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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.

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.

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).

Zusammenfassung. Hintergrund: Patienten mit neurologischen Erkrankungen sehen sich mit einer Vielzahl motorischer und nicht-motorischer Problemlagen konfrontiert, die eine umfassende interdisziplinäre Behandlung erfordern. Hier greift die neurologische Rehabilitation. Psychologisch fundierte Interventionen bilden dabei einen wesentlichen Baustein der multimodalen und interdisziplinären Behandlung. In der klinischen Praxis fällt es jedoch oft schwer, aus der Vielzahl von Leitlinien zu ganz bestimmten Störungsaspekten konkrete Informationen für die Behandlung zu gewinnen und auf den Einzelfall anzuwenden. Vor diesem Hintergrund wurden im Rahmen zweier Projekte evidenzbasierte Praxisempfehlungen für psychologische Interventionen in der neurologischen Rehabilitation entwickelt, die das gesamte interdisziplinäre Team darin unterstützen sollen, auf den Patienten individuell zugeschnittene Einzelfallentscheidungen treffen zu können. Methode: In Phase I des Entwicklungsprozesses wurde zunächst eine systematische Literaturrecherche (Schritt 1) und parallel eine bundesweite Befragung aller neurologischen Rehabilitationseinrichtungen hinsichtlich ihrer strukturellen und prozeduralen Gegebenheiten (Schritt 2) durchgeführt. In Phase II diskutierte und konsentierte ein interdisziplinäres Expertengremium die in Phase I erarbeitete erste Version der Praxisempfehlungen (Schritt 3). Ziel von Phase III war der Einbezug von Klinikern und Patienten, daher wurde die erste Version als Konsultationsfassung deutschlandweit an die leitenden Psychologinnen/Psychologen und Ärztinnen/Ärzte aller neurologischen Rehabilitationseinrichtungen versandt (Schritt 4) und in indikationsspezifischen Fokusgruppen mit Patienten diskutiert (Schritt 5). Rückmeldungen und Anmerkungen wurden abschließend in Phase IV mit dem Expertengremium abgestimmt und die Praxisempfehlungen final konsentiert (Schritt 6). Nachdem zunächst die Praxisempfehlungen für Patienten nach Schlaganfall entwickelt wurden, konnten in einem Folgeprojekt die Indikationsbereiche Multiple Sklerose und Idiopathisches Parkinson-Syndrom nach analogem Vorgehen in die Praxisempfehlungen Schlaganfall integriert werden. Ergebnisse: Inhaltlich unterscheiden die Praxisempfehlungen für die drei Indikationsbereiche zwei Hauptkomplexe: 1) Die Allgemeinen Vorbemerkungen einschließlich der strukturellen Rahmenbedingungen und Prozessanforderungen sowie 2) Empfehlungen zu Diagnostik und Therapie. Letztere unterteilen sich weiter in die Teile A bis E, welche 34 für die neurologische Rehabilitation relevante Aspekte abdecken und z. T. weiter unterteilt sind in Empfehlungen zu Diagnostik, Therapie, Nachsorge sowie Anmerkungen, sodass insgesamt 191 verschiedene Empfehlungsbereiche vorliegen. Adressiert werden in den Teilen A bis E die Problemlagen in den Bereichen „Partizipation – Übergeordnete Ziele der Rehabilitation“ (Teil A), „Kognition“ (Teil B), „Affektivität und Verhalten“ (Teil C), „Risikofaktoren“ (Teil D) sowie „Spezifische Aspekte und Spezielle Problemlagen“ (Teil E). Mit einer durchschnittlichen Zustimmung von jeweils 97 % (Range Schlaganfall: 88–100 %; Range Multiple Sklerose/Idiopathisches Parkinson-Syndrom: 91–100 %) wurden die Praxisempfehlungen von leitenden Psychologen und Ärzten (= Schritt 4) weit akzeptiert. Diskussion: Damit umfassen die „Praxisempfehlungen für psychologische Interventionen in der neurologischen Rehabilitation: Multiple Sklerose, Idiopathisches Parkinson-Syndrom und Schlaganfall“ detaillierte, evidenzbasierte und gleichzeitig breit konsentierte Empfehlungen, die individualisierte Einzelfallentscheidungen im gesamten interdisziplinären Team unterstützen können.

We thank Prof. Sidiropoulos for commenting on our article.1 Indeed, other studies targeted the posterior subthalamic area (PSA) more ventrally, and there might exist a certain degree of current spread from the ventral intermediate nucleus of the thalamus (VIM) into the PSA and vice versa, especially at higher amplitudes. However, we2 and others3 implanted contacts at similar z coordinates before.

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.

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.

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.

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.

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.

Deep brain stimulation alleviates tremor of various origins. Several regions like the ventralis intermediate nucleus of thalamus, the caudal zona incerta, and the posterior subthalamic region are generally targeted. Previous work with fiber tractography has shown the involvement of the cerebello-thalamo-cortical network in tremor control.To report the results of a prospective trial in a group of patients with tremor who underwent post hoc tractographic analysis after treatment with traditional thalamic deep brain stimulation.A total of 11 patients (aged 64 ± 17 years, 6 male) were enrolled (essential tremor [6], Parkinson tremor [3], and myoclonic tremor in myoclonus dystonia [2]). Patients received 1 (3 patients), 2 (7 patients), or 3 (1 patient) quadripolar electrodes. A 32-direction diffusion tensor magnetic resonance imaging sequence was acquired preoperatively. Tractography was processed postoperatively for evaluation and the dentato-rubro-thalamic tract (DRT) was individually tracked. Electrode positions were determined with helical computed tomography. Electric fields (EFs) were simulated according to individual stimulation parameters in a standardized atlas brain space (ICBM-MNI 152).Tremor was reduced in all patients (69.4% mean) on the global (bilateral) tremor score. Effective contacts were located inside or in proximity to the DRT. In moderate tremor reduction (2 patients), the EFs were centered on its anterior border. In good and excellent tremor reduction (9 patients), EFs focused on its center.Deep brain stimulation of the cerebello-thalamo-cortical network reduces tremor. The DRT connects 3 traditional target regions for deep brain stimulation in tremor disease. Tractography techniques can be used to directly visualize the DRT and, therefore, optimize target definition in individual patients.

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.

IntroductionPallidal 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.MethodsPatients with isolated dystonia at time of surgery, and

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. Naive 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.

Objective: To test the effects of stochastic whole body vibration (WBV) we performed a double-blind randomized controlled study. Methods: Patientswereallocatedeithertotheexperimental orsham group. Theexperimental groupreceived 5cyclesof stochastic WBV on three days, each cycle consisting of 5 stimulus trains of 60 seconds duration (frequency 6.5 Hz) and 60 seconds resting time between stimuli. Patients allocated to the control group received a sham treatment with 1 Hz. Unified Parkinson's Disease Rating Scale, part III (UPDRSIII) was performed after treatment at baseline, after the first series on day 1 and on day 5. Results: The reduction of subscores included in UPDRS III relative to baseline served as primary outcome measure. After the five-day course bradykinesia was improved in 14 of 18 patients (77.8%) and postural stability in 8 of 18 (44.4%). Speech and facial expression remained unchanged in both groups. Tremor (p = 0,027) and postural stability (p = 0,048) showed a reduction also, but did not reached level of significance ( p< 0,01); UPDRSIII sum score was improved by 26,7%. Conclusion: Stochastic whole body vibration may offer a supplementation to canonical physical treatments of PD motor symptoms.

Background Deep brain stimulation (DBS) has been proven to alleviate tremor of various origins. Distinct regions have been targeted. One explanation for good clinical tremor control might be the involvement of the dentatorubrothalamic tract (DRT) as has been suggested in superficial (thalamic) and inferior (posterior subthalamic) target regions. Beyond a correlation with atlas data and the postmortem evaluation of patients treated with lesion surgery, proof for the involvement of DRT in tremor reduction in the living, the scope of this work, is elusive. Objective To report a case of unilateral refractory tremor in tremor-dominant Parkinson disease treated with thalamic DBS. Methods Preoperative diffusion tensor imaging (DTI) was performed. Correlation with individual DBS electrode contact locations was obtained through postoperative fusion of helical computed tomography (CT) data with DTI fiber tracking. Results Tremor was alleviated effectively. An evaluation of the active electrode contact position revealed clear involvement of the DRT in tremor control. A closer evaluation of clinical effects and side effects revealed a highly detailed individual fiber map of the subthalamic region with DTI fiber tracking. Conclusion This is the first time the involvement of the DRT in tremor reduction through DBS has been shown in the living. The combination of DTI with postoperative CT and the evaluation of the electrophysiological environment of distinct electrode contacts led to an individual detailed fiber map and might be extrapolated to refined DTI-based targeting strategies in the future. Data acquisition for a larger study group is the topic of our ongoing research.

Background: A patient controller (PC) is an optional device for patients with deep brain stimulation (DBS) to have limited control of their stimulator system. Objectives: We investigated the impact of a PC on DBS safety, most notably the handling/prevention of unexpected DBS failure in patients with Parkinson’s disease (PD). Methods: PD patients with subthalamic DBS were educated in the use of a PC. After a first impulse generator (IPG) replacement, data on the use of the PC were obtained from the patients’ records and by a patient questionnaire. Results: A total of 27 patients with IPG replacements after 4.4 ± 0.8 years (118.8 patient-years) were included. Thirteen patients transiently used the PC to optimize stimulation amplitudes. Eighteen patients reported events when they used the PC to ensure DBS being on. No accidental switch off by environmental electromagnetism was confirmed. In contrast, 4 patients accidentally turned the IPG off with the PC. Sixteen patients regularly checked the IPG battery but only 1 patient noted a low battery status before quarterly control visits. Of the 27 patients, 26 had anticipated and only 1 an unanticipated IPG replacement. Conclusions: A PC is not needed for patient safety. However, in some patients, a PC is helpful to optimize stimulation amplitudes and to increase the patients’ own perception of safety.

In patients with essential tremor (ET) already treated with chronic deep brain stimulation (DBS) of the nucleus ventralis intermedius (VIM) we investigated whether optimization of stimulation parameters could improve clinical tremor suppression, and whether this putative effect could be sustained over time. Twenty-three ET patients with VIM-DBS participated in the prospective study. All electrode contacts were tested systematically and stimulation parameters were optimized over the course of 2 days. Clinical tremor rating scale (TRS) was videotaped before, directly after the optimization and at a 10 weeks follow-up and evaluated blindly and independently by two clinicians. For stimulation effect optimization we increased the number of active contacts whereas the total charge applied to the tissue was kept constant. TRS hemi-body scores decreased significantly after optimization. At the 10 weeks follow-up, however, the improvement had faded and was no longer significant. The activities of daily living (ADL) remained significantly improved. Systematic optimization of VIM-DBS parameters in ET patients leads to a short term improvement which habituates over time. Our results provide further evidence for a tolerance effect in chronic VIM stimulation thereby suggesting that frequently alternating stimulation protocols should be tested in future studies of ET patients treated with VIM-DBS.

Object Impulse generators (IPGs) for deep brain stimulation (DBS) need to be replaced when their internal batteries fail or when technical problems occur. New IPGs are routinely programmed with the previous stimulation parameters. In this study, the authors evaluate the stability of symptom control after such IPG replacements. Methods The authors retrospectively analyzed the outcome of 56 IPG replacements in 42 patients with various movement disorders treated using DBS. Results Stable symptom control was found in 65% of single-channel IPG replacements and 53% of dual-channel IPG replacements. Worsening of symptoms resulted primarily from changes in stimulation effects requiring reprogramming of stimulation parameters (17% of dual-channel IPG and 25% of single-channel IPG). In 14% of dualchannel IPG replacements, instability resulted from erroneous extension adjustment with change in laterality. A new short circuit of active with previously inactive contacts of the quadripolar stimulation lead resulted in a worsening of symptoms in 4% of replacements. Conclusions Replacement of the IPG requires careful follow-up of patients with DBS to ensure stable symptom control.

To assess the differential effects of bilateral deep brain stimulation of the subthalamic nucleus on proximal and distal muscle groups of the upper limb in Parkinson's disease. Eight parkinsonian subjects with chronic bilateral stimulation of the subthalamic nucleus performed index finger tapping (differentially drawing upon distal arm muscles), horizontal pointing (differentially drawing upon proximal arm muscles) and a complex reach-to-grasp task with cubes of different sizes, which involved both proximal and distal arm muscles. An ultrasound based system was used for kinematic motion analysis. Subjects were investigated in two clinical conditions: on and off subthalamic nucleus stimulation. Clinical symptom severity was rated with the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore. Stimulation of the subthalamic nucleus improved the UPDRS motor subscore (68 %). Bradykinesia of index finger tapping and horizontal pointing were equally improved by subthalamic nucleus stimulation. In contrast, in a complex reach-tograsp task bradykinesia was differentially ameliorated for the grasp component. The data suggest that bilateral stimulation of the subthalamic nucleus improves bradykinesia of both distal and proximal muscles of the arm and hand in Parkinson's disease; however, dependent upon task complexity proximal and distal movement components may be affected differentially. Kinematic motion analysis is an efficient tool to objectively evaluate the beneficial effects of subthalamic nucleus stimulation on dexterity in Parkinson's disease.

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), andUPDRSIIIsum 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.

International audience; 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.

International audience; 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

We followed up 11 patients for up to 5 years after bilateral pallidal deep brain stimulation for advanced Parkinson's disease. Dyskinesias remained significantly reduced until the last assessment. The initial improvement of off-period motor symptoms and fluctuations, however, was not sustained and gradually declined. Beneficial effects of pallidal deep brain stimulation on activities of daily living in the on- and off-period were lost after the first year. Replacement of pallidal electrodes into the subthalamic nucleus in four patients could restore the initial benefit of deep brain stimulation and allowed a significant reduction of dopaminergic drug therapy.

Recently, stimulation-induced hypogeusia in thalamic deep brain stimulation (DBS) for essential tremor has been described in two case reports,1 ,2 suggesting an exceptional occurrence. Surprisingly, an inquiry among 16 patients with thalamic DBS revealed that half of them suffered from stimulation-induced hypogeusia. We hypothesise that the distance between the volume of activated tissue (VAT) and the assumed course of gustatory fibres determines the manifestation of this side effect. We expect to observe shorter distances or even an overlap in patients with stimulation-induced hypogeusia, and a correlation between these distances and the gustometry performance. Informed consent was obtained from the 16 patients, who suffered from essential tremor (11), tremor-dominant Parkinson’s disease (3) or dystonic head tremor (2), respectively. Two patients with a tremor-dominant Parkinson’s disease had received a unilateral DBS-system. None of the patients reported taste disturbances prior to DBS implantation. Six patients refused to take part in the gustometry. The medial lemniscus (ML) and dentato-rubro-thalamic tract (DRT) were determined tractographically in relation to effective electrode contact positions, and the surrounding electric field was visualised as VAT (figure 1A–C). For details regarding imaging, tractography and calculation of electric fields, please refer to our previous publication.3 The gustatory pathway is not traceable tractographically due to its small volume and curved course. However, the human gustatory tract between the nucleus of the solitary tract and the thalamic ventral posteromedial nucleus has been defined by lesion cases, suggesting a course adjacent to the medial margin of the ML at their entrance into the thalamus.4 Thus we used the position of the medial margin of the ML as a substitute measurement for the position of the gustatory tract in this …

Object. The goal of this study was to relate the degree of clinical improvement and that of energy consumption to the anatomical position of electrode poles used for long-term stimulation. Methods. The authors conducted a retrospective analysis of 15 consecutive patients in whom targeting of the subthalamic nucleus (STN) had been performed using ventriculography, three-dimensional (3D) magnetic resonance (MR) imaging, and 3D computerized tomography, together with macrostimulation and teleradiographic control of the electrode position. In these patients the follow-up period ranged from 6 to 12 months. Postoperative improvement in contralateral motor symptoms, which was assessed by assigning a lateralized motor subscore of the Unified Parkinson's Disease Rating Scale (UPDRS), and stimulus intensity required for optimal treatment results were correlated with the intracerebral position of the active electrode pole. Bilateral high-frequency stimulation of the STN improved the UPDRS motor score during the medication-off period by an average of 60.5% compared with that at baseline. Repeated transfer of stereotactic coordinates from postoperative teleradiography to treatment-planning MR images documented the proper localization of the most distal electrode pole (pole 0) in the targeted STN. Nevertheless, in most cases the best clinical improvement was achieved using electrode poles that were located several millimeters above the electrode tip. If the relative improvement in motor symptoms was correlated with the required electrical energy for chronic stimulation, the best coefficient was observed for active electrode poles projecting onto white matter dorsal to the STN. Conclusions. This observation makes blocking or activation of large fiber connections arising in the STN or running nearby more likely than electrical interference with cell bodies inside the STN. Anatomical correlates may be the pallidothalamic bundle (including Field H of Forel and the thalamic fascicle), the pallidosubthalamic tract, and/or the zona incerta.

Focal lesions of brainstem, thalamus, and subcortical white matter may cause movement disorders that are clinically indistinguishable from cerebellar symptoms. It is suspected that ataxia in these cases is due to damage of efferent or afferent pathways of the cerebellum. However, the precise anatomical correlate often remains undefined. We used deterministic diffusion tensor magnetic resonance imaging (DTI) tractography to study the anatomical relationship between lesions causing ataxia and efferent cerebellar pathways. Study subjects were six male patients with focal lesions of different etiology (demyelination, hemorrhage, ischemia, neoplasm) outside the cerebellum. Five patients had cerebellar-like ataxia with prominent contralateral upper limb involvement. One patient with an almost midline mesencephalic lesion had a symmetrical ataxic syndrome. We used 3T MRI (Intera, Philips Medical Systems, Best, Netherlands) and DTI tractography (32 directions, StealthViz DTI, Medtronic Navigation, Louisville, USA) to delineate the dentato-rubro-thalamo-cortical tract (DRT). In all patients, tractography demonstrated focal lesions affecting the DRT in different locations. We conclude that in vivo mapping of cerebral pathways using DTI tractography in patients with focal extracerebellar brain lesions may provide direct evidence of circumscribed damage to the DRT, causing unilateral cerebellar-like ataxia. Also, a unilateral mesencephalic lesion at the level of the crossing of the DRT may cause bilateral ataxia.

We report the failure of bilateral globus pallidus internus deep brain stimulation to improve chorea in a patient with chorea-acanthocytosis. Prior to this surgery the patient had experienced a striking but short lived amelioration of symptoms with clozapine therapy.

Deep-brain stimulation of the subthalamic nucleus and internal globus pallidus are both surgical options in advanced Parkinson's disease. The best target is still debated with data suggesting better motor outcome in subthalamic stimulation but higher rates of psychiatric problems. Failure of pallidal stimulation within the first 2 years has been described. Here, we report a patient with good response to pallidal neurostimulation who developed a secondary failure after 10 years of treatment which was successfully reversed by reimplanting the electrodes into the subthalamic nucleus. This case suggests that a controlled comparison of treatment efficacy of pallidal and subthalamic neurostimulation may require a very long follow-up period to yield reliable results.

Incubation of cultured cortical astrocytes with tumor necrosis factor alpha (TNF alpha) led to a marked reduction of membrane potential. Here we report that this depolarization depends on activation of protein kinase C (PKC), since it could be blocked by the PKC antagonists staurosporine and H7 and it could be mimicked by direct activation of PKC using the phorbol ester phorbol 12-myristate 13 acetate (PMA). Analyses of whole cell currents revealed a reduction of inwardly rectifying K+ currents whereas K+ outward currents were not affected. We conclude that TNF alpha induces changes of basic electrophysiological properties of astrocytes which are similar to those induced by proliferation or an in vitro model of traumatic injury.

Diffusion tensor imaging (DTI) is more than just a useful adjunct to invasive techniques like optogenetics which recently have tremendously influenced our understanding of the mechanisms of deep brain stimulation (DBS). In combination with other technologies, DTI helps us to understand which parts of the brain tissue are connected to others and which ones are truly influenced with neuromodulation. The complex interaction of DBS with the surrounding tissues-scrutinized with DTI-allows to create testable hypotheses that can explain network interactions. Those interactions are vital for our understanding of the net effects of neuromodulation. This work naturally was first done in the field of movement disorder surgery, where a lot of experience regarding therapeutic effects and only a short latency between initiation of neuromodulation and alleviation of symptoms exist. This chapter shows the journey over the past 10 years with first applications in DBS toward current research in affect regulating network balances and their therapeutic alterations with the neuromodulation technology.

Diffusion tensor imaging (DTI) is more than just a useful adjunct to invasive techniques like optogenetics which recently have tremendously influenced our understanding of the mechanisms of deep brain stimulation (DBS). In combination with other technologies, DTI helps us to understand which parts of the brain tissue are connected to others and which ones are truly influenced with neuromodulation. The complex interaction of DBS with the surrounding tissues-scrutinized with DTI-allows to create testable hypotheses that can explain network interactions. Those interactions are vital for our understanding of the net effects of neuromodulation. This work naturally was first done in the field of movement disorder surgery, where a lot of experience regarding therapeutic effects and only a short latency between initiation of neuromodulation and alleviation of symptoms exist. This chapter shows the journey over the past 10 years with first applications in DBS toward current research in affect regulating network balances and their therapeutic alterations with the neuromodulation technology.

Oral medication still remains the mainstay for treating Parkinson’s disease (PD). Since the introduction in the late 60ies levodopa is regarded as the gold standard because of the best efficacy on akinesia and rigidity compared to other drugs like dopamine agonists or anticholinergics (Poewe et al., 2010). However, oral dopaminergic treatment of motor symptoms is complicated by the development of motor fluctuations and dyskinesias. These complications can be observed in 40 % after 5 years and 80 % after 10 years PD duration. Moreover, tremor can be refractory to oral medication. During the past 15 years deep brain stimulation (DBS) has become an important therapeutic option for patients with these motor complications. DBS has been approved in Europe for the treatment of tremor in 1995 and for advanced PD in 1998. Approval by the Food and Drug Administration (FDA) was given for tremor in 1997 and for advanced PD in 2002. The main targets for DBS are the subthalamic nucleus (STN), the internal globus pallidus (GPi) and the ventral intermediate (Vim) thalamic nucleus. DBS is a symptomatic treatment and does not influence the progression of the disease (Hilker et al., 2005). Therefore, the number of patients eligible for DBS is limited. Experts estimate that some 10 to 15 % of PD patients are suitable candidates. The implantation of stimulation electrodes is not therapeutic in itself. Apart from the precise electrode localization the subsequent programming of optimal stimulation parameters and adjustment of medication is mandatory (Deuschl et al., 2006). An increasing number of PD patients are treated by DBS so that more and more doctors and care givers involved in the treatment of PD patients are regularly concerned with the special demands of these patients. The following chapter gives an overview on specific issues in the post-operative management of PD patients with DBS.

Electrode fractures are known hardware problems in patients with deep brain stimulation (DBS) and require surgical revision. Short circuits, loose connections or disconnections of only single contacts of the common quadripolar stimulation electrodes are more subtle dysfunctions and can result in decreased efficacy of DBS. Measuring the impedances of electrodes helps detect such technical dysfunctions. This study evaluates the frequency and clinical implications of abnormal impedance measurements. We retrospectively analyzed findings of systematic impedance checks in 591 consecutive patients with DBS for various movement disorders treated in our DBS center between 2005 and 2010. A technical dysfunction was found in 36 out of 1,142 electrodes (3.2%). Short circuits (22 electrodes) were more frequent than disconnections of single contacts (8 electrodes) or loose contacts (6 electrodes). Moreover, after 109 replacements of impulse generators another 16 electrodes revealed technical dysfunctions, again with short circuits (9 electrodes) exceeding disconnections of single contacts (5 electrodes) and loose contacts (2 electrodes). Most of the short circuits occurred immediately after surgical interventions. In contrast, among dysfunctions occurring later during long-term DBS, disconnections and loose contacts prevailed. Surgical revision was performed in 4 of the overall 52 electrodes with dysfunctions, whereas in the other electrodes adjustment of stimulation parameters resulted in stable and satisfying symptom control. Technical dysfunctions of stimulation electrodes or extension leads are rare but important sources of unsatisfying DBS efficacy. In the majority of cases DBS programming or reprogramming allows avoiding surgical revision.

Deep brain stimulation (DBS) can alleviate tremor of various origins. A number of regions are targeted. In recent work our group was able to show the involvement of the dentato-rubro-thalamic tract (drt) in tremor control with fiber tracking techniques. Here we report for the first time the successful use of magnetic resonance tractography in combination with traditional landmark-based targeting techniques to perform the implantation of a bilateral DBS system in a patient with dystonic head tremor.We report on a 37-year-old female with long-standing pure head tremor from myoclonus dystonia. She was identified as a candidate for thalamic DBS. The use of head fixation in a stereotactic frame would blur target symptoms (head tremor) during surgery and was therefore avoided. Her dentate-rubro-thalamic tracts were visualized with preoperative diffusion tensor imaging (DTI) and tractography, and then directly targeted stereotactically with DBS electrodes.Three months after implantation, tremor control was excellent (90%). A close evaluation of the active electrode contact positions revealed clear involvement of the drt.This is the first time that direct visualization of fiber tracts has been employed for direct targeting and successful movement disorder tremor surgery. In the reported case, additional knowledge about the position of the drt, which previously has been shown to be a structure for modulation to achieve tremor control, led to a successful implantation of a DBS system, although there was a lack of intra-operatively testable tremor symptoms. In concordance with studies in optogenetic neuromodulation, fiber tracts are the emerging target structures for DBS. The routine integration of DTI tractography into surgical planning might be a leading path into the future of DBS surgery and will add to our understanding of the pathophysiology of movement disorders. Larger study populations will have to prove these concepts in future research.

Background The posterior subthalamic area (PSA), ventral to the intercommissural line (ICL) and the ventral intermediate nucleus (VIM), has been suggested as a promising target for deep brain stimulation (DBS) in patients suffering from essential tremor (ET). In this study the clinical benefit of VIM and PSA DBS on postural tremor suppression was systematically evaluated in a two step approach with a 3D ultrasound kinematic analysis tool. Methods We defined the exact position of 40 VIM-DBS-electrodes from 21 ET patients. In a first experiment with a subgroup of electrodes we subsequently activated a thalamic and a contact below ICL (sub-ICL) with equal parameter settings for within subject comparison. In a second step, we divided all electrodes into two groups, i.e. one group with activated thalamic and the other group with activated contacts below ICL and performed a group comparison under patients' individual stimulation parameters. Here, the corrected amplitude required for tremor suppression was analyzed separately for both groups. Results Within subject comparison with equal parameter settings revealed a significant improvement of sub-ICL compared to thalamic stimulation. In contrast, group comparison under patients' individual stimulation did not show any significant difference in tremor suppression between VIM and PSA DBS. Although higher corrected stimulation amplitude was needed in the thalamic group this difference was not significant. Conclusion The data suggest that sub-ICL stimulation may be more efficient compared to thalamic stimulation but equally effective when patients' individual stimulation parameters are used.

We report a patient in whom deep brain stimulation of the ventral intermediate nucleus of the thalamus (Vim) for treating dystonia reversibly induced stuttering at suboptimal stimulation parameters. Adjustments of stimulation parameters resulted in excellent control of dystonic motor symptoms and complete resolution of speech dysfluency. This is the first report on stuttering as an adverse effect of Vim stimulation which is primarily used to treat tremors of various etiologies.

Impulse generators (IPGs) for deep brain stimulation (DBS) need to be replaced when their internal batteries fail or when technical problems occur. New IPGs are routinely programmed with the previous stimulation parameters. In this study, the authors evaluate the stability of symptom control after such IPG replacements.The authors retrospectively analyzed the outcome of 56 IPG replacements in 42 patients with various movement disorders treated using DBS.Stable symptom control was found in 65% of single-channel IPG replacements and 53% of dual-channel IPG replacements. Worsening of symptoms resulted primarily from changes in stimulation effects requiring reprogramming of stimulation parameters (17% of dual-channel IPG and 25% of single-channel IPG). In 14% of dualchannel IPG replacements, instability resulted from erroneous extension adjustment with change in laterality. A new short circuit of active with previously inactive contacts of the quadripolar stimulation lead resulted in a worsening of symptoms in 4% of replacements.Replacement of the IPG requires careful follow-up of patients with DBS to ensure stable symptom control.

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

Bilateral high-frequency stimulation of the internal globus pallidus (GPi) and the subthalamic nucleus (STN) both alleviate akinesia, rigidity, and tremor in idiopathic Parkinson's disease. To test the specific effect of these procedures on gait, we used quantitative gait analysis in addition to relevant subscores of the Unified Parkinson's Disease Rating Scale in a group of 10 patients with advanced Parkinson's disease treated by GPi stimulation and eight patients treated by STN stimulation. Patients were assessed before and 3 months after surgery. Thirty age-matched healthy subjects served as controls. The non-random selection allowed a descriptive but no direct statistical comparison of the respective procedure. Gait analysis showed significant stimulation-induced improvements of spatiotemporal gait and step parameters in both patient groups. Moreover, the effects on step length and cadence suggested a differential effect of both basal ganglia targets. Hence, the increase in gait velocity in the STN group was almost exclusively due to a significant increase in step length, while in the GPi group statistically non-significant increases in both step length and cadence contributed. © 2001 Movement Disorder Society.

The authors retrospectively compared 1-year results of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN; n = 16) and internal pallidum (GPi) (n = 11) in advanced PD and found about equal improvements in "off" period motor symptoms, dyskinesias, and fluctuations. STN stimulation reduced medication requirements by 65% and required significantly less electrical power. These advantages contrasted with a need for more intensive postoperative monitoring and a higher incidence of adverse events related to levodopa withdrawal.