John Yianni

Deep brain stimulation for dystonia.

Abstract: Within the past few years, there has been a renaissance of functional neurosurgery for the treatment of dystonic movement disorders. In particular, deep brain stimulation (DBS) has widened the spectrum of therapeutical options for patients with otherwise intractable dystonia. It has been introduced only with a delay after DBS became an accepted treatment for advanced Parkinson’s disease (PD). In this overview, the authors summarize the current status of its clinical application in dystonia. Deep brain stimulation for dystonia has been developed from radiofrequency lesioning, but it has replaced the latter largely in most centers. The main target used for primary dystonia is the posteroventral globus pallidus internus (GPi), and its efficacy has been shown in generalized dystonia, segmental dystonia, and complex cervical dystonia. The optimal target for secondary dystonias is still unclear, but some patients appear to benefit more from thalamic stimulation. The improvement of dystonia with chronic DBS frequently is delayed, in particular concerning tonic dystonic postures. Because more energy is needed for stimulation than in other movement disorders such as PD, more frequent battery replacements are necessary, which results in relatively higher costs for chronic DBS. The study of intraoperative microelectrode recordings and of local field potentials by the implanted DBS electrodes has yielded new insights in the pathophysiology of dystonia. Larger studies are underway presently to validate the observations being made.

Globus pallidus internus deep brain stimulation for dystonic conditions: A prospective audit

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured target in the treatment of patients with dystonia. The results of 25 consecutive patients with medically intractable dystonia (12 with generalised dystonia, 7 with spasmodic torticollis, and 6 with other types of dystonia) treated with GPi stimulation are reported. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS benefited all groups, resulting in clear and progressive improvements in their condition. This study clearly demonstrates that DBS of the GPi provides amelioration of intractable dystonia.

Deep brain stimulation for generalised dystonia and spasmodic torticollis.

Dystonia appears distinct from the other tremulous disorders in that improvement following deep brain stimulation frequently appears in a delayed and progressive manner. The rate of this improvement and the point at which no further progress can be expected are presently unknown. The establishment of these parameters is important in the provision of accurate and relevant prognostic information to these patients, their carers, and their treating physicians. We studied 12 consecutive patients with generalised dystonia (n=6) and spasmodic torticollis (n=6) who underwent bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) and were followed up for a minimum of 2 years postoperatively. Standard rating scales were used to quantify their neurological improvement. Both groups experienced a statistically significant improvement in their rating scores at both one and two years following surgery. At 2 years follow-up, the spasmodic torticollis group exhibited a 59% improvement in their total Toronto Western Spasmodic Torticoilis Rating Scale (TWSTRS) rating score and the generalised dystonia group attained a 46% improvement in their overall Burke, Fahn and Marsden Dystonia Rating Scale (BFMDRS) evaluation. Ninety-five percent of the final improvement was attained by 6.4 months in the generalised dystonia group and by 6.6 months in those with spasmodic torticollis. There was no significant improvement after one year postoperatively. These findings add further support to GPi DBS as an effective treatment for generalised dystonia and spasmodic torticollis, and furnish important information as to the expected rate of improvement and the point at which no further gains can be reasonably anticipated.

Post‐operative progress of dystonia patients following globus pallidus internus deep brain stimulation

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured intervention for patients with dystonia. Here we report our results in 20 patients with medically intractable dystonia treated with GPi stimulation. The series comprised 14 patients with generalized dystonia and six with spasmodic torticollis. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS clearly benefited both patient groups. Data conveying the rate of change in neurological function following intervention are also presented, demonstrating the gradual but progressive and sustained nature of improvement following stimulation of the GPi in dystonic patients.

Removing ECG noise from surface EMG signals using adaptive filtering.

Surface electromyograms (EMGs) are valuable in the pathophysiological study and clinical treatment for dystonia. These recordings are critically often contaminated by cardiac artefact. Our objective of this study was to evaluate the performance of an adaptive noise cancellation filter in removing electrocardiogram (ECG) interference from surface EMGs recorded from the trapezius muscles of patients with cervical dystonia. Performance of the proposed recursive-least-square adaptive filter was first quantified by coherence and signal-to-noise ratio measures in simulated noisy EMG signals. The influence of parameters such as the signal-to-noise ratio, forgetting factor, filter order and regularization factor were assessed. Fast convergence of the recursive-least-square algorithm enabled the filter to track complex dystonic EMGs and effectively remove ECG noise. This adaptive filter procedure proved a reliable and efficient tool to remove ECG artefact from surface EMGs with mixed and varied patterns of transient, short and long lasting dystonic contractions.

The sensory and motor representation of synchronized oscillations in the globus pallidus in patients with primary dystonia

In 15 patients with primary dystonia (six cervical and nine generalized dystonias) who were treated with bilateral chronic pallidal stimulation, we investigated the sensorimotor modulation of the oscillatory local field potentials (LFPs) recorded from the pallidal electrodes. We correlated these with the surface electromyograms in the affected muscles. The effects of involuntary, passive and voluntary movement and muscle-tendon vibration on frequency ranges of 0-3 Hz, theta (3-8 Hz), alpha (8-12 Hz), low (12-20 Hz) and high beta (20-30 Hz), and low (30-60 Hz) and high gamma (60-90 Hz) power were recorded and compared between cervical and generalized dystonia groups. Significant decreases in LFP synchronization at 8-20 Hz occurred during the sensory modulation produced by voluntary or passive movement or vibration. Voluntary movement also caused increased gamma band activity (30-90 Hz). Dystonic involuntary muscle spasms were specifically associated with increased theta, alpha and low beta (3-18 Hz). Furthermore, the increase in the frequency range of 3-20 Hz correlated with the strength of the muscle spasms and preceded them by approximately 320 ms. Differences in modulation of pallidal oscillation between cervical and generalized dystonias were also revealed. This study yields new insights into the pathophysiological mechanisms of primary dystonias and their treatment using pallidal deep brain stimulation.

Different mechanisms may generate sustained hypertonic and rhythmic bursting muscle activity in idiopathic dystonia

Despite that deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favored intervention for patients with medically intractable dystonia, the pathophysiological mechanisms of dystonia are largely unclear. In eight patients with primary dystonia who were treated with bilateral chronic pallidal stimulation, we correlated symptom-related electromyogram (EMG) activity of the most affected muscles with the local field potentials (LFPs) recorded from the globus pallidus electrodes. In 5 dystonic patients with mobile involuntary movements, rhythmic EMG bursts in the contralateral muscles were coherent with the oscillations in the pallidal LFPs at the burst frequency. In contrast, no significant coherence was seen between EMG and LFPs either for the sustained activity separated out from the compound EMGs in those 5 cases, or in the EMGs in 3 other cases without mobile involuntary movements and rhythmic EMG bursts. In comparison with the resting condition, in both active and passive movements, significant modulation in the GPi LFPs was seen in the range of 8-16 Hz. The finding of significant coherence between GPi oscillations and rhythmic EMG bursts but not sustained tonic EMG activity suggests that the synchronized pallidal activity may be directly related to the rhythmic involuntary movements. In contrast, the sustained hypertonic muscle activity may be represented by less synchronized activity in the pallidum. Thus, the pallidum may play different roles in generating different components of the dystonic symptom complex.

Optimising coherence estimation to assess the functional correlation of tremor-related activity between the subthalamic nucleus and the forearm muscles

Application of coherence estimation needs not only to correctly estimate coherence values but also to efficiently test the statistical significance of the estimates. In the present report, we have explained the approach of optimising a coherence estimator by restricting its normalised bias error and random error. In addition to the commonly used independence threshold, two more tests based on the probability of detection and the exact confidence interval have been proposed for detecting the significance of the coherence estimates. All three methods have been used to evaluate the significant functional correlation between oscillatory field potentials (FPs) in the subthalamic nucleus (STN) and the surface electromyogram (EMG) of the forearm muscles during tremor in Parkinsons disease.

Extracting burst and tonic components from surface electromyograms in dystonia using adaptive wavelet shrinkage.

The compound surface electromyograms (EMGs) recorded from patients with dystonia commonly contains superimposed bursting and tonic activity representing various motor symptoms. It is desirable to differentially extract them from the compound EMGs so that different symptoms can be more specifically investigated and different mechanisms revealed. A non-linear denoising approach based on wavelet transformation was investigated by applying soft thresholding to the wavelet coefficients. Thresholds were determined according to three different principles and two models. Different techniques for wavelet shrinkage were investigated for separating burst and tonic activity in the compound EMGs. The combination of Steins unbiased risk estimate principle with a non-white noise model proved optimal for separating burst and tonic activity. These turned out to be exponentially related; and the temporal relationships between antagonist muscle contractions could now be seen clearly. We conclude that adaptive soft-thresholding wavelet shrinkage provides effective separation of burst and tonic activity in the compound EMG in dystonia. This separation should improve our understanding of the pathophysiology of dystonia.

N-of-1 Trials for Assessing the Efficacy of Deep Brain Stimulation in Neuropathic Pain.

The objective of this study is to determine the usefulness of single‐patient, randomised, controlled trials (N‐of‐1 trials) in assessing the efficacy of deep brain stimulation (DBS) in neuropathic pain. Seven patients with various causes of intractable neuropathic pain underwent insertion of deep brain stimulating electrodes into the periventricular gray area or ventroposterolateral nucleus of the thalamus. Preoperatively, pain was measured using Visual Analog Scales (VAS) and the McGill Pain Questionnaire (MPQ). At 6 months, these pain assessments were repeated. At this point all patients were entered into a N‐of‐1 trial with the DBS on and off. Data were analyzed using the Wilcoxon and Student t‐tests. Following placement of the deep brain stimulator, VAS scores were significantly reduced in six of seven patients. McGill Pain Scores (MPS) showed pain reduction in four of seven. The results of the N‐of‐1 trials were most similar to the MPQ scores and showed that three of seven patients could accurately predict whether the DBS was on or off. In the N‐of‐1 trials, the time between changing the DBS from on to off (or vice versa) had an effect on the results and probably underestimated the efficacy. We conclude that N‐of‐1 trials are a useful tool for assessing DBS efficacy.