Progressive supranuclear palsy (PSP)
Progressive supranuclear palsy (PSP)
Progressive supranuclear palsy (PSP) is a less well-known neurodegenerative brain condition which is sometimes misdiagnosed as Parkinson’s disease or Alzheimer’s disease (or other forms of dementia). Because of the similarity to some Parkinson's symptoms during the early stages of the disease, PSP is included in a group of diseases called Parkinson’s Plus Syndrome or Atypical Parkinsonism. However, PSP progresses much faster, causes more severe symptoms, responds very poorly to Parkinson's medication, and has a significantly reduced life expectancy.
PSP is a distinct brain disease that not only displays motor symptoms, but also causes some form of mental impairment, which explains why PSP is also one of a group of diseases under the umbrella of so-called frontotemporal dementias (FTD).
The term PSP stands for Progressive meaning ‘gradually getting worse’; Supranuclear meaning ‘above the nuclei of the brain’ (an area that controls eye movements among other things); and palsy meaning ‘paralysis’. PSP is also known as Steele-Richardson-Olszewski syndrome, from the family names of the three Canadian physicians who first described the condition in 1963.
PSP is linked to a pathological accumulation of a protein called tau in certain areas of the brain. The normal function of tau is to provide support for nerve cells (acting like a skeleton for a cell). In PSP, tau forms into clumps that are thought to damage nerve cells or nerve endings in the brain stem, basal ganglia and cerebral cortex areas. These areas control balance, thought processes, eye movements, speech and the ability to swallow.
PSP affects people over the age of 40, but symptoms begin on average after the age of 60. Men are affected slightly more often than women. PSP is also a rare disease (or orphan disease) affecting 5-6 people per 100,000.
What causes PSP?
The symptoms of PSP are caused by a gradual deterioration of brain cells in several areas of the brain. One of these areas, the substantia nigra, is also affected in Parkinson’s and damage to it accounts for the symptoms that PSP and Parkinson’s have in common. However, several other important areas that are affected in PSP are normal in Parkinson’s, and vice versa. And, under the microscope, the appearance of the damaged brain cells in PSP is quite different from those in Parkinson’s and instead resembles the degeneration seen in Alzheimer’s. In addition, the location of the damaged cells is quite different in PSP and Alzheimer's; PSP lacks amyloid plaques, which are deposits of waxy protein that are a hallmark of Alzheimer's. However, Alzheimer's and PSP share the misfolding of tau; hence, researchers hope that a potential therapy for PSP could also help Alzheimer's patients. Diseases that have misfolded tau as their common denominator are called tauopathies.
Unfortunately, no one yet knows what triggers the cells to degenerate in the first place. As mentioned above, there is an abnormal accumulation of the normal protein tau in the brain cells that are degenerating in PSP. These clumps of tau, once they reach a size that can be seen through a microscope, are called neurofibrillary tangles. We do not know whether the problem is that the tau is defective from the time of its manufacture, or if it is damaged later, or even if it remains normal but is produced in excess.
There is evidence that chemicals in the environment or diet may contribute to the cause of PSP. Surveys of PSP patients have shown, on average, lower educational attainment in people with PSP. This suggests that part of the cause of PSP may be certain occupational factors exposing people to different chemicals than are encountered by people with more sedentary or office-bound occupations. Another possibility is that people with less education tend to live in areas closer to industrial sites, some of which may generate toxins.
PSP is a sporadic disease and only very rarely runs in families. Fewer than one in 20 people with PSP knows of even one other family member with PSP and detailed neurological examination of relatives of people with PSP shows no more definite abnormalities than examination of relatives of healthy people. However, research does suggest that some people may be more genetically disposed to it.
Some of the most common symptoms of PSP are:
- poor balance and unsteady gait or walking
- frequent falls, generally backwards
- slowed movements
- rigidity or stiffness
- cramped writing
- blurred eyesight, gaze palsy (the inability to look up or down), slow blinking, difficulty in maintaining eye contact, tunnel vision and sensitivity to light
- soft, slow, and slurred speech
- difficulty in swallowing
- anxiety and/or depression, and loss of motivation
- personality change (loss of interest in ordinary pleasurable activities or increased irritability; difficulty resisting impulses; inappropriate behaviour)
- difficulty synthesizing several different ideas into a new idea or plan
- slowing of thought
- difficulty finding words (aphasia).
As the illness progresses, symptoms will increase. The course of the illness varies from one person to another, and some symptoms may only appear in the later stages. The order in which symptoms appear varies in each person, depending on the area of the brain affected.
PSP can be difficult to diagnose and is quite easy to confuse with other conditions with similar symptoms. There is no specific laboratory test or imaging approach to definitively diagnose PSP. Scanning techniques, such as brain magnetic resonance imaging, may show some shrinkage at the top of the brain stem. Other imaging tests can help to display activity in the brain areas which are affected by neurodegeneration in general.
According to the National Institutes of Health, the “initial complaints in PSP are typically vague and fall into these categories: 1) symptoms of disequilibrium, such as unsteady walking or abrupt and unexplained falls without loss of consciousness; 2) visual complaints, including blurred vision, difficulties in looking up or down, double vision, light sensitivity, burning eyes, or other eye trouble; 3) slurred speech; and 4) various mental complaints such as slowness of thought, impaired memory, personality changes, and changes in mood. An initial diagnosis is based on the person’s medical history and a physical and neurological exam”.
A specialist doctor, usually a neurologist or movement disorder specialist, will make those careful observations over time to reach a diagnosis. This process can take two or three years. This lengthy diagnosis period can be frustrating for all concerned, but research into faster, more accurate diagnosis is under way.
PSP and Parkinson’s
PSP is often confused with Parkinson’s due to the similarity of symptoms, particularly stiffness, bradykinesia and movement difficulties. Both PSP and Parkinson's cause parkinsonism - a combination of stiffness, slowness and clumsiness. This is why PSP may be difficult to distinguish from Parkinson's early on. However, shaking (tremor), while prominent in about 70 percent of people with Parkinson's, occurs in only about 10 percent of people with PSP. More commonly, tremor occurring in PSP is irregular, mild and present only when the hands are in use, not at rest as in Parkinson's.
One notable difference is that people with PSP find it hard to look up or down, whereas people with Parkinson's may experience other eye-related problems, including double vision, uncontrolled blinking or excessive watering. However, this may not be obvious in the early stages of the illness.
Another difference concerns posture. People with PSP tend to stand straight or tilt their heads backwards (resulting in backwards falls), while people with Parkinson's usually bend forwards.
Problems with speech and swallowing tend to be more common and severe in PSP than in Parkinson's and are often more apparent earlier. The sense of smell may remain intact in PSP whereas it is often lost in Parkinson's. Lastly and perhaps most obviously, tremor – almost universal in people with Parkinson’s – is rare in PSP.
Most drugs for Parkinson's enhance, replace, or mimic a brain chemical called dopamine. Parkinson's responds better to such drugs than does PSP because dopamine deficiency is by far Parkinson’s most important abnormality. In PSP, deficiencies of several other brain chemicals are at least as severe as the dopamine deficiency, and no good way exists to replace those.
Progressive Supranuclear Palsy treatment and management
There is no specific treatment for PSP. Because it is a complex illness, a combination of approaches will probably be suggested.
Unfortunately, few medications are currently available to treat PSP effectively. Parkinson’s medicines are generally not very effective, although 20-30% of PSP patients respond quite well to levodopa at least initially. An experienced doctor or neurologist should always be involved in managing medication.
Health professionals such as physiotherapists, speech and language therapists, occupational therapists, specialist nurses, dieticians and social workers can all offer help, advice and support for those with PSP. Tell your doctor about any symptoms and difficulties so that he or she can put you in touch with the right member of the team. For example, in many countries an occupational therapist or physiotherapist will be able to provide gait assessment and suggest equipment and practical strategies. A speech and language therapist can advise on overcoming difficulties with speech, eating and swallowing. Palliative medicine can be a great help. For example, muscle relaxants or gentle massage can help with cramps; bathing eyes with cotton wool dipped in cooled boiled water can ease the extreme dryness of the eyes due lack of eyelid blinking. Botox or Myobloc, two types of botulinum toxin, are a different sort of drug that can be useful for people whose PSP is complicated by blepharospasm (involuntary closure of the eyelids). Botox can be carefully injected by a neurologist into the eyelid muscles as a temporary remedy for this. Botox can also be used for involuntary turning or bending of the head that occurs in PSP, but injecting it into the neck muscles can sometimes cause slight weakness of the nearby swallowing muscles. In PSP, where swallowing is already impaired in many people, the use of Botox in neck muscles should be approached with caution.
As the illness progresses, there is an increased risk of complications such as pneumonia due to an inability to swallow. If swallowing becomes too difficult, it may be necessary to introduce a feeding or PEG tube – for more information see Speech & language therapy.