Neurologische Klinik und Poliklinik
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- ischemic stroke (27)
- multiple sclerosis (22)
- Parkinson's disease (18)
- Parkinson’s disease (18)
- deep brain stimulation (18)
- neuroinflammation (18)
- Multiple Sklerose (17)
- stroke (17)
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- Schlaganfall (16)
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- Neurologische Klinik und Poliklinik (519)
- Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie) (26)
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- Neurochirurgische Klinik und Poliklinik (17)
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- Medizinische Klinik und Poliklinik I (16)
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- 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)
The present cumulative dissertation summarizes three clinical studies, which examine
subgroups of patients within the fibromyalgia syndrome (FMS). FMS entails chronic pain and
associated symptoms, and its pathophysiology is incompletely understood (1). Previous studies
show that there is a subgroup of patients with FMS with objective histological pathology of the
small nerve fibers of the peripheral nervous system (PNS). Another subgroup of FMS patients
does not show any signs of pathological changes of the small nerve fibers. The aim of this
dissertation was to compare FMS patients with healthy controls, and these two FMS subgroups
for differences in the central nervous system (CNS) in order to explore possible interactions
between PNS and the CNS. Regarding the CNS, differences of FMS patients with healthy
controls have already been found in studies with small sample sizes, but no subgroups have yet
been identified. Another aim of this thesis was to test whether the subgroups show a different
response to different classes of pain medication. The methods used in this thesis are structural
and functional magnetic resonance imaging (MRI), magnetic resonance diffusion imaging and
magnetic resonance spectroscopy. For the evaluation of clinical symptoms, we used
standardized questionnaires. The subgroups with and without pathologies of the PNS were
determined by skin biopsies of the right thigh and lower leg based on the intraepidermal nerve
fiber density (IENFD) of the small nerve fibers.
1) In the first MRI study, 43 female patients with the diagnosis of FMS and 40 healthy
control subjects, matched in age and body mass index, were examined with different MRI
sequences. Cortical thickness was investigated by structural T1 imaging, white matter integrity
by diffusion tensor imaging and functional connectivity within neuronal networks by functional
resting state MRI. Compared to the controls, FMS patients had a lower cortical volume in
bilateral frontotemporoparietal regions and the left insula, but a higher cortical volume in the
left pericalcarine cortex. Compared to the subgroup without PNS pathology, the subgroup with
PNS pathology had lower cortical volume in both pericalcarine cortices. Diffusion tensor
imaging revealed an increased fractional anisotropy (FA) of FMS patients in corticospinal
pathways such as the corona radiata, but also in regions of the limbic systems such as the fornix
and cingulum. Subgroup comparison again revealed lower mean FA values of the posterior
thalamic radiation and the posterior limb of the left internal capsule in the subgroup with PNS
pathology. In the functional connectivity analysis FMS patients, compared to controls, showed
a hypoconnectivity between the right median frontal gyrus and the posterior cerebellum and
the right crus cerebellum, respectively. In the subgroup comparisons, the subgroup with PNS
pathology showed a hyperconnectivity between both inferior frontal gyri, the right posterior
parietal cortex and the right angular gyrus. In summary, these results show that differences in
brain morphology and functional connectivity exist between FMS patients with and without
PNS pathology. These differences were not associated with symptom duration or severity and,
in some cases, have not yet been described in the context of FMS. The differences in brain
morphology and connectivity between subgroups could also lead to a differential response to
treatment with centrally acting drugs. Further imaging studies with FMS patients should take
into account this heterogeneity of FMS patient cohorts.
2) Following the results from the first MRI study, drug therapies of FMS patients and
their treatment response were compared between PNS subgroups. As there is no licensed drug
for FMS in Europe, the German S3 guideline recommends amitriptyline, duloxetine and
pregabalin for temporary use. In order to examine the current drug use in FMS patients in
Germany on a cross-sectional basis, 156 patients with FMS were systematically interviewed.
The drugs most frequently used to treat pain in FMS were non-steroidal anti-inflammatory
drugs (NSAIDs) (28.9%), metamizole (15.4%) and amitriptyline (8.8%). Pain relief assessed by
patients on a numerical rating scale from 0-10 averaged 2.2 points for NSAIDs, 2.0 for
metamizole and 1.5 for amitriptyline. Drugs that were discontinued for lack of efficacy and not
for side effects were acetaminophen (100%), flupirtine (91.7%), selective serotonin reuptake
inhibitors (81.8%), NSAIDs (83.7%) and weak opioids (74.1%). Patients were divided into
subgroups with and without PNS pathology as determined by skin biopsies. We found no
differences in drug use and effect between the subgroups. Taken together, these results show
that many FMS patients take medication that is not in accordance with the guidelines. The
reduction of symptoms was best achieved with metamizole and NSAIDs. Further longitudinal
studies on medication in FMS are necessary to obtain clearer treatment recommendations.
3) Derived from previous pharmacological and imaging studies (with smaller case
numbers), there is a hypothesis in the FMS literature that hyperreactivity of the insular cortex
may have an impact on FMS. The hyperreactivity seems to be due to an increased concentration
of the excitatory neurotransmitter glutamate in the insular cortex of FMS patients. The
hypothesis is supported by magnetic resonance spectroscopy studies with small number of
cases, as well as results from pharmacological studies with glutamate-inhibiting medication.
Studies from animal models have also shown that an artificially induced increase in glutamate
in the insular cortex can lead to reduced skin innervation. Therefore, the aim of this study was
to compare glutamate and GABA concentrations in the insular cortex of FMS patients with
those of healthy controls using magnetic resonance imaging. There was no significant
difference of both neurotransmitters between the groups. In addition, there was no correlation
between the neurotransmitter concentrations and the severity of clinical symptoms. There
were also no differences in neurotransmitter concentrations between the subgroups with and
without PNS pathology. In conclusion, our study could not show any evidence of a correlation
of glutamate and GABA concentrations with the symptoms of FMS or the pathogenesis of
subgroups with PNS pathologies.
CNS imaging characteristics in fibromyalgia patients with and without peripheral nerve involvement
(2022)
We tested the hypothesis that reduced skin innervation in fibromyalgia syndrome is associated with specific CNS changes. This prospective case–control study included 43 women diagnosed with fibromyalgia syndrome and 40 healthy controls. We further compared the fibromyalgia subgroups with reduced (n = 21) and normal (n = 22) skin innervation. Brains were analysed for cortical volume, for white matter integrity, and for functional connectivity. Compared to controls, cortical thickness was decreased in regions of the frontal, temporal and parietal cortex in the fibromyalgia group as a whole, and decreased in the bilateral pericalcarine cortices in the fibromyalgia subgroup with reduced skin innervation. Diffusion tensor imaging revealed a significant increase in fractional anisotropy in the corona radiata, the corpus callosum, cingulum and fornix in patients with fibromyalgia compared to healthy controls and decreased FA in parts of the internal capsule and thalamic radiation in the subgroup with reduced skin innervation. Using resting-state fMRI, the fibromyalgia group as a whole showed functional hypoconnectivity between the right midfrontal gyrus and the posterior cerebellum and the right crus cerebellum, respectively. The subgroup with reduced skin innervation showed hyperconnectivity between the inferior frontal gyrus, the angular gyrus and the posterior parietal gyrus. Our results suggest that the subgroup of fibromyalgia patients with pronounced pathology in the peripheral nervous system shows alterations in morphology, structural and functional connectivity also at the level of the encephalon. We propose considering these subgroups when conducting clinical trials.
Background:
Methylphenidate (MPH) is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). MPH binds to the dopamine (DA) transporter (DAT), which has high density in the striatum. Assessments of the striatal dopamine transporter by single positron emission computed tomography (SPECT) in childhood and adolescent patients are rare but can provide insight on how the effects of MPH affect DAT availability. The aim of our within-subject study was to investigate the effect of MPH on DAT availability and how responsivity to MPH in DAT availability is linked to clinical symptoms and cognitive functioning.
Methods
Thirteen adolescent male patients (9–16 years) with a diagnosis of ADHD according to the DSM-IV and long-term stimulant medication (for at least 6 months) with MPH were assessed twice within 7 days using SPECT after application of I-123-β-CIT to examine DAT binding potential (DAT BP). SPECT measures took place in an on- and off-MPH status balanced for order across participants. A virtual reality continuous performance test was performed at each time point. Further clinical symptoms were assessed for baseline off-MPH.
Results
On-MPH status was associated with a highly significant change (−29.9%) of striatal DAT BP as compared to off-MPH (t = −4.12, p = 0.002). A more pronounced change in striatal DAT BP was associated with higher off-MPH attentional and externalizing symptom ratings (Pearson r = 0.68, p = 0.01). Striatal DAT BP off-MPH, but not on-MPH, was associated with higher symptom ratings (Pearson r = 0.56, p = 0.04).
Conclusion
Our findings corroborate previous reports from mainly adult samples that MPH changes striatal DAT BP availability and suggest higher off-MPH DAT BP, likely reflecting low baseline DA levels, as a marker of symptom severity.
Die tiefe Hirnstimulation ist eine etablierte und hocheffiziente operative Behandlungsmethode für Patienten mit idiopathischem Parkinson- Syndrom (IPS). Als Zielgebiet dient in den meisten Fällen der Nucleus subthalamicus. Die Indikationen zur Implantation einer tiefen Hirnstimulation (THS) sind medikamentös nicht behandelbare motorische Fluktuationen und Dyskinesien oder ein medikamentös nicht kontrollierbarer Tremor.
Bislang erfolgt eine kontinuierliche Stimulation. Little et al. konnten jedoch bereits in ihrer 2013 veröffentlichen Studie zeigen, dass eine adaptive Stimulation, gemessen am UPDRS, um 27 % effektiver war und entsprechend die Stimulationszeit um 56 % gesenkt werden konnte.
Voraussetzung für die Anwendbarkeit einer adaptiven Stimulation im klinischen Alltag ist der Nachweis eines oder mehrerer Physiomarker, welche als Rückkopplungssignal für den Stimulationsbeginn dienen. Diese Marker müssen verlässlich mit dem Auftreten und der Ausprägung der Bewegungsstörungen korrelieren. Die Systeme müssen die Signale auslesen und entsprechend darauf reagieren können, damit ein sogenanntes Closed- loop- Verfahren entstehen kann. Bei diesen Markern handelt es sich um sogenannte lokale Feldpotenzialaktivitäten, das heißt niederfrequente Potentialänderungen von Zellen in subkortikalen Arealen des Gehirns, welche über Elektroden der THS abgeleitet werden können. Der Stimulator Activa PC+S (Medtronic) ermöglicht es erstmalig Aufzeichnungen von LFP- Daten, außerhalb eines experimentellen Laboraufbaus, mittels dauerhaft implantiertem Gerät vorzunehmen und damit auch Langzeitanalysen durchzuführen.
Erkenntnisse vergangener Studien ergaben, dass die synchronisierte, pathologisch gesteigerte oszillatorische Aktivität im Beta-Frequenzband (13- 35 Hz) eine bedeutende Rolle im Bezug auf die Pathophysiologie des IPS spielt und als krankheitsspezifische Aktivität gilt. Es konnte bereits belegt werden, dass die Verbesserung der motorischen Symptome (Bradykinese und Rigor) mit dem Ausmaß der Suppression der Betaband- Aktivität korreliert. Die Betabandaktivität als lokale Feldpotentialaktivität kann als Physiomarker einer adaptiven Stimulation dienen.
Unser Hauptaugenmerk galt daher der Analyse der Betabandaktivität oder anderer Frequenzbereiche während des Schlafes um hier die THS bedarfsgerecht einzusetzen. Hierfür wurden nächtliche subkortikale LFP- Aufzeichnungen parallel zur Schlaf- Polysomnographie durchgeführt. Zudem erfolgte in der vorliegenden Arbeit sowohl in unserem Vorversuch als auch in unserem Hauptversuch die Anwendung des UPDRS Teil III zur Erfassung der motorischen Symptome, sowie die Durchführung von Fragebögen zur Erfassung der nicht- motorischen Symptome, insbesondere des Schlafes vor und nach Implantation der tiefen Hirnstimulation.
Wir konnten belegen, dass es nach Implantation der THS zu einer Erhöhung der Schlafeffizienz und zu einer Erhöhung des Anteils der Schlafstadien II und III und damit einhergehend zu einer Steigerung der Schlafqualität kommt. Übereinstimmend mit anderen Studien konnten wir zeigen, dass sich die Motorik unter Stimulation deutlich verbessert. Im Vorversuch reduzierte sich der mittlere präoperative MDS- UPDRS III im MedsOFF verglichen mit dem mittleren postoperativ MDS- UPDRS III im MedsOFF/StimON um 37 %. In der PC+S- Studie imponierte eine Reduktion um 67%. Zudem zeigte sich eine Reduktion der nicht- motorischen Symptome durch die THS, insbesondere in der Kategorie Schlaf. Die Ergebnisse der vorliegenden Arbeit ergaben außerdem, dass die Betabandaktivität im Schlafstadium II und vor allem im Schlafstadium III am geringsten ist. Im Schlafstadium I und REM ist die Betabandaktivität höher als im Schlafstadium II und III. Hierbei war entscheidend, dass die Patienten eine klar abgrenzbare Betabandaktivität im Wachstadium aufwiesen und die Elektrodenkontakte im dorsolateralen Kerngebiet des STN lokalisiert waren.
Gegenläufig dazu verhält sich die Deltaaktivität. Sie ist im Schlafstadium II und besonders im Stadium III am höchsten. Stadium I ist mit durchschnittlich um 7,3 % niedriger als im Wachstadium. Am geringsten ist sie jedoch im REM-Schlafstadium.
Indem wir mit der Betabandaktivität und Deltaaktivität in den einzelnen Schlafstadien einen stabilen und reproduzierbaren Physiomarker finden konnten, sind wir unserem Ziel der adaptiven THS ein Stück näher gekommen.
Background
Regulatory CD4\(^+\)CD25\(^+\)FoxP3\(^+\) T cells (Treg) are a subgroup of T lymphocytes involved in maintaining immune balance. Disturbance of Treg number and impaired suppressive function of Treg correlate with Parkinson’s disease severity. Superagonistic anti-CD28 monoclonal antibodies (CD28SA) activate Treg and cause their expansion to create an anti-inflammatory environment.
Methods
Using the AAV1/2-A53T-α-synuclein Parkinson’s disease mouse model that overexpresses the pathogenic human A53T-α-synuclein (hαSyn) variant in dopaminergic neurons of the substantia nigra, we assessed the neuroprotective and disease-modifying efficacy of a single intraperitoneal dose of CD28SA given at an early disease stage.
Results
CD28SA led to Treg expansion 3 days after delivery in hαSyn Parkinson’s disease mice. At this timepoint, an early pro-inflammation was observed in vehicle-treated hαSyn Parkinson’s disease mice with elevated percentages of CD8\(^+\)CD69\(^+\) T cells in brain and increased levels of interleukin-2 (IL-2) in the cervical lymph nodes and spleen. These immune responses were suppressed in CD28SA-treated hαSyn Parkinson’s disease mice. Early treatment with CD28SA attenuated dopaminergic neurodegeneration in the SN of hαSyn Parkinson’s disease mice accompanied with reduced brain numbers of activated CD4\(^+\), CD8\(^+\) T cells and CD11b\(^+\) microglia observed at the late disease-stage 10 weeks after AAV injection. In contrast, a later treatment 4 weeks after AAV delivery failed to reduce dopaminergic neurodegeneration.
Conclusions
Our data indicate that immune modulation by Treg expansion at a timepoint of overt inflammation is effective for treatment of hαSyn Parkinson’s disease mice and suggest that the concept of early immune therapy could pose a disease-modifying option for Parkinson’s disease patients.
Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis.
(2017)
Background:
MP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS).
Methods:
MP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P\(_{1}\) receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro.
Results:
FTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220\(^{+}\) B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs.
Conclusions:
The data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE.
Hintergrund und Ziel
Telemedizinische Schlaganfall-Netzwerke tragen dazu bei, die Schlaganfallversorgung und insbesondere den Zugang zu zeitkritischen Schlaganfalltherapien in vorrangig strukturschwachen, ländlichen Regionen zu gewährleisten. Ziel ist eine Darstellung der Nutzungsfrequenz und regionalen Verteilung dieser Versorgungsstruktur.
Methoden
Die Kommission „Telemedizinische Schlaganfallversorgung“ der Deutschen Schlaganfall-Gesellschaft führte eine Umfragestudie in allen Schlaganfall-Netzwerken durch.
Ergebnisse
In Deutschland sind 22 telemedizinische Schlaganfall-Netzwerke aktiv, welche insgesamt 43 Zentren (pro Netzwerk: Median 1,5, Interquartilsabstand [IQA] 1–3) sowie 225 Kooperationskliniken (pro Netzwerk: Median 9, IQA 4–17) umfassen und an einem unmittelbaren Zugang zur Schlaganfallversorgung für 48 Mio. Menschen teilhaben. Im Jahr 2018 wurden 38.211 Telekonsile (pro Netzwerk: Median 1340, IQA 319–2758) durchgeführt. Die Thrombolyserate betrug 14,1 % (95 %-Konfidenzintervall 13,6–14,7 %), eine Verlegung zur Thrombektomie wurde bei 7,9 % (95 %-Konfidenzintervall 7,5–8,4 %) der ischämischen Schlaganfallpatienten initiiert. Das Finanzierungssystem ist uneinheitlich mit einem Vergütungssystem für die Zentrumsleistungen in nur drei Bundesländern.
Diskussion
Etwa jeder 10. Schlaganfallpatient wird telemedizinisch behandelt. Die telemedizinischen Schlaganfall-Netzwerke erreichen vergleichbar hohe Lyseraten und Verlegungen zur Thrombektomie wie neurologische Stroke-Units und tragen zur Sicherstellung einer flächendeckenden Schlaganfallversorgung bei. Eine netzwerkübergreifende Sicherstellung der Finanzierung und einheitliche Erhebung von Qualitätssicherungsdaten haben das Potenzial diese Versorgungsstruktur zukünftig weiter zu stärken.
Treatment-induced neuropathy in diabetes (TIND) — Developing a disease model in type 1 diabetic rats
(2021)
Treatment-induced neuropathy in diabetes (TIND) is defined by the occurrence of an acute neuropathy within 8 weeks of an abrupt decrease in glycated hemoglobin-A1c (HbA1c). The underlying pathogenic mechanisms are still incompletely understood with only one mouse model being explored to date. The aim of this study was to further explore the hypothesis that an abrupt insulin-induced fall in HbA1c may be the prime causal factor of developing TIND. BB/OKL (bio breeding/OKL, Ottawa Karlsburg Leipzig) diabetic rats were randomized in three groups, receiving insulin treatment by implanted subcutaneous osmotic insulin pumps for 3 months, as follows: Group one received 2 units per day; group two 1 unit per day: and group three 1 unit per day in the first month, followed by 2 units per day in the last two months. We serially examined blood glucose and HbA1c levels, motor- and sensory/mixed afferent conduction velocities (mNCV and csNCV) and peripheral nerve morphology, including intraepidermal nerve fiber density and numbers of Iba-1 (ionized calcium binding adaptor molecule 1) positive macrophages in the sciatic nerve. Only in BB/OKL rats of group three, with a rapid decrease in HbA1c of more than 2%, did we find a significant decrease in mNCV in sciatic nerves (81% of initial values) after three months of treatment as compared to those group three rats with a less marked decrease in HbA1c <2% (mNCV 106% of initial values, p ≤ 0.01). A similar trend was observed for sensory/mixed afferent nerve conduction velocities: csNCV were reduced in BB/OKL rats with a rapid decrease in HbA1c >2% (csNCV 90% of initial values), compared to those rats with a mild decrease <2% (csNCV 112% of initial values, p ≤ 0.01). Moreover, BB/OKL rats of group three with a decrease in HbA1c >2% showed significantly greater infiltration of macrophages by about 50% (p ≤ 0.01) and a decreased amount of calcitonin gene related peptide (CGRP) positive nerve fibers as compared to the animals with a milder decrease in HbA1c. We conclude that a mild acute neuropathy with inflammatory components was induced in BB/OKL rats as a consequence of an abrupt decrease in HbA1c caused by high-dose insulin treatment. This experimentally induced neuropathy shares some features with TIND in humans and may be further explored in studies into the pathogenesis and treatment of TIND.
Inflammatory mechanisms in the pathophysiology of diabetic peripheral neuropathy (DN) — new aspects
(2021)
The pathogenesis of diabetic neuropathy is complex, and various pathogenic pathways have been proposed. A better understanding of the pathophysiology is warranted for developing novel therapeutic strategies. Here, we summarize recent evidence from experiments using animal models of type 1 and type 2 diabetes showing that low-grade intraneural inflammation is a facet of diabetic neuropathy. Our experimental data suggest that these mild inflammatory processes are a likely common terminal pathway in diabetic neuropathy associated with the degeneration of intraepidermal nerve fibers. In contrast to earlier reports claiming toxic effects of high-iron content, we found the opposite, i.e., nutritional iron deficiency caused low-grade inflammation and fiber degeneration while in normal or high non-heme iron nutrition no or only extremely mild inflammatory signs were identified in nerve tissue. Obesity and dyslipidemia also appear to trigger mild inflammation of peripheral nerves, associated with neuropathy even in the absence of overt diabetes mellitus. Our finding may be the experimental analog of recent observations identifying systemic proinflammatory activity in human sensorimotor diabetic neuropathy. In a rat model of type 1 diabetes, a mild neuropathy with inflammatory components could be induced by insulin treatment causing an abrupt reduction in HbA1c. This is in line with observations in patients with severe diabetes developing a small fiber neuropathy upon treatment-induced rapid HbA1c reduction. If the inflammatory pathogenesis could be further substantiated by data from human tissues and intervention studies, anti-inflammatory compounds with different modes of action may become candidates for the treatment or prevention of diabetic neuropathy.
Prädiktion des Verschlusses großer intrakranieller Arterien anhand präklinischer Schlaganfallscores
(2021)
2015 konnte in mehreren Studien ESCAPE, EXTENDED IA, MR CLEAN, REVASCAT, SWIFT-PRIME eine signifikante Überlegenheit der mechanischen Thrombektomie verglichen mit der alleinigen i. v. Lysetherapie mit rtPA bezogen auf Revaskularisierung bei Patienten mit einer LVO (large vessel occlusion) nachgewiesen werden. Diese neue Therapiemöglichkeit erforderte eine Aufteilung der Patienten die von einer Thrombektomie profitieren (LVO) und der Patienten, die keiner Thrombektomie zugeführt werden können (nLVO). Die zentrale Fragestellung der Studie ist: Kann ein symptomorientierter Schlaganfallscore die Wahrscheinlichkeit eines großen intrakraniellen Gefäßverschlusses mit hinreichender Präzision vorhersagen und kann auf Basis dieser Vorhersage ein Patient direkt in ein übergeordnetes Schlagfanfallzentrum gebracht werden, obwohl sich dadurch eine Bridging Lysetherapie verzögern würde?
Um diesen Fragen auf den Grund zu gehen führten wir eine monozentrische Querschnittstudie durch, in deren Rahmen 215 Patienten rekrutiert wurden. Die Rekrutierung erfolgte mittels eines aus Subitems bereits etablierter Schlafanfallscores (FAST, CPSS, LAPSS, 3ISS, RACE), zusammengesetzten Fragebogens. Die ausgefüllten Fragebögen wurde in Excel digitalisiert und mittels SPSS, Signifikanz und Odds Ratio berechnet. Anschließend wurde aus den signifikanten Subitems mit der höchsten Odds Ratio ein neuer einfach anzuwendender Schlaganfallscore, bestehend aus den präklinisch erhobenen Daten gebildet (Würzburg Score of Large Vessel Occlusions, WOLVE- Score). Weiter wurden Signifikanz, Odds Ratio, Sensitivität und Spezifität des WOLVE-Score mit denen der oben genannten etablieren Scores verglichen.