Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Introduction:

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a progressive autoimmune disease that destroys the myelin sheaths of peripheral nerves (latov; Janssen et al). Individuals with this nervous system disorder tend to present physically with symmetrical weakness, balance problems, impaired sensation and diminished reflexes in addition to problems at a neurological level (latov, Janssen et al., 2018). The long term nature of this condition leads to abnormalities in gait and impairments in both psychological and social functioning (Janssen et al., 2018).

Clinically Relevant Anatomy:

The human nervous system can be divided into 2 parts. The central nervous system, which includes the brain and spinal cord, and the peripheral nervous system, which contains all nerves that supply the rest of the body. Surrounding the peripheral nerves is a white, fatty layer of myelin that is made up of glial cells, termed Scwhann cells. The myelin coating generated by the Schwann cells assists the axons in transmitting faster neural impulses to receptor sites, such as organs and muscles. In CIDP this myelin is destroyed resulting in nerve conduction changes and impairments, such as limb weakness and sensory loss. (textbook-)

Pathophysiology:

CIDP can be distinguished into two categories; typical and atypical cases. Symmetric motor/sensory impairments with proximal and distal weakness and areflexia, slowed conduction rate, temporal dispersion, and/or a conduction block occurs in typical cases of CIDP. Atypical cases can present in a number of different ways. Most commonly atypical cases are purely sensory or predominantly sensory, multifocal with persistent conduction block, and cases that present with similar and bilateral distal symptoms. (LEWIS)  Pathological changes have been seen to be more pronounced in the spinal nerve roots, major plexuses, and proximal nerve trunks. Magnetic resonance imaging (MRI) studies following patients for an extended period of time have concluded that nerve hypertrophy and/or gadolinium enhancement are more prominent in these areas.  (Mathey, Pollard)

Gadolinium- define!

Immunopathology:

When looking at the immunopathology of CIDP the two important cells to analyze are T and B lymphocytes. They both play a primary role along with macrophage cells in myelin phagocytosis as seen within nerve lesions of CIDP. Additionally, T cells play an important role in the increased permeability of the blood nerve barrier as seen on MRI studies of inflammatory neuropathies. A high percentage of patients with CIDP have been shown to have positive outcomes to plasma exchange therapy. This suggest that the antibody or other soluble factors are pathogenic in this disease. (Mathey and Pollard).

Epidemiology:

Incidence: CIDP is suspected to be vastly underestimated, in part due to underreporting, uncertainty in making the diagnosis and diagnostic criteria inconsistencies (latov). Many research studies report different distributions of cases with diagnostic numbers as low as 0.5 per 100,000 children and 1 to 2 per 100,000 adults (koller) to as high as 8 per 100,000 (foundation guidelines)

Gender: Although research is limited, there is a slight predilection for men (gorson, lewis)

Age: Individuals diagnosed with CIDP are generally aged 40-60, although children and elderly people may be affected (Gorson)

Clinical Presentation:

Individuals often report difficulty with walking, climbing stairs, balance and manual dexterity, which is attributed to the progressive, symmetric limb weakness and sensory loss. It is commonly seen to affect proximal muscles in the early stages and then progressively move to the distal limbs. Numbing, buzzing and tingling may be characteristic of sensory loss reported by patients and neuropathic pain is less often reported. (Garson)

On the contrary, some individuals may not present with these symptoms, which makes diagnosis much more difficult and can take many years, leaving patients with no answers and increased frustration. (Wolfe and Greer, 2015).

After complete subjective and objective history in addition to further medical investigations, which may take multiple months after symptom onset, the following aspects have been recognized as major cardinal features of CIDP (lewis):

1. Progression over at least 2 months

2. Predominant motor symptoms

3. Symmetric involvement of arms and legs

4. Proximal muscles involved along with distal muscles

5. Deep tendon reflexes reduction or absence

6. Cerebrospinal fluid (CSF) protein elevation without pleocytosis

7. Nerve conduction evidence of a primary demyelinating neuropathy

Differential Diagnosis:

• Multifocal motor neuropathy
• Diabetic polyneuropathy
• Fibromyalgia
• Multiple sclerosis
• Amyotrophic lateral sclerosis (ALS)
• Guillain-Barre syndrome (GBS)
• Neuropathy associated with: nutritional deficiencies, critical illness, toxins, systemic inflammatory diseases

Lewis, koller^^^

Global muscle weakness of the upper and lower extremities, the reduction of deep tendon reflexes and aggressive course of the disease are distinguishing factors between CIDP and chronic length-dependent peripheral neuropathies (Lewis, 2007).

The demyelinating form of Guillain-Barre syndrome (GBS), which is a form of acute inflammatory demyelinating polyneuropathy (AIDP), and CIDP are quite similar in nature and are differentiated by their time of progression (Lewis, 2007). GBS often occurs after an identifiable infectious illness, vaccination or surgery, 3-4 weeks prior to the onset of symptoms.  In comparison, CIDP often does not have an easily identifiable antecedent event and progresses for 8 weeks or more. (lewis, Garson).

As stated previously, CIDP is suspected to be vastly underestimated (latov). On the contrary, there is research suggesting that a misdiagnosis of CIDP commonly occurs in other neurologic conditions (allen/lewis). This misdiagnosis is attributed to the lack of implementation of specific clinically relevant criteria and electrodiagnostic criteria. One study even determined that a whopping, “Forty-seven percent of patients referred with a diagnosis of CIDP failed to meet minimal CIDP diagnostic requirements,” (allen & lewis). The amount of underreporting and misdiagnoses demonstrates the importance of implementing the most current and valid diagnostic criteria.

Diagnostic Procedures

It is not uncommon for CIDP to go undiagnosed for months to years depending on a patient's symptoms. This could be due to symptoms not being prominent enough to affect an individual's day to day routine and cause concern to visit their physician. In addition, the presence of non debilitating symptoms makes it difficult to give a definitive diagnosis of CIDP in the early stages, even after follow up with their physician (Wolfe and Greer, 2015).  Diagnosing CIDP depends upon the appearance of the demyelination process found during electrophysiological testing. According to a study performed by Mathey & Pollard  a possible criterion method has been developed in order to determine whether an individual has CIDP by looking at the demyelination process. This process is defined by the presentation of any of the following in at least two nerves: (Mattey & Pollard)

• prolongation of distal latency
• reduction in motor conduction velocity
• prolongation of F waves
• partial conduction block
• abnormal temporal dispersion
• prolonged distal compound muscle action potential (CMAP) duration and one other demyelinating parameter in one other nerve

Since the pathological changes in polyradiculoneuropathies such as CIDP or GBS involve proximal regions mainly, these regions need to be examined electrophysiolgoically by testing F waves.  The purpose is to look for a proximal conduction block or for recording evoked potentials, however, routine studies may sometimes be normal.

Features that support a diagnosis include the following:(Mathey, pollard)

A) Elevated CSF protein without an increased leukocyte count

B) MRI evidence of gadolinum enhancement or nerve root plexus hypertrophy

C) Nerve biopsy finding of primary demyelination

D) Improvement following immunotherapy

It has also been noted that motor fibres tend to be more affected compared to sensory nerves and this is taken into consideration during the diagnosis stage (Lewis, 2007). Another diagnosing feature of CIDP is that it tends to affect more of the proximal muscles first, typically causing torso weakness in early stages (Lewis, 2007).

According to the American Academy of Neurology in order to have a definitive diagnosis both a cerebrospinal fluid sample must be taken, as well as a nerve biopsy (Koller). However, there is a current controversy regarding the need for the biopsy to be performed in order to be included in the diagnosis (Lewis, 2007). Other possible ways to confirm or reject a diagnose include: lab studies based on serum glucose, glycated hemoglobin, thyroid function studies, hepatitis profiles, HIV testing and serum immunofixation electrophoresis (Lewis, 2007).

Management/Interventions

Most therapies used to treat CIDP aim to block immune processes in order to stop inflammation and demyelination, in addition to preventing secondary axonal degeneration. Patients who respond to treatment must continue until their condition is stabilized or maximum improvement occurs. Improvements are measured with comparable signs such as improvement in sensation, strength and the performance of activities of daily living (ADL’s). Further treatment/maintenance therapy is provided to assist the individual with the intention to reduce the frequency of relapses and slow disease progression. Patients should be aware that infections, systemic conditions and neurotoxic drugs can negatively influence the symptoms of CIDP. (koller) Additionally, treatments also aim to reduce patient symptoms, such as weakness and pain, and improve overall functional status (Gorson)

Occupational therapists can prescribe gait aids, specialized tools and ankle foot orthotics, if necessary, to assist individuals with functional tools for ADL’s and ambulation. Psychologists may also be an important part of the interprofessional team as they can address symptoms that often accompany a diagnosis of a chronic disease and change in functional status, such as depression, anxiety or frustration. (Gorson)

Medical Management

• Intravenous immunoglobulin
• Corticosteroids
• Plasma exchange
• Immunosuppressive therapy

Research by Koller it suggests that 60 to 80 percent of patients that are treated with intravenous immunoglobulin, corticosteroids or plasma exchange have improvements in their condition, but the long-term prognosis varies according to when the therapy is initiated and the degree of associated axonal loss.

The following describes the process of choosing medical management as suggested by Vallat: