What is Chronic Inflammatory Demyelinating Polyradiculoneuropathy (Inflammation of Nerve Roots and Peripheral Nerves)?
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was first identified in 1890. It is a disorder where the body’s immune system attacks the nerves and nerve roots. The disease causes weakness evenly across near and far muscles and is a type of chronic acquired demyelinating polyneuropathies (CADP).
CIDP can show up in different forms. The “typical” or “classical” form involves a gradually worsening weakness that is more focused on the muscles than the senses, with the senses of position and vibration gravely affected more than the senses of pain and temperature. Interestingly, CIDP is closely related to acute inflammatory demyelinating polyradiculoneuropathy (AIDP), a similar nerve-attacking disease that is a form of Guillain-Barré syndrome (GBS).
To tell these two diseases apart, doctors look at how quickly the disease progresses and whether there are any episodes of getting worse, then better. It’s critical to diagnose the disease correctly to start the right treatment and manage the disease properly.
CIDP can show up in unusual ways, reacting differently to the immune system and treatments. The disease can have just one episode, various episodes, or it can continually get worse. To determine a diagnosis of CIDP, the symptoms have to be present for at least two months. Doctors will look for worsening symptoms over this time, perform tests to spot evidence of nerve damage, and observe how the symptoms respond to treatments that control the immune system.
What Causes Chronic Inflammatory Demyelinating Polyradiculoneuropathy (Inflammation of Nerve Roots and Peripheral Nerves)?
Most people with CIDP, a nervous system disease, develop it for unknown reasons, although some people get it after experiencing a respiratory or gastrointestinal infection. The exact organism causing this condition hasn’t been discovered yet. CIDP can also be connected to other diseases such as systemic lupus, HIV, and hepatitis B or C. It is believed that numerous factors may cause immune cells to attack the insulation of the nerves in the peripheral nervous system. Evidence shows that activated immune cells can cross into the nerves from the blood and trigger the production of various disease-fighting substances like cytokines, tumor necrosis factor, interferons, and interleukins. The presence of certain types of proteins and components of the immune system on the insulated nerve fibers indicates that the body’s immune response is involved.
Around half of CIDP cases follow a usual course, with symptoms like progressive, symmetrical sensory issues and muscle weakness getting worse over at least 8 weeks. There are also some atypical versions of the disease, which include antibody-positive, predominantly sensory, predominantly motor, Lewis-Sumner syndrome (a disease causing sensory and motor issues that occur in several different areas), and DADS neuropathy, which targets the extremities.
Around 10% of patients with CIDP have autoantibodies against proteins located in or near important parts of nerve fibers. These autoantibodies are mostly of a specific kind that does not activate immune response components. The main proteins targeted by these autoantibodies are different variations of neurofascin and contactin-1. Neurofascin-155, found in 4% to 18% of patients with CIDP, is present on Schwann cells (a type of cell in the nervous system), while Neurofascin-186, found in less than 2% of patients, is on the region of the nerve that initiates nerve impulses. Antibodies against Contactin-1 are found in 2.2% to 8.7% of patients. People with Contactin-1 antibodies usually present with a form of the disease that primarily affects motor nerves and causes nerve damage.
The disease pathway in patients with antibodies against these nerve proteins is different from that in typical CIDP. Ongoing research is being done to further classify these variants. Also, these variants are generally less responsive to initial treatment with anti-inflammatories and intravenous immunoglobulins. Some studies suggest that certain immune system-specific genes may be more prevalent in people with CIDP compared to healthy people, while other studies found no actual genetic link.
Risk Factors and Frequency for Chronic Inflammatory Demyelinating Polyradiculoneuropathy (Inflammation of Nerve Roots and Peripheral Nerves)
CIDP, or Chronic Inflammatory Demyelinating Polyneuropathy, is a condition that affects more men than women, with about twice as many men affected. It’s not a very common condition, with about 0.3 out of 100,000 patients diagnosed each year. On the whole, anywhere from 0.8 to 8.9 out of 100,000 people have this condition. CIDP tends to become more common as people get older, but it can also occur in children. The average age of someone with CIDP is 60.
The exact number of people who have CIDP can vary. This is because the symptoms can look different in different people and doctors around the world might use different criteria to diagnose it. For instance, young people tend to experience relapses and are more likely to have symptoms that mainly affect the motor nerves.
- CIDP affects more men than women at a ratio of 2:1.
- An average of 0.3 out of every 100,000 patients are diagnosed with CIDP each year.
- The condition is found in 0.8 to 8.9 out of 100,000 people.
- CIDP becomes more common with advancing age, but can also occur in children.
- The average age of patients with CIDP is 60.
- Diagnosis rates vary due to the different symptoms and diagnostic criteria used around the world.
- Young people with CIDP are more likely to have relapses and motor nerve symptoms.
Signs and Symptoms of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (Inflammation of Nerve Roots and Peripheral Nerves)
The Chronic Inflammatory Demyelinating Polyradiculoneuritis (CIDP) is a condition that affects the nerves. Almost half to more than half of all cases have a symmetrical distribution of the problem, covering both sides of the body equally. The disease usually progresses slowly but around a third of patients may have their condition fluctuate, getting better and worse periodically.
When checking for CIDP, doctors will collect a detailed history from the patient. They will ask about things like whether the patient has experienced:
- Weakness in the limbs
- Symptoms that change over weeks or months
- Difficulty with tasks such as climbing or descending stairs, getting up from a seated position or reaching overhead
- Problems with walking
- More falls than usual
- Problems with fine motor skills, like doing up buttons
- Difficulty opening doors or jars
- Tripping or dragging feet caused by foot drop
- Tingling or burning sensations in the hands or feet
The doctor will then do a thorough examination, focusing on certain areas such as:
- Musculoskeletal
- Neurological
The assessment can include looking for muscle weakness, tremors, foot drop and whether muscle control is normal. The doctor may test sensory abilities such as detecting position, vibration, pain, and temperature. The doctor might also examine the involvement of cranial nerves and check for symptoms related to the autonomic nervous system (controlling body functions like heart rate and digestion).
CIDP can come in different forms. Some people have a version of the disease which is largely located in the distant regions of the limbs. Others may have a multifocal form where the signs and nerve conduction problems are not equally distributed. There are also forms of the disease which predominately affect either the motor or sensory nerves, and some forms primarily affect the roots of the nerves near the spine. It is important to note that the course and type of CIDP can vary from person to person.
Regular monitoring of a person’s condition over time, along with repeating the examination after treatment, can be helpful in making a diagnosis of CIDP.
Testing for Chronic Inflammatory Demyelinating Polyradiculoneuropathy (Inflammation of Nerve Roots and Peripheral Nerves)
Diagnosing Chronic Inflammatory Demyelinating Polyneuropathy (or CIDP) can be tough because it comes in different shapes depending on individual people. However, it’s critical that we identify it ASAP because we can treat it. Early detection and treatment can keep the disease from getting worse and avoid harm to the axons, the long, threadlike part of nerve cells. Nevertheless, half of the time, CIDP might have been wrongly diagnosed.
There aren’t tests available that can confirm you have CIDP. Instead, doctors use tests to eliminate other diseases that resemble CIDP or are linked to it. People who might have CIDP are tested for fasting serum glucose or oral glucose tolerance, glycated hemoglobin, serum calcium, serum creatinine, complete blood count, serum aminotransferase levels, thyroid function, serum protein electrophoresis (SPEP) and immunofixation, and serum free light chain assay.
All these tests are necessary because if you have neuropathies associated with something known as a monoclonal gammopathy of undetermined significance, it can seem like you have typical CIDP. More tests might be useful based on your particular situation, such as tests for Borrelia burgdorferi, C-reactive protein, antinuclear antibodies, and angiotensin-converting enzyme, among others.
There are several sets of requirements used to diagnose CIDP. The diagnosis demands a mix of clinical, electrodiagnostic, and supportive info. The 2021 diagnostic criterion from the European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS) is 83% sensitive and 94% specific. First, it classifies potential CIPD patients as “typical CIDP” or “CIDP variant” based on symptoms and physical examination findings.
For typical CIDP, you need to have a slowly worsening, stepwise, or consecutive symmetrical weakness, and sensory trouble in 2 or more limbs for 2 months or more. Your cranial nerves may be affected, and you’ll have reduced tendon reflexes in all your extremities.
For CIDP variants, you need to have one from several criteria, such as predominantly distal, asymmetric symptoms, pure motor symptoms, and pure sensory symptoms. After this, doctors should conduct electrodiagnostic tests.
The doctors will then evaluate nerve signals from nerves around the body. These tests can tell the difference between a problem related to myelination (how nerves get insulated) or axons (the nerve fibers). You can have axon damage as a primary issue or secondary to demyelination, which doesn’t rule out CIDP. Depending on the results, CIDP may be classified as either definite or possible.
If you show a definite CIDP, but the initial diagnostic test isn’t conclusive, a follow-up test may be considered.
MRI and Ultrasound are utilized to a lesser degree. They don’t recommend an MRI as a diagnostic tool for CIDP unless it’s a probable case. Where it can help is by signifying that CIDP is more likely if nerves show enlargement or increased intensity.
Cerebrospinal fluid analysis: In CIDP, it’s normal to find high levels of proteins and a few extra cells (a condition known as Albuminocytologic dissociation). However, to exclude CIDP, it is unusual to have a cell count of greater than 10 cells/mm3.
Remember that there is no one-size-fits-all test for CIDP. Diagnosis depends on several clinical, lab, and imaging results, which may not all lead to a definitive answer. In such cases, a nerve biopsy may be considered helpful as it can rule out other nerve-related diseases.
Coming to summarize, diagnosing CIDP can be quite complex, depending on whether a patient has typical CIDP or an atypical version. A range of clinical and electrodiagnostic criteria must be met, alongside supporting information from test results. Now if any of these criteria aren’t met, and if Borrelia burgdorferi, diphtheria, drug or toxin exposure causes the patient’s neuropathy, CIDP can be excluded from the diagnosis.
Treatment Options for Chronic Inflammatory Demyelinating Polyradiculoneuropathy (Inflammation of Nerve Roots and Peripheral Nerves)
If you have chronic inflammatory demyelinating polyneuropathy (CIDP), the first treatment choices that doctors may use are corticosteroids, an infusion of special proteins called intravenous immunoglobulin (IVIG), or an activity called plasma exchange. But, because of the potential long-term side-effects of corticosteroids, IVIG or plasma exchange are often preferred. IVIG is usually easier to administer than plasma exchange. Both plasma exchange and IVIG generally work faster than glucocorticoids (a type of corticosteroid).
Corticosteroids are great for patients with a less severe onset of symptoms because a fast response isn’t as necessary and they’re more likely to experience remission, which means symptom-free periods. They’re also useful for patients who keep having flare-ups despite getting IVIG or other maintenance treatments.
Other treatments include immunosuppressive agents like azathioprine, cyclosporine, tacrolimus, and mycophenolate. These drugs suppress or reduce the strength of the body’s immune response and are used for maintenance therapy in CIDP. Around 40% of patients will achieve remission or recovery with this set of treatments.
The 2008 ICE trial studied the use of IVIG in CIDP and showed it’s effective and safe for both initiating and maintaining treatment. It also successfully prevents regular flare-ups. The study recommended a series of IVIG doses starting with 2 grams per kilogram of body weight. This initial dose should be given over 2 to 5 days, and then monthly maintenance doses should follow for the next few months to determine how effective the treatment is.
Plasma exchange is another treatment that works well for CIDP. However, it is often reserved for severe cases or patients who aren’t responding to corticosteroids and IVIG due to its availability and the requirement of repeat venous access or the placement of a permanent catheter.
When the standard treatments aren’t suitable for a patient, or they aren’t working, doctors might consider other options like steroid-sparing agents for maintenance therapy. There are no standard guidelines on how long this therapy should continue, but it usually lasts for approximately 6 months. Targeted therapies, like rituximab and alemtuzumab, are potential alternatives for patients not responding to the first line of treatment.
Physical, occupational, and rehabilitation therapy can also play a crucial role in getting patients with CIDP back to their optimal functional status. Through these therapies, healthcare professionals can improve a patient’s mobility, strength, coordination, and independence in their daily activities, promoting a higher quality of life.
What else can Chronic Inflammatory Demyelinating Polyradiculoneuropathy (Inflammation of Nerve Roots and Peripheral Nerves) be?
When doctors are trying to diagnose CIDP (Chronic Inflammatory Demyelinating Polyneuropathy), they also consider many other conditions that could cause similar symptoms. These potential diagnoses include:
- AIDP (Acute Inflammatory Demyelinating Polyneuropathy)
- Multifocal motor neuropathy
- DADS with monoclonal IgM gammopathy and anti-MAG (Distal acquired demyelinating symmetric neuropathy)
- Chronic ataxic neuropathy with ophthalmoplegia, IgM paraprotein, cold agglutinins, and disialosyl antibodies (an immune condition affecting nerves)
- POEMS syndrome (a disorder that affects many different body systems)
- Demyelinating neuropathy caused by medications that block tumor necrosis factor-α, or checkpoint inhibitors (common drugs used for autoimmune disorders and cancer treatment)
- Infections such as Lyme disease, diphtheria, hepatitis B or C, or HIV
- Charcot-Marie-Tooth disease (a group of inherited disorders that affect the nerves)
- Hereditary neuropathy with liability to pressure palsies (a condition that causes numbness and muscle weakness)
- Transthyretin (TTR) familial amyloid polyneuropathy (a hereditary disorder that affects nerves)
- Abuse of Pyridoxine (also known as Vitamin B6)
- Diabetic or non-diabetic lumbosacral radiculopathy-plexopathy (nerve damage in the lower back)
- Chemotherapy-induced demyelinating neuropathy (nerve damage caused by cancer treatment)
- PNS lymphoma (cancer in the lymphatic tissue in peripheral nerves) and systemic amyloidosis (an abnormal protein build-up condition)
- Hypertension (high blood pressure)
- Thromboembolic events (blood clots)
- Increased risk of infection
- Bone marrow suppression
- Nephrotoxicity (kidney damage)
- Malignancies such as lymphoma (cancers)
- Aspiration pneumonia
- Atelectasis (collapsed lung)
- Respiratory failure due to swallowing and breathing dysfunction
- Gastrointestinal motility abnormalities
- Bladder function issues
- Orthostatic hypotension
- Cardiac conduction defects (heart rhythm abnormalities)
Other causes related to toxins and metabolism can include:
Doctors must thoroughly consider each of these possible conditions, carry out the appropriate tests, and interpret the results carefully to accurately diagnose CIDP.
What to expect with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (Inflammation of Nerve Roots and Peripheral Nerves)
About two-thirds of patients with CIDP, a disorder afflicting the peripheral nerves, respond positively to standard treatments such as IVIG, glucocorticoids, or plasma exchange. However, roughly 10% to 15% show resistance to these treatments. Additionally, close to 40% of patients can reach a state of recovery or no further disease progression, but some may still have persistent symptoms that are unaffected by immune-boosting therapies.
A recent study from South England found that 54% of patients suffered severe disability at some point in their disease due to CIDP. Over time, the risk of the disease returning increases. Doctors can reduce the immune-suppressing therapy once patients’ conditions have stabilized and aren’t worsening.
In a study involving 40 patients, Dyck and others found that 72% needed immune-suppressing treatment while 27% achieved a state of no disease activity without treatment.
Possible Complications When Diagnosed with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (Inflammation of Nerve Roots and Peripheral Nerves)
About 54% of cases initially thought to be CIDP, a type of neurological condition, turn out to be misdiagnosed. As a result, these patients end up on long-term treatments meant to suppress their immune system, but these treatments often provide little or no benefit. Notably, despite there being several treatment options available, a majority of patients diagnosed with CIDP remain somewhat disabled. Moreover, patients might experience several side effects due to treatment, including high blood pressure, blood clots, increased chance of getting infections, bone marrow damage, kidney toxicity and even certain types of cancer like lymphoma.
There are also problems that can occur due to the disease itself, such as aspiration pneumonia, atelectasis, and respiratory failure due to difficulties with swallowing and breathing. Issues with autonomic function, typically affecting involuntary body processes, could lead to problems with bowel movements, bladder functions, a sudden drop in blood pressure upon standing up (orthostatic hypotension) and heart rhythm abnormalities.
Complications and Side Effects:
Preventing Chronic Inflammatory Demyelinating Polyradiculoneuropathy (Inflammation of Nerve Roots and Peripheral Nerves)
CIDP is a nerve disorder that gradually leads to weakness and lower feeling in arms and legs. This condition happens due to repeated damage and repair of the protective covering of nerves. CIDP is often misdiagnosed, resulting in unnecessary medical costs and exposure to potentially harmful treatments. Therefore, a referral to a nerve and muscle specialist may be necessary to properly diagnose the condition.
Patients must be aware that symptoms can vary and it may be necessary to consult with a specialist in nerve disorders and muscle diseases. Both patients and their caregivers need to know that CIDP can either come and go or continue to worsen. This highlights the importance of diagnosing and treating the condition early to prevent it from getting worse or causing disability. There are different medications available and each one has its own advantages and disadvantages.
Even though the disease can last a long time, it can cause side effects from the medication, and treatment can be expensive, patients should find hope in the fact that many people with CIDP see considerable improvement with treatment, and up to 40% get completely better.