Every Day

May - July 2006 Issue

In-House Lab Streamlines
Skin, Muscle and Nerve Biopsies

Isabel P. Collins, MD

Medical College of Wisconsin Neurologist

Froedtert & the Medical College of Wisconsin have one of only two labs in Wisconsin that are equipped to perform and interpret biopsies for neuromuscular diseases. The Muscle and Nerve Laboratory is supervised and run by specialists with specific expertise in neuromuscular diseases and pathology. Having specialists on-site to do this complex work streamlines the diagnostic process and helps in determining the proper treatment course for patients with muscle or nerve diseases.

Q: What is a biopsy?

It’s a minor surgical procedure in which a piece or pieces of tissue, whether muscle or skin or nerve, are removed for microscopic examination.

Q: How is a biopsy used in the treatment of muscle, skin and nerve diseases?

A muscle biopsy is done in patients suspected of having a myopathy, or muscle disease, with symptoms such as muscle weakness or pain. The biopsy allows us to distinguish whether the symptoms are arising from a problem with the nerve or the muscle. If it is a muscle disease, the biopsy may provide a more specific diagnosis, such as polymyositis or dermatomyositis, which are types of inflammatory muscle diseases that can respond to treatment. Other times, it does not provide a specific diagnosis, but provides information regarding a patient’s muscle disease that, when combined with the clinical picture and results of other tests, allows a treating physician to arrive at a diagnosis and a treatment plan.

A nerve biopsy is usually performed in a patient with a known neuropathy, or nerve disease. It is not performed in everyone with a neuropathy. On the contrary, it is only performed in a few select patients. Most commonly, the biopsy is done in patients who are suspected of having vasculitis, which is an inflammation of the blood vessels within the nerves. This is a potentially treatable condition, but requires the use of steroids or strong medications that suppress the immune system.

A skin biopsy is usually done in patients suspected of having what is called a small fiber neuropathy. It is a condition that typically presents with burning pain, often in the feet. There are several potential causes for a small fiber neuropathy, such as diabetes or HIV and AIDS, but more often than not, this condition is idiopathic, meaning a cause cannot be identified. The most definitive way of establishing a diagnosis is by directly examining the small nerve fibers in the skin.

Q: Is this the only way to diagnose neuromuscular diseases?

No. The most important thing really is a good neuromuscular examination. Before a biopsy is done, an electromyography (EMG) and blood tests are usually done first. Many times, a diagnosis can be arrived at without having to proceed with a biopsy. This is particularly true in the case of nerve diseases. It is also true for some muscular dystrophies, many of which can be diagnosed with DNA testing in the blood. For other muscle diseases, though, a biopsy is often required to arrive at a more specific diagnosis.

Q: What are some of the symptoms that might bring patients to the point where they have these kinds of biopsies?

The typical symptoms of nerve diseases are numbness, tingling, pain and sometimes weakness. Muscle diseases are characterized by muscle weakness, with or without pain. As previously mentioned, skin biopsies are most commonly done in patients with burning pain.

Q: What is the process for me as a patient?

For a skin biopsy, we cleanse and numb the area that is to be biopsied. We then employ an instrument that “punches” out a three-millimeter piece of skin. It takes about 15 minutes. Sometimes, we may decide to put in a single suture, which allows for quicker wound healing.

Muscle and nerve biopsies are more involved.

The most common nerve taken in a nerve biopsy is the sural nerve, which runs down the back of the leg. This is usually the nerve of choice, because it is a pure sensory nerve. Its only function is to provide sensation on the outside of the foot. So it will not cause any weakness if it is removed. Also, at around the level of the ankle, it comes close to the surface of the skin. So, it is very easily located. But it is very important that we choose the nerve that is most likely to help you arrive at a diagnosis.

We perform the nerve biopsy in an outpatient surgical procedure room using standard sterile technique. The incision is usually about 2.5 cm long. The nerve is anesthetized so for the majority of patients, this procedure is not painful. The skin opening is usually closed with a special glue or we use a suture.

For a muscle biopsy, again the choice of muscle to be biopsied is very important. Optimally, you want to biopsy a muscle that is only moderately affected. Some muscle diseases affect muscles in a “patchy” manner — some muscles are affected, but not others, and, in fact, sometimes only parts of a muscle are affected.

For the procedure itself, we cleanse and numb the skin over the muscle to be biopsied. Then we make a small incision and usually remove two to three small pieces of muscle tissue. The wound is closed with absorbable sutures and the skin is sealed. The procedure takes about 45 minutes to an hour. We are able to identify the severity of the muscle involvement, based upon the results.

Q: What happens once a biopsy is performed?

The tissue is taken to the Muscle and Nerve Laboratory where it is sliced into very thin sections. We use different stains to allow us to see the overall appearance and the various structures of the muscle or nerve.

We may use histochemical stains. These are stains that allow us to screen for problems with muscle metabolism. Depending on what we see, we may do further biochemical testing to further evaluate for specific enzyme abnormalities.

We may also use immunohistochemical stains. This is a technique wherein antibodies are used to allow us to assess for the presence or absence of specific proteins. This is used, for instance, when we are trying to identify the specific protein that may be missing or abnormal in muscular dystrophies such as Duchenne’s or Becker’s muscular dystrophy as well as some other muscular dystrophies. We also do immunohistochemical staining if we see inflammatory cells in a nerve or muscle and want to specifically identify what kind of inflammatory cells they are.

We are also equipped with our own electron microscope. Electronmicroscopy allows us to look at tissue at a very high magnification. This allows us to look at structures or abnormalities that may be too small to be seen by a light microscope.

Depending on what the initial stains show, we sometimes proceed with DNA testing. DNA testing can be done on the blood in many cases, but for some mitochondrial diseases, for instance, muscle tissue is required.

Q: What makes the process at the lab here different?

One distinction of our Neuromuscular Clinic is that we are able to offer a complete package — a comprehensive neuromuscular evaluation, electrodiagnostic and autonomic testing, a biopsy if necessary, and interpretation of the biopsy in proper clinical context.

The biopsy itself is performed by a neuromuscular specialist who has a grasp of why the biopsy is being performed and is able to choose the most appropriate muscle for biopsy, taking just the right amount of tissue that he or she anticipates will be necessary — not too much and not too little.

It is of paramount importance that a biopsy be interpreted in clinical context. Ideally, the pathologist should have some understanding of the history, symptoms and exam findings that prompted the biopsy. Our decision to perform special stains is dependent on our knowledge of what we are looking for ... what the possibilities might be. Also, sometimes, the biopsy shows “non-specific changes,” meaning abnormalities are seen, but they are not specific to any single disease. Hence, arriving at a diagnosis requires correlation of the biopsy findings with the clinical picture. This correlation is best performed by someone with expertise in neuromuscular diseases.

We do receive a lot of muscle tissue from biopsies performed at outside institutions. This is alright, but, ideally, the tissue should be accompanied by as much information as possible regarding the patient’s clinical history.

Q: What developments do you see on the immediate horizon?

DNA testing is now available to diagnose some hereditary conditions where biopsies were used in the past. Examples are some of the types of Charcot-Marie-Tooth Disease — a hereditary neuropathy that affects the nerves that control many muscles in the body, and certain forms of muscular dystrophy. In the future, as techniques expand and improve, more inherited conditions may be diagnosed using DNA, eliminating the need for biopsies in those cases.

Source: Every Day

Date: May - July 2006 Issue