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Subthalamic Nucleus (subthalamic + nucleus)
Selected AbstractsMultiple-Cell Spike Density and Neural Noise Level Analysis by Semimicroelectrode Recording for Identification of the Subthalamic Nucleus During Surgery for Parkinson's DiseaseNEUROMODULATION, Issue 1 2008Toshikazu Kano MD ABSTRACT Objective.,, For targeting the subthalamic nucleus (STN), we attempted to quantify the changes in multiple cell activities by computing the neural noise level and multiple-cell spike density (MSD). Methods.,, We analyzed the neural noise level and MSD by stepwise recording at every 0.25-mm increment during the final tracking in 90 sides of 45 patients with Parkinson's disease. The MSD was analyzed with cut-off levels ranging from 1.2- to 2.0-fold the neural noise level in the internal capsule or zona incerta in each trajectory. Results.,, The dorsal boundary of the STN was identified from an increase in the neural noise ratio in all sides. The ventral boundary was identifiable, however, from a decrease in the neural noise ratio in only 70 sides (78%). In contrast, both the dorsal and ventral boundaries were clearly identified from an increase and a decrease in the MSD, respectively, in all of the 90 sides. Conclusion.,, MSD analysis by semimicroelectrode recording represents a useful, practical, and apparently reliable means for identifying the boundaries of the STN. [source] Relevance Of Multi-channel Microelectrode Recording in Deep Brain Stimulation of the Subthalamic Nucleus (STN) in Parkinson's DiseaseNEUROMODULATION, Issue 3 2003Servello A [source] MRI verified STN stimulation site , gait improvement and clinical outcomeEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2010E. L. Johnsen Background:, Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in alleviating Parkinson's disease (PD) symptoms (tremor, rigidity and bradykinesia) and may improve gait and postural impairment associated with the disease. However, improvement of gait is not always as predictable as the clinical outcome. This may relate to the type of gait impairment or localization of the active DBS contact. Methods:, The active contact was visualized on peri-operative magnetic resonance imaging in 22 patients with idiopathic PD, consecutively treated with bilateral STN DBS. Stimulation site was grouped as either in the dorsal/ventral STN or medial/lateral hereof and anterior/posterior STN or medial/lateral hereof. The localization was compared with relative improvement of clinical outcome (UPDRS-III). In 10 patients, quantitative gait analyses were performed, and the improvement in gait performance was compared with stimulation site in the STN. Results:, Of 44 active contacts, 77% were inside the nucleus, 23% were medial hereof. Stimulation of the dorsal half improved UPDRS-III significantly more than ventral STN DBS (P = 0.02). However, there were no differences between anterior and posterior stimulation in the dorsal STN. Step velocity and length improved significantly more with dorsal stimulation compared with ventral stimulation (P = 0.03 and P = 0.02). Balance during gait was also more improved with dorsal stimulation compared with ventral stimulation. Conclusions:, Deep brain stimulation of the dorsal STN is superior to stimulation of the ventral STN. Possible different effects of stimulation inside the nucleus underline the need for exact knowledge of the active stimulation site position to target the most effective area. [source] Deep brain stimulation mechanisms: beyond the concept of local functional inhibitionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2010Jean-Michel Deniau Abstract Deep brain electrical stimulation has become a recognized therapy in the treatment of a variety of motor disorders and has potentially promising applications in a wide range of neurological diseases including neuropsychiatry. Behavioural observation that electrical high-frequency stimulation of a given brain area induces an effect similar to a lesion suggested a mechanism of functional inhibition. In vitro and in vivo experiments as well as per operative recordings in patients have revealed a variety of effects involving local changes of neuronal excitability as well as widespread effects throughout the connected network resulting from activation of axons, including antidromic activation. Here we review current data regarding the local and network activity changes induced by high-frequency stimulation of the subthalamic nucleus and discuss this in the context of motor restoration in Parkinson's disease. Stressing the important functional consequences of axonal activation in deep brain stimulation mechanisms, we highlight the importance of developing anatomical knowledge concerning the fibre connections of the putative therapeutic targets. [source] Neuronal activity in the subthalamic nucleus modulates the release of dopamine in the monkey striatumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2009Yasushi Shimo Abstract The primate subthalamic nucleus (STN) is commonly seen as a relay nucleus between the external and internal pallidal segments, and as an input station for cortical and thalamic information into the basal ganglia. In rodents, STN activity is also known to influence neuronal activity in the dopaminergic substantia nigra pars compacta (SNc) through inhibitory and excitatory mono- and polysynaptic pathways. Although the anatomical connections between STN and SNc are not entirely the same in primates as in rodents, the electrophysiologic and microdialysis experiments presented here show directly that this functional interaction can also be demonstrated in primates. In three Rhesus monkeys, extracellular recordings from SNc during microinjections into the STN revealed that transient pharmacologic activation of the STN by the acetylcholine receptor agonist carbachol substantially increased burst firing of single nigral neurons. Transient inactivation of the STN with microinjections of the GABA-A receptor agonist muscimol had the opposite effect. While the firing rates of individual SNc neurons changed in response to the activation or inactivation of the STN, these changes were not consistent across the entire population of SNc cells. Permanent lesions of the STN, produced in two animals with the fiber-sparing neurotoxin ibotenic acid, reduced burst firing and firing rates of SNc neurons, and substantially decreased dopamine levels in the primary recipient area of SNc projections, the striatum, as measured with microdialysis. These results suggest that activity in the primate SNc is prominently influenced by neuronal discharge in the STN, which may thus alter dopamine release in the striatum. [source] Prior pallidotomy reduces and modifies neuronal activity in the subthalamic nucleus of Parkinson's disease patientsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2008A. Zaidel Abstract Parkinson's disease (PD) patients with prior radio-frequency lesions in the internal segment of the globus pallidus (GPi, pallidotomy), whose symptoms have deteriorated, may be candidates for further invasive treatment such as subthalamic deep brain stimulation (STN DBS). Six patients with prior pallidotomy (five unilaterally; one bilaterally) underwent bilateral STN DBS. The microelectrode recordings (MERs, used intraoperatively for STN verification), ipsilateral and contralateral to pallidotomy, and MERs from 11 matched PD patients who underwent bilateral STN DBS without prior pallidotomy were compared. For each trajectory, average, variance and mean successive difference (MSD, a measure of irregularity) of the root mean square (RMS) of the STN MER were calculated. The RMS in trajectories ipsilateral to pallidotomy showed significant reduction of the mean average and MSD of STN activity when compared with trajectories from patients without prior pallidotomy. The RMS parameters contralateral to pallidotomy tend to lie between those ipsilateral to pallidotomy and those without prior pallidotomy. The average STN power spectral density of oscillatory activity was notably lower ipsilateral to pallidotomy than contralateral, or without prior pallidotomy. The finding that pallidotomy reduces STN activity and changes firing characteristics, in conjunction with the effectiveness of STN DBS despite prior pallidotomy, calls for reappraisal and modification of the current model of the basal ganglia (BG) cortical network. It highlights the critical role of direct projections from the BG to brain-stem structures and suggests a possible GPi,STN reciprocal positive-feedback mechanism. [source] Biochemical and electrophysiological changes of substantia nigra pars reticulata driven by subthalamic stimulation in patients with Parkinson's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2006Salvatore Galati Abstract To understand the events underlying the clinical efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN), electrophysiological recordings and microdialysis evaluations were carried out in the substantia nigra pars reticulata (SNr), one of the two basal ganglia (BG) nuclei targeted by STN output, in patients with Parkinson's disease (PD). Clinically effective STN-DBS caused a significant increase of the SNr firing rate. The poststimulus histogram (PSTH) showed an excitation peak at 1.92,3.85 ms after the STN stimulus. The spontaneous discharge of SNr neurons was driven at the frequency of the stimulation (130 Hz), as shown in the autocorrelograms (AutoCrl). The fast Fourier transform (FFT) analysis showed a peak at 130 Hz, and a less pronounced second one at 260 Hz. Accordingly, in the distribution of the interspike intervals (ISIs), the mode was earlier, and skewness more asymmetric. Biochemically, the increased excitatory driving from the STN was reflected by a clear-cut increase in cyclic guanosine 3',5'-monophosphate (cGMP) levels in the SNr. These results indicate that the beneficial effect of DBS in PD patients is paralleled with a stimulus-synchronized activation of the STN target, SNr. Our findings suggest that, during STN-DBS, a critical change towards a high-frequency oscillatory discharge occurs. [source] Lesions to the subthalamic nucleus decrease impulsive choice but impair autoshaping in rats: the importance of the basal ganglia in Pavlovian conditioning and impulse controlEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2005Catharine A. Winstanley Abstract Although the subthalamic nucleus (STN) is involved in regulating motor function, and inactivation of this structure relieves the motor symptoms in Parkinsonian patients, recent data indicate that corticosubthalamic connections are involved in both the regulation of attention and the ability to withhold from responding. Considerable evidence suggests that the neural circuitry underlying such behavioural disinhibition or impulsive action can be at least partially dissociated from that implicated in impulsive decision-making and it has been suggested that the tendency to choose impulsively is related to the ability to form and use Pavlovian associations. To explore these hypotheses further, STN-lesioned rats were tested on the delay-discounting model of impulsive choice, where impulsivity is defined as the selection of a small immediate over a larger delayed reward, as well as in a rodent autoshaping paradigm. In contrast to previous reports of increased impulsive action, STN lesions decreased impulsive choice but dramatically impaired the acquisition of the autoshaping response. When the STN was lesioned after the establishment of autoshaping behaviour, lesioned subjects were more sensitive to the omission of reward, indicative of a reduction in the use of Pavlovian associations to control autoshaping performance. These results emphasize the importance of the STN in permitting conditioned stimulus,unconditioned stimulus associations to regulate goal-seeking, a function which may relate to the alterations in impulsive choice observed in the delay-discounting task. These data bear a striking similarity to those observed after lesions of the orbitofrontal cortex and are suggestive of an important role for corticosubthalamic connections in complex cognitive behaviour. [source] Synaptic release of dopamine in the subthalamic nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2004Stephanie J. Cragg Abstract The direct modulation of subthalamic nucleus (STN) neurons by dopamine (DA) neurons of the substantia nigra (SN) is controversial owing to the thick caliber and low density of DA axons in the STN. The abnormal activity of the STN in Parkinson's disease (PD), which is central to the appearance of symptoms, is therefore thought to result from the loss of DA in the striatum. We carried out three experiments in rats to explore the function of DA in the STN: (i) light and electron microscopic analysis of tyrosine hydroxylase (TH)-, dopamine ,-hydroxylase (D,H)- and DA-immunoreactive structures to determine whether DA axons form synapses; (ii) fast-scan cyclic voltammetry (FCV) to determine whether DA axons release DA; and (iii) patch clamp recording to determine whether DA, at a concentration similar to that detected by FCV, can modulate activity and synaptic transmission/integration. TH- and DA-immunoreactive axons mostly formed symmetric synapses. Because D,H-immunoreactive axons were rare and formed asymmetric synapses, they comprised the minority of TH-immunoreactive synapses. Voltammetry demonstrated that DA release was sufficient for the activation of receptors and abolished by blockade of voltage-dependent Na+ channels or removal of extracellular Ca2+. The lifetime and concentration of extracellular DA was increased by blockade of the DA transporter. Dopamine application depolarized STN neurons, increased their frequency of activity and reduced the impact of ,-aminobutyric acid (GABA)-ergic inputs. These findings suggest that SN DA neurons directly modulate the activity of STN neurons and their loss may contribute to the abnormal activity of STN neurons in PD. [source] Dopaminergic and non-dopaminergic pharmacological hypotheses for gait disorders in Parkinson's diseaseFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2010David Devos Abstract Gait disorders form one component of the axial disorders observed in Parkinson's disease (PD). Indeed, short steps with a forward-leaning stance are diagnostic criteria for PD in the early stages of the condition. Gait disorders also represent a major source of therapeutic failure in the advanced stages of PD (with the appearance of freezing of gait and falls) because they do not respond optimally to the two hand late-stage therapeutics , levodopa and electrical subthalamic nucleus (STN) stimulation. The late onset of doparesistance in these disorders may be linked to propagation of neurodegeneration to structures directly involved in gait control and to non-dopaminergic neurotransmitter systems. The coeruleus locus (a source of noradrenaline) is rapidly and severely affected, leading to a major motor impact. The pedunculopontine nucleus (PPN) and lateral pontine tegmentum (rich in acetylcholine) are both involved in gait. Degenerative damage to the serotoninergic raphe nuclei appears to be less severe, although serotonin-dopamine interactions are numerous and complex. Lastly, dopaminergic depletion leads to glutamatergic hyperactivity of the efferent pathways from the the STN to the PPN. However, the relationships between the various parkinsonian symptoms (and particularly gait disorders) and these pharmacological targets have yet to be fully elucidated. The goal of this review is to develop the various pathophysiological hypotheses published to date, in order to underpin and justify ongoing fundamental research and clinical trials in this disease area. [source] Neuroimaging predictors for depressive symptoms in cerebral small vessel diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 10 2010Jian Hui Fu Abstract Objective Although cerebral small vessel disease (SVD) is closely associated with late life depression, patients with even severe SVD may have no depressive symptoms. We postulate that concurrent brain atrophy may also involve in the pathogenesis of depressive symptoms in SVD. We aimed to investigate the relevance of brain atrophy in predicting depressive symptoms among patients with severe SVD. Methods We recruited 45 lacunar stroke patients who had diffuse white matter lesion (WML) and varying severity levels of depressive symptoms. We used a quantitative hybrid warping method to determine the volume of 99 brain regions for each patient. We assessed severity of depressive symptoms using the depression score of the hospital anxiety and depression scale (HADS-D). We first performed correlation analysis of each brain variable with the depression score. Significant variables were then entered separately into linear regression analysis to explore predictors of HADS-D, with adjustment of relevant clinical variables. Results The mean age (SD) of the 45 participants was 74.6 (8.3) years. The mean HADS-D score was 3.5, with score ranging from 0 to15. Variables that had a significant correlation coefficient with HADS-D were gender, hypertension, Oxford handicap scale, left inferior frontal gyrus, right subthalamic nucleus, left posterior limb of internal capsule, and right cerebellum. Regression analyses showed that only left inferior frontal gyrus atrophy (,,=,,0.354, p,=,0.017) predicted HADS-D score after adjusted for other relevant clinical variables. Conclusion Concurrent atrophy of left inferior frontal gyrus is associated with depressive symptoms in elderly patients with severe SVD. Copyright © 2009 John Wiley & Sons, Ltd. [source] Cognition following bilateral deep brain stimulation surgery of the subthalamic nucleus for Parkinson's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2009Casey H. Halpern Abstract Objective Parkinson's disease (PD) is a neurodegenerative disorder characterized by significant motor dysfunction and various non-motor disturbances, including cognitive alterations. Deep brain stimulation (DBS) is an increasingly utilized therapeutic option for patients with PD that yields remarkable success in alleviating disabling motor symptoms. DBS has additionally been associated with changes in cognition, yet the evidence is not consistent across studies. The following review sought to provide a clearer understanding of the various cognitive sequelae of bilateral subthalamic nucleus (STN) DBS while taking into account corresponding neuroanatomy and potential confounding variables. Design A literature search was performed using the following inclusion criteria: (1) at least five subjects followed for a mean of at least 3 months after surgery; (2) pre- and postoperative cognitive data using at least one standardized measure; (3) adequate report of study results using means and standard deviations. Results Two recent meta-analyses found mild post-operative impairments in verbal learning and executive function in patients who underwent DBS surgery. However, studies have revealed improved working memory and psychomotor speed in the ,on' vs ,off' stimulation state. A deficit in language may be a consequence of the surgical procedure. Conclusions While cognitive decline has been observed in some domains, our review of the data suggests that STN DBS is a worthwhile and safe method to treat PD. Copyright © 2008 John Wiley & Sons, Ltd. [source] Influence of the frequency parameter on extracellular glutamate and ,-aminobutyric acid in substantia nigra and globus pallidus during electrical stimulation of subthalamic nucleus in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003François Windels Abstract High-frequency stimulation (HFS) of the subthalamic nucleus (STN) proves to be an efficient treatment for alleviating motor symptoms in Parkinson's disease (PD). However, the mechanisms of HFS underlying these clinical effects remain unknown. Using intracerebral microdialysis, we previously reported that HFS induces, in normal rats, a significant increase of extracellular glutamate (Glu) in the globus pallidus (GP in rats or GPe in primates) and the substantia nigra pars reticulata (SNr), whereas ,-aminobutyric acid (GABA) was increased only in the SNr. Bradykinesia can be improved by STN stimulation in a frequency-dependent manner, a plateau being reached around 130 Hz. The aim of the present study was to determine whether neurochemical changes are also frequency dependent. Electrical STN stimulation was applied at various frequencies (10, 60, 130, and 350 Hz) in normal rats. The results show that, for Glu, the amplitude of increase detected in GP and SNr is maximal at 130 Hz and is maintained at 350 Hz. No modifications of GABA were observed in GP whatever the frequency applied, whereas, in SNr, GABA increased from 60 to 350 Hz. Our results provide new neurochemical data implicating STN target structures in deep-brain-stimulation mechanisms. © 2003 Wiley-Liss, Inc. [source] Influence of deep brain stimulation and levodopa on sensory signs in Parkinson's disease,MOVEMENT DISORDERS, Issue 9 2010Janne Gierthmühlen MD Abstract To examine the effects of levodopa (L -dopa) and deep brain stimulation of the subthalamic nucleus (STN-DBS) on sensory symptoms and signs in Parkinson's disease (PD). Seventeen patients with PD were included. (1) Presence of sensory symptoms and (2) effects of L -dopa and STN-DBS on sensory symptoms and signs [assessed by quantitative sensory testing (QST)] were examined 6 months after starting STN-DBS. In addition, in 12 of these patients, presence of sensory symptoms prior and post STN-DBS was compared. Pain was most frequently nociceptive. In about 30,40%, pain and sensory symptoms were associated with PD motor symptoms. In most of these cases, pain responded to L -dopa. Intensity of pain was reduced post STN-DBS compared to pre STN-DBS. L -Dopa had no influence on detection thresholds, whereas STN-DBS improved thermal detection thresholds. However, thermal and mechanical pain thresholds were uninfluenced by L -dopa or STN-DBS. Although some patients reported an improvement of pain with STN-DBS or L -dopa, objectively pain sensitivity as assessed by QST was not altered by STN-DBS or L -dopa suggesting that there is no evidence for a direct modulation of central pain processing by L -dopa or STN-DBS. © 2010 Movement Disorder Society [source] Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease,MOVEMENT DISORDERS, Issue 5 2010Elena Moro MD Abstract We report the 5 to 6 year follow-up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinson's disease (PD) patients. Thirty-five STN patients and 16 GPi patients were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinson's Disease Rating Scale (UPDRS) assessed with a prospective cross-over double-blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off- and on-medication states with and without stimulation, activities of daily living (ADL), anti-PD medications, and dyskinesias. In double-blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN, P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with off-stimulation, regardless of the sequence of stimulation. In open assessment, both STN- and GPi-DBS significantly improved the off-medication motor UPDRS when compared with before surgery (STN, P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti-PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long-term efficacy of STN and GPi DBS in advanced PD. Although the surgical targets were not randomized, there was a trend to a better outcome of motor signs in the STN-DBS patients and fewer adverse events in the GPi-DBS group. © 2010 Movement Disorder Society [source] Dysfunction of the subthalamic nucleus induces behavioral and movement disorders in monkeys,MOVEMENT DISORDERS, Issue 8 2009Carine Karachi MD Abstract High-frequency stimulation of the subthalamic nucleus (STN) in parkinsonian patients is reported to induce psychiatric effects. The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative, and limbic anatomo-functional territories. Thus, a specific neuronal dysfunction of the STN sensorimotor territory could lead to abnormal movements, whereas a dysfunction of the associative or limbic territory could lead to behavioral disturbances. To test this hypothesis, neuronal dysfunction of the STN was induced by microinjections of the GABA agonist muscimol, or antagonist bicucculline, in various parts of the nucleus in three monkeys. Stereotyped behaviors (licking and biting fingers) and/or violent hyperactivity were obtained with bicuculline injected into the anteromedial, associative, and limbic territories, whereas injections of muscimol induced no major effects. Abnormal limb movements (contralateral ballism) were obtained after muscimol or bicuculline injections into the posterolateral, sensorimotor territory. Control injections localized around the STN induced other effects (mainly torticollis), which underlines the specificity of STN injection effects. Our study supports the hypothesis that the anteromedial part of the STN is involved in behavioral control. © 2009 Movement Disorder Society [source] Replacement of dopaminergic medication with subthalamic nucleus stimulation in Parkinson's disease: Long-term observation,MOVEMENT DISORDERS, Issue 4 2009Luigi M. Romito MD Abstract Stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease (PD), but the medication requirements after implant are poorly known. We performed a long-term prospective evaluation of 20 patients maintained at stable dopaminergic therapy for 5 years after bilateral STN implants, who were evaluated 6 months, 1 year, 3 years, and 5 years after surgery. We measured, during the entire observation period, the effect of deep brain stimulation on motor and functional outcome measures, the levodopa equivalent daily dose and the total electrical energy delivered. At 5 years, the UPDRS motor score had improved by 54.2% and levodopa equivalent dose was reduced by 61.9%, compared with preimplant. Dopaminergic medication remained stable during the observation period, but energy was progressively increased over time. Rest tremor, rigidity, gait, lower and upper limb akinesia, and total axial score were improved in decreasing order. Postural stability and speech improved transiently, whereas on-period freezing of gait, motor fluctuations and dyskinesias recovered durably. Functional measures did not show improvement in autonomy and daily living activities after STN implant. Chronic STN stimulation allows to replace for dopaminergic medications in the long-term at the expense of an increase of the total energy delivered. This is associated with marked improvement of motor features without a matching benefit in functional measures. © 2008 Movement Disorder Society [source] Recurrent hemichorea following a single infarction in the contralateral subthalamic nucleusMOVEMENT DISORDERS, Issue 4 2009So-Young Park MD [source] Beta activity in the subthalamic nucleus during sleep in patients with Parkinson's disease,MOVEMENT DISORDERS, Issue 2 2009Elena Urrestarazu MD Abstract The recordings of local field potentials in the subthalamic nucleus in patients with Parkinson's disease (PD), carried out through the stimulators implanted to treat the motor symptoms of the disease, show a prominent basal ("off") activity in the beta range, which is attenuated after dopaminergic therapy. A recent study described improvement of parkinsonian features during rapid eyes movements (REM) sleep. We describe, for the first time, the changes in activity of the subthlamic nucleus (STN) during different sleep stages in Parkinson's disease with special interest in the beta band. Ten patients with PD treated with deep brain stimulation of the STN were studied. Subthalamic local field potentials (LFPs) were recorded through the stimulation electrodes during wakefulness ("off" medication) and different sleep stages. In Stage 2 and slow-wave sleep, a significant decrease of beta activity was recorded. During REM sleep, beta power values were similar to wakefulness values or even higher. These findings indicate that STN activity is modulated and modified during different sleep stages. The increased beta activity during REM sleep is a new but unexpected finding, which requires further analysis. © 2008 Movement Disorder Society [source] Dexmedetomidine and arousal affect subthalamic neurons,MOVEMENT DISORDERS, Issue 9 2008William Jeffrey Elias MD Abstract Stereotactic neurosurgeons hesitate to employ sedation in cases requiring microelectrode recording (MER). We report our experience with dexmedetomidine during MER of subthalamic nucleus (STN). Eleven Parkinsonian patients received dexmedetomidine during deep brain stimulation surgery. Seven received continuous IV infusions during MER in the STN. The bispectral index (BIS) was used to estimate the level of consciousness. The quality of MER was evaluated as a function of BIS, clinical arousal, and dexmedetomidine dose. MER during wakefulness (BIS > 80; 0.1 to 0.4 mcg/kg/hr dexmedetomidine) was similar to the unmedicated state. Subthalamic MER was reduced when the patient was asleep or unarousable (BIS < 80). Anxiolysis persisted for hours. Arousal affects STN neurons. Dexmedetomidine "cooperative sedation," from which the patient is easily aroused, provides interpretable STN MER and prolonged anxiolysis. We suggest dexmedetomidine infusions without a loading dose, a relatively low infusion rate, and discontinuation after completion of the bur holes. © 2008 Movement Disorder Society [source] Participation of the subthalamic nucleus in executive functions: An intracerebral recording studyMOVEMENT DISORDERS, Issue 4 2008Marek Balá Abstract The objective of our work was to find whether the subthalamic nucleus (STN) is directly involved in cognitive activities, specifically in executive functions. Ten patients with idiopathic Parkinson's disease had P3 potentials recorded by externalized deep brain electrodes that were implanted in the STN or in its immediate vicinity. Two contacts of each electrode were positioned inside the STN according to clinical effect, perioperative microrecording, and stimulation. The P3 waves were recorded following the auditory stimulus in a standard oddball paradigm. They were compared with the P3 waves elicited from a protocol modified by a dual task with an increased demand on executive functions. The P3 potentials with a steep amplitude gradient evoked by the modified protocol were detected by the contacts in 8 of the 14 available electrodes, located either inside the STN or in its immediate vicinity. The modified protocol led to an increased latency of the P3 potential in 8 of 14 electrodes. No local field potentials of the standard P3 potentials were recorded. The P3 potentials related to the increased demand on executive functions were detected by the STN contacts known to have the best effect on Parkinsonian motor signs. This could suggest that the STN takes part in the executive function processing. © 2007 Movement Disorder Society [source] Paradoxical aspects of parkinsonian tremorMOVEMENT DISORDERS, Issue 2 2008Paul S. Fishman MD Abstract Although resting tremor is the most identifiable sign of Parkinson's disease, its underlying basis appears to be the most complex of the cardinal signs. The variable relationship of resting tremor to other symptoms of PD has implications for diagnosis, prognosis, medical and surgical treatment. Structural lesions very rarely cause classic resting tremor, with likely contributions to tremor by a network of neurons both within and outside the basal ganglia. Patients with only resting tremor show dopaminergic deficits with radioligand imaging, but severity of tremor correlates poorly in such dopamine imaging studies. Correlation of tremor severity to changes in radioligand studies is also limited by the use of mostly qualitative measures of tremor severity. A complex pharmacologic basis of parkinsonian resting tremor is supported by treatment studies. Although levodopa is clearly effective for resting tremor, several agents have shown efficacy that appears to be superior or additive to that of levodopa including anticholinergics, clozapine, pramipexole, and budipine. Although the thalamus has the greatest body of evidence supporting its role as an effective target for surgical treatment of tremor, recent studies suggest that the subthalamic nucleus may be a reasonable alternative target for patients with Parkinson's disease and severe tremor as the predominant symptom. © 2007 Movement Disorder Society [source] Gender differences in patients with Parkinson's disease treated with subthalamic deep brain stimulationMOVEMENT DISORDERS, Issue 8 2007Ettore Accolla MD Abstract We investigated gender-differences in clinical phenomenology and response to deep brain stimulation (DBS) of the subthalamic nucleus (STN) in a group of patients with advanced Parkinson's disease (PD). Thirty-eight consecutive patients with PD (22 men and 16 women), bilaterally implanted for DBS of the STN, were evaluated 1 month before and 11 to 14 months after surgery. Gender differences in severity of the disease (HY and UPDRS), ability in the activities of daily living (ADL, UPDRS II), tremor and rigidity (UPDRS III), bradykinesia (UPDRS III and hand tapping test), levodopa-induced dyskinesias (LIDs, UPDRS IV), and levodopa equivalent daily dosage (LEDD) were analyzed before and after intervention. We found a predominantly male population, with no gender-related differences in age at onset, disease progression rate, or severity of disease. Nevertheless, women had more severe LIDs than men, only before the intervention. Bradykinesia was significantly less responsive to any kind of treatment (pharmacologic and neurosurgical) in women than in men. Finally, although STN-DBS induced similar total benefits in both genders, postoperative assessment suggested that the ADL improved more in women than in men. Women and men with advanced PD appear to differ in some clinical features and in response to dopaminergic and STN-DBS treatment. © 2007 Movement Disorder Society [source] Deep brain stimulation and medication for parkinsonian tremor during secondary tasksMOVEMENT DISORDERS, Issue 8 2007Molly M. Sturman PhD Abstract This study examined the efficacy of subthalamic nucleus (STN), deep brain stimulation (DBS), and medication for resting tremor during performance of secondary tasks. Hand tremor was recorded using accelerometry and electromyography (EMG) from 10 patients with Parkinson's disease (PD) and ten matched control subjects. The PD subjects were examined off treatment, on STN DBS, on medication, and on STN DBS plus medication. In the first experiment, tremor was recorded in a quiet condition and during a cognitive task designed to enhance tremor. In the second experiment, tremor was recorded in a quiet condition and during isometric finger flexion (motor task) with the contralateral limb at 5% of the maximal voluntary contraction (MVC) that was designed to suppress tremor. Results showed that: (1) STN DBS and medication reduced tremor during a cognitive task that exacerbated tremor, (2) STN DBS normalized tremor frequency in both the quiet and cognitive task conditions, whereas tremor amplitude was only normalized in the quiet condition, (3) a secondary motor task reduced tremor in a similar manner to STN DBS. These findings demonstrate that STN DBS still suppresses tremor in the presence of a cognitive task. Furthermore, a secondary motor task of the opposite limb suppresses tremor to levels comparable to STN DBS. © 2007 Movement Disorder Society [source] Effect of medical and surgical interventions on health-related quality of life in Parkinson's diseaseMOVEMENT DISORDERS, Issue 6 2007Pablo Martinez-Martin MD Abstract Motor-related parameters are the standard outcome parameters for treatment interventions. Nonetheless, subjective appraisals about the consequences of treatment on health-related quality of life (HRQoL) are meanwhile established and may uncover important aspects of interventions. We have reviewed the literature with a defined search strategy and collected 61 clinical trials, which have used HRQoL as a planned outcome parameter. The articles were rated similarly as for the Task Force report of the Movement Disorder Society on interventions for Parkinson's disease (PD), but the relevant outcome parameter was HRQoL. We found that unilateral pallidotomy, deep brain stimulation of the subthalamic nucleus, and rasagiline are efficacious to improve the HRQoL of PD patients. For many other interventions, the efficacy to improve HRQoL in the PD setting cannot be considered to be proven so far. HRQoL should be part of future trial designs and more research is necessary to understand the determinants of QoL in PD. © 2007 Movement Disorder Society [source] Lower urinary tract symptoms and bladder control in advanced Parkinson's disease: Effects of deep brain stimulation in the subthalamic nucleusMOVEMENT DISORDERS, Issue 2 2007Kristian Winge MD Abstract Deep brain stimulation in the subthalamic nucleus (STN) leads to significant improvement in motor function in patients with advanced Parkinson's disease (PD). In this prospective study including 16 patients with PD, we investigated (1) lower urinary tract symptoms (LUTS) by questionnaires International Prostate Symptom Score (IPSS, symptoms only) and Danish Prostate Symptom Score (DanPSS, symptoms and bother of symptoms) and (2) bladder control (assessed by urodynamics) before and after implantation of electrodes in the STN. PD symptoms (Unified Parkinson's Disease Rating Scale score) improved significantly (P < 0.0001), and symptoms of overactive bladder (IPSS) decreased along with the troublesome symptoms of overactive bladder (DanPSS; P < 0.01 for both). Urodynamic parameters before and after implantation of electrodes in the STN, evaluated with and without the stimulation on, did not change significantly. © 2006 Movement Disorder Society [source] Rapidly progressive sporadic dentatorubral pallidoluysian atrophy with intracytoplasmic inclusions and no CAG repeat expansionMOVEMENT DISORDERS, Issue 12 2006Alberto J. Espay MD Abstract A 48-year-old man developed progressive hemidystonia and postural impairment with falls, followed by choreoathetosis, hyporeflexia, ataxia, supranuclear vertical gaze palsy, and dementia, lasting only 3.5 years from symptom onset to death. Family history and genetic testing were unrevealing. Neuropathology showed findings identical to genetic dentatorubral pallidoluysian atrophy (DRPLA), except for the absence of intranuclear inclusions and the presence of intracytoplasmic inclusions in the pons, striatum, thalamus, and subthalamic nucleus. This case expands the clinical and neuropathological spectrum of DRPLA and supports the hypothesis that aggregates may not be intrinsically pathogenic. © 2006 Movement Disorder Society [source] Effects of levodopa and subthalamic nucleus stimulation on cognitive and affective functioning in Parkinson's diseaseMOVEMENT DISORDERS, Issue 10 2006Aurélie Funkiewiez MA Abstract In Parkinson's disease (PD), levodopa and subthalamic nucleus (STN) stimulation lead to major improvement in motor symptoms. Effects of both treatments on cognition and affective status are less well understood. Motor, cognitive, and affective symptoms may relate to the dysfunctioning of parallel cortico,striatal loops. The aim of this study was to assess cognition, behavior, and mood, with and without both treatments in the same group of PD patients. A group of 22 nondemented PD patients was included in this study. Patients were tested twice before surgery (off and on levodopa) and twice 3 months after surgery (OFF and ON STN stimulation, off levodopa). Cognitive and affective effects of STN stimulation and levodopa had some common, but also different, effects. STN stimulation improved performance on the planning test, associated with the dorsolateral prefrontal cortex. However, the treatments had opposite effects on tests associated with the orbitofrontal cortex; specifically, levodopa impaired while STN stimulation improved performance on the extinction phase of a reversal/extinction task. Acutely, both treatments improved motivation and decreased fatigue and anxiety. On chronic treatment (3 months after surgery), depression improved, whereas apathy worsened 3 months after surgery. To conclude, there were significant but contrasting effects of levodopa and STN stimulation on cognition and affective functions. © 2006 Movement Disorder Society [source] Electrophysiological mapping for the implantation of deep brain stimulators for Parkinson's disease and tremorMOVEMENT DISORDERS, Issue S14 2006Robert E. Gross MD Abstract The vast majority of centers use electrophysiological mapping techniques to finalize target selection during the implantation of deep brain stimulation (DBS) leads for the treatment of Parkinson's disease and tremor. This review discusses the techniques used for physiological mapping and addresses the questions of how various mapping strategies modify target selection and outcome following subthalamic nucleus (STN), globus pallidus internus (GPi), and ventralis intermedius (Vim) deep brain stimulation. Mapping strategies vary greatly across centers, but can be broadly categorized into those that use microelectrode or semimicroelectrode techniques to optimize position prior to implantation and macrostimulation through a macroelectrode or the DBS lead, and those that rely solely on macrostimulation and its threshold for clinical effects (benefits and side effects). Microelectrode criteria for implantation into the STN or GPi include length of the nucleus recorded, presence of movement-responsive neurons, and/or distance from the borders with adjacent structures. However, the threshold for the production of clinical benefits relative to side effects is, in most centers, the final, and sometimes only, determinant of DBS electrode position. Macrostimulation techniques for mapping, the utility of microelectrode mapping is reflected in its modification of electrode position in 17% to 87% of patients undergoing STN DBS, with average target adjustments of 1 to 4 mm. Nevertheless, with the absence of class I data, and in consideration of the large number of variables that impact clinical outcome, it is not possible to conclude that one technique is superior to the other in so far as motor Unified Parkinson's Disease Rating Scale outcome is concerned. Moreover, mapping technique is only one out of many variables that determine the outcome. The increase in surgical risk of intracranial hemorrhage correlated to the number of microelectrode trajectories must be considered against the risk of suboptimal benefits related to omission of this technique. © 2006 Movement Disorder Society [source] Long-term effects of bilateral subthalamic nucleus stimulation on health-related quality of life in advanced Parkinson's diseaseMOVEMENT DISORDERS, Issue 6 2006Andrew Siderowf MD, MSCE Abstract We evaluated the long-term effects of subthalamic nucleus (STN) stimulation on health-related quality of life (HRQL) in patients with advanced Parkinson's disease (PD). STN stimulation improves motor function and decreases medication requirements in patients with advanced PD. The impact of STN stimulation on HRQL is less well established, especially beyond 1 year after surgery. We report HRQL outcomes for 18 patients with advanced PD. Patients were evaluated with the Parkinson's Disease Questionnaire-39 (PDQ-39), the Medical Outcome Study Short Form (SF-36), and the EuroQol visual analogue scale (VAS) before surgery, 6 months postoperatively, and at a long-term follow-up visit (mean, 35.9 months; range, 18,57 months after surgery). Preoperative scores on HRQL measures were compared to results obtained at short- and long-term follow-up evaluations. The VAS and all domains of the PDQ-39 except for cognition, communication, and social support showed marked improvements at 6 months after surgery. At the long-term follow-up, there were sustained improvements in the VAS (63% improvement; P = 0.0009) and in several domains of the PDQ-39 [mobility: 20%, P = 0.01; activities of daily living (ADL): 29%, P = 0.005; emotional well-being: 26%, P = 0.02; stigma: 43%, P = 0.003; and bodily discomfort: 35%, P = 0.007]. At the long-term evaluation, only the vitality domain of the SF-36 was significantly improved from baseline (16%; P = 0.01). In this selected group of patients, many of the short-term gains in HRQL persist beyond 18 months after STN implantation. Benefits in nonmotor aspects of HRQL such as bodily discomfort and stigma appear to be among the most durable. © 2006 Movement Disorder Society [source] | ||||||||||||||||||||||||||||