In the article, "Tau forms in CSF as a reliable biomarker forprogressive supranuclear palsy," Dr. Borroni and her coauthors(Neurology®2008;71:1796–1803) looked at specific medicaltests that could help physicians accurately diagnose this illness.Progressive supranuclear palsy (PSP) is rare and has similaritiesto several other progressive neurologic disorders. Because ofthis, they looked at the results of these tests not only inpeople with PSP, but also in those who had the "similar" illnesses.In addition, the authors compared the results of the tests totest results of people who did not have progressive neurologicdisease.
Dr. Borroni and coauthors carefully studied the tests resultsfor 166 people. All had undergone a detailed history, physicalexamination, and neurologic examination. All were monitoredfor more than 2 years. The reason for this long period of monitoringis that the illnesses, especially when they begin, can looklike something else. As the illness progresses and other symptomsdevelop, the diagnosis becomes more clear. By following thisgroup for more than 2 years, Dr. Borroni minimized any errorsin diagnosis.
Of the 166 people, 21 were diagnosed with PSP. One hundred twenty-fivepeople had progressive neurologic conditions such as Parkinsondisease and Alzheimer disease. There were also a few other illnesses.Twenty-seven patients acted as the "controls." They were "normal."This last group needs more explaining. The "controls" were agroup of people who had an MRI and lumbar puncture for otherreasons. For instance, they may have had a headache, and inthe process of evaluating the headache, these tests were needed.Although not entirely "normal," as this group had experienceda neurologic symptom (for example, headache), they did not havea progressive neurologic illness.
A subset of patients had a specialized MRI of the brain andbrainstem. Dr. Borroni used a specialized kind of MRI technologycalled voxel-based morphometry (VBM). Everyone is differenton the outside; similarly, we have slight differences in ourbrains as well. VBM is one way to "eliminate" the differencesbetween people, allowing for more accurate measurements. VBMtechnology is not used on the whole brain. Instead, it focuseson specific regions of the brain. This is important in illnessessuch as PSP, which primarily affects deep brain structures suchas the brainstem.
Dr. Borroni also studied each person’s cerebrospinal fluid(CSF). She did this by carefully analyzing the kinds of proteinsthat were in the CSF. Because CSF surrounds the brain, componentsof CSF can give physicians important clues as to what is occurringwithin the brain itself. In certain neurologic illnesses, theCSF will contain a specific protein called tau. Dr. Borronilooked at looked at two types of tau. She then calculated theratio between the two tau subtypes. She analyzed each patient(for both types), and then compared the results between peoplewith different neurologic illnesses.
The first discovery was that people with PSP had a specificratio of tau proteins. The ratio was lower in people with PSP.This ratio was significantly different not only from the controlgroup, but also was different from other types of progressiveneurologic illnesses. Not only this, but as the illness worsened,the ratio became ever smaller. In other words, there was a correlationnot only between the illness and a low tau ratio, but the worsethe PSP was, the lower the ratio became.
Next, Dr. Borroni looked at the MRIs, focusing her attentionon the VBM images. In patients with a low tau ratio, a significantlydecreased amount of nerve cells was seen in the brainstem. Thisdifference was not seen in other parts of the brain.
When a progressive neurologic illness begins, the kinds of problemsthat occur, such as memory problems, may not point to a specificdiagnosis. Only later, as more symptoms develop, does the diagnosisbecome clearer. Studies like the one that Dr. Borroni has publishedshow how medical testing can help. Testing of this kind canmake diagnosis more accurate. In addition, it can give the physiciana tool that allows him or her to make the diagnosis earlier.Although there is no known treatment for PSP today, this maychange as research progresses. Earlier identification of illnessmay then lead to improved treatment.
Progressive supranuclear palsy (PSP) is a rare brain illness.It affects about 5 people in 100,000, which means that thereare probably about 20,000 people in the United States that havePSP. It typically starts after age 60. It is progressive, whichmeans that it worsens over time. The term supranuclear refersto the region of brain that PSP affects the most. Palsy simplymeans weakness, another effect caused by the illness.
In the vast majority of people, the cause is unknown. Scientistsare looking for environmental causes such as an exposure tocertain toxins. Another possibility is that the illness mightbe caused by a virus that the person had when he or she wasyounger. Although the virus caused little or no problems atthe time, it may have set a chain of events in motion that laterresulted in PSP. In rare cases, the illness is genetic. Forthis reason, scientists are also looking for genes that eithercause the illness or ones that might predispose someone to gettingthe illness. For instance, a person might need to have the geneand also be exposed to a specific toxin in order to developPSP.
PSP can cause problems with movement and coordination, whichtranslates into problems with balance and walking. Some of thesymptoms of this, such as stiffness, resemble symptoms of Parkinsondisease (PD). PSP causes problems with the movement of the eyes.When this happens, people feel that their vision is blurred,or they may experience double vision. As the illness worsens,depression and personality changes become more common. Memorycan be affected, in a way that is nearly identical with Alzheimerdisease (AD). In some people, swallowing becomes a problem,and a feeding tube, usually placed directly into the stomach,is needed.
The reason that PSP affects so many different brain functionshas to do with the area of the brain that it affects the most:the brainstem. The brainstem is a small region of the brain,but it contains many different important structures. For instance,the control of the eyes requires careful input from a smallnumber of nerve cells that live in the brainstem. For eye movementsto occur smoothly, these cells are in constant communicationwith each other and with other parts of the brain. When thebrainstem starts having problems, it is easy to see how theeyes might be affected.
For the brain to do all of things that it needs to do, differentbrain areas have to be connected together. Of course, for thebrain to direct the body’s movements, it must have excellentconnections with the muscles. The place where all of the connectionsgo from the brain to the body is the brainstem. In short, anillness that affects the brainstem can affect the ability toperform smooth, graceful movements.
PSP starts out very slowly and gradually gets worse. Becauseeveryone is different, the first signs of PSP differ among individuals.For instance, some people may have the eye movement problemsfirst, while others have more difficulties with movement inthe beginning. In some, the memory problems start first. Becauseof this, PSP may initially be diagnosed as something else, suchas PD or AD. As the illness worsens, however, and other symptomsarise, the diagnosis of PS becomes much clearer.
To some degree, the choice of medical tests depends on the specificsituation. However, everyone with PSP will have had a physicaland neurologic examination in their doctor’s office. Thephysician carefully looks for any signs or symptoms of PSP.Often, the doctor will order an MRI of the brain (and brainstem).Sometimes the MRI will show changes in the brainstem, supportingthe diagnosis of PSP; however, in many people, these changesare very subtle. Specialized MRIs, such as the one used in Dr.Borroni’s paper, can help increase the chance of pickingup on these abnormalities. However, the abnormalities on MRIin people with PSP can also be seen in other illnesses likePD and AD. Although the MRI can be very helpful, it does notmake the diagnosis all by itself.
If memory is a problem, memory testing may be needed. Calledneuropsychological testing, the memory "test" is actually abattery of tests which are designed to assess many differentareas of thinking, attention, and, of course, memory. Neuropsychologicaltesting can identify certain patterns of brain dysfunction,not only helping to establish the diagnosis, but assisting inthe selection of the best possible treatment(s).
There is no known treatment for PSP at this time. Until oneis available, doctors treat the symptoms of the illness. Forinstance, when a person has the movement problems that are similarto PD, he may respond to levodopa, a medicine that is oftenused to treat PD. There are medicines that can help improvethe memory problems in AD. These can be used to help memoryproblems in PSP. Physical therapy can help to maintain strengthand mobility. Often, a person with PSP will require a combinationof therapies, usually under the direction of a team of medicalspecialists.
Current research is aimed both at understanding PSP better,as in Dr. Borroni’s paper, and at improving the treatmentfor PSP. These two aspects of research go hand-in-hand. As weunderstand an illness more fully, we can devise better and betterways of treating it. Because of the overlap between PSP andother progressive neurologic illnesses, research in one areamay spill over into another. For instance, research in AD mayhelp to unlock the key to understanding PSP.
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WHAT DID THE AUTHORS...
WHAT DID THE AUTHORS...
