Therapy for the periodic paralyses (2)

Location: Naarden, The Netherlands


The fourth ENMC workshop dealing with the periodic paralyses was held on 23rd and 24th March 2001 in Naarden, The Netherlands, as a follow up to the November 2000 87th meeting previously reported. It was attended by 8 active participants from Germany, Italy, the Netherlands, the United Kingdom and the USA, with representations in absentia from French participants. This workshop concentrated on the detail of the protocols for the previously proposed multi-centre trials for periodic paralysis. It also reviewed the progress of the various working parties that have been set up to cover different aspects of the proposed trials. Progress in the development of new outcome measures required for the trial was discussed. These include assessment of the reliability of neurophysiological studies in periodic paralysis, quantitative measures for myotonia that would be associated with some hyperkalaemic periodic paralyses and the soon to be completed UK validation of a muscle disease specific individualised quality of life measure. The detailed amendments of the protocol for the principal proposed multi-centre trial; a head to head comparison of dichlorphenamide versus acetazolamide were broadly agreed and will be distributed to the wider group for approval. Further protocol development for trials of novel treatments was discussed. Strategies for obtaining trial funding were also discussed

An extended report of the meeting will be submitted for publication in Neuromuscular Disorders.

Dr. Michael Rose (United Kingdom)

NMD in Gypsies

Location: Naarden, The Netherlands


The ENMC consortium on Neuromuscular Disorders in the Roma population held its first meeting in Naarden, the Netherlands, on March 9-11, 2001. It was attended by 20 active participants from Australia, Bulgaria, France, Germany, Hungary, Italy, The Netherlands, Portugal, Romania, Spain, Slovenia, United Kingdom and the USA. The meeting was inspired by the memory of Serge Reinhardt, a Roma from France, who suffered from a neuromuscular disorder and who stimulated research in this field.
The meeting started with a review of the history and biological background of the Roma, followed by clinical features, neurophysiological and neuropathological findings and genetic investigations of several neuromuscular diseases, common, and in some cases unique to, Gypsies.
The following disorders have been discussed in particular depth, on basis of experience and research done in the different countries: Gamma-sarcoglycanopathy (LGMD2C), Distal Myopathy of Nonaka type, Congenital Myasthenic Syndrome 1a (CMS1a), Hereditary Motor and Sensory Neuropathies types Lom and Russe (HSMN-L and -R), Congenital Cataract Facial Dysmorphism Neuropathy Syndrome (CCFDN) and Spinal Muscular Atrophy (SMA). In some of these diseases a founder mutation has been discovered. In many cases the underlying protein abnormality is still unknown. Findings were presented from a seven year countrywide survey in Bulgaria among the Roma population on the occurrence of clinical cases of hereditary neuromuscular diseases. A session was dedicated to observations on complex families with independent occurrence of several distinct neuromuscular disorders.
Preventive and epidemiological aspects were discussed, as well as the social context in which these disorders occur, especially regarding the current political changes in the Central and Eastern European Countries.
In the last session priorities for further research and interventions were defined. Among them were the establishment of collaborative studies, the elaboration of protocols and the development of national and international reference centres.

An extended report of the meeting will be submitted for publication in Neuromuscular Disorders.

Dr. Carmen Navarro (Vigo, Spain) and Dr. Luba Kalaydjieva (Perth, Australia)

A full issue of Acta Myologica is dedicated to the above topic
(reference: Acta Myologica Vol XX – December 2001, ISSN 1128-2460)

contacts Acta Myologica:
Gaetano Conte Academy, Viale dei Pini 101 – 80131 Napoli – Italy
tel./fax: ++39-081-7414775

Spinal Muscular Atrophy

Location: Naarden, The Netherlands


14 Doctors and scientists from 7 countries gathered in Naarden, The Netherlands, from 9th to 10th February 2001 for the 10th ENMC workshop on Spinal Muscular Atrophy. The focus of this workshop was to review the current experience in clinical trials in SMA, consider the available drugs with a rationale in this disorder, and plan the organisation of a project called European Spinal Muscular Atrophy Randomised Trial (EuroSMART). Currently it appears that patients with SMA aged 5 to 60 could be easily and reliably evaluated in order to test the efficacy of an intervention in an appropriate designed trial. The available drugs with some rationale in SMA and amyotrophic lateral sclerosis (ALS) were reviewed in details taking in consideration also their safety profile in paediatric and adult patients. There are new animal models of SMA that may be suitable for testing the efficacy of new and existing molecules. A study was presented which showed contrasting results on the willingness of patients and their parents to participate in clinical trials. However the recent experience of the ongoing Italian SMART with Gabapentin showed a great interest in randomised trials and only rare cases of “non-willingness to participate”. Finally there was a general consensus on the opportunity to generate an European SMART study under the auspices of the ENMC. This 4 year European project will produce a common protocol of evaluation through different key centers in Europe. The project will be submitted for financial support at the October call of the 5th European Union Framework Programme.

Dr. L. Merlini (Bologna, Italy)

An extended report of this meeting is published in Neuromuscular Disorders, Volume 12, No.2, February 2002.

Central Core Disease (CCD)

The first ENMC workshop on central core disease (CCD) was held in Hilversum on 19th and 20th January 2001. Seventeen participants from Belgium, France, Germany and the United Kingdom attended this meeting. (The participants covered the various specialties working on central core disease: neurologists, paediatric neurologists, neuropathologists, geneticists, a physiopathologist and an anaesthesiologist). Central core disease is a congenital myopathy, clinically characterized by generalized muscle weakness and morphologically defined by the presence of cores on staining for oxidative enzymes. Autosomal dominant inheritance is highly predominant. However, several sporadic cases have been presented at the workshop. Clear autosomal recessive inheritance has not been reported yet. The association with malignant hyperthermia susceptibility, a well-established characteristic in this disease, has been reviewed. In asymptomatic individuals with malignant hyperthermia susceptibility, confirmed by an in vitro contracture test, core lesions as well as type 1 fibre predominance are occasionally visualized. It was agreed not to diagnose ‘central core disease’ in these subjects however, because of the absence of a clinical correlate. Linkage to the ryanodine receptor gene (RYR1) on chromosome 19q was demonstrated some 10 years ago. Recently, several RYR1 mutations, cosegretating with clinical and/or histological findings have been identified. A detailed update of available genetic data was realized. The importance of longitudinal sections, electron microscopy and possibly immunocytochemistry has been stressed especially to distinguish central cores from minicores. The guidelines for the diagnosis of central core disease, defined at a previous ENMC workshop on congenital myopathies, were reconsidered and revised, providing inclusion and exclusion criteria for forthcoming collaborative genetic studies. All centres present agreed upon collaborative projects e.g. the installation of a European databank on central core disease including documentation of sporadic cases, magnetic resonance imaging of the muscle, further study of ryanodine receptor gene (RYR1) mutations and histological, immunohistochemical and electronmicroscopic studies.
A summary of the results of the workshop will be presented at the annual meeting of the European Malignant Hyperthermia Group, Paris, May 2001.

An extended report of this meeting is published inNeuromuscular Disorders, Volume 12, No.6, August 2002.

Dr. H. De Cauwer, (Antwerp, Belgium)
Prof. Dr. L. Heytens (Antwerp, Belgium)