Written by Matthew J. Barrett, an associate professor of neurology and a movement disorder specialist at Virginia Commonwealth University in Richmond, Virginia.
I often repeat her presentation to medical students: my only patient ever to fall walking into a clinic visit had progressive supranuclear palsy (PSP).
Her impaired postural reflexes were no match for a set of brick steps. Perhaps she didn't notice the ramp, or didn't appreciate how rapidly her balance had deteriorated. Fortunately, her injuries that day were only minor. As is often the case with PSP, that would not always be the case.
In June 1963, neurologist Dr James Richardson reported eight cases of what would come to be called PSP at the American Neurological Association meeting. A year later, he and his neurologist colleagues John Steele and Jerzy Olszewski first described the disease in the literature.
The classical PSP syndrome—called "Richardson syndrome"—is characterized by poor balance, vertical gaze abnormalities, executive dysfunction, and speech impairment. Falls are frequent, and often injurious. Patients can also present with impaired facial expressions, changes in mood, and waning dexterity. Given its rarity and diffuse array of symptoms, PSP is often misdiagnosed as Parkinson disease, or even Alzheimer disease.
The challenge for clinicians is that PSP is an incredibly varied condition, with not all patients presenting the same way. Beyond the classic symptoms, they may also experience a freezing gait, or corticobasal syndrome, an atypical form of parkinsonism. PSP pathology can even present with predominant language impairment, known as "primary progressive aphasia."
I'll call my patient Mrs X. Once she was in the exam room, her abnormal eye movements, changes in speech, and reduced facial expressions confirmed the diagnosis suggested by her falls. She showed classic signs of this little known neurodegenerative disease.
Not surprisingly, she and her husband had never heard of PSP. Most medical students will never learn about it unless they encounter it during their neurology rotation. I reviewed the prognosis and treatment options and introduced an ongoing clinical trial, in which she ultimately enrolled.
Over many visits, I learned about her grandson, whose soccer games she often attended with her husband. We bantered about the local college basketball team. As her disease progressed, I learned how devoted her husband was to her and how appreciative she was for his care. Given the grievous combination of physical and mental impairment that comes with PSP, having support from friends and family can be an essential part of care.
PSP is rare, but not as rare as once thought. The disorder occurs in about 5 in 100,000 persons, a prevalence similar to that of amyotrophic lateral sclerosis. However, given that clinicians have only recently come to appreciate the disease, it is probably underdiagnosed, or misdiagnosed as another movement disorder.
Medications rarely help the motor symptoms of PSP. Falls intensify; speech and swallowing worsen....
The early symptoms of PSP can mimic those of Parkinson disease, which is much more common. The lack of response to medications used for Parkinson disease—namely, levodopa—and PSP's more rapid progression can lead to the diagnosis being revised. Singer Linda Ronstadt recently publicly shared that she has PSP, which negatively affected her ability to sing. It was first reported that she had Parkinson disease.
The cause of PSP is unknown. Pathologic reports show that the brains of people with the condition have accumulations of tau protein, a finding also seen in other "tauopathies," such as Alzheimer disease and chronic traumatic encephalopathy. And although variants in the gene coding for tau have been associated with PSP, the condition rarely runs in families. It's for the most part a sporadic condition.
Unlike in Parkinson disease, medications rarely help the motor symptoms of PSP. Physical, occupational, and speech therapy, on the other hand, can be useful, encouraging patients to develop compensatory mechanisms and strategies to reduce falls and improve speech and swallowing. But ultimately, falls intensify; speech and swallowing worsen; and independence is eventually lost.
As is the case with all neurodegenerative diseases, the major unmet need in PSP is a treatment that stops or slows the disorder—in other words, a disease-modifying therapy. A number of ongoing treatment trials are investigating monoclonal antibodies directed at tau. Many believe that the accumulation of abnormal tau is pathogenic in PSP, and that clearing it from the extracellular space will disrupt the spread of further pathology. Time will tell whether this strategy pans out.
A silver lining to the rapid decline seen in patients with PSP is that changes in neurologic functioning are easily measured. As more and more therapies are tested, any disease-modifying effect should be evident relatively quickly, which is not the case in many other neurodegenerative disorders, such as Alzheimer disease.
It is a helpless feeling to watch patients worsen, yet have no way to stop their disease or even improve their symptoms. Participating in clinical trials is one way for patients and providers to combat the helplessness. Providing compassionate, multidisciplinary care, when that is all that is available, is another.
Watching Mrs X decline over time, especially her increasingly impaired ability to walk safely, only confirmed for me the importance of developing treatments to lessen the burden of PSP.
