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CIDP or DPN?

Todd Levine, MD, Neurology, discusses the challenges of distinguishing CIDP from diabetic neuropathy.

Transcript

CIDP or DPN?

Todd Levine, MD, Neurology, discusses the challenges of distinguishing CIDP from diabetic neuropathy.

Hi, I'm Dr Todd Levine, and I want to talk to you today about distinguishing diabetic neuropathy from CIDP, and the challenges this often involves.

So here's a typical case scenario. It's a 51-year-old woman who has type 2 diabetes. For the past 10 years she's had a history of fatigue, as well as numbness in her feet, and some balance difficulty. But in the past 6 months the symptoms have really gotten significantly worse. On exam, she has an elevated BMI, with a weight of 160 pounds, and a height of 5 foot 2 inches. She's on oral agents for her diabetes, as well as medications for her hypertension.

On physical exam, she has normal proximal muscle strength, but she has decreased strength in both her hands and her feet, with her feet being worse. She has decreased sensation, and she has reduced reflexes in her legs. On exam, she has difficulty walking, and she's been using a wheelchair sometimes, and she's not been able to work as a housekeeper.

Nerve conduction studies were performed, and this is really where the confusion comes in. Because look at this electrophysiology, and at first blush you would say there's a lot of features here that might suggest she has demyelination. The left median motor distal latency is prolonged at 6.8 meters per second. The left ulnar distal latency is prolonged at 4.1 meters per second. And there is significant slowing in the ulnar nerve across the elbow at 27 meters per second. Also, as is not unusual in these patients with long-standing diabetes, the peroneal motor, tibial motor, and sural sensory were all absent.

So what allows us to make an accurate diagnosis in this person? Well number 1, you see this loss of bulk in her intrinsic foot muscles, which tells us that the process has been going on for a long time, long enough to have atrophy. Secondly, the weakness is all distal. She has significant sensory loss, but the reflexes are really only lost distally in correlation with the weakness.

Even though, then, we see that there are changes that might suggest demyelination, you then look closer and you see that these are all areas of entrapment, which are very common in patients with diabetes, and all long latencies such as carpal tunnel syndrome. So really the best that we can conclude here is that this patient has diabetic neuropathy, with both some demyelinating, and axonal abnormalities. But not enough to convince us that this is CIDP.

So what allows us to distinguish CIDP from a diabetic neuropathy? Well the first is the distribution of the weakness. In CIDP the weakness is both distal and proximal, whereas in diabetic neuropathy it's predominantly distal. Secondly, in CIDP the patients primarily complained of motor involvement, much more so than sensory loss, and actually rarely have pain, whereas in diabetic neuropathy, the complaints are predominately sensory, and pain is a big part of it. Much more so than motor.

You can see the reflexes in patients with CIDP are usually diffusely absent, as opposed to just in diabetics where they're absent at the ankles. And lastly it's the time course; patients with CIDP progress for more than 8 weeks, but usually months, 2, 4, 6 months, whereas patients with diabetic neuropathy progress over many years.

Now the association between diabetes and CIDP is also an area of a lot of controversy. There have been some studies that look at the prevalence of CIDP in patients with diabetes, and they conclude that CIDP is actually more prevalent in patients with diabetes. There have then been other studies that look at the presence of diabetes in patients with CIDP, and they concluded that there's no significant difference between these 2 groups. Therefore the literature really is highly inconclusive as to whether or not patients with CIDP are more commonly associated with diabetes, or whether it's just the association of 2 individual diseases.

So what are the important take-home messages? When you're considering the possibility that a patient has CIDP, particularly in a patient with diabetes, you need to look for the classic, typical CIDP signs and symptoms. The patients have to have some metric, proximal, and distal weakness, and global hyperreflexia.

Secondly, to be convinced that it's CIDP, you need to see a change in the progression of their neuropathy. So you may see a patient like this, that has a 10-year history of diabetes, but then over the last few months they've fallen off of the cliff. That tells us that they've developed a new disease, not just a progression of the same disease. On the other hand if the symptoms are just slowly progressive over years and years, that's very unlikely to be CIDP, and much more likely to simply be diabetic neuropathy.

Next, again think about the motor symptoms versus the sensory symptoms. CIDP patients have much more prominent motor signs; diabetic neuropathy patients have much more prominent sensory signs. And bear in mind, if you're going to diagnose a demyelinating change on a nerve conduction study in a patient with diabetes, you need to see convincing conduction block, or convincing conduction velocity slowing with preserved amplitudes in order to make that call appropriately.

So it's clear that CIDP can be misdiagnosed in diabetics. The diabetics can have conduction velocity slowing, and they can have both axonal and demyelinating changes. And also bear in mind that diabetics can have elevated CSF protein in excess of 100 milligrams per milliliter.

On the other hand, CIDP can be missed in our diabetic patients. The key feature is really this change in motor function. While diabetics can have some weakness, toe extensors or ankle extensors, they do not have significant proximal muscle weakness. So when you see a patient with rapidly progressive or sub acutely progressive muscle weakness, and the association with diabetes, you need to consider the possibility that this might be CIDP.

And the important fact here is that the response rate to patients with CIDP who have diabetes is the same as that in patients with CIDP without diabetes. Therefore these patients are very treatable as long as you make the appropriate diagnosis.

So my final recommendations are avoid diagnosing CIDP in patients with a length-dependent slowly evolving neuropathy, particularly if the symptoms are sensory. In addition, don't base a diagnosis of demyelinating changes on the nerve conduction study on just the peroneal nerve, particularly in diabetics, because this nerve very often can be slowed even into the high twenties and not be significant. Furthermore, don't make a diagnosis of CIDP based on conduction slowing at sites of compression…so the wrist, across the elbow, or even across the fibular head.

If symptoms and signs lead you to believe that this patient has CIDP in association with diabetes, there is no reason to change their first-line therapies. They respond just as well. And if it's confusing, and difficult to manage that patient, always consider a second opinion, because these patients that have 2 different diagnoses, both diabetic neuropathy and CIDP, can be very challenging.

I hope you found this talk to be very helpful, and you'll keep these things in mind when you diagnose your patients with CIDP who have diabetes.

Transcript

CIDP or DPN?

Todd Levine, MD, Neurology, discusses the challenges of distinguishing CIDP from diabetic neuropathy.

Hi, I'm Dr Todd Levine, and I want to talk to you today about distinguishing diabetic neuropathy from CIDP, and the challenges this often involves.

So here's a typical case scenario. It's a 51-year-old woman who has type 2 diabetes. For the past 10 years she's had a history of fatigue, as well as numbness in her feet, and some balance difficulty. But in the past 6 months the symptoms have really gotten significantly worse. On exam, she has an elevated BMI, with a weight of 160 pounds, and a height of 5 foot 2 inches. She's on oral agents for her diabetes, as well as medications for her hypertension.

On physical exam, she has normal proximal muscle strength, but she has decreased strength in both her hands and her feet, with her feet being worse. She has decreased sensation, and she has reduced reflexes in her legs. On exam, she has difficulty walking, and she's been using a wheelchair sometimes, and she's not been able to work as a housekeeper.

Nerve conduction studies were performed, and this is really where the confusion comes in. Because look at this electrophysiology, and at first blush you would say there's a lot of features here that might suggest she has demyelination. The left median motor distal latency is prolonged at 6.8 meters per second. The left ulnar distal latency is prolonged at 4.1 meters per second. And there is significant slowing in the ulnar nerve across the elbow at 27 meters per second. Also, as is not unusual in these patients with long-standing diabetes, the peroneal motor, tibial motor, and sural sensory were all absent.

So what allows us to make an accurate diagnosis in this person? Well number 1, you see this loss of bulk in her intrinsic foot muscles, which tells us that the process has been going on for a long time, long enough to have atrophy. Secondly, the weakness is all distal. She has significant sensory loss, but the reflexes are really only lost distally in correlation with the weakness.

Even though, then, we see that there are changes that might suggest demyelination, you then look closer and you see that these are all areas of entrapment, which are very common in patients with diabetes, and all long latencies such as carpal tunnel syndrome. So really the best that we can conclude here is that this patient has diabetic neuropathy, with both some demyelinating, and axonal abnormalities. But not enough to convince us that this is CIDP.

So what allows us to distinguish CIDP from a diabetic neuropathy? Well the first is the distribution of the weakness. In CIDP the weakness is both distal and proximal, whereas in diabetic neuropathy it's predominantly distal. Secondly, in CIDP the patients primarily complained of motor involvement, much more so than sensory loss, and actually rarely have pain, whereas in diabetic neuropathy, the complaints are predominately sensory, and pain is a big part of it. Much more so than motor.

You can see the reflexes in patients with CIDP are usually diffusely absent, as opposed to just in diabetics where they're absent at the ankles. And lastly it's the time course; patients with CIDP progress for more than 8 weeks, but usually months, 2, 4, 6 months, whereas patients with diabetic neuropathy progress over many years.

Now the association between diabetes and CIDP is also an area of a lot of controversy. There have been some studies that look at the prevalence of CIDP in patients with diabetes, and they conclude that CIDP is actually more prevalent in patients with diabetes. There have then been other studies that look at the presence of diabetes in patients with CIDP, and they concluded that there's no significant difference between these 2 groups. Therefore the literature really is highly inconclusive as to whether or not patients with CIDP are more commonly associated with diabetes, or whether it's just the association of 2 individual diseases.

So what are the important take-home messages? When you're considering the possibility that a patient has CIDP, particularly in a patient with diabetes, you need to look for the classic, typical CIDP signs and symptoms. The patients have to have some metric, proximal, and distal weakness, and global hyperreflexia.

Secondly, to be convinced that it's CIDP, you need to see a change in the progression of their neuropathy. So you may see a patient like this, that has a 10-year history of diabetes, but then over the last few months they've fallen off of the cliff. That tells us that they've developed a new disease, not just a progression of the same disease. On the other hand if the symptoms are just slowly progressive over years and years, that's very unlikely to be CIDP, and much more likely to simply be diabetic neuropathy.

Next, again think about the motor symptoms versus the sensory symptoms. CIDP patients have much more prominent motor signs; diabetic neuropathy patients have much more prominent sensory signs. And bear in mind, if you're going to diagnose a demyelinating change on a nerve conduction study in a patient with diabetes, you need to see convincing conduction block, or convincing conduction velocity slowing with preserved amplitudes in order to make that call appropriately.

So it's clear that CIDP can be misdiagnosed in diabetics. The diabetics can have conduction velocity slowing, and they can have both axonal and demyelinating changes. And also bear in mind that diabetics can have elevated CSF protein in excess of 100 milligrams per milliliter.

On the other hand, CIDP can be missed in our diabetic patients. The key feature is really this change in motor function. While diabetics can have some weakness, toe extensors or ankle extensors, they do not have significant proximal muscle weakness. So when you see a patient with rapidly progressive or sub acutely progressive muscle weakness, and the association with diabetes, you need to consider the possibility that this might be CIDP.

And the important fact here is that the response rate to patients with CIDP who have diabetes is the same as that in patients with CIDP without diabetes. Therefore these patients are very treatable as long as you make the appropriate diagnosis.

So my final recommendations are avoid diagnosing CIDP in patients with a length-dependent slowly evolving neuropathy, particularly if the symptoms are sensory. In addition, don't base a diagnosis of demyelinating changes on the nerve conduction study on just the peroneal nerve, particularly in diabetics, because this nerve very often can be slowed even into the high twenties and not be significant. Furthermore, don't make a diagnosis of CIDP based on conduction slowing at sites of compression…so the wrist, across the elbow, or even across the fibular head.

If symptoms and signs lead you to believe that this patient has CIDP in association with diabetes, there is no reason to change their first-line therapies. They respond just as well. And if it's confusing, and difficult to manage that patient, always consider a second opinion, because these patients that have 2 different diagnoses, both diabetic neuropathy and CIDP, can be very challenging.

I hope you found this talk to be very helpful, and you'll keep these things in mind when you diagnose your patients with CIDP who have diabetes.


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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.

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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.

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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.

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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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