Saturday, February 12, 2011

Early Warning on Alzheimer’s through Spinal Fluid Tests

Early detection of the Alzheimer’s Disease is extremely important, since it may give an opportunity for the patients to take measures, delaying, or even conserving, for long the negative signs of the illness occurrence. Yes, there is no magical cure yet, but the medicine has already relatively efficient ways to offer ongoing maintenance measures to the patients. Detecting the disease at a very early stage, before the brain has suffered a lot of damage, may mean that treatments can be developed to stop the progression of disease. Current medications for Alzheimer’s, which are typically prescribed once memory impairment becomes obvious, may ease symptoms for a time but do nothing to stop the underlying disease.

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The Scientists are making steady gains toward developing tests that can predict whether patients with mild cognitive difficulties or even no symptoms at all are likely to progress to full-blown Alzheimer’s disease. The latest research, published in August 2010 in the Archives of Neurology, a journal of the American Medical Association, found that a test of spinal fluid performed exceptionally well in identifying patients with Alzheimer’s or on the way to developing it.

Researchers have identified a protein "signature" in the spinal fluid of patients with Alzheimer's disease, which could represent an important advance in its diagnosis. The signature was found in the cerebrospinal fluid (CSF) of 90% of people with a diagnosis of Alzheimer's disease and 72% of people with mild cognitive impairment (MCI) -- a disorder that often progresses to Alzheimer's.

Researchers measured concentrations of three proteins previously identified as potential biological indicators, or biomarkers, for Alzheimer's and MCI: amyloid-beta, tau, and phospho-tau. Low levels of the amyloid protein amyloid-beta 1-42, along with high levels of total tau and elevated phospho tau 181 (P-tau 181), identified Alzheimer's disease in three independent study groups, reports Hugo Vanderstichele, PhD, of the Belgian biotech company Innogenetics.

Along with colleagues from the Alzheimer's Disease Neuroimaging Initiative, which paid for the research, Vanderstichele developed the protein profile and tested it on spinal fluid taken from roughly 100 older people with no evidence of memory loss, as well as 200 people with MCI and 100 with Alzheimer's disease. The researchers tested the samples without knowing the clinical status of the patients who supplied them.

The Alzheimer's signature was identified in nine out of 10 samples from patients with Alzheimer's disease and in just over two-thirds of patients with MCI. Thirty-six percent of people with no known cognitive impairment also exhibited the signature. These results were validated in CSF samples from two other studies. In one, the protein signature indicative of Alzheimer's was seen in 64 of 68 autopsy-confirmed cases of the disease. In another, all 57 patients with MCI followed for five years exhibited the protein profile.

It is not clear why more than a third of people without memory declines had the Alzheimer's biomarkers. It could be that the biomarker changes occur long before symptoms of Alzheimer's do, says neurologist John H. Growdon, MD, of Massachusetts General Hospital. "These may be people who are able to tolerate a high burden of these toxic (proteins) without developing symptoms," he says.

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What is Cerebrospinal fluid (CSF) analysis?

Cerebrospinal fluid (CSF) analysis is a laboratory test to examine a sample of the fluid surrounding the brain and spinal cord. This fluid is a clear, watery liquid that protects the central nervous system from injury and cushions it from the surrounding bone structure. It contains a variety of substances, particularly glucose (sugar), protein, and white blood cells from the immune system. The fluid is withdrawn through a needle in a procedure called a lumbar puncture.


In some circumstances, a lumbar puncture to withdraw a small amount of CSF for analysis may lead to serious complications. Lumbar puncture should be performed only with extreme caution, and only if the benefits are thought to outweigh the risks, in certain conditions. For example, in people who have blood clotting (coagulation) or bleeding disorders, lumbar puncture can cause bleeding that can compress the spinal cord. If there is a large brain tumor or other mass, removal of CSF can cause the brain to droop down within the skull cavity (herniate), compressing the brain stem and other vital structures, and leading to irreversible brain damage or death. These problems are easily avoided by checking blood coagulation through a blood test and by doing a computed tomography scan (CT) or magnetic resonance imaging (MRI) scan before attempting the lumbar puncture. In addition, a lumbar puncture procedure should never be performed at the site of a localized skin infection on the lower back because the infection may be introduced into the CSF and may spread to the brain or spinal cord.


The procedure to remove cerebrospinal fluid is called a lumbar puncture, or spinal tap, because the area of the spinal column used to obtain the sample is in the lumbar spine, or lower section of the back. In rare instances, such as a spinal fluid blockage in the middle of the back, a doctor may perform a spinal tap in the neck. The lower lumbar spine (usually between the vertebrae known as L4-5) is preferable because the spinal cord stops near L2, and a needle introduced below this level will miss the spinal cord and encounter only nerve roots, which are easily pushed aside.

A lumbar puncture takes about 30 minutes. Patients can undergo the test in a doctor's office, laboratory, or outpatient hospital setting. Sometimes it requires an inpatient hospital stay. If the patient has spinal arthritis, is extremely uncooperative, or obese, it may be necessary to introduce the spinal needle using x-ray guidance.

In order to get an accurate sample of cerebrospinal fluid, it is critical that a patient is in the proper position. The spine must be curved to allow as much space as possible between the lower vertebrae, or bones of the back, for the doctor to insert a lumbar puncture needle between the vertebrae and withdraw a small amount of fluid. The most common position is for the patient to lie on his or her side with the back at the edge of the exam table, head and chin bent down, knees drawn up to the chest, and arms clasped around the knees. (Small infants and people who are obese may need to curve their spines in a sitting position.) People should talk to their doctor if they have any questions about their position because it is important to be comfortable and to remain still during the entire procedure. In fact, the doctor will explain the procedure to the patient (or guardian) so that the patient can agree in writing to have it done (informed consent). If the patient is anxious or uncooperative, a short-acting sedative may be given.

During a lumbar puncture, the doctor drapes the back with a sterile covering that has an opening over the puncture site and cleans the skin surface with an antiseptic solution. Patients receive a local anesthetic to minimize any pain in the lower back.

The doctor inserts a hollow, thin needle in the space between two vertebrae of the lower back and slowly advances it toward the spine. A steady flow of clear cerebrospinal fluid, normally the color of water, will begin to fill the needle as soon as it enters the spinal canal. The doctor measures the cerebrospinal fluid pressure with a special instrument called a manometer and withdraws several vials of fluid for laboratory analysis. The amount of fluid collected depends on the type and number of tests needed to diagnose a particular medical disorder.

In some cases, the doctor must remove and reposition the needle. This occurs when there is not an even flow of fluid, the needle hits bone or a blood vessel, or the patient reports sharp, unusual pain.

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Patients can go about their normal activities before a lumbar puncture. Experts recommend that patients relax before the procedure to release any muscle tension, since the lumbar puncture needle must pass through muscle tissue before it reaches the spinal canal. A patient's level of relaxation before and during the procedure plays a critical role in the test's success.


For most people, the most common side effect after the removal of CSF is a headache. This occurs in 10-30% of adult patients and in up to 40% of children. It is caused by a decreased CSF pressure related to a small leak of CSF through the puncture site. These headaches usually are a dull pain, although some people report a throbbing sensation. A stiff neck and nausea may accompany the headache. Lumbar puncture headaches typically begin within two days after the procedure and persist from a few days to several weeks or months.

Since an upright position worsens the pain, patients with a lumbar puncture headache can control the pain by lying in a flat position and taking a prescription or non-prescription pain relief medication, preferably one containing caffeine. In rare cases, the puncture site leak is "patched" using the patient's own blood.

People should talk to their doctor about complications from a lumbar puncture. In most cases, this test to analyze CSF is a safe and effective procedure. Some patients experience pain, difficulty urinating, infection, or leakage of cerebrospinal fluid from the puncture site after the procedure.

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