Search

BackgroundDeep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for motor and non-motor symptoms in advanced Parkinson’s disease (PD). However, considerable interindividual variability of outcomes exists. Neuroimaging based biomarkers, such as neurite orientation dispersion and density imaging (NODDI), a biophysical model based MRI-technique, have been proposed to predict clinical outcomes and therefore inform preoperative patient counselling.ObjectiveTo detect microstructural properties of brain areas associated with short-term non-motor outcomes following STN-DBS in PD.MethodsIn this prospective open-label study, 37 PD patients underwent diffusion MRI and comprehensive clinical assessments at preoperative baseline and 6-month follow-up. Neurite density index (NDI), orientation dispersion index (ODI), and fractional anisotropy (FA) were derived. Whole brain voxel-wise analysis assessed associations between microstructural metrics and non-motor outcomes corrected for multiple comparisons using a permutation-based approach.ResultsIntact microstructure within specific areas including right insular cortex, right putamen, right cingulum, and bilateral corticospinal tract were associated with greater postoperative improvement of non-motor symptom burden. Furthermore, microstructural properties of distinct brain regions were associated with postoperative changes in sleep, attention/memory, and urinary symptoms.ConclusionMicrostructural properties of distinct brain areas predict non-motor outcomes in DBS for PD. Therefore, diffusion MRI can support preoperative patient counselling and treatment selection by identifying patients with above-or below-average non-motor responses.

Background: The satisfaction with life and, in particular, with treatment in Parkinson’s disease (PD) is understudied. Objective: To explore a new 7-item rating tool assessing satisfaction with life and treatment (SLTS-7) in PD. Methods: In this cross-sectional, multi-center study, including patients screened for advanced therapies, psychometric characteristics of the SLTS-7 were analyzed. An exploratory factor analysis identified the underlying factorial structure of the SLTS-7. Results: 117 patients were included, and the data quality of the SLTS-7 was excellent (computable data 100%), and acceptability measures satisfied standard criteria. Besides the global assessment (item 1), the exploratory factor analysis produced item 2 (physical satisfaction) as an independent item and two factors among the remaining items: items 3–5 (psycho-social satisfaction), and items 6 and 7 (treatment satisfaction). Cronbach’s alpha was 0.89, indicative of high internal consistency. The SLTS-7 total score correlated moderately with motor symptoms and weakly with non-motor symptoms total scores. SLTS-7 showed the highest correlations with the European Quality of Life with 5 items (EQ-5D) visual analog scale (0.43–0.58, p

Introduction: Deep brain stimulation (DBS) is a well-established treatment for patients with Parkinson's disease (PD) improving quality of life, motor, and non-motor symptoms. However, non-motor effects in PD subtypes are understudied. We hypothesized that patients with 'postural instability and gait difficulty' (PIGD) experience more beneficial non-motor effects than 'tremor-dominant' patients undergoing DBS for PD.Methods: In this prospective, observational, international multicentre study with a 6-month follow-up, we assessed the Non-Motor Symptom Scale (NMSS) as primary and the following secondary outcomes: Unified PD Rating Scale-motor examination (UPDRS-III), Scales for Outcomes in PD (SCOPA)-activities of daily living (ADL) and -motor complications, PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose (LEDD). We analysed within-group longitudinal changes with Wilcoxon signed-rank test and Benjamini-Hochberg correction for multiple comparisons. Additionally, we explored outcome between-group differences of motor subtypes with Mann-Whitney U-tests.Results: In 82 PIGD and 33 tremor-dominant patients included in this study, baseline NMSS total scores were worse in PIGD patients, both groups experienced postoperative improvements of the NMSS sleep/fatigue domain, and between-group differences in postoperative outcomes were favourable in the PIGD group for the NMSS total and miscellaneous domain scores.Conclusions: This study provides evidence of a favourable outcome of total non-motor burden in PIGD compared to tremor-dominant patients undergoing DBS for PD. These differences of clinical efficacy on non-motor aspects should be considered when advising and monitoring patients with PD undergoing DBS.Keywords: Deep brain stimulation; Nonmotor symptoms; Postural instability and gait difficulty; Quality of life; Tremor-dominant.

Bimanual coordination is impaired in Parkinson’s disease affecting patients’ ability to perform activities of daily living and to maintain independence. Conveyance of information between cortical and subcortical areas is essential for bimanual coordination and relies on the integrity of cerebral microstructure. As pathological deposition of alpha-synuclein compromises microstructure in Parkinson’s disease, we investigated the relationship between microstructural integrity and bimanual coordination using diffusion-weighted MRI in 23 patients with Parkinson’s disease (mean age ± standard deviation: 56.0 ± 6.45 years; 8 female) and 26 older adults (mean age ± standard deviation: 58.5 ± 5.52 years). Whole-brain analysis revealed specific microstructural alterations between patients and healthy controls matched for age, sex, handedness, and cognitive status congruent with the literature and known Parkinson’s disease pathology. A general linear model revealed distinct microstructural alterations associated with poor bimanual coordination in Parkinson’s disease, corrected for multiple comparisons using a permutation-based approach. Integrating known functional topography, we conclude that distinct changes in microstructure cause an impediment of structures involved in attention, working memory, executive function, motor planning, motor control, and visual processing contributing to impaired bimanual coordination in Parkinson’s disease.

Purpose of review: To provide an update on paraneoplastic cerebellar degeneration (PCD), the involved antibodies and tumors, as well as management strategies. Recent findings: PCD represents the second most common presentation of the recently established class of immune mediated cerebellar ataxias (IMCAs). Although rare in general, PCD is one of the most frequent paraneoplastic presentations and characterized clinically by a rapidly progressive cerebellar syndrome. In recent years, several antibodies have been described in association with the clinical syndrome related to PCD; their clinical significance, however, has yet to be determined. The 2021 updated diagnostic criteria for paraneoplastic neurologic symptoms help to establish the diagnosis of PCD, direct cancer screening, and to evaluate the presence of these newly identified antibodies. Recognition of the clinical syndrome and prompt identification of a specific antibody are essential for early detection of an underlying malignancy and initiation of an appropriate treatment, which represents the best opportunity to modulate the course of the disease. As clinical symptoms can precede tumor diagnosis by years, co-occurrence of specific symptoms and antibodies should prompt continuous surveillance of the patient. Summary: We provide an in-depth overview on PCD, summarize recent findings related to PCD, and highlight the transformed diagnostic approach.

BackgroundThe effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson’s disease (PD) are understudied.ObjectiveTo investigate clinical predictors of STN-DBS effects on ICB.MethodsIn this prospective, open-label, multicentre study in patients with PD undergoing bilateral STN-DBS, we assessed patients preoperatively and at 6-month follow-up postoperatively. Clinical scales included the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), PD Questionnaire-8, Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale in addition to levodopa-equivalent daily dose total (LEDD-total) and dopamine agonists (LEDD-DA). Changes at follow-up were analysed with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We explored predictors of QUIP-RS changes using correlations and linear regressions. Finally, we dichotomised patients into ‘QUIP-RS improvement or worsening’ and analysed between-group differences.ResultsWe included 55 patients aged 61.7 years±8.4 with 9.8 years±4.6 PD duration. QUIP-RS cut-offs and psychiatric assessments identified patients with preoperative ICB. In patients with ICB, QUIP-RS improved significantly. However, we observed considerable interindividual variability of clinically relevant QUIP-RS outcomes as 27.3% experienced worsening and 29.1% an improvement. In post hoc analyses, higher baseline QUIP-RS and lower baseline LEDD-DA were associated with greater QUIP-RS improvements. Additionally, the ‘QUIP-RS worsening’ group had more severe baseline impairment in the NMSS attention/memory domain.ConclusionsOur results show favourable ICB outcomes in patients with higher preoperative ICB severity and lower preoperative DA doses, and worse outcomes in patients with more severe baseline attention/memory deficits. These findings emphasise the need for comprehensive non-motor and motor symptoms assessments in patients undergoing STN-DBS.Trial registration numberDRKS00006735.

Background: Sleep disturbances and neuropsychiatric symptoms are some of the most common nonmotor symptoms in Parkinson’s disease (PD). The effect of subthalamic stimulation (STN-DBS) on these symptoms beyond a short-term follow-up is unclear. Objective: To examine 36-month effects of bilateral STN-DBS on quality of sleep, depression, anxiety, and quality of life (QoL) compared to standard-of-care medical therapy (MED) in PD. Methods: In this prospective, controlled, observational, propensity score matched, international multicenter study, we assessed sleep disturbances using the PDSleep Scale-1 (PDSS), QoL employing the PDQuestionnaire-8 (PDQ-8), motor disorder with the Scales for Outcomes in PD (SCOPA), anxiety and depression with the Hospital Anxiety and Depression Scale (HADS), and dopaminergic medication requirements (LEDD). Within-group longitudinal outcome changes were tested using Wilcoxon signed-rank and between-group longitudinal differences of change scores with Mann-Whitney U tests. Spearman correlations analyzed the relationships of outcome parameter changes at follow-up. Results: Propensity score matching applied on 159 patients (STN-DBS n = 75, MED n = 84) resulted in 40 patients in each treatment group. At 36-month follow-up, STN-DBS led to significantly better PDSS and PDQ-8 change scores, which were significantly correlated. We observed no significant effects for HADS and no significant correlations between change scores in PDSS, HADS, and LEDD. Conclusions: We report Class IIb evidence of beneficial effects of STN-DBS on quality of sleep at 36-month follow-up, which were associated with QoL improvement independent of depression and dopaminergic medication. Our study highlights the importance of sleep for assessments of DBS outcomes.

Bimanual motor control declines during healthy ageing, affecting the ability of older adults to maintain independence. Age-related changes in neural dynamics of movement preparation that underlie reduced bimanual motor control, however, remain largely elusive. Here, we assessed effective connectivity within a prefrontal-premotor network of 19 young and 20 older adults during the preparatory phase of complex bimanual movements using high-density electroencephalography and Dynamic Causal Modelling of evoked responses. We found that excitatory interhemispheric prefrontal to premotor coupling in older adults predicted age-group association and poor motor-performance. In contrast, excitatory intrahemispheric prefrontal to premotor coupling enabled older adults to maintain motor-performance at the cost of lower movement speed. Our results disentangle the complex interplay in the prefrontal-premotor network underlying reduced bimanual control and the well-known speed-accuracy trade-off seen in older adults. We anticipate these coupling patterns to be potential biomarkers for healthy ageing and a possible future target of non-invasive brain-stimulation.

Deep brain stimulation of the subthalamic nucleus is an effective and established therapy for patients with advanced Parkinson’s disease improving quality of life, motor symptoms and non-motor symptoms. However, there is a considerable degree of interindividual variability for these outcomes, likely due to variability in electrode placement and stimulation settings. Here, we present probabilistic mapping data from a prospective, open-label, multicentre, international study to investigate the influence of the location of subthalamic nucleus deep brain stimulation on non-motor symptoms in patients with Parkinson’s disease. A total of 91 Parkinson’s disease patients undergoing bilateral deep brain stimulation of the subthalamic nucleus were included, and we investigated NMSScale, NMSQuestionnaire, Scales for Outcomes in Parkinson’s disease-motor examination, -activities of daily living, and -motor complications, and Parkinson’s disease Questionnaire-8 preoperatively and at 6-month follow-up after surgery. Leads were localized in standard space using the Lead-DBS toolbox and individual volumes of tissue activated were calculated based on clinical stimulation settings. Probabilistic stimulation maps and non-parametric permutation statistics were applied to identify voxels with significant above or below average improvement for each scale and analysed using the DISTAL atlas. All outcomes improved significantly at follow-up. Significant spatial distribution patterns of neurostimulation were observed for NMSScale total score and its mood/apathy and attention/memory domains. For both domains, voxels associated with below average improvement were mainly located dorsal to the subthalamic nucleus. In contrast, above average improvement for mood/apathy was observed in the ventral border region of the subthalamic nucleus and in its sensorimotor subregion and for attention/memory in the associative subregion. A trend was observed for NMSScale sleep domain showing voxels with above average improvement located ventral to the subthalamic nucleus. Our study provides evidence that the interindividual variability of mood/apathy, attention/memory, and sleep outcomes after subthalamic nucleus deep brain stimulation depends on the location of neurostimulation. This study highlights the importance of holistic assessments of motor and non-motor aspects of Parkinson’s disease to tailor surgical targeting and stimulation parameter settings to patients’ personal profiles.

Bimanual coordination is impaired in Parkinson's disease (PD), affecting patients' quality of life. Besides dysfunction of the basal ganglia network, alterations of cortical oscillatory coupling, particularly between prefrontal and (pre-)motoric areas, are thought to underlie this impairment. Here, we studied 16 PD patients OFF and ON medication and age-matched healthy controls recording high-resolution electroencephalography (EEG) during performance of spatially coupled and uncoupled bimanual finger movements. Dynamic causal modeling (DCM) for induced responses was used to infer task-induced effective connectivity within a network comprising bilateral prefrontal cortex (PFC), lateral premotor cortex (lPM), supplementary motor area (SMA), and primary motor cortex (M1). Performing spatially coupled movements, excitatory left-hemispheric PFC to lPM coupling was significantly stronger in controls compared to unmedicated PD patients. Levodopa-induced enhancement of this connection correlated with increased movement accuracy. During performance of spatially uncoupled movements, PD patients OFF medication exhibited inhibitory connectivity from left PFC to SMA. Levodopa intake diminished these inhibitory influences and restored excitatory PFC to lPM coupling. This restoration, however, did not improve motor function. Concluding, our results indicate that lateralization of prefrontal to premotor connectivity in PD can be augmented by levodopa substitution and is of compensatory nature up to a certain extent of complexity.