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  • 1
    In: European Journal of Cancer, Elsevier BV, Vol. 130 ( 2020-05), p. 102-113
    Materialart: Online-Ressource
    ISSN: 0959-8049
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2020
    ZDB Id: 1120460-6
    ZDB Id: 1468190-0
    ZDB Id: 82061-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: European Journal of Nuclear Medicine and Molecular Imaging, Springer Science and Business Media LLC, Vol. 50, No. 2 ( 2023-01), p. 423-434
    Kurzfassung: Early after [ 18 F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [ 18 F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease controls and healthy controls. Here, we investigated whether early-phase [ 18 F]PI-2620 PET has an additive value for biomarker based evaluation of 4RTs. Methods Seventy-eight patients with 4RTs (71 ± 7 years, 39 female), 79 patients with other neurodegenerative diseases (67 ± 12 years, 35 female) and twelve age-matched controls (69 ± 8 years, 8 female) underwent dynamic (0–60 min) [ 18 F]PI-2620 PET imaging. Regional perfusion (0.5–2.5 min p.i.) and tau load (20–40 min p.i.) were measured in 246 predefined brain regions [standardized-uptake-value ratios (SUVr), cerebellar reference] . Regional SUVr were compared between 4RTs and controls by an ANOVA including false-discovery-rate (FDR, p   〈  0.01) correction. Hypoperfusion in resulting 4RT target regions was evaluated at the patient level in all patients (mean value − 2SD threshold). Additionally, perfusion and tau pattern expression levels were explored regarding their potential discriminatory value of 4RTs against other neurodegenerative disorders, including validation in an independent external dataset ( n  = 37), and correlated with clinical severity in 4RTs (PSP rating scale, MoCA, activities of daily living). Results Patients with 4RTs had significant hypoperfusion in 21/246 brain regions, most dominant in thalamus, caudate nucleus, and anterior cingulate cortex, fitting to the topology of the 4RT disease spectrum. However, single region hypoperfusion was not specific regarding the discrimination of patients with 4RTs against patients with other neurodegenerative diseases. In contrast, perfusion pattern expression showed promise for discrimination of patients with 4RTs from other neurodegenerative diseases (AUC: 0.850). Discrimination by the combined perfusion-tau pattern expression (AUC: 0.903) exceeded that of the sole tau pattern expression (AUC: 0.864) and the discriminatory power of the combined perfusion-tau pattern expression was replicated in the external dataset (AUC: 0.917). Perfusion but not tau pattern expression was associated with PSP rating scale ( R  = 0.402; p  = 0.0012) and activities of daily living ( R  =  − 0.431; p  = 0.0005). Conclusion [ 18 F]PI-2620 perfusion imaging mirrors known topology of regional hypoperfusion in 4RTs. Single region hypoperfusion is not specific for 4RTs, but perfusion pattern expression may provide an additive value for the discrimination of 4RTs from other neurodegenerative diseases and correlates closer with clinical severity than tau pattern expression.
    Materialart: Online-Ressource
    ISSN: 1619-7070 , 1619-7089
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 2098375-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S6 ( 2022-12)
    Kurzfassung: 4‐repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R‐tauopathies are progressive‐supranuclear‐palsy (PSP) and corticobasal‐syndrome (CBS) characterized by tau accumulation in subcortical nuclei as well as cortical neuronal dysfunction, as shown by PET‐assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces diaschisis‐like neuronal dysfunction in functionally connected cortical regions. Method We included 47 patients with clinically diagnosed PSP or CBS who underwent structural MRI and 18 F‐PI‐2620 tau‐PET. PI‐2620 PET was recorded using a dynamic one‐shot, two‐stop acquisition protocol, to determine an early 0.5‐2.5min post‐tracer‐injection perfusion window for assessing cortical neuroinjury in 200 cortical ROIs of the Schaefer atlas, as well as a 20‐40min post‐tracer‐injection window to determine 4R‐tau load in 32 subcortical ROIs of the TIAN atlas. We determined tau epicenters as 10% of subcortical ROIs with highest tau‐PET, and assessed the connectivity of tau epicenters to cortical ROIs using an age‐matched 3T resting‐state fMRI template derived from 69 healthy elderly. Using linear regression, we assessed whether i) higher subcortical tau‐PET was associated with overall reduced cortical perfusion and ii) whether cortical hypoperfusion was observed preferentially in regions closely connected to subcortical tau epicenters. Result As hypothesized, higher subcortical tau‐PET was associated with lower cortical perfusion (R=‐0,37, p‐value: 〈 0,011, Fig.1). Using group‐average tau‐PET and perfusion‐PET, we found that the seed‐based connectivity pattern of subcortical tau epicenters predicted cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicenter showed stronger hypoperfusion (R=‐0,16, p‐value: 〈 0,023, Fig.2A). This association was also observed on the subject level, as indicated by overall negative b‐values of the association between tau epicenter connectivity and cortical perfusion (one‐sample t‐test: t‐value: ‐3,45, p‐value: 〈 0,001, Fig.3). Conclusion In 4R‐tauopathies subcortical tau‐accumulation is associated with remote neuronal dysfunction in functionally connected cortical regions. This suggests that subcortical tau pathology may induce diaschisis‐like cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity.
    Materialart: Online-Ressource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2022
    ZDB Id: 2201940-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 2 ( 2023-02-13), p. 600-611
    Kurzfassung: Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease cohort with special focus on clinical, serological and genetic predictors of the immunotherapy response and long-term outcome. Patients were recruited from the GENERATE (German Network for Research on Autoimmune Encephalitis) registry. Along with clinical parameters, anti-IgLON5 immunoglobulin (Ig)G in serum and CSF, anti-IgLON5 IgG1-4, IgA and IgM in serum, neurofilament light chain and glial fibrillary acidic protein in serum as well as human leukocyte antigen-genotypes were determined. We identified 53 patients (symptom onset 63.8 ± 10.3 years, female:male 1:1.5). The most frequent initial clinical presentations were bulbar syndrome, hyperkinetic syndrome or isolated sleep disorder [at least one symptom present in 38% (20/53)]. At the time of diagnosis, the majority of patients had a generalized multi-systemic phenotype; nevertheless, 21% (11/53) still had an isolated brainstem syndrome and/ or a characteristic sleep disorder only. About one third of patients [28% (15/53)] reported subacute disease onset and 51% (27/53) relapse-like exacerbations during the disease course. Inflammatory CSF changes were evident in 37% (19/51) and increased blood-CSF-barrier permeability in 46% (21/46). CSF cell count significantly decreased, while serum anti-IgLON5 IgG titre increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 [55% (24/44)] was associated with higher serum anti-IgLON5 IgG titres. Neurofilament light chain and glial fibrillary acidic protein in serum were substantially increased (71.1 ± 103.9 pg/ml and 126.7 ± 73.3 pg/ml, respectively). First-line immunotherapy of relapse-like acute-to-subacute exacerbation episodes resulted in improvement in 41% (11/27) of patients and early initiation within the first 6 weeks was a predictor for therapy response. Sixty-eight per cent (36/53) of patients were treated with long-term immunotherapy and 75% (27/36) of these experienced no further disease progression (observation period of 20.2 ± 15.4 months). Long-term immunotherapy initiation during the first year after onset and low pre-treatment neurofilament light chain were significant predictors for a better outcome. In conclusion, subacute disease onset and early inflammatory CSF changes support the primary role of autoimmune mechanisms at least at initial stages of anti-IgLON5 disease. Early immunotherapy, prior to advanced neurodegeneration, is associated with a better long-term clinical outcome. Low serum neurofilament light chain at treatment initiation may serve as a potential biomarker of the immunotherapy response.
    Materialart: Online-Ressource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2023
    ZDB Id: 1474117-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S1 ( 2022-12)
    Kurzfassung: 4‐repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R‐tauopathies are progressive‐supranuclear‐palsy (PSP) and corticobasal‐syndrome (CBS) characterized by tau accumulation in subcortical nuclei as well as cortical neuronal dysfunction, as shown by PET‐assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces diaschisis‐like neuronal dysfunction in functionally connected cortical regions. Method We included 47 patients with clinically diagnosed PSP or CBS who underwent structural MRI and 18 F‐PI‐2620 tau‐PET. PI‐2620 PET was recorded using a dynamic one‐shot, two‐stop acquisition protocol, to determine an early 0.5‐2.5min post‐tracer‐injection perfusion window for assessing cortical neuroinjury in 200 cortical ROIs of the Schaefer atlas, as well as a 20‐40min post‐tracer‐injection window to determine 4R‐tau load in 32 subcortical ROIs of the TIAN atlas. We determined tau epicenters as 10% of subcortical ROIs with highest tau‐PET, and assessed the connectivity of tau epicenters to cortical ROIs using an age‐matched 3T resting‐state fMRI template derived from 69 healthy elderly. Using linear regression, we assessed whether i) higher subcortical tau‐PET was associated with overall reduced cortical perfusion and ii) whether cortical hypoperfusion was observed preferentially in regions closely connected to subcortical tau epicenters. Result As hypothesized, higher subcortical tau‐PET was associated with lower cortical perfusion (R=‐0,37, p‐value: 〈 0,011, Fig.1). Using group‐average tau‐PET and perfusion‐PET, we found that the seed‐based connectivity pattern of subcortical tau epicenters predicted cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicenter showed stronger hypoperfusion (R=‐0,16, p‐value: 〈 0,023, Fig.2A). This association was also observed on the subject level, as indicated by overall negative b‐values of the association between tau epicenter connectivity and cortical perfusion (one‐sample t‐test: t‐value: ‐3,45, p‐value: 〈 0,001, Fig.3). Conclusion In 4R‐tauopathies subcortical tau‐accumulation is associated with remote neuronal dysfunction in functionally connected cortical regions. This suggests that subcortical tau pathology may induce diaschisis‐like cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity.
    Materialart: Online-Ressource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2022
    ZDB Id: 2201940-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-01-29)
    Kurzfassung: The differential impact of complete and incomplete bilateral vestibulopathy (BVP) on spatial orientation, visual exploration, and navigation-induced brain network activations is still under debate. In this study, 14 BVP patients (6 complete, 8 incomplete) and 14 age-matched healthy controls performed a navigation task requiring them to retrace familiar routes and recombine novel routes to find five items in real space. [ 18 F]-fluorodeoxyglucose-PET was used to determine navigation-induced brain activations. Participants wore a gaze-controlled, head-fixed camera that recorded their visual exploration behaviour. Patients performed worse, when recombining novel routes (p  〈  0.001), whereas retracing of familiar routes was normal (p = 0.82). These deficits correlated with the severity of BVP. Patients exhibited higher gait fluctuations, spent less time at crossroads, and used a possible shortcut less often (p  〈  0.05). The right hippocampus and entorhinal cortex were less active and the bilateral parahippocampal place area more active during navigation in patients. Complete BVP showed reduced activations in the pontine brainstem, anterior thalamus, posterior insular, and retrosplenial cortex compared to incomplete BVP. The navigation-induced brain activation pattern in BVP is compatible with deficits in creating a mental representation of a novel environment. Residual vestibular function allows recruitment of brain areas involved in head direction signalling to support navigation.
    Materialart: Online-Ressource
    ISSN: 2045-2322
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2021
    ZDB Id: 2615211-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 268, No. 1 ( 2021-01), p. 367-376
    Kurzfassung: To evaluate the diagnostic accuracy and safety of extended stereotactic brain biopsy (ESBB) in a single center cohort with suspected primary angiitis of the central nervous system (PACNS). Methods A standardized stereotactic biopsy targeting MRI-positive lesions and collecting samples from the meninges and the cortex as well as from the white matter was performed in 23 patients with clinically suspected PACNS between 2010 and 2017. The relationship between biopsy yield and clinical characteristics, cerebrospinal fluid parameters, MR-imaging, time point of biopsy and exact localization of biopsy as well as number of tissue samples were examined. Results PACNS was confirmed in 7 of 23 patients (30.4%). Alternative diagnoses were identified in 7 patients (30%). A shorter time period between the onset or worsening of symptoms ( p  = 0.018) and ESBB significantly increased the diagnostic yield. We observed only minor and transient postoperative complications in 3 patients (13.0%). ESBB led to a direct change of the therapeutic regime in 13 of 23 patients (56.5%). Careful neuropathological analysis furthermore revealed that cortical samples were crucial in obtaining a diagnosis. Conclusion ESBB is a safe approach with good feasibility, even in critically ill patients, and high diagnostic accuracy in patients with suspected PACNS changing future therapies in 13 of 23 patients (56.5%). Early biopsy after symptom onset/worsening is crucial and (sub)acute MRI-lesions should be targeted with a particular need for biopsy samples from the cortical layer.
    Materialart: Online-Ressource
    ISSN: 0340-5354 , 1432-1459
    RVK:
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2021
    ZDB Id: 1421299-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    Springer Science and Business Media LLC ; 2022
    In:  Journal of Neurology Vol. 269, No. 2 ( 2022-02), p. 982-996
    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 269, No. 2 ( 2022-02), p. 982-996
    Kurzfassung: To approach the clinical value of MRI with vessel wall imaging (VWI) in patients with central nervous system vasculitis (CNSV), we analyzed patterns of VWI findings both at the time of initial presentation and during follow-up. Methods Stenoocclusive lesions, vessel-wall contrast enhancement (VW-CE) and diffusion-restricted lesions were analyzed in patients with a diagnosis of CNSV. On available VWI follow-up, progression, regression or stability of VW-CE were evaluated and correlated with the clinical status. Results Of the 45 patients included, 28 exhibited stenoses visible on MR angiography (MRA-positive) while 17 had no stenosis (MRA-negative). VW-CE was found in 2/17 MRA-negative and all MRA-positive patients ( p   〈  0.05). 79.1% (53/67) of stenoses showed VW-CE. VW-CE was concentric in 88.3% and eccentric in 11.7% of cases. Diffusion-restricted lesions were found more frequently in relation to stenoses with VW-CE than without VW-CE ( p   〈  0.05). 48 VW-CE lesions in 23 patients were followed over a median time of 239.5 days. 13 VW-CE lesions (27.1%) resolved completely, 14 (29.2%) showed partial regression, 17 (35.4%) remained stable and 4 (8.3%) progressed. 22/23 patients received immunosuppressive therapy for the duration of follow-up. Patients with stable or progressive VW-CE were more likely ( p   〈  0.05) to have a relapse (14/30 cases) than patients with partial or complete regression of VW-CE (5/25 cases). Conclusion Concentric VW-CE is a common finding in medium/large-sized vessel CNSV. VW-CE might represent active inflammation in certain situations. However, follow-up VWI findings proved ambiguous as persisting VW-CE despite immunosuppressive therapy and clinical remission was a frequent finding.
    Materialart: Online-Ressource
    ISSN: 0340-5354 , 1432-1459
    RVK:
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2022
    ZDB Id: 1421299-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
    Online-Ressource
    Wiley ; 2020
    In:  Psychophysiology Vol. 57, No. 11 ( 2020-11)
    In: Psychophysiology, Wiley, Vol. 57, No. 11 ( 2020-11)
    Kurzfassung: The current study demonstrates top‐down contingent capture with color matching versus color non‐matching abrupt‐onset cues. In three experiments, we show that only abrupt‐onset cues with the same color as the target capture attention. Our results are based on participants' reaction times and their event‐related potentials. Our study closes an important gap in the literature and addresses the speculations about potential bottom‐up capture by abrupt onsets hidden in the cue‐target interval.
    Materialart: Online-Ressource
    ISSN: 0048-5772 , 1469-8986
    URL: Issue
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2020
    ZDB Id: 1484299-3
    SSG: 5,2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Journal of Stroke and Cerebrovascular Diseases, Elsevier BV, Vol. 32, No. 8 ( 2023-08), p. 107187-
    Materialart: Online-Ressource
    ISSN: 1052-3057
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2023
    ZDB Id: 2052957-0
    Standort Signatur Einschränkungen Verfügbarkeit
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