John D. Pollard

European federation of neurological societies/peripheral nerve society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - First Revision

Background:  Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been previously published in European Journal of Neurology and Journal of the Peripheral Nervous System.

European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of multifocal motor neuropathy. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society - first revision

A European Federation of Neurological Societies/Peripheral Nerve Society consensus guideline on the definition, investigation, and treatment of multifocal motor neuropathy (MMN) was published in 2006. The aim is to revise this guideline. Disease experts considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed to in an iterative fashion. The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for MMN, investigations to be considered, and principal recommendations for treatment.

European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - First Revision

Background: Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been published (J Peripher Nerv Syst 2005; 10: 220–228, Eur J Neurol 2006; 13: 326–332). Objectives: To revise these guidelines. Methods: Disease experts, including a representative of patients, considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed in an iterative fashion.

Long-term subcutaneous interferon beta-1a therapy in patients with relapsing-remitting MS

Objective: To conduct systematic long-term follow-up (LTFU) of patients in the Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) study to provide up to 8 years of safety, clinical and MRI outcomes on subcutaneous (SC) interferon (IFN) β-1a in relapsing-remitting multiple sclerosis (RRMS). Methods: The original cohort of 560 patients was randomized to IFNβ-1a, 44 or 22 μg three times weekly (TIW) or to placebo; after 2 years, patients on placebo were rerandomized to active treatment and the blinded study continued for a further 4 years. The LTFU visit was scheduled 7 to 8 years after baseline. Results: LTFU was attended by 68.2% of the original PRISMS study cohort (382/560 patients). 72.0% (275/382) were still receiving IFNβ-1a SC TIW. Patients originally randomized to IFNβ-1a 44 μg SC TIW showed lower Expanded Disability Status Scale progression, relapse rate and T2 burden of disease up to 8 years compared with those in the late treatment group. Brain parenchymal volume did not show differences by treatment group. Overall, 19.7% of patients progressed to secondary progressive MS between baseline and LTFU (75/381). No new safety concerns were identified and treatment was generally well tolerated. Conclusions: Despite the limitations inherent in any long-term study (for example, potential differences between returning and nonreturning patients), these results indicate that patients with relapsing-remitting multiple sclerosis can experience sustained benefit over many years from early interferon β-1a subcutaneous therapy three times weekly compared with patients whose treatment is delayed. This effect was more apparent in the patients receiving the higher dose.

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society

Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and randomized trials and systematic reviews of treatment have been published. The objective is to prepare consensus guidelines on the definition, investigation and treatment of CIDP. Disease experts and a patient representative considered references retrieved from MEDLINE and Cochrane Systematic Reviews in May 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (1) intravenous immunoglobulin (IVIg) or corticosteroids should be considered in sensory and motor CIDP (level B recommendation); (2) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (3) if IVIg and corticosteroids are ineffective plasma exchange (PE) should be considered (level A recommendation); (4) If the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (5) Symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).

Inflammatory infiltrates in sural nerve biopsies in Guillain-Barre syndrome and chronic inflammatory demyelinating neuropathy.

Prompted by observations in experimental autoimmune neuritis we reanalyzed immunohistochemically the inflammatory infiltrates in sural nerve biopsies of 22 cases with Guillain‐Barré syndrome (GBS) and 13 cases with chronic inflammatory demyelinating polyneuropathy (CIDP). Endoneurial infiltration of CD3+ T cells was found in 20 cases of GBS (median 5.5 cells/mm2) and in 10 cases of CIDP (5 cells). Epineurial T cells were present in all GBS cases (19.5 cells) and in 11 CIDP cases (21 cells). CD68+ macrophages were abundant in these neuropathies and often occurred in endoneurial perivascular clusters. In GBS subgroups the number of endoneurial T cells was significantly higher in patients with hypoesthesia and abnormal electrophysiological findings in the sural nerve. In CIDP hypoesthesia was associated with significantly higher numbers of macrophages. Our study also indicates that other factors including the time point of biopsy or previous corticosteroid treatment may influence the inflammatory cell profile. Quantifying cell infiltration may aid in establishing the diagnosis of an immunoneuropathy in patients with mild and noncharacteristic pathology.

Prevalence of chronic inflammatory demyelinating polyneuropathy in New South Wales, Australia

A prevalence study of chronic inflammatory demyelinating polyneuropathy (CIDP) was performed in New South Wales (NSW), Australia, with a prevalence day of August 6, 1996, which coincided with a national census. The population of NSW was 5,995,544, and the crude prevalence of CIDP was 1.9 per 100,000 population. It was higher in male patients than in female patients, and the age‐specific prevalence reached a maximum of 6.7 per 100,000 population in the 70‐ to 79‐year‐old age group. The prevalence in the city of Newcastle, with a population of 448,663, was 2.0 per 100,000 population and is representative of the whole of NSW. The estimated crude annual incidence was 0.15 per 100,000 population. The mean age of onset was 47.6 years (median, 53.5 years), 51% of patients had a relapsing‐remitting course, the mean duration on prevalence day was 7.1 years (median, 5 years), and 87% of patients were able to walk without walking aids or other assistance.

European Federation of Neurological Societies/Peripheral Nerve Society Guideline* on management of chronic inflammatory demyelinating polyradiculoneuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society

Abstract  Background: Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and randomized trials and systematic reviews of treatment have been published. Objectives: The aim of this guideline was to prepare consensus guidelines on the definition, investigation, and treatment of CIDP. Methods: Disease experts and a representative of patients considered references retrieved from MEDLINE and Cochrane Systematic Reviews in May 2004 and prepared statements that were agreed in an iterative fashion. Recommendations: The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were as follows: (1) intravenous immunoglobulin (IVIg) or corticosteroids should be considered in sensory and motor CIDP (level B recommendation); (2) IVIg should be considered as the initial treatment in pure motor CIDP (good practice point); (3) if IVIg and corticosteroids are ineffective, plasma exchange should be considered (level A recommendation); (4) if the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (good practice point); and (5) symptomatic treatment and multidisciplinary management should be considered (good practice point).

P0 protein is a target antigen in chronic inflammatory demyelinating polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is widely regarded as an autoimmune disorder, although the autoantigen remains unknown. In this study, the sera of 21 CIDP patients were examined by immunofluorescence for antimyelin activity and by Western blotting for binding to myelin proteins. Six sera contained anti‐P0 immunoglobulin G antibodies, and four of these caused conduction block and demyelination following intraneural injection in experimental animals. Absorption with P0 protein eliminated the demyelinating activity. These results show that P0 is an autoantigen in some patients with CIDP. Since P0 possesses powerful adhesion properties and is largely responsible for myelin compaction, the demonstration of demyelination by human anti‐P0 antibodies provides new insight into this important and common immunopathological process.

Chronic polyneuropathy of undetermined cause.

The case histories of 519 patients with peripheral neuropathy on whom sural nerve biopsy had been performed were reviewed. In 67 patients (50 males, 17 females) (13%) who had symptoms of a symmetrical polyneuropathy for more than one year, the cause remained undiagnosed in spite of intensive investigation. Patients with inflammatory neuropathy were not included, but represented 17% of the whole series. The mean age of onset of symptoms was 50.6 years, and the median time from onset of symptoms to initial investigation was 2 years. Males were affected more commonly than females in a ratio of 3:1. The clinical features in 43 patients were those of a mixed motor and sensory neuropathy, in 17 patients a predominantly sensory neuropathy and in 7 patients a predominantly motor neuropathy. The mean CSF protein was 0.73 g/l and in only six patients was it greater than 1 g/l. Nerve conduction studies most commonly demonstrated mild slowing of motor conduction and impairment of sensory conduction. The usual pathological changes on sural nerve biopsy were those of chronic axonal degeneration. Forty seven patients (70%) were re-examined at intervals of time which ranged from 4 months to 12 years after their initial presentation and nerve biopsy (median, 3 years). As a group, they were only mildly disabled, the condition had a very slowly progressive course and there had been little change in their disability. A possible aetiological factor was found in 17 of the 47 patients (36%) and included malignancy, alcoholism, and benign paraproteinaemia. It is concluded that with intensive investigation the cause of chronic polyneuropathy of duration greater than one year remains undetermined in only about 13% of patients and that continued follow-up is worthwhile since a diagnosis may be established on re-examination.