Prof Michael Okun: My Take

When most people think of Huntington's disease, they picture chorea, the involuntary, dance-like movements that have become the hallmark of this condition. However, Huntington's is not simply a disease of too much movement. It is also a disease of too little movement, including bradykinesia (slowness), rigidity, impaired walking and difficulty initiating movements. This important new analysis from the PROOF-HD trial, published in Neurology, reminds us that suppressing chorea by reducing dopamine signaling may come at a price. Investigators examined patients in the placebo arm of the trial and found that those receiving antidopaminergic medications experienced greater worsening in functional capacity, cognition, overall motor performance and composite Huntington's disease scores compared with those not receiving these medications. Although chorea improved, other motor features, including bradykinesia, tended to worsen. Importantly, the associations were observed with both VMAT2 inhibitors, which reduce dopamine availability, and antipsychotics, which block dopamine receptors, with higher medication exposure also associated with greater decline. These findings do not prove that the drugs accelerate the underlying disease, since patients requiring treatment may already have more severe symptoms. My bottom line for clinicians is that treating Huntington's disease should never be reduced to treating chorea. The choice of medication, mechanism of dopamine suppression and dose all matter. We should use the lowest effective dose, reassess the need for treatment, and carefully monitor walking, swallowing, cognition, bradykinesia and everyday function. Our goal should not be simply to make the dancing stop. It should be to help the person with Huntington's disease function better and live better. https://www.neurology.org/doi/pdf/10.1212/WNL.0000000000218627

What resonates most with me about this important new study by Gallini and colleagues in JAMA Network Open is that even when we account for scientific bias, the burden of chronic traumatic encephalopathy (CTE) among former NFL players remains alarmingly high. Previous brain donation studies suggested that more than 90% of former NFL players had CTE, but critics correctly pointed out that individuals with neurological symptoms were more likely to donate their brains. In this study of 2,362 deceased former NFL players, researchers addressed this selection bias and estimated that 74.5% had CTE pathology at death, with a conservative analysis still suggesting nearly 64%. They also estimated that 27.2% had experienced dementia during life, although this does not establish that CTE caused their dementia. These findings do not mean that three out of four living NFL players have CTE, nor that everyone with CTE pathology develops dementia. However, they raise serious questions about the long-term consequences of repetitive head impacts. As a neurologist, I believe we must move beyond debating whether the problem exists and focus more urgently on prevention, safer sports participation, better biomarkers, and protecting young developing brains. My biggest takeaway is that we should not have to wait until someone dies to understand what years of repetitive head impacts have done to their brain. The future of CTE research must be about protecting the living, not simply counting the damage in the dead. https://cutt.ly/JyUWjDur

Not all recipes are created equal, especially when you're living with Parkinson's disease! In this short video, Dr. Michael Okun, neurologist and Parkinson's expert, introduces The Parkinson's Plate and shares how to approach choosing recipes that support healthier eating while living with Parkinson's. Learn how to think about food choices and make nutrition a practical part of your Parkinson's care plan. Eating well doesn't have to be complicated, and small choices in the kitchen can make a meaningful difference. The goal isn't a perfect diet. It's finding foods and recipes that work for you. https://www.youtube.com/shorts/7bAnewSmM9E

As a movement disorders neurologist, I have always been fascinated by the possibility that some of the most influential figures in American history lived with the same neurological conditions we treat in our clinics today. Two particularly compelling examples are John Adams, our second president, and his second cousin Samuel Adams, a leader of the American Revolution whose name now appears on one of America's most recognizable beer labels. In two remarkable historical investigations published in Neurology in 2001 and Movement Disorders in 2005, neurologist Elan Louis and his colleague Patricia Kavanagh examined original letters, diaries, and handwriting samples, uncovering persuasive evidence that both men lived with essential tremor. Samuel's shaking began by his early forties, affected his hands, head, and voice, and progressively interfered with his ability to write. In his signature on the Declaration of Independence, the letter S shows subtle tremulousness, particularly when compared with John's steadier signature immediately below it. By age seventy-one, Samuel could no longer write his own correspondence and relied on others to take dictation. His daughter and grandchildren also reportedly developed tremor, strengthening the case for a familial disorder. John Adams had a somewhat different course. His tremor was detectable in handwriting samples as early as age twenty-five, and over the ensuing decades his letters became increasingly difficult to read. In his later years, he described his hands shaking so severely that writing became extraordinarily difficult, and observers reported that he sometimes needed assistance eating. Although the researchers considered whether John might also have developed parkinsonism late in life, they concluded that essential tremor was the most likely diagnosis. What resonates with me is how much these historical documents reveal about the human experience of a disease that is too often dismissed as a minor inconvenience. These were men who helped shape a nation, yet something as ordinary as holding a pen or bringing food to the mouth became a daily struggle. And what about the Samuel Adams beer label? No evidence there.

What resonates most with me about this fascinating new study in JAMA Psychiatry is the possibility that psilocybin may do more than improve mood in Parkinson’s disease; it may also influence biological pathways involved in neurodegeneration. In this small, nonrandomized pilot study, 12 individuals with Parkinson’s and mood dysfunction received two doses of psilocybin, and blood samples from nine participants revealed intriguing changes in markers of inflammation and mitochondrial stress. The researchers observed significant reductions in a composite inflammatory index that persisted 30 days after treatment, along with short-term reductions in GDF-15, a marker associated with mitochondrial stress. These findings are especially interesting because inflammation and mitochondrial dysfunction are two important biological processes implicated in Parkinson’s disease. However, we must be cautious. This was a very small study without a placebo group, and changes in blood biomarkers do not establish that psilocybin protects dopamine neurons, slows disease progression, or modifies Parkinson’s pathology. What excites me most is not the psychedelic itself, but the possibility that we may be uncovering new connections between mood, inflammation, mitochondrial health, and neurodegeneration. We need larger randomized trials, longer follow-up, and direct measures of brain biology before drawing conclusions about treatment. The real question is whether we can move beyond treating symptoms and begin targeting the biological processes driving Parkinson’s disease. This study opens an interesting door, but we are still a long way from knowing what lies on the other side. https://cutt.ly/DyUWvMEF

Exciting things are happening at the Norman Fixel Institute for Neurological Diseases at the University of Florida! Our November newsletter highlights the remarkable progress our teams are making in research, patient care, innovation, and education. From expanding our research and technology innovation spaces and advancing deep brain stimulation and Parkinson’s prevention to earning national recognition as a Comprehensive Care Center for multiple sclerosis, our faculty and staff continue to push the boundaries of what is possible in neurological care. We are also celebrating extraordinary achievements across our Fixel family and recognizing the persons with disease, families, and care partners who inspire our work every day. At Fixel, we believe that the person with disease is the sun, and everything we do should revolve around improving their lives. We invite you to be part of our journey! Follow us on social media fixelinstitute and subscribe to our FREE monthly newsletter to discover the latest breakthroughs, inspiring stories, and exciting developments from our team. Read our November newsletter here and help us spread the word about our mission to prevent the preventable and treat the treatable! Our amazing editor is Grace Huff. https://fixel.ufhealth.org/newsletter/fixel-internal-newsletter-november-2026/

Is the Parkinson's pandemic growing, or are we confusing more cases w/ more risk? Incidence refers to the number of new cases of a disease developing over a specific period. Prevalence refers to the total number of folks living w/ that disease. These are two very different measures, and understanding the difference matters. Daniele Urso and colleagues describe in a new viewpoint paper in Movement Disorders why the worldwide burden of Parkinson's disease continues to grow, even though the risk of developing Parkinson's may not be increasing in many countries. Key points: - Population-based studies from several countries suggest that age-adjusted Parkinson's incidence has remained stable or declined, despite a growing number of folks living w/ the disease. - Population aging, longer survival and improved recognition of Parkinson's can increase prevalence even when the underlying risk of developing the disease remains unchanged. - Most available incidence studies come from high-income countries, leaving major gaps in our understanding of trends in low- and middle-income countries, where approximately 85% of the world's population lives. My take: This is an important and provocative paper, particularly because I was one of the authors who helped introduce the concept of the Parkinson pandemic. What resonates w/ me is that we must distinguish the growing number of folks living w/ Parkinson's from the changing risk of developing it. Both matter, however they answer different questions. The authors are correct to challenge us to improve our measurements. I would caution against interpreting these findings as evidence that environmental risks are disappearing or that prevention is becoming less urgent. Pesticides, solvents, air pollution and other potentially modifiable exposures remain important areas of investigation. The absence of a consistent increase in age-adjusted incidence in selected countries does not mean we have solved the Parkinson's problem. It means we need better data, particularly from countries that have historically been underrepresented. The decline or leveling in some European countries is important given they have been aggressive in banning.

Neuromelanin-sensitive MRI has made great strides. What resonates most with me about this important 2026 Movement Disorders systematic review and meta-analysis by Akande and colleagues is the possibility that we are moving closer to actually visualizing and measuring the biological progression of Parkinson’s disease, rather than relying primarily on clinical symptoms. Across 39 studies involving 1,983 people with Parkinson’s, neuromelanin-sensitive MRI demonstrated meaningful associations between loss of signal in the substantia nigra and worsening motor symptoms, longer disease duration, and more advanced disease stages. Particularly compelling was the distinction between the substantia nigra, which correlated predominantly with motor disability, and the locus coeruleus, which was more closely associated with cognition, mood, sleep, and autonomic dysfunction. This reminds us that Parkinson’s is much more than a dopamine deficiency or a movement disorder. Four longitudinal studies also suggested that neuromelanin MRI measures may decline over time, raising the exciting possibility of tracking neurodegeneration and evaluating future disease-modifying therapies. We must remain cautious: imaging protocols require standardization, and these measures are not yet validated progression biomarkers. The real opportunity is to move beyond measuring how a person with Parkinson’s performs on an examination toward measuring what is actually happening inside the brain. That could fundamentally change how we design clinical trials and ultimately deliver personalized Parkinson’s care. https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.70588

Can the vegetables you choose at the grocery store make a difference in Parkinson’s disease? Nutrition expert Emily Truscott and I explore the produce aisle and discuss practical ways to make healthier food choices. How about the question of buying chopped or not chopped? Learn why vegetables are an important part of a balanced Parkinson’s diet, how to think about nutrition when shopping, and why simple everyday decisions can support overall health and well-being. This is Part 3 of our Parkinson’s grocery shopping series, designed to help people with Parkinson’s and their families turn nutrition advice into practical action, one grocery aisle at a time. https://youtube.com/shorts/eZ1ygVvYfhU?feature=share

Could deep brain stimulation change not only brain circuits, but also the genes that help those circuits communicate? This may be an important next chapter in deep brain stimulation (DBS). Gene expression refers to how brain cells turn specific genes on or off to influence their function. Neuronal assemblies are groups of brain cells that fire together to process information. Haley Moore and colleagues describe in a new paper in Nature how electrical stimulation of human brain tissue can strengthen coordinated neuronal activity and activate specific genetic programs involved in synaptic plasticity. The implications for the future of DBS are exciting. Key points: - Electrical stimulation strengthened neuronal assemblies, increasing coordinated firing and changing how neurons participated in functional brain networks. - Stimulation produced cell-type-specific changes in gene expression, particularly in excitatory neurons, involving genes such as FOS, EGR1, BDNF and HOMER1 that are linked to neuronal activity and synaptic function. - By combining electrical recordings and single-cell genomic analyses, the researchers connected stimulation-induced changes in brain activity to molecular pathways and identified related signatures following stimulation in living human brains. My take: This study resonates deeply w/ me because it challenges us to think beyond the traditional view that DBS works simply by turning abnormal brain circuits on or off. What if stimulation is also changing the biological machinery that determines how brain cells communicate, reorganize and adapt? We have long suspected that plasticity contributes to DBS outcomes, however directly linking stimulation, neuronal assemblies and gene regulation in human tissue represents an important advance. Could we eventually use molecular signatures to select better targets, personalize stimulation parameters and potentially promote more durable therapeutic effects? This is especially relevant as we move toward adaptive DBS, where stimulation responds to changing brain activity. We should remember that this was primarily a mechanistic study of human temporal cortex, not a clinical trial.

Join our UF/IFAS Food-as-Medicine Field Day virtually on Wednesday, October 28, at 9:00 a.m. EST No registration required—join via Zoom below! Zoom Meeting Details Meeting ID: 675 182 123 Passcode: 654321 Join link: https://ufl.zoom.us/j/675182123?pwd=dDJobUQ0cHl3TkpuMTVheUhON1p4dz09

Genetic testing in Parkinson’s: We have the technology, but do we have the expertise? What resonates with me about this important new Movement Disorders paper by Alessio Di Fonzo and Francesca Magrinelli is their reminder that genetic testing is advancing faster than our ability to interpret the results and explain what they mean to patients and families. We can now identify genetic changes associated with Parkinson’s disease, dystonia, ataxia, and other movement disorders, sometimes opening doors to targeted treatments and clinical trials. But finding a genetic variant is not the same as understanding its significance. For example, carrying a GBA1 or LRRK2 variant does not necessarily mean someone will develop Parkinson’s disease, and a result that is misunderstood can create unnecessary anxiety or lead to inappropriate medical decisions. The authors provide compelling clinical examples in which expert interpretation changed a diagnosis, identified a treatable condition, or uncovered an important risk for family members. I particularly agree with their call to train more neurologists in neurogenetics, integrate genetic counselors into our clinical teams, and create dedicated positions for specialists who can translate complex genetic findings into meaningful care. As we move toward precision medicine, I worry that we are investing heavily in sequencing technology without making equivalent investments in the people who must interpret and communicate the results. My takeaway is simple: A genetic test should never be the end of the conversation. It should be the beginning of better-informed, more personalized care. https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.70594