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

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

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

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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

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

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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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Early Extubation Tied to Better Outcome After Stroke Thrombectomy – Medscape

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

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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

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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

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

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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 -…

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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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Companies profiled in the report

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

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The Neurovascular or Interventional Neurology Devices market report gathers together the key trends influencing the growth of the industry with respect to competitive scenarios and regions in which the business has been successful. In addition, the study analyzes the various limitations of the industry and uncovers opportunities to establish a growth process. In addition, the report also includes a comprehensive research on industry changes caused by the COVID-19 pandemic, helping investors and other stakeholders make informed decisions.

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The report includes pivotal details about the manufactured products, and in-depth company profile, remuneration, and other production patterns.

The research study encompasses information pertaining to the market share that every company holds, in tandem with the price pattern graph and the gross margins.

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

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

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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

Therapeutic Options for Peripheral Neuropathy in Parkinson Disease – Neurology Advisor

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Peripheral neuropathy is frequently seen in patients with Parkinsons disease (PD) and may increase the functional disability in these individuals. A review article published in Neurological Sciences discussed the etiology of peripheral neuropathy in the context of PD.

Previous studies have shown that peripheral neuropathy can adversely affect the lives of patients with PD. As limited data are available on small fiber neuropathy (SFN) and effective treatments for peripheral neuropathy in PD, the current review focused on the etiology, pathological mechanisms, subtypes, and management of the neurological problem in PD.

The exact pathogenic mechanism of neuropathy in PD is not entirely clear and there are many potential factors involved in the disease process, including medication, mitochondrial dysfunction, oxidative stress, and genetic susceptibility.

Diagnosis

The diagnosis is based on clinical findings along with nerve conduction studies and electromyography. As some neuropathies may present with normal findings on peripheral nerves testing, a thorough patient history is vital.

The initial investigation of peripheral neuropathy often includes glucose tolerance testing, fasting glucose levels, measurement of vitamin B12, methylmalonic acid (MMA), homocysteine (Hcy), and serum protein electrophoresis.

The diagnosis of SFN is commonly difficult to be made on the basis of peripheral nerve testing and clinical criteria are more important. Intraepidermal nerve fiber density in skin biopsy or analysis of quantitative sensory testing can help in establishing the diagnosis.

Additional tools that may aid in the diagnosis and severity assessment of SFN include autonomic testing utilizing a variety of reflex tests, intraepidermal electrical stimulation tests, corneal confocal microscopy, and microneurography.

Parkinson Disease Treatment and Neuropathy

Levodopa, the gold standard treatment for PD, may play an important role in the development of peripheral neuropathy . Long-term use of levodopa can lead to increased levels of Hcy and MMA which have been linked to neuropathy, as well as increased risk for cardiovascular diseases, neurodegenerative diseases, and neural tube defects. While many studies have pointed at B12 deficiency as the potential cause for levodopa-associated neuropathy, others suggested that folate deficiency is a more important cause.

As not all patients taking levodopa develop neuropathy, experts have suggested there may be a genetic susceptibility for the development of neuropathy in some patients. Potential candidate genes involved in PN with PD may be the parkin or MTHFR genes.

Levodopa-carbidopa intestinal gel (LCIG) are additional treatment options that were found to be associated with peripheral neuropathy. Studies have suggested a higher incidence of neuropathy in PD patients treated with duodopa or LCIG. While limited data exist on the risk for SFN, there are reports suggesting an association between LCIG treatment with neuropathy of small fibers.

Administration of catechol-O-methyltransferase (COMT) inhibitors may attenuate the levodopa-induced increase in plasma Hcy and MMA levels. However, due to the limited available data, more studies are required to better understand the efficacy of COMT inhibitors in preventing peripheral neuropathy.

Treatments of Peripheral Neuropathy

The data on treatment of peripheral neuropathy in PD remain limited and additional studies are needed to explore the benefits of cobalamin injections with folate supplements and COMT inhibitors, especially in levodopa-treated patients. Novel treatment options include electromagnetic and laser therapy.

At this point in time, COMT inhibitors, such as entacapone, are the main treatment options for peripheral neuropathy. One study has shown that the addition of COMT inhibitors may improve levodopa-associated neuropathy. However, as COMT inhibitors were not found to be effective against peripheral neuropathy secondary to causes other than levodopa exposure, other therapeutic options are needed.

Combination of vitamin B12 and methylcobalamin is recommended by some experts in the field and there are reports this may improve pain and paresthesia, but most of the data are based on studies in patients with diabetic neuropathy.

Several enzymes and genetic markers were suggested as therapeutic targets for peripheral neuropathy and have shown promising results. Furthermore, monoclonal antibodies may prove to be useful, as there are reports from patients with malignant tumors in which the combination of bendamustine-rituximab was found to alleviate immune-mediated neuropathies. Early reports have suggested a potential role for ultrasound guided vitamin B12 injections.

Future studies should investigate the toxic effects of elevated Hcy and MMA levels in patients with PD along with viable treatment options that include vitamin B12 and folate therapy. Large scale studies are required in order to understand the role and efficacy of COMT-Is along with other IPD interventions in [peripheral neuropathy], concluded the investigators.

Reference

Paul DA, Qureshi ARM, Rana AQ. Peripheral neuropathy in Parkinsons disease [published online May 1, 2020]. Neurol Sci. doi:10.1007/s10072-020-04407-4

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Therapeutic Options for Peripheral Neuropathy in Parkinson Disease - Neurology Advisor

Duke Neurology congratulates the graduating residency class of 2020 | Duke Department of Neurology – Duke Department of Neurology

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The Duke Neurology residency class of 2020 held their graduation virtually this week, celebrating the completion of their four years of training and contributions to our Department amidst departmental growth, a continuing global pandemic, and numerous other challenges.

Our graduating class of residents will complete their neurology training in fellowships across the field of neurology, both at Duke and in other leading academic institutions across the country.

Congratulations to you all. Youre an amazing class of residents and truly phenomenal doctors. Make yourselves proud of yourselves as we are of you, said Assistant Professor Shreyansh Shah, MD, who shared hosting duties for the graduation. Thanks for selecting us and letting Duke Neurology be a part of your training.

Our graduating residents have selected the following fellowship programs for next year:

The ceremony included a homemade blues song by Associate Professor Emeritus Marvin Rozear, MD, who has been a mainstay of the Neurology Residency program for four decades.

Graduation closed with the presentation of awards to faculty and residents, with winners selected by this years graduating class. Assistant Professor Scott Le, DO, received the 2020 Marvin Rozear Common Sense Award. Assistant Professor Scott Strine, DO, received the 2020 Eun-Lyu Lee Excellence in Teaching Award. Graduating resident Abhi Kapuria, MD, received both the E. Wayne Massey Teaching Award and the Chief Resident Research Award for 2020.

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Neurologists on the Front Lines: The Burden of COVID-19 on… : Neurology Today – LWW Journals

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Article In Brief

Disparities in access to health care, WiFi services, comorbidities, and even clean running water have led to a disproportionate number of COVID-19 cases among Native American populations. Neurologists who serve the Navajo Nation discuss the conditions that have led to those increases.

The novel coronavirus has hit Native American communities in the United States at such an alarming rate that Doctors Without Borders has sent teams of medical professionals to the American Southwest to help the Navajo Nation, which as of May 12 had more than 3,100 cases of COVID-19 and more than 100 deaths among its population of roughly 175,000 people.

If the Navajo Nation's reservation, which spreads across New Mexico, Arizona, and a corner of Utah, were a state, as of May 11, it would have the second-highest per capita rate of confirmed coronavirus cases in the countrybehind only New York. And as of May 14, 60 percent of the people who had died from COVID-19 in New Mexico were Native American, although they make up only 11 percent of the state's population.

Neurologists who work with the Navajo Nation and other Native communities told Neurology Today that the situation dramatically illustrates the historical inequities in access to health care, infrastructure and services affecting these communities, noting that many people who do not live in the area do not understand the difficulties of life on the reservation.

The Navajo Nation covers some 27,000 square miles, with about six people per square mile. There's a lot of space and not a whole lot of people, so you would think it would be easy to socially distance, says David M. Labiner, MD, professor and head of the department of neurology at the University of Arizona in Tucson.

But more than 30 percent of Navajos don't have running water at home. They have to haul water in on a truck every few days, which means there isn't the opportunity to wash hands as frequently and for as long as necessary. And to get their water supplies from water stations, or to get food from small general stores, people often have to break social distancing guidelines.

Amazon Fresh and Instacart don't deliver to remote areas of Arizona and New Mexico where you can drive for miles on unpaved roads without seeing a house. A lot of my patients don't have electricity in their homes, or necessarily reliable access to mail or phone or internet, said Mike Stitzer, MD, director of the Native American Neurology Service at Winslow Indian Health Care Center in Arizona, who has been a member of AAN's Diversity Leadership Program and its Health Care Disparities Task Force. Dr. Stitzer is also an enrolled member of the Enterprise Rancheria Estom Yumeka Maidu tribe.

There is also a lot of intergenerational living, with multiple generations of families living either in the same house or right next to each other, sharing food and water. It may be 20 or 30 miles to your nearest neighbor, but if a case makes it to one person in a family group, there's a high chance it will spread to everybody.

Access to health care can also be challenging. There are seven sites that serve the Navajo Nation: Chinle Comprehensive Health Care Center (60 beds), Tuba City Regional Health Care (73 beds), Northern Navajo Medical Center (69 beds), Gallup Indian Medical Center (99 beds), including six ICU beds), Tshootsoo Medical Center (56 beds, including ICU beds), Crownpoint Health Care Facility ( 32 beds), and Sage Memorial Hospital (25 beds), Dr. Labiner said.

But even though the network of facilities is very capable of providing care, when conditions become serious, people have to travel a long way for access to specialists, said Dr. Labiner.

It's not that Native communities are not working to stem the spread of the coronavirusin fact, precisely the opposite. The Navajo Nation has actually been significantly more proactive in addressing the risks of COVID-19 than many other states and governments, said Dr. Stitzer.

The first cases here appeared probably in early March. There had been a religious gathering in Chilchinbito, in the eastern part of Arizona, that drew hundreds of people from all over the Nation, and one person at that gathering later turned out to have tested positive. Within a week or two, we started seeing cases trickling out and as soon as that happened, the Nation began talking about social distancing and shelter in place for anything but essential servicesweeks before anyone else in Arizona was doing it.

The Nation also put out orders for residents to wear cloth masks in public in late March and enacted a nightly curfew on March 30, followed by complete weekend curfews. They have police on the road issuing citations, and there are thousand-dollar fines for violations, said Dr. Stitzer. We've also been very proactive at our health center, with a dedicated screening protocol and separate waiting rooms for anyone with any possible respiratory symptoms by the end of February.

The per capita testing rate for COVID-19 is also much higher among the Navajo Nation than in the surrounding region, Dr. Stitzer said. As of May 14, the Nation had conducted conducted 19,441 tests for its population of 175,000, compared with 175,455 for the state of Arizona (population approximately 7.3 million)which comes out to approximately 111 tests per 1,000 people in the Navajo Nation and 24 tests per 1,000 people in Arizona.

Despite these extraordinary efforts, a disproportionate burden continues to fall on Native peoplesand on the health care systems that serve them.

The pandemic is only magnifying the health care disparities faced by Native Americans, said Cumara O'Carroll, MD, MPH, an assistant professor of neurology at the Mayo Clinic in Scottsdale, AZ, who provides stroke services to patients at Tuba City Regional Health Care through a telestroke network. Dr. O'Carroll was also a participant in the AAN's Diversity Leadership Program.

We know that there are a number of factors contributing to the high rates of infection in the Navajo Nation, and some of that is increased susceptibility from pre-existing underlying medical conditions like diabetes, hypertension, coronary artery disease, and obesitymany of which are the same risk factors for stroke, of course. In this country, we have barriers to care that fall across racial and ethnic lines, and those barriers and disparities are exacerbated and accelerated in a pandemic like this one.

Health care systems serving the Native community, such as Tuba City, are struggling to get access to medical supplies, personal protective equipment, and other resources, Dr. O'Carroll said. What we are seeing and hearing is that they are being expected to provide the same level of services that they have always provided, but with fewer resources. Their system is being overwhelmed by more and more patients, and the patients who are coming in are critically ill.

As an example, she described a recent telestroke call with some physicians in Tuba City. We have algorithms and systems in place when someone comes in with stroke symptoms, and they are fine-tuned through many years of work, she said.

But because clinicians and staff are being spread so thin, these systems are breaking down. In this case, we had a patient with clear stroke symptoms who needed a CT scan immediately. They said to me, Doctor, we understand, but it can't be done immediately because we have a long line of critical patients waiting for care. This is a facility that usually runs very smoothly with a superior caliber of physicians. They're very resourceful. They can do it all. You could sense their frustration and stress. This pandemic is resulting, at times, in delays in care for acute stroke interventions. People are still getting treatment, but not in the timeline we are accustomed to pre-pandemic.

The Navajo Area Indian Health Service (IHS) does not have many hospital beds. There are just over 400 beds for the entire Navajo Nation. I don't know how many are ICU beds, but it's not more than a handful, and the same goes for ventilators, Dr. Stitzer said.

For comparison, the major tertiary care center for northern Arizona, Flagstaff Medical Center, has approximately 300 beds, of which about 55 are ICU. While none of the major hospitals in Arizona has been overwhelmed like New York and New Jersey have, the IHS hospitals in the eastern portion of the Navajo Nation have been very busy.

By mid-May, the state's hospitals have been hovering at only about 21 percent of ICU beds free, while it had been approximately 30 percent or so for March and the first half of April, Dr. Stitzer added.

Beds in use have slowly crept up over the second half of April. The cases per week in the state also continue to increase. With Arizona starting to roll back distancing measures, I am nervous that this will result in a spike of new cases. That would both make it harder to transfer the very ill patients out of the IHS hospitals to locations with more ICU beds, and also increase the chances of more cases coming from Arizona into the Navajo Nation.

To ease the burden on health care facilities in any outbreak areas, patients with non-emergent conditions are being urged to take advantage of newly expanded telehealth optionsbut the digital divide in Native communities means that this option, too, is less accessible to them.

Federal funding was given to the Navajo Nation several years ago to improve rural broadband and cellular service, and most of our patients do have cellphones at this point and many have smartphones, said Dr. Stitzer. But data are not yet reliable or fast enough for most people to do video chats. We have been able to do some successful video telemedicine visits, but my clinic often has been relying on telephone visits. However, patients may not have enough minutes to make all the calls they need.

Dr. Stitzer hopes that the response to COVID-19 will help start the spark of long term change needed to correct the massive, historical institutional challenges to improving health outcomes for Native Americans, such as the rate of poverty and issues associated with that, such as food deserts.

We need the rest of the country to understand the lack of resources that many of our patients have, and what this pandemic has meant to them. The fact COVID-19 is much more deadly in the elderly population is especially tough as they have a special place in Din society. They hold the traditions, language, etc. and pass it down to the younger generations. So a family and community losing someone is this group is hit particularly hard. It's not exactly equivalent, but my small tribe in Northern California, Estom Yumeka Maidu, has almost lost our spoken language as the elders are passing on. It's only minimally recorded and written down, so once it's gone it's gone. I have some understanding of what the loss of each elder to the tribe's culture is like, and it can be really difficult.

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Neurologists on the Front Lines: The Burden of COVID-19 on... : Neurology Today - LWW Journals

Stroud family to take part in 20km challenge for rare neurological condition – Stroud News and Journal

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A young couple from Stroud have joined forces with their family in Spain to take part in the Marvel Superhero at Home challenge to raise awareness for the rare and often unheard about neurological condition ataxia.

Thomas and Samantha will undertake a triathlon with Thomas's dad Brian to raise awareness of the condition which effects three members of their family, including Brian who lives in Spain.

Brian, along with his brother Nigel and sister Susan all suffer with ataxia.

Nigel was first diagnosed in his late teens in the 1980s, and then Brian and Susan were diagnosed.

Brian said: "At the time of diagnosis ataxia was virtually unheard of, now it's a little better but the vast majority of people have never heard of it hence the need to raise awareness."

Brian and his siblings are all from Stroud, although he now lives in Spain, while his sister Susan lives in New Zealand and his brother lives on Stamford.

Thomas and Laura, Brian's children, still live in Stroud.

The rare condition predominantly impacts mobility, co-ordination and speech.

People with ataxia are often wrongly perceived to be drunk because of their strange gait, lack of mobility and slurred speech.

Brian said:"It is a life limiting degenerative condition where from diagnosis the only certainty is that it will get worse.

"It is ageless, impacting adults and children alike, and in the UK there are only around 10,000 adults and 500 children with ataxia."

The superhero challenge means the family will have to complete a 20km distance between June 15 and July 15 that can be completed anywhere and in any way.

Brian, his son Thomas and Thomas's wife Samantha have all decided to undertake the 'triathlon' challenge between them by swimming, cycling and walking.

The challenge will raise money for Ataxia UK and the family have already exceeded their sponsorship target.

To donate visit: bit.ly/2UYrXeO

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Stroud family to take part in 20km challenge for rare neurological condition - Stroud News and Journal

Teva Presented New Data at the European Academy of Neurology Congress Evaluating the AJOVY (fremanezumab) Experience in Populations with…

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Additional analyses examine the impact of migraine in France, Spain and the United Kingdom

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) presented a wide range of important new data on AJOVY (fremanezumab) and the societal and economic impact of migraine in Europe at the 6th Congress of the European Academy of Neurology (EAN). This years EAN congress was a virtual meeting due to the global coronavirus pandemic.

The fremanezumab data included pooled analyses of the AJOVY Phase 3 clinical trials (FOCUS, HALO-episodic migraine (EM) and HALO-chronic migraine (CM)) which focused on the safety, efficacy and improved quality-of-life for patients experiencing difficult-to-treat migraine. Post-hoc analyses were also evaluated in patients who may experience challenges when managing their migraine due to comorbidities.

Migraine creates a significant disease and economic burden. With more than one billion people impacted globallyi, migraine is the second leading global cause of years lived with disabilityii and annual costs of the disease in the U.S. and EU are $200 billion.iii,iv

"Migraine imposes physical, emotional and societal burdens worldwide and yet available treatment options are often unsatisfactory for many patients," said Joshua M. Cohen, MD, MPH, FAHS, Senior Director, Global Medical Affairs Therapeutic Area Lead Migraine & Headache, Teva. "As a leader in neurology and migraine treatment, Tevas goal is to continue evaluating the impact of AJOVY across various patient populations to ensure that reliable and relevant information is available to healthcare professionals when considering treatment options."

Pooled Analysis Shows Impact of AJOVY in Patients with Migraine

Pooled analyses of the Phase 3 FOCUS, HALO-EM and HALO-CM clinical trials in patients 60 years of age or older with EM or CM, examined treatment with fremanezumab versus placebo over 12 weeks. Reductions from baseline in monthly migraine days, headache days of at least moderate severity, and days with acute headache medication use over 12 weeks were significantly greater with quarterly and monthly fremanezumab versus placebo (all P0.0103).

The analyses also examined early onset of efficacy and improved headache-related disability, health-related quality-of-life, productivity, and satisfaction in this patient population. Additionally, the analyses looked at cardiovascular adverse events in fremanezumab and placebo treated patients in this group, regardless of whether or not they had a cardiovascular medical history.

Cardiovascular Safety of AJOVY

Additional pooled analyses of the Phase 3 trials were also conducted to examine cardiovascular safety across all patients. The analyses were performed in migraine patients with cardiovascular/cerebrovascular risk factors (e.g., diabetes mellitus, hyperlipidemia, obesity, hypertension, hormonal birth control pill use) (n=499). The overall incidence of cardiovascular adverse events in these patients were low and comparable between fremanezumab and placebo treated groups. An increase in the number of risk factors did not seem to correlate with an increase in frequency of cardiac and vascular adverse events. Additionally, the analyses examined patients with migraine using cardiovascular medications at baseline (n=280), and patients using concomitant triptans (n=1,123) with those who did not use triptans. Similar to the overall trial populations, the most common adverse events reported in all of these subgroups were injection site reactions.

Disease and Economic Burden of Migraine in Europe

Two analyses evaluated the economic and disease burden of migraine across patients in the United Kingdom, France and Spain. The first analysis found that CM patients experienced greater disability caused by migraine versus EM patients. CM patients also reported lower health status than EM patients for their most recent migraine. The second evaluation, which included examining electronic medical records from 84,266 adult patients with EM and CM, found CM patients had more migraine-related consultations with their general practitioners than EM patients. Additionally, average quarterly treatment costs were higher for CM patients in all three countries.

These results point to substantial migraine disability and unmet treatment needs across the three countries. They also associate migraine with a significant healthcare and economic burden that includes higher costs for CM patients.

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Accessing Teva EAN Presentations

The ePresentations and ePosters shared by Teva at EAN can be accessed by healthcare professionals through the EAN conference website. The sessions will be available at no cost and will also be on-demand for EAN members from 27 May onward.

Additional resources on migraine, including articles, videos, publications summaries, podcasts and webinars can be accessed on Neurologybytes. Neurologybytes is a platform published by Teva to support neurologists in accessing timely, bite-sized content on the latest research developments and clinical care perspectives in the world of migraine and multiple sclerosis (MS).

Information for Europe about AJOVYcan be found here.

Adverse events should be reported.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events. Reporting forms and information can be found at https://www.hpra.ie. Adverse events should also be reported to Teva please refer to local numbers.

About Teva

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has been developing and producing medicines to improve peoples lives for more than a century. We are a global leader in generic and specialty medicines with a portfolio consisting of over 3,500 products in nearly every therapeutic area. Around 200 million people around the world take a Teva medicine every day and are served by one of the largest and most complex supply chains in the pharmaceutical industry. Along with our established presence in generics, we have significant innovative research and operations supporting our growing portfolio of specialty and biopharmaceutical products. Learn more at http://www.tevapharm.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding new analysis of fremanezumab Injection which are based on managements current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to:

and other factors discussed in our Quarterly Report on Form 10-Q for the first quarter of 2020 and our Annual Report on Form 10-K for the year ended December 31, 2019, including in the sections captioned "Risk Factors" and "Forward Looking Statements." Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements.

i Global Burden of Disease 2016 Disease and Injury Incidence and Prevalence Collaborators. Lancet 2017;390:121159.

ii Saylor D, Steiner TJ. The Global Burden of Headache. Semin Neurol 2018 Apr;38(2):182-190.

iii Gooch CL, et al. Ann Neurol 2017;81:47984.

iv Linde M, et al. Eur J Neurol 2012;19:70311.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200524005015/en/

Contacts

IR Contacts United States Kevin C. Mannix (215) 591-8912Ran Meir 972 (3) 926-7516

PR Contacts United States Doris Li (973) 265-3752Israel Yonatan Beker 972 (54) 888 5898

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Teva Presented New Data at the European Academy of Neurology Congress Evaluating the AJOVY (fremanezumab) Experience in Populations with...

Amid the COVID-19 Pandemic, Neurologists in Canada Report Pulling Back from EMD Serono’s Mavenclad and Sanofi Genzyme’s Lemtrada, While Roche’s…

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Use in treatment-nave patients drives recent growth of Biogen's Tecfidera and Genzyme's Aubagio in Canada, as reported switch share has remained flat over the past year - reflecting the continued shift in using established oral agents earlier in the multiple sclerosis treatment algorithm

EXTON, Pa., May 27, 2020 /PRNewswire/ -- The COVID-19 pandemic has (at least temporarily) transformed neurology practices and multiple sclerosis (MS) patient management patterns across Canada, according to the most recent report included in Spherix's RealTime Dynamix: Multiple Sclerosis (Canada) service. The report, which collected the responses of 50 Canadian neurologists surveyed between April 6th and May 2nd, found that 90% of respondents indicate the novel coronavirus outbreak has had a high impact on their practice. While preference for induction versus escalation treatment was clearly on the rise prior to the pandemic, new data suggest a potentially transient reversion to more conservative disease-modifying therapy (DMT) treatment patterns.

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Neurologists express hesitation to prescribe or re-dose patients with immunosuppressive DMTs, namely Roche's Ocrevus, Sanofi Genzyme's Lemtrada, and EMD Serono's Mavenclad, due to increased risk of complications or death among MS patients infected with the novel coronavirus. One surveyed neurologist states "becoming more aggressive in [the] treatment of highly active MS" prior to the COVID-19 pandemic, which has now resulted in "more caution with immune-suppressing therapies." This mindset has resulted in a leveling off of reported shares for the immunosuppressant DMTs.

Along with the trajectory of COVID-19 spread, the permanency of COVID-19-related impacts on high-efficacy DMT use remains uncertain. Neurologists anticipate Mavenclad and Ocrevus use to rebound over the next six months, suggesting optimism that MS patient management may soon return to normal. Conversely, Lemtrada share has declined and is projected to remain depressed in the future, bringing into question whether COVID-19 has simply hastened shrinking use of the DMT that may have already occurred as a result of new reports of vascular and immune-related safety concerns.

Regardless, strong preference for Ocrevus, as well as continued uptake among patients recently started on or switched to a new DMT, hints at potential resiliency to COVID-19-related disruption for Roche's brand. The DMT has now established a clear lead within the recently switched segment, following a 60% increase in reported share of recent switches compared to one year ago. Moreover, Ocrevus use among recent new starts has also grown over the same time period, despite caution in early-line DMT treatment paradigms with respect to DMTs that could impact immune response.

Among DMTs considered to be less/not immunosuppressive, uptake of Biogen's Tecfidera and Sanofi Genzyme's Aubagio for MS patients starting on their first DMT has propelled overall oral DMT class share of first-line prescribing to more than twice that of the interferon, glatiramer acetate (GA), and monoclonal antibody (mAb) DMT classes. Aubagio and Tecfidera alone currently account for more than half of recent DMT initiations. In fact, neurologists are more likely to prefer Aubagio than other agents for treatment-nave patients diagnosed with relapsing remitting MS (RRMS) presenting with less active disease. Amid considerable success within the new start patient segment, shares for Aubagio and Tecfidera among recently switched patients have remained relatively stable, resulting in moderate overall growth in use of these established oral DMTs which is being driven by a shift to earlier use in the treatment algorithm.

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While COVID-19 remains a concern, neurologist conservatism may limit uptake of any new DMTs. Nearly two thirds of respondents claim they are currently less likely than normal to prescribe any DMT recently approved or that may be approved in the coming months. Novartis' Mayzent, which received Health Canada approval in March, may be somewhat insulated from this apprehension as the first non-injectable DMT indicated to treat active secondary progressive MS (SPMS). Neurologists agree that Mayzent could become their preferred option in active SPMS, and some already say they would choose the agent over other DMTs for patients with active SPMS or disease transitioning from RRMS to SPMS. Nevertheless, with many neurologists believing that DMTs approved for RRMS are also effective in SPMS, the new market entrant will face considerable competition from high-efficacy DMTs indicated for RRMS, especially Ocrevus, upon expansion of market access and provincial formulary coverage.

Bristol Myers Squibb's Zeposia (ozanimod) and Janssen's ponesimod, late-stage pipeline S1P receptor modulators, will most likely be classified as immunomodulators that may impact immune response. Thus, as with Novartis' Gilenya and Mayzent, both agents, if approved, may face a suboptimal environment upon launch depending upon the length of the COVID-19 pandemic. Few neurologists express high interest in either Zeposia or ponesimod compared to other assessed pre-market DMTs, even those with immunosuppressive mode of action, such as Novartis' ofatumumab.

The next wave of the RealTime Dynamix series will continue to closely track Mayzent's launch, as well as provide a prelaunch assessment of ofatumumab. Spherix's assessment of unmet needs, along with analysis of DMT preferences by MS subtype, will further illustrate which pre-market DMTs have the most potential and likely confirm Aubagio's dominance in early RRMS and Ocrevus' sway in primary progressive MS.

About RealTime DynamixRealTime Dynamix: Multiple Sclerosis (Canada)is an independent service providing strategic guidance through rapid and comprehensive semiannual reports, which include market trending, launch tracking, and a fresh infusion of unique content with each wave. The next semiannual report publishes in November.

About Spherix Global InsightsSpherix Global Insights is a hyper-focused market intelligence firm that leverages our own independent data and expertise to provide strategic guidance, so biopharma stakeholders make decisions with confidence. We specialize in select immunology, nephrology, and neurology markets.

All company, brand or product names in this document are trademarks of their respective holders.

For more information contact:Meg Stabb, Neurology Insights DirectorEmail:info@spherixglobalinsights.comwww.spherixglobalinsights.com

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Amid the COVID-19 Pandemic, Neurologists in Canada Report Pulling Back from EMD Serono's Mavenclad and Sanofi Genzyme's Lemtrada, While Roche's...

Why some drugs work and others don’t in treating neurological disorders – UC Riverside

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Neuromodulatory systems in the brain heavily influence behavioral and cognitive processes. Understanding how these systems modulate perceptual behavior is a crucial steppingstone toward unraveling their roles in brain functions.

One particular neuromodulatory system is the noradrenergic system. Dysfunction of this system is linked to several neurological disorders, such as attention deficit hyperactivity disorder and post-traumatic stress disorder, and is a main target of current drug-administered treatments. But how these drugs work is not well understood.

In a paper published in the journal Neuropharmacology, UC Riversides Hongdian Yang and colleagues provide evidence that activating and suppressing the noradrenergic system in mice affects behavior and motivation in different but not opposite directions, laying the groundwork for understanding why some drugs work while others fail in treating neurological disorders.

We found that using drugs, commonly given to humans, to perturb the noradrenergic system in mice causally affects their motivational state and behavior, said Yang, an assistant professor of molecular, cell and systems biology, whose research focuses on neural circuit mechanisms underlying sensory perception, with potential applications in addressing anxiety and stress-related neurological disorders. Systemic activation and local activation of this system have different effects on behavior and motivation. Since drugs are administered in humans in a systemic manner, their possible off-target effects need to be considered in future work on drug design, drug effects, animal work, and interpreting results.

The researchers found that both localized and systemic suppression of the noradrenergic system impaired tactile detection in mice by reducing motivation. They were surprised to find that while locally activating the system enabled the mice to perform in a near-optimal regime, systemic activation of the system impaired their behavior by promoting impulsivity.

The research paper is the first from the Yang lab since he joined UCR in 2016. Yang received his bachelor's degree in physics from China's Nanjing University, and his doctorate in biophysics from the University of Maryland, College Park. He did postdoctoral research at Johns Hopkins University.

Yang was joined in the research by Jim McBurney-Lin, Yina Sun, Lucas S. Tortorelli, Quynh Anh Nguyen, and Sachiko Haga-Yamanaka of UCR.

The research was supported by UCR startup funds, a UC Regents Faculty Fellowship, a Klingenstein-Simons Fellowship Award in Neuroscience, and grants from the National Institute of Neurological Disorders and Stroke to Yang.

The research paper is titled Bidirectional pharmacological perturbations of the noradrenergic system differentially affect tactile detection.

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Why some drugs work and others don't in treating neurological disorders - UC Riverside