Refine
Has Fulltext
- yes (54)
Is part of the Bibliography
- yes (54) (remove)
Year of publication
Document Type
- Journal article (54)
Language
- English (54) (remove)
Keywords
- Parkinson’s disease (13)
- deep brain stimulation (13)
- Parkinson's disease (8)
- subthalamic nucleus (6)
- dopamine (5)
- neuroinflammation (4)
- basal ganglia (3)
- cervical dystonia (3)
- ischemic stroke (3)
- length of stenosis (3)
- mesencephalic locomotor region (3)
- photothrombotic stroke (3)
- stroke (3)
- Parkinson disease (2)
- base of support (2)
- carotid atherosclerosis (2)
- carotid stenosis (2)
- carotid ultrasound (2)
- cerebellar tDCS (2)
- degree of stenosis (2)
- dementia (2)
- disease (2)
- dystonia (2)
- essential tremor (2)
- gait (2)
- gait initiation (2)
- local field potentials (2)
- movement disorders (2)
- multiple sclerosis (2)
- neurodegeneration (2)
- neuroprotection (2)
- outcomes (2)
- second hit (2)
- split-belt treadmill (2)
- tremor (2)
- walking (2)
- 5IA-SPECT (1)
- A53T (1)
- Alzheimer’s disease (1)
- Amplitude (1)
- Braak (1)
- DARPA (1)
- DBS biomarkers (1)
- DBS programming (1)
- DOPA-responsive-dystonia (1)
- DYT1 (1)
- Dystonia (1)
- F-18-FDG PET (1)
- GCH1 (1)
- GFAP (1)
- GFAP-astrocytopathies (1)
- LSVT-big therapy (1)
- Lewy-like pathology (1)
- MIBG scintigraphy (1)
- NPC1 gene (1)
- NPC2 gene (1)
- Niemann–Pick disease type C (1)
- Parkinson (1)
- Parkinsons disease (1)
- Parkionson's disease (1)
- Pointing error (1)
- Proprioception (1)
- T cells (1)
- Tourette syndrome (1)
- Training (1)
- [18F]FDG positron emission tomography (1)
- accuracy (1)
- adult-onset (1)
- alpha-7 nicotinic acetylcholine receptor (1)
- ankles (1)
- anthropometric measurement (1)
- anthropometric measurements (1)
- antigen-presenting cells (1)
- apomorphine (1)
- areas (1)
- arm (1)
- autoantibodies (1)
- balance (1)
- beta oscillation (1)
- beta oscillations (1)
- beta power (1)
- bilateral internal carotid artery stenosis (1)
- binding (1)
- biological locomotion (1)
- blood-brain barrier (1)
- botulinum toxin (1)
- brain (1)
- brain metabolic alterations (1)
- brain networks (1)
- brain stem (1)
- care tempis (1)
- cerebellum (1)
- children (1)
- choline acetyltransferase (1)
- cholinergic activity (1)
- chronic stimulation (1)
- clinical approach (1)
- clinical diagnosis (1)
- clinical outcome (1)
- closed-loop (1)
- cognitive decline (1)
- coherence analysis (1)
- computer vision (1)
- consolidation (1)
- continuous theta burst stimulation (cTBS) (1)
- coordination (1)
- cortical excitability (1)
- cortical silent period (1)
- criteria (1)
- deep brain stimulation (DBS) (1)
- depression (1)
- diagnostic markers (1)
- digital medicine (1)
- directional deep brain stimulation (1)
- dopamine acetylcholine (1)
- duodenal levodopa infusion (1)
- exome sequencing (1)
- experimental stroke (1)
- eye movement disorders (1)
- family caregiver (1)
- freezing of gait (1)
- freezing of gait (FOG) (1)
- functional MRI (1)
- functional neuroanatomy (1)
- future directions (1)
- gene-environment interaction (1)
- globus pallidus pars interna (GPi) (1)
- guidelines (1)
- high contrast (1)
- hospitals (1)
- human neurons (1)
- image-guided programming (1)
- imaging (1)
- induced neural stem cells (1)
- infarction volume (1)
- informal care (1)
- internal carotid artery stenosis (1)
- invasive electric stimulation (1)
- just noticeable difference (JND) (1)
- kinematics (1)
- levodopa-induced dyskinesia (1)
- locomotor adaptation (1)
- locus coeruleus (1)
- major depression (1)
- mortality (1)
- motor control (1)
- motor-evoked potentials (MEP) (1)
- mouse model (1)
- movement (1)
- movements (1)
- multiple system atrophy (1)
- musical syntax (1)
- mutation (1)
- neuroimmunology (1)
- neurology (1)
- neuronal apoptosis (1)
- neuronal network (1)
- neurophysiology (1)
- neuroscience (1)
- nicotinic receptors (1)
- non-motor features (1)
- noradrenalin (1)
- norepinephrine (1)
- nucleus ventralis intermedius (1)
- nystagmus (1)
- outcome (1)
- pallidal stimulation (1)
- parkinson disease (1)
- parkinsons disease (1)
- pathophysiology (1)
- pedunculopontine nucleus (PPN) (1)
- peripheral injury (1)
- peripheral nervous system (1)
- pet (1)
- photothrombosis (1)
- physical therapy modalities (1)
- pilot project (1)
- plaque cross-sectional area (1)
- plasma oxysterols (1)
- post-traumatic stress disorder (1)
- posture (1)
- precision medicine (1)
- progression (1)
- psychophysics (1)
- quality (1)
- randomized controlled double-blind study (1)
- randomized controlled trial (1)
- rat (1)
- reach-to-grasp movement (1)
- regulatory T cells (1)
- resting tremor (1)
- rett (1)
- rhythm perception (1)
- risk (1)
- risk of fall (1)
- segmental centers of mass (1)
- skilled forelimb movements (1)
- skin biopsy (1)
- soleus muscles (1)
- spinal-cord (1)
- stimulation (1)
- stroke care (1)
- subthalamic nucleus (STN) (1)
- synapse (1)
- synaptic vesicles (1)
- syndrome (1)
- target considerations (1)
- telemedicine (1)
- telemedicine network (1)
- term follow-up (1)
- thrombolysis (1)
- tight junctions (1)
- time (1)
- time perception (1)
- transcranial magnetic simulation (TMS) (1)
- transient ischemic attack (1)
- transmission electron microscopy (1)
- treatment-resistant depression (1)
- velocity (1)
- vertebrobasilar insufficiency (1)
- vertigo (1)
- vestibular (1)
- videooculography (1)
- white matter lesions (1)
- α-synuclein (1)
- α-synuclein-specific T cells (1)
Institute
- Neurologische Klinik und Poliklinik (54)
- Klinik und Poliklinik für Nuklearmedizin (9)
- Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie) (5)
- Neurochirurgische Klinik und Poliklinik (5)
- Institut für Klinische Epidemiologie und Biometrie (3)
- Institut für Virologie und Immunbiologie (3)
- Institut für Klinische Neurobiologie (2)
- Pathologisches Institut (2)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (1)
- Institut für Anatomie und Zellbiologie (1)
- Institut für Molekulare Infektionsbiologie (1)
- Klinik und Poliklinik für Hals-, Nasen- und Ohrenkrankheiten, plastische und ästhetische Operationen (1)
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie (1)
- Medizinische Klinik und Poliklinik II (1)
- Physiologisches Institut (1)
Background
Eye movement abnormalities are commonplace in neurological disorders. However, unaided eye movement assessments lack granularity. Although videooculography (VOG) improves diagnostic accuracy, resource intensiveness precludes its broad use. To bridge this care gap, we here validate a framework for smartphone video-based nystagmography capitalizing on recent computer vision advances.
Methods
A convolutional neural network was fine-tuned for pupil tracking using > 550 annotated frames: ConVNG. In a cross-sectional approach, slow-phase velocity of optokinetic nystagmus was calculated in 10 subjects using ConVNG and VOG. Equivalence of accuracy and precision was assessed using the “two one-sample t-test” (TOST) and Bayesian interval-null approaches. ConVNG was systematically compared to OpenFace and MediaPipe as computer vision (CV) benchmarks for gaze estimation.
Results
ConVNG tracking accuracy reached 9–15% of an average pupil diameter. In a fully independent clinical video dataset, ConVNG robustly detected pupil keypoints (median prediction confidence 0.85). SPV measurement accuracy was equivalent to VOG (TOST p < 0.017; Bayes factors (BF) > 24). ConVNG, but not MediaPipe, achieved equivalence to VOG in all SPV calculations. Median precision was 0.30°/s for ConVNG, 0.7°/s for MediaPipe and 0.12°/s for VOG. ConVNG precision was significantly higher than MediaPipe in vertical planes, but both algorithms’ precision was inferior to VOG.
Conclusions
ConVNG enables offline smartphone video nystagmography with an accuracy comparable to VOG and significantly higher precision than MediaPipe, a benchmark computer vision application for gaze estimation. This serves as a blueprint for highly accessible tools with potential to accelerate progress toward precise and personalized Medicine.
Highlights
• Beta-Guided programming is an innovative approach that may streamline the programming process for PD patients with STN DBS.
• While preliminary findings from our study suggest that Beta Titration may potentially mitigate STN overstimulation and enhance symptom control,
• Our results demonstrate that beta-guided programming significantly reduces programming time, suggesting it could be efficiently integrated into routine clinical practice using a commercially available patient programmer.
Background
Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson's disease (PD). Clinical outcomes after DBS can be limited by poor programming, which remains a clinically driven, lengthy and iterative process. Electrophysiological recordings in PD patients undergoing STN-DBS have shown an association between STN spectral power in the beta frequency band (beta power) and the severity of clinical symptoms. New commercially-available DBS devices now enable the recording of STN beta oscillations in chronically-implanted PD patients, thereby allowing investigation into the use of beta power as a biomarker for DBS programming.
Objective
To determine the potential advantages of beta-guided DBS programming over clinically and image-guided programming in terms of clinical efficacy and programming time.
Methods
We conducted a randomized, blinded, three-arm, crossover clinical trial in eight Parkinson's patients with STN-DBS who were evaluated three months after DBS surgery. We compared clinical efficacy and time required for each DBS programming paradigm, as well as DBS parameters and total energy delivered between the three strategies (beta-, clinically- and image-guided).
Results
All three programming methods showed similar clinical efficacy, but the time needed for programming was significantly shorter for beta- and image-guided programming compared to clinically-guided programming (p < 0.001).
Conclusion
Beta-guided programming may be a useful and more efficient approach to DBS programming in Parkinson's patients with STN-DBS. It takes significantly less time to program than traditional clinically-based programming, while providing similar symptom control. In addition, it is readily available within the clinical DBS programmer, making it a valuable tool for improving current clinical practice.
Inflammation in the brain and gut is a critical component of several neurological diseases, such as Parkinson’s disease (PD). One trigger of the immune system in PD is aggregation of the pre-synaptic protein, α-synuclein (αSyn). Understanding the mechanism of propagation of αSyn aggregates is essential to developing disease-modifying therapeutics. Using a brain-first mouse model of PD, we demonstrate αSyn trafficking from the brain to the ileum of male mice. Immunohistochemistry revealed that the ileal αSyn aggregations are contained within CD11c+ cells. Using single-cell RNA sequencing, we demonstrate that ileal CD11c\(^+\) cells are microglia-like and the same subtype of cells is activated in the brain and ileum of PD mice. Moreover, by utilizing mice expressing the photo-convertible protein, Dendra2, we show that CD11c\(^+\) cells traffic from the brain to the ileum. Together these data provide a mechanism of αSyn trafficking between the brain and gut.
Topological differences and confounders of mental rotation in cervical dystonia and blepharospasm
(2023)
Mental rotation (mR) bases on imagination of actual movements. It remains unclear whether there is a specific pattern of mR impairment in focal dystonia. We aimed to investigate mR in patients with cervical dystonia (CD) and blepharospasm (BS) and to assess potential confounders. 23 CD patients and 23 healthy controls (HC) as well as 21 BS and 19 hemifacial spasm (HS) patients were matched for sex, age, and education level. Handedness, finger dexterity, general reaction time, and cognitive status were assessed. Disease severity was evaluated by clinical scales. During mR, photographs of body parts (head, hand, or foot) and a non-corporal object (car) were displayed at different angles rotated within their plane. Subjects were asked to judge laterality of the presented image by keystroke. Both speed and correctness were evaluated. Compared to HC, CD and HS patients performed worse in mR of hands, whereas BS group showed comparable performance. There was a significant association of prolonged mR reaction time (RT) with reduced MoCA scores and with increased RT in an unspecific reaction speed task. After exclusion of cognitively impaired patients, increased RT in the mR of hands was confined to CD group, but not HS. While the question of whether specific patterns of mR impairment reliably define a dystonic endophenotype remains elusive, our findings point to mR as a useful tool, when used carefully with control measures and tasks, which may be capable of identifying specific deficits that distinguish between subtypes of dystonia.
Background and purpose
The aim was to characterize a combined vestibular, ocular motor and postural syndrome induced by deep brain stimulation (DBS) of the subthalamic nucleus in a patient with Parkinson's disease.
Methods
In a systematic DBS programming session, eye, head and trunk position in roll and pitch plane were documented as a function of stimulation amplitude and field direction. Repeat ocular coherence tomography was used to estimate ocular torsion. The interstitial nucleus of Cajal (INC), zona incerta (ZI) and ascending vestibular fibre tracts were segmented on magnetic resonance imaging using both individual and normative structural connectomic data. Thresholded symptom-associated volumes of tissue activated (VTA) were calculated based on documented stimulation parameters.
Results
Ipsilateral ocular tilt reaction and body lateropulsion as well as contralateral torsional nystagmus were elicited by the right electrode in a current-dependent manner and subsided after DBS deactivation. With increasing currents, binocular tonic upgaze and body retropulsion were observed. Symptoms were consistent with an irritative effect on the INC. Symptom-associated VTA was found to overlap with the dorsal ZI and the ipsilateral vestibulothalamic tract, while lying rather distant to the INC proper. A ZI-to-INC ‘incerto-interstitial’ tract with contact to the medial-uppermost portion of the VTA could be traced.
Conclusion
Unilateral stimulation of INC-related circuitry induces an ipsilateral vestibular, ocular motor and postural roll-plane syndrome, which converts into a pitch-plane syndrome when functional activation expands bilaterally. In this case, tractography points to an incerto-interstitial pathway, a tract previously only characterized in non-human primates. Directional current steering proved useful in managing this rare side effect.
Background
Regulatory CD4\(^+\)CD25\(^+\)FoxP3\(^+\) T cells (Treg) are a subgroup of T lymphocytes involved in maintaining immune balance. Disturbance of Treg number and impaired suppressive function of Treg correlate with Parkinson’s disease severity. Superagonistic anti-CD28 monoclonal antibodies (CD28SA) activate Treg and cause their expansion to create an anti-inflammatory environment.
Methods
Using the AAV1/2-A53T-α-synuclein Parkinson’s disease mouse model that overexpresses the pathogenic human A53T-α-synuclein (hαSyn) variant in dopaminergic neurons of the substantia nigra, we assessed the neuroprotective and disease-modifying efficacy of a single intraperitoneal dose of CD28SA given at an early disease stage.
Results
CD28SA led to Treg expansion 3 days after delivery in hαSyn Parkinson’s disease mice. At this timepoint, an early pro-inflammation was observed in vehicle-treated hαSyn Parkinson’s disease mice with elevated percentages of CD8\(^+\)CD69\(^+\) T cells in brain and increased levels of interleukin-2 (IL-2) in the cervical lymph nodes and spleen. These immune responses were suppressed in CD28SA-treated hαSyn Parkinson’s disease mice. Early treatment with CD28SA attenuated dopaminergic neurodegeneration in the SN of hαSyn Parkinson’s disease mice accompanied with reduced brain numbers of activated CD4\(^+\), CD8\(^+\) T cells and CD11b\(^+\) microglia observed at the late disease-stage 10 weeks after AAV injection. In contrast, a later treatment 4 weeks after AAV delivery failed to reduce dopaminergic neurodegeneration.
Conclusions
Our data indicate that immune modulation by Treg expansion at a timepoint of overt inflammation is effective for treatment of hαSyn Parkinson’s disease mice and suggest that the concept of early immune therapy could pose a disease-modifying option for Parkinson’s disease patients.
Deep brain stimulation (DBS) of the subthalamic nucleus or the globus pallidus is an established treatment for Parkinson’s disease (PD) that yields a marked and lasting improvement of motor symptoms. Yet, DBS benefit on gait disturbances in PD is still debated and can be a source of dissatisfaction and poor quality of life. Gait disturbances in PD encompass a variety of clinical manifestations and rely on different pathophysiological bases. While gait disturbances arising years after DBS surgery can be related to disease progression, early impairment of gait may be secondary to treatable causes and benefits from DBS reprogramming. In this review, we tackle the issue of gait disturbances in PD patients with DBS by discussing their neurophysiological basis, providing a detailed clinical characterization, and proposing a pragmatic programming approach to support their management.
Recovery of upper limb (UL) impairment after stroke is limited in stroke survivors. Since stroke can be considered as a network disorder, neuromodulation may be an approach to improve UL motor dysfunction. Here, we evaluated the effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) in rats on forelimb grasping using the single-pellet reaching (SPR) test after stroke and determined costimulated brain regions during STN-HFS using 2-[\(^{18}\)F]Fluoro-2-deoxyglucose-([\(^{18}\)F]FDG)-positron emission tomography (PET). After a 4-week training of SPR, photothrombotic stroke was induced in the sensorimotor cortex of the dominant hemisphere. Thereafter, an electrode was implanted in the STN ipsilateral to the infarction, followed by a continuous STN-HFS or sham stimulation for 7 days. On postinterventional day 2 and 7, an SPR test was performed during STN-HFS. Success rate of grasping was compared between these two time points. [\(^{18}\)F]FDG-PET was conducted on day 2 and 3 after stroke, without and with STN-HFS, respectively. STN-HFS resulted in a significant improvement of SPR compared to sham stimulation. During STN-HFS, a significantly higher [\(^{18}\)F]FDG-uptake was observed in the corticosubthalamic/pallidosubthalamic circuit, particularly ipsilateral to the stimulated side. Additionally, STN-HFS led to an increased glucose metabolism within the brainstem. These data demonstrate that STN-HFS supports rehabilitation of skilled forelimb movements, probably by retuning dysfunctional motor centers within the cerebral network.
Neurodegeneration by α-synuclein-specific T cells in AAV-A53T-α-synuclein Parkinson’s disease mice
(2022)
Background
Antigen-specific neuroinflammation and neurodegeneration are characteristic for neuroimmunological diseases. In Parkinson’s disease (PD) pathogenesis, α-synuclein is a known culprit. Evidence for α-synuclein-specific T cell responses was recently obtained in PD. Still, a causative link between these α-synuclein responses and dopaminergic neurodegeneration had been lacking. We thus addressed the functional relevance of α-synuclein-specific immune responses in PD in a mouse model.
Methods
We utilized a mouse model of PD in which an Adeno-associated Vector 1/2 serotype (AAV1/2) expressing human mutated A53T-α-Synuclein was stereotactically injected into the substantia nigra (SN) of either wildtype C57BL/6 or Recombination-activating gene 1 (RAG1)\(^{-/-}\) mice. Brain, spleen, and lymph node tissues from different time points following injection were then analyzed via FACS, cytokine bead assay, immunohistochemistry and RNA-sequencing to determine the role of T cells and inflammation in this model. Bone marrow transfer from either CD4\(^{+}\)/CD8\(^{-}\), CD4\(^{-}\)/CD8\(^{+}\), or CD4\(^{+}\)/CD8\(^{+}\) (JHD\(^{-/-}\)) mice into the RAG-1\(^{-/-}\) mice was also employed. In addition to the in vivo studies, a newly developed A53T-α-synuclein-expressing neuronal cell culture/immune cell assay was utilized.
Results
AAV-based overexpression of pathogenic human A53T-α-synuclein in dopaminergic neurons of the SN stimulated T cell infiltration. RNA-sequencing of immune cells from PD mouse brains confirmed a pro-inflammatory gene profile. T cell responses were directed against A53T-α-synuclein-peptides in the vicinity of position 53 (68–78) and surrounding the pathogenically relevant S129 (120–134). T cells were required for α-synuclein-induced neurodegeneration in vivo and in vitro, while B cell deficiency did not protect from dopaminergic neurodegeneration.
Conclusions
Using T cell and/or B cell deficient mice and a newly developed A53T-α-synuclein-expressing neuronal cell culture/immune cell assay, we confirmed in vivo and in vitro that pathogenic α-synuclein peptide-specific T cell responses can cause dopaminergic neurodegeneration and thereby contribute to PD-like pathology.
Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a steroid-responsive meningoencephalomyelitis, sometimes presenting with atypical clinical signs such as movement disorders or psychiatric and autonomic features. Beyond clinical presentation and imaging, diagnosis relies on detection of GFAP-antibodies (AB) in CSF. Using quantitative behavioral, serologic, and immunohistochemical analyses, we characterize two patients longitudinally over 18–24 months who presented with rapidly progressive neurocognitive deterioration in the context of GFAP-AB in CSF and unremarkable cranial MRI studies. Intensified immunotherapy was associated with clinical stabilization. The value of GFAP-AB screening in selected cases of rapidly progressive dementias is discussed.