Einleitung Die aneurysmale Subarachnoidalblutung und ihre Komplikationen stellen eine akut lebensbedrohliche Erkrankung dar. Aufgrund einer hohen Letalität und Morbidität sowie zahlreichen, nicht modifizierbaren Risikofaktoren und fehlenden eindeutigen Präventionsmaßnahmen bleibt diese Krankheit eines der aktuellen Themen der Neurochirurgie. Ziel Ziel dieser Studie ist der Vergleich der Behandlungsergebnisse von Patienten mit aneurysmaler SAB im Klinikum Chemnitz mit aktuellen Literaturdaten. Material und Methode In dieser Arbeit wurden die Daten von insgesamt 200 Patienten mit aneurysmaler Subarachnoidalblutung retrospektiv zusammengefasst. Es wurde eine Populationsanalyse zusammen mit einer Analyse der Korrelationen zwischen verschiedenen Ausgangs- und Verlaufsparametern mit dem allgemeinen Outcome und der Mortalität durchgeführt. Zusätzlich erfolgte eine Follow-up-Analyse der Mortalität und Morbidität bei 108 Patienten. Im statistischen Modell wurden eine Uni- und Bivariatanalyse sowie binäre und multinomiale logistische Regression angewendet. Kaplan-Meier-Kurven in Verbindung mit Cox-Regressionsanalysen wurden zur Beurteilung der Mortalität eingesetzt. Die Ergebnisse wurden mit Literaturdaten verglichen. Das Votum der Ethikkommission der TU Dresden liegt vor (EK 181052014 vom 15.09.2014). Ergebnisse Von 200 Patienten mit einem Durchschnittsalter von 52 J (20-82 J, Medianalter 51 ± 13,6 J) waren 69 Patienten männlich (34,5 %), 131 – weiblich (65,2 %). Das männlich : weiblich Verhältnis betrug 1:1,9. Der klinische Schweregrad der Patienten bei Aufnahme wurde durch die WFNS- und die HH-Skalen evaluiert. Zusätzlich wurden die BNI- und Fisher-Skalen zwecks Evaluation des radiologischen Schweregrades der aSAB eingesetzt. Die Patientendistribution anhand der WFNS-Skala war: WFNS °I – 42,0 %, WFNS °II – 10,0 %, WFNS °II – 16,5 %, WFNS °IV – 22,5%, WFNS °V – 9,0 %. Die Verteilung der Patienten durch die HH-Skala war vergleichbar. 14,5 % der Patienten hatten eine BNI 1, 41,5 % - BNI 2, 32,0 % – BNI 3, 10,5 % - BNI 4, 1,5 % - BNI 5 Blutung. Bei 5,5 % der Patienten lag eine Fisher 1, 10,5 %– Fisher 2, 28,0% - Fisher 3 und 56,0 % - Fisher 4 SAB vor. 77,5 % der Aneurysmata waren klein (<11mm), 18,5 % - groß (11-25mm), 4 % - Giant (>25mm). Die Aneurysmen war meist im Bereich der Acom (41,5 %) und MCA (36,5 %) lokalisiert. Insgesamt 94,5 % der Aneurysmen gehörten zur vorderen Zirkulation. Die primäre Mortalitätsrate betrug 14,5 %. 21,5% der Patienten hatten einen mRS von 0-1 bei Entlassung, 26,0 % - einen mRS 2-3, 38,0 % - einen mRS 4-5. Die mittlere Follow-up-Dauer betrug 71,3 ± 43,2 Monate (Spannweite 2-168 Monate). Von den initial Überlebenden und im Follow-up eingeschlossenen Patienten sind 10,2 % im Verlauf verstorben. 48,1 % hatten einen mRS 0-1, 30,6% mRS 2-3, 11,1 % - mRS 4-5. Diskussion Das Outcome der Patienten mit einer aSAB trägt einen multifaktoriellen Charakter. Die wesentlichen Prädiktoren des Outcomes sind das Alter, der klinische und radiologische Schweregrad der Blutung, die Notwendigkeit der Versorgung eines posthämorrhagischen Hydrozephalus (temporäre und dauerhafte CSF-Ableitung), ein Vasospasmus, DIND und Entgleisun-gen im Serum-Natrium-Spiegel. Die Mortalitätsrate bei der primären Versorgung der Patienten mit einer aSAB in unserer Ko-horte ist um etwa 5 % niedriger als in der Literatur angegeben. Die Mortalitätsrate steigert sich allmählich während der ersten 3 Wochen. Sie wird im Wesentlichen vom Patientengeschlecht, dem klinischen und radiologischen Schweregrad der Blutung, der Notwendigkeit einer Akutversorgung eines aufgetretenen Hydrozephalus, einem Vasospasmus, Entgleisungen im Serum-Natrium-Spiegel sowie der Notwendigkeit einer CSF-Dauerableitung beeinflusst. Die Notwendigkeit einer CSF-Außenableitung bei Aufnahme korreliert mit einem schlechten Zustand der Patienten bei Entlassung und im Follow-up. Der Vasospasmus ist ein unabhängiger Prädiktor eines primär schlechten Outcomes und einer hohen Mortalität, zeigt sich aber als nicht signifikanter Faktor im Langzeit-Follow-up. Die Shuntpflicht ist bei Patienten mit Elektrolytentgleisungen, beidseitigen EVDs und DIND 3-4fach erhöht, beeinflusst jedoch nur die primäre Morbidität/Mortalität. Entgleisungen im Serum-Natrium-Spiegel zeigten sich als unabhängiger Prädiktor eines schlechten Outcomes und erhöhter Mortalität sowohl während des stationären Aufenthaltes, als auch im Langzeit-Follow-up. Die Notwendigkeit einer dekompressiven Kraniektomie wiederspiegelt sich in einem niedrigen BI der Patienten im primären Outcome und ist Prädiktor eines schlechten Outcomes und erhöhter Mortalität im Langzeit-Follow-up.

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Background: Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) has been extensively investigated, but the impact of collateralization remains unclear. We investigated the predictive value of collateral activation for delayed cerebral ischemia (DCI)-related infarctions and functional outcome. Methods: Data from 43 patients with CVS (January 2014 to August 2021) were evaluated for the angiographic presence of leptomeningeal and ophthalmic collaterals (anterior falcine artery (AFA), supratrochlear artery (STA), dorsal nasal artery (DNA)) on internal carotid artery angiograms. Vasospasm-related infarction and the modified Rankin Scale (mRS) score after six months were chosen as the endpoints. Results: 77% of the patients suffered from DCI-related infarctions. In 233 angiograms (at hospitalization, before spasmolysis, after six months), positive vessel signs were observed in 31 patients for STA, 35 for DNA, and 31 for AFA. The STA sign had the highest positive (84.6%) and negative (85.7%) predictive value for unfavorable outcome (mRS 4–6) in patients aged 50 years. DNA and AFA signs were not meaningful predictors for either endpoint. Leptomeningeal collaterals showed a positive Pearson’s correlation with the STA sign in 87.5% (p = 0.038) without providing any prediction for either endpoint. Conclusions: The STA sign is associated with clinical outcome in patients with CVS after SAH aged 50 years, and was correlated with the occurrence of leptomeningeal collaterals.

Background: Cerebral vasospasm (CVS) continues to account for high morbidity and mortality in patients surviving the initial aneurysmal subarachnoid hemorrhage (SAH). Nimodipine is the only drug known to reduce delayed cerebral ischemia (DCI), but it is believed not to affect large vessel CVS. Milrinone has emerged as a promising option. Our retrospective study focused on the effectiveness of the intra-arterial application of both drugs in monotherapy and combined therapy. Methods: We searched for patients with aneurysmal SAH, angiographically confirmed CVS, and at least one intra-arterial pharmacological angioplasty. Ten defined vessel sections on angiograms were assessed before and after vasodilator infusion. The improvement in vessel diameters was compared to the frequency of DCI-related cerebral infarction before hospital discharge and functional outcome reported as the modified Rankin Scale (mRS) score after 6 months. Results: Between 2014 and 2021, 132 intra-arterial interventions (144 vascular territories, 12 bilaterally) in 30 patients were analyzed for this study. The vasodilating effect of nimodipine was superior to milrinone in all intradural segments. There was no significant intergroup difference concerning outcome in mRS (p = 0.217). Only nimodipine or the combined approach could prevent DCI-related infarction (both 57.1%), not milrinone alone (87.5%). Both drugs induced a doubled vasopressor demand due to blood pressure decrease, but milrinone alone induced tachycardia. Conclusions: The monotherapy with intra-arterial nimodipine was superior to milrinone. Nimodipine and milrinone may be used complementary in an escalation scheme with the administration of nimodipine first, complemented by milrinone in cases of severe CVS. Milrinone monotherapy is not recommended.

Patients who are treated in an intensive care unit need continuous monitoring in orderfor clinicians to be prepared to intervene should a secondary event occur. For patientstreated at the neurointensive care unit (NICU) who have suffered a subarachnoid hemorrhage (SAH) this secondary event could be ischemia, resulting in a lack of blood flow.Blood flow can be measured using magnetic resonance imaging (MRI). The process is facilitated with a software called NOVA. Repeated measurements can therefore be performedas a way to monitor the patients, which in this context would be referred to as longitudinalmeasurements. As more data can be collected ways of analyzing and visualizing the datain a comprehensible way is needed. The aim of this thesis was therefore to develop and implement a method for analyzing and visualizing the longitudinal MR measurement data.With this aim in mind two research questions were relevant. The first one was how NOVAflow longitudinal measurements can be visualized to simplify interpretation by cliniciansand the second one was in what ways the longitudinal data can be analyzed. A graphicaluser interface (GUI) was created to present the developed analysis and visualization tool.Development of the tool progressed using feedback from supervisors and neurosurgeons.Visualization and analysis was done through plots of blood velocity and blood flow as themain component as well as a 2D vessel map. The final implementation showed multipleexamples of how the longitudinal data could be both visualized and analyzed. The resultstherefore provided a tool to analyze and visualize NOVA flow longitudinal measurementsin a way which was easily interpreted. Further improvements of the tool is possible andan area of improvement could involve increasing the adaptability of the tool.

Objective: Dissecting aneurysms (DAs) of the vertebrobasilar territory manifesting with subarachnoid hemorrhage (SAH) are associated with significant morbi-mortality, especially in the case of re-hemorrhage. Sufficient reconstruction of the affected vessel is paramount, in particular, if a dominant vertebral artery (VA) is impacted. Reconstructive options include stent-assisted coiling and flow diversion (FD). The latter is technically less challenging and does not require catheterization of the fragile aneurysm. Our study aims to report a multicentric experience with FD for reconstruction of DA in acute SAH. Materials and Methods: This retrospective study investigated 31 patients (age: 30–78 years, mean 55.5 years) who had suffered from SAH due to a DA of the dominant VA. The patients were treated between 2010 and 2020 in one of the following German neurovascular centers: University Hospital Leipzig, Katharinenhospital Stuttgart, BG Hospital Bergmannstrost Halle/Saale, and Heinrich-Braun-Klinikum Zwickau. Clinical history, imaging, implanted devices, and outcomes were reviewed for the study. Results: Reconstruction with flow-diverting stents was performed in all cases. The p64 was implanted in 14 patients; one of them required an additional balloon expandable stent to reconstruct severe stenosis in the target segment. One case demanded additional liquid embolization after procedural rupture, and in one case, p64 was combined with a PED. Further 13 patients were treated exclusively with the PED. The p48MW-HPC was used in two patients, one in combination with two additional Silk Vista Baby (SVB). Moreover, one patient was treated with a single SVB, one with a SILK+. Six patients died [Glasgow Outcome Scale (GOS) 1]. Causes of death were periprocedural re-hemorrhage, thrombotic occlusion of the main pulmonary artery, and delayed parenchymal hemorrhage. The remaining three patients died in the acute–subacute phase related to the severity of the initial hemorrhage and associated comorbidities. One patient became apallic (GOS 2), whereas two patients had severe disability (GOS 3) and four had moderate disability (GOS 4). Eighteen patients showed a complete recovery (GOS 5). Conclusion: Reconstruction of VA-DA in acute SAH with flow-diverting stents is a promising approach. However, the severity of the condition is reflected by high overall morbi-mortality, even despite technically successful endovascular treatment.

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disease with mean age of 59 years. SAH accounts for 5% of all stroke and more than one quarter of potential life years lost through stroke. With the advanced neurosurgical methods of today two thirds of the patients survive. We know, however, that various cognitive, psychiatric and physical impairments are common that affect quality of life, social life, and the ability to work in the aftermath of SAH. The overall aim constituting this PhD dissertation is to better understand some of the challenges often faced by those surviving SAH. Two SAH patient cohorts have been studied. The first followed 96 consecutively included patients during the first year after ictus. Spasticity and cognitive impairment was assessed after 6 months and the Swedish stroke register follow-up form was used to investigate family support and the use of medical and social services. Return to work was assessed at 12 months. The second cohort assessed attention deficits using the test of variables of attention (T.O.V.A.) at 7 months after ictus in 19 patients with moderate to good recovery. Spasticity was just as common in our SAH patients as after other stroke, though it was rarely treated pharmacologically. By assessing cognitive impairment at 6 months after ictus using the Montreal cognitive assessment, 68% of the patients could be correctly predicted as having returned/not returned to work at 12 months. Seventeen percent of the patients had not had a follow-up appointment 6 months after ictus. These patients were older, more often living alone, had a lower quality of life, more depressive symptoms and more cognitive impairment compared to those having had a follow-up appointment. Twenty percent had had a follow-up in primary care. Seventy-eight percent of those with moderate to severe disability were living in their own accommodations. Fifty-eight percent of the patients had attention deficits. Challenges after SAH were common and often dealt with in the home environment of the patients. The results of this thesis highlight the importance of assisting the patients and their relatives in their struggle back to life after SAH.

Die Kopplung zwischen neuronaler Aktivität und cerebralem Blutfluss ist ein fundamentaler Prozess, der alle cerebralen Funktionen begleitet. Das Thema meiner Habilitation ist die Entdeckung einer neuen Ischämievariante, bei der neuronale Aktivierung eine cerebrale Ischämie auslöst, indem sich die Kopplung zwischen neuronaler Aktivierung und cerebralem Blutfluss umkehrt. Diese Umkehrung wird durch Produkte roter Blutkörperchen im Subarachnoidalraum hervorgerufen. Die eigentümlichste Eigenschaft dieser Ischämievariante ist ihre Wanderung im cerebralen Cortex gemeinsam mit der Welle neuronaler Aktivierung. Deshalb habe ich das Phänomen cortical spreading ischaemia genannt. Das vorgestellte tierexperimentelle Modell könnte für die verzögerten ischämischen neurologischen Defizite nach Subarachnoidalblutung Implikationen besitzen. Die Verbindung mit diesem klinischen Syndrom basiert auf: (a) der Induktion der cortical spreading ischaemia durch Produkte roter Blutkörperchen im Subarachnoidalraum, (b) der Übereinstimmung im Läsionsmuster mit corticalen ischämischen Infarkten, und (c) den therapeutischen Effekten von Nimodipin und mässiger hypervolämischer Hämodilution im klinischen Syndrom und im Tiermodell. Mit Hilfe dieses Modells ist es zum ersten Mal gelungen, experimentell die Hypothese zu bestätigen, dass Produkte roter Blutkörperchen eine cerebrale Ischämie induzieren können. Ich hoffe, dass das Modell dazu beitragen wird, neue Strategien bei der Behandlung von Patienten mit Subarachnoidalblutung zu entwickeln. / The coupling between neuronal activity and cerebral blood flow is a fundamental process, which underpins all cerebral functions. The topic of my Habilitation is the discovery of a new variant of ischaemia in which neuronal activation triggers a cerebral ischaemic event through the inversion of the coupling between neuronal activation and cerebral blood flow. This inversion occurs when red blood cell products are present in the subarachnoid space. The most distinct feature of this variant of ischaemia is its propagation in the cerebral cortex together with the wave of neuronal activation. Therefore, I named the phenomenon cortical spreading ischaemia . The presented animal model may have implications for the delayed ischaemic neurological deficits after subarachnoid haemorrhage. The link with this clinical syndrome has been based: (a) on the induction of cortical spreading ischaemia by red blood cell products in the subarachnoid space, (b) the correspondence between the characteristic patterns of the cortical ischaemic lesions, and (c) the therapeutic effects of nimodipine and moderate hypervolaemic haemodilution in clinical syndrome and animal model. With the aid of this model, it was possible to experimentally confirm the hypothesis that red blood cell products can induce cerebral ischaemia. I hope that the model will contribute to develop new strategies for the treatment of patients with subarachnoid haemorrhage.

Hemorragia subaracnoidea aneurismática (HSAa) é considerada causa importante de morte e de sequelas neurológicas. A taxa de mortalidade desta doença pode alcançar 50% nos primeiros dois meses após sangramento de aneurisma encefálico. Apesar dos avanços científicos da modernidade, o resultado do tratamento da HSAa não mudou nos últimos anos. O presente estudo avaliou o papel de 14 biomarcadores genéticos, incluindo o polimorfismo (SNP) do gene eNOS, em pacientes da Amazônia com HSAa, para verificar as alterações alélicas associadas ao risco de vasoespasmo encefálico e déficit neurológico tardio. Avaliou-se a ancestralidade desta amostra de pacientes em que se utilizou 48 marcadores para identificar possível etnia associada à predisposição ao VE. Investigou-se 14 biomarcadores genéticos no tocante à resposta inflamatória encefálica na HSAa. Foram avaliados 265 doentes que foram divididos em dois grupos: grupo I (pacientes com vasoespasmo encefálico) e grupo 2 (pacientes sem vasoespasmo). A média das idades foi 51 anos, havia 224 mulheres (84%) e 124 pacientes (46,79%) apresentaram vasoespasmo encefálico (VE). A maior incidência de VE ocorreu na idade entre 50 e 59 anos. Tabagismo e hipertensão arterial sistêmica foram os fatores de risco mais associados à VE. Aneurismas encefálicos de tamanho pequeno e médio predominaram nesta casuística. As escalas amarela e vermelha do VASOGRADE associaram-se ao risco de VE (p < 0,001). Não houve variação na distribuição ancestral entre os grupos estudados e o que ocorre na população brasileira saudável na região Amazônica. O gene da eNOS com seus respectivos polimorfismos T-786C e 27VNTR4 correlacionaram-se com VE. Outros marcadores observados foram TP53, CASP8, ACE2, IL4 e XRCC1. O gene TP53 (modelo recessivo alelo 1) mostrou-se ser um fator protetor de VE, enquanto que genes com mutações INDEL CASP8 (modelo recessivo alelo 2) e o XRCC1 (modelo recessivo alelo 1) mostraram tendência ao desenvolvimento de VE com risco 2 vezes maior e 1,4 vezes maior que o grupo II (p < 0,001). Conclui-se que SNPs da eNOS se correlacionam com desenvolvimento de VE sintomático pós-HSAa. Este estudo também mostrou o papel dos marcadores inflamatórios na HSAa, o que auxiliaria na condução da terapia clínica. / Aneurysmal subarachnoid hemorrhage (aSAH) is a leading cause of premature death and neurological disability. It is considered as a devastating condition that accounts to 50% of mortality during the first two months after a hemorrhagic event. Despite foremost advances in the clinical management of post-aSAH patients, the rates of mortality and morbidity have not changed in recent years. This study appraised the role of 14 genetic biomarkers, including the eNOS polymorphism (SNP) between Amazon\'s patients with aSAH, as means to document how variant alleles are related to a higher disposition to cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). 265 patients were evaluated and then divided into two clusters: Group I (with symptomatic CV) and group II (presenting no symptomatic CV). The median ages of patients were 51.61 years of age, 224 (84.52%) were women and 124 patients (46.97%) had symptoms of cerebral vasospasm (CV). Tobacco smoking and systemic arterial hypertension are the risk factors most associated to CV. In the course of this research, most aneurysms found were small and medium-sized. The score VASOGRADE yellow and VASOGRADE red presented a high risk of CV (p < 0.001). We established a panel of 48 ancestry informative markers for estimating which ethnicity could present a predisposition to CV. There was no variation in the ancestral distribution between study groups and healthy brazilian folk over the Amazon region. The eNOS gene with its polymorphisms T-786C and 27 VNTR4 were correlated to CV. Other markers were accomplished: TP53, CASP8, ACE2, IL4, and XRCC1. The TP53 gene (recessive genetic model allele 1) supporting evidence of the protective role to CV. Whilst other genes with INDEL mutation like as CASP8 (recessive model allele 2) and the XRCC1 (recessive model allele 1) indicated a propensity to spread out CV with odds 2-fold higher, and 1.414 times greater than group II (p < 0.001). It follows that eNOS SNPs correlate to a positive association with a syntomatic CV post-aSAH. Also, this study showed up the role of inflammatory markers at aSAH to a further educated therapeutic choice for a better clinical response