Clinical Neurology: Harmeet Singh, MD: Leesburg, VA

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Harmeet Singh, MD is a neurology specialist with over 20 years of professional experience. Dedicated to helping his patients regain control of their lives, Dr. Singh provides the latest in neurological treatment options along with compassionate, patient-centered care at Clinical Neurology, in Leesburg, Virginia.

After completing medical school at Dayanand Medical College & Hospital, Ludhiana in India, Dr. Singh went on to complete his residency and fellowship at Temple University Hospital in Philadelphia.

As a neurology specialist, Dr. Singh understands the exhausting nature of living with chronic conditions and he works hard to offer an array of cutting-edge and alternative treatment options to let his patients have a direct role in how they receive comfort and care. Whether it's acupuncture, Botox, or more classic treatment options for neurological conditions, Dr. Singh knows that each treatment option has its place.

Combining experience in a wide variety of treatment and testing options with friendly, knowledgeable staff and a focus on personalized patient care, Dr. Singh is the leading neurology outpatient doctor in northern Virginia. Clinical Neurology is currently accepting new patients from Leesburg, Lansdowne, Ashburn, Purcellville, Sterling, Herndon and surrounding areas.

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Clinical Neurology: Harmeet Singh, MD: Leesburg, VA

Adverse Events Reported to Be Higher for Neurological In-Patients in Canadian Study: What Can Be Done? – LWW Journals

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Samson, Kurt

doi: 10.1097/01.NT.0000521707.42281.48

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A retrospective, population-based study found that 11 adverse events (AEs) occurred for every 100 admissions for neurological conditions in hospitals in Canada. Outside experts pointed to system errors and problems with communication especially in handing off patients to other doctors as likely causes of problems.

Nearly 50 percent of adverse events that occur in hospitals are preventable, experts in patient safety told Neurology Today, which is why new data from a Canadian study showing that patients with neurological conditions had significantly more complications that those in the general hospital population are disturbing. The report, they said, speaks to the need for evidence-based best practices that better promote hospital safety.

Published in the June 14 online edition of Neurology, the retrospective, population-based study looked at discharge data for 177,612 pediatric and adult patients with neurological conditions from 115 Alberta health care facilities from 2009 to 2015. The report found 11 adverse events (AEs) occurred for every 100 admissions for neurological conditions this, compared with an earlier (2004) Canadian Adverse Events Study that found 7.5 AEs per 100 patients admitted for any condition at a representative sample of Canadian hospitals. [For more detailed findings, see Data on Adverse Events in Neurological Conditions.]

In the new study, AEs occurred most often in patients with spinal cord injury, stroke, Alzheimer disease and related dementia (ADRD), and traumatic brain injury (TBI). Infections and respiratory complications were the most common AEs except in brain tumor and spinal cord injury patients. Patients with spinal cord injury had 5.4 times greater odds of an AE compared to those with other neurological conditions. Adverse events were also more common in older patients and in those with higher comorbidity scores.

Neurological patients with AEs had 2.4 times the odds of dying compared to those without AEs, said lead author Nathalie Jett, MD, professor of neurology and community health sciences at the University of Calgary Cumming School of Medicine and Canada Research Chair in Neurological Health Services Research at the Hotchkiss Brain Institute & O'Brien Institute for Public Health.

Our findings support previous reports that hospitalized patients are at great risk for AEs, with higher estimates reported in this neurological population compared to the prior Canadian study in the general hospital population.

She noted that a number other international studies have reported that around 37 percent to 51 percent of AEs in hospital patients are preventable.

There are several of steps that can be taken to minimize the risk of AEs in neurological patients such as determining fall risk on admission, avoiding sedating medications, assessing swallowing function early, implementing deep venous thrombosis prophylaxis when necessary and doing careful medication reconciliation so patients do not miss any critical drugs on admission, noted Dr. Jett.

The time is right to carefully explore the reasons for these AEs and to develop and implement standardized clinical care pathways to reduce the rates of AEs for hospitalized neurological patients, she said.

The study authors assessed adverse events from discharge data for patients with one of nine neurological conditions: ADRD, brain tumor, epilepsy, motor neuron disease, multiple sclerosis, parkinsonism/Parkinson disease, spinal cord injury, traumatic brain injury, and stroke.

The researchers included 15 AEs in 18 categories: infections; ulcers; endocrinological AEs; venous thromboembolic; cardiac; respiratory; hemorrhagic; drug-related; fluid-related; obstetrical; fetal; surgical; traumatic; anesthetic; delirium-related; other CNS issues; gastrointestinal; and falls.

Among spinal cord patients, AEs occurred in 39.4 out of every 100 admissions, and among these patients, surgery-related AEs accounted for the highest proportion of AEs followed by infections and respiratory-related AEs (24.4 percent, 23.9 percent, and 16.7 percent, respectively).

The reason for the high proportion of AEs in those with a spinal cord injury is likely multifactorial, Dr. Jett told Neurology Today. Spinal cord patients were more likely to have a surgical AE, she noted, adding that these patients have more procedures and interventions in the hospital.

Commenting on the study, Don B. Smith, MD, FAAN, clinical professor of neurology and director of the Colorado Neurological Institute at the University of Colorado Health Sciences Center, said: The adverse events reported here are clinically significant. Neurologists will rightly be concerned that this paper supports previous reports that neurological patients are more frequently affected by AEs than are non-neurological patients.

The paper is a valuable contribution to the patient safety movement by offering insights into the frequency and types of AEs that affect neurological patients, he said. If confirmed by other studies, the findings may help to stratify and specify the types of AE risks across different types of neurological patients, and such information could be valuable in predicting and preventing adverse events.

Dr. Smith cautioned, however, that the paper was a retrospective, observational study that used ICD-10-CA codes to identify both neurological diagnoses and adverse events. The latter is something that has not yet been validated, and the sensitivity and specificity of administrative data in identifying AEs are not precisely known, he told Neurology Today. It is unfortunate that the researchers were not able to determine which of these adverse events were preventable, he added.

There are many strategies to mitigate the risk of adverse events in hospitals, but limited evidence of their effectiveness, Dr. Smith noted. Preventable harm is usually due to a system failure rather than the actions of individual health care providers. One of the most important root causes is a failure in communication, something that is particularly prone to occur during transitions of care. As a starting point for exploring this issue, I would recommend the AAN's NeuroLearn courses on patient safety.

Janis Miyasaki, MD, FAAN, professor and director of the Movement Disorders Program at the University of Alberta, in Edmonton, noted that throughout Canada the nursing ratios vary across hospitals, regions, and provinces.

In addition, she said, registered nurses have increasingly been replaced by licensed practical nurses.In some hospitals neurology patients are deemed to be lighter care than other groups of patients.

She told Neurology Today that access to neurologists and neurosurgeons could be relevant as a trend, as well.

There are approximately 775 neurologists in Canada compared to [approximately] 14,000 in the US, and the Canadian population is approximately a 9:1 ratio to US, so the neurology workforce is certainly an issue throughout North America.

The findings are pretty generalizable to hospitals in the United States, and are not surprising, said Eric J. Thomas, MD, MPH, professor and director of the University of Texas Houston-Memorial Hermann Center for Healthcare Quality and Safety. Certainly, these results are reason for more focus on improvement, he said.

Although there are evidence-based guidelines that, if followed consistently, might prevent many of these AEs, especially for stroke, best practices are lacking, he told Neurology Today.

Dr. Thomas noted that the study did not address the effect of long MD trainee hours spent on the ward or transitions of care from one shift to another. He said these factors might play a role in higher AEs in patients, adding that other studies have found that increased numbers of shifts, with concurrent increases in handoffs, increase the risk for adverse events.

The solution is not necessarily to make clinicians work longer and thereby reduce handoffs, but rather to improve the way handoffs are conducted and to improve the information in electronic health records, he said.

An important first step is to recognize that AEs among neurological patients are most often the product of multiple failures at various levels within the system of care, rather than at one person or level, said John C. Probasco, MD, assistant professor and medical director of the Inpatient General Neurology Service at Johns Hopkins Hospital in Baltimore.

With that in mind, he said, it is most important to engage all members of the care team in monitoring and reporting events, as well as having a system in place for making such reports. Reporting should include everything from near-misses to the most harmful events. A system for report review is also needed to address the specific event as well as to help identify areas for improvement to prevent future events.

In addition, care team members should be engaged in developing, implementing, and monitoring the impact of any AE interventions.

Finally, it is important to provide feedback to care team members that their report has been noted and steps are being taken to address opportunities or challenges they have identified, ideally with their involvement. This model can be applied not only at the hospital or health system level but at the level of care units and provider teams.

Dr. Probasco agreed with Dr. Thomas that shift length and frequency put both neurologists in training and in practice at risk for cognitive and emotional fatigue, a set-up for AEs to occur.

Sound and consistent sign-out practices are one demonstrated and practical way to reduce communication failures at the point of care transition, he said. Overall, a balance must be struck between the risks posed by shift length and frequency with those posed by care transitions.

* Infections were highest among brain tumor patients (23.6 percent), while surgery-related AEs accounted for a higher proportion of AEs than did respiratory-related AEs (20.0 percent vs 12.1 percent).

* Hemorrhagic issues accounted for 13.5 percent more than respiratory problems.

* Patients under 18 years old with a spinal cord injury or a traumatic brain injury had fewer AEs than those who were 18 or older, while younger patients with a stroke or motor neuron disease had more AEs than those who were older.

* Admissions with ADRD had the greatest proportion of comorbidities, closely followed by stroke and brain tumor. The co-occurrence of neurological conditions was 7 percent, with the highest proportion in patients with PD (32.5 percent) and the lowest in those with multiple sclerosis (8.1 percent).

* The median length of stay was eight days and was highest for spinal cord injuries, ADRD, and parkinsonism/Parkinson disease, while the overall mortality was 9.1 per 100 admissions, and was highest among those with motor neuron disease at 18 per 100 admissions.

* Those with ADRD represented the higher proportion of admitted patients (37 percent), followed by stroke (24.4 percent) and epilepsy (12.9 percent), and of all admissions, 6.9 percent were re-admissions. Readmissions were higher in patients with motor neuron disease, brain tumor, and ADRD.

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Adverse Events Reported to Be Higher for Neurological In-Patients in Canadian Study: What Can Be Done? - LWW Journals

Valley Medical Center | Neurology

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The Neurology Clinic aims to provide the highest level of care to patients with a focus on obtaining and maintaining satisfactory functionality for the patient.

Electromyography and Nerve Conduction Studies play a central role in the evaluation of patients with neuromuscular disorders. EMG/NCS are performed by testing the electrical activity of muscles and measure the conductivity of the nerves.These studies are most commonly used to diagnose disorders of the peripheral nervous system, in order to localize the nerve lesion, provide further information regarding the underlying nerve pathophysiology and assess the severity of the disorder. Disorders include those affecting motor neurons (e.g., amotrophic lateral sclerosis or ALS), nerve roots (e.g., sciatica), plexuses, peripheral nerves (e.g., carpal tunnel, tennis elbow), neuromuscular junctions (e.g., myasthenia gravis), and muscles (e.g., muscular dystrophy). The Institutes outpatient clinic has the capability to perform up to 8 Electromyography and Nerve Conduction Studies (EMG/NCS) per day.

Neuroscience Institute neuropsychologists evaluate cognitive, behavioral and emotional functioning in patients with a variety of neurological conditions, including seizures, brain tumors, strokes, traumatic brain injury or dementia. They also conduct pre- and post-surgical evaluations of patients with epilepsy.

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Valley Medical Center | Neurology

News from the International Congress of Parkinson’s Disease and Movement Disorders: Smartphone Monitoring of PD … – LWW Journals

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Hurley, Dan

doi: 10.1097/01.NT.0000521718.33696.b8

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VANCOUVERThe first clinical trial to employ a smartphone app to continuously measure symptoms associated with Parkinson's disease (PD) has found the technology to be well-accepted by patients during 24 weeks of use and highly correlated with traditional clinical measures, according to a poster presented here on June 6 at the International Congress of Parkinson's Disease and Movement Disorder?s.

Indeed, the smartphone measurements proved sensitive enough to detect upper-limb tremors that were not reported or present during standard physician-administered assessments.

If you compare healthy control data to the patients rated as having no tremor, the data from the smartphone is clearly picking up a tremor, said Michael Lindemann, PhD, from Roche's Innovation Center in Basel, Switzerland, on behalf of the research team.

It's not only consistent with how physicians have measured the disease so far, it actually augments the picture, offering a unique window into patients' day-to-day life in an unobtrusive fashion, Dr. Lindemann said.

Incorporated into a phase 1 clinical trial of a drug under development by Roche and Prothena Biosciences, the study involved 44 patients with early-stage PD. The research also included 35 healthy controls recruited in a separate study using an identical approach. Patients were asked to carry out six tests of symptoms every morning, including sustained phonation, gait, balance, dexterity, rest tremor, and postural tremor. In addition, they were asked to carry the smartphone with them throughout the day so that the device's accelerometer and gyroscope could passively monitor their movements. Results were compared to standard clinical measures, including the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) obtained by clinicians.

Adherence to the protocol was surprisingly good throughout the duration of the trial. Patients performed the six active tests on average at least three times per week, although slowly dropping from over 75 percent adherence at the outset of the trial to about 50 percent by the end. Likewise, the patients carried the smartphone with them to permit passive monitoring about six hours per day at the outset of the trial, dropping to about four hours per day by the end. Even so, that was enough to generate a total of 24,104 hours of passive monitoring during the course of the study.

The smartphones' measurements of the patients' performance of the daily tests were generally consistent with the physicians' ratings on the MDS-UPDRS for these symptoms: rest tremor (p=0.04); postural tremor (p=0.010); dexterity (p=0.04); balance (p<0.001); and gait (p<0.001).

Moreover, active test features for healthy controls were often significantly different from PD patients whose motor symptoms were scored as 0 (that is, absent), suggesting that active test data collected in the two weeks before and after a clinical visit may augment the clinical picture obtained at site visits, the poster stated.

Using machine learning to detect the patients' walking, standing, sitting and other movements during passive monitoring, the study found significantly lower gait activity (36 percent less) than healthy controls, reflecting less mobility. It also detected 17 percent fewer standing up/sitting down transitions per hour compared to healthy controls, and 38 percent fewer turns per hour while walking than healthy controls.

Commenting on the study, E. Ray Dorsey, MD, MBA, professor of neurology and director of the Center for Health and Technology at the University of Rochester Medical Center in New York, said: This is the first time a smartphone has been incorporated into a clinical trial in Parkinson's disease. This is actually a big deal. Rather than just conducting assessments twice a year in the clinic, this study shows you can obtain continuous, objective assessments in the real world. It could be especially useful in drug trials, to see if somebody is showing an improvement over the course of a study. That would be powerful information.

This report was one of several reports from the Neurology Today Conference Reporter coverage of the International Congress of Parkinson's Disease and Movement Disorders. Look for more coverage from the meeting here: http://bit.ly/NTCR-MDS-NT.

In an upcoming issue of Neurology Today, we will provide broader look at the challenges and opportunities of using wearable technologies in neurology clinical trials.

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News from the International Congress of Parkinson's Disease and Movement Disorders: Smartphone Monitoring of PD ... - LWW Journals

Leading Child Neurologist and Autism Expert Isabelle Rapin, MD, Dies – LWW Journals

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Talan, Jamie

doi: 10.1097/01.NT.0000521711.65152.03

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Called the mother of autism, Isabelle Rapin, MD, died in June at the age of 89. Neurologists she trained with share the role she had in shaping their views and careers in pediatric neurology.

Swiss-born child neurologist Isabelle Rapin, MD, who arrived at work to Albert Einstein College of Medicine almost every day for more than six decades, died in June at the age of 89.

Formidable in ways that changed the world for children with autism and their parents, her work helped debunk major misconceived notions about the disorder that it was a single disease, that it was a psychiatric syndrome caused by so-called refrigerator (emotionally cold) mothers, and that it could be caused by vaccinations.

She delivered more than 550 presentations and invited lectures, as visiting professor, symposium organizer or participant, at universities and hospitals around the world. Her research, lectures, and publications were amplified by the thousands of doctors from around the globe that she taught and mentored during the course of her career.

Dr. Rapin was a behavioral neurologist before the term was coined. And her science of autism would become the foundation for the field. She published a paper parsing the contributors to the autism epidemic in Neurology just a month before her death from bacterial pneumonia. Her family is working to publish her next manuscript on why congenital blindness might cause autism, and what this implies about brain development and organization.

Dr. Rapin met and married her soul-mate, Harold Oaklander, during her first year at Einstein. Together they brought four children into the world in the space of five years while she was building her career. The concept that professional women could have it all would not emerge for another half century. She was the first female faculty member at Einstein, and she was its longest-living member. She had no interest in working anywhere else.

Her interest in the human brain was so profound that she arranged an academic autopsy after the death of her brother, a mathematics professor in Switzerland, and brought his brain to the Bronx where she supervised Einstein pathologists to study its delicate tissues. From this, they published the first known neuropathological study of Asperger syndrome. She so enjoyed accompanying her daughter Anne Louise Oaklander, MD, FAAN, a neurologist at Massachusetts General Hospital (and a member of Neurology Today's editorial advisory board), to their renowned brain cutting conference, that she left instructions that her own brain and spinal cord be studied there as well.

Isabelle Rapin was born and raised in Lausanne, Switzerland. Her father was a university professor of English literature. With his wife, an American who graduated from Vassar before her married life in Switzerland, they raised their three children as dual citizens who were fully bilingual in English and French. All would go on to graduate degrees in science and math. Summers with her mother's Connecticut family encouraged Isabelle to seek professional opportunities in the United States after she completed medical school at the University of Lausanne.

Her pediatric internship at Bellevue Hospital and neurology residency at Columbia exposed her to two legends in American neurology: Fred Plum, MD, and Houston Merritt, MD. It was a time when residents lived in the hospital as house officers and took calls every other night. The only female neurology resident, she was judged as sub-par and told she would need to repeat her arduous first year to remain in the residency. She did so, and for the rest of her life told this story to encourage the young people she mentored, including her children: Persevere when times are hard, especially when people say you are not good enough. Have faith in yourself. Put your head down and just keep working.

In 1958, Albert Einstein was a newly-minted medical school in New York, and the dean wanted to create a pediatric neurology specialty. Dr. Rapin, well trained in both specialties, was the obvious appointment. She was interested in communication disorders, particularly the congenital deafness caused by in utero exposure to rubella, and she pushed the then-radical idea that early diagnosis and intensive education could prevent or ameliorate the mental retardation and disability that were felt to be inevitable at that time. Her insights took hold and helped to end the routine practice of institutionalizing and segregating the deaf. For years, she treated children and taught at St. Joseph's School for the Deaf to help deaf children acquire language by other means, including sign language, which improved their brain development and their futures. Her protg, Oliver Sacks, credited her with developing his interest in the senses and later dedicated his book The Mind's Eye to her.

She then began to study how inherited disorders of metabolism caused brain damage, and to explore autism. She believed that this was a common final pathway for many problems in the brain's language systems. She emphasized that autism was a syndrome with many causes, and not a disease. Although known as demanding to her residents, she was known to kick off her shoes and get down on the ground to play with her young patients. She also knew how important it was to support the families. She loved children, knew how to interact with them, and always emphasized the potential each child has, said Dr. Oaklander. It was a treat to watch her play with her grandchildren, while delighting in the normalcy of their own milestones.

Her deep caring, intellect and thinking about patients and their issues is what made her such a force in the field, said Daniel Geschwind, MD, PhD, endowed professor of neurology, psychiatry and human genetics at University of California, Los Angeles. She is one of the last of a generation of great clinician-scientists. Dr. Geschwind and his colleagues started a bi-annual course on autism at Cold Spring Harbor Laboratory and asked Dr. Rapin to give an introduction to the history of autism.

Dr. Geschwind said that she appeared intimidating but it was because of her desire to get at the truth. She would come across crusty but that was like a coating for delicious chocolate candy. She was actually very warm, delightful, compassionate and funny.

Roberto F. Tuchman, MD, FAAN, met Isabelle Rapin in 1986 when he was considering Einstein's child neurology program, and she went on to become his mentor there and lifelong friend. He loved rounding with her. She would discuss a case and rattle off a differential diagnosis and a possible pathology and link everything she was saying back to the behavior and clinical symptoms. She was beautifully descriptive. Dr. Tuchman created a database of all of the autistic patients she had seen at Einstein. I would read her notes and I could almost see the patient before me, he said. This database, and the videos Dr. Rapin would take of the children, led to many insights about the road to autism.

It all started with her need to understand the substrate of language and communication disorders, said Solomon (Nico) Moshe, MD, professor of neurology at Albert Einstein College of Medicine and another of her former fellows. She was an amazing neurologist. She always said: Every patient can teach you something. You just have to listen.

Mark F. Mahler, MD, FAAN, the Saul K. Korey professor and chair of neurology at Albert Einstein College of Medicine, agreed. She was a European intellect, he said. They used to close the library together at midnight. Her humility, her breadth of knowledge and her unique perspective on these disorders was inspiring.

Dr. Rapin was known for keeping long hours, and Dr. Oaklander said that their mother delivered several of her children while she was at work. Sorry, she would say politely. I can't help you finish. I have to walk over to the maternity ward. Despite this, her rich life outside of her Einstein world was rather surprising for those who met her professionally. She was the family's main cook and gardener. They lived in a large apartment in Manhattan and enjoyed their weekend and vacation retreat, Klinkenberg, a pre-revolutionary war Dutch stone house on the Hudson River that they restored and still own. She loved reading. And she especially loved her husband Harold. She was a fabulous person, he said. She had a great mind.

They had many prominent visitors at Klinkenberg, including her close friend Oliver Sacks, MD.

In addition to her commitments to patients and her family, she found time for organizational and administrative leadership. The first director of pediatric neurology at Einstein, she helped launch the International Child Neurology Association. She served on study sections of the National Institutes of Health, and then as a member of their National Advisory Council, a position now held by Dr. Oaklander. The AAN celebrated her achievements with the President's Award in 2010. She became the first vice president of the American Neurological Association in 1981. She had won the International Society for Research in Autism Lifetime achievement award.

A decade ago, Dr. Tuchman saw his mentor at the International Society for Autism Research. You know, Dr. Rapin told her friend, I am the oldest person presenting a poster here. Indeed, she was almost 80. (Her husband, almost 96, still teaches a program on unemployment that he founded at Cornell University while in his 80's.) Dr. Rapin would officially retire in 2012 at the age of 84, but she never stopped working. For the past several years, scoliosis was the only thing that kept her down. I became her wheelchair without wheels, said her husband.

In an autobiography published in the Journal of Child Neurology in 2001, Dr. Rapin wrote: Consider every patient a potential source of new knowledge, describe what you see, pursue your interests vigorously, and learn to cut corners and prioritize. Find a good mentor, enjoy what you do, and be lucky.

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Leading Child Neurologist and Autism Expert Isabelle Rapin, MD, Dies - LWW Journals

Meet Joseph Safdieh, MD, FAAN, Neurology Today’s Incoming Editor-in-Chief – LWW Journals

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Shaw, Gina

doi: 10.1097/01.NT.0000521710.88023.2d

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Joseph Safdieh, MD, FAAN, incoming editor-in-chief of Neurology Today, discusses his passion for education and the people that shaped his journey in neurology.

Growing up in the close-knit Sephardic Jewish community in Gravesend, Brooklyn, in the 1980s and 1990s, Joseph Safdieh, MD, FAAN, knew well what was expected of him. Like his father, a retailer, and his uncles, who worked in the fabric business, he and his two younger brothers would, of course, grow up and start a business career, get married, and have a family. Education was valued, but not to the extent that young people in his family thought much about going to college.

College was maybe a nice thing to do, but the main expectation for men, anyway was that you would go into business. But that never sat well with me, said Dr. Safdieh, an associate professor of neurology and director of the medical student neurology clerkship at Weill Cornell Medical College in New York, who succeeds Steven P. Ringel, MD, FAAN, as editor-in-chief of Neurology Today, as of July 1.

I sensed that even though building your own business is something you can be proud of, it wasn't something that would satisfy me.

Naturally inquisitive, Dr. Safdieh loved both learning and teaching from an early age. I was the nerd. I wore the glasses. I wrote multiple choice questions for my classmates in seventh grade, and had little study groups, he said. Even then, I loved the process of learning by explaining things to others.

So for high school, his parents enrolled him at the Yeshiva of Flatbush, a Jewish day school offering a wider variety of options and interests. The school had graduated many doctors, and even a few Nobel laureates. I spent a lot of time in high school thinking about how I could best blend my love for science with my love for teaching and learning, he said. Even at that early point, I was thinking that I'd love to go into medicine but not just see patients I also wanted to figure out how to pursue my passion for teaching.

With New York City in his bones, Dr. Safdieh had no desire to venture far afield for college, so he entered New York University. His heavy load of AP credits meant that he could finish college in three years, but that gave him even less time to figure out his path. Serendipitously, his freshman year 1995-1996 was also the year that New York University, long known for its strong neuroscience graduate program, decided to launch an undergraduate neuroscience major.

Apparently, many of the faculty weren't thrilled by the idea because they felt they'd have to babysit college kids, he said. So they initially only allowed 15-20 students to enter the major that first year. I got in, and I was thrilled because it was a very competitive group, and it allowed me to become a neuroscience major.

Dr. Safdieh quickly became fascinated with biopsychopharmacology, and how drugs like antidepressants and seizure medications affect the brain. The mystery was intriguing to me how much we were actually doing, but how little we knew about just why we were doing what we were doing. We knew about neurotransmitters and receptors that did this and that, but it was very hand-wavy as to why.

The 1990s, of course, was the decade of the brain, with an explosion of brain research that reached critical mass just as Dr. Safdieh was entering NYU Langone School of Medicine and he already knew what he wanted to do. At our first medical school orientation, people were asking each other what specialty they were thinking of going into, and everybody would say things like, maybe pediatrics, maybe internal medicine, maybe this, maybe that, he said. But I knew I wanted to be a neurologist. I had such intellectual curiosity about the brain and how it works and how little we understand it. The kidneys, the liver, the lungs, the heart they all exist to provide an environment that the brain needs to survive. Everything else can be replaced, but not the brain. We are what our brain is.

Dr. Safdieh's first mentor in neurology was his clerkship director, Richard M. Hanson, MD, who headed the neurology clerkship at the Veterans Administration New York Harbor Hospital. His logical, systematic and organized approach to the specialty helped the young neurologist get his head around the complex specialty. What I love about neurology is that even though we don't fully understand the brain and how it works, when you see a patient with a neurological symptom, there's a structured approach to it that can be taught and can make things that are seemingly complicated very approachable, he says. Dr. Hanson is the first person who taught me that. He took that logical approach but in a very humanistic way.

When it came time to interview for his neurology residency, Dr. Safdieh found himself feeling like an oddity. He was graduating at the top of his class from medical school, but unlike most of his peers, he had little interest in pursuing a career in basic or clinical research. Instead, his interest in becoming an academic neurologist was pursuing a career in neurology education. I wanted to de-mystify neurology, he said. That was my career objective: helping people who don't think they understand neurology recognize that they can care for a patient with a neurologic symptom. I do love research, but again, I especially love the lessons it teaches us.

In interview after interview at top-ranked academic institutions, when Dr. Safdieh mentioned his desire for a career in neurology education, They looked at me like I had three heads. Until his interview at NewYork-Presbyterian/Weill Cornell, with Lisa DeAngelis, MD, FAAN, the chair of neurology at Memorial Sloan-Kettering Cancer Center (and since 2011, chair of the AAN's Science Committee).

Dr. DeAngelis asked what he wanted to do in his career, and bracing himself for the usual blank response, Dr. Safdieh answered honestly that he loved teaching and wanted to be a neurology educator. She actually lit up! She said, I know exactly who you need to speak to, a great mentor at the University of Rochester. If you match here, I'll make sure you meet him.

True to her word, after Dr. Safdieh ranked Cornell number one in his match list and successfully matched there, Dr. DeAngelis introduced him to noted neurology education expert Ralph Jozefowicz, MD, FAAN. I wasn't his resident, so he had no real incentive to help me, but he took me under his wing and checked in with me every few months to help me solidify this nebulous concept of how I could operationalize my interest in neurology education.

At the end of his residency, Dr. Safdieh completed a two-month elective in Rochester through the American Neurological Association, as a visiting instructor in one of Dr. Jozefowicz's courses.

With such a welcoming environment for his passion for education, it's little wonder that Dr. Safdieh remained at Weill-Cornell after completing his residency, where his current chair, Matthew Fink, MD, FAAN, has allowed him to pursue his vision of developing a division of neurology education. He's a rock for me. He's the kind of person that never really says no. He always figures out a way to make happen what you need, he says. Even though this division does not generate revenue, because we're not billing patients or getting grants, we've figured out how to make it work, because he's always looking for the betterment of the department as a whole.

Weill Cornell was no exception to the general rule in most academic medical centers, where the education leg of the classic three-legged stool was the wobbly one. Everybody thinks about research and clinical practice, and education is peripheral, Dr. Safdieh said. But I've been given the freedom to start from the ground up, developing a brand-new formal clerkship curriculum for neurology medical students. We've set up a weekly three-hour time slot to go through that curriculum, developed a study plan, and most importantly, reframed the way we teach everything. We've changed it from Let's learn about this disease or that medication, to Let's learn how you ask patients questions when they present with a symptom. A medical student who's not going to be a neurologist doesn't need to know everything about Parkinson's or epilepsy, but they do need to know the right questions to ask a patient with tremor or seizure or back pain. If we're going to eradicate neurophobia among medical students, everybody who graduates from this program has to learn not to become paralyzed when they see a patient with a neurological symptom.

Success begets success. His new program quickly became recognized by medical students as the strongest of the clerkships, prompting inquiries from the dean's office about just what those guys in the neurology clerkship were doing and how it could be generalized. And more resources were funneled into the program allowing for the hiring of an associate clerkship director and more staff to run a sub-internship program. Most recently, department chair Dr. Fink was able to hire another faculty member, whose clinical specialty is in movement disorders but who will also serve as a longitudinal career mentor for students interested in neurology, throughout the four years of medical school.

We know from surveys that about one-quarter to one-third of entering medical students have some interest in neuroscience, but only a small percentage become neurologists, Dr. Safdieh says. Are we turning students off or teaching them the wrong way? I hope that providing this support can boost those numbers.

Even in his down time, it's hard to get Dr. Safdieh to stop learning and teaching. Wandering the streets of his beloved New York with his 14-year-old daughter and ten-year-old son and his soon-to-be husband, he indulges in his passion for urban design. (Dr. Safdieh married young in the Orthodox tradition, and he and his ex-wife divorced amicably and now share custody.)

I'm very interested in the history of how cities and transportation systems developed, he explained. I love walking around the city and looking at a building, closing my eyes and imagining who lived in that building 150 years ago.

On his nightstand at the moment are Power Broker, Robert Caro's Pulitzer Prize-winning book about urban planner Robert Moses and his influence on New York, and the famous Ron Chernow biography Alexander Hamilton.

Dr. Safdieh also travels annually to Weill Cornell's branch medical school in Qatar to teach medical students. It's a fabulous experience to see how people practice medicine in other countries and look at it from an international perspective.

He sees Neurology Today as a way to pursue his educational goals on a national level. We're focusing on high-level science and clinical advances, synthesized in a way that a neurologist, who's already in love with the field, can access, digest, and apply them to patients without having to scour the literature to find all that stuff. To me, Neurology Today is about education.

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At the Bench: Inspired by a Brother, AAN Scholarship Awardee Investigates Brain Metabolism Disorders – LWW Journals

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Hurley, Dan

doi: 10.1097/01.NT.0000521715.10826.a9

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Isaac Marin-Valencia, MD, recipient of an AAN Clinical Research Training Scholarship, is studying clinical and molecular aspects of pontocerebellar hypoplasia, a brain metabolism disorder so rare it is virtually unseen in the United States. Here, he discusses his research.

BOSTONFrom the Canary Islands to New York by way of Spain and Texas, Isaac Marin-Valencia, MD, has dedicated his career to investigating pediatric neurologic diseases as exotic as his homeland.

The recipient of an AAN Clinical Research Training Scholarship, Dr. Marin-Valencia is studying clinical and molecular aspects of pontocerebellar hypoplasia, a brain metabolism disorder so rare it is virtually unseen in the United States.

All our patients are in the Middle East, because of the high rates of consanguinity, Dr. Marin-Valencia said during a break from the AAN Annual Meeting here in April. I've been to Cairo, to work with collaborators in hospitals there.

Born and raised in the Canary Islands, the Spanish archipelago off the coast of Morocco, Dr. Marin-Valencia grew up with a younger brother, Abimael, who had autism and epilepsy. He decided when he was six to become a doctor to help Abimael.

He was the reason for my career path, Dr. Marin-Valencia said. He's the inspiration for me to continue working on brain disorders that don't have treatments.

After graduating from medical school at the University of Las Palmas de Gran Canaria, he completed his four-year residency in pediatrics at Sant Joan de Deu Hospital of Barcelona. It was there he met Juan Pascual, MD, PhD, a pediatric neurologist who became his mentor.

I was very impressed by his knowledge and expertise is in brain metabolism disorders, Dr. Marin-Valencia said.

It was in Barcelona that he first began seeing young patients with the disorders that Dr. Pascual specialized in treating. I learned a lot about biochemistry and got fascinated, he said.

In 2008, he moved to the University of Texas-Southwestern Medical Center, to pursue postdoctoral research in pediatric neurology. Three years later, a poster of his won a grand prize at the university's postdoctoral research symposium, becoming the basis of a paper, published in the journal Cell Metabolism, that overturned 50 years of scientific dogma.

The so-called Warburg effect, named after Nobel Prize winner Otto Warburg, had been based on his in vitro observation that cancer cells preferentially metabolize glucose to lactate, even in the presence of sufficient oxygen in the mitochondria.

Dr. Marin-Valencia and colleagues disproved the long-held assumption that the same process holds true in vivo, using human glioblastomas implanted into the mouse brain to show that the cells' mitochondria oxidize glucose.

Determined to get back to his primary interest in metabolic disorders of the brain, he moved to Rockefeller University in 2015 to study human genetics and developmental neurobiology.

My background until then was in biochemistry and electrophysiology, Dr. Marin-Valencia said. I was missing two important pieces of the puzzle. Most of these metabolic disorders are genetic, and therefore they affect development of the brain. Learning these two areas have helped me to have a global picture about these disorders. If you're an expert in just one thing, you're going to miss other important facets that could be essential to understand and improve the diseases. Making more connections, meeting other investigators, associating with other laboratories all of that enriches my knowledge and way of thinking.

Under the mentorship of Joseph Gleeson, MD, a pediatric neurologist and neurogeneticist at University of California, San Diego, who has identified some 200 genetic mutations linked to brain disorders, Dr. Marin-Valencia is now looking for genes associated with pontocerebellar hypoplasia.

We use zebrafish and mice, Dr. Marin-Valencia said. We knock out or knock down genes and then see if there is a problem in the development of the brain. From the developmental standpoint, we want to replicate the disease in the animal model, to see what kind of cells are compromised and when the problem is first manifested. Then we go down to the cell and molecular level to localize where the gene is expressed and what the product of the gene is, where the protein is located in the cell and what its role is. Once we know all that, once we sort out the mechanism, we try to development new therapies.

Asked if he has yet identified a particular gene associated with pontocerebellar hypoplasia, he paused and said, I cannot tell you. It's not published yet.

Ultimately, his goal is to identify treatments for diseases that are now untreatable, something Dr. Gleeson's research has already done for a number of pediatric brain diseases.

One of the major problems we have in neurology is that we have few treatments for these devastating diseases that kill children at a very early age, Dr. Marin-Valencia said. There are things we can do to alleviate pain, to alleviate suffering, to provide a better quality of life. But from the biochemical and genetic standpoint, we cannot do much to change the outcome of many of these diseases.

Might his research into pontocerebellar hypoplasia one day lead to a treatment? It's a long way, Dr. Marin-Valencia said, but we are working to get there.

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A Noninvasive Novel Method of Deep Brain Stimulation in Animal Model – LWW Journals

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Moran, Mark

doi: 10.1097/01.NT.0000521712.72776.d2

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An international group of researchers delivered high frequencies of electrical stimulation through electrodes placed outside the brain of a mouse, to selectively target neurons in the hippocampus without an incision and without affecting the overlying cortex. The method has potential for translation to humans, but as the authors and independent experts report, much more work is needed.

An innovative method of delivering noninvasive deep brain stimulation appears to activate brain areas resulting in motor changes in a mouse model that could, potentially, prove relevant to treatment of Parkinson's disease and other movement and psychiatric disorders in humans, according to a report published in the June 1 issue of Cell.

Using a novel method known as temporal interference, an international group of researchers delivered high frequencies of electrical stimulation through electrodes placed outside the brain, to selectively target neurons in the hippocampus without an incision and without affecting the overlying cortex.

Human application is unlikely very soon, but the report has stirred interest among experts in movement disorders as a possible answer to a problem: how to deliver deep brain stimulation known to be effective in neuropsychiatric disorders without the risks associated with the traditionally invasive procedure.

Traditional deep brain stimulation requires opening the skull and implanting an electrode, which can have complications, and only a small number of people can do this kind of neurosurgery, the senior study author Edward Boyden, PhD, associate professor of biological engineering and brain and cognitive sciences at MIT, told Neurology Today. Our technology could be useful, should human trials prove effective, as a wearable device that could be worn by patients with severe conditions. Conceivably it could help with conditions where occasional stimulationfor instance, for half an hourresults in plasticity that helps relieve symptoms. The strategy could also be useful to researchers in mapping parts of the brain involved with neurological disorders so that better DBS positioning may become possible.

Dr. Boyden is quick to point out the hurdles that must be overcome before the strategy could be employed in humans. We haven't yet done any peer-reviewed studies on the human brain, although we have begun studies, he said. Our technology is not as focal as traditional DBS, and for conditions where stimulation must be constant, a standard implant might be more secure and easier to maintain.

The temporal interference strategy he and colleagues used involves the manipulation of high-frequency electrical currents delivered via electrodes placed outside the mouse scalp. The currents are too fast to drive neurons, but they interfere with one another in such a way that where they intersect, deep in the brain, a small region of low-frequency current is generated inside neurons. This low-frequency current can be used to drive neurons' electrical activity, while the high-frequency current passes through surrounding tissue with no effect.

By tuning the frequency of these currents and changing the location of the electrodes, the researchers can control the location of the brain tissue that receives the low-frequency stimulation. You can go for deep targets and spare the overlying neurons, although the spatial resolution is not yet as good as that of deep brain stimulation, Dr. Boyden said.

Moreover, by shifting the site of stimulation, Dr. Boyden and colleagues could activate different parts of the motor cortex and prompt the mice to move their limbs, ears, or whiskers.

The strategy appears to be safe, based on this study. We found that TI [temporal interference] stimulation at amplitudes sufficient to recruit deep brain structures, such as the hippocampus, did not alter the neuronal and synaptic integrity of the underlying tissue 24 hours after stimulation, Dr. Boyden and colleagues wrote. Additional time points other than 24-hours post stimulation may provide in the future a more detailed picture of the safety of TI stimulation.

Commenting on the report, Michele Tagliati, MD, FAAN, director of the Movement Disorders Program at Cedars Sinai, Los Angeles, said: This is extremely exciting. The practice of brain stimulation is limited by one fundamental problem you have to stick a wire electrode in the brain. That is a limitation to the willingness of physicians to recommend the surgery and of patients to undergo it.

Finding a noninvasive way to stimulate the brain has been a holy grail in this field, Dr. Tagliati said. In my opinion, this is a credible strategy that can really advance the field by providing something that we have been trying to do for a long time noninvasive stimulation of key parts of the brain that can benefit patients with movement disorders. There is an enormous amount of work yet to do refining this strategy, and I would not expect to see this in the clinic anytime soon. However, I would not be surprised if it advances to phase 2 safety trials very soon.

Joseph Jankovic, MD FAAN, professor of neurology, Distinguished Chair in Movement Disorders, and director of the Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine, was somewhat more circumspect. The study provides a proof of principle that relatively non-invasive electrical stimulation of deep brain structures is feasible, he told Neurology Today. This should be added to a growing list of techniques, such as optogenetic manipulation of neuronal networks, that require a great deal of animal work before it can be applied clinically. While I agree with the authors that the prospects for noninvasive DBS using electricity are potentially exciting, I am very skeptical that it might be rapidly deployable in human clinical trials.

There are many unanswered questions before this technique can be applied for movement disorders, epilepsy or psychiatric disorders, Dr. Jankovic said. One question is whether the electrical stimulation can be delivered continuously in the target nucleus without untoward effects. Another question is related to the method of delivery. Would the patients require wearing a helmet device that would deliver electricity in a way to make the treatment portable?

Finally, I think there are serious safety concerns about the effect of chronic electricity on various brain structures, he said.

Nevertheless, he said, the strategy is a breakthrough. This is an important study conducted by a highly-regarded group of researchers, Dr. Jankovic said. It addresses a hugely unmet need, namely the ability to normalize abnormal brain circuitry in patients with dysfunction in the cortico-striatal-thalamic pathway in patients with Parkinson's disease, dystonia, Tourette syndrome and other hyperkinetic movement disorders, without invading the brain by either implanting stimulating electrodes or creating a lesion via focused ultrasound.

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Severe Childhood Deprivation Tied to Adult Neurological Issues – PsychCentral.com

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Childhood adversity appears to have a significant impact on neuropsychological functioning in adulthood, according to a new study of adults who had been adopted as children from neglectful Romanian orphanages.

The findings, published in the journal Psychological Medicine, also show that neuropsychological difficulties may explain why early adversity is linked to attention-deficit hyperactivity disorder (ADHD) in later life.

For the study, a team of U.K. researchers from the University of Southampton, the University of Bath and Kings College London analyzed neuropsychological function in 70 young adults who had been exposed to severely depriving conditions in Romanian orphanages during Nicolae Ceausescus regime and subsequently adopted by British families. The adoptees were compared to 22 British adoptees of similar ages who had not suffered childhood deprivation.

As part of the study, the adoptees were asked to complete tests designed to evaluate their neuropsychological functioning in five areas: controlling their responses (inhibitory control), prospective memory, decision-making, emotional recognition and cognitive ability (IQ).

Prospective memory is the ability to remember to do something in the future, such as remembering to go to an appointment or what you need to buy if you dont have a shopping list. ADHD and autism spectrum disorder (ASD) symptoms were assessed through questionnaires completed by the adoptees parents.

The findings reveal that the Romanian adoptees had lower IQs and performed less well on the other four tests when compared to the adoptees who had not suffered deprivation.

In addition, the adoptees with the lowest IQs and the greatest problems in prospective memory were more likely to show ADHD symptoms in adulthood than those without neuropsychological difficulties. The researchers found no direct link between ASD symptoms and neuropsychological performance.

The latest work is part of the wider English and Romanian Adoptees study, a collaborative research project between the University of Southampton and Kings College London which began shortly after the fall of the communist regime in Romania.

Children living in the institutions were subjected to extremely poor hygiene, insufficient food, little affection and no social or cognitive stimulation. The study analyzes the mental health and brain development of 165 children who spent time in Romanian institutions and who were adopted by families in the UK when aged between two weeks and 43 months.

This study contributes to our changing understanding of the power of the early environment to shape brain development, showing that the effects of institutional deprivation on cognition can still be seen after more than twenty years of positive experience in high functioning and loving adoptive families leads us to acknowledge that there are limits to the brains recuperative powers, said Professor Edmund Sonuga-Barke, the principal investigator of the study

Sonuga-Barke began the study while working at the University of Southampton and is now based at the Institute of Psychiatry, Psychology & Neuroscience at Kings College London.

The study highlights that institutional deprivation can have long-lasting effects on a range of neuropsychological functions that are important in everyday life, such as memory and general intellectual ability, said Dr. Dennis Golm, lecturer in psychology at the University of Southampton.

Our findings also emphasize the importance of improving the quality of care for children in institutions.

Source: University of Southampton

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Minocyline Found to Have a Role in Early MS Treatment – LWW Journals

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Fitzgerald, Susan

doi: 10.1097/01.NT.0000521713.03202.29

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A new study found that minocycline may slow the progression of multiple sclerosis (MS) in patients who have early signs of the disease, but independent MS experts disagree about the efficacy of the treatment.

Minocycline, an inexpensive decades-old antibiotic, may slow the progression of multiple sclerosis (MS) in patients who have early signs of the disease, according to a randomized, controlled trial reported in the June 1 issue of The New England Journal of Medicine.

The study found that minocycline reduced the risk of conversion from a first demyelinating event, also known as clinically isolated syndrome (CIS), to a diagnosis of MS compared with placebo over six months.

Minocycline, traditionally used to treat severe acne, has been shown in animal and laboratory studies to have anti-inflammatory and neuroprotective effects, and a few smaller human trials suggested it may have a place in MS treatment, either alone or in combination with other drugs. The results from this new trial conducted in Canada created a buzz in the MS community, but opinions vary on whether minocycline is poised to become part of the standard lineup of MS drugs.

The study, funded by the Multiple Sclerosis Society of Canada and carried out at 12 Canadian MS clinics, was designed to assess whether minocycline reduced the risk of conversion from a first clinical demyelinating event to a diagnosis of MS as defined by the 2005 McDonald criteria, which were in effect when the study began in 2009. Patients were eligible for the study if they had had a single clinically isolated demyelinating event such as optic neuritis or a brainstem, cerebral, cerebellar or myelopathy syndrome within the previous 180 days, and had at least two lesions larger than 3 mm in diameter on T2-weighted magnetic resonance imaging (MRI) of the brain. (One lesion had to be ovoid, periventricular or infratentorial, which is typical of demyelinating disease.)

A total of 142 patients were randomized to 100 mg of minocycline twice daily (72) or placebo (70). The primary endpoint was conversion to MS based on the 2005 McDonald criteria within six months. Secondary outcomes included conversion to MS within 24 months and changes on MRI at six months and 24 months change in lesion volume on T2-weighted MRI, cumulative number of new lesions enhanced on T1-weighted MRI, and cumulative combined number of unique lesions.

The unadjusted risk of conversion to MS within six months was 33.4 percent in the minocycline group compared to 61 percent in the placebo group. After adjusting for the number of enhancing lesions at baseline, the risk of conversion at six months was 43 percent for minocycline, 61.5 percent for placebo.

The adjusted risk difference of 18.5 percentage points at 6 months is similar to that with other disease-modifying therapies for multiple sclerosis, reported the researchers, led by Luanne Metz, MD, section chief of neurology and program leader for multiple sclerosis for the University of Calgary and Alberta Health Services.

Analysis of the data was complicated by the fact that during the trial period the 2005 McDonald criteria for MS were replaced by 2010 criteria, which would have reclassified some of the participants in this trial as having multiple sclerosis at the initial presentation, the researchers reported.

Dr. Metz said that minocycline continued to show a positive effect even when that point was taken into consideration. I would say that whatever way we analyzed the data, we came out with similar results, she said.

Those who received minocycline were more likely to drop out of the trial and to have side effects including rash, dizziness and teeth discoloration, though Dr. Metz said such side effects aren't any worse than those found with other therapies and they are not serious.

Dr. Metz said she believed there is now sufficient Level I evidence to support the use of minocycline in early MS treatment, if only as an interim drug as an MS diagnosis is being sorted out.

She noted that MS drugs can cost over $50,000 annually, as opposed to $500 or so for minocycline. Most of the people in the world can't afford those drugs, she said, and minocycline is taken orally, not injected, which is another advantage. If we look globally, minocycline is an important consideration.

Dr. Metz said her team is considering whether to do additional clinical testing of minocycline for either CIS or relapsing-remitting MS, but she said it would be unethical to do a placebo-controlled trial since there are proven treatment options for patients.

Bianca Weinstock-Guttman, MD, professor of neurology at the State University of New York University at Buffalo and director of the Jacobs MS Center for Treatment and Research, said that while the study on minocycline was interesting, it was difficult to imagine this would go further and become a routine part of clinical care. A larger, longer-term study would be needed to further assess the drug's effectiveness for MS, she said, and even then, patients and clinicians would be prone to wanting newer MS drugs.

For now, you really can't go and recommend this to patients, Dr. Weinstock-Guttman told Neurology Today.

On the other hand, Amit Bar-Or, MD, FRCPC, professor of neurology, director of the Center for Neuroinflammation and chief of the multiple sclerosis division at the University of Pennsylvania Perelman School of Medicine, said the study is important and provides a rationale for pursuing minocycline as a potential therapy for MS.

He said the oral antibiotic is generally safe and well-tolerated and is also quite inexpensive compared to the existing MS medications.

Dr. Bar-Or said the minocycline study was a nice example of translational medicine taking laboratory and animal research findings and testing them in the clinical setting. He also complimented the MS Society of Canada for sponsoring the study, an important step because the pharmaceutical industry is typically less attracted to a molecule that will not be sold under patent for a higher price.

Dr. Weinstock-Guttman noted, however, that the exact mechanisms by which minocycline may impact MS are not fully understood, but it is known that the drug can penetrate the blood-brain barrier and research in animal models supports that it has anti-inflammatory, neuroprotective effects. The neuroprotective effect may be related to anti-apoptotic properties and inhibitory activity on microglia, she said. The drug may also help in MS by preventing T-cell migration into the central nervous system, she added.

She said the latest results from Canada still leave many clinical questions unanswered about the potential role of minocycline in MS therapy, including whether the drug in the long run can reduce disease activity and limit disability.

The study, whose enrollment stretched from 2009 to 2013 due to some enrollment difficulties, was in some ways overtaken by advances in MS drug therapy and a growing tendency in MS practice to begin treatment at the earliest possible signs of disease.

A study published last year with 11 years of follow-up found an advantage to starting treatment with interferon beta 1-b at the time of CIS diagnosis instead of waiting until a patient converted to MS. The study did not look at other MS drugs. The dilemma for clinicians is that it's not necessarily easy to predict which patients with will go on to MS, though over two-thirds of people do over a period of eight to ten years.

Emmanuelle Waubant, MD, PhD, FAAN, professor of neurology at the University of California, San Francisco and the Race to Erase MS medical director, said she thought the Canadian results were partially muddled by the fact that the placebo group had more active disease at the beginning, which means they were more likely to convert to MS than the minocycline group.

Dr. Waubant said that at least six new MS drugs have come on the market since the study was launched, all with higher effectiveness and tested over longer periods of time in larger studies. Given that patients now have many options, the likelihood of minocycline becoming commonly used for MS is close to nil, Dr. Waubant said. However, having this proof-of-concept study may help develop new treatment strategies.

In addition to more therapy options, the criteria for diagnosing CIS and MS also continue to evolve, with new revised McDonald criteria in the works, she said.

The landscape is constantly changing, and that is a challenge when you conduct clinical trials, Dr. Waubant said.

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Are Telerobotic Devices the Answer to Stroke Care… : Neurology Today – LWW Journals

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A telerobotic system for endovascular care, in the early phases of development, could provide stroke treatment in remote and hard-to-reach places.

A bedside robotic unit and a remote physician workspace, allowing real-time surgery to be controlled from a remote location, may well represent a future strategy for providing endovascular care for stroke in remote and hard-to-reach places, suggests a paper published in late November 2019 in the Journal of Neurosurgery.

Although more institutions are now able to provide endovascular care than ever before, there is also a greater need for comprehensive care teams to deliberate on the complex questions about pathology and symptomatology after patients' initial presentations, Gavin W. Britz, MD, MBA, MPH, professor and chair of the department of neurological surgery, and colleagues from Houston Methodist Hospital, wrote in the paper.

These resources can be hard to find in hospitals that do not see a large enough volume of such patients, they noted. The use of telemedicine and teleoperated robots may offer a potential solution for disseminating interventional stroke care to smaller regional or rural centers, they said.

The cockpit-like design of the system allows a physician to sit at a remote radiation-shielded workstation and use a set of touchscreen controls and joysticks that are then translated to the movements of the local robotic device.

The robotic unit features an extended reach arm, a robotic drive mechanism, and a single-use cassette containing all the necessary endovascular tools, including angiographic and hemodynamic monitors and foot pedalcontrolled fluoroscopy.

The software for the system, which was cleared by the US Food and Drug Administration in 2018, was initially developed for endovascular percutaneous coronary intervention (PCI) procedures.

A 2019 study in EClinicalMedicine reported that it had successfully demonstrated the system's use for PCI in five individuals from a 20-mile distance. And a feasibility study by Dr. Britz and colleagues in Neurosurgery last June demonstrated the device's ability to navigate the cerebrovascular system, manipulate the guidewires and microcatheters routinely used for endovascular intervention, and successfully deploy coils and stents in a live animal.

But while the use of telemedicine and teleoperated robots may bridge the gaps in interventional stroke care in smaller regional or rural centers, operational and financial challenges remain, independent stroke and neurovascular care experts said. They told Neurology Today they look forward to a future where this technology would be safe, effective, and feasible, but said that it was much too early to consider this a viable reality.

Indeed, the authors of the current study acknowledged the high cost of the device would be a potential barriercoming in at $650,000 per unit, with another $650-$750 for its single-use accessory cartridgesin addition to the investment needed to hire and train the surgical technicians and other operating room staff. They suggested that non-tertiary hospitals may be able to spread out some of those expenses between cardiovascular and neuro-interventional services, however.

The study authors acknowledged that there was still a lot of work to be done before the system would be ready for primetime, including performing preliminary trials of intracranial endovascular procedures such as angiography, coilings, and stent deployments in humans safely as a proof of capability.

Tests of the system need to be performed to mirror a range of potential scenarios in multiple subjects with diverse anatomical locations and complexities, the study authors wrote. In addition, Remote procedures would need to be performed in coordination with locations where adequate contingency options (such as experienced neuro-interventionalists) also exist onsite, they added.

Only then, by studying the metrics and outcomes of robotically performed procedures and comparing them to those of the hub-and-spoke or diffused care models, can a decision be made regarding the efficacy of the device and its capability to address deficiencies in the status quo, Dr. Britz and colleagues concluded, adding, however, that they believe these hurdles can be overcome.

In an accompanying editorial, Jeffrey T. Nelson, MD, and Nicholas C. Bambakidis, MD, both from the University Hospitals Cleveland Medical Center, acknowledged the relevance of future research into the development of neuroendovascular robotics. But they said its use as a solution to our current access issues in the delivery of stroke care seems premature....If and when a telerobotic neurointerventional procedure is available, it may prove to be a useful adjunct to stroke treatment if the technical limitations are overcome. For now, we must continue to develop systems of stroke care that provide access to all patients with acute ischemic stroke.

Independent experts who spoke with Neurology Today agreed that these interventions were an exciting prospect but they were far from ready for widespread use.

The challenge of making endovascular thrombectomy more accessible to patients living in rural areas is very complex as the number of patients who would be treated locally at a small rural hospital is not sufficient to support an interventionalist, Carolyn A. Cronin, MD, PhD, associate professor of neurology and director of the vascular neurology fellowship program at the University of Maryland School of Medicine, acknowledged. This article presents a novel idea to respond to that challenge, she said.

However, Dr. Cronin added, Even if the interventionalist could be off-site, there are still many resources that would be needed locally and also may be cost-prohibitive. These include a fully capable endovascular suite with biplane imaging, technicians familiar with neurointerventional procedures and all the different devices in use, and an interventionalist to obtain vascular access.

She added that supplementary training would be necessary for the neurointerventionalists who would be using the robotic equipment in order to ensure they would be equally as competent with the procedures remotely as they are in person which is a time and cost consideration.

Telerobotic surgery would be an intriguing potential option but needs further study regarding both the safety and quality of the intervention done remotely and also whether it would be financially viable, Dr. Cronin concluded.

Pooja Khatri, MD, MSc, FAAN, professor of neurology at the University of Cincinnati (UC) and co-director of the UC Stroke Team, agreed that the article was very intriguing and did a good job of laying out the currently available evidence and pros and cons of telerobotic stroke intervention.

The concept of using telerobotics for mechanical embolectomy makes intuitive sense, compared to open surgery, when one considers that the operator is already using a screen to guide his or her work even in person. But much more work is to be done before we get there, she cautioned.

The technical tradeoffs for the operator seem to be tactile feedback for mechanical precision, and early data from cardiac trials suggest that these tradeoffs might not sacrifice technical safety or efficacy. The question will be whether the same will be true in the brain. The brain has more twists and turns in arteries, and more to lose with delays and complications.

Dr. Khatri said an important factor will be the availability of stable, strong, and fast internet connections at all participating centers.

It is exciting to consider the advantages of these systems, Dr. Khatri said, including expedited access for patients in much more remote areas to a highly effective and highly time sensitive treatment.

There are many questions that need to be answered before this can happen, however, including: Who sets up the procedure and takes the first steps? Who steps in when there are procedural failures and complications?

As the editorial lays out nicely, the need to expand access to neurointerventional care is urgent and the road to development of telerobotics is relatively long. We can't wait for telerobotics to expand our workforce and resources for acute stroke care, Dr. Khatri said.

At the same time, even with an adequate workforce and resources countrywide, the authors make a compelling case for robotics enhancing care even when the interventionist is there in person.

Dr. Khatri said she was looking forward to seeing the data from these technologies in humans with stroke.

Drs. Britz, Khatri and Cronin had no relevant disclosures to report.

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Study Shows Hyperbaric Oxygen Therapy (HBOT) Protocols Can Improve Cognitive Function in Stroke Patients – BioSpace

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TEL AVIV, Israel, Feb. 27, 2020 /PRNewswire/ -- The Sagol Center for Hyperbaric Medicine and Researchat Shamir Medical Center, one of the largest hyperbaric medicine centers in the world, announced study results indicating its hyperbaric oxygen therapy (HBOT) protocols induce significant improvement in most cognitive domains of patients who suffered stroke even months to years after the event.

The retrospective analysis study, published in Restorative Neurology and Neuroscience, demonstrated that through elevating oxygen concentration in the blood and injured brain tissue, the Sagol Center's HBOT protocols supply the energy needed for brain tissue recovery regardless of the stroke location or cause.

"Despite nearly half of stroke survivors suffering from differing degrees of cognitive dysfunction, most rehabilitative efforts focus on restoring motor functions," said Shai Efrati, MD, Director of the Sagol Center for Hyperbaric Medicine and Research, Shamir Medical Center, and study co-author. "Our study shows that stroke-related cognitive deficits can be treated as brain wounds, regardless of the stroke's location or origin ischemic or hemorrhagic. The rehabilitation potential lies in the metabolic characteristics of the chronic damage, or brain wound. By utilizing our HBOT protocols, the injured but viable brain tissue can be recovered even years after the acute insult."

Stroke is the second highest cause of mortality and the third leading cause of disability worldwide. When stroke occurs, whether ischemic or hemorrhagic, dysfunction typically presents in the affected brain region and impacts more than one cognitive domain such as memory or attention. Cognitive recovery after stroke mainly transpires within the first 30 days, with some patients gaining additional mild improvement up to 90 days after.

The study evaluated the sustained impact of Sagol's HBOT protocols on all aspects of cognitive function including memory, executive function, visuospatial skills, verbal function, attention, information processing and motor skills. Results demonstrated clinically significant improvement in cognitive function in most evaluated cognitive domains after HBOT.

The study found the following:

Of the 351 patients assessed for eligibility, a total of 162 patients met the inclusion criteria for the final analysis. Criteria comprised the receipt of treatment after more than three months post-injury, the completion of the Sagol Center HBOT protocols and at least two cognitive evaluations, conducted using a fully computerized cognitive testing battery (NeuroTrax test battery). Patients were treated in a multi-place hyperbaric chamber at the Sagol Center.

"This is the largest cohort of stroke patients who have undergone strict cognitive, imaging and neurological assessments to evaluate the rehabilitation potential of HBOT treatment," said Amir Hadanny, MD, Chief Medical Research Officer at the Sagol Center for Hyperbaric Medicine and Research, Shamir Medical Center, and lead author of the study."To identify the true cognitive and clinical impact of our protocols, all patients were evaluated with two validated alternate forms of the cognitive test battery prior to and post-HBOT. Significant improvements were demonstrated in all cognitive domains including memory, information processing speed, attention and executive functions. We are thrilled to bring a new hope to stroke patients worldwide."

About the Sagol Center for Hyperbaric Medicine and Research at Shamir Medical Center

The Sagol Center for Hyperbaric Medicine and Research at Shamir Medical Center (formerly Assaf Harofeh Medical Center), is a leader in advancing our understanding of the impact of hyperbaric medicine on cognitive and physical function. Serving as one of the largest Hyperbaric centers worldwide, the Sagol Center offers highly advanced large multi-place chambers, treating more than 200 patients daily. Research conducted at the Center has proven that brain rejuvenation is possible across a wide range of neurological pathologies and illnesses.

Media Contact:Nicole GrubnerFinn Partners for The Sagol Center for Hyperbaric Medicine and Research+1-929-222-8011nicole.grubner@finnpartners.com

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Severity of Traumatic Brain Injury and its Effect on Headache Characteristics – Neurology Advisor

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Headache is common following traumatic brain injury (TBI) and the severity of the head injury has significant effects on the headache characteristics, according to study results published in PM & R.

Headache is a common symptom after TBI and frequently is persistent. The researchers previously reported on the results of 2 separate studies, showing that following moderate to severe TBI headache incidence was 71% and prevalence was 44% at 12 months, while following mild TBI the incidence and prevalence at 12 months were 91% and 58%, respectively.

The goal of the current study was to explore headache symptoms in patients following moderate to severe TBI compared with patients with mild TBI. Furthermore, they investigated these data from 2 different clinical perspectives: symptom-based specialists (including psychiatrists, neurologists or primary care providers) or headache specialists.

The study included prospective enrollments of patients after hospitalization for TBI. Baseline data from patients with moderate to severe TBI was collected during inpatient rehabilitation and from patients with mild TBI within 1 week of injury. The researchers completed telephone follow-up at 1 year post-TBI. Self-reported headache characteristics included headache frequency, pain intensity, headache impact on daily life using the Headache Impact Test-6 (HIT-6), and depressive symptoms using the Physician Health Questionnaire (PHQ-9) measured 1 year after TBI.

The study cohort included 535 subjects (mean age, 44 years), including 346 patients with moderate to severe TBI and 189 patients with mild TBI who completed the assessment at 12 months post-injury. Most causes of injury were vehicular crashes (57%) and falls (26%).

A third of patients (33%; n=115) with moderate-to-severe TBI and more than half (58%; n=109) of patients with mild TBI had a new or worse headache at 12 months post-injury. Migraine or probable migraine-type and tension type headache were more common in patients with mild TBI (28% and 19%, respectively) compared with patients with moderate to severe TBI (20% and 5%, respectively). Significantly more patients with moderate to severe TBI reported no headache (55% vs 33%).

The impact of headache on daily function was significantly greater in patients with mild TBI, as severe impact on daily function according to HIT-6 score was more common in that group compared to patients with moderate to severe TBI (24% vs 14%). Furthermore, moderate or severe pain was more common in patients with mild TBI compared with patients with moderate to severe head injury (42% vs 27%, respectively).

When the researchers isolated patients who had a new or worse headache at 1 year, they found that headache frequency and pain scores were both higher in the moderate to severe TBI group, but there was no difference between groups in headache impact.

Approximately one-third (35%) of patients with TBI and headache reported significant depressive symptoms at 1 year after TBI compared with 13% of patients with TBI and no headache. There was no difference in depressive symptoms between patients with mild and moderate to severe TBI groups.

Providers of patients with TBI are more likely to evaluate and treat headache in individuals sustaining a mild TBI vs moderate to severe TBI. Headache specialists may encounter patients with moderate to severe TBI who report more frequent headache and greater pain intensity compared with patients with mild TBI.

The researchers acknowledged several study limitations, including the smaller sample size in the mild TBI group, defining only 1 headache type per person, determining headache type by responses to a questionnaire, and the fact that no physical examination was performed.

These findings underscore the need for appropriate evaluation of the clinical symptoms and impact of headache, but also on possible psychiatric co-morbid conditions such as depression after TBI, concluded the researchers. They add that these findings also suggest, follow-up on symptoms such as headache needs to continue long after the acute period as persistence of headache is common.

Reference

Hoffman JM, Lucas S, Dikmen S, Temkin N. Clinical perspectives on headache after traumatic brain injury [published online January 31, 2020]. PM R. doi:10.1002/pmrj.12338

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Severity of Traumatic Brain Injury and its Effect on Headache Characteristics - Neurology Advisor

Multiple Sclerosis Drug Costs Nearly Tripled Over 7 Years – Pharmacy Times

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The cost of prescription drugs for patients with multiple sclerosis (MS) nearly tripled over 7 years and the generic version of 1 of the most common drugs had little overall effect on prices, according to a study published in Neurology.

The study examined costs for disease-modifying drugs for patients with MS between 2011 and 2017 based on a Medicaid database. Researchers found spending on 15 MS drugs within the Medicaid program increased from $453 million to $1.32 billion during this time.

Increased spending was driven by increases in prescription costs that doubled during the 7 years, according to the study. Most of the drugs cost more than $70,000 per year on average and costs for these drugs are among the highest spending areas for private insurers, as well as Medicare and Medicaid.

After adjusting for average rebate amounts paid to the Medicaid program, spending was lower but still more than doubled from $278 million to $600 million per year. Spending more than doubled from $2.00 per Medicaid enrollee to $4.06 per enrollee during the study period. However, researchers found that some of the increase was due to the expansion of Medicaid through the Affordable Care Act.

A generic version of the drug glatiramer acetate was introduced in 2015. The study showed that when the generic version was introduced, the cost of the brand name drug immediately increased by $441 per prescription, followed by a slowing of the upward monthly trend.

Before the introduction of the generic drugs, the maker of the brand name drug worked to push its market share from the 20 mg dose to the 40 mg dose, which was not interchangeable with the new generic. The low market share for the generic drug was also because of the generic drug at 20 mg at approximately the same cost as the 40 mg dose when it launched, Daniel Hartung, PharmD, MPH, study author said in a press release.

A second company introduced a generic version of glatiramer acetate in October 2017, near the end of the study. By the end of 2017, 36% of all glatiramer acetate was generic, according to Hartung. Despite this release, there is an urgent need for more robust competition from generics for these MS drugs.

One limitation of the study is that it is based on the Medicaid program for patients from low-income households and patients with disabilities. It may not reflect the entire population of patients with MS, the authors noted.

ReferenceStudy: MS Drug Costs Nearly Triple over Seven Years, Even With Introduction of Generic [press release]. American Academy of Neurology. Published January 15, 2020. https://www.aan.com/PressRoom/Home/PressRelease/3766. Accessed January 20, 2020.

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Multiple Sclerosis Drug Costs Nearly Tripled Over 7 Years - Pharmacy Times

Neuromodulation Market drivers of growth analyzed in a new research report – Technology Magazine

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Neuromodulation Market size is projected to experience significant growth from 2019 to 2025.Neuromodulation market will experience a significant growth in the forth coming years, due to increasing prevalence of neurological disorders. As per a study by NCBI, it has been estimated that about 30 million people are diagnosed with some form of neurological disorder in India, and the rate of prevalence is growing with time. Hence, supporting the growth of the neuromodulation market.

Recent technological advancements in the field of neuromodulation devices will augment the growth of the market. Technological enhancements such as Spinal Cord Stimulation (SCS) has been proven as one of the most efficient therapy for the management of intractable pain syndromes. Such technological advancements will support the neuromodulation market growth in the forecast time frame.

Unavailability of favorable reimbursement policies for neurological ailments will restrain the growth of the market. Furthermore, lack of trained professionals in the field neurological treatment solutions will be a hindrance. Hence, the aforementioned reasons might assist in declining the market growth.

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The transcutaneous supraorbital neurostimulator is an FDA approved neuromodulation device for both acute and preventive treatment of migraine. It is estimated to witness a considerable growth in the forecast period due to rising prevalence of migraine headache. The easy accessibility and efficient outcomes of the device helps in augmenting the demand of the product thus, increasing the growth of neuromodulation market.

The internal neuromodulation market is driven by the growing incidence of Parkinsons disease, failed back surgeries, urinary incontinence and other related syndromes. As well as, it is experiencing a new surge of technological enhancements. For instance, there has been major technical advancements of burst stimulation and high-frequency in the Traditional (40-50 Hz) spinal column stimulation cutting down its ineffectiveness in certain criteria. Thus, augmenting market growth.

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Depression is the leading cause of disease burden worldwide and major contributor in the rising incidence of disability. The global prevalence of depressive symptoms has been rising in the recent years and the majority of case are increasing among the millennials. Hence, the rising prevalence of depressions and depressive symptoms will boost the growth of the neuromodulation devices market.

Polymeric bio materials are used because of the flexibility, biocompatible nature, ease of fabrication and as well as their wide range of electrical, mechanical, thermal and chemical behaviors when combined with different materials as composites. Hence, the growing use of neuromodulation devices will augment the market of polymeric bio material market.

Clinics are expected to hold majority of the share in the field of neuromodulation market, as neurological therapy solutions are mostly available in the clinical settings. The state of art facilities available in the clinics for the treatment of neurological syndromes will augment the growth of the market.

U.S neuromodulation market is estimated to hold the majority of market share owing to advancements in technology in and venture capital investments by major market players. Hence technological advancements coupled with capital investments for product pipelines by major players will boost the growth of the market. Apart from U.S., India is another country leading the neuromodulation market, this is due to increasing prevalence of chronic pain related syndromes and other neurological diseases.

Some of the key industry players operating in neuromodulation market are, Medtronic, Inc, ST. Jude Medical, Inc., Nevro Corporation, Neurosigma, Inc., Boston Scientific Corporation, Cyberonics, Inc., Biocontrol Medical, Neuropace, Inc., Synapse Biomedical, Inc., Neuronetics, Inc. These companies opt for mergers, acquisitions and partnerships in order to increase their efficiency and sustain in the market by providing better solutions. Additionally, they are even focused on technological advancements and miniaturization of their devices.

Company Profiles:

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Neuromodulation Market drivers of growth analyzed in a new research report - Technology Magazine

Could Essential Tremor Be Caused by Overactive Brain Waves? – Technology Networks

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The source of essential tremor--a movement disorder that causes involuntary trembling of the hands, arms, and head--has been enigmatic, impeding the development of effective treatments for a condition that affects 4% of people over 40.

Now a new study from Columbia University Irving Medical Center and NewYork-Presbyterian suggests the tremors are caused by overactive brain waves at the base of the brain, raising the possibility of treating the disorder with neuromodulation to calm the oscillations.

"Past studies have identified changes in brain structure in people with essential tremor, but we didn't know how those changes caused tremors," says Sheng-Han Kuo, MD, the study's senior author and assistant professor of neurology at Columbia University Vagelos College of Physicians and Surgeons.

"This study pins down how those structural changes affect brain activity to drive tremor."

The study was published online today in Science Translational Medicine.

Essential tremor is the most common movement disorder in the United States, affecting about 10 million Americans (approximately eight times as many people as Parkinson's disease). The condition causes involuntary, rhythmic trembling, usually in the hands, and is exacerbated during such activities as buttoning a shirt or using utensils. Although essential tremor is not life-threatening, it can severely impact quality of life.

Some beta blockers and anti-epileptic drugs can reduce symptoms, but they carry side effects, such as fatigue and shortness of breath. They also don't work very well in essential tremor patients, which Kuo says isn't surprising since the cause of the condition hasn't been well understood.

The researchers have previously identified structural changes in the cerebellum of essential tremor patients and used a new cerebellar encephalogram (EEG) technique to search for unusual brain waves in this part of the brain.

Among 20 essential tremor patients examined with cerebellar EEG, most had strong oscillations (between 4 and 12 Hz) in the cerebellum that were not found in any of the 20 control subjects. Patients with more severe tremors had stronger oscillations.

The researchers first discovered the cerebellar oscillations in mice that had developed tremors closely resembling those seen in essential tremor patients.

The tremors could be turned on and off by stimulating certain neurons in the mouse brain, alternately suppressing and unleashing the oscillations. "These results established a causal relationship between the brain oscillations and tremor, which cannot be directly tested in patients," says Kuo, who is also an assistant attending neurologist at NewYork-Presbyterian/Columbia University Irving Medical Center.

In previous studies of postmortem brain tissue from essential tremor patients, the Columbia team discovered that patients with essential tremor had an abnormally high number of synapses, or connections, between two types of nerve cells in the brain's cerebellum--climbing fibers and Purkinje cells.

In the current study, again using postmortem brain tissue, the researchers found that the formation of these synapses appears to be influenced by a protein called glutamate receptor delta 2 (GluR?2). "When this protein is underexpressed, any excess synapses that form between climbing fibers and Purkinje cells are not eliminated, resulting in too many neuronal connections," says Kuo.

When the team reduced expression of GluR?2 in mice, the animals developed tremors similar to those seen in humans. Restoring GluR?2 function suppressed the tremors, proving that the protein plays a key role in essential tremor.

The study opens several new possibilities for treatment of essential tremor, Kuo says.

"Using cerebellar EEG as a guide, we may be able to use neuromodulation techniques such as tDCS or TMS (transcranial direct-current stimulation or transcranial magnetic stimulation) to reduce tremor, or even drugs to reduce transmission between the climbing fibers and Purkinje cells."

Kuo is also working to develop medications that increase GluR?2 expression in the brain, which may reduce tremor.

Reference: Pan, M.-K., Li, Y.-S., Wong, S.-B., Ni, C.-L., Wang, Y.-M., Liu, W.-C., Lu, L.-Y., Lee, J.-C., Cortes, E. P., Vonsattel, J.-P. G., Sun, Q., Louis, E. D., Faust, P. L., & Kuo, S.-H. (2020). Cerebellar oscillations driven by synaptic pruning deficits of cerebellar climbing fibers contribute to tremor pathophysiology. Science Translational Medicine, 12(526). https://doi.org/10.1126/scitranslmed.aay1769

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Could Essential Tremor Be Caused by Overactive Brain Waves? - Technology Networks

Clinical Pearls and Pitfalls of Automated CT Perfusion for Acute Ischemic Stroke – Neurology Advisor

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Acute cerebral perfusion imaging should be part of the routine evaluation of patients with acute ischemic stroke secondary to large vessel occlusion presenting beyond 6 hours from time last known well, and may help identify those who may benefit from endovascular perfusion therapy. However, it is important to understand the limitations of automated CT perfusion (CTP), which are detailed in a review published in Neurology.

The clinical benefit of endovascular reperfusion therapy was impressive in 2 randomized trials (DAWN and DEFUSE 3) for patients with acute ischemic stroke with larger vessel occlusion who presented beyond 6 hours from last known well and were deemed to be good candidates based on cerebral perfusion imaging. The capability to perform and interpret perfusion imaging, either CTP or magnetic resonance perfusion-weighted imaging, should be available in every center treating patients with acute stroke.

A few commercially available, automated software packages, such as RAPID automated perfusion postprocessing software, can detect the presence of irreversible brain tissue injury, based on cerebral blood flow compared with that seen in contralateral perfused tissue by CTP or magnetic resonance perfusion, and assist in selecting appropriate candidates for endovascular therapy.

Simply put, CTP consists of a sequence of images obtained during the wash-in and the wash-out of an intravenous iodinated contrast agent. This is followed by transferring the source images to the workstation with the dedicated postprocessing software, which provides calculation of hemodynamic parameters. The automated assessment overcomes possible observer variability associated with subjective inspection.

There are disagreements about the quantitative thresholds between the ischemic core (the critically hypoperfused tissue with low cerebral blood flow) and the ischemic penumbra (the potentially salvageable tissue that may recover if reperfusion is achieved), and different software packages recommend slightly different thresholds. The automated software RAPID generated specific thresholds to identify good candidates for delayed endovascular: relative cerebral blood flow <30% and Tmax (time from the start of the scan until the maximum intensity of contrast bolus arrives at each voxel) >6 seconds.

Although perfusion imaging can be very valuable, there are several diagnostic pitfalls and challenges, and the review details the common technical and clinical pitfalls, along with practical pearls.

Technical pitfalls refer to the image quality from a technical standpoint and include several important challenges:

Clinical challenges to consider in routine practice:

Magnetic resonance perfusion is less quantitative compared with CTP and requires the use of echo planar imaging, which can have multiple artifacts. Furthermore, MRI is not as commonly available in urgent cases.

Lead author Achala Vagal, MD, professor of radiology at the University of Cincinnati Medical Center, Ohio, told Neurology Advisor, CTP is an important tool in the triage and treatment decision making in acute ischemic stroke. However, like any other technique, it is imperative to understand its limitations, especially when these decisions have to be made quickly. She goes on to add that automated CTP output maps are now available within minutes on our PACS, phones and emails; all the more reason to be cognizant of the pitfalls leading to inaccurate estimations of core and penumbra. A quick checklist can be very helpful.

Reference

Vagal A, Wintermark M, Nael K, et al. Automated CT perfusion imaging for acute ischemic stroke: pearls and pitfalls for real-world use. Neurology. 2019;93(20):888-898

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Clinical Pearls and Pitfalls of Automated CT Perfusion for Acute Ischemic Stroke - Neurology Advisor

Max Wiznitzer, MD, Pediatric Neurology, UH Cleveland …

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Dr. Max Wiznitzer is a graduate of Northwestern University School of Medicine. He trained in pediatrics and developmental disorders at Cincinnati Childrens Hospital and in pediatric neurology at Childrens Hospital of Philadelphia.

He then did a National Institutes of Health funded fellowship in disorders of higher cortical functioning in children at the Albert Einstein College of Medicine, Bronx, NY. Since 1986, he has been a pediatric neurologist at Rainbow Babies & Childrens Hospital in Cleveland. He is a professor of pediatrics and neurology at Case Western Reserve University.

Dr. Wiznitzer has a longstanding interest in neurodevelopmental disabilities, especially attention deficit hyperactivity disorder and autism, and has been involved in local, state and national committees and initiatives, including autism treatment research, Ohio autism service guidelines, autism screening, and early identification of developmental disabilities He is on the editorial board of Lancet Neurology and Journal of Child Neurology and the Professional Advisory Board of CHADD, the national ADHD advocacy organization, and lectures nationally and internationally about various neurodevelopmental disabilities.

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Max Wiznitzer, MD, Pediatric Neurology, UH Cleveland ...

T3D Therapeutics Closes $15M Financing to Advance Phase 2 Development of T3D-959 in a New Approach to Treating Alzheimer’s Disease. – BioSpace

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RESEARCH TRIANGLE PARK, N.C., Nov. 4, 2019 /PRNewswire/ -- T3D Therapeutics, a clinical stage drug development company engaged in the development of T3D-959, a new orally administered treatment for Alzheimer's disease (AD), announced today that it has closed on a $15 million financing from a cornerstone investor. These funds, along with support from the National Institute on Aging (NIA), part of NIH, completes the funding needed to begin the PIONEER Study of T3D-959, a novel, metabolic-focused AD drug treatment.

"We believe T3D-959 has the potential to be Alzheimer's disease remedial, to either slow, stop, or even reverse the course of disease as a single drug therapy," said Chief Executive OfficerJohn Didsbury, Ph.D. "Our drug works to overcome aberrant glucose (sugar) and lipid (fat) metabolism in the brain that is inherent in AD. This dysfunctional metabolism causes protein mis-folding which in turn leads to plaques, tangles and inflammation."

Warren Strittmatter, M.D., Chief Medical Officer of T3D Therapeutics,Emeritus Professor of Neurology at Duke University Medical Center and Alzheimer's Association Zenith Award winner said, "We are eager to expand our testing of T3D-959 in Alzheimer's patients in this new Phase 2 study since it uniquely targets mechanisms which we believe underlie the development of the memory deficits in this disorder."

About PIONEER

The Phase 2 PIONEER study (Prospective therapy to Inhibit and Overcome Alzheimer's Disease Neurodegeneration via Brain EnErgetics and Metabolism Restoration) is expected to initiate patient dosing in early 2020. PIONEER is adouble-blind, placebo-controlled, parallel-group Phase 2 safety and efficacy study expected to enroll up to 256 adults with mild-to-moderate Alzheimer's disease (MMSE 16-26). PIONEER will enroll subjects who will receive one of three different doses of T3D-959 or a placebo for 24 weeks. PIONEER is projected to start enrolling subjects in the first quarter of 2020.

PIONEER is supported by the NIA under award number R01AG061122.

About T3D Therapeutics, Inc.

T3D Therapeutics, Inc. is a privately-held, Research Triangle Park, NC-based company. The Company has an exclusive license to T3D-959, its lead product candidate, and a platform of structurally-related molecules. T3D Therapeutics' mission is to develop and commercialize T3D-959 for the treatment of Alzheimer's disease and Mild Cognitive Impairment. T3D-959 is a small molecule, orally-delivered, brain-penetrating dual nuclear receptor agonist designed to improve glucose and lipid metabolism dysfunctions present in AD and other neurodegenerative disorders.

For more information visit http://www.t3dtherapeutics.com/.

Investor Contact|

John Didsbury, Ph.D., CEOT3D Therapeutics, Inc.1-919-237-4897Email: info@t3dtherapeutics.com

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T3D Therapeutics Closes $15M Financing to Advance Phase 2 Development of T3D-959 in a New Approach to Treating Alzheimer's Disease. - BioSpace

Best supplements for the brain: This supplement could reduce risk of neurological diseases – Express

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While the brain only weighs around three pounds and is the size of two clenched fists, it is a highly complex organ made up of many different parts. Much like muscles and joints, certain cells in the brain can stiffen up too and this causes declines in memory and cognitive abilities. The normal ageing process brings subtle changes in cognitive abilities and as one reaches middle age, the brain changes from subtle to measurable ways. The overall volume of the brain begins to shrink in the 30s or 40s with the rate of shrinkage increasing around age 60. Thankfully, there are a few ways one can improve brain health and taking a creatine supplement may help.

Creatine is the number one supplement for improving performance in the gym, however, it has also been shown to help with the brain and protecting against neurological disease.

Creatine is an amino acid found only in animal flesh but most abundantly in skeletal muscle flesh.

It is not an essential amino acid as it can be synthesised from other amino acids found in plant foods.

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Best supplements for tiredness: Taking a certain vitamin has been proven to boost energy

Creatine is a substance that is found naturally in muscle cells. It helps muscles produce energy during heavy lifting or high-intensity exercise.

Chemically speaking, it shares many similarities with amino acids. When a person supplements, they increase their stores of phosphocreatine.

This is a form of stored energy in the cells, as it helps your body produce more of a high-energy molecule called ATP.

ATP is often called the bodys energy currency and when a person has more ATP, the body can better perform.

Just like the muscles, the brain stores phosphocreatine and requires plenty of ATP for optimal function.

Researchers who study cognition and athletic performance often advised on creatine supplements.

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What the studies say

In a study with the US National Library of Medicine National Institutes of Health, creatines effect on improved repercussion and neuroprotection was analysed.

The study noted that stroke leads to energy failure and subsequent neuronal cell loss.

Creatine and phosphocreatine constitute a cellular energy buffering and transport system and dietary creatine supplementation was shown to protect neutrons in several models.

In another study, oral creatine supplements were analysed on how it improves brain performance.

The study said: Creatine supplementation is in widespread use to enhance sports fitness performance and has been trialled successfully in the treatment of neurological and neuromuscular disease.

"Creatine plays a pivotal role in brain energy homeostasis.

"Creatine supplementation had a significant positive effect on both memory and intelligence.

Every brain changes with age and mental decline is very common being one of themes feared consequences of ageing.

However, cognitive impairment is not inevitable.

Along with taking supplements to boost the brains health, other proven ways to improve brain health include reducing stress, taking more naps, meditation, exercising, improving health conditions and being vigilant with your diet.

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Best supplements for the brain: This supplement could reduce risk of neurological diseases - Express