Effects Of STN-DBS Research Articles

Neuro-psychiatric therapy during chronic subthalamic stimulation in Parkinson's disease

Background Neuro-psychiatric (NP) disturbances are highly prevalent in patients with Parkinson's disease (PD) and contribute to worsen quality of life. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is commonly utilized as surgical treatment for advanced PD with motor complications. The effectiveness of the procedure on motor symptoms is well established whereas the effects of STN-DBS on NP symptoms are less clear. The aim of our study was to analyze the postoperative pharmacological therapy for NP symptoms in a group of STN-DBS treated PD patients. Such therapy provides indirect information about the evolution of underlying NP disturbances during the follow-up in this group of PD patients. Methods NP therapy (benzodiazepines, antidepressants, antipsychotics) was assessed in 48 consecutive PD patients treated by STN-DBS, preoperatively and postoperatively after 4 months, 1 year and 3 years. Motor symptoms were evaluated by the Unified PD Rating Scale (UPDRS) and levodopa equivalence daily dose (LEDD) was calculated. Cognitive, mood and anxiety assessments were performed with appropriate rating scales. Results The number of patients treated with antidepressant drugs gradually increased during the follow-up. The use of antipsychotic drugs was stable until 1 year, with a subsequent increase at 3 years. Benzodiazepines were given to fewer patients immediately after surgery. Conclusions Pharmacological treatment supplies further information about NP symptoms in the follow-up of PD patients undergoing STN stimulation.

Unmasking psychiatric symptoms after STN deep brain stimulation in Parkinson’s disease

Stereotactic implantation of electrodes for deep brain stimulation (DBS) in the subthalamic nucleus (STN) is a well-established treatment for Parkinson's disease. The treatment gives stable effect over years on the motor symptoms of Parkinson's disease. Psychiatric effects of STN-DBS have attracted increasing attention, with a growing number of reports on psychiatric side effects or exacerbations of known psychiatric disease. However, little is known about the possible unmasking of hidden psychiatric symptoms after surgery. The aim of this clinical commentary is to illustrate unmasking of psychiatric disease by STN-DBS through the presentation of a case from our clinic. A patient with Parkinson's disease underwent implantation of STN stimulation electrodes with good results on his motor symptoms. He did not disclose his previous psychiatric history. Soon after the onset of stimulation he developed affective symptoms with manic, aggressive and depressive behaviour, and also an attempted suicide. The stimulation was reduced and his dopaminergic medication increased after the attempted suicide. His previous history of depression and anxiety was now revealed. He received psychiatric attention, and the affective symptoms resolved. The effect of the stimulation on motor symptoms remained stable. The unmasking of previous psychiatric problems after STN stimulation may be an underestimated problem. It is necessary to fully penetrate the psychiatric anamnesis, especially in patients with a strong wish to be operated and a consequent reluctance to reveal previous problems. Patients with a previous history of a psychiatric disorder are not the best candidates for implantation of STN electrodes.

Effect of Subthalamic Nucleus Stimulation on Severe Striatal Hand Deformity in Parkinson’s Disease: A Case Report

Striatal hand is a deformity encountered in Parkinson's disease and other parkinsonisms. It is characterized by extension that occurs at all the interphalangeal joints, flexion at the metacarpophalangeal joints, and ulnar deviation. It can be differentiated from levodopa-induced dystonia and primary dystonia, since the deformity exists continuously even during sleep. We experienced a case of Parkinson's disease with severe striatal hand deformity which was successfully treated by deep brain stimulation of the subthalamic nucleus (STN-DBS). Although the precise mechanism remains unclear, rigidity is assumed to contribute to the limb deformities. Based on our experience, it seems possible therefore that the effect of STN-DBS on the hand deformity was a secondary effect on muscular rigidity. STN-DBS is assumed to represent a useful treatment option for striatal hand deformity.

Pedunculopontine nucleus deep brain stimulation changes spinal cord excitability in Parkinson’s disease patients

Bilateral peduncolopontine nucleus (PPN) and subthalamic nucleus (STN) deep brain stimulation (DBS) was performed in six-advanced Parkinson's disease (PD) patients. We report the effect of both PPN-DBS (25 Hz) and STN-DBS (185 Hz) on patient spinal reflex excitability by utilizing the soleus-Hoffman reflex (HR) threshold. Compared to controls (n = 9), patients showed an increase of HR-threshold, which was scarcely affected by levodopa, but significantly reduced by DBS. In particular, we found that PPN-DBS alone, or plus STN-DBS induced a complete recovery of HR-threshold up to control values. The HR-threshold changes, although do not allow to investigate the contribution of specific intraspinal pathways, suggest that PPN may play a key-role in modulating spinal excitability in PD possibly by improving the basal ganglia-brainstem descending system activity.

Thalamocortical Relay Fidelity Varies Across Subthalamic Nucleus Deep Brain Stimulation Protocols in a Data-Driven Computational Model

The therapeutic effectiveness of deep brain stimulation (DBS) of the subthalamic nucleus (STN) may arise through its effects on inhibitory basal ganglia outputs, including those from the internal segment of the globus pallidus (GPi). Changes in GPi activity will impact its thalamic targets, representing a possible pathway for STN-DBS to modulate basal ganglia-thalamocortical processing. To study the effect of STN-DBS on thalamic activity, we examined thalamocortical (TC) relay cell responses to an excitatory input train under a variety of inhibitory signals, using a computational model. The inhibitory signals were obtained from single-unit GPi recordings from normal monkeys and from monkeys rendered parkinsonian through arterial 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection. The parkinsonian GPi data were collected in the absence of STN-DBS, under sub-therapeutic STN-DBS, and under therapeutic STN-DBS. Our simulations show that inhibition from parkinsonian GPi activity recorded without DBS-compromised TC relay of excitatory inputs compared with the normal case, whereas TC relay fidelity improved significantly under inhibition from therapeutic, but not sub-therapeutic, STN-DBS GPi activity. In a heterogeneous model TC cell population, response failures to the same input occurred across multiple TC cells significantly more often without DBS than in the therapeutic DBS case and in the normal case. Inhibitory signals preceding successful TC relay were relatively constant, whereas those before failures changed more rapidly. Computationally generated inhibitory inputs yielded similar effects on TC relay. These results support the hypothesis that STN-DBS alters parkinsonian GPi activity in a way that may improve TC relay fidelity.

Prior pallidotomy reduces and modifies neuronal activity in the subthalamic nucleus of Parkinson's disease patients

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.

Improved sensory gating of urinary bladder afferents in Parkinson's disease following subthalamic stimulation

In addition to motor symptoms, patients with Parkinson's disease (PD) show deficits in sensory processing. These deficits are thought to result from deficient gating of sensory information due to basal ganglia dysfunction in PD. Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been shown to improve sensory deficits in PD, e.g. STN-DBS normalizes the perception of urinary bladder filling in patients with PD. This study aimed at investigating how STN-DBS modulates the processing of urinary bladder information to elucidate the (patho-)physiology of sensory gating mechanisms in PD. Nine PD patients with bilateral STN-DBS switched on (STN-DBS ON) or off (STN-DBS OFF) were studied during dynamic bladder filling and an empty bladder condition (for control), while changes in regional cerebral blood flow (rCBF) were measured by PET. Urinary bladder filling led to an increased rCBF in the periaqueductal grey (PAG), the posterior thalamus, the insular cortex as well as in the right frontal cortex and the cerebellum bilaterally. A significant interaction between bladder condition and STN-DBS was observed in the posterior thalamus and the insular cortex, with enhanced modulation of these areas during STN-DBS ON compared to STN-DBS OFF. Furthermore, regression analyses revealed a modulation of the neural activity in the thalamus and the insular cortex by the PAG activity during STN-DBS ON only. Thus, STN-DBS led to a significant enhancement of afferent urinary bladder information processing. The data suggest that STN-DBS facilitates the discrimination of different bodily states by supporting sensory perception and the underlying neural mechanisms. Furthermore, this is the first imaging study, which shows an effect of STN-DBS on sensory gating in PD patients and its neural basis.

Unilateral vs. bilateral STN DBS effects on working memory and motor function in Parkinson disease

Bilateral subthalamic nucleus deep brain stimulation (STN DBS) can reduce working memory while improving motor function in Parkinson disease (PD), but findings are variable. One possible explanation for this variability is that the effects of bilateral STN DBS on working memory function depend in part on functional or disease asymmetry. The goal of this study was to determine the relative contributions of unilateral DBS to the effects seen with bilateral DBS. Motor (Unified Parkinson Disease Rating Scale Part III, UPDRS) and working memory function (Spatial Delayed Response, SDR) were measured in 49 PD patients with bilateral STN DBS while stimulators were Both-off, Left-on, Right-on and Both-on in a randomized, double-blind manner. Patients were off PD medications overnight. Effects of unilateral DBS were compared to effects of bilateral STN DBS. Mean UPDRS and SDR responses to Left-on vs. Right-on conditions did not differ ( p > .20). However, improvement in contralateral UPDRS was greater and SDR performance was more impaired by unilateral DBS in the more affected side of the brain than in the less affected side of the brain ( p = .008). The effect of unilateral DBS on the more affected side on contralateral UPDRS and SDR responses was equivalent to that of bilateral DBS. These results suggest that motor and working memory function respond to unilateral STN DBS differentially depending on the asymmetry of motor symptoms.

NEUROPSYCHOLOGICAL EFFECTS AFTER CHRONIC SUBTHALAMIC STIMULATION AND THE TOPOGRAPHY OF THE NUCLEUS IN PARKINSON'S DISEASE

The neuropsychological effects of chronic subthalamic nucleus (STN)-deep brain stimulation (DBS) as a treatment for Parkinson's disease are variable. Whether these side effects result from the target per se or current diffusion into neighboring structures is uncertain. In this study, the relationship between clinical outcomes and coordinates of active contact are analyzed and compared between patients with and without neuropsychological sequelae. Thirty-eight Parkinsonian patients who underwent bilateral STN-DBS were enrolled in this retrospective cohort study. They were followed for at least 12 months. During the follow-up period, they were divided into two groups for comparison; Group A included patients with neuropsychological side effects and Group B was composed of patients without neuropsychological side effects. The position of the active contact of the electrode was defined with postoperative magnetic resonance imaging scans according to the midcommissural line. Active contact coordinates and clinical outcomes were compared for the two groups. Among the 38 Parkinsonian patients who underwent STN-DBS, eight patients who had neuropsychological side effects were assigned to Group A; the other 30 patients were assigned to Group B. In Groups A and B, the mean follow-up periods were 13.9 and 12.1 months, respectively, the Unified Parkinson's Disease Rating Scale motor score was improved by 53.4 and 45.2% (P = 0.24), respectively, and the levodopa equivalent daily dosage was decreased by 68.4 and 46.4% (P = 0.16), respectively. The mean coordinates of active contact in both Groups A and B were x = 10.1 and 10.5 mm, respectively, y = -2.8 and -3.9 mm, respectively, and z = -6.3 and -6.2 mm, respectively, relative to the midcommissural point. A significant difference was observed on the y axis (P = 0.01). When taking spatial influence into consideration, the neuropsychological effects of chronic STN-DBS were related to a significant anteriorly located active contact within the ventral STN in this preliminary study. This might suggest the existence of topography of STN in patients with Parkinson's disease concerning limbic and associative circuits.

Different cerebral cortical areas influence the effect of subthalamic nucleus stimulation on parkinsonian motor deficits and freezing of gait

Inconsistent response in freezing of gait (FOG) with levodopa treatment or STN DBS makes the pathogenesis difficult to understand. We studied brain areas associated with the expression of STN DBS effect on parkinsonian motor deficits and FOG. Ten Parkinson's disease patients with typical FOG were included. One month before STN DBS, we performed [(18)F]-deoxyglucose PET scans and measured the UPDRS motor and modified FOG (mFOG) scores during levodopa off and on periods. At two months after STN DBS, same rating scores were measured. The percentage improvement of mFOG and UPDRS motor scores by STN DBS during levodopa off period was calculated. We searched for brain areas in which glucose metabolism correlated with the improvement of mFOG and UPDRS motor scores by DBS. During levodopa off period, STN DBS improved the UPDRS motor scores by 32.3% and the mFOG scores by 56.6%. There was no correlation between the improvements of both scores. The improvement of UPDRS motor score by DBS correlated with the metabolic activities of rostral supplementary motor area (Brodmann's area 8; BA8), anterior cingulate cortex (BA32), and prefrontal cortex (BA9). On the other hand, there was a positive correlation between the improvement of mFOG score by DBS and the metabolic activity of the parietal, occipital, and temporal sensory association cortices. In conclusion, dysfunction of different cerebral cortical areas limits the beneficial effects of DBS on parkinsonian motor deficits and FOG.

NEUROSURGERY AT AN EARLIER STAGE OF PARKINSON DISEASE

We compliment Schupbach et al., who report the results of a randomized controlled trial for the use of deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients at an early stage of Parkinson disease (PD).1 There are some concerns that we would like addressed. First, previous studies have shown STN-DBS to be associated with adverse effects on cognition, mood, and behavior.2 An evaluation of STN-DBS effects on social adjustment showed that 10 of 29 patients (35%) had a new psychiatric disorder following surgery.3 Marital conflicts occurred in 17 of 24 couples, and only 9 of 16 patients went back to work after surgery. These adverse effects are only briefly addressed in the present article, even though all 10 surgically treated patients developed transient (n = 9) or permanent (n = 1) psychiatric problems. Second, the primary outcome was quality of life assessed with the Parkinson Disease Questionnaire (PDQ-39). This is a self-report scale; therefore, the results may be …

Mood stability during acute stimulator challenge in Parkinson's disease patients under long‐term treatment with subthalamic deep brain stimulation

Acute and chronic behavioral effects of subthalamic stimulation (STN-DBS) for Parkinson's disease (PD) are reported in the literature. As the technique is relatively new, few systematic studies on the behavioral effects in long-term treated patients are available. To further study the putative effects of STN-DBS on mood and emotional processing, 15 consecutive PD patients under STN-DBS for at least 1 year, were tested ON and OFF stimulation while on or off medication, with instruments sensitive to short-term changes in mood and in emotional discrimination. After acute changes in experimental conditions, mood core dimensions (depression, elation, anxiety) and emotion discrimination processing remained remarkably stable, in the face of significant motor changes. Acute stimulator challenge in long-term STN-DBS-treated PD patients does not appear to provoke clinically relevant mood effects.

3.224 Neuropsychological effects of bilateral STN DBS in advanced Parkinson's disease

3.224 Neuropsychological effects of bilateral STN DBS in advanced Parkinson's disease

Neuropsychological Effects of Bilateral Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson’s Disease

Objective: Although a relatively new technique, bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the treatment of advanced cases of Parkinson’s disease (PD) shows considerable promise. While the benefits of the STN stimulation for the treatment of motor symptoms of PD are well established, some studies have reported negative neuropsychological outcomes, especially in elderly patients. The objective of the present study was to investigate the neuropsychological effects of bilateral STN-DBS in a small sample of elderly patients with PD. Methods: Six patients with PD (mean age 73.0 ± 10.45 years) were assessed both before and approximately 6 months after DBS surgery in six neuropsychological domains. These domains included orientation, estimated IQ, attention/working memory, language, memory, and visual-spatial functioning. Additionally, depressive symptoms were assessed using the Geriatric Depression Scale. Daily doses of antiparkinsonian medications, in levodopa equivalents, were also compared pre- and postoperatively. Results: Antiparkinsonian medications were reduced postoperatively by a mean of 65%, from a mean levodopa equivalent dosage of 987 mg/day to 346 mg/day. Category fluency, a word generation task within the language domain, was the only test in which participants demonstrated a statistically significant decline in performance. Participants demonstrated a mean score decrease of 41% (p < 0.05) in category fluency. Conclusions: The pathophysiology of the observed deficit remains ill defined. However, despite a small sample size, the study provides further evidence that bilateral STN-DBS in PD patients can be associated with negative neuropsychological outcome in word fluency, especially in elderly patients. Implications regarding patient selection for bilateral STN-DBS and recommendations for future research are further discussed.

Differential Effects of L-Dopa and Subthalamic Stimulation on Depressive Symptoms and Hedonic Tone in Parkinson's Disease

Differential Effects of L-Dopa and Subthalamic Stimulation on Depressive Symptoms and Hedonic Tone in Parkinson's Disease

Hypomania as an adverse effect of subthalamic nucleus stimulation: report of two cases

Mania following subthalamic nucleus (STN) deep brain stimulation (DBS) is well described and obvious to both the patient and their physician. The authors describe two patients who developed hypomania following STN-DBS but were unaware of their mood disturbance. Two Parkinson's patients with no previous mood disorders received bilateral STN electrodes. Both experienced dramatic improvement in their motor function and neither complained of any side effects. Their families reported detrimental hypomanic behaviour. Readjusting the stimulation parameters resolved the hypomania with continued motor benefits. The authors draw attention to potential adverse effects of STN-DBS that might be neglected by patients.

Beyond verbal fluency: Investigating the long-term effects of bilateral subthalamic (STN) deep brain stimulation (DBS) on language function in two cases

Cognitive functioning has been described as largely impervious to chronic STN-DBS administered over 12-month periods. In relation to the domain of language, however, the effects of STN-DBS are yet to be thoroughly delineated. Verbal fluency tasks represent an almost exclusively applied index of linguistic proficiency relative to neuropsychological research within this population. Comprehensive investigations of the impact of STN-DBS on language function, however, have never been undertaken. The more precise elucidation of the role of the STN in the mediation of language processes, by way of assessments which probe language comprehension and production mechanisms, served as the primary focus of this research. Longitudinal analysis also afforded consideration of the way in which cognitive-linguistic circuits respond to STN-DBS over time. Bilateral STN-DBS primarily effected clinically reliable fluctuations (i.e., both improvements and declines) in performance in both subjects on tasks demanding cognitive-linguistic flexibility in the formulation and comprehension of complex language. Of particular note, both subjects demonstrated a cumulative increase in the proportion of reliable post-operative improvements achieved over time. The findings of this research lend support to models of subcortical participation in language which endorse a role for the STN, and suggest that bilateral STN-DBS may serve to enhance the proficiency of basal ganglia-thalamocortical linguistic circuits over time.

Subthalamic stimulation activates internal pallidus: Evidence from cGMP microdialysis in PD patients

Parkinson's disease patients benefit from deep brain stimulation (DBS) in subthalamic nucleus (STN), but the basis for this effect is still disputed. In this intraoperative microdialysis study, we found elevated cGMP extracellular concentrations in the internal segment of the globus pallidus, despite negligible changes in glutamate levels, during a clinically effective STN-DBS. This supports the view that a clinically beneficial effect of STN-DBS is paralleled by an augmentation (and not an inactivation) of the STN output onto the GPi.

High-frequency stimulation of the subthalamic nucleus reverses limb-use asymmetry in rats with unilateral 6-hydroxydopamine lesions

Deep brain stimulation (DBS) is a widely used clinical treatment for Parkinson's disease (PD). A rodent model of DBS is a necessary tool for understanding the neural mechanisms of this method. Our previous study showed that high-frequency stimulation (HFS) of the subthalamic nucleus (STN) improved treadmill locomotion in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of nigrostriatal dopamine (DA) neurons. The present study tested DBS effects on limb-use asymmetry (LUA) during vertical/lateral exploration in a cylindrical chamber in rats with similar unilateral nigrostriatal DA lesions. Limb-use asymmetry assessment has been used to detect functional capacity over a wide range of dopamine depletion. Before lesioning, rats exhibited regular rearing activity and used both forelimbs equally often to support weight during exploration of the walls of the cylinder. After unilateral nigrostriatal DA lesioning, rats displayed reduced rearing activity and predominant use of the ipsilateral (good) forelimb to touch the wall. HFS of the STN, but not of other nearby regions surrounding the STN, in the lesioned rats restored normal rearing activity and reversed the limb-use asymmetry caused by the unilateral DA depletion. This study is consistent with the possibility that there can be beneficial effects of STN-DBS on behavioral impairments in unilateral DA-depleted rats and may suggest an appropriate rodent model for DBS study.

Deep brain stimulation for the treatment of Parkinson's disease.

Deep brain stimulation (DBS) is increasingly accepted as an adjunct therapy for Parkinson's disease (PD). It is considered a surgical treatment alternative for patients with intractable tremor or for those patients who are affected by long-term complications of levodopa therapy such as motor fluctuations and severe dyskinesias. Thalamic stimulation in the ventral intermediate nucleus (Vim) leads to a marked reduction of contralateral tremor but has no beneficial effect on other symptoms of Parkinson's disease. The subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi) are targeted for the treatment of advanced Parkinson's disease. Several studies have proven the efficacy of STN-DBS and GPi-DBS in alleviating off motor symptoms and dyskinesias. Sub-thalamic nucleus deep brain stimulation is currently considered superior to GPi-DBS because the antiakinetic effect seems to be more pronounced, allows a more marked reduction of antiparkinsonian medication, and requires less stimulation energy. More recently, however, a number of reports on possible psychiatric and behavioral side effects of STN-DBS have been a matter of concern. Given the chronic nature of PD and the noncurative approach of DBS, both targets will need to be reevaluated on the basis of their long-term efficacy and their impact on quality of life. Despite the rapidly increasing numbers of DBS procedures, surprisingly few controlled clinical trials are available that address important clinical issues such as: When should DBS be applied during the course of disease? Which patients should be selected? Which target should be considered? Which guidelines should be followed during postoperative care? Here is summarized the available evidence on DBS as a therapeutic tool for the treatment of Parkinson's disease and the current state of debate on open issues.