US Burden of Disorders Affecting the Nervous System - Part 2

In the second episode of this two-part series, Dr. Stacey Clardy and Dr. John Ney discuss why deaths from neurologic conditions are decreasing, but disability is rising, and what this shift means for future care.  Show citation:  Ney JP, Steinmetz JD, Anderson-Benge E, et al. US Burden of Disorders Affecting the Nervous System: From the Global Burden of Disease 2021 Study. JAMA Neurol. 2026;83(1):20-34. doi:10.1001/jamaneurol.2025.4470  Show transcript:  Dr. Stacey Clardy: Hi, this is Stacey Clardy from the Salt Lake City VA and the University of Utah. I've been talking with John Ney from Yale about why neurologic disease now represents the top source of disability in the United States. John, for the minute, deaths from neurologic conditions are declining overall, right? But disability is increasing. So what does that shift mean for how we, the health system, should be planning for neurologic care? Dr. John Ney: I would say overall, both deaths and disability are increasing as a function of greater life expectancy in the population and, then relative to 1990, a greater increase in population of 50 million individuals came into the US either through birth or immigration during that time. So both of those are going up when we actually look by adjusting for age and per 100,000 individuals, both are actually going down, but not at a rate that we would like. So I think there's a lot more work to do. Dr. Stacey Clardy: Understood. Amongst our growing population, neurologic disability is still the leading cause and not less of a problem. For more details, we really get into the specifics and break this down by states even, take a listen to the full-length neurology podcast. And also check out the paper, it is packed with all of the data. It's in JAMA Neurology. It's titled: US Burden of Disorders Affecting the Nervous System from the Global Burden of Disease 2021 study.

Dr. Tesha Monteith and Dr. Michael Eller discuss the implications of CGRP therapies in migraine treatment, particularly for patients with vascular risk factors or a history of stroke.  Show citation: Eller MT, Schwarzová K, Gufler L, et al. CGRP-Targeted Migraine Therapies in Patients With Vascular Risk Factors or Stroke: A Review. Neurology. 2025;105(2):e213852. doi:10.1212/WNL.0000000000213852  Show transcript:  Dr. Tesha Monteith: Hi, this is Tesha Monteith with the Neurology Minute. I've just been speaking with Michael Eller from the Department of Neurology Medical University of Innsbruck, Austria on the neurology podcast on his paper, CGRP Targeted Migraine Therapies in Patients with Vascular Risk Factors or Stroke: A Review. Hi, Michael. Dr. Michael Eller: Hello. Dr. Tesha Monteith: Why don't you summarize your general approach to use of CGRP targeted therapies in patients that might be at risk for vascular events when considering safety? Dr. Michael Eller: Yeah. About acute vascular events, we should stop CGLP targeted drugs immediately. When we come to post-stroke, we should reassess the necessity of these targeted treatments after recovery. We suggest a minimum of three months pause after ischemic stroke to allow early recovery and remodeling, and then restart only after individualized benefit risk review. In high-risk primary prevention, so no stroke yet, but elevated risk, if the patients are 65 years or older with established cardiovascular disease, we should prefer traditional preventives. And if CGLP targeted therapy is essential, we should consider Gepants cautiously due to their shorter half lives. We should avoid CGLP targeted treatments in small vessel disease, distal stenosis, Raynaud's phenomenon, and uncontrolled hypertension. For acute migraine treatment, we can consider gepants or ditans as alternatives to triptans and NSAIDs in relevant stroke risk or post-stroke patients, individualized to comorbidities. Dr. Tesha Monteith: Great. And we should say that the label updates include hypertension and Raynaud's phenomenon as potential vascular complications. Otherwise, these are more theoretical risks based on what we know about CGRP. Dr. Michael Eller: Yes, I totally agree because large studies did not show any elevated cardiovascular risk signals. And for post-marketing databases, we did not see any elevated cardiovascular risk so far. However, in pre-clinical settings, studies showed large infarct size in pretreated mice. Dr. Tesha Monteith: Great. Well, thank you again for doing this work. It was a phenomenal read and congratulations. Dr. Michael Eller: Thank you. Dr. Tesha Monteith: This is Tesha Monteith. Thank you for listening to the Neurology Minute.

In part one of this two-part series, Dr. Stacey Clardy and Dr. John Ney break down the key message neurologists need to understand from this update and offer guidance on how to clearly convey it to patients. Show citation:  Ney JP, Steinmetz JD, Anderson-Benge E, et al. US Burden of Disorders Affecting the Nervous System: From the Global Burden of Disease 2021 Study. JAMA Neurol. 2026;83(1):20-34. doi:10.1001/jamaneurol.2025.4470  Show transcript:  Dr. Stacey Clardy: Hi, this is Stacey Clardy from the Salt Lake City VA in the University of Utah. I've been talking with John Ney from Yale about a global burden of disease analysis showing that disorders affecting nervous system health are the leading cause of disability in the United States. This is probably not too surprising to any neurologist, but very important that they rigorously went through to prove what we experience in clinics. So John, for the Minute, when neurologists do hear it though, when they hear it out loud that more than half of the US population is affected by neurologic conditions, we're still a little skeptical. That's one in two, right? What's the single most important thing we need to understand about how that number was calculated and how to communicate it to our patients and our communities? Dr. John Ney: It's not just the sum of all conditions added up and then translated into the entire population. It's really looking at unique persons with a condition affecting the nervous system. And certainly our top two are tension type headache and migraine, but then we also get into diabetic neuropathy with 17 million individuals, stroke and Alzheimer's with six million and five million respectively. So individuals, unique persons may have more than one of these conditions, but 180 million or more persons in the United States or 54% of the population actually has at least one of these conditions. Dr. Stacey Clardy: So important that we understand this, these numbers. This matters to our patients when we're explaining it to them. Sometimes they feel alone, but this really also matters when we're talking about what we need for our patients as neurologists, more research, more resources. If you want to learn more, listen to the full-length podcast. We get into the discussion, even breaking it down by states and conditions, and a bit more of the health economics and what informs these numbers. And also check out the paper in JAMA Neurology. It's titled US Burden of Disorders Affecting the Nervous System from the Global Burden of Disease 2021 Study.

In part two of this four-part series, Casey Kozak discusses Hover's sign, the most well-known test for FND.  Show transcript:  Casey Kozak:  Welcome back to Neurology Minute. My name is Casey Kozak with Rutgers, and today we're continuing our examination of functional neurological disorder. That is physical examination. This episode is dedicated to Hoover's sign, probably the most well-known test for FND, and in my humble opinion, one of the most confusing maneuvers to learn. So today, we're going back to the origin using Dr. Charles Franklin Hoover's original description. Maybe you've heard of Hoover's Sign, but when do we use it? Hoover's sign is useful when a patient presents with one-sided lower extremity weakness, and FND is on the differential. Because the test relies on one healthy leg, you can't perform Hoover's test on a patient with total lower-body paralysis. Now, how to perform Hoover's test. First, have the patient lie on their back and place their hand under the heel of the patient's weak leg. Then ask the patient to raise their strong leg off the plane of the bed. What do you expect to happen? Dr. Hoover made the astute observation that muscular resistance offered by the leg on the bed will be pressed onto the bed with the same force which is exhibited in lifting the strong leg off the bed. This is based on the principle that when one limb flexes, the contralateral limb extends. In this way, the leg on the bed acts as a sort of counterbalance to assist the action of raising the other leg. Okay, but what does this mean for our examination? Well, if a patient's leg was paralyzed as the result of a stroke, for example, the patient would not be able to create that downward resistance. In a patient with functional leg weakness, however, this action is still possible. Therefore, Hoover's sign is present if the weak leg produces a downward force into the bed while the strong leg is lifted, which you will be able to feel as their heel pressing into your hand. So to summarize, you're looking for a down pressure from the patient's weak leg when you ask them to raise their unaffected leg. Time to break for some practice. Join us in our next episode when we'll look at some other helpful maneuvers for functional weakness. 

In part one of this four-part series, Casey Kozak breaks down tremors observed during the physical examination of FND.  Show transcript:  Casey Kozak: Welcome back to Neurology Minute. This is Casey Kozak with Rutgers, and today we'll be discussing a very important and evolving topic, that is Functional Neurological Disorder, or FND. If you're a regular fan of the Minute, you'll have already heard a great miniseries on FND by Jon Stone and Gabriela Gilmour, which focuses on diagnosis and treatment. If you haven't listened yet, I encourage you to check it out. In this series, we're going to focus in on physical exam findings associated with FND to help you excel on the floors. Talking about the physical exam, it's important to keep in mind that FND looks different for every patient. However, some general characteristics of symptoms may include inconsistency, variability, selectivity of impairment, meaning mismatch of impairment with different tasks, distractibility, suggestibility, and incongruence with symptoms seen in other neurological disorders. Since tremors are one of the most common presentations of FND, we'll start there. Even while taking their history, you may notice features consistent with FND. And in fact, this is a great time to make natural observations of the patient and their symptoms. Unlike tremors associated with degenerative movement disorders like Parkinson's, functional tremors may exhibit variability of frequency and amplitude, especially during periods of shifted attention. You can further evaluate the tremor using the entrainment test. To perform the entrainment test, ask the patient to make a tapping motion. As the patient taps, look for a change in frequency in their tremor. The frequency of the tremor may begin to match the frequency of the patient's tapping. Any change in the tremor while the patient is tapping is considered a positive finding. Alternatively, you can also test the whack-a-mole sign. To elicit the whack-a-mole sign, the examiner holds down the tremulous body part while looking for the emergence of a tremor in a different body part. This finding is consistent with a functional tremor, as tremors related to neurodegenerative diseases do not jump limbs. Let's break now to practice. Join us again for our next episode where we will turn to functional weakness. See you then.

Dr. Margarita Fedorova discusses possible environmental exposures and their risk of Parkinson disease.  Show citation:  Dorsey ER, De Miranda BR, Hussain S, et al. Environmental toxicants and Parkinson's disease: recent evidence, risks, and prevention opportunities. Lancet Neurol. 2025;24(11):976-986. doi:10.1016/S1474-4422(25)00287-X  Show transcript:  Dr. Margarita Fedorova: Welcome to Neurology Minute. My name is Margarita Fedorova and I'm a neurology resident at the Cleveland Clinic. Today, we're reviewing some information about possible environmental exposures and their risk of Parkinson disease. As we see in diagnose patients with Parkinson, they often want to know why they developed it and some emerging studies may offer insights. A recent personal view published in The Lancet Neurology by Ray Dorsey and colleagues in November 2025 examined associations between three environmental exposures and Parkinson's disease; pesticides, dry cleaning chemicals and air pollution. Since only five to 15% of Parkinson's cases have an identifiable genetic cause, environmental factors are an important area of investigation. Dorsey and colleagues describe studies showing that pesticide exposure is associated with Parkinson's risk. One example is Paraquat, an herbicide widely used in agriculture. It's banned in over 30 countries, but remains legal in the United States. In a population-based US study, residents living or working near areas where Paraquat was sprayed at twice the risk of developing Parkinson's, suggesting residential proximity alone may confer risk. Other pesticide exposures may show similar patterns. The organic chlorides, DGT and gildren are used in various agricultural areas. They're fat-soluble compounds that accumulate over decades. Postmortem studies found that when brains with lewd pathology and some studies suggest developmental exposure may increase risk of neurodegeneration years later. There have also been risks possibly associated with chemicals used in dry cleaning and metal degreasing. Trichloroethylene or TCE is one such chemical that was found in high amounts in the water at Camp Lejeune in North Carolina. A study of over 170,000 marines stationed there showed a 70% increase in risk of developing Parkinson's compared to marines at a non-contaminated base. What's particularly striking is the timing. Marines were exposed at an average age of 20 and the exposure lasted just over two years, yet disease manifested 34 years later. This suggests a long latency period between exposure and disease onset. TCE is also concerning because it evaporates from contaminated groundwater and can seep into buildings. As of 2000, 30% of US groundwater was contaminated with TCE. The third category of environmental exposure is air pollution. Studies from Canada, South Korea, Taiwan, and the UK show association between exposure to fine particular matter known as PM 2.5 in nitrogen dioxide with increased Parkinson's risk. These pollutants come from vehicle emissions, industrial sources, and combustion processes. The studies suggest that chronic exposure to these air pollutants may contribute to neurodegeneration through inflammatory and oxidative stress mechanisms. Unlike pesticides and dry cleaning chemicals, the magnitude of increased risk is often modest, typically ranging from one to 20%. However, the potential impact at large since almost everyone worldwide, 99% of people breathe on healthy air. For us as clinicians, this underscores the importance of taking detailed environmental histories. When patients ask, "Why me?" We can acknowledge that environmental exposures may have contributed to their disease. It's important to note that these studies show associations, but they don't confirm clear causation. Regardless, they may provide some answers to patients asking about the etiology of their Parkinson's or even the risks to others. That's your neurology minute for today. Keep exploring and we'll see you next time. If you want to read more, please find the paper by Ray Dorsey, titled Environmental Toxicants and Parkinson's Disease: Recent Evidence and Prevention Opportunities, published online in The Lancet Neurology in November 2025.

In the second episode of this two-part series, Drs. Justin Abbatemarco, Valérie Biousse, and Nancy J. Newman discuss the risk of non-arteritic ischemic optic neuropathy and how to counsel patients around GLP-1 medications.  Show transcript:  Dr. Justin Abbatemarco: Hello and welcome back. This is Justin Abbatemarco again with Valarie Biousse and Nancy Newman talking about non-arteritic ischemic optic neuropathy. I think the other major point that we had a discussion in the podcast was around the GLP-1 medications, which you mentioned have been truly life-changing for diabetes management and obesity. Can we talk about the risk of non-arteritic ischemic optic neuropathy and how you're counseling patients around this class of medications? Dr. Nancy J. Newman:  Absolutely. This is probably one of the most difficult things we are dealing with because it is something that is in process and progress right now. We don't have all the information yet, but it would appear that there is likely a small association of about slightly less than two times risk in patients who are taking these medications of having NAION with a resultant still very, very small overall risk. And it is not necessarily causal. This has prompted the European Medicines Agency to say that these patients should have their GLP-1 RAs stopped if they have NAION. Our own FDA and certainly the American Academy of Ophthalmology and the North American Neuro-Ophthalmology Society have not taken that step, but have suggested that this be shared decision-making, not only with the person who makes this diagnosis of an NAION in the patient, but with their primary care doctor or the provider who has felt that a GLP-1 receptor agonist is important for this patient's treatment and health. Dr. Justin Abbatemarco: More to come. We're going to have you back to have discussions as we learn more and better understand the disease and how we help our patients with both their diagnosis and treatment. Thank you so much for your time. 

In part one of this two-part series, Drs. Justin Abbatemarco, Valérie Biousse, and Nancy J. Newman discuss common myths around non-arteritic ischemic optic neuropathy (NAION). Show transcript:  Dr. Justin Abbatemarco: Hello and welcome. This is Justin Abbatemarco, and I just got done interviewing Valérie Biousse and Nancy Newman on all things around non-arteritic anterior ischemic optic neuropathy. I think one of my favorite takeaways from our interview were breaking some common myths around this disorder. Valérie and Nancy, could you maybe talk about one or two that you think are important that people should know are not true about this disease? Dr. Nancy J. Newman: So thing number one is that it's just another stroke of the eye. We know that it likely does have some vascular background to it, but the reality is it's not a stroke like neurologists know a stroke. You don't need to do an embolic workup. It has to do likely with the anatomy that a person is born with or that they acquire that crowds the front of their optic nerve. Secondly, thing number two, that it's a disease only of old people. I think that we know that you can be as young as age 11 and have this happen, mostly because you have a small, crowded optic nerve head. Thing number three, steroids really have not been proven to be helpful in this disorder and should likely not be used unless you are trying to decrease the optic nerve head edema, and the patient is insisting that they have some treatment. Dr. Justin Abbatemarco: So helpful. Please come back and check out the full podcast episodes where we dive into some of these elements in a little bit more detail.   

In part one of this two-part series, Drs. Justin Abbatemarco, Valérie Biousse, and Nancy J. Newman discuss common myths around non-arteritic ischemic optic neuropathy (NAION). Show transcript:  Dr. Justin Abbatemarco: Hello and welcome. This is Justin Abbatemarco, and I just got done interviewing Valérie Biousse and Nancy Newman on all things around non-arteritic anterior ischemic optic neuropathy. I think one of my favorite takeaways from our interview were breaking some common myths around this disorder. Valérie and Nancy, could you maybe talk about one or two that you think are important that people should know are not true about this disease? Dr. Nancy J. Newman: So thing number one is that it's just another stroke of the eye. We know that it likely does have some vascular background to it, but the reality is it's not a stroke like neurologists know a stroke. You don't need to do an embolic workup. It has to do likely with the anatomy that a person is born with or that they acquire that crowds the front of their optic nerve. Secondly, thing number two, that it's a disease only of old people. I think that we know that you can be as young as age 11 and have this happen, mostly because you have a small, crowded optic nerve head. Thing number three, steroids really have not been proven to be helpful in this disorder and should likely not be used unless you are trying to decrease the optic nerve head edema, and the patient is insisting that they have some treatment. Dr. Justin Abbatemarco: So helpful. Please come back and check out the full podcast episodes where we dive into some of these elements in a little bit more detail.   

Dr. Margarita Fedorova outlines how genetic, environmental, and pathological factors interact in Parkinson's disease and what this means for patient counseling.  Show citation:  Blauwendraat C, Morris HR, Van Keuren-Jensen K, Noyce AJ, Singleton AB. The temporal order of genetic, environmental, and pathological risk factors in Parkinson's disease: paving the way to prevention. Lancet Neurol. 2025;24(11):969-975. doi:10.1016/S1474-4422(25)00271-6  Show transcript:  Dr. Margarita Federova: Welcome to Neurology Minute. My name is Margarita Fedorova, and I'm a neurology resident at the Cleveland Clinic. Today we're exploring a framework for understanding how genetic, environmental, and pathological factors interact in Parkinson's disease and what this means for how we counsel our patients. A personal view paper by Blauwendraat and colleagues, published in The Lancet Neurology in September 2025, addresses a critical question. We've identified over 100 genetic loci for Parkinson's, but how do they act? The common saying is genetics loads the gun and environment pulls the trigger, but this paper suggests the relationship may be more complex. The key tool here is alpha-synuclein seeding amplification assays or SAAs. These detect misfolded alpha-synuclein protein in cerebrospinal fluid. Over 90% of Parkinson's patients test positive for misfolded alpha-synuclein using this assay. But here's what's notable. 2% to 16% of neurologically healthy older adults also test positive with prevalence increasing with age. This means there are more asymptomatic people with detectable alpha-synuclein pathology than people with actual Parkinson's disease. Most of these asymptomatic individuals will never develop symptoms. This raises an important question. What determines who converts to a disease and who doesn't? By integrating SAA results with genetic data, researchers can examine whether genetic factors drive initial protein misfolding or whether they modulate the response to pathology triggered by environmental or random events. Preliminary data suggests polygenic risk scores don't strongly associate with SAA positivity in healthy older adults. In other words, people with high genetic risk for Parkinson's aren't necessarily more likely to have misfolded alpha-synuclein if they're healthy. This suggests most Parkinson's genetic risk factors may not be causing initial misfolding. Instead, they may be determining what happens afterward, such as whether the pathology progresses to clinical disease. LRRK2 mutations support this model. About 33% of LRRK2 related Parkinson's patients are SAA-negative compared to only 7% in sporadic disease. This means many people with LRRK2 mutations develop Parkinson's without the typical alpha-synuclein pathology. LRRK2 mutations also show varied pathology. Sometimes alpha-synuclein, sometimes tau, sometimes neither. This suggests LRRK2 may modulate responses to different initiating events rather than directly causing protein misfolding. What does this mean for us as clinicians? Asymptomatic SAA-positive individuals could represent a window for intervention. If we can understand what protects them from converting to disease or what triggers that conversion, we could enable earlier identification of at risk individuals and potentially intervene before symptoms develop. The authors call for large scale studies using SAAs in older populations, combined with genetic analysis and longitudinal follow-up. By integrating pathological biomarkers with genetic and environmental data, we can better understand the temporal sequence of events in development of Parkinson's. This approach could fundamentally change how we think about disease prevention and early intervention, potentially allowing us to identify at risk individuals before symptoms appear and develop targeted prevention strategies. That's your neurology minute for today. Keep exploring, and we'll see you next time. If you want to read more, please find the paper by Cornelis Blauwendraat et al titled The Temporal Order of Genetic, Environmental and Pathological Risk Factors in Parkinson's Disease: Paving the Way to Prevention, published online in September 2025 in Lancet Neurology.