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To determine the effect of electrode contact location on efficacy of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) for primary generalised dystonia (PGD).A consecutive series of 15 patients with PGD (10 females, mean age 42 years, seven DYT1) who underwent bilateral GPi DBS, were assessed using the Burke-Fahn-Marsden (BFM) dystonia scale before and 6 months after surgery. The position of the stimulated electrode contact(s) was determined from the postoperative stereotactic MRI. Contralateral limb and total axial BFM subscores were compared with the location of the stimulated contact(s) within the GPi.The mean total BFM score decreased from 38.9 preoperatively to 11.9 at 6 months, an improvement of 69.5% (p0.00001). Cluster analysis of the stimulated contact coordinates identified two groups, distributed along an anterodorsal to posteroventral axis. Clinical improvement was greater for posteroventral than anterodorsal stimulation for the arm (86% vs 52%; p0.05) and trunk (96% vs 65%; p0.05) and inversely correlated with the y coordinate. For the leg, posteroventral and anterodorsal stimulation were of equivalent efficacy. Overall clinical improvement was maximal with posteroventral stimulation (89% vs 67%; p0.05) and inversely correlated with the y (A-P) coordinate (r = -0.62, p0.05).GPi DBS is effective for PGD but outcome is dependent on contact location. Posteroventral GPi stimulation provides the best overall effect and is superior for the arm and trunk. These results may be explained by the functional anatomy of GPi and its outflow tracts.

Background: Botulinum toxin type A (BoNT-A) has become the treatment of choice for most types of focal dystonia. Objective: To investigate the efficacy of BoNT-A injections in patients with writer’s cramp in a doubleblind,randomised, placebo-controlled trial and to evaluate the follow-up results. Methods: Forty participants were randomised to treatment with either BoNT-A or placebo injections in two sessions. Trial duration was 12 weeks. The primary outcome measure was the patients’ choice to continue with the treatment, despite its possible disadvantages. Secondary outcome measures included several clinical rating scales on the levels of impairment and disability. Assessments were made at baseline and 2 months (secondary outcomes) and 3 months (primary outcome). Duration of follow-up was 1 year. Results: 39 patients completed the trial. Fourteen of 20 patients (70%) receiving BoNT-A reported a beneficial effect and chose to continue treatment, versus 6 of 19 patients (31.6%) in the placebo group (p = 0.03). The changes on most of the clinical rating scales were significantly in favour of BoNT-A. Side effects reported were hand weakness, which was mostly mild and always transient, and pain at the injection site. After 1 year, 20 of 39 patients were still under treatment with a positive effect. Conclusion: Treatment with BoNT-A injections led to a significantly greater improvement compared with placebo, according to patients’ opinion and clinical assessment scales. Weakness in the hand is an important side effect of BoNT-A injections, but despite this disadvantage, most patients preferred to continue treatment. About 50% of our patients were still under treatment after 1 year.

Background: Focal task specific dystonia occurs preferentially during performance of a specific task. There may be an inefficiently high grip force when doing manipulative tasks other than the trigger task, possibly reflecting a generalised impairment of sensory-motor integration. Objective: To examine how well subjects with writer’s cramp (n = 4) or musician’s cramp (n = 5) adapted their grip force when lifting a new object or catching a weight. Methods: Nine patients with focal hand dystonia and 10 controls were studied. Experiments addressed different motor behaviours: (A) lifting and holding an object; (B) adjusting grip force in anticipation of or in reaction to a change in load force by catching a small weight dropped expectedly or unexpectedly into a hand held receptacle. Results: In (A), patients produced a grip force overshoot during the initial lifts; force overflow was most pronounced in those with writer’s cramp. Patients and controls adjusted their grip force to object weight within one or two lifts, though patients settled to a steady force level above normal. In (B), patients with focal hand dystonia and normal controls showed similar predictive grip force adjustments to expected changes in object load, suggesting that this aspect of sensory-motor integration was normal. Patients had a shorter latency of grip force response than controls after an unexpected load increase, reflecting either a greater level of preparatory motor activity or a disinhibited spinal reflex response. Conclusions: The overall increased grip force in patients with focal hand dystonia is likely to be a prelearned phenomenon rather than a primary disorder of sensory-motor integration.

Objective: To identify factors predicting improvement in motor disability in writer's cramp treated with botulinum toxin (BTX). Methods: 47 patients with writer's cramp were treated with BTX and were evaluated by the same neurologists at initial referral, after each BTX injection, and when the effect of BTX was maximal at the time of the study. Patients and examiners simultaneously and independently rated the efficacy of BTX injections. Self assessment was a global clinical impression of the impact of treatment on writing quality, writing speed, writing errors, and legibility of handwriting; for objective assessment, the examiners used the Burke-Fahn-Marsden (BFM) scale. Results: On the BFM scale, there was a significant improvement (p

Background: The relationship between prior trauma and primary adult-onset dystonia is not well understood. Previous uncontrolled observations and exploratory case–control studies have yielded contradictory results. Objective: To analyse the association between cranial dystonia and prior head trauma. Methods: An ad hoc multicentre case–control study was performed using a semistructured interview to collect detailed information on the history of head trauma before disease onset in five Italian tertiary referral centres for movement disorders. The presence of a history of head trauma and of post-traumatic sequelae (loss of consciousness, bone fractures, scalp/facial wounds) before disease onset was recorded from 177 patients with primary adult-onset cranial dystonia and from 217 controls with primary hemifacial spasm matched by age strata and sex. Differences between groups were assessed by Mann–Whitney U test and Fisher’s exact test, and the relationship between prior head trauma and case/control status was analysed by multivariate logistic regression models. Results: No association was found between vault/maxillofacial trauma and cranial dystonia. Most reported traumas occurred several years before disease onset. None of the main post-traumatic sequelae altered the chance of developing cranial dystonia compared with patients with primary hemifacial spasm, nor did head trauma modify the age at onset of cranial dystonia. Conclusions: These results do not support prior head trauma as a possible environmental factor modifying the risk of developing late-onset cranial dystonia. The lack of association may have pathogenetic and medical–forensic implications.

Background: A fundamental feature underlying many movement disorders is increased variability in the motor response. Despite abnormalities of grip force control in people with dystonia, it is not clear whether dystonia is also associated with increased variability in force output and whether force variability in dystonia is affected by the presence or absence of visual feedback. Objective: To examine force variability in 16 patients with writer's cramp and 16 matched controls. Methods: The variability of force output at the wrist under conditions of both vision and no vision was examined. The underlying frequency structure of the force signal was also compared across groups. Participants produced isometric wrist flexion to targets at 25% and 50% of their maximum voluntary contraction strength under conditions of both vision and no vision. Results: Similar levels of force variability were observed in patients with dystonia and controls at the lower force levels, but patients with dystonia were less variable in their force output than controls at the higher force level. This reduction in variability in people with dystonia at 50% maximum voluntary contraction was not affected by vision. Although a similar dominant frequency in force output was observed in people with dystonia and controls, a reduced variability in the group with dystonia at the higher force level was due to reduced power in the 0-4-Hz frequency bin. Conclusions: The first evidence of a movement disorder with reduced variability is provided. The findings are compatible with a model of dystonia, which includes reduced cortical activation in response to sensory input from the periphery and reduced flexibility in motor output.

Clinical experience suggests an important role of the indirect basal ganglia pathway in the genesis of childhood onset generalised dystonia, but it has been difficult to reconcile the increased muscle activity in dystonia with the current model of basal ganglia function in which the indirect pathway is considered primarily inhibitory. The aim of this study was to present a modification of the direct–indirect pathway model, in which the indirect pathway is inverting rather than purely inhibitory, so that while high signals are inhibited, low signals are amplified. As the basal ganglia may be a feedback loop that modifies cortical activity, instability from excessive gain in this feedback loop could explain features of dystonia. A detailed mathematical model is provided, together with simulations of cortical cell population spiking behaviour when connected through a basal ganglia loop. The simulations show that increased gain in the indirect pathway relative to the direct pathway can lead to unstable uncontrolled synchronous oscillations in cortex and basal ganglia. This behaviour could result in dystonia. The model provides a consistent explanation for the association of dystonia with parkinsonism and disorders characterised by dopamine depletion, the ability to treat some dystonias with dopamine, the ability of neuroleptic drug treatment to cause an acute dystonic reaction treatable with anticholinergic drugs, and the ability of pallidotomy or deep brain stimulation of the internal pallidum to alleviate symptoms of generalised dystonia.