of natural poisons on the planet are creating a number of effective medicines with the potential for many more. One of the most promising venom-derived drugs to date comes from the deadly Fraser Island funnel web spider of Australia, which halts cell death after a heart attack. Blood flow to the heart is reduced after a heart attack, which makes the cell environment more acidic and leads to cell death. The drug, a protein called Hi1A, is scheduled for clinical trials next year. In the lab, it was tested on the cells of beating human hearts. It was found to block their ability to sense acid, “so the death message is blocked, cell death is reduced, and we see improved heart cell survival,” said Nathan Palpant, a researcher at the University of Queensland in Australia who helped make the discovery. © 2022 The New York Times Company

Keyword: Pain & Touch; Neurotoxins
Link ID: 28315 - Posted: 05.04.2022

Ellen Phiddian Tricyclic antidepressants have long been known to have more than one purpose: among other things, they can alleviate pain – particularly nerve pain. Recent research has finally established why these tricyclic antidepressants (TCAs) can help with nerve pain. The discovery could lead to the rapid development of pain relief medications that don’t include the side effects of TCAs. Nerve pain comes from a variety of sources – including cancer, diabetes, trauma, multiple sclerosis, and infections. These treatments could address a range of different types of nerve pain. It turns out the drugs inhibit a key protein in our nerves, called an N-type calcium channel. These N-type calcium channels are shaped like tiny gates, allowing positively charged calcium ions, or Ca2+, through them. This helps with the transmission of pain signals in the body. Researchers have long been keen to find things that “close” the gate of these calcium channels because that’s likely to have analgesic effects. Adjunct Professor Peter Duggan, a researcher with the CSIRO and senior collaborator on the project, says that he and his colleagues initially stumbled across TCAs from a very different direction: they were investigating the toxins of venomous marine cone snails. “A few of the components in that toxin are actually painkillers and they block these calcium ion channels very, very effectively,” says Duggan. The cone snail toxin has the potential to be very dangerous to people, as well as needing to be administered in an impractical way, so the researchers started looking at similar compounds that might have some of the same properties.

Keyword: Pain & Touch; Depression
Link ID: 28312 - Posted: 05.04.2022

By Helen Ouyang After an hour-and-a-half bus ride last November, Julia Monterroso arrived at a white Art Deco building in West Hollywood, just opposite a Chanel store and the Ivy, a restaurant famous for its celebrity sightings. Monterroso was there to see Brennan Spiegel, a gastroenterologist and researcher at Cedars-Sinai who runs one of the largest academic medical initiatives studying virtual reality as a health therapy. He started the program in 2015 after the hospital received a million-dollar donation from an investment banker on its board. Spiegel saw Monterroso in his clinic the week before and thought he might be able to help alleviate her symptoms. Monterroso is 55 and petite, with youthful bangs and hair clipped back by tiny jeweled barrettes. Eighteen months earlier, pain seized her lower abdomen and never went away. After undergoing back surgery in September to treat a herniated disc — and after the constant ache in her abdomen worsened — she had to stop working as a housecleaner. Eventually, following a series of tests that failed to reveal any clear cause, she landed in Spiegel’s office. She rated her pain an 8 on a 10-point scale, with 10 being the most severe. Chronic pain is generally defined as pain that has lasted three months or longer. It is one of the leading causes of long-term disability in the world. By some measures, 50 million Americans live with chronic pain, in part because the power of medicine to relieve pain remains woefully inadequate. As Daniel Clauw, who runs the Chronic Pain and Fatigue Research Center at the University of Michigan, put it in a 2019 lecture, there isn’t “any drug in any chronic-pain state that works in better than one out of three people.” He went on to say that nonpharmacological therapy should instead be “front and center in managing chronic pain — rather than opioids, or for that matter, any of our drugs.” Virtual reality is emerging as an unlikely tool for solving this intractable problem. The V.R. segment in health care alone, which according to some estimates is already valued at billions of dollars, is expected to grow by multiples of that in the next few years, with researchers seeing potential for it to help with everything from anxiety and depression to rehabilitation after strokes to surgeons strategizing where they will cut and stitch. In November, the Food and Drug Administration gave authorization for the first V.R. product to be marketed for the treatment of chronic pain. © 2022 The New York Times Company

Keyword: Pain & Touch; Vision
Link ID: 28304 - Posted: 04.27.2022

By Brittany Shammas and Timothy Bella William Husel, an Ohio doctor who was accused of killing 14 patients with what prosecutors described as “wildly excessive” doses of fentanyl between 2015 and 2018, was acquitted on all counts of murder Wednesday, concluding one of the most significant murder cases of its kind against a health-care professional. Husel, a onetime physician of the year trained at the Cleveland Clinic, faced one count of murder for each of the 14 critically ill patients he was accused of killing. The jury deliberated for seven days before finding him not guilty on all 14 counts in what was one of the largest murder trials in Ohio history. He had been charged with causing or hastening their deaths amid a period of lax oversight of fentanyl at Mount Carmel West, a Catholic hospital in Columbus. Husel would have faced life in prison with just one guilty verdict. While the synthetic opioid is significantly more powerful than morphine and has wreaked havoc on American streets, it can provide pain relief in medical settings that is crucial to end-of-life care. The alleged victims in the Ohio case suffered critical medical conditions including overdoses, cancer, strokes and internal bleeding. Prosecutors acknowledged that all were being kept alive on ventilators and that many of them were dying. “In truth, William Husel was an innocent man, and thank goodness the justice system prevailed,” Jose Baez, one of Husel’s defense attorneys, told reporters. The 46-year-old’s acquittal came after a two-month trial that triggered a debate on end-of-life medical care. Husel and Baez argued in the trial that the doctor offered comfort care for dying patients and was not trying to kill them. They pointed out that the doctor’s actions did not occur in secret — nurses were the ones to administer the doses — and alleged that hospital officials made Husel the villain after realizing the systemic failures at play. The fallout over the allegations at Mount Carmel West had repercussions: the firing of 23 employees; the resignation of the hospital’s chief executive, chief clinical officer and chief pharmacy officer; and Medicare and Medicaid funding for the institution was put in jeopardy. © 1996-2022 The Washington Post

Keyword: Pain & Touch; Drug Abuse
Link ID: 28297 - Posted: 04.23.2022

Liam Drew James Johnson hopes to drive a car again one day. If he does, he will do it using only his thoughts. In March 2017, Johnson broke his neck in a go-carting accident, leaving him almost completely paralysed below the shoulders. He understood his new reality better than most. For decades, he had been a carer for people with paralysis. “There was a deep depression,” he says. “I thought that when this happened to me there was nothing — nothing that I could do or give.” But then Johnson’s rehabilitation team introduced him to researchers from the nearby California Institute of Technology (Caltech) in Pasadena, who invited him to join a clinical trial of a brain–computer interface (BCI). This would first entail neurosurgery to implant two grids of electrodes into his cortex. These electrodes would record neurons in his brain as they fire, and the researchers would use algorithms to decode his thoughts and intentions. The system would then use Johnson’s brain activity to operate computer applications or to move a prosthetic device. All told, it would take years and require hundreds of intensive training sessions. “I really didn’t hesitate,” says Johnson. The first time he used his BCI, implanted in November 2018, Johnson moved a cursor around a computer screen. “It felt like The Matrix,” he says. “We hooked up to the computer, and lo and behold I was able to move the cursor just by thinking.” Johnson has since used the BCI to control a robotic arm, use Photoshop software, play ‘shoot-’em-up’ video games, and now to drive a simulated car through a virtual environment, changing speed, steering and reacting to hazards. “I am always stunned at what we are able to do,” he says, “and it’s frigging awesome.” © 2022 Springer Nature Limited

Keyword: Brain imaging; Robotics
Link ID: 28292 - Posted: 04.20.2022

ByKelly Servick An experimental pain drug that may offer an alternative to opioids has shown promise in two small clinical trials for acute pain, its developer announced today. Vertex Pharmaceuticals’s compound, called VX-548, outperformed a placebo in phase 2 trials for two types of postsurgical pain, the company said in a press release. The results pave the way for larger trials that could lead to regulatory approval. “This is a major advance in the effort to supersede opioids,” says John Wood, a neurobiologist at University College London who has studied the cellular channel that VX-548 targets. “These results are terrific, and the side effect profile is very good.” Opioids are powerful pain relievers, but they can cause side effects including slowed breathing, and they come with the potential for addiction. An epidemic of overdose deaths has prompted a hunt for safer alternatives. The new trials grew out of research into sodium channels on the surface of pain-sensing neurons, which let them fire electrical signals. One such channel, called Nav1.8, is crucial to relaying pain signals to the spinal cord from nerves throughout the body. People with genetic mutations that make Nav1.8 hyperactive can suffer pain even in the absence of injury. But relieving pain by blocking either Nav1.8 or another channel, Nav1.7, has proved difficult. One issue is their structure closely resembles those of other sodium channels, which regulate vital functions in the heart, muscles, and brain. To be safe, a compound needs to target the channel of interest and not accidentally target these other, critical channels. Vertex has spent years developing highly specific Nav1.8-blocking drugs, but it has abandoned previous candidates before they reached pivotal phase 3 trials. One drug, known as VX-150, succeeded in three phase 2 clinical studies but never advanced to larger ones, in part because its high dose might be impractical for clinical use. “We wanted to have higher potency,” explains Vertex Chief Scientific Officer David Altshuler. © 2022 American Association for the Advancement of Science.

Keyword: Pain & Touch
Link ID: 28265 - Posted: 04.02.2022

By Lisa Sanders, M.D. The 51-year-old man sat at his desk preparing for his next online meeting when he suddenly became aware of a familiar stiffness and exhaustion. Had he slept badly? Or was this the beginning of one of his strange episodes? As the symptoms worsened, he had his answer. He knew that when he started to feel this way, the only recourse was to get into bed before he got any weaker. As he made his way slowly down the hall, his legs felt heavy, as if he were wearing ankle weights. Just lifting them was real work. He passed his wife’s home office without a word. She knew just from looking at him that he would probably have to spend the rest of the day in bed. For much of their 30-year marriage, he had these strange spells; he would suddenly feel exhausted and weak and have to lie down. He couldn’t work. He was a software engineer, and any mental exertion was too much for him. Once the fatigue fully set in — maybe after the first hour or so — he couldn’t walk, couldn’t stand, couldn’t even sit up. It was as if his body was totally out of gas, worse than how it felt when he ran a marathon. He would lie in a dark room, too weak to even hold up a book and too tired to think. But by the next morning, he would usually be fine, brimming with energy and enthusiasm, like normal. It was so strange. After more than 20 years, they both had come to expect these episodes. For most of that time, the spells were infrequent, maybe once a month. But recently they became more frequent. The monthly episodes became weekly, then a couple of times a week. They often came, as they did that morning, out of nowhere. Just before leaving his office, he sent an email to the woman he was to meet online. Sorry, he wrote, I’m not feeling well. Could we reschedule? Seeing a Psychiatrist Over the years the man saw many doctors. They had their theories, but so far none panned out. A few were convinced that he had periodic paralysis, a disorder sometimes linked to thyroid disease, where patients become temporarily paralyzed by too much or too little potassium in the bloodstream. But his potassium was always normal, even during these episodes. © 2022 The New York Times Company

Keyword: Pain & Touch
Link ID: 28263 - Posted: 04.02.2022

Allison Whitten Every time you reach for your coffee mug, a neuroscientific mystery takes shape. Moments before you voluntarily extend your arm, thousands of neurons in the motor regions of your brain erupt in a pattern of electrical activity that travels to the spinal cord and then to the muscles that power the reach. But just prior to this massively synchronized activity, the motor regions in your brain are relatively quiet. For self-driven movements like reaching for your coffee, the “go” signal that tells the neurons precisely when to act — instead of the moment just before or after — has yet to be found. In a recent paper in eLife, a group of neuroscientists led by John Assad at Harvard Medical School finally reveals a key piece of the signal. It comes in the form of the brain chemical known as dopamine, whose slow ramping up in a region lodged deep below the cortex closely predicted the moment that mice would begin a movement — seconds into the future. Dopamine is commonly known as one of the brain’s neurotransmitters, the fast-acting chemical messengers that are shuttled between neurons. But in the new work, dopamine is acting as a neuromodulator. It’s a term for chemical messengers that slightly alter neurons to cause longer-lasting effects, including making a neuron more or less likely to electrically communicate with other neurons. This neuromodulatory tuning mechanism is perfect for helping to coordinate the activity of large populations of neurons, as dopamine is likely doing to help the motor system decide precisely when to make a movement. The new paper is one of the latest results to expand our knowledge of the crucial and varied roles that neuromodulators play in the brain. With recent advances in technology, neuroscientists can now view neuromodulators at work in networks that traverse the entire brain. The new findings are overturning some long-held views about these modulators adrift in the brain, and they’re revealing exactly how these molecules allow the brain to flexibly change its internal state amid ever-changing environments. All Rights Reserved © 2022

Keyword: Movement Disorders; Drug Abuse
Link ID: 28251 - Posted: 03.23.2022

Linda Geddes A completely locked-in patient is able to type out words and short sentences to his family, including what he would like to eat, after being implanted with a device that enables him to control a keyboard with his mind. The findings, published in Nature Communications, overturn previous assumptions about the communicative abilities of people who have lost all voluntary muscle control, including movement of the eyes or mouth, as well as giving a unique insight into what it’s like to be in a “locked in” state. Locked-in syndrome – also known as pseudocoma - is a rare condition, where people are conscious and can see, hear, and smell, but are unable to move or speak due to complete paralysis of their voluntary muscles, eg as a result of the progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS). Advertisement Some can communicate by blinking or moving their eyes, but those with completely locked-in syndrome (CLIS) cannot even control their eye muscles. In 2017, doctors at the University of Tübingen in Germany enabled three patients with CLIS to answer “yes” or “no” to questions by detecting telltale patterns in their brain activity, using a technology called functional near-infrared spectroscopy (fNIRS). The advance generated widespread media coverage, and prompted the parents of the current patient, who was diagnosed with ALS in 2015, to write to the medical team, saying he was losing the ability to communicate with his eye movements, and could they help. The problem with using fNIRS to help CLIS patients to communicate is that it is relatively slow, and only gives the correct answer 70% of the time, meaning questions have to be repeated to get a reliable answer. “It was always our goal to enable a patient in a completely locked down state to spell out words, but with a classification accuracy of 70%, it is almost impossible to enable free spelling,” said Dr Ujwal Chaudhary, a biomedical engineer and managing director of ALS Voice gGmbH in Mössingen, Germany, who co-led the research. © 2022 Guardian News & Media Limited

Keyword: ALS-Lou Gehrig's Disease ; Movement Disorders
Link ID: 28250 - Posted: 03.23.2022

By Linda Searing The more fit you are, the less likely you may be to develop Alzheimer’s disease — with those who are the most fit having a 33 percent lower risk for this dementia than the least fit, according to a report to be presented to the American Academy of Neurology at its annual meeting next month. FAQ: What to know about the omicron variant of the coronavirus D.C.-based researchers, from the Washington VA Medical Center and George Washington University, tested and tracked 649,605 veterans (average age 61) for nearly a decade. Based on their cardiorespiratory fitness, participants were divided into five categories, from lowest to highest fitness level. 10-minute exercising may slow progression to dementia for those with mild cognitive impairment The researchers found that, as fitness improved, people’s chances of developing the ailment decreased. Compared with the least-fit group, those slightly more fit had a 13 percent lower risk for Alzheimer’s; the middle group was 20 percent less likely to develop the disease; the next higher group was 26 percent less likely; with the odds reaching a 33 percent lower risk for those in the most-fit group. Alzheimer’s is the most common type of dementia. It is a progressive brain disorder that, over time, destroys memory and thinking skills and interferes with the ability to carry out daily tasks. About 6 million Americans 65 and older have Alzheimer’s. There are no proven ways to cure the disease. © 1996-2022 The Washington Post

Keyword: Alzheimers
Link ID: 28239 - Posted: 03.16.2022

Gabino Iglesias The Man Who Tasted Words is a deep dive into the world of our senses — one that explores the way they shape our reality and what happens when something malfunctions or functions differently. Despite the complicated science permeating the narrative and the plethora of medical explanations, the book is also part memoir. And because of the way the author, Dr. Guy Leschziner, treats his patients — and how he presents the ways their conditions affect their lives and those of the people around them — it is also a very humane, heartfelt book. We rely on vision, hearing, taste, smell, and touch to not only perceive the reality around us but also to help us navigate it by constantly processing stimuli, predicting what will happen based on previous experiences, and filling the gaps of everything we miss as we construct it. However, that truth, the "reality" we see, taste, hear, touch, and smell, isn't actually there; our brains, with the help of our nervous system continuously build it for us. But sometimes our brains or nervous system have a glitch, and that has affects reality. The Man Who Tasted Words carefully looks at — and tries to explain — some of the most bizarre glitches. Sponsor Message "What we believe to be a precise representation of the world around us is nothing more than an illusion, layer upon layer of processing of sensory information, and the interpretation of that information according to our expectations," states Leschziner. When one of those senses doesn't work correctly, that illusion morphs in ways that significantly impact the lives of those whose nervous systems or brain work differently. Paul, for example, is a man who feels no pain. While this sounds like a great "flaw" to have, Leschziner shows it's the opposite. Pain helps humans learn "to avoid sharp or hot objects." It teaches that certain things in our environment are potentially harmful, tells us when we've had an injury and makes us protect it, and even lets us know there's an infection in our body so we can go to the doctor. © 2022 npr

Keyword: Consciousness
Link ID: 28233 - Posted: 03.11.2022

By Jan Hoffman For years, Dr. Xiulu Ruan was one of the nation’s top prescribers of quick-release fentanyl drugs. The medicines were approved only for severe breakthrough pain in cancer patients, but Dr. Ruan dispensed them almost exclusively for more common ailments: neck aches, back and joint pain. According to the Department of Justice, he and his partner wrote almost 300,000 prescriptions for controlled substances from 2011 to 2015, filled through the doctors’ own pharmacy in Mobile, Ala. Dr. Ruan often signed prescriptions without seeing patients, prosecutors said. Dr. Ruan has been serving a 21-year sentence in federal prison, convicted in 2017 for illegally prescribing opioids and related financial crimes. To collect millions of dollars in fines, the government seized houses, beach condos and bank accounts belonging to him and his business partner, as well as 23 luxury cars, such as Bentleys, Lamborghinis and Ferraris. On Tuesday, lawyers both for Dr. Ruan and for Dr. Shakeel Kahn, who is serving 25 years on charges related to pill mill clinics in Arizona and Wyoming will argue before the Supreme Court of the United States that the criminal standard the physicians faced is applied inconsistently among the federal circuits. In asking that the doctors’ convictions be overturned, they want the court to establish a uniform standard that permits doctors to raise a “good faith” defense. Juries could then consider whether doctors subjectively believed they were using their best medical judgment. The likelihood of these two doctors being set free is small, legal experts believe, but the court’s decision on the broader legal questions could have significant implications for the latitude doctors can take in prescribing potentially addictive painkillers and other restricted medications. The cases confront an uneasy relationship between law and medicine. In an era when overdose deaths are soaring, how should the law balance letting physicians exercise their best judgment with stopping egregious outliers? © 2022 The New York Times Company

Keyword: Drug Abuse; Pain & Touch
Link ID: 28226 - Posted: 03.02.2022

By Gina Kolata Dr. John Q. Trojanowski, a neuropathologist whose work was at the forefront of research on Alzheimer’s and other neurodegenerative diseases, died on Feb. 8 in a hospital in Philadelphia. He was 75. His wife and longtime collaborator, Virginia M.-Y. Lee, said the cause was complications of chronic spinal cord injuries. Dr. Trojanowski “was a giant in the field,” said Leslie Shaw, a professor with Dr. Trojanowski in the department of pathology and laboratory medicine at the University of Pennsylvania — adding that he meant that in two ways. At 6 feet 4 inches, Dr. Trojanowski towered over his colleagues. And, Dr. Shaw said, he was also a towering figure in his field, whose scientific contributions were “phenomenal” because they combined pathology and biochemistry to figure out what goes wrong, and why, when people get diseases as disparate as Alzheimer’s, Parkinson’s and A.L.S. The results can lead to improved diagnosis and potential treatments. Key to the work Dr. Trojanowski did with Dr. Lee was their establishment of a brain bank: stored brains from patients with diseases like Alzheimer’s and Parkinson’s, as well as from people without degenerative brain diseases. It allowed them to compare the brains of people with and without the conditions and ask what proteins were involved in the diseases and what brain regions were affected. Among their first quests was an attempt to solve the mystery of strange areas in the brains of people with Alzheimer’s. Known as tangles and first described by Alois Alzheimer himself at the turn of the 20th century, they look like twisted strands of spaghetti in dying nerve cells. In 1991, Dr. Trojanowski and Dr. Lee determined that the regions are made up of a malformed protein called tau, which causes the structure of nerve cells to collapse. At a time when most Alzheimer’s researchers and drug companies were focused on a different protein, amyloid, Dr. Trojanowski and Dr. Lee insisted that tau was equally important. They then discovered that it also played a central role in a rare group of degenerative dementias known as frontotemporal lobar degeneration. © 2022 The New York Times Company

Keyword: Alzheimers; ALS-Lou Gehrig's Disease
Link ID: 28225 - Posted: 03.02.2022

By Amanda Coletta Health officials in New Brunswick released a long-awaited report Thursday into a mysterious and debilitating neurological disorder that has struck dozens of people with bizarre symptoms — including a belief that family members have been replaced by impostors — stumped doctors and stoked fears across the province. The conclusion? There is no new disorder. “The oversight committee has unanimously agreed that these 48 people should never have been identified as having a neurological syndrome of unknown cause, and that based on the evidence reviewed, no such syndrome exists,” said Jennifer Russell, chief medical officer of health for the Canadian province. “Public Health concurs with these findings. But I stress again, this does not mean that these people aren’t seriously ill. It means they are ill with a known neurological condition.” The report’s authors say the 48 cases in what was thought to be a cluster were randomly allocated to pairs of neurologists who reviewed them and presented their findings to an oversight committee of six New Brunswick neurologists and other officials. The committee said none of the cases met the full criteria of the case definition. But that finding, coming at the end of an investigation marred by accusations of opacity from the start and allegations that Canada’s top scientists and experts from around the world had been abruptly shut out of the process, appeared unlikely to assuage alarm in the province and more likely to deepen mistrust. Patients and their family members questioned the committee’s findings Thursday, saying the province has not carried out the relevant testing and opted to “abandon scientific rigor in exchange for political expediency.” © 1996-2022 The Washington Post

Keyword: Stress; Prions
Link ID: 28222 - Posted: 02.26.2022

by Laura Dattaro Some genomic areas that help determine cerebellar size are associated with autism, schizophrenia and bipolar disorder, according to a new study. But heritable genetic variants across the genome that also influence cerebellar size are not. The cerebellum sits at the base of the skull, below and behind the much larger cerebrum. It coordinates movement and may also play roles in social cognition and autism, according to previous research. The new work analyzed genetic information and structural brain scans from more than 33,000 people in the UK Biobank, a biomedical and genetic database of adults aged 40 to 69 living in the United Kingdom. A total of 33 genetic sequence variants, known as single nucleotide polymorphisms (SNPs), were associated with differences in cerebellar volume. Only one SNP overlapped with those linked to autism, but the association should be explored further in other cohorts, says lead investigator Richard Anney, senior lecturer in bioinformatics at Cardiff University in Wales. “There’s lots of caveats to say why it might be worth following up on,” Anney says. “But from this data alone, it’s not telling us there’s a major link between [autism] and cerebellar volume.” So far, cognitive neuroscientists have largely ignored the cerebellum, says Jesse Gomez, assistant professor of neuroscience at Princeton University, who was not involved in the work. The new study represents a first step in better understanding genetic influences on the brain region and its role in neurodevelopmental conditions, he says. “It’s a fun paper,” Gomez says. “It’s the beginning of what’s an exciting revolution in the field.” Of the 33 inherited variants Anney’s team found, 5 had not previously been significantly associated with cerebellar volume. They estimated that the 33 variants account for about 50 percent of the differences in cerebellar volume seen across participants. © 2022 Simons Foundation

Keyword: Autism; Genes & Behavior
Link ID: 28215 - Posted: 02.23.2022

Linda Geddes A simple test could end years of uncertainty for people with relatively common neurological conditions, new research has found. Historically, obtaining a definitive diagnosis for conditions including Huntingdon’s disease and some forms of amyotrophic lateral sclerosis has been difficult, because, although the cause of the symptoms is genetic, knowing which test to carry out has resulted in delays of many years. Now, a new study suggests that whole genome sequencing (WGS) can quickly and accurately detect the most common inherited neurological disorders, and could be implemented in routine clinical practice with immediate effect. “It is very exciting because it opens up the vista of a test that could end the diagnostic odyssey for many patients,” said Prof Sir Mark Caulfield from Queen Mary University of London and former chief scientist at Genomics England. “This work paves the way for this to be implemented immediately within the NHS.” WGS is already offered to people in England with rare disorders or childhood cancers through the NHS Genomic Medicine Service. However, the technique wasn’t thought to work on people with ‘repeat expansion disorders’ caused by the insertion of short repetitive chunks of DNA into the genetic code – in some cases, stretching across long distances – because they can be difficult to quantify. Such disorders are relatively common, affecting around one in 3,000 people, and include neurodegenerative and movement disorders such as Fragile X syndrome, Huntington’s disease, Friedreich’s ataxia, and some forms of amyotrophic lateral sclerosis or frontal lobe dementia. © 2022 Guardian News & Media Limited

Keyword: Huntingtons; Genes & Behavior
Link ID: 28210 - Posted: 02.19.2022

By Jan Hoffman The federal government on Thursday proposed new guidelines for prescribing opioid painkillers that remove its previous recommended ceilings on doses for chronic pain patients and instead encourage doctors to use their best judgment. But the overall thrust of the recommendations was that doctors should first turn to “nonopioid therapies” for both chronic and acute pain, including prescription medications like gabapentin and over-the-counter ones like ibuprofen, as well as physical therapy, massage and acupuncture. Though still in draft form, the 12 recommendations, issued by the Centers for Disease Control and Prevention, are the first comprehensive revisions of the agency’s opioid prescribing guidelines since 2016. They walk a fine line between embracing the need for doctors to prescribe opioids to alleviate some cases of severe pain while guarding against exposing patients to the well-documented perils of opioids. Dr. Samer Narouze, president of the American Society of Regional Anesthesia and Pain Medicine, an association of clinicians, praised the tone, level of detail and focus of the project. “It’s a total change in the culture from the 2016 guidelines,” he said, characterizing the earlier edition as ordering doctors to “just cut down on opioids — period.” By contrast, the new proposal “has a much more caring voice than a policing one, and it’s left room to preserve the physician-patient relationship,” added Dr. Narouze, chairman of the Center for Pain Medicine at Western Reserve Hospital in Cuyahoga Falls, OH. The 229-page document warns of addiction, depressed breathing, altered mental status and other dangers associated with opioids, but it also notes that the drugs serve an important medical purpose, especially for easing the immediate agony from traumatic injuries such as burns and crushed bones. In those instances when opioids seem the way to go, the recommendations said, doctors should start with the lowest effective dose and prescribe immediate-release pills rather than long-acting ones. © 2022 The New York Times Company

Keyword: Drug Abuse; Pain & Touch
Link ID: 28207 - Posted: 02.16.2022