Neurologische Klinik und Poliklinik
Refine
Has Fulltext
- yes (521)
Year of publication
Document Type
- Journal article (353)
- Doctoral Thesis (165)
- Report (2)
- Book (1)
Keywords
- ischemic stroke (27)
- multiple sclerosis (22)
- Parkinson's disease (19)
- deep brain stimulation (19)
- Parkinson’s disease (18)
- neuroinflammation (18)
- Multiple Sklerose (17)
- stroke (17)
- Fabry disease (16)
- Schlaganfall (16)
- neuropathic pain (15)
- Polyneuropathie (14)
- inflammation (13)
- Medizin (12)
- Parkinson-Krankheit (12)
- pain (11)
- Neuropathie (10)
- subthalamic nucleus (10)
- neuropathy (9)
- Schmerz (8)
- biomarker (8)
- dopamine (8)
- dystonia (8)
- neurology (8)
- Charcot-Marie-Tooth (7)
- cytokines (7)
- macrophages (7)
- mouse model (7)
- neurodegeneration (7)
- small fiber neuropathy (7)
- B cells (6)
- Fabry-Krankheit (6)
- Hautbiopsie (6)
- MS (6)
- Makrophage (6)
- Maus (6)
- Neurodegeneration (6)
- Neuropathischer Schmerz (6)
- Pain (6)
- Parkinson (6)
- acute ischemic stroke (6)
- antibodies (6)
- autoantibodies (6)
- depression (6)
- fibromyalgia syndrome (6)
- skin biopsy (6)
- Autoantikörper (5)
- B7-H1 (5)
- Biomarker (5)
- Dystonie (5)
- EAE (5)
- Entzündung (5)
- Fibromyalgie (5)
- Immunsystem (5)
- MRI (5)
- Makrophagen (5)
- Neurofascin (5)
- Parkinson disease (5)
- Ranvier-Schnürring (5)
- basal ganglia (5)
- blood-brain barrier (5)
- gene expression (5)
- magnetic resonance imaging (5)
- middle cerebral artery occlusion (5)
- movement disorders (5)
- neuroprotection (5)
- polyneuropathy (5)
- skin punch biopsy (5)
- traumatic brain injury (5)
- tremor (5)
- walking (5)
- ALS (4)
- CCI (4)
- Charcot-Marie-Syndrom (4)
- Cytokines (4)
- GFAP (4)
- Myelin (4)
- Nervenfaser (4)
- Neuroinflammation (4)
- Neuronale Plastizität (4)
- Neuropathy (4)
- Propriozeption (4)
- Puppenhandillusion (4)
- T-Lymphozyt (4)
- blood–brain barrier (4)
- cervical dystonia (4)
- disease (4)
- factor XII (4)
- gait initiation (4)
- immunohistochemistry (4)
- inflammasome (4)
- macrophage (4)
- mechanical thrombectomy (4)
- mice (4)
- microRNA (4)
- motor learning (4)
- mutation (4)
- myelin (4)
- platelets (4)
- regulatory T cells (4)
- thrombo-inflammation (4)
- Autoantibodies (3)
- Biopsie (3)
- Blut-Hirn-Schranke (3)
- CMT (3)
- COVID-19 (3)
- Carotisstenose (3)
- Caspr (3)
- Chemokine (3)
- DYT1 (3)
- ELISPOT (3)
- Entmarkung (3)
- Fabry (3)
- Fabry-associated pain (3)
- Gehirn (3)
- Genexpression (3)
- Guillain-Barré-Syndrom (3)
- HBMEC (3)
- Inflammation (3)
- Langerhans cells (3)
- Macrophage (3)
- Mausmodell (3)
- Mice (3)
- Multiple sclerosis (3)
- NLRP3 (3)
- Natalizumab (3)
- Nervendegeneration (3)
- Neuralgie (3)
- Neuromyelitis optica spectrum disorders (NMOSD) (3)
- Optic neuritis (3)
- PNP (3)
- Peripheres Nervensystem (3)
- Rehabilitation (3)
- Synuclein <alpha-> (3)
- T cells (3)
- T-lymphocytes (3)
- Ultraschalldiagnostik (3)
- Ureaplasma parvum (3)
- Zytokine (3)
- adaptive immune system (3)
- aging (3)
- animal models (3)
- anxiety (3)
- autoantibody (3)
- biomarkers (3)
- brain (3)
- cerebellar tDCS (3)
- cerebral ischemia (3)
- children (3)
- chronic pain (3)
- closed head injury (3)
- cognitive impairment (3)
- complement (3)
- corneal confocal microscopy (3)
- criteria (3)
- degeneration (3)
- dementia (3)
- enzyme replacement therapy (3)
- essential tremor (3)
- experimental autoimmune encephalomyelitis (3)
- experimental stroke (3)
- expression (3)
- fibromyalgia (3)
- gait analysis (3)
- genetics (3)
- heart failure (3)
- immune cells (3)
- immune system (3)
- kinematics (3)
- length of stenosis (3)
- local field potentials (3)
- lymphocytes (3)
- meningitis (3)
- mesencephalic locomotor region (3)
- miRNA (3)
- microglia (3)
- neurofascin (3)
- neurofilament light chain (3)
- neuroimmunology (3)
- neuropathischer Schmerz (3)
- neutrophils (3)
- photothrombotic stroke (3)
- quality of life (3)
- rehabilitation (3)
- rubber hand illusion (3)
- stroke unit (3)
- tMCAO (3)
- therapy (3)
- thrombolysis (3)
- tight junctions (3)
- transcranial magnetic stimulation (3)
- transplantation (3)
- trial (3)
- AQP4 (2)
- Acetylcholinrezeptor (2)
- Altern (2)
- Alzheimer’s disease (2)
- Antikörper (2)
- Arteria carotis interna (2)
- B-lymphocytes (2)
- BDNF (2)
- Basalganglien (2)
- CIDP (2)
- CNS (2)
- CSF-1 (2)
- Cerebrospinal fluid (2)
- Charcot-Marie-Tooth disease (2)
- Cortactin (2)
- Crush (2)
- Cytokine (2)
- Degeneration (2)
- Diabetes mellitus (2)
- Diagnosis (2)
- Dystonia (2)
- Elektrophysiologie (2)
- Encephalopathia hepatica (2)
- Enzyme replacement therapy (2)
- Evoziertes Potenzial (2)
- Fabry genotype (2)
- Fabry phenotype (2)
- Fc-receptor (2)
- Fibromyalgia (2)
- Fibromyalgia syndrome (2)
- Glatiramer acetate (2)
- Guillain-Barre-Syndrome (2)
- Guillain-Barré syndrome (2)
- HLA-G (2)
- Haut (2)
- Hautstanzbiopsie (2)
- IENFD (2)
- Ischemic stroke (2)
- Komplement (2)
- Körperselbstgefühl (2)
- Körperwahrnehmung (2)
- LTD (2)
- Langzeitdepression (2)
- Lewy-like pathology (2)
- Longitudinally extensive transverse myelitis (LETM) (2)
- MBP (2)
- MCC950 (2)
- MCP-1 (2)
- Mechanisms (2)
- Meningitis (2)
- Microglia (2)
- Morbus Fabry (2)
- Motorisches Lernen (2)
- Multiple Sclerosis (2)
- Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) (2)
- NEUROWIND (2)
- NMOSD (2)
- NMR-Tomographie (2)
- NOAC (2)
- Nervenbiopsie (2)
- Neuroimmunologie (2)
- Neuronal ceroid lipofuscinosis (2)
- Nucleus subthalamicus (2)
- Outcome survey (2)
- PET (2)
- Peripheral nervous system (2)
- Proprioception (2)
- Quantitative sensorische Testung (2)
- Schwann cell (2)
- Schwann-Zelle (2)
- Serotonin (2)
- Small fiber Neuropathie (2)
- Small fiber neuropathy (2)
- Spinalganglion (2)
- Stroke (2)
- Stroke unit (2)
- T lymphocytes (2)
- T-Lymphozyten (2)
- TDMT (2)
- Tiermodell (2)
- Tourette syndrome (2)
- Transkranielle magnetische Stimulation (2)
- Treatment (2)
- TrkB (2)
- Ultraschall (2)
- Ureaplasma urealyticum (2)
- Zentralnervensystem (2)
- accuracy (2)
- alpha-synuclein (2)
- amyotrophic-lateral-sclerosis (2)
- animal model (2)
- anticoagulation (2)
- atrial fibrillation (2)
- autoimmune (2)
- autoimmunity (2)
- axonal damage (2)
- axonaler Schaden (2)
- balance (2)
- base of support (2)
- beta oscillations (2)
- binding (2)
- biopsy (2)
- blood brain barrier (2)
- blood flow (2)
- blood pressure (2)
- blood-brain-barrier (2)
- c-Fos (2)
- caregiver burden (2)
- carotid atherosclerosis (2)
- carotid stenosis (2)
- carotid ultrasound (2)
- case report (2)
- central nervous system (2)
- cerebral autoregulation (2)
- cerebrospinal fluid (2)
- cerebrovascular disorders (2)
- chemokines (2)
- chronic cerebrovascular disease (2)
- chronic kidney disease (2)
- colony-stimulating factor (2)
- consolidation (2)
- contact-kinin system (2)
- contactin (2)
- cytokine (2)
- degree of stenosis (2)
- demyelination (2)
- diabetic neuropathy (2)
- diagnosis (2)
- diagnostic markers (2)
- differential diagnosis (2)
- dimethyl fumarate (2)
- disability (2)
- diseases of the nervous system (2)
- echocardiography (2)
- edema (2)
- electrophysiology (2)
- endoglin (2)
- endothelial cells (2)
- exercise (2)
- freezing of gait (2)
- gait (2)
- gene (2)
- generalized cerebral edema (2)
- glial fate modulation (2)
- glial fibrillary acidic protein (2)
- globotriaosylceramide (2)
- glycine receptor (2)
- glycoprotein receptor Ib (2)
- guidelines (2)
- hearing loss (2)
- hypoxia (2)
- immunomodulation (2)
- in vivo imaging (2)
- induced pluripotent stem cells (2)
- infarction (2)
- inflammatory neuropathy (2)
- ion channels (2)
- ischemic penumbra (2)
- just noticeable difference (JND) (2)
- lesions (2)
- leukocytes (2)
- locomotor adaptation (2)
- locus coeruleus (2)
- machine learning (2)
- major depression (2)
- miR-21 (2)
- miRNS (2)
- mitochondria (2)
- mortality (2)
- motor control (2)
- mouse models (2)
- multiple system atrophy (2)
- multiple-sclerosis (2)
- musical syntax (2)
- nerve biopsy (2)
- nerve fibers (2)
- nerve fibres (2)
- neurological disorders (2)
- neuronal plasticity (2)
- neurons (2)
- neuroscience (2)
- node of Ranvier (2)
- opioids (2)
- outcomes (2)
- pain questionnaire (2)
- pain-related evoked potentials (2)
- parkinson's disease (2)
- passive transfer (2)
- pathogenesis (2)
- peripheral nervous system (2)
- peripheral neuropathy (2)
- photothrombosis (2)
- physical activity (2)
- preclinical research (2)
- predictive value (2)
- prognosis (2)
- protein (2)
- psychophysics (2)
- quantitative sensory testing (2)
- randomized controlled trial (2)
- rat (2)
- relapse (2)
- renal system (2)
- resting tremor (2)
- reversible posterior leukoencephalopathy syndrome (2)
- second hit (2)
- small fiber pathology (2)
- spinal cord (2)
- spinal cord injury (2)
- split-belt treadmill (2)
- striatum (2)
- stroke care (2)
- synaptic vesicles (2)
- systems biology (2)
- tDCS (2)
- telemedicine (2)
- thrombosis (2)
- time perception (2)
- transient ischemic attack (2)
- transient middle cerebral artery occlusion (2)
- ultrasound (2)
- velocity (2)
- voluntary movement (2)
- von Willebrand factor (2)
- α-synuclein (2)
- (Para-)nodale Autoantikörper (1)
- 2B (1)
- 3D fluoroscopy (1)
- 3D structure (1)
- 3D-Struktur (1)
- 5-Dihydroxycinnamat (1)
- 5-HIAA (1)
- 5-HTT Knock Out (1)
- 5-dihydroxycinnamate (1)
- 5IA-SPECT (1)
- 65-kda isoform (1)
- A delta-Faser (1)
- A-delta fibers (1)
- A53T (1)
- A53T mutation (1)
- A53T-Mutation (1)
- ACE (1)
- ADHD (1)
- ALS mimic (1)
- ALS treatment (1)
- ALSIN gene (1)
- APERIO (1)
- APERIO Hybrid (1)
- AQP (1)
- ASC (1)
- ASIC 3 (1)
- ATF3 (1)
- Abciximab (1)
- Adaptive cell transfer (1)
- Adaptives Immunsystem (1)
- Adaptorproteine (1)
- Adult patients (1)
- Affekt (1)
- Agalsidase beta (1)
- Agalsidase beta therapy (1)
- Agaphelin (1)
- Age (1)
- Agrin (1)
- Alemtuzumab (1)
- Alkoholische Polyneuropathie (1)
- Allodynie (1)
- Alpha galactosidase (1)
- Alpha-Synuclein (1)
- Alter (1)
- Alzheimer disease (1)
- Alzheimer’s dementia (1)
- Amitriptylin (1)
- Amplitude (1)
- Amyotrophic Lateral Sclerosis (ALS) (1)
- Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5) (1)
- Anderson-Fabry Disease (1)
- Aneurysma (1)
- Animal models (1)
- Anosognosie (1)
- Anti-Neurofascin-Autoantikörper-assoziierten Neuropathie (1)
- Antibody index (1)
- Antigen CD8 (1)
- Antikoagulation (1)
- Antiparanodal Autoantibodies (1)
- Anxiety (1)
- Apoptosis (1)
- Approved immunomodulators (1)
- Aquaporin 4 (1)
- Aquaporin-4 antibodies (AQP4-Ig, NMO-IgG)G (1)
- Aquaporin-4 antibodies (AQP4-IgG) (1)
- Aquaporin-4 antibodies (AQP4-IgG, NMO-IgG) (1)
- Aquaporin4 (1)
- Arteria cerebri media (1)
- Arterial Diameters (1)
- Arterial water (1)
- Asomatognosie (1)
- Ataxia (1)
- Atrial fibrillation (1)
- Atrophie (1)
- Autoantigen (1)
- Autoimmun (1)
- Autoimmunität (1)
- Autophagie (1)
- Autophagie <Physiologie> (1)
- Axon (1)
- Axon degeneration (1)
- Axonal degeneration (1)
- Azathioprine (1)
- Aδ- and C-fibers (1)
- B-Lymphocyten (1)
- BB/OKL rats (1)
- BCI (1)
- Barkhof criteria (1)
- Barthel Index (1)
- Barthel-Index modified Rankin-Scale (1)
- Barthel-Index modifizierte Rankin-Skala (1)
- Basal Ganglia (1)
- Basal ganglia (1)
- Beam-Walking-Test (1)
- Beta-glucocerebrosidase (1)
- Bewegungsstörung (1)
- Bildgebung (1)
- Biopsiediagnostik von entzündlichen Polyneuropathien (1)
- Blutgerinnungsfaktor XII (1)
- Borrelien (1)
- Borreliose (1)
- Borreliosis (1)
- Braak (1)
- Brain (1)
- Brain atrophy (1)
- Brain edema (1)
- Brain ischemia (1)
- Brain-derived neurotrophic factor (1)
- Brainstem encephalitis (1)
- C-Faser (1)
- C-reactive protein (1)
- C.376A>G (p.S126G) (1)
- C1-inhibitor (1)
- C57BL/6 mice (1)
- CAS (1)
- CCL2 (1)
- CCS (1)
- CD105 (1)
- CD133 (1)
- CD19 (1)
- CD52 (1)
- CEA (1)
- CLN3 (1)
- CMV (1)
- CNS Myelination (1)
- CNS disease (1)
- CNS imaging (1)
- CNS integrity (1)
- COMPLEX 1 (1)
- COU254 (1)
- CRM (1)
- CRPS (1)
- CSF (1)
- CSF-1 Rezeptor (1)
- CSF-1 Rezeptor Inhibitor (1)
- CSF-1 receptor (1)
- CSF-1 receptor inhibitor (1)
- CSF-1-Rezeptor-Inhibitor (1)
- CSVD (1)
- CXCL10 (1)
- CXCL4 (1)
- CXCL5 (1)
- CXCL7 (1)
- CXCL8 (1)
- CXCR2 (1)
- Ca2+ homeostasis (1)
- Ca2+ ion analysis (1)
- Ca2+ leak (1)
- Ca2+ oscillation (1)
- Campylobacter jejuni (1)
- Capsaicin (1)
- Capsaicin receptor (1)
- Carotis (1)
- Carotischirurgie (1)
- Caspase (1)
- Caspr1 (1)
- Cell Index (1)
- Cell therapy (1)
- Cell-based assays (1)
- Central Nervous System (1)
- Cerebellitis (1)
- Cerebral blood flow (1)
- Cerebral small vessel disease (1)
- Cerebral vasospasm (1)
- Cerebral-ischemia (1)
- Cgrin (1)
- Charcot-Marie-Tooth Neuropathie (1)
- Charcot-Marie-Tooth Neuropathy (1)
- Charcot-Marie-Tooth syndrom (1)
- Charcot-Marie-Tooth-Hoffmann-Syndrom (1)
- Charcot–Marie–Tooth disease (1)
- Charcot–Marie–Tooth disease type 1A (1)
- Chemokine Receptor (1)
- Chemokinrezeptors (1)
- CholinomiRs (1)
- Chronic Constriction Injury (1)
- Chronic heart failure (1)
- Chronic neuropathic pain (1)
- Chronische Niereninsuffizienz (1)
- Chronischer Schmerz (1)
- Cisterna magna (1)
- Clinical manifestations (1)
- Clinically silent stroke (1)
- Coefficient (1)
- Cognitive behavior (1)
- Cognitive decline (1)
- Cold (1)
- Computertomographie (1)
- Connexin32 deficient mice (1)
- Connexin32-defiziente Maus (1)
- Consortium to Establish a Registry for Alzheimer's Disease (1)
- Contactin (1)
- Contactin 1 (1)
- Corneal confocal microscopy (1)
- Corneale confocale Mikroskopie (1)
- Cortico-striatal projection neurons (1)
- Crespi effect (1)
- Cyclophosphamid (1)
- Cyclophosphamide (1)
- D313Y genotype (1)
- DARPA (1)
- DBS biomarkers (1)
- DBS programming (1)
- DOPA-responsive-dystonia (1)
- DRD1 (1)
- DYT-TOR1A (1)
- Deep Brain Stimulation (1)
- Deeskalation (1)
- Deeskalationstherapie (1)
- Deflazacort (1)
- Dekompressionskraniektomie (1)
- Delphi procedure (1)
- Demenz (1)
- Demyelinating peripheral neuropathy (1)
- Demyelination (1)
- Demyelinisierung (1)
- Dendritische Zelle (1)
- Denervierung (1)
- Devic Maus (1)
- Devic mice (1)
- Devic’s syndrome (1)
- Diabetic polyneuropathy (1)
- Diabetische Neuropathie (1)
- Diabetische Polyneuropathie (1)
- Dialyse (1)
- Diapedese (1)
- Dimethylfumarat (1)
- Diplopia Internuclear ophthalmoplegia (INO) (1)
- Disease (1)
- Donor lymphocytes (1)
- Dopamine (1)
- Dorsal Root Ganglion (1)
- Dorsal root ganglion (1)
- Dose reduction (1)
- Double hemorrhage model (1)
- Drosophila (1)
- Duchenne dystrphy (1)
- Durchblutung (1)
- Dyskinesie (1)
- EAAT2 (1)
- ECM (1)
- EEG (1)
- EEG data (1)
- EMG (1)
- ER Ca2+ imaging (1)
- ER Ca2+ store (1)
- ERK1/2 (1)
- ERT (1)
- ET (1)
- Edema (1)
- Effekte von Contactin-1-IgG-Patientenantikörpern im Zellkulturmodell (1)
- El Escorial (1)
- Electrophysiology (1)
- Embryonalentwicklung (1)
- Emotionales Verhalten (1)
- Encephalitis (1)
- Endarteriektomie (1)
- Endothelzelle (1)
- English version (1)
- Entzündungsreaktion (1)
- Entzündungsschmerz (1)
- Enzephalitis (1)
- Epilepsy (1)
- Epitop (1)
- Erbliche Neuropathien (1)
- Ereigniskorreliertes Potenzial (1)
- Erregbarkeit (1)
- Escalation therapy (1)
- Eskalationstherapie (1)
- Essentieller Tremor (1)
- EuroQol Five Dimension Five Level Scale (EQ-5D-5L) (1)
- Evoked potentials (1)
- Evozierte Potenziale (1)
- Experimental stroke (1)
- Experimentaltumor (1)
- Experimenteller Schlaganfall (1)
- Expression (1)
- F-18-FDG PET (1)
- FOSMN (1)
- FOXP3 (1)
- FP-CIT SPECT (1)
- FSHD (1)
- FTY720 (1)
- FTY720-P (1)
- FXII (1)
- FXIIa inhibitor rHA-Infestin (1)
- Fabry cardiomyopathy (1)
- Fabry nephropathy (1)
- Fabry’s disease (1)
- Facial nerve palsy (1)
- Facioscapulohumeral muscular dystrophy (1)
- Factor messenger-RNA (1)
- Fatigue (1)
- Fc-Rezeptor (1)
- Fibroblasten (1)
- Fibroblasts (1)
- Fluoreszenz (1)
- Fluoreszenzmikroskopie (1)
- Focal dystonie (1)
- Frabin/Fgd4 (1)
- Funktionelle Kernspintomografie (1)
- GABAergic neurons (1)
- GAP 43 (1)
- GCH1 (1)
- GFAP-astrocytopathies (1)
- GLA KO mouse model (1)
- GP-IIb/IIIa-Antagonist (1)
- GP-IIb/IIIa-antagonist (1)
- GPCR (1)
- GRAID (1)
- Gait initiation (1)
- Gedächtnis (1)
- Gefäßverschluss (1)
- Gehirn-Computer-Schnittstelle (1)
- Gene-expression (1)
- Genetik (1)
- Genmutation (1)
- Geriatrics (1)
- Geriatrie (1)
- Geste (1)
- Gland (1)
- Glial fibrillary acidic protein (1)
- Glioblastoma (1)
- Glioma stem cells (1)
- Glutamic-acid decarboxylase anxiety (1)
- Guillain-Barr'e-Syndrom (1)
- Guillain-Barré Syndrom (1)
- HMGB1 (1)
- HMSN (1)
- HMSN immune cells (1)
- HPF (1)
- HRUS (1)
- Hautzelle (1)
- Head-injury (1)
- Hearing loss (1)
- Heat Hyperalgesia (1)
- Hemodynamic depression (1)
- Heparin (1)
- Hepatische Enzephalopathie (1)
- Hereditary spastic paraplegia (1)
- Hereditäre Neuropathien (1)
- Hereditäre spastische Spinalparalyse (1)
- Hereditäre spastsiche Paraplegie (1)
- Heriditary sensor and motor neuropathy (1)
- Heriditäre sensomotorische Neuropathie (1)
- Herpesvirus 6 (1)
- Hirnblutung (1)
- Hirndruck (1)
- Hirnstimulation (1)
- Hirnödem (1)
- Hornhaut (1)
- Hyperalgesia (1)
- Hyperalgesie (1)
- IBA-1 (1)
- ICB (1)
- ICH (1)
- IL-15 (1)
- IL-22 binding protein isoform (1)
- IL-4 (1)
- IL22RA2 (1)
- IPND criteria (1)
- IVIG (1)
- IVIg (1)
- Identification (1)
- Idiopathisches Parkinson-Syndrom (1)
- IgG (1)
- IgG4 (1)
- Ih (1)
- Imaging (1)
- Immune cells (1)
- Immune system (1)
- Immunfluoreszenz (1)
- Immunmodulation (1)
- Immunoblot (1)
- Immunreaktion (1)
- Immunzellen (1)
- Impfung (1)
- Improvement (1)
- Infarkt (1)
- Infections (1)
- Inflamamtion (1)
- Influenza (1)
- Infrarotspektroskopie (1)
- Inherited neuropathies (1)
- Innervation (1)
- Insulin (1)
- Integrin (1)
- Integrin alpha-4 (1)
- IntelliCage (1)
- Interferon <beta-> (1)
- Interferon beta (1)
- Interleukin-18 (1)
- Interleukin-4 (1)
- Interleukin-6 (1)
- Interleukin-6-Deficient mice (1)
- International consensus diagnostic criteria for neuromyelitis optica spectrum disorders (1)
- Intractable nausea and vomiting (1)
- Intraepidermale Nervenfaserdichte (1)
- Intrathekale Applikation (1)
- Intravascular coagulation (1)
- Intrinsische Gerinnungskaskade (1)
- Ischemia (1)
- Ischämischer Schlaganfall (1)
- Ixolaris (1)
- JCV (1)
- K+ channel (1)
- K2P channels (1)
- KCNK5 (1)
- K\(_{2P}\)5.1 (1)
- Kaliumkanal (1)
- Kallikrein-Kinin-System (1)
- Kleinfaserneuropathie (1)
- Kleinfaseruntersuchungen (1)
- Kleinhirn (1)
- Knochentumor (1)
- Ko-inhibitorischer Signalweg (1)
- Kognition (1)
- Kognition bei mHE (1)
- Komplement <Immunologie> (1)
- Komplementsystem (1)
- Konfokale Mikroskopie (1)
- Konsolidierung (1)
- Kontrastmittel (1)
- Kopfschemata (1)
- Kortikobasales Syndrom (1)
- Kostimulation (1)
- Kreuzreaktivität (1)
- Kritische Flimmerfrequenz (1)
- L-DOPA (1)
- LI-rTMS (1)
- LIMP-2 (1)
- LSVT-big therapy (1)
- LVO (1)
- Ladder-Rung-Walking-Test (1)
- Laktat (1)
- Landouzy-Déjerine-Atrophie (1)
- Langzeitpotenzierung (1)
- Latenzänderung (1)
- Lebensqualität bei mHE (1)
- Lebensqualität nach stroke (1)
- Leukemia Inhibitory Factor (1)
- Lewy-Pathologie (1)
- Limb girdle muscular dystrophy (LGMD) (1)
- Liquor cerebrospinalis (1)
- Lokale Feldpotentialaktivität (1)
- Long COVID (1)
- Longitudinally extensive transverse myelitis (1)
- Lyme-Krankheit (1)
- Lyme-disease (1)
- Lymphozyten (1)
- Lymphozyten mediierter Angriff auf Neurone (1)
- Lysosomal storage disease (1)
- Ländliche Klinik (1)
- M-CSF (1)
- M. Fabry (1)
- M.Fabry (1)
- MDL-28170 (1)
- MIBG scintigraphy (1)
- MIC ligands (1)
- MMN (1)
- MMP9 (1)
- MOC fibers (1)
- MOG (1)
- MOG-IgG (1)
- MPZ (P0) (1)
- MRI criteria (1)
- MRI lesion study (1)
- MRT (1)
- MRT-Läsionsstudie (1)
- MSSS (1)
- Macrophages (1)
- Magnetic resonance imaging (1)
- Magnetic-resonance (1)
- Matched pairs (1)
- McDonald criteria (1)
- Mediated Inflammatory Hyperalgesia (1)
- Medium spiny neurons (1)
- Meige syndrome (1)
- Memory dysfunction (1)
- Meningoencephalitis (1)
- Meningoenzephalitis (1)
- Merkel cell density (1)
- Merkel cells (1)
- Merkelzelle (1)
- Mesencephal Locomotor Region (1)
- Mesenchymal stem/stromal cells (1)
- Mesenzephale Lokomotor Region (1)
- Methotrexate (1)
- Methyl-2 (1)
- Methylmalonsäure (1)
- Microarray (1)
- Middle cerebral artery infarction (1)
- Migräne (1)
- Mikroblutung (1)
- Mikroglia (1)
- Mikroglobulin <beta-2-> (1)
- Mikroneurographie (1)
- Mitoxantron (1)
- Miyoshi myopathy (1)
- Model (1)
- Molecular-weight heparin (1)
- Mononeuropathie (1)
- Monopolar depression (1)
- Morbus Parkinson (1)
- Morphologie <Biologie> (1)
- Motoneuron (1)
- Motoneuronen (1)
- Motor Control (1)
- Motor cortex (1)
- Motor learning (1)
- Motor nerve biopsy (1)
- Motor plasticity (1)
- Motoradaptation (1)
- Motorische Endplatte (1)
- Motorkonsolidierung (1)
- Mucopolysaccharidosis IIIa (1)
- Multiple Sclerosis Society of Canada (1)
- Multiplen Sklerose (1)
- Multisensorische Integration (1)
- Musikwahrnehmung (1)
- Muskel (1)
- Muskelhypertonie (1)
- Muster (1)
- Myasthenia gravis (1)
- Myatrophische Lateralsklerose (1)
- Mycobacterium caprae (1)
- Mycobacterium tuberculosis complex (1)
- Myelin oligodendrocyte glycoprotein (MOG) antibodies (1)
- Myelinopathie (1)
- Myelinopathy (1)
- Myelinprotein (1)
- Myelitis (1)
- Myeloma (1)
- Myoblast (1)
- Myoblasten (1)
- Myopathie (1)
- Mysthenia Gravis (1)
- NADPH oxidase inhibitors (1)
- NAP-2 (1)
- NETs (1)
- NF-\(\kappa\)B (1)
- NF-κB (1)
- NKG2D (1)
- NKG2D ligands (1)
- NLG (1)
- NMO (1)
- NMO-IGG (1)
- NPC1 gene (1)
- NPC2 gene (1)
- NPSI (1)
- NaV1.9 (1)
- Nahinfrarot-Spektroskopie (1)
- Natriumkanal (1)
- Nav1.8 (1)
- Nav1.9 (1)
- Necrosis-factor-Alpha (1)
- Nerve growth-factorcopy (1)
- Nervenregeneration (1)
- Nervenregeneration ; Periphere Nervenverletzung ; Neuromuskuläre Krankheit ; Axonverletzung ; Entmarkung (1)
- Nervensonographie (1)
- Nervenultraschall (1)
- Nestin (1)
- Neuroborreliose (1)
- Neurodegenerative Erkrankung (1)
- Neurofascin-155-IgG4-(Para-)nodopathie (1)
- Neurofascin-155-IgM (1)
- Neurofeedback (1)
- Neurogenic inflammation (1)
- Neurogeriatrie (1)
- Neurologie (1)
- Neuromyelitis Optica (1)
- Neuromyelitis optica (1)
- Neuromyelitis optica (NMO) (1)
- Neuromyelitis optica antibodies (NMO-IgG) (1)
- Neuronale Ceroid Lipofuszinose (1)
- Neuropathic Pain (1)
- Neuroplastizität (1)
- Neuropsychologie (1)
- Neuropsychologischer Test (1)
- Neuroregeneration (1)
- Neurotrophe Faktoren (1)
- Neurotrophic Factors (1)
- Neurotrophic factors (1)
- Neurotrophine (1)
- Neutralisation <Chemie> (1)
- Neutrophil (1)
- NfL (1)
- Nicht-motorische Begleitsymptome (1)
- Nicotinischer Acetylcholinrezeptor (1)
- Niederfrequenzstimulation (1)
- Niemann–Pick disease type C (1)
- Nociceptor (1)
- Nodo-parandopathy (1)
- Nozizeptor (1)
- OCB (1)
- ON-Freezing (1)
- Ofatumumab (1)
- Oligoclonal bands (1)
- Oncostatin-M-Receptor (1)
- Opioid receptor (1)
- Opioidrezeptor (1)
- Optical coherence tomography (1)
- Optikusnervenscheidendurchmesser (1)
- Orai2 (1)
- Oral anticoagulation (1)
- Osteopontin (1)
- Outcome (1)
- P300 Welle (1)
- PD-1 (1)
- PD-L1 (1)
- PF4 (1)
- PHES (1)
- PI3K isoforms (1)
- PML (1)
- PMP22 (1)
- PPAR-gamme (1)
- PREP (1)
- Pain questionnaire (1)
- Pain-related evoked potentials (1)
- Pan-Neurofascin-IgG3 (1)
- Paradoxical heat sensation (1)
- Paranodale und nodale Autoantikörper (1)
- Paranodopathie (1)
- Parkinson Krankheit (1)
- Parkinson's Disease (1)
- Parkinsons disease (1)
- Parkionson's disease (1)
- Partial Sciatic Transection (1)
- Passiv-Transfer (1)
- Pathomechanismus (1)
- Pathophysiologie (1)
- Patient Reported Outcome (1)
- Pedunculopontiner tegmentaler Nukleus (1)
- Perfusion (1)
- Peripheral Inflammation (1)
- Periphere Nerven (1)
- Periphere mononukleäre Zellen (1)
- Pharmacological management (1)
- Phosphodiesterasehemmer (1)
- Photothrombotic Stroke (1)
- Physiotherapie (1)
- Pilzkörper (1)
- Plasma extravasation (1)
- Plasmakallikrein (1)
- Plasmakallikrein ischämischer Schlaganfall (1)
- Plastizität (1)
- Platelets (1)
- Pleckstrin homology containing family member 5 (Plekhg5) (1)
- Pointing error (1)
- Polyneuropathy (1)
- Pregnancy (1)
- Procalcitonin (1)
- Prodigy (1)
- Prognose (1)
- Prognostik (1)
- Progressive supranuclear palsy (1)
- Proton Magnetic Resonance Spectroscopy (1)
- Protonen (1)
- Protonenspektroskopie (1)
- Psychologische Diagnostik (1)
- Psychophysik (1)
- QSART (1)
- QST (1)
- Quality of life (1)
- Quantitativ Sensorische Testung (1)
- Quantitative Sensorische Testung (1)
- Quantitativer sudomotorischer Axonreflextest (1)
- R-715 (1)
- RAG-1 (1)
- RECK (1)
- RKIP (1)
- RNA extraction (1)
- RT-PCR (1)
- Randomized controlled trial (1)
- Randomized controlled-trial (1)
- Ranvier'sche Schnürringe (1)
- Rasmussen-Syndrom (1)
- Rat (1)
- Rat Sensory Neurons (1)
- Rats (1)
- Ratte (1)
- Raumwahrnehmung (1)
- Receptors (1)
- Regeneration (1)
- Regenerative medicine (1)
- Regulatorische T-Zellen (1)
- Regulatory T cells (1)
- Resilienz (1)
- Respiratory insufficiency (1)
- Retinal degeneration (1)
- Revaskularisierung (1)
- Rheumatoid-Arthritis (1)
- Rho-GTPase Cdc42 (1)
- Rhombencephalitis (1)
- Rhythmusperzeption (1)
- Richardson-Olszewski-Syndrome (1)
- Rituximab (1)
- Rochester diabetic neuropathy (1)
- SARS-CoV (1)
- SB332235 (1)
- SERCA (1)
- SGLT2 inhibitors (1)
- SHRSP (1)
- SMA (1)
- SNI (1)
- SOD1 mutations (1)
- SPECT (1)
- SPG17 (1)
- SPG4 (1)
- SREBP (1)
- STAIR (1)
- STDT (1)
- STEMI (1)
- Sars-CoV-2 (1)
- Schlaganfall-Netzwerk (1)
- Schmerz-assoziierte elektrisch evozierte Potentiale (1)
- Schmerz-assoziierte evozierte Potenziale (1)
- Schmerzerfassung (1)
- Schmerzforschung (1)
- Schmerzfragebogen (1)
- Schmerzzeichnungen (1)
- Schreibkrampf (1)
- Schub (1)
- Schwann Zellen (1)
- Schwann cell dedifferentiation (1)
- Schwann cell differentiation (1)
- Schwann cells (1)
- Schwann-cells (1)
- Schwann´sche Zelle (1)
- Schweißdrüse (1)
- Schädel-Hirn-Trauma (1)
- Score (1)
- Screening questionnaire (1)
- Secondary stroke prevention (1)
- Sekundärprävention (1)
- Sensitivity (1)
- Sensorik <Neurophysiologie> (1)
- Serotonin-Reuptake-Hemmer (1)
- Sigaltransduktionsweg (1)
- Signaltransduktion (1)
- Silver-syndrome (1)
- Sjorgens-syndrome (1)
- Skelettmuskel (1)
- Skin biopsy (1)
- Small Fiber Neuropathie (1)
- Small fiber dysfunction (1)
- Small-fiber neuropathy (1)
- Sonic hedgehog (1)
- Sonographie (1)
- Sphingosine 1-Phosphate (1)
- Spinalganglienneuron (1)
- Stammganglienblutung (1)
- Stenosis degree (1)
- Stenosis length (1)
- Stent (1)
- Stereologie (1)
- Stiff-Person-Syndrom (1)
- Stim (1)
- Stimuli (1)
- Striatum (1)
- Stroke Manager (1)
- Stroke-Unit (1)
- Subarachnoid (1)
- Subarachnoid hemorrhage (1)
- Subarachnoidalblutung (1)
- Suralisbiopsien (1)
- Suralisneurographie (1)
- Survey (1)
- Synapse (1)
- Synaptic plasticity (1)
- System involvement (1)
- T cell activation (1)
- T cell line (1)
- T lymphocyte (1)
- T- Lymphozyt (1)
- T-PA (1)
- T-cell epitope (1)
- T-cell repertoire (1)
- T-cells (1)
- T-lymphocyte (1)
- T-zell epitope (1)
- T-zell repertoir (1)
- TAP Alertness (1)
- TASK2 (1)
- TBI (1)
- TIMP-1 (1)
- TIND (1)
- TLO (1)
- TMS (1)
- TNF (1)
- TNF alpha (1)
- TNF-R1 (1)
- TNF-R2 (1)
- TNF-Rezeptor-1 (1)
- TNF-Rezeptor-2 (1)
- TNF-receptor-1 (1)
- TNF-receptor-2 (1)
- TNF-receptors (1)
- TNF-α (1)
- TNFα (1)
- TOR1A (1)
- TRP (1)
- TRP Channels (1)
- TRPV 1 (1)
- TSPO (1)
- Tdp-43 (1)
- Telemedizin (1)
- Temporal Discrimination Threshold (1)
- Therapy (1)
- Thermal Hyperalgesia (1)
- Thrombektomie (1)
- Thrombo-inflammation (1)
- Thromboinflammation (1)
- Thrombolyse (1)
- Thrombozyt (1)
- Thrombus (1)
- Thrombus formation (1)
- Thymom (1)
- Tiefe Hirnstimulation (1)
- Topiramat (1)
- Topiramate (1)
- Tor1a (1)
- Torticollis (1)
- Training (1)
- Transkranielle Magnetstimulation (1)
- Transverse Myelitis (1)
- Transverse myelitis (1)
- Trauma (1)
- Trem2 (1)
- Trepanation (1)
- Triamcinolon (1)
- Trick (1)
- Tryptophan hydroxylase-2 (Tph2) (1)
- Tuberkulose (1)
- Tumor-Nekrose-Faktor (1)
- Tumor-Nekrose-Faktor <alpha> (1)
- Tumor-Nekrose-Faktor <alpha>-Inhibitor (1)
- Type 1 diabetes (1)
- Umfragestudie (1)
- Ureaplasma species (1)
- Urämie (1)
- VCAM (1)
- VCAM-1 (1)
- VR1 (1)
- Vaccination (1)
- Vascular system (1)
- Vaskulitische Polyneuropathie (1)
- Vasodilatator-stimuliertes Phosphoprotein (1)
- Vasodilator-Stimulated Phosphoprotein (1)
- Venlafaxin (1)
- Verbesserung (1)
- Vergleich (1)
- ViMS (1)
- Viral (1)
- Virus (1)
- Visuomotorisches Lernen (1)
- Vitamin D (1)
- Vitamin D-Mangel (1)
- Vitamin-B12-Mangel (1)
- Volon A (1)
- Von-Willebrand-factor (1)
- Western blot (1)
- White matter lesions (1)
- Wiederbelebung (1)
- Wingerchuk criteria 2006 and 2015 (1)
- Wissenschaftlicher Nachwuchs (1)
- Würzburg / Universität Würzburg (1)
- X-Chromosom (1)
- X-Inaktivierung (1)
- X-chromosomal inactivation (1)
- XAV-939 (1)
- ZNS (1)
- Zeitwahrnehmung (1)
- Zellkultur (1)
- Zentralnervensystems (1)
- Zonula Occludens-1 (1)
- Zytokin (1)
- [18F]FDG positron emission tomography (1)
- abciximab (1)
- acid sphingomyelinase (1)
- activation (1)
- activity-dependent slowing (1)
- acute lymphoblastic leukaemia (1)
- acute management of stroke (1)
- acute neurology (1)
- acute stroke imaging (1)
- acute stroke management (1)
- acute stroke outcome (1)
- adhesion molecules (1)
- adrenal medulla (1)
- adsorption (1)
- adult-onset (1)
- advanced therapy medicinal products (1)
- afferents (1)
- age (1)
- aggression (1)
- agrin (1)
- albumin (1)
- algorithm (1)
- alias pilot trial (1)
- allodynia (1)
- alpha-7 nicotinic acetylcholine receptor (1)
- alpha-galactosidase A (1)
- alpha‐synuclein (1)
- alpha‐synuclein propagation (1)
- alpha‐synuclein seeding (1)
- amitriptyline (1)
- amygdala (1)
- amyloidosis (1)
- amyotrophe Lateralsklerose (1)
- amyotrophic lateral sclerosis (1)
- amyotrophic lateral sclerosis (ALS) (1)
- analgesia (1)
- analgesic medication (1)
- aneurysm surgery (1)
- angiography (1)
- animal behavior (1)
- ankles (1)
- anodic stimulation (1)
- antagomir (1)
- anthropometric measurement (1)
- anthropometric measurements (1)
- anti-Amphiphysin Antikörper (1)
- anti-amphiphysin antibodies (1)
- anti-aquaporin-4 antibody (1)
- anti-contactin-1 (1)
- antibody (1)
- anticoagulants (1)
- antidepressants (1)
- antigen-presenting cells (1)
- antithrombotic (1)
- apoE (1)
- apoe (1)
- apomorphine (1)
- apoplexy (1)
- aquaporin 4 (1)
- aquaporin-4 autoantibodies (1)
- areas (1)
- arm (1)
- artery occlusion (1)
- asomatognosia (1)
- assistive devices (1)
- association (1)
- association studies in genetics (1)
- assoziative Paarstimulation (1)
- astrocyte (1)
- astrocytes (1)
- astrogliosis (1)
- atherosclerosis (1)
- atrophy Kennedys-disease (1)
- attention deficit/hyperactivity disorder (ADHD) (1)
- attenuation of disease (1)
- atypical chemokine receptor 3 (1)
- auditorisches Neurofeedback Training (1)
- auditory (1)
- autoantibody (aAb) (1)
- autoantigen (1)
- autoimmune encephalitis (1)
- autoimmune neuroinflammation (1)
- autoimmune nodopathy (1)
- autoimmunität (1)
- autophagy (1)
- autoradiography (1)
- axon growth (1)
- axon guidance molecules (1)
- axonal degeneration (1)
- axonal integrity (1)
- axonal transcriptome (1)
- axonal transport (1)
- axonopathic changes (1)
- back pain (1)
- barrier (1)
- barrier integrity (1)
- basal forebrain cholinergic neurons (1)
- basal ganglia hemorrhage (1)
- behavioral disorders (1)
- beta oscillation (1)
- beta power (1)
- beta2 Mikroglobulin knock-out Mäuse (1)
- beta2 microglobulin knock-out mice (1)
- bilateral internal carotid artery stenosis (1)
- bilateral motor network (1)
- binding analysis (1)
- biological locomotion (1)
- biopsies (1)
- blood (1)
- blood CSF barrier (1)
- blood coagulability (1)
- blood coagulation (1)
- blood nerve barrier (1)
- blood sedimentation (1)
- body diagram (1)
- body ownership (1)
- bone (1)
- bone-marrow (1)
- botulinum neurotoxin (1)
- botulinum toxin (1)
- bradykinesia (1)
- bradykinin (1)
- brain dynamics (1)
- brain edema (1)
- brain endothelium (1)
- brain metabolic alterations (1)
- brain networks (1)
- brain state (1)
- brain stem (1)
- burning pain (1)
- bystander activation (1)
- c-fibre (1)
- calpain (1)
- capsaicin (1)
- cardiac imaging (1)
- cardiac magnetic resonance imaging (1)
- cardiovascular disease (1)
- care (1)
- care tempis (1)
- caregiver (1)
- caudate nucleus (1)
- celiac disease (1)
- cell adhesion (1)
- cell binding assay (1)
- cellular therapy (1)
- cerebellar vermis hypoplasia (1)
- cerebellum (1)
- cerebral arteries (1)
- cerebral blood flow (1)
- cerebral endothelial cell (1)
- cerebral endothelial cells (1)
- cerebral inflammation (1)
- cerebral microbleeds (1)
- cerebral small vessel disease (1)
- cerebrale Ischämie (1)
- cerebrospinal fluid culture (1)
- cerebrospinal-fluid (1)
- cerebrovascular diseases (1)
- chitinase-3-like protein 1 (1)
- choline acetyltransferase (1)
- cholinergic activity (1)
- cholinergic system (1)
- chronic constriction nerve injury (1)
- chronic constriction nerve injury (CCI) (1)
- chronic heart failure (1)
- chronic inflammatory demyelinating polyneuropathy (1)
- chronic stimulation (1)
- chronic stress (1)
- chronische Multiple Sklerose (1)
- circuitopathies (1)
- classification (1)
- claudin-1 (1)
- clinical approach (1)
- clinical diagnosis (1)
- clinical neurology (1)
- clinical outcome (1)
- clinical phenotype (1)
- clip control (1)
- closed-loop (1)
- cluster analysis (1)
- co-inhibitory signalling (1)
- coagulation (1)
- coagulation factor XIIa (1)
- cochlea (1)
- cognitive (1)
- cognitive decline (1)
- cognitive function (1)
- coherence (1)
- coherence analysis (1)
- collagens (1)
- collateral circulation (1)
- colony stimulating factor 1 (1)
- compensatory strategies (1)
- complement deposition (1)
- complex regional pain syndrome (1)
- comprehension (1)
- computed tomography (1)
- computer vision (1)
- computerized tomography (1)
- contact activation system (1)
- contactin-associated protein 1 (1)
- continuous theta burst stimulation (cTBS) (1)
- contrast (1)
- contrast-enhanced MRI (1)
- contrastmedium (1)
- conversion (1)
- coordination (1)
- coping (1)
- corneale confocale Mikroskopie (1)
- cortical activation (1)
- cortical excitability (1)
- cortical oscillatory activity (1)
- cortical pathology (1)
- cortical silent period (1)
- cortico-striatal synapse (1)
- corticobasal syndrome (1)
- costimulation (1)
- critical flimmer frequency (1)
- crossover trial (1)
- crush (1)
- cue (1)
- cutaneous innervation (1)
- cutaneous patch (1)
- cutting edge (1)
- dSPN (1)
- dSTORM (1)
- damage cool aid (1)
- darbepoetin alpha (1)
- data filtering (1)
- decompressive hemicraniectomy (1)
- decreasing autonomy (1)
- deep brain stimulation (DBS) (1)
- deep brain-stimulation (1)
- dekompressive Hemikraniektomie (1)
- delayed cerebral infarction (1)
- delays progression (1)
- demography (1)
- demyelinating disease (1)
- demyelinating polyneuropathy (1)
- demyelinating polyradiculoneuropathy (1)
- dendric cells (1)
- dendritic cells (1)
- dendritische Zellen (1)
- dermal B cells (1)
- design (1)
- developmental signaling (1)
- diabetes mellitus (1)
- diagnosis in Fabry disease (1)
- diagnostic delay (1)
- diagnostic medicine (1)
- diagnostics (1)
- diapedesis (1)
- diffuse (1)
- digital medicine (1)
- direct pathway (1)
- directional deep brain stimulation (1)
- disease model (1)
- disease progression (1)
- disease severity (1)
- disease-modifying therapy (1)
- disorder (1)
- domain potassium channels (1)
- dopamine acetylcholine (1)
- dopamine transporter (DAT) (1)
- dopaminergic cells (1)
- dorsal root ganglion neuron (1)
- drug (1)
- duodenal levodopa infusion (1)
- dysferlinopathy (1)
- early-onset isolated dystonia (1)
- edoxaban (1)
- effects (1)
- efficacy (1)
- ejection fraction (1)
- elderly (1)
- electroencephalography (1)
- electromyography (1)
- element (1)
- embolic stroke (1)
- emergency care (1)
- emotion (1)
- emulsions (1)
- encephalitis (1)
- endothelin-1 (1)
- endotheliopathy (1)
- enteropathy (1)
- enzyme assays (1)
- enzyme-linked immunoassays (1)
- epidermis (1)
- epitope (1)
- etanercept (1)
- event-related desynchronization (1)
- evoked potentials (1)
- excitability (1)
- exome sequencing (1)
- experimental (1)
- experimental autoimmune neuritis (1)
- experimental design (1)
- expert opinion (1)
- extensiv transverse myelitis (1)
- extracellular domain (1)
- eye movement disorders (1)
- fMRI Analyse (1)
- facial pain (1)
- factor XI (1)
- familial amyloidotic polyneuropathy (1)
- family caregiver (1)
- fatigue (1)
- fear (1)
- fear memory (1)
- feasibility (1)
- feeling of bodily self (1)
- female Fabry patients (1)
- females (1)
- fetal (1)
- fibers (1)
- fibroblast (1)
- fibromyalgia sydrome (1)
- fine-mapping (1)
- finger-tapping task (1)
- finger-tapping task (FTT) (1)
- fingolimod (1)
- flotillin-1 lipid rafts (1)
- fluorine (1)
- focal (1)
- focal brain lesion (1)
- focal cerebral ischemia (1)
- focal cerebral-ischemia (1)
- fokale Dystonie (1)
- fosfomycin (1)
- fractionator (1)
- free radical scavenger (1)
- freezing of gait (FOG) (1)
- fullerenes (1)
- functional MRI (1)
- functional connectivity (1)
- functional neuroanatomy (1)
- functional status (1)
- fungal infection (1)
- future directions (1)
- gadofluorine (1)
- gadolinium-DTPA (1)
- gait modulation (1)
- gait-phase prediction (1)
- galactomannan (1)
- gender (1)
- gene mutations (1)
- gene variant (1)
- gene-by-environment interaction (1)
- gene-environment interaction (1)
- gene-environmental interaction (1)
- generalized cerebellar atrophy (1)
- genome-wide association study (1)
- genotype-phenotype correlation (1)
- genotype/phenotype correlation (1)
- gephyrin (1)
- geste (1)
- giant cell arteritis (1)
- glia (1)
- glial damage (1)
- glioblastoma multiforme (1)
- globus pallidus (1)
- globus pallidus pars interna (GPi) (1)
- glucocerebrosidase mutation (1)
- glycation end products (1)
- glycine receptor (GlyR) (1)
- glycine receptor autoantibodies (1)
- glycoprotein Ib (1)
- glycoprotein VI (1)
- glycoprotein receptor Ibα (1)
- glycosylation (1)
- granzyme B (1)
- gridle muscular-dystrophy (1)
- growth (1)
- growth pattern (1)
- gustatory dysfunction (1)
- health behavior (1)
- health-related quality of life (1)
- health-related quality of life (HRQoL) (1)
- hemicraniectomy (1)
- hemoglobin (1)
- hemorrhagic transformation (1)
- heparin (1)
- hereditary motor and sensory neuropathy (1)
- hereditary neuropathy (1)
- hereditary spastic paraplegia (1)
- hereditary spastic paraplegia (HSP) (1)
- hereditäre Neuropathien (1)
- hereditäre periphere Neuropathie (1)
- hereditäre sensomotorische Neuropathie (1)
- hernia repair (1)
- hexanucleotide repeat (1)
- high contrast (1)
- hip (1)
- hippocampus (1)
- histology (1)
- homotypic fusion and protein sorting (1)
- hospitals (1)
- human (1)
- human brain endothelium (1)
- human brain microvascular endothelial cells (1)
- human cerebral endothelial cells (1)
- human muscle-cells (1)
- human neurons (1)
- humans (1)
- hyperalgesia (1)
- hypercholesterolemia (1)
- hyperekplexia (1)
- hypothermia (1)
- hypoxic-ischemic encephalopathy (1)
- hypoxische Enzephalopathie (1)
- i.v. thrombolysis (1)
- iNOS-Synthase (1)
- iPSC (1)
- idiopathic inflammatory myopathies (1)
- image quality (1)
- image-guided programming (1)
- imaging (1)
- immaturity (1)
- immune (1)
- immune-response (1)
- immunisation (1)
- immunofluorescence (1)
- immunofluoreszenz (1)
- immunoglobulin-G (1)
- immunzellen (1)
- implants (1)
- in-vivo (1)
- incidence (1)
- increased risk (1)
- induced neural stem cells (1)
- inducible expression (1)
- inducible nitric oxide synthase (1)
- inebilizumab (1)
- inertial measurement units (1)
- infantile neuronal ceroid lipofuscinosis (1)
- infarction size (1)
- infarction volume (1)
- infection (1)
- inflammatory cascades (1)
- inflammatory demyelinating polyradiculoneuropathy (1)
- inflammatory pain (1)
- informal care (1)
- informal caregiving (1)
- informed consent (1)
- inherited metabolic disorders (1)
- inherited peripheral neuropathy (1)
- injection site reactions; (1)
- innate immune system (1)
- innervation (1)
- integrin α2 (1)
- integrins (1)
- intensity of attention (1)
- interference (1)
- interleukin-1 receptor antagonist (1)
- interleukin-8 (1)
- internal carotid artery stenosis (1)
- internal globus pallidus (1)
- internal medicine (1)
- internet-based intervention (1)
- interval timing (1)
- interview (1)
- intra-limb anticipatory postural adjustments (1)
- intracerebral hemorrhage (1)
- intracranial bleeding (1)
- intracranial hemorrhage (1)
- intractable hiccup (1)
- intraepidermal nerve fiber density (1)
- intraepidermal nerve fibre density (1)
- intraoperative (1)
- intrathecal (1)
- intrathecal application (1)
- intrathekal (1)
- intravenous immunoglobulin (1)
- intravenous thrombolysis (1)
- invasive electric stimulation (1)
- ipsilateral motor evoked potential (1)
- ipsilateral motor network (1)
- iron (1)
- iron dyshomeostasis (1)
- iron oxide nanoparticles (1)
- ischemia (1)
- ischemia/reperfusion injury (1)
- ischemic cascade (1)
- kallikrein-kinin system (1)
- kallikrein–kinin system (1)
- kinesthesia (1)
- kinin receptor (1)
- kinin receptors (1)
- kleinkalibrige Nervenfasern (1)
- knees (1)
- knockout (1)
- large vessel occlusion (1)
- latency shift (1)
- learning (1)
- levodopa (1)
- levodopa-induced dyskinesia (1)
- linkage (1)
- liponeurocytoma (1)
- locomotion (1)
- locomotor network (1)
- long-term pain (1)
- longitudinally extensive transverse myelitis (1)
- lymphokine-activated killer (1)
- lyso-Gb3 (1)
- lysosomal dysfunction (1)
- lysosomal enzyme (1)
- lysosomal storage disease (1)
- lyso‐Gb3 (1)
- mRNA expression (1)
- magnesium (1)
- makrophagen (1)
- malignant middle cerebrial artery infarction (1)
- maligner Mediainfarkt (1)
- management (1)
- mast cells (1)
- matrix metalloproteinases (1)
- mechanical energy (1)
- mechanisms (1)
- medial ganglionic eminence (1)
- medication therapy failure (1)
- medikamentöse Sekundärprävention bei stroke (1)
- medulloblastoma (1)
- memory (1)
- meningoencephalitis (1)
- mental health (1)
- mental rotation (1)
- mesenchymal stem and stromal cells (1)
- mesenchymal stem cells (1)
- metaanalysis (1)
- methylphenidate (1)
- miR-182-5p (1)
- miRNA expression patterns (1)
- miRNA polymorphisms (1)
- miRNA-based analgesic (1)
- miRNA-based diagnostics (1)
- mice impact (1)
- microangiopathy (1)
- microscopy (1)
- microsphere/macrosphere (1)
- microtubules (1)
- midbrain (1)
- migraine (1)
- migraineur (1)
- minimal hepatische Enzephalopathie (1)
- minocycline (1)
- mixed fiber neuropathy (1)
- mixed methods (1)
- molecular biology (1)
- molecular mechanism (1)
- molecular mimicry (1)
- molecular signature (1)
- monocycline (1)
- monocytes (1)
- monomethyl fumarate (1)
- morphology (1)
- motoneuron (1)
- motoneuron disease (1)
- motor (1)
- motor axonal neuropathy (1)
- motor cortex (1)
- motor evoked potential (MEP) (1)
- motor function (1)
- motor neuron disease (1)
- motor neuropathy (1)
- motor proteins (1)
- motor-evoked potentials (MEP) (1)
- motorisches Lernen (1)
- mouse (1)
- mouse brain microvascular endothelial cell cultur (1)
- movement (1)
- movement disorder (1)
- movements (1)
- multiple sklerosis (1)
- multisensorische Integration (1)
- multisensory integration (1)
- muscle atrophy (1)
- muscle strength (1)
- mushroom-body (1)
- musikalische Syntax (1)
- musk myasthenia gravis (1)
- myasthenia gravis (1)
- myelin biology and repair (1)
- myelin protein zero (1)
- myelination (1)
- myoblast (1)
- myocardial infarction (1)
- myopathy (1)
- nACh-Rezeptor (1)
- natalizumab (1)
- natural history (1)
- natural killer cells (1)
- near infrared spectroscopy (1)
- near-infrared spectroscopy (1)
- neonatal meningitis (1)
- nerve conduction studies (1)
- nerve tumor (1)
- nerve-fibers (1)
- nervous system (1)
- nervous-system (1)
- neural apoptosis (1)
- neural biomarkers (1)
- neural stem cell (1)
- neural stem cells (1)
- neuralgia (1)
- neurobehavioural deficits (1)
- neuroborreliosis (1)
- neurocritical care (1)
- neurocytoma (1)
- neurofilaments (1)
- neurogen (1)
- neuroleukemiosis (1)
- neurological (1)
- neurological complications (1)
- neurological examination (1)
- neuromelanin (1)
- neuromuskuläre Endplatte (1)
- neuronal apoptosis (1)
- neuronal ceroid lipofuscinosis (1)
- neuronal differentiation (1)
- neuronal network (1)
- neuronal stem cells (1)
- neurone (1)
- neuronopathy (1)
- neurophysiology (1)
- neuroplasticity (1)
- neuropsychology (1)
- neuroregeneration (1)
- neurorepair (1)
- neurotrophins (1)
- neutralization (1)
- neutrophil (1)
- nicotinamide (1)
- nicotinic receptors (1)
- nociceptive Schwann cells (1)
- nociceptor sensitization (1)
- node of ranvier (1)
- nodes of Ranvier (1)
- non-motor features (1)
- nonalcoholic steatohepatitis (1)
- noradrenalin (1)
- noradrenaline (1)
- norepinephrine (1)
- novo renal transplantation (1)
- nucleus ventralis intermedius (1)
- nystagmus (1)
- object recognition memory (1)
- obstacle avoidance (1)
- occlusion (1)
- olfactory dysfunction (1)
- olfactory testing (1)
- oligodendroglia (1)
- on-site examination (1)
- online systems (1)
- ontactin 1 (1)
- opioid (1)
- opioidreceptor (1)
- optic nerve sheath diameter (1)
- optic neuritis (1)
- optical coherence tomography (1)
- orofacial pain (1)
- orofazialer Schmerz (1)
- oscillations (1)
- outcome (1)
- outer hair cell (OHC) (1)
- oxidative stress (1)
- p.R245H (1)
- p.S298P (1)
- p38 mitogen-activated protein kinase (1)
- p57kip2 (1)
- pain drawings (1)
- pain pattern (1)
- pain related evoked potentials (1)
- pain sensation (1)
- pain-associated behavior (1)
- paired associative stimulation (1)
- pallidal stimulation (1)
- pandemic (1)
- paranode (1)
- paranodopathy (1)
- paraparesis (1)
- parkinson disease (1)
- parkinsons disease (1)
- passiv transfer (1)
- pathology section (1)
- pathophysilogical mechanisms (1)
- pathophysiology (1)
- pathway analysis (1)
- pathways (1)
- patient reported outcome measures (1)
- patient triage (1)
- pattern (1)
- pedunculopontine nucleus (PPN) (1)
- pegylated insulin-like growth factor 1 (1)
- peptide (1)
- periperal nerve (1)
- peripheral blood mononuclear cells (1)
- peripheral injury (1)
- peripheral nerve (1)
- peripheral nerve injury (1)
- peripheral nerve involvement (1)
- peripheral nerve trauma (1)
- peripheral nerves (1)
- peripheral nervous-system (1)
- permanent and transient middle cerebral artery occlusion (1)
- pet (1)
- ph (1)
- pharmacology (1)
- phosphodiesterase inhibitor (1)
- phosphorylated tau protein (1)
- physical therapy modalities (1)
- physiology (1)
- pilot project (1)
- placebo-controlled (1)
- plaque cross-sectional area (1)
- plasma extravasation (1)
- plasma oxysterols (1)
- plasminogen (1)
- plasticity (1)
- platelet activation (1)
- platelet aggregation (1)
- pleasant touch (1)
- point-of-care echocardiography (1)
- pointing task (1)
- polymorphism (1)
- polymorphisms inflammation (1)
- polymyositis (1)
- population-based (1)
- position estimation (1)
- post-processing (1)
- post-traumatic stress disorder (1)
- postherpetic neuralgia (1)
- postural control (1)
- posture (1)
- potassium channels (1)
- potent inducer (1)
- precision medicine (1)
- predictive coding (1)
- prednisone (1)
- prefrontal cortex (1)
- premotor cortex (1)
- presynaptic inhibition (1)
- preterm birth (1)
- preventive treatment (1)
- procalcitonin (1)
- progression (1)
- progressive ataxia (1)
- progressive encephalitis with rigidity and myoclonus (PERM) (1)
- progressive multiple sclerosis (1)
- progressive supranuclear palsy (1)
- proinflammatory cytokine (1)
- protein and mRNA expression (1)
- proteins (1)
- proteolipid protein (1)
- proteolipid protein gene (1)
- proteomics (1)
- protons (1)
- prä-post Design (1)
- prämotorischer Cortex (1)
- psychiatric disorders (1)
- psychological support (1)
- psychosocial resilience (1)
- purmorphamine (1)
- putamen (1)
- quality (1)
- quality control (1)
- quality of life (QoL) (1)
- quality-control (1)
- qutenza (1)
- randomized controlled double-blind study (1)
- rasmussen encephalitis (1)
- rat brain microvascular endothelial cell culture (1)
- rat hepatocytes (1)
- rats (1)
- reach-to-grasp movement (1)
- reaction-time tasks (1)
- receptor (1)
- receptor tyrosine kinase (1)
- recombinant tissue-type plasminogen activator (1)
- recommendations (1)
- recovery (1)
- recurrence (1)
- reflex (1)
- regeneration (1)
- regional heterogeneity (1)
- regulation (1)
- regulatorische T Zellen (1)
- regulatory cells (1)
- reinnervation (1)
- relapsing multiple sclerosis (1)
- relapsing-remitting multiple sclerosis (1)
- religiosity (1)
- renal function (1)
- reoxygenation (1)
- reperfusion (1)
- reperfusion injury (1)
- reproducible outcome measure (1)
- reserpinized rat model (1)
- resilience (1)
- responsivity (1)
- retinal ganglion cells (1)
- retinocochleocerebral (1)
- retrograde Marker (1)
- retrograde tracers (1)
- rett (1)
- rhythm perception (1)
- rhythmperception (1)
- risk (1)
- risk factors (1)
- risk of fall (1)
- rt-PA (1)
- rural clinics (1)
- rutabaga (1)
- safety and tolerability (1)
- scale (1)
- schmerz-assoziierte elektrisch-evozierte Potenziale (1)
- sciatic nerve (1)
- sciatic nerve injury (1)
- sciatic nerves (1)
- search filter (1)
- secondary infarct growth (1)
- secretome (1)
- segmental centers of mass (1)
- sensomotorisch (1)
- sensory (1)
- sensory neurons (1)
- seronegative (1)
- seropositive (1)
- serotonin (1)
- serotonin transporter (1)
- serum (1)
- sex addiction (1)
- shedding (1)
- shingles (1)
- siRNA (1)
- signal peptide (1)
- signal transduction pathway (1)
- simulation training (1)
- single photon emission computed tomography (SPECT) (1)
- skewed (1)
- skilled forelimb movements (1)
- skin cells (1)
- skin diseases (1)
- skin tumors (1)
- small fiber tests (1)
- small molecule (1)
- small nerve fibers (1)
- small vessel disease (1)
- small-fiber neuropathy (1)
- small-fiber-Neuropathie (1)
- small-molecule Inhibitoren (1)
- small-molecule inhibitors (1)
- socioeconomic status (1)
- software (1)
- soleus muscles (1)
- soluble endoglin (1)
- somatic resilience (1)
- somatosensory temporal discrimination (1)
- somatosensory-evoked-potentials (1)
- spannungsgesteuerter Natriumkanal (1)
- spatial attention (1)
- sphingolipids (1)
- spinal muscular atrophy (1)
- spinal-cord (1)
- spinal-cord-injury (1)
- startle disease (1)
- stenosis (1)
- stent-retriever device (1)
- steroids (1)
- stiff-person syndrome (SPS) (1)
- stimulation (1)
- stimulationsinduzierte Plasitzität (1)
- store-operated Ca2+ entry (1)
- stress (1)
- striatal dopaminergic dysregulation (1)
- stroke management (1)
- stroke networks (1)
- stromal cells (1)
- study (1)
- subarachnoid hemorrhage (1)
- subcutaneous injection (1)
- substance-P (1)
- subthalamic nucleus (STN) (1)
- sural nerve (1)
- survey (1)
- swimming (1)
- switch (1)
- symptom control (1)
- symptom-specific treatment (1)
- synapse (1)
- synaptic plasticity (1)
- synaptic transmission (1)
- syndrome (1)
- system (1)
- systematic review (1)
- systemic inflammation (1)
- systolic dysfunction (1)
- target considerations (1)
- task retention (1)
- telemedicine network (1)
- temporal discrimination threshold (1)
- teriflunomide (1)
- term follow-up (1)
- tetrahydroisoquinoline derivates (1)
- tetraparesis (1)
- threshold discrimination identification test (1)
- thrombemboli (1)
- thromboemboli (1)
- thromboembolic clot model (1)
- thromboembolic stroke (1)
- thromboinflammation (1)
- thrombolysis (tPA) (1)
- thrombus formation (1)
- thymoma (1)
- tics (1)
- tiefe Hirnstimulation (1)
- time (1)
- timing (1)
- tissue resident T cells (1)
- tissue-plasminogen activator (1)
- tnf (1)
- tolerance (1)
- toleranz (1)
- tool (1)
- topography (1)
- torsinA (1)
- torticollis (1)
- transcranial direct current stimulation (1)
- transcranial magnetic simulation (TMS) (1)
- transgenic mouse model (1)
- transient middle cerebral artery (1)
- transient middle cerebral artery occlusion model (1)
- transient receptor potential vanilloid 1 (TRPV1) (1)
- transkranielle Gleichstromstimulation (tDCS) (1)
- translation (1)
- translational research (1)
- translational stroke research (1)
- transmission electron microscopy (1)
- treatment options (1)
- treatment-induced neuropathy in diabetes (TIND) (1)
- treatment-resistant depression (1)
- triamcinolone acetonide (1)
- trick (1)
- trigeminal nerve (1)
- trigeminal neuropathy (1)
- troponin (1)
- tuberculous meningitis (1)
- tumor (1)
- tumor immunity (1)
- ultrasound imaging (1)
- under-dosing (1)
- up-regulation (1)
- upper limb (1)
- validation (1)
- variants of unknown significance (1)
- vascular cell adhesion molecule-1 (1)
- vascular dementia (1)
- vascular homeostasis (1)
- vascular permeability (1)
- vasculopathy (1)
- venlafaxine (1)
- versus (1)
- vertebrobasilar insufficiency (1)
- vertebrobasilar stroke (1)
- vertigo (1)
- vessel patency (1)
- vestibular (1)
- videooculography (1)
- virtual reality (1)
- visual activity (1)
- visual pathways (1)
- visuoadaptive motor task (1)
- visuomotorisches Lernen (1)
- volume regulation (1)
- vs (1)
- weight drop (1)
- white blood cells (1)
- white matter disease (1)
- white matter hyperintensities (1)
- white matter lesions (1)
- zeitliche Wahrnehmungsschwellen (1)
- zerebelläre Gleichstromstimulation (1)
- zerebrale Endothelzelle (1)
- zerebrale Endothelzellen (1)
- Ältere (1)
- α-Galactosidase A (1)
- α-Synuclein (1)
- α-synuclein-specific T cells (1)
- α‐GalA 3D‐structure (1)
- β-APP (1)
- “bulbar-onset” ALS (bALS) (1)
- “limb-onset” ALS (lALS) (1)
Institute
- Neurologische Klinik und Poliklinik (521)
- Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie) (26)
- Graduate School of Life Sciences (19)
- Neurochirurgische Klinik und Poliklinik (18)
- Institut für Klinische Epidemiologie und Biometrie (16)
- Institut für Klinische Neurobiologie (16)
- Medizinische Klinik und Poliklinik I (16)
- Rudolf-Virchow-Zentrum (16)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (14)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (13)
Schriftenreihe
Sonstige beteiligte Institutionen
- Datenintegrationszentrum Würzburg (DIZ) (1)
- Institut für Musikphysiologie und Musiker-Medizin der Hochschule für Musik, Theater und Medien, Hannover (1)
- Interdisziplinäre Biomaterial- und Datenbank Würzburg (ibdw) (1)
- Interdisziplinäres Amyloidosezentrum Nordbayern (1)
- KfH Nierenzentrum (1)
- Klinische Studienzentrale (Universitätsklinikum) (1)
- Politecnico di Milano (1)
- Sahin Lab, F.M. Kirby Neurobiology Center Boston Children’s Hospital, Department of Neurology, Harvard Medical School (1)
- Wurzburg Fabry Center for Interdisciplinary Therapy (FAZIT), Wurzburg, Germany (1)
- Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), University of Würzburg, Würzburg, Germany (1)
Dimethyl fumarate attenuates lymphocyte infiltration and reduces infarct size in experimental stroke
(2023)
Ischemic stroke is associated with exacerbated tissue damage caused by the activation of immune cells and the initiation of other inflammatory processes. Dimethyl fumarate (DMF) is known to modulate the immune response, activate antioxidative pathways, and improve the blood–brain barrier (BBB) after stroke. However, the specific impact of DMF on immune cells after cerebral ischemia remains unclear. In our study, male mice underwent transient middle cerebral artery occlusion (tMCAO) for 30 min and received oral DMF (15 mg/kg) or a vehicle immediately after tMCAO, followed by twice-daily administrations for 7 days. Infarct volume was assessed on T2-weighted magnetic resonance images on days 1 and 7 after tMCAO. Brain-infiltrating immune cells (lymphocytes, monocytes) and microglia were quantified using fluorescence-activated cell sorting. DMF treatment significantly reduced infarct volumes and brain edema. On day 1 after tMCAO, DMF-treated mice showed reduced lymphocyte infiltration compared to controls, which was not observed on day 7. Monocyte and microglial cell counts did not differ between groups on either day. In the acute phase of stroke, DMF administration attenuated lymphocyte infiltration, probably due to its stabilizing effect on the BBB. This highlights the potential of DMF as a therapeutic candidate for mitigating immune cell-driven damage in stroke.
The pathophysiology of tremor in Parkinson’s disease (PD) is evolving towards a complex alteration to monoaminergic innervation, and increasing evidence suggests a key role of the locus coeruleus noradrenergic system (LC-NA). However, the difficulties in imaging LC-NA in patients challenge its direct investigation. To this end, we studied the development of tremor in a reserpinized rat model of PD, with or without a selective lesioning of LC-NA innervation with the neurotoxin DSP-4. Eight male rats (Sprague Dawley) received DSP-4 (50 mg/kg) two weeks prior to reserpine injection (10 mg/kg) (DR-group), while seven male animals received only reserpine treatment (R-group). Tremor, rigidity, hypokinesia, postural flexion and postural immobility were scored before and after 20, 40, 60, 80, 120 and 180 min of reserpine injection. Tremor was assessed visually and with accelerometers. The injection of DSP-4 induced a severe reduction in LC-NA terminal axons (DR-group: 0.024 ± 0.01 vs. R-group: 0.27 ± 0.04 axons/um\(^2\), p < 0.001) and was associated with significantly less tremor, as compared to the R-group (peak tremor score, DR-group: 0.5 ± 0.8 vs. R-group: 1.6 ± 0.5; p < 0.01). Kinematic measurement confirmed the clinical data (tremor consistency (% of tremor during 180 s recording), DR-group: 37.9 ± 35.8 vs. R-group: 69.3 ± 29.6; p < 0.05). Akinetic–rigid symptoms did not differ between the DR- and R-groups. Our results provide preliminary causal evidence for a critical role of LC-NA innervation in the development of PD tremor and foster the development of targeted therapies for PD patients.
Autoantikörper gegen nodo-paranodale Proteine des Ranvier’schen Schnürrings wie
Neurofascin-155 (NF-155), Contactin-1 und Caspr wurden in der Literatur bei
Patienten/Patientinnen mit Immunneuropathien beschrieben. Bei zwei bis zehn Prozent
der Patienten/Patientinnen mit Immunneuropathien können Autoantikörper gegen
Isoformen des Neurofascin detektiert werden. Patienten/Patientinnen mit
Autoantikörpern gegen NF-155 weisen gemeinsame klinische Merkmale auf, unter
anderem einen schweren Verlauf mit subakutem Beginn, vorwiegend motorischen
Defiziten, Tremor und einem schlechten Ansprechen auf eine Therapie mit intravenösen
Immunglobulinen (IVIG). Ein Grund für Letzteres könnte sein, dass es sich überwiegend
um Autoantikörper der Subklasse IgG4 handelt, die als anti-inflammatorisch gelten und
kein Komplement aktivieren. Neben der IgG4-Subklasse können bei manchen
Erkrankten auch die proinflammatorischen IgG-Subklassen 1 bis 3 nachgewiesen
werden. Bei der Anti-Pan-Neurofascin (155/140/186) Polyneuropathie zeigt sich klinisch
häufig ein fulminanter Phänotyp mit IgG3 Prädominanz. Das Ziel dieser Studie war, die
Autoantikörper-induzierte Komplementablagerung zu detektieren, sowie die Rolle der
IgG Subklasse und die Effekte von IVIG auf Antikörperbindung, Komplementaktivierung
und Effektorfunktionen zu untersuchen.
Hierzu wurde das Serum von 212 Probanden/-innen mit der Verdachtsdiagnose einer
entzündlichen Neuropathie auf Autoantikörper gegen NF-155 mittels ELISA und
Bindungsversuchen an Mäusezupfnerven gescreent. Im Fall eines positiven
Ergebnisses dienten zellbasierte Bindungsversuche mit NF-155-transfizierten HEK-293-
Zellen als Bestätigungstest. Die Effekte unterschiedlicher IVIG Konzentrationen auf die
Antikörperbindung und Komplementablagerung wurden in ELISA,
Komplementbindungsassays und zellbasierten Verfahren getestet. Außerdem wurde
mithilfe von LDH-Zytotoxizitätsmessungen die Komplement-induzierte Zelllyse sowie die
Effekte von IVIG untersucht. Klinische Daten wurden retrospektiv ausgewertet.
Fünf Patienten/Patientinnen mit hohen Autoantikörpertitern gegen NF-155 und ein
Patient mit Anti-Pan-Neurofascin Autoantikörpern konnten in der Studie detektiert
werden. Der Patient mit Autoantikörpern gegen alle drei Isoformen des Neurofascins und
IgG3-Prädominanz zeigte die deutlichste Komplementablagerung. Bei drei
Patienten/Patientinnen, die IgG1, IgG2 und IgG4 aufwiesen, war eine Aktivierung des
Komplementsystems zu beobachten, während bei zwei Patienten mit prädominanter
IgG4-Antikörpersubklasse keine Komplementablagerung nachweisbar war. Bei
Letzteren war eine Therapie mit IVIG in der Vorgeschichte erfolglos, während es bei zwei
der Patienten/Patientinnen mit anderen IgG-Subklassen und Komplementbindung unter
IVIG Therapie zu einer mäßigen bis deutlichen Symptombesserung in der Akutphase
kam. Eine Koinkubation mit IVIG führte in den ELISA basierten und zellbasierten
Versuchen zu keinem Effekt auf die Autoantikörperbindung an das Zielantigen, jedoch
zu einer deutlichen Reduktion der Antikörper-vermittelten Komplementbindung. Diese
Reduktion war sowohl bei Koinkuabtion von IVIG mit dem Komplementfaktor C1q als
auch bei Präinkubation von IVIG vor C1q Gabe zu sehen. Bei zwei der
Patienten/Patientinnen mit hohen Komplementablagerungen konnte eine erhöhte
Zytotoxizität nachgewiesen werden, welche bei Zugabe von IVIG verringert wurde.
Schlussfolgernd ist die Autoantikörper-induzierte Komplementablagerung abhängig von
der prädominanten IgG Subklasse. IVIG führt zu einer deutlichen,
konzentrationsabhängigen Reduktion der Komplementablagerung, sowie möglicher
zytotoxischer Effektorfunktionen wie die Zytolyse myelinisierter Schwannzellen oder
Nervenaxonen. Darüber hinaus könnte die Subklassenanalyse von Erkrankten das
Therapieansprechen auf IVIG vorhersagen und sollte daher eine wichtige Rolle in der
Diagnostik der Nodo-Paranodopathie spielen. IVIG sowie andere über das
Komplementsystem wirkende Therapeutika können in der Behandlung der schwer
betroffenen Patienten/Patientinnen, insbesondere bei Anti-Pan-Neurofascin positiver
Neuropathie, in Betracht gezogen werden.
In dieser Arbeit wurde die Krankheitsprogression im Parkinson-Mausmodell hm2α-SYN-39 mit zunehmendem Alter charakterisiert. Die Mäuse wurden in 4 Altersgruppen (2-3, 7-8, 11-12, 16-17 Monate) mit motorischen Verhaltenstests auf einen Parkinson-Phänotyp untersucht. Zudem erfolgten Untersuchungen des dopaminergen Systems zur Detektion von neurochemischen Veränderungen und einer Neurodegeneration im nigrostriatalen Trakt. Weiterhin wurden neuroinflammatorische Prozesse des adaptiven und angeborenen IS in der SN und im Striatum mittels immunhistochemischer Färbungen beurteilt.
Ein Parkinson-Phänotyp in diesem Mausmodell zeigte sich nur leicht ausgeprägt, sodass der Rotarod- und Zylinder-Test lediglich den Hinweis auf eine nicht-signifikante Einschränkung der Motorik erbrachte. Dennoch ergab die stereologische Quantifizierung TH- und Nissl-positiver Zellen in der SNpc der hm2α-SYN-39 Mäuse eine altersabhängige, signifikant-progrediente Reduktion der dopaminergen Neurone mit zunehmendem Alter. Eine signifikant niedrigere TH-positive Zellzahl dieser tg Mäuse zeigte sich ab einem Alter von 16-17 Monaten verglichen zu gleichaltrigen wt Tieren. Dagegen war die Neurodegeneration im Striatum etwas weniger ausgeprägt. Die tg Mäuse präsentierten im Alter von 16-17 Monaten eine nicht-signifikante Erniedrigung der dopaminergen Terminalen verglichen zu gleichaltrigen wt Tieren. Ein DA-Mangel im Striatum der tg Mäuse konnte mittels HPLC bestätigt werden. Bis zum Alter von 16-17 Monaten wurde eine signifikante Reduktion der DA-Level von 23,2 % verglichen zu gleichaltrigen wt Mäusen gezeigt. Außerdem erniedrigt waren die striatalen Level von NA und 5-HAT bei tg Mäusen, passend zu den bisherigen Ergebnissen bei Parkinson-Patienten.
Immunhistochemische Untersuchungen einer Neuroinflammation im nigrostriatalen Trakt ergaben eine tendenziell erhöhte Infiltration von CD4- und CD8-positiven T-Zellen bei hm2α-SYN-39 Mäusen mit zunehmendem Alter, wobei die Infiltration CD8-positiver Zellen ausgeprägter war als bei CD4-positiven Zellen. Eine noch deutlichere neuroinflammatorische Reaktion zeigte das angeborene IS. Hierbei ergab die immunhistologische Quantifizierung CD11b-positiver mikroglialer Zellen einen hochsignifikanten Anstieg im nigrostriatalen Trakt bei hm2α-SYN-39 Mäusen schon im jungen Alter.
Zusammenfassend präsentierte dieses Parkinson-Mausmodell eine langsam-progrediente Parkinson-Pathologie mit begleitender Neuroinflammation im nigrostriatalen Trakt während des Alterns, wobei die Immunantwort der mikroglialen Zellen zu einem früheren Zeitpunkt einsetzte als die T-Zellinfiltration und Neurodegeneration. Dieses Mausmodell bietet zahlreiche Möglichkeiten zur zukünftigen Erforschung der Pathophysiologie beim MP. Generell weist diese Arbeit auf eine bedeutende Rolle neuroinflammatorischer Prozesse in der Krankheitsprogression der Parkinsonerkrankung hin und soll dazu ermutigen Neuroinflammation durchaus intensiver in tg Tiermodellen zu untersuchen.
Background
Ischemic stroke immediately evokes a strong neuro-inflammatory response within the vascular compartment, which contributes to primary infarct development under vessel occlusion as well as further infarct growth despite recanalization, referred to as ischemia/reperfusion injury. Later, in the subacute phase of stroke (beyond day 1 after recanalization), further inflammatory processes within the brain parenchyma follow. Whether this second wave of parenchymal inflammation contributes to an additional/secondary increase in infarct volumes and bears the potential to be pharmacologically targeted remains elusive. We addressed the role of the NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome in the subacute phase of ischemic stroke.
Methods
Focal cerebral ischemia was induced in C57Bl/6 mice by a 30-min transient middle cerebral artery occlusion (tMCAO). Animals were treated with the NLRP3 inhibitor MCC950 therapeutically 24 h after or prophylactically before tMCAO. Stroke outcome, including infarct size and functional deficits as well as the local inflammatory response, was assessed on day 7 after tMCAO.
Results
Infarct sizes on day 7 after tMCAO decreased about 35% after delayed and about 60% after prophylactic NLRP3 inhibition compared to vehicle. Functionally, pharmacological inhibition of NLRP3 mitigated the local inflammatory response in the ischemic brain as indicated by reduction of infiltrating immune cells and reactive astrogliosis.
Conclusions
Our results demonstrate that the NLRP3 inflammasome continues to drive neuroinflammation within the subacute stroke phase. NLRP3 inflammasome inhibition leads to a better long-term outcome—even when administered with a delay of 1 day after stroke induction, indicating ongoing inflammation-driven infarct progression. These findings may pave the way for eagerly awaited delayed treatment options in ischemic stroke.
Sowohl neurologische Erkrankungen als auch der natürliche Alterungsprozess gehen regelhaft mit einem Untergang von Neuronen einher und bedingen neurologische Funktionsverluste. Diese mit Hilfe nicht-invasiver Techniken, beispielsweise tDCS, zu reduzieren, stellt ein wichtiges Ziel der neurowissenschaftlichen Forschung dar. Neben Arbeiten, die tDCS-Effekte auf das motorische Lernen bei Stimulation des motorischen Kortex nachweisen konnten, gibt es auch Hinweise für solche Effekte bei Stimulation des Kleinhirns. Allerdings besteht derzeit noch eine hohe Variabilität und damit einhergehend eine schlechte Vergleichbarkeit der Studien bezüglich ihrer Stimulationsbedingungen. Das Ansprechen unterschiedlicher Altersgruppen bleibt unklar.
In der vorliegenden Arbeit wurden die Effekte zerebellärer a-tDCS auf das motorische Lernen bei gesunden älteren Probanden untersucht. Im Cross-over-Design wurde zu unterschiedlichen Zeitpunkten (vor bzw. nach der motorischen Aufgabe) stimuliert und im 24-Stunden-Verlauf die Langzeitwirkung evaluiert. Gruppe A erhielt vor einer motorischen Übungsaufgabe eine zerebelläre Stimulation, entweder als a-tDCS oder Scheinstimulation, Gruppe B nach der Übungsaufgabe. Zur Überprüfung der Effekte auf das Sequenzlernen diente der Finger-Tapping-Task. Der Lernerfolg wurde anhand der Genauigkeit, der Sequenzdauer und des Skill-Index gemessen.
Die Ergebnisse deuten darauf hin, dass eine zerebelläre a-tDCS vor einer Übungsaufgabe zu einer Verbesserung der Konsolidierung der Fähigkeit, eine Zahlenfolge möglichst schnell und gleichzeitig genau einzutippen, führt, während die Stimulation nach einer Übungsaufgabe das motorische Lernen nicht zu beeinflussen scheint. Insgesamt stützen die Ergebnisse zum Teil die bisherigen Hinweise, dass eine zerebellär applizierte a-tDCS das motorische Lernen verbessern kann. Aufgrund einiger Limitationen, besonders der geringen Gruppengröße, verbleibt dieses Ergebnis jedoch vorläufig und bedarf einer Bestätigung in größeren Probandengruppen. Es bleibt von hohem Interesse, die optimalen Bedingungen für die Anwendung von tDCS am Kleinhirn zu definieren, um motorische Lernprozesse positiv zu beeinflussen. Dies ist die Voraussetzung dafür, zerebelläre tDCS mittelfristig auch zu therapeutischen Zwecken anwenden zu können.
(1) Background: The first-line treatment for patients with focal or segmental dystonia with a craniocervical distribution is still the intramuscular injection of botulinum neurotoxin (BoNT). However, some patients experience primary or secondary treatment failure from this potential immunogenic therapy. Deep brain stimulation (DBS) may then be used as a backup strategy in this situation. (2) Methods: Here, we reviewed the current study literature to answer a specific question regarding the efficacy and safety of the use of DBS, particularly for cervical dystonia (CD) and Meige syndrome (MS) in patients with documented treatment failure under BoNT. (3) Results: There are only two studies with the highest level of evidence in this area. Despite this clear limitation, in the context of the narrowly defined research question of this paper, it is possible to report 161 patients with CD or MS who were included in studies that were able to show a statistically significant reduction in dystonic symptoms using DBS. Safety and tolerability data appeared adequate. However, much of the information is based on retrospective observations. (4) Conclusions: The evidence base in this area is in need of further scientific investigation. Most importantly, more randomized, controlled and double-blind trials are needed, possibly including a head-to-head comparison of DBS and BoNT.
Background: Aging increases individual susceptibility to falls and injuries, suggesting poorer adaptation of balance responses to perturbation during locomotion, which can be measured with the locomotor adaptation task (LAT). However, it is unclear how aging and lifestyle factors affect these responses during walking. Hence, the present study investigates the relationship between balance and lifestyle factors during the LAT in healthy individuals across the adult lifespan using a correlational design. Methods: Thirty participants aged 20–78 years performed an LAT on a split-belt treadmill (SBT). We evaluated the magnitude and rate of adaptation and deadaptation during the LAT. Participants reported their lifelong physical and cognitive activity. Results: Age positively correlated with gait-line length asymmetry at the late post-adaptation phase (p = 0.007). These age-related effects were mediated by recent physical activity levels (p = 0.040). Conclusion: Our results confirm that locomotor adaptive responses are preserved in aging, but the ability to deadapt newly learnt balance responses is compromised with age. Physical activity mediates these age-related effects. Therefore, gait symmetry post-adaptation could effectively measure the risk of falling, and maintaining physical activity could protect against declines in balance.
"Eignet sich die kritische Flimmerfrequenz zur Diagnose einer minimal hepatischen Enzephalopathie?"
(2024)
Korrelation und Kontingenzprüfung von Kritischer Flimmerfrequenz als diagnostischem Mittel bei minimal hepatischer Enzephalopathie mit anderen etablierten diagnostischen Mitteln und beschreibenden Parametern.
In den Ergebnissen lediglich Korrelation mit Alertness Testung in der Testbatterie.
Minimal hepatische Enzephalopathie braucht zur Diagnostik mindestens 2 verschiedene ergänzende diagnostische Verfahren (neuropsychologisch und -physiologisch), um sicher entdeckt werden zu können. Bei nur einem Testverfahren blieben zahlreiche Betroffene unentdeckt. Möglicherweise ist das verschiedenen pathophysiologischen Subgruppen geschuldet.
Glycine receptor β–targeting autoantibodies contribute to the pathology of autoimmune diseases
(2024)
Background and Objectives
Stiff-person syndrome (SPS) and progressive encephalomyelitis with rigidity and myoclonus (PERM) are rare neurologic disorders of the CNS. Until now, exclusive GlyRα subunit–binding autoantibodies with subsequent changes in function and surface numbers were reported. GlyR autoantibodies have also been described in patients with focal epilepsy. Autoimmune reactivity against the GlyRβ subunits has not yet been shown. Autoantibodies against GlyRα1 target the large extracellular N-terminal domain. This domain shares a high degree of sequence homology with GlyRβ making it not unlikely that GlyRβ-specific autoantibody (aAb) exist and contribute to the disease pathology.
Methods
In this study, we investigated serum samples from 58 patients for aAb specifically detecting GlyRβ. Studies in microarray format, cell-based assays, and primary spinal cord neurons and spinal cord tissue immunohistochemistry were performed to determine specific GlyRβ binding and define aAb binding to distinct protein regions. Preadsorption approaches of aAbs using living cells and the purified extracellular receptor domain were further used. Finally, functional consequences for inhibitory neurotransmission upon GlyRβ aAb binding were resolved by whole-cell patch-clamp recordings.
Results
Among 58 samples investigated, cell-based assays, tissue analysis, and preadsorption approaches revealed 2 patients with high specificity for GlyRβ aAb. Quantitative protein cluster analysis demonstrated aAb binding to synaptic GlyRβ colocalized with the scaffold protein gephyrin independent of the presence of GlyRα1. At the functional level, binding of GlyRβ aAb from both patients to its target impair glycine efficacy.
Discussion
Our study establishes GlyRβ as novel target of aAb in patients with SPS/PERM. In contrast to exclusively GlyRα1-positive sera, which alter glycine potency, aAbs against GlyRβ impair receptor efficacy for the neurotransmitter glycine. Imaging and functional analyses showed that GlyRβ aAbs antagonize inhibitory neurotransmission by affecting receptor function rather than localization.
Highlights
• The GLA variant S126G is not associated with Fabry symptoms in the presented case
• S126G has no effect on α-GAL A activity or Gb3 levels in this patient
• S126G sensory neurons show no electrophysiological abnormalities
Abstract
Fabry disease (FD) is a life-limiting disorder characterized by intracellular globotriaosylceramide (Gb3) accumulations. The underlying α-galactosidase A (α-GAL A) deficiency is caused by variants in the gene GLA. Variants of unknown significance (VUS) are frequently found in GLA and challenge clinical management. Here, we investigated a 49-year old man with cryptogenic lacunar cerebral stroke and the chance finding of the VUS S126G, who was sent to our center for diagnosis and initiation of a costly and life-long FD-specific treatment. We combined clinical examination with in vitro investigations of dermal fibroblasts (HDF), induced pluripotent stem cells (iPSC), and iPSC-derived sensory neurons. We analyzed α-GAL A activity in iPSC, Gb3 accumulation in all three cell types, and action potential firing in sensory neurons. Neurological examination and small nerve fiber assessment was normal except for reduced distal skin innervation. S126G iPSC showed normal α-GAL A activity compared to controls and no Gb3 deposits were found in all three cell types. Baseline electrophysiological characteristics of S126G neurons showed no difference compared to healthy controls as investigated by patch-clamp recordings. We pioneer multi-level cellular characterization of the VUS S126G using three cell types derived from a patient and provide further evidence for the benign nature of S126G in GLA, which is of great importance in the management of such cases in clinical practice.
Introduction:
Fibromyalgia syndrome (FMS) and small fiber neuropathy (SFN) are distinct pain conditions that share commonalities and may be challenging as for differential diagnosis.
Objective:
To comprehensively investigate clinical characteristics of women with FMS and SFN to determine clinically applicable parameters for differentiation.
Methods:
We retrospectively analyzed medical records of 158 women with FMS and 53 with SFN focusing on pain-specific medical and family history, accompanying symptoms, additional diseases, and treatment. We investigated data obtained using standardized pain, depression, and anxiety questionnaires. We further analyzed test results and findings obtained in standardized small fiber tests.
Results:
FMS patients were on average ten years younger at symptom onset, described higher pain intensities requiring frequent change of pharmaceutics, and reported generalized pain compared to SFN. Pain in FMS was accompanied by irritable bowel or sleep disturbances, and in SFN by paresthesias, numbness, and impaired glucose metabolism (P < 0.01 each). Family history was informative for chronic pain and affective disorders in FMS (P < 0.001) and for neurological disorders in SFN patients (P < 0.001). Small fiber pathology in terms of skin denervation and/or thermal sensory threshold elevation was present in 110/158 (69.7 %) FMS patients and 39/53 (73.6 %) SFN patients. FMS patients mainly showed proximally reduced skin innervation and higher corneal nerve branch densities (p<0.001) whereas SFN patients were characterized by reduced cold detection and prolonged electrical A-delta conduction latencies (P < 0.05).
Conclusions:
Our data show that FMS and SFN differ substantially. Detailed pain, drug and family history, investigating blood glucose metabolism, and applying differential small fiber tests may help to improve diagnostic differentiation and targeted therapy.
Background
Complex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed.
Methods
We systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute (< 12 months) and 6 chronic (> 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells.
Results
Intraepidermal Schwann cells were detected in human skin of the finger—but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other—but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin.
Conclusions
Diagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.
Hereditary spastic paraplegias (HSPs) are genetically-determined, neurodegenerative disorders characterized by progressive weakness and spasticity of the lower limbs. Spastic paraplegia type 11 (SPG11) is a complicated form of HSP, which is caused by mutations in the SPG11 gene encoding spatacsin, a protein possibly involved in lysosomal reformation. Based on our previous studies demonstrating that secondary neuroinflammation can be a robust amplifier of various genetically-mediated diseases of both the central and peripheral nervous system, we here test the possibility that neuroinflammation may modify the disease outcome also in a mouse model for SPG11. Spg11-knockout (Spg11-/-) mice develop early walking pattern and behavioral abnormalities, at least partially reflecting motor, and behavioral changes typical for patients. Furthermore, we detected a progressive increase in axonal damage and axonal spheroid formation in the white and grey matter compartments of the central nervous system of Spg11-/- mice. This was accompanied by a concomitant substantial increase of secondary inflammation by cytotoxic CD8+ and CD4+ T-lymphocytes. We here provide evidence that disease-related changes can be ameliorated/delayed by the genetic deletion of the adaptive immune system. Accordingly, we provide evidence that repurposing clinically approved immunomodulators (fingolimod/FTY720 or teriflunomide), that are in use for treatment of multiple sclerosis (MS), also improve disease symptoms in mice, when administered in an early (before neural damage) or late (after/during neural damage) treatment regime.
This work provides strong evidence that immunomodulation can be a therapeutic option for the still untreatable SPG11, including its typical neuropsychological features. This poses the question if inflammation is not only a disease amplifier in SPG11 but can act as a unifying factor also for other genetically mediated disorders of the CNS. If true, this may pave the way to therapeutic options in a wide range of still untreatable, primarily genetic, neurological disorders by repurposing approved immunomodulators.
Safety and tolerability of SGLT2 inhibitors in cardiac amyloidosis — a clinical feasibility study
(2024)
Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis. In these most frequent subtypes, cardiac involvement is the most common organ manifestation. Because cardiac and renal function frequently deteriorate over time, even under best available treatment, SGLT2i emerge as a promising treatment option due to their reno- and cardioprotective properties. We retrospectively analyzed patients with cardiac amyloidosis, who received either dapagliflozin or empagliflozin. Out of 79 patients, 5.1% had urinary tract infections; 2 stopped SGLT2i therapy; and 2.5% died unrelated to the intake of SGLT2i. No genital mycotic infections were observed. As expected, a slight drop in the glomerular filtration rate was noted, while the NYHA functional status, cardiac and hepatic function, as well as the 6 min walk distance remained stable over time. These data provide a rationale for the use of SGLT2i in patients with amyloidosis and concomitant cardiac or renal dysfunction. Prospective randomized data are desired to confirm safety and to prove efficacy in this increasingly important group of patients.
Ischemia-reperfusion injury (I/R injury) is a common complication in ischemic stroke (IS) treatment, which is characterized by a paradoxical perpetuation of tissue damage despite the successful re-establishment of vascular perfusion. This phenomenon is known to be facilitated by the detrimental interplay of platelets and inflammatory cells at the vascular interface. However, the spatio-temporal and molecular mechanisms underlying these cellular interactions and their contribution to infarct progression are still incompletely understood. Therefore, this study intended to clarify the temporal mechanisms of infarct growth after cerebral vessel recanalization. The data presented here could show that infarct progression is driven by early blood-brain-barrier perturbation and is independent of secondary thrombus formation. Since previous studies unravelled the secretion of platelet granules as a molecular mechanism of how platelets contribute to I/R injury, special emphasis was placed on the role of platelet granule secretion in the process of barrier dysfunction. By combining an in vitro approach with a murine IS model, it could be shown that platelet α-granules exerted endothelial-damaging properties, whereas their absence (NBEAL2-deficiency) translated into improved microvascular integrity. Hence, targeting platelet α-granules might serve as a novel treatment option to reduce vascular integrity loss and diminish infarct growth despite recanalization.
Recent evidence revealed that pathomechanisms underlying I/R injury are already instrumental during large vessel occlusion. This indicates that penumbral tissue loss under occlusion and I/R injury during reperfusion share an intertwined relationship. In accordance with this notion, human observational data disclosed the presence of a neutrophil dominated immune response and local platelet activation and secretion, by the detection of the main components of platelet α-granules, within the secluded vasculature of IS patients. These initial observations of immune cells and platelets could be further expanded within this thesis by flow cytometric analysis of local ischemic blood samples. Phenotyping of immune cells disclosed a yet unknown shift in the lymphocyte population towards CD4+ T cells and additionally corroborated the concept of an immediate intravascular immune response that is dominated by granulocytes. Furthermore, this thesis provides first-time evidence for the increased appearance of platelet-leukocyte-aggregates within the secluded human vasculature. Thus, interfering with immune cells and/or platelets already under occlusion might serve as a potential strategy to diminish infarct expansion and ameliorate clinical outcome after IS.
Early-onset torsion dystonia (DYT-TOR1A, DYT1) is an inherited hyperkinetic movement disorder caused by a mutation of the TOR1A gene encoding the torsinA protein. DYT-TOR1A is characterized as a network disorder of the central nervous system (CNS), including predominantly the cortico-basal ganglia-thalamo-cortical loop resulting in a severe generalized dystonic phenotype. The pathophysiology of DYTTOR1A is not fully understood. Molecular levels up to large-scale network levels of the CNS are suggested to be affected in the pathophysiology of DYT-TOR1A. The reduced penetrance of 30% - 40% indicates a gene-environmental interaction, hypothesized as “second hit”. The lack of appropriate and phenotypic DYT-TOR1A animal models encouraged us to verify the “second hit” hypothesis through a unilateral peripheral nerve trauma of the sciatic nerve in a transgenic asymptomatic DYT-TOR1A rat model (∆ETorA), overexpressing the human mutated torsinA protein. In a multiscale approach, this animal model was characterized phenotypically and pathophysiologically.
Nerve-injured ∆ETorA rats revealed dystonia-like movements (DLM) with a partially generalized phenotype. A physiomarker of human dystonia, describing increased theta oscillation in the globus pallidus internus (GPi), was found in the entopeduncular nucleus (EP), the rodent equivalent to the human GPi, of nerve-injured ∆ETorA rats. Altered oscillation patterns were also observed in the primary motor cortex. Highfrequency stimulation (HFS) of the EP reduced DLM and modulated altered oscillatory activity in the EP and primary motor cortex in nerve-injured ∆ETorA rats. Moreover, the dopaminergic system in ∆ETorA rats demonstrated a significant increased striatal dopamine release and dopamine turnover. Whole transcriptome analysis revealed differentially expressed genes of the circadian clock and the energy metabolism, thereby pointing towards novel, putative pathways in the pathophysiology of DYTTOR1A dystonia.
In summary, peripheral nerve trauma can trigger DLM in genetically predisposed asymptomatic ΔETorA rats leading to neurobiological alteration in the central motor network on multiple levels and thereby supporting the “second hit” hypothesis. This novel symptomatic DYT-TOR1A rat model, based on a DYT-TOR1A genetic background, may prove as a valuable chance for DYT-TOR1A dystonia, to further investigate the pathomechanism in more detail and to establish new treatment strategies.
Development Of A Human iPSC-Derived Cortical Neuron Model Of Adaptor- Protein-Complex-4-Deficiency
(2024)
Adaptor-protein-4-deficiency (AP-4-deficiency) is an autosomal-recessive childhood- onset form of complicated hereditary spastic paraplegia (HSP) caused by bi-allelic loss- of-function mutations in one of the four subunits of the AP-4-complex. These four conditions are named SPG47 (AP4B1, OMIM #614066), SPG50 (AP4M1, OMIM #612936), SPG51 (AP4E1, OMIM #613744) and SPG52 (AP4S1, OMIM #614067), respectively and all present with global developmental delay, progressive spasticity and seizures. Imaging features include a thinning of the corpus callosum, ventriculomegaly and white matter changes. AP-4 is a highly conserved heterotetrameric complex, which is responsible for polarized sorting of transmembrane cargo including the autophagy- related protein 9 A (ATG9A). Loss of any of the four subunits leads to an instable complex and defective sorting of AP-4-cargo. ATG9A is implicated in autophagosome formation and neurite outgrowth. It is missorted in AP-4-deficient cells and CNS-specific knockout of Atg9a in mice results in a phenotype reminiscent of AP-4-deficiency. However, the AP-4-related cellular phenotypes including ATG9A missorting have not been investigated in human neurons.
Thus, the aim of this study is to provide the first human induced pluripotent stem cell- derived (iPSC) cortical neuron model of AP-4-deficiency to explore AP-4-related phenotypes in preparation for a high-content screening. Under the hypothesis that AP-4- deficiency leads to ATG9A missorting, elevated ATG9A levels, impaired autophagy and neurite outgrowth in human iPSC-derived cortical neurons, in vitro biochemical and imaging assays including automated high-content imaging and analysis were applied. First, these phenotypes were investigated in fibroblasts from three patients with compound heterozygous mutations in the AP4B1 gene and their sex-matched parental controls. The same cell lines were used to generate iPSCs and differentiate them into human excitatory cortical neurons.
This work shows that ATG9A is accumulating in the trans-Golgi-network in AP-4- deficient human fibroblasts and that ATG9A levels are increased compared to parental controls and wild type cells suggesting a compensatory mechanism. Protein levels of the AP4E1-subunit were used as a surrogate marker for the AP-4-complex and were decreased in AP-4-deficient fibroblasts with co-immunoprecipitation confirming the instability of the complex. Lentiviral re-expression of the AP4B1-subunit rescues this corroborating the fact that a stable AP-4-complex is needed for ATG9A trafficking. Surprisingly, autophagic flux was present in AP-4-deficient fibroblasts under nutrient- rich and starvation conditions. These phenotypic markers were evaluated in iPSC-derived cortical neurons and here, a robust accumulation of ATG9A in the juxtanuclear area was seen together with elevated ATG9A protein levels. Strikingly, assessment of autophagy markers under nutrient-rich conditions showed alterations in AP-4-deficient iPSC- derived cortical neurons indicating dysfunctional autophagosome formation. These findings point towards a neuron-specific impairment of autophagy and need further investigation. Adding to the range of AP-4-related phenotypes, neurite outgrowth and branching are impaired in AP-4-deficient iPSC-derived cortical neurons as early as 24h after plating and together with recent studies point towards a distinct role of ATG9A in neurodevelopment independent of autophagy.
Together, this work provides the first patient-derived neuron model of AP-4-deficiency and shows that ATG9A is sorted in an AP-4-dependent manner. It establishes ATG9A- related phenotypes and impaired neurite outgrowth as robust markers for a high-content screening. This disease model holds the promise of providing a platform to further study AP-4-deficiency and to search for novel therapeutic targets.
In dieser Arbeit wurde durch das immunhistochemische Anfärben von nodalen (Natriumkanäle, NF), paranodalen (Caspr, NF) und internodalen (MBP) Proteinen der in Fingerhautbiopsien vorhanden Nervenfasern untersucht, ob eine Veränderung der typischen Verteilungsmuster dieser Proteine, eine demyelinisierende Polyneuropathie anzeigen kann. Dazu wurden am Universitätsklinikum Würzburg prospektiv 93 Polyneuropathie-Patienten und 25 Kontrollpersonen rekrutiert. Bei allen Patienten wurden Hautstanzbiospien am Zeigefinger durchgeführt. Bei 35 Patienten mit schweren oder unklaren Verläufen, wurden konsiliarisch Nervus suralis Biopsien durchgeführt. Aus einem Abschnitt von 27 dieser Biopsien, konnten im Rahmen dieser Arbeit Zupfnervenpräparate angefertigt und analog zu den Hautbiopsien ausgewertet werden. Aus der Routinediagnostik der Klinik flossen weiterhin die Ergebnisse der elektrophysiologischen Routinediagnostik und der Histologiebefund der Nervus suralis Biopsien in die Auswertung ein.
Zusammenfassend kamen veränderte Natriumkanalbanden in Fingerhautbiopsien signifikant häufiger bei Patienten mit elektrophysiologisch als demyelinisierend befundeten Polyneuropathien, als bei Patienten mit elektrophysiologisch als axonal befundeten Polyneuropathien vor. Vielfach fanden sich veränderte Natriumkanalbanden inmitten para- und internodal unauffälliger Schnürringe und umgekehrt. Diese Beobachtung stützt die bereits in Vorarbeiten vorgeschlagene und in der aktuellen Leitlinie zur Diagnostik für Polyneuropathien aufgegriffene Entität der Paranodopathien (Uncini, Susuki, & Yuki, 2013). Möglich wäre, dass eine veränderte Verteilung der Natriumkanäle die schnelle Leitfähigkeit beeinträchtigen und somit trotz intakter Bemarkung, elektrophysiologisch das Bild einer demyelinisierenden Neuropathie vermittelt. Ein direkter Zusammenhang zwischen dem Auftreten von doppelten und verlängerten Natriumkanalbanden und einzelnen Messwerten (z.B. Amplituden und Latenzzeiten) fand sich nicht. Auch in den Zupfnervenpräparaten der Nervus suralis Biopsien, konnten o.g. Verteilungsmuster untersucht werden. Deren Vorkommen zeigte sich als unabhängig vom elektrophysiologischen und histologischen Befund, von der Ätiologie der PNP und von den gefundenen Veränderungen in den Hautbiopsien des betreffenden Patienten.
Das mR-Paradigma beschreibt die Fähigkeit Objekte gedanklich zu drehen und erfordert dabei komplexe neuronale Prozesse. Bisherige Studien konnten nicht klären, ob es ein spezifisches Muster der Beeinträchtigung im mR-Test bei fokalen Dystonien gibt. Die übergeordnete Fragestellung der vorliegenden Arbeit war, ob eine verlangsamte Reaktion bei der mR von körperlichen Abbildungen einen stabilen Endophänotyp fokaler Dystonien darstellt. Die Zielsetzung war die Überprüfung der Hypothesen, 1) dass bisherige Ergebnisse, die eine verlängerte Reaktionszeit von CD-Patienten bei der mR von körperlichen Abbildungen aufzeigten, reproduzierbar sind und 2) dass eine erhöhte Reaktionszeit bei der mR von körperlichen Abbildungen auch bei Patienten mit BSP vorliegt. Um dabei die mR möglichst spezifisch zu untersuchen, wurden folgende sekundäre Hypothesen formuliert: a) die kognitive Leistungsfähigkeit und b) das allgemeine Reaktionsvermögen der Teilnehmer stellen potenzielle Störfaktoren für die Reaktionszeit bei der mR-Aufgabe dar. Diese wurden neben der Händigkeit und der allgemeinen Geschicklichkeit systematisch erhoben.
23 CD-Patienten und 23 gesunde Kontrollpersonen sowie 21 BSP- und 19 HFS-Patienten wurden hinsichtlich Geschlechterverteilung, Alter und Bildungsstand verglichen. Zudem wurden Händigkeit, Fingergeschicklichkeit, allgemeine Reaktionszeit und kognitiver Status jedes Teilnehmers erhoben. Im mR-Test wurden Fotos von Körperteilen (Hand, Fuß oder Kopf) und einem nicht-körperlichen Objekt (Auto) gezeigt, die in sechs verschiedene Winkelgrade um die eigene Achse in der Bildebene rotiert waren. Die Teilnehmer wurden gebeten, die Lateralität des dargestellten Bildes per Tastendruck anzugeben. Bewertet wurden sowohl Geschwindigkeit als auch Richtigkeit der Antworten.
Im Vergleich zu gesunden Kontrollpersonen schnitten CD- und HFS-Patienten bei der mR der Hände schlechter ab, während die BSP-Patienten vergleichbare Leistungen zeigten. Es bestand ein signifikanter Zusammenhang zwischen einer verlängerten mR-Reaktionszeit und reduzierten MoCA-Scores sowie einer erhöhten mR-Reaktionszeit und verlängerter allgemeiner Reaktionszeit. Nach Ausschluss der Patienten mit MCI zeigten CD-Patienten, nicht jedoch HFS-Patienten, im Vergleich zur gesunden Kontrollgruppe weiterhin verlangsamte Reaktionszeiten der Hände.
Die vorliegende Studie konnte die Frage, ob eine verlangsamte Reaktion bei der mR von körperlichen Abbildungen einen stabilen Endophänotyp fokaler Dystonien darstellt, nicht sicher beantworten. Es stellte sich jedoch heraus, dass Kognition und allgemeine Reaktionszeit starke Einflussfaktoren bei der mR-Aufgabe sind. Dies wurde in den früheren Arbeiten nicht berücksichtigt und stellt daher ein neues und wichtiges Ergebnis dar. Die verlangsamte Reaktion bei der mR der Hände bei CD-Patienten auch nach Ausschluss von Patienten mit MCI lässt ein spezifisches Defizit der Fähigkeit der mR vermuten. Das Vorliegen einer tiefergreifenden zugrundeliegenden Netzwerkstörung, die sich auf die Leistung im mR-Test auswirkt, wäre dabei denkbar.
Charcot-Marie-Tooth (CMT) Neuropathien stellen als häufigste erblich bedingte neurologische Erkrankungen eine Gruppe genetisch heterogener, chronisch progredienter peripherer Polyneuropathien dar. Die Lebensqualität der Patienten ist bei fehlender kurativer Therapieoption vor allem durch motorische und sensorische Defizite deutlich eingeschränkt. In verschiedenen Studien konnte die pathophysiologische Relevanz einer sekundären Entzündungsreaktion, insbesondere durch Makrophagen und Lymphozyten vermittelt, in Mausmodellen dreier CMT1 Subtypen (CMT1A, CMT1B, CMT1X) aufgezeigt werden. Auch in Folge einer Läsion peripherer Nerven ist eine akute Entzündungsreaktion von entscheidender Bedeutung, wobei sich bereits Gemeinsamkeiten zwischen der postläsionalen Waller´schen Degeneration (WD) und CMT1 Neuropathien identifizieren ließen. Während die aktive Beteiligung der Autophagie Schwann´scher Zellen (hier kurz SZ Autophagie genannt) an der Myelindegradation im Falle einer WD jedoch vielfach beschrieben wurde, ist Ähnliches in CMT1 Neuropathien bisher nur unzureichend untersucht. Da in einer Studie in Cx32def Mausmodellen der CMT1X Erkrankung auch nach Reduktion endoneuraler Makrophagen anhaltende Demyelinisierung beobachtet werden konnte, sollte das Vorkommen von SZ Autophagie sowie deren mögliche Beeinflussung durch Makrophagen in diesen Myelinmutanten untersucht werden.
In der vorliegenden Arbeit wurden sowohl Wildtyp (Wt) Mäuse in ex vivo und in vivo Modellen einer WD als auch Cx32def Myelinmutanten zweier Altersstufen (4 und 12 Monate) mit einem niedermolekularen CSF1-Rezeptor-Inhibitor (CSF1RI) zur Reduktion endoneuraler Makrophagen behandelt, wobei sich vergleichende histochemische bzw. immunhistochemische Analysen peripherer Nerven behandelter und unbehandelter Tiere anschlossen.
Im Rahmen der Etablierung immunhistochemischer Methodik zeigte sich hierbei unter den kontrollierten Bedingungen einer ex vivo Ischiasnervenkultur eine vermehrte Aktivierung der SZ Autophagie in behandelten Wt Mäusen. Auch 4 Monate alte behandelte Cx32def Tiere wiesen, verglichen mit unbehandelten Myelinmutanten bzw. Wt Mäusen derselben Altersstufe, eine vermehrte autophagische Aktivität in SZ auf. Diese scheint sich jedoch im weiteren Verlauf der Erkrankung zu reduzieren, da im Falle der 12 Monate alten Cx32def Modelltiere weniger autophagisch aktive SZ Profile bzw. kaum Unterschiede zwischen behandelten und unbehandelten Tieren beobachtet werden konnten.
Die Ergebnisse lassen somit eine mögliche aktive Beteiligung von SZ Autophagie insbesondere in der Pathophysiologie der frühen Phase einer CMT1X Erkrankung sowie deren Beeinflussung durch endoneurale Makrophagen vermuten. Dies sollte vornehmlich in der Entwicklung von Therapiestrategien der CMT1X bedacht werden, da sich eine frühe Reduktion pathophysiologisch relevanter endoneuraler Makrophagen somit auch nachteilig auf die Myelinintegrität auswirken könnte.