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Deep brain stimulation improves orthostatic regulation of patients with Parkinson disease.

OBJECTIVE: To evaluate whether subthalamic nucleus (STN) stimulation has an effect on the orthostatic regulation of patients with Parkinson disease (PD), we studied cardiovascular regulation during on and off phases of STN stimulation. METHODS: We examined 14 patients with PD (mean age 58.1 +/- 5.8 years, 4 women, 10 men) with bilateral STN stimulators. Patients underwent 3 minutes of head-up tilt (HUT) testing during STN stimulation and after 90 minutes interruption of stimulation. We monitored arterial blood pressure (BP), RR intervals (RRI), respiration, and skin blood flow (SBF). Baroreflex sensitivity (BRS) was assessed as the square root of the ratio of low-frequency power of RRI to the low-frequency power of systolic BP for coherences above 0.5. RESULTS: During the on phase of the STN stimulation, HUT induced no BP decrease, a significant tachycardia, and a significant decrease of SBF. During the off phase of stimulation, HUT resulted in significant decreases in BPsys and RRI and only a slight SBF decrease. HUT induced no change of BRS during stimulation, but lowered BRS when the stimulator was off (p < 0.05). CONCLUSIONS: STN stimulation of patients with PD increases peripheral vasoconstriction and BRS and stabilizes BP, thereby improving postural hypotension in patients with PD. The results indicate that STN stimulation not only alleviates motor deficits but also influences autonomic regulation in patients with PD.

Autonomic Pathways↗

Operative techniques and morbidity with subthalamic nucleus deep brain stimulation in 100 consecutive patients with advanced Parkinson's disease.

OBJECTIVE: Subthalamic nucleus (STN) stimulation for patients with medically refractory Parkinson disease (PD) is expanding. Reported experience has provided some indication of techniques, efficacy, and morbidity, but few centres have reported more than 50 patients. To expand this knowledge, we reviewed our experience with a large series of consecutive patients. METHODS: From March 1999 to September 2003, 191 subthalamic stimulator devices (19 unilateral) were implanted in 100 patients with PD at New York Presbyterian Hospital/Columbia University Medical Center. Sixteen patients had undergone a prior surgery for PD (pallidotomy, thalamotomy, or fetal transplant). Microelectrode guided implantations were performed using techniques similar to those described previously. Electrode implantation occurred 1-2 weeks before outpatient pulse generator implantation. RESULTS: Reductions of dyskinesias and off severity/duration were similar to prior published reports. Morbidity included: 7 device infections (3.7%), 1 cerebral infarct, 1 intracerebral haematoma, 1 subdural haematoma, 1 air embolism, 2 wound haematomas requiring drainage (1.0%), 2 skin erosions over implanted hardware (1.0%), 3 periprocedural seizures (1.6%), 6 brain electrode revisions (3.1%), postoperative confusion in 13 patients (6.8%), and 16 battery failures (8.4%). Of the 100 patients, there were no surgical deaths or permanent new neurological deficits. The average hospital stay for all 100 patients was 3.1 days. CONCLUSION: Subthalamic stimulator implantation in a large consecutive series of patients with PD produced significant clinical improvement without mortality or major neurological morbidity. Morbidity primarily involved device infections and hardware/wound revisions.

Adult↗

Deep brain stimulation for Parkinson's disease: patient selection and motor outcomes.

DBS is a safe and effective option for the treatment of patients with advanced PD. To ensure a successful outcome, however, it is important to select the appropriate candidates. The ideal candidate has idiopathic PD, suffers from complications of chronic levodopa therapy despite optimal medical management, and has no cognitive impairment or active psychiatric issues. Although the exact mechanism of how DBS exerts its effects remains under investigation, it is clearly apparent that bilateral stimulation of either the GPi or STN effectively helps the motor symptoms of PD. While many surgical centers favor stimulation of the STN over the GPi, there is accumulating evidence that STN stimulation may result in adverse non-motor outcomes such as depression. Future studies will be needed in order to determine the best site of stimulation, the exact mechanisms of DBS, and the long-term outcomes of both motor and non-motor symptoms. As our understanding of these components becomes clearer, we will be able to optimize the treatment and management for those whose lives are affected by Parkinson's disease.

Deep Brain Stimulation↗

[Deep brain stimulation and motor cortex and spinal cord stimulation in the treatment of movement disorders and pain syndromes -- the theoretical baseline and practical guidelines].

The authors present the current views on the use of electrical stimulation in selected movement disorders (Parkinson's disease, dystonia) and pain syndromes (central and neuropathic pain) refractory to pharmacological therapy. Stimulation should be applied in cases with an established diagnosis (especially Parkinson's disease and dystonia) and with a lack of efficacy despite the best available medical therapy. Therefore it should be the last treatment option, except of generalized dystonia, where it seems to be nowadays the treatment of choice. Suggested selection criteria are based on experience of different centers and on current medical literature. They are published to make the procedure more rational and more available in Poland.

Deep Brain Stimulation↗

Is there a role for physiotherapy during deep brain stimulation surgery in patients with Parkinson's disease?

In our center, a physiotherapist is present in the operative room to bring relief to the Parkinsonian patient during subthalamic nucleus stimulation surgery under local anesthesia. This study searched to determine the causes of pain and suffering during bilateral electrode implantation and to assess the role of physiotherapy. Ninety-two consecutive patients operated on between 2001 and 2004 were included in this retrospective study. A questionnaire with eight items was developed and mailed to the patients. Seventy-five responses to questionnaires were available. All patients except one experienced physical pain and psychological suffering, alleviated by physiotherapy. These preliminary results need to be confirmed in a prospective randomized study.

Antiparkinson Agents↗

The effect of subthalamic nucleus deep brain stimulation on precision grip abnormalities in Parkinson's disease.

We have studied grip force performance in a group of 10 patients who were in a stable state after implantation of bilateral stimulating electrodes in the subthalamic nuclei (Stn) to counter drug-resistant or drug-induced symptoms of advanced Parkinson's disease. The patients were required to use a precision grip to lift an object which recorded grip force development and lift dynamics. Lifting was performed with stimulation on and with stimulation off under optimal medication. Post-operatively, dyskinesia was absent in all patients in both conditions, but in the 'off' state the patients showed the profound bradykinesia and excessive levels of grip force development associated with Parkinson's disease from its early stages. In the stimulation 'on' state both the rate of grip force development and the speed of the lifting phase were increased significantly. The excessive levels of grip force present in the stimulation 'off' state, and present from the early stages of the disease, however, were even more marked with Stn stimulation on. It is suggested that this results from a failure to modify stored motor programs developed over a long period under the influence of bradykinesia, leading to an inappropriately prolonged duration of grip force development when this influence is removed by Stn stimulation. Thus although Stn stimulation achieved a dramatic improvement in the mobility of the patients in general, and in the dynamics of hand movements specifically, by improving rates of force development and lifting dynamics, it does not restore, and may even worsen, the ability to match lifting parameters to actual conditions.

Aged↗

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.

Aged↗

Deep brain stimulation: overview and update.

OBJECTIVE: To summarize the techniques for physiological localization that contribute to increased accuracy in the surgical treatment of movement disorders. METHODS: Initial targeting through imaging referenced to stereotactic atlas are confirmed through physiological localization. Spontaneous recording, elicited recording, evoked potentials and stimulation provided physiological localization for target confirmation in the placement of lesions or DBS. RESULTS: Imaging and stereotactic techniques produce inaccuracy that may be address by physiological localization. Microelectrode recording from basal ganglia and thalamic sites provides signature neuronal patterns to confirm and guide the trajectory. Spontaneous and elicited neuronal response are recorded from microelectrodes. CONCLUSIONS: Accuracy of movement disorders surgery is enhance through use of physiological localization. A multimodality approach provides techniques that allow localization in a variety of patient and environmental conditions.

Brain↗

Depression and intelligence in patients with Parkinson's disease and deep-brain stimulation.

The goal of this study is to examine the association of depression with intelligence and education in patients with Parkinson's disease treated with bilateral subthalamic nucleus stimulation (STN-DBS). The literature has been contradictory concerning depression in Parkinson's disease patients. Some studies have shown less depression in Parkinson's disease patients with more education not treated with STN-DBS. Other recently published studies indicate that STN-DBS improves the depression associated with Parkinson's disease. No studies have examined the correlation of these factors with depression in Parkinson's disease patients treated with STN-DBS. We administered the Beck Depression Inventory (BDI) pre- and postoperatively to 21 Parkinson's disease patients (seven women, 14 men, ages 49-75) who underwent STN-DBS. The postoperative scores of the lower 50th percentile (n=8) of the Verbal Comprehensive Index of the Wechsler Adult Intelligence Scale (WAIS-III) decreased significantly (P=0.036), while the upper 50th percentile (n=13) remained nearly constant (P=0.802). Furthermore, as the education increased from highschool to graduate level, patients demonstrated less improvement in depressive symptoms postoperatively. These findings suggest that Parkinson's disease patients with lower intelligence test scores and less education benefit more with regards to depressive symptomatology after STN-DBS than patients with higher scores and education.

Deep Brain Stimulation↗

Deep brain stimulation in intraoperative MRI environment - comparison of imaging techniques and electrode fixation methods.

We performed 118 consecutive DBS cases from November 1999 to June 2002. Intraoperatively there were 10 cases studied with fluoroscopy, 73 with 0.2 Tesla (T) MRI and 35 with 1.5 T MRI. Ten electrodes were secured by Medtronic caps, 25 by methyl methacrylate with titanium miniplates, and 82 by Navigus caps. The 3-dimensional displacement between the planned target and actual electrode position (3DD) was determined by fusing the postoperative MRI with the preoperative imaging. The 3DD for using Medtronic caps, methyl methacrylate with miniplates, and Navigus caps were 4.80 +/- 3.16, 2.64 +/- 1.26 and 2.23 +/- 1.15 mm (mean +/- SD), respectively. Navigus caps had statistically significant accuracy (P = 0.03) in holding the electrode when compared with Medtronic caps, and it facilitated electrode revision. The fixation devices significantly affect the final vertical position of the electrode. The 3DD for fluoroscopy, 0.2 T and 1.5 T MRI cases were 4.80 +/- 3.16, 2.31 +/- 1.21 and 2.34 +/- 1.14 mm (mean +/- SD), respectively. No statistically significant difference (P = 0.91) in 3DD was demonstrated between 0.2 T and 1.5 T MRI cases. The presence of intraoperative 1.5 T MRI allowed near real-time electrode position confirmation and early detection of hemorrhagic complications. Satisfactory microelectrode recording was feasible in low-field 0.2 T and high-field 1.5 T MRI environments. Further studies on performing DBS in real-time intraoperative MRI are warranted.

Adolescent↗

Targeting the subthalamic nucleus for deep brain stimulation: technical approach and fusion of pre- and postoperative MR images to define accuracy of lead placement.

OBJECTIVES: To define the role of magnetic resonance imaging (MRI) and intraoperative electrophysiological recording in targeting the subthalamic nucleus (STN) in Parkinson's disease and to determine accuracy of electrode placement. PATIENTS AND METHODS: We implanted 54 electrodes into the STN in 27 patients. Target planning was done by coordinate guidelines and visualising the STN on MRI and defined in relation to the mid-point of the AC-PC line. Intraoperative microelectrode recording was used. We adjusted electrode positions for placement in the centre of the STN electrical activity and verified this on postoperative MRI in 16 cases, which were fused to the preoperative images to measure actual error in electrode placement in the three axes. RESULTS: Based on coordinate calculation and MRI localisation, the mean of the target was 11.5 mm lateral, 2.5 mm posterior and 4.1 mm inferior to the mid-point of the AC-PC line. Fifty good electrophysiological recordings of the STN (average length 4.65 mm) were achieved and target point adjusted in 90% of lead placements. The mean of the final target after electrophysiological correction was 11.7 mm lateral, 2.1 mm posterior, and 3.8 mm inferior to the mid-point. The distance from the centre of the electrode artefact to the final target used after electrophysiological recording on the fused images was 0.48 mm, 0.69 mm, and 2.9 mm in the x, y, and z axes, respectively. No postoperative MRI related complication was observed. CONCLUSION: Both direct visualisation of the STN on MRI and intraoperative electrophysiological recording are important in defining the best target. Individual variations exist in the location of the STN target. Fewer tracks were required to define STN activity on the side operated first. Our current stereotactic method of electrode placement is relatively accurate.

Adult↗

A randomized trial of deep-brain stimulation for Parkinson's disease.

BACKGROUND: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08). CONCLUSIONS: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).

Activities of Daily Living↗

Deep brain stimulation inactivity can produce unexpected high electrode impedances when reactivated, leading to a false conclusion of wire fracture.

Two months after bilateral DBS surgery in a patient with PD, the stimulator had to be removed temporarily due to an infection. After successful antibiotic treatment, a new stimulator and extension wire were reimplanted 2 months later. Intraoperative testing of the replacement device yielded unusually high electrode impedances and low currents on one lead across all four contacts. Since the results did not change on repeated measurements, a lead fracture was suspected. Visual inspection of the exposed hardware, however, did not reveal any obvious defects. It was then decided to activate the lead for a prolonged time with significant currents. Subsequent impedance measurements yielded normal values and after the patient awoke from anesthesia, good symptom control was again achieved. It is advisable if a lead fracture is suspected under similar circumstances to 'condition' the electrode with high currents. Failure to do so could lead to a false conclusion of a lead fracture and unnecessary stereotactic surgery to replace it.

Aged↗

Deep brain stimulation surgery for Parkinson's disease: the role of neuropsychological assessment.

Neuropsychological assessment has two primary roles in the DBS process. First, assessment of cognitive and emotional functioning ensures that only appropriate candidates undergo this surgical procedure. Patients with dementia, cognitive performance suggestive of an additional neuropathological process, or significant psychiatric impairments should not undergo DBS. Second, neuropsychological assessment is essential to determine the cognitive and emotional outcomes following surgery. At the present time, a disruption in verbal fluency is the only consistent cognitive decline associated with DBS. While worsening of depression and the development of symptoms of mania are potential side effects from DBS, more studies find that DBS is associated with improvements in emotional functioning. Based on the growing understanding of the risk factors and potential side effects to DBS, neuropsychological assessment is necessary to ensure that patients selected to undergo this surgical intervention will likely have positive cognitive and emotional outcomes, in addition to the expected benefits in motor functioning.

Brain↗

Deep brain stimulation in epilepsy with particular reference to the subthalamic nucleus.

Alternative methods, for the treatment of medically refractory epileptic patients, who cannot be treated by resective surgery, such as chronic deep brain neurostimulation, are under development. Such methods have been used in the cerebellum, various thalamic nuclei, and in the caudate nucleus. In Grenoble, encouraged by the suppressive effects of pharmacological or electrical inhibition of the STN on different types of seizure in animal models of epilepsy, and by our experience with STN high frequency stimulation (HFS) in patients with movement disorders, we have evaluated the high frequency stimulation of the subthalamic nucleus (STN HFS). STN HFS was performed in five patients suffering from medically intractable seizures and considered unsuitable for resective surgery. A 67% to 80% reduction in seizure frequency was observed in three patients, with a partial symptomatic epilepsy of the central region. An additional patient suffering from severe myoclonic epilepsy (Dravet syndrome) also responded to STN HFS, with a weaker reduction of seizure frequency. The fifth patient who suffered from an autosomal dominant frontal lobe epilepsy with insulo-frontal seizures did not show any improvement. These results suggest that stimulation of STN could be a promising treatment for patients with drug-resistant epilepsy who would not benefit from conventional surgery.

Adolescent↗

Does deep brain stimulation of the nucleus ventralis intermedius affect postural control and locomotion in Parkinson's disease?

The purpose of this study was to evaluate the effect of unilateral stimulation of the nucleus ventralis intermedius (VIM) on parkinsonian signs like postural stability and locomotion with respect to the severity of Parkinson's disease (PD). Seven patients with idiopathic PD were included in the study. Changes in visual cues on postural stability and step initiation were assessed on a fixed platform system with VIM stimulation switched either on (VIM ON) or off (VIM OFF), and compared with a control group of seven age-matched normal individuals. Sway scores (area and path) were significantly (p <0.05) higher in the parkinsonian patients with VIM OFF than with VIM ON as well as compared with the control subjects. No correlation was obtained between extent of sway scores and severity of contralateral tremor after cessation of VIM stimulation. Locomotion parameters, by contrast, were not influenced by VIM stimulation: latency until step initiation and walking-cycle time were the same among parkinsonian patients as among normal individuals, both in the presence and in the absence of VIM stimulation. In conclusion, our results indicate that tremor suppression by VIM stimulation improves postural stability.

Aged↗