Frequently Asked Questions
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Progressive Supranuclear Palsy (PSP)
In general, a “palsy” is a weakness or paralysis of a part of the body. The term “supranuclear” refers to the nature of the eye problem in PSP. Although some patients with PSP describe their symptom as “blurring,” the actual problem is an inability to aim the eyes properly because of weakness or paralysis (palsy) of the muscles that move the eyeballs. These muscles are controlled by nerve cells residing in clusters or “nuclei” (NUKE-lee-eye) near the base of the brain in the brainstem. Most other brain problems that affect eye movements originate in those nuclei, but in PSP, the problem lies in parts of the brain that control those eye-movement nuclei themselves. These “higher” control areas are what the prefix “supra” in “supranuclear” refers to.
Sometimes, complicated disease names are avoided by the use of the name of the physician who discovered the disease. However, for PSP, there were three such physicians and the string of names – Steele, Richardson, and Olszewski (ol-SHEF-skee) – is even less convenient than the descriptive name. Steele-Richardson-Olszewski syndrome is rarely used these days as a synonym for PSP. Incidentally, although Drs. Richardson and Olszewski are deceased, Dr. John C. Steele, who was a neurology resident (i.e., a trainee) when he collaborated in the original description of PSP, still does neurological research and serves as Honorary Chairman of CurePSP.
The most common first symptom, occurring on average in the 60’s, is loss of balance while walking. This may take the form of unexplained falls or of a stiffness and awkwardness in the walk that can resemble Parkinson’s disease. Sometimes the falls are described by the person experiencing them as attacks of dizziness. This often prompts the doctor to suspect an inner ear problem or hardening of the arteries supplying the brain.
Other common early symptoms are forgetfulness and changes in personality. The latter can take the form of a loss of interest in ordinary pleasurable activities or increased irritability and cantankerousness. These mental changes are misinterpreted as depression or even as senility. Less common early symptoms include trouble with eyesight, slurring of speech and mild shaking of the hands. Difficulty driving a car, with several accidents or near misses, is common early in the course of PSP. The exact reason for this problem is not clear.
The same general area of the brain that controls eye movement also controls movements of the mouth, tongue, and throat, and these movements also weaken in PSP. Speech becomes slurred in most patients after 3 or 4 years, on average, although it is the first symptom in a few patients. In Parkinson’s disease, the speech problem is characterized by soft volume and rapid succession of words. In PSP, however, the speech may have an irregular, explosive quality (called spastic speech, a drunken quality (ataxic speech) or may have the features of speech in Parkinson’s disease. Most commonly, there is a combination of at least two of these three features in the speech of PSP.
An erroneous impression of senility or dementia can be created by the PSP patient’s combination of speech difficulty, slight forgetfulness, slow (albeit accurate) mental responses, personality change, apathy and poor eye contact during conversation. Dementia of a sort does occur in many people with PSP, however, and is discussed below.
Swallowing tough foods or thin liquids can become difficult because of throat muscle weakness or incoordination. This tends to occur later than the walking, visual and speech problems, but can become very troublesome if the patient tends to choke on food. Unlike the other difficulties in PSP, this one can sometimes pose a danger for the patient – the danger of food going down the wrong pipe into the breathing passages, termed aspiration. Usually, difficulty managing thin liquids precedes difficulty with solid food. This is because in PSP, the swallowing muscles have difficulty creating a watertight seal separating the path to the stomach from the path to the lungs. The same is true for the swallowing difficulty of many neurological diseases. For non-neurologic conditions such as stricture of the esophagus, however, the difficulties start with solid foods.
Repeated, minor, often unnoticed episodes of small amounts of food and drink dripping into the lungs can cause pneumonia. Often, it is not apparent to the physician or family that the PSP patient’s pneumonia is in fact the result of subtle aspiration. But aspiration pneumonia is the most common cause of death in PSP.
In most cases, the visual problem is at least as important as the walking difficulty, though it does not appear, on average, until 3 to 5 years after the walking problem. Because the main difficulty with the eyes is in aiming them properly, reading often becomes difficult. The patient finds it hard to shift down to the beginning of the next line automatically after reaching the end of the first line. This is very different from just needing reading glasses. An eye doctor unfamiliar with PSP may be baffled by the patient’s complaint of being unable to read a newspaper despite normal ability to read the individual letters on an eye chart. Some patients have their mild cataracts extracted in a vain effort to relieve such a visual problem.
Another common visual problem is an inability to maintain eye contact during conversation. This can give the mistaken impression that the patient is senile, hostile, or uninterested. The same eye movement problem can create the symptom of “tunnel vision” and can interfere with driving a car.
The most common eye movement problem in PSP is an impaired ability to move the eyes up or down. This can interfere with eating or with descending a flight of stairs, among other things. This problem is not usually as vexing for the patient and family as the inability to maintain eye contact or to coordinate eye movements while reading, but is much easier for the doctor to detect. This reduction in vertical eye movement is usually the first clue to the doctor that the diagnosis is PSP. Other conditions, particularly Parkinson’s disease and normal aging, can sometimes cause difficulty moving the eyes up. However, PSP is nearly unique in also causing problems moving the eyes down.
Yet another eye problem in PSP can be abnormal eyelid movement — either too much or too little. A few patients experience forceful involuntary closing of the eyes for a few seconds or minutes at a time, called blepharospasm. Others have difficulty opening the eyes, even though the lids seem to be relaxed, and will try to use the muscles of the forehead, or even the fingers, in an effort to open the eyelids (apraxia of lid opening). About 20 percent of patients with PSP eventually develop one of these problems. Others, on the contrary, have trouble closing the eyes and blink very little. While about 15 to 25 blinks per minute are normal, people with PSP blink, on average, only about 3 or 4 times per minute. This can allow the eyes to become irritated. They often react by producing extra tears, which, in itself, can become annoying.
The symptoms of PSP are caused by a gradual deterioration of brain cells in a few tiny but important places in the base of the brain. The most important such place, the “substantia nigra” (sub-STAN-cha NYE-gra), is also affected in Parkinson’s disease and damage to it accounts for the symptoms that PSP and Parkinson’s have in common. However, several important areas are affected in PSP that are normal in Parkinson’s (and vice-versa). Moreover, under the microscope, the appearance of the damaged brain cells in PSP is quite different from those in Parkinson’s and resembles, rather, the degeneration in Alzheimer’s disease. However, the location of the damaged cells is quite different in PSP and Alzheimer’s. Furthermore, in PSP there are no amyloid plaques, deposits of waxy protein that are a hallmark of brain cells in Alzheimer’s.
No one knows yet, but we have some clues. The more important is that in the brain cells that are degenerating in PSP, there is an abnormal accumulation of a normal protein called “tau.” These clumps of tau are called “neurofibrillary tangles.” The normal function of tau is to help support the internal “skeleton” of the brain cells whose long extensions make contact with other brain cells. We don’t know whether the problem is that the tau is defective from the time of its manufacture or whether it becomes damaged later. We also don’t know if the problem is that the brain cells are deprived of the normal function of tau or if the problem is that tau aggregates into clumps that are themselves toxic.
A clue to what is going wrong with tau protein is that most of the tau protein in the neurofibrillary tangles of PSP are of one type called “four-repeat” tau. In the normal brain cells, there are equal amounts of four-repeat and three-repeat tau. The “repeat” number refers to the number of copies of the part of the protein that binds it to another component of the cell’s internal skeleton, the microtubules. So in PSP, the problem may be that too much four-repeat tau is made, or that too little three-repeat tau is made, the result being clumps of four-repeat tau.
There is evidence that chemicals in the environment or diet may contribute to the cause of PSP. Surveys of PSP patients have hinted at a predilection for rural living and, on average, lesser educational attainment in people with PSP. This suggests that part of the cause of PSP is certain occupational factors exposing people to different chemicals than are encountered by non-rural people or those with more sedentary, office-bound occupations.
One important clue to a possible dietary factor in the cause of PSP comes from the island of Guadeloupe in the Caribbean. People there are far more likely to develop PSP and other “atypical parkinsonisms” than are people elsewhere. A questionnaire survey on Guadeloupe revealed that people with PSP-like illnesses there were more likely than others to have consumed two native fruits called “sweetsop” and “soursop.” These fruits have since been shown to harbor toxins that when given to laboratory rats cause damage to the brain very similar to human PSP. We don’t yet know what, if any, foods in the Western diet contain similar toxins.
PSP only very rarely runs in families. Fewer than one in 100 people with PSP knows of even one other family member with PSP. However a variant in the gene on chromosome 17 that encodes the tau protein is more common in PSP than in the rest of the population. The variant is called the “H1 haplotype.” About 95% of people with PSP have this variant on both of their copies of chromosome 17, while this is true for only about 60% of the rest of us. So clearly, the H1 haplotype is (nearly) necessary but far from sufficient to cause the disease. There is evidence that what this variant is doing wrong is directing the brain cells to produce too much tau protein. The theory is that the excess tau forms neurofibrillary tangles and that these, or an early, embryonic form of them, damages the cells.
One very large family with PSP in multiple members has a variant in a gene other than the tau gene. The specific gene has not yet been identified. Similarly, two other genetic variant that are ordinarily associated with hereditary Parkinson’s disease – the parkin gene (PARK2) and the dardarin gene (PARK8) can in some cases cause changes in the brain very similar to what happens in PSP. This means that there may be many different genetic contributors to PSP with no single one laying claim to the title of “the PSP gene.” It also means that PSP, Parkinson’s, and perhaps other neurodegenerative disorders may share come causative factors.
Both PSP and Parkinson’s disease cause stiffness, slowness, and clumsiness, a combination called parkinsonism. This is why early on, PSP may be difficult to distinguish from Parkinson’s disease. However, shaking (tremor), while prominent in about two-thirds of people with Parkinson’s disease, occurs in only about one in twenty people with PSP. A more common type of tremor occurring in PSP is irregular, mild and present only when the hand is in use, not at rest as in Parkinson’s disease.
Patients with PSP usually stand up straight or occasionally even tilt the head backwards and tend to fall backwards, while those with Parkinson’s usually are bent forwards. The problems with vision, speech, and swallowing are much more common and severe in PSP than in Parkinson’s. Parkinson’s causes more difficulty using the hands and more stiffness in the limbs than does PSP. Finally, the medications that are so effective for Parkinson’s disease are of much less benefit in PSP.
The mainstay of drugs for Parkinson’s disease are those that enhance, replace or mimic a brain chemical called dopamine. Parkinson’s responds better to such drugs than does PSP because in PD, deficiency of dopamine is by far the most important abnormality, while 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. Also, in PSP, there is damage to the brain cells that receive the dopamine-encoded messages, while these remain intact in Parkinson’s.
Although mental confusion in patients with PSP is more apparent than real, most patients do eventually develop some degree of mental impairment. Some are mislabeled as having Alzheimer’s disease. This is not very different from the situation in Parkinson’s disease.
In PSP, the dementia, if it does occur, does not feature the memory problem that is so apparent in Alzheimer’s disease. Rather, the dementia of PSP is characterized by slowed thought and difficulty synthesizing several different ideas into a new idea or plan. These mental functions are performed mostly by the front part of the brain (the frontal lobes). In Alzheimer’s, on the other hand, the problem is mostly in the part of the brain just above the ears (the temporal lobes), where memory functions are concentrated.
Alzheimer’s disease also includes either difficulty with language (such as trouble recalling correct names of common objects) or difficulty finding one’s way around a previously familiar environment. Fortunately, these symptoms almost never occur in PSP. Nevertheless, the “frontal” problems of PSP can interfere to a major degree with the ability to function independently, and the patient’s irritability in some cases can make it difficult for caregivers to help.
Slowing of thought can cause major problems for people with PSP by making it difficult to partake in conversation. A question may be answered with great accuracy and detail, but with a delay of several minutes. Probably the most important aspect of the dementia of PSP is apathy. People with PSP seem to lose interest in their surroundings, again creating the impression of loss of thinking ability and interfering with family interactions.
Several medications, all available only by prescription, can help PSP in some cases.
This is the brand name for a combination of “levodopa” and “carbidopa.” Levodopa is the component that helps the disease symptoms. Carbidopa simply helps prevent the nausea that levodopa alone can cause. When levodopa came along in the late 1960’s, it was a revolutionary advance for Parkinson’s but, unfortunately, it is of only modest benefit in PSP. It can help the slowness, stiffness and balance problems of PSP to a degree, but usually not the mental, speech, visual or swallowing difficulties. It usually loses its benefit after two or three years, but a few patients with PSP never fully lose their responsiveness to Sinemet.
Some patients with PSP require large dosages, up to 1,500 milligrams of levodopa as Sinemet per day, to see an improvement. The dosage should be pushed to at least that level, under the close supervision of a physician, unless a benefit or intolerable side effects occur sooner. The most common side effects of Sinemet in patients with PSP are confusion, hallucinations, and dizziness. These generally disappear after the drug is stopped. The most common side effect in patients with Parkinson’s disease, involuntary writhing movements (“chorea” or “dyskinesias”), occur very rarely in PSP, even at high Sinemet dosages.
Patients with PSP should generally receive the standard Sinemet (or generic levodopa/carbidopa) preparation rather than the controlled-release (Sinemet CR or generic levodopa/carbidopa ER) form. The CR form is absorbed from the intestine into the blood slowly and can be useful for people with Parkinson’s disease who respond well to Sinemet but need to prolong the number of hours of benefit from each dose.
In PSP, however, such response fluctuations almost never occur. Because Sinemet CR is sometimes absorbed very little or erratically, a poor CR response in a patient with PSP might be incorrectly blamed on the fact that the disease is usually unresponsive to the drug. Such a patient might actually respond to the standard form, which reaches the brain in a more predictable way.
A new formulation of levodopa-carbidopa is Parcopa, which dissolves under the tongue. For people with PSP who cannot swallow medication safely, this could be useful. Another approach for such patients is to crush a regular levodopa-carbidopa tablet into a food or beverage that is easily swallowed. Another new formulation of levodopa-carbidopa combines those two drugs with a third drug, entacapone, in the same tablet. This is called Stalevo. The entacapone slows the rate at which dopamine is broken down. It is useful for patients with Parkinson’s whose levodopa-carbidopa works well but only for a few hours per dose. This situation rarely, if ever, occurs in PSP.
Dopamine receptor agonists
There are four such drugs on the market – Parlodel (generic name, bromocriptine), Permax (pergolide), Mirapex (pramipexole), and Requip (ropinirole). These are helpful in most people with Parkinson’s disease, but in PSP, they rarely give any benefit beyond that provided by carbidopa/levodopa. One careful trial of Mirapex showed no benefit at all in PSP.
The main possible side effects of the dopamine receptor agonists are hallucinations and confusion, which can be more troublesome for PSP than for Parkinson’s. They can also cause excessive involuntary movements, dizziness, and nausea.
Another group of drugs that has been of some modest success in PSP are the antidepressant drugs. The anti-PSP benefit of these drugs is not related to their ability to relieve depression. The best antidepressant drug for the movement problems of PSP is probably Elavil (generic name, amitriptyline). It has been used against depression since the early 1960’s. The dosage should start at 10 mg once daily, preferably at bedtime. It can be increased slowly and taken divided into at least two doses per day. Past 40 mg per day, the likelihood of side effects increases to an unacceptable level for most patients. Elavil is also a good sleep medication for some elderly people and may provide this benefit in PSP if taken at bedtime. One important side effect in some people is constipation. Others are dry mouth, confusion, and difficulty urinating (in men). Unfortunately, some patients with PSP find that their balance difficulty worsens on Elavil.
This drug (generic name, amantadine) has been used for Parkinson’s since the 1960s. Because it affects more than just the dopamine system, it can be effective in PSP even if Sinemet is not. It seems to help the gait disorder more than anything else, however, its benefit generally lasts only a few months. Its principal potential side effects are dry mouth, constipation, confusion, and swelling of the ankles.
In the past 15 years, research trials have been completed with the drugs physostigmine, idazoxan, and methysergide. While each showed initial promise and prompted an optimistic article or two in a prestigious neurological journal, none has proven effective enough to justify use in patients. The most recent trial was of efaroxan, a drug similar to idazoxan, but it, too, proven ineffective. Cognex (tacrine), Aricept (donepezil), and Reminyl (galantamine) are drugs that enhance the activity of the brain chemical acetylcholine and are modestly useful against the dementia of Alzheimer’s disease. But they do not help the mental difficulties of PSP. A fourth anti-Alzheimer drug, Namenda (memantine), acts on a different brain chemical, glutamate. It works no better for PSP than the others and in addition can cause confusion and agitation in those patients.
A different sort of drug that can be useful for people whose PSP is complicated by blepharospasm is Botox or Myobloc (two types of botulinum toxin). This substance is produced by certain bacteria that can contaminate food. Its poisonous action occurs because it weakens muscles. A very dilute solution of the toxin can be carefully injected by a neurologist into the eyelid muscles as a temporary remedy for abnormal involuntary eyelid closure.
Botox can also be used for involuntary turning or bending of the head that occurs in PSP, but injection of Botox into the neck muscles can sometimes cause slight weakness of the swallowing muscles, which are nearby. In PSP, where swallowing is already impaired in many patients, caution should be used when considering use of Botox in neck muscles.
Not so far, unfortunately. The operations for Parkinson’s disease fall into two categories. One is based on the theory that the output of the basal ganglia (the group of nuclei that control movement to the rest of the brain) is overactive in Parkinson’s. The operations dampen down this overactivity. The main operations for this purpose are pallidotomy, which is rarely performed nowadays, and subthalamic nucleus stimulation, which is the most common Parkinson’s operation at present. In PSP, the area of the basal ganglia from which the output comes it itself damaged, so its activity is already dampened down. The operations would only make things worse.
The other category of operation for Parkinson’s attempts to replace the lost dopamine-producing brain cells. The reason this is unlikely to work for PSP is that while in Parkinson’s, most of the movement problem is caused by loss of the main dopamine-producing nucleus, the substantia nigra, while in PSP, the movement problems are caused by loss of many other nuclei in addition. Many of those other nuclei receive their input from the substantia nigra, so replacing only the first “link in the chain” will not help much. It would be impractical to replace cells in all of the nuclei involved in PSP – it would require too much trauma to the brain.
Probably the most important part of dealing with PSP is for the patient’s family to understand that the problems with visual inattention and personality changes are part of the illness. The patient is not lacking will power nor “faking.” Furthermore, many of the problems in PSP are intermittent and can be aggravated by the patient’s mental or emotional state. For example, walking, writing, and eating may be poor one hour and better the next. The family should understand that these fluctuations are not under the patient’s conscious control and that nagging and shouting usually just make matters worse. A wise policy is to be prepared to take advantage of the “good” periods to have an outing, a relaxing shower, or some other activity that would be more difficult during the “bad” times.
Walking aids are often important for patients with PSP. Because of the tendency to fall backwards, if a walker is required it should be weighted in front with sandbags over the lower rung. A better but more expensive solution is a large, heavy walker resembling a small shopping cart with three or four fat, soft rubber wheels and a hand brake. The tendency to fall backwards can also be countered by the use of built-up heels. Leg braces are not helpful because the problem in PSP is coordination and balance rather than actual muscle weakness.
Shoes with smooth soles are often better than rubber-soled athletic shoes. In many people with PSP, the gait disorder includes some element of “freezing,” a phenomenon that makes it difficult to lift a foot from the ground to initiate gait. Such people can fall if they move their body forward before the foot moves. In these cases, a smooth sole could make it easier to slide the first foot forward.
Handrails installed in the home, especially in the bathroom, may also be helpful. The difficulty in looking down dictates that low objects such as throw rugs and low coffee tables be removed from the patient’s living space.
To remedy the difficulty of looking down, bifocals or special glasses called prisms are sometimes prescribed for people with PSP. These are sometimes worth trying, but are usually of limited value because there is not only a problem moving the eyes in PSP, but also a problem directing the person’s attention (the “mind’s eye”) to objects located below the eyes. If this additional problem exists, special glasses would not help.
Formal physical therapy is of no proven benefit in PSP, but certain exercises done in the home by oneself on a regular schedule can keep the joints limber. Exercise also has a clear psychological benefit that improves the sense of well-being of anyone with a chronic illness. For specific exercises, consult one of the books for patients with Parkinson’s disease or the pamphlets distributed by the national Parkinson organizations. The special balance problems in PSP dictate caution in performing any exercises while standing. Many useful exercises can be performed seated in a chair or lying on a mat. Using a stationary bicycle is usually feasible as long as there is help in mounting and dismounting safely.
One of the hotter topics is new imaging procedures for diagnosing PSP. New ways of using magnetic resonance imaging (MRI), functional MRI, positron emission tomography, single-photon emission computed tomography, and transcranial ultrasound all are being developed. The purpose is to diagnose PSP earlier and more accurately and perhaps to track changes of the disease over time as a tool to be used in future trials of drugs that may slow or reverse the degenerative process.
Another promising area of research in PSP is inquiry into the reasons for tau to aggregate into neurofibrillary tangles. The abnormal ratio of four-repeat to three-repeat tau was mentioned above, and much current research is aimed at discovering what it is about the H1 haplotype of tau that causes damage.
There are other possible causes of tau misbehavior beside defects in its gene. In the field of neurodegenerative disorders in general, there is much current interest in what happens to proteins after they are manufactured “post-translational modification.” In PSP, we have known for 20 years that the tau protein has too many phosphate groups attached. The enzymes that attach phosphates to proteins are called “kinases,” and there are dozens of kinds of kinases at work in brain cells. Which of them, if any, are working abnormally in PSP is a question. Perhaps the abnormal phosphorylation is merely a healthy response of the brain cells to a potentially deleterious protein clump. Another example of post-translational modification of relevance to PSP is “transglutamination,” where the amino acid glutamine links tau protein molecules to one another into clumps. It may be possible to inhibit the enzyme, “transglutaminase,” that does this, potentially halting the progression of PSP.
Creating “animal models” of PSP is another active area of research. A PSP-like illness in laboratory animals can tremendously speed the process of trying new treatments. This can be accomplished by giving animals toxins, as has been done in rats given the toxic component of sweetsop and soursop, and also by genetically manipulating lab animals by implanting an abnormal tau gene into a fertilized egg and allowing the animal to grow, transmitting that defect to its young. This has been done for roundworms, fruit flies, mice, and rats. Testing of new treatments or prevention for PSP in such animals is under way in laboratories around the world and is an important step in finding a cure for PSP and related diseases.
Another very important way to help PSP, CBD, and MSA research is to make arrangements to donate your brain after death. CurePSP financially supports the Eloise H. Troxel Memorial Brain Bank located at the Mayo Clinic in Jacksonville, FL.
The funding CurePSP gives to the brain bank assists with their work. CurePSP does not provide help with the brain donation itself which is entirely handled by the Mayo Clinic. For information about the brain bank or any questions regarding a past donation, please contact the mayo brain bank coordinator, Jessica Tranovich at 904-953-2439.
Brains donated there are stored and used only for research in PSP, CBD, MSA, and related diseases by legitimate researchers after their proposals are examined and approved by the Foundation’s Scientific Advisory Board. Donating to a brain bank does not interfere with funeral arrangements and costs the family a few hundred dollars for expenses of brain removal and transportation.
The family will receive at no charge a full diagnostic report from the Mayo Clinic pathologist, Dennis W. Dickson, MD, who is one of the world’s foremost authorities on PSP, CBD, and related brain diseases. Further information is available from CurePSP. There are many other brain banks throughout the country, generally located at major university hospitals.
Visit our Brain Donation page to learn more.
See our support group page here.
The value of membership in a group of other people with the same problem is tremendous. You can exchange helpful tips on ways to cope physically and psychologically with the limitations of the illness and can learn more about the problem and its treatment from guest speakers. Many large medical centers have a Parkinson support group that welcomes members with PSP, CBD, and MSA. While there are far fewer people with any of these brain diseases than PD in one geographical area, several dozen successful PSP, CBD, or MSA support groups have been organized in the U.S., usually in more densely populated areas. All it takes is one organizer with some time and energy.
A major goal of CurePSP is to increase awareness of PSP, CBD, MSA, and related brain diseases among the public and the medical profession in order allow its correct diagnosis. If, as we suspect, PSP, CBD, and MSA prove to be much more common than has been assumed, improved diagnosis may allow local support groups to flourish, will foster the growth of the Foundation, and will draw the attention of more researchers to finding the cause and cure of this unique and puzzling illness.
Corticobasal Degeneration (CBD)
Corticobasal degeneration (CBD) is a rare neurological disease in which parts of the brain deteriorate or degenerate. CBD is also known as corticobasal ganglionic degeneration, or CBGD. Several regions of the brain degenerate in CBD. The cortex, or outer layer of the brain, is severely affected, especially the fronto-parietal regions, located near the center-top of the head. Other, deeper brain regions are also affected, including parts of the basal ganglia, hence the name “corticobasal” degeneration. The combined loss of brain tissue in all these areas causes the symptoms and findings seen in people with CBD.
Unfortunately, the cause of CBD is entirely unknown. There is currently no strong evidence to suggest CBD is an inherited disease, and no other risk factors, such as toxins or infections, have been identified.
Studies of brain tissue of individuals with CBD show certain characteristic cell changes. Similar, although not identical, changes are observed in two other neurodegenerative diseases, Pick’s disease and progressive supranuclear palsy. These changes, involving a brain protein called tau, have provided researchers some initial clues in their search for the causes of CBD.
Symptoms of CBD usually begin after age 60. The initial symptoms of CBD are often stiffness, shakiness, jerkiness, slowness, and clumsiness, in either the upper or lower extremities. Other initial symptoms may include dysphasia (difficulty with speech generation), dysarthria (difficulty with articulation), difficulty controlling the muscles of the face and mouth, or walking and balance difficulties. Symptoms usually begin on one side of the body, and spread gradually to the other. Some patients (probably more than commonly recognized in the past) may have memory or behavioral problems as the earliest or presenting symptoms.
CBD is a progressive disease, meaning the symptoms worsen over time. Over the course of one to several years, most people with CBD gradually worsen, with symptoms progressing to involve upper and lower extremities and other body regions.
Symptoms of advanced CBD include:
- parkinsonism (rigidity, slow movements, postural instability)
- myoclonus (sudden, brief jerky movements)
- dystonia, including blepharospasm
- speech difficulty
- mild-to-moderate cognitive impairment (memory loss, difficulty planning or executing unrehearsed movements, dementia)
- sensory loss
- “alien hand/limb” phenomenon (difficulty controlling the movements of a limb, which seems to undertake movements on its own, sometimes combined with a feeling that the limb is not one’s own)
Early in the disease course, it is often difficult to distinguish CBD from similar neurodegenerative diseases. Diagnosis of CBD involves a careful neurological exam, combined with one or more types of laboratory evaluations. Electrophysiological studies, including an EEG (electroencephalogram), may show changes in brain function over time that are consistent with the neurodegeneration. CT or MRI scans can also be used in this way, providing images of asymmetric atrophy of the fronto-parietal regions of the brain’s cortex, the regions most frequently involved in the disease.
Unfortunately, there are no drugs or other therapies that can slow the progress of the disease, and very few that offer symptomatic relief. Tremor and myoclonus may be controlled somewhat with drugs such as clonazepam. Baclofen may help reduce rigidity somewhat. Levodopa and other dopaminergic drugs used in Parkinson’s disease are rarely beneficial, but may help some CBD patients.
Physical therapy exercises may be useful to maintain range of motion of stiff joints. This may prevent pain and contracture (muscle shortening), and help maintain mobility. Occupational therapy may be used to design adaptive equipment that supports the activities of daily living, thus helping to maintain more functional independence. Speech therapy is used to improve articulation and volume.
A person with CBD will usually become immobile due to rigidity within five years of symptom onset, and may require a gastrostomy tube for feeding at some point before that. Most often, within ten years of onset, pneumonia or other bacterial infections may lead to life-threatening complications.
Multiple System Atrophy (MSA)
Multiple system atrophy, or MSA, is a rare, adult-onset, neurological disease that impacts movement, coordination, and, often, the autonomic nervous system. MSA is commonly referred to as an atypical parkinsonism, or sometimes as a Parkinson’s-plus diagnosis, because of its overlap with certain symptoms of Parkinson’s disease.
MSA is considered rare, affecting about two to five individuals for every 100,000 people.
Currently, about 13,000 people are diagnosed with MSA in the United States. This compares with about 30,000-40,000 people with progressive supranuclear palsy (PSP), which is a different type of atypical parkinsonism disorder; about 1 million with Parkinson’s disease; and 5 million with Alzheimer’s disease. This means that in the U.S., about five people are newly diagnosed with MSA each day. However, these figures for MSA are probably underestimates because many people with MSA are misdiagnosed with another condition, such as Parkinson’s disease.
MSA involves multiple circuits in the brain, each of which explains one of its several categories of recognizable symptoms. These major symptom groups include:
– Parkinsonism, which refers to slowness, smallness, and stiffness of movement, as well as tremor and changes in gait and balance. Other common problems related to movement in parkinsonism include reduced arm swing with walking, small or cramped handwriting, soft voice, and reduced facial expression.
– Cerebellar ataxia, which is caused by disease in the cerebellum (located at the back of the brain) and its connections. Common symptoms are a staggering, drunken-like gait, imbalance, uncoordinated movements, difficulty reaching for things with the arms, sloppy handwriting, and slurred speech.
– Autonomic nervous system failure, including severe blood pressure fluctuations when changing positions, difficulty with urination, constipation, difficulty swallowing, reduced sweating, and sexual dysfunction.
– Spasticity, which refers to muscle stiffness or tightness that creates resistance to being stretched. When your doctor taps on your arm or leg with a reflex hammer, you may notice that your limb jumps. MSA can exaggerate these reflexes, interfering with voluntary movement.
To diagnose MSA, a neurologist will gather a person’s medical history, including neurological symptoms, and will perform a physical examination. At this time, there is no specific test of body fluids nor imaging test of the brain that makes the diagnosis. A brain MRI can show changes in parts of the brain that would support the MSA diagnosis, but because changes in the brain do not always show up on an MRI, particularly in the first few years of symptoms, brain MRI cannot be relied upon as the sole diagnostic test. Your neurologist may decide to use other tests, such as a DaTscan, positron emission tomography (PET) scan, or autonomic nervous system testing, to help support the diagnosis of MSA. However, like the brain MRI, these tests can only support the diagnosis but are not sensitive enough nor specific enough to make the diagnosis alone. Given the rarity of the disease, many people with MSA face a long and confusing diagnosis journey. It is common to go through a number of tests, specialists, and diagnoses. It is our hope that better awareness of MSA, especially within the medical community, will lead to earlier and more accurate diagnosis.
Most brain disorders affect more than one set of circuits or areas of the brain, so why does MSA deserve the term “multiple”? It’s because it was once three different diseases. The cerebellar type of MSA (MSA-C) used to be known as olivopontocerebellar atrophy (OPCA); the parkinsonian subtype (MSA-P) was called striatonigral degeneration (SND); and MSA with disproportionate autonomic symptoms was called Shy-Drager syndrome. By 1989, scientists discovered that the abnormalities under the microscope in the three conditions were identical except for their locations, which overlapped significantly. They coined the term “multiple system atrophy” as a tribute to the historical notion of three disorders in one. Still, sometimes we still hear these older names used.
In 2020 alone, almost 500 research papers on MSA were published in scientific journals. As scientists understand more about the various neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, progressive supranuclear palsy, Lou Gehrig’s disease, and MSA, many commonalities among them are being revealed. There is hope that as researchers find prevention or ways of halting the progression of any of these diseases, the discovery could apply to MSA as well. Some drug companies looking for a way to slow or halt the progression of Parkinson’s disease are testing their treatments in MSA first, or simultaneously, in relation to the accumulation of the abnormally folded protein, alpha-synuclein. This has brought a wealth of new treatment trials in MSA. There is also research being done to better understand and manage the low blood pressure challenges associated with MSA.