Monday Pharmaceutical Mystery: What Medication May Be Causing Neurological Symptoms? – Pharmacy Times

Monday Pharmaceutical Mystery: What Medication May Be Causing Neurological Symptoms?

She has been in the hospital for 5 days and during that time the doctors did all the expensive tests looking for blood clots, ischemia,inflammation, infection, and malignancies in the brain andnervoussystem. But they find nothing. The doctor says he is at a loss to what is causing JKs symptoms.

As the pharmacist for the team, you review JKs medications, and the dosages according to her weight of 86 kg and renal function of eCrCl of 45 ml/min.

Mystery: Which is the medication dose you want to lower and why?

Solution: Gabapentin. JK had a decline in renal function, as verified by changes in SrCr, and that caused gabapentin to accumulate to toxic levels. JK will need a new lower dose to stay symptom-free.Renal disease for gabapentin are as follows: eCrCl 30-59ml/min 700mg bid, eCrCl 15-29 ml/min 700mg qd, eCrCl <15 ml/min 300mg/day.1

Drug levels for gabapentin can easily accumulate and reach toxic levels when renal function declines or when the recommended dosage is exceeded. I believe this is an under recognized problem that can be easily addressed by pharmacists.2

REFERENCES

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Monday Pharmaceutical Mystery: What Medication May Be Causing Neurological Symptoms? - Pharmacy Times

Interventional Neurology Device Market Outlook, Recent Trends and Growth Forecast 2020-2025 – The Research Process

Latest update on Interventional Neurology Device Market Analysis report published with an extensive market research, Interventional Neurology Device market growth analysis and Projection by 2025. this report is highly predictive as it holds the over all market analysis of topmost companies into the Interventional Neurology Device industry. With the classified Interventional Neurology Device market research based on various growing regions this report provide leading players portfolio along with sales, growth, market share and so on.

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Treatment of Cerebral Aneurysms, Treatment of Cerebral Vasospasm and Vertebroplasty

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Embolization & coiling and Neurothrombectomy Devices

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Wave Life Sciences to Highlight Preclinical ADAR Editing Data and Neurology Programs at TIDES and OTS Annual Meetings – GlobeNewswire

CAMBRIDGE, Mass., Sept. 15, 2020 (GLOBE NEWSWIRE) -- Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage genetic medicines company committed to delivering life-changing treatments for people battling devastating diseases, announced today that it will highlight its ADAR (adenosine deaminases acting on RNA)-mediated RNA editing technology (ADAR editing) and its neurology programs in Huntingtons disease (HD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) at upcoming conferences, including the TIDES: Oligonucleotide and Peptide Therapeutics 2020 meeting and the 16th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS), taking place on September 15-18, 2020 and September 27-30, 2020, respectively.

At TIDES and OTS, Wave will share how it is developing ADAR editing as a potentially best-in-class RNA editing approach with applicability across multiple genetic diseases. Notably, one of Waves presentations at TIDES will include the companys first ADAR editing data in ex vivo retina samples from non-human primates (NHPs). These data add to the growing body of in vitro and in vivo data the company has generated, which include editing in the liver of NHPs and the central nervous system in a humanized mouse model, in support of ADAR editing as an emerging platform capability at Wave.

Another presentation at TIDES will highlight Waves neurology pipeline, including its C9orf72 variant-selective silencing program for ALS and FTD, as well as its SNP3 program for HD, both of which are expected to initiate clinical development with the submission of clinical trial applications in the fourth quarter of 2020.

Details of Data Presentations

TIDES: Oligonucleotide and Peptide Therapeutics 2020 meeting

16th Annual Meeting of the Oligonucleotide Therapeutics Society

About PRISMPRISM is Wave Life Sciences proprietary discovery and drug development platform that enables genetically defined diseases to be targeted with stereopure oligonucleotides across multiple therapeutic modalities, including silencing, splicing and editing. PRISM combines the companys unique ability to construct stereopure oligonucleotides with a deep understanding of how the interplay among oligonucleotide sequence, chemistry and backbone stereochemistry impacts key pharmacological properties. By exploring these interactions through iterative analysis ofin vitroandin vivooutcomes and machine learning-driven predictive modeling, the company continues to define design principles that are deployed across programs to rapidly develop and manufacture clinical candidates that meet pre-defined product profiles.

About Wave Life Sciences Wave Life Sciences (Nasdaq: WVE) is a clinical-stage genetic medicines company committed to delivering life-changing treatments for people battling devastating diseases. Wave aspires to develop best-in-class medicines across multiple therapeutic modalities using PRISM, the companys proprietary discovery and drug development platform that enables the precise design, optimization and production of stereopure oligonucleotides. Driven by a resolute sense of urgency, the Wave team is targeting a broad range of genetically defined diseases so that patients and families may realize a brighter future. To find out more, please visit http://www.wavelifesciences.com and follow Wave on Twitter @WaveLifeSci.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, the development of ADAR editing as a potentially best-in-class RNA editing approach and emerging platform capability at Wave; the potential for Waves preclinical data, including data from and its neurology programs in Huntingtons disease (HD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD); and the expected timing for the initiation of clinical development for Waves C9orf72 variant-selective silencing program for ALS and FTD, as well as its SNP3 program for HD. The words may, will, could, would, should, expect, plan, anticipate, intend, believe, estimate, predict, project, potential, continue, target and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, the risks and uncertainties described in the section entitled Risk Factors in Waves most recent Annual Report on Form 10-K filed with theSecurities and Exchange Commission(SEC), as amended, and in other filings Wave makes with theSECfrom time to time. Wave undertakes no obligation to update the information contained in this press release to reflect subsequently occurring events or circumstances

Investor Contacts:Kate Rausch617-949-4827krausch@wavelifesci.com

Graham Morrell781-686-9600gmorrell@wavelifesci.com

Media Contact:Alicia Suter617-949-4817asuter@wavelifesci.com

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Wave Life Sciences to Highlight Preclinical ADAR Editing Data and Neurology Programs at TIDES and OTS Annual Meetings - GlobeNewswire

Beebe warning parents of Acute Flaccid Myelitis, they say don’t ignore symptoms and go to the doctors – 47abc – WMDT

DELAWARE Beebe Healthcare is warning parents to monitor symptoms in children for a polio-like virus.

The CDC recently sent out an alert on Acute Flaccid Myelitis saying they expect a higher number of cases this year.

This rare polio-like neurological condition typically impacts kids.

A doctor at Beebe said they are not sure why cases are supposed to be higher, but since the virus was first recognized in 2014, there has been an increase in the number of cases in even numbered years; and because of this they are stressing that parents keep an eye out for symptoms that include respiratory problems, fever, muscle weakness, and trouble speaking or swallowing.

I think the bigger things is dont ignore symptoms because of fear of going to the doctor, I think we are hopeful that because everybody has been social distancing and everybody has been masking the spike may be still might not happen, Nicole Ryan, a pediatric neurologist, said.

Doctors told us the virus can be spread from person to person, so parents should be enforcing the same type of precautions that they are taking for the COVID-19 pandemic.

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Beebe warning parents of Acute Flaccid Myelitis, they say don't ignore symptoms and go to the doctors - 47abc - WMDT

Neurologic Disorders Therapeutics Market 2020 | Know The Latest Covid19 Impact Analysis And Strategies Of Key Players: Biogen Inc., F. Hoffmann-La…

Neurologic Disorders Therapeutics Market Research Report provides a complete analytical study that provides all the details of key players such as company profile, product portfolio, capacity, price, cost and revenue during the forecast period from 2020 to 2026. A Neurologic Disorders Therapeutics market that includes Future Trends, Current Growth Factors, Meticulous Opinions, Facts, Historical Data and Statistically Supported And Industry-Validated Market Data.

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Biogen Inc., F. Hoffmann-La Roche Ltd., Johnson & Johnson Services Inc., Novartis AG, Pfizer Inc. are some of the major organizations dominating the global market.(Other Players Can be Added per Request)

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On the basis of Types, Neurologic Disorders Therapeutics Market is segmented into- Central Nervous System (CNS), Peripheral Nervous System (PNS)

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Neurologic Disorders Therapeutics Market 2020 | Know The Latest Covid19 Impact Analysis And Strategies Of Key Players: Biogen Inc., F. Hoffmann-La...

Global Neurology EMR Software Market 2020 Impact of COVID-19, Future Growth Analysis and Challenges | NueMD, Greenway Health, AdvancedMD,…

The report contains a thorough summary of Neurology EMR Software Market that includes several well-known organizations, key market players who are leading in terms of sales, variable market change, revenue, end-user demands, conformity through trustworthy services, restricted elements, products and other processes. Technical advancements, surplus capacity in developing markets, market bifurcation, globalization, regulations and environmental guidelines, production and packaging are some trends that are explained in the market report.

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NueMDGreenway HealthAdvancedMDAthenahealthPrognoCIS by BizmaticsKareoAprima EHR SoftwareAzalea HealtheClinicalWorksCureMDChartLogic EHR SuiteDocLinks

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The Neurology EMR Software market research report investigates the market as far as income and developing business sector patterns and drivers and incorporates a cutting-edge examination and estimates for different market portions, significant players and every single land area till 2027 and the worldwide pandemic of COVID-19 calls for rethinking of business methodologies. This Neurology EMR Software market report incorporates the effect investigation vital for the equivalent.

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Global Neurology EMR Software market report client gets detailed and verified data about the business. Likewise, this report covers the top to bottom factual investigation and the market elements and requests which give an entire situation of the business. The report gives the distinctive business challenges which are affecting business sector development a positive and negative way.

Global Neurology EMR Software Market Segmentation By Type:

Type IType II

Global Neurology EMR Software Market Segmentation By Applications:

Medical FacilitiesResearch InstitutesOthers

Global Neurology EMR Software Market Segmentation By Regions:

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The report also provides the current industry value according to the demand. This report consists the all over the information regarding the Neurology EMR Software market. By using this report user get a clear perspective on the Neurology EMR Software market conditions, trends, and coming period outlook for various segments.

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The Neurology EMR Software market report offers the current state of the market around the world. The report began with the market outline and key components of the Neurology EMR Software market which assumes a significant job for clients to settle on the business choice. It additionally offers the key focuses to upgrade the development in the Neurology EMR Software market. Some fundamental ideas are likewise secured by reports, for example, item definition, its application, industry esteem chain structure and division which help the client to break down the market without any problem. Also, the report covers different factors, for example, arrangements, efficient and innovative which are affecting the Neurology EMR Software business and market elements.

Chapters Define in TOC (Table of Content) of the Report:

Chapter 1: Market Overview, Drivers, Restraints and Opportunities, Segmentation overviewChapter 2: Market Competition by ManufacturersChapter 3: Production by RegionsChapter 4: Consumption by RegionsChapter 5: Production, By Types, Revenue and Market share by TypesChapter 6: Consumption, By Applications, Market share (%) and Growth Rate by ApplicationsChapter 7: Complete profiling and analysis of ManufacturersChapter 8: Manufacturing cost analysis, Raw materials analysis, Region-wise manufacturing expenses.Chapter 9: Industrial Chain, Sourcing Strategy and Downstream BuyersChapter 10: Marketing Strategy Analysis, Distributors/TradersChapter 11: Market Effect Factors AnalysisChapter 12: Market ForecastChapter 13: Neurology EMR Software Research Findings and Conclusion, Appendix, methodology and data source.

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Global Neurology EMR Software Market 2020 Impact of COVID-19, Future Growth Analysis and Challenges | NueMD, Greenway Health, AdvancedMD,...

Coronavirus: What does Covid-19 do to the brain? – BBC News

Image caption Consultant neurologist Arvind Chandratheva points out brain damage on a scan

Stroke, delirium, anxiety, confusion, fatigue - the list goes on. If you think Covid-19 is just a respiratory disease, think again.

As each week passes, it is becoming increasingly clear that coronavirus can trigger a huge range of neurological problems.

Several people who've contacted me after comparatively mild illness have spoken of the lingering cognitive impact of the disease - problems with their memory, tiredness, staying focused.

But it's at the more severe end that there is most concern.

Chatting to Paul Mylrea, it's hard to imagine that he had two massive strokes, both caused by coronavirus infection.

The 64-year-old, who is director of communications at Cambridge University, is eloquent and, despite some lingering weakness on his right side, able-bodied.

He has made one of the most remarkable recoveries ever seen by doctors at the National Hospital for Neurology and Neurosurgery (NHNN) in London.

His first stroke happened while he was in intensive care at University College Hospital. Potentially deadly blood clots were also found in his lungs and legs, so he was put on powerful blood-thinning (anticoagulant) drugs.

A couple of days later he suffered a second, even bigger stroke and was immediately transferred to the NHNN in Queen Square.

Consultant neurologist Dr Arvind Chandratheva was just leaving hospital when the ambulance arrived.

"Paul had a blank expression on his face," he says. "He could only see on one side and he couldn't figure out how to use his phone or remember his passcode.

"I immediately thought that the blood thinners had caused a bleed in the brain, but what we saw was so strange and different."

Paul had suffered another acute stroke due to a clot, depriving vital areas of the brain of blood supply.

Tests showed that he had astonishingly high levels of a marker for the amount of clotting in the blood known as D-dimer.

Normally these are less than 300, and in stroke patients can rise to 1,000. Paul Mylrea's levels were over 80,000.

"I've never seen that level of clotting before - something about his body's response to the infection had caused his blood to become incredibly sticky," says Dr Chandratheva.

During lockdown there was a fall in the number of emergency stroke admissions. But in the space of two weeks, neurologists at the NHNN treated six Covid patients who'd had major strokes. These were not linked to the usual risk factors for stroke such as high blood pressure or diabetes. In each case they saw very high levels of clotting.

Part of the trigger for the strokes was a massive overreaction by the immune system which causes inflammation in the body and brain.

Dr Chandratheva projected Paul's brain images on a wall, highlighting the large areas of damage, shown as white blurs, affecting his vision, memory, coordination, and speech.

The stroke was so big that doctors thought it likely he would not survive, or be left hugely disabled.

"After my second stroke, my wife and daughters thought that was it, they would never see me again," Paul says. "The doctors told them there was not much they could do except wait. Then I somehow survived and have been getting progressively stronger."

One of the first encouraging signs was Paul's ability with languages - he speaks six - and he would switch from English to Portuguese to speak to one of his nurses.

"Unusually he learned several of his languages as an adult, and this will have created different wiring connections in the brain which have survived his stroke," says Dr Chandratheva.

Paul says he cannot read as fast as he used to, and is sometimes forgetful, but that's hardly surprising given the areas of damage in his brain.

His physical recovery has also been impressive, which doctors attribute to his previous very high level of fitness.

"I used to cycle for an hour a day, do a couple of gym sessions a week and swim in the river. My cycling and diving days are over, but I hope to get back to swimming," Paul says.

A study in the Lancet Psychiatry found brain complications in 125 seriously ill coronavirus patients in UK hospitals. Nearly half had suffered a stroke due to a blood clot while others had brain inflammation, psychosis, or dementia-like symptoms.

One of the report authors, Prof Tom Solomon of the University of Liverpool, told me, "It's clear now that this virus does cause problems in the brain whereas initially we thought it was all about the lungs. Part of it is due to lack of oxygen to the brain. But there appear to be many other factors, such as problems with blood clotting and a hyper-inflammatory response of the immune system. We should also ask whether the virus itself is infecting the brain."

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In Canada, neuroscientist Prof Adrian Owen has launched a global online study of how the virus affects cognition. Owen said: "We already know that ICU survivors are vulnerable to cognitive impairment. So as the number of recovered Covid-19 patients continues to climb, it's becoming increasingly apparent that getting sent home from the ICU is not the end for these people. It's just the beginning of their recovery."

"Sars and Mers, which are both caused by coronaviruses, were associated with some neurological disease, but we've never seen anything like this before," Dr Michael Zandi, consultant neurologist at the NHNN, told me. "The closest comparison is the 1918 flu pandemic. We saw then there was a lot of brain disease and problems that emerged over the next 10-20 years."

As the BBC's medical correspondent, since 2004 I have reported on global disease threats such as bird flu, swine flu, Sars and Mers - both coronaviruses - and Ebola. I've been waiting much of my career for a global pandemic, and yet when Covid-19 came along, the world was not as ready as it could have been. Sadly, we may have to live with coronavirus indefinitely. Here, I will be reflecting on that new reality.

A mysterious neurological syndrome known as encephalitis lethargica appeared around the end of World War One and went on to affect more than a million people worldwide. There is limited evidence of its causes, and whether the trigger was influenza or a post-infectious autoimmune disorder.

As well as a sleepiness coma, some patients had movement disorders that looked like Parkinson's disease, which affected them for the rest of their lives.

In his book Awakenings, the neurologist Oliver Sacks told the story of a group of patients who'd been frozen in sleep for decades, and how he used the drug L-Dopa to temporarily free them from their locked-in state.

We should be careful before reading too much into comparisons between Covid-19 and the 1918 Spanish flu pandemic. But with so many Covid patients having neurological symptoms, it will be important to look at the long-term effects on the brain.

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Coronavirus: What does Covid-19 do to the brain? - BBC News

Why COVID-19’s long-term health effects are a cause for concern – Arab News

DUBAI: What was first identified as another respiratory disease akin to the common flu has taken the lives of over 600,000 people around the world in just six months.

The latest strain of the coronavirushas been described as an invisible enemy, slowly revealing new symptoms as the global scientific community continues investigations into it.

Since the first outbreak of the coronavirusdisease (COVID-19), traced to a wet market in Wuhan, China, in late 2019, the infection quickly developed into a full-fledged pandemic, with over 15 million cases reported to date. Symptoms have multiplied, leaving puzzled experts determined to find a cure.

Findings published this month appear to confirm growing concerns about the infections link to serious and potentially fatal brain disorders as well as cardiovascular complications.

Chief Scientific Officer Dr. Jeff Drew carries out research into the virus at the Stabilitech laboratory in the UK. (AFP)

Were seeing things in the way COVID-19 affects the brain that we havent seen before with other viruses, said Michael Zandi, a consultant neurologist at the National Hospital for Neurology and Neurosurgery in London, after the publication of new research in the scientific journal Brain.

Common flu-like signs such as fever, dry cough and sore throat were the first set of symptoms reported at the start of the pandemic. However, the list rapidly expanded to include shortness of breath, loss of taste and smell, nausea and several more symptoms just months later.

Today, the biggest concern among health professionals is the virus insidious impact on the brain, with more than 300 studies of COVID-19 patients worldwide showing neurological abnormalities.

One study published in Brain involving 43 patients 24 males and 19 females confirmed a range of neurological complications in mildly affected and recovering patients.

Commenting on the new findings, Gregory Poland, an infectious diseases and vaccine expert at the Mayo Clinic in Rochester, Minnesota, said the virus impact on the brain is variable and can range from having no visible impact to causing large vessel occlusions, known more commonly as very large strokes.

With the virus refusing to discriminate based on age or color, severe cases have been reported among young and relatively healthy individuals as well as those with pre-existing conditions and the elderly.

Gregory Poland, an infectious diseases and vaccine expert at the Mayo Clinic in Rochester, Minnesota

Obviously, the risk goes higher the more severe the disease; large vessel occlusions in young people have occurred with moderate to severe COVID-19 cases. But it can happen to people anywhere along that spectrum, Poland told Arab News.

In the neurologic realm, the studys findings showed that patients suffered from encephalopathy; stroke; inflammation of the central nervous system; peripheral nerve problems; cognitive and mental health issues, with delirium, psychosis and several cases of Guillain-Barre syndrome, an immune reaction that attacks the nerves and causes paralysis.

Dr. Taoufik Al-Saadi, chief medical officer and chair of the Neurology Department at the American Center of Psychiatry and Neurology in the UAE

Other symptoms included depression, anxiety and brain fog as well as a loss of smell, taste and sleep in mild and asymptomatic patients.

Another study, Neurological associations of COVID-19, published on the Lancet Neurology website, confirmed that a growing number of case reports and series from around the world described the same array of neurological manifestations, noting the virus is of a scale not seen since the 1918 influenza pandemic.

According to Poland, health care systems are recognizing that theres going to be a greatly enhanced need for rehabilitation and recovery centers after the COVID-19 pandemic as a result of the latest outcomes.

His views are echoed by Dr. Taoufik Al-Saadi, chief medical officer and chair of the Neurology Department at the American Center of Psychiatry and Neurology in the UAE, who pointed out that although most individuals are inclined to experience a mild or asymptomatic disease course, some have required ventilatory support.

Data suggest that one in five infected individuals are hospitalized, and one in 10 individuals are admitted to the intensive care unit (ICU), requiring ventilatory support, due to acute illness in response to this infection, he said.

The main issue in survivors of these cases is the physical, cognitive and mental impairment that may persist for several years beyond hospital discharge. Indeed, 80 percent of ICU survivors with confirmed COVID-19 may follow that course, Al-Saadi told Arab News.

Cases of memory impairment, depression, anxiety, post-traumatic stress-like disorders have all been reported in up to 30 percent of these patients and may last up to several years following hospital discharge, said Al-Saadi.

These complications would certainly affect survivors of this disease in all aspects of their everyday life whether functioning at work, home or in the social sphere, he said.

Additionally, cognitive, physical and mental problems could result in chronic pain conditions, further causing sleep disorders, which could ultimately affect the overall quality of life. What frightens the scientific community even more is that the long-term impact of such neurological effects has not yet been determined.

However, the virus potential long-term health effects do not stop at causing damage to the brain. Scientists are increasingly recognizing the cardiovascular side effects of the virus, with reports of markers of cardiac injury even in young people.

According to Poland, cases of COVID-19 have resulted in inflammation of the heart (myocarditis), decreased heart-muscle function (cardiomyopathy), irregular heart rhythms (arrhythmias) and dilation of coronary and other blood vessels due to vascular inflammation as well as blood clots.

For patients with a prior history of cardiovascular disorders and increased risk factors, such as hypertension and diabetes, chances of heart complications significantly rise when infected with COVID-19.The British Heart Foundation confirms these findings, noting that this strain of the virus has been found to increase the risk of blood clotting or thrombosis, leading to cardiovascular problems and, in some cases, organ failure.

The term COVID toe has also been coined in reference to painful red or purple swollen patches on the feet, usually the toes of infected patients, a condition known as Chilblains and typically associated with exposure to cold weather.

Some experts have linked COVID toe to blood clots and other neurological issues caused by the virus.

Examining the plethora of symptoms and conditions triggered by the virus, Poland believes experts must not yet discuss the long-term health effects of COVID-19 on patients as research is still in its infancy.

What we can say is that early indicators of pulmonary fibrosis and scarring are irreversible. We have seen myocarditis and cardiomyopathy, some of which can improve, but we dont know if they will completely improve, he said.

Poland also referred to a group of patients he calls the long-haulers who have developed almost a chronic fatigue-like symptom accompanied by an assortment of symptoms as result of infection with the virus. For these patients, the virus impact is long-lasting.

Evidence of kidney and liver damage has also been reported in cases around the world, with no clear indication of the long-term consequences.

Similarly, the impact of COVID-19 on pregnant women and their unborn children is yet to be defined with certainty.

With science yet to answer so many questions, Polands prognostication is no more reassuring than the available findings on virus. My guess, he said, is that young, healthy people will recover, and older people will have a more difficult time getting back to baseline, if at all.

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Twitter: @jumana_khamis

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Why COVID-19's long-term health effects are a cause for concern - Arab News

Improving treatment for psychogenic seizures: This is a group of patients that we are taking less seriously – Newswise

Benjamin Tolchin was awarded the 2020EpilepsiaPrize for Clinical Science Research for his article, "Randomized controlled trial of motivational interviewing for psychogenic nonepileptic seizures."

Newswise Early in Ben Tolchins neurology residency at Columbia University Medical Center in New York, a young woman was admitted to the epilepsy monitoring unit. Her stay was prolonged and complex; ultimately, she was diagnosed with psychogenic non-epileptic seizures (PNES). Tolchin found a psychotherapist who agreed to provide treatment, and the woman was discharged with a plan.

It seemed like a big accomplishment, like wed done this incredible thing, Tolchin said. Until months later when he saw the woman againthis time in the medical intensive care unit. She had been aggressivelyand improperlytreated for prolonged seizures (status epilepticus) at another hospital. She was now battling ventilator-associated pneumonia. The woman had never started treatment with the psychotherapist.

All the unnecessary harm that was doneit made an impression on me, he said. PNES causes real morbidity; it affects quality of life, it causes disability, and there are iatrogenic complications.

The standard algorithm for diagnosis and treatment didnt work, at least in this young womans case. And as Tolchin saw more cases of PNES, he discovered that she was more the rule than the exception.

I had the experience again and again, that the standard of care was not providing these people with what they need, he said.

Closing the gap between diagnosis and treatment

Tolchin began researching non-adherence in people with PNES. He learned that 60% drop out of psychotherapy within 16 weeks, and about 85% drop out within a year and a half. He also learned that people who stick with treatment have fewer seizures, better quality of life, and less use of emergency services.

Tolchin designed a study using motivational interviewing (MI) as an intervention to improve treatment adherence in people with PNES. MI is a counseling style that focuses on eliciting the patients own motivations and reasons for behavior change. Originally developed for substance use disorders, MI has been shown effective for improving adherence with multiple types of medical interventions. Tolchins study was one of the first to use MI to improve adherence with a psychotherapeutic intervention, and the first to test the technique for psychogenic seizures.

The more conventional, didactic technique is that you tell the patient they have to go to therapy because it will help them, Tolchin said. With MI, you help them identify whats problematic in their life and how they might be able to overcome those problems.

The idea is to make treatment initiation and adherence into the patients decision, not the physicians.

Sixty people with PNES were included in the study. All were referred to psychotherapy, and 30 were randomized to also receive a half-hour of MI counseling before any psychotherapy was provided.

After 16 weeks, 65% of those receiving MI were adherent to psychotherapy, compared with 31% of controls. The MI group also had significantly fewer seizures and better quality of life. About 31% of the MI group became seizure free, compared with about 11% of controls, but because of the relatively small sample size, the difference did not reach statistical significance (p=0.095).

Tolchin was trained in MI and conducted all the sessions. He suggested that neurologists, nurses, social workers, and other health care professionals could be trained in the technique and use it not only for people with PNES, but also those with epilepsy.

Using MI as a tool for medication adherence, psychotherapy, or any other treatment is reasonable, Tolchin said. It can provide significant benefit, and its a low-cost investment.

There is a growing awareness

Now assistant professor of neurology at Yale School of Medicine, Tolchin is designing an app that uses MI and cognitive behavioral therapy techniques to help people with PNES. Wed like to use it as a bridge to in-person, one-on-one psychotherapy, he said. But many patients arent able to find a psychotherapist experienced with PNES, or if they can, they may have to wait months for an appointment.

With an undergraduate background in philosophy and ethics, Tolchin views the treatment of patients with PNES and other functional neurological disorders as an ethical issue. There is a significant amount of bias and stigma, he said. People are treated as if theyre not really suffering, as if theyre faking, rather than dealing with a truly debilitating disorder. Its an ethical problem in that there is a group of patients we are taking less seriously and treating with less compassion and concern, merely because of the etiology of their condition.

However, he has seen positive changes even in the past decade. Theres a growing awareness among neurologists, epileptologists, emergency-room physicians, that these are serious disorders and that effective treatment is available, Tolchin said. To see patients who maybe 10 years ago would not have received treatment and now are getting itthats a gratifying thing.

About the ILAE Journal Prizes

Each year, the ILAE awards one Basic Science and one Clinical Science Prize to the first authors of original research articles published in Epilepsia which,in the opinion of the Awards Committee, have contributed the most significant advances to knowledge and understanding in the field of epilepsy.

The prize is intended to stimulate excellence in epilepsy research and reward young researchers for outstanding contributions to the field.

Watch the 2020 Journal Prize Symposium on YouTube, including a talk by Dr. Tolchin about his research.

##

Founded in 1909, the International League Against Epilepsy (ILAE) is a global organization with more than 120 national chapters.

Through promoting research, education and training to improve the diagnosis, treatment and prevention of the disease, ILAE is working toward a world where no persons life is limited by epilepsy.

To learn more, visit ourwebsite(available in multiple languages) or find us onFacebook.

We're also on Twitter inEnglish,French,Japanese,PortugueseandSpanish.

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Improving treatment for psychogenic seizures: This is a group of patients that we are taking less seriously - Newswise

People with Multiple Sclerosis Have Increased Macrovascular… : Neurology Today – LWW Journals

Article In Brief

Patients with multiple sclerosis (MS) are at increased risk for all-cause mortality, mortality related to cardiovascular issues, and macrovascular events. Experts discuss the need to carefully monitor MS patients for cardiovascular risk.

People with multiple sclerosis (MS) are at a greater risk of macrovascular events, all-cause mortality, and mortality related to cardiovascular issues, according to a large population study recently published in JAMA Neurology.

Derived from more than 12,000 people with MS matched with about six controls each, the findings offer a rigorous portrait of the cardiovascular risks that MS patients face, and the researchers say, point to the need for careful assessment of these risks to pave the way for the best outcomes. The findings also underscored the heightened risks of women with MS, who fared worse on most of the outcomes that investigators explored.

We thought this study could offer an important contribution to the current knowledge on the association between MS and increased vascular risk and mortality, said Raffaele Palladino, PhD, a research associate in primary care and public health at the Imperial College of London and assistant professor of public health at the University of Naples.

Evidence from previous population-based studies is sparse and many of the previously published studies were conducted in specific settings with limited generalizability to the general population. Furthermore, evidence on sex-related differences is still limited, while this was a focus of the present study.

The data came from the UK Clinical Practice Research Datalink, one of the world's largest electronic medical records databases, covering 7 percent of the UK population and representative of the populace in age, sex and race, and ethnicity. Researchers reviewed MS cases from 1987 to 2018, with an average follow-up of about 11 years. Subjects were considered to have MS only if they had 3 documented MS events.

Researchers found that those with MS had a 32 percent increased risk of any macrovascular diseasewhich included acute coronary syndrome, cerebrovascular disease or peripheral artery diseasecompared with those without MS (HR=1.32; 95% CI: 1.15-1.52). Women with MS had a 49 percent increased risk of any macrovascular disease (HR=1.49; 95% CI: 1.26-1.77).

There were no differences seen in men for macrovascular outcomes when all years were considered, but researchers did find a difference when considering only MS cases from 2002 to 2018the period during which MRI criteria had become standard for diagnosing MS. In that period, men had a 67 percent increased risk of any macrovascular disease (HR=1.67; 95% CI: 1.15-2.43).

People with MS had a 3.5-fold increased risk of all-cause mortality compared with those without the disease (HR=3.46; 95% CI: 3.28-3.65) and 47 percent increased risk of cardiovascular disease mortality (subdistribution HR=1.47; 95% CI: 1.27-1.71). There was a 3.5-fold increased risk for women with MS (HR = 3.52; 95% CI: 3.28-3.77) in all-cause mortality and a 30 percent increased risk for women with MS for cardiovascular mortality (HR=1.30; 95% CI: 1.04-1.62), compared with those who did not have MS.

Men with MS had a 2.7-fold increased risk of all-cause mortality compared with those without MS (HR=2.74; 95% CI: 2.35-3.18), and they had a 54 percent increased risk of cardiovascular disease mortality (subdistribution HR=1.54; 95% CI: 1.06-2.23).

We would recommend aggressive vascular risk monitoring and possibly treatment especially in women with MS, Dr. Palladino said.

This appeared to be the first population-level study to look at the effect of lipid-lowering medications of people with MS on all-cause mortality, researchers said. About 3 percent of the study population was taking a lipid-lowering drug in the index year, the year of the first MS event2.7 percent in those with MS, 95 percent of which were statins, and 2.9 percent in controls, 94 percent of which were statins.

Compared with the controls who were not taking lipid-lowering medications, those with MS who were not taking these drugs had a 3.6-fold increased all-cause mortality (HR=3.62; 95% CI, 3.43-3.83). But compared to controls taking lipid-lowering drugs, those with MS taking these drugs had just a two-fold increased all-cause mortality (HR=1.95; 95% CI: 1.58-2.42).

Lipid-lowering medications seemed to have a protective association with all-cause mortality in people with MS, Dr. Palladino sad. Therefore, a thorough vascular risk assessment should be performed in people with MS at time of diagnosis and follow-up visits to identify those who might benefit the most from intensive vascular risk reduction strategies, which might include lipid-lowering treatment.

Overall, he said, the findings point to the need for careful management of MS patients when it comes to their cardiovascular risk.

Vascular risk and vascular comorbidities assessment should become integrated into the care of people with MS, given the adverse impacts of vascular comorbidities on the MS disease trajectory and cardiovascular outcomes in people with MS, he said. This will require a collaborative approach with primary care.

Shiv Saidha, MD, associate professor of neurology at Johns Hopkins, said the study is highly informative, confirming prior findingsthat those with MS have a heightened risk of macrovascular diseasewhile also containing some findings that are new.

The study findings are in alignment with prior studies, and not unsurprisingly this study also found that people with MS have a higher all-cause, as well as cardiovascular disease-related mortality, he said. This being said, the finding that people with MS treated with lipid lowering agents such as statins may have a lower mortality rate is both novel and instructive.

He said that clinical care of people with MS has included increased attention to smoking cessation and tight control and management of vascular comorbidities, in light of mounting data that worse outcomes are linked with these habits and comorbidities.

Dr. Saidha said the findings should serve as a reminder for clinicians to counsel patients on factors that could promote vascular health. But he said the field needs to learn more about the causality involved here.

Mechanistically, it is important to elucidate the basis for why people with MS may be more susceptible to macrovascular disease/complications, he said. This could have an impact on how best to manage vascular risk specifically among people with MS, as well as potentially lead to the identification of novel targets/strategies to aid the management of MS. Moreover, while the current study did account for some traditional vascular risk factors, it did not account for the effect of MS disability/activity levels, diet, BMI, or other lifestyle factors, which in various combinations, may have major roles in the pathogenic risk for underlying vascular dysfunction. Alternatively, there may be other directly MS-related pathobiological underpinnings.

Sharon G. Lynch, MD, FAAN, professor of neurology and neuroimmunology division chief at the University of Kansas School of Medicine, said the findings of a modest correlation with MS and cerebrovascular disease dovetail with findings at her center a few years ago showing a similar correlation between MS and stroke.

Several things come to mind that could help to explain this, including reduced exercise in the MS populations, diet, and other lifestyle issues, Dr. Lynch said.

She said she has not noticed that there is a major, increased risk of vascular problems among her MS patients. But she said the findings suggest that awareness of the risk among primary care providers would be helpful.

For the most past, I recommend exercise and a healthy diet and, of course, smoking cessation in all of my patients, regardless of vascular risk. I don't manage other risk factors such as diabetes, hyperlipidemia, or hypertension personally, but instead, encourage them to work with their primary care provider for management of these risk factors, she said. I don't know that clinical care should change in specific way (in light of the study), but we do need to encourage our patients to take care of their health in general, rather than focusing solely on MS.

Drs. Palladino and Gutierrez had no relevant disclosures. Dr. Saidha has received consulting fees from Medical Logix for the development of CME programs in neurology and has served on scientific advisory boards for Biogen, Genentech Corporation, EMD Serono, and Celgene. He is the principal of investigator-initiated studies funded by Genentech Corporation and Biogen Idec and received support from the Race to Erase MS Foundation. He has received equity compensation for consulting from JuneBrain LLC, a retinal imaging device developer. He is also the site investigator of a trial sponsored by MedDay Pharmaceuticals.

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People with Multiple Sclerosis Have Increased Macrovascular... : Neurology Today - LWW Journals

Repetitive Head Impacts Increases the Hazard of Death Among NFL Players – Neurology Advisor

Increasing repetitive headimpacts are associated with an increased hazard of death among professionalfootball players in the National Football League (NFL), a study in the JAMANetwork Open suggests.

The study was aretrospective review of all-cause mortality data from 14,366 football playersduring the 1969 to 2017 NFL seasons. Only data up to July 1, 2018, were includedin this analysis. Pro Football Reference records were used to identify thenumber of seasons and games played by participants. The exposure of interestwas the professional football cumulative head impact index (pfCHII), which wascalculated for 13,912 NFL players. The pfCHII, which quantified the amount andseverity of repetitive head impacts, combined the reported football historywith helmet accelerometer studies in professional players.

A total of 763 of the 14,366players in the initial cohort (5.3%) had died over the follow-up period. Themedian pfCHII among the 13,912 players in the pfCHII analysis was 32.63(interquartile range, 13.71-66.12). The pfCHII scores ranged from 14.18 forwide receivers to 84.34 for offensive linemen. For every 1-log increase inpfCHII, there was a significant increase in the hazard of death for the 1969 to2017 football seasons (hazard ratio [HR], 2.02; 95% CI, 1.21-3.37; P=.01). Additionally, the quadratic pfCHII was significant for the hazard ofdeath during this period (HR, 0.91; 95% CI, 0.85-0.98; P =.01).

Limitations of this study included the variability in measurements of repetitive head impacts across the specified seasons, the inability to adjust for race/ethnicity, and the inclusion of only professional football players vs players who participated in college, high school, or youth football programs.

The investigators of thisstudy suggest that the reduction in repetitive head impacts from playingfootball or other activities through additional rule and equipment changes maybe associated with reduced mortality.

Reference

Kmush BL, Mackowski M, Ehrlich J, Walia B, Owora A, Sanders S. Association of professional football cumulative head impact index scores with all-cause mortality among national football league players. JAMA Netw Open. 2020;3(5):e204442

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Repetitive Head Impacts Increases the Hazard of Death Among NFL Players - Neurology Advisor

Early Extubation Tied to Better Outcome After Stroke Thrombectomy – Medscape

The shorter, the better when it comes to time spent on a ventilator for stroke patients who undergo mechanical thrombectomy, new research suggests.

A study of more than 400 patients showed that those who were extubated within 6 hours were more than twice as likely to have a better outcome than those extubated later. Also for these patients, the rate of developing pneumonia was lower.

Dr Simon Fandler-Hfler

These findings are important because data regarding ventilation time for stroke patients are "scarce," investigator Simon Fandler-Hfler, MD, Department of Neurology, Medical University of Graz, Austria, told Medscape Medical News.

"Our results indicate that patients with an anterior circulation occlusion, which account for 85% to 95% of all thrombectomies, should be extubated as early as safely possible," Fandler-Hfler said.

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2020, which was being held online because of the COVID-19 pandemic.

The study included 441 consecutive adult patients (mean age, 69 years) who underwent mechanical thrombectomy under general anesthesia as treatment foran anterior circulation large-vessel occlusion stroke. The patients were evenly matched with regard to sex.

The researchers categorized the participants into those who were extubated within 6 hours (early extubation) after thrombectomy, those extubated within 6 to 24 hours after (delayed extubation), and those extubated after more than 24 hours (late extubation).

The primary outcome was a favorable Modified Rankin Scale (mRS) score of 02 three months post stroke.

Although the median ventilation time was 3 hours, individually, it ranged widely from 1 to 530 hours. More than half of the patients (57.7%) were extubated early; 27.7% were in the delayed group, and 14.5% were in the late group.

Results showed that 42.6% of patients had a favorable outcome.

When analyzed as a continuous variable, ventilation time strongly correlated with mRS scores at 3 months (P < .001).

Significant predictors of adverse outcomes included age (P < .001), hypertension (P < .001), chronic heart disease (P = .02), diabetes mellitus (P = .002), atrial fibrillation (P = .001), and National Institutes of Health Stroke Scale (NIHSS) score at admission (P < .001).

Patients who underwent successful recanalization also had significantly better outcomes.

Of those extubated early, about three quarters had a good outcome; fewer than half (45%) had bad outcomes, Fandler-Hfler reported.

"We found that those patients with early extubation had significantly better outcomes," he said, compared with those whose extubation was delayed (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.53 3.76; P < .001).

Early pneumonia within the stroke unit or neurointensive care unit was strongly associated with ventilation time. For the patients in the early group, the rate of pneumonia was only 9.6%, compared with 20.6% for the delayed group.

Fandler-Hfler found the results for those who received less ventilation "surprising" and said the results could have an impact on clinical practice.

Chronic heart disease and pneumonia were more prevalent in the late group than in the other groups. Also, for the patients in the late group, NIHSS scores were significantly higher at admission, and successful recanalization was less frequent.

For with regard to mRS scores at 3 months, participants who underwent ventilation the longest "really had very bad outcomes," Fandler-Hfler said.The mortality rate for those patients was more than 50%.

He acknowledged that "it was no surprise that patients who were intubated for several days had worse outcomes."

The researchers also examined the reasons why some patients were extubated later than others. Stroke complications, including brain edema, insufficient alertness, seizures, and respiratory insufficiency, played a role.

Delayed extubation was also strongly associated with admission "outside of core working hours," when fewer doctors and nurses were available, Fandler-Hfler said.

Within core hours, almost 90% of patients were extubated early; but outside these hours, only 50% of patients were extubated early (OR, 6.6; 95% CI, 3.59 10.22; P < .001)

"This means that an intervention with potential complications such as an extubation could, and often will, be delayed until the next day if it's not deemed necessary to do it straightaway," said Fandler-Hfler.

There are usually ongoing discussions about which interventions should be performed as soon as possible and which can wait until the next day, he noted.

"Our research indicates that the specific intervention of extubation after stroke thrombectomy should be performed as early as safely possible," he said.

This can take place after the intervention in the angiography suite or directly after admission to an intensive care unit after the procedure, Fandler-Hfler added.

Findings from the study were published recently in the European Journal of Neurology.

Fandler-Hfler has reported no relevant financial relationships.

Congress of the European Academy of Neurology (EAN) 2020: Oral session. Presented May 25, 2020.

Eur J Neurol. Published online March 17. 2020. Abstract

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Early Extubation Tied to Better Outcome After Stroke Thrombectomy - Medscape

Overcoming Untreated Epilepsy in the Developing World: the Way Forward – WFN News

The medical world thinks of the developed and developing societies in terms of diagnostic and treatment differences. However, there are realities that are common to both spheres concerning most medical conditions.

As a medical student, one would read of common disorders that were not being treated. Epilepsy was a striking example. In many rural Indian communities, up to 90 epilepsy patients out of every 100 were not getting treatment. In bureaucratese, this was a treatment gap of 90 percent.

The treatment of epilepsy has since evolved. Over two-dozen antiepileptic drugs are currently available. Many drugs are off patent and generically manufactured, and available in India and other developing nations at reasonable prices. But the epilepsy treatment gap of up to 90 percent still exists in many rural Indian communities! So, why has nothing changed for the lot of millions of epilepsy patients?

Let us humanize the numbers. By using calculations from an often-quoted epilepsy prevalence figure of 1 percent of the population, at least 12 million Indians are struggling with epilepsy.1 Large prevalence studies are unavailable, and many experts agree that this number is more likely to be closer to 15 million or even higher. This implies that more than 10 million epilepsy patients in India are untreated. Extrapolating worldwide, there are more than 50 million epilepsy patients and at least 40 million of these reside in developing countries. The estimate is that 75 percent of patients in developing countries are outside the domain of any kind of effective treatment. This implies at least 30 million untreated persons.

Ironically, epilepsy is one of the relatively easily controllable neurological diseases.

What is life like with untreated epilepsy? Most persons with epilepsy who do not have any other neurological illness are essentially normal at all times other than during their seizures. A seizure generally lasts for a few minutes during which, amongst other things, the person is unaware of his or her surroundings, and after which the person may remain confused for a variable amount of time or may sleep off the effects. In either case, the individual is back to normal within a few hours, often without even requiring a trip to the doctor's clinic or the emergency room.

Then what is the great problem about having untreated active epilepsy with an occasional seizure? Imagine having brief episodes of unawareness just once or twice in a month, in six months or even in a year, but not knowing when these would happen. So, you may be driving to work, crossing the street, climbing a tree, in bed with your partner, swimming in the pool, or speaking mid-sentence in that all important meeting. Suddenly, out of the blue, you start convulsing or just fidgeting with your buttons or speaking in an unintelligible jargon or wet your clothes in full public gaze. How would it feel to know that you had done either of these, and then have to go back to the same people in front of whom this had happened? Well, that is assuming that these people agree to work or socialize with you after witnessing a seizure.

The economic impact of untreated epilepsy is formidable in all societies. Many untreated epilepsy patients remain unemployable, especially if local attitudes consider it to be a contagious disease, a mental illness, or a demonic possession. Thus, they are removed as contributors to the economy. Even if they are poor and have minimum wage jobs, this still adds up to a substantial amount of money loss because of the millions affected.

There are other grave consequences of untreated epilepsy. If the patient is of school or college age, they are very likely to have to drop out. This is either due to their parents' fear that their child may be injured during a seizure, or on the insistence of teachers. With limited scope for education, landing a good job later in life is subsequently reduced. The intrigue and misinformation surrounding epilepsy reduces social acceptance of patients. Any relationship, including a stable marriage, especially for women with epilepsy, is unlikely. Abandonment of women with epilepsy and their children from marital relationships is common. Such women, with little or no education, no skills and sometimes also with small children to take care of, are often left at the mercy of an impoverished community.

So, is epilepsy difficult to treat? No. Epilepsy is a relatively easy disease to treat in most patients. The diagnosis is clinical and based upon eliciting a history of stereotyped episodes during which the patient may behave abnormally, have involuntary movements or jerks, generally become unaware of his surroundings and then recover in a short time. After the clinical diagnosis, a couple of investigations EEG and brain imaging may be done. Investigations may help in deciding the best anti-epileptic drug, in prognosticating how long the treatment is likely to be needed, and how responsive to treatment the patient's epilepsy might be.

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(At time of publication, May 2016) Mamta Bhushan Singh, MD, DM is an additional professor, department of neurology, All India Institute of Medical Sciences, New Delhi, India.

Michael Finkel is a retired neurologist, and a member of the AAN, Child Neurology Society, ENS, EFNS, and BMA. He is a fellow of the AAN..

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Overcoming Untreated Epilepsy in the Developing World: the Way Forward - WFN News

Ligand Announces Icagen’s Expansion of Collaboration with Roche to Develop and Commercialize Therapies for Neurological Diseases – BioSpace

Collaboration initiates second Roche program utilizing Icagens ion channel drug discovery platform

SAN DIEGO--(BUSINESS WIRE)-- Ligand Pharmaceuticals Inc. Incorporated (NASDAQ: LGND) and Icagen, a Ligand Company, announced today the expansion of Icagens license agreement with Roche to develop and commercialize small molecule ion channel modulators for the treatment of neurological disorders, by adding a second program to the agreement. The new program incorporates Icagens ion channel technology and expertise and is directed at a specific novel ion channel target relevant to neurodegenerative disease. The new program is in addition to ongoing work on another novel CNS target.

Icagens collaboration with Roche was a key value-driver in the acquisition of the Icagen business, and we are very pleased to see this expansion and extension of the relationship, said John Higgins, Chief Executive Officer of Ligand. This type of deal fits perfectly within the Ligand strategy to establish and leverage partnerships with global leaders in the industry as they look to access our technology for their drug discovery and development needs. The Icagen team has been a great addition to Ligands business.

"We are pleased to extend and expand our collaboration with Roche and its drug discovery team in Basel," said Icagen Site Head Douglas Krafte, PhD. "Our initial neurology program with Roche continues to make great progress and we hope to assist Roche in bringing multiple meaningful therapies to patients in areas of neurological disease with major unmet needs through both our initial and this new program."

Terms of Expanded Icagen and Roche Collaboration

Under the terms of the license agreement, Roche made a cash upfront payment and will provide research funding to Icagen. In addition, Icagen is eligible to potentially receive development and commercial milestone payments of up to $274 million and royalty payments should a drug be commercialized from any of the collaborations programs.

Icagen will be responsible for most preclinical activities up to lead optimization with both Icagen and Roche applying resources to identify candidates for entry into IND-enabling studies. Roche will be responsible for the further development and commercialization of the program.

About Icagen, a Ligand Company

Icagen, a Ligand Company, is a preclinical drug discovery company focused on ion channel and transporter drug discovery with research facilities located in Durham, N.C. Icagen partners with the pharmaceutical industry to develop first-in-class therapies for patients in need, typically under arrangements in which we work closely with our partners through the time of clinical candidate selection and our partners are responsible for the clinical development and commercialization. Icagen, a Ligand Company, is a subsidiary of Ligand Pharmaceuticals Incorporated. For more information, please visit http://www.ligand.com.

About Ligand Pharmaceuticals

Ligand is a revenue-generating biopharmaceutical company focused on developing or acquiring technologies that help pharmaceutical companies discover and develop medicines. Our business model creates value for stockholders by providing a diversified portfolio of biotech and pharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure. Our goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable, diversified and lower-risk business than a typical biotech company. Our business model is based on doing what we do best: drug discovery, early-stage drug development, product reformulation and partnering. We partner with other pharmaceutical companies to leverage what they do best (late-stage development, regulatory management and commercialization) to ultimately generate our revenue. Ligands OmniAb technology platform is a patent-protected transgenic animal platform used in the discovery of fully human mono- and bispecific therapeutic antibodies. The Captisol platform technology is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. The Vernalis Design Platform (VDP) integrates protein structure determination and engineering, fragment screening and molecular modeling, with medicinal chemistry, to help enable success in novel drug discovery programs against highly-challenging targets. Ab Initio technology and services for the design and preparation of customized antigens enable the successful discovery of therapeutic antibodies against difficult-to-access cellular targets. Icagen, a Ligand Company, focuses on ion channel and transporter drug discovery as it partners with the pharmaceutical industry to develop first-in-class therapies for patients in need. Ligand has established multiple alliances, licenses and other business relationships with the worlds leading pharmaceutical companies including Amgen, Merck, Pfizer, Sanofi, Janssen, Takeda, Gilead Sciences and Baxter International. For more information, please visit http://www.ligand.com.

Follow Ligand on Twitter @Ligand_LGND.

Forward-Looking Statements

This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. Words such as plans, believes, expects, anticipates, and will, and similar expressions, are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding the potential benefits of the Icagen/Roche license and collaboration agreement programs. Actual events or results may differ from Ligand's expectations due to risks and uncertainties inherent in Ligands business, including, without limitation, that there can be no assurance that either the original or expansion Roche program with Icagen will be able to successfully identify any desirable drug candidates or that any drug candidates developed in such programs would be clinically or commercially successful, all of which might result in the potential milestone payments and royalties not being earned. The failure to meet expectations with respect to any of the foregoing matters may reduce Ligand's stock price. Additional information concerning these and other risk factors affecting Ligand can be found in prior press releases available at http://www.ligand.com as well as in Ligand's public periodic filings with the Securities and Exchange Commission available at http://www.sec.gov. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release, including the possibility of additional contract revenue we may receive. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

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Ligand Announces Icagen's Expansion of Collaboration with Roche to Develop and Commercialize Therapies for Neurological Diseases - BioSpace

The Gut-Brain Connection – HSC Newsbeat

University of New Mexico scientists played a key role in new research demonstrating for the first time that changes in the gut microbiome may help trigger human neurovascular disease.

Members of New Mexico Hispanic families who share a genetic predisposition for dangerous brain bleeds known as cerebral cavernous malformations (CCM) were recruited for the study, published earlier this week in Nature Communications.

The research team found that high levels of inflammation-promoting bacteria in the digestive tract secrete lipopolysaccharide molecules, which in turn drive clusters of abnormally dilated vessels in the brain to leak blood into the surrounding tissue.

In severe cases, the condition causes seizures or stroke-like symptoms and often requires surgery, said Atif Zafar, MD, an assistant professor in the UNM Department of Neurology.

Many CCM cases appear to arise spontaneously, but Zafar and Leslie Morrison, MD, a retired professor of Neurology, have previously shown that people with northern New Mexican Hispanic ancestry are at a somewhat higher risk because of a long-ago mutation in a single ancestor that has been passed down through generations.

Both contributed to the new study, along with two dozen other researchers from The University of Chicago, the University of Pennsylvania, University of California, San Francisco and the Angioma Alliance.

These families willingness to participate in studies has allowed the researchers to build a rich database used in the new study, which was led by UChicago scientists, Zafar said. Our main strength was the number of familial CCM cases that UNM has, while the Chicago group is the largest CCM patient site overall.

UNM is one of the few CCM Centers of Excellence in the world, said Zafar, who serves as the centers director. "We want to thank dozens of our New Mexican families, patients and healthy folks with the diagnosis of familial and sporadic CCM who participated in this trial and are the main force behind the advancements in the field.

Patients shared stool samples and their medical records for the study, which found close correlations between the prevalence of certain bacterial strains in the gut and the severity of their symptoms.

The researchers suggest that altering the diet or microbiome composition might be a way of treating the condition.

"The next step includes confirming the mini-variations that may be present even within the CCM population and to see if we can create an algorithm that can correlate how these specific gut microbiomes manipulate the severity of the disease in the CCM population, Zafar said. We still have a lot of work to do.

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The Gut-Brain Connection - HSC Newsbeat

Studies by Pennsylvania’s AHN Neurologists Improve Understanding of Stroke Therapy Risks in Patients with Chronic Health Conditions – Cath Lab Digest

Pittsburgh, Pa (Sept. 2, 2020_ Intravenous thrombolysis may put stroke patients with chronic kidney disease (CKD) at a higher risk for intracranial bleeding and mortality, according to a recent study published in the journal Neurology by researchers at the Allegheny Health Network (AHN) Neuroscience Institute. The study, Intravenous thrombolysis in patients with chronic kidney disease: A systematic review and meta-analysis, surveyed various studies published across different countries and assessed the association of CKD among more than 60,000 acute ischemic stroke patients undergoing IV thrombolytic therapy.

According to the CDC, stroke kills about 140,000 Americans each year, accounting for approximately one out of every 20 deaths. Nearly 90 percent of strokes are classified as acute ischemic strokes which take place when a blood clot or narrowed artery obstructs blood flow to the brain. Within minutes, the lack of oxygenated blood to the brain can cause a severe, permanent neurological injury, and even death.

Patients who suffer an acute ischemic stroke and arrive early to the hospital are often administered IV thrombolysis to dissolve dangerous clots in blood vessels, improve blood flow, and prevent damage to tissues and organs, said Konark Malhotra, MD, vascular neurologist at Allegheny General Hospital (AGH) and the AHN Neuroscience Institute, and principal investigator of the study. We wanted to better understand how this course of treatment with IV thrombolytic therapy may impact an already vulnerable population with a specific chronic condition like chronic kidney disease.

In the systematic review, Dr. Malhotra and his colleagues evaluated outcomes with special attention being paid to intracranial bleeding, three-month mortality and functional independence rates with regard to a patients mobility and ability to maintain high levels of self-sufficiency.

Across 20 independent studies that were analyzed, a significant correlation was determined to exist between CKD and worsened clinical outcomes most notably, a higher risk of intracranial bleeding and mortality.

The primary causation of worsened outcomes presents an opportunity for further research. A likely contributing factor is the high rate of comorbidities seen in the study population; for example, hypertension and diabetes are the leading causes of chronic kidney disorder, said Ashis Tayal, MD, neurologist and director of the AGH Stroke Center.

In addition to Dr. Malhotra and Dr. Tayal, other neurologists who contributed to the study include Aristeidis H. Katsanos, Nitin Goyal, Henrik Gensicke, Panayiotis D. Mitsias, Gian Marco De Marchis, Eivind Berge, Anne W. Alexandrov, Andrei V. Alexandrov and Georgios Tsivgoulis.

In anotherstudypublished earlier this year in the AHA Journal ofHypertension, Dr. Malhotras team provided additional insight on how clinical outcomes of acute ischemic stroke patients who undergo stroke thrombectomy procedures are impacted by elevated blood pressure levels.

Dr. Malhotra performed a systematic review and pooled results from 25 published studies involving 6,500 patients who underwent acute stroke thrombectomy. This study analyzed the association of blood pressure systolic and diastolic before, during or after acute stroke thrombectomy with various clinical outcomes. The authors found that higher blood pressure levels negatively affect stroke related outcomes such as intracranial bleeding, death and functional independence in daily living.

Studies such as those led by Dr. Malhotra and his team are essential to improving our understanding of chronic disease management and developing better therapeutic strategies that can make a life-changing difference for stroke patients, continued Dr. Tayal.

AHN was recently recognized by the American Stroke Association for its excellence in stroke care. In August, the Network announced six Network hospitals earned Gold Plus Elite and Silver Plus designations for its adherence to guideline-directed therapies and protocols which in turn improves patient outcomes and decreases stroke recurrence rates.

For more information on the AHN Neuroscience Institute, visit ahn.org.

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Studies by Pennsylvania's AHN Neurologists Improve Understanding of Stroke Therapy Risks in Patients with Chronic Health Conditions - Cath Lab Digest

COVID-19: Responding to the business impacts of Neurology Devices Market: New Investment Opportunities Emerge to Augment Segments in Sector by 2029 -…

The recently published market study by MRRSE highlights the current trends that are expected to influence the dynamics of the Neurology Devices market in the upcoming years. The report introspects the supply chain, cost structure, and recent developments pertaining to the Neurology Devices market in the report and the impact of the COVID-19 on these facets of the market. Further, the micro and macro-economic factors that are likely to impact the growth of the Neurology Devices market are thoroughly studied in the presented market study.

According to the report, the Neurology Devices market is expected to grow at a CAGR of ~XX% during the forecast period, 20XX-20XX and attain a value of ~US$ XX by the end of 20XX. The report is a valuable source of information for investors, stakeholders, established and current market players who are vying to improve their footprint in the current Neurology Devices market landscape amidst the global pandemic.

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The leading players in the global neurology devices market that have been profiled in the report are: Medtronic, Boston Scientific Group, St. Jude Medical, Cyberonics, and Covidien.

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COVID-19: Responding to the business impacts of Neurology Devices Market: New Investment Opportunities Emerge to Augment Segments in Sector by 2029 -...

Neurovascular or Interventional Neurology Devices Market 2020 Size by Product Analysis, Application, End-Users, Regional Outlook, Competitive…

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Uncovering the neurological connections to COVID-19 | Penn Today – Penn Today

More than seven months into the battle against COVID-19, scientists have gained a better understanding of the disease and its symptoms while finding new and improved ways to test and treat patients. But countless mysteries remain. Why does COVID-19 cause some patients to lose their sense of smell and taste? What are the psychiatric andneurological complicationsnow associated with COVID-19 infectionsand can these issues be prevented?

Currently, there are a variety of research efforts across Penn to uncover the neurological implications of the disease, including stroke, neuroinflammation, and loss of smell.

Even thoughinitialreportssuggested a significant risk of stroke in patients hospitalized with COVID-19, research led byBrett Cucchiara, an associate professor of neurology at the Perelman School of Medicine, published inStroke, showed a low risk.

Yes, there is a connection between stroke and COVID-19, but we dont want people to overly worry about this, Cucchiara says. Its important to understand that the risk of stroke for those suffering from COVID-19 is fairly lowits impacting about two percentof patients hospitalized for the virus. And for every patient hospitalized, there are maybe 10 or 20 who arentperhaps even more considering those who are asymptomatic. That small percentage still merits continued investigation, Cucchiara added. He and his team are continuing to look at the linkage between stroke and COVID-19 to learn more about the virus and improve treatment for patients.

Read more at Penn Medicine News.

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Uncovering the neurological connections to COVID-19 | Penn Today - Penn Today

Phase 1 Trial Suggests PD01A Is Safe in Parkinson Disease Treatment – Neurology Advisor

Repeated administrations of PD01A were found to be safe and well tolerated over an extended time period in patients with Parkinson disease (PD), according to phase 1 study results published in Lancet Neurology.

PD01A is an immunotherapy that targets oligomeric -synuclein, a potential driver of neuronal dysfunction in patients with PD. Study researchers sought to evaluate the safety and tolerability of PD01A in patients with PD. A total of 24 patients with PD aged between 45 and 65 years (mean age, 54.9 years) were recruited from a single center in Austria and enrolled into this first-in-human phase 1 trial of PD01A.

All patients were on a stable treatment regimen for PD for 3 months prior to enrollment. Patients were randomly assigned to receive 4 subcutaneous administrations of either 15 g (n=12) or 75 g (n=12) PD01A that were injected into the upper arms. These patients were followed up for 52 weeks and then an additional 39 weeks.

After the 39-week follow-up, patients were randomly assigned to receive the first booster immunization with PD01A at 15 g (n=10) or 75 g (n=12). The follow-up period after the second randomization was 24 weeks. Patients then received a second booster of 75 g PD01A and were followed up for another 52 weeks. Study researchers examined the primary outcomes safety and tolerability with patient diary data and investigator assessments at each visit. These outcome assessments focused on all local or systemic treatment-emergent adverse events (TEAEs).

Approximately 87% of patients (n=21) received all 6 administrations of PD01A and completed between 221 and 259 weeks in the study. All patients in the study experienced 1 adverse event (AE), but the majority of these events were deemed unrelated to treatment from this study. Local injection site reactions, while transient, were the only treatment-related AE reported in this study (n=23). A total of 500 TEAEs were reported by all patients across the follow-up period. The systemic TEAEs possibly related to treatment and reported in 2 patients were fatigue (n=4), headache (n=3), myalgia (n=3), muscle rigidity (n=2), and tremor (n=2).

Investigators observed no abnormalities on MRI after baseline; however, they observed 1 treatment-unrelated microhemorrhage event in the 15 g group. In the 15 g dose group, the geometric group mean titer of antibodies against the immunizing peptide PD01 increased from a baseline of 1:46 to 1:3580 at 12 weeks. In the 75 g dose group, the geometric group mean titer of antibodies increased from 1:76 at baseline to 1:2462 at week 12. Over a 2-year period, antibody titers returned to baseline. These titers were capable of being reactivated following a booster immunization from week 116 onwards, subsequently reaching geometric group mean titers of up to 1:20218.

Limitations of the study included the small sample size, the lack of a placebo group, and the inclusion of patients from a single center in Austria, which may reduce generalizability of the findings.

Investigators concluded that their findings of a sustained -synuclein-specific antibody response, suggests immunization with PD01A might be a promising strategy for long-term management of PD.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors disclosures.

Reference

Volc D, Poewe W, Kutzelnigg A, et al. Safety and immunogenicity of the -synuclein active immunotherapeutic PD01A in patients with Parkinsons disease: a randomised, single-blinded, phase 1 trial. Lancet Neurol. 2020;19(7):591-600.

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Phase 1 Trial Suggests PD01A Is Safe in Parkinson Disease Treatment - Neurology Advisor