Refine
Has Fulltext
- yes (317)
Year of publication
Document Type
- Journal article (317) (remove)
Language
- English (317) (remove)
Keywords
- ischemic stroke (26)
- Parkinson’s disease (15)
- deep brain stimulation (15)
- multiple sclerosis (15)
- Fabry disease (14)
- neuroinflammation (14)
- Parkinson's disease (12)
- Medizin (11)
- stroke (11)
- inflammation (9)
- neuropathic pain (9)
- pain (8)
- subthalamic nucleus (7)
- B cells (6)
- acute ischemic stroke (6)
- biomarker (6)
- depression (6)
- dopamine (6)
- dystonia (6)
- fibromyalgia syndrome (6)
- mouse model (6)
- neurology (6)
- MS (5)
- antibodies (5)
- blood-brain barrier (5)
- cytokines (5)
- neurodegeneration (5)
- neuroprotection (5)
- traumatic brain injury (5)
- GFAP (4)
- MRI (4)
- blood–brain barrier (4)
- disease (4)
- factor XII (4)
- immunohistochemistry (4)
- macrophages (4)
- magnetic resonance imaging (4)
- mechanical thrombectomy (4)
- middle cerebral artery occlusion (4)
- movement disorders (4)
- mutation (4)
- neuropathy (4)
- platelets (4)
- small fiber neuropathy (4)
- thrombo-inflammation (4)
- tremor (4)
- walking (4)
- COVID-19 (3)
- EAE (3)
- Fabry-associated pain (3)
- Gehirn (3)
- HBMEC (3)
- Mice (3)
- Multiple sclerosis (3)
- Neurodegeneration (3)
- Neuromyelitis optica spectrum disorders (NMOSD) (3)
- Optic neuritis (3)
- Pain (3)
- Parkinson disease (3)
- Ureaplasma parvum (3)
- animal models (3)
- anxiety (3)
- autoantibodies (3)
- basal ganglia (3)
- biomarkers (3)
- brain (3)
- cerebellar tDCS (3)
- cerebral ischemia (3)
- cervical dystonia (3)
- children (3)
- closed head injury (3)
- criteria (3)
- enzyme replacement therapy (3)
- essential tremor (3)
- experimental autoimmune encephalomyelitis (3)
- expression (3)
- gait initiation (3)
- gene expression (3)
- genetics (3)
- inflammasome (3)
- kinematics (3)
- length of stenosis (3)
- local field potentials (3)
- lymphocytes (3)
- macrophage (3)
- mesencephalic locomotor region (3)
- mice (3)
- myelin (3)
- neutrophils (3)
- photothrombotic stroke (3)
- quality of life (3)
- regulatory T cells (3)
- skin punch biopsy (3)
- tMCAO (3)
- therapy (3)
- tight junctions (3)
- transplantation (3)
- trial (3)
- Alzheimer’s disease (2)
- Autoantibodies (2)
- B7-H1 (2)
- Cerebrospinal fluid (2)
- Charcot-Marie-Tooth (2)
- DYT1 (2)
- Diagnosis (2)
- ELISPOT (2)
- Enzyme replacement therapy (2)
- Fabry genotype (2)
- Fabry phenotype (2)
- Fibromyalgia syndrome (2)
- Glatiramer acetate (2)
- Guillain-Barre-Syndrome (2)
- Inflammation (2)
- Longitudinally extensive transverse myelitis (LETM) (2)
- Maus (2)
- Mechanisms (2)
- Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) (2)
- NEUROWIND (2)
- NLRP3 (2)
- NOAC (2)
- Neuronal ceroid lipofuscinosis (2)
- Neuropathy (2)
- Outcome survey (2)
- PET (2)
- Schlaganfall (2)
- T cells (2)
- T lymphocytes (2)
- T-lymphocytes (2)
- Tourette syndrome (2)
- Treatment (2)
- Ureaplasma urealyticum (2)
- accuracy (2)
- adaptive immune system (2)
- amyotrophic-lateral-sclerosis (2)
- atrial fibrillation (2)
- autoantibody (2)
- base of support (2)
- beta oscillations (2)
- binding (2)
- blood brain barrier (2)
- blood flow (2)
- blood pressure (2)
- c-Fos (2)
- caregiver burden (2)
- carotid atherosclerosis (2)
- carotid stenosis (2)
- carotid ultrasound (2)
- central nervous system (2)
- cerebral autoregulation (2)
- chronic cerebrovascular disease (2)
- chronic pain (2)
- cognitive impairment (2)
- colony-stimulating factor (2)
- contact-kinin system (2)
- degree of stenosis (2)
- dementia (2)
- diagnosis (2)
- differential diagnosis (2)
- disability (2)
- echocardiography (2)
- edema (2)
- electrophysiology (2)
- endoglin (2)
- endothelial cells (2)
- experimental stroke (2)
- fibromyalgia (2)
- gait (2)
- gait analysis (2)
- gene (2)
- generalized cerebral edema (2)
- glial fate modulation (2)
- globotriaosylceramide (2)
- glycoprotein receptor Ib (2)
- guidelines (2)
- hearing loss (2)
- heart failure (2)
- hypoxia (2)
- immune cells (2)
- immunomodulation (2)
- in vivo imaging (2)
- induced pluripotent stem cells (2)
- ion channels (2)
- ischemic penumbra (2)
- lesions (2)
- leukocytes (2)
- machine learning (2)
- major depression (2)
- meningitis (2)
- microRNA (2)
- microglia (2)
- mitochondria (2)
- mortality (2)
- mouse models (2)
- multiple system atrophy (2)
- multiple-sclerosis (2)
- nerve fibers (2)
- neurofilament light chain (2)
- neurons (2)
- opioids (2)
- outcomes (2)
- pathogenesis (2)
- photothrombosis (2)
- polyneuropathy (2)
- predictive value (2)
- protein (2)
- randomized controlled trial (2)
- rat (2)
- relapse (2)
- renal system (2)
- reversible posterior leukoencephalopathy syndrome (2)
- second hit (2)
- spinal cord (2)
- split-belt treadmill (2)
- synaptic vesicles (2)
- thrombosis (2)
- transient ischemic attack (2)
- transient middle cerebral artery occlusion (2)
- velocity (2)
- von Willebrand factor (2)
- 2B (1)
- 3D fluoroscopy (1)
- 5IA-SPECT (1)
- 65-kda isoform (1)
- A-delta fibers (1)
- A53T (1)
- ADHD (1)
- ALS (1)
- ALS mimic (1)
- ALS treatment (1)
- ALSIN gene (1)
- APERIO (1)
- APERIO Hybrid (1)
- ASC (1)
- Adaptive cell transfer (1)
- Adult patients (1)
- Agalsidase beta (1)
- Agalsidase beta therapy (1)
- Alemtuzumab (1)
- Alpha galactosidase (1)
- Alzheimer disease (1)
- Alzheimer’s dementia (1)
- Amplitude (1)
- Amyotrophic Lateral Sclerosis (ALS) (1)
- Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5) (1)
- Anderson-Fabry Disease (1)
- Animal models (1)
- Antibody index (1)
- Antiparanodal Autoantibodies (1)
- Anxiety (1)
- Apoptosis (1)
- Aquaporin-4 antibodies (AQP4-Ig, NMO-IgG)G (1)
- Aquaporin-4 antibodies (AQP4-IgG) (1)
- Aquaporin-4 antibodies (AQP4-IgG, NMO-IgG) (1)
- Arterial Diameters (1)
- Arterial water (1)
- Ataxia (1)
- Atrial fibrillation (1)
- Axon degeneration (1)
- Axonal degeneration (1)
- Azathioprine (1)
- Aδ- and C-fibers (1)
- B-lymphocytes (1)
- BB/OKL rats (1)
- Barkhof criteria (1)
- Beta-glucocerebrosidase (1)
- Biomarker (1)
- Braak (1)
- Brain (1)
- Brain atrophy (1)
- Brain edema (1)
- Brain ischemia (1)
- Brainstem encephalitis (1)
- C.376A>G (p.S126G) (1)
- C1-inhibitor (1)
- C57BL/6 mice (1)
- CCI (1)
- CCS (1)
- CD105 (1)
- CD133 (1)
- CD52 (1)
- CIDP (1)
- CLN3 (1)
- CMV (1)
- CNS (1)
- CNS Myelination (1)
- CNS disease (1)
- CNS imaging (1)
- CNS integrity (1)
- COMPLEX 1 (1)
- COU254 (1)
- CRPS (1)
- CSF (1)
- CSVD (1)
- CXCL4 (1)
- CXCL5 (1)
- CXCL7 (1)
- CXCL8 (1)
- CXCR2 (1)
- Ca2+ homeostasis (1)
- Ca2+ ion analysis (1)
- Ca2+ leak (1)
- Ca2+ oscillation (1)
- Capsaicin receptor (1)
- Caspase (1)
- Cell Index (1)
- Cell therapy (1)
- Cell-based assays (1)
- Cerebellitis (1)
- Cerebral blood flow (1)
- Cerebral small vessel disease (1)
- Cerebral vasospasm (1)
- Cerebral-ischemia (1)
- Charcot-Marie-Tooth disease (1)
- Charcot–Marie–Tooth disease (1)
- Charcot–Marie–Tooth disease type 1A (1)
- CholinomiRs (1)
- Chronic heart failure (1)
- Chronic neuropathic pain (1)
- Cisterna magna (1)
- Clinical manifestations (1)
- Clinically silent stroke (1)
- Coefficient (1)
- Cognitive behavior (1)
- Cognitive decline (1)
- Cold (1)
- Computertomographie (1)
- Corneal confocal microscopy (1)
- Crespi effect (1)
- Cytokines (1)
- D313Y genotype (1)
- DARPA (1)
- DBS biomarkers (1)
- DBS programming (1)
- DOPA-responsive-dystonia (1)
- Deflazacort (1)
- Delphi procedure (1)
- Demyelinating peripheral neuropathy (1)
- Devic’s syndrome (1)
- Diabetes mellitus (1)
- Diabetic polyneuropathy (1)
- Diplopia Internuclear ophthalmoplegia (INO) (1)
- Disease (1)
- Donor lymphocytes (1)
- Dose reduction (1)
- Double hemorrhage model (1)
- Duchenne dystrphy (1)
- Durchblutung (1)
- Dystonia (1)
- EEG data (1)
- ER Ca2+ imaging (1)
- ER Ca2+ store (1)
- ERK1/2 (1)
- Edema (1)
- El Escorial (1)
- Electrophysiology (1)
- English version (1)
- Epilepsy (1)
- EuroQol Five Dimension Five Level Scale (EQ-5D-5L) (1)
- Evoked potentials (1)
- Experimental stroke (1)
- Expression (1)
- F-18-FDG PET (1)
- FOSMN (1)
- FP-CIT SPECT (1)
- FTY720 (1)
- FTY720-P (1)
- FXII (1)
- FXIIa inhibitor rHA-Infestin (1)
- Fabry (1)
- Fabry cardiomyopathy (1)
- Fabry nephropathy (1)
- Facial nerve palsy (1)
- Factor messenger-RNA (1)
- Fc-receptor (1)
- Fibromyalgia (1)
- Fibromyalgie (1)
- Frabin/Fgd4 (1)
- GABAergic neurons (1)
- GCH1 (1)
- GFAP-astrocytopathies (1)
- GRAID (1)
- Gene-expression (1)
- Gland (1)
- Glial fibrillary acidic protein (1)
- Glioblastoma (1)
- Glioma stem cells (1)
- Glutamic-acid decarboxylase anxiety (1)
- Guillain-Barré syndrome (1)
- Guillain-Barré-Syndrom (1)
- HMGB1 (1)
- Head-injury (1)
- Hearing loss (1)
- Heat Hyperalgesia (1)
- Hemodynamic depression (1)
- Hyperalgesia (1)
- IBA-1 (1)
- IL-15 (1)
- IL-22 binding protein isoform (1)
- IL-4 (1)
- IL22RA2 (1)
- IPND criteria (1)
- IVIg (1)
- Identification (1)
- IgG (1)
- Immune system (1)
- Infections (1)
- Innervation (1)
- Insulin (1)
- IntelliCage (1)
- Interferon beta (1)
- Interleukin-18 (1)
- Interleukin-6 (1)
- Interleukin-6-Deficient mice (1)
- International consensus diagnostic criteria for neuromyelitis optica spectrum disorders (1)
- Intractable nausea and vomiting (1)
- Intravascular coagulation (1)
- Ischemia (1)
- Ischemic stroke (1)
- JCV (1)
- K+ channel (1)
- K2P channels (1)
- KCNK5 (1)
- K\(_{2P}\)5.1 (1)
- Kaliumkanal (1)
- L-DOPA (1)
- LI-rTMS (1)
- LIMP-2 (1)
- LSVT-big therapy (1)
- LTD (1)
- Langerhans cells (1)
- Leukemia Inhibitory Factor (1)
- Lewy-like pathology (1)
- Limb girdle muscular dystrophy (LGMD) (1)
- Longitudinally extensive transverse myelitis (1)
- Lysosomal storage disease (1)
- MCC950 (1)
- MDL-28170 (1)
- MIBG scintigraphy (1)
- MIC ligands (1)
- MMP9 (1)
- MOC fibers (1)
- MOG-IgG (1)
- MRI criteria (1)
- MSSS (1)
- Macrophage (1)
- Macrophages (1)
- Magnetic resonance imaging (1)
- Magnetic-resonance (1)
- McDonald criteria (1)
- Mediated Inflammatory Hyperalgesia (1)
- Memory dysfunction (1)
- Meningitis (1)
- Merkel cell density (1)
- Mesenchymal stem/stromal cells (1)
- Methotrexate (1)
- Microglia (1)
- Migräne (1)
- Miyoshi myopathy (1)
- Model (1)
- Molecular-weight heparin (1)
- Monopolar depression (1)
- Motor cortex (1)
- Motor nerve biopsy (1)
- Motor plasticity (1)
- Mucopolysaccharidosis IIIa (1)
- Multiple Sklerose (1)
- Mycobacterium caprae (1)
- Mycobacterium tuberculosis complex (1)
- Myelin oligodendrocyte glycoprotein (MOG) antibodies (1)
- Myelitis (1)
- Myeloma (1)
- NADPH oxidase inhibitors (1)
- NAP-2 (1)
- NETs (1)
- NF-\(\kappa\)B (1)
- NF-κB (1)
- NKG2D (1)
- NKG2D ligands (1)
- NMO-IGG (1)
- NMOSD (1)
- NMR-Tomographie (1)
- NPC1 gene (1)
- NPC2 gene (1)
- NPSI (1)
- Natalizumab (1)
- Necrosis-factor-Alpha (1)
- Nerve growth-factorcopy (1)
- Nestin (1)
- Neuralgie (1)
- Neurogenic inflammation (1)
- Neuroinflammation (1)
- Neuromyelitis optica (NMO) (1)
- Neuromyelitis optica antibodies (NMO-IgG) (1)
- Neurotrophic factors (1)
- Neutrophil (1)
- NfL (1)
- Niemann–Pick disease type C (1)
- Nodo-parandopathy (1)
- OCB (1)
- Ofatumumab (1)
- Oligoclonal bands (1)
- Oncostatin-M-Receptor (1)
- Opioid receptor (1)
- Optical coherence tomography (1)
- Orai2 (1)
- Oral anticoagulation (1)
- Osteopontin (1)
- Outcome (1)
- PD-L1 (1)
- PF4 (1)
- PI3K isoforms (1)
- PML (1)
- PPAR-gamme (1)
- Pain questionnaire (1)
- Pain-related evoked potentials (1)
- Paradoxical heat sensation (1)
- Parkinson (1)
- Parkinsons disease (1)
- Parkionson's disease (1)
- Perfusion (1)
- Peripheral Inflammation (1)
- Peripheral nervous system (1)
- Pharmacological management (1)
- Plasma extravasation (1)
- Pleckstrin homology containing family member 5 (Plekhg5) (1)
- Pointing error (1)
- Pregnancy (1)
- Prodigy (1)
- Progressive supranuclear palsy (1)
- Proprioception (1)
- Quality of life (1)
- R-715 (1)
- RECK (1)
- RKIP (1)
- RNA extraction (1)
- Randomized controlled trial (1)
- Randomized controlled-trial (1)
- Rat (1)
- Rat Sensory Neurons (1)
- Rats (1)
- Receptors (1)
- Regenerative medicine (1)
- Respiratory insufficiency (1)
- Retinal degeneration (1)
- Rheumatoid-Arthritis (1)
- Rho-GTPase Cdc42 (1)
- Rhombencephalitis (1)
- Richardson-Olszewski-Syndrome (1)
- Rituximab (1)
- Rochester diabetic neuropathy (1)
- SARS-CoV (1)
- SB332235 (1)
- SERCA (1)
- SHRSP (1)
- SNI (1)
- SOD1 mutations (1)
- SPG4 (1)
- SREBP (1)
- STAIR (1)
- STEMI (1)
- Schwann cell (1)
- Schwann cell dedifferentiation (1)
- Schwann cell differentiation (1)
- Schwann-cells (1)
- Screening questionnaire (1)
- Secondary stroke prevention (1)
- Sensitivity (1)
- Serotonin (1)
- Silver-syndrome (1)
- Sjorgens-syndrome (1)
- Skelettmuskel (1)
- Skin biopsy (1)
- Small fiber dysfunction (1)
- Small fiber neuropathy (1)
- Small-fiber neuropathy (1)
- Sonic hedgehog (1)
- Sphingosine 1-Phosphate (1)
- Stim (1)
- Stimuli (1)
- Stroke (1)
- Stroke unit (1)
- Subarachnoid (1)
- Subarachnoid hemorrhage (1)
- Survey (1)
- System involvement (1)
- T cell activation (1)
- T-PA (1)
- T-cells (1)
- TASK2 (1)
- TBI (1)
- TDMT (1)
- TIMP-1 (1)
- TIND (1)
- TLO (1)
- TMS (1)
- TNF-α (1)
- TNFα (1)
- TOR1A (1)
- TRP Channels (1)
- TSPO (1)
- Tdp-43 (1)
- Therapy (1)
- Thermal Hyperalgesia (1)
- Thrombus (1)
- Thrombus formation (1)
- Training (1)
- Transverse Myelitis (1)
- Transverse myelitis (1)
- Tryptophan hydroxylase-2 (Tph2) (1)
- Tuberkulose (1)
- Type 1 diabetes (1)
- Ureaplasma species (1)
- VCAM-1 (1)
- Vaccination (1)
- Vasodilatator-stimuliertes Phosphoprotein (1)
- Vasodilator-Stimulated Phosphoprotein (1)
- Von-Willebrand-factor (1)
- Western blot (1)
- Wingerchuk criteria 2006 and 2015 (1)
- X-chromosomal inactivation (1)
- XAV-939 (1)
- Zonula Occludens-1 (1)
- [18F]FDG positron emission tomography (1)
- acid sphingomyelinase (1)
- activation (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)
- adult-onset (1)
- advanced therapy medicinal products (1)
- afferents (1)
- age (1)
- aggression (1)
- aging (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)
- amygdala (1)
- amyotrophic lateral sclerosis (1)
- amyotrophic lateral sclerosis (ALS) (1)
- analgesia (1)
- analgesic medication (1)
- aneurysm surgery (1)
- angiography (1)
- animal behavior (1)
- animal model (1)
- ankles (1)
- antagomir (1)
- anthropometric measurement (1)
- anthropometric measurements (1)
- anti-aquaporin-4 antibody (1)
- anti-contactin-1 (1)
- anticoagulants (1)
- anticoagulation (1)
- antidepressants (1)
- apoE (1)
- apoe (1)
- apomorphine (1)
- aquaporin 4 (1)
- aquaporin-4 autoantibodies (1)
- areas (1)
- arm (1)
- artery occlusion (1)
- assistive devices (1)
- association (1)
- association studies in genetics (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)
- autoantibody (aAb) (1)
- autoimmune (1)
- autoimmune neuroinflammation (1)
- autophagy (1)
- autoradiography (1)
- axonal degeneration (1)
- axonal integrity (1)
- axonal transcriptome (1)
- axonal transport (1)
- axonopathic changes (1)
- back pain (1)
- balance (1)
- barrier (1)
- barrier integrity (1)
- basal forebrain cholinergic neurons (1)
- behavioral disorders (1)
- beta oscillation (1)
- beta power (1)
- bilateral internal carotid artery stenosis (1)
- binding analysis (1)
- biological locomotion (1)
- biopsies (1)
- biopsy (1)
- blood (1)
- blood coagulability (1)
- blood coagulation (1)
- blood nerve barrier (1)
- bone-marrow (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)
- calpain (1)
- capsaicin (1)
- cardiac imaging (1)
- cardiac magnetic resonance imaging (1)
- cardiovascular disease (1)
- care (1)
- care tempis (1)
- caregiver (1)
- case report (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 microbleeds (1)
- cerebral small vessel disease (1)
- cerebrospinal fluid (1)
- cerebrospinal fluid culture (1)
- cerebrospinal-fluid (1)
- cerebrovascular diseases (1)
- cerebrovascular disorders (1)
- chemokines (1)
- chitinase-3-like protein 1 (1)
- choline acetyltransferase (1)
- cholinergic activity (1)
- cholinergic system (1)
- chronic constriction nerve injury (CCI) (1)
- chronic kidney disease (1)
- chronic stimulation (1)
- chronic stress (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)
- 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 (1)
- complement deposition (1)
- comprehension (1)
- computed tomography (1)
- computer vision (1)
- consolidation (1)
- contact activation system (1)
- continuous theta burst stimulation (cTBS) (1)
- contrast (1)
- contrast-enhanced MRI (1)
- conversion (1)
- coordination (1)
- coping (1)
- corneal confocal microscopy (1)
- cortical activation (1)
- cortical excitability (1)
- cortical oscillatory activity (1)
- cortical pathology (1)
- cortical silent period (1)
- crossover trial (1)
- cue (1)
- cutaneous innervation (1)
- cutaneous patch (1)
- cutting edge (1)
- damage cool aid (1)
- darbepoetin alpha (1)
- data filtering (1)
- decreasing autonomy (1)
- deep brain stimulation (DBS) (1)
- deep brain-stimulation (1)
- degeneration (1)
- delayed cerebral infarction (1)
- delays progression (1)
- demography (1)
- demyelinating disease (1)
- demyelinating polyradiculoneuropathy (1)
- demyelination (1)
- dendric cells (1)
- design (1)
- developmental signaling (1)
- diabetes mellitus (1)
- diabetic neuropathy (1)
- diagnosis in Fabry disease (1)
- diagnostic delay (1)
- diagnostic markers (1)
- diagnostic medicine (1)
- diagnostics (1)
- diffuse (1)
- digital medicine (1)
- dimethyl fumarate (1)
- directional deep brain stimulation (1)
- disease model (1)
- disease progression (1)
- disease severity (1)
- disease-modifying therapy (1)
- diseases of the nervous system (1)
- disorder (1)
- domain potassium channels (1)
- dopamine acetylcholine (1)
- dopamine transporter (DAT) (1)
- drug (1)
- duodenal levodopa infusion (1)
- dysferlinopathy (1)
- edoxaban (1)
- effects (1)
- efficacy (1)
- ejection fraction (1)
- electromyography (1)
- element (1)
- embolic stroke (1)
- emulsions (1)
- encephalitis (1)
- endothelin-1 (1)
- endotheliopathy (1)
- enteropathy (1)
- enzyme assays (1)
- enzyme-linked immunoassays (1)
- epidermis (1)
- event-related desynchronization (1)
- exercise (1)
- exome sequencing (1)
- experimental (1)
- experimental autoimmune neuritis (1)
- experimental design (1)
- expert opinion (1)
- extensiv transverse myelitis (1)
- eye movement disorders (1)
- facial pain (1)
- factor XI (1)
- familial amyloidotic polyneuropathy (1)
- family caregiver (1)
- fatigue (1)
- fear (1)
- fear memory (1)
- feasibility (1)
- female Fabry patients (1)
- females (1)
- fibers (1)
- fibroblast (1)
- finger-tapping task (1)
- fingolimod (1)
- flotillin-1 lipid rafts (1)
- fluorine (1)
- focal (1)
- focal brain lesion (1)
- focal cerebral ischemia (1)
- focal cerebral-ischemia (1)
- fosfomycin (1)
- free radical scavenger (1)
- freezing of gait (1)
- freezing of gait (FOG) (1)
- fullerenes (1)
- functional MRI (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)
- generalized cerebellar atrophy (1)
- genome-wide association study (1)
- genotype-phenotype correlation (1)
- genotype/phenotype correlation (1)
- gephyrin (1)
- glial damage (1)
- glial fibrillary acidic protein (1)
- glioblastoma multiforme (1)
- globus pallidus (1)
- globus pallidus pars interna (GPi) (1)
- glycation end products (1)
- glycine receptor (1)
- glycine receptor (GlyR) (1)
- glycine receptor autoantibodies (1)
- glycoprotein Ib (1)
- glycoprotein VI (1)
- glycoprotein receptor Ibα (1)
- granzyme B (1)
- gridle muscular-dystrophy (1)
- growth (1)
- growth pattern (1)
- health behavior (1)
- health-related quality of life (1)
- health-related quality of life (HRQoL) (1)
- hemicraniectomy (1)
- hemorrhagic transformation (1)
- hereditary motor and sensory neuropathy (1)
- hereditary spastic paraplegia (HSP) (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 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)
- i.v. thrombolysis (1)
- idiopathic inflammatory myopathies (1)
- image quality (1)
- image-guided programming (1)
- imaging (1)
- immaturity (1)
- immune (1)
- immune system (1)
- immune-response (1)
- immunofluorescence (1)
- immunoglobulin-G (1)
- in-vivo (1)
- incidence (1)
- increased risk (1)
- induced neural stem cells (1)
- inducible expression (1)
- inertial measurement units (1)
- infantile neuronal ceroid lipofuscinosis (1)
- infarction (1)
- infarction size (1)
- infarction volume (1)
- inflammatory cascades (1)
- inflammatory demyelinating polyradiculoneuropathy (1)
- inflammatory neuropathy (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)
- interference (1)
- interleukin-1 receptor antagonist (1)
- interleukin-8 (1)
- internal carotid artery stenosis (1)
- internet-based intervention (1)
- interval timing (1)
- interview (1)
- intracranial bleeding (1)
- intracranial hemorrhage (1)
- intractable hiccup (1)
- intraepidermal nerve fiber density (1)
- intraepidermal nerve fibre density (1)
- intraoperative (1)
- intrathecal application (1)
- intravenous immunoglobulin (1)
- intravenous thrombolysis (1)
- invasive electric stimulation (1)
- iron (1)
- iron dyshomeostasis (1)
- iron oxide nanoparticles (1)
- ischemia (1)
- ischemia/reperfusion injury (1)
- ischemic cascade (1)
- just noticeable difference (JND) (1)
- kallikrein-kinin system (1)
- kallikrein–kinin system (1)
- kinesthesia (1)
- kinin receptor (1)
- kinin receptors (1)
- knees (1)
- large vessel occlusion (1)
- learning (1)
- levodopa-induced dyskinesia (1)
- linkage (1)
- liponeurocytoma (1)
- locomotion (1)
- locomotor adaptation (1)
- locus coeruleus (1)
- long-term pain (1)
- lymphokine-activated killer (1)
- lyso-Gb3 (1)
- lysosomal dysfunction (1)
- lysosomal enzyme (1)
- lysosomal storage disease (1)
- lyso‐Gb3 (1)
- magnesium (1)
- management (1)
- matrix metalloproteinases (1)
- mechanical energy (1)
- mechanisms (1)
- medial ganglionic eminence (1)
- medulloblastoma (1)
- mental health (1)
- mesenchymal stem and stromal cells (1)
- mesenchymal stem cells (1)
- metaanalysis (1)
- methylphenidate (1)
- miR-182-5p (1)
- miR-21 (1)
- miRNA (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)
- mixed fiber neuropathy (1)
- mixed methods (1)
- molecular signature (1)
- monocycline (1)
- monocytes (1)
- monomethyl fumarate (1)
- motoneuron disease (1)
- motor (1)
- motor axonal neuropathy (1)
- motor control (1)
- motor cortex (1)
- motor evoked potential (MEP) (1)
- motor function (1)
- motor learning (1)
- motor neuron disease (1)
- motor neuropathy (1)
- motor proteins (1)
- motor-evoked potentials (MEP) (1)
- mouse (1)
- mouse brain microvascular endothelial cell cultur (1)
- movement (1)
- movements (1)
- multiple sklerosis (1)
- muscle atrophy (1)
- muscle strength (1)
- musical syntax (1)
- musk myasthenia gravis (1)
- myasthenia gravis (1)
- myelination (1)
- myocardial infarction (1)
- natural history (1)
- near-infrared spectroscopy (1)
- neonatal meningitis (1)
- nerve biopsy (1)
- nerve fibres (1)
- nerve tumor (1)
- nerve-fibers (1)
- nervous system (1)
- nervous-system (1)
- neural apoptosis (1)
- neural stem cell (1)
- neural stem cells (1)
- neuralgia (1)
- neurobehavioural deficits (1)
- neuroborreliosis (1)
- neurocritical care (1)
- neurocytoma (1)
- neurofascin (1)
- neurofilaments (1)
- neuroimmunology (1)
- neuroleukemiosis (1)
- neurological complications (1)
- neurological disorders (1)
- neurological examination (1)
- neuromelanin (1)
- neuronal apoptosis (1)
- neuronal differentiation (1)
- neuronal network (1)
- neuronal stem cells (1)
- neuronopathy (1)
- neurophysiology (1)
- neuroplasticity (1)
- neurorepair (1)
- neutrophil (1)
- nicotinamide (1)
- nicotinic receptors (1)
- nociceptor sensitization (1)
- nodes of Ranvier (1)
- non-motor features (1)
- nonalcoholic steatohepatitis (1)
- noradrenalin (1)
- norepinephrine (1)
- novo renal transplantation (1)
- nucleus ventralis intermedius (1)
- nystagmus (1)
- object recognition memory (1)
- obstacle avoidance (1)
- occlusion (1)
- oligodendroglia (1)
- online systems (1)
- ontactin 1 (1)
- opioid (1)
- optical coherence tomography (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 pattern (1)
- pain questionnaire (1)
- pain sensation (1)
- pain-associated behavior (1)
- pain-related evoked potentials (1)
- pallidal stimulation (1)
- pandemic (1)
- paranodopathy (1)
- paraparesis (1)
- parkinson disease (1)
- parkinsons disease (1)
- passive transfer (1)
- pathology section (1)
- pathophysiology (1)
- pathway analysis (1)
- pathways (1)
- patient reported outcome measures (1)
- patient triage (1)
- pedunculopontine nucleus (PPN) (1)
- pegylated insulin-like growth factor 1 (1)
- peptide (1)
- periperal nerve (1)
- peripheral injury (1)
- peripheral nerve involvement (1)
- peripheral nervous system (1)
- peripheral nervous-system (1)
- peripheral neuropathy (1)
- permanent and transient middle cerebral artery occlusion (1)
- pet (1)
- ph (1)
- phosphorylated tau protein (1)
- physical activity (1)
- physical therapy modalities (1)
- pilot project (1)
- placebo-controlled (1)
- plaque cross-sectional area (1)
- plasma extravasation (1)
- plasma oxysterols (1)
- plasminogen (1)
- platelet activation (1)
- platelet aggregation (1)
- point-of-care echocardiography (1)
- pointing task (1)
- polymorphism (1)
- polymorphisms inflammation (1)
- polymyositis (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)
- preclinical research (1)
- prednisone (1)
- prefrontal cortex (1)
- presynaptic inhibition (1)
- preterm birth (1)
- preventive treatment (1)
- prognosis (1)
- progression (1)
- progressive ataxia (1)
- progressive encephalitis with rigidity and myoclonus (PERM) (1)
- progressive supranuclear palsy (1)
- proinflammatory cytokine (1)
- protein and mRNA expression (1)
- proteins (1)
- proteolipid protein (1)
- proteolipid protein gene (1)
- proteomics (1)
- psychological support (1)
- psychophysics (1)
- purmorphamine (1)
- quality (1)
- quality control (1)
- quality of life (QoL) (1)
- quality-control (1)
- quantitative sensory testing (1)
- qutenza (1)
- randomized controlled double-blind study (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)
- recurrence (1)
- reflex (1)
- regional heterogeneity (1)
- regulation (1)
- regulatory cells (1)
- rehabilitation (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)
- responsivity (1)
- resting tremor (1)
- retinal ganglion cells (1)
- retinocochleocerebral (1)
- rett (1)
- rhythm perception (1)
- risk (1)
- risk factors (1)
- risk of fall (1)
- rt-PA (1)
- scale (1)
- sciatic nerve (1)
- sciatic nerves (1)
- search filter (1)
- secondary infarct growth (1)
- secretome (1)
- segmental centers of mass (1)
- sensory neurons (1)
- serotonin (1)
- serum (1)
- sex addiction (1)
- shedding (1)
- shingles (1)
- signal peptide (1)
- single photon emission computed tomography (SPECT) (1)
- skilled forelimb movements (1)
- skin biopsy (1)
- skin diseases (1)
- skin tumors (1)
- small vessel disease (1)
- small-fiber neuropathy (1)
- socioeconomic status (1)
- software (1)
- soleus muscles (1)
- soluble endoglin (1)
- somatosensory temporal discrimination (1)
- somatosensory-evoked-potentials (1)
- sphingolipids (1)
- spinal cord injury (1)
- spinal muscular atrophy (1)
- spinal-cord (1)
- spinal-cord-injury (1)
- startle disease (1)
- stent-retriever device (1)
- steroids (1)
- stiff-person syndrome (SPS) (1)
- stimulation (1)
- store-operated Ca2+ entry (1)
- stress (1)
- striatum (1)
- stroke care (1)
- stroke unit (1)
- stromal cells (1)
- study (1)
- subarachnoid hemorrhage (1)
- subcutaneous injection (1)
- substance-P (1)
- subthalamic nucleus (STN) (1)
- swimming (1)
- switch (1)
- symptom-specific treatment (1)
- synapse (1)
- synaptic transmission (1)
- syndrome (1)
- system (1)
- systematic review (1)
- systems biology (1)
- systolic dysfunction (1)
- target considerations (1)
- task retention (1)
- telemedicine (1)
- telemedicine network (1)
- temporal discrimination threshold (1)
- teriflunomide (1)
- term follow-up (1)
- tetrahydroisoquinoline derivates (1)
- tetraparesis (1)
- thrombemboli (1)
- thromboemboli (1)
- thromboembolic clot model (1)
- thromboembolic stroke (1)
- thromboinflammation (1)
- thrombolysis (1)
- thrombus formation (1)
- tics (1)
- time (1)
- time perception (1)
- timing (1)
- tissue-plasminogen activator (1)
- tool (1)
- topography (1)
- torsinA (1)
- transcranial direct current stimulation (1)
- transcranial magnetic simulation (TMS) (1)
- transgenic mouse model (1)
- transient middle cerebral artery (1)
- transient receptor potential vanilloid 1 (TRPV1) (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)
- trigeminal nerve (1)
- trigeminal neuropathy (1)
- troponin (1)
- tuberculous meningitis (1)
- tumor immunity (1)
- ultrasound imaging (1)
- under-dosing (1)
- up-regulation (1)
- validation (1)
- variants of unknown significance (1)
- vascular dementia (1)
- vascular homeostasis (1)
- vascular permeability (1)
- vasculopathy (1)
- vertebrobasilar insufficiency (1)
- vertigo (1)
- vessel patency (1)
- vestibular (1)
- videooculography (1)
- virtual reality (1)
- visual activity (1)
- visual pathways (1)
- volume regulation (1)
- voluntary movement (1)
- weight drop (1)
- white blood cells (1)
- white matter hyperintensities (1)
- white matter lesions (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 (317) (remove)
Sonstige beteiligte Institutionen
- Datenintegrationszentrum Würzburg (DIZ) (1)
- Interdisziplinäre Biomaterial- und Datenbank Würzburg (ibdw) (1)
- Klinische Studienzentrale (Universitätsklinikum) (1)
- Wurzburg Fabry Center for Interdisciplinary Therapy (FAZIT), Wurzburg, Germany (1)
- Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), University of Würzburg, Würzburg, Germany (1)
Background
Postherpetic neuralgia (PHN) is the painful complication of a varicella zoster virus reactivation. We investigated the systemic and local gene expression of pro- and anti-inflammatory cytokine expression in patients with PHN.
Methods
Thirteen patients with PHN at the torso (Th4-S1) were recruited. Skin punch biopsies were obtained from the painful and the contralateral painless body area for intraepidermal nerve fiber density (IENFD) and cytokine profiling. Additionally, blood was withdrawn for systemic cytokine expression and compared to blood values of healthy controls. We analyzed the gene expression of selected pro- and anti-inflammatory cytokines (tumor necrosis factor-alpha [TNF] and interleukins [IL]-1β, IL-2, and IL-8).
Results
IENFD was lower in affected skin compared to unaffected skin (p<0.05), while local gene expression of pro- and anti-inflammatory cytokines did not differ except for two patients who had 7fold higher IL-6 and 10fold higher IL-10 gene expression in the affected skin compared to the contralateral unaffected skin sample. Also, the systemic expression of cytokines in patients with PHN and in healthy controls was similar.
Conclusion
While the systemic and local expression of the investigated pro- and anti-inflammatory cytokines was not different from controls, this may have been influenced by study limitations like the low number of patients and different disease durations. Furthermore, other cytokines or pain mediators need to be considered.
Interleukin-4 (IL-4) is an anti-inflammatory and analgesic cytokine that induces opioid receptor transcription. We investigated IL-4 knockout (ko) mice to characterize their pain behavior before and after chronic constriction injury (CCI) of the sciatic nerve as a model for neuropathic pain. We investigated opioid responsivity and measured cytokine and opioid receptor gene expression in the peripheral and central nervous system (PNS, CNS) of IL-4 ko mice in comparison with wildtype (wt) mice. Naïve IL-4 ko mice displayed tactile allodynia (wt: 0.45 g; ko: 0.18 g; p<0.001), while responses to heat and cold stimuli and to muscle pressure were not different. No compensatory changes in the gene expression of tumor necrosis factor-alpha (TNF), IL-1β, IL-10, and IL-13 were found in the PNS and CNS of naïve IL-4 ko mice. However, IL-1β gene expression was stronger in the sciatic nerve of IL-4 ko mice (p<0.001) 28 days after CCI and only IL-4 ko mice had elevated IL-10 gene expression (p = 0.014). Remarkably, CCI induced TNF (p<0.01), IL-1β (p<0.05), IL-10 (p<0.05), and IL-13 (p<0.001) gene expression exclusively in the ipsilateral spinal cord of IL-4 ko mice. The compensatory overexpression of the anti-inflammatory and analgesic cytokines IL-10 and IL-13 in the spinal cord of IL-4 ko mice may explain the lack of genotype differences for pain behavior after CCI. Additionally, CCI induced gene expression of μ, κ, and δ opioid receptors in the contralateral cortex and thalamus of IL-4 ko mice, paralleled by fast onset of morphine analgesia, but not in wt mice. We conclude that a lack of IL-4 leads to mechanical sensitivity; the compensatory hyperexpression of analgesic cytokines and opioid receptors after CCI, in turn, protects IL-4 ko mice from enhanced pain behavior after nerve lesion.
High-Dose Capsaicin for the Treatment of Neuropathic Pain: What We Know and What We Need to Know
(2014)
Neuropathic pain is a frequent and disabling condition with diverse underlying etiologies and is often difficult to treat. Systemic drug treatment is often limited in efficacy. Furthermore, adverse effects may be a limiting factor when trying to reach the necessary dose. Analgesics that can be applied topically have the potential to largely overcome this problem. They may be of particular advantage in localized neuropathic pain syndromes such as postherpetic neuralgia or small fiber neuropathy. Capsaicin, the pungent component of chili peppers, is a natural ligand of the transient receptor potential vanilloid 1 channel and has long been used as topically applicable cream with concentrations of 0.025 to 0.075%. In 2009, a high-concentration transdermal capsaicin 8% patch (Qutenza ; Acorda Therapeutics, Inc., Ardsley, NY, USA; Astellas Pharma Europe Ltd., Chertsey, Surrey, UK) was introduced for the treatment of peripheral neuropathic pain syndromes other than of diabetic origin in adults. It has since been widely used in diverse neuropathic pain disorders. In this review article, we summarize current knowledge on Qutenza, its advantages and problems, and expose unmet needs.
Background
The X-chromosomally linked life-limiting Fabry disease (FD) is associated with deposits of the sphingolipid globotriaosylceramide 3 (Gb3) in various tissues. Skin is easily accessible and may be used as an additional diagnostic and follow-up medium. Our aims were to visualize skin Gb3 deposits in FD patients applying immunofluorescence and to determine if cutaneous Gb3 load correlates with disease severity.
Methods
At our Fabry Center for Interdisciplinary Therapy we enrolled 84 patients with FD and 27 healthy controls. All subjects underwent 5-mm skin punch biopsy at the lateral lower leg and the back. Skin samples were processed for immunohistochemistry using antibodies against CD77 (i.e. Gb3). Cutaneous Gb3 deposition was quantified in a blinded manner and correlated to clinical data.
Results
We found that Gb3 load was higher in distal skin of male FD patients compared to healthy controls (p<0.05). Men (p<0.01) and women (p<0.05) with a classic FD phenotype had higher distal skin Gb3 load than healthy controls. Men with advanced disease as reflected by impaired renal function, and men and women with small fiber neuropathy had more Gb3 deposits in distal skin samples than males with normal renal function (p<0.05) and without small fiber neuropathy. Gb3 deposits were not different between patients with and without enzyme replacement therapy.
Conclusions
Immunofluorescence on minimally invasive skin punch biopsies may be useful as a tool for assessment and follow-up in FD patients.
Objectives
The pathogenesis of fibromyalgia syndrome (FMS) is unclear. Transcranial ultrasonography revealed anechoic alteration of midbrain raphe in depression and anxiety disorders, suggesting affection of the central serotonergic system. Here, we assessed midbrain raphe echogenicity in FMS.
Methods
Sixty-six patients underwent transcranial sonography, of whom 53 were patients with FMS (27 women, 26 men), 13 patients with major depression and physical pain (all women), and 14 healthy controls (11 women, 3 men). Raphe echogenicity was graded visually as normal or hypoechogenic, and quantified by digitized image analysis, each by investigators blinded to the clinical diagnosis.
Results
Quantitative midbrain raphe echogenicity was lower in patients with FMS compared to healthy controls (p<0.05), but not different from that of patients with depression and accompanying physical pain. Pain and FMS symptom burden did not correlate with midbrain raphe echogenicity as well as the presence and severity of depressive symptoms.
Conclusion
We found reduced echogenicity of the midbrain raphe area in patients with FMS and in patients with depression and physical pain, independent of the presence or severity of pain, FMS, and depressive symptoms. Further exploration of this sonographic finding is necessary before this objective technique may enter diagnostic algorithms in FMS and depression.
Background
Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain and associated symptoms. We investigated cerebral activation in FMS patients by functional near-infrared spectroscopy (fNIRS).
Methods
Two stimulation paradigms were applied: a) painful pressure stimulation at the dorsal forearm; b) verbal fluency test (VFT). We prospectively recruited 25 FMS patients, ten patients with unipolar major depression (MD) without pain, and 35 healthy controls. All patients underwent neurological examination and all subjects were investigated with questionnaires (pain, depression, FMS, empathy).
Results
FMS patients had lower pressure pain thresholds than patients with MD and controls (p < 0.001) and reported higher pain intensity (p < 0.001). Upon unilateral pressure pain stimulation fNIRS recordings revealed increased bilateral cortical activation in FMS patients compared to controls (p < 0.05). FMS patients also displayed a stronger contralateral activity over the dorsolateral prefrontal cortex in direct comparison to patients with MD (p < 0.05). While all three groups performed equally well in the VFT, a frontal deficit in cortical activation was only found in patients with depression (p < 0.05). Performance and cortical activation correlated negatively in FMS patients (p < 0.05) and positively in patients with MD (p < 0.05).
Conclusion
Our data give further evidence for altered central nervous processing in patients with FMS and the distinction between FMS and MD.
Skin cytokine expression in patients with fibromyalgia syndrome is not different from controls
(2014)
Background
Fibromyalgia syndrome (FMS) is a chronic pain syndrome of unknown etiology. There is increasing evidence for small nerve fiber impairment in a subgroup of patients with FMS. We investigated whether skin cytokine and delta opioid receptor (DOR) gene expression in FMS patients differs from controls as one potential contributor to small nerve fiber sensitization.
Methods
We investigated skin punch biopsies of 25 FMS patients, ten patients with monopolar depression but no pain, and 35 healthy controls. Biopsies were obtained from the lateral upper thigh and lower calf. Gene expression of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF), interleukin (IL)-6, and IL-8 and of the anti-inflammatory cytokine IL-10 was analyzed using quantitative real-time PCR and normalizing data to 18sRNA as housekeeping gene. Additionally, we assessed DOR gene expression.
Results
All cytokines and DOR were detectable in skin samples of FMS patients, patients with depression, and healthy controls without intergroup difference. Also, gene expression was not different in skin of the upper and lower leg within and between the groups and in FMS patient subgroups.
Conclusions
Skin cytokine and DOR gene expression does not differ between patients with FMS and controls. Our results do not support a role of the investigated cytokines in sensitization of peripheral nerve fibers as a potential mechanism of small fiber pathology in FMS.
Background
Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP).
Methods
In this case–control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function.
Results
All Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients.
Conclusion
Small fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction.
A high load of white matter lesions and enlarged basilar arteries have been shown in selected patients with Fabry disease, a disorder associated with an increased stroke risk. We studied a large cohort of patients with Fabry disease to differentially investigate white matter lesion load and cerebral artery diameters. We retrospectively analyzed cranial magnetic resonance imaging scans of 87 consecutive Fabry patients, 20 patients with ischemic stroke, and 36 controls. We determined the white matter lesion load applying the Fazekas score on fluid-attenuated inversion recovery sequences and measured the diameters of cerebral arteries on 3D-reconstructions of the time-of-flight-MR-angiography scans. Data of different Fabry patient subgroups (males – females; normal – impaired renal function) were compared with data of patients with stroke and controls. A history of stroke or transient ischemic attacks was present in 4/30 males (13%) and 5/57 (9%) females with Fabry disease, all in the anterior circulation. Only one man with Fabry disease showed confluent cerebral white matter lesions in the Fazekas score assessment (1%). Male Fabry patients had a larger basilar artery (p<0.01) and posterior cerebral artery diameter (p<0.05) compared to male controls. This was independent of disease severity as measured by renal function and did not lead to changes in arterial blood flow properties. A basilar artery diameter of >3.2 mm distinguished between men with Fabry disease and controls (sensitivity: 87%, specificity: 86%, p<0.001), but not from stroke patients. Enlarged arterial diameters of the posterior circulation are present only in men with Fabry disease independent of disease severity.
Objective: We investigated cerebral opioid receptor binding potential in patients with fibromyalgia syndrome (FMS) using positron-emission-tomography (PET) and correlated our results with patients’ systemic interleukin-4 (IL-4) gene expression.
Methods: In this pilot study, seven FMS patients (1 man, 6 women) agreed to participate in experimental PET scans. All patients underwent neurological examination, were investigated with questionnaires for pain, depression, and FMS symptoms. Additionally, blood for IL-4 gene expression analysis was withdrawn at two time points with a median latency of 1.3 years. Patients were investigated in a PET scanner using the opioid receptor ligand F-18-fluoro-ethyl-diprenorphine ([18F]FEDPN) and results were compared with laboratory normative values.
Results: Neurological examination was normal in all FMS patients. Reduced opioid receptor binding was found in mid cingulate cortex compared to healthy controls (p < 0.005). Interestingly, three patients with high systemic IL-4 gene expression had increased opioid receptor binding in the fronto-basal cortex compared to those with low IL-4 gene expression (p < 0.005).
Conclusion: Our data give further evidence for a reduction in cortical opioid receptor availability in FMS patients as another potential central nervous system contributor to pain in FMS.
Fabry disease is an X-linked lysosomal storage disorder due to impaired activity of alpha-galactosidase A with intracellular accumulation of globotriaosylceramide. Associated small fiber pathology leads to characteristic pain in Fabry disease. We systematically assessed sensory system, physical activity, metabolic parameters, and morphology of male and female mice with alpha-galactosidase A deficiency (Fabry ko) from 2 to 27 months of age and compared results with those of age- and gender-matched wild-type littermates of C57Bl/6J background. Results From the age of two months, male and female Fabry mice showed mechanical hypersensitivity (p < 0.001 each) compared to wild-type littermates. Young Fabry ko mice of both genders were hypersensitive to heat stimulation (p < 0.01) and developed heat hyposensitivity with aging (p < 0.05), while cold hyposensitivity was present constantly in young (p < 0.01) and old (p < 0.05) Fabry ko mice compared to wild-type littermates. Stride angle increased only in male Fabry ko mice with aging (p < 0.01) in comparison to wild-type littermates. Except for young female mice, male (p < 0.05) and female (p < 0.01) Fabry ko mice had a higher body weight than wild-type littermates. Old male Fabry ko mice were physically less active than their wild-type littermates (p < 0.05), had lower chow intake (p < 0.001), and lost more weight (p < 0.001) in a one-week treadmill experiment than wild-type littermates. Also, Fabry ko mice showed spontaneous pain protective behavior and developed orofacial dysmorphism resembling patients with Fabry disease.
Conclusions. Mice with alpha-galactosidase A deficiency show age-dependent and distinct deficits of the sensory system. alpha-galactosidase A-deficient mice seem to model human Fabry disease and may be helpful when studying the pathophysiology of Fabry-associated pain.
Background: To perform a systematic review and meta-analysis on cytokine levels in patients with fibromyalgia syndrome (FMS). Methods: Through December 2010 we systematically reviewed the databases PubMed, MEDLINE, and PsycINFO and screened the reference lists of 22 review articles for suitable original articles. Original articles investigating cytokines in patients with FMS were included. Data were extracted by two independent authors. Differences of the cytokine levels of FMS patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed applying methodological scores: modified Center of Evidence Based Medicine, Newcastle-Ottawa-Scale, and Würzburg Methodological Quality Score. Results: Twenty-five articles were included investigating 1255 FMS patients and 800 healthy controls. Data of 13/25 studies entered meta-analysis. The overall methodological quality of studies was low. The results of the majority of studies were not comparable because methods, investigated material, and investigated target cytokines differed. Systematic review of the selected 25 articles revealed that FMS patients had higher serum levels of interleukin (IL)-1 receptor antagonist, IL-6, and IL-8, and higher plasma levels of IL-8. Meta-analysis of eligible studies showed that FMS patients had higher plasma IL-6 levels compared to controls (SMD = -0.34 [-0.64, -0.03] 95% CI; p = 0.03). The majority of investigated cytokines were not different between patients and controls. Conclusions: The pathophysiological role of cytokines in FMS is still unclear. Studies of higher quality and with higher numbers of subjects are needed.
Introduction/Aims
Schwann cell clusters have been described at the murine dermis-epidermis border. We quantified dermal Schwann cells in the skin of patients with small-fiber neuropathy (SFN) compared with healthy controls to correlate with the clinical phenotype.
Methods
Skin punch biopsies from the lower legs of 28 patients with SFN (11 men, 17 women; median age, 54 [range, 19-73] years) and 9 healthy controls (five men, four women, median age, 34 [range, 25-69] years) were immunoreacted for S100 calcium-binding protein B as a Schwann cell marker, protein-gene product 9.5 as a pan-neuronal marker, and CD207 as a Langerhans cell marker. Intraepidermal nerve fiber density (IENFD) and subepidermal Schwann cell counts were determined.
Results
Skin samples of patients with SFN showed lower IENFD (P < .05), fewer Schwann cells per millimeter (P < .01), and fewer Schwann cell clusters per millimeter (P < .05) than controls. When comparing SFN patients with reduced (n = 13; median age, 53 [range, 19-73] years) and normal distal (n = 15, median age, 54 [range, 43-68] years) IENFD, the number of solitary Schwann cells per millimeter (p < .01) and subepidermal nerve fibers associated with Schwann cell branches (P < .05) were lower in patients with reduced IENFD. All three parameters correlated positively with distal IENFD (P < .05 to P < .01), whereas no correlation was found between Schwann cell counts and clinical pain characteristics.
Discussion
Our data raise questions about the mechanisms underlying the interdependence of dermal Schwann cells and skin innervation in SFN. The temporal course and functional impact of Schwann cell presence and kinetics need further investigation.
Background:
Clinical reasoning in Neurology is based on general associations which help to deduce the site of the lesion. However, even “golden principles” may occasionally be deceptive. Here, we describe the case of subacute flaccid tetraparesis due to motor cortical lesions. To our knowledge, this is the first report to include an impressive illustration of nearly symmetric motor cortical involvement of encephalitis on brain MRI.
Case presentation:
A 51 year old immunocompromized man developed a high-grade pure motor flaccid tetraparesis over few days. Based on clinical presentation, critical illness polyneuromyopathy was suspected. However, brain MRI revealed symmetrical hyperintensities strictly limited to the subcortical precentral gyrus. An encephalitis, possibly due to CMV infection, turned out to be the most likely cause.
Conclusion:
While recognition of basic clinical patterns is indispensable in neurological reasoning, awareness of central conditions mimicking peripheral nervous disease may be crucial to detect unsuspected, potentially treatable conditions.
Background: Compensation of brain injury in multiple sclerosis (MS) may in part work through mechanisms involving neuronal plasticity on local and interregional scales. Mechanisms limiting excessive neuronal activity may have special significance for retention and (re-)acquisition of lost motor skills in brain injury. However, previous neurophysiological studies of plasticity in MS have investigated only excitability enhancing plasticity and results from neuroimaging are ambiguous. Thus, the aim of this study was to probe long-term depression-like central motor plasticity utilizing continuous theta-burst stimulation (cTBS), a non-invasive brain stimulation protocol. Because cTBS also may trigger behavioral effects through local interference with neuronal circuits, this approach also permitted investigating the functional role of the primary motor cortex (M1) in force control in patients with MS. Methods: We used cTBS and force recordings to examine long-term depression-like central motor plasticity and behavioral consequences of a M1 lesion in 14 patients with stable mild-to-moderate MS (median EDSS 1.5, range 0 to 3.5) and 14 age-matched healthy controls. cTBS consisted of bursts (50 Hz) of three subthreshold biphasic magnetic stimuli repeated at 5 Hz for 40 s over the hand area of the left M1. Corticospinal excitability was probed via motor-evoked potentials (MEP) in the abductor pollicis brevis muscle over M1 before and after cTBS. Force production performance was assessed in an isometric right thumb abduction task by recording the number of hits into a predefined force window. Results: cTBS reduced MEP amplitudes in the contralateral abductor pollicis brevis muscle to a comparable extent in control subjects (69 ± 22% of baseline amplitude, p < 0.001) and in MS patients (69 ± 18%, p < 0.001). In contrast, postcTBS force production performance was only impaired in controls (2.2 ± 2.8, p = 0.011), but not in MS patients (2.0 ± 4.4, p = 0.108). The decline in force production performance following cTBS correlated with corticomuscular latencies (CML) in MS patients, but did not correlate with MEP amplitude reduction in patients or controls. Conclusions: Long-term depression-like plasticity remains largely intact in mild-to-moderate MS. Increasing brain injury may render the neuronal networks less responsive toward lesion-induction by cTBS.
Background
Atrial fibrillation (AF) is present in 15–20% of patients with acute ischemic stroke. Oral anticoagulation reduces the risk of AF-related recurrent stroke but clinical guideline recommendations are rather vague regarding its use in the acute phase of stroke. We aimed to assess the current clinical practice of medical stroke prevention in AF patients during the acute phase of ischemic stroke.
Methods
In April 2017, a standardized anonymous questionnaire was sent to clinical leads of all 298 certified stroke units in Germany.
Results
Overall, 154 stroke unit leads participated (response rate 52%). Anticoagulation in the acute phase of stroke is considered feasible in more than 90% of AF patients with ischemic stroke. Clinicians assume that about two thirds of all AF patients (range 20–100%) are discharged on oral anticoagulation. According to local preferences, acetylsalicylic acid is given orally in the majority of patients with delayed initiation of oral anticoagulation. A non-vitamin K-dependent oral anticoagulant (NOAC) is more often prescribed than a vitamin K-dependent oral anticoagulant (VKA). VKA is more often chosen in patients with previous VKA intake than in VKA naive patients. In the minority of patients, stroke unit leads discuss the prescription of a specific oral anticoagulant with the treating general practitioner. Adherence to medical stroke prevention after hospital discharge is not assessed on a regular basis in any patient by the majority of participating stroke centers.
Conclusions
Early secondary stroke prevention in AF patients in German stroke units is based on OAC use but prescription modalities vary in clinical practice.
Background. Missed or delayed detection of progressive neuronal damage after traumatic brain injury (TBI) may have negative impact on the outcome. We investigated whether routine follow-up CT is beneficial in sedated and mechanically ventilated trauma patients. Methods. The study design is a retrospective chart review. A routine follow-up cCT was performed 6 hours after the admission scan. We defined 2 groups of patients, group I: patients with equal or recurrent pathologies and group II: patients with new findings or progression of known pathologies. Results. A progression of intracranial injury was found in 63 patients (42%) and 18 patients (12%) had new findings in cCT 2 (group II). In group II a change in therapy was found in 44 out of 81 patients (54%). 55 patients with progression or new findings on the second cCT had no clinical signs of neurological deterioration. Of those 24 patients (44%) had therapeutic consequences due to the results of the follow-up cCT. Conclusion. We found new diagnosis or progression of intracranial pathology in 54% of the patients. In 54% of patients with new findings and progression of pathology, therapy was changed due to the results of follow-up cCT. In trauma patients who are sedated and ventilated for different reasons a routine follow-up CT is beneficial.
Background
Serotonin (5-hydroxytryptamin, 5-HT) is an indolamine platelet agonist, biochemically derived from tryptophan. 5-HT is secreted from the enterochromaffin cells into the gastrointestinal tract and blood. Blood 5-HT has been proposed to regulate hemostasis by acting as a vasoconstrictor and by triggering platelet signaling through 5-HT receptor 2A (5HTR2A). Although platelets do not synthetize 5-HT, they take 5-HT up from the blood and store it in their dense granules which are secreted upon platelet activation.
Objective
To identify the molecular composite of the 5-HT uptake system in platelets and elucidate the role of platelet released 5-HT in thrombosis and ischemic stroke. Methods: 5-HT transporter knockout mice (5Htt\(^{-/-}\)) were analyzed in different in vitro and in vivo assays and in a model of ischemic stroke.
Results
In 5Htt\(^{-/-}\) platelets, 5-HT uptake from the blood was completely abolished and agonist-induced Ca2+ influx through store operated Ca\(^{2+}\) entry (SOCE), integrin activation, degranulation and aggregation responses to glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) were reduced. These observed in vitro defects in 5Htt\(^{-/-}\) platelets could be normalized by the addition of exogenous 5-HT. Moreover, reduced 5-HT levels in the plasma, an increased bleeding time and the formation of unstable thrombi were observed ex vivo under flow and in vivo in the abdominal aorta and carotid artery of 5Htt\(^{-/-}\) mice. Surprisingly, in the transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke 5Htt\(^{-/-}\) mice showed nearly normal infarct volume and the neurological outcome was comparable to control mice.
Conclusion
Although secreted platelet 5-HT does not appear to play a crucial role in the development of reperfusion injury after stroke, it is essential to amplify the second phase of platelet activation through SOCE and plays an important role in thrombus stabilization.
Spinal muscular atrophy (SMA) is a disabling disease that affects not only the patient’s health-related quality of life (HRQoL), but also causes a high caregiver burden (CGB). The aim of this study was to evaluate HRQoL, CGB, and their predictors in SMA. In two prospective, cross-sectional, and multi-center studies, SMA patients (n = 39) and SMA patient/caregiver couples (n = 49) filled in the EuroQoL Five Dimension Five Level Scale (EQ-5D-5L) and the Short Form Health Survey 36 (SF-36). Caregivers (CGs) additionally answered the Zarit Burden Interview (ZBI) and the Hospital Anxiety and Depression Scale (HADS). Patients were clustered into two groups with either low or high HRQoL (EQ-5D-5L index value <0.259 or >0.679). The latter group was mostly composed of ambulatory type III patients with higher motor/functional scores. More severely affected patients reported low physical functioning but good mental health and vitality. The CGB (mean ZBI = 22/88) correlated negatively with patients’ motor/functional scores and age. Higher CGB was associated with a lower HRQoL, higher depression and anxiety, and more health impairments of the CGs. We conclude that patient and CG well-being levels interact closely, which highlights the need to consider the health of both parties while evaluating novel treatments.
Comprehensive investigation in motor neuron disease is vital not to miss a treatable differential diagnosis. Neuroborreliosis should be considered during an ALS work‐up. However, false‐positive CSF results do occur, and thus, results should be interpreted carefully in context of all clinical test results.