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What is a biomarker?
A biomarker is a biological feature or characteristic that can be used to predict or measure the progression of disease or the response to treatment. It is perhaps easiest to understand the concept of a biomarker by considering an example. “Serum cholesterol” is a good example of a biomarker of the risk of cardiovascular and cerebrovascular disease. What this means is that people with elevated cholesterol levels are at an increased risk for having a heart attack or stroke. Biomarkers are sometimes divided up into several different types. A ‘diagnostic’ biomarker is a measurable biological characteristic that is helpful in diagnosing a particular condition. A ‘therapeutic’ biomarker is one that predicts a response to treatment, and a ‘prognostic’ biomarker provides information about what the future holds for someone with a particular disease. Electromyography (EMG) is currently the only biomarker of any real value in ALS. EMG can show the presence of motor neuron dysfunction at a time when this is not clinically apparent. EMG, therefore, is a good diagnostic biomarker.
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What is a Cutometer?
The cutometer is a device that can be used to measure the elastic properties of skin. A small probe is gently pressed against the skin and suction is applied. This creates a vacuum and the skin is lifted, stretched and then released. These deflections are optically recorded and quantified. The test is entirely non-invasive and painless. It carries no risk of damaging the skin.
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What is EIM?
EIM stands for “electrical impedance myography”. The development of EIM was motivated by the desire to find a muscle test that does not require the insertion of needles into the muscle (see ‘What is EMG?’ above). EIM is an entirely non-invasive and painless procedure; in fact it is practically imperceptible. Sticky electrodes are placed on the hands and feet as well as over muscles of particular interest. A high-frequency, but very low intensity current is passed through the muscles, and measurements are made. EIM provides information about the physical or mechanical properties of muscle.
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Can EIM or cutometry be used to detect ALS in advance of the onset of symptoms?
The short answer is that these tests do not currently provide sufficient information to tell whether ALS has yet begun. Our hope, however, is that our research will permit us eventually to use these techniques to determine whether ALS has begun even before symptoms begin.
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What is the rationale for studying the skin in ALS?
It has long been recognized that patients with ALS tend not to develop bedsores despite the immobility that develops as the disease progresses. This has led some investigators to hypothesize that there is something different about the skin in ALS. In the past it has only been possible to study the skin by taking a biopsy and examining the skin under a microscope. With the Cutometer we now have an ability to measure certain properties (notably the elasticity and plasticity) of the skin without the need for a biopsy. Our collaborators have previously shown that the viscoelastic properties of skin differ between patients with ALS and healthy controls.
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What is an MRI?
MRI stands for magnetic resonance imaging. MRI can be used to take a picture of the inside of a living thing such as a person or an animal. Unlike x-rays that use ionizing radiation, MRI uses radiofrequency waves, and so an MRI scan carries no risk of exposure to radiation. The radiofrequency waves create a magnetic field, which in turn ‘excites’ atoms in the tissue being imaged. The pattern of “excitation” and “relaxation” of these atoms can be used to generate a three-dimensional picture of body organs, such as the brain and spinal cord.
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What is an EMG?
EMG stands for “electromyography”, which literally means a recording of the electrical activity of muscles. The electrical activity of a muscle is recorded by putting a thin needle into the muscle. The needle acts as a microphone to amplify the sound made by the muscle when it contracts and when it is relaxed. These sounds are recorded and can be interpreted by a neurologist to learn something about the health of nerves and muscles. The term EMG is often used to include, not only the procedure for recording the electrical activity of muscle, but also a test known as nerve conduction studies (NCS). NCS are performed without needles. Instead, sticky electrodes are placed on the skin overlying a nerve or muscle. Gentle electrical shocks are administered, and the responses from nerve and muscle recorded using the sticky electrodes. The shocks are initially quite soft, but the intensity is gradually increased to find out how well the nerve is working.
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What is a lumbar puncture?
A lumbar puncture (LP) is also known as a spinal tap. An LP entails the placement of a needle into the lower back, between the bones of the spine. This is done either with you lying on your side curled up in the fetal position or sitting upright and rounding your back. The skin and underlying tissues of the lower back are injected with numbing medicine. After the skin has been appropriately cleansed, a needle is inserted into the lower back into the fluid-containing sac that surrounds the spinal cord and nerve roots. The needle is inserted below the level of the spinal cord so there is no risk of damage to the spinal cord.
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What are the complications of a lumbar puncture?
The most common complication of a lumbar puncture is a headache, sometimes called a “spinal headache”. Spinal headaches occur most often in young women, but can affect anyone. Perhaps about 1 in 10 people will develop a headache following a spinal tap. To reduce the risk of a spinal headache you should lie down for 30-60 minutes after having an LP. You should also drink lots of fluids, including caffeinated beverages. If the headache persists, your doctor may need to give you intravenous caffeine or perform what is known as a blood patch.
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What are stem cells?
To understand what stems cells are, it is helpful to begin by appreciating that there are many different kinds of cells in the human body – nerve cells, heart cells, liver cells, skin cells, etc. These different cells have “differentiated” to become specialized in performing important tasks for the brain, heart, liver and skin respectively. Stem cells, on the other hand, are the “master” cells of the human body. They are unspecialized or undifferentiated, but they have two important properties. The first is that they are able to make copies of themselves. The second is that they have the potential to differentiate into any type of cell. Given appropriate conditions, therefore, a stem cell can be encouraged to differentiate into a nerve cell.
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If I undergo MRI (or cutometry or EIM) more than once, is it possible to tell whether there has been any change between the two test sessions?
Our hope is that it will be possible to measures changes in the brain, nerves, muscle or skin using techniques such as MRI, MUNE, EIM and cutometry. However, since this is precisely the question that we are trying to research, it is likely that we will not yet be able to provide you with a personalized answer as to whether your brain, nerves, muscle or skin have changed.
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