Ivo N. van Schaik

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.

Randomized, controlled trial of miglustat in Gaucher's disease type 3.

To evaluate the efficacy and safety of miglustat, concomitant with enzyme replacement therapy (ERT), in patients with Gauchers disease type 3 (GD3).

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).

Pulsed high-dose dexamethasone versus standard prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy (PREDICT study): a double-blind, randomised, controlled trial

BACKGROUND Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in patients treated with standard oral prednisolone. METHODS In eight neuromuscular centres in the Netherlands and one in the UK, patients aged 18 years or older who had newly diagnosed definite or probable CIDP were randomly assigned to a treatment regimen of either pulsed high-dose dexamethasone or standard oral prednisolone. Randomisation was done with a random number generator. The primary outcome measure was remission at 12 months, defined as improvement of at least three points on the Rivermead mobility index and improvement of at least one point on the inflammatory neuropathy cause and treatment disability scale. Analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN07779236. FINDINGS Between December, 2003, and December, 2008, 40 patients were treated: 24 received dexamethasone and 16 received prednisolone. At 12 months, 16 patients were in remission: ten in the dexamethasone group and six in the prednisolone group (odds ratio [OR] 1.2, 95% CI 0.3-4.4). Most adverse events were minor and did not differ substantially between treatment groups; however, sleeplessness and Cushings face occurred more often in the prednisolone group. INTERPRETATION Pulsed high-dose dexamethasone treatment did not induce remission more often than prednisolone treatment. A substantial proportion of patients were in remission at 12 months in both treatment groups. High-dose dexamethasone could be considered as induction therapy in CIDP, but comparison with intravenous immunoglobulin treatment is needed. FUNDING The Prinses Beatrix Fonds (MAR01-0213) and the Department of Neurology, Academic Medical Center.

Subcutaneous immunoglobulin therapy for multifocal motor neuropathy

The objective of this study was to investigate whether subcutaneous immunoglobulin (SCIg) treatment is feasible and safe in maintaining muscle strength of patients with multifocal motor neuropathy (MMN). Patients fulfilling the EFNS/PNS criteria for definite MMN treated with intravenous immunoglobulin (IVIg) were switched to weekly SCIg in a single-center, open-label pilot intervention study. The first group of patients started with a SCIg dose equivalent to 50% of the IVIg maintenance dose. In case of deterioration, patients received a loading dose of IVIg and doubling of SCIg dose. The second group started with a dose equivalent to the IVIg maintenance dose. Primary outcome was the Medical Research Council (MRC) sum score from 10 muscle groups. Secondary outcomes were grip and pinch strength, dexterity, disability, quality of life, adverse events, and serum immunoglobulin concentrations. Ten patients were included, five in both groups. In the first group, one patient withdrew informed consent due to local adverse events, four deteriorated. In the second group, four out of five patients maintained muscle strength with SCIg during the 6 months follow-up. Local adverse events were frequent, especially during first weeks of treatment, but generally well tolerated. Seven mild systemic adverse events were reported, all but one in the first week of treatment. In some, but not all MMN patients in this study, SCIg therapy was feasible and safe and maintained strength as well as IVIg. SCIg may be a viable alternative maintenance therapy in some patients with MMN currently receiving IVIg.

The natural history of Charcot–Marie-Tooth type 1A in adults: a 5-year follow-up study

Charcot-Marie-Tooth type 1A is the most prevalent hereditary demyelinating polyneuropathy. The aim of this study was to investigate the natural history of the disease in adults during a 5-year follow-up and to compare the changes over time with those found in normal ageing. In a cohort of 46 adult Charcot-Marie-Tooth type 1A patients, impairments and physical disability were scored at baseline and at 1, 3 and 5 years. Standardized nerve conduction studies and electromyography were performed at baseline and at 5 years. Twenty-six healthy age- and sex-matched controls were evaluated at baseline and at 5 years. Forty-four of 46 Charcot-Marie-Tooth type 1A patients (range 17-69 years) and 26 controls (range 25-65 years) completed the 5-year follow-up. The decrease in muscle strength and in compound muscle action potential amplitudes was similar for patients and controls alike. However, in contrast to the control group, physical disability increased over time in the patient group. In patients, muscle strength and physical disability after 5 years were closely related to these parameters at baseline. None of the other assessed baseline characteristics, i.e. age, gender, compound muscle action potential amplitude and motor nerve conduction velocity, predicted the extent of deterioration of muscle strength or physical disability. In adult Charcot-Marie-Tooth type 1A patients, the decline in axonal function and in muscle strength may reflect, to a considerable extent, a process of normal ageing. The slow increase in physical disability in adulthood may well be explained by decreased reserves and compensatory mechanisms together with progression of skeletal deformations due to muscle weakness.

Chronic inflammatory demyelinating polyneuropathy disease activity status: recommendations for clinical research standards and use in clinical practice

Defining long‐term outcomes in chronic inflammatory demyelinating polyneuropathy (CIDP) has been complicated by varying definitions of treatment response and differing scales measuring impairment or disability. An expert panel was convened to devise a CIDP Disease Activity Status (CDAS) and to classify long‐term outcome by applying it to 106 patients with a consensus diagnosis of CIDP. Sixty of these cases were graded blindly by three independent reviewers to assess inter‐rater reliability. The mean duration of follow‐up was 6.4 years (range, 3 months–23 years). Eleven percent of patients were classified as cured (stable examination and off treatment for ≥5 years), 20% were in remission (stable and off treatment for <5 years), 44% had stable active disease but required ongoing therapy for at least 1 year, 7% were improving after recent initiation of therapy, and 18% had unstable active disease (treatment naïve or treatment refractory). Excellent inter‐rater reliability was observed (kappa scores: 0.93–0.97; p < 0.0001). The CDAS is considered a simple and reproducible tool to classify patients with CIDP according to disease activity and treatment status that can be applied easily in practice and potentially to select patients for clinical trials.

Miglustat (Zavesca) in type 1 Gaucher disease: 5-year results of a post-authorisation safety surveillance programme.

Miglustat (Zavesca®) is an orally‐available substrate reduction therapy (SRT) for treatment of mild‐to‐moderate type 1 Gaucher disease (GD1) in adult patients unsuitable for enzyme replacement therapy (ERT). Miglustat has not been evaluated in children with GD1, and is not used during pregnancy and breast‐feeding. A non‐interventional, prospective, web‐based safety surveillance programme was initiated at the time of the European launch of miglustat in 2003, and is ongoing. We report the first 5 years of collected data, focusing on neurological manifestations.

Familial cortical myoclonic tremor with epilepsy : A single syndromic classification for a group of pedigrees bearing common features

Fifty Japanese and European families with cortical myoclonic tremor and epilepsy have been reported under various names. Unfamiliarity with the syndrome often leads to an initial misdiagnosis of essential tremor or progressive myoclonus epilepsy. A detailed overview of the literature is lacking and is the scope of this study. Disease characteristics are adult onset, distal action tremor and myoclonus, epileptic seizures, autosomal dominant inheritance, benign course, effectiveness of antiepileptic drugs, and possibly cognitive decline. A channelopathy is hypothesized to be the basis of the disease. Despite phenotypic and genetic differences between the Japanese and European pedigrees, the clinical and electrophysiological data point toward one syndrome. To avoid confusion in literature and possible misdiagnosis of patients, we propose to use one description and suggest “familial cortical myoclonic tremor with epilepsy” (FCMTE). In addition, we put forward diagnostic criteria to give a starting point from which to conduct genetic studies.