a strong reaction!

April 10, 2007 at 9:17 am

[QUOTE]”What an arrogant s…-bag”! [/QUOTE] Allaug. Prof Richard Hughes is definitely not arrogant. He is quite eminent in the contribution that he has made to the investigation and treatment of peripheral neuropathies.
He was a tremendous support to Glennys Sanders in the founding of the GBS Support Group UK, is on the Medical Advisory Board and on that of GBSFI.

At GBSG UK conferences he has always had the ability to inform his listeners in readily understandable ways and certainly not as if he was addressing a group of fellow neurologists. The last thing we would call him is that particular description!”

I have not yet seen the article. In an article “Management of Inflammatory Neuropathies” (2003) co-written with Dr Robert Hadden of the West London Neurosciences Centre on JNNP Online there was a section on Paraproteinaemic Demyelinating Neuropathy. They described anti-MAG IgM as the best defined PDN condition. They went on: Mild slowly progressive disease is best left untreated. In more severe cases, IVIg has a transient beneficial effect (level 1b evidence). Fludarabine and rituximab have seemed effective in small series of severely affected patients.

That was 3+ years before the GBSFI symposium. Further on a joint task force of the European Federation of Neurological Studies and the Peripheral Nerve Society published PDN guidelines. The task force included Prof Hughes and Richard Hadden (team leader?).
It includes:[QUOTE]IgM PDN.
A recent Cochrane review of anti-MAG paraproteinemic neuropathy concluded that there is so far inadequate reliable evidence to recommend any particular immunotherapy (Lunn and Nobile-Orazio, 2003). The same conclusion may be extended to IgM paraprotein-associated neuropathy without anti-MAG antibodies. Based on evidence regarding the pathogenicity of anti-MAG antibodies, therapy has been directed at reducing circulating IgM or anti-MAG antibodies by removal [plasma exchange (PE)], inhibition [intravenous immunoglobulin (IVIg)], or reduction of synthesis (corticosteroids, immunosuppressive agents, cytotoxic agents, or interferon-α). Only five controlled studies on a total of 97 patients have been performed (Lunn and Nobile-Orazio, 2003). [/QUOTE]
The humanized monoclonal antibody (Rituximab) against the CD20 antigen was tested in several recent open pilot trials. In an open prospective study, over 80% of 21 patients with neuropathy with IgM antibodies to neural antigens (including seven with PDN and anti-MAG IgM) improved in strength after 1 and 2 years, compared with none of 13 untreated patients (Pestronk et al., 2003) (class III). The average improvement in strength was 13% at 1 year and 23% at 2 years. However, it was not reported how many patients with anti-MAG antibodies improved or whether Rituximab improved the sensory ataxia, the most frequently disabling feature. No response to Rituximab was observed in two patients, including one with an IgM monoclonal gammopathy-associated chronic motor neuropathy with anti-ganglioside IgM antibodies (Rojas-Garcia et al., 2003). Six of nine patients with chronic polyneuropathy with IgM monoclonal gammopathy and anti-MAG IgM treated with Rituximab in an open phase II study had detectable improvement (defined as ≥2 points improvement in the neuropathy impairment score), two remained stable, and one worsened (Renaud et al., 2003). However, only two patients had clinically useful improvement (≥10 points), and four had marginal improvement (5 or less) (class IV).

Good practice points for treatment of IgM PDN

1 In patients without significant disability, consideration should be given to withholding immunosuppressive or immunomodulatory treatment, providing symptomatic treatment for tremor and paresthesiae, and giving reassurance that symptoms are unlikely to worsen significantly for several years.

2 In patients with significant disability or rapid worsening, IVIg or PE should be considered as initial treatment, although their efficacy is unproven.

3 In patients with moderate or severe disability, immunosuppressive treatment should be considered, although its long-term efficacy remains unproven. Preliminary reports suggest that Rituximab may be a promising therapy.

4 More research is needed.

The whole report may be found at: [url]http://www.blackwell-synergy.com/doi/full/10.1111/j.1085-9489.2006.00059.x[/url]