Publications by authors named "Andrea Kuhn"

Background: Parkinson's disease (PD) is characterized by hypokinetic motor symptoms, tremor, and various non-motor symptoms with frequent fluctuations of symptoms in advanced disease stages. Invasive therapies, such as deep brain stimulation (DBS), ablative therapies, and continuous subcutaneous or intrajejunal delivery of dopaminergic drugs via pump therapies are available for the management of this complex motor symptomatology and may also impact non-motor symptoms. The recent update of the clinical guideline on PD by the German Neurological Society (Deutsche Gesellschaft für Neurologie e.

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Elevated beta (β; 13-30 Hz) synchronization within the subthalamic nucleus (STN) characterizes bradykinesia in Parkinson's disease (PD). β oscillations may serve as biomarkers for off-period motor symptoms and control signals for adaptive, closed-loop deep brain stimulation (DBS) in PD. However, their relation to striatal dopaminergic denervation and PD progression remains uncertain.

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Background: Pallidal neurostimulation is an effective treatment for severe isolated dystonia, but long-term data from clinical trials are lacking.

Objectives: To evaluate long-term efficacy and safety of pallidal neurostimulation in patients with isolated generalized or segmental dystonia.

Methods: Extension study of the prospective multicenter trial (n = 40; July 2002 to May 2004), all patients received effective stimulation and underwent regular follow-up.

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Background: Comprehensive clinical data regarding factors influencing the individual disease course of patients with movement disorders treated with deep brain stimulation might help to better understand disease progression and to develop individualized treatment approaches.

Methods: The clinical core data set was developed by a multidisciplinary working group within the German transregional collaborative research network ReTune. The development followed standardized methodology comprising review of available evidence, a consensus process and performance of the first phase of the study.

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Background: Patients with Progressive Supranuclear Palsy (PSP) suffer from several neuropsychological impairments. These mainly affect the frontal lobe and subcortical brain structures. However, a scale for the assessment of cognitive and neuropsychiatric disability in PSP is still missing.

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Article Synopsis
  • Dystonia is a common movement disorder with a complex genetic background, showing significant variability in its clinical presentation and genetics.
  • The study involved exome sequencing of nearly 1,924 patients, mainly from two major registries, focusing on those with genetic prescreening negative results and early age at onset.
  • Researchers discovered 137 likely pathogenic variants in 51 genes among the patients, with many being novel, highlighting the challenges in diagnosing and understanding the disorder's genetic links.
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Subthalamic (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients not only improves kinematic parameters of movement but also modulates cognitive control in the motor and non-motor domain, especially in situations of high conflict. The objective of this study was to investigate the relationship between DBS-induced changes in functional connectivity at rest and modulation of response- and movement inhibition by STN-DBS in a visuomotor task involving high conflict. During DBS ON and OFF conditions, we conducted a visuomotor task in 14 PD patients who previously underwent resting-state functional MRI (rs-fMRI) acquisitions DBS ON and OFF as part of a different study.

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Background: Segmented electrodes for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) enable directional current steering leading to expanded programming options.

Objective: This retrospective study covering a longitudinal period of up to 7 years compares the efficacy of segmented and non-segmented leads in motor symptom alleviation and reduction of dopaminergic medication in PD patients treated in a specialized center and assesses the long-term use of directional steering in clinical routine.

Methods: Demographic data and clinical scores before surgery and at 12-month follow-up (12MFU) as well as stimulation parameters at 12MFU and last follow-up (LFU) were assessed in all patients implanted with segmented leads between 01/2016 and 12/2019 and non-segmented leads in a corresponding time-period.

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  • Dystonia is a movement disorder linked to an imbalance in brain pathways involving the striatum and internal pallidum, but its neuronal causes are not fully understood.
  • This study conducted invasive recordings from ten dystonia patients using deep brain stimulation electrodes to observe brain activity across different basal ganglia nuclei.
  • Findings showed that low-frequency brain activity between the striatum and internal pallidum correlates with the severity of dystonic symptoms, highlighting the importance of the direct striato-pallidal pathway in the disorder's development.
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Background: Comprehensive characterization of the metabolome in cerebrospinal fluid (CSF) and serum by Nuclear Magnetic Resonance (NMR) spectroscopy may identify biomarkers and contribute to the understanding of the pathophysiology of neurological diseases.

Methods: Metabolites were determined by NMR spectroscopy in stored CSF/serum samples of 20 patients with Parkinson's disease, 25 patients with other neuro-degenerative diseases, 22 patients with cerebral ischemia, 48 patients with multiple sclerosis, and 58 control patients with normal CSF findings. The data set was analysed using descriptive and multivariate statistics, as well as machine learning models.

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  • A large-scale genome-wide association study (GWAS) was conducted with over 6000 participants to investigate genetic risk factors for isolated dystonia, aiming to improve upon earlier studies that found no significant genetic links.
  • The study included 4303 dystonia patients and 2362 healthy controls, analyzing various factors like age of onset and affected body areas, but ultimately failed to identify any common genetic variants associated with dystonia.
  • The findings suggest that isolated dystonia may not be influenced by common genetic variations, highlighting the need for more extensive studies like whole-genome sequencing to uncover potential genetic contributions.
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Background: The dichotomy between the hypo- versus hyperkinetic nature of Parkinson's disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections.

Methods: Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores.

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Magnetoencephalography (MEG) allows the non-invasive measurement of brain activity at millisecond precision combined with localization of the underlying generators. So far, MEG-systems consisted of superconducting quantum interference devices (SQUIDS), which suffer from several limitations. Recent technological advances, however, have enabled the development of novel MEG-systems based on optically pumped magnetometers (OPMs), offering several advantages over conventional SQUID-MEG systems.

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  • Current estimates of genetic variants linked to Parkinson's disease (PD) show limitations and biases across different populations, complicating patient recruitment for clinical trials focused on genetic therapies.
  • The Rostock Parkinson's disease (ROPAD) study analyzes data from 12,580 PD patients across 16 countries, revealing that 14.8% had a genetic test positive for PD-related variants, particularly in specific genes like GBA1 and LRRK2.
  • Findings indicate higher positivity rates in patients with earlier onset (age ≤ 50) or a positive family history, emphasizing the need for more extensive genetic investigation to improve patient stratification for future clinical trials.
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Background: Postoperative delirium (POD) is a serious complication following deep brain stimulation (DBS) but only received little attention. Its main risk factors are higher age and preoperative cognitive deficits. These are also main risk factors for long-term cognitive decline after DBS in Parkinson's disease (PD).

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  • The study aimed to create a shorter version of the Progressive Supranuclear Palsy quality of life scale (PSP-QoL) to make it easier for patients, especially those with cognitive impairments, to complete.
  • Involved a retrospective analysis of data from 245 PSP patients in Germany, resulting in a condensed 12-item scale that covers mental and physical aspects of daily living.
  • The new scale, called the PSP-ShoQoL, showed strong correlations with existing measures of quality of life and demonstrated its sensitivity to changes over time.
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  • Recent studies have found a brain network linked to improvement in Parkinson's disease (PD) after deep brain stimulation (DBS), called the PD response network.
  • The study explored how noninvasive multifocal transcranial direct current stimulation (tDCS) affects motor symptoms in PD by targeting this network.
  • Results showed that active tDCS led to a significant reduction in PD symptoms compared to sham stimulation, suggesting noninvasive stimulation can effectively improve motor function in PD patients.
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The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown.

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Excessive stride variability is a characteristic feature of cerebellar ataxias, even in pre-ataxic or prodromal disease stages. This study explores the relation of variability of arm swing and trunk deflection in relationship to stride length and gait speed in previously described cohorts of cerebellar disease and healthy elderly: we examined 10 patients with spinocerebellar ataxia type 14 (SCA), 12 patients with essential tremor (ET), and 67 healthy elderly (HE). Using inertial sensors, recordings of gait performance were conducted at different subjective walking speeds to delineate gait parameters and respective coefficients of variability (CoV).

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Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases.

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Dystonia is a neurological movement disorder characterised by abnormal involuntary movements and postures, particularly affecting the head and neck. However, current clinical assessment methods for dystonia rely on simplified rating scales which lack the ability to capture the intricate spatiotemporal features of dystonic phenomena, hindering clinical management and limiting understanding of the underlying neurobiology. To address this, we developed a visual perceptive deep learning framework that utilizes standard clinical videos to comprehensively evaluate and quantify disease states and the impact of therapeutic interventions, specifically deep brain stimulation.

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Article Synopsis
  • Deep Brain Stimulation (DBS) effectively improves symptoms of Parkinson's disease, including tremor, bradykinesia, rigidity, and axial symptoms, by stimulating specific white matter tracts.
  • A study involving 237 patients identified distinct brain tracts linked to improvements in each symptom, with tremor associated with the primary motor cortex and cerebellum, and axial symptoms linked to the supplementary motor cortex and brainstem.
  • An introduced algorithm utilizes these symptom-tract connections to tailor DBS settings for individual patients, aiming to enhance treatment effectiveness based on the most impactful symptoms for each person.
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Parkinson's disease (PD) can lead to gait impairment and Freezing of Gait (FoG). Recent advances in cueing technologies have enhanced mobility in PD patients. While sensor technology and machine learning offer real-time detection for on-demand cueing, existing systems are limited by the usage of smartphones between the sensor(s) and cueing device(s) for data processing.

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Deep brain stimulation (DBS) of the subthalamic nucleus (STN) produces an electrophysiological signature called evoked resonant neural activity (ERNA); a high-frequency oscillation that has been linked to treatment efficacy. However, the single-neuron and synaptic bases of ERNA are unsubstantiated. This study proposes that ERNA is a subcortical neuronal circuit signature of DBS-mediated engagement of the basal ganglia indirect pathway network.

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