Selective peripheral denervation for cervical dystonia: long-term follow-up.

OBJECTIVE: 61 procedures with selective peripheral denervation for cervical dystonia were retrospectively analysed concerning surgical results, pain, quality of life (QoL) and recurrences. METHODS: The patients were assessed with the Tsui torticollis scale, Visual Analogue Scale (VAS) for pain and Fugl-Meyer scale for QoL. Evaluations were performed preoperatively, early postoperatively, at 6 months, then at a mean of 42 (13-165) months. All patients underwent electromyogram at baseline, which was repeated in cases who presented with recurrence of symptoms after surgery. RESULTS: Six months of follow-up was available for 55 (90%) of the procedures and late follow-up for 34 (56%). The mean score of the Tsui scale was 10 preoperatively. It improved to 4.5 (p<0.001) at 6 months, and 5.3 (p<0.001) at late follow-up. VAS for pain improved from 6.5 preoperatively to 4.2 (p<0.001) at 6 months and 4 (p<0.01) at late follow-up. The Fugl-Meyer score for QoL improved from 43.3 to 46.6 (p<0.05) at 6 months, and to 51.1 (p<0.05) at late follow-up. Major reinnervation and/or change in the dystonic pattern occurred following 29% of the procedures, and led in 26% of patients to reoperation with either additional denervation or pallidal stimulation. CONCLUSIONS: Selective peripheral denervation remains a surgical option in the treatment of cervical dystonia when conservative measures fail. Although the majority of patients experience a significant relief of symptoms, there is a substantial risk of reinnervation and/or change in the pattern of the cervical dystonia.

Aim for the Suprasternal Notch: Technical Note to Avoid Bowstringing after Deep Brain Stimulation.

BACKGROUND: Bowstringing may occur when excessive fibrosis develops around extension cables in the neck after deep brain stimulation (DBS) surgery. Though the occurrence of this phenomenon is rare, we have noted that it tends to cause maximal discomfort when the cables cross superficially over the convexity of the clavicle. We hypothesise that bowstringing may be avoided by directing the extension cables towards the suprasternal notch. METHODS: When connecting DBS leads to an infraclavicular pectoral implantable pulse generator (IPG), tunnelling is directed towards the suprasternal notch, before being directed laterally towards the IPG pocket. In previously operated patients with established fibrosis, the fibrous tunnel is opened and excised as far cranially as possible, allowing medial rerouting of cables. Using this approach, we reviewed our series of patients who underwent DBS surgery over 10 years. RESULTS: In 429 patients, 7 patients (2%) with cables tunnelled over the convexity of the clavicle complaining of bowstringing underwent cable exploration and rerouting. This eliminated bowstringing and provided better cosmetic results. When the cable trajectory was initially directed towards the suprasternal notch, no bowstringing was observed. CONCLUSION: The tunnelling trajectory appears to influence postoperative incidence of fibrosis associated with DBS cables. Modifying the surgical technique may reduce the incidence of this troublesome adverse event.

Predictive factors of speech intelligibility following subthalamic nucleus stimulation in consecutive patients with Parkinson's disease.

Speech changes after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) can be variable, with the majority of patients experiencing speech deterioration over time. The aim of this study was to describe the perceptual characteristics of speech following chronic STN-DBS and to analyze clinical and surgical factors that could predict speech change. Fifty-four consecutive patients (34 men; mean age ± standard deviation (SD), 58.8 ± 6.3 years; mean ± SD disease duration, 12.5 ± 4.7 years; mean ± SD levodopa equivalent, 1556 ± 671 mg/day; mean ± SD Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) off-medication score, 48.1 ± 17.9 [range, 20-89]; and mean ± SD UPDRS-III on-medication score, 12.4 ± 7.8 [range, 2-31]) participated in this study. They were assessed before and at 1 year after surgery using the Assessment of Intelligibility for the Dysarthric Speech, the perceptual scale from Darley et al., and the UPDRS-III. Speech intelligibility deteriorated on average by 14.4% (P = 0.0006) after 1 year of STN-DBS when off-medication and by 12.3% (P = 0.001) when on-medication. The effect on speech was not linked to age at surgery, unlike the effect on motor outcome. The most significant predictive factors for deterioration of speech intelligibility when patients were off-medication/on-stimulation were lower preoperative speech intelligibility on-medication, longer disease duration, and medially placed left hemisphere active electrode contact. Speech change after STN-DBS is variable and multifactorial. Consistent preoperative speech evaluation would help inform patients about the possible effects of surgery. Appropriate consideration of speech deficits might assist surgical targeting, particularly of the left electrode.

Movement-related changes in local and long-range synchronization in Parkinson's disease revealed by simultaneous magnetoencephalography and intracranial recordings.

Functional neurosurgery has afforded the opportunity to assess interactions between populations of neurons in the human cerebral cortex and basal ganglia in patients with Parkinson's disease (PD). Interactions occur over a wide range of frequencies, and the functional significance of those >30 Hz is particularly unclear. Do they improve movement, and, if so, in what way? We acquired simultaneously magnetoencephalography and direct recordings from the subthalamic nucleus (STN) in 17 PD patients. We examined the effect of synchronous and sequential finger movements and of the dopamine prodrug levodopa on induced power in the contralateral primary motor cortex (M1) and STN and on the coherence between the two structures. We observed discrete peaks in M1 and STN power at 60-90 Hz and at 300-400 Hz. All these power peaks increased with movement and levodopa treatment. Only STN activity at 60-90 Hz was coherent with activity in M1. Directionality analysis showed that STN gamma activity at 60-90 Hz tended to drive gamma activity in M1. The effects of levodopa on both local and distant synchronization at 60-90 Hz correlated with the degree of improvement in bradykinesia-rigidity as did local STN activity at 300-400 Hz. Despite this, there were no effects of movement type, nor interactions between movement type and levodopa in the STN, nor in the coherence between STN and M1. We conclude that synchronization at 60-90 Hz in the basal ganglia cortical network is prokinetic but likely through a modulatory effect rather than any involvement in explicit motor processing.

An international survey of deep brain stimulation procedural steps.

BACKGROUND: Deep brain stimulation (DBS) surgery is standard of care for the treatment of certain movement disorders. OBJECTIVE: We sought to characterize the spectrum of steps performed in DBS surgery, at centers around the world where this surgery is performed. METHODS: We identified the main steps in DBS surgery workflow and grouped these 19 steps into 3 phases (preoperative, operative, and postoperative). A survey tool, informed by a pilot survey, was administered internationally by trained study personnel at high- and low-volume DBS centers. Procedural components, duration, and surgeon motivational factors were assessed. Cluster analysis was used to identify procedural and behavioral clusters. RESULTS: One hundred eighty-five procedure workflow surveys (143 DBS centers) and 65 online surveys of surgeon motivational drivers were completed (45% response rate). Significant heterogeneity in technique, operative time, and surgeon motivational drivers was reported across centers. CONCLUSIONS: We provide a description of the procedural steps involved in DBS surgery and the duration of these steps, based on an international survey. These data will enable individual surgeons and centers to examine their own experience relative to colleagues at other centers and in other countries. Such information could also be useful in comparing efficiencies and identifying workflow obstacles between different hospital environments.

Bilateral deep brain stimulation for cervical dystonia in patients with previous peripheral surgery.

BACKGROUND: There are no data available concerning whether patients with cervical dystonia who have recurrent or new symptoms after peripheral denervation surgery benefit similarly from pallidal deep brain stimulation compared with patients who receive primarily pallidal stimulation. METHODS: Data on 7 cervical dystonia patients with recurrent or progressive dystonia after peripheral denervation who underwent pallidal stimulation were prospectively collected. Deep brain stimulation was performed in Mannheim/Hannover, Germany, or in Umea, Sweden. To the subgroup from Mannheim/Hannover, a second group of patients without previous peripheral surgery was matched. Assessments included the Toronto Western Spasmodic Torticollis Rating Scale and the Burke-Fahn-Marsden dystonia rating scale, as well as the Tsui scale in the Swedish patients. RESULTS: The 4 patients from Mannheim/Hannover experienced sustained improvement from pallidal stimulation by a mean of 57.5% according to the Toronto Western Spasmodic Torticollis Rating Scale (P < .05) and by a mean of 69.5% according to the Burke-Fahn-Marsden dystonia rating scale (P < .05) at long-term follow-up of 40.5 months. The patients from Umea had a mean Tsui score of 7 prior to surgery and a mean score of 3 at the mean follow-up of 8 months (62.5%). In the matched group the Toronto Western Spasmodic Torticollis Rating Scale improved by 58.8% and the Burke-Fahn-Marsden dystonia rating scale by 67% (P < .05) at long-term follow-up (mean, 41.5 months). CONCLUSIONS: Patients who had prior peripheral surgery for cervical dystonia experience improvement from subsequent pallidal stimulation that is comparable to that of de novo patients.

Verbal fluency in patients receiving bilateral versus left-sided deep brain stimulation of the subthalamic nucleus for Parkinson's disease.

The purpose of this study was to investigate the relative effects of unilateral (left-sided) versus bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on verbal fluency. To do this, 10 Parkinson's disease patients with predominantly bilateral motor symptoms who received bilateral STN DBS were compared with 6 patients suffering from predominantly unilateral symptoms who received STN DBS on the left side only. The results suggest that unilateral STN DBS of the speech dominant hemisphere is associated with significantly less declines in measures of verbal fluency as compared to bilateral stimulation.

Resting oscillatory cortico-subthalamic connectivity in patients with Parkinson's disease.

Both phenotype and treatment response vary in patients with Parkinson's disease. Anatomical and functional imaging studies suggest that individual symptoms may represent malfunction of different segregated networks running in parallel through the basal ganglia. In this study, we use a newly described, electrophysiological method to describe cortico-subthalamic networks in humans. We performed combined magnetoencephalographic and subthalamic local field potential recordings in thirteen patients with Parkinson's disease at rest. Two spatially and spectrally separated networks were identified. A temporoparietal-brainstem network was coherent with the subthalamic nucleus in the alpha (7-13 Hz) band, whilst a predominantly frontal network was coherent in the beta (15-35 Hz) band. Dopaminergic medication modulated the resting beta network, by increasing beta coherence between the subthalamic region and prefrontal cortex. Subthalamic activity was predominantly led by activity in the cortex in both frequency bands. The cortical topography and frequencies involved in the alpha and beta networks suggest that these networks may be involved in attentional and executive, particularly motor planning, processes, respectively.

Shaping reversibility? Long-term deep brain stimulation in dystonia: the relationship between effects on electrophysiology and clinical symptoms.

Long-term results show that benefits from chronic deep brain stimulation in dystonia are maintained for many years. Despite this, the neurophysiological long-term consequences of treatment and their relationship to clinical effects are not well understood. Previous studies have shown that transcranial magnetic stimulation measures of abnormal long-term potentiation-like plasticity (paired associative stimulation) and GABAa-ergic inhibition (short-interval intracortical inhibition), which are seen in dystonia, normalize after several months of deep brain stimulation. In the present study, we examine the same measures in a homogenous group of 10 DYT1 gene-positive patients after long-term deep brain stimulation treatment for at least 4.5 years. Recordings were made 'on' deep brain stimulation and after stopping deep brain stimulation for 2 days. The results show that: (i) on average, prior to discontinuing deep brain stimulation, the paired associative stimulation response was almost absent and short-interval intracortical inhibition was reduced compared with normal. This pattern differs from that in both healthy volunteers and from the typical pattern of enhanced plasticity and reduced inhibition seen in deep brain stimulation-naïve dystonia. It is similar to that seen in untreated Parkinson's disease and may relate to thus far unexplained clinical phenomena like parkinsonian symptoms that have sometimes been observed in patients treated with deep brain stimulation. (ii) Overall, there was no change in average physiological or clinical status when deep brain stimulation was turned off for 2 days, suggesting that deep brain stimulation had produced long-term neural reorganization in the motor system. (iii) However, there was considerable variation between patients. Those who had higher levels of plasticity when deep brain stimulation was 'on', had the best retention of clinical benefit when deep brain stimulation was stopped and vice versa. This may indicate that better plasticity is required for longer term retention of normal movement when deep brain stimulation is off. (iv) Patients with the highest plasticity 'on' deep brain stimulation were those who had been receiving stimulation with the least current drain. This suggests that it might be possible to 'shape' deep brain stimulation of an individual patient to maximize beneficial neurophysiological patterns that have an impact on clinical status. The results are relevant for understanding long-term consequences and management of deep brain stimulation in dystonia.

Impact of parameters of radiofrequency coagulation on volume of stereotactic lesion in pallidotomy and thalamotomy.

BACKGROUND: One of the many reasons why lesional surgery for movement disorders has been more or less abandoned may have been the difficulty in predicting the shape and size of the stereotactic radiofrequency (RF) lesion. OBJECTIVES: To analyse the contribution of various RF coagulation parameters towards the volume of pallidotomies and thalamotomies. METHODS: The relationship between temperature of coagulation, length of coagulated area and duration of coagulation on the one hand, and lesion volume on the other was retrospectively evaluated. Lesion diameters were measured on stereotactic thin-slice CT and MRI scans, and volumes of lesions were calculated concerning 36 pallidotomies and 14 thalamotomies in 46 patients who were operated using the same RF generator and same RF electrode. RESULTS: The coagulation temperature, length of coagulated area and duration of coagulation were all correlated to the lesion volume. However, for a given length of coagulated area, the lesion´s size was most strongly influenced by the temperature. Despite this clear correlation, and the relatively homogenous coagulation parameters, the lesions' volumes were markedly scattered. CONCLUSIONS: The volume of the stereotactic RF lesions could be correlated with the coagulation parameters, especially the temperature, at a group level, but could not be predicted in individual patients based solely on the RF coagulation parameters.

Stereotactic techniques and perioperative management of DBS in dystonia.

This article reviews the available literature related to the surgical technique for implantation of deep brain stimulation (DBS) hardware for the treatment of dystonia. Topics covered include stereotactic targeting, selection of specific hardware components, site of placement of the cable connectors and pulse generators, and postoperative documentation of electrode location. Techniques in stereotactic neurosurgery are rapidly evolving, and there is no Class I evidence to unequivocally validate any specific technique described. Nevertheless, the guidelines provided may assist surgical teams in tailoring a rational approach to DBS implantation in dystonia.

Intraoperative neurophysiology in DBS for dystonia.

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) has been demonstrated to be an effective therapy for the treatment of primary dystonia as well as tardive dystonia. Results for other forms of secondary dystonia have been less consistent. Although a number of target sites have been explored for the treatment of dystonia, most notably the motor thalamus, the target of choice remains the sensorimotor portion of the GPi. Although the optimal site within the GPi has not been determined, most centers agree that the optimal site involves the posteroventral lateral "sensorimotor" portion of the GPi. Microelectrode recording (MER) can be used to identify boundaries of the GPi and nearby white matter tracts, including the corticospinal tract and optic tract, and the sensorimotor GPi. However, whether or not the use of MER leads to improved outcomes compared with procedures performed without MER has not been determined. Currently, there is no evidence to support or refute the hypothesis that mapping structures with MER provides better short- or long-term outcomes. Centers using MER do not report a preference of one system over another, but there have not been any studies to compare the relative benefits or risks of using more than 1 electrode simultaneously. Comparison studies of different target structures and targeting techniques in dystonia have not been performed. Additional research, which includes comparative studies, is needed to advance our understanding and optimization of DBS targets, techniques, and approaches along with their relative benefits and risks in dystonia.

Deep brain stimulation effects in dystonia: time course of electrophysiological changes in early treatment.

Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABA(A) -ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia.

Targeting of the pedunculopontine nucleus by an MRI-guided approach: a cadaver study.

Laboratory evidence suggests that the pedunculopontine nucleus (PPN) plays a central role in the initiation and maintenance of gait. Translational research has led to reports on deep brain stimulation (DBS) of the rostral brainstem in parkinsonian patients. However, initial clinical results appear to be rather variable. Possible factors include patient selection and the wide variability in anatomical location of implanted electrodes. Clinical studies on PPN DBS efficacy would, therefore, benefit from an accurate and reproducible method of stereotactic localization of the nucleus. The present study evaluates the anatomical accuracy of a specific protocol for MRI-guided stereotactic targeting of the PPN in a human cadaver. Imaging at 1.5 and 9.4 T confirmed electrode location in the intended region as defined anatomically by the surrounding fiber tracts. The spatial relations of each electrode track to the nucleus were explored by subsequent histological examination. This confirmed that the neuropil surrounding each electrode track contained scattered large neurons morphologically consistent with those of the subnucleus dissipatus and compactus of the PPN. The results support the accuracy of the described specific MR imaging protocol.

Skewering the subthalamic nucleus via a parietal approach.

BACKGROUND/AIMS: A frontal burr hole around the level of the coronal suture is the conventional entry point when performing subthalamic nucleus (STN) deep brain stimulation (DBS). However, alternative approaches may sometimes be necessary. METHODS: We present a report of delayed hardware erosion through the scalp in the left frontal region after successful bilateral STN DBS for Parkinson's disease. The left STN was retargeted via a parietal entry point. RESULTS: Significant improvement in UPDRS motor score (59%) was obtained with bilateral stimulation 6 months after re-operation. The literature was examined for similar approaches and the rationale, risks and benefits of non-frontal entry points in functional neurosurgery were explored. CONCLUSION: Together with a brief review of STN anatomy, this report demonstrates that the parietal approach to the STN remains a viable option in addition to the more traditional frontal access.

MRI-guided subthalamic nucleus deep brain stimulation without microelectrode recording: can we dispense with surgery under local anaesthesia?

AIMS: Subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) is traditionally performed under local anaesthetic (LA). STN visualization and routine validation of electrode location on stereotactic MRI may allow surgery under general anaesthesia (GA). This study compares the clinical outcome of MRI-guided STN DBS performed under LA or GA in a consecutive patient series. METHODS: Unified Parkinson's Disease Rating Scale motor scores (UPDRS-III) in 14 GA patients (mean age 56.1 years, disease duration 13.8 years) were compared with those of 68 LA patients (mean age 57.5 years, disease duration 15.2 years). RESULTS: Baseline UPDRS-III were worse in the GA group, both on medication (GA: 20.9 ± 10.8; LA: 13.2 ± 7.8, p < 0.01) and off medication (GA: 57.9 ± 16.6; LA: 48.2 ± 15.7, p < 0.05). On stimulation off medication motor scores significantly improved in both groups (GA: 27.3 ± 11.8, mean 12-month follow-up; LA: 23.7 ± 11.8, mean 14-month follow-up). The percentage improvement was similar in both groups (GA: 52.8%; LA: 50.8%, p = 0.96). Transient surgical complications occurred in 1 GA and 7 LA patients. CONCLUSIONS: MRI-guided STN DBS under GA with routine stereotactic verification of lead location did not have a negative effect on efficacy or safety. Surgery under GA is a viable option in patients who would find it hard to tolerate awake surgery due to disease severity, comorbidities or anxiety.

Deep brain stimulation of the subthalamic nucleus versus the zona incerta in the treatment of essential tremor.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for essential tremor (ET). Currently the ventrolateral thalamus is the target of choice, but the posterior subthalamic area (PSA), including the caudal zona incerta (cZi), has demonstrated promising results, and the subthalamic nucleus (STN) has been suggested as a third alternative. The objective of the current study was to evaluate the effect of STN DBS in ET and to compare this to cZi DBS. METHODS: Four patients with ET were implanted with two ipsilateral electrodes, one in the STN and one in the cZi. All contacts were evaluated concerning the acute effect on tremor, and the effect of chronic DBS in either target was analyzed. RESULTS: STN and cZi both proved to be potent targets for DBS in ET. DBS in the cZi was more efficient, since the same degree of tremor reduction could here be achieved at lower energy consumption. Three patients became tremor-free in the treated hand with either STN or cZi DBS, while the fourth had a minor residual tremor after stimulation in either target. CONCLUSION: In this limited material, STN DBS was demonstrated to be an efficient treatment for ET, even though cZi DBS was more efficient. The STN may be an alternative target in the treatment of ET, pending further investigations to decide on the relative merits of the different targets.

An approach to deep brain stimulation for severe treatment-refractory Tourette syndrome: the UK perspective.

Deep brain stimulation (DBS) is an emerging therapeutic option for severe, treatment-resistant Tourette Syndrome (TS), with about 40 cases reported in the scientific literature over the last decade. Despite the production of clinical guidelines for this procedure from both European and USA centres, a number of unresolved issues still persist, mainly in relation to eligibility criteria and brain targets. The present article illustrates the UK perspective on DBS in TS and proposes consensus-based recommendations for double-blind controlled trials.

Technology of deep brain stimulation: current status and future directions.

Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential tremor and dystonia, and is also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and Alzheimer disease. Modern DBS systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. Advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how DBS is viewed and delivered to patients. Breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of DBS. In this Review, we provide a comprehensive overview of the technical development of DBS, from its origins to its future. Understanding the evolution of DBS technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.

Optimized beamforming for simultaneous MEG and intracranial local field potential recordings in deep brain stimulation patients.

Insight into how brain structures interact is critical for understanding the principles of functional brain architectures and may lead to better diagnosis and therapy for neuropsychiatric disorders. We recorded, simultaneously, magnetoencephalographic (MEG) signals and subcortical local field potentials (LFP) in a Parkinson's disease (PD) patient with bilateral deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN). These recordings offer a unique opportunity to characterize interactions between the subcortical structures and the neocortex. However, high-amplitude artefacts appeared in the MEG. These artefacts originated from the percutaneous extension wire, rather than from the actual DBS electrode and were locked to the heart beat. In this work, we show that MEG beamforming is capable of suppressing these artefacts and quantify the optimal regularization required. We demonstrate how beamforming makes it possible to localize cortical regions whose activity is coherent with the STN-LFP, extract artefact-free virtual electrode time-series from regions of interest and localize cortical areas exhibiting specific task-related power changes. This furnishes results that are consistent with previously reported results using artefact-free MEG data. Our findings demonstrate that physiologically meaningful information can be extracted from heavily contaminated MEG signals and pave the way for further analysis of combined MEG-LFP recordings in DBS patients.