Pathophysiology of Chronic Inflammatory Demyelinating Polyneuropathy: Insights into Classification and Therapeutic Strategy
Abstract Chronic inflammatory demyelinating polyneuropathy (CIDP) is classically defined as polyneuropathy with symmetric involvement of the proximal and distal portions of the limbs. In addition to this “typical CIDP”, the currently prevailing diagnostic criteria proposed by the European Federation...
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2020-05-01
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| Series: | Neurology and Therapy |
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| Online Access: | https://doi.org/10.1007/s40120-020-00190-8 |
| _version_ | 1797209022564139008 |
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| author | Haruki Koike Masahisa Katsuno |
| author_facet | Haruki Koike Masahisa Katsuno |
| author_sort | Haruki Koike |
| collection | DOAJ |
| description | Abstract Chronic inflammatory demyelinating polyneuropathy (CIDP) is classically defined as polyneuropathy with symmetric involvement of the proximal and distal portions of the limbs. In addition to this “typical CIDP”, the currently prevailing diagnostic criteria proposed by the European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS) define “atypical CIDP” as encompassing the multifocal acquired demyelinating sensory and motor (MADSAM), distal acquired demyelinating symmetric (DADS), pure sensory, pure motor, and focal subtypes. Although macrophage-induced demyelination is considered pivotal to the pathogenesis of CIDP, recent studies have indicated the presence of distinctive mechanisms initiated by autoantibodies against paranodal junction proteins, such as neurofascin 155 and contactin 1. These findings led to the emergence of the concept of nodopathy or paranodopathy. Patients with these antibodies tend to show clinical features compatible with typical CIDP or DADS, particularly the latter. In contrast, classical macrophage-induced demyelination is commonly found in some patients in each major subtype, including the typical CIDP, DADS, MADSAM, and pure sensory subtypes. Differences in the distribution of lesions and the repair processes underlying demyelination by Schwann cells may determine the differences among subtypes. In particular, the preferential involvement of proximal and distal nerve segments has been suggested to occur in typical CIDP, whereas the involvement of the middle nerve segments is conspicuous in MADSAM. These findings suggest that humoral rather than cellular immunity predominates in the former because nerve roots and neuromuscular junctions lack blood–nerve barriers. Treatment for CIDP consists of intravenous immunoglobulin (IVIg) therapy, steroids, and plasma exchange, either alone or in combination. However, patients with anti-neurofascin 155 and contactin 1 antibodies are refractory to IVIg. It has been suggested that rituximab, a monoclonal antibody to CD20, could have efficacy in these patients. Further studies are needed to validate the CIDP subtypes defined by the EFNS/PNS from the viewpoint of pathogenesis and establish therapeutic strategies based on the pathophysiologies specific to each subtype. |
| first_indexed | 2024-04-24T09:48:06Z |
| format | Article |
| id | doaj.art-d243a2efdb254818bd40c53c8cb1ce2f |
| institution | Directory Open Access Journal |
| issn | 2193-8253 2193-6536 |
| language | English |
| last_indexed | 2024-04-24T09:48:06Z |
| publishDate | 2020-05-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Neurology and Therapy |
| spelling | doaj.art-d243a2efdb254818bd40c53c8cb1ce2f2024-04-14T11:33:46ZengAdis, Springer HealthcareNeurology and Therapy2193-82532193-65362020-05-019221322710.1007/s40120-020-00190-8Pathophysiology of Chronic Inflammatory Demyelinating Polyneuropathy: Insights into Classification and Therapeutic StrategyHaruki Koike0Masahisa Katsuno1Department of Neurology, Nagoya University Graduate School of MedicineDepartment of Neurology, Nagoya University Graduate School of MedicineAbstract Chronic inflammatory demyelinating polyneuropathy (CIDP) is classically defined as polyneuropathy with symmetric involvement of the proximal and distal portions of the limbs. In addition to this “typical CIDP”, the currently prevailing diagnostic criteria proposed by the European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS) define “atypical CIDP” as encompassing the multifocal acquired demyelinating sensory and motor (MADSAM), distal acquired demyelinating symmetric (DADS), pure sensory, pure motor, and focal subtypes. Although macrophage-induced demyelination is considered pivotal to the pathogenesis of CIDP, recent studies have indicated the presence of distinctive mechanisms initiated by autoantibodies against paranodal junction proteins, such as neurofascin 155 and contactin 1. These findings led to the emergence of the concept of nodopathy or paranodopathy. Patients with these antibodies tend to show clinical features compatible with typical CIDP or DADS, particularly the latter. In contrast, classical macrophage-induced demyelination is commonly found in some patients in each major subtype, including the typical CIDP, DADS, MADSAM, and pure sensory subtypes. Differences in the distribution of lesions and the repair processes underlying demyelination by Schwann cells may determine the differences among subtypes. In particular, the preferential involvement of proximal and distal nerve segments has been suggested to occur in typical CIDP, whereas the involvement of the middle nerve segments is conspicuous in MADSAM. These findings suggest that humoral rather than cellular immunity predominates in the former because nerve roots and neuromuscular junctions lack blood–nerve barriers. Treatment for CIDP consists of intravenous immunoglobulin (IVIg) therapy, steroids, and plasma exchange, either alone or in combination. However, patients with anti-neurofascin 155 and contactin 1 antibodies are refractory to IVIg. It has been suggested that rituximab, a monoclonal antibody to CD20, could have efficacy in these patients. Further studies are needed to validate the CIDP subtypes defined by the EFNS/PNS from the viewpoint of pathogenesis and establish therapeutic strategies based on the pathophysiologies specific to each subtype.https://doi.org/10.1007/s40120-020-00190-8DemyelinationElectron microscopyMacrophageNode of RanvierParanodePathogenesis |
| spellingShingle | Haruki Koike Masahisa Katsuno Pathophysiology of Chronic Inflammatory Demyelinating Polyneuropathy: Insights into Classification and Therapeutic Strategy Neurology and Therapy Demyelination Electron microscopy Macrophage Node of Ranvier Paranode Pathogenesis |
| title | Pathophysiology of Chronic Inflammatory Demyelinating Polyneuropathy: Insights into Classification and Therapeutic Strategy |
| title_full | Pathophysiology of Chronic Inflammatory Demyelinating Polyneuropathy: Insights into Classification and Therapeutic Strategy |
| title_fullStr | Pathophysiology of Chronic Inflammatory Demyelinating Polyneuropathy: Insights into Classification and Therapeutic Strategy |
| title_full_unstemmed | Pathophysiology of Chronic Inflammatory Demyelinating Polyneuropathy: Insights into Classification and Therapeutic Strategy |
| title_short | Pathophysiology of Chronic Inflammatory Demyelinating Polyneuropathy: Insights into Classification and Therapeutic Strategy |
| title_sort | pathophysiology of chronic inflammatory demyelinating polyneuropathy insights into classification and therapeutic strategy |
| topic | Demyelination Electron microscopy Macrophage Node of Ranvier Paranode Pathogenesis |
| url | https://doi.org/10.1007/s40120-020-00190-8 |
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