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Challenges with Nerve Conduction Studies

Mark B. Bromberg, MD, PhD, Neurology, presents the challenges and technical issues of using nerve conduction studies to diagnose CIDP.

Transcript

Challenges with Nerve Conduction Studies

Mark B. Bromberg, MD, PhD, Neurology, presents the challenges and technical issues of using nerve conduction studies to diagnose 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.

Today, I'd like to talk to you about some of the challenges and technical issues applying nerve conduction studies to try to diagnose primary demyelination in CIDP. One of the challenges in applying nerve conduction criteria to try to diagnose CIDP is that not every patient fulfills criteria. In other words, the sensitivity for criteria may not be 100%.

And that's illustrated here, and so, you can see that we have a plot of nerve conduction values from different groups of patients. On the left-hand side of these figures, we've got the values from patients with CIDP, and on the middle, we have patients with diabetic neuropathy, and on the right, we have patients with motor neuron disease, or ALS. And then, we're showing the distal latency, F-wave latency, and conduction block, and we're also showing the laboratory lower limits of normal. Now, if you factor in the change in conduction velocity, distal latency, and F-wave latency in patients with ALS, which is a pure axonal neuropathy, that is listed as the 75% or 125%.

And then you look at the distribution of CIDP patients. Some of them are even in the normal range. So individual nerves in patients with CIDP may be normal, and that's why that nerve does not fulfill criteria. So with the spectrum of changes amongst nerves within patients with CIDP, that range means that you cannot get 100% who fulfill all of the diagnostic criteria.

Another point to keep in mind is that you can look at individual nerves and talk about their conduction velocity and things like that. But, the whole nerve consists of many nerve fibers that are in tight proximity. And so, you have ions moving back and forth with the action potentials along the nerves at the nodes of Ranvier. But some of the ion flows can indirectly affect neighboring nerve fibers, which could influence their conduction velocity. It could artificially increase them, or it could artificially slow them. So that's another reason why, even though we feel there's underlying pathology for individual nerves, it may be disguised because of the milieu that the nerve fibers are conducting in.

The criteria are relatively complicated to apply, and so one way is to have a guideline. These are not the formal criteria for drug trials. But these are guidelines for you to keep in mind that are relatively simplified, and if a patient begins to fulfill those, then you can say that there's greater slowing than expected for the degree of axonal loss, and then I will consider a primary demyelinating neuropathy.

And these values come from amyotrophic lateral sclerosis, or ALS, which is a pure axonal neuropathy. Taking those data, it found that conduction velocity is rarely slower than 25%, or the value is going to be greater than 75% of the lower limit of normal, and distal latency is not going to be prolonged more than 25%, so the values are going to be less than 125% of the upper limit of normal. And the same thing with F-wave latencies.

So, if you find values that are outside of that, then that makes you think that there's slowing greater than expected for axonal loss, and then you may want to go back to the formal criteria to see if your patient fits into that.

So, here's what you could do. You could take your laboratory's limits of normal, and this is what we have in our laboratory, and then you can see the ones in red are the values that if you are greater than those would make you think that there's primary demyelination.

So far, we're focused on motor nerve conduction values because frequently, the sensory may be absent. If you have an absent response, you don't know whether that's due to demyelination or axonal loss.

But if the neuropathy is relatively mild, you may have some sensory responses, and there is a pattern that's been observed empirically that in primary demyelinating neuropathies, if you compare the median sensory response to the sural sensory response, if the median is abnormal in any way and the sural is normal in any way, that abnormal median/normal sural is found more often in primary demyelinating neuropathies than it is found in any other neuropathy. It's not exclusive, because you do find it in diabetic polyneuropathy. But, if you do find an abnormal median and a normal sural, then that is supportive. The reason why you might find that pattern is that, if you look in the diagram there, for the median, you tend to be recording at the very ends of the nerves, so you're looking where there's distal pathology. But for practical reasons, in the sural nerve you're recording a little more proximal and so you're not where the very terminal pathology is.

So, you may ask, well how can this be? And so, the diagram on the right illustrates that. For practical reasons, when you're recording the median sensory potential, your electrodes are out on the end of the digit and you're at the very terminal portions of the nerve fibers. In contrast, on the sural nerve, your electrodes are placed more proximally, and so if the brunt of the pathology is at the very distal ends, you'll include that with the median responses, but you will miss that with the sural responses.

There are strategies for testing for suspected CIDP. The first is at least test for distal nerves. And so, in the upper extremity, there is the median and the ulnar, and in the lower extremity, there is the peroneal and the tibial. One advantage of the ulnar nerve is that you can test it by stimulating in the axilla and get an additional 200 mm of distance that'll help you look for evidence of abnormal temporal dispersion. If you don't find sufficient nerves to fulfill criteria, or if the neuropathy is severe and you have absent responses in the legs, then you may want to test a nerve on the other side. Testing nerves proximally is challenging except for the ulnar nerve because you may be over- or under-stimulating the median nerve in the arm. And it's very difficult to stimulate some nerves in the legs proximally, especially the tibial nerve.

Now, there are some caveats. Back to the tibial nerve, it's practical experience that when you stimulate in the popliteal fossa or at the knee, you get a much lower amplitude even if you turn the intensity up to maximum. And this is not due to conduction block. This is due to the fact that there may be different volume conduction compared to stimulating distally and proximally. So you cannot use the drop in amplitude to proximal stimulation in the tibial nerve as evidence for conduction block. For the peroneal or the fibular nerve across the fibular head, you have to be careful looking for slowed conduction, because it may be difficult to accurately measure the distance from below the fibular head into the popliteal fossa.

And as we talked about for the median nerve, it's a little challenging when you stimulate it in the axilla not to overstimulate and bring in ulnar enervated muscles that are also in the thenar eminence where the recording electrodes are.

And finally, Erb's point can be very difficult because the nerves are relatively deep and there may be insufficient current coming out of the stimulator even if you are at supramaximal.

Now there is another tip that occasionally that can be helpful, and that is you can look for changes in nerve conduction that are distal to your normal sites. So here's an example from the literature where they're recording over the extensor digitorum brevis muscle and they're stimulating the peroneal nerve, in this case at their usual site, 8 cm. And you can see that there is a pretty robust response. But if they move the stimulating electrode a little more distally, the amplitude drops off markedly and that's the opposite you would expect if it were a normal nerve. The amplitude would grow a little bit. So sometimes, you can get evidence for pathology between your normal stimulating site distally and the recording site.

Occasionally a question, the difference between a person who has diabetes and whether they have superimposed CIDP on top of that. And this can be a challenge, and there are some groups who feel that CIDP is more common amongst patients who have an initial underlying diabetic neuropathy. Now, that literature is a little bit debatable, but it does happen. You can have a person who has a diabetic neuropathy and then develops CIDP.

So the question is, how would you distinguish between the 2? The first is the clinical course. Diabetic neuropathies tend to be relatively slowly progressive, maybe over months and certainly over years, where CIDP has a much more rapid onset. And so, if you have a patient who's had a slowly progressive peripheral neuropathy, and then over a relatively short time period, their neuropathy worsens and includes proximal weakness in a symmetric distribution, then clinically, you can think that they may have superimposed CIDP on top of a diabetic neuropathy.

But for the nerve conductions, admittedly that can be challenging. So if you look on the left-hand part of the slide, you see that the clear histograms would be normal nerve conduction over several nerves there, and the shaded histograms are showing that there is general slowing associated with diabetes. Now on the right-hand side, you see nerve conduction data from patients with CIDP and 2 kinds of diabetic neuropathy. And you can see there's an overlap.

So what you're looking for in addition to the clinical history, which is a clue, you're looking for greater slowing than you might expect for a diabetic neuropathy, but it can be challenging because there is slowing in a diabetic neuropathy.

So one question arises as to whether you would use nerve conductions to follow your patient's clinical response, to prove that they're getting better or to show that they are getting worse. We have a lot of data from the ICE trial. The ICE trial was a large and long duration trial, treating patients with CIDP with intravenous immunoglobulin.

So one of the outcomes measures was to do serial nerve conduction studies, and the findings were, number 1, in patients who clinically improved, some of their nerve conduction metrics, the amplitude, the timing, also improved. But sometimes they didn't change, and sometimes they got worse. So, the outcome of that is that it's not reliable using nerve conductions to follow your patients clinically.

The other issue in using nerve conduction studies to assess the degree of pathology is that the amplitude of the compound potential can vary in a normal nerve based on where the recording electrode is placed. So in the cartoon you see of the hand there, those black blotches represent where an electrode was placed over the muscle, and on the right-hand side, you can see the subsequent waveforms. So this is a normal nerve, and you can see that the waveform amplitudes vary markedly based on small changes in position. So if the original study was not conducted with optimization of the electrode position, in a subsequent study, if the amplitude is higher or lower, you do not know if that reflects pathology or if it just reflects a slightly different positioning of the electrode.

There are situations where it might be worthwhile to repeat nerve conduction studies. So, if you've seen a patient for a long time and you'd like to know if there is a greater degree of axonal loss, then looking for major changes in the compound potential amplitude could help you with that. Or, if you inherit a patient that is new to you and you want to see what their status is at the time you see them, it may be worthwhile getting a set of nerve conduction studies as your personal baseline.

Keep in mind that when you do your nerve conduction studies, if you have no response, then you have no real information. For the compound muscle potential, if you want to assess the degree of axonal loss, what you could do is to take the compound muscle action potential amplitudes from all the nerves on one side and add those together, and that sum could be compared to the lower limit of normal for all those nerves to see what percentage of the lower limit of normal the patient's nerves are, and that would give you a rough idea of the degree of axonal loss.

You could use needle EMG just to see if you have denervation in both distal and proximal muscles. Also keep in mind that, as you treat the patient and the initial demyelination changes over to remyelination, even if the patient is very strong, because the remyelination will give you shorter internode lengths, the nerve conduction study timing measures, distal latency and conduction velocity, may not return to normal even if the clinical response is better.

So your clinical judgment of the patient is the best measure compared to nerve conduction as to how well the patient is doing. Here's an example of how the needle EMG may help you a little bit. So, on the left-hand side, you can see that, with the weak activation, you got a normal number of motor units. The middle panel shows you a moderate loss of axons where, for this particular trace segment, you only see 2 motor units. And the one on the right is extreme axonal loss because you have a single motor unit firing 4 times, or 40 Hz. So again, the needle EMG only gives you a very rough approximation of the degree of axonal loss.

I hope that the information I've provided you today helps you understand the underlying pathology of CIDP and how we can use nerve conduction studies to make that diagnosis, and further, some of the pitfalls and challenges in using nerve conduction studies.

Transcript

Challenges with Nerve Conduction Studies

Mark B. Bromberg, MD, PhD, Neurology, presents the challenges and technical issues of using nerve conduction studies to diagnose 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.

Today, I'd like to talk to you about some of the challenges and technical issues applying nerve conduction studies to try to diagnose primary demyelination in CIDP. One of the challenges in applying nerve conduction criteria to try to diagnose CIDP is that not every patient fulfills criteria. In other words, the sensitivity for criteria may not be 100%.

And that's illustrated here, and so, you can see that we have a plot of nerve conduction values from different groups of patients. On the left-hand side of these figures, we've got the values from patients with CIDP, and on the middle, we have patients with diabetic neuropathy, and on the right, we have patients with motor neuron disease, or ALS. And then, we're showing the distal latency, F-wave latency, and conduction block, and we're also showing the laboratory lower limits of normal. Now, if you factor in the change in conduction velocity, distal latency, and F-wave latency in patients with ALS, which is a pure axonal neuropathy, that is listed as the 75% or 125%.

And then you look at the distribution of CIDP patients. Some of them are even in the normal range. So individual nerves in patients with CIDP may be normal, and that's why that nerve does not fulfill criteria. So with the spectrum of changes amongst nerves within patients with CIDP, that range means that you cannot get 100% who fulfill all of the diagnostic criteria.

Another point to keep in mind is that you can look at individual nerves and talk about their conduction velocity and things like that. But, the whole nerve consists of many nerve fibers that are in tight proximity. And so, you have ions moving back and forth with the action potentials along the nerves at the nodes of Ranvier. But some of the ion flows can indirectly affect neighboring nerve fibers, which could influence their conduction velocity. It could artificially increase them, or it could artificially slow them. So that's another reason why, even though we feel there's underlying pathology for individual nerves, it may be disguised because of the milieu that the nerve fibers are conducting in.

The criteria are relatively complicated to apply, and so one way is to have a guideline. These are not the formal criteria for drug trials. But these are guidelines for you to keep in mind that are relatively simplified, and if a patient begins to fulfill those, then you can say that there's greater slowing than expected for the degree of axonal loss, and then I will consider a primary demyelinating neuropathy.

And these values come from amyotrophic lateral sclerosis, or ALS, which is a pure axonal neuropathy. Taking those data, it found that conduction velocity is rarely slower than 25%, or the value is going to be greater than 75% of the lower limit of normal, and distal latency is not going to be prolonged more than 25%, so the values are going to be less than 125% of the upper limit of normal. And the same thing with F-wave latencies.

So, if you find values that are outside of that, then that makes you think that there's slowing greater than expected for axonal loss, and then you may want to go back to the formal criteria to see if your patient fits into that.

So, here's what you could do. You could take your laboratory's limits of normal, and this is what we have in our laboratory, and then you can see the ones in red are the values that if you are greater than those would make you think that there's primary demyelination.

So far, we're focused on motor nerve conduction values because frequently, the sensory may be absent. If you have an absent response, you don't know whether that's due to demyelination or axonal loss.

But if the neuropathy is relatively mild, you may have some sensory responses, and there is a pattern that's been observed empirically that in primary demyelinating neuropathies, if you compare the median sensory response to the sural sensory response, if the median is abnormal in any way and the sural is normal in any way, that abnormal median/normal sural is found more often in primary demyelinating neuropathies than it is found in any other neuropathy. It's not exclusive, because you do find it in diabetic polyneuropathy. But, if you do find an abnormal median and a normal sural, then that is supportive. The reason why you might find that pattern is that, if you look in the diagram there, for the median, you tend to be recording at the very ends of the nerves, so you're looking where there's distal pathology. But for practical reasons, in the sural nerve you're recording a little more proximal and so you're not where the very terminal pathology is.

So, you may ask, well how can this be? And so, the diagram on the right illustrates that. For practical reasons, when you're recording the median sensory potential, your electrodes are out on the end of the digit and you're at the very terminal portions of the nerve fibers. In contrast, on the sural nerve, your electrodes are placed more proximally, and so if the brunt of the pathology is at the very distal ends, you'll include that with the median responses, but you will miss that with the sural responses.

There are strategies for testing for suspected CIDP. The first is at least test for distal nerves. And so, in the upper extremity, there is the median and the ulnar, and in the lower extremity, there is the peroneal and the tibial. One advantage of the ulnar nerve is that you can test it by stimulating in the axilla and get an additional 200 mm of distance that'll help you look for evidence of abnormal temporal dispersion. If you don't find sufficient nerves to fulfill criteria, or if the neuropathy is severe and you have absent responses in the legs, then you may want to test a nerve on the other side. Testing nerves proximally is challenging except for the ulnar nerve because you may be over- or under-stimulating the median nerve in the arm. And it's very difficult to stimulate some nerves in the legs proximally, especially the tibial nerve.

Now, there are some caveats. Back to the tibial nerve, it's practical experience that when you stimulate in the popliteal fossa or at the knee, you get a much lower amplitude even if you turn the intensity up to maximum. And this is not due to conduction block. This is due to the fact that there may be different volume conduction compared to stimulating distally and proximally. So you cannot use the drop in amplitude to proximal stimulation in the tibial nerve as evidence for conduction block. For the peroneal or the fibular nerve across the fibular head, you have to be careful looking for slowed conduction, because it may be difficult to accurately measure the distance from below the fibular head into the popliteal fossa.

And as we talked about for the median nerve, it's a little challenging when you stimulate it in the axilla not to overstimulate and bring in ulnar enervated muscles that are also in the thenar eminence where the recording electrodes are.

And finally, Erb's point can be very difficult because the nerves are relatively deep and there may be insufficient current coming out of the stimulator even if you are at supramaximal.

Now there is another tip that occasionally that can be helpful, and that is you can look for changes in nerve conduction that are distal to your normal sites. So here's an example from the literature where they're recording over the extensor digitorum brevis muscle and they're stimulating the peroneal nerve, in this case at their usual site, 8 cm. And you can see that there is a pretty robust response. But if they move the stimulating electrode a little more distally, the amplitude drops off markedly and that's the opposite you would expect if it were a normal nerve. The amplitude would grow a little bit. So sometimes, you can get evidence for pathology between your normal stimulating site distally and the recording site.

Occasionally a question, the difference between a person who has diabetes and whether they have superimposed CIDP on top of that. And this can be a challenge, and there are some groups who feel that CIDP is more common amongst patients who have an initial underlying diabetic neuropathy. Now, that literature is a little bit debatable, but it does happen. You can have a person who has a diabetic neuropathy and then develops CIDP.

So the question is, how would you distinguish between the 2? The first is the clinical course. Diabetic neuropathies tend to be relatively slowly progressive, maybe over months and certainly over years, where CIDP has a much more rapid onset. And so, if you have a patient who's had a slowly progressive peripheral neuropathy, and then over a relatively short time period, their neuropathy worsens and includes proximal weakness in a symmetric distribution, then clinically, you can think that they may have superimposed CIDP on top of a diabetic neuropathy.

But for the nerve conductions, admittedly that can be challenging. So if you look on the left-hand part of the slide, you see that the clear histograms would be normal nerve conduction over several nerves there, and the shaded histograms are showing that there is general slowing associated with diabetes. Now on the right-hand side, you see nerve conduction data from patients with CIDP and 2 kinds of diabetic neuropathy. And you can see there's an overlap.

So what you're looking for in addition to the clinical history, which is a clue, you're looking for greater slowing than you might expect for a diabetic neuropathy, but it can be challenging because there is slowing in a diabetic neuropathy.

So one question arises as to whether you would use nerve conductions to follow your patient's clinical response, to prove that they're getting better or to show that they are getting worse. We have a lot of data from the ICE trial. The ICE trial was a large and long duration trial, treating patients with CIDP with intravenous immunoglobulin.

So one of the outcomes measures was to do serial nerve conduction studies, and the findings were, number 1, in patients who clinically improved, some of their nerve conduction metrics, the amplitude, the timing, also improved. But sometimes they didn't change, and sometimes they got worse. So, the outcome of that is that it's not reliable using nerve conductions to follow your patients clinically.

The other issue in using nerve conduction studies to assess the degree of pathology is that the amplitude of the compound potential can vary in a normal nerve based on where the recording electrode is placed. So in the cartoon you see of the hand there, those black blotches represent where an electrode was placed over the muscle, and on the right-hand side, you can see the subsequent waveforms. So this is a normal nerve, and you can see that the waveform amplitudes vary markedly based on small changes in position. So if the original study was not conducted with optimization of the electrode position, in a subsequent study, if the amplitude is higher or lower, you do not know if that reflects pathology or if it just reflects a slightly different positioning of the electrode.

There are situations where it might be worthwhile to repeat nerve conduction studies. So, if you've seen a patient for a long time and you'd like to know if there is a greater degree of axonal loss, then looking for major changes in the compound potential amplitude could help you with that. Or, if you inherit a patient that is new to you and you want to see what their status is at the time you see them, it may be worthwhile getting a set of nerve conduction studies as your personal baseline.

Keep in mind that when you do your nerve conduction studies, if you have no response, then you have no real information. For the compound muscle potential, if you want to assess the degree of axonal loss, what you could do is to take the compound muscle action potential amplitudes from all the nerves on one side and add those together, and that sum could be compared to the lower limit of normal for all those nerves to see what percentage of the lower limit of normal the patient's nerves are, and that would give you a rough idea of the degree of axonal loss.

You could use needle EMG just to see if you have denervation in both distal and proximal muscles. Also keep in mind that, as you treat the patient and the initial demyelination changes over to remyelination, even if the patient is very strong, because the remyelination will give you shorter internode lengths, the nerve conduction study timing measures, distal latency and conduction velocity, may not return to normal even if the clinical response is better.

So your clinical judgment of the patient is the best measure compared to nerve conduction as to how well the patient is doing. Here's an example of how the needle EMG may help you a little bit. So, on the left-hand side, you can see that, with the weak activation, you got a normal number of motor units. The middle panel shows you a moderate loss of axons where, for this particular trace segment, you only see 2 motor units. And the one on the right is extreme axonal loss because you have a single motor unit firing 4 times, or 40 Hz. So again, the needle EMG only gives you a very rough approximation of the degree of axonal loss.

I hope that the information I've provided you today helps you understand the underlying pathology of CIDP and how we can use nerve conduction studies to make that diagnosis, and further, some of the pitfalls and challenges in using nerve conduction studies.


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Thrombosis may occur with immune globulin products, including GAMUNEX-C. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. For patients at risk of thrombosis, administer GAMUNEX-C at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.

Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IVIG) products in predisposed patients. Patients predisposed to renal dysfunction include those with any degree of preexisting renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IVIG products containing sucrose. GAMUNEX-C does not contain sucrose. For patients at risk of renal dysfunction or failure, administer GAMUNEX-C at the minimum concentration available and the minimum infusion rate practicable.

GAMUNEX-C is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin. It is contraindicated in IgA-deficient patients with antibodies against IgA and history of hypersensitivity.

Severe hypersensitivity reactions may occur with IVIG products, including GAMUNEX-C. In case of hypersensitivity, discontinue GAMUNEX-C infusion immediately and institute appropriate treatment.

Monitor renal function, including blood urea nitrogen (BUN), serum creatinine, and urine output in patients at risk of developing acute renal failure.

Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IVIG treatment, including GAMUNEX-C.

There have been reports of aseptic meningitis, hemolytic anemia, and noncardiogenic pulmonary edema (transfusion-related acute lung injury [TRALI]) in patients administered with IVIG, including GAMUNEX-C.

The high-dose regimen (1g/kg x 1-2 days) is not recommended for individuals with expanded fluid volumes or where fluid volume may be a concern.

Because GAMUNEX-C is made from human blood, it may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

Do not administer GAMUNEX-C subcutaneously in patients with ITP because of the risk of hematoma formation.

Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure. Assess renal function, including measurement of BUN and serum creatinine, before the initial infusion of GAMUNEX-C and at appropriate intervals thereafter.

Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies, because of the potentially increased risk of thrombosis.

If signs and/or symptoms of hemolysis are present after an infusion of GAMUNEX-C, perform appropriate laboratory testing for confirmation.

If TRALI is suspected, perform appropriate tests for the presence of antineutrophil antibodies and anti-HLA antibodies in both the product and patient's serum.

After infusion of IgG, the transitory rise of the various passively transferred antibodies in the patient's blood may yield positive serological testing results, with the potential for misleading interpretation.

In clinical studies, the most common adverse reactions with GAMUNEX-C were headache, pyrexia, hypertension, chills, rash, nausea, arthralgia, and asthenia (in CIDP); cough, rhinitis, pharyngitis, headache, asthma, nausea, fever, diarrhea, and sinusitis with intravenous use (in PIDD) and local infusion-site reactions, fatigue, headache, upper respiratory tract infection, arthralgia, diarrhea, nausea, sinusitis, bronchitis, depression, allergic dermatitis, migraine, myalgia, viral infection, and pyrexia with subcutaneous use (in PIDD); and headache, ecchymosis, vomiting, fever, nausea, rash, abdominal pain, back pain, and dyspepsia (in ITP).

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).

Please see accompanying full Prescribing Information for GAMUNEX-C.

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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