Workshop reportReport of the 95th European Neuromuscular Centre (ENMC) sponsored International Workshop Cognitive Impairment in Neuromuscular Disorders, Naarden, The Netherlands, 13–15 July 2001
Introduction
As many neuromuscular disorders involve brain as well as muscle, the European Neuromuscular Centre (ENMC) consortium on cognitive impairment in neuromuscular disorders held its first meeting in Naarden (The Netherlands) on the 13–15 July 2001. It was attended by 15 participants from the United Kingdom, France and Italy.
In his introductory remarks, Prof. N. Bresolin (Milan, Italy) convenor and chairman of the Consortium, outlined the objectives of the workshop: to gather a panel of experts (clinical, geneticists and basic scientists), to review the available scientific information and find a common strategy of clinical analysis, establishing the criteria of selection of the patients and to define the objectives of shared research projects.
Over the last 10 years several approaches concerning possible correlation between molecular defects in genes mainly responsible for muscular diseases and cognitive impairment or between neuroradiological analysis and mental retardation have been published. In order to identify the particular features of neurofunctional, cognitive, psychiatric and visual deficit in neuromuscular disorders, different groups reported their experience on a wide spectrum of patients. Possible correlations between gene/protein alterations and cognitive impairment were discussed in Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), myotonic dystrophy, limb-girdle muscular dystrophies, congenital myopathies and mitochondrial myopathies.
Section snippets
Duchenne and Becker muscular dystrophies
The first session was concentrated on the molecular basis of cognitive impairment in DMD and BMD and on the neuropsychological profile of Duchenne patients.
Duchenne himself had already noted a ‘caractere obtus’ in many of the children affected by the neuromuscular disease. More specific work in identifying the characters of this intellectual phenotype was done by Karagan and colleagues [1] in 1980: they found a basic language deficit. Leibowitz and Dubowitz [2] found significant impairment in
Animal models and molecules interacting with dystrophin in the central nervous system (CNS)
The second part of the workshop was devoted to animal model studies and to new molecules possibly interacting with dystrophin at the neuronal and glial level.
Dr Vaillend (Orsay Cedex-France) described the cognitive abilities of two dystrophic mutant mice considered to be models of DMD: the mdx mouse which is deficient in full-length dystrophin in both muscle and brain, and the mdx3Cv mouse lacking all the dystrophin-gene products including the C-terminal short products normally expressed in the
Myotonic dystrophy
In the last part of the workshop some of the neuromuscular disorders different from DMD and Becker muscular dystrophy have been discussed.
Dr K. Murphy (London-United Kingdom) presented a review of the brain effects of myotonic dystrophy.
MD is the most common form of adult muscular dystrophy; it is a pleiotropic autosomal dominant disease involving skeletal muscles, lens, heart, lungs, gastrointestinal tract, bone, skin, CNS and PNS (peripheral nervous system) [25]. The disorder is caused by an
Congenital myopathies and sarcoglycanopathies
Moving to the subject of the congenital myopathies, Andrea Martinuzzi and Emanuela Russo, from ‘E. Medea’ Scientific Institute, Conegliano Research Centre, described their studies in a small group of patients.
Congenital myopathies are a heterogeneous group of muscle diseases in which cognitive status can be affected even severely. Correlation with a specific molecular however is lacking, especially for those forms for which no molecular definition is available.
Patients with congenital
Mitochondrial encephalomyopathies
Dr A.C. Turconi (Bosisio P-Italy) presented a neuropsychological and neuroimaging study in mitochondrial encephalomyopathies.
ME are a multisystemic group of diseases, characterized by a wide range of biochemical and genetic mitochondrial defects with a variable mode of inheritance.
With the aim to study the presence of a common and specific cognitive defects and the possible correlations with related brain areas, a group of ME patients underwent neuropsychological tests and MR imaging (MRI) and
Conclusions
The avalanche of interesting data already present in the literature, needs a formal organization; our proposal for this workshop on cognitive impairment in neuromuscular disorders aimed to gather a panel of experts, to review the available scientific information and find a common strategy of analysis of the patients, establishing the criteria of selection of the patients and to define the objectives of the common research project.
The participants agreed to organize themselves in groups having
Acknowledgements
This Workshop was made possible thanks to the financial support of the ENMC and ENMC main sponsors: Association Française contre le Myopathies (France); Deutsche Gesellschaft für Muskelkranke (Germany); Telethon Foundation (Italy); Muscular Dystrophy Campaign (United Kingdom); Muskelsvinfonden (Finland); Prinses Beatrix Fonds (The Netherlands); Schweizerische Stiftung für die Erforschung der Muskelkrankheiten (Switzerland); Verein zur Erforschung von Muskelkrankheiten bei Kindern (Austria); and
References (35)
- et al.
Absence of brain Dp140 isoform and cognitive impairment in Becker muscular dystrophy
Lancet
(1999) - et al.
Spatial discrimination learning and CA1 hippocampal synaptic plasticity in mdx and mdx3cv mice lacking dystrophin-brain isoforms
Neuroscience
(1998) - et al.
Synaptic signaling by nitric oxide
Curr Opin Neurobiol
(1997) - et al.
Behavioral characterization of mdx3cv mice deficient in C-terminal dystrophins
Neuromuscul Disord
(1999) - et al.
Spatial discrimination learning and CA1 hippocampal synaptic plasticity in mdx and mdx3cv mice lacking dystrophin-brain isoforms
Neuroscience
(1998) - et al.
Alternative splicing of dystrobrevin regulates the stoichiometry of syntrophin binding to the dystrophin protein complex
Curr Biol
(2000) - et al.
Molecular basis of myotonic dystrophy: expansion of trinucleotide (CGT) repeat at the 3′ end of a transcript encoding a protein kinase family member
Cell
(1992) - et al.
Impaired cerebral glucose metabolism in myotonic dystrophy: a triplet-size dependent phenomenon
Neuromuscul Disord
(1998) - et al.
Primary beta-sarcoglycanopathy manifesting as recurrent exercise-induced myoglobinuria
Neuromuscul Disord
(2001) - et al.
Focal cognitive impairment in mitochondrial encephalomyopathies: neuropsycological and neuroimaging study
J Neurol Sci
(1999)
Intellectual functioning in Duchenne muscular dystrophy: a review
Psychol Bull
Intellect and behavior in Duchenne muscular dystrophy
Dev Med Child Neurol
Duchenne muscular dystrophy
2nd
Absence of mental retardation in a large DMD gene deletion involving brain dystrophin promoter
Neurology
Characterization of a 4.8 kb transcript from the Duchenne muscular dystrophy locus expressed in Schwannoma cells
Hum Mol Genet
Dp140: a novel 140 kDa CNS transcript from the dystrophin locus
Hum Mol Genet
Loss of Dp140 dystrophin and intellectual impairment in Duchenne dystropphy
Neurology
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