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Nerve Pathology In CIDP

Mark B. Bromberg, MD, PhD, Neurology, discusses the use of nerve conduction studies to estimate nerve pathology in CIDP.

Transcript

Nerve Pathology In CIDP

Mark B. Bromberg, MD, PhD, Neurology, discusses the use of nerve conduction studies to estimate nerve pathology in CIDP.

My name is Mark Bromberg, I'm a professor of neurology at the University of Utah. I began my career with a doctoral degree in neurophysiology. When I decided to go into clinical medicine, I chose neurology with a subspecialization in nerve and muscle disorders and clinical neurophysiology. What I'd like to talk now is estimating the underlying nerve pathology using primarily nerve conduction studies.

I do want to point out that there is a relationship with respect to conduction velocity between the diameter of the nerve fiber and the rate of conduction. So you can see on the left upper side, we have a normal nerve, and there we have 4 different nerve fibers. The bottom one is the largest diameter, the top one is the smallest diameter, and the largest diameter fiber has the longest internode length. In other words, the length of the Schwann cell is longest in the largest fibers and with saltatory conduction you can appreciate that the nerve impulse goes rapidly under the myelin, takes time to regenerate at the node of Ranvier, and then goes under the next myelin sheath.

If you look at the top nerve fiber, there you can see that it's not going to go rapidly very far before it takes the time to regenerate. Then the graph on the right, you can see that there is a linear relationship, so the larger the diameter fiber, the longer the internode length and, hence, the faster the conduction velocity. And I always like to have kind of a rough number in mind, so a 10-micron diameter fiber has an internode length of about a millimeter.

Now, if you look on the left on the lower side, we have demyelination and subsequent remyelination. And when you remyelinate, you lose that linear relationship. So sometimes you remyelinate with shorter segments and so the previously normal fibers that conducted rapidly, if they remyelinate, they'll conduct slowly. And one corollary to this is that if you have a patient with CIDP and you treat them and they become markedly stronger, you may not have nerve conduction studies that normalize.

Now, here are some pictures of pathology under the microscope. On the top left, you can see that it's electron micrograph and there's a myelinated fiber that has undergone demyelination and subsequent remyelination, and there's something called onion bulb formation. Then on the upper right, you can see there can be mixed pathology, and so the arrow points to axonal loss with regrowth of new axons. And on the bottom, you can see a process called teased-fiber examination, where they take a nerve sample out and they try to tease apart individual nerve fibers, very similar to what I showed you in the previous slide. And you can see, the arrow there is showing a segment of focal demyelination.

And then again, here are 2 electron micrographs. On the left you can see the tight density of normal number of axons, and on the right you can see a marked loss where you have primary axonal loss. And then, again on the upper part there, you see a teased fiber that is normal, and then the one below that you can see there is focal demyelination, which could cause block of the impulse along that fiber. That would be an example of focal conduction block that you could attribute to demyelination.

But as I mentioned earlier, under the microscope you may see no structural pathology, and that gets to a functional block at the node of Ranvier. And so this is a rather complex slide but appreciate that there's a horizontal line there and everything below that is the axon. Then, everything above that is going to be the myelin. And we're looking at the area where the compact myelin makes a transition to the node of Ranvier, which is going to be slightly to the left of the middle. And so, you can appreciate in the little figurines there…different colors that there are some, in minute amounts, small structural proteins that are essential for the integrity of the myelin and the integrity of how the myelin connects to the axon.

In CIDP we don't always know what causes the antibody-mediated attack on the myelin, but in a few examples we think that the epitope is going to be one of those areas that are circled with a small protein there. Something to keep in mind and we'll probably learn more about this in the future. But at this point, we don't always know what initiates the attack of antibodies at the myelin to cause primary demyelination.

I thank you for your time, and I hope that my talk with you has helped you understand some of the aspects of diagnosing CIDP.

Transcript

Nerve Pathology In CIDP

Mark B. Bromberg, MD, PhD, Neurology, discusses the use of nerve conduction studies to estimate nerve pathology in CIDP.

My name is Mark Bromberg, I'm a professor of neurology at the University of Utah. I began my career with a doctoral degree in neurophysiology. When I decided to go into clinical medicine, I chose neurology with a subspecialization in nerve and muscle disorders and clinical neurophysiology. What I'd like to talk now is estimating the underlying nerve pathology using primarily nerve conduction studies.

I do want to point out that there is a relationship with respect to conduction velocity between the diameter of the nerve fiber and the rate of conduction. So you can see on the left upper side, we have a normal nerve, and there we have 4 different nerve fibers. The bottom one is the largest diameter, the top one is the smallest diameter, and the largest diameter fiber has the longest internode length. In other words, the length of the Schwann cell is longest in the largest fibers and with saltatory conduction you can appreciate that the nerve impulse goes rapidly under the myelin, takes time to regenerate at the node of Ranvier, and then goes under the next myelin sheath.

If you look at the top nerve fiber, there you can see that it's not going to go rapidly very far before it takes the time to regenerate. Then the graph on the right, you can see that there is a linear relationship, so the larger the diameter fiber, the longer the internode length and, hence, the faster the conduction velocity. And I always like to have kind of a rough number in mind, so a 10-micron diameter fiber has an internode length of about a millimeter.

Now, if you look on the left on the lower side, we have demyelination and subsequent remyelination. And when you remyelinate, you lose that linear relationship. So sometimes you remyelinate with shorter segments and so the previously normal fibers that conducted rapidly, if they remyelinate, they'll conduct slowly. And one corollary to this is that if you have a patient with CIDP and you treat them and they become markedly stronger, you may not have nerve conduction studies that normalize.

Now, here are some pictures of pathology under the microscope. On the top left, you can see that it's electron micrograph and there's a myelinated fiber that has undergone demyelination and subsequent remyelination, and there's something called onion bulb formation. Then on the upper right, you can see there can be mixed pathology, and so the arrow points to axonal loss with regrowth of new axons. And on the bottom, you can see a process called teased-fiber examination, where they take a nerve sample out and they try to tease apart individual nerve fibers, very similar to what I showed you in the previous slide. And you can see, the arrow there is showing a segment of focal demyelination.

And then again, here are 2 electron micrographs. On the left you can see the tight density of normal number of axons, and on the right you can see a marked loss where you have primary axonal loss. And then, again on the upper part there, you see a teased fiber that is normal, and then the one below that you can see there is focal demyelination, which could cause block of the impulse along that fiber. That would be an example of focal conduction block that you could attribute to demyelination.

But as I mentioned earlier, under the microscope you may see no structural pathology, and that gets to a functional block at the node of Ranvier. And so this is a rather complex slide but appreciate that there's a horizontal line there and everything below that is the axon. Then, everything above that is going to be the myelin. And we're looking at the area where the compact myelin makes a transition to the node of Ranvier, which is going to be slightly to the left of the middle. And so, you can appreciate in the little figurines there…different colors that there are some, in minute amounts, small structural proteins that are essential for the integrity of the myelin and the integrity of how the myelin connects to the axon.

In CIDP we don't always know what causes the antibody-mediated attack on the myelin, but in a few examples we think that the epitope is going to be one of those areas that are circled with a small protein there. Something to keep in mind and we'll probably learn more about this in the future. But at this point, we don't always know what initiates the attack of antibodies at the myelin to cause primary demyelination.

I thank you for your time, and I hope that my talk with you has helped you understand some of the aspects of diagnosing CIDP.


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Terms to know

IG=immune globulin, CIDP=chronic inflammatory demyelinating polyneuropathy, PIDD=primary immunodeficiency disease, ITP=idiopathic thrombocytopenic purpura, Sub Q=subcutaneous, IV=intravenous, ICE=10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) CIDP efficacy.

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