Motor Chronic Inflammatory Demyelinating Polyneuropathy Research Articles

CIDP Variants

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous syndrome that has several variants. Although they share macrophage-associated demyelination, clinical, neurophysiological, and pathological investigations have demonstrated that each subtype has a different pathophysiology. Multifocal CIDP exhibits a chronic course with asymmetrical symptoms. Its neurophysiological significance involves multifocal demyelination at intermediate nerve sites. Distal CIDP has a prolonged chronic course, presenting sensory and motor symptoms in a length-dependent manner. Furthermore, it frequently coexists with IgG M proteinemia or other hematologic disorders. Motor CIDP displays symmetric muscle weakness similar to typical CIDP but lacks sensory involvement. Often, motor CIDP is associated with malignancy or inflammatory diseases. Although acute deterioration after corticosteroid therapy in patients with motor CIDP is well-known, the available evidence to support this is limited.

Neuromuscular ultrasound in combination with nerve conduction studies helps identify inflammatory motor neuropathies from lower motor neuron syndromes.

Identifying patients with inflammatory motor neuropathies (IMNs) is warranted since effective treatments are available and the prognosis of these patients differs from that of amyotrophic lateral sclerosis patients. Between January 2019 and May 2022, 102 consecutive treatment-naïve lower motor neuron syndrome (LMNS) patients were recruited; these patients were suspected of having multifocal motor neuropathy, pure motor chronic inflammatory demyelinating polyneuropathy or amyotrophic lateral sclerosis with initial lower motor neuron presentation. Neuromuscular ultrasound (US) and nerve conduction studies (NCSs) were conducted at baseline. Relevant diagnostic investigations were performed if clinically warranted. The proposed US evidence of IMN was as follows: (i) nerve enlargement at ≥1 of the predetermined sites or (ii) absence of high intensity fasciculations in predefined muscle groups. Final diagnoses were made by experienced physicians after a prolonged follow-up period (≥12 months). IMN patients were defined as LMNS patients who experienced convincing improvements in response to immunotherapies. IMN patients without electrodiagnostic demyelinating features were diagnosed with treatment-responsive LMNS (TR-LMNS). In total, 16 patients were classified as IMN, including nine chronic inflammatory demyelinating polyneuropathy/multifocal motor neuropathy patients and seven TR-LMNS patients. Six TR-LMNS patients were identified by neuromuscular US. The sensitivity and specificity of NCSs, nerve US and muscle US were 56.3% and 100%, 43.8% and 90.7% and 68.8% and 97.7%, respectively. When these three modalities were combined, the sensitivity and specificity were 93.8% and 88.4%, respectively. Neuromuscular US studies are supplementary modalities to NCSs, and the combined use of these techniques might improve the identification of IMNs in LMNS patients.

Motor chronic inflammatory demyelinating polyneuropathy in a child

Motor chronic inflammatory demyelinating polyneuropathy (M-CIDP) is a form of atypical CIDP. This article presents a clinical observation of M-CIDP in a 15-year-old boy, as well as a description of laboratory and instrumental diagnostic data. The boy had a chronic development (> 2 months) of flaccid tetraparesis, predominantly of the proximal muscles of the limbs, without sensory disorders. According to electroneuromyography, there were signs of demyelinating lesions of the proximal parts of the peripheral nerves. There was an increase in the thickness of the nerves of the upper limbs according to ultrasound. In the liquor protein-cell dissociation, as well as in the blood, IgG antibodies to the surface glycoprotein S of the SARS-CoV-2 coronavirus were found. The clinical and neurophysiological picture corresponded to the reliable criteria for CIDP. The therapy with intravenous immunoglobulins had a significant positive effect in the form of an increase in the strength of the limb muscles.

Clinical and long-term characteristics of the subtypes of chronic inflammatory demyelinating polyneuropathy

To clarify the clinical and long-term characteristic of each subtype of chronic inflammatory demyelinating polyneuropathy (CIDP). We evaluated data from 30 consecutive CIDP patients who met the criteria proposed by the European Federation of Neurological Societies and the Peripheral Nerve Society. Patients were classified as having typical CIDP (t-‍CIDP) (10/30, 33%), multifocal acquired demyelinating sensory and motor (MADSAM) (12/30, 40%), DADS (4/30, 13%), sensory CIDP (3/30, 10%) or motor CIDP (1/30, 3%). Nerve conduction studies showed more prolonged distal motor latencies/F-wave latencies and slower motor nerve conduction in the typical CIDP group than in the MADSAM group. Intravenous immunoglobulin (IVIg) was effective in 80% (8/10) of t-‍CIDP, 100% (12/12) of MADSAM, 100% (4/4) of DADS, and 100% (3/3) of sensory CIDP cases. Maintenance therapy with immunoglobulin was administered in patients with t-‍CIDP (5/10, 50%), MADSAM (9/12, 75%), DADS (1/4, 25%), and sensory CIDP (2/3, 67%). There were no patients with CIDP, in whom CIDP subtype was transformed from the initial diagnosis during five years of follow-up. Percentage of MADSAM was the most common phenotype in our cohort of CIDP patients, and IVIg/immunoglobulin maintenance was effective for MADSAM as well as t-‍CIDP in contrast to findings from the previous reports.

Treatment Approaches for Atypical CIDP.

The variants of chronic inflammatory demyelinating polyneuropathy (CIDP) differ not just in their clinical, pathological and electrophysiological characteristics, but often in their indifferent response to conventional immunosuppressive agents which are effective in typical CIDP. High quality evidence is lacking as far as the management of these atypical variants is concerned. In this review, we summarize the treatment approaches to each of these CIDP variants based on existing data. Distal acquired demyelinating symmetric polyneuropathy (DADS) has the phenotype of a symmetric, demyelinating sensory, length-dependent polyneuropathy and is frequently associated with paraproteinemia and anti myelin associated glycoprotein (MAG) antibodies. While the management of idiopathic DADS (DADS-I) is the same as CIDP, DADS-M responds suboptimally and has a favorable response to rituximab. Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) manifests as a chronic progressive demyelinating mononeuropathy multiplex which can evolve to a confluent pattern indistinguishable from CIDP. Evidence favors treating MADSAM with conventional immunomodulatory therapy (IMT), but this disorder responds less favorably than CIDP. Some patients present with purely sensory symptoms, known as pure sensory CIDP or chronic inflammatory sensory polyradiculoneuropathy (CISP), the latter localizing to a pre-ganglionic pathology. Both respond well to first line IMT, particularly to intravenous immunoglobulin (IVIG), but patients relapse without maintenance therapy. Pure motor CIDP resembles multifocal motor neuropathy with conduction block (MMNCB), but the previously reported worsening status after steroid treatment was not reproduced in recent studies, and IVIG remains the first-line therapy. Some focal forms of CIDP defy exact classification, but respond well to first-line IMT including IVIG. Overall, atypical CIDP responds to treatment with first-line IMT, but has a suboptimal response compared to CIDP. There is evidence for effectiveness with agents such as rituximab, especially in DADS-M, and this medication can also be used in cases refractory to conventional IMTs. Rituximab is also effective in CIDP with IgG4 antibodies which has distinct clinical features and is mostly refractory to first-line IMT.

CIDP Antibodies Target Junction Proteins and Identify Patient Subgroups

ObjectiveTo discover systemic characteristics in the repertoires of targeted autoantigens in chronic inflammatory demyelinating polyneuropathy (CIDP), we detected the entire autoantigen repertoire of patients and controls and analyzed them systematically.MethodsWe screened 43 human serum samples, of which 22 were from patients with CIDP, 12 from patients with other neuropathies, and 9 from healthy controls via HuProt Human Proteome microarrays testing about 16,000 distinct human bait proteins. Autoantigen repertoires were analyzed via bioinformatical autoantigenomic approaches: principal component analysis, analysis of the repertoire sizes in disease groups and clinical subgroups, and overrepresentation analyses using Gene Ontology and PantherDB.ResultsThe autoantigen repertoires enabled the identification of a subgroup of 10/22 patients with CIDP with a younger age at onset and a higher frequency of mixed motor and sensory CIDP. IV immunoglobulin therapy responders targeted 3 times more autoantigens than nonresponders. No CIDP-specific autoantibody is present in all patients; however, anchoring junction components were significantly targeted by 86.4% of patients with CIDP. There are potential novel CIDP-specific autoantigens such as the myelination- or axo-glial structure–related proteins actin-related protein 2/3 complex subunit 1B, band 4.1-like protein 2, cadherin-15, cytohesin-1, epidermal growth factor receptor, ezrin, and radixin.ConclusionsThe repertoire of targeted autoantigens of patients with CIDP differs in a systematic degree from those of controls. Systematic autoantigenomic approaches can help to understand the disease and to discover novel bioinformatical tools and novel autoantigen panels to improve diagnosis, treatment, prognosis, or patient stratification.

Motor chronic inflammatory demyelinating polyneuropathy (CIDP) in 17 patients: Clinical characteristics, electrophysiological study, and response to treatment

Motor chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare and poorly described subtype of CIDP. We aimed to study their clinical and electrophysiological characteristics and response to treatment. From a prospective database of CIDP patients, we included patients with definite or probable CIDP with motor signs and without sensory signs/symptoms at diagnosis. Patients were considered to have pure motor CIDP (PM-CIDP) if sensory conductions were normal or to have motor predominant CIDP (MPred-CIDP) if ≥2 sensory nerve action potential amplitudes were abnormal. Among the 700 patients with CIDP, 17 (2%) were included (PM-CIDP n = 7, MPred-CIDP n = 10); 71% were male, median age at onset was 48 years (range: 13-76 years), 47% had an associated inflammatory or infectious disease or neoplasia. At the more severe disease stage, 94% of patients had upper and lower limb weakness, with distal and proximal weakness in 4 limbs for 56% of them. Three-quarters (75%) responded to intravenous immunoglobulins (IVIg) and four of five patients to corticosteroids including three of three patients with MPred-CIDP. The most frequent conduction abnormalities were conduction blocks (CB, 82%) and F-wave abnormalities (88%). During follow up, 4 of 10 MPred-CIDP patients developed mild sensory symptoms; none with PM-CIDP did so. Patients with PM-CIDP had poorer outcome (median ONLS: 4; range: 22-5) compared to MPred-CIDP (2, range: 0-4; P = .03) at last follow up. This study found a progressive clinical course in the majority of patients with motor CIDP as well as frequent associated diseases, CB, and F-wave abnormalities. Corticosteroids might be considered as a therapeutic option in resistant IVIg patients with MPred-CIDP.

P19-S Can nerve conduction studies help to distinguish motor CIDP and MMN?

Motor chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) share exclusively motor peripheral nerves involvement. Differentiation is based mainly on clinical symptoms, but sometimes it can be difficult. The aim was electrophysiological evaluation of motor CIDP and MMN patients according to frequency of conduction block (CB) and demyelination. Material and methods retrospective analysis of nerve conduction studies (NCS) of patients fullfiling EFNS/PNS criteria for definite or probable CIDP or MMN, diagnosed in our department, was used. EFNS/PNS criteria for CIDP were applied to define demyelination and CB. 13 patients were included: 6 with motor CIDP, 7 with MMN; in CIDP there were 2M and 4F, age 21–70 yrs, mean 41.3 yrs, in MMN 3 M and 4F, age 34–61 yrs, mean 43.7 yrs. 6–8 motor nerves were examined in every patient, nerves with amplitude of compound motor action potential (CMAP) Results At least one CB was found in every CIDP and MMN patient. Number of CB per segment was 0,18 in CIDP and 0,20 in MMN. Conduction velocity (CV) reduction was revealed in 1 CIDP patient in 3 segments and in 4 MMN patients in 1–2 segments (segments with CB and entrapment sites were excluded). Distal CMAP duration increase was found in at least one nerve in every CIDP patient (in 1–5 nerves, mean 2,5) and in 2 MMN patients in 1–2 nerves. Conclusion NCS alone can not distinguish CIDP from MMN, although it seems that distal CMAP duration increase is more common feature in CIDP.

Przewlekła zapalna polineuropatia demielinizacyjna z wybiórczym zajęciem nerwów ruchowych – opis przypadku

Chronic inflammatory demyelinating polyneuropathy is a disease with muscle weakness and sensory disorder. The nerve injury is believed to be due to autoimmune process. Symptoms usually develop gradually and can follow a relapsing-remitting or a progressive course. Apart from the classic form, a number of variants of the entity have been described with heterogeneous clinical manifestation. In this article we present a case of pure motor chronic inflammatory demyelinating polyneuropathy. Possible methods of treatment and the therapy used in this case have been described.

Pure Motor Chronic Inflammatory Demyelinating Polyneuropathy: Relationship to Multifocal Motor Neuropathy with Conduction Block (P06.137)

Objective: To report two cases of pure motor chronic inflammatory demyelinating polyneuropathy (CIDP), response to therapy, and possible relationship to multifocal motor neuropathy with conduction block (MMN). Background Motor CIDP is a rare variant of classic CIDP that is not well understood in regard to both its pathogenesis and appropriate treatment. The few studies that have been published suggest that unlike classic CIDP, motor CIDP does not respond well to corticosteroids. Design/Methods: Two motor CIDP patients are presented, one of whom has high titers to anti-GM1 antibodies. Results: Patient 1 is a 48 year old woman with a history of CIDP who developed worsening of her strength and diffuse wasting and fasciculations concerning for motor neuron disease. She was found to have an elevated titer of anti-GM1 antibodies of 1:102,400 and a pure motor demyelinating neuropathy with secondary axonal degeneration by electrodiagnosis. The patient failed to respond to weekly IVIG therapy and then worsened with corticosteroids, becoming bed-bound and requiring non-invasive ventilation. Despite weekly rituximab infusions, she continued to declined and was started on monthly plasma exchange and intravenous cyclophosphamide. She can now walk and her anti-GM1 antibody titer has fallen to 1:12,800. Patient 2 is a 56 year old man who presented with a three month history of fasciculations, progressive wasting, and diffuse weakness requiring a wheelchair after failing to respond to single courses of both IVIG and plasma exchange. His electrodiagnostic testing revealed findings similar to the first patient. He was restarted on weekly IVIG and, after 12 courses, finally recovered his ability to walk. Conclusions: Motor CIDP may be more resistant to treatment than classic CIDP. High titers of anti-GM1 antibodies and paradoxical worsening with corticosteroids in some patients could also support a distinct pathogenesis more similar to MMN. Abundant fasciculations seen in this disorder may mistakenly suggest motor neuron disease. Disclosure: Dr. Thyerlei has nothing to disclose. Dr. Weiss has received personal compensation for activities with Walgreens, CSL Behring and Talecris Biotherapeutics as a consultant and/or speaker.

Chronic inflammatory demyelinating polyneuropathy in a patient with hyperIgEaemia

We herein report the case of a 46 year old man with chronic inflammatory demyelinating polyneuropathy (CIDP) with hyperIgEaemia. The patient presented with bilateral weakness, generalized hyporeflexia, and mild paresthesia of the fingers of both hands. Nerve conduction studies revealed multiple sites of motor conduction block in the absence of sensory abnormalities. Muscle strength increased, as did compound muscle action potential (CMAP) amplitude immediately after the intravenous infusion of immunoglobulin (IVIg). Serum IgE levels also fluctuated in parallel with his relapsing–remitting clinical course. We propose that pure motor CIDP may be immune mediated and suggest that IgE-mediated allergy may be one potential cause of this condition.

Different clinical, electrophysiological and immunological features of CIDP associated with paraproteinaemia.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is frequently associated with monoclonal gammopathies of undetermined significance (MGUS), Waldenström disease and osteosclerotic myeloma. There are still controversies about the role of these paraproteinaemias in determining the clinical features and the response to treatment of CIDP. We review the clinical, electrophysiological and immunological features and the response to treatment of patients with CIDP associated with paraproteinaemias. The available literature suggest some conclusions: presence of antimyelin-associated glycoprotein (MAG) antibody (Ab) identifies patients with mainly sensory CIDP and low response to treatment; CIDP associated with IgM-paraproteinaemia without anti-MAG Ab probably are similar to CIDP not associated with paraproteinaemia as well as CIDP with IgG- or IgA-MGUS; however, some patients with IgA-MGUS can show features similar to CIDP with IgM paraproteinaemia and anti-MAG Ab. Low response to immunomodulating treatment in patients with mainly motor CIDP should prompt a careful research of an underlying osteosclerotic myeloma.

Pure motor chronic inflammatory demyelinating polyneuropathy

We describe four patients affected by chronic inflammatory demyelinating polyneuropathy (CIDP) in a pure motor form. Selective involvement of motor fibers was suggested by the absence of sensory symptoms, normal sensation at neurological examination and normal findings on electrophysiological testing of sensory fibres and sural nerve biopsy. The onset of the disease occurred at a young age (3-29 years) and the clinical course was relapsing-remitting. Over a follow-up period of 1.5-14 years, periodical clinical and electrophysiological examinations showed that selective involvement of motor fibers remained a constant feature. Electromyography and nerve conduction studies continued to show a purely demyelinating neuropathy without signs of axonal impairment. All patients were steroid-unresponsive, whereas they considerably improved after being treated with immunoglobulins. Two patients were treated with interferon alpha and showed a good response. In conclusion, the occurrence in our four patients of pure motor involvement over a long period of time during which several relapses occurred, suggests that pure motor CIDP may represent the result of a specific immunological process rather than of a random distribution of inflammation throughout peripheral nerves.