Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Epidemiology

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) comprises a small but important subset of chronic childhood polyneuropathies. One series identified childhood CIDP in 11/125 (9%) of all children with a chronic polyneuropathy confirmed by sural nerve biopsy. A second series reported CIDP in 35/249 (14%) of all children diagnosed with a sensorimotor polyneuropathy.

CIDP can present from infancy to late adulthood. The mean age of childhood CIDP onset is 8 to 9 years, but it can appear at any age. No gender predilection is observed. The overall annual incidence of CIDP (all ages) is estimated to be 0.15 per 100,000 per year. By comparison the annual incidence of acute inflammatory demyelinating polyradiculoneuropathy, or Guillain-Barré syndrome, has been estimated to be 1.3 per 100,000 per year (range 0.4 to 4.0) reflecting a 10-fold higher annual incidence of the acute form of the disease. The overall prevalence of CIDP is estimated at 1–2 per 100,000 with disease prevalence increasing with advancing age. An Australian study reported the prevalence of childhood CIDP to be 0.5 per 100,000, increasing more than 12-fold to 6.7 per 100,000 among 70- to 79-year-old adults.

Pathogenesis

CIDP is an autoimmune disease resulting from a loss of immunologic self-tolerance. Cellular and humoral factors both contribute to autoimmune attack as autoreactive T and B lymphocytes, antibodies, and complement target myelinated peripheral nerves. Molecular mimicry is believed to be the mechanism underlying the autoimmune attack in CIDP. Molecular mimicry occurs when an individual is exposed to a new exogenous antigen (i.e. viral or bacterial infection) or when a normal endogenous intracellular protein becomes exposed to the immune system as a result of trauma, cancer, or a degenerative disease. The antigenic determinant known as the epitope is identified as foreign by the host’s immune system and targeted for cellular and humoral immune attack. While this process is essential for normal immune functioning, in circumstances where the foreign epitope resembles normal host tissue it can lead to an ongoing autoimmune attack redirected toward the host’s own tissue. In CIDP, the autoimmune attack is directed toward peripheral nerves and nerve roots. Only about one-third of children with CIDP can point to an inciting or antecedent event in the months prior to disease onset. Even among children with an acute inflammatory neuropathy such as Guillain-Barré syndrome, where less time has passed between potential preceding infection and disease onset, only two-thirds of patients recall prior infectious symptoms. Nevertheless, there are multiple levels of evidence to support an autoimmune basis for CIDP regardless of the initiating event.

Animal models of experimental allergic neuritis show a strong clinical and pathological resemblance to human CIDP. By injecting components of peripheral nerve myelin such as myelin protein zero (MPZ) or peripheral myelin protein 22 (PMP22) into the blood of healthy animals, a syndrome of chronic neuritis can be induced that is clinically and pathologically analogous to human CIDP. Affected animals show chronic inflammatory changes in their endoneurium as well as onion bulb formation similar to that seen in sural nerves of humans with CIDP. Such experiments were important in confirming an autoimmune basis for CIDP, redirecting attention away from a potential infectious cause. Later studies confirmed that passive transfer of serum or purified IgG from human CIDP patients to healthy rats can induce conduction block and demyelination. Antibody-mediated disease offers an explanation for specific types of inflammatory nerve disease such as Miller Fisher syndrome (MFS). This subtype of Guillain-Barré syndrome is characterized by ataxia, areflexia, and ophthalmoplegia and shows a very strong association with anti-GQ1b antibodies, which opsonize the GQ1b protein that is highly expressed on motor nerves innervating extraocular muscles. Unlike MFS, there has been no convincing antibody link to CIDP. Fewer than 10% of all CIDP patients have anti-ganglioside, anti-sulfatide, or other autoantibodies. Although an antibody-mediated attack does not appear to be the main immune process in patients with CIDP, the link with an autoimmune process is clear. T-lymphocytes remain important in the pathophysiology of CIDP. Sural nerve biopsies of adult CIDP patients show a correlation between the abundance of T lymphocytes in the endoneurium and the severity of demyelination.

Finally, support for autoimmunity in CIDP is supported by response of patients to immunomodulating therapies such as intravenous immunogloblins (IVIg), plasma exchange (PLEX), and corticosteroids, which will be described in greater detail later in this chapter.

Clinical Features

Three main areas must be considered by the clinician evaluating a child with possible chronic inflammatory demyelinating polyradiculoneuropathy. The first is to determine if the child exhibits the necessary clinical features to meet diagnostic criteria for CIDP. The second is to confirm the duration of symptoms that are reported. Finally, it is important to ascertain if the child demonstrates any clinical features potentially consistent with one of the many CIDP mimics, raising clinical suspicion of an alternative diagnosis and possibly excluding CIDP.

Children with CIDP demonstrate clinical signs and symptoms consistent with a sensorimotor polyneuropathy. Generalized muscle weakness and reduced or absent deep tendon reflexes are the two mandatory clinical criteria required for diagnosis of CIDP ( Box 21.1 ). Children will often have evidence of both proximal and distal muscle weakness, owing to the patchy immune attack along the entire length of the peripheral nerves. Weakness in CIDP patients is typically symmetrical; significant asymmetry should raise suspicion for alternative diagnoses. Hyporeflexia or areflexia is an early clinical feature of an inflammatory polyneuropathy and reflects involvement of both sensory afferents and—to a lesser degree—motor efferent fibers in this disease.