Services and laboratories » "Giorgio Spagnol" Neuroimmunology Clinic, for the Diagnosis and Treatment of Disimmune Neuropathies » Research activities

Main research field: immunopathogenetic mechanism and immune therapy of dysimmune neuropathies.
Summary of the research performed in the last 5 years (references listed at the end by progressive order of citation and area of research):

1. Neuropathy associated with monoclonal gammopathy.
   We continued our studies on the pathogenesis and treatment of neuropathy associated with IgM monoclonal gammopathy. In particular we observed that high titers of antibodies to the myelin-associated glicoprotein (MAG) does not only correlate with the presence of neuropathy but in those asymptomatic predict the development of a clinically manifest neuropathy. We also completed a long-term follow-up studies on 26 patients with this neuropathy confirming the usually favorable long-term prognosis in the majority of affected patients. In this study and in later reviews we also analyzed the response to treatment of this neuropathy highlighting the need for more efficient and safer therapies for this neuropathy. We also participated to a multicentre trial on the effectiveness of IVIg in this neuropathy which showed a marginal effect of this therapy in the neuropathy. We also analyzed the clinical, immunological pathological features of the neuropathy and the response to therapy in patients with high titers of IgM antibodies to sulfatide, GQ1b and GM2 showing in the latter study the ability of these antibodies to cause neural damage in vitro in the presence of complement. We also analyzed the clinical features an pathogenetic mechanism of neuropathies associated with IgG and IgA monoclonal gammopathy.
   
2. Multifocal motor neuropathy and other motor neuropathy and neuronopathy.
   Multifocal motor neuropathy (MMN) is a recently identified disorders characterized by progressive asymmetric predominantly upper limb weakness with multifocal motor conduction block . The diagnostic criteria of MMN has been recently discussed at an ad-hoc international conference. These include the presence of high titers of serum anti-GM1 IgM antibodies whose measurement is however far from being standardized among different laboratories. MMN improve with cyclophoshamide and may worsen with steroids and plasmaexchange. We confirmed the consistent improvement of most MMN patients after treatment with high dose intravenous immunoglobulins (IVIg) which decreased however after several years. We also further analyzed the electrophysiological abnormalities which may distinguish this neuropathy from motor neuron disease. We also analyzed whether, similarly to GBS, MMN was associated with an antecedent Campylobacter Jejuni infection but found no relation. We also reviewed the effect of immune therapies in other motor neuropathies and motor neuron diseases including amyotrophic lateral sclerosis.
   
3. Guillain Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and other dysimmune neuropathies.
   GBS is acute polyradiculoneuropathy frequently occurring after an antecedent infection, as also observed in a recent case-control study performed in Lombardia, including Campylobacter jejuni infection. GBS is often associated with high titers of antibodies to ganglioside whose diagnostic and pathogenetic relevance and clinical correlate remain debated. Among the related clinical variant of GBS is Miller Fisher syndrome (MFS) which we confirmed by an NMR studies to be related to peripheral nerve damage. MFS is associated with high titers of antibodies to the ganglioside GQ1b which we contributed to show that can alter neural transmission in vitro. We also participated in an European randomized trial which showed the similar effectiveness of IVIg and prednisolone in CIDP. We also reviewed the pathogenetic relevance of anti-neural antibodies in dysimmune neuropathies and the response of these neuropathies to IVIg therapy.