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A Review of CIDP

Todd Levine, MD, Neurology, presents a history of CIDP and overview of how to diagnose it.

Transcript

A Review of CIDP

Todd Levine, MD, Neurology, presents a history of CIDP and overview of how to diagnose it.

Hi, I'm Dr Todd Levine. I'm going to talk to you today about diagnosing chronic inflammatory demyelinating polyneuropathy.

I thought I'd start with a little history and take you back to 1958, when Dr James Austin first summarized 32 cases of a recurrent polyneuropathy. He diagnosed the patients as having a polyradiculopathy on the basis of a very consistent clinical picture, spinal fluid abnormalities, and pathological data. He was also the first to suggest that their weakness was from conduction block in the nerves affecting the myelin rather than due to direct axonal damage. In this initial paper in 1958, he also described the patients as being responsive to corticosteroids.

Despite almost 60 years of research into this disease, the exact cause of CIDP still remains unknown. However, we do believe that this is primarily an autoimmune or autoinflammatory process. We have several theories, which include activated T lymphocytes, which can cross the blood-brain barrier, secrete inflammatory cytokines, and activate microphages. In addition, we now know there is clearly decreased FC gamma B receptors and autoantibody production from the activated B cells. These autoantibodies seem to modulate demyelination and then recruit in macrophages, which can then produce secondary axonal damage. This complement activation produces inflammatory mediators, as well as lytic membrane attack complexes, all of which produce the characteristic clinical pattern that we now call CIDP.

These patients that have CIDP all present with a very characteristic clinical picture. They have progressive symmetric proximal and distal muscle weakness, as well as sensory loss and decreased reflexes. Very often, the disease begins with numbness or tingling or paresthesias in the arms or legs, and the disease has a very progressive, step-wise course over the next 2 months.

In some cases, however, there is a clear relapsing remitting pattern. In contrast to Guillain-Barré, this disease progresses more than 8 weeks. Also, Guillain-Barré will usually involve the cranial nerves, or have respiratory or autonomic involvement, which is very rare in CIDP.

CIDP can occur at any age, from the pediatric age until greater than 85, but most commonly occurs in middle age, between 40 and 60. The estimated prevalence varies in different research studies between 1 to 8.9 per 100,000.

So what are the different criteria to diagnose CIDP? Well, any time I flash up a slide that shows you 4 sets of criteria, the first thing you should realize is we probably don't have 1 consistent criteria that we always know works. If we go back to 1991 and the AAN criteria, and go forward to the EFNS criteria, the 1 set of symptoms that are consistent among these different criteria are the symmetric proximal and distal weakness, the sensory loss, and the decreased reflexes. That clinical picture for CIDP really has not changed over the past 25 years.

We look at additional studies to help us confirm the diagnosis, and these include EMG nerve conduction studies, spinal fluid, and nerve biopsies. For your patients' benefit, the one good thing these days is that a nerve biopsy to diagnose CIDP is very rare. In addition, the spinal fluid is really only used as confirmation, and to rule out other diseases. So, if you see a patient that has something that looks like CIDP, but they have a pleocytosis in their CSF, it should make you question that diagnosis.

And then the last point that you'll see on the slide is that the EFNS criteria has emphasized the fact that a response to treatment with immunomodulatory therapy in patients with CIDP is a confirmatory diagnostic test. We know most of these patients will respond to first-line therapy if they're diagnosed appropriately.

So what are the take-home messages about diagnosing CIDP? The first is that CIDP is a clinical diagnosis. It should be made based on clinical presentation, and the electrodiagnostics, the lab evaluations, CSF, and nerve biopsy are really all supportive evidence. In addition, bear in mind that there are many atypical forms of CIDP, and these can look very different than the typical symmetric proximal and distal weakness and sensory loss than we talked about in this lecture, and you're going to hear more about in our other lectures. And finally, bear in mind that there are very few treatable neuropathies, and that CIDP is one of the most treatable neuropathies. And the longer we go without diagnosing and treating our patients, the more progressive their symptoms will be and less likely to be reversible in the long run.

Thank you for joining me, and I hope you found this lecture to be helpful.

Transcript

A Review of CIDP

Todd Levine, MD, Neurology, presents a history of CIDP and overview of how to diagnose it.

Hi, I'm Dr Todd Levine. I'm going to talk to you today about diagnosing chronic inflammatory demyelinating polyneuropathy.

I thought I'd start with a little history and take you back to 1958, when Dr James Austin first summarized 32 cases of a recurrent polyneuropathy. He diagnosed the patients as having a polyradiculopathy on the basis of a very consistent clinical picture, spinal fluid abnormalities, and pathological data. He was also the first to suggest that their weakness was from conduction block in the nerves affecting the myelin rather than due to direct axonal damage. In this initial paper in 1958, he also described the patients as being responsive to corticosteroids.

Despite almost 60 years of research into this disease, the exact cause of CIDP still remains unknown. However, we do believe that this is primarily an autoimmune or autoinflammatory process. We have several theories, which include activated T lymphocytes, which can cross the blood-brain barrier, secrete inflammatory cytokines, and activate microphages. In addition, we now know there is clearly decreased FC gamma B receptors and autoantibody production from the activated B cells. These autoantibodies seem to modulate demyelination and then recruit in macrophages, which can then produce secondary axonal damage. This complement activation produces inflammatory mediators, as well as lytic membrane attack complexes, all of which produce the characteristic clinical pattern that we now call CIDP.

These patients that have CIDP all present with a very characteristic clinical picture. They have progressive symmetric proximal and distal muscle weakness, as well as sensory loss and decreased reflexes. Very often, the disease begins with numbness or tingling or paresthesias in the arms or legs, and the disease has a very progressive, step-wise course over the next 2 months.

In some cases, however, there is a clear relapsing remitting pattern. In contrast to Guillain-Barré, this disease progresses more than 8 weeks. Also, Guillain-Barré will usually involve the cranial nerves, or have respiratory or autonomic involvement, which is very rare in CIDP.

CIDP can occur at any age, from the pediatric age until greater than 85, but most commonly occurs in middle age, between 40 and 60. The estimated prevalence varies in different research studies between 1 to 8.9 per 100,000.

So what are the different criteria to diagnose CIDP? Well, any time I flash up a slide that shows you 4 sets of criteria, the first thing you should realize is we probably don't have 1 consistent criteria that we always know works. If we go back to 1991 and the AAN criteria, and go forward to the EFNS criteria, the 1 set of symptoms that are consistent among these different criteria are the symmetric proximal and distal weakness, the sensory loss, and the decreased reflexes. That clinical picture for CIDP really has not changed over the past 25 years.

We look at additional studies to help us confirm the diagnosis, and these include EMG nerve conduction studies, spinal fluid, and nerve biopsies. For your patients' benefit, the one good thing these days is that a nerve biopsy to diagnose CIDP is very rare. In addition, the spinal fluid is really only used as confirmation, and to rule out other diseases. So, if you see a patient that has something that looks like CIDP, but they have a pleocytosis in their CSF, it should make you question that diagnosis.

And then the last point that you'll see on the slide is that the EFNS criteria has emphasized the fact that a response to treatment with immunomodulatory therapy in patients with CIDP is a confirmatory diagnostic test. We know most of these patients will respond to first-line therapy if they're diagnosed appropriately.

So what are the take-home messages about diagnosing CIDP? The first is that CIDP is a clinical diagnosis. It should be made based on clinical presentation, and the electrodiagnostics, the lab evaluations, CSF, and nerve biopsy are really all supportive evidence. In addition, bear in mind that there are many atypical forms of CIDP, and these can look very different than the typical symmetric proximal and distal weakness and sensory loss than we talked about in this lecture, and you're going to hear more about in our other lectures. And finally, bear in mind that there are very few treatable neuropathies, and that CIDP is one of the most treatable neuropathies. And the longer we go without diagnosing and treating our patients, the more progressive their symptoms will be and less likely to be reversible in the long run.

Thank you for joining me, and I hope you found this lecture to be helpful.


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GAMUNEX®-C (immune globulin injection [human], 10% caprylate/chromatography purified) is indicated for the treatment of primary humoral immunodeficiency disease (PIDD) in patients 2 years of age and older, idiopathic thrombocytopenic purpura (ITP) in adults and children, and chronic inflammatory demyelinating polyneuropathy (CIDP) in adults.

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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