ArticlesPallidal deep brain stimulation in patients with primary generalised or segmental dystonia: 5-year follow-up of a randomised trial
Introduction
Primary dystonias comprise a clinically and aetiologically heterogeneous group of idiopathic movement disorders characterised by sustained muscle contractions, causing repetitive twisting movements or abnormal postures.1 The course of the disease is chronic and no cure is available. Despite the availability of peripheral denervation by botulinum toxin and systemic drug treatment with various combinations of anticholinergic, antidopaminergic, and muscle relaxing drugs, severe forms of primary dystonia are notoriously difficult to manage medically and can result in substantial motor handicap and social stigma.1 Deep brain stimulation (DBS) of the internal globus pallidus has been established as a surgical treatment alternative. Several randomised and open-label studies have reported a reduction of motor symptoms by 50–80%, an alleviation of dystonia-associated pain, and a subsequent improvement in quality of life after bilateral pallidal neurostimulation. DBS is now applied worldwide and the benefit-to-risk ratio of the therapy for dystonia is under scrutiny. A crucial question in this regard is whether or not the generally satisfactory response reported in early short-term studies is sustained after prolonged follow-up, because dystonia is a chronic disorder that requires lifelong symptomatic treatment. A controlled 3-year study of patients with generalised dystonia2 and an open-label series with up to 10 years of follow-up in mixed dystonia populations3, 4, 5, 6, 7, 8, 9, 10 suggest a sustained benefit from pallidal neurostimulation, but some of these reports also raise concern about secondary treatment failures.2, 5, 10
We have previously reported the results of the first prospective, blinded, and sham-controlled trial of neurostimulation for primary generalised or segmental dystonia in a large cohort of patients recruited from multiple centres in Germany, Austria, and Norway.11 Idiopathic segmental dystonia is defined by dystonic symptoms in at least two adjacent body segments, but differs in several other regards from primary generalised dystonia: it has a much higher prevalence, typically manifests in adults, frequently involves the neck and face area, shows less tendency to spread to other body areas, and is rarely caused by genetic mutations.1 Both forms of dystonia, however, can cause severe disability justifying a surgical treatment and were therefore included in our original trial. We found a significant effect of 3–6 months of neurostimulation in the masked and open assessments.11 Most patients consented to participate in an open-label extension study with annual follow-up visits for a period of up to 5 years after the activation of the neurostimulation device. Here we describe the development of motor and non-motor symptoms, disability, and adverse events throughout the 5-year period.
Section snippets
Study design and patients
In the parent trial, 40 patients with severe generalised or segmental idiopathic dystonia were implanted with a pallidal neurostimulation device and then randomly assigned to either sham neurostimulation or neurostimulation for a period of 3 months.11 Thereafter, all patients completed a 6-month period of active neurostimulation. Patients were recruited between July, 2002, and May, 2004, at ten academic centres in Germany, Norway, and Austria and had to fulfil the following inclusion criteria:
Results
38 of 40 patients agreed to a study extension. At variable intervals throughout the 5-year period reported here, another three patients withdrew their consent for the long-term extension. The 5-year visit was attended by a total of 32 of 35 patients still in the trial (figure 1).
The clinical baseline characteristics of the study population are shown in table 1. The unmasked investigators tended to score dystonia severity (BFMDRS motor score) higher (7·0 [SD 9·6] points at baseline and 1·5 [8·1]
Discussion
This prospective long-term follow-up of patients with dystonia treated by bilateral pallidal neurostimulation shows sustained improvements in dystonia ratings for up to 5 years after surgery. The mean 67% reduction of dystonia severity at 3 years and 60% reduction at 5 years compared with baseline in the per-protocol population closely match the benefit described by the only other controlled study (the SPIDY [French Stimulation du Pallidum Interne dans la Dystonie] trial) following patients
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