The study evaluated whether the activity of the indoleamine 2,3 dioxygenase (IDO) enzyme is increased post-stroke and contributes to the development of post-stroke depression (PSD) via tryptophan (TRP) depletion and neurotoxic kynurenine (KYN) metabolite production. The activity of IDO was measured using the KYN/TRP ratio. Participants were assessed for depression severity using the Center for Epidemiological Studies Depression Scale (CES-D). Blood TRP, KYN, large neutral amino acids and cytokines were measured and compared. Fifty-four (mean age=69.9±15.2, male=52.7%, mean NIHSS=7.3±4.6) patients within 28.9±40.3 days of stroke were separated into two groups: non-depressed (n=38, CES-D=6.1±4.9) and those with significant depressive symptoms (n=16, CES-D=26.8±10.8). Higher mean KYN/TRP ratios were demonstrated in stroke patients with depressive symptoms (non-depressed=69.3±36.9 vs. depressive symptoms=78.3±42.0, F3,50=4.61, p=0.006) after controlling for LNAA (p=0.026) and hypertension (p=0.039). As the KYN/TRP ratio reflects decreased TRP and increased neurotoxic KYN metabolites, both mechanisms may play an etiological role in PSD.

The study evaluated whether the activity of the indoleamine 2,3 dioxygenase (IDO) enzyme is increased post-stroke and contributes to the development of post-stroke depression (PSD) via tryptophan (TRP) depletion and neurotoxic kynurenine (KYN) metabolite production. The activity of IDO was measured using the KYN/TRP ratio. Participants were assessed for depression severity using the Center for Epidemiological Studies Depression Scale (CES-D). Blood TRP, KYN, large neutral amino acids and cytokines were measured and compared. Fifty-four (mean age=69.9±15.2, male=52.7%, mean NIHSS=7.3±4.6) patients within 28.9±40.3 days of stroke were separated into two groups: non-depressed (n=38, CES-D=6.1±4.9) and those with significant depressive symptoms (n=16, CES-D=26.8±10.8). Higher mean KYN/TRP ratios were demonstrated in stroke patients with depressive symptoms (non-depressed=69.3±36.9 vs. depressive symptoms=78.3±42.0, F3,50=4.61, p=0.006) after controlling for LNAA (p=0.026) and hypertension (p=0.039). As the KYN/TRP ratio reflects decreased TRP and increased neurotoxic KYN metabolites, both mechanisms may play an etiological role in PSD.

Bakgrund: Fatigue (hjärntrötthet) är ett tillstånd som kan uppkomma till följd av exempelvis en stroke och förklaras som en extrem trötthet som inte går att vila bort. Detta är ett tillstånd som många gånger kan upplevas som ett problem efter en stroke. Syfte: Att belysa hur det är att leva med fatigue till följd av stroke. Metod: En litteraturstudie bestående av nio vetenskapliga artiklar med kvalitativ ansats genomfördes för att besvara syftet. Artiklarna kvalitetsgranskades och en innehållsanalys av artiklarnas resultat utfördes. Resultat: Post-stroke fatigue kunde upplevas påfrestande och inverkade negativt på livet. Sömn och vila tog upp mycket tid och nya rutiner krävdes för att orka med det vardagliga livet. Det blev svårare att upprätthålla samma sociala liv som tidigare. Informationen som gavs till patienterna upplevdes som bristfällig och vårdpersonalen kunde uppfattas okunniga om fatigue till följd av stroke. De personer som hade en ökad kunskap om fatigue kunde lättare hantera och anpassa sig till situationen. Slutsats: Att arbeta personcentrerat kan underlätta för att upptäcka vårdbehovet av fatigue. För att upptäcka vårdbehovet kan en större kunskap hos sjuksköterskorna behövas än vad patienterna upplever att de har. Kunskapen om post-stroke fatigue kan utökas genom att implementera det i sjuksköterskeutbildningen.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21669号 / 医博第4475号 / 新制||医||1035(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 村井 俊哉, 教授 古川 壽亮, 教授 宮本 享 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Aims: a review of the literature on non-pharmacological interventions for post-stroke depression (PSD) was completed with the aim of examining issues regarding the design and methodology of trials for non-pharmacological interventions for PSD. The empirical research study used a constructivist Grounded Theory approach to explore specialist stroke professionals' conceptualisations of post-stroke emotional lability (PSEL). The author also aimed to examine how staff experienced, understood and identified PSEL in clinical practice, and particularly how they differentiated it from PSD. Method: A systematic review of RCT and non-RCT studies was conducted to address the first aim. In relation to the second aim, a qualitative investigation of specialist professionals' conceptualisations of PSEL was conducted using Charmaz' (2006) version of constructivist Grounded Theory. Results: The systematic review highlighted the importance of appropriate sampling methods, multiple treatment design, rigorous data collection, the implementation and monitoring of interventions, assessment of participant suitability for the intervention, and issues related to long-term sustainability (follow-up) when designing and evaluating non-pharmacological interventions for PSD. The qualitative investigation yielded a conceptual model of how specialist professionals conceptualise and identify PSEL in their clinical practice. Conclusions and implications: The findings from the systematic review and the qualitative investigation highlighted a range of issues for specialist stroke services. The systematic review emphasised the importance of further evaluation and consideration of carefully planned randomised controlled trials for investigating non-pharmacological interventions for PSD. The qualitative study indicated a need for further guidance on the assessment and identification of PSEL, training for staff, and further examination of the caused of PSEL.

Background Stroke is a major cause of disability worldwide. After treatment in a specialized stroke unit, early supported discharge (ESD) followed by home rehabilitation has shown to be an effective way to improve patient outcome and quality of care for persons with mild to moderate stroke. ESD service is recommended in the national and international guidelines for stroke care, but has only partially been implemented in Sweden. Following stroke, fatigue is a common consequence that often becomes more evident when the patient comes home. Currently, there is insufficient evidence about how to measure, treat and handle post-stroke fatigue. The overall aim of this thesis was to evaluate and implement early supported discharge (ESD) based on stroke patients experience after discharge from the stroke unit and local conditions. The aim was also to evaluate post-stroke fatigue with a potentially valid and reliable scale and finally to prepare for a study to evaluate cardiorespiratory training as a part of ESD service for patients with post-stroke fatigue. Methods In paper I, nine strategically chosen patients were interviewed of their experience of falling ill, the hospital stay, discharge, contact with health care after discharge and their request of support. Papers II-III describe and evaluate the development, content, implementation and effects of a locally adopted method for early supported discharge (Umeå Stroke Center ESD) in modern stroke care. Paper II included 153 consecutive patients and paper III, 30 232 patients with first-ever stroke registered in the Riksstroke registry in Sweden. Paper II evaluated number of patients/year, clinical and functional health status, satisfaction in relation to needs, accidental falls/other injuries and resources with the result summarized in a value compass. The implementation process was evaluated retrospectively by means of Consolidated Framework for Implementation (CFIR). Paper III evaluated patient reported outcome measurements (PROMs) at 3 months. The primary outcome in paper III was satisfaction with the rehabilitation after discharge. Secondary outcomes were information about stroke provided, tiredness/fatigue, pain, dysthymia/depression, general health status and dependence in activities of daily living (mobility, toilet hygiene and dressing). Multivariable logistic regression models for each PROM was used to analyze associations between PROMs and ESD/no ESD. In Paper IV, the Fatigue Assessment scale (FAS) was translated into Swedish and evaluated regarding psychometric properties when self-administered by persons with mild to moderate stroke. 72 consecutively patients selected from the stroke unit admission register received a letter including three questionnaires: the FAS, the Short Form Health Survey (SF-36) subscale for vitality and the Geriatric Depression Scale GDS-15. A second letter with FAS was sent within 2 weeks, for re-test evaluation. Paper V is a study protocol for a planned randomized controlled trial (RCT) of 50 consecutive stroke patients will who receive stroke unit care followed by ESD-service at Umeå Stroke Center, University Hospital, Umeå, Sweden. Paper V will investigate if a structured cardiorespiratory interval training program (CITP) added to the ESD-service may result in relieved post-stroke fatigue and increased oxygen uptake. Results The interviews in Paper I revealed three main categories with subcategories: “Responsible and implicated”, “Depersonalized object for caring measures” and “The striving for repersonalization and autonomy”. The findings indicate that coming home gave the informants’ important insights and understanding of the stroke, its consequences and was also an important factor for the recovery. Paper II-III showed that it is possible to develop and implement an adapted ESD service for stroke patients based on the patients’ experiences and requests, evidence-based recommendations and local conditions. The ESD service reduced dependence of activity, increased mobility with seemingly no increased risk of accidental falls or other injuries. The patient satisfaction in relation to needs regarding the ESD was high. Paper III showed that patients that received ESD were more satisfied with rehabilitation after discharge, had less need for assistance with ADL and less dysthymia/depression compared to patients that did not receive ESD. Study IV showed that the Swedish FAS used at home as a selfadministered questionnaire is a reliable and valid questionnaire for measuring fatigue in persons with mild to moderate stroke. The internal consistency was good, the agreement between the test and retest reliability for individual items (weighted kappa) was for the majority of items good or moderate. The relative reliability for total scores was good and the absolute reliability was 9 points. The Swedish FAS had no floor nor ceiling effects and correlated both with the SF-36, subscale for vitality and the GDS-15 indicating convergent construct validity, but not divergent construct validity. Conclusion It is possible to develop and implement ESD care for stroke patients based on patients’ experience and needs, evidence-based principles and local conditions. Early supported discharge (ESD) in the setting of modern stroke unit care appears to have positive effects on rehabilitation in the subacute phase. The Swedish FAS used at home as a self-administered questionnaire is reliable and valid for measuring fatigue in persons with mild to moderate stroke.

This cross-sectional study examined neurobiologic correlates of depression in ischemic stroke patients. Depression severity was measured with a standardized scale (Center for Epidemiologic Studies Depression Scale; CES-D). Eighty-two patients (53.1% male, mean (± SD) age 71.9 ± 14.2 years, mean (± SD) National Institutes of Health Stroke Scale (NIHSS) score 4.6±4.7, mean (± SD) CES-D score 12.6 ± 10.8) were recruited. A linear regression controlling for age and stroke severity (NIHSS) determined that the kynurenine to tryptophan ratio (β= -0.105, p=0.369) was not significantly associated with CES-D (primary hypothesis) (overall model R2=0.069, F3,73=1.805, p=0.154). Secondary analyses suggested one instance of cytokines favouring inflammatory states in mild depressive symptomatology; IFN-Ɣ/IL-10 (OR, 2.17; 95% CI, 1.02-4.64, p=0.045). For the most part however, inclusion of cytokines and neuroimaging correlates such as atrophy, lesion location and white matter changes were non-significant. Longitudinal studies are necessary to identify the possible neurobiologic correlates of depressive symptoms post-stroke.

This cross-sectional study examined neurobiologic correlates of depression in ischemic stroke patients. Depression severity was measured with a standardized scale (Center for Epidemiologic Studies Depression Scale; CES-D). Eighty-two patients (53.1% male, mean (± SD) age 71.9 ± 14.2 years, mean (± SD) National Institutes of Health Stroke Scale (NIHSS) score 4.6±4.7, mean (± SD) CES-D score 12.6 ± 10.8) were recruited. A linear regression controlling for age and stroke severity (NIHSS) determined that the kynurenine to tryptophan ratio (β= -0.105, p=0.369) was not significantly associated with CES-D (primary hypothesis) (overall model R2=0.069, F3,73=1.805, p=0.154). Secondary analyses suggested one instance of cytokines favouring inflammatory states in mild depressive symptomatology; IFN-Ɣ/IL-10 (OR, 2.17; 95% CI, 1.02-4.64, p=0.045). For the most part however, inclusion of cytokines and neuroimaging correlates such as atrophy, lesion location and white matter changes were non-significant. Longitudinal studies are necessary to identify the possible neurobiologic correlates of depressive symptoms post-stroke.

Understanding the underlying coordination mechanisms that lead to a patient’s poor walking performance is critical in developing effective rehabilitation interventions. However, most common measures of rehabilitation effectiveness do not provide information regarding underlying coordination mechanisms. The overall goal of this research was to analyze the relationship between two potential measures of walking performance (step length asymmetry and module composition) and underlying walking mechanics. Experimental analyses were used to analyze the walking mechanics of hemiparetic subjects grouped by step length asymmetry. All groups had impaired plantarflexor function and the direction of asymmetry provided information regarding the compensatory mechanism used to overcome this plantarflexor impairment. Those subjects who walked with longer paretic than nonparetic steps compensated using increased output from the nonparetic leg, while those with symmetric steps compensated using a bilateral hip strategy. These results suggest that step length asymmetry may provide information regarding underlying coordination mechanisms that can be used to guide rehabilitation efforts. Another way to assess walking performance is to directly analyze deficits in muscle coordination. Recent studies have suggested that complex muscle activity during walking may be generated using a reduced neural control strategy organized around the co-excitation of multiple muscles, or modules, which may provide a useful framework for characterizing coordination deficits. Simulation analyses using modular control were performed to understand how modules contribute to important biomechanical functions of non-impaired walking and how the generation of these functions is altered in groups of post-stroke hemiparetic subjects who commonly merged different sets of non-impaired modules. The non-impaired simulation found that six modules are needed to generate the three-dimensional tasks of walking (support, forward propulsion, mediolateral balance control and leg swing control). When the plantarflexor module was merged with the module controlling the knee extensors and hip abductors, forward propulsion and ipsilateral leg swing were impaired. When the module controlling the hamstrings was merged with the module controlling the knee extensors and hip abductors, forward propulsion, body support and mediolateral balance control were impaired. These results suggest that module analysis may provide useful information regarding the source of walking deficits and can be used to guide rehabilitation efforts. / text

Stroke är ett akut och livshotande tillstånd som drabbar cirka 30 000 människor i Sverige varje år. Stroke kan leda till fysisk och kognitiv nedsättning men även till psykiska symptom som depression och nedstämdhet. Syftet med studien är att beskriva hur sjuksköterskan kan identifiera strokerelaterad depression samt att främja hälsa hos dessa patienter. Litteraturstudien baseras på en kvalitativ och åtta kvantitativa artiklar som beskriver hur sjuksköterskan i mötet med patienten kan förbättra hälsa. För att sjuksköterskan ska kunna identifiera patienter som drabbats eller ligger i riskzonen för att drabbas av post stroke depression (PSD), studerades olika screeninginstrument, som skulle kunna vara användbara för att identifiera PSD. Många instrument var inte tillrättalagda för att kunna användas på patienter med kognitiv nedsättning, vilket flertalet av de strokedrabbade har. Tidigare kardiovaskulär sjukdom och psykisk ohälsa sågs som en risk för att drabbas av PSD. PSD ger en skadlig påverkan på både den fysiska och den psykiska hälsan, vilket i förlängningen ger en negativ inverkan på livskvaliteten. Socialt stöd från sjuksköterskan främjade livskvalitet hos patienten och dess närstående. Om strokerelaterad depression i ett tidigt skede uppmärksammas och behandlas, så kan den fysiska rehabiliteringen ge ett bättre resultat och därmed förbättra patientens hälsa. Ett problem som sjuksköterskan möter då hon ska identifiera PSD, är tidsbristen i vården, då det ofta krävs en mer tät kontakt för att kunna uppmärksamma skillnader i patientens hälsa. Sjuksköterskan bör inta en lyhörd och följsam roll för att se patientens livsvärld och det som inkluderas i den, så som de närstående och patientens sociala aktiviteter.