Scope of CIDP could be broadened to ‘syndrome’ status

By Jennifer Lubell

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As experts revise the guideline on management of chronic inflammatory demyelinating polyneuropathy, some in the clinical neurology field are calling for a regrouping of CIDP under a more general, overarching term, “CIDP syndrome” (CIDPS). This would include four immune-mediated forms that share similar characteristics to CIDP, Peter Y. K. Van den Bergh, MD, PhD, and colleagues suggested in an editorial in the Journal of the Peripheral Nervous System (J Peripher Nerv Syst. 2020 Mar;25[1]:4-8. doi: 10.1111/jns.12364).

“Typical and atypical CIDP are part of a much larger group of immune-mediated neuropathies. We feel that those we discuss not only belong to this group of disorders but bear similarities with CIDP,” Dr. Van den Bergh, professor of neurology at Université Catholique de Louvain and director and coordinator of the Neuromuscular Reference Centre at University Hospital St Luc in Brussels, said in an interview.

Challenges of diagnosing atypical CIDP

CIDP is a complex and heterogeneous disorder. In general, typical CIDP can be confidently diagnosed as the clinical syndrome, and is well known by neuromuscular specialists. The main challenge is the atypical forms. These have been added to the CIDP spectrum “because they have in common inflammatory demyelination and response to treatment. Yet we do not know whether the pathogenesis and treatments of these atypical forms is the same as typical CIDP,” Dr. Van den Bergh said.

Dr. Peter Y. K. Van den Bergh

Experts call for a regrouping of the term to include typical and atypical forms under “CIDP syndrome.”

There is no gold standard for diagnosing typical and atypical CIDP. As a result, most people misdiagnosed with CIDP (up to 90% in some cases) are assigned some type of atypical CIDP.

Revisions to the 2010 European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) guideline on management of CIDP plan to address these difficulties. As Dr. Van den Bergh and colleagues emphasize in their paper, a number of conditions resembling CIDP have their own specificities and need proper diagnosis for appropriate patient management. “Having these related disorders under one umbrella like CIDPS may help make a correct diagnosis and to further our understanding of the pathophysiology,” said Dr. Van den Bergh, who chairs the CIDP guideline task force.

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Broadening the terms

The paper discusses four conditions that the authors believe should be included under the CIDPS umbrella: anti–myelin-associated glycoprotein (MAG) neuropathy, chronic neuropathies associated with IgG4 antibodies against paranodal/nodal proteins, chronic immune sensory polyradiculopathy (CISP), and multifocal motor neuropathy (MMN).

Each of these conditions share similar attributes to CIDP. Anti-MAG neuropathy is an IgM paraproteinemic neuropathy, which resembles distal CIDP because of distal sensory loss and often weakness. These patients have myelin-specific antibodies and often respond poorly to usual CIDP treatments.

Up to 10% of patients fulfilling clinical and electrophysiological EFNS/PNS criteria for CIDP have chronic neuropathies associated with IgG4 antibodies against paranodal/nodal proteins. These patients have antibodies directed against proteins at the nodes of Ranvier. “Although these neuropathies resemble CIDP, diagnosing them correctly is very important because their management is different,” Dr. Van den Bergh said. 

CISP is an inflammatory demyelinating disorder with pure sensory symptoms and signs. “Therefore, it resembles sensory CIDP but sensory (and motor) nerve conductions are normal, indicating that it is not a peripheral neuropathy but rather a sensory radiculopathy. However, immune treatment like for CIDP is usually successful,” he continued.

MMN is a motor neuropathy resembling multifocal CIDP – however, the latter is a sensorimotor neuropathy. Unlike multifocal CIDP, patients with MMN do not improve on immune treatments other than intravenous immunoglobulin.

Although these neuropathies resemble CIDP, diagnosing them correctly is very important because their management is different.

Guideline to address the nosologic position of four disorders

The revised CIDP guideline, which will be published jointly in the European Journal of Neurology and the Journal of the Peripheral Nervous System, “will pay more attention to the definition and diagnosis of the atypical CIDP forms to differentiate these from other disorders,” Dr. Van den Bergh said. Specifically, it will address the four immune-mediated neuropathies resembling CIDP that he and his colleagues believe should be part of the CIDPS. This is especially true with CISP and the IgG4-mediated paranodal/nodal neuropathies.

Richard A. Lewis, MD, director of the electromyography laboratory and professor of neurology at Cedars-Sinai Medical Center, Los Angeles, and another member of the task force to reassess and revise the CIDP guideline, agreed with Dr. Van den Bergh’s approach to carefully distinguish between CIDP and related conditions. CIDP is a syndrome and, even within that syndrome, “there are disorders that have some features in common with ‘typical CIDP’ but do not respond to the same treatments,” Dr. Lewis said in an interview.

Anti-MAG neuropathy, for example, doesn’t respond to many of the treatments for CIDP. “It has different clinical, physiologic, and pathologic features, as well as different treatment options,” Dr. Lewis said. The situation is the same for disorders with IgG4 antibodies against paranodal/nodal proteins.

Right now, the guideline committee is working on the optimal approach to categorize these disorders, he continued. “The reason we struggle with this classification is that we want neurologists to recognize the different conditions that should be treated as CIDP but also those that mimic the disorder and should be treated in a different way. Ultimately we hope that the guidelines will lead to more accurate diagnoses and more focused therapies.”

Dr. Van den Bergh anticipates the guidelines will be released in early 2021.

Dr. Richard A. Lewis