Prof Michael Okun: My Take

The academic Parkinson's and movement disorders workforce is at a crossroads. Are we under threat of losing our best clinician-researchers? What does academic medicine mean? Academic medicine refers to health care providers who care for patients while also teaching the next generation and conducting research to improve the future of medicine. Mahajan and colleagues describe in a new paper in Movement Disorders Clinical Practice the current state of the academic movement disorders workforce in the United States and the challenges threatening its future. Key points: - More than half of surveyed academic movement disorders neurologists reported considering leaving their current position or academic medicine during the previous year. - The leading reasons included pressure to see more patients, inadequate salary, poor clinical support and loss of professional autonomy. - The author argues that improving retention will require reducing administrative burden, strengthening research support, investing in faculty development and restoring balance to the missions of patient care, education and research. My take: This paper resonated deeply w/ me. Academic movement disorders has never simply been about generating revenue (term RVUs commonly used). It is about caring for the most complex patients, training future leaders and discovering tomorrow's treatments. If we lose sight of that mission, everyone loses, especially the folks living w/ Parkinson's disease, dystonia, Huntington's disease, Tourette syndrome and many other neurological disorders. Burnout is frequently a systems problem, not an individual problem. Protecting academic medicine means protecting the future of neurology. Here are 4 points that resonated w/ me: 1- We must value teaching, mentoring and discovery just as much as clinical productivity. 2- Administrative burden and inadequate support steal time from patients, research and education. 3- Recruiting and retaining talented academic neurologists will require meaningful investment in wellness, autonomy and career development. 4- As the Parkinson pandemic grows, we cannot afford to lose the next generation of movement disorders specialists.

Can we predict Alzheimer's disease by measuring when biomarkers change, instead of simply measuring how much is there? Biomarkers are measurable biological signals, such as blood proteins or brain imaging findings, that help track disease processes before symptoms become obvious. Pelkmans, Bikou, and Salvadó describe in a new Brain commentary how modeling the timing of biomarker changes may move us closer to predicting an individual's risk of future cognitive decline rather than simply describing where they are today. Key points: - The commentary highlights new work showing that the timing of changes in plasma p-tau217, amyloid PET, tau PET, and cognition may be more informative than simply comparing biomarker levels at one point in time. - Strong coupling between biomarker timing and cognitive decline was observed in the Alzheimer's Disease Neuroimaging Initiative (ADNI), while weaker coupling in the population-based Mayo Clinic Study of Aging suggests aging is influenced by multiple interacting pathologies. - The authors argue that future prediction models should integrate Alzheimer's biomarkers w/ vascular disease, inflammation, α-synuclein, TDP-43, resilience, and other biological factors to better predict who will experience cognitive decline. My take: This commentary captures an important shift in Alzheimer's disease research. We are moving beyond asking whether a biomarker is abnormal and beginning to ask when it becomes abnormal. Timing may ultimately prove just as important as the biomarker itself. The future will likely require integrating multiple biological pathways rather than relying on a single test to predict cognitive decline. Here are 3 points that resonated w/ me: 1- Alzheimer's disease does not unfold the same way in every person, and understanding individual timing may improve prediction and personalize care. 2- Blood biomarkers such as plasma p-tau217 continue to emerge as powerful tools that may help identify disease years before symptoms become disabling. 3- Aging brains frequently contain more than one disease process, so cognitive decline cannot always be explained by Alzheimer's pathology alone.

Best gift ever from our graduating fellow Dr. Tejas Mehta who will be heading to University of Missouri to join another former Fixel fellow Dr. Shah to grow a highly impactful multidisciplinary clinical-research Parkinson's and movement disorders program. Go Tigers!

One of the discussions that really resonated with me at the Aspen Movement Disorders Course centered on a deceptively simple question: is "palatal myoclonus" really myoclonus? Joe Jankovic made the case that myorhythmia may actually be a more accurate term, as the movements are slow and remarkably rhythmic, yet the palate lacks the agonist-antagonist muscle pairs that define classic tremor. Mark Hallett and I in past Aspen course years found ourselves playfully pondering whether a Yiddish-inspired description such as "tremor-ish" might better capture the clinical reality than forcing these movements into imperfect categories. The conversation also highlighted how our understanding continues to evolve. What was once broadly labeled palatal myoclonus is now recognized to include several distinct entities, including primary palatal hyperkinesia with ear clicking, which is increasingly appreciated as often representing a functional movement disorder, alongside multiple forms of secondary palatal movement disorders resulting from structural lesions. These are the kinds of conversations that make Aspen special. They remind us that movement disorders are rarely static, and that thoughtful debate over terminology often reflects much deeper advances in understanding biology, diagnosis, and ultimately patient care.

One of the discussions that really resonated with me at the Aspen Movement Disorders Course was why some people with Wilson's disease have a much more difficult clinical course than others, even when they receive appropriate treatment. Susan Fox shared a memorable case of hers highlighting white matter changes on MRI, which sparked an important conversation about emerging evidence that genetics may help explain these differences. Early studies suggest that patients carrying loss-of-function variants in the ATP7B gene may experience worse transplant-free survival despite chelation therapy, raising the possibility that genotype may one day help guide prognosis, counseling, and perhaps even individualized treatment strategies. We are still in the early chapters of this story, but it is an important reminder that Wilson's disease is not a single disease with a single trajectory. Understanding the biology underlying these genetic differences may ultimately help explain why some patients respond remarkably well while others face a much more challenging journey.

One of the most interesting discussions at the Aspen Movement Course centered on persons with a long-standing unilateral rest tremor, sometimes accompanied by a postural tremor, but without clear bradykinesia. Years ago, Professor David Brooks and colleagues used 18F-dopa PET imaging to show that the vast majority of these individuals already had evidence of nigrostriatal dopaminergic degeneration, supporting a diagnosis of Parkinson's disease rather than essential tremor or a functional movement disorder. Subsequent DaT imaging studies and careful long-term clinical follow-up have repeatedly confirmed these early observations. Another important pearl is that younger-onset Parkinson's disease may present with a fine, rapid tremor that can even appear myoclonic at first glance, creating additional diagnostic challenges. The lesson is simple: not every isolated tremor is essential tremor, and careful longitudinal examination, supported when appropriate by biomarkers, remains one of the most powerful tools in arriving at the correct diagnosis.

One of the most practical discussions at the 36th Annual Aspen Movement Course centered on a terrific new JAMA review of restless legs syndrome (RLS). What really resonated with our faculty was the simplicity of the diagnostic and treatment flow charts, which translate a complex disorder into a stepwise approach clinicians can use immediately. The review reinforces starting with the essential diagnostic criteria while carefully considering common mimics, risk factors, and associated conditions, then emphasizes checking serum ferritin and transferrin saturation early because iron deficiency remains one of the most treatable contributors to RLS. We especially liked the updated treatment algorithm: replenish iron first when stores are low, transition to gabapentinoids (gabapentin, gabapentin enacarbil, or pregabalin) as preferred first-line therapy for patients with bothersome, frequent symptoms, reserve as-needed levodopa or dopamine agonists for those with only infrequent symptoms, and thoughtfully escalate to combination strategies, low-dose opioids, peroneal nerve stimulation, or carefully monitored dopamine agonists for refractory disease. If you use an agonist be ready for augmentation. This paper provides an outstanding example of how a well-designed clinical flow chart can help clinicians deliver evidence-based, individualized care while minimizing complications such as augmentation.

One of the best discussions at the Aspen course was the use of the term parkinsonism. Parkinsonism is a broad clinical syndrome characterized by bradykinesia possibly accompanied by rest tremor, rigidity, and/or postural instability, regardless of the underlying cause. Levodopa-responsive parkinsonism refers to patients whose symptoms improve substantially with levodopa therapy, most commonly those with Parkinson's disease, though some other conditions may also show partial responsiveness. Most experts don't use the word parkinsonism to describe the common levodopa responsive condition. Atypical parkinsonism describes a group of neurodegenerative disorders, such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB), which often have additional neurological features, progress more rapidly, and typically exhibit a limited or short-lived response to levodopa. In contrast, secondary parkinsonism results from an identifiable external or acquired cause, including dopamine-blocking medications, vascular disease, toxins, normal pressure hydrocephalus, brain injury, infections, or metabolic disorders, and treatment focuses on addressing the underlying cause rather than the neurodegenerative process itself. While these categories may overlap clinically, distinguishing among them is essential because prognosis, treatment, and expected response to dopaminergic therapy differ substantially.

One topic that generated lively discussion at the Aspen Movement Disorders Course was whether the next generation of wearable, AI-driven closed-loop devices might finally begin to fulfill the promise of treating tremor. Many experts remain appropriately skeptical because earlier wearable technologies often failed to deliver meaningful, sustained clinical benefit. However, the randomized JAMA Neurology trial by Ondo and colleagues offers an intriguing glimpse of what may be different this time. Their transcutaneous peripheral nerve stimulation (TPNS) system continuously adapts stimulation to the person's own tremor physiology, and the study demonstrated meaningful improvements in activities of daily living that became more pronounced over 90 days compared with sham treatment. While this is not a cure and longer-term studies are still needed, it represents an important shift from "always on" stimulation toward intelligent, personalized, closed-loop therapy. Time will ultimately judge whether this and other AI-enabled wearable systems become part of routine tremor care, but the field finally appears to be moving beyond simple gadgets toward data-driven neuromodulation that learns, adapts, and may improve quality of life.

What really resonated with me during our discussions at the 36th Annual Aspen Movement Course was the application of the Gartner Hype Cycle to stem cell therapies for Parkinson's disease. The excitement surrounding several new clinical studies is real, and it should be. We are witnessing remarkable scientific advances and, for the first time, there is growing evidence that transplanted dopaminergic cells can survive, integrate, and improve motor symptoms in some people. But the Gartner curve reminds us that every transformative technology passes through predictable stages: an initial breakthrough, a Peak of Inflated Expectations, a Trough of Disillusionment as challenges become apparent, and eventually a Slope of Enlightenment leading to a Plateau of Productivity where therapies find their appropriate place in clinical care. I believe we are somewhere near that peak today. The promise is enormous, but so are the challenges, including graft survival, immune suppression, manufacturing, cost, scalability, and long-term safety. Most importantly, we must remember what these therapies are designed to do. They primarily restore dopamine to the nigrostriatal motor system, meaning they have the greatest potential to improve symptoms such as slowness, stiffness, and tremor. They are unlikely, at least in their current form, to halt the broader neurodegenerative process or fully address the gait impairment, balance problems, speech changes, swallowing difficulties, cognitive decline, or other non-motor features that often emerge as Parkinson's progresses. The future is bright, but our responsibility is to balance hope with honesty. That is how we move from hype to meaningful progress for the people we serve.

The Fixel UF fellows are awesome and it was an honor having all of our senior movement fellows and our neurosurgery fellow attend all 5 days of the Aspen Movement Course. Yes, they learned and yes they had some fun too.

One of the most thought-provoking ideas from Joe Jankovic's presentation in Aspen this morning was the concept that many movements do not fit neatly into the categories of either "voluntary" or "involuntary." Instead, there is a fascinating gray zone of semi-voluntary movements, where conditions such as tics, functional movement disorders, stereotypies, compulsions, perseveration, and utilization behaviors exist along a spectrum. Tics, in particular, often come with a premonitory urge that can be temporarily suppressed, but suppression comes at a cost and the movement eventually emerges. This framework resonated deeply with me because it provides a more accurate and compassionate way to think about these disorders. As we continue to educate the public, it is especially important in an era when celebrities like Billie Eilish have been unfairly accused of "faking" their tics. The science tells a much more nuanced story. Tics are neither simply voluntary nor simply involuntary; they occupy a unique space in between. Appreciating this gray zone not only advances our understanding of the neurobiology of movement disorders but also helps replace skepticism with empathy for the millions of people living with these conditions.