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Background: Management of patients with coma of unknown etiology (CUE) is a major challenge in most emergency departments (EDs). CUE is associated with a high mortality and a wide variety of pathologies that require differential therapies. A suspected diagnosis issued by pre-hospital emergency care providers often drives the first approach to these patients. We aim to determine the accuracy and value of the initial diagnostic hypothesis in patients with CUE. Methods: Consecutive ED patients presenting with CUE were prospectively enrolled. We obtained the suspected diagnoses or working hypotheses from standardized reports given by prehospital emergency care providers, both paramedics and emergency physicians. Suspected and final diagnoses were classified into I) acute primary brain lesions, II) primary brain pathologies without acute lesions and III) pathologies that affected the brain secondarily. We compared suspected and final diagnosis with percent agreement and Cohen's Kappa including sub-group analyses for paramedics and physicians. Furthermore, we tested the value of suspected and final diagnoses as predictors for mortality with binary logistic regression models. Results: Overall, suspected and final diagnoses matched in 62% of 835 enrolled patients. Cohen's Kappa showed a value of kappa = .415 (95% CI .361-.469, p < .005). There was no relevant difference in diagnostic accuracy between paramedics and physicians. Suspected diagnoses did not significantly interact with in-hospital mortality (e.g., suspected class I: OR .982, 95% CI .518-1.836) while final diagnoses interacted strongly (e.g., final class I: OR 5.425, 95% CI 3.409-8.633). Conclusion: In cases of CUE, the suspected diagnosis is unreliable, regardless of different pre-hospital care providers' qualifications. It is not an appropriate decision-making tool as it neither sufficiently predicts the final diagnosis nor detects the especially critical comatose patient. To avoid the risk of mistriage and unnecessarily delayed therapy, we advocate for a standardized diagnostic work-up for all CUE patients that should be triggered by the emergency symptom alone and not by any suspected diagnosis.

Der mediale Temporallappen (MTL) und seine Bedeutung für das Gedächtnis sind seit Jahrzehnten Gegenstand der wissenschaftlichen Diskussion. Bislang besteht kein Konsens über das Zusammenspiel seiner einzelnen neuroanatomischen Untereinheiten bei der Verarbeitung und Repräsentation von Gedächtnisinhalten. Die Funktion des Hippokampus steht dabei aufgrund seiner zentralen Lage und besonderen Konnektivität vorrangig im Fokus des Interesses. Trotz umfangreicher Untersuchungen an Menschen und Tiermodellen fehlt gegenwärtig eine umfassende Theorie seiner Funktion, da der Hippokampus mit mehreren zum Teil gegensätzlich erscheinenden Domänen des Gedächtnisses in Verbindung gebracht wird. Problematisch ist in diesem Zusammenhang das Fehlen eines einheitlichen humanen Läsionsmodells in der bisherigen Literatur, was die eindeutige Interpretation von Läsionsstudien oftmals erschwert. Die vorliegende Arbeit präsentiert Daten aus neuropsychologischen Untersuchungen an Patienten mit umschriebenen chirurgischen Läsionen des MTL. Es wird gezeigt, dass der Hippokampus entgegen der traditionellen Lehrmeinung auch an Kurzzeitgedächtnisprozessen beteiligt ist und dass dabei eine Spezialisierung auf räumlich-assoziative Gedächtnisinhalte vorliegt. Nicht-räumliche Assoziationen scheinen hingegen unabhängig vom Hippokampus repräsentiert zu werden. Darüber hinaus werden anhand einer vergleichenden Läsionsstudie Belege für Kompensationsmechanismen erbracht, welche von der Ätiologie der MTL-Läsion abhängig sind und deren Effizienz das Ausmaß funktioneller Defizite nach Läsionen des MTL mitbestimmt. Rückschlüsse auf Struktur-Funktions-Beziehungen in Läsionsstudien müssen solche Kompensationsprozesse berücksichtigen., For decades, the medial temporal lobe (MTL) and its role in memory have been the subject of intense scientific discussion. In this context, the hippocampus has been of particular interest due to its central position within the MTL. To date, there is no consensus on how the hippocampus and adjacent regions of the MTL interact during processing and representation of memory content. Experimental work in humans and animal models suggests involvement of the hippocampus in multiple memory domains, some of which appear to be conflicting. As a consequence, there is currently no comprehensive theory of hippocampal function. The discussion is complicated by the lack of an integrative experimental model of human hippocampal dysfunction which is why an unambiguous interpretation of human lesion studies is difficult. This thesis presents data from behavioural studies on patients with circumscribed surgical lesions of the MTL performing delayed-match-to-sample tasks with different stimulus material. In contrast to the traditional view, it shows that the hippocampus is also involved in short term memory, at least with stimulus material that contains spatial associations. On the other hand, the representation of non-spatial associations seems to be largely independent of the hippocampus. Furthermore, evidence of compensational mechanisms following hippocampal damage in the early stages of brain maturation is presented. It is proposed that the efficiency of these mechanisms co-determines the magnitude and pattern of functional deficits following damage to the MTL. Conclusions drawn from lesion studies about structure-function-relationships must take into account these compensational mechanisms.