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When it's not CIDP

Todd Levine, MD, Neurology, covers considerations for patients who have demyelination on nerve conduction studies but may not have CIDP.

Transcript

When it's not CIDP

Todd Levine, MD, Neurology, covers considerations for patients who have demyelination on nerve conduction studies but may not have CIDP.

Hi, my name is Todd Levine, and I want to talk a bit today about what to think when you find a patient that has demyelinating nerve conduction studies, though where it may not be CIDP. So when should you suspect that a patient's neuropathy, even if it has demyelinating changes on the nerve conduction studies, is not CIDP?

Well, the first and most important is when the disorder does not meet EFNS/PNS criteria. And primarily, what we mean by that is the clinical criteria. So this would be a patient that does not have typical proximal and distal muscle weakness with sensory loss and decreased reflexes, but whose nerve conduction studies look demyelinating.

The other reason to think that a patient's demyelinating changes on their nerve conduction studies are not CIDP is if the patient does not respond to immunomodulatory therapies the way that you would expect. And this is even part of the inclusion criteria for EFNS/PNS diagnostic algorithm for CIDP. And lastly, always bear in mind the fact that the patient's other concurrent illnesses might cause similar changes.

So what types of diseases are we talking about that may present with nerve conduction slowing, but not be CIDP? Well, the one that we're all aware of, and the most important, is distinguishing an inherited neuropathy from an acquired neuropathy. So what I mean by that is patients with Charcot-Marie-Tooth. But we also see many patients who have paraprotein-related neuropathies, such as POEMS, or anti-MAG, or IgM-related neuropathies that can have demyelinating changes that are not CIDP.

We'll also discuss how amyloid can look like CIDP. And lastly, we'll go in depth into a discussion about diabetic neuropathy and how that can be confused for CIDP.

So what allows us to distinguish an inherited neuropathy from an acquired demyelinating neuropathy? Well, the thing that we're taught most is that inherited neuropathies are uniform. That the conduction slowing is everywhere on every nerve exactly the same. And while that's true for CMT Type 1A, we now know that there are many inherited neuropathies that can have more patchy conduction velocity slowing.

We also know that patients can have inherited neuropathies that do not conform to a typical dominant inheritance pattern, either due to recessive disorders or de novo mutations. On the other hand, the acquired neuropathies will have both proximal and distal weakness. Their changes on the nerve conduction studies are almost always non-uniform, and therefore, more likely to have temporal dispersion or conduction block. And the CSF protein is much more likely to be increased in patients with acquired neuropathies than in patients with inherited neuropathies.

Now, the paraprotein neuropathies are a big problem for us in patients that have demyelinating neuropathies. And the reason is, that we know that both IgM and IgG paraproteins can be associated with peripheral neuropathies. The IgM paraproteins are much more likely to be associated with demyelinating neuropathies and the IgG more likely to be axonal.

We also know that the incidence of IgG paraproteins increases even in normals over the age of 60 to as much as 5% of the population. So what that means is if you screened 100 patients with peripheral neuropathy, 5 of them would have an IgG paraprotein, which may be completely unrelated to their neuropathy.

Now, if patients have an IgM paraprotein and have a peripheral neuropathy, about 50% of those will have specific auto antibodies against MAG. These anti-MAG neuropathies usually look different than the typical acquired demyelinating neuropathies. They're much more sensory, much more distal, and usually have very long distal latencies, as opposed to the conduction velocity slowing. There also is more prominent sensory ataxia and tremor in patients with anti-MAG neuropathies.

Now, amyloid neuropathy can occur in 1 of 2 ways. You can have an acquired amyloid neuropathy with free light chains that deposit in the nerves. Or you can have an inherited neuropathy usually due to mutations in the transthyretin gene. The clinical picture of patients with amyloid neuropathy and with CIDP overlap, as well as the electrophysiologic changes. In addition, the CSF protein in patients with amyloid neuropathy is just as likely to be elevated as in patients with CIDP.

We typically only think of amyloid neuropathy when the amyloid is deposited widely. So patients have cardiac involvement, renal involvement, and other organ system failure. But it turns out that many patients can have primarily a demyelinating neuropathy due to amyloid. And therefore, in patients where you suspect CIDP, particularly those that do not respond, you should consider additional tissue biopsies or transthyretin analysis.

POEMS syndrome stands for polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes. Many of these patients will have an osteosclerotic myeloma and should always have a bone survey to look for that.

Both POEMS and CIDP can have changes of a patchy acquired demyelinating neuropathy. But generally, POEMS syndrome patients have less involvement of distal latencies and will have much more axonal loss, particularly early in the course of the disease, than patients with CIDP. Finally, POEMS patients usually have much more uniform demyelination, sometimes even to the point of looking like Charcot-Marie-Tooth than patients with CIDP.

B12 deficiency can cause a neuropathy, and most of us think of B12 deficiency as causing a typical mixed axonal neuropathy and demyelinating process. But several studies have shown up to 10 or 11% of patients with B12 deficiency can have only demyelinating features. And 1 report showed that B12 deficiency can be primarily demyelinating, even to the point of having conduction block, which was then reversed once the patient got replaced with B12. Most of us will check our patients for B12 deficiency, but it's an important thing to keep in mind.

I hope you can see that there are many diseases other than CIDP that can have demyelinating changes on their nerve conduction studies. The key feature that should make us think about these more rare diagnoses is a patient that doesn't respond to therapy. I hope you found this talk helpful and will keep these diagnoses in mind as you approach your more difficult, challenging demyelinating patients.

Transcript

When it's not CIDP

Todd Levine, MD, Neurology, covers considerations for patients who have demyelination on nerve conduction studies but may not have CIDP.

Hi, my name is Todd Levine, and I want to talk a bit today about what to think when you find a patient that has demyelinating nerve conduction studies, though where it may not be CIDP. So when should you suspect that a patient's neuropathy, even if it has demyelinating changes on the nerve conduction studies, is not CIDP?

Well, the first and most important is when the disorder does not meet EFNS/PNS criteria. And primarily, what we mean by that is the clinical criteria. So this would be a patient that does not have typical proximal and distal muscle weakness with sensory loss and decreased reflexes, but whose nerve conduction studies look demyelinating.

The other reason to think that a patient's demyelinating changes on their nerve conduction studies are not CIDP is if the patient does not respond to immunomodulatory therapies the way that you would expect. And this is even part of the inclusion criteria for EFNS/PNS diagnostic algorithm for CIDP. And lastly, always bear in mind the fact that the patient's other concurrent illnesses might cause similar changes.

So what types of diseases are we talking about that may present with nerve conduction slowing, but not be CIDP? Well, the one that we're all aware of, and the most important, is distinguishing an inherited neuropathy from an acquired neuropathy. So what I mean by that is patients with Charcot-Marie-Tooth. But we also see many patients who have paraprotein-related neuropathies, such as POEMS, or anti-MAG, or IgM-related neuropathies that can have demyelinating changes that are not CIDP.

We'll also discuss how amyloid can look like CIDP. And lastly, we'll go in depth into a discussion about diabetic neuropathy and how that can be confused for CIDP.

So what allows us to distinguish an inherited neuropathy from an acquired demyelinating neuropathy? Well, the thing that we're taught most is that inherited neuropathies are uniform. That the conduction slowing is everywhere on every nerve exactly the same. And while that's true for CMT Type 1A, we now know that there are many inherited neuropathies that can have more patchy conduction velocity slowing.

We also know that patients can have inherited neuropathies that do not conform to a typical dominant inheritance pattern, either due to recessive disorders or de novo mutations. On the other hand, the acquired neuropathies will have both proximal and distal weakness. Their changes on the nerve conduction studies are almost always non-uniform, and therefore, more likely to have temporal dispersion or conduction block. And the CSF protein is much more likely to be increased in patients with acquired neuropathies than in patients with inherited neuropathies.

Now, the paraprotein neuropathies are a big problem for us in patients that have demyelinating neuropathies. And the reason is, that we know that both IgM and IgG paraproteins can be associated with peripheral neuropathies. The IgM paraproteins are much more likely to be associated with demyelinating neuropathies and the IgG more likely to be axonal.

We also know that the incidence of IgG paraproteins increases even in normals over the age of 60 to as much as 5% of the population. So what that means is if you screened 100 patients with peripheral neuropathy, 5 of them would have an IgG paraprotein, which may be completely unrelated to their neuropathy.

Now, if patients have an IgM paraprotein and have a peripheral neuropathy, about 50% of those will have specific auto antibodies against MAG. These anti-MAG neuropathies usually look different than the typical acquired demyelinating neuropathies. They're much more sensory, much more distal, and usually have very long distal latencies, as opposed to the conduction velocity slowing. There also is more prominent sensory ataxia and tremor in patients with anti-MAG neuropathies.

Now, amyloid neuropathy can occur in 1 of 2 ways. You can have an acquired amyloid neuropathy with free light chains that deposit in the nerves. Or you can have an inherited neuropathy usually due to mutations in the transthyretin gene. The clinical picture of patients with amyloid neuropathy and with CIDP overlap, as well as the electrophysiologic changes. In addition, the CSF protein in patients with amyloid neuropathy is just as likely to be elevated as in patients with CIDP.

We typically only think of amyloid neuropathy when the amyloid is deposited widely. So patients have cardiac involvement, renal involvement, and other organ system failure. But it turns out that many patients can have primarily a demyelinating neuropathy due to amyloid. And therefore, in patients where you suspect CIDP, particularly those that do not respond, you should consider additional tissue biopsies or transthyretin analysis.

POEMS syndrome stands for polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes. Many of these patients will have an osteosclerotic myeloma and should always have a bone survey to look for that.

Both POEMS and CIDP can have changes of a patchy acquired demyelinating neuropathy. But generally, POEMS syndrome patients have less involvement of distal latencies and will have much more axonal loss, particularly early in the course of the disease, than patients with CIDP. Finally, POEMS patients usually have much more uniform demyelination, sometimes even to the point of looking like Charcot-Marie-Tooth than patients with CIDP.

B12 deficiency can cause a neuropathy, and most of us think of B12 deficiency as causing a typical mixed axonal neuropathy and demyelinating process. But several studies have shown up to 10 or 11% of patients with B12 deficiency can have only demyelinating features. And 1 report showed that B12 deficiency can be primarily demyelinating, even to the point of having conduction block, which was then reversed once the patient got replaced with B12. Most of us will check our patients for B12 deficiency, but it's an important thing to keep in mind.

I hope you can see that there are many diseases other than CIDP that can have demyelinating changes on their nerve conduction studies. The key feature that should make us think about these more rare diagnoses is a patient that doesn't respond to therapy. I hope you found this talk helpful and will keep these diagnoses in mind as you approach your more difficult, challenging demyelinating patients.


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The most serious adverse reactions in clinical studies were pulmonary embolism (PE) in 1 subject with a history of PE (in CIDP), an exacerbation of autoimmune pure red cell aplasia in 1 subject (in PIDD), and myocarditis in 1 subject that occurred 50 days post-study drug infusion and was not considered drug related (in ITP).

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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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