Objective: While cavernous carotid aneurysms can cause neurological symptoms, their often-uneventful natural course and the increasing options of intravascular aneurysm closure call for educated decision-making. However, evidence-based guidelines are missing. Here, we report 64 patients with cavernous carotid aneurysms, their respective therapeutic strategies, and follow-up. Methods: We included all patients with cavernous carotid aneurysms who presented to our clinic between 2014 and 2020 and recorded comorbidities (elevated blood pressure, diabetes mellitus, and nicotine consumption), PHASES score, aneurysm site, size and shape, therapeutic strategy, neurological deficits, and clinical follow-up. Results: The mean age of the 64 patients (86% female) was 53 years, the mean follow-up time was 3.8 years. A total of 22 patients suffered from cranial nerve deficit. Of these patients, 50% showed a relief of symptoms regardless of the therapy regime. We found no significant correlations between aneurysm size or PHASES score and the occurrence of neurological symptoms. Conclusion: If aneurysm specific symptoms persist over a longer period of time, relief is difficult to achieve despite aneurysm treatment. Patients should be advised by experts in neurovascular centers, weighing the possibility of an uneventful course against the risks of treatment. In this regard, more detailed prospective data is needed to improve individual patient counseling.

Ziel dieser Arbeit ist es, Ergebnisse der endovaskulären Rekonstruktion bei akut rupturierten, dissezierenden Aneurysmen der dominanten intrakraniellen Vertebralarterien mit hämodynamischen Implantaten (Flow-Diverter) zu untersuchen, einschließlich klinischer und verfahrenstechnischer Aspekte sowie klinischer Ergebnisse, um Machbarkeit, Sicherheit und Wirksamkeit dieses Ansatzes darzustellen. Zur Bearbeitung dieser sehr seltenen, jedoch klinisch relevanten Konstellation wurden zwischen 2010 und 2020 in vier neurovaskulären Zentren bzw. Fachabteilungen 31 Patienten im Alter von 30–78 Jahren (x̄ 55,5 Jahre) erfasst, die aufgrund eines Dissektionsaneurysmas der dominanten A. vertebralis eine Subarachnoidalblutung erlitten und bei denen dissezierende Aneurysmen einer dominanten A. vertebralis mit flußrichtenden Stents behandelt wurden. Beteiligte Kliniken waren das Universitätsklinikum Leipzig, das Katharinenhospital Stuttgart, das Berufsgenossenschaftliche Krankenhaus Bergmannstrost Halle/Saale und das Heinrich-Braun-Klinikum Zwickau. Von den 31 Patienten hatten 11 das dissezierende Aneurysma an der rechtsseitigen dominanten Vertebralarterie, während die restlichen Patienten das dissezierende Aneurysma an der linksseitigen dominanten Vertebralarterie hatten. Bei sechs Patienten betraf das dissezierende Aneurysma morphologisch die A. basilaris. In allen Fällen wurde eine Gefäßrekonstruktion mit unterschiedlichen flussumlenkenden Stents durchgeführt. Ein Fall erforderte eine zusätzliche Flüssigkeitsembolisation nach einer Verfahrensruptur, in drei Fällen war ein additives Coiling notwendig und in weiteren drei Fällen wurden unterschiedliche Flow Diverter Modelle miteinander und/oder mit Koronarstents kombiniert. Die Kriterien der klinischen Verlaufsbeurteilung erfolgten anhand der Glasgow Outcome Scale (GOS). Zur Einteilung des Schweregrades der Subarachnoidalblutung wurde anhand der Bildgebung die Fisher-Skala und anhand der Klinik die Klassifikation nach Hunt und Hess verwendet. Neun von 31 Patienten (29 %) erreichten nur ein ungünstiges Outcome (GOS 1–3). Fünf der sechs im Rahmen der SAB verstorbenen Patienten (GOS 1) zeigten bereits schwere Defizite vor der endovaskulären Behandlung (Grad III-V nach Hunt und Hess). Ein Patient mit GOS 2 erlitt ein apallisches Syndrom nach einer vorausgegangenen frühen erneuten Blutung innerhalb von 24 h nach der Behandlung. Zwei Patienten wiesen eine schwere Behinderung (GOS 3) auf und vier erlangten ihre Selbstständigkeit im Alltag zurück (GOS 4). Achtzehn Patienten zeigten eine vollständige Genesung (GOS 5). Zusammengefasst zeigt die Arbeit, dass die rekonstruktive Behandlung von rupturierten dissezierenden Aneurysmen der dominanten Vertebralarterie mit Flow- Diverter-Stents ein technisch sicherer und effektiver Ansatz in einer akuten Situation mit komplexem Lokalbefund ist, für deren interventionelle Behandlung bisher keine anderen wirksamen Optionen oder standardisierten Behandlungspfade definiert wurden. Die Schwere der Erkrankung spiegelt sich trotz technisch erfolgreicher endovaskulärer Behandlung dennoch in relativ hohen Morbiditäts- (23%) und Mortalitätsraten (19%) wider, die ohne ursächliche endovaskulären Behandlung allerdings in Mortalitätsraten von etwa 50 % gipfeln würden.:1. Einführung 1.1 Einleitung 3 1.2 Arterielle Dissektionen des vertebrobasilären Stromgebietes 1.2.1 Epidemiologie 5 1.2.2 Ätiologie 5 1.2.3 Anatomie 6 1.2.4 Pathophysiologie 10 1.2.5 Klinische Symptomatik 11 1.2.6 Diagnostik 12 1.2.7 Therapieoptionen und Einordnung der vorliegenden Arbeit 16 1.2.8 Klinische Ergebnisse und Prognose 21 1.3 Abkürzungsverzeichnis 23 1.4 Abbildungsverzeichnis 24 2. Publikationsmanuskript 25 Flow Diversion for Reconstruction of Intradural Vertebral Artery Dissecting Aneurysms Causing Subarachnoid Hemorrhage – A Retrospective Study From Four Neurovascular Centers 3. Zusammenfassung 35 4. Literaturverzeichnis 38 5. Darstellung des eigenen wissenschaftlichen Beitrages 46 6. Erklärung über die eigenständige Abfassung der Arbeit 47 7. Lebenslauf 48 8. Danksagung 51

Background and Purpose: Flow diversion is increasingly used as an endovascular treatment for intracranial aneurysms. In this retrospective multicenter study, we analyzed the safety and efficacy of the treatment of intracranial, unruptured, or previously treated but recanalized aneurysms using Flow Re-Direction Endoluminal Device (FRED) Jr with emphasis on midterm results. Materials and Methods: Clinical and radiological records of 150 patients harboring 159 aneurysms treated with FRED Jr at six centers between October 2014 and February 2020 were reviewed and consecutively included. Clinical outcome was measured by using the modified Rankin Scale (mRS). Anatomical results were assessed according to the O’Kelly-Marotta (OKM) scale and the Cekirge-Saatci Classification (CSC) scale. Results: The overall complication rate was 24/159 (16%). Thrombotic-ischemic events occurred in 18/159 treatments (11%). These resulted in long-term neurological sequelae in two patients (1%) with worsening from pre-treatment mRS 0–2 and mRS 4 after treatment. Complete or near-complete occlusion of the treated aneurysm according to the OKM scale was reached in 54% (85/158) at 6-month, in 68% (90/133) at 1-year, and in 83% (77/93) at 2-year follow-up, respectively. The rates of narrowing or occlusion of a vessel branch originating from the treated aneurysm according to the CSC scale were 11% (12/108) at 6-month, 20% (17/87) at 1-year, and 23% (13/57) at 2-year follow-up, respectively, with all cases being asymptomatic. Conclusions: In this retrospective multicenter study, FRED Jr was safe and effective in the midterm occlusion of cerebral aneurysms. Most importantly, it was associated with a high rate of good clinical outcome.

Les avancées technologiques endovasculaires des dernières décennies ont été nombreuses ; la diversion de flux en fait partie. Lorsqu’une nouvelle approche permet de traiter de façon efficace et sûre un certain nombre de patients présentant des défis jusque-là difficiles à surmonter, son adoption en pratique clinique peut-être précoce, voire prématurée. Nous avons dans un premier travail réalisé une revue systématique sur les stents dits «Flow Diverters» (FD) et les modèles animaux. Puis nous avons mené quatre expérimentations animales évaluant l’efficacité des FDs dans différents modèles d’anévrismes canins adaptés à l’hypothèse de travail par l’application d’une méthodologie rigoureuse. Nous avons été en mesure de montrer que la technique de diversion de flux est plus à même d’occlure les anévrismes avec de petits collets, des anévrismes dont la branche couverte par le FD est occluse, ou encore quand la porosité du FD en regard de l’anévrisme est diminuée par l’opérateur. Dans le sixième travail, nous avons expérimenté les résultats de la mise en place d’un clip chirurgical sur ces FDs avant d’en déconseiller la pratique. Puis nous avons étudié la variabilité dans la décision des opérateurs d’implanter un FD pour le traitement d’un anévrisme à l’aide d’un questionnaire et ainsi montré l’importante variabilité présente. Enfin nous rapportons le design de l’étude randomisée, pragmatique, multicentrique FIAT (Flow diversion In Aneurysm Treatment) ainsi que ces résultats. / Flow Diversion is one of the relevant technical improvements of the past decade in the endovascular treatment of cerebral aneurysms. When the efficacy and safety of a new tool allow treating challenging aneurysms, this adoption in daily practice can be fast even if the benefit of use is not clearly, scientifically show. We performed a systematic review of studies of these stents called “Flow Diverters” (FD) in animal models. Then we performed 4 animal studies in models we create in order to isolate the propriety of the FD we wanted to study. By using this methodology, we have been able to show that Flow Diversion is more likely to occlude small neck aneurysms, aneurysms in which the jailed branch has been occluded, or when the operator compact the FD in order to decrease the porosity of the device. In a 6th study, we test the result of the use of a clip to occlude a FD. Regarding the results of the test, we recommand to avoid clipping FDs.Then by using a questionaire; we showed the poor agreement of using FD in daily practice by using clinical vignettes. Then we presented the design and the result of the first randomized clinical study on flow diverters FIAT (Flow diversion In Aneurysm Treatment).

Background and Purpose: Low-profile flow diverter stents (FDS) quite recently amended peripheral segments as targets for hemodynamic aneurysm treatment; however, reports on outcomes, especially later than 3 months, are scarce. This study therefore reports our experience with the novel silk vista baby (SVB) FDS and respective outcomes after 8 and 11 months with special respect to specific adverse events. Materials and Methods: Forty-four patients (mean age, 53 years) harboring 47 aneurysms treated with the SVB between June 2018 and December 2019 were included in our study. Clinical, procedural, and angiographic data were collected. Follow-ups were performed on average after 3, 8, and 11 months, respectively. Treatment effect was assessed using the O’Kelly Marotta (OKM) grading system. Results: Overall, angiographic follow-ups were available for 41 patients/45 aneurysms. Occlusion or significant reduction in aneurysmal perfusion (OKM: D1, B1–B3 and A2–A3) was observed in 98% of all aneurysms after 8 months. Only 2% of the treated aneurysms remained morphologically unaltered and without an apparent change in perfusion (OKM A1). Adverse events in the early post-interventional course occurred in seven patients; out of them, mRS-relevant morbidity at 90 days related to FDS treatment was observable in two patients. One death occurred in the context of severe SAH related to an acutely ruptured dissecting aneurysm of the vertebral artery. Conclusion: The SVB achieves sufficient occlusion rates of intracranial aneurysms originating from peripheral segments, which are comparable to prior established conventional FDS with acceptably low complication rates. However, alteration of a hemodynamic equilibrium in distal localizations requires special attention to prevent ischemic events.

L'anévrisme intracrânien est la prédisposition mortelle la plus fréquente chez le sujet jeune. Sa compréhension demeure limitée alors que nous assistons au développement de nouveaux traitements endovasculaires permettant le traitement d'anévrismes de plus en plus complexes. L'essentiel des études sur le sujet repose sur des séries cliniques peu informatives, l'utilisation de méthodes de simulation numérique limitées et cible presque exclusivement les phénomènes mécaniques intrasacculaires sans tenir compte des conséquences de l'anévrisme sur l'artère porteuse. In vitro, l'utilisation d'anévrismes en silicone au sein d'un simulateur cardiovasculaire a permis d'objectiver un impact de l'anévrisme sur l'écoulement au sein du vaisseau porteur caractérisé par une diminution de sa résistance. In vivo, cet effet a été objectivé et mesuré en IRM de flux par l'analyse des courbes de débit volumétrique. Le flux sanguin en aval des anévrismes était caractérisé par une démodulation systolo-diastolique avec diminution des index de résistance et de pulsatilité. Cet effet était fortement corrélé au volume de l'anévrisme. Les stents flow diverters permettaient une « reconstruction hémodynamique » mesurable du vaisseau porteur en restaurant un flux normo-modulé et des index de pulsatilité et de résistance dans les limites de la normale. Une méthode originale pour la segmentation de l'artère carotide interne en IRM en contraste de phase 2D a été proposée. Elle se base sur l'application de la Transformée de Fourier sur les images de phase et la prise en compte de la cohérence temporelle des vitesses au sein du voxel. La méthode a été caractérisée et comparée à deux méthodes de référence / Intracranial aneurysms are the most common lethal predisposition amongst young adults. Its understanding remains limited to date while the development of new innovative endovascular treatments are increasingly available and allow for the treatment of more and more complex aneurysms with a non negligeable rate of complications. Most of the previous studies on intracranial aneurysms are based on low informative clinical series and the use of limited numerical simulation methods. They almost exclusively target the intrasaccular mechanical phenomena irrespective of the changes in the parent vessel induced by the aneurysm. In vitro, the use of silicone aneurysms embedded in a cardiovascular simulator showed an impact of the aneurysm on the the parent vessel flow conditions characterized by a decrease of its resistance. In vivo, flow MRI allowed to quantify this effect by analyzing the volumetric flow rate curves. Downstream to the aneurysm, the blood flow was dampened and presents a systolic diastolic demodulation with a collapse of resistive and pulsatility indexes. This effect was strongly correlated to the aneurysm volume. The flow diverter stents allowed for a measurable « hemodynamic reconstruction » of the parent vessel by restoring a normo modulated flow, and normal resistive and pulsatility indexes. An original method for the segmentation of internal carotid artery in 2D phase contrast MRI was proposed. It is based on the application of the Fourier Transform on the phase images and by taking into account the temporal coherence of velocities within the voxel. The method was characterized and compared to two reference methods

Background: Data on the safety and efficacy of flow diverters (FD) for the treatment of unruptured internal carotid artery (ICA) aneurysms with compressive neuro-ophthalmological symptoms (NOS) are scarce and comprise mainly small case series. Methods: We performed a search of three databases and included series with ≥10 patients, with unruptured aneurysms of the ICA and NOS, treated with FD. Random-effects analysis of treatment results and safety was performed. Results: A total of 22 studies reporting on 594 patients were included. Pooled proportions of NOS recovery, improvement, transient and permanent worsening were: 47.4% (95% CI 35.0% to 60.1%); 74.5% (95% CI 67.9% to 80.2%); 7.1% (95% CI 3.3% to 14.7%); and 4.9% (95% CI 3.2% to 7.4%), respectively. Rates of complete recovery and improvement in patients with isolated visual symptoms were 30.6% (95% CI 12.5% to 57.7%) and 56.6% (95% CI 42.3% to 69.9%). Isolated oculomotor symptoms recovered completely in 47.8% (95% CI 29.9% to 66.3%) and improved in 78% (95% CI 69.2% to 84.9%). Morbidity occurred in 5% (95% CI 2.8% to 9%) and mortality in 3.9% (95% CI 2% to 7.5%) of patients. An increased likelihood of symptom improvement was observed when treatment was performed early (<1 month) after symptom onset (OR=11.22, 95% CI 3.9% to 32.5%). Conclusion: Flow diversion promotes recovery or improvement of compressive symptoms in a large proportion of patients but is associated with significant rates of morbidity and mortality. Transient and permanent NOS worsening is not uncommon. Early treatment is of utmost importance, as it increases the likelihood of symptom improvement more than 10-fold.