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Brain bleeds in older adults linked to amyloid deposits in blood vessels – News-Medical.Net

A common type of brain bleed in older adults, known as subdural hemorrhage, is associated with the presence of amyloid deposits in cerebral blood vessels, according to a study led by researchers at Weill Cornell Medicine, NewYork-Presbyterian and Yale School of Medicine. The study is the first to link cerebral vessel amyloid to subdural hemorrhages and should lead to a better understanding of both conditions.

For the study, which appears Dec. 26 in JAMA Neurology, the researchers analyzed two large population-based cohorts covering more than 600,000 participants in the United Kingdom and United States. They found that patients with amyloid deposits in the cerebral vesselsa condition called cerebral amyloid angiopathy (CAA)were at least five times more likely to experience subdural hemorrhages, compared with patients without CAA.

At present, clinicians generally don't consider isolated subdural hemorrhages as part of the spectrum of cerebral amyloid angiopathy. So, if this link is established, then clinicians will start to screen and evaluate subdural hemorrhage patients for underlying CAA, which would be a major paradigm shift and could lead to better care and better outcomes."

Dr. Santosh Murthy, study co-senior author, associate professor of neurology at Weill Cornell Medicine and the associate chief of the division of neurocritical care at New York-Presbyterian/Weill Cornell Medical Center

The study's other co-senior author was Dr. Guido Falcone, associate professor of neurology at Yale School of Medicine. The study's first author was Dr. Cyprien Rivier, a postdoctoral associate in the Falcone laboratory.

Subdural hemorrhages are bleeds from blood vessels that occur on the outer surface of the brain below its largest covering membrane, known as the dura. They result in trapped blood called subdural hematomas, which can put a dangerous amount of pressure on the brain, and usually require surgical removal. Subdural hemorrhages affect nearly 125,000 Americans per year, and, because of the aging population, are on their way to becoming the most common reason for brain surgery among adult patients.

CAA features amyloid beta protein aggregates in the walls of blood vessels within and just above the brain. The condition is very common in older adultsespecially Alzheimer's patients, who also have amyloid deposits in other brain tissue. However, although CAA can trigger bleeding from any of the vessels where it is found, neurologists generally have considered subdural hemorrhage a separate clinical phenomenon, induced mainly by mechanical stresses on vessels due to age-related brain shrinkage.

Even so, there have been hints of a connection between the two. Roughly one-fifth of patients with CAA brain bleeds also have coexisting subdural hemorrhages, and there is some evidence that subdural hemorrhages are more common when CAA signs are more prominent on brain MRI scans. Drs. Murthy and Falcone and their colleagues therefore set up the new study as an initial investigation of this potential link.

Their analysis made use of two ongoing, long-term, population-based health studies, the UK's Biobank Program and the U.S. National Institutes of Health's All of Us Research Program, which includes data from participants enrolled by the New York City Consortium of Columbia University Irving Medical Center, Weill Cornell Medicine, NYC Health + Hospitals/Harlem and NewYork-Presbyterian. In datasets covering a total of 645,231 people, they compared the rates of subdural hemorrhages in those who did and didn't have a prior CAA diagnosis.

In the larger UK-based dataset, 3 of the 126 people with CAA and 649 of the 487,097 without CAA had a subdural hemorrhage during a median follow-up period of about 20 years. In the researchers' analysis, this implied about 7.6 times greater risk of subdural hemorrhage for the CAA group. Confirming the link, the researchers estimated about 5.2 times greater risk for CAA patients in the U.S. dataset.

The authors cautioned that while this apparent statistical linkage does not, in itself, imply that CAA causes subdural hemorrhages, it does encourage further investigation.

"The next logical step is to do a multicenter prospective study looking for the presence of amyloid using PET scans in patients who present with an isolated subdural hemorrhage," Dr. Murthy said.

Currently there are no specific treatments for CAA. It is possible that anti-amyloid therapies, which have been recently approved for use in Alzheimer's disease, will be tested in patients with CAA in the future. But in principle, Dr. Murthy added, screening subdural hemorrhage patients for CAA could uncover many patients who would benefit from such treatments when they become available.

The work described in this study was supported by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, grant number K23NS105948.

Source:

Journal reference:

Rivier, C. A., et al. (2023). Cerebral Amyloid Angiopathy and Risk of Isolated Nontraumatic Subdural Hemorrhage. JAMA Neurology. doi.org/10.1001/jamaneurol.2023.4918.

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Pioneering New Treatments in Deep Brain Stimulation for Parkinson’s Disease – Research Blog – Duke University

Note: Each year, we partner with Dr. Amy Shecks students at the North Carolina School of Science and Math to profile some unsung heroes of the Duke research community. This is the second of eight posts.

Meet a star in the realm of academic medicine Dr. Kyle Todd Mitchell!

A man who wears many hats a neurologist with a passion for clinical care, an adventurous researcher, and an Assistant Professor of Neurology at Duke Mitchell finds satisfaction in the variety of work, which keeps him driven and up to date in all the different areas.

Dr. Mitchells educational journey is marked by excellence, including a fellowship at the University of California San Francisco School of Medicine, a Neurology Residency at Washington University School of Medicine, and an M.D. from the Medical College of Georgia. Beyond his professional accolades, he leads an active life, enjoying running, hiking, and family travels for rejuvenation.

Dr. Mitchells fascination with neurology ignited during his exposure to the field in medical school and residency. It was a transformative moment when he witnessed a patient struggling with symptoms experience a sudden and remarkable improvement through deep brain stimulation. This therapy involves the implantation of a small electrode in the brain, offering targeted stimulation to control symptoms and bringing relief to individuals grappling with the challenges of Parkinsons Disease.

You dont see that often in medicine, almost like a light switch, things get better and that really hooked me, he said. The mystery and complexity of the brain further captivated him. Everything comes in as a bit of a mystery, I liked the challenge of how the brain is so complex that you can never master it.

Dr. Mitchells research is on improving deep brain stimulation to alleviate the symptoms of Parkinsons disease, the second most prevalent neurodegenerative disorder, which entails a progressive cognitive decline with no cure. Current medications exhibit fluctuations, leading to tremors and stiffness as they wear off. Deep brain stimulation (DBS), FDA-approved for over 20 years, provides a promising alternative.

Dr. Mitchells work involves creating adaptive algorithms that allow the device to activate when needed and deactivate so it is almost like a thermostat. He envisions a future where biomarkers recorded from stimulators could predict specific neural patterns associated with Parkinsons symptoms, triggering the device accordingly. Dr. Mitchell is optimistic, stating that the technology is very investigational but very promising.

A key aspect of Dr. Mitchells work is its interdisciplinary nature, involving engineers, neurosurgeons, and fellow neurologists. Each member of the team brings a unique expertise to the table, contributing to the collaborative effort required for success. Dr. Mitchell emphasizes, None of us can do this on our own.

Acknowledging the challenges they face, especially when dealing with human subjects, Dr. Mitchell underscores the importance of ensuring research has a high potential for success. However, the most rewarding aspect, according to him, is being able to improve the quality of life for patients and their families affected by debilitating diseases.

Dr. Mitchell has a mindset of constant improvement, emphasizing the improvement of current technologies and pushing the boundaries of innovation.

Its never just one clinical trial we are always thinking how we can do this better, he says.

The pursuit of excellence is not without its challenges, particularly when attempting to improve on already effective technologies. Dr. Mitchell juggles his hats of being an educator, caregiver, and researcher daily. So let us tip our own hats and be inspired by Dr. Mitchells unwavering dedication to positively impact the lives of those affected by neurological disorders.

Guest post by Amy Lei, North Carolina School of Science and Math, Class of 2025.

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Is It Time to See a Neurologist for Your Headaches? – Everyday Health

The averageheadachedoesnt require a call to a neurologist or even your family doctor. But if youre experiencing frequent headaches and usingmedication for them regularly, thats a different story.

If you have a history of headaches that come once or twice a month and go away when you take an over-the-counter (OTC) medication such asacetaminophen (Tylenol) or ibuprofen (Aleve), you may not need to seek further treatment, saysSandhya Kumar, MD, a neurologist andheadache specialistat Wake Forest Baptist in Winston-Salem, North Carolina.

If youre having headaches more than four times a month, especially if they are debilitating and keeping you home from work, you should see a provider for diagnosis and medication, says Dr. Kumar.

As a general rule, for nonsevere headaches, your family doctor is a great person to start with. Approximately 7 out of 10 people talk to their primary care doctor first, according to theAmerican Headache Society.

If the recommended treatments are not working well or you have unusual symptoms, your doctor may refer you to a neurologist, who specializes in disorders of the brain and nervous system.

Possible signs that you may need to see a specialist for your headaches include:

According to headache expertPeter Goadsby, MD, PhD, a professor of neurology at the UCLA GoldbergMigraineProgram in Los Angeles, a valuable tool in diagnosis is your headache history.

A thorough history, aided by your detailed notes, can pinpoint causes, triggers, and even potential solutions. Make careful notes about your headache experiences before you go to the doctor. Include the following:

Dr. Goadsby recommends using a monthly calendar so that the pattern of headache days is clearly visible to you and your doctor.

If you are having severe or disabling headaches, dont wait a full month to call for an appointment make notes about what you recall or are experiencing and see a doctor as soon as you can.

The tests your doctor orders will depend in part on what they suspect could be causing your headaches and whether its a primary headache such as amigraineor tension headache or a secondary headache, which means that its a symptom of another health concern.

Although primary headaches can be painful and debilitating, they arent life-threatening.

Secondary headaches are much rarer and can be the sign of a serious health issue sometimes even one that requires urgent medical attention.

The process of diagnosis may include the following:

Medical HistoryYour doctor will want to know about any other health conditions you have as well as any medications, supplements, or herbal treatments you take.

Family HistoryBe prepared to provide details about any family members who have headaches or migraine at what age their headaches started and any other health diagnoses they may have. As Goadsby notes, Very often, family members wont know theyve got migraine, but they will know they are prone to headaches. Since migraine has a strong genetic component, a family history of migraine-like symptoms is an indicator that your headaches are also being caused by migraine.

Physical ExamYour doctor will examine you, paying close attention to yourhead,neck, and shoulders, which can all contribute to headache pain in various ways.

Neurological ExamA neurological exam may include tests of your vision, hearing, short-term memory, reflexes, sensation, balance, and coordination.

Blood TestsBlood tests may be ordered to rule out infection and other health conditions that have headache as a symptom.

Spinal Fluid TestThis may be necessary if your doctor suspects that your headaches are caused by certain types of infection or by bleeding in your brain.

UrinalysisA urine sample may be ordered to help rule out infection and other health conditions.

Imaging TestsComputed tomography(CT) or magnetic resonance imaging (MRI) scans may be ordered. These imaging tests can show structures in your head, neck, or elsewhere in the body that may be causing your headaches.

Neuroimaging Tests These may be done during a headache episode to get a clearer picture of what is going on during an actual headache.

Electroencephalogram (EEG)This test can show your doctor whether there are changes in brain wave activity. It can help diagnose brain tumors, seizures, head injury, and swelling in the brain.

Working closely with your family practitioner and a neurologist, if needed, will bring you closer toheadache relief.

Warning signsthat you need immediate medical attention for your headache ormigraineinclude:

RELATED:When Should You Worry About Your Headache and Seek Immediate Help?

Additional reporting byBecky Upham.

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Brain Plaques Point to Who’ll Need Alzheimer’s Treatment Most – HealthDay

TUESDAY, Dec. 26, 2023 (HealthDay News) -- Are you necessarily at higher risk of Alzheimer's disease just because you're 80, and not 75? New research shows it's more complex than that.

The findings suggest that it's the pace of buildup in the brain of Alzheimer's-linked amyloid protein plaques that matters most, not age.

Our findings are consistent with studies showing that the amyloid accumulation in the brain takes decades to develop," said study lead author Dr. Oscar Lopez, a professor of neurology at the University of Pittsburgh.

His team's findings were published Dec. 22 in the journal Neurology.

Neuroscientists have long known that the slow but steady accumulation of amyloid-beta protein plaques within brain tissue is a hallmark of Alzheimer's disease, although whether it actually causes the illness is still debated.

Rates of dementia do rise with advancing age, but is age alone the key factor?

To find out, Lopez' team examined amyloid buildup in the brains of 94 people who were 85 at the time they enrolled in the study. All were tracked for 11 years or until they died, and all received two PET scans of their brains during that time.

The researchers compared levels of amyloid buildup seen in those scans to those seen in scans from a younger group of patients (in their 60s) observed in a prior Australian trial.

As expected, amyloid plaque buildup rose over time, regardless of how much of the protein had infiltrated a participant's brain at the time they joined the Pittsburgh study.

Plaques seemed to accumulate faster among people in their 80s, however, compared to people in their late 60s', Lopez' team reported.

None of the elderly people in Lopez' trial who developed dementia were without some plaque buildup in their brains, confirming its key role in the disease.

Most importantly, when brain plaque buildup began seemed key to how soon dementia set in.

For example, people who were already displaying amyloid buildup in their PET scans at age 80 (when they enrolled in the study) developed dementia two years earlier than folks without such early buildup, the Pittsburgh team found.

Finally, the long-term links between amyloid beta buildup and other brain health indicators was more strongly linked to dementia than just the short-term growth of plaque on its own, Lopez' group added.

That's consistent with other studies, which found that amyloid buildup "takes decades to develop, and occurs in the context of other brain pathologies," Lopez said in a university news release.

Lopez, who also directs Pitts Alzheimer's Disease Research Center, said that "understanding of the timing of the presence of these pathologies will be critical for the implementation of future primary prevention therapies.

More information

Find out more about Alzheimer's disease and the brain at the Alzheimer's Association.

SOURCE: University of Pittsburgh, news release, Dec. 22, 2023

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The key to brain-based adjustments: traditional chiropractic + functional neurology – Chiropractic Economics

Joseph Schneider December 22, 2023

I consider myself a patient as well as a healer. I remember lying in my hospital bed after I suffered a stroke in May 2017. I could not move the right side of my body, and I thought all my hopes and dreams had gone away, including my hopes of ever practicing as a functional neurologist and DC again or being able to work with my patients. Prior to that, I suffered three concussions from various sports injuries and motor vehicle accidents. My brain went through a lot.

I am grateful to my colleagues in chiropractic functional neurology, and the knowledge I gained from extensive experience with my patients. Through it all, I have learned a lot about brain recovery from overcoming my stroke and now I am committed to helping my patients achieve optimal health without medications and/or surgeries. Now I have a vision to help other DCs learn about the future innovations in technology, and the research and breakthroughs happening today, which that will enable chiropractic functional neurologists to lead the field in brain regeneration.

At my clinic, I work to heal hurt brains at my clinic, where all the treatment plans incorporate chiropractic adjustments, functional neurology and the most cutting-edge modalities available. Those modalities include the latest technology to accelerate patient outcomes, such as oxygen therapy, multi-axis rotating chair therapy, neurofeedback, interactive noninvasive imaging studies, vibration therapy and photobiomodulation (low-level light therapy).

The most important aspect of any brain-specific program is to have an impact that changes the patients life in four critical areas: 1. work relationships, 2. recreation, 3. household chores and 4. sleep. The goal is to make life more dynamic and vibrant for the individual.,

Many patients come to my clinic after they have exhausted all other methods. My website is full of video testimonials from patients who regained their health thanks to the latest technologies the center uses for brain improvement. Brain-specific rehabilitation is a combination of functional medicine and functional neurology. All the pieces have to be put in place for maximum improvement and outcome. In addition, there is a different and very specific order for each patient. There isEach usually has a collection of symptoms, and they all need to be traced back to the systems in the body and treated holistically and synergistically.

Some patients experienced asymptomatic concussions. Perhaps the injury occurred 20 years ago, and they thought they were OK, but lately have noticed signs of dementia, brain fog and emotional challenges. These symptoms, we know, are related to the degeneration of the brain over time as a result of past trauma. The good news is we can help people at any point. We treat many patients who have struggled for years since their brain injury.

I started studying functional neurology in 1989 with Ted Carrick, DC, PhD, MS-HPEd. Carrick has been my friend, my mentor and my doctor after my stroke. In the 1990s, at the beginning of my career, I used to go to seminars with Carrick before I got board-certified in neurology. After a weekend of learning, I would go back to my practice and I would start to look at eye movements, balance, finger-pointed-at-the-nose things for looking at metric movements and dysmetria for the cerebellum. I looked carefully at my patients because Carricks big lesson was to know normal.

The brain is the master control system of the body, so as chiropractors we use spinal manipulation as a way of improving function throughout the body. Our rightful place is to continue to have our examination skills at a level in which we can look at the function of the brain and the brains interaction with the body. And looking at most of the contemporary diseases today, such as movement disorders, dystonia, visual issues, visual dysfunction, vertigo, dizziness and balance issues, chiropractors can improve their skills and understanding of the issues by observing patients and absorbing abnormal findings. Traditional chiropractic methods combined with brain-based adjustments can improve patient outcomes.

You may wonder if DCs can use their technique to change brain function. The answer isyes! Its called brain-based adjustments. There are ways of adjusting the spine that have a brain effect. If you want to, you can take your practice to the point where you start evaluating brain function through examination techniques and diagnostic technologies. By evaluating in this way, you can rate function and create a baseline for the patient. Then you can use different technologies and exercise systems to actually improve the pathways in the brain through connectivity and also take neurons from stem cells and create new neurons in the cortical areas.

Once I understood the brain was the master control system of the body, a light went off in my brain, and I knew I wanted to be a DC. I was an engineer, so people I told would ask me, Why do you want to be a chiropractor? Why not be a medical doctor? But I said, No, I want to change the master control system of the body. And thats what I did. I left my engineering career and went off to New York Chiropractic. When I look back, I realize, my love of chiropractic prompted my love of changing brains. Now every single patient that who comes to my office gets adjusted.

JOSEPH SCHNEIDER, DC, is a Board Certified Chiropractic Neurologist. He graduated from New York Chiropractic College in 1987. Schneider is in clinical practice at Hope Pain Relief in Chadds Ford, Penn.

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NeurologyLive Year in Review 2023: Top Stories in Movement Disorders – Neurology Live

The NeurologyLive staff was hard at work in 2023, covering clinical news and data readouts from all over the United States and the world, across a number of key neurology subspecialty areas. From major study data and FDA decisions to medical society conference sessions and expert conversations, the team spent all year bringing the latest news and updates to the website's front page.

Among our key focus areas is movement disorders, which include a number of complex diseases that have benefitted greatly from recent advances in medical care and therapeutic development. Although major news itemssuch as first-time approvals or new guidelinesoften appear among the top pieces our team produces, sometimes smaller stories reach those heights for other reasons, such as clinical impact and interest, or concerns about other facets of care, for example. Whatever the reason for the attention these stories got, their place here helps provide an understanding of the themes in this field.

Here, we'll highlight some of the most-read content on NeurologyLive this year. Click the buttons to read further into these stories.

Exploratory findings from a phase 3 randomized, controlled trial (NCT03329508) assessing P2B001 (Pharma Two B), a low dose combination of extended-release pramipexole and rasagiline, in Parkinson disease (PD) showed efficacy that was comparable to extended-release pramipexole (Prami-ER) alone, but with reduced sleep-related and dopaminergic adverse events (AEs). Pharma Two B planned to submit a new drug application for P2B001 to the FDA in 2023.

Newly announced findings from a triple-blinded, randomized controlled trial showed that treatment with SYMBYX Neuro infrared light therapy helmet significantly improved symptoms of Parkinson disease (PD) in areas of facial expression, upper and lower limb coordination and movement, walking gait, and tremor. Using the standardized Movement Disorder Society Unified Parkinsons Disease Rating Scale-III (UPDRS-III), compared with the placebo group, those on the light therapy improved 24% to 58% over baseline across all 5 areas tested, unlike the placebo group, which demonstrated statistically valid improvement in lower limb coordination and movement only.

After showing positive results in a phase 3 clinical program, the FDA has accepted Revance Therapeutics supplemental new biologics license application (sBLA) for daxibotulinumtoxinA injection (Daxxify), as a new treatment for adults with cervical dystonia. The agency ultimately approved the therapy on August 15, 2023. DaxibotulinumtoxinA is an acetylcholine release inhibitor and neuromuscular blocking agent indicated for the temporary improvement of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adults. To date, the therapy has shown promising results in 2 phase 3 studies of cervical dystonia, ASPEN-1 (NCT03608397) and ASPEN-OLS (NCT03617367).

Despite years of use of gold-standard therapy levodopa, therapeutic development in Parkinson disease has advanced rapidly and expanded to numerous novel pathways and targets. MedStar Georgetown's team of Katelynn Getchell; Gonul Ozay, MD; Brian Nagle, MD; Irma Zhang, MD; Luke Lovelace; Emma Waldon, RN; Yasar Torres-Yaghi, MD; and Fernando L. Pagn, MD explore this in depth.

Topline data from the Synuclein-One Study of CND Life Sciences Syn-One Test, an -synuclein skin biopsy test used for the detection of the pathology in Parkinson disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and pure autonomic failure (PAF), suggest that the test is sensitive and specific in said detection of phosphorylated -synuclein. As misdiagnosis remains a consistent challenge in neurodegenerative disorderssome estimates suggest a misdiagnosis rate of 30%this represents an opportunity to address this clinical obstacle.

Using prospective cohort studies of community-dwelling elders followed up to 20 years, findings published in Neurology identified specific cognitive and functional declines in patients who developed incident Parkinson disease (PD). There were important sex differences as well, as men with incident PD had a steeper decline in executive function compared with women, but only women with incident PD exhibited detectably faster prediagnostic decline in global cognition.

BIAL R&D announced the dosing of the first patient in its phase 2 clinical trial, ACTIVATE (NCT05819359), to investigate BIA 28-6156, an allosteric activator of the enzyme beta-glucocerebrosidase (GCase), as a treatment of patients with genetically-mutated Parkinson disease (PD). The trial, which includes those with a mutation in the glucocerebrosidase 1 (GBA1) gene (GBA-PD), otherwise the most common genetic risk factor of the disease, is screening patients across sites in North America and with a Europe-based trial planned to initiate in the third quarter of 2023.

Biogen and Denali have announced that they are discontinuing a portion of the clinical development program for BIIB122 (also known as DNL151), an investigational small molecule inhibitor of LRRK2 in development for the treatment of Parkinson disease (PD). As a result of this decision, the phase 3 LIGHTHOUSE study (NCT05418673), which was initiated in September 2022, will be terminated.

New data from a first-in-human phase 1 study (NCT04802733) assessing bemdaneprocel (BlueRock Therapeutics/Bayer), an investigational cell therapy, showed that the agent met its primary objective of safety, with encouraging results on other measures of motor and nonmotor outcomes. Based on these results, the companies are planning for a phase 2 trial that is expected to begin enrolling patients in the first half of 2024.

The FDA has issued a complete response letter (CRL) to Amneal Pharmaceuticals for IPX203, an oral formulation of carbidopa/levodopa (CD/LD) extended-release capsules designed for the treatment of Parkinson disease. The reasons behind the decision were not based on efficacy or manufacturing for the agent, but rather established safety for an ingredient of the therapy. Amneal plans to work closely with the FDA to address the comments and align on the best path forward.

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