Fear of Progression is Determined by Anxiety and Self-Efficacy but not Disease-Specific Parameters in Patients with Parkinson's Disease: Preliminary Data from a Multicenter Cross-Sectional Study.

BACKGROUND: Fear of progression (FoP) is a reactive, conscious concern about chronic disease progression and its consequences which may limit quality of life substantially. Only one study has examined FoP in Parkinson's disease (PD), showing the second highest FoP scores among chronic diseases. OBJECTIVE: To examine FoP prevalence and to exploratorily analyze determinants of FoP in PD. METHODS: Within a multicenter cross-sectional study, 120 PD inpatients (age: 64.45±9.20; 60.8% male; UPDRS-III: 28.86±16.12) were examined with the FoP questionnaire (FoP-Q; max. 20 points). Stepwise multiple linear regression analysis examined sociodemographic, clinical, and (neuro-) psychological determinants of FoP. RESULTS: With a mean FoP-Q score of 8.08±2.17, 63.0% of the patients were classified with moderate FoP and 17.6% with dysfunctional (i.e., severe) FoP. The highest scores were shown for the subscale 'loss of autonomy'. Increased levels of anxiety, less self-efficacy, female gender, current employment, and lower health literacy were identified as significant determinants associated with FoP. CONCLUSION: With more than 80% of patients showing moderate to dysfunctional FoP, it must be regarded as a frequent symptom in PD, which needs to be further understood and addressed in clinical practice. Clinical parameters like PD duration and severity were no determinants for FoP, indicating that FoP awareness must be considered by professionals at all disease stages.

Feasibility of Music-Assisted Treadmill Training in Parkinson's Disease Patients With and Without Deep Brain Stimulation: Insights From an Ongoing Pilot Randomized Controlled Trial.

Background: Music-assisted treadmill training (MATT) is a new therapeutic approach for Parkinson's disease (PD) patients, combining treadmill training with rhythmic auditory cueing and visual feedback. PD studies have shown larger positive effects on motor outcomes than usual treadmill training. However, effects on cognition, in contrast, are less clear. Existing studies provided intensive training protocols and included only stable medicated patients. Thus, a pilot randomized controlled trial was designed to analyze the feasibility of a shorter training protocol as well as preliminary effects on cognition, motor function, and patient-centered outcomes in a rehabilitation setting where PD patients with and without deep brain stimulation (DBS) undergo adaptation of medication and DBS settings. Here, we present the results from the feasibility analysis of the still ongoing trial. Methods: Non-demented PD patients with and without DBS were recruited during their inpatient rehabilitation and randomized to an experimental group (EG; 20 min MATT) or an active control group (CG; 20 min bike ergometer training). The trainings took place for 8 consecutive days and were added to the usual rehabilitation. Feasibility was assessed with the following parameters: patients' study protocol acceptance, study protocol transferability into clinical routine, training-induced adverse events, and patients' training perception. Results: Thirty-two patients (EG: n = 15; CG: n = 17; 72% DBS) were included. The study protocol was well-accepted (inclusion rate: 84%). It was transferable into clinical routines; dropout rates of 40% (EG) and 18% (CG) were observed. However, an in-depth analysis of the dropout cohort did not reveal intervention-related dropout reasons. The MATT and the standard ergometer training showed no adverse events and were positively perceived by PD patients with and without DBS. Conclusion: MATT was shown to be a feasible, safe, and enjoyable treatment option in PD patients with and without DBS. Furthermore, the dropout cohort analysis revealed some exciting first insights into possible dropout reasons that go beyond the form of intervention. Therefore, research would benefit from a common practice of dropout analyses, as this would enhance our understanding of patients' therapy adherence and expectations.

DBS dysfunction mimicking transient ischemic attacks-a case report.

We report on a patient with thalamic deep brain stimulation (DBS) for essential tremor who was admitted to a stroke unit with transient vertigo, dysarthria, and gait disturbance. Transient ischemic attacks were assumed but fluctuating neurological symptoms persisted until presentation to a DBS center. Here, unstable high monopolar impedances of the right-hemispheric electrode contacts were detected. Surgical revision revealed a fracture of the pocket adaptor connecting this electrode to the impulse generator. Replacement resulted in stable impedances and remitted the transient neurological symptoms. Emergency and stroke doctors should be aware of neurological symptoms induced by technical dysfunctions in DBS.

Unstable impedance of a single electrode contact resulting in loss of DBS therapy-a case report.

Open and short circuits of electrode contacts are important technical dysfunctions of DBS. Here, we report on another type of dysfunction restricted to a single electrode contact: impedance instability within regular absolute values. After 9-year subthalamic DBS, a Parkinson patient developed unilateral motor symptoms and intermittent dysaesthesia due to impedance instability of the active contact. DBS efficacy could be restored without surgical revision by activation of the neighboring contact. During 3-year-follow-up, impedances of the dysfunctional contact varied between 1 and 3 kΩ whereas the other three contacts remained stable. Impedance documentation is crucial to identify such dysfunctions.

DBS of the PSA and the VIM in essential tremor: A randomized, double-blind, crossover trial.

OBJECTIVE: To evaluate deep brain stimulation (DBS) of the posterior subthalamic area (PSA) in essential tremor (ET) and compare it to the ventral intermediate nucleus of the thalamus (VIM) in terms of stimulation efficacy, efficiency, and side effects. METHODS: DBS leads were implanted such that contacts were placed in the VIM, on the intercommissural line, and in the PSA. Thirteen patients with ET entered a randomized, double-blind crossover phase and completed a 1-year follow-up. RESULTS: PSA-DBS significantly reduced tremor severity and improved quality of life. There were no relevant differences in quality and frequency of stimulation side effects between VIM and PSA, with a tendency toward greater tremor improvement with PSA stimulation. Clinical benefit was achieved at significantly lower stimulation amplitudes in the PSA. The majority of patients remained with PSA-DBS after 1 year. CONCLUSION: In accordance with previous retrospective investigations, our prospective data suggest that PSA-DBS is at least equally effective as but possibly more efficient than VIM-DBS. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with essential tremor, PSA-DBS is not significantly different from VIM-DBS in suppressing tremor, but clinical benefit from PSA-DBS is attained at lower stimulation amplitudes.

DBS Electrodes With Single Disconnected Contacts: Long-Term Observation and Implications for the Management.

OBJECTIVES: To evaluate the long-term course of quadripolar DBS electrodes with disconnected single contacts that cannot be used for DBS. MATERIALS AND METHODS: Quadripolar electrodes with open circuits of single contacts or monopolar impedances >6500 Ω were identified from a cohort of 2082 electrodes from 1044 patients with variable movement disorders. The long-term course was analyzed from follow-up data. RESULTS: Disconnected contacts were found in 58 electrodes (2.8%) from 49 patients (4.7%). The dysfunction was restricted to one contact in 51 electrodes (87.9%), two contacts in 5 electrodes (8.6%), three contacts in 2 electrodes (3.4%). Onset was related to surgery (implantation, impulse generator replacement, or other surgical revision) in 34 electrodes (58.6%), trauma in 2 electrodes, undetermined in 11 electrodes, and occurred spontaneously after previous normal measurements in 11 electrodes (19.0%). Repeated measurements at follow-ups of ≥3 months were available in 39 electrodes. In 16 electrodes (41.0%) abnormal impedances persisted constantly during observations up to 11½ years (47 ± 35 months, median 41 months). In 21 electrodes (53.8%) abnormal impedances remained restricted to the initial contact(s) but varied considerably between measurements during up to six years (39 ± 18 months, median 38 months). Only two electrodes (5.1%) with initially one disconnected contact developed a disconnection of a second contact. CONCLUSIONS: Disconnections of single contacts occur with increasing cumulative incidence during long-term DBS. Surgery is the main causative risk factor. In the majority of electrodes, the dysfunction remains restricted to the initial contact(s).

Postoperative rehabilitation after deep brain stimulation surgery for movement disorders.

Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy for a set of neurological and psychiatric conditions and especially movement disorders such as Parkinson's disease, essential tremor and dystonia. Recent developments have improved the DBS technology. However, no unequivocal algorithms for an optimized postoperative care exist so far. The aim of this review is to provide a synopsis of the current clinical practice and to propose guidelines for postoperative and rehabilitative care of patients who undergo DBS. A standardized work-up in the DBS centers adapted to each patient's clinical state and needs is important, including a meticulous evaluation of clinical improvement and residual symptoms with a definition of goals for neurorehabilitation. Efficient and complete information transfer to subsequent caregivers is essential. A coordinated therapy within a multidisciplinary team (trained in movement disorders and DBS) is needed to achieve the long-range maximal efficiency. An optimized postoperative framework might ultimately lead to more effective results of DBS.

Long-Term Stability of Short Circuits in Deep Brain Stimulation.

OBJECTIVES: To evaluate the long-term course of DBS electrodes with short-circuited contacts. MATERIALS AND METHODS: Electrodes with bipolar impedances below 150 Ω were identified from a cohort of 1044 patients with 2082 electrodes for variable movement disorders. The long-term course was analyzed from follow-up data. RESULTS: Short circuits were found in 62 electrodes (3.0%) from 60 patients (5.7%). They were restricted to two contacts in 57 electrodes (91.9%) and included more than two contacts in five electrodes. Onset was related to surgery (implantation, impulse generator replacements, or other surgical revisions) in 42 electrodes (67.7%). The onset was undetermined in 11 electrodes. In eight electrodes (12.9%) with previously normal impedances, the short circuit occurred spontaneously during long-term DBS and in one electrode after a fall. Repeated impedance checks at follow-ups of ≥3 months were available in 41 electrodes with short circuits. Twenty-six electrodes (63.4%) showed stable low impedances during observation up to nine years and two months (median 29 months). In four electrodes low impedances were stable until surgical revisions. In eight electrodes (19.5%) with observation up to nine years and seven months (median 54 months), short circuits were only detected intermittently but remained restricted to two contacts. In three electrodes (7.3%) intermittent short circuits between more than two contacts were found during long-term DBS. CONCLUSIONS: An increasing cumulative incidence demonstrates the clinical importance of short circuits. In the majority of electrodes, short circuits are restricted and remain restricted to two contacts during long-term stimulation.

Causes of failure of pallidal deep brain stimulation in cases with pre-operative diagnosis of isolated dystonia.

INTRODUCTION: Pallidal deep brain stimulation (GPi-DBS) is an effective therapy for isolated dystonia, but 10-20% of patients show improvement below 25-30%. We here investigated causes of insufficient response to GPi-DBS in isolated dystonia in a cross-sectional study. METHODS: Patients with isolated dystonia at time of surgery, and <30% improvement on the Burke-Fahn-Marsden dystonia-rating-scale (BFMDRS) after ≥6 months of continuous GPi-DBS were videotaped ON and OFF stimulation, and history, preoperative videos, brain MRI, medical records, stimulation settings, stimulation system integrity, lead location, and genetic information were obtained and reviewed by an expert panel. RESULTS: 22 patients from 11 centres were included (8 men, 14 women; 9 generalized, 9 segmental, 3 focal, 1 bibrachial dystonia; mean (range): age 48.7 (25-72) years, disease duration 22.0 (2-40) years, DBS duration 45.5 (6-131) months). Mean BFMDRS-score was 31.7 (4-93) preoperatively and 32.3 (5-101) postoperatively. Half of the patients (n = 11) had poor lead positioning alone or in combination with other problems (combined with: other disease n = 6, functional dystonia n = 1, other problems n = 2). Other problems were disease other than isolated inherited or idiopathic dystonia (n = 5), fixed deformities (n = 2), functional dystonia (n = 3), and other causes (n = 1). Excluding patients with poor lead location from further analysis, non-isolated dystonia accounted for 45.5%, functional dystonia for 27.3%, and fixed deformities for 18.2%. In patients with true isolated dystonia, lead location was the most frequent problem. CONCLUSION: After exclusion of lead placement and stimulation programming issues, non-isolated dystonia, functional dystonia and fixed deformities account for the majority of GPi-DBS failures in dystonia.

The Effect of Uni- and Bilateral Thalamic Deep Brain Stimulation on Speech in Patients With Essential Tremor: Acoustics and Intelligibility.

BACKGROUND: Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is performed to suppress medically-resistant essential tremor (ET). However, stimulation induced dysarthria (SID) is a common side effect, limiting the extent to which tremor can be suppressed. To date, the exact pathogenesis of SID in VIM-DBS treated ET patients is unknown. OBJECTIVE: We investigate the effect of inactivated, uni- and bilateral VIM-DBS on speech production in patients with ET. We employ acoustic measures, tempo, and intelligibility ratings and patient's self-estimated speech to quantify SID, with a focus on comparing bilateral to unilateral stimulation effects and the effect of electrode position on speech. METHODS: Sixteen German ET patients participated in this study. Each patient was acoustically recorded with DBS-off, unilateral-right-hemispheric-DBS-on, unilateral-left-hemispheric-DBS-on, and bilateral-DBS-on during an oral diadochokinesis task and a read German standard text. To capture the extent of speech impairment, we measured syllable duration and intensity ratio during the DDK task. Naïve listeners rated speech tempo and speech intelligibility of the read text on a 5-point-scale. Patients had to rate their "ability to speak". RESULTS: We found an effect of bilateral compared to unilateral and inactivated stimulation on syllable durations and intensity ratio, as well as on external intelligibility ratings and patients' VAS scores. Additionally, VAS scores are associated with more laterally located active contacts. For speech ratings, we found an effect of syllable duration such that tempo and intelligibility was rated worse for speakers exhibiting greater syllable durations. CONCLUSION: Our data confirms that SID is more pronounced under bilateral compared to unilateral stimulation. Laterally located electrodes are associated with more severe SID according to patient's self-ratings. We can confirm the relation between diadochokinetic rate and SID in that listener's tempo and intelligibility ratings can be predicted by measured syllable durations from DDK tasks.

Rapid battery depletion and loss of therapy due to a short circuit in bipolar DBS for essential tremor.

Technical dysfunctions have been reported reducing efficacy of deep brain stimulation (DBS). Here, we report on an essential-tremor patient in whom a short circuit in bipolar DBS resulted not only in unilateral loss of therapy but also in high current flow and thereby rapid decline of the impulse-generator battery voltage from 2.83 V a week before the event to 2.54 V, indicating the need for an impulse-generator replacement. Immediate re-programming restored therapeutic efficacy. Moreover, the reduction in current flow allowed the battery voltage to recover without immediate surgical intervention to 2.81 V a week later.

Deep brain stimulation of the posterior subthalamic area and the thalamus in patients with essential tremor: study protocol for a randomized controlled pilot trial.

BACKGROUND: Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is effective in medication refractory essential tremor (ET). In recent years, evidence has accumulated that the region ventral to the VIM, the posterior subthalamic area (PSA), might be an equally or even more effective target for electrode implantation. However, this evidence is primarily based on case series, cross-sectional observations, and retrospective data. METHODS/DESIGN: A prospective crossover pilot study investigating the effects of PSA stimulation in medication refractory ET patients was designed. In this study, bilateral electrodes are implanted such that at least one of the electrode contacts is located in the PSA and VIM, respectively. This implantation approach allows (1) a prospective double-blind investigation of the effects of PSA stimulation compared to baseline, as well as (2) a crossover comparison between VIM and PSA stimulation with respect to tremor suppression and side effect profiles. DISCUSSION: The results of this double-blinded, prospective study will allow a better understanding of the effects and side effects of PSA compared to VIM-DBS in patients with ET. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00004235 . Registered on 4 July 2012.

Arachnophobia alleviated by subthalamic nucleus stimulation for Parkinson's disease.

We report on a Parkinson patient with motor fluctuations and dyskinesias in whom deep brain stimulation (DBS) of the subthalamic nucleus (STN) not only improved motor symptoms but also pre-existing arachnophobia. Arachnophobia had been unchanged by the course of Parkinson's disease but rapidly improved with STN-DBS. Both, motor effects and the improvement of arachnophobia were stable during 2 years follow-up. To our knowledge this is the first report on STN stimulation effects on a specific phobia.

Postural Stability in Parkinson's Disease Patients Is Improved after Stochastic Resonance Therapy.

Background. Postural instability in Parkinson's disease (PD) increases the risk of falls and is not improved by pharmacological therapy. Objective. We performed a double-blind, randomized sham-controlled study to test the effects of stochastic resonance (whole body vibration) therapy on postural stability in PD. Methods. Fifty-six PD participants were allocated to either experimental or sham groups. The experimental group received four series of vibration over eight days, with each series consisting of six stimulus trains of 60-second duration using a randomized whole body vibration. Participants allocated to the control group received a sham treatment. Results. Within-group analysis revealed that postural stability in the experimental group improved by 17.5% (p = 0.005) comparing experimental and sham groups. The between-group analysis of change after treatment comparing both groups also showed a significant improvement of postural stability (p = 0.03). Only in the within-group analysis several items were improved after Bonferroni correction, too, rigor 41.6% (p = 0.001), bradykinesia 23.7% (p = 0.001), tremor 30.8% (p = 0.006), and UPDRSIII sum score 23.9% (p = 0.000), but did not reach the level of significance in the between-group analysis. Conclusions. Stochastic resonance therapy significantly enhanced postural stability even in individuals with increased risk of falling. Thus it offers a potential supplementation to canonical treatments of PD.

Referring Parkinson's disease patients for deep brain stimulation: a RAND/UCLA appropriateness study.

In 2005, a European expert panel developed and validated an electronic tool to support the appropriate referral of patients with Parkinson's disease (PD) for the consideration of deep brain stimulation (DBS). Since new evidence has become available over the last decade an update of the tool is necessary. A world-wide expert panel (71 neurologists and 11 neurosurgeons) used the RAND/UCLA Appropriateness Method to assess the appropriateness of referral for 1296 scenarios (9-point scale). Scenarios were permutations of 8 clinical variables relevant to the decision of referral. Appropriateness of referral was calculated on the basis of the median score and the extent of agreement. Compared to 2005, the impact of clinical variables on the appropriateness of referral was similar for severity of on-off fluctuations, dyskinesias and refractory tremor (positive association, p < 0.001), and cognitive impairment (negative association, p < 0.001). A relatively stronger negative impact was seen for levodopa-unresponsive gait and balance disturbances as well as older age, the latter most likely due to a higher cut-off value (75 versus 70 years in the previous study). The impact of PD duration on the appropriateness of referral was less pronounced than in 2005. The contribution of the newly included variable 'non-motor side effects of anti-PD medication' was very modest. Based on these results the panel produced new recommendations on the appropriateness of referral for the evaluation of DBS in PD patients. Differences from the previous study reflect the new clinical evidence, particularly related to the use of DBS in an earlier stage of PD. The validation of the updated recommendations is in progress.

Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson's disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study.

BACKGROUND: High-frequency deep brain stimulation (DBS) with a single electrical source is effective for motor symptom relief in patients with Parkinson's disease. We postulated that a multiple-source, constant-current device that permits well defined distribution of current would lead to motor improvement in patients with Parkinson's disease. METHODS: We did a prospective, multicentre, non-randomised, open-label intervention study of an implantable DBS device (the VANTAGE study) at six specialist DBS centres at universities in six European countries. Patients were judged eligible if they were aged 21-75 years, had been diagnosed with bilateral idiopathic Parkinson's disease with motor symptoms for more than 5 years, had a Hoehn and Yahr score of 2 or greater, and had a Unified Parkinson's disease rating scale part III (UPDRS III) score in the medication-off state of more than 30, which improved by 33% or more after a levodopa challenge. Participants underwent bilateral implantation in the subthalamic nucleus of a multiple-source, constant-current, eight-contact, rechargeable DBS system, and were assessed 12, 26, and 52 weeks after implantation. The primary endpoint was the mean change in UPDRS III scores (assessed by site investigators who were aware of the treatment assignment) from baseline (medication-off state) to 26 weeks after first lead implantation (stimulation-on, medication-off state). This study is registered with ClinicalTrials.gov, number NCT01221948. FINDINGS: Of 53 patients enrolled in the study, 40 received a bilateral implant in the subthalamic nucleus and their data contributed to the primary endpoint analysis. Improvement was noted in the UPDRS III motor score 6 months after first lead implantation (mean 13·5 [SD 6·8], 95% CI 11·3-15·7) compared with baseline (37·4 [8·9], 34·5-40·2), with a mean difference of 23·8 (SD 10·6; 95% CI 20·3-27·3; p<0·0001). One patient died of pneumonia 24 weeks after implantation, which was judged to be unrelated to the procedure. 125 adverse events were reported, the most frequent of which were dystonia, speech disorder, and apathy. 18 serious adverse events were recorded, three of which were attributed to the device or procedure (one case each of infection, migration, and respiratory depression). All serious adverse events resolved without residual effects and stimulation remained on during the study. INTERPRETATION: The multiple-source, constant-current, eight-contact DBS system suppressed motor symptoms effectively in patients with Parkinson's disease, with an acceptable safety profile. Future trials are needed to investigate systematically the potential benefits of this system on postoperative outcome and its side-effects. FUNDING: Boston Scientific.

Utilization of predefined stimulation groups by essential tremor patients treated with VIM-DBS.

OBJECTIVE: To identify the utilization and general acceptance of switching between predefined stimulation groups in essential tremor (ET) patients treated with deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus. METHODS: Thirty-eight patients treated with VIM-DBS completed a telephone survey. This was designed to identify the general utilization of patient controllers and the specific usage of stimulation groups. RESULTS: Thirty-eight patients were interviewed via phone. More than half (21 of 38 patients, 55%) of all contacted ET patients were aware of the possibility of switching between pre-defined stimulation programs themselves. Again, more than half of these patients (13 of the 21 patients) switch between the different programs on a regular basis (8 monthly, 2 weekly, and 3 daily), mainly due to occurring side effects. Age did not differ between the group of patients switching between stimulation groups, and those who did not (65.38 years (±11.36) vs. 69.15 years (±9.92), p = 0.297). CONCLUSION: Some patients frequently use different stimulation settings, mainly to be able to control side effects when necessary. All patients - independent of their age - and especially patients with stimulation induced side effects, should therefore be informed about the possibility to switch between predefined stimulation groups. We propose a training for patients by specialized nurses, to give them confidence in handling the patient controllers.