Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Eichhorst¹ first described recurrent polyneuritis in 1890. Sporadic case reports followed,^{2 - 5} including a case series by Hoestermann⁵ in 1914 that described a 50-year-old man who experienced 6 bouts of polyneuropathy between 1870 and 1900. During his fourth episode,

he complained of a furry, numb feeling in his feet and hands and weakness when lifting the arms. The complaints increased and soon led to severe paresis of the extremities. As with all previous episodes his bowel and bladder were spared.^{5 (p117)}

These early cases differed from acute polyneuritis (Guillain-Barré syndrome) in their relapsing nature and usually by their more gradual onset. A report from 1929 that described a case of recurrent polyneuropathy in a 45-year-old man further demonstrates the cardinal clinical features of relatively symmetric proximal and distal weakness, hyporeflexia or areflexia, and to a lesser degree, sensory disturbances. This patient complained of

weakness of the legs with unsteadiness of gait, especially in the dark, and of tingling and loss of sensation in the tips of his fingers. These symptoms cleared up after several weeks, but he later had four similar attacks, with complete recovery in the intervals. . . . His arms became so weak that he could not raise them at the shoulders, and the muscles of the legs wasted and the feet became dropped. There was never any pain, nor any weakness of the sphincters. . . . There was no history of any similar disease in other members of his family. . . . He then had a steppage gait, with complete bilateral foot-drop, and also considerable weakness of the gastrocnemii and of the flexors of the toes. Flexion and extension of the hips and knees were only slightly weakened. . . . In his arms the deltoids were weak, so that the arms could not be completely abducted at the shoulder, and flexion of the forearms was also feeble. . . . Knee-jerks and Achilles-jerks absent. . . . There was slight numbness of the finger tips, and he was apt to let small objects slip from his fingers, but there was no objective loss of tactile sensation or to pin-prick of the hands or arms, trunk, or feet and legs.^{6 (p110)}

Elevation of cerebrospinal fluid protein without pleocytosis (albuminocytologic dissociation) was reported in a case of relapsing polyneuritis in 1931.⁷ Fifteen years earlier, Guillain, Barré, and Strohl⁸ had reported this laboratory finding in 2 French soldiers with acute polyneuritis.

In 1955 and 1956, Waksman and Adams^{9 - 10} produced acute neuropathy in animals by injection of homologous or heterologous peripheral nerve tissue combined with Freund adjuvant. Several years later, an experimental model of chronic EAN was developed.^{11 - 12} The acute and chronic EAN models provided compelling evidence that Guillain-Barré syndrome and the condition that would later be called CIDP were not caused by an infectious, toxic, or spontaneous process. Waksman and Adams argued that the underlying mechanism of EAN was autoimmune; that EAN was

due to an immunologic (allergic) process is in the final analysis largely based on the nature of the technique used to produce them, on the existence of the characteristic latent period, and on the inflammatory character of the lesions in the absence of an infectious agent.^{9 (p228)}

During the late 1950s and early 1960s, increased understanding and use of nerve conduction studies in the field of human neuromuscular disease led to improved characterization of polyneuropathies. With the guidance of Edward Lambert, MD, at the Mayo Clinic (Rochester, Minn), Henriksen¹³ studied nerve conduction velocities in healthy individuals and subjects with various neuromuscular diseases including several likely cases of CIDP. In his thesis, Henriksen presciently suggested that "a wide field seems open for the clinical diagnostic use of measurements of conduction velocity in peripheral nerves."^{13 (p1)} He reported reduced conduction velocities of the ulnar nerve in patients with polyneuritis "in whom the duration of the illness was greater than three months,"^{13 (p27)} as well as in cases of Guillain-Barré syndrome (Figure 1). This 1956 publication was the first demonstration of the sometimes dramatic conduction slowing seen in cases of what was likely CIDP. That same year, Lambert¹⁴ also reported these observations. During the next 5 years, other investigators confirmed the typical electrodiagnostic features of similar cases.^{15 - 17} Later, Wilbourn¹⁸ and then Lewis and Sumner¹⁹ pointed out that conduction block and differential slowing of conduction between and within nerves were common in acquired demyelinating polyneuropathies such as CIDP but rare in inherited demyelinating polyneuropathies.

Nerve conduction studies in animals with EAN demonstrated that conduction slowing and conduction block were associated with segmental demyelination. In 1962, Kaeser and Lambert reported reduced nerve conduction velocities in EAN, suggesting that "[i]t may be that relatively slight alterations of the myelin sheath can greatly impair the conduction velocity."^{20 (p35)} Cragg and Thomas found that the changes in nerve conduction in EAN appear to indicate

that many of the fibres develop a conduction block. Since only occasional fibres undergoing Wallerian degeneration were seen, this must mean that the conduction block is related to the demyelinating process or to axonal damage short of Wallerian degeneration.^{21 (p112)}

The concept of segmental demyelination causing conduction block was not new, having been reported by Denny-Brown and Brenner²² following experiments with tourniquet paralysis of the cat sciatic nerve. Segmental demyelination was later found to be the predominant histopathologic feature of the human sural nerve in cases of CIDP.²³

Cortisone and adrenocorticotropic hormone became available in the late 1940s and were shown to be efficacious for rheumatoid arthritis in 1949. Whereas many cases of corticosteroid-responsive polyneuropathy were reported during the next 3 decades,^{24 - 27} the report by Austin²⁷ was particularly remarkable because it demonstrated successful corticosteroid therapy for a patient with 20 episodes of relapsing polyradiculoneuropathy:

Each of the 20 bouts in this case offers two opportunities to observe the effect of drug—both in relation to its onset and to its recovery. In these 40 events, observed over five years, this patient has had a consistent, reproducible and predictable pattern of response to ACTH [corticotropin], cortisone, prednisone and placebos. In 21 of these 40 observations, improvement either began shortly after hormones were first given or after dosage was significantly increased. In 16 observations, bouts began after dosage was cut. In the remaining three placebo control observations, significant progression occurred each of three times during oral, intravenous, and intramuscular placebo periods.^{27 (p176)}

In 1975, Dyck and colleagues proposed diagnostic criteria in a landmark publication that described 53 patients with "chronic inflammatory polyradiculoneuropathy."^{28 (p621)} They noted that

[T]oday it is often possible to identify this disorder by its natural history, electrodiagnostic characteristics, cerebrospinal fluid findings, and pathology. The descriptive term "chronic inflammatory polyradiculoneuropathy" is preferred by us over possible alternative names because it emphasizes the inflammatory nature, the protracted course, and the anatomic involvement.^{28 (p621)}

The authors rejected previous terms for the condition as being too inclusive (hypertrophic neuropathy), too exclusive (relapsing neuropathy or recurrent neuropathy), outdated (idiopathic neuropathy), or incorrect (neuronitis). The term steroid-responsive polyneuropathy was not chosen partly because the efficacy of steroid treatment had not been established. The current term, chronic inflammatory demyelinating polyradiculoneuropathy, was first used by Dyck et al²⁹ in a study that demonstrated the efficacy of prednisone for some but not all cases of CIDP. Clinical trials later demonstrated the efficacy of intravenous immunoglobulin and plasma exchange.^{30 - 31} Today prednisone, intravenous immunoglobulin, and plasma exchange remain the mainstays of treatment for CIDP.

Corresponding author and reprints: Ted M. Burns, MD, University of Virginia, Department of Neurology, Box 800394, Charlottesville, VA 22908.

Accepted for publication June 18, 2003.

I thank Annemarei Ranta, MD, for the translation of German text.