Subthalamic Nucleus Deep Brain Stimulation In Patients Research Articles

7-Tesla Magnetic Resonance Imaging Scanning in Deep Brain Stimulation for Parkinson's Disease: Improving Visualization of the Dorsolateral Subthalamic Nucleus.

Identifying the dorsolateral subthalamic nucleus (STN) for deep brain stimulation (DBS) in Parkinson's disease (PD) can be challenging due to the size and double-oblique orientation. Since 2015 we implemented 7-Tesla T2 weighted magnetic resonance imaging (7 T T2) for improving visualization and targeting of the dorsolateral STN. We describe the changes in surgical planning and outcome since implementation of 7 T T2 for DBS in PD. By comparing two cohorts of STN DBS patients in different time periods we evaluated the influence of 7 T T2 on STN target planning, the number of microelectrode recording (MER) trajectories, length of STN activity and the postoperative motor (UPDRS) improvement. From February 2007 to January 2014, 1.5 and 3-Tesla T2 guided STN DBS with 3 MER channels was performed in 76 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 3.9 ± 1.5 mm. From January 2015 to January 2022 7 T T2 and MER-guided STN DBS was performed in 182 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 5.1 ± 1.3 mm and used MER channels decreased from 3 to 1. Average UPDRS improvement was comparable. Implementation of 7 T T2 for STN DBS enabled a refinement in targeting. Combining classical DBS targeting with dorsolateral STN alignment may be used to determine the optimal trajectory. The improvement in dorsolateral STN visualization can be used for further target refinements, for example adding probabilistic subthalamic connectivity, to enhance clinical outcome of STN DBS.

Evidence of Improved Verbal Fluency Following Unilateral Right Hemisphere Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease (S51.007)

<h3>Objective:</h3> To investigate verbal fluency following unilateral subthalamic nucleus deep brain stimulation (STN-DBS). <h3>Background:</h3> STN-DBS is safe and effective for motor symptoms, but a widely replicated cognitive outcome following bilateral STN-DBS is verbal fluency decline. Since non-motor symptoms, including mild cognitive impairment and dementia are a significant cause of disability in Parkinson’s disease (PD), reducing the risk of DBS-related cognitive decline is important. Compared to bilateral STN-DBS, little is known about unilateral STN-DBS effects on verbal fluency <h3>Design/Methods:</h3> We enrolled 31 PD patients who underwent unilateral STN-DBS in a randomized, cross-over, double-blind study (SUNDIAL). Targets were based on treatment of the most symptomatic side (<i>n</i> = 17 left STN-DBS; 14 right STN-DBS). At 2-, 4-, and 6-months post-surgery, all participants completed a verbal fluency measure (FAS/CFL), and stimulation type (directional versus ring) was randomized. Welch’s two-sample t-test was used to compare verbal fluency baseline scores and the effects of hemisphere and stimulation on cognition were analyzed using linear mixed effects models. Covariates included age, education, and levodopa equivalents at each time point. <h3>Results:</h3> Left STN-DBS patients scored lower on a verbal fluency task than right STN-DBS patients (t(20.66) = −2.49, p = 0.02) at baseline. Following DBS surgery, we observed declines in verbal fluency over the study duration only in the left STN-DBS group (<i>p</i> = 0.02), while the right STN-DBS group improved (<i>p</i>&lt;.001). Stimulation type was not associated with verbal fluency performance. <h3>Conclusions:</h3> After adjusting for age, education, and levodopa equivalent dose, we found group-level verbal fluency declines following unilateral left STN-DBS and improved verbal fluency following unilateral right STN-DBS. In contrast with bilateral STN-DBS where verbal fluency declines are often reported, it is possible that selecting unilateral right STN-DBS to control left-sided symptoms may be a modifiable risk factor to potentially reduce the likelihood of verbal fluency declines in patients with PD. <b>Disclosure:</b> Dr. Del Bene has nothing to disclose. The institution of Roy C Martin, 4854 has received research support from NIH. Ms. Brinkerhoff has received research support from National Institute of Neurological Disorders and Stroke. Dr. Olson has nothing to disclose. The institution of Dr. Nelson has received research support from NIH. Dr. Marotta has nothing to disclose. Mr. Gonzalez has nothing to disclose. Dr. Mills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tilosia. The institution of Dr. Mills has received research support from NINDS. The institution of Dr. Mills has received research support from MJFF. The institution of Dr. Mills has received research support from GKC. The institution of Dr. Kamath has received research support from NIH. Dr. Bentley has nothing to disclose. Dr. Walker has nothing to disclose.

The mortality of patients with Parkinson's disease with deep brain stimulation.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in improving motor function in patients with Parkinson's disease (PD). This study aimed to investigate mortality associated with bilateral STN DBS in patients with PD and to assess the factors associated with mortality and causes of death after DBS. We reviewed the medical records of 257 patients with PD who underwent bilateral STN DBS at the Movement Disorder Center at Seoul National University Hospital between March 2005 and November 2018. Patients were evaluated preoperatively, at 3, 6, and 12 months after surgery and annually thereafter. The cause and date of death were obtained from interviews with caregivers or from medical certificates at the last follow-up. Of the 257 patients with PD, 48 patients (18.7%) died, with a median time of death of 11.2 years after surgery. Pneumonia was the most common cause of death. Older age of disease onset, preoperative falling score while on medication, and higher preoperative total levodopa equivalent daily dose were associated with a higher risk of mortality in time-dependent Cox regression analysis. These results confirm the mortality outcome of STN DBS in patients with advanced PD.

Nomogram to Predict Cognitive State Improvement after Deep Brain Stimulation for Parkinson's Disease.

Purpose: Parkinson’s disease (PD) is a common neurodegenerative disease, for which cognitive impairment is a non-motor symptom (NMS). Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for PD. This study established a nomogram to predict cognitive improvement rate after STN-DBS in PD patients. Methods: We retrospectively analyzed 103 PD patients who underwent STN-DBS. Patients were followed up to measure improvement in MoCA scores one year after surgery. Univariate and multivariate logistic regression analyses were used to identify factors affecting improvement in cognitive status. A nomogram was developed to predict this factor. The discrimination and fitting performance were evaluated by receiver operating characteristics (ROC) analysis, calibration diagram, and decision curve analysis (DCA). Results: Among 103 patients, the mean improvement rate of the MoCA score was 37.3% and the median improvement rate was 27.3%, of which 64% improved cognition, 27% worsened cognition, and 8.7% remained unchanged. Logistic multivariate regression analysis showed that years of education, UPDRSIII drug use, MoCA Preop, and MMSE Preop scores were independent factors affecting the cognitive improvement rate. A nomogram model was subsequently developed. The C-index of the nomogram was 0.98 (95%CI, 0.97–1.00), and the area under the ROC was 0.98 (95%CI 0.97–1.00). The calibration plot and DCA demonstrated the goodness-of-fit between nomogram predictions and actual observations. Conclusion: Our nomogram could effectively predict the possibility of achieving good cognitive improvement one year after STN-DBS in patients with PD. This model has value in judging the expected cognitive improvement of patients with PD undergoing STN-DBS.

Short Versus Conventional Pulse-Width Deep Brain Stimulation in Parkinson's Disease: A Randomized Crossover Comparison.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for selected Parkinson's disease patients with motor fluctuations, but can adversely affect speech and axial symptoms. The use of short pulse width (PW) has been shown to expand the therapeutic window acutely, but its utility in reducing side effects in chronic STN-DBS patients has not been evaluated. To compare the effect of short PW settings using 30-μs with conventional 60-μs settings on stimulation-induced dysarthria in Parkinson's disease patients with previously implanted STN-DBS systems. In this single-center, double-blind, randomized crossover trial, we assigned 16 Parkinson's disease patients who had been on STN-DBS for a mean of 6.5 years and exhibited moderate dysarthria to 30-μs or 60-μs settings for 4 weeks followed by the alternative PW setting for a further 4 weeks. The primary outcome was difference in dysarthric speech measured by the Sentence Intelligibility Test between study baseline and the 2 PW conditions. Secondary outcomes included motor, nonmotor, and quality of life measures. There was no difference in the Sentence Intelligibility Test scores between baseline and the 2 treatment conditions (P = 0.25). There were also no differences noted in motor, nonmotor, or quality of life scores. The 30-μs settings were well tolerated, and adverse event rates were similar to those at conventional PW settings. Post hoc analysis indicated that patients with dysarthria and a shorter duration of DBS may be improved by short PW stimulation. Short PW settings using 30 μs did not alter dysarthric speech in chronic STN-DBS patients. A future study should evaluate whether patients with shorter duration of DBS may be helped by short PW settings. © 2019 International Parkinson and Movement Disorder Society.

Reader response: Deep brain stimulation improves restless legs syndrome in patients with Parkinson disease.

Several studies assessed the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on restless legs syndrome (RLS) symptoms in patients with Parkinson disease (PD) with conflicting results.1–5 As underlined by Klepitskaya et al.,1 one crucial variable is dopaminergic therapy, as emergence of RLS after STN DBS in patients with PD has been reported after abrupt decrease of dopaminergic treatment.3 Klepitskaya et al. argued that, in a previous study we conducted,5 patients with emergence of RLS after STN DBS took a higher dose and had a more significant reduction of dopamine agonists compared to those without emergence with RLS. Yet, we actually reported the opposite, showing an emergence of RLS in patients with PD with a higher dose of dopamine agonists postoperatively and with a lesser decrease of dopamine agonists after STN DBS.5

Is lowering stimulation frequency a feasible option for subthalamic deep brain stimulation in Parkinson's disease patients with dysarthria?

BackgroundThe long-term effect of subthalamic nucleus deep brain stimulation (STN-DBS) on dysarthria can be detrimental. A transient beneficial effect of low-frequency stimulation (LFS) has been reported.Objective: to investigate if the magnitude of dysarthria could predict the effect of LFS on speech in STN-DBS PD patients and to verify whether the benefit is maintained over time. Methodsa cohort study, comparing 10 PD patients with severe speech impairment (MDS-UPDRS item 3.1 ≥ 3) with 10 PD patients with mild speech impairment (MDS-UPDRS item 3.1 ≤ 2), all submitted to STN-DBS. Patients were tested in: MED OFF/STIM OFF, MED OFF/STIM ON (130 Hz, high frequency stimulation [HFS]), MED OFF/STIM ON (60 Hz - LFS) and MED ON with both HFS and LFS. The following was assessed in all conditions: voice (fundamental frequency and jitter), speech (articulatory diadochokinesis [DDK], pitch variability, rate and intelligibility) and motor performance (MDS-UPDRS-III). ResultsLFS compared to no stimulation and HFS, in the absence of l-dopa effect, significantly improved DDK and speech intelligibility for sentence, among patients with severe speech impairment. During the l-dopa effect, comparing LFS vs. HFS, there was a significant improvement of speech intelligibility in both groups.Five patients with severe speech impairment opted to maintain LFS. After six months, speech benefit was maintained but treatment adjustments were required. ConclusionsLFS may offer both an immediate and long-lasting improvement of speech in a subgroup of STN-DBS patients with severe speech impairment during HFS. Nevertheless, its effect on motor symptoms may not be preserved over time.

Neuropsychiatric complications and neuroimaging characteristics after deep brain stimulation surgery for Parkinson's disease.

Psychiatric complications after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease patients are common. The aim of this study was to evaluate a possible role of cortical thickness, cortical and subcortical volume for neuropsychiatric complications after STN-DBS implantation surgery. Twenty-two Parkinson's disease patients underwent STN-DBS. Control group consisted of 18 healthy volunteers who were matched by age and gender. All Parkinson's disease patients and control subjects underwent neuropsychological assessment and brain MRI. Control group subjects had normal MRI and neurocognitive testing results. Seven (31.8%) Parkinson's disease patients developed neuropsychiatric complications (psychosis and delirium) after STN-DBS implantation surgery with full recovery in short follow up. Two Parkinson's disease patients were excluded from further analysis, because they did not match image processing and analysis quality control. Volumetric analysis showed significant differences in cortical thickness between STN-DBS patients with and without postoperative neuropsychiatric complications in 13 gyruses on the right hemisphere (superior frontal, caudal middle frontal, pars triangularis and opercularis, temporal lobe, superior and inferior parietal, supramarginal) and in 7 gyruses on the left hemisphere (caudal middle frontal, inferior and middle temporal, pre and postcentral, superior parietal and supramarginal). White matter volume analysis showed also its reduction in the left caudal middle frontal area. Moreover, white matter volume and surface area reduction implicating that this area can be the most important for postoperative neuropsychiatric complication risk. Study results suggest that neuropsychiatric complications are common in Parkinson's disease patients after STN-DBS implantation and can be associated with excitation of frontal-striatum-thalamus and temporal-parietal circuits.

Association of MRI Measurements with Cognitive Outcomes After STN‐DBS in Parkinson's Disease

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for improving the motor symptoms of Parkinson's disease (PD). Overall, cognitive function remains stable after STN-DBS in most patients. However, cognitive decline, specifically in the verbal fluency domain, is seen in a subset of STN-DBS patients. Currently, predictors of cognitive decline in PD patients treated with STN-DBS are not well known. Thus, identification of presurgical predictors might provide an important clinical tool for better risk-to-benefit assessment. This study explores whether whole brain white matter lesion (WML) volume, or hippocampal and forebrain volumes, measured quantitatively on MRI, are associated with cognitive changes following STN-DBS in PD patients. We conducted a retrospective study using presurgical, and ≥ 6-month postsurgical neuropsychological (NP) evaluation scores from 43 PD patients with STN-DBS. Mean pre/post NP test scores for measures of executive function, attention, verbal fluency, memory, and visuospatial function were analyzed and correlated with WML volume, and brain volumetric data. Although cognitive measures of verbal fluency, executive function, attention, memory, and visuospatial function showed declines following STN-DBS, we observed limited evidence that white matter lesion burden or cortical atrophy contributed to cognitive change following STN-DBS. These results suggest that post-STN-DBS cognitive changes may be unrelated to presurgical WML burden and presence of cortical atrophy.

Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation.

Parkinson's disease is associated with altered neural activity in the motor cortex. Chronic high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in suppressing parkinsonian motor symptoms and modulates cortical activity. However, the anatomical pathways responsible for STN DBS-mediated cortical modulation remain unclear. Cortical evoked potentials (cEP) generated by STN DBS reflect the response of cortex to subcortical stimulation, and the goal of this study was to determine the neural origin of STN DBS-generated cEP using a two-step approach. First, we recorded cEP over ipsilateral primary motor cortex during different frequencies of STN DBS in awake healthy and unilateral 6-OHDA-lesioned parkinsonian rats. Second, we used a detailed, biophysically based model of the thalamocortical network to deconstruct the neural origin of the recorded cEP. The in vivo cEP included short (R1)-, intermediate (R2)-, and long-latency (R3) responses. Model-based cortical responses to simulated STN DBS matched remarkably well the in vivo responses. The short-latency response was generated by antidromic activation of layer 5 pyramidal neurons, whereas recurrent activation of layer 5 pyramidal neurons via excitatory axon collaterals reproduced the intermediate-latency response. The long-latency response was generated by polysynaptic activation of layer 2/3 pyramidal neurons via the cortico-thalamic-cortical pathway. Antidromic activation of the hyperdirect pathway and subsequent intracortical and cortico-thalamo-cortical synaptic interactions were sufficient to generate cortical potential evoked by STN DBS, and orthodromic activation through basal ganglia-thalamus-cortex pathways was not required. These results demonstrate the utility of cEP to determine the neural elements activated by STN DBS that might modulate cortical activity and contribute to the suppression of parkinsonian symptoms. NEW & NOTEWORTHY Subthalamic nucleus (STN) deep brain stimulation (DBS) is increasingly used to treat Parkinson's disease (PD). Cortical potentials evoked by STN DBS in patients with PD exhibit consistent short-latency (1-3 ms), intermediate-latency (5-15 ms), and long-latency (18-25 ms) responses. The short-latency response occurs as a result of antidromic activation of the hyperdirect pathway comprising corticosubthalamic axons. However, the neural origins of intermediate- and long-latency responses remain elusive, and the dominant view is that these are produced through the orthodromic pathway (basal ganglia-thalamus-cortex). By combining in vivo electrophysiology with computational modeling, we demonstrate that antidromic activation of the cortico-thalamic-cortical pathway is sufficient to generate the intermediate- and long-latency cortical responses to STN DBS.

Long term follow-up on quality of life and its relationship to motor and cognitive functions in Parkinson's disease after deep brain stimulation

IntroductionWe aimed to examine temporal changes in health-related quality of life (HRQOL) and its relationship with motor and cognitive functions in patients with Parkinson's disease (PD) after subthalamic nucleus deep brain stimulation (STN-DBS). MethodsIn total, 31 patients with PD were enrolled in this study (mean age: 66.7±0.9years; mean disease duration: 11.6±3.7years). Participants completed the Unified Parkinson's Disease Rating Scale and the Parkinson's Disease Questionnaire-39. Cognitive function was assessed using the Mini Mental State Examination, the Frontal Assessment Battery, and the Montreal Cognitive Assessment. Postoperative evaluation was performed at three months, one year, three years, and five years after surgery; temporal changes in the correlation between HRQOL and motor and cognitive functions were evaluated at all follow-up periods. ResultsAll patients completed postoperative clinical evaluations after three months, after one year. Of the 31 participants, twelve completed postoperative clinical evaluations after three years and seven after five years. Motor functions showed significant improvement over the five-year follow-up period. The mobility subdomain of the HRQOL worsened whereas the total score did not change significantly over years. Cognitive functions were not significantly impaired during follow-up periods. HRQOL was basically not significantly correlated with motor and cognitive functions during the follow-up period. ConclusionsThe mobility subdomain of the HRQOL worsened after surgery, and the improvement in motor functions was basically not correlated with HRQOL after STN-DBS in patients with PD. Cognitive functions were not significantly impaired during follow-up periods.

Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease in Hong Kong: A Prospective Territory-Wide 2-Year Follow-Up Study

We assessed the effects of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease at the 1-year and 2-year follow-up evaluations. Unified Parkinson's Disease Rating Scale (UPDRS) motor score at "off" medication ("on" DBS) and quality-of-life assessments (39-item Parkinson's Disease Questionnaire [PDQ-39]) were conducted. The percentage of awake "on" time and awake "off" time and levodopa requirement were also assessed. A 2-year prospective study was conducted of 25 consecutive patients from 3 DBS referral centers in Hong Kong. The patients were treated with bilateral stimulation of the STN. Assessments were performed at 1 year and 2 years after DBS and were compared with the baseline. The 2-year outcome assessments were completed by 18 patients. The mean UPDRS motor score improvement was 57% in the first year and 45% in the second year. PDQ-39 showed significant improvement in quality of life for 2 consecutive years. The levodopa requirement decreased 63% in the first year and 55.9% in the second year. The awake "on" time was doubled in the first year and sustained in the second year. Awake "off" time was reduced from 28.1% to 5.9% in the first year and returned to 10.6% in the second year. Improvement of UPDRS motor score, reduction in awake "off" time, and decrease of daily levodopa dosage all were main factors correlated with the improvement in PDQ-39 summary index. The effects of STN DBS in patients with Parkinson disease in Hong Kong were satisfactory. The results showed that reduction in UPDRS motor score, awake "off"-time, and daily levodopa dosage were the major drivers of overall improvement in PDQ-39.

Greater improvement in LRRK2 G2019S patients undergoing Subthalamic Nucleus Deep Brain Stimulation compared to non-mutation carriers.

BackgroundBilateral subthalamic nucleus deep brain stimulation (STN-DBS) of parkinson’s disease (PD) patients has demonstrated to improve motor performance and to reduce dopa-induced dyskinesia. An association between the occurrence of dyskinesias and LRRK2 (leucine-rich repeat kinase 2) G2019S gene mutations has recently been suggested. The aim of this study is to discover the impact of the G2019S mutation (with high incidence in the authors’ native Algeria) on the symptom response of PD in patients who underwent STN-DBS.MethodsWe carried out a comparative statistical study for the clinical evaluation and neuropsychological assessment of 27 Algerian PD STN-DBS patients, both G2019S mutation carriers (MC) and non-carriers (NC). A multiple correspondence analysis (MCA) was then conducted to compare the results with those from groups of individuals with similar modalities.ResultsThe MCA revealed that MC and NC PD patients showed two different patterns of clinical evaluations. The group of idiopathic patients showed some differences compared to the clinical evaluations, depending on gender. No association was found between the G2019S mutation and the Mini Mental State Examination scores (MMSE), and MC patients appeared more susceptible to dyskinesia than NC patients. In NC patients, we found two cases with Parkin mutations who had a different “honeymoon” period and different initial symptoms. The results showed considerable improvement of motor unified parkinson’s disease rating scale III (UPDRS-III) in a situation of stimulation without medication in the MC patients with a percentage of improvement (51.1 %) over the required 30 % compared to the NC patients (25.5 %). The same result was observed for the Schwab and England’s activities of daily living scale (S and E scale), which thus demonstrated a greater effectiveness of DBS for MC patients than for NC patients. However, the Hoehn and Yahr scale (H and Y Scale) showed the same significance in a situation of stimulation for MC and NC patients. In this later group, the best scores of UPDRS-III were observed for patients with the Parkin mutation before they underwent surgery.ConclusionsThis study shows that surgical treatment probably has a more significant impact on LRRK2 G2019S MC than on idiopathic patients.

In Parkinson's disease on a probabilistic Go/NoGo task deep brain stimulation of the subthalamic nucleus only interferes with withholding of the most prepotent responses.

The evidence on the impact of subthalamic nucleus deep brain stimulation (STN-DBS) on action restraint on Go/NoGO reaction time (RT) tasks in Parkinson’s disease (PD) is inconsistent; with some studies reporting no effect and others finding that STN stimulation interferes with withholding of responses and results in more commission errors relative to STN-DBS off. We used a task in which the probability of Go stimuli varied from 100 % (simple RT task) to 80, 50 and 20 % (probabilistic Go/NoGo RT task), thus altering the prepotency of the response and the difficulty in withholding it on NoGo trials. Twenty PD patients with STN-DBS, ten unoperated PD patients and ten healthy controls participated in the study. All participants were tested twice; the order of on versus off stimulation for STN-DBS PD patients was counterbalanced. Both STN-DBS and unoperated PD patients were tested on medication. The results indicated that STN-DBS selectively decreased discriminability when the response was most prepotent (high—80 %, as compared to low Go probability trials—50 and 20 %). Movement times were faster with STN stimulation than with DBS off across different Go probability levels. There was neither an overall nor a selective effect of STN-DBS on RTs depending on the level of Go probability. Furthermore, compared to healthy controls, both STN-DBS and unoperated PD patients were more prone to making anticipatory errors; which was not influenced by STN stimulation. The results provide evidence for ‘load-dependent’ effects of STN stimulation on action restraint as a function of the prepotency of the Go response.

Patients' reluctance to undergo deep brain stimulation for Parkinson's disease

BackgroundMany patients with advanced Parkinson's disease (PD) are reluctant to undergo the subthalamic nucleus deep brain stimulation (STN-DBS) when surgery is warranted. Reasons for this reluctance have not been examined. We undertook to establish the rate and causes of this reluctance for STN-DBS in patients with advanced PD. MethodsA reluctant group was defined as patients who were hesitant to undergo DBS. Clinical information included age, onset age, disease duration, the Unified Parkinson Disease Rating Scale, Hoehn and Yahr stage and levodopa equivalent dose when they were evaluated with a view to consider surgery. ResultsWe enrolled 186 patients who underwent STN-DBS. 84 patients (45%) belonged to the reluctant group. Between the reluctant and the non-reluctant, there were no differences in preoperative characteristics. Main reasons for hesitation were fear of complications (74%) and economic burden (50%). The main reasons that they finally underwent the DBS were confidence in the doctor's decision (80%) and encouragement from their family (36%). ConclusionsBuilding trust between patients and physicians is an important factor in guiding patients to undergo this treatment. To reduce the reluctance to undergo DBS at the appropriate time, we need to find effective ways of reducing their psychological and economic burden.

Body weight gain in patients with bilateral deep brain stimulation for dystonia.

In patients with Parkinson's disease, significant weight gain following chronic deep brain stimulation (DBS) has been reported. Recently, relevant weight gain could be demonstrated also following subthalamic nucleus DBS in patients with primary cervical dystonia. Prospective analyses of body weight changes following DBS in patients with dystonia, however, have not been published so far. We aimed to analyse the changes of body weight following DBS in patients with dystonia. The body mass index (BMI) of 17 consecutive patients with segmental or generalised dystonia (mean age 54.6±16.1years) treated with bilateral DBS of the globus pallidus internus (GPi) (n=14) or the thalamic ventral intermediate nucleus (n=3) was measured preoperatively (pre-OP) and at three follow-up (FU) time points post-DBS surgery (FU1=7months, FU2=17months, FU3=72months). All patients benefited from marked improvement in their dystonia. The mean BMI pre-OP (SD) was 22.5 (±3.7)kg/m(2) and increased stepwise to 24.0 (±3.3)kg/m(2) at FU1, 24.4 (±3.7)kg/m(2) at FU2 and 24.9 (±3.7)kg/m(2) at FU3 (p<0.05 at all three FUs compared to pre-OP). Relative BMI increase and improvement of dystonia were correlated (p=0.025). Chronic bilateral GPi DBS in patients with dystonia is associated with significant body weight gain, in particular during the first 6months post-OP. This probably is a result of improvement of dystonic motor symptoms and recovery of eating dysfunction rather than a target-specific phenomenon.

Constant Current versus Constant Voltage Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease

Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established therapy for advanced Parkinson's disease (PD). Motor efficacy and safety have been established for constant voltage (CV) devices and more recently for constant current (CC) devices. CC devices adjust output voltage to provide CC stimulation irrespective of impedance fluctuation, while the current applied by CV stimulation depends on the impedance that may change over time. No study has directly compared the clinical effects of these two stimulation modalities. Objective: To compare the safety and clinical impact of CC STN DBS to CV STN DBS in patients with advanced PD 2 years after surgery. Methods: Patients were eligible for inclusion if they had undergone STN DBS surgery for idiopathic PD, had been implanted with a Medtronic Activa PC and if their stimulation program and medication had been stable for at least 1 year. This single-center trial was designed as a double-blind, randomized, prospective study with crossover after 2 weeks. Motor equivalence of the 2 modalities was confirmed utilizing part III of the Unified Parkinson's Disease Rating Scale (UPDRS). PD diaries and multiple subjective and objective evaluations of quality of life, depression, cognition and emotional processing were evaluated on both CV and on CC stimulation. Analysis using the paired t test with Bonferroni correction for multiple comparisons was performed to identify any significant difference between the stimulation modalities. Results: 8 patients were recruited (6 men, 2 women); 1 patient did not complete the study. The average age at surgery was 56.7 years (range 47-63). Disease duration at the time of surgery was 7.5 years (range 3-12). Patients were recruited 23.8 months (range 22.5-24) after surgery. At the postoperative study baseline, this patient group showed an average motor improvement of 69% (range 51-97) as measured by the change in UPDRS part III with stimulation alone. Levodopa equivalent medication was reduced on average by 67% (range 15-88). Patients were poorly compliant with PD diaries, and these did not yield useful information. The minor deterioration in quality-of-life scores (Parkinson's Disease Questionnaire-39, Quality of Life Enjoyment and Satisfaction Questionnaire) with CC stimulation were not statistically significant. Two measures of depression (Hamilton Rating Scale D17, Quick Inventory of Depressive Symptomatology - Self-Report) showed a nonsignificant lower score (less depression) with CC stimulation, but a third (Beck Depression Inventory) showed equivalence. Cognitive testing (Mini Mental State Examination) and emotional processing (Montreal Affective Voices) were equivalent for CC and CV. Conclusion: CC STN DBS is safe. For equivalent motor efficacy, no significant difference could be identified between CC and CV stimulation for nonmotor evaluations in PD patients 2 years after surgery.

Weight gain following subthalamic nucleus deep brain stimulation: a PET study.

Several hypotheses have been put forward to explain weight gain after deep brain stimulation (DBS), but none provides a fully satisfactory account of this adverse effect. We analyzed the correlation between changes in brain metabolism (using positron emission tomography [PET] imaging) and weight gain after bilateral subthalamic nucleus DBS in patients with Parkinson's disease. Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose 3 months before and 4 months after the start of subthalamic nucleus deep brain stimulation in 23 patients with Parkinson's disease. Motor complications (United Parkinson's Disease Rating Scale [UPDRS]-IV scores) and dopaminergic medication were included in the analysis to control for their possible influence on brain metabolism. Mean ± standard deviation (SD) body mass index increased significantly by 0.8 ± 1.5 kg/m(2) (P = 0.03). Correlations were found between weight gain and changes in brain metabolism in limbic and associative areas, including the orbitofrontal cortex (Brodmann areas [BAs] 10 and 11), lateral and medial parts of the temporal lobe (BAs 20, 21, 22,39 and 42), anterior cingulate cortex (BA 32), and retrosplenial cortex (BA 30). However, we found no correlation between weight gain and metabolic changes in sensorimotor areas. These findings suggest that changes in associative and limbic processes contribute to weight gain after subthalamic nucleus DBS in Parkinson's disease.

Evaluating Indirect Subthalamic Nucleus Targeting with Validated 3-Tesla Magnetic Resonance Imaging

Background/Objectives: Indirect targeting of the subthalamic nucleus (STN) is commonly utilized at deep brain stimulation (DBS) centers around the world. The superiority of either midcommissural point (MCP)-based or red nucleus (RN)-based indirect targeting remains to be established. Methods: The location of the STN was determined and statistically compared to MCP- and RN-based predictions in 58 STN DBS patients, using a validated 3-tesla MRI protocol. The influence of additional neuroanatomical parameters on STN midpoint location was evaluated. Linear regression analysis was utilized to produce an optimized MCP/RN targeting model. Targeting coordinates at 1.5 T were compared to results at 3 T. Results: Accuracy and precision for RN-based targeting was superior to MCP-based targeting to predict STN midpoint location for each coordinate dimension (p < 0.01 and p < 0.05, respectively). RN-based targeting was statistically equivalent to an optimized regression-based targeting strategy incorporating multiple neuroanatomical parameters, including third-ventricle width and overall brain size. RN-based targeting at 1.5 T yielded equivalent coordinates to targeting at 3 T. Conclusions: RN-based targeting is statistically superior to MCP-based STN targeting and accommodates broad variations in neuroanatomical parameters. Neurosurgeons utilizing indirect targeting of the STN may consider favoring RN-based over MCP-based indirect targeting methods.

Brittle Dyskinesia Following STN but not GPi Deep Brain Stimulation.

BackgroundThe aim was to describe the prevalence and characteristics of difficult to manage dyskinesia associated with subthalamic nucleus (STN) deep brain stimulation (DBS). A small subset of STN DBS patients experience troublesome dyskinesia despite optimal programming and medication adjustments. This group of patients has been referred to by some practitioners as brittle STN DBS-induced dyskinesia, drawing on comparisons with brittle diabetics experiencing severe blood sugar regulation issues and on a single description by McLellan in 1982. We sought to describe, and also to investigate how often the “brittle” phenomenon occurs in a relatively large DBS practice.MethodsAn Institutional Review Board-approved patient database was reviewed, and all STN and globus pallidus internus (GPi) DBS patients who had surgery at the University of Florida from July 2002 to July 2012 were extracted for analysis.ResultsThere were 179 total STN DBS patients and, of those, four STN DBS (2.2%) cases were identified as having dyskinesia that could not be managed without the induction of an “off state,” or by the precipitation of a severe dyskinesia despite vigorous stimulation and medication adjustments. Of 75 GPi DBS cases reviewed, none (0%) was identified as having brittle dyskinesia. One STN DBS patient was successfully rescued by bilateral GPi DBS.DiscussionUnderstanding the potential risk factors for postoperative troublesome and brittle dyskinesia may have an impact on the initial surgical target selection (STN vs. GPI) in DBS therapy. Rescue GPi DBS therapy may be a viable treatment option, though more cases will be required to verify this observation.