Chronic inflammatory demyelinating polyradiculoneuropathy: can a diagnosis be made in patients not fulfilling electrodiagnostic criteria?

BACKGROUND AND PURPOSE: The aim was to identify the clinical and diagnostic investigations that may help to support a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in patients not fulfilling the European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria. METHODS: The data from patients with a clinical diagnosis of CIDP included in a national database were retrospectively reviewed. RESULTS: In all, 535 patients with a diagnosis of CIDP were included. This diagnosis fulfilled the EFNS/PNS criteria in 468 patients (87.2%) (definite in 430, probable in 33, possible in three, while two had chronic immune sensory polyradiculopathy). Sixty-seven patients had a medical history and clinical signs compatible with CIDP but electrodiagnostic studies did not fulfill the EFNS/PNS criteria for CIDP. These patients had similar clinical features and frequency of abnormal supportive criteria for the diagnosis of CIDP compared to patients fulfilling EFNS/PNS criteria. Two or more abnormal supportive criteria were present in 40 (61.2%) patients rising to 54 (80.6%) if a history of a relapsing course as a possible supportive criterion was also included. Increased cerebrospinal fluid proteins and response to immune therapy most frequently helped in supporting the diagnosis of CIDP. Response to therapy was similarly frequent in patients fulfilling or not EFNS/PNS criteria (87.3% vs. 85.9%). CONCLUSIONS: Patients with a clinical diagnosis of CIDP had similar clinical findings, frequency of abnormal supportive criteria and response to therapy compared to patients fulfilling EFNS/PNS criteria. The presence of abnormal supportive criteria may help in supporting the diagnosis of CIDP in patients with a medical history and clinical signs compatible with this diagnosis but non-diagnostic nerve conduction studies.

Risk factors for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): antecedent events, lifestyle and dietary habits. Data from the Italian CIDP Database.

BACKGROUND AND PURPOSE: The role of lifestyle and dietary habits and antecedent events has not been clearly identified in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Information was collected about modifiable environmental factors and antecedent infections and vaccinations in patients with CIDP included in an Italian CIDP Database. Only patients who reported not having changed their diet or the lifestyle habits investigated in the study after the appearance of CIDP were included. The partners of patients with CIDP were chosen as controls. Gender-matched analysis was performed with randomly selected controls with a 1:1 ratio of patients and controls. RESULTS: Dietary and lifestyle data of 323 patients and 266 controls were available. A total of 195 cases and 195 sex-matched controls were used in the analysis. Patients eating rice at least three times per week or eating fish at least once per week appeared to be at decreased risk of acquiring CIDP. Data on antecedent events were collected in 411 patients. Antecedent events within 1-42 days before CIDP onset were reported by 15.5% of the patients, including infections in 12% and vaccinations in 1.5%. Patients with CIDP and antecedent infections more often had an acute onset of CIDP and cranial nerve involvement than those without these antecedent events. CONCLUSIONS: The results of this preliminary study seem to indicate that some dietary habits may influence the risk of CIDP and that antecedent infections may have an impact on the onset and clinical presentation of the disease.

Cell-cycle progression and apoptosis in K562 and Molt-4 cells after cell-to-cell transmission of HTLV-I: modulation by interferons.

Human T-cell leukemia virus type I (HTLV-I) is mainly propagated by cell division and therefore the virus-driven proliferation of infected cells can represent a predisposing condition to final development of adult T-cell leukemia (ATL) in vivo. To correlate virus expression and cell cycle progression of recipient cells after acute infection with HTLV-I, K562 multipotent erytholeukemia and Molt-4 T-lymphoma cells were used as recipient cells in a cell-to-cell virus transmission model. Cell cycle progression was studied by flow cytometry during one duplication cycle of recipient cells and transcription of HTLV-I was evaluated during the same time course. The antiproliferative and antiviral effects of recombinant interferons alpha, beta and gamma were also evaluated on cell cycle progression and HTLV-I expression. Transcription of HTLV-I in immortalised virus-donor MT-2 T-cells was found to be related to cell cycle. After coculturing recipient K562 or Molt-4 cells with lethally irradiated, non-dividing virus-donor MT-2 cells, progression into cell cycle of recipient cells was delayed. A pre-G(1) peak, corresponding to 6-11 % apoptotic cells, was identified in cocultured Molt-4/MT-2 cells and not in Molt-4 controls, and was not affected by treatment with IFNs. Notably, no such peak was identified either in control or in cocultured K562 cells. During this time course, transcription of the viral subgenomic mRNA encoding for the env-pX region was prevalently observed. Treatment with IFNalpha and especially with IFNbeta at the onset of the cultures inhibited the growth of both control and virus-exposed recipient cells. IFNgamma was less effective. A clearcut reduction of the percentage of cells entering the S phase was observed only after treatment with IFNbeta. At the same time, in IFNbeta-treated cocultures a marked inhibition of transcription of viral mRNA was observed, suggesting that, during acute infection, treatment with IFNbeta contributes to reduce the infection of recipient cells by down-regulating both the cellular proliferation rate and virus transcription in infected cells.

Antiviral activity of individual versus combined treatments with interferon alpha, beta and gamma on early infection with HTLV-I in vitro.

We have shown previously that infection of mononuclear cells derived from neonatal cord (CBMC) or adult peripheral (PBMC) blood with HTLV-1 can be controlled in vitro by treatment with interferon (IFN) alpha, beta or gamma. The activity of IFNs was mainly related to the induction of an active antiviral competence in host's immune effector cells. The antiviral activity of IFN-boosted CBMC could be ascribed both to a positive regulation of cell-mediated immunity and to inhibition of viral infection. Data described herein provide further information on the mechanisms of the antiviral activity of IFNs and compare the activity of each type of IFN with the association of alpha + beta, alpha + gamma and beta + gamma IFNs, at a concentration of 100 or 1000 IU/ml. When added at the onset of the co-culture of CBMC with lethally irradiated, virus-donor MT-2 cells, IFNs could protect host CBMC by inhibiting HTLV-1 infection in terms of reduced proviral integration and a lower percentage of virus-positive cells, until 4 weeks of culture. Infection of CBMC was inhibited at a comparable extent by either individual or combined IFN treatments. However, a clearcut inhibition of HTLV-I transcription was found only when alpha 100 + beta 1000 IU/ml and especially alpha 1000 + gamma 100 IU/ml combined treatments were tested. When the chronically infected, virus-producing MT-2 cells were treated with IFNs, a remarkable inhibition of HTLV-I transcription was found only after multiple treatments. However, MT-2 cells became resistant to the antiviral activity of IFN gamma, but not to that of IFN alpha or beta. These data provide further information on the control of HTLV-I replication mediated by IFNs at different steps of the viral life cycle, being therefore relevant to the clinical use of combined IFNs in the treatment of acute infection. Moreover, IFNs could be used to prevent the establishment of a persistent infection, which is a prerequisite for developing adult T-cell leukemia (ATL) and/or virus-associated myelopathy.

Differential interference of alpha, beta or gamma interferons with HTLV-I integration and expression in vitro.

Alpha, beta and gamma interferons (IFNs) can exert a powerful and direct antiviral activity against HTLV-I and can also modulate positively some cell-mediated immune functions of the host cell. These multiple effects of IFNs can induce a long-lasting inhibition of viral infection in recipient cells, probably by "priming" the host cell to an active antiviral competence. It has to be underlined that each IFN was active differentially on the replicative cycle of HTLV-I, thus suggesting the possibility of a complementary action of IFNs in inhibiting HTLV-I infection. This might be relevant to a possible therapeutical approach for prevention of HTLV-I related diseases.