Carl Kelly loved repairing clocks and tinkering with small engines, a hobby he pursued full-time after he retired from a 29-year career with Norfolk Southern Railway in 2003. Ten years later, Carl started having problems with his vision and fine motor skills. He would miss his mouth and drop food when eating and struggled with the tiny pieces of clocks and engines.

About a year after those symptoms appeared, Carl, who was 69 at the time, began falling—when he took out the garbage or even stood up from his chair—for no apparent reason. The falls were especially unsettling to the Air Force veteran, who was still very active, walking four miles a day. “At first, we thought the falls were related to his vision or age or an inner ear problem,” says his wife, Patricia. “But it was happening three or four times a day.”

The couple sought advice at a Veterans Affairs clinic near their home in Altoona, PA, where a physician suggested physical therapy and ordered an MRI scan but did not provide a diagnosis. Over the following months, Carl's symptoms worsened; he could no longer drive safely or walk unassisted. Increasingly worried, the Kellys met with a neurologist at the VA hospital in Pittsburgh. Carl had another MRI and was told that his brain showed signs of damage and nothing could be done about it. But he still had no firm diagnosis.

In the hopes of improving his balance and strength, Carl signed up for physical therapy at a clinic that specialized in treating people with neurologic conditions. After a while, the therapist said he thought Carl had Parkinson's disease and suggested that Carl and Patricia seek input from a neurologist who specialized in movement disorders like Parkinson's.

After a thorough examination and a review of his two previous MRI scans and medical records from the VA, the neurologist diagnosed Carl with progressive supranuclear palsy (PSP), a rare neurodegenerative condition that affects movement and cognitive function. The neurologist explained that the disease is similar to Parkinson's, but the progression is more rapid, and muscles eventually stiffen to the point that even swallowing is difficult.

“Everything the neurologist told us would happen—from the rapid progression to the five to seven years he had left—happened,” says Patricia. The COVID-19 pandemic prevented Patricia from being with Carl when he died in May 2020, five years after he was diagnosed.

In people with PSP, damage to the supranuclear areas of the brain—which lie outside nerve cell clusters called nuclei that control eye movements—can lead to vision problems such as double vision, trouble looking up and down (known as supranuclear vertical gaze palsy), and difficulty keeping the eyes open, says Alex Pantelyat, MD, FAAN, director of the Johns Hopkins Atypical Parkinsonism Center in Baltimore. Other symptoms include poor balance and impaired executive function, he says. In addition, apathy can be a neuropsychiatric consequence of PSP.

The cause of the condition is unknown, but experts believe it's related to the gradual buildup of abnormal tau protein in the nervous system. In normal brains, tau helps stabilize cell structure and transport materials, Dr. Pantelyat explains, but in PSP “it forms abnormal clumps, which the cells have trouble clearing.” This leads to loss of brain cells over time.

Difficult to Diagnose

Getting a diagnosis usually doesn't happen until the disease has progressed significantly, as the Kellys experienced. Lack of a definitive test is part of the problem, says Lawrence I. Golbe, MD, emeritus professor of neurology at Rutgers Robert Wood Johnson Medical School in New Brunswick, NJ, and chief clinical officer for CurePSP, a patient support and research organization in New York City.

To diagnose the disorder, neurologists rely on a set of criteria that includes repeated unprovoked falls within a three-year span, progressive gait freezing, and supranuclear vertical gaze palsy. They also order MRI or PET scans, which don't generally show findings suggestive of the disease until the middle or later stages, says Dr. Golbe, who notes that a definitive diagnosis can be established only through an autopsy. “Symptoms start to appear after just a few brain cells are lost,” he says. “But to see a clear difference between normal aging and PSP on an MRI, the loss of brain cells needs to be significant.”

Finding ways to diagnose PSP sooner is an important area of research, says Dr. Golbe. “Families need to know what they're dealing with. It's very stressful to go from doctor to doctor and undergo uncomfortable, sometimes expensive or invasive tests such as lumbar punctures, electromyography, electroencephalograms, cardiac stress testing, and various blood tests.” Furthermore, he says, researchers conducting clinical trials “want patients as early as possible in the course of the disease, because that's when treatment would be most useful to participants.”

PSP is considered an “atypical parkinsonian disorder,” says Dr. Pantelyat. That means it has similar symptoms to Parkinson's disease—such as tremor, muscle stiffness, slowness of movement, loss of fine motor control, stooped posture, and balance and walking problems—which is why PSP is difficult to distinguish from Parkinson's in the early stages. With PSP, balance problems tend to be more severe, vision is affected, and patients often experience urinary and gastrointestinal dysfunction that causes incontinence and constipation. Disturbed sleep and slurred or slow speech also are common symptoms.

Progression depends on the type of PSP, says Dr. Pantelyat. Some symptoms may stabilize while others suddenly worsen. PSP-Parkinsonism, a variant most similar to Parkinson's disease, progresses more slowly than one called Richardson's syndrome. “It is not unusual for patients with PSP-Parkinsonism to live for 10 or 12 years after diagnosis,” Dr. Pantelyat says.

Downward Trajectory

There is no cure or disease-modifying drug for PSP, so physicians generally focus on palliative care and maximizing quality of life, says Dr. Pantelyat. They may prescribe medications for symptoms such as urinary urgency, excessive saliva, dystonia (involuntary muscle contractions leading to abnormal positions/movements of various body parts), and insomnia, and recommend occupational and physical therapy to help patients retain as much function as possible. Seeing a specialist at a designated CurePSP Center of Care, even for a one-time consultation, may be worthwhile for clinical recommendations, education, and resources, says Jori Fleisher, MD, MSCE, FAAN, associate professor of neurologic sciences at Rush University in Chicago. To locate one, visit CurePSP Centers of Care.

Carl Kelly was prescribed levodopa (Sinemet), a drug often used to treat Parkinson's, but it wasn't very effective, and the dose had to be increased frequently, says Patricia. “Levodopa isn't useful for PSP unless it's PSP-Parkinsonism,” says Dr. Golbe. “And even then, it doesn't work nearly as well as it does for Parkinson's disease.” If PSP is misdiagnosed as Parkinson's and the patient is prescribed levodopa and doesn't respond, that may lead a doctor to suspect PSP, says Dr. Golbe, who contributed (as did Dr. Pantelyat) to a consensus paper in Frontiers in Neurology in July 2021 on best practices for managing PSP.

Two years after Carl began noticing symptoms, he moved to a long-term care facility, hopeful that a 30-day intensive physical therapy regimen would enable him to return home. “Once he got there, his condition started to slide,” says Patricia. “He worked very hard in his physical therapy sessions but did not improve.”

The couple decided it was best for him to remain in the facility, where his condition continued to worsen. Early on, Patricia was able to bring him home for short visits during the holidays or take him for long car rides. “I had a wheelchair at home, so once he was in the house, he was okay. He loved coming home, even if it was only for a few hours.”

Inevitably, though, Carl's ability to function faltered. He began choking when he ate and eventually needed help swallowing even pureed and liquid food. He became incontinent and was unable to stand to get in and out of his wheelchair and bed. He couldn't speak or communicate, which was extremely distressing. “I can't imagine how terrible it must have been for him to hear me talk and not be able to respond,” says Patricia.

She made flash cards of words that he could give a thumbs up or down to, but eventually he could no longer do that. “The man who loved to walk, talk, eat, dance, go on trips, go to the casinos, work on model trains, and fix just about anything, and who adored his family, was trapped in his body,” his wife says.

The Kellys' experience is typical for people with advanced PSP and part of why the condition is so heartbreaking. “The patient can understand—there's no problem with hearing or comprehension,” says Dr. Golbe. “The glitch is in processing combined with motor problems that make it difficult to move the mouth and throat to create speech.”

Caring for someone with PSP is mentally and physically challenging, and it is important for caregivers to watch their own health and to lean on a support network. “I'm a very strong person emotionally, but it really does take a toll on you,” says Patricia Kelly. “The VA reminded me that I had to take care of myself to be able to take care of Carl.”

While Carl was living in the extended-care facility, Patricia visited him every day except Monday. She also worked as a paralegal two days a week, relied on nearby family for support, and spent time with friends. Patient organizations also can be helpful. “They have good information and allow families to connect,” says Dr. Golbe. “It's amazing how many people continue to be involved [with patient organizations] so they can pass on what they've learned.”

Despite the bleak diagnosis, there is reason for hope, says Dr. Golbe. “Pharmaceutical companies and academic institutions are investing in many clinical trials, which may lead to drugs that can arrest the course of the disease even for those on the journey now.”

Progressive Supranuclear Palsy Research

Cryogenic electron microscopy is a promising tool for understanding and possibly treating progressive supranuclear palsy (PSP), says Lawrence I. Golbe, MD, emeritus professor of neurology at Rutgers Robert Wood Johnson Medical School in New Brunswick, NJ. “This microscope technique enables scientists to see individual molecules of problematic tau proteins by freezing them,” says Dr. Golbe. Seeing a frozen snapshot of the malformed protein may allow researchers to design drugs or antibodies that could be cloned to fit into and “repair” the irregular molecules.

In addition to this line of research, current clinical trials are exploring whether drugs that have been used to treat other conditions, such as HIV infection and spinal muscular atrophy, can reduce tau production, protect neurons, or prevent cell death in PSP, says Alex Pantelyat, MD, FAAN, director of the Johns Hopkins Atypical Parkinsonism Center in Baltimore.

For information about trials, visit ClinicalTrails.gov and type “progressive supranuclear palsy” in the search field. One trial that's currently recruiting participants involves the safety and efficacy of the Novartis Pharmaceuticals drug NIO752, which is an antisense oligonucleotide (ASO). In the study, the ASO—a small stretch of RNA that helps reduce problematic tau proteins—has to be injected directly into the spinal fluid, says Dr. Golbe. Novartis is seeking people between the ages of 45 and 75 who've been diagnosed with PSP within the past five years. The trial will take place at multiple sites across the United States. For more information, email or call 888-669-6682.

Resources for Progressive Supranuclear Palsy

• Progressive Supranuclear Palsy Overview 
• Cure PSP; 800-457-4777
• International Parkinson and Movement Disorder Society; 414-276-2145
• National Institute of Neurological Disorders and Stroke; 800-352-9424
• National Organization for Rare Disorders; 617-249-7300