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PubMed2005

Effect of subthalamic stimulation on mood state in Parkinson's disease: evaluation of previous facts and problems.

In an attempt to clarify the effect of deep brain stimulation (DBS) to the subthalamic nucleus (STN) on mood state, previous evidence and problems were evaluated through a systematic literature search. Twenty three articles reported the effect of STN DBS on mood state in Parkinson's disease (PD), and antidepressant, depressant, and mania-induced effects were reported in 16.7-76%, 2-33.3%, and 4.2-8.1% of the patients treated with STN DBS, respectively. Most articles reported larger subgroups showing antidepressant effects than those showing depressant effects. The average depression scale score of all subjects was improved or unchanged after STN DBS. Although there was a limitation due to the varied results, it was suggested that, in general, STN DBS had an antidepressant effect in PD. However, the studies reporting severe depressant symptoms, such as suicidal attempts, after STN DBS indicated the importance of careful attention to mood state as well as to motor symptoms after STN DBS. It may be crucial to reduce the variation in the results by, for example, the use of standardized protocols and the precise verification of the stimulated region in further investigations to address this issue.

Affect↗

PubMed2005

Bilateral subthalamic nucleus stimulation improves health-related quality of life in Parkinsonian patients.

Parkinson's disease (PD) is a common neurological disorder. Recently, bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an option in the treatment of severe PD. We measured the health-related quality of life (HRQoL) of 27 parkinsonian patients, who underwent a bilateral STN-operation. The instruments used for the evaluation of the HRQoL were the Parkinson's Disease Questionnaire (PDQ-39) and the Finnish version of the Nottingham Health Profile (NHP). We found that the quality of life significantly improved when measured with both HRQoL scales. Clinical improvement and improvement in HRQoL were positively correlated.

Aged↗

PubMed2006

Direct effect of subthalamic nucleus stimulation on levodopa-induced peak-dose dyskinesia in patients with Parkinson's disease.

We examined the direct effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) on levodopa-induced peak-dose dyskinesia in 45 patients with Parkinson's disease (PD) without reducing the levodopa dosage during the early period after surgery. In 8 patients (18%), the dyskinesia was quickly attenuated by bipolar stimulation in an experimental trial (5 min) with the contacts placed within the area above the STN. In contrast, bipolar stimulation using contacts placed within the STN itself tended to provoke or exacerbate the dyskinesia, indicating that dyskinesia could be inhibited by stimulation of the areas above the STN rather than the STN itself. In an attempt to control the cardinal symptoms of PD and dyskinesia at the same time, we employed bipolar stimulation with a longer interpolar distance as a therapeutic procedure (2 weeks), using contacts within the STN as a cathode and contacts within the area above the STN as an anode. Bilateral STN-DBS significantly attenuated the dyskinesia as evaluated by the dyskinesia severity rating scale (p < 0.05). In 24 patients (53%), almost complete control of the dyskinesia was observed. The contacts used as an anode in these patients were located more dorsally compared to those of the remaining patients, suggesting again that the dyskinesia was inhibited by stimulation of the areas above the STN rather than the STN itself. In the area above the STN, pallidothalamic, pallidosubthalamic and subthalamopallidal fibers are densely distributed. It appears that stimulation of these fibers may cause effects similar to thalamic or pallidal DBS and therefore inhibit peak-dose dyskinesia. Bipolar STN-DBS with contacts placed within the area above the STN as an anode appears to represent a useful option for controlling both the cardinal symptoms of PD and peak-dose dyskinesia at the same time.

Antiparkinson Agents↗

PubMed2005

Only physical aspects of quality of life are significantly improved by bilateral subthalamic stimulation in Parkinson's disease.

BACKGROUND: The well known global improvement of quality of life (QoL) after bilateral high frequency chronic deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) is in contrast to behavioral disturbances as observed after surgery. Indeed the impact of DBS on physical versus mental aspects of QoL in PD remains unknown. OBJECTIVE: To assess the influence of bilateral STN DBS on physical versus mental aspects of QoL in Parkinson's disease. METHODS: The results of 27 patients for the Unified Parkinson's disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire 39 (PDQ39) and Short Form 36 health survey questionnaire (SF36) were compared before surgery and after 12 months of bilateral STN DBS. RESULTS: Comparing off-dopa conditions before versus 12 months after surgery, both UPDRS part II and part III significantly improved: 32.6% and 52%, respectively. UPDRS part I scores did not change significantly at 12 months. As for PDQ39, the global score significantly improved after surgery (21.1 %) as did four subscores: mobility (25.6 %), activity of daily living (34.5 %), stigma (40.1 %) and bodily discomfort (30 %). Three PDQ39 subscores, however, showed no significant changes: emotional well-being (10.7 %), social support (3.2%) and cognition (8.5 %) and one item even worsened: communication (-7.7 %). In SF36, only physical items significantly improved. CONCLUSION: Using clinician's based rating scale, bilateral STN DBS showed significant improvement in PD patients at 12 month follow up. However, using patient's self-assessment scales, the clinical benefit of STN DBS was more subtle: physical items of QoL significantly improved, whereas mental items such as emotional well-being, social support, cognition and communication showed no improvement. Our results are suggestive of a dissociation of motor and non-motor symptoms control after bilateral STN DBS in PD patients.

Adult↗

PubMed2006

Stimulating debate: ethics in a multidisciplinary functional neurosurgery committee.

Multidisciplinary healthcare committees meet regularly to discuss patients' candidacy for emerging functional neurosurgical procedures, such as Deep Brain Stimulation (DBS). Through debate and discussion around the surgical candidacy of particular patients, functional neurosurgery programs begin to mold practice and policy supported both by scientific evidence and clear value choices. These neurosurgical decisions have special considerations not found in non-neurologic committees. The professional time used to resolve these conflicts provides opportunities for the emergence of careful, ethical practices simultaneous with the expansion of therapy applications.

Aged↗

PubMed2005

The effect of subthalamic nucleus stimulation on kinaesthesia in Parkinson's disease.

BACKGROUND: Parkinson's disease is accompanied by deficits in passive motion and limb position sense. OBJECTIVE: To investigate whether deep brain stimulation of the subthalamic nucleus (STN-DBS) reverses these proprioceptive deficits. METHODS AND RESULTS: A passive movement task was applied to nine patients with Parkinson's disease and bilateral chronic STN-DBS and to seven controls. Thresholds for 75% correct responses were 0.9 degrees for controls, 2.5 degrees for Parkinson's disease patients when stimulation was OFF, and 2.0 degrees when stimulation was ON. CONCLUSIONS: STN-DBS improves kinaesthesic deficits in Parkinson's disease, but does not lead to a full recovery of proprioceptive function.

Adult↗

PubMed2006

Surgical treatment of movement disorders.

A substantial body of evidence has accumulated regarding the efficacy and safety of neurosurgery for Parkinson's disease, essential tremor, and dystonia. Surgery for movement disorders (thalamotomy, pallidotomy, and subthalamic nucleotomy or subthalamotomy) was largely ablative (lesion-based). Given the safety and anatomy-preservation advantage, long-term electrical stimulation of these same targets (thalamus, globus pallidus, and subthalamic nucleus) is discussed as the treatment of choice. High-frequency deep brain stimulation procedures replicate the effects of ablative interventions, but do not require making a destructive brain lesion. This article outlines patient eligibility for surgery, targeting techniques, intraoperative findings, and potential complications and discusses the outcomes expected for each of the major interventions for which clinical trial data are available.

Brain↗

PubMed2006

[Electrophysiology of subthalamic nucleus in normal and Parkinson's disease].

Subthalamic nucleus (STN) has been known to play an important role in the regulation of cortico-basal ganglia-thalamo-cortical loop. STN neurons have pacemaking activitiy and their firing pattern can switch from spike mode to bursting mode when membrane potential becomes hyperpolarized. Recent study has shown that STN neurons show marked increase in burst and oscillatory activity during the dopamine-depleting state of Parkinson's disease (PD). This electrophysiological change in activity is now considered as an characterstic pathophysiological feature of PD. High frequency stimulation of STN can modify and "normalize" the activity of STN neurons in the pathophysiologial state. This electrophysiological treatment applied to STN, known as deep brain stimulation (DBS) clinically, ameliorates the symptoms of PD effectively, and is becoming a standard treatment in patients with advanced PD. This article would review the basic researches concerning electrical activities of STN and try to extend the basic knowledge into clinical applications.

Basal Ganglia↗

PubMed2005

Comparison of 2-dimensional magnetic resonance imaging and 3-planar reconstruction methods for targeting the subthalamic nucleus in Parkinson disease.

OBJECTIVE: The study aims to compare 2-dimensional (2D) and 3-planar (3P) reconstruction magnetic resonance imaging (MRI) methods of targeting the optimal region of the subthalamic nucleus (STN) for chronic stimulation in patients with Parkinson disease. METHODS: We studied 14 patients with Parkinson disease treated with bilateral STN deep brain stimulation (DBS) (28 STN targets). Electrode implantation was based on direct and indirect targeting based upon the position of the anterior and posterior commissures using 2D MRI, with selection of the final target based on microelectrode recording. Optimal settings, including the contacts used, were determined during the clinical follow-up. The position of the best contact was defined with postoperative MRI. Optimal contact position was compared to targets calculated by the direct method from the preoperative 2D MRI and 3P reconstruction. Optimal contact position was also compared to the indirect targets calculated from the preoperative 2D MRI and 3P reconstruction. The distance between the targets and the position of the best contact were calculated. RESULTS: The mean improvement in OFF-period Unified Parkinson Disease Rating Scale III subscores with STN DBS was 52%. The mean distance between the optimal contact position and the direct target was 4.66 mm (SD = 1.33) using the 2D MRI and 3.49 mm (SD = 1.29) using the 3P reconstruction (t test, P < .001). The mean distance between the optimal contact and the indirect target was 3.42 mm (SD = 1.34) using the 2D MRI and 2.61 mm (SD = 0.97; t test, P = .001) using the 3P reconstruction. The variance of the direct target was less using the 3P reconstruction than using the 2D MRI (F test, P = .002), indicating greater precision. Similarly, the variance of the indirect target using the 3P reconstruction was less than using the 2D MRI (F test, P = .012). CONCLUSION: Indirect and direct targets chosen using 3P reconstruction more closely approximate the position of the clinically optimal contact than targets chosen using 2D MRI.

Deep Brain Stimulation↗

PubMed1999

Changes in cerebral blood oxygenation of the frontal lobe induced by direct electrical stimulation of thalamus and globus pallidus: a near infrared spectroscopy study.

OBJECTIVE: Blood oxygenation level dependent (BOLD) contrast functional MRI images show activated cortical areas by detecting a reduced concentration of deoxyhaemoglobin (deoxy-Hb) during neuronal activity; however, near infrared spectroscopy (NIRS) has shown various patterns of cerebral blood oxygenation (CBO) changes in the frontal lobe during cognitive tasks. To determine if various patterns of CBO changes occur in the frontal lobe when the brain is directly stimulated, changes in CBO in the frontal lobe induced by deep brain stimulation in patients with implanted electrodes were evaluated. METHODS: Six patients were studied, including five with Parkinson's disease and one with essential tremor. To reduce tremor or rigidity, the electrodes were implanted at the thalamic nucleus ventralis intermedius (VIM: three Parkinson's disease and one essential tremor) or the globus pallidus internus (GPi: two Parkinson's disease). Using NIRS, changes of deoxy-Hb, oxyhaemoglobin (oxy-Hb) and total haemoglobin (total Hb) were measured in the bilateral frontal lobes during various stimulus conditions. RESULTS: High frequency (120 Hz) GPi stimulation consistently increased oxy-Hb and total Hb with a decrease of deoxy-Hb in an intensity and time dependent manner. Oxy-Hb and total Hb increased immediately after the onset of stimulation and then gradually decreased when stimulation was continued. By contrast, high frequency (120 Hz) VIM stimulation decreased oxy-Hb, deoxy Hb and total Hb in an intensity dependent manner. In the severe tremor patient with VIM stimulation, frequency response was examined by decreasing stimulus frequencies; deoxy-Hb increased at high frequencies (70-40 Hz), and then decreased below the control level at low frequencies (30-0 Hz), whereas oxy-Hb and total Hb increased consistently at high and low frequencies. CONCLUSION: The electrical stimulation of GPi and VIM caused various CBO changes in the frontal lobe, which were similar to those found during cognitive tasks. Such a multiplicity of CBO changes in the frontal lobe may be caused by complex neuronal circuits in the frontal lobe which has many neuronal connections to other cortical areas or the basal ganglia.

Aged↗

PubMed2006

Cognitive outcome 5 years after bilateral chronic stimulation of subthalamic nucleus in patients with Parkinson's disease.

AIM: To assess the long-term cognitive and behavioural outcome after bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients affected by Parkinson's disease, with a 5-year follow-up after surgery. METHODS: 11 patients with Parkinson's disease treated by bilateral DBS of STN underwent cognitive and behavioural assessments before implantation, and 1 and 5 years after surgery. Postoperative cognitive assessments were carried out with stimulators turned on. RESULTS: A year after surgery, there was a marginally significant decline on a letter verbal fluency task (p = 0.045) and a significant improvement on Mini-Mental State Examination (p = 0.009). 5 years after surgery, a significant decline was observed on a letter verbal fluency task (p = 0.007) and an abstract reasoning task (p = 0.009), namely Raven's Progressive Matrices 1947. No significant postoperative change was observed on other cognitive variables. No patient developed dementia 5 years after surgery. A few days after the implantation, two patients developed transient manic symptoms with hypersexuality and one patient developed persistent apathy. CONCLUSION: The decline of verbal fluency observed 5 years after implantation for DBS in STN did not have a clinically meaningful effect on daily living activities in our patients with Parkinson's disease. As no patient developed global cognitive deterioration in our sample, these findings suggest that DBS of STN is associated with a low cognitive and behavioural morbidity over a 5-year follow-up, when selection criteria for neurosurgery are strict.

Aged↗

PubMed2005

Disease progression continues in patients with advanced Parkinson's disease and effective subthalamic nucleus stimulation.

OBJECTIVES: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications, has been thought to inhibit STN hyperactivity and therefore decrease progression of PD. METHODS: In a prospective two centre study, disease progression was determined by means of serial (18)F-fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery. RESULTS: Depending on the method of PET data analysis used in the two centres, annual progression rates relative to baseline were 9.5-12.4% in the caudate and 10.7-12.9% in the putamen. CONCLUSIONS: This functional imaging study is the first to demonstrate a continuous decline of dopaminergic function in patients with advanced PD under clinically effective bilateral STN stimulation. The rates of progression in patients with STN DBS were within the range of previously reported data from longitudinal imaging studies in PD. Therefore this study could not confirm the neuroprotective properties of DBS in the STN target.

Aged↗

PubMed2004

Surgical and hardware complications of subthalamic stimulation: a series of 160 procedures.

OBJECTIVE: To assess the surgical and hardware complications in a series of 81 consecutive patients undergoing subthalamic (STN) deep brain stimulation (DBS) for Parkinson disease (PD). METHODS: The authors prospectively documented surgical and hardware complications occurring at the time of surgery and at subsequent neurologic and surgical evaluations for an average of 17 months, ranging from 1 to 54 months. RESULTS: No patient had a serious surgical complication resulting in death or permanent neurologic deficit. One patient had an intracranial hemorrhage but with no permanent deficit. In follow-up, 2.5% had infections requiring system removal, 3.7% had infections requiring implantable pulse generator (IPG) removal, 12.5% had misplaced leads, and 26.2% had hardware complications including lead migration, lead fracture, extension erosion, extension fracture, and IPG malfunction. CONCLUSION: Serious complications leading to permanent neurologic deficit are rare after STN DBS for advanced PD. However, long-term follow-up demonstrated that hardware complications are relatively common, having occurred in approximately 26% of these patients.

Adult↗

PubMed2006

STN stimulation alters pallidal-frontal coupling during response selection under competition.

To investigate the effects of bilateral subthalamic nucleus (STN) stimulation on patterns of brain activation during random number generation (RNG), a task that requires suppression of habitual counting and response selection under competition. We used H(2)(15)O positron emission tomography to investigate the changes of regional cerebral blood flow (rCBF) induced by bilateral STN stimulation during a RNG task, in six patients with Parkinson's disease. Paced RNG at 1 Hz was compared with a control counting task. Both tasks were performed off medication with deep brain stimulation on and off. Subthalamic nucleus stimulation had a negative effect on performance of fast-paced RNG, leading to reduced randomness and increased habitual counting. Subthalamic nucleus stimulation also induced a reduction of rCBF in the left dorsal frontal gyrus, inferior frontal gyrus, dorsolateral prefrontal cortex, posterior and right anterior cingulate, and an increase of rCBF in the right internal globus pallidum (GPi) during RNG. Stimulation of the STN significantly altered pallidal coupling with frontal and temporal areas compared with when the stimulators were off. In conclusion, during RNG: (i) STN stimulation activates its output neurons to the GPi; (ii) STN stimulation induces increased inhibition of a prefrontal-cingulate network. This is the first direct evidence that STN stimulation significantly alters pallidal coupling with prefrontal, cingulate, and temporal cortices during performance of a task that requires response selection under competition.

Cerebrovascular Circulation↗

PubMed2005

Long-term anti-kindling effects of desynchronizing brain stimulation: a theoretical study.

In a modeling study we show that desynchronization stimulation may have powerful anti-kindling effects. For this, we incorporate spike-timing-dependent plasticity into a generic network of coupled phase oscillators, which serves as a model network of synaptically interacting neurons. Two states may coexist under spontaneous conditions: a state of uncorrelated firing and a state of pathological synchrony. Appropriate stimulation protocols make the network learn or unlearn the pathological synaptic interactions, respectively. Low-frequency periodic pulse train stimulation causes a kindling. Permanent high-frequency stimulation, used as golden standard for deep brain stimulation in medically refractory movement disorders, basically freezes the synaptic weights. In contrast, desynchronization stimulation, e.g., by means of a multi-site coordinated reset, has powerful long-term anti-kindling effects and enables the network to unlearn pathologically strong synaptic interactions. We propose desynchronization stimulation for the therapy of movement disorders and epilepsies.

Brain↗

PubMed2003

Thalamic field potentials in chronic central pain treated by periventricular gray stimulation -- a series of eight cases.

Chronic deep brain stimulation (DBS) of the periventricular gray (PVG) has been used for the treatment of chronic central pain for decades. In recent years motor cortex stimulation (MCS) has largely supplanted DBS in the surgical management of intractable neuropathic pain of central origin. However, MCS provides satisfactory pain relief in about 50-75% of cases, a range comparable to that reported for DBS (none of the reports are in placebo-controlled studies and hence the further need for caution in evaluating and comparing these results). Our experience also suggests that there is still a role for DBS in the control of central pain. Here we present a series of eight consecutive cases of intractable chronic pain of central origin treated with PVG DBS with an average follow-up of 9 months. In each case, two electrodes were implanted in the PVG and the ventroposterolateral thalamic nucleus, respectively, under guidance of corneal topography/magnetic resonance imaging image fusion. The PVG was stimulated in the frequency range of 2-100 Hz in alert patients while pain was assessed using the McGill-Melzack visual analogue scale. In addition, local field potentials (FPs) were recorded from the sensory thalamus during PVG stimulation. Maximum pain relief was obtained with 5-35 Hz stimulation while 50-100 Hz made the pain worse. This suggests that pain suppression was frequency dependent. Interestingly, we detected low frequency thalamic FPs at 0.2-0.4 Hz closely associated with the pain. During 5-35 Hz PVG stimulation the amplitude of this potential was significantly reduced and this was associated with marked pain relief. At the higher frequencies (50-100 Hz), however, there was no reduction in the FPs and no pain suppression. We have found an interesting and consistent correlation between thalamic electrical activity and chronic pain. This low frequency potential may provide an objective index for quantifying chronic pain, and may hold further clues to the mechanism of action of PVG stimulation. It may be possible to use the presence of these slow FPs and the effect of trial PVG DBS on both the clinical status and the FPs to predict the probable success of future pain control in individual patients.

Adult↗

PubMed2002

Rate of interictal events and spontaneous seizures in epileptic rats after electrical stimulation of hippocampus and its afferents.

PURPOSE: Deep brain stimulation has been used by several investigators to prevent the occurrence of spontaneous seizures in patients with intractable epilepsy. With the kainic acid rat model of spontaneous recurrent seizures, we examined the consequences of subthreshold electrical stimulation of commissural pathways and perforant path on the synaptic plasticity, rate of interictal epileptiform events (IIEs), and spontaneous seizures in kainic acid (KA)-treated rats epileptic rats. METHODS: Recording microelectrodes were implanted bilaterally in the dentate gyrus and entorhinal cortex. Stimulating electrodes were implanted into the rostral part of the right hippocampus and right perforant path. Stimulation was performed daily with 200 Hz/0.5-s duration trains, 10-min duration 1-Hz train, or 2-h, 1-Hz train and 2-h duration, 50-Hz trains. Integrated amplitude of evoked potentials, rate of IIE, and spontaneous seizures was analyzed before and after stimulation. RESULTS: High-frequency tetani evoked long-term potentiation in 50% of epileptic rats compared with 100% of control rats. No long-term depression was observed after 1-Hz train. Decrease rate of IIE was found during 1-Hz and 50-Hz stimulation and returned to the basal level within 30-60 min. No significant change of the spontaneous seizure rate was found. CONCLUSIONS: Epileptic brain is less prone to plastic changes compared with the normal brain. Daily 2-h electrical stimulation with either low or high frequency does not have a long-term effect on the rate of interictal events and spontaneous seizures.

Afferent Pathways↗

PubMed2004

Transcranial magnetic stimulation of the human motor cortex influences the neuronal activity of subthalamic nucleus.

The critical role of the subthalamic nucleus (STN) in the control of movement and parkinsonian symptoms is well established. Research in animals suggests that the cerebral cortex plays an important role in regulating the activity of the STN but this control is not known in humans. The most extensive cortical innervation of the STN originates from motor areas. Here, we used transcranial magnetic stimulation (TMS) during intraoperative single-unit recordings from STN, in six patients with Parkinson's disease (PD) undergoing implantation of deep brain stimulators, to determine whether TMS of the motor cortex (MC) modulates the activity of STN and to investigate in vivo the functional organization of the corticosubthalamic circuit in the human brain. Single-pulse TMS of the MC induced an excitation in 74.9% of neurons investigated. This activation was followed by a long-lasting inhibition of the STN neuronal activity that did not correlate with PD severity. Responsive neurons to TMS of the hand area of motor cortex were located mainly in the lateral and dorsal region of the subthalamus while unresponsive cells had a prevalently medial distribution. This is the first report of TMS-induced modulation of STN neuronal activity in humans. These findings open up new avenues for in vivo studies of corticosubthalamic interactions in human brain and PD.

Action Potentials↗