The year 2019 turned out to be a memorable year for singing icon Linda Ronstadt. The most successful female singer of the 1970s became one of the five recipients of the Kennedy Center Honors. In addition, Ronstadt is the subject of a new CNN Films , "Linda Ronstadt: The Sound of My Voice."
But these accolades are bittersweet. In 2000, she began to have difficulty singing. As CNN's Anderson Cooper, "I couldn't hear the top end of my voice. I couldn't hear the part that I used to get in tune. My throat would clutch up. It would just be like I had a cramp or something." She was initially diagnosed as having Parkinson's disease, and by 2009 she had to retire from singing. A re-evaluation in late 2019 changed her diagnosis to the rare brain disorder, progressive supranuclear palsy (PSP).
Ronstadt told Cooper that her illness has had a major impact on her life: "Everything becomes a challenge. Brushing your teeth, taking a shower... I find creative new ways to do things. I'm like a toddler. Eating is hard.... I've had to relearn how to eat. You could carve a new brain map if you're patient and willing to do that, but it's hard."
When asked by Cooper what advice she would give to "people facing obstacles, or facing Parkinson's -- maybe some people who have just received diagnoses," she replied, without hesitation: "Acceptance."
What is Progressive Supranuclear Palsy?
PSP is an uncommon brain disorder that affects movement, gait and balance, speech, swallowing, vision, mood and behavior, and thinking. The disease results from damage to nerve cells in the brain. The disease damages certain parts of the brain above nerve cell clusters called nuclei (supranuclear). These nuclei particularly control eye movements. One of the classic signs of the disease is an inability to aim and move the eyes properly, which individuals may experience as blurring of vision.
Estimates vary, but only about three to six in every 100,000 people worldwide, or approximately 20,000 Americans, have PSP -- making it much less common than Parkinson's disease (an estimated 50,000 Americans are diagnosed each year). Symptoms of PSP begin on average after age 60 but may occur earlier. Men are affected more often than women.
What are the symptoms?
The pattern of signs and symptoms can be quite different from person to person, but usually fall into one of four patterns:
- Richardson Syndrome: Named after one of the doctors who identified PSP as a distinct entity in 1963. It consists of "gait and balance impairment, a wide-eyed staring facial expression, abnormal speech, memory and cognitive impairment, and a slowing or loss of voluntary eye movement, particularly in the downward direction (supranuclear ophthalmoplegia)," according to the advocacy and support group .
- Atypical Parkinsonism: Present with slowness with muscle rigidity and occasional tremor. They may initially respond to levodopa.
- Corticobasal syndrome (CBS): These patients present with bizarre rigidity and dystonia. The neurodegeneration in CBS is markedly asymmetric, with symptoms starting on one side of the body and remaining worse on that side.
- Akinesia and gait freeing: These patients have hesitant initiation of gait and a tendency to freeze when turning or crossing a threshold (such as a doorway).
As the disease progresses, most people will begin to develop a blurring of vision and problems controlling eye movement. In fact, eye problems, in particular slowness of eye movements, usually offer the first definitive clue that PSP is the proper diagnosis. Individuals affected by PSP especially have trouble voluntarily shifting their gaze vertically (i.e., downward and/or upward) and also can have trouble controlling their eyelids. This can lead to a need to move the head to look in different directions, involuntary closing of the eyes, prolonged or infrequent blinking, or difficulty in opening the eyes. Another common visual problem is an inability to maintain eye contact during a conversation. This can give the mistaken impression that the person is hostile or uninterested.
People with PSP often show alterations of mood and behavior, including depression and apathy. Some show changes in judgment, insight, and problem-solving, and may have difficulty finding words. They may lose interest in ordinary pleasurable activities or show increased irritability and forgetfulness. Individuals may suddenly laugh or cry for no apparent reason, they may be apathetic, or they may have occasional angry outbursts, also for no apparent reason. Speech usually becomes slower and slurred and swallowing solid foods or liquids can be difficult. Other symptoms include slowed movement, monotone speech, and a mask-like facial expression. Since many symptoms of PSP are also seen in individuals with Parkinson's disease, particularly early in the disorder, PSP is often misdiagnosed as Parkinson's disease.
How is PSP different from Parkinson's disease?
Both PSP and Parkinson's disease cause stiffness, movement difficulties, and clumsiness, but PSP is more rapidly progressive as compared to Parkinson's disease. People with PSP usually stand exceptionally straight or occasionally even tilt their heads backward (and tend to fall backward). This is termed "axial rigidity." Those with Parkinson's disease usually bend forward. Problems with speech and swallowing are much more common and severe in PSP than in Parkinson's disease, and tend to show up earlier in the course of the disease. Eye movements are abnormal in PSP but close to normal in Parkinson's disease.
Both diseases share other features: onset in late middle age, bradykinesia (slow movement), and rigidity of muscles. Tremor, very common in individuals with Parkinson's disease, is rare in PSP. Although individuals with Parkinson's disease markedly benefit from the drug levodopa, people with PSP respond minimally and only briefly to this drug. Also, people with PSP show accumulation of the protein tau in affected brain cells, while people with Parkinson's disease show accumulation of a different protein, called alpha-synuclein.
What causes PSP?
The exact cause of PSP is unknown. The symptoms of PSP are caused by a gradual deterioration of brain cells mainly in the brain stem. One of these areas, the substantia nigra, is also affected in Parkinson's disease, and damage to this region of the brain accounts in part for the motor symptoms that PSP and Parkinson's have in common.
The hallmark of the disease is the accumulation of abnormal deposits of the protein tau in nerve cells in the brain. The protein tau is associated with microtubules – structures that support a nerve cell's long processes, or axons, that transmit information to other nerve cells. The accumulation of tau puts PSP in the group of disorders called the tauopathies, which also includes other disorders such as Alzheimer's disease, corticobasal degeneration, and some forms of frontotemporal degeneration.
PSP is usually sporadic, occurring infrequently and without known cause; in very few cases the disease results from mutations in the MAPT gene, which then provides faulty instructions for making tau to the nerve cell. Recent research suggests that the disease is at least partially genetic, along with various environmental factors.
Is there any treatment?
There is currently no effective treatment for PSP, although scientists are searching for better ways to manage the disease. PSP symptoms usually do not respond to medications. Drugs prescribed to treat Parkinson's disease, such as ropinirole, rarely provide additional benefit. In some individuals the slowness, stiffness, and balance problems of PSP may respond to some degree to antiparkinsonian agents, such as levodopa, but the effect is usually minimal and short-lasting. Excessive eye closing can be treated with botulinum injections. Some antidepressant drugs may provide benefit beyond treating depression, such as pain relief and decreasing drooling.
Recent approaches to therapeutic development for PSP have focused primarily on the clearance of abnormally accumulated tau in the brain. One ongoing clinical trial will determine the safety and tolerability of a compound that prevents accumulation of tau in preclinical models. Other studies are exploring improved tau imaging agents that will be used to assess disease progression and improvement in response to treatment.
Clinical trials for patients with PSP can be found at .
Non-drug treatment for PSP can take many forms. Individuals frequently use weighted walking aids because of their tendency to fall backward. Bifocals or special glasses called prisms are sometimes prescribed for people with PSP to remedy the difficulty of looking down. Formal physical therapy is of no proven benefit in PSP, but certain exercises can be done to keep the joints limber.
What is the prognosis?
The disease gets progressively worse, with people becoming severely disabled within three to five years of onset. Affected individuals are predisposed to serious complications, such as pneumonia, choking, head injury, and fractures. The most common cause of death is pneumonia. With good attention to medical and nutritional needs, it is possible for individuals with PSP to live a decade or more after the first symptoms of the disease.
Sources: , .
Michele R. Berman, MD, and Mark S. Boguski, MD, PhD, are a wife and husband team of physicians who have trained and taught at some of the top medical schools in the country, including Harvard, Johns Hopkins, and Washington University in St. Louis. Their mission is both a journalistic and educational one: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.