Research
Since the Dystonia Society was first established in 1983, there has been a great deal of research worldwide into the causes and treatments of the condition.
The Dystonia Society actively encourages research into dystonia, both its causes and its treatments. We also monitor all published research to identify new breakthroughs around the world, and publish reviews of main research findings in our members’ newsletter.
The Society has also been able to provide ‘seed-funding’ to a range of research projects.
Research Update
Dr Tom Warner, Medical Adviser to the Dystonia Society, reviews recent research reports from around the world.
In the three months of October – December 2003, electronic literature searches have shown that there have been over one hundred scientific and medical articles about dystonia. this review looks at a selection of some of the more important studies.
Clinical Studies:
Jahanshahi M et al. Cognitive executive function in dystonia. (Mov Disord. 2003;18:1470-1481).
In this study, Marjan Jahanshahi and co-workers investigated the cognitive function in 10 patients with idiopathic dystonia, and compared them with those in age and IQ matched controls. Five of the patients had torticollis, two had arm dystonia and three had generalised dystonia. A battery of psychological tests was performed, and the good news is that for most tests, patients with dystonia did not differ significantly from controls. Only the test looking at working memory, or how the brain plans tasks showed a difference. In patients with very different neurological disorders such as Parkinson’s disease or Huntington’s disease, individuals performed very poorly on these tests. Again this shows the differences between dystonia patients and those with neurodegenerative conditions, where there is actual loss of brain cells.
Draganski B et al. Motor circuit grey mater changes in idiopathic cervical dystonia. (Neurology 2003;61:1228-1231).
This fascinating paper looked at individuals with idiopathic cervical dystonia (spasmodic torticollis). They used sophisticated MRI scans to look at the structure of the brain in great detail. They found that there was an increase in the density of the grey matter in the motor cortex (the area where the cell bodies of all the nerve cells are on the outer surface of the brain), in the cerebellum (part of the brain situated posteriorly involved in co-ordination), and in the globus pallidus (area of the basal ganglia, which has long been suspected as being involved in producing dystonic movements). The results show that there are subtle changes in brain structure in primary or idiopathic dystonia. It was suggested by the authors that this actually represents changes or adaptations in the brain as a result of dystonia rather than being the absolute cause. The involvement of the cerebellum was fascinating, as it may represent a consequence of the abnormal head posture seen in patients with cervical dystonia.
Clinical/experimental treatment of dystonia:
Siebner HR et al. Patients with focal arm dystonia have increased sensitivity to slow-frequency repetitive TMS of the dorsal premotor cortex. (Brain 2003; 126:2710-1725).
This comprehensive study from Kailash Bhatia’s group in London, used functional imaging and PET scans to study changes in blood flow in the brains of patients with primary focal dystonia. This was performed before and after repetitive transcranial magnetic stimulation (TMS) of the premotor cortex. They found that, in healthy subjects and patients with dystonia, a single session of repetitive TMS can produce a powerful and widespread change in regional synaptic activity as indicated by cerebral blood flow. The patients all had focal arm dystonia or writer’s cramp. The good news was that a single session had a demonstrable effect on cortical circuitry and some of the changes thought to underlie dystonia. The bad news, however, was that when tested clinically an hour after the end of the TMS, there were no effects on handwriting or clinical scoring of hand movements. This either means that the effect was very transient or that longer stimulation is required. The key point about this paper was that some of the changes in the brain circuitry in dystonia appear to be reversible, and therefore amenable to other ways of treatment.
Molecular studies:
The commonest form of inherited dystonia is caused by a mutation within the DYTI gene. This causes a form of childhood onset generalised dystonia affecting the limbs and trunk. There has been much study of the DYTI gene and its protein, torsin A, and how this mutation can cause problems. One of the difficulties is that no one knows what the normal torsinA protein does.
Liu Z et al. Characterisation of human torsinA and its dystonia associated mutant form. (Biochem J. 2003;374:117-122).
In this study, Liu and colleagues looked at normal and mutant torsin A in cells. These studies show that normal torsinA appears to be actively involved in a structure in cells called the endoplasmic reticulum. This is equivalent to the factory of the cells involved in processing proteins which provide
the structure and all functions of cells. Their work suggested that the mutation produces a structurally distinct, possibly misfolded, form of torsinA which cannot be properly processed in the endoplasmic reticulum pathway.
Kusteje et al. Recombinant expression, purification, and comparative characterization of torsinA and its torsion dystonia-associated variant ∆E-torsinA. (Biochemistry. 2003;42:15333-15341). This is another study looking at torsinA function. They used a system which allowed them to obtain sufficient quantity and purity of torsinA protein to permit detailed biochemical and biophysical characterisation. They found that the mutation did seem to stop the protein functioning in terms of the way utilised energy. They suggested that the abnormal mutant form of torsinA actually gained a new function allowing it to affect cellular processes, and in the end lead to dystonia.