What is CIDP? Understanding Chronic Inflammatory Demyelinating Polyneuropathy

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a rare but treatable autoimmune neurological condition that affects between 0.8 to 8.9 per 100,000 people. 

It disrupts nerve signal transmission by causing demyelination in nerves (demyelination is the process of losing the myelin sheath, a protective, fatty covering that surrounds nerve fibers in the nervous system; in CIPD, the immune system attacks the myelin sheath).

This process leads to symptoms such as muscle weakness, numbness, and fatigue. CIDP can be challenging to diagnose due to varied symptoms, but prompt treatment is essential for improving outcomes and managing disease progression.

In this article we’ll cover the symptoms, causes, diagnosis, treatment options, and ways to manage life with CIDP.

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What is CIDP?

Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is a rare autoimmune disease that affects the peripheral nerves, causing gradual muscle weakness and numbness in the arms and legs. 

The condition results from inflammation that damages the myelin sheath, the protective layer around nerves; this damage disrupts nerve signal transmission. People with CIDP usually have weakness on both sides of their body and experience sensory issues that affect their balance and coordination. 

Reflexes are often reduced or absent, and although pain is typically mild, many patients struggle with sensing body position and detecting vibrations.

Pathophysiology of CIDP 

In CIDP, an autoimmune disorder, the immune system mistakenly attacks the myelin sheath that protects nerves and transmits nerve signals; this damage disrupts normal nerve signal transmission, causing progressive muscle weakness and sensory loss, balance issues, and decreased reflexes. 

Motor and sensory impairments generally affect both sides of the body equally, but the severity and progression of symptoms can differ from person to person. Some people may experience a slow, steady increase in symptoms, while others may stabilize for a time and then have relapses.

Although a rare disease, CIDP is treatable, and early diagnosis and intervention can improve long-term outcomes.

Different Types of CIDP

CIDP, which is characterized by autoimmune destruction of the myelin sheaths, has different subtypes. 

The main types include:

Typical CIDP

This is the most common form of CIDP, causing gradual, symmetrical muscle weakness and sensory loss in the arms and legs. 

Symptoms appear slowly over at least 8 weeks and affect both the upper and lower parts of the limbs. Reflexes are usually reduced, and standard treatments like corticosteroids and IVIG often provide moderate improvement.

Atypical CIDP Variants

• Distal CIDP: primarily affects the lower limbs, with weakness and sensory loss in the feet and legs.

• Multifocal CIDP (MADSAM): also called Lewis-Sumner Syndrome, this rare subtype causes uneven symptoms that usually affect the arms in more than one spot.

• Focal CIDP: affects a single limb or specific areas, like the arm or leg nerves.

• Motor CIDP: only involves motor symptoms, like muscle weakness, without affecting sensation.

• Sensory CIDP: involves only sensory symptoms, like numbness or tingling, without muscle weakness.

CIDP with Nodal and Paranodal Antibodies

In some cases of CIDP, patients have specific antibodies that target proteins in nerve junctions (called nodes of Ranvier or paranodal regions). 

These patients tend to have unique symptoms like tremors, balance issues, and sometimes facial nerve involvement, and they often don’t respond well to standard treatments.

This form of CIDP, known as “autoimmune nodopathy” or “paranodopathy,” differs from typical CIDP in a few key ways. 

While typical CIDP is a gradual, symmetrical nerve disorder that usually responds well to standard treatments, antibody-associated CIDP is marked by IgG4 antibodies causing more severe sensory loss and coordination issues, high protein levels in spinal fluid, and nerve swelling.

Also, while typical CIDP symptoms appear symmetrically and gradually, patients with antibody associated CIDP often have an earlier and more aggressive symptom onset.

These classifications help doctors choose the most effective treatments. For instance, patients with antibody-related CIDP may respond better to biologic treatments like rituximab, while others might benefit more from corticosteroids or IVIG.

Symptoms and Early Signs

Common symptoms and early signs of CIPD include the following:

Primary Early Symptoms 

Early symptoms of CIDP include:

• Weakness in the arms and legs, which may progressively worsen

• Difficulty with movements that require strength, such as climbing stairs or lifting objects

• Sensory loss, especially in the ability to feel vibration and body position

• Reduced or absent reflexes, particularly in the legs

• Numbness, tingling, or burning sensations in the hands and feet

Progression and Severity 

CIDP has symptoms that range from mild to severe, typically worsening over at least two months. The disease course varies widely: some individuals experience a gradual, steady decline, while others may have symptoms that stabilize or improve with treatment. 

Without appropriate intervention, CIDP can lead to significant disability, muscle atrophy, and loss of coordination, sometimes necessitating mobility aids. 

Standard treatments, such as IVIG, corticosteroids, and plasma exchange, are generally effective but often require ongoing administration to prevent symptom progression or relapse.

Red Flags for Early Diagnosis 

Early detection is critical. Symptoms that should prompt a medical evaluation include progressive weakness over more than eight weeks, loss of reflexes, and difficulty with coordination or balance. 

Early diagnosis can lead to earlier intervention, potentially preventing severe disability.

Causes and Risk Factors

Underlying causes of CIDP are not entirely clear, although certain factors have been identified. 

Genetic and Environmental Influences 

While CIDP is not typically inherited, there may be a genetic predisposition in some individuals. Additionally, environmental factors such as exposure to infections, may influence susceptibility.

Risk Factors in Certain Populations 

CIDP tends to affect middle-aged and older adults more frequently, with a higher incidence in men. Conditions like diabetes may also increase the risk of developing CIDP, although these associations are still being explored.

Diagnosing CIDP

Diagnosing CIDP begins with a thorough clinical examination and includes additional diagnostic testing.

Clinical Evaluation 

Diagnosing CIDP begins with a thorough medical history and physical examination. 

CIDP usually shows as gradually worsening, symmetrical muscle weakness and sensory issues, especially affecting vibration and position senses more than pain or temperature. 

Symptoms must last for at least eight weeks for a diagnosis. 

Diagnostic Tests 

CIDP diagnosis often involves several tests:

• Nerve Conduction Studies and Electromyography (EMG): these tests evaluate the electrical activity in muscles and nerves and are essential for detecting the slowing or blockage of nerve signals caused by demyelination.

• Supporting Tests: the following tests can be helpful to rule CIDP in or out by providing important clues:

• Lumbar Puncture: analysis of cerebrospinal fluid can show elevated protein levels, a common finding in CIDP.

• MRI: imaging can help detect nerve root inflammation, particularly in the spinal region. 

• Nerve Biopsy: in certain settings, a nerve biopsy may be recommended to exclude other diagnoses.

CIDP Diagnostic Guidelines

The European Academy of Neurology/Peripheral Nerve Society (EFNS/PNS) diagnostic guidelines for typical CIDP include:

• Clinical Signs: progressive, symmetric weakness in both proximal (close to the body) and distal (far from the body) limbs, with sensory impairment that primarily affects the sense of position and vibration.

• Electrodiagnostic Tests:

• Abnormal motor conduction in at least two nerves (e.g., prolonged distal motor latency or slowed nerve conduction speed).

• Sensory conduction abnormalities in at least two nerves.

• Possible CIDP can also be diagnosed with two or more supportive criteria (such as elevated protein in cerebrospinal fluid or partial improvement with immunotherapy).

These criteria, which focus on detecting nerve demyelination, help differentiate CIDP from other neuropathies.

Differential Diagnosis and Diagnostic Challenges with CIDP

CIDP can be misdiagnosed, so a thorough workup is essential. 

Misdiagnosis of CIDP

CIDP is often misdiagnosed, with studies suggesting that up to half of people diagnosed with CIDP in the U.S. may actually have a different condition. 

Key diagnostic issues include difficulty in identifying "atypical" CIDP types, misreading nerve conduction tests, over-relying on unclear CSF protein levels, and interpreting improvements after immunotherapy as proof of CIDP. 

To improve diagnosis, experts recommend using specific CIDP guidelines, tracking objective measures of progress, and getting second opinions from specialized CIDP centers.

Differential Diagnosis 

The differential diagnosis for CIDP includes many common conditions with similar symptoms; while many of these common conditions are listed below, other neurologic conditions should also be ruled out before diagnosing CIDP. 

For typical CIDP, doctors consider amyloidosis, Guillain-Barré syndrome, POEMS syndrome, multiple myeloma, and vitamin B12 deficiency. 

In cases of distal CIDP, diabetic neuropathy (nerve damage due to high blood sugar levels) and vasculitic neuropathy (nerve damage from blood vessel inflammation) are more common possibilities, although other conditions are also possible. 

For sensory CIDP, toxic neuropathies, including those caused by chemotherapy or too much vitamin B6, are often considered, but again, there may be other possible causes. 

Because many neurological disorders can mimic CIDP, a thorough diagnostic workup is essential to correctly identify CIDP and rule out other conditions.

CIDP Treatment and Management Options

Your healthcare provider may recommend the following:

First-Line Treatments 

According to EFNS/PNS guidelines, treatment often begins with therapies designed to suppress the immune system’s attack on the nerves. Common options include:

• Corticosteroids: often the first line of treatment for CIDP, but these medications may worsen symptoms in motor-dominant cases.

• Intravenous Immunoglobulin (IVIg): commonly preferred for patients with motor-dominant CIDP, as it is generally safer than corticosteroids for these cases.

• Plasma Exchange: effective but less convenient to administer, so it's less frequently used.

Maintenance Therapy

• Subcutaneous Immunoglobulin (SCIg): this is used as a maintenance treatment, especially for patients who respond well to IVIg.

Additional Medications

• Immunosuppressive Drugs: these are considered if primary treatments (IVIg, corticosteroids, plasma exchange) don’t fully control symptoms.

Pain Management

• Medications: neuropathic pain may be managed with drugs like tricyclic antidepressants, pregabalin, or gabapentin.

Lifestyle and Supportive Care

The EFNS/PNS guidelines also recommend the following for CIDP patients: 

• Physical Therapy and Exercise: these help maintain strength and flexibility.

• Balanced Diet: a healthy, anti-inflammatory diet supports overall health and may improve symptoms.

• Foot Care: essential for avoiding complications due to weakened nerves.

• Assistive Devices: orthotics or other supports may be recommended based on individual needs.

• Patient Support Groups: connecting with others can provide emotional support and additional resources.

CIDP Prognosis

About 90% of the people with CIDP improve with treatment, although about 50% of these patients may relapse. 

Overall long-term prognosis is good for people with CIDP diagnosed at a younger age. 

However, people who don’t receive any treatment for CIDP may develop permanent nerve damage that results in disability.

Functional Medicine Lab Tests to Consider

In certain settings, considering additional testing may shed light on underlying processes and ways to support a person’s overall health.

• Inflammation Markers: inflammatory markers such as CRP, ESR, IL-6, and TNF-alpha are useful for assessing overall inflammation levels and may be valuable to monitor as part of treatment response.

• Nutrient Panels: testing for nutrients including vitamins B6, B12, and folate; vitamin D; magnesium and others can help identify deficiencies that may impact nerve health.

• Oxidative Stress Markers: 8-OH-dG, an indicator of DNA oxidative damage, and F2-isoprostanes, which reflect lipid peroxidation, are valuable in assessing oxidative stress, which can exacerbate nerve damage.

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FAQ: Common Questions about CIDP

This section provides quick answers to common questions about CIDP. 

Is CIDP curable? 

CIDP is currently not curable, but it is manageable with treatment. Many patients experience symptom improvement and can lead fulfilling lives.

How does CIDP differ from Guillain-Barré Syndrome? 

While both are autoimmune neuropathies, CIDP progresses more slowly and is chronic, whereas Guillain-Barré Syndrome (GBS) is typically an acute, rapidly progressing condition.

What are the long-term outcomes of CIDP treatment? 

With treatment, many patients achieve stable or improved functioning. However, long-term outcomes vary, with some experiencing recurring symptoms.