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PubMed2006

Thalamic sensory relay nucleus stimulation for the treatment of peripheral deafferentation pain.

We applied chronic deep brain stimulation (DBS) of the thalamic nucleus ventralis caudalis (Vc) for the treatment of peripheral deafferentation pain. The subjects included 11 cases of phantom limb pain and 7 of root or nerve injury pain without phantom sensation. In the phantom limb pain patients, the spike density markedly increased in the same area of the Vc where microstimulation induced paresthesia in the part with phantom sensation. Reorganization of the receptive field representation within the Vc was also demonstrated by microrecording and microstimulation. In the root or nerve injury pain patients with severe allodynia and without phantom sensation, oscillating neural hyperactivity appeared when the allodynia was induced during single-cell recording in the Vc. In both groups stimulation of these areas with the DBS electrode was useful for achieving pain reduction. Inhibition of spinothalamic tract neurons, restoration of the original receptive field representation and modulation of thalamocortical rhythmic oscillations are proposed to play important roles in a possible mechanism of Vc-DBS for the treatment of deafferentation pain.

Causalgia↗

PubMed2005

[Motor cortex stimulation for Parkinson's disease and dystonia: lessons from transcranial magnetic stimulation? A review of the literature].

INTRODUCTION: Over the last few years, deep brain stimulation techniques, with targets such as the subthalamic nucleus or the pallidum, have bee found to be beneficial in the treatment of Parkinson's disease and dystonia. Conversely, therapeutic strategies of cortical stimulation have not yet been validated in these diseases, although they are known to be associated with various cortical dysfunctions. Transcranial magnetic stimulation (TMS) is a valuable tool for non-invasive study of the role played by the motor cortex in the pathophysiology of movement disorders, in particular by assessing various cortical excitability determinants using single or paired pulse paradigms. In addition, repetitive TMS (rTMS) trains can be used to study the effects of transient activity changes of a targeted cortical area. BACKGROUND: Studies with TMS revealed significant motor cortex excitability changes, particularly regarding intracortical inhibitory pathways, both in Parkinson's disease and in dystonia, and these changes can be distinguished owing to the resting state or to the phases of movement preparation or execution. However, more specific correlation between electrophysiological features and clinical symptoms remains to be established. In addition, the stimulation of various cortical targets by rTMS protocols applied at low or high frequencies have induced some clear clinical effects. PERSPECTIVES: The TMS effects are and will remain applied in movement disorders to better understand the role played by the motor cortex, to assess various types of treatment and appraise the therapeutic potential of cortical stimulation. CONCLUSION: TMS provides evidence for motor cortex dysfunction in Parkinson's disease or dystonia. Moreover, rTMS results have opened new perspectives for therapeutic strategies of implanted cortical stimulation. By these both aspects, TMS techniques show their usefulness in the assessment of movement disorders.

Deep Brain Stimulation↗

PubMed2004

A qualitative analysis of nonresponse: management of treatment-refractory obsessive-compulsive disorder.

Serotonin reuptake inhibitors (SRIs), especially potent ones given at high doses over long periods of time, are often effective in the treatment of obsessive-compulsive disorder (OCD). However, a large percentage of patients do not respond to treatment with SRIs, and those who do respond often do not fully remit, which should be the standard goal of treatment in OCD. If a patient has been treated for several months and has not yet responded to treatment with several SRIs, the physician should perform a careful assessment of resistant and/or residual clinical symptoms and any comorbid conditions to determine which next-step treatment would be the most appropriate. One strategy for patients who have not responded to treatment with an SRI is to switch them to a serotonin-norepinephrine reuptake inhibitor, because some patients may respond better to agents that target multiple systems. Another promising approach is the augmentation of SRIs with neuroleptics. In addition, open trials have shown that intravenous (IV) clomipramine and IV citalopram may be effective in the treatment of resistant OCD. Novel pharmacotherapeutic treatments and electroconvulsive therapy have been attempted, with mixed success. Recently, researchers have been studying repetitive transcranial magnetic stimulation, vagal nerve stimulation, and neurosurgical approaches such as gamma knife capsulotomy and deep brain stimulation to learn if these procedures are effective in treating treatment-resistant OCD. Repetitive transcranial magnetic stimulation has possibilities not only as a therapy but also as an instrument that can help researchers describe the neurocircuitries involved in OCD. More results are needed before the effectiveness of the nonpharmacologic treatments for OCD can be determined.

Adrenergic Uptake Inhibitors↗

PubMed2005

Pallidal stimulation reduces treatment-induced dyskinesias in "minimal-change" multiple system atrophy.

Deep brain stimulation therapy is increasingly gaining acceptance in the management of levodopa-induced dyskinesia and fluctuations in idiopathic Parkinson's disease. It is generally not recommended for the other forms of parkinsonism such as progressive supranuclear palsy or multiple system atrophy where the response to levodopa is usually poor and disease progression more rapid, making any benefit short-lived. Here, we present an autopsy-confirmed case of "minimal-change" multiple system atrophy in whom pallidal stimulation surgery was effective in abolishing severe levodopa-induced dyskinesia.

Deep Brain Stimulation↗

PubMed2005

Pallidal stimulation in dystonia: effects on cognition, mood, and quality of life.

Bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) alleviates symptoms in patients with dystonia but its effects on cognition, neuropsychiatric status, and quality of life have not been examined. This is a case series report of 15 consecutive patients with different forms of dystonia who underwent bilateral implantation of DBS electrodes in the GPi. The patients were evaluated preoperatively and after 3-12 months of DBS with tests of cognition (Mattis Dementia Rating Scale, Stroop Test, Trail Making Test, Phonemic and Category Word Fluency, Digit Span, Rey Auditory Verbal Learning Test, Tonic and Phasic Alertness), neuropsychiatric status (Beck Depression and Anxiety Inventories, Montgomery Asberg Depression Rating Scale, Snaith-Hamilton Pleasure Scale, Brief Psychiatric Rating Scale), quality of life, and motor functions. GPi DBS significantly improved dystonic symptoms, functional abilities, and quality of life allowing for a significant reduction of antidystonic medications. No deterioration was observed in cognitive scores and neuropsychiatric measures. The present case series report thus provides preliminary evidence for the safety of GPi DBS regarding cognitive and neuropsychiatric functions in patients with dystonia.

Adolescent↗

PubMed2005

Brain networks underlying the clinical effects of long-term subthalamic stimulation for Parkinson's disease: a 4-year follow-up study with rCBF SPECT.

UNLABELLED: The motor improvement derived from high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) is maintained over time after surgery. The aim of the present prospective follow-up study was to assess regional cerebral blood flow (rCBF) changes related to such improvement in the long term. METHODS: Ten PD patients with STN-DBS underwent 3 rCBF SPECT studies at rest-once preoperatively in the off-drug condition and the other 2 postoperatively in the off-drug/on-stimulation conditions at 5 +/- 2 and 42 +/- 7 mo. Patients were administered with Unified Parkinson Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) scale, and Schwab and England (S&E) scale. Statistical parametric mapping was used to investigate rCBF changes during long-term STN stimulation in comparison with preoperative rCBF and the relationship between rCBF and UPDRS scores was used as a covariate of interest. RESULTS: All patients showed a maximum clinical improvement during the first months after surgery and remained rather stable during further follow-up. The effect of STN-DBS from the pre- to the postoperative condition at 5 mo was to produce rCBF increases in the presupplementary motor area (pre-SMA), premotor (PMC), and dorsolateral prefrontal cortices. From the postoperative condition at 5 mo to that at 42 mo, the STN stimulation produced further rCBF increases in these frontal areas, and also in the primary motor/sensory cortices, globus pallidi, ventral lateral thalamic nuclei, cerebellum, pons, and midbrain entailing the substantia nigra (P < 0.0001). A correlation was detected between the improvement in motor scores and the rCBF increase in the pre-SMA and PMC (P < 0.0001). No correlation was present between the daily consumption of levodopa and the rCBF. CONCLUSION: Our study suggests that the long-term STN stimulation leads to improvement in neural activity in the frontal motor/associative areas. After an rCBF increase during the first months of stimulation, these regions showed a further increment in the later phase, which was accompanied by an increased activity in subcortical structures. The correlation between motor improvement and rCBF increase in higher order motor cortical areas suggests that even in the long term, as well as in the short term, the STN-DBS achieves its therapeutic benefit by restoring the activity within these cortical regions.

Antiparasitic Agents↗

PubMed2005

Efficient internal pallidal stimulation in Gilles de la Tourette syndrome: a case report.

The usefulness of deep brain stimulation (DBS) of thalamic nuclei in Gilles de la Tourette syndrome (GTS) has recently been advocated. We report on a 14-month follow-up study of a patient with intractable GTS in whom bilateral DBS of the internal globus pallidus was carried out. Tic frequency per minute decreased by 73% in the postoperative phase and in particular the vocal tics became less intense. Pronation/ supination bradykinesia of the left extremities was a well-tolerated, permanent side effect. Pallidal DBS could become a valuable rescue therapy for otherwise intractable GTS.

Adult↗

PubMed2005

Influence of bilateral Stn-stimulation on psychiatric symptoms and psychosocial functioning in patients with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease. There is some evidence that subthalamic stimulation not only affects motor function, but also mood, behaviour and cognition. In the present study we investigated the effects of subthalamic stimulation on psychiatric symptoms and psychosocial functioning in a consecutive series of patients with Parkinson's disease. 33 patients were assessed three times prior to surgery and at three, nine weeks as well as three, six and twelve months after surgery. We found significant improvements in depression, anxiety, psychological symptoms and distress after surgery. In most cases the amelioration followed surgery and was stable in the course of time. Individual analysis indicated deterioration in three patients despite motor improvement. The results suggest that stimulation of the subthalamic nucleus has a positive influence on psychiatric symptoms, psychosocial functioning and distress. We observed a decline in a minority of patients.

Adult↗

PubMed2005

Motor and non motor effects during intraoperative subthalamic stimulation for Parkinson's disease.

Spatial distribution of the clinical effects induced by deep brain stimulation during the intraoperative investigation of the subthalamic nucleus (STN) for Parkinson's disease (PD) was analysed in 17 patients under local anesthesia. The stimulation parameters were 130 hertz, 100 micros, and voltage ranged from 0.05 to 5 volts. Optimal motor response was assessed as the total and lasting disappearance of wrist rigidity on the side opposite to stimulation. Among the adverse effects induced by stimulation, special attention was given to frequently observed autonomic effects (AE). Full motor response was achieved in 49.2% of the 301 points evaluated,with a mean voltage (MV) of 0.94 volts; paresthesiae occurred in 6.6% (MV: 2 volts), dystonia in 10.6% (MV: 3.4 volts), autonomic effects in 19.6% (MV: 3.1 volts) and oculomotor effects in 31.6% (MV: 3 volts). The motor target was located in the posterodorsal part of the nucleus and the optimal point for motor response was close to the superior limit of the nucleus. Whereas other adverse effects occurred relatively far from the motor target, AE occurred with statistic significance near this point. Their neural substrates, such as limbic system and their relationship with postoperative behavioral disorders, are discussed.

Adult↗

PubMed2006

Subthalamic stimulation modulates cortical control of urinary bladder in Parkinson's disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for off-period motor symptoms and dyskinesias in advanced Parkinson's disease. Clinical studies have shown that STN-DBS also ameliorates urinary bladder function in Parkinson's disease patients by delaying the first desire to void and increasing bladder capacity. This study aimed at investigating the effect of STN-DBS on the neural mechanisms underlying cerebral bladder control. Using PET to measure changes in regional cerebral blood flow (rCBF), 11 patients with bilateral STN-DBS were studied during urodynamic bladder filling in STN-DBS ON and OFF condition. A filled bladder led to a significant increase of rCBF in the anterior cingulate cortex, which was further enhanced during STN-DBS OFF. A significant interaction between bladder state and STN-DBS was observed in lateral frontal cortex with increased rCBF when the bladder was filled during STN-DBS OFF. The data suggest that STN-DBS ameliorates bladder dysfunction and that this modulation may result from facilitated processing of afferent bladder information.

Adult↗

PubMed2005

Quantitative assessments of the effect of bilateral subthalamic stimulation on multiple aspects of sensorimotor function for patients with Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective for the treatment of advanced Parkinson's disease. Most studies have evaluated the effectiveness of DBS of the STN using clinical motor scores or simple timed tests of motor function. There have been few studies that quantitatively assessed the outcome of STN DBS using multiple testing paradigms. In the current study, 11 patients who had bilateral STN DBS were quantitatively evaluated under four conditions using gait, postural control, and gait initiation. The four conditions included the medication on/stimulation on (M_on/S_on), medication on/stimulation off (M_on/S_off), medication off/stimulation on (M_off/S_on), and medication off/stimulation off (M_off/S_off) conditions. DBS of the STN significantly increased walking speed with and without levodopa, but had no influence on the cadence. The addition of levodopa had a minimal additional effect on walking speed. The effect of STN DBS on gait initiation approached the significant level. The mean values of lateral body sway during quiet standing increased moderately with medication and/or DBS, but the changes were not statistically significant. Future studies need to determine whether or not there is a potential negative effect of STN DBS on the postural control.

Adult↗

PubMed2004

Comparative cognitive effects of bilateral subthalamic stimulation and subcutaneous continuous infusion of apomorphine in Parkinson's disease.

Bilateral subthalamic deep brain stimulation (STN-DBS) and continuous subcutaneous infusion of apomorphine (APM-csi) can provide a comparable improvement on motor function in patients with advanced Parkinson's disease (PD), but the mechanisms by which both therapies exert their effects are different. We analyzed the cognitive effects of APM-csi. We also compared neuropsychological effects induced by STN-DBS and APM-csi in advanced PD to ascertain the neuropsychological aspects relevant in determining the therapeutic procedure that is the most appropriate in a particular patient. We studied 9 patients treated with STN-DBS and 7 patients with APM-csi. Neuropsychological measures included Rey's Auditory-Verbal Learning, Stroop, Trail Making, phonetic verbal fluency, and Judgment of Line Orientation tests. In the APM-csi group, significant changes were not observed in the neuropsychological tests performance. By contrast, in the STN-DBS group, moderate worsening was found in phonetic verbal fluency and Stroop Naming scores that was partially reversible at long-term follow-up and did not have consequences on regular activities. Consequently, these findings could be interpreted as being not relevant in deciding the most suitable treatment in a given patient.

Aged↗

PubMed2005

Subthalamic stimulation for Parkinson disease: determination of electrode location necessary for clinical efficacy.

OBJECT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) performed using intraoperative microelectrode recording (MER) to adjust electrode placement has become a widely used treatment for patients with advanced Parkinson disease (PD). Few studies have been conducted to examine the location of implanted electrodes relative to the intended target, and even fewer have been undertaken to investigate the degree to which variations in the location of these electrodes impacts their clinical efficacy. This study was performed to examine these issues. METHODS: The authors located 52 bilaterally implanted DBS electrode tips on postoperative magnetic resonance (MR) images obtained in 26 consecutive patients. Postoperative and preoperative planning MR images were merged to determine the DBS electrode tip coordinates relative to the midcommissural point. Surgical records listed the intended target coordinates for each DBS electrode tip. Clinical outcome assessment included the Unified PD Rating Scale (UPDRS) motor score at 1 year, standardized questionnaires, and routine follow-up visits. The mean difference between electrode tip location and intended target for all 52 electrodes was less than 2 mm in all axes. Only one electrode was farther than 3 mm from the intended target, and this was the only electrode that had to be replaced due to lack of clinical efficacy (lack of tremor suppression); its reimplantation 4 mm more medially provided excellent tremor control. High correlation coefficients indicate that the MR imaging analysis accurately determined the anatomical location of the electrode tips. Blinded videotape reviews of UPDRS motor scores comparing effects of stimulation in patients who were "on" and "off" medication identified subgroups in whom there was minimal and maximal stimulation response. Patients in these subgroups had no differences between the MR imaging-determined actual electrode tip location and its intended location. Similarly, improvements of dyskinesias and severity of symptoms encountered during the wearing-off period for the drug did not correlate with variations of electrode tip location. CONCLUSIONS: The findings in this study lead the authors to suggest that a DBS electrode placed anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) provides similar clinical efficacy. Future studies may be warranted to evaluate prospectively the degree to which MER modification of the anatomically and/or image-determined target improves clinical efficacy of DBS electrodes.

Adult↗

PubMed2005

Frequency-correlated decreases of motor cortex activity associated with subthalamic nucleus stimulation in Parkinson's disease.

According to the classical model of basal ganglia organization, deep brain stimulation (DBS) in the subthalamic nucleus (STN) for the treatment of Parkinson's disease (PD) blocks overactive excitatory projections to inhibitory basal ganglia output structures. This would release the break on thalamofrontal neurons alleviating the poverty of movement, the hallmark of PD. Such parallels to a functional lesion certainly simplify the mechanism of STN DBS. Here, we applied parametric analyses of H2(15)O positron emission tomography (PET) scans at rest while systematically varying stimulation frequency in 6 patients with STN DBS for akinetic PD. A strong positive correlation of rCBF to increasing stimulation frequency was detected around the STN bilaterally. More importantly, we show that gradual increases in STN stimulation frequency are tightly correlated with decreases in motor cortex activity. This demonstrates an active modulation of resting activity within the subcortical stimulation target and within motor cortex by STN DBS. Rather than a possible downstream effect, we propose to consider the tight correlations between DBS frequency and motor cortex activity in the context of an upstream modulation of direct efferents to the STN from primary motor and premotor cortices.

Aged↗

PubMed2006

Effects of GPi stimulation on human thalamic neuronal activity.

OBJECTIVE: Determine the effects of globus pallidus interna (GPi) deep brain stimulation (DBS) on ventral oralis posterior nucleus of the thalamic (Vop) neuronal activity. METHODS: Microelectrode recordings in Vop during high frequency DBS GPi in a patient with dystonia. RESULTS: Twelve (48%) of 25 neurons in five locations neurons decreased their average discharge frequency, 2 (8%) increased and 11(44%) demonstrated no overall change. The patterns of responses were complex with periods of increase and decreased activity. All neurons were inhibited for the time period 3.5-5ms following the DBS pulse. Eighty-eight percent of neurons showed brief but highly consistent increases in the first 1ms following stimulation, 52% showed increased activities from 1.5 to 3ms. Twenty-four percent of neurons increased activity following inhibition. CONCLUSIONS: These findings are consistent with DBS activation of GPi axons to Vop and probable antidromic activation of Vop axons. SIGNIFICANCE: The physiological effects of DBS are far more complicated and will escape any theory that does not address the mechanisms of DBS as stimulation of a complex network of interactions. Further, the findings of post-inhibitory rebound increased raises questions about the role in inhibition in the current concepts of basal ganglia physiology.

Adult↗

PubMed2006

Rhythmic cortical EEG synchronization with low frequency stimulation of the anterior and medial thalamus for epilepsy.

OBJECTIVE: To investigate the neurophysiological characteristics and prognostic impact of EEG synchronization with low frequency thalamic stimulation in patients with intractable epilepsy. METHODS: Electrical stimuli were delivered through deep brain stimulating (DBS) electrodes at 2, 5 or 10Hz to the anterior nucleus (AN) and the dorsomedial nucleus (DM) of six patients using the implanted programmable stimulation device. EEGs were recorded from 27 scalp electrodes. "Modeled" responses for 5 and 10Hz stimulation were computed based on the cerebral responses (CRs) evoked by "single pulse" (2Hz) stimulation and compared with the recorded EEG results. RESULTS: Rhythmic cortical 5Hz EEG synchronization occurred in 4/6 patients, with stimulation at 6/11 AN and 5/11 DM sites. Three of four patients with synchronization, but neither of the two patients without, had a significant reduction in seizure frequency. The magnitude of 5 and 10Hz EEG synchronization was positively related to the amplitudes of "single pulse" CRs. Simple temporal superposition of "single pulse" CRs resulted in "modeled" responses with strikingly similar morphology and scalp voltage distribution. CONCLUSIONS: Rhythmic EEG synchronization with low frequency stimulation primarily reflects spatiotemporal summation (interference) of "single pulse" CRs. SIGNIFICANCE: Rhythmic EEG synchronization might not serve as a physiologic verification of optimal localization of DBS electrodes. Its usefulness for the prediction of clinical efficacy is questionable.

Adult↗

PubMed2005

Stimulation of the globus pallidus internus for childhood-onset dystonia.

We report the results of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in 12 patients with childhood-onset generalized dystonia refractory to medication, including 3 patients with status dystonicus. There were 8 patients who had DYT1-negative primary dystonia, 1 had DYT1-positive dystonia, and 3 had symptomatic dystonia. Stimulation was effective in all but 1 patient. Dystonic postures and movements of the axis and limbs responded to DBS to a greater extent than oromandibular dystonia and fixed dystonic postures. These findings provide further evidence that pallidal stimulation is an effective treatment for intractable childhood-onset dystonia, including status dystonicus, and together with previous findings, suggest that it should be considered the treatment of choice for these conditions.

Adolescent↗

PubMed2006

Restless legs syndrome in Parkinson's disease patients may improve with subthalamic stimulation.

We report on 6 advanced Parkinson's disease (PD) patients who underwent bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery whose restless legs syndrome (RLS) improved postoperatively. Despite a mean 56% decrease in their levodopa equivalents postoperatively, their RLS scores dropped by a mean of 84% (100% in three). Our findings suggest that bilateral STN DBS surgery can improve RLS in patients with advanced PD.

Aged↗