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The ventrolateral thalamic nucleus (VL), as part of the ‘motor thalamus’, is main relay station of cerebellar and pallidal projections. It comprises anterior (VLa) and posterior (VLpd and VLpv) subnuclei. Though the fibre architecture of cerebellar and pallidal projections to of the VL nucleus has already been focus in a numerous amount of in vitro studies mainly in animals, probabilistic tractography now offers the possibility of an in vivo comparison in healthy humans. In this study we performed a (a) qualitative and (b) quantitative examination of VL-cerebellar and VL-pallidal pathways and compared the probability distributions between both projection fields in the VL after an (I) atlas-based and (II) manual-based segmentation procedure. Both procedures led to high congruent results of cerebellar and pallidal connectivity distributions: the maximum of pallidal projections was located in anterior and medial parts of the VL nucleus, whereas cerebellar connectivity was more located in lateral and posterior parts. The median connectivity for cerebellar connections in both approaches (manual and atlas-based segmentation) was VLa > VLpv > VLpd, whereas the pallidal median connectivity was VLa ~ VLpv > VLpd in the atlas-based approach and VLpv > VLa > VLpd in the manual approach.

Exaggerated subthalamic beta oscillatory activity and increased beta range cortico-subthalamic synchrony have crystallized as the electrophysiological hallmarks of Parkinson's disease. Beta oscillatory activity is not tonic but occurs in 'bursts' of transient amplitude increases. In Parkinson's disease, the characteristics of these bursts are altered especially in the basal ganglia. However, beta oscillatory dynamics at the cortical level and how they compare with healthy brain activity is less well studied. We used magnetoencephalography (MEG) to study sensorimotor cortical beta bursting and its modulation by subthalamic deep brain stimulation in Parkinson's disease patients and age-matched healthy controls. We show that the changes in beta bursting amplitude and duration typical of Parkinson's disease can also be observed in the sensorimotor cortex, and that they are modulated by chronic subthalamic deep brain stimulation, which, in turn, is reflected in improved motor function at the behavioural level. In addition to the changes in individual beta bursts, their timing relative to each other was altered in patients compared to controls: bursts were more clustered in untreated Parkinson's disease, occurring in 'bursts of bursts', and re-burst probability was higher for longer compared to shorter bursts. During active deep brain stimulation, the beta bursting in patients resembled healthy controls' data. In summary, both individual bursts' characteristics and burst patterning are affected in Parkinson's disease, and subthalamic deep brain stimulation normalizes some of these changes to resemble healthy controls' beta bursting activity, suggesting a non-invasive biomarker for patient and treatment follow-up.

BACKGROUND: Levodopa‐carbidopa intestinal gel (LCIG) effectively reduces off time and dyskinesia and increases on time in advanced Parkinson's disease (PD). However, patients with LCIG‐infusion experience frequent complications and some discontinue treatment early on. OBJECTIVES: The objectives of this study were to find predictive factors for early dropout from the LCIG infusion, analyze the treatment burden on the tertiary health care system, and explore changes in medication during the LCIG treatment. METHODS: LCIG‐infusion was administrated to 103 patients between July 2006 and May 2020 at the Helsinki University Hospital, accumulating 350 years of follow‐up data. We evaluated, retrospectively, changes in medication during treatment, discontinuation of the infusion, and adverse events from the patient records. RESULTS: Living alone was a predictive factor for early dropout (OR = 3.88; 95% CI = 1.03–14.66; P = 0.045). The treatment burden on the tertiary health care system increased after the initiation of LCIG infusion mostly because of common complications related to the infusion system (median change of in‐ and out‐patient visits +1, P = 0.03). Mean levodopa equivalent daily dose (LEDD) rose from baseline to 6 months (1246.7 vs. 1684.9, P = 0.001) and stabilized thereafter. Patients commonly switched from “polypharmacy” to “LCIG‐only” or “LCIG + oral levodopa” medication‐groups during long‐term treatment. CONCLUSIONS: Recurrent complications related to the infusion system increase the treatment burden on tertiary healthcare system after the initiation of LCIG‐infusion. Most patients continue long‐term with the infusion. Few patients discontinue infusion during the first year after initiation and living alone appears to be a risk factor for this outcome.

Background Although deep brain stimulation of the globus pallidus internus (GPi-DBS) is an established treatment for many forms of dystonia, including generalized as well as focal forms, its effects on brain (dys-)function remain to be elucidated, particularly for focal and segmental dystonia. Clinical response to GPi-DBS typically comes with some delay and lasts up to several days, sometimes even weeks, once stimulation is discontinued. Objective This study investigated how neural activity during rest and motor activation is affected by GPi-DBS while excluding the potential confound of altered feedback as a result of therapy-induced differences in dystonic muscle contractions. Methods Two groups of patients with focal or segmental dystonia were included in the study: 6 patients with GPi-DBS and 8 without DBS (control group). All 14 patients had cervical dystonia. Using (H2O)-O-15 PET, regional cerebral blood flow was measured at rest and during a motor task performed with a nondystonic hand. Results In patients with GPi-DBS (stimulation ON and OFF), activity at rest was reduced in a prefrontal network, and during the motor task, sensorimotor cortex activity was lower than in patients without DBS. Within-group contrasts (tapping > rest) showed less extensive task-induced motor network activation in GPi-DBS patients than in non-DBS controls. Reduced sensorimotor activation amounted to a significant group-by-task interaction only in the stimulation ON state. Conclusions These findings support previous observations in generalized dystonia that suggested that GPi-DBS normalizes dystonia-associated sensorimotor and prefrontal hyperactivity, indicating similar mechanisms in generalized and focal or segmental dystonia. Evidence is provided that these effects extend into the OFF state, which was not previously demonstrated by neuroimaging. (c) 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Objective: To assess the effects of different frequencies of thalamic Deep-Brain-Stimulation (DBS) on cognitive performance of patients suffering from Essential Tremor (ET). Methods: In 17 ET-patients with thalamic-DBS, Tremor-Rating-Scale (TRS), standardized phonemic and semantic verbal fluency (VF), Stroop-Color-Word-Test and Digit-span-test were investigated in three randomized stimulation-settings: i) high-frequency stimulation (HFS), ii) low-frequency stimulation (LFS) and iii) OFF-stimulation (DBS-OFF). Paired-samples t-test for TRS and one-way repeated measures analysis of variance for cognitive performance were calculated. Results: Tremor was reduced during HFS (MeanTRS-HFS = 12.9 ± 9.6) compared to DBS-OFF (MeanTRS-OFF = 44.4 ± 19.8, P .05), phonemic and semantic VF differed significantly between the three conditions (FPvf = 5.28, FSvf = 3.41, both P .05). Conclusions: HFS compared to LFS or DBS-OFF significantly reduced tremor but simultaneously worsened VF while working memory and cognitive inhibition remained unaffected. In contrast, LFS enhanced VF but did not ameliorate tremor. The data emphasize the relevance of thalamocortical loops for verbal fluency but also suggest that more sophisticated DBS-regimes in ET may improve both motor and cognitive performance.

Background Pallidal deep brain stimulation (GPi-DBS) effectively ameliorates idiopathic dystonia, although approximately 15% of patients respond insufficiently. Although various thalamic and subthalamic targets have been suggested for dystonic tremor, no systematic studies have been published on thalamic DBS in dystonic tremor. We assessed the effect of thalamic/subthalamic area DBS (Th-DBS) on dystonic head tremor and dystonia in a single-blind design. Methods Dystonic head tremor and dystonia before and 3 months after surgery were quantified via blinded video-ratings using the Fahn-Tolosa-Marin-Tremor-Scale and the Burke-Fahn-Marsden-Dystonia-Rating-Scale in seven patients with idiopathic cervical or segmental dystonia, dystonic head tremor, and bilateral Th-DBS. Pain, side effects, adverse events, and stimulation parameters were assessed. Results Th-DBS improved dystonic tremor and dystonia (P

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

Secondary dystonia encompasses a heterogeneous group with different etiologies. Cerebral palsy is the most common cause. Pharmacological treatment is often unsatisfactory. There are only limited data on the therapeutic outcomes of deep brain stimulation in dyskinetic cerebral palsy. The published literature regarding deep brain stimulation and secondary dystonia was reviewed in a meta-analysis to reevaluate the effect on cerebral palsy. The Burke-Fahn-Marsden Dystonia Rating Scale movement score was chosen as the primary outcome measure. Outcome over time was evaluated and summarized by mixed-model repeated-measures analysis, paired Student t test, and Pearson's correlation coefficient. Twenty articles comprising 68 patients with cerebral palsy undergoing deep brain stimulation assessed by the Burke-Fahn-Marsden Dystonia Rating Scale were identified. Most articles were case reports reflecting great variability in the score and duration of follow-up. The mean Burke-Fahn-Marsden Dystonia Rating Scale movement score was 64.94 ± 25.40 preoperatively and dropped to 50.5 ± 26.77 postoperatively, with a mean improvement of 23.6% (P < .001) at a median follow-up of 12 months. The mean Burke-Fahn-Marsden Dystonia Rating Scale disability score was 18.54 ± 6.15 preoperatively and 16.83 ± 6.42 postoperatively, with a mean improvement of 9.2% (P < .001). There was a significant negative correlation between severity of dystonia and clinical outcome (P < .05). Deep brain stimulation can be an effective treatment option for dyskinetic cerebral palsy. In view of the heterogeneous data, a prospective study with a large cohort of patients in a standardized setting with a multidisciplinary approach would be helpful in further evaluating the role of deep brain stimulation in cerebral palsy. © 2013 Movement Disorder Society.

In response to the correspondence by Albanese and co-workers, we discuss etiology as a factor predicting outcome of pallidal DBS in dystonia, reanalysing our dataset on causes of non-response to pallidal DBS in isolated dystonia by looking only at patients with a diagnosis of idiopathic dystonia at time of surgery.

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.

Background Reports about neural oscillatory activity in the globus pallidus internus (GPi) have targeted general (GD) and cervical dystonia (CD), however to our knowledge they are nonexistent for tardive dystonia (TD). Methods Local field potentials (LFPs) from seven CD and five TD patients were recorded intraoperatively. We compared LFP power in thetadelta, alpha and beta band during rest and sensory palmar stimulation (SPS) in patients with general anesthesia and local/analgo sedation. Results We found prominent LFP power activity in thetadelta for both CD and TD. Unlike TD, a significant difference between rest and SPS was revealed for CD. Conclusions Our data support the presence of LFP oscillatory activity in CD and TD. Thetadelta power modulation in the GPi is suggested as a signature for sensory processing in CD.

Inconsistent findings regarding the effects of dopaminergic medication (MED) and deep brain stimulation (DBS) of the subthalamic nucleus (STN) on decision making processes and impulsivity in Parkinson's disease (PD) patients have been reported. This study investigated the influence of MED and STN-DBS on decision-making under risk. Eighteen non-demented PD patients, treated with both MED and STN-DBS (64.3±10.2years, UPDRS III MED off, DBS off 45.5±17.1) were tested with the Game of Dice Task (GDT) which probes decision-making under risk during four conditions: MED on/DBS on, MED on/DBS off, MED off/DBS on, and MED off/DBS off. Task performance across conditions was compared analyzing two GDT-parameters: (i) the "net score" indicating advantageous decisions, and (ii) the patient's ability to use negative feedback. Significantly higher GDT net scores were observed in Med on in contrast to Med off conditions as well as in DBS on versus DBS off conditions. However, no effect of therapy for the patient's ability to make use of negative feedback could be detected. The data suggest a positive influence of both MED and STN-DBS on making decisions under risk in PD patients, an effect which seems to be mediated by mechanisms other than the use of negative feedback.

Pallidal deep brain stimulation (GPi-DBS) effectively ameliorates idiopathic dystonia, although approximately 15% of patients respond insufficiently. Although various thalamic and subthalamic targets have been suggested for dystonic tremor, no systematic studies have been published on thalamic DBS in dystonic tremor. We assessed the effect of thalamic/subthalamic area DBS (Th-DBS) on dystonic head tremor and dystonia in a single-blind design.Dystonic head tremor and dystonia before and 3 months after surgery were quantified via blinded video-ratings using the Fahn-Tolosa-Marin-Tremor-Scale and the Burke-Fahn-Marsden-Dystonia-Rating-Scale in seven patients with idiopathic cervical or segmental dystonia, dystonic head tremor, and bilateral Th-DBS. Pain, side effects, adverse events, and stimulation parameters were assessed.Th-DBS improved dystonic tremor and dystonia (P 0.05; 57.1% and 70.4%, respectively). Head tremor amplitude and pain were also improved (P 0.05; 77.5% and 90.0%, respectively). Side effects included dysarthria, gait disturbance, slowness of movement, and weight gain.Dystonic head tremor and dystonia can be improved with Th-DBS.

Deep brain stimulation (DBS) has proven to be a successful therapeutic approach in several patients with movement disorders such as Parkinson's disease and dystonia. Hitherto its application was mainly restricted to advanced disease patients resistant to medication or with severe treatment side effects. However, there is now growing interest in earlier application of DBS, aimed at improving clinical outcomes, quality of life, and avoiding psychosocial consequences of chronic disease-related impairments. We address the clinical and ethical aspects of two "early" uses of DBS, (1) DBS early in the course of the disease, and (2) DBS early in life (i.e. in children). Possible benefits, risks and burdens are discussed and thoroughly considered. Further research is needed to obtain a careful balance between exposing vulnerable patients to potential severe surgical risks and excluding them from a potentially good outcome.

Different tremor entities such as Essential Tremor (ET) or tremor in Parkinson's disease (PD) can be ameliorated by the implantation of electrodes in the ventral thalamus for Deep Brain Stimulation (DBS). The exact neural mechanisms underlying this treatment, as well as the specific pathophysiology of the tremor in both diseases to date remain elusive. Since tremor-related local field potentials (LFP) have been shown to cluster with a somatotopic representation in the subthalamic nucleus, we here investigated the neurophysiological correlates of tremor in the ventral thalamus in ET and PD using power and coherence analysis. Local field potentials (LFPs) at different recording depths and surface electromyographic signals (EMGs) from the extensor and flexor muscles of the contralateral forearm were recorded simultaneously in twelve ET and five PD patients. Data analysis revealed individual electrophysiological patterns of LFP-EMG coherence at single and double tremor frequency for each patient. Patterns observed varied in their spatial distribution within the Ventral lateral posterior nucleus of the thalamus (VLp), revealing a specific topography of 'tremor clusters' for PD and ET. The data strongly suggest that within VLp individual tremor-related electrophysiological signatures exist in ET and PD tremor.

Background: Deep brain stimulation (DBS) is highly successful in treating Parkinson’s disease (PD), dystonia, and essential tremor (ET). Until recently implantable neurostimulators were nonrechargeable, battery-driven devices, with a lifetime of about 3–5 years. This relatively short duration causes problems for patients (e.g. programming and device-use limitations, unpredictable expiration, surgeries to replace depleted batteries). Additionally, these batteries (relatively large with considerable weight) may cause discomfort. To overcome these issues, the first rechargeable DBS device was introduced: smaller, lighter and intended to function for 9 years. Methods: Of 35 patients implanted with the rechargeable device, 21 (including 8 PD, 10 dystonia, 2 ET) were followed before and 3 months after surgery and completed a systematic survey of satisfaction with the rechargeable device. Results: Overall patient satisfaction was high (83.3 ± 18.3). Dystonia patients tended to have lower satisfaction values for fit and comfort of the system than PD patients. Age was significantly negatively correlated with satisfaction regarding process of battery recharging. Conclusions: Dystonia patients (generally high-energy consumption, severe problems at the DBS device end-of-life) are good, reliable candidates for a rechargeable DBS system. In PD, younger patients, without signs of dementia and good technical understanding, might have highest benefit.

Secondary dystonia encompasses a heterogeneous group with different etiologies. Cerebral palsy is the most common cause. Pharmacological treatment is often unsatisfactory. There are only limited data on the therapeutic outcomes of deep brain stimulation in dyskinetic cerebral palsy. The published literature regarding deep brain stimulation and secondary dystonia was reviewed in a meta-analysis to reevaluate the effect on cerebral palsy. The Burke-Fahn-Marsden Dystonia Rating Scale movement score was chosen as the primary outcome measure. Outcome over time was evaluated and summarized by mixed-model repeated-measures analysis, paired Student t test, and Pearson's correlation coefficient. Twenty articles comprising 68 patients with cerebral palsy undergoing deep brain stimulation assessed by the Burke-Fahn-Marsden Dystonia Rating Scale were identified. Most articles were case reports reflecting great variability in the score and duration of follow-up. The mean Burke-Fahn-Marsden Dystonia Rating Scale movement score was 64.94 ± 25.40 preoperatively and dropped to 50.5 ± 26.77 postoperatively, with a mean improvement of 23.6% (P.001) at a median follow-up of 12 months. The mean Burke-Fahn-Marsden Dystonia Rating Scale disability score was 18.54 ± 6.15 preoperatively and 16.83 ± 6.42 postoperatively, with a mean improvement of 9.2% (P.001). There was a significant negative correlation between severity of dystonia and clinical outcome (P.05). Deep brain stimulation can be an effective treatment option for dyskinetic cerebral palsy. In view of the heterogeneous data, a prospective study with a large cohort of patients in a standardized setting with a multidisciplinary approach would be helpful in further evaluating the role of deep brain stimulation in cerebral palsy. © 2013 Movement Disorder Society.

Bodyflying is a flying sport similar to skydiving. The experience of bodyflying is close to that of skydiving, however, bodyflying does not require a jump out of a plane or a parachute, the flight is enabled by a vertical air stream column with a speed of up to 180 km/h in a vertical wind tunnel. Bodyflying has been considered to be a sports activity in a completely safe environment with no serious complications. We report two cases of traction lesions of the brachial plexus during first-time bodyflying with predominant affection of the root C6. To the best of our knowledge, this pattern of traction injury of the brachial plexus has not yet been reported. Immediately following a bodyflying teaching session, a 35-year-old male noticed a marked weakness in arm and finger flexion and to a lesser degree in arm extension of the left upper limb. Furthermore, he observed numbness of the radial side of the left forearm. Contrast-enhanced magnetic resonance imaging of the cervical spine was unremarkable. On examination of the left upper limb, there was weakness in biceps flexion [grade 4-/5 according to the British Medical Research Council grading system (BMRC)], triceps extension (grade 4?/5), and wrist/finger flexors (grade 4?/5). Examination of sensation was diminished over the radial aspect of the left forearm extending down over the first three digits (C6). The biceps and brachioradialis reflexes were absent on the left side. Electroneurographic examinations of nerve conduction velocities and amplitudes of the left median and ulnar nerve were unremarkable, but F-wave studies of the left median nerve (see Fig. 1) demonstrated an increased latency on the left (C6). Electromyographic needle examination (EMG) revealed no abnormal spontaneous activity, but recruitment was predominantly reduced in the left biceps (see Fig. 2) and slightly reduced in the left deltoid (C5/C6), whereas it was normal in the left triceps (C7). Because of acute weakness of the left arm during a firsttime bodyflying session, a 17-year-old female had to interrupt the session. Immediately following the session, the patient was unable to move her left arm and she noticed a numbness of the radial side of the left forearm. On examination of the left upper limb, strength testing demonstrated flaccid paresis in shoulder abduction and anteversion (grade 4/5), biceps flexion and supination/ pronation of the forearm (grade 2/5), and wrist/finger flexors (grade 4/5) without affection of intrinsic muscles of the hand. Sensation was diminished over the radial aspect of the left forearm extending down over the first two digits. The biceps reflex was absent and the brachioradialis reflex was diminished on the left. Nerve conduction velocity studies of sensory nerves demonstrated a slightly decreased left median nerve response (C6). The EMG revealed abnormal spontaneous activity in the left biceps brachii muscle and recruitment was markedly reduced. There was no abnormal spontaneous activity in the left deltoideus and brachioradialis, but recruitment was reduced, indicative of a lesion of the C5 and C6 segment. Misjudgement of vertical air stream with a speed of up to 180 km/h can result in uncoordinated compensating movements of the arms. In this situation, an inadvertent relaxation of the arm muscles can cause the arm to be overextended or overelevated by the strong vertical air stream and may thereby cause a traction lesion of the brachial plexus. Additionally, the bodyflying instructor’s N. Galldiks (&) K. A. M. Pauls G. R. Fink W. F. Haupt Department of Neurology, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany e-mail: norbert.galldiks@uk-koeln.de