Acute Asymmetric Sensorimotor Variant of Chronic Inflammatory Demyelinating Polyneuropathy Triggered by mRNA-1273 COVID-19 Vaccination.

PURPOSE: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) developing in the postvaccination period was distinctly unusual and its course was rarely well described. We aimed to clearly depict the clinical features of acute-onset multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) caused by mRNA-1273 COVID-19 vaccination. CASE REPORT: A 74-year-old man noticed weakness of hands 2-3 days after he accepted the second dose of mRNA-1273 COVID-19 vaccine. He soon became unable to walk within one week. Initially, muscle power of bilateral hand grasping was most severely affected. He had stayed on at the nadir for 3.5 months until the diagnosis of CIDP was made. Nerve conduction studies showed typical evidences of acquired demyelinating, but no sural spare pattern. He was treated with intermittent pulse steroid therapy. Two weeks after treatment, INCAT disability score improved from 10 to 4, but remained at 4 thereafter: arm disability score was 3 and that of leg was 1, which suggested muscles of upper limbs were more severely affected. CONCLUSION: Diagnosis of acute-onset MADSAM was challenging at the beginning of this disease. For vaccine-triggered CIDP, time to symptom onset could be as short as 2-3 days. Delay in recognition may influence the remission of this disease. Muscles of upper limbs were more affected than those of lower limbs. Intermittent steroid pulse therapy would be an alternative to daily oral steroid therapy. Keyword: chronic inflammatory demyelinating polyradiculoneuropathy, COVID-19 vaccination.

Distal Chronic Inflammatory Demyelinating Polyneuropathy Following COVID-19 Vaccination in a Patient with Solitary Plasmacytoma: A Case Report and Literature Review.

We herein report a rare case of distal chronic inflammatory demyelinating polyneuropathy (CIDP) following coronavirus disease 2019 (COVID-19) vaccination. A 39-year-old woman with a solitary plasmacytoma developed general weakness 7 days after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine, which had progressed for 3 months. A neurological examination revealed limb weakness with areflexia. Serological tests identified the presence of IgG antibodies against anti-GM1 and anti-GM2 gangliosides. Comprehensive evaluations met the criteria of distal CIDP. Intravenous immunoglobulin, intravenous methylprednisolone, oral prednisolone, and plasma exchange were administered, and she gradually improved. Physicians should be aware of CIDP as a rare complication of COVID-19 vaccination.

Chronic inflammatory demyelinating polyneuropathy after SARS-CoV2 vaccination: update of the literature and patient characterization.

Since the beginning of worldwide vaccination against COVID-19 disease, some reports have revealed a possible relationship between SARS CoV2 vaccination and chronic inflammatory demyelinating polyneuropathy (CIDP). We reviewed the available evidences regarding this topic, adding three new cases to those reported so far, with the purpose to outline the characteristics of these post-vaccinal CIDP. Seventeen subjects were studied. A total of 70.6% of CIDP cases were related to viral vector vaccines, most occurring after the administration of the first dose. CIDPs that occurred after the second dose (17%) were temporally associated with mRNA vaccines. The clinical course and electrophysiology of all patients met the criteria for acute-subacute CIDP (A-CIDP). Administration of the viral vector vaccine was significantly correlated with a higher probability of having cranial nerve impairment (p = 0.004). The electrophysiological phenotype, laboratory and imaging data, and first-line therapies were substantially similar to those of the classical CIDP. The take-home message of the present paper is that the SARS CoV2 vaccine, especially the AstraZeneca vaccine, may be associated with inflammatory neuropathies with acute onset, often indistinguishable from Guillain-Barré syndrome (GBS). Hence, the importance of tracked prospectively patients with GBS occurred post-SARS-CoV2 vaccine. Distinguishing GBS from A-CIDP is crucial because treatment strategies and long-term prognosis are different.

Two Case Reports of Chronic Inflammatory Demyelinating Polyneuropathy After COVID-19 Vaccination.

The occurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) related to coronavirus disease 2019 (COVID-19) has rarely been reported. We describe two patients who were diagnosed with CIDP after COVID-19 vaccination. A 72-year-old man presented with a progressive tingling sensation and weakness below both knees for two weeks. He had been vaccinated against COVID-19 (mRNA-1273 vaccine) a month before the appearance of symptoms. Demyelinating polyneuropathy was observed in the nerve conduction studies (NCS). Intravenous immunoglobulin (IVIg) was administered under the diagnosis of Guillain-Barré syndrome (GBS), and his symptoms were improved. However, his symptoms relapsed at 10 weeks from the onset. Oral prednisolone, azathioprine, and IVIg were administered as treatment. The second case was a 50-year-old man who complained of a bilateral leg tingling sensation and gait disturbance lasting four weeks. He had received the Ad26.COV2.S vaccine against COVID-19 five weeks prior. Demyelinating polyneuropathy was observed in the NCS. He was treated with oral prednisolone, azathioprine, and IVIg for CIDP because his symptoms had lasted for more than 12 weeks from the onset. A causal relationship has not been established between COVID-19 vaccination and CIDP; however, CIDP may follow COVID-19 vaccination. As CIDP treatment is different from that for GBS, clinicians should closely monitor patients diagnosed with GBS associated with COVID-19 whether they deteriorate after initial treatment.

Assessment of Expression of SOCS Genes in Acquired Immune-Mediated Polyneuropathies.

Acquired immune-mediated polyneuropathies are classified to some subtypes among them are acute and chronic inflammatory demyelinating polyradiculoneuropathies (AIDP and CIDP). These two conditions share some common signs and underlying mechanisms. Based on the roles of Suppressor of cytokine signaling (SOCS) genes in the modulation of immune system reactions, these genes might be involved in the pathogenesis of these conditions. We evaluated expression of SOCS1-3 and SOCS5 genes in the leukocytes of 32 cases of CIDP, 19 cases of AIDP and 40 age- and sex-matched controls using real time PCR method. The Bayesian regression model was used to estimate differences in mean values of genes expressions between cases and control group. Expression levels of SOCS1 and SOCS2 were significantly lower in male patients compared with controls. This sex-specific pattern was also observed for SOCS3 down-regulation. Based on the area under curve values in Receiver Operating Characteristics (ROC) curve, diagnostic powers of SOCS1, SOCS2, SOCS3 and SOCS5 genes in the mentioned disorder were 0.61, 0.73, 0.68 and 0.58, respectively. Expression of none of genes was correlated with age of enrolled cases. The current study shows evidences for participation of SOCS genes in the pathophysiology of acquired immune-mediated polyneuropathies.

Expression Analysis of Protein Inhibitor of Activated STAT in Inflammatory Demyelinating Polyradiculoneuropathy.

Protein inhibitors of activated STAT (PIAS) are involved in the regulation of the JAK/STAT signaling pathway and have interactions with NF-κB, p73 and p53. These proteins regulate immune responses; therefore dysregulation in their expression leads to several immune-mediated disorders. In the present study, we examined expression of PIAS1-4 in peripheral blood of patients with acute/chronic inflammatory demyelinating polyradiculoneuropathy (AIDP/CIDP) compared with healthy subjects. We demonstrated down-regulation of all PIAS genes in both AIDP and CIDP cases compared with controls. Similarly, comparisons in gender-based groups revealed down-regulation of these gene0s in patients of each gender compared with gender-matched controls. There was no significant difference in expression of PIAS genes between AIDP and CIDP cases. Based on the area under the receiver operating characteristic curves, PIAS1-4 genes could distinguish between inflammatory demyelinating polyradiculoneuropathy and healthy status with accuracy values of 0.87, 0.87, 0.79 and 0.80, respectively. In differentiation between AIDP cases and healthy controls, these values were 0.92, 0.92, 0.83 and 0.86, respectively. Finally, PIAS1-4 genes could discriminate CIDP from healthy status with accuracy values of 0.82, 0.83, 0.75 and 0.75, respectively. The current study underscores the role of PIAS genes in the pathogenesis of inflammatory demyelinating polyradiculoneuropathy and their potential usage as biomarkers.

The Wide Spectrum of Pathophysiologic Mechanisms of Paraproteinemic Neuropathy.

Monoclonal gammopathy is encountered quite frequently in the general population. This type of hematologic abnormality may be mild, referred to as monoclonal gammopathy of undetermined significance or related to different types of hematologic malignancies. The association of a peripheral neuropathy with monoclonal gammopathy is also fairly common, and hemopathy may be discovered in an investigation of peripheral neuropathy. In such a situation, it is essential to determine the exact nature of the hematologic process in order not to miss a malignant disease and thus initiate the appropriate treatment (in conjunction with hematologists and oncologists). In this respect, nerve biopsy (discussed on a case-by-case basis) is of great value in the management of such patients. We therefore propose to present the objectives and main interests of nerve biopsy in this situation.

[Chronic paraneoplastic inflammatory demyelinating polyradiculoneuritis secondary to nasal natural killer lymphoma]. / Une polyradiculonévrite inflammatoire démyélinisante chronique paranéoplasique secondaire à un lymphome natural killer nasal.

We here report a single case of chronic paraneoplastic inflammatory demyelinating polyradiculoneuritis secondary to a nasal natural killer (NK) non-Hodgkin T lymphoma.

Diabetes and Metabolic Disorders and the Peripheral Nervous System.

PURPOSE OF REVIEW: This article provides an up-to-date review of the manifestations of neuropathy seen in the setting of diabetes and other metabolic disorders. RECENT FINDINGS: Although a number of metabolic disorders cause or are associated with peripheral neuropathy, the neuropathies associated with glucose dysregulation make up the vast majority of cases. Recent investigations have determined major differences in the neuropathies associated with type 1 and type 2 diabetes. Neuropathy in type 1 diabetes is closely linked to glycemic control, whereas neuropathy in type 2 diabetes is linked to dyslipidemia, central obesity, hypertension, insulin resistance, and glucose control. Although length-dependent axonal distal symmetric polyneuropathy is the most common clinical presentation, diabetes is also associated with acute, asymmetric, painless, and autonomic neuropathies. SUMMARY: The prevalence of diabetes and metabolic syndrome is increasing across the globe. The need to recognize and treat the wide array of clinical manifestations of neuropathy detected in individuals with metabolic disorders will continue to grow. As a consequence, an increasing number of well-trained physicians who can manage these patients is needed. At present, treatment is largely focused on prevention and symptomatic management. Investments into funding for both basic and clinical science are necessary to bring novel therapeutic interventions into clinical practice.

[Chronic inflammatory demyelinating polyradiculoneuropathy with myelopathy due to massively enlarged nerve roots].

We report a 77-year-old man who presented with numbness and weakness of the feet bilaterally, that had progressed over 13 years. He was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) on the basis of nerve conduction studies and a sural nerve biopsy; however, he was inadequately treated and his weakness had progressed. At 76 years of age, he developed spasticity in the legs as well as bladder and rectal incontinences. Gd-enhanced MRI revealed severe compression of the cervical cord by massively enlarged nerve roots. A cervical laminectomy was performed to decompress the cervical cord. A fascicular biopsy of the C5 dorsal root showed a prominent lymphocyte infiltration and edema. Repeated methylprednisolone pulse therapy and IVIg ameliorated the weakness. We concluded that the main cause of nerve root hypertrophy in this patient was active inflammation.

Rituximab in refractory chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a disorder in which early effective treatment is important to minimize disability from axonal degeneration. It has been suggested that some patients with CIDP may benefit from rituximab therapy, but there is no definitive evidence for this. METHODS: Baseline and post-rituximab-therapy neuromuscular Medical Research Council (MRC) sum scores, Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, and functional status were assessed in 11 patients with refactory CIDP. RESULTS: The MRC sum score, INCAT disability score, and functional status improved in all patients after rituximab therapy. DISCUSSION: Our study provides evidence of the efficacy of rituximab therapy in at least some patients with CIDP. A placebo-controlled study to assess the effectiveness of rituximab therapy in CIDP with and without nodal antibodies is required to identify disease markers that predict responsiveness.

Distinctive patterns of peripheral neuropathy across the spectrum of plasma cell disorders.

Many patients with plasma cell disorders suffer from peripheral neuropathy, but differential diagnosis with chronic inflammatory demyelinating polyneuropathy (CIDP) is difficult. We aimed to (1) identify factors useful for differential diagnosis between peripheral neuropathy associated with plasma cell disorders versus CIDP and (2) determine whether neuropathy presentations and severity varied across the spectrum of different plasma cell disorders. A retrospective chart review of 18 monoclonal gammopathy of unknown significance (MGUS) patients, 15 POEMS syndrome patients and 34 CIDP patients between January 2005 and December 2016 was conducted. The peripheral neuropathy associated with plasma cell disorders seemed to be more sensory oriented compared to CIDP. MGUS patients were significantly older than CIDP patients (median age 70 vs. 59, respectively, p = 0.027). POEMS syndrome patients showed significantly higher platelet count at the time of neuropathy presentation compared to CIDP (p = 0.028). Lambda type MGUS patients were associated with less severe symptoms compared to POEMS syndrome patients despite harboring lambda monoclonal gammopathy as a common denominator. Kappa type MGUS patients showed predominantly axonal type neuropathy compared to its counterpart and POEMS syndrome. Careful inspection of clinical profiles and symptoms of patients presenting with neuropathy can help to discriminate those with underlying plasma cell disorders. The phenotype of neuropathy, platelet count and age at presentation seem to be the most useful indicators.

[A women with aplastic anemia developed chronic inflammatory demyelinating polyneuropathy].

A 66-year-old female developed chronic inflammatory demyelinating polyneuropathy (CIDP) one year after the diagnosis of aplastic anemia. High-dose intravenous immunoglobulin (IVIg) therapy, followed by IVIg maintenance therapy, rapidly improved her weakness and hyperesthesia in four extremities. In addition, pancytopenia caused by aplastic anemia also improved following IVIg treatment in parallel. This is the first report to show the co-existence of CIDP and aplastic anemia, and a common pathomechanism may be present in these two rare autoimmune disorders.

Incidence, Risk Factors, and Outcome of Immune-Mediated Neuropathies (IMNs) following Haploidentical Hematopoietic Stem Cell Transplantation.

Immune-mediated neuropathies (IMNs) following hematopoietic stem cell transplantation have been described recently, which, excluding Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, may present with atypical patterns. This retrospective, nested, case-control study reviewed data from 3858 patients who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) during the past 10 years at a single center, and 40 patients (1.04%) with IMN following haplo-HSCT were identified. Chronic graft-versus-host disease (cGVHD) (P = .043) and cytomegalovirus (CMV) viremia (P = .035) were recognized as independent risk factors for the development of IMN after haplo-HSCT. There were no significant differences in overall survival (P = .619), disease-free survival (P = .609), nonrelapse mortality (P = .87), or the incidence of relapse (P = .583) between patients with and without IMN after haplo-HSCT. However, patients with post-transplant IMN were at higher risk of developing cGVHD (P = .012) than patients who did not develop IMN. Twenty-four of the 40 patients with IMN (60%) attained neurologic improvement after treatments including vitamins B1 and B12 and/or immunomodulatory agents. However, 19 (47.5%) patients still had persistent motor/sensory deficits despite receiving timely treatment. More studies are needed to help develop standardized diagnostic and therapeutic strategies for patients with post-transplant IMN.

Chronic inflammatory demyelinating polyneuropathy: update on diagnosis, immunopathogenesis and treatment.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated neuropathy typically characterised by symmetrical involvement, and proximal as well as distal muscle weakness (typical CIDP). However, there are several 'atypical' subtypes, such as multifocal acquired demyelinating sensory and motor neuropathy (Lewis-Sumner syndrome) and 'distal acquired demyelinating symmetric neuropathy', possibly having different immunopathogenesis and treatment responses. In the absence of diagnostic and pathogenetic biomarkers, diagnosis and treatment may be difficult, but recent progress has been made in the application of neuroimaging tools demonstrating nerve hypertrophy and in identifying subgroups of patients who harbour antibodies against nodal proteins such as neurofascin and contactin-1. Despite its relative rarity, CIDP represents a significant economic burden, mostly due to costly treatment with immunoglobulin. Recent studies have demonstrated the efficacy of subcutaneous as well as intravenous immunoglobulin as maintenance therapy, and newer immunomodulating drugs can be used in refractory cases. This review provides an overview focusing on advances over the past several years.

Polyneuropathies and chronic inflammatory demyelinating polyradiculoneuropathy in multiple sclerosis.

BACKGROUND: Polyneuropathies co-occurring with multiple sclerosis (MS) may be underdiagnosed while causing additional disability burden. OBJECTIVE: To determine polyneuropathy presence and type in MS and compare MS with chronic inflammatory demyelinating polyradiculoneuropathy (MS-CIDP) versus MS with other non-inflammatory polyneuropathies. METHODS: Retrospective chart review of Mayo Clinic cases diagnosed with MS and polyneuropathy. Serum from MS-CIDP for pan-IgG autoantibodies to neurofascin-155 were tested when available. RESULTS: From 1980-2013, 133 co-existing MS/ polyneuropathy cases were identified. Twenty-eight MS patients had inflammatory neuropathy (11 CIDP, 5 plexopathy, 2 vasculitis, 4 monoclonal gammopathy-associated, 6 other), 15 inherited neuropathy (8 axonal, 7 demyelinating), 32 diabetic sensorimotor polyneuropathy, and 58 other. 109 had neuropathy beginning simultaneous to or after MS diagnosis (82%). Compared to MS cases with other polyneuropathy subtypes, MS-CIDP cases had absent or reduced ankle reflexes (100 vs. 70%, p = 0.04), earlier age of neuropathy recognition (52 vs. 58 years, p = 0.048), worse impairment (NIS 27 vs. 22 points, p < 0.03), and more acquired demyelinating electrophysiology features (46% vs. 9%, p < 0.003). Of MS-CIDP cases with available serum, 1-in-3 had IgG4 autoantibodies to neurofascin-155. CONCLUSION: (1) Polyneuropathies occurring in MS contribute to neurological disability. (2) Diagnosing polyneuropathies in people with MS is challenging and, likely, under-diagnosed. Recognition is important as some polyneuropathies (e.g., CIDP) are treatable. (3) The probable over-representation of inflammatory neuropathy (especially CIDP) in MS suggests a shared dysimmune pathogenesis, supported by autoantibodies to neurofascin-155.