Plötslig och oväntad död är något sjuksköterskan kan komma att uppleva i sitt yrkesverksamma liv. Plötslig och oväntad död innebär att en person avlider oväntat och att döden inträffar upp till 24 timmar efter symtomdebut, oberoende på om tidigare symtom på bakomliggande sjukdom är känd. Syftet med studien var att belysa sjuksköterskans upplevelser av patienters plötsliga och oväntade död. Det gjordes genom en litteraturstudie som innebär att på ett systematisk sätt identifiera och undersöka vetenskapliga artiklar. Många sjuksköterskor upplever känslor såsom sorg, skuld och otillräcklighet vid patienters plötsliga och oväntade död. Det är först när rätt tid och plats ges som sjuksköterskan får lov att ge utlopp för sina känslor. Dessutom har anhörigas reaktioner en stark inverkan på sjuksköterskans upplevelse av den egna kapaciteten. Copingstrategier är av vikt, både för att kunna möta anhöriga men även för att kunna hantera de egna känslorna. Mer forskning bör genomföras eftersom att plötslig och oväntad död är en händelse som upplevs vara svårhanterlig för sjuksköterskan. Också utbildning i hanteringen av plötsliga och oväntade dödsfall är av betydelse då det är något som sjuksköterskan kan komma att ställas inför och på grund av att kunskapen inom ämnet är bristfällig. / Sudden and unexpected death is something that the nurse may experience in his or her professional life. Sudden and unexpected death means that a person dies unexpectedly and that the death occurs within 24 hours after the first symptoms, regardless whether an underlying disease is known. The purpose of this study was to elucidate the nurses’ experience of patients sudden and unexpected death. This was done by a literature research which means that in a systematic way identify and examine scientific articles. Many nurses are experiencing feelings such as grief, guilt and inadequacy when a patient sudden and unexpected dies. It is only when the right time and place is given that the nurse is allowed to vent his or her own feelings. In addition, the reactions from relatives have a strong impact on the nurse’s experience of his or her own capacity. Coping strategies are of importance, both in beeing able to meet relatives but also to be able to manage his or her own emotions. More research should be conducted since sudden and unexpected death is an event that is perceived as difficult to handle for the nurse. Education in handling sudden and unexpected deaths is of importance since it is something that the nurse probably will encounter and because the knowledge within the subject is inadequate.

Bakgrund: I Sverige dör cirka 90 000 personer varje år. Majoriteten av dessa är förväntade dödsfall relaterat till ålder och sjukdomar. Plötslig död innefattar mord, suicid, olycksfall eller akut sjukdom. I mötet med anhöriga efter plötslig död har sjuksköterskan till uppgift att delge stöd och information. Det finns många studier gjorda på hur anhöriga upplever bemötandet i vården men desto mindre forskning om hur sjuksköterskan upplever mötet med anhöriga vid plötslig död. Syfte: Att beskriva sjuksköterskans upplevelse av att möta anhöriga vid plötslig död på sjukhus. Metod: Kvalitativ intervjustudie där 10 sjuksköterskor, från två olika avdelningar från ett sjukhus i södra delen av Sverige, har intervjuats.  Intervjuerna bearbetades och har analyserats genom en kvalitativ innehållsanalys. Resultat: Studien resulterade i tre huvudkategorier; Kräver professionalitet, Anhörigas reaktioner påverkar och Behöver vara personlig. Slutsats: Hur sjuksköterskan möter och bemöter anhöriga är ett viktigt moment i vården och för den familjecentrerade omvårdnaden. Sjuksköterskor som påträffar plötsliga dödsfall i sitt yrke upplever att det är komplext att möta anhöriga vid dessa situationer. / Background: Approximately 90 000 people die each year in hospitals throughout Sweden. The majority of these are expected deaths related to age and disease. The causes of sudden death include homicide, suicide, accidental or acute illness. When this occurs, nurses are responsible for sharing support and information with the relatives. There have been many studies conducted on the experience of family members and the treatment they receive in hospitals. However, there is less research present on the experiences of nurses when meeting families after sudden death. Aims: To describe nurses' experience of meeting relatives, when sudden death occurs in a hospital. Method: Qualitative interview study where a total of 10 nurses participated in the interviews, from two different departments of a hospital, in southern Sweden. The interviews were analyzed using a qualitative content analysis. Results: The study resulted in three main categories; Require professionalism, Relatives` reactions effects and Need to be personal. Conclusion: How the nurse meets and treats families is an important part of the care and the family-centered care. Nurses who encounters sudden death in the professional experience that it is complex to meet relatives after sudden death.

Background: Parents of children with epilepsy have been shown to have higher rates of depression, anxiety and stress in comparison to parents of children without epilepsy due to the impact of caring for a child with a chronic condition. A systematic review of existing literature aimed to identify qualitative research that examined parents' experiences of caring for their children with epilepsy. Methods: The systematic review explored the experiences that parents have in caring for their child with epilepsy. A search of electronic databases for qualitative literature was completed. The quality of all eligible articles papers was assessed, and findings from studies were synthesised. Results: Twelve studies met inclusion criteria for the review; findings suggest that parents need time to process their child's diagnosis of epilepsy; they cope with this in differing ways and are motivated to learn how to adapt and cope with parenting their child with epilepsy. Conclusions: Parents of children with epilepsy may experience symptoms of stress, this may motivate them to learn how best to care for their child. Empirical Paper Abstract Background: Parents' experiences of being told about sudden unexpected death in epilepsy (SUDEP) may be particularly challenging to cope with. As little is known about how mothers understand and make sense of SUDEP, a qualitative research project aimed to explore mothers' experiences. It was hoped this would be helpful for clinicians to understand in order to assist them in providing information to parents in a way that minimises distress. Methods: The empirical article explored mother's experiences of being told about SUDEP and the subsequent impact of this for 11 mothers of children with epilepsy. Interpretative Phenomenological Analysis methodology was utilised, with themes derived from interpretation of interview transcripts, in order to describe the experiences of the participants. Results: Within the empirical study, five themes emerged. The way in which mothers found out about SUDEP seemed to have a link to their perception of risk and how they subsequently managed feelings of uncertainty and the psychological impact of knowing about SUDEP. Mothers' recommendations to clinicians included when, how and what to tell other parents, and were based on their own helpful and unhelpful experiences of being informed about SUDEP. Conclusions: In being told about SUDEP, mothers may struggle to make sense of it and this can be associated with an increase in anxiety. However, clinicians can reduce potential distress by carefully timing when and how they tell parents, and by making sure information is clear and relevant for the child in question.

Epilepsy is a neurological disorder that is characterized by aberrant electrical activity in the brain resulting in at least two unprovoked seizures over a period longer than 24 hours. Approximately 60% of individuals with epilepsy are diagnosed with temporal lobe epilepsy (TLE) and about one third of those individuals do not respond well to anti-seizure medications. This places those individuals at high risk for sudden unexpected death in epilepsy (SUDEP). SUDEP is defined as when an individual with epilepsy, who is otherwise healthy, dies suddenly and unexpectedly for unknown reasons. SUDEP is one of the leading causes of death in individuals with acquired epilepsies (i.e. not due to genetic mutations), such as TLE. Previous studies utilizing genetic models of epilepsy have suggested that circuitry within the vagal complex of the brainstem may play a role in SUDEP risk. Gamma-aminobutyric acid (GABA) neurons of the nucleus tractus solitarius (NTS) within the vagal complex receive, filter, and modulate cardiorespiratory information from the vagus nerve. GABAergic NTS neurons then project to cardiac vagal motor neurons, eventually effecting parasympathetic output to the periphery. In this study, a mouse model of TLE was used to assess the effect of epileptogenesis on GABAergic NTS neuron function and determine if functional alterations in these neurons impact SUDEP risk. It was discovered that mice with TLE (i.e. TLE mice) have significantly increased mortality rates compared to control animals, suggesting that SUDEP occurs in this model. Using whole cell electrophysiology synaptic and intrinsic properties of GABAergic NTS neurons were investigated in TLE and control mice. Results suggest that during epileptogenesis, GABAergic NTS neurons become hyperexcitable, potentially due to a reduction in A-type potassium channel current and increased excitatory synaptic input. Increases in hyperexcitability have been shown to be associated with an increased risk of spreading depolarization and action potential inactivation leading to neuronal quiescence. This may lead to a decreased inhibition of parasympathetic tone, causing cardiorespiratory collapse and SUDEP in TLE.

Bakgrund: I vårdyrket är det ofrånkomligt för sjuksköterskor att möta döden och det finns skillnader på väntad och oväntad död. Dödsfallet för närstående som förlorat en person i plötslig död kan upplevas som en traumatisk händelse. En krisreaktion kan uppträda och närstående kan vara i behov av emotionell omvårdnad från hälso- och sjukvården. Det visar även att andra typer av stöd kunde hjälpa att lindra lidandet. Syfte: Syftet är att beskriva betydelsen av emotionell omvårdnad för att lindra lidandet hos närstående som förlorat en person i plötslig död. Metod: Den valda designen för denna studie var en icke-systematisk litteraturöversikt, där analysen genomfördes med hjälp av en integrerad analys. Studien baserades på 35 vetenskapliga artiklar där 17 av artiklarna inkluderades i resultatet, från databaserna CINAHL och PubMed. Resultat: Resultatet visade att emotionell omvårdnad kan ha betydelse för närståendes lidande. De upplevde känslomässig påverkan vilket skapade bland annat rädsla, sömnproblematik och beteendeförändringar. Lidande, stöd och kommunikation redovisas som viktiga faktorer. Genom att sjuksköterskor visade medmänsklighet och öppenhet för döden förbättrade det hälsan hos närstående. Slutsats: Närstående kan behöva emotionell omvårdnad efter en plötslig död av en person, eftersom det visade lindra lidandet. Därför kan sjuksköterskor behöva mer information om påverkan av plötslig död hos närstående för att täcka kunskapsluckan. / Background: In the healthcare profession it is inevitable for nurses to meet death and there is a difference between expected death and unexpected death. The death for the next of kin who loses a loved one in sudden death can be perceived as an traumatic experience. A crisis reaction can take place and the next of kin will be in need of emotionally care from the healthcare. It also shows other types of support who can relieve the suffering. Aim: The aim of this study was to describe the importance of emotional support to relieve the suffering of the next of kin who lost a person in sudden death. Method: The chosen design for this study was a non-systematic literature review, the articles have been analyzed through integrated analysis. The study was based on 35 scientific articles and 17 of the articles was included in the result, from databases CINAHL and PubMed. Results: Results showed that emotionally care can have significance for suffering of the next of kin. They experienced a emotional impact which included fear, problem to sleep and behavioral changes. Suffering, support and communication where reported as important factors. When the nurses showed humanity and where open to death, it did improve the health for the next of kin. Conclusions: The next of kin may need emotional care after an unexpected death of a person, because it shows relieve suffering. For that reason, nurses may require more information on the impact of the sudden death of next of kin to cover the knowledge gap.

Bakgrund: Många dödsfall sker idag på sjukhus och detta indikerar att sjuksköterskor mest troligt kommer att uppleva plötsliga eller oväntade dödsfall någon gång under deras yrkesverksamhet. Syfte: Syftet med litteraturstudien var att beskriva sjuksköterskor upplevelser när patienter plötsligt eller oväntat dör på sjukhus. Metod: En litteraturstudie genomfördes baserad på åtta kvalitativa studier. Databassökning genomfördes i CINAHL och PubMed. Analys genomfördes enligt Fribergs femstegsmodell. Resultat: Vid analysen framkom fem teman. De fem teman var: Sjuksköterskans känslor och reaktioner vid plötsligt eller oväntat dödsfall, Hinder vid omhändertagande av patienter och anhöriga, Sjuksköterskans hantering av plötsligt eller oväntat dödsfall, Kommunikation - en viktig men krävande uppgift och Bristfällig utbildning. Konklusion: Sjuksköterskor upplever att plötsliga eller oväntade dödsfall är svåra att hantera. För att klara av denna svåra uppgift kan sjuksköterskor behöva kompetensutveckling i form av utbildning samt informellt och formellt stöd. Vidare forskning inom detta problemområde skulle kunna bidra till en ökad förståelse gällande hur sjuksköterskor upplever, hanterar samt påverkas av plötsliga eller oväntade dödsfall. / Background: Many deaths occur today in hospitals and this indicates that nurses are most likely to experience sudden or unexpected deaths at some point during their professional worklife. Aim: The aim of this litterature study was to describe nurses' experiences when patients die suddenly or unexpectedly in hospital. Methods: A literature study was conducted based on eight qualitative studies. The database search was conducted in CINAHL and PubMed. Fribergs five-step model was used to analyze the studies. Results: Five themes emerged during the analysis. The themes were: The nurse's feelings and reactions in the event of a sudden or unexpected death, Obstacles when caring for patients and relatives, The nurse's management of a sudden or unexpected death, Communication - an important but demanding task and Inadequate education. Conclusion: Nurses find that sudden or unexpected deaths are difficult to deal with. To cope with this difficult task, nurses need competence development in the form of education as well as informal support. Further research regarding this subject could contribute to an increased understanding of how nurses experience, manage and are affected by sudden or unexpected deaths.

Doctor of Public Health / For many years the major cause of infant mortality in NSW has been the result of Sudden Infant Death Syndrome (SIDS). Statistics show the area defined as 'Western Sydney' is no exception, and in 2002, a report prepared by the Epidemiology, Indicators, Evaluation and Research Unit (EIRE) in Western Sydney presented data indicating SIDS rates in the area were higher than the state average. In particular, two Local Government Areas (LGAs) had clusters of SIDS deaths. Previous Australian research identified a higher risk of SIDS and other causes of infant mortality in Aboriginal and Torres Strait Islander populations. The areas of Western Sydney where SIDS rates were higher than expected were home to Aboriginal, Torres Strait Islander and Pacific Island residents. The number of SIDS deaths in Aboriginal infants did not explain the higher than expected rate of SIDS in the areas under investigation. Studies undertaken in New Zealand and the Pacific Islands have identified higher than expected risk of SIDS in Maori and Pacific Island communities in those countries, although this has never been studied in Pacific Island residents living in Australia. The reasons for these communities exhibiting a higher than normal SIDS rate is not completely understood, but can be partially explained by behavioural practices which are known to impact adversely on the risk of SIDS. This study sought to investigate the level of knowledge concerning the prevention of sudden and unexpected death in infants (SUDI) in three key groups of infant caregivers: general practitioners, nurses and parents living or working in the area geographically defined by Sydney West Area Health Service (WSAHS). In addition, the study sought to identify any variation in knowledge of SIDS reduction strategies in the three groups under study, and to investigate factors influencing knowledge and practice in these participants. The study findings were then used as a basis on which to develop strategies and recommendations to enhance the delivery of safe sleeping messages through the health care system. Using a combination of qualitative and quantitative methods, this cross-sectional study highlights a number of issues around infant care practices and the major influences on new parents living in a multicultural community. Results of the study showed there is a large variation in knowledge around safe sleeping practices (including SIDS reduction strategies) in all the groups studied. Although educational campaigns are conducted regularly, many general practitioners and parents are confused about the key SIDS reduction messages and still place infants in sleeping positions considered unsafe. While nurses and midwives were aware of the SIDS reduction strategies, they still occasionally used infant sleeping positions considered unsafe. General practitioners born overseas in a country where English is not the first language were less likely to be familiar with safe sleeping messages, including SIDS reduction strategies. Families from a Culturally and Linguistically Diverse (CALD) background were less likely to have seen SIDS information in their own language than families who spoke English, and as a result were more likely to use traditional methods of infant care, including co-sleeping with siblings and parents and side or tummy sleeping. CALD parents were more likely to rely on herbal remedies and friends and family for assistance, than English speaking parents who accessed health professionals as the first point of call when infants were unwell. The study identified a relatively recent practice, which until reported in this study, has not been documented in the literature. The practice of draping infant prams with blankets originated from the Cancer Council of Australia guidelines which recommend covering a pram with a light muslin wrap to protect infants’ skin from the sun. It appears parents have misinterpreted this message and are covering infant prams with blankets to encourage sleep, even when sun exposure is not an issue. Research suggests that poor air quality around the head of an infant may affect an infant’s arousal response. While no research has been conducted on the air quality around an infants head when covered by a heavy blanket in a pram, it is possible based on research into air quality around infants, that that this practice may increase the risk of sudden and unexpected death in an infant. In conclusion, this study found that multiple changes to the SIDS reduction messages since the initial ‘Reduce the Risks’ Campaign have led to confusion about ways of preventing SIDS in GPs, nurses and parents in Western Sydney. The study makes seven recommendations aimed at improving knowledge of safe sleeping practices in these groups, and optimizing health outcomes for infants using a collaborative approach to service delivery and future initiatives.

Abstract Autonomic dysfunction in epilepsy is widely recognized. Both partial and generalized epilepsies affect autonomic functions during interictal, ictal and postictal states. Interestingly, there is increasing evidence of interictal autonomic nervous system dysfunction as evidenced by reduced heart rate (HR) variability in patients with epilepsy. Reduced HR variation has also been detected in many other chronic diseases and it has been shown to be associated with unfavourable prognosis with an increased risk of mortality in various heart diseases. Recently, more attention has also been paid to possible association of decreased HR variability with sudden unexpected death in epilepsy (SUDEP). However, the clinical significance of the observed changes in cardiovascular regulation in patients with epilepsy is still poorly outlined and there are no long-term studies about changes in HR variation in relation to epilepsy. This study was designed to evaluate long-term changes in autonomic cardiovascular regulation in patients with temporal lobe epilepsy (TLE) and also to evaluate HR variation during vagus nerve stimulation (VNS) treatment in patients with refractory epilepsy, using 24-hour ambulatory ECG recordings. Special attention was paid to changes in HR variation and to circadian HR fluctuation over time. The results of this study show that autonomic cardiovascular regulation is affected both in patients with well-controlled TLE and in patients with refractory TLE, and that the cardiovascular dysregulation also presents itself with changes in circadian HR variability, with more pronounced alterations observed during the night time. HR variability was also found to decrease progressively with time in patients with chronic refractory TLE with uncontrolled seizures. VNS treatment was not observed to alter HR variation. / Tiivistelmä Epilepsiapotilailla esiintyy autonomisen hermoston toiminnan häiriöitä. Näitä häiriöitä voidaan todeta epilepsiakohtausten aikana, heti kohtausten jälkeen ja kohtausten välillä sekä paikallisalkuisissa että yleistyneissä epilepsioissa. Viimeaikaisissa tutkimuksissa on osoitettu kardiovaskulaarisen säätelyjärjestelmän häiriöiden voivan ilmentyä alentuneena sydämen sykevaihteluna epilepsiakohtausten väliaikoina. Sydänsairauksien yhteydessä sykevaihtelun vähenemisen on osoitettu liittyvän kohonneeseen kuolemanriskiin. Epilepsiapotilailla alentuneen sydämen sykevaihtelun on epäilty liittyvän epilepsiapotilailla ilmenevien odottamattomien ja ilman selkeää syytä tapahtuvien äkkikuolemien (SUDEP) lisääntyneeseen riskiin. Kertyneestä tiedosta huolimatta alentuneen sykevaihtelun kliininen merkitys epilepsiapotilailla on edelleen epäselvä. Pitkäaikaisseurantatutkimuksia sydämen sykevaihtelun muutoksista epilepsiapotilailla ei ole julkaistu. Tämän tutkimuksen tarkoituksena oli selvittää ohimolohkoepilepsiaan liittyviä pitkäaikaisia interiktaalisia (kohtausten välillä esiintyviä) kardiovaskulaarisia ilmentymiä. Lisäksi haluttiin tutkia vaikeahoitoisessa epilepsiassa käytetyn hoitomuodon, vagushermostimulaation, mahdollisia vaikutuksia sydämen toimintaan. Erityisesti haluttiin analysoida sykevaihtelun vuorokausirytmiä. Tulokset osoittavat autonomisen hermoston kardiovaskulaarisen säätelyjärjestelmän toiminnan olevan häiriintyneen sekä vaikeahoitoisilla että hyvähoitoisilla ohimolohkoalkuista epilepsiaa sairastavilla potilailla. Sydämen sykevariaatio on alentunut erityisesti yöaikaan. Lisäksi sydämen sykevaihtelu alenee pitkäaikaisseurannassa vaikeahoitoista epilepsiaa sairastavilla potilailla, joilla ilmenee toistuvia epileptisiä kohtauksia. Vagusstimulaatio ei aiheuttanut muutoksia syketaajuuden vaihteluun.

Thesis (MScMedSc)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Background: Sudden infant death syndrome (SIDS) is considered the second most frequent cause of infant mortality worldwide. Research specifically pertaining to SIDS is limited in the South African setting. Identifiable causes for sudden infant death remain challenging despite full medico-legal investigations inclusive of autopsy, scene visit and ancillary studies. Viral infections could contribute to some sudden unexpected death in infancy (SUDI) cases, especially since a multitude of respiratory viruses have been detected from autopsy specimens. The specific contribution of viruses in the events preceding death, including the subsequent involvement of the immature immune response in infants, still warrants deciphering. Infancy is characterised by marked vulnerability to infections due to immaturities of their immune systems that may only resolve as infants grow older when these sudden deaths rarely still occur. In South Africa there is a lack of a standard protocol for investigations into the causes of SIDS, including the lack of standard guidelines as to which specimens should be taken, which viruses should be investigated and which laboratory assays should be utilised. Objectives: In this prospective descriptive study we aimed to investigate the prevalence of viruses in SUDI and SIDS cases at Tygerberg Forensic Pathology Service (FPS) Mortuary over a one year period. The primary aim was to explore possible respiratory viral infections in SUDI and SIDS cases and to determine the usefulness of molecular techniques to detect viruses from SUDI cases. To determine the significance of viruses, we assessed signs of infection from lung histology. The secondary objectives included collecting demographic data to investigate possible risk factors for SUDI and to look for possible similarities between viruses confirmed in living hospitalised infants at Tygerberg, during the study period compared to viruses detected from SUDI cases. Methods: Between May 2012 and May 2013 samples were collected from 148 SUDI cases presenting at Tygerberg FPS Mortuary. As part of the mandatory routine investigations into SUDI, shell vial culture (SVC) results were collected from lung and liver tissue specimens and bacterial culture results were collected from left and right lung and heart swabs at autopsy. To investigate the possibility of viruses implicated in some of the infant deaths we used the Seeplex® RV15 Ace detection multiplex polymerase chain reaction (PCR) assay to establish the frequency of 13 ribonucleic acid (RNA) respiratory viruses (influenza A and B, human parainfluenza 1-4, human coronavirus [OC43, 229E/NL63], human rhinovirus A, B and C, respiratory syncytial virus A and B, human enterovirus and human metapneumovirus) from RNA extracted from tracheal and lower left and right lung lobe swabs. Tissue from the lower left and right lung lobes were also assessed for histology signs of infection. Results: During our study we confirmed multiple known demographic risk factors for SIDS, such as the age peak around 1-3 months, the male predominance, bed-sharing, sleeping in the prone position, heavy wrapping in warm blankets, prenatal smoke exposure, and socio-economic factors. With the Seeplex® RV15 Ace detection assay between one and three viruses were detected in 59.5% (88/148) of cases. Of the 88 cases that had viruses detected, 75% (66/88) had one virus and 25% (22/88) had co-detections of two to three viruses. The most common viruses detected were HRV in 77% (68/88) of cases, RSV in 18% (16/88) of cases and HCoV in 14% (12/88) of cases. Many of the viruses we detected from our cases are included in the SVC test that forms part of the medico-legal laboratory investigation for all SUDI cases at Tygerberg FPS Mortuary. SVCs were positive in 9.5% (14/148) of all cases only. We showed that the SVC method is potentially missing most of the 13 respiratory viruses we investigated that could contribute to death in some of the SUDI cases. Conclusion: In some cases that had a Cause of Death Classification - SIDS, the PCR viruses detected cannot be ignored, especially when it is supported by histological evidence of infection. We thus propose that the use of PCR could alter a Cause of Death Classification from SIDS to Infection in some of these cases. Further research is needed to determine the significance of detecting viruses from SUDI cases wherein no significant histological evidence of infection was observed. This questions whether PCR may be too sensitive and is detecting past and latent viral infections that do not play any role in the cause of death. The histological picture also requires further characterisation to determine if it accurately predicts infections or lethal events and can truly support virology findings, especially in young infants whose immune systems are still maturing. Without determining the true prevalence of viruses in SUDI cases and the viral-specific immune response, the contribution of virus-specific infections to this syndrome will remain largely undetermined. / AFRIKAANSE OPSOMMING: Agtergrond: Wiegiedood (“SIDS/SUDI”) word beskou as die tweede mees algemene oorsaak van sterftes in kinders jonger as een jaar wêreldwyd. Toegewyde SIDS-spesifieke navorsing in die Suid-Afrikaanse samelewing is beperk. Dit bly steeds „n uitdaging om oorsake te probeer identifiseer vir hierdie onverwagte sterftes in kinders (SUDI) ten spyte van volledige medies-geregtelike ondersoeke, insluitende die lykskouing, ondersoek van die doodstoneel en aanvullende ondersoeke. Virusinfeksies kan aansienlik bydra tot sommige onverwagte sterftes in kinders, aangesien verskeie respiratoriese virusse alreeds aangetoon is in monsters verkry tydens outopsies. Die spesifieke rol wat virusse speel in die prosesse wat die dood voorafgaan, asook die bydraende rol van „n onder-ontwikkelde immuunrespons in babas, regverdig verdere ondersoek. Die eerste jaar van lewe word gekenmerk deur verhoogde vatbaarheid vir infeksies weens die ontwikkelende immuunstelsels soos wat babas ouer word, en die voorkoms van SUDI neem stelselmatig af met „n toename in ouderdom. In Suid-Afrika bestaan daar tans geen standaard protokol vir die ondersoek van wiegiedood nie en daar is ook nie standaard riglyne oor die tipe monsters wat geneem moet word, watter virusse ondersoek moet word en watter laboratorium toetse uitgevoer moet word nie. Doelstellings: In hierdie prospektiewe beskrywende studie is gepoog om die virusse wat in gevalle van wiegiedood of SUDI voorkom te ondersoek. Die studie is uitgevoer by die Tygerberg Geregtelike Patologie Dienste lykshuis oor 'n tydperk van een jaar. Molekulêre tegnieke om virusse aan te toon in hierdie gevalle is gebruik om spesifieke virusinfeksies te ondersoek. Die resultate is met histologiese tekens van infeksie in longweefsel gekorreleer. Demografiese data is verder versamel om moontlike risikofaktore vir wiegiedood te ondersoek. Dit is verder vergelyk met virusse wat met dieselfde diagnostiese tegnieke in babas geïdentifiseer is wat tydens die studieperiode in Tygerberg Hospitaal opgeneem was met lugweginfeksies. Metodes: Monsters van 148 SUDI gevalle wat by die Tygerberg lykshuis opgeneem is, is versamel tussen Mei 2012 en Mei 2013. As deel van die roetine ondersoeke in SUDI gevalle, was selkultuur resultate verkry van long en lewer weefsel, asook bakteriële kulture van deppers wat van beide longe en hart geneem was tydens die lykskouings. „n Seeplex® RV15 Ace polimerase kettingreaksie (PKR) toets is gebruik om die teenwoordigheid van virusse te ondersoek wat moontlik by die babasterftes betrokke kon wees. Trageale- en longdeppers wat tydens die lykskouings versamel was, was getoets vir 13 ribonukleïensure (RNS) respiratoriese virusse (influenza A and B, human parainfluenza 1-4, human coronavirus [OC43, 229E/NL63], human rhinovirus A, B and C, respiratory syncytial virus A and B, human enterovirus and human metapneumovirus). Resultate: Ons studie het verskeie bekende demografiese risikofaktore vir SUDI bevestig, byvoorbeeld „n ouderdomspiek tussen een en drie maande ouderdom, manlike predominansie, deel van „n bed met ander persone, slaap posisie op die maag, styf toedraai in warm komberse, blootstelling aan sigaretrook voor geboorte en sosio-ekonomiese faktore. Die Seeplex® RV15 Ace toets het tussen een en drie virusse geïdentifiseer in 59.5% (88/148) van die gevalle. Uit die 88 gevalle waarin virusse opgespoor was, was selgs een virus in 75% (66/88) van gevalle gevind en twee en drie virusse in 25% (22/88). Die mees algemene virusse was HRV in 77% (68/88) van gevalle, RSV in 18% (16/88) van gevalle en HCoV in 14% (12/88) van gevalle. Baie van die virusse wat tydens hierdie studie ondersoek was, was ingesluit in die roetine selkultuur toets wat deel vorm van die standaard medies-geregtelike laboratoriumondersoeke in alle SUDI gevalle by die Tygerberg lykshuis, alhoewel die selkulture positief was in slegs 9.5% (14/148) van gevalle. Ons het gevind dat baie respiratoriese virusse potensieel gemisdiagnoseer word wat „n rol kon speel in of bydra tot die dood van sommige SUDI gevalle. Gevolgtrekking: In sommige gevalle waarin SIDS geklassifiseer is as die oorsaak van dood, kan die virusse wat met PKR toetse opgespoor is nie geïgnoreer word nie, veral waar die bevinding ondersteun word deur histologiese bewyse van infeksie. Ons stel dus voor dat die gebruik van PKR toetse die oorsaak van dood klassifikasie kan verander van SIDS na Infeksie in sommige van hierdie gevalle. Verdere navorsing is nodig om die waarde van gelyktydige opsporing van virusse in SUDI gevalle te bepaal wanneer daar geen noemenswaardige histologiese bewyse van infeksie gevind word nie. Dit bevraagteken of die PKR toets dalk te sensitief is en gevolglik vorige en latente virusinfeksies identifiseer wat nie noodwendig 'n rol in die oorsaak van dood speel nie. Die diagnostiese en kliniese waarde van die histologiese beeld in terme van die rol van virusinfeksies as bydraende oorsaak van dood moet verder ondersoek word, veral in jong kinders wie se immuunstelsels nog nie volledig ontwikkel is nie. Indien die werklike voorkoms van virusse in SUDI gevalle en die virus-spesifieke immuunrespons nie bepaal word nie, sal die rol van virus-spesifieke infeksies in hierdie sindroom grootliks onbekend bly. / Harry Crossley Foundation / Poliomyelitis Research Foundation (PRF) / National Health Laboratory Services Research Trust

La mort soudaine inattendue (SUDEP) est fréquemment rapportée chez les patients qui souffrent d'épilepsie et compte pour près de 17% des décès dans cette population. Bien que son étiologie soit restée longtemps incertaine, des études menées sur des cas de victimes de SUDEP suggèrent fortement l'implication de l'apnée post-ictale dans la survenue de ce type de décès. Afin d'élucider les mécanismes physiopathologique de la SUDEP, il était nécessaire de mettre en place un modèle animal qui présente à la fois des crise spontanées récurrentes comme dans le syndrome épileptique et des altérations respiratoires. Dans une première partie, nous mettons en évidence la présence d'altérations respiratoires (RAs) chez 30 à 50% des rats qui présentent une épilepsie suite à un état de mal épileptique (SE) induit par l'administration de pilocarpine. Ces RAs, que nous avons assimilées à des apnées, ont été mises en évidence par thermochimie respiratoire et se traduisent par une diminution de la consommation en oxygène, dont la durée peut varier entre 20 secondes et 13 minutes. La présence des RAs est associée à des altérations du système sérotoninergique au niveau du tronc cérébral, où sont concentrés la majorité des groupes de neurones impliqués dans la régulation et dans la modulation de la fonction respiratoire. Nous montrons que de nombreux gènes du système sérotoninergique sont dérégulés lors de la mise en évidence des RAs ; toutefois, seules les altérations touchant le récepteur 5-HT2c semblent être associées au maintien des RAs. Ce résultat est d'autant plus important qu'il avait été montré que la délétion de ce récepteur chez les souris peut conduire à un arrêt respiratoire fatal suite à une crise épileptique, provoquée ou spontanée. Dans une seconde partie, nous montrons que la surface de la zone présentant un hypersignal T2 dans le système limbique ventral des rats épileptiques est prédictive de la présence de RAs. En outre, des différences d'expression du récepteur 5-HT2c similaires à celles qui avaient été observées dans le tronc cérébral sont retrouvées entre les rats épileptiques selon qu'ils présentent ou pas des RAs. Les résultats de cette thèse impliquent donc le récepteur 5-HT2c dans la survenue et/ou le maintien des altérations respiratoires associées à l'épilepsie. Dans le contexte de la SUDEP, nos résultats ouvrent comme première perspective clinique celle de développer des traitements permettant de cibler spécifiquement le récepteur 5-HT2c chez les patients qui présenteraient un risque de survenue de la SUDEP. La seconde perspective clinique serait de pouvoir identifier ces patients à risque à partir de biomarqueurs tels que les anomalies de signal T2 que nous avons identifiées dans la région limbique ventrale qui inclut notamment l'insula, dont il a été montré qu'elle contribue à la modulation de la fonction respiratoire / Pas de résumé anglais