Comparing treatment options for chronic inflammatory neuropathies and choosing the right treatment plan

Introduction: Chronic inflammatory neuropathies are disorders caused by an immune response to peripheral nerve. They include chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and neuropathy associated with anti-MAG IgM monoclonal gammopathy and other less frequent neuropathies. Several immune therapies have been proven to be effective in these neuropathies even if the best therapeutic option is still unsettled. Areas covered: The authors reviewed the literature to compare the efficacy and safety of currently used immune therapies in these neuropathies. The authors also analyzed the effect of other immune suppressive agents and of biological agents including rituximab, eculizumab, natalizumab, alemtuzumab and fingolimod that were found effective in other autoimmune diseases. Expert commentary: Despite the reported efficacy of a number of new immune therapies in some patients with immune mediated neuropathies, their efficacy has not been so far confirmed in randomized controlled studies. High-dose intravenous immunoglobulin (IVIg) (and subcutaneous immunoglobulin [SCIg] for maintenance treatment), steroids and plasma exchange remain the only therapy of proven efficacy in CIDP, IVIg in MMN and, with certain limits, rituximab and, occasionally plasma exchange in neuropathy associated with anti-MAG antibodies. New biological agents are also on the horizon but their efficacy needs to be proved in controlled studies

Gateway vectors for efficient artificial gene assembly in vitro and expression in yeast Saccharomyces cerevisiae

Peer reviewedPublisher PD

Deferred Radiotherapy After Debulking of Non-functioning Pituitary Macroadenomas: Clinical Outcomes

Background: To describe the outcome for a cohort of patients with non-functioning pituitary macroadenomas (NFPMA), managed by debulking surgery with radiation therapy delayed until progression.Methods: Two hundred and sixty-seven patients were treated surgically for pituitary tumors at our institution between 1997 and 2005. One hundred and twenty-six patients met the inclusion criteria of NFPMA. They were followed for at least 2 years.Results: At presentation, 58% of patients had objectively decreased visual function, 66% had endocrine abnormalities, and 46% had headaches. Of the entire cohort, 75% of tumors abutted the optic chiasm and 87% had suprasellar extension. Over a median follow up of 112 months from surgery, 52% of patients had evidence of radiographic tumor progression, and 39% required additional treatment. There was a significant difference freedom from progression and in the number of patients receiving additional treatment with preoperative adenoma size of < 2 vs. ≥2 cm (p < 0.05).Conclusion: Close observation with radiation therapy delayed until the time of progression is an appropriate option for patients presenting with initial adenoma size < 2 cm, and can be considered for those with initial sizes up to 4 cm, as the majority of patients do not require further intervention for 10 or more years, thereby meaningfully postponing the risks of radiotherapy

Frequency and time to relapse after discontinuing 6-month therapy with IVIg or pulsed methylprednisolone in CIDP

Background: We reported that 6-month therapy with intravenous immunoglobulin (IVIg) was more frequently effective or tolerated than intravenous methylprednisolone (IVMP) in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We now retrospectively compared the proportion of patients who eventually worsened after discontinuing therapy and the median time to clinical worsening. Methods: By March 2013, data were available from 41 of the 45 patients completing the trial with a median follow-up after therapy discontinuation of 42 months (range 1-60). Three patients withdrew during the original study and one failed to respond to either of the therapies. No patient received a diagnosis alternative to CIDP during the follow-up. Results: Twenty-eight of the 32 patients treated with IVIg (as primary or secondary therapy after failing to respond to IVMP) improved after therapy (87.5%) as compared with 13 of the 24 patients treated with IVMP as primary or secondary therapy (54.2%). After a median follow-up of 42 months (range 1-57), 24 out of 28 patients responsive to IVIg (85.7%) worsened after therapy discontinuation. The same occurred in 10 out of 13 patients (76.9%) responsive to IVMP (p=0.659) after a median follow-up of 43 months (range 7-60). Worsening occurred 1-24 months (median 4.5) after IVIg discontinuation and 1-31 months (median 14) after IVMP discontinuation (p=0.0126). Conclusions: A similarly high proportion of patients treated with IVIg or IVMP eventually relapse after therapy discontinuation but the median time to relapse was significantly longer after IVMP than IVIg. This difference may help to balance the more frequent response to IVIg than to IVMP in patients with CIDP

Corticosteroids in chronic inflammatory demyelinating polyneuropathy : a retrospective, multicentre study, comparing efficacy and safety of daily prednisolone, pulsed dexamethasone, and pulsed intravenous methylprednisolone

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) can be treated with corticosteroids or intravenous immunoglobulins. Various corticosteroid regimens are currently used in CIDP, but it is unknown whether they are equally efficacious. In this retrospective study, we compared efficacy and safety of three corticosteroid regimens in CIDP patients. Methods: We included treatment na\uefve patients that fulfilled the EFNS/PNS criteria for CIDP. Patients were treated with corticosteroids according to the local protocol of three CIDP expertise centres. Corticosteroid regimens consisted of daily oral prednisolone, pulsed oral dexamethasone, or pulsed intravenous methylprednisolone. Outcomes were number of responders to treatment, remission rate of treatment responders, overall probability of 5-year remission, and the occurrence of adverse events. Results: A total of 125 patients were included. Sixty-seven (54%) patients received daily prednisone or prednisolone, 37 (30%) pulsed dexamethasone, and 21 (17%) pulsed intravenous methylprednisolone. Overall, 60% (95% CI 51\u201369%) responded to corticosteroids, with no significant difference between the three treatment regimens (p = 0.56). From the 75 responders, 61% (95% CI 50\u201373%) remained in remission, during a median follow-up of 55\ua0months (range 1\u2013197\ua0months). The probability of responders reaching 5-year remission was 55% (95% Cl 44\u201370%), with no difference between the three groups. Adverse events leading to a change in treatment occurred in ten patients (8%). Two patients had a serious adverse event. Conclusion: Corticosteroids lead to improvement in 60% of patients and to remission in 61% of treatment responders. There were no differences between treatment modalities in terms of efficacy and safety

Unraveling gene expression profiles in peripheral motor nerve from Amyotrophic Lateral Sclerosis patients : insights into pathogenesis

The aim of the present study is to investigate the molecular pathways underlying amyotrophic lateral sclerosis (ALS) pathogenesis within the peripheral nervous system. We analyzed gene expression changes in human motor nerve diagnostic biopsies obtained from eight ALS patients and seven patients affected by motor neuropathy as controls. An integrated transcriptomics and system biology approach was employed. We identified alterations in the expression of 815 genes, with 529 up-regulated and 286 down-regulated in ALS patients. Up-regulated genes clustered around biological process involving RNA processing and protein metabolisms. We observed a significant enrichment of up-regulated small nucleolar RNA transcripts (p = 2.68 1710-11) and genes related to endoplasmic reticulum unfolded protein response and chaperone activity. We found a significant down-regulation in ALS of genes related to the glutamate metabolism. Interestingly, a network analysis highlighted HDAC2, belonging to the histone deacetylase family, as the most interacting node. While so far gene expression studies in human ALS have been performed in postmortem tissues, here specimens were obtained from biopsy at an early phase of the disease, making these results new in the field of ALS research and therefore appealing for gene discovery studies