Objective clinical registration of tremor, bradykinesia, and rigidity during awake stereotactic neurosurgery: a scoping review.

Tremor, bradykinesia, and rigidity are incapacitating motor symptoms that can be suppressed with stereotactic neurosurgical treatment like deep brain stimulation (DBS) and ablative surgery (e.g., thalamotomy, pallidotomy). Traditionally, clinicians rely on clinical rating scales for intraoperative evaluation of these motor symptoms during awake stereotactic neurosurgery. However, these clinical scales have a relatively high inter-rater variability and rely on experienced raters. Therefore, objective registration (e.g., using movement sensors) is a reasonable extension for intraoperative assessment of tremor, bradykinesia, and rigidity. The main goal of this scoping review is to provide an overview of electronic motor measurements during awake stereotactic neurosurgery. The protocol was based on the PRISMA extension for scoping reviews. After a systematic database search (PubMed, Embase, and Web of Science), articles were screened for relevance. Hundred-and-three articles were subject to detailed screening. Key clinical and technical information was extracted. The inclusion criteria encompassed use of electronic motor measurements during stereotactic neurosurgery performed under local anesthesia. Twenty-three articles were included. These studies had various objectives, including correlating sensor-based outcome measures to clinical scores, identifying optimal DBS electrode positions, and translating clinical assessments to objective assessments. The studies were highly heterogeneous in device choice, sensor location, measurement protocol, design, outcome measures, and data analysis. This review shows that intraoperative quantification of motor symptoms is still limited by variable signal analysis techniques and lacking standardized measurement protocols. However, electronic motor measurements can complement visual evaluations and provide objective confirmation of correct placement of the DBS electrode and/or lesioning. On the long term, this might benefit patient outcomes and provide reliable outcome measures in scientific research.

The Relevance of Intraoperative Clinical and Accelerometric Measurements for Thalamotomy Outcome.

Thalamotomy alleviates medication-refractory tremors in patients with movement disorders such as Parkinson's Disease (PD), Essential tremor (ET), and Holmes tremor (HT). However, limited data are available on tremor intensity during different thalamotomy stages. Also, the predictive value of the intraoperative tremor status for treatment outcomes remains unclear. Therefore, we aimed to quantify tremor status during thalamotomy and postoperatively. Data were gathered between January 2020 and June 2023 during consecutive unilateral thalamotomy procedures in patients with PD (n = 13), ET (n = 8), and HT (n = 3). MDS-UPDRS scores and tri-axial accelerometry data were obtained during rest, postural, and intention tremor tests. Measurements were performed intraoperatively (1) before lesioning-probe insertion, (2) directly after lesioning-probe insertion, (3) during coagulation, (4) directly after coagulation, and (5) 4-6 months post-surgery. Accelerometric data were recorded continuously during the coagulation process. Outcome measures included MDS-UPDRS tremor scores and accelerometric parameters (peak frequency, tremor amplitude, and area under the curve of power (AUCP)). Tremor intensity was assessed for the insertion effect (1-2), during coagulation (3), post-coagulation effect (1-4), and postoperative effect (1-5). Following insertion and coagulation, tremor intensity improved significantly compared to baseline (p < 0.001). The insertion effect clearly correlated with the postoperative effect (ρ = 0.863, p < 0.001). Both tremor amplitude and AUCP declined gradually during coagulation. Peak frequency did not change significantly intraoperatively. In conclusion, the study data show that both the intraoperative insertion effect and the post-coagulation effect are good predictors for thalamotomy outcomes.

The Intraoperative Microlesion Effect Positively Correlates With the Short-Term Clinical Effect of Deep Brain Stimulation in Parkinson's Disease.

OBJECTIVE: During the surgical procedure of deep brain stimulation (DBS), insertion of an electrode in the subthalamic nucleus (STN) frequently causes a temporary improvement of motor symptoms, known as the microlesion effect (MLE). The objective of this study was to determine the correlation between the intraoperative MLE and the clinical effect of DBS. MATERIALS AND METHODS: Thirty Parkinson's disease (PD) patients with Movement Disorder Society (MDS) Unified Parkinson's Disease Rating Scale (UPDRS) part III (MDS-UPDRS III) scores during bilateral STN-DBS implantation were included in this retrospective study. MDS-UPDRS III subscores (resting tremor, rigidity, and bradykinesia) of the contralateral upper extremity were used. During surgery, these subscores were assessed directly before and after insertion of the electrode. Also, these subscores were determined in the outpatient clinic after 11 weeks on average (on-stimulation). All assessments were performed in an off-medication state (at least 12 hours of medication washout). RESULTS: Postinsertion MDS-UPDRS motor scores decreased significantly compared to preinsertion scores (p < 0.001 for both hemispheres). The MLE showed a positive correlation with the clinical effect of DBS in both hemispheres (rho = 0.68 for the primarily treated hemisphere, p < 0.001, and rho = 0.59 for the secondarily treated hemisphere, p < 0.01). CONCLUSION: The MLE has a clinically relevant correlation with the effect of DBS in PD patients. These results suggest that the MLE can be relied upon as evidence of a clinically effective DBS electrode placement.

STN-DBS electrode placement accuracy and motor improvement in Parkinson's disease: systematic review and individual patient meta-analysis.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective neurosurgical treatment for Parkinson's disease. Surgical accuracy is a critical determinant to achieve an adequate DBS effect on motor performance. A two-millimetre surgical accuracy is commonly accepted, but scientific evidence is lacking. A systematic review and meta-analysis of study-level and individual patient data (IPD) was performed by a comprehensive search in MEDLINE, EMBASE and Cochrane Library. Primary outcome measures were (1) radial error between the implanted electrode and target; (2) DBS motor improvement on the Unified Parkinson's Disease Rating Scale part III (motor examination). On a study level, meta-regression analysis was performed. Also, publication bias was assessed. For IPD meta-analysis, a linear mixed effects model was used. Forty studies (1391 patients) were included, reporting radial errors of 0.45-1.86 mm. Errors within this range did not significantly influence the DBS effect on motor improvement. Additional IPD analysis (206 patients) revealed that a mean radial error of 1.13±0.75 mm did not significantly change the extent of DBS motor improvement. Our meta-analysis showed a huge publication bias on accuracy data in DBS. Therefore, the current literature does not provide an unequivocal upper threshold for acceptable accuracy of STN-DBS surgery. Based on the current literature, DBS-electrodes placed within a 2 mm range of the intended target do not have to be repositioned to enhance motor improvement after STN-DBS for Parkinson's disease. However, an indisputable upper cut-off value for surgical accuracy remains to be established. PROSPERO registration number is CRD42018089539.

Treatment of subcutaneous nodules after infusion of apomorphine; a biopsy-controlled study comparing 4 frequently used therapies.

This study aimed to provide clinical evidence for existing treatments of subcutaneous nodules after subcutaneous infusion of apomorphine, using a biopsy-controlled prospective crossover design of four treatments. We demonstrated that dilution of apomorphine significantly improved patient satisfaction, while subcutaneous hydrocortisone reduced nodule size, however with no differences in the histopathology.

Long-Term Patient-Reported Outcome of Radiofrequency Thalamotomy for Tremor.

BACKGROUND: Thalamotomy is an endorsed treatment for medication-refractory tremor. It used to be the standard, but nowadays deep brain stimulation (DBS) has become the treatment option of choice. Nevertheless, DBS has the disadvantage of hardware failure, battery replacement, and frequent setting adjustment. Radiofrequency (RF) thalamotomy lacks these issues, is relatively inexpensive, and has a broad applicability in patients with significant comorbidity. Therefore, we analyzed the long-term patient-reported outcome of RF thalamotomy in a cohort of patients with an otherwise intractable tremor. METHODS: A single-center cohort of 27 consecutive patients with intractable tremor was assessed after unilateral RF thalamotomy. Over time, 4 patients had died because of non-related causes. In total, 21 patients responded to a telephone survey to assess their personal judgment on postoperative tremor severity, using a validated tremor scale, adverse events, recurrence, and patient satisfaction. The median time between surgery and telephone survey was 39 months (range 12-126). Seven patients had an additional analysis with postoperative imaging, video-assisted electromyography tremor registration, and a self-reported treatment effect (SRTE) assessment. RESULTS: Nineteen out of 21 patients (90.5%) reported absence or significant improvement of their tremor. The rating score (WHIGET/UPDRS-III) dropped significantly from a mean of 3.57 preoperatively to 1.05 postoperatively (p < 0.001). Eleven patients (52.4%) reported adverse events, but the majority (76.2%) did not consider the adverse events to be severe. SRTE assessment showed a direct postoperative effect of 89.6 of 100 points (SD 10.8), with a gradual decrease to 75.3 (SD 23.5) during follow-up. CONCLUSIONS: RF thalamotomy is a very effective long-term treatment for medication-refractory tremor and should therefore be considered in patients with a refractory unilateral tremor.

[Deep brain stimulation for movement disorders]. / Diepe hersenstimulatie voor bewegingsstoornissen.

Deep brain stimulation (DBS) is a treatment which uses high-frequency electric stimulation to suppress pathological brain activity. DBS has been applied for over 30 years now, particularly in patients with severe movement disorders, such as Parkinson's disease, dystonia and tremor. Although there is clearly scientific evidence for the effectiveness of DBS in these three movement disorders, the effect size of the treatment remains limited. Furthermore, DBS is not curative and can only be applied in a select subset of patients. In this article, we discuss the key indications and contraindications for DBS, and the outcomes achieved when it is applied in the aforementioned movement disorders. We discuss the most notable controversies and new developments in the field of deep brain stimulation, in order to offer referrers and fellow healthcare professionals an accessible introduction to this mode of therapy.

Parkinson's disease and long-term exposure to outdoor air pollution: A matched case-control study in the Netherlands.

BACKGROUND: There is some evidence to suggest an association between ambient air pollution and development of Parkinson's disease (PD). However, the small number of studies published to date has reported inconsistent findings. OBJECTIVES: To assess the association between long-term exposure to ambient air pollution constituents and the development of PD. METHODS: Air pollution exposures (particulate matter with aerodynamic diameter <10 µm [PM10], <2.5 µm [PM2.5], between 2.5 µm and 10 µm [PMcoarse], black carbon, and nitrogen oxides [NO2 and NOx]) were predicted based on land-use regression models developed within the "European Study for Air Pollution Effects" (ESCAPE) study, for a Dutch PD case-control study. A total of 1290 subjects (436 cases and 854 controls). were included and 16 years of exposure were estimated (average participant starting age: 53). Exposures were categorized and conditional logistic regression models were applied to evaluate the association between ambient air pollution and PD. RESULTS: Overall, no significant, positive relationship between ambient air pollutants and PD was observed. The odds ratio (OR) for PD associated with an increase from the first quartile of NO2 (<22.8 µg/m3) and the fourth (>30.4 µg/m3) was 0.87 (95% CI: 0.54, 1.41). For PM2.5 where the contrast in exposure was more limited, the OR associated with an increase from the first quartile PM2.5 (<21.2 µg/m3) to the fourth (>22.3 µg/m3) was 0.50 (95% CI: 0.24, 1.01). In a subset of the population with long-term residential stability (n = 632), an increased risk of PD was observed (e.g. OR for Q4 vs Q1 NO2:1.37, 95% CI: 0.71, 2.67). CONCLUSIONS: We found no clear association between 16 years of residential exposure to ambient air pollution and the development of PD in The Netherlands.

Accuracy of Intraoperative Computed Tomography in Deep Brain Stimulation-A Prospective Noninferiority Study.

INTRODUCTION: Clinical response to deep brain stimulation (DBS) strongly depends on the appropriate placement of the electrode in the targeted structure. Postoperative MRI is recognized as the gold standard to verify the DBS-electrode position in relation to the intended anatomical target. However, intraoperative computed tomography (iCT) might be a feasible alternative to MRI. MATERIALS AND METHODS: In this prospective noninferiority study, we compared iCT with postoperative MRI (24-72 hours after surgery) in 29 consecutive patients undergoing placement of 58 DBS electrodes. The primary outcome was defined as the difference in Euclidean distance between lead tip coordinates as determined on both imaging modalities, using the lead tip depicted on MRI as reference. Secondary outcomes were difference in radial error and depth, as well as difference in accuracy relative to target. RESULTS: The mean difference between the lead tips was 0.98 ± 0.49 mm (0.97 ± 0.47 mm for the left-sided electrodes and 1.00 ± 0.53 mm for the right-sided electrodes). The upper confidence interval (95% CI, 0.851 to 1.112) did not exceed the noninferiority margin established. The average radial error between lead tips was 0.74 ± 0.48 mm and the average depth error was determined to be 0.53 ± 0.40 mm. The linear Deming regression indicated a good agreement between both imaging modalities regarding accuracy relative to target. CONCLUSIONS: Intraoperative CT is noninferior to MRI for the verification of the DBS-electrode position. CT and MRI have their specific benefits, but both should be considered equally suitable for assessing accuracy.

Substituting the Target After Unsatisfactory Outcome of Deep Brain Stimulation in Advanced Parkinson's Disease: Cases From the NSTAPS Trial and Systematic Review of the Literature.

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN) are established treatment option in Parkinson's disease (PD). If DBS does not provide the desired effect, re-operation to the alternative target is a treatment option, but data on the effect of re-operation are scarce. OBJECTIVES: The objective of this study is to evaluate the clinical effect of re-operation the alternative target after failure of initial STN or GPi DBS for Parkinson's disease. MATERIALS AND METHODS: We descriptively analyzed the baseline characteristics, the effect of initial surgery and re-operation of eight NSTAPS (Netherlands SubThalamic and Pallidal Stimulation) patients and six previously published cases that underwent re-operation to a different target. RESULTS: In the NSTAPS cohort, two of the eight patients showed more than 30% improvement of off-drug motor symptoms after re-operation. The initial DBS leads of these patients were off target. In the cases from the literature, 30% off-drug motor improvement was seen in all three patients re-operated from GPi to STN and none of the three patients re-operated from STN to GPi. Only one of the three cases from the literature where any improvement was seen with the operation had a confirmed on target lead location after the first surgery, while the other two patients did not undergo post-operative imaging after the first surgery. CONCLUSIONS: Re-operation to a different target due to lack of effect appears to have a limited chance of leading to objective improvement if the leads were correctly placed during initial surgery.

Environmental exposure to pesticides and the risk of Parkinson's disease in the Netherlands.

BACKGROUND: Exposure to pesticides has been linked to Parkinson's disease (PD), although associations between specific pesticides and PD have not been well studied. Residents of rural areas can be exposed through environmental drift and volatilization of agricultural pesticides. OBJECTIVES: Our aim was to investigate the association between lifetime environmental exposure to individual pesticides and the risk of PD, in a national case-control study. METHODS: Environmental exposure to pesticides was estimated using a spatio-temporal model, based on agricultural crops around the residential address. Distance up to 100m from the residence was considered most relevant, considering pesticide drift potential of application methods used in the Netherlands. Exposure estimates were generated for 157 pesticides, used during the study period, of which four (i.e. paraquat, maneb, lindane, benomyl) were considered a priori relevant for PD. RESULTS: A total of 352 PD cases and 607 hospital-based controls were included. No significant associations with PD were found for the a priori pesticides. In a hypothesis generating analysis, including 153 pesticides, increased risk of PD was found for 21 pesticides, mainly used on cereals and potatoes. Results were suggestive for an association between bulb cultivation and PD. CONCLUSIONS: For paraquat, risk estimates for the highest cumulative exposure tertile were in line with previously reported elevated risks. Increased risk of PD was observed for exposure to (a cluster of) pesticides used on rotating crops. High correlations limited our ability to identify individual pesticides responsible for this association. This study provides some evidence for an association between environmental exposure to specific pesticides and the risk of PD, and generates new leads for further epidemiological and mechanistic research.

Occupational exposure to solvents, metals and welding fumes and risk of Parkinson's disease.

OBJECTIVES: The aim of this study was to investigate the potential association between occupational exposure to solvents, metals and/or welding fumes and risk of developing Parkinson's disease (PD). METHODS: Data of a hospital based case-control study including 444 PD patients and 876 age and sex matched controls was used. Occupational histories and lifestyle information of cases and controls were collected in a structured telephone interview. Exposures to aromatic solvents, chlorinated solvents and metals were estimated by linking the ALOHA+ job-exposure matrix to the occupational histories. Exposure to welding fumes was estimated using self-reported information on welding activities. RESULTS: No statistically significant associations with any of the studied metal and solvent exposures were found. However, for self-reported welding activities we observed non-statistically significant reduced risk estimates (third tertile cumulative exposure: OR = 0.51 (95% CI: 0.21-1.24)). CONCLUSIONS: The results of our study did not provide support for an increased chance on developing PD after occupational exposure to aromatic solvents, chlorinated solvents or exposure to metals. The results showed reduced risk estimates for welding, which is in line with previous research, but no clear explanation for these findings is available.

Extremely low-frequency magnetic field exposure, electrical shocks and risk of Parkinson's disease.

PURPOSE: Previous studies did not provide strong evidence for an increased Parkinson's disease (PD) risk after exposure to extremely low-frequency magnetic fields (ELF-MF), but were limited in their scope to address other exposures related to the use of electricity such as electrical shocks. We evaluated the associations of PD with exposure to ELF-MF, electrical shocks and having worked in "electrical occupations." METHODS: We conducted a hospital-based case-control study, including 444 PD patients and 876 age- and sex-matched controls. Occupational histories were collected in telephone interviews and were linked to job-exposure matrices on ELF-MF exposure and on electrical shocks. In addition, questions on use of household appliances involving ELF-MF exposure, experienced electrical shocks and potential confounders were asked. RESULTS: No association of PD risk with any of the evaluated exposures related to electricity was observed. We did, however, observe quite consistently reduced risk estimates across the majority of the exposure categories explored. Given the results of the previous studies and the absence of any postulated mechanism, this is unlikely to represent a true protective effect of ELF-MF or electrical shocks on the occurrence of PD. CONCLUSIONS: The results of this study suggest that no association exists between PD and exposure to ELF-MF, electrical shocks or having worked in "electrical occupations."

Occupational exposure to pesticides and endotoxin and Parkinson disease in the Netherlands.

OBJECTIVES: Previous research has indicated that occupational exposure to pesticides and possibly airborne endotoxin may increase the risk of developing Parkinson disease (PD). We studied the associations of PD with occupational exposure to pesticides, specifically to the functional subclasses insecticides, herbicides and fungicides, and to airborne endotoxin. In addition we evaluated specific pesticides (active ingredients) previously associated with PD. METHODS: We used data from a hospital-based case-control study, including 444 patients with PD and 876 age and sex matched controls. Exposures to pesticides from application and re-entry work were estimated with the ALOHA+job-exposure matrix and with an exposure algorithm based on self-reported information on pesticide use. To assess exposure to specific active ingredients a crop-exposure matrix was developed. Endotoxin exposure was estimated with the DOM job-exposure matrix. RESULTS: The results showed almost no significant associations. However, ORs were elevated in the higher exposure categories for pesticides in general, insecticides, herbicides and fungicides, and below unity for endotoxin exposure. The analyses on specific active ingredients showed a significant association of PD risk with the fungicide benomyl. CONCLUSIONS: This study did not provide evidence for a relation between pesticide exposure and PD. However, the consistently elevated ORs in the higher exposure categories suggest that a positive association may exist. The possible association with the active ingredient benomyl requires follow-up in other studies. This study did not provide support for a possible association between endotoxin exposure and PD.

A case-control study of the protective effect of alcohol, coffee, and cigarette consumption on Parkinson disease risk: time-since-cessation modifies the effect of tobacco smoking.

The aim of this study was to investigate the possible reduced risk of Parkinson Disease (PD) due to coffee, alcohol, and/or cigarette consumption. In addition, we explored the potential effect modification by intensity, duration and time-since-cessation of smoking on the association between cumulative pack-years of cigarette smoking (total smoking) and PD risk. Data of a hospital based case-control study was used including 444 PD patients, diagnosed between 2006 and 2011, and 876 matched controls from 5 hospitals in the Netherlands. A novel modeling method was applied to derive unbiased estimates of the potential modifying effects of smoking intensity, duration, and time-since-cessation by conditioning on total exposure. We observed no reduced risk of PD by alcohol consumption and only a weak inverse association between coffee consumption and PD risk. However, a strong inverse association of total smoking with PD risk was observed (OR=0.27 (95%CI: 0.18-0.42) for never smokers versus highest quartile of tobacco use). The observed protective effect of total smoking was significantly modified by time-since-cessation with a diminishing protective effect after cessation of smoking. No effect modification by intensity or duration of smoking was observed indicating that both intensity and duration have an equal contribution to the reduced PD risk. Understanding the dynamics of the protective effect of smoking on PD risk aids in understanding PD etiology and may contribute to strategies for prevention and treatment.

The added value of semimicroelectrode recording in deep brain stimulation of the subthalamic nucleus for Parkinson disease.

OBJECT: Accurate placement of the leads is crucial in deep brain stimulation (DBS). To optimize the surgical positioning of the lead, a combination of anatomical targeting on MRI, electrophysiological mapping, and clinical testing is applied during the procedure. Electrophysiological mapping is usually done with microelectrode recording (MER), but the relatively undocumented semimicroelectrode recording (SMER) is a competing alternative. In this study the added value and safety of SMER for optimal lead insertion in the subthalamic nucleus (STN) in a consecutive cohort of patients with Parkinson disease (PD) was assessed. METHODS: Between 2001 and 2010, a consecutive single-center cohort of 46 patients with PD underwent DBS of the STN (85 lead insertions). After exclusion of 11 lead insertions for mostly technical reasons, 74 insertions were included for the assessment. Anatomical target localization was based on either 1.5-T MRI or fused 3-T MRI with CT, with reference to anterior commissure-posterior commissure coordinates. Electrophysiological mapping was performed with SMER. Intraoperative clinical testing was dominant in determining the final lead position. The target error was defined as the absolute distance between the anatomical or electrophysiological target and the final lead position. The effect of SMER on anatomical target error reduction and final target selection was analyzed. Also, the anatomical and electrophysiological target error was judged against the different imaging strategies. For safety evaluation, the adverse events related to all lead insertions were assessed. RESULTS: The use of SMER significantly reduced the anatomical target error from 1.7 (SD 1.6) mm to 0.8 (SD 1.3) mm (p < 0.0001). In particular, the anatomical target error based on 1.5-T MRI was significantly reduced by SMER, from 2.3 (SD 1.5) mm to 0.1 (SD 0.5) mm (p < 0.001). Anatomical target error reduction based on 3-T MRI fused with CT was not significantly influenced by SMER (p = 0.2), because the 3-T MRI-CT combination already significantly reduced the anatomical target error from 2.3 (SD 1.5) mm to 1.5 (SD 1.5) mm compared with 1.5-T MRI (p = 0.03). No symptomatic intracerebral hemorrhage was reported. Intracerebral infection was encountered in 1 patient following lead insertion. CONCLUSIONS: Semimicroelectrode recording has added value in targeting the STN in DBS for patients with PD based on 1.5-T MRI. The use of SMER does not significantly reduce the anatomical target error in procedures with fused 3-T MRI-CT studies and therefore might be omitted. With the absence of hemorrhagic complications, SMER-guided lead implantation should be considered a safe alternative to MER.

Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial.

BACKGROUND: Patients with advanced Parkinson's disease often have rapid swings between mobility and immobility, and many respond unsatisfactorily to adjustments in pharmacological treatment. We assessed whether globus pallidus pars interna (GPi) deep brain stimulation (DBS) gives greater functional improvement than does subthalamic nucleus (STN) DBS. METHODS: We recruited patients from five centres in the Netherlands who were aged 18 years or older, had idiopathic Parkinson's disease, and had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. By use of a computer-generated randomisation sequence, we randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a minimisation procedure according to drug use (levodopa equivalent dose <1000 mg vs ≥1000 mg) and treatment centre. Patients and study assessors (but not those who assessed adverse events) were masked to treatment allocation. We had two primary outcomes: functional health as measured by the weighted Academic Medical Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and on phase) and a composite score for cognitive, mood, and behavioural effects up to 1 year after surgery. Secondary outcomes were symptom scales, activities of daily living scales, a quality-of-life questionnaire, the occurrence of adverse events, and drug use. We used the intention-to-treat principle for all analyses. This trial is registered with www.controlled-trials.com, number ISRCTN85542074. FINDINGS: Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients, assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant difference in either of our primary outcomes: mean change in weighted ALDS (3·0 [SD 14·5] in the GPi group vs 7·7 [23·2] in the STN group; p=0·28) and the number of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62 patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0·94). Secondary outcomes showed larger improvements in off-drug phase in the STN group compared with the GPi group in the mean change in unified Parkinson's disease rating scale motor examination scores (20·3 [16·3] vs 11·4 [16·1]; p=0·03), the mean change in ALDS scores (20·3 [27·1] vs 11·8 [18·9]; p=0·04), and medication (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 [521]; p=0·01). We recorded no difference in the occurrence of adverse events between the two groups. Other secondary endpoints showed no difference between the groups. INTERPRETATION: Although there was no difference in our primary outcomes, our findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinson's disease. FUNDING: Stichting Internationaal Parkinson Fonds, Prinses Beatrix Fonds, and Parkinson Vereniging.

[Treatment of drooling in patients with parkinsonism]. / Behandeling van overmatige speekselvloed bij patiënten met parkinsonisme.

Between 50% and 60% of patients with parkinsonism suffer from severe drooling (sialorrhoea). Sialorrhoea is a major social problem with medical risks as well, e.g. aspiration pneumonia. Sialorrhoea is not caused by increased production of saliva, but by impaired swallowing, leading to storage of saliva in the anterior part of the mouth. Sialorrhoea can be treated by anticholinergics, botulinum toxin injections, surgery and radiotherapy of the salivary glands. The optimal treatment of sialorrhoea needs to be determined individually, for which a decision tree is available.

Managing Parkinson's disease with continuous dopaminergic stimulation.

The pathophysiology of Parkinson's disease is marked by the loss of dopaminergic neurons, which leads to striatal dopaminergic deficiency. This causes resting tremor, hypokinesia, rigidity, bradykinesia, and loss of postural reflexes. Most current treatments for Parkinson's disease aim to restore striatal dopamine signaling by increasing the supply of dopamine with oral levodopa (L-dopa), stimulating dopamine receptors directly using dopamine agonists, or inhibiting the reuptake of endogenous dopamine. L-dopa is standard therapy for patients with Parkinson's disease. However, with continued treatment and disease progression, the response to oral dopaminergic drugs becomes unstable and motor fluctuations emerge, including off periods and dyskinesia. Direct duodenal-administered infusible L-dopa/carbidopa is effective for the management of refractory motor fluctuations in some patient populations. However, enteral infusions cannot mimic the function of the normal dopaminergic brain, and around-the-clock constant-rate administration carries the risk of causing refractory off periods associated with severe immobility and hyperpyrexia. Subthalamic nucleus (STN) deep brain stimulation (DBS) is also a promising treatment. DBS passes a high-frequency electrical current into the target area, mimicking the effect of lesioning the stimulated area. However, this treatment requires invasive surgery and is appropriate for a limited segment of the patient population. This supplement provides a rationale for the use of continuous dopaminergic receptor stimulation and offers guidelines on the individualization of treatment decisions, with special focus on continuous L-dopa infusion and STN DBS. Erik Wolters, MD, PhD, offers an introduction to the impact of continuous L-dopa infusion. Andrew J. Lees, MD, FRCP, provides an overview of the physiologic response to L-dopa and reviews clinical pharmacologic studies of intravenous and intraduodenal L-dopa. Jens Volkmann, MD, discusses selection criteria for STN DBS and duodenal L-dopa/carbidopa infusion. Teus van Laar, MD, PhD, and Ad Hovestadt, MD, discuss the first data from a Dutch cohort study of duodenal L-dopa/carbidopa.

Radiotherapy to the salivary glands as treatment of sialorrhea in patients with parkinsonism.

This study investigated retrospectively the long-term efficacy and safety of radiotherapy (RT) to the major salivary glands as treatment of sialorrhea in patients with parkinsonism. Twenty-eight patients received a bilateral dose of 12 Gy to the parotid and part of the submandibular glands between 2001 and 2006. Severity of sialorrhea and adverse events were assessed at 1 and 6 months post-RT and finally in the first quarter of 2007. Item 6 of the activities of daily living-section of the Unified Parkinson's Disease Rating Scale was used as primary endpoint. Quality of life (QoL) pre- and post-RT was investigated using a shortened Parkinson's Disease Questionnaire-8. Sialorrhea had improved significantly at 1 month post-RT and this effect was maintained for at least 1 year. Most frequent adverse events were loss of taste and a dry mouth; however, 75% of these adverse events were transient. QoL had improved significantly on the long term. The clinical global impression scores at the final follow-up showed that 80% of patients were satisfied. It was concluded that RT is an effective and safe treatment of sialorrhea on the long term in patients with parkinsonism.