Virus discovery in chronic inflammatory demyelinating polyneuropathy.

The events triggering and/or sustaining the auto-immune response underlying chronic inflammatory demyelinating polyneuropathy (CIDP) are unknown. Similar to Guillain-Barré syndrome (GBS), a viral infection might play a role in CIDP. In this study, an virus detection method (VIDISCA-next generation sequencing) capable of detecting known and unknown viruses, was used to analyze the virome in serum of 47 CIDP patients at different time points of the disease and, when available, in cerebrospinal fluid (CSF) samples (N: 17). Serum samples of GBS patients (N:24) and healthy controls (N:114) were used for comparisons. In 5/47 (10.6%; 95% CI: 4-23) CIDP samples, 10/24 (42%; 95% CI: 22-63) GBS samples and 32/114 (28.1%; 95% CI: 20-37) healthy controls samples, anelloviruses were detected, generally regarded as a non-pathogenic species. Parvovirus B19 and GB virus C were found in two CIDP samples (4%). Parvovirus B19, HIV-1 and GB virus C were found in three GBS samples (13%). In 2/17 CIDP CSF samples, an anellovirus and polyomavirus were detected, probably due to contamination during lumbar puncture. No sequences of other viruses were detected in serum or CSF. A (persistent) viral infection sustaining the auto-immune response in CIDP seems therefore unlikely.

Hyperacute relapse of Lewis-Sumner syndrome during influenza A (H1N1) virus infection.

BACKGROUND: Lewis-Sumner Syndrome (LSS) is considered an asymmetric sensory-motor variant of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), mostly affecting the limbs distally, with electrophysiological evidence of multifocal motor conduction blocks. Cranial nerve involvement is present in a minority. Various well-known infectious agents, directly or via the host's immune responses, may trigger or exacerbate acute and chronic peripheral neuropathies, which may manifest clinically through a multitude of signs and symptoms. CASE PRESENTATION: We present the case of a 57-year-old male with Lewis-Sumner Syndrome, whose clinical course was quite stable over many years. He developed severe hyperacute relapse of his neuropathic disease in the context of active pneumonia due to influenza A (H1N1) virus infection. During this exacerbation, besides the obvious worsening of the previous asymmetric limb involvement, the patient also manifested left peripheral facial palsy and dysphagia that rapidly evolved over minutes, mimicking a stroke. The patient also showed rapid recovery, with marked improvement of the acute neuropathic dysfunction, immediately after initiation of treatment with oseltamivir. Our hypothesis is that the direct modulation of Na + ion channel activity in the host's peripheral nerve cell by H1N1 viral proteins could cause acute and potentially reversible dysfunction in the conduction of nerve action potentials. Direct viral neuritis could also have been the cause. Immunomodulatory agents, namely IVIg, were not administered due to the swift clinical improvement noticed in the following days. CONCLUSIONS: We aim to raise awareness of the possibility of atypical neurological presentations of viral infections, especially relevant in the context of the pandemic the world is now facing.

[Improvement of human T-lymphotropic virus type 1 associated demyelinating neuropathy with corticosteroid therapy].

The patient was a 58-year-old man, who was hospitalized with progressive bilateral leg weakness, and sensory impairment in all four extremities. Chronic inflammatory demyelinating polyneuropathy (CIDP) was suspected based on an electrophysiological examination, and intravenous immunoglobulin therapy (IVIg) was initiated. However, his symptoms progressed. The serum and cerebrospinal fluid were positive for human T-lymphotropic virus type 1 (HTLV-1) antibodies; hence the patient was diagnosed as having HTLV-1 associated neuropathy. After administration of corticosteroid, muscle strength markedly improved. Thus, our findings suggest that rather than IVIg, corticosteroid therapy is recommended for the treatment of CIDP like neuropathy in HTLV-1 infected patients.

Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

BACKGROUND: Human endogenous retroviruses HERV-W encode a pro-inflammatory protein, named MSRV-Env from its original identification in Multiple Sclerosis. Though not detected in various neurological controls, MSRV-Env was found in patients with chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs). This study investigated the expression of MSRV in CIDP and evaluated relevant MSRV-Env pathogenic effects. METHODS: 50 CIDP patients, 19 other neurological controls (ONDs) and 65 healthy blood donors (HBDs) were recruited from two different countries. MSRV-env and -pol transcripts, IL6 and CXCL10 levels were quantified from blood samples. MSRV-Env immunohistology was performed in distal sensory nerves from CIDP and neurological controls biopsies. MSRV-Env pathogenic effects and mode of action were assayed in cultured primary human Schwann cells (HSCs). FINDINGS: In both cohorts, MSRV-env and -pol transcripts, IL6 positivity prevalence and CXCL10 levels were significantly elevated in CIDP patients when compared to HBDs and ONDs (statistically significant in all comparisons). MSRV-Env protein was detected in Schwann cells in 5/7 CIDP biopsies. HSC exposed to or transfected with MSRV-env presented a strong increase of IL6 and CXCL10 transcripts and protein secretion. These pathogenic effects on HSC were inhibited by GNbAC1, a highly specific and neutralizing humanized monoclonal antibody targeting MSRV-Env. INTERPRETATION: The present study showed that MSRV-Env may trigger the release of critical immune mediators proposed as instrumental factors involved in the pathophysiology of CIDP. Significant MSRV-Env expression was detected in a significant proportion of patients with CIDP, in which it may play a role according to its presently observed effects on Schwann cells along with previously known effects on immune cells. Experimental results also suggest that a biomarker-driven therapeutic strategy targeting this protein with a neutralizing antibody such as GNbAC1 may offer new perspectives for treating CIDP patients with positive detection of MSRV-Env expression. FUNDING: Geneuro-Innovation, France.

Epstein-Barr virus antibodies in serum and cerebrospinal fluid from multiple sclerosis, chronic inflammatory demyelinating polyradiculoneuropathy and amyotrophic lateral sclerosis.

Elevated anti-Epstein-Barr virus (EBV) antibody levels are present in serum of Multiple sclerosis (MS) patients but literature lacks of studies comparing anti-EBV antibody levels between MS and other neurological diseases. We evaluate anti-VCA IgG and IgM, anti-EBNA1 IgG, anti-Cytomegalovirus IgG and IgM titres in serum and cerebrospinal fluid (CSF) of 267 MS, 50 Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and 88 Amyotrophic Lateral Sclerosis (ALS) patients. We found increased titres of anti-EBV-IgG in serum and CSF of MS subjects as compared to CIDP and ALS patients thus providing additional evidence for a possible involvement of EBV in MS.

Dysregulated Epstein-Barr virus infection in patients with CIDP.

Ubiquitous viruses have frequently been proposed as a cause or trigger of chronic immune-mediated diseases. Infections are reported to be temporally associated with clinical exacerbations in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We examined immunological parameters of herpesvirus infections in untreated patients with CIDP compared to demographically matched controls. Patients with CIDP were uniformly seropositive for EBV-specific IgG and the disease was associated with a moderately enhanced IgG reactivity to EBV-encoded antigens expressed during both B cell transformation and productive viral replication. Moreover, cellular EBV copy numbers were 3-fold increased in patients with CIDP. In contrast, humoral immune responses to other herpesviruses (HCMV, HSV) as well as virus-specific IgM responses were unchanged in CIDP. These data indicate that host-pathogen interactions during chronic EBV infection are dysregulated in treatment-naïve patients with CIDP.

Concomitant chronic inflammatory demyelinating polyneuropathy and myasthenia gravis following cytomegalovirus infection.

We describe a patient who concomitantly developed chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) following cytomegalovirus (CMV) infection. Whereas CIDP and MG presumably have different immunopathogeneses, a number of reports presented cases with CIDP and MG, some of which were concomitant cases. Several reports described association between CIDP or MG, and CMV infection, although the association is still a matter of controversy. This is the first report of patients with concomitant CIDP and MG following CMV infection. The association may be coincidental, but the possibility that CMV infection triggered development of both CIDP and MG simultaneously cannot be excluded.

[Human herpesvirus-8 DNA in patients with certain demyelinating disorders]. / Demyelinizasyonla karakterize bazi hastaliklarda insan herpesvirus-8 DNA varliginin arastirilmasi.

Infectious etiology of the demyelinating diseases is an intensive matter of research. Among the suspected pathogens, herpesviruses had attracted particular attention because of their capacity to remain latent in nervous tissues, axonal transportation of some members within neurons, relapsing-remitting characteristic of the infections, and capability of inducing demyelination both in human host and animal models. Human herpesvirus-8 (HHV-8) is the least studied of this group even some of the HHV-8 related disorders such as HIV associated Castleman's disease, some lymphomas, monoclonal gammopathy of uncertain significance (MGUS), may be seen in patients with demyelinating conditions. The aim of this study was the investigation of a probable relationship between HHV-8 infection and certain demyelinating diseases. For this purpose, the presence of HHV-8 DNA has been investigated by polymerase chain reaction in the blood samples of 14 multiple sclerosis (MS), six chronic inflammatory demyelinizing polyneuropathy (CIDP), three Guillain-Barre syndrome (GBS), and one Miller-Fisher syndrome patients, together with 24 age- and sex-matched healthy subjects as control. As a result, one of MS, two of CIDP and all of the GBS patients were found HHV-8 DNA positive, whereas all the subjects in control group were negative. Although the interpretation of the results of this study does not seem to be possible owing to the limited number of patients, it emphasizes the need for larger scale, detailed studies on this subject since no other report dealing with this matter has been encountered in the literature.

Chronic inflammatory demyelinating polyneuropathy caused by HIV infection in a patient with asymptomatic CMT 1A.

It is well known that patients with Charcot-Marie-Tooth (CMT) disease are liable to present with episodes of cortisone-responsive demyelination, and a superimposed inflammatory component has been suggested. We report a patient who presented with a chronic inflammatory demyelinating polyneuropathy due to a recent HIV infection, which revealed a previously asymptomatic CMT 1A disease documented by identification of the characteristic duplication on the p11.2 region of chromosome 17. The inflammatory process was characterized by pathologic findings on a superficial peroneal nerve biopsy, and the patient improved significantly after corticotherapy. This report gives support to the hypothesis of a genetic susceptibility to inflammatory demyelinating processes in certain CMT kindreds.