Localization of motor and verbal fluency effects in subthalamic DBS for Parkinson's disease

IntroductionSubthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson's disease (PD) but can worsen verbal fluency (VF). An optimal site of stimulation for overall motor improvement has been previously identified using an atlas-independent, fully individualized, field-modeling approach. This study examines if cardinal motor components (bradykinesia, tremor, and rigidity) share this identified optimal improvement site and if there is co-localization with a site that worsens VF.MethodsAn atlas-independent, field-modeling approach was used to identify sites of maximal STN DBS effect on overall and cardinal motor symptoms and VF in 60 patients. Anatomic coordinates were referenced to the STN midpoint. Symptom severity was assessed with the MDS-UPDRS part III and established VF scales.ResultsSites for improved bradykinesia and rigidity co-localized with each other and the overall part III site (0.09 mm lateral, 0.93 mm posterior, 1.75 mm dorsal). The optimal site for tremor was posterior to this site (0.10 mm lateral, 1.40 mm posterior, 1.93 mm dorsal). Semantic and phonemic VF sites were indistinguishable and co-localized medial to the motor sites (0.32 mm medial, 1.18 mm posterior, 1.74 mm dorsal).ConclusionThis study identifies statistically distinct, maximally effective stimulation sites for tremor improvement, VF worsening, and overall and other cardinal motor improvements in STN DBS. Current electrode sizes and voltage settings stimulate all of these sites simultaneously. However, future targeted lead placement and focused directional stimulation may avoid VF worsening while maintaining motor improvements in STN DBS.     

Stimulation of the subthalamic nucleus in a patient with Parkinson disease and essential tremor

BACKGROUND: The preferred surgical target for the treatment of Parkinson disease (PD) is either the internal globus pallidus or the subthalamic nucleus (STN); the target for treatment of essential tremor (ET) is the thalamic subnucleus ventralis intermedius (Vim). Some patients with PD have coexistent ET, and the identification of a single surgical target to treat both parkinsonian motor symptoms and ET would be of practical importance. OBJECTIVE: To describe the use of the STN target in deep brain stimulator (DBS) surgery to treat PD motor symptoms and the action-postural tremor of ET. DESIGN: Case report. PATIENT: A 62-year-old man had a greater than 30-year history of action-postural tremor in both hands, well controlled with beta-blockers for more than 20 years. He developed resting tremor, bradykinesia, and rigidity on his right side that progressed to his left side during the past 10 years. Dopaminergic medication improved his rigidity and bradykinesia, with only mild improvement of his resting tremor and no effect on his action-postural tremor. INTERVENTIONS: Left pallidotomy followed by placement of a left DBS in the Vim and subsequent placement of a right STN DBS. MAIN OUTCOME MEASURES: Control of symptoms of PD and ET. RESULTS: The left pallidotomy controlled the patient's parkinsonian motor symptoms on the right side of his body, but did not affect the action-postural component of his tremor. The symptoms on the left side of the body, including both an action-postural and a resting tremor (as well as the rigidity and bradykinesia), improved after placement of a single right STN DBS. CONCLUSION: Placement of an STN DBS should be considered as the procedure of choice for surgical treatment of patients with a combination of PD and ET.     

Dissociation of motor symptoms during deep brain stimulation of the subthalamic nucleus in the region of the internal capsule

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can be an effective treatment for the motor symptoms of Parkinson's disease. The therapeutic benefits are voltage-dependent and, in many cases, limited by the appearance of side effects, including muscle contractions. We have observed a number of clinical cases where improvements in rigidity were accompanied by a worsening of bradykinesia. Considering the anatomic position of STN and current approaches to implantation of the DBS lead, we hypothesized that this dissociation of motor symptoms arises from activation of pyramidal tract fibers in the adjacent internal capsule. The objective of this study was to assess the physiological basis for this dissociation and to test our hypothesis that the underlying etiology of this paradox is activation of fibers of the internal capsule. The effect of STN DBS at 80% of motor threshold for each of the four contacts was evaluated for its effect on rigidity, bradykinesia, and akinesia in a single primate with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Consistent with our observations in humans, this near-threshold stimulation was found to improve rigidity while bradykinesia and akinesia worsened. Worsening bradykinesia in the face of improvement of other motor signs in Parkinson's disease (PD) patients is suggestive of activation of pyramidal tract (PT) fibers during stimulation. This phenomenon may occur without overt muscle contraction and improved rigidity.     

Motor outcomes and adverse effects of deep brain stimulation for dystonic tremor: A systematic review

Dystonic tremor (DT) is defined as the tremor in body parts affected by dystonia. Although deep brain stimulation (DBS) has been used to manage medically-refractory DT patients, its efficacy has not been well established. The objective of this study is to provide an up-to-date systematic review of DBS outcomes for DT patients. We conducted a literature search using Medline, Embase, and Cochrane Library databases in February 2020 according to the PRISMA guidelines. From 858 publications, we identified 30 articles involving 89 DT patients who received DBS of different targets. Thalamic DBS was the most common (n = 39) and improved tremor by 40–50% potentially in the long-term over five years with variable effects on dystonic symptoms. Globus pallidus internus (GPi), subthalamic, and subthalamic nucleus (STN) DBS improved both tremor and dystonic symptoms; however, data were limited. A few studies have reported better tremor and dystonia outcomes with combinations of different targets. Concerning adverse effects, gait/balance disorders, and ataxia seemed to be more common among patients treated with thalamic or subthalamic DBS, whereas parkinsonian adverse effects were observed only in patients treated with subthalamic or GPi DBS. Comparative benefits and limitations of these targets remain unclear because of the lack of randomized controlled trials. In conclusion, DBS of these targets may improve tremor with a variable effect on dystonia with different adverse effect profiles. The shortcomings in the literature include long-term motor outcomes, quality of life outcomes, optimal DBS targeting, and DBS programming strategy.     

Temporal changes in movement time during the switch of the stimulators in Parkinson's disease patients treated by subthalamic nucleus stimulation

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a very effective therapy for the advanced phase of Parkinson's disease (PD). The functional inhibition of this nucleus is responsible for a significant improvement of cardinal motor symptoms of PD. The aim of the study was the assessment of the effectiveness of STN DBS on bradykinesia by the analysis of movement time (MT) in 2 conditions: with the stimulators turned on ('stim-on') or off ('stim-off'). METHODS: After pharmacological wash-out, 10 patients submitted to bilateral STN DBS were studied with an MT analyser in 3 phases: stim-on, stim-off and stim-on again, in order to establish the time course of MT lengthening, the posteffect duration and the latency of the effect of STN DBS. MT data were then compared with the UPDRS motor scores. RESULTS: After turning off the stimulators, MT progressively increases, reaching a plateau after about 30 min, which then lasts for the subsequent observation time (2 h). A significant elongation is achieved after the first 5 min. Upon pulse generator activation, MT shows a dramatic shortening, already significant after 2 min. Moreover, we observed a significant correlation between MT and the severity of PD, higher with bradykinesia than with rigidity or tremor. CONCLUSION: Our findings show a relevant effect of STN DBS on MT, a parameter strongly related to bradykinesia. This study confirms the effectiveness of STN inhibition on the whole parkinsonian triad, suggesting that this target can be considered a proper choice for the surgical treatment of advanced PD.     

Deep brain stimulation therapy for involuntary movements]

During the last decade, it has become clear that deep brain stimulation (DBS) therapy provides a dramatic improvement in the symptoms of movement disorders. We have experienced DBS in 110 patients with various types of involuntary movements, and confirmed the benefits of stimulation of the thalamic nucleus ventralis intermedius (Vim), internal globus pallidus (GPi) and subthalamic nucleus (STN) in these patients. DBS therapy affords the best effect on tremor when the Vim is selected as the stimulation site. DBS therapy is also useful for controlling rigidity when the GPi or STN is stimulated. Improvements of bradykinesia and gait disturbance are often induced by DBS therapy involving the GPi or STN. Dopa-induced dyskinesia can be attenuated effectively by the direct and/or indirect effects of DBS therapy. DBS of the Vim also provides excellent control of post-stroke involuntary movements, including hemiballism and hemichoreoathetosis. Dystonia in young patients is controlled effectively by DBS of GPi. Ablative procedures for control of involuntary movement disorders, such as thalamotomy and pallidotomy, always carry a risk associated with creating additional lesions in an already damaged brain. In contrast, there is not such a risk in DBS therapy. This modality of therapy is an important option in treating involuntary movements.     

The impact on Parkinson's disease of electrical parameter settings in STN stimulation

BACKGROUND: The main advantage of deep brain stimulation (DBS) in the treatment of PD is that the electrical settings can be adjusted to optimize benefits and minimize adverse effects. The main objective of this study was to discover how varying these electrical parameters impacted on parkinsonian motor signs. METHODS: Twelve patients with PD with chronic bilateral subthalamic nucleus (STN) stimulation were selected. The authors evaluated the effects of a variation in the voltages, frequencies, and pulse widths on tremor, bradykinesia, and rigidity using two different paradigms: one in which the total electrical energy delivered was held constant, and one in which this was varied. Up to 26 parameter conditions were tested under double blind randomized conditions. RESULTS: Voltages >or=3 V and frequencies >or=130 Hz led to the greatest improvement in all three parkinsonian signs. A rate of 5 Hz significantly worsened akinesia. The combination of the highest voltage with the narrowest pulse width was most effective. CONCLUSIONS: This study confirms that the most beneficial effects induced by STN stimulation are obtained at high frequencies and that voltage is the most critical factor to obtain adequate alteration in STN activity. The mechanisms by which STN DBS improves parkinsonism remain speculative.     

Deep brain stimulation for Parkinson's disease

Deep brain stimulation (DBS) is making a major impact in patients with advanced Parkinson's disease who continue to be disabled despite the best available medical therapy. Stimulation of the internal segment of the globus pallidus (GPi) or the subthalamic nucleus (STN) can improve tremor, rigidity, bradykinesia and gait disturbances in Parkinson's disease and improve the day-to-day activities of patients with these disabling symptoms. While the mechanism of action of DBS remains poorly understood, the success of technique in the treatment of movement disorders is bringing into question traditional concepts of the organization and of the basal ganglia and spearheading a re-examination of the nature and function of brain areas involved in the control of movement. Future developments in this rapidly advancing area will include the elucidation of the mechanism of action of DBS and technical advances in surgical techniques, in electrode design and in choosing better stimulation parameters. These advances will improve the scope and effectiveness of DBS and expand its clinical indications.     

Unilateral caudal zona incerta deep brain stimulation for Parkinsonian tremor

BackgroundThe subthalamic nucleus is currently the target of choice in deep brain stimulation (DBS) for Parkinson's disease (PD), while thalamic DBS is used in some cases of tremor-dominant PD. Recently, a number of studies have presented promising results from DBS in the posterior subthalamic area, including the caudal zona incerta (cZi). The aim of the current study was to evaluate cZi DBS in tremor-dominant Parkinson's disease.Methods14 patients with predominately unilateral tremor-dominant PD and insufficient relief from pharmacologic therapy were included and evaluated according to the motor part of the Unified Parkinson Disease Rating Scale (UPDRS). The mean age was 65 ± 6.1 years and the disease duration 7 ± 5.7 years. Thirteen patients were operated on with unilateral cZi DBS and 1 patient with a bilateral staged procedure. Five patients had non-L-dopa responsive symptoms. The patients were evaluated on/off medication before surgery and on/off medication and stimulation after a minimum of 12 months after surgery.ResultsAt the follow-up after a mean of 18.1 months stimulation in the off-medication state improved the contralateral UPDRS III score by 47.7%. Contralateral tremor, rigidity, and bradykinesia were improved by 82.2%, 34.3%, and 26.7%, respectively. Stimulation alone abolished tremor at rest in 10 (66.7%) and action tremor in 8 (53.3%) of the patients.ConclusionUnilateral cZi DBS seems to be safe and effective for patients with severe Parkinsonian tremor. The effects on rigidity and bradykinesia were, however, not as profound as in previous reports of DBS in this area.     

Effects of rTMS on Parkinson’s disease: a longitudinal fMRI study

Parkinson’s disease is a movement disorder whose principal symptoms are tremor, rigidity, bradykinesia and postural instability. Initially, drugs like l-dopa or dopaminergic agonists are able to control these symptoms, but with the progress of the disease these drugs become less effective. Previous studies have reported that repetitive transcranial magnetic stimulation (rTMS) can improve these motor symptoms. The objective of this study was to investigate the neural mechanisms through which 25 Hz rTMS may improve motor symptoms in Parkinson’s disease. In a double-blind placebo-controlled study, we evaluated the effects of 25 Hz. rTMS in 10 Parkinson’s disease patients. Fifteen rTMS sessions were performed over the primary cortex on both hemispheres (one after the other) during a 12-week period. The patients were studied using functional magnetic resonance imaging during performance of a simple tapping and a complex tapping task, 1 week before the administration of the first rTMS session and just after the last session. rTMS improved bradykinesia, while functional magnetic resonance imaging showed different cortical patterns in prefrontal cortex when patients performed the complex tapping test. Furthermore, the improvement in bradykinesia is associated with caudate nucleus activity increases in simple tapping. Finally, we observed a relative change in functional connectivity between the prefrontal areas and the supplementary motor area after rTMS. These results show a potential beneficial effect of repetitive transcranial magnetic stimulation on bradykinesia in Parkinson’s disease which is substantiated by neural changes observed in functional magnetic resonance imaging.     

The Intraoperative Microlesion Effect Positively Correlates With the Short-Term Clinical Effect of Deep Brain Stimulation in Parkinson's Disease

ObjectiveDuring the surgical procedure of deep brain stimulation (DBS), insertion of an electrode in the subthalamic nucleus (STN) frequently causes a temporary improvement of motor symptoms, known as the microlesion effect (MLE). The objective of this study was to determine the correlation between the intraoperative MLE and the clinical effect of DBS.Materials and MethodsThirty Parkinson's disease (PD) patients with Movement Disorder Society (MDS) Unified Parkinson's Disease Rating Scale (UPDRS) part III (MDS-UPDRS III) scores during bilateral STN-DBS implantation were included in this retrospective study. MDS-UPDRS III subscores (resting tremor, rigidity, and bradykinesia) of the contralateral upper extremity were used. During surgery, these subscores were assessed directly before and after insertion of the electrode. Also, these subscores were determined in the outpatient clinic after 11 weeks on average (on-stimulation). All assessments were performed in an off-medication state (at least 12 hours of medication washout).ResultsPostinsertion MDS-UPDRS motor scores decreased significantly compared to preinsertion scores (p < 0.001 for both hemispheres). The MLE showed a positive correlation with the clinical effect of DBS in both hemispheres (rho = 0.68 for the primarily treated hemisphere, p < 0.001, and rho = 0.59 for the secondarily treated hemisphere, p < 0.01).ConclusionThe MLE has a clinically relevant correlation with the effect of DBS in PD patients. These results suggest that the MLE can be relied upon as evidence of a clinically effective DBS electrode placement.     

双侧丘脑底核脑深部刺激术治疗帕金森病13例报告

目的 探讨双侧丘脑底核（STN）脑深部刺激术（DBS）治疗帕金森病的临床经验。方法 从2002年到2005年共完成了13例帕金森病的双侧丘脑底核DBS，根据STN解剖学定位，靶点的理论坐标值是X=11-13mm，Y=0-2mm，Z=0-4mm，通过立体定向技术在双侧丘脑底核植入刺激电极，并于锁骨下方植入脑深部电刺激器。结果 随访时间为6个月到3年，3例震颤为主病人的症状完全缓解，即震颤完全消失；僵直和运动迟缓为主要症状者的症状缓解程度达90％以上，其中以四肢肌肉僵直的效果较好，运动迟缓也有明显缓解，但是有1例病人双侧肢运动协调性差。所有患者植物神经功能症状有较明显改善，如便秘、流涎、出汗和浮肿等均有改善。结论 DBS治疗帕金森病，是帕金森病治疗的一个里程碑似的进步。它可以明显地缓解帕金森病的主要症状和体征，对运动迟缓、僵直和震颤等均有较理想的效果。     

Surgery insight: Deep brain stimulation for movement disorders

Over the past two decades, deep brain stimulation (DBS) has supplanted lesioning techniques for the treatment of movement disorders, and has been shown to be safe and efficacious. The primary therapeutic indications for DBS are essential tremor, dystonia and Parkinson's disease. In the case of Parkinson's disease, DBS is effective for treating the primary symptoms--tremor, bradykinesia and rigidity--as well as the motor complications of drug treatment. Progress has been made in understanding the effects of stimulation at the neuronal level, and this knowledge should eventually improve the effectiveness of this therapy. Preliminary studies also indicate that DBS might be used to treat Tourette's syndrome, obsessive-compulsive disorder, depression and epilepsy. As we will discuss in this review, the success of DBS depends on an appropriate rationale for the procedure, and on collaborations between neurologists and neurosurgeons in defining outcomes.     

Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation.

OBJECTIVE: To compare the effects of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) with bilateral STN DBS in advanced PD. METHODS: Our initial 10 consecutive patients with medication-refractory motor fluctuations and levodopa-induced dyskinesias undergoing chronic bilateral STN DBS underwent a standardized evaluation of unilateral and bilateral STN DBS in the medication-off state 6 to 18 months after electrode implantation. RESULTS: Bilateral STN DBS improved the mean total Unified Parkinson's Disease Rating Scale motor score by 54%, whereas unilateral stimulation improved motor scores only 23%. Unilateral STN DBS improved postural stability and gait 14%, other axial motor features 19%, and overall parkinsonism in limbs contralateral to stimulation by 46%, including an 86% improvement in contralateral tremor. However, bilateral STN DBS resulted in greater improvement in each of these domains, including limb function, i.e., the reduction in scores from the limbs on one side was greater with bilateral than with unilateral stimulation of the contralateral STN. CONCLUSIONS: Bilateral STN DBS improves parkinsonism considerably more than unilateral STN DBS; bilateral simultaneous electrode implantation may be the most appropriate surgical option for patients with significant bilateral disability. Unilateral STN DBS results in moderate improvement in all aspects of off-period parkinsonism and improves tremor as much as is typically reported with DBS of the ventral intermedius nucleus of the thalamus (Vim). For this reason, STN DBS may be a more appropriate choice than Vim DBS or thalamotomy for parkinsonian tremor. Some patients with highly asymmetric tremor-dominant PD might be appropriately treated with unilateral instead of bilateral STN DBS.     

Thalamic,subthalamic nucleus and internal pallidum stimulation in Parkinson’s disease

The limits of drug therapy in severe forms of Parkinson’s disease have lead to a renewal of functional neurosurgery of the basal ganglia and the thalamus. Deep brain stimulation (DBS) of these structures was developed with the aims of reducing the morbidity of surgery and of offering an adaptative treatment. DBS was first applied to the thalamus in patients with severe tremor. Tremor of the hemibody is greatly reduced by stimulation of the contralateral electrode in 85% of the cases. There is little change in other symptoms. However, motor fluctuations and dyskinesias are a more frequent problem than severe tremor, in attempt to treat these symptoms, DBS has recently been applied to the subthalamic nucleus (STN) and the internal pallidum (GPi). STN stimulation greatly decreases off motor symptoms and motor fluctuations, which allows a reduction of drug dosage and consequently of dyskinesias. GPi stimulation decreases dyskinesias in most patients, but the effect on off motor symptoms is more variable from one series to another, from very good to nil. The severe morbidity of DBS applied to these 3 targets is low. Comparative studies of the cost and the efficacy of DBS and lesions applied to these different targets are now required.

     

Tremor reduction by subthalamic nucleus stimulation and medication in advanced Parkinson’s disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proved to be effective for tremor in Parkinson’s disease (PD). Most of the recent studies used only clinical data to analyse tremor reduction. The objective of our study was to quantify tremor reduction by STN DBS and antiparkinsonian medication in elderly PD patients using an objective measuring system. Amplitude and frequency of resting tremor and re-emergent resting tremor during postural tasks were analysed using an ultrasound-based measuring system and surface electromyography. In a prospective study design nine patients with advanced PD were examined preoperatively off and on medication, and twice postoperatively during four treatment conditions: off treatment, on STN DBS, on medication, and on STN DBS plus medication. While both STN DBS and medication reduced tremor amplitude, STN DBS alone and the combination of medication and STN DBS were significantly superior to pre- and postoperative medication. STN DBS but not medication increased tremor frequency, and off treatment tremor frequency was significantly reduced postoperatively compared to baseline. These findings demonstrate that STN DBS is highly effective in elderly patients with advanced PD and moderate preoperative tremor reduction by medication. Thus, with regard to the advanced impact on the other parkinsonian symptoms, STN DBS can replace thalamic stimulation in this cohort of patients. Nevertheless, medication was still effective postoperatively and may act synergistically. The significantly superior efficacy of STN DBS on tremor amplitude and its impact on tremor frequency in contrast to medication might be explained by the influence of STN DBS on additional neural circuits independent from dopaminergic neurotransmission. Received in revised form: 27 April 2006     

Short latency activation of cortex by clinically effective thalamic brain stimulation for tremor

Deep brain stimulation (DBS) relieves disabling symptoms of neurologic and psychiatric diseases when medical treatments fail, yet its therapeutic mechanism is unknown. We hypothesized that ventral intermediate (VIM) nucleus stimulation for essential tremor activates the cortex at short latencies, and that this potential is related to the suppression of tremor in the contralateral arm. We measured cortical activity with electroencephalography in 5 subjects (seven brain hemispheres) across a range of stimulator settings, and reversal of the anode and cathode electrode contacts minimized the stimulus artifact, allowing visualization of brain activity. Regression quantified the relationship between stimulation parameters and both the peak of the short latency potential and tremor suppression. Stimulation generated a polyphasic event‐related potential in the ipsilateral sensorimotor cortex, with peaks at discrete latencies beginning less than 1 ms after stimulus onset (mean latencies 0.9 ± 0.2, 5.6 ± 0.7, and 13.9 ± 1.4 ms, denoted R1, R2, and R3, respectively). R1 showed more fixed timing than the subsequent peaks in the response (P < 0.0001, Levene's test), and R1 amplitude and frequency were both closely associated with tremor suppression (P < 0.0001, respectively). These findings demonstrate that effective VIM thalamic stimulation for essential tremor activates the cerebral cortex at approximately 1 ms after the stimulus pulse. The association between this short latency potential and tremor suppression suggests that DBS may improve tremor by synchronizing the precise timing of discharges in nearby axons and, by extension, the distributed motor network to the stimulation frequency or one of its subharmonics. © 2012 Movement Disorder Society     

Deep brain stimulation exacerbates hypokinetic dysarthria in a rat model of Parkinson's disease

Motor symptoms of Parkinson's disease (PD) follow the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) treats some parkinsonian symptoms, such as tremor, rigidity, and bradykinesia, but may worsen certain medial motor symptoms, including hypokinetic dysarthria. The mechanisms by which DBS exacerbates dysarthria while improving other symptoms are unclear and difficult to study in human patients. This study proposes an animal model of DBS‐exacerbated dysarthria. We use the unilateral, 6‐hydroxydopamine (6‐OHDA) rat model of PD to test the hypothesis that DBS exacerbates quantifiable aspects of vocalization. Mating calls were recorded from sexually experienced male rats under healthy and parkinsonian conditions and during DBS of the subthalamic nucleus. Relative to healthy rats, parkinsonian animals made fewer calls with shorter and less complex vocalizations. In the parkinsonian rats, putatively therapeutic DBS further reduced call frequency, duration, and complexity. The individual utterances of parkinsonian rats spanned a greater bandwidth than those of healthy rats, potentially reducing the effectiveness of the vocal signal. This utterance bandwidth was further increased by DBS. We propose that the parkinsonism‐associated changes in call frequency, duration, complexity, and dynamic range combine to constitute a rat analog of parkinsonian dysarthria. Because DBS exacerbates the parkinsonism‐associated changes in each of these metrics, the subthalamic stimulated 6‐OHDA rat is a good model of DBS‐induced hypokinetic dysarthria in PD. This model will help researchers examine how DBS alleviates many motor symptoms of PD while exacerbating parkinsonian speech deficits that can greatly diminish patient quality of life. © 2015 Wiley Periodicals, Inc.     

Thalamic deep brain stimulation for essential tremor: recommendations for long-term outcome analysis

OBJECTIVES: Determine the efficacy of thalamic deep brain stimulation (DBS) for tremor control among individuals with essential tremor (ET). METHODS: A clinical series of 52 consecutive individuals undergoing placement of a DBS system for treatment of ET completed an unblinded battery of subjective and objective measures at postoperative intervals of one, three, and 12 months, and annually thereafter up to three years. The assessment battery included measures of tremor and activities of daily living. RESULTS: Both subjective and objective measures showed that stimulation was associated with significant improvement at nearly every postoperative interval as compared to pre-operative and stimulation 'off' ratings of activities of daily living functioning, midline tremor, contralateral upper extremity tremor, and contralateral lower extremity tremor. Ipsilateral tremor showed some improvement with stimulation, but only within the first three months. Trend analysis showed stable tremor control. Stimulation settings remained largely unchanged after the first three months. Dysarthria was more common among those with bilateral stimulation. A range of missing data estimation methods were performed, and subsequent analyses corroborated the main findings of the study. CONCLUSION: Thalamic DBS is generally a well-tolerated and effective treatment for ET. Methodological and analytical recommendations are provided for the evaluation of long-term outcome.     

Deep brain stimulation for Parkinson’s disease: Australian referral guidelines

The advent of deep brain stimulation (DBS) has been an important advance in the treatment of Parkinson’s disease (PD). DBS may be employed in the management of medication-refractory tremor or treatment-related motor complications, and may benefit between 4.5% and 20% of patients at some stage of their disease course. In Australia, patients with PD are reviewed by specialised DBS teams who assess the likely benefits and risks associated with DBS for each individual. The aim of these guidelines is to assist neurologists and general physicians identify patients who may benefit from referral to a DBS team. Common indications for referral are motor fluctuations and/or dyskinesias that are not adequately controlled with optimised medical therapy, medication-refractory tremor, and intolerance to medical therapy. Early referral for consideration of DBS is recommended as soon as optimised medical therapy fails to offer satisfactory motor control.