Transient Ischemic Attack (TIA) is a prominent risk factor for subsequent stroke, and its associated morbidity, mortality, and health care costs. Studies have demonstrated up to 80% reductions in subsequent stroke rate with prompt, optimized protocols for rapid TIA evaluation and treatment. National Stroke Association (NSA) and American Heart Association (AHA) guidelines have recommended institution of protocols assuring timely completion of the recommended testing, and evaluation by a stroke expert within 48 hours. However, limited literature exists on the implementation of guideline-based care in rural regions, and the few studies related to TIA suggest that barriers including difficulty accessing services and poorly updated TIA knowledge amongst rural, non-neurologist providers exist despite national guidelines. Behavior change theories have suggested that evaluating factors hindering or motivating behavior change may aid in tailoring implementation of guideline-based practices. This descriptive study sought to understand ED health care providers' perceived barriers to implementation of NSA/AHA TIA guidelines in a rural state. All healthcare providers in each of the state's emergency departments were invited by email to complete an online anonymous survey assessing knowledge of present TIA guidelines and perceived barriers to implementation of these guidelines in their practice setting using a modified Barriers and Facilitators Assessment Instrument (BFAI). After completing the knowledge based questions, respondents were presented a brief educational overview of the guidelines to ensure adequate familiarity with the TIA guidelines to complete the BFAI. Thirty-nine respondents completed the survey. Twenty-seven worked at regional or academic medical centers, and 12 worked at critical access hospitals representing the more rural regions of the state. Consistent with prior work, the most notable finding of this study was a low awareness of the present TIA guidelines amongst ED providers, with none of the survey respondents correctly identifying all items consistent with the evaluation guidelines for TIA. In addition to a low awareness of the guidelines, a number of perceived barriers to implementation were identified, which may inform efforts at implementation, and/or offer a model for similar barrier assessment elsewhere.

INTRODUCTION: The association of Sleep-Related Movement Disorders (SRMDs) such as Restless Legs Syndrome (RLS) and Periodic Limb Movements (PLMs) with cerebrovascular disease is underexplored. Emerging evidence links them to vascular disease, for which white matter hyperintensities (WMHs) are a well-recognized biomarker. METHODS: We conducted a cross-sectional hospital-based observational study in which high-risk TIA and minor stroke patients were assessed for vascular risk factors, WMHs and polysomnography-determined sleep variables. RESULTS: Ninety-seven patients were enrolled, of whom 44 completed polysomnography. Twenty-five percent had RLS, which was associated with lower quality of life. Independent of the effect of classical vascular risk factors, PLMs (but not RLS) were associated with WMHs on linear regression analyses (p=0.016). CONCLUSIONS: SRMDs are prevalent after minor stroke/TIA. RLS is associated with poor quality of life, while PLMs are associated with WMHs. Whether PLMs are implicated in the pathogenesis of WMHs or whether WMHs exacerbate PLMs remains uncertain.

Background: The ideal treatment strategy for patients with cryptogenic stroke and patent foramen ovale (PFO) is not yet clear. Previous randomized controlled trials (RCTs) comparing transcatheter PFO closure with medical therapy in patients with cryptogenic stroke to prevent recurrent ischemic stroke showed mixed results. This meta-analysis aims to compare rates of recurrent stroke, transient ischemic attack (TIA) and all-cause mortality with PFO closure and medical therapy vs. medical therapy alone. Methods: PubMed and the Cochrane Center Register of Controlled Trials were searched for studies published through June 2018, comparing PFO closure plus medical therapy versus medical therapy alone. Six RCTs (n = 3750) comparing PFO closure with medical therapy were included in the analysis. End points were recurrent stroke, TIA and all-cause mortality. The odds ratios (OR) with 95% confidence interval (CI) were computed and p < 0.05 was considered as a level of significance. Results: A total of 1889 patients were assigned to PFO closure plus medical therapy and 1861 patients were assigned to medical therapy only. Risk of recurrent stroke was significantly lower in the PFO closure plus medical therapy group compared to medical therapy alone. (OR 0.47, 95% CI 0.33–0.67, p < 0.0001). Rate of TIA was similar between the two groups (OR 0.76, 95% CI 0.52–1.14), p = 0.18). There was no difference in all-cause mortality between two groups (OR 0.73, CI 0.33–1.58, p = 0.42). Patients undergoing PFO closure were more likely to develop transient atrial fibrillation than medical therapy alone (OR: 5.85; CI: 3.06–11.18, p ≤0.0001) whereas the risk of bleeding was similar between the groups (OR: 0.93; CI: 0.55–1.57, p = 0.78). Conclusions: The results of this meta-analysis suggest that transcatheter closure of PFO plus medical therapy is superior to medical therapy alone for the prevention of recurrent cryptogenic stroke. However, PFO closure in these patients has not been shown to reduce the risk of recurrent TIA or all-cause mortality. There is a higher rate of transient atrial fibrillation post PFO closure device placement, the long-term effects of which have yet to be studied.

Background: Early differentiation between transient ischemic attack (TIA) and minor ischemic stroke (MIS) impacts on the patient’s individual diagnostic work-up and treatment. Furthermore, estimations regarding persisting impairments after MIS are essential to guide rehabilitation programs. This study evaluated a combined clinical- and serum biomarker-based approach for the differentiation between TIA and MIS as well as the mid-term prognostication of the functional outcome, which is applicable within the first 24 h after symptom onset. Methods: Prospectively collected data were used for a retrospective analysis including the neurological deficit at admission (National Institutes of Health Stroke Scale, NIHSS) and the following serum biomarkers covering different pathophysiological aspects of stroke: Coagulation (fibrinogen, antithrombin), inflammation (C reactive protein), neuronal damage in the cellular [neuron specific enolase], and the extracellular compartment [matrix metalloproteinase-9, hyaluronic acid]. Further, cerebral magnetic resonance imaging was performed at baseline and day 7, while functional outcome was evaluated with the modified Rankin Scale (mRS) after 3, 6, and 12 months. Results: Based on data from 96 patients (age 64 ± 14 years), 23 TIA patients (NIHSS 0.6 ± 1.1) were compared with 73 MIS patients (NIHSS 2.4 ± 2.0). In a binary logistic regression analysis, the combination of NIHSS and serum biomarkers differentiated MIS from TIA with a sensitivity of 91.8% and a specificity of 60.9% [area under the curve (AUC) 0.84]. In patients with NIHSS 0 at admission, this panel resulted in a still acceptable sensitivity of 81.3% (specificity 71.4%, AUC 0.69) for the differentiation between MIS (n = 16) and TIA (n = 14). By adding age, remarkable sensitivities of 98.4, 100, and 98.2% for the prediction of an excellent outcome (mRS 0 or 1) were achieved with respect to time points investigated within the 1-year follow-up. However, the specificity was moderate and decreased over time (83.3, 70, 58.3%; AUC 0.96, 0.92, 0.91). Conclusion: This pilot study provides evidence that the NIHSS combined with selected serum biomarkers covering pathophysiological aspects of stroke may represent a useful tool to differentiate between MIS and TIA within 24 h after symptom onset. Further, this approach may accurately predict the mid-term outcome in minor stroke patients, which might help to allocate rehabilitative resources.

Idiopathic normal pressure hydrocephalus (INPH) is a dementia treatable by insertion of a cerebrospinal fluid shunt. It has been suggested that INPH has similar pathophysiological mechanisms as cerebrovascular disease, but the vascular risk factor (VRF) profile of INPH patients has not been assessed using a modern epidemiological approach. The cognitive symptoms of INPH resemble the symptoms of depression, but the prevalence of depression among INPH patients is unknown. In addition, few studies investigate the impact of shunting on the quality of life (QoL), and no study has investigated the impact of comorbidity on QoL in INPH patients. The objective of this dissertation was to present the VRF profile of INPH and to investigate the hypothesis that INPH may be a subgroup of vascular dementia. Additional objectives were to assess the prevalence of depression in INPH patients and to investigate the impact of shunting and comorbidities on QoL in INPH. In the first cohort, the prevalence of possible INPH was assessed through clinical and radiological examinations in patients with a transient ischemic attack (TIA), consecutively admitted to the same hospital during 2006-2008. In the second cohort, VRFs, vascular disease and QoL were analysed in INPH patients consecutively shunted 2008-2010 in five out of six neurosurgical centres in Sweden. Patients remaining after inclusion (n=176, within the age-span 60-85 years and not having dementia) were compared to population-based age- and gender-matched controls (n=368, same inclusion criteria as for the INPH patients). Assessed VRFs were: hypertension, diabetes, obesity, hyperlipidemia, psychosocial factors (stress and depression), smoking, alcohol intake, physical activity and, dietary pattern. Cardiovascular, cerebrovascular and peripheral vascular disease as well as QoL were also assessed. Parameters were assessed through questionnaires, clinical examinations, measurements, ECG and, blood samples. In the first cohort, 4% of the TIA patients had clinically and radiologically verified INPH. In the second cohort, VRFs were overrepresented among the INPH patients compared with the controls. The VRFs independently associated with INPH were: hyperlipidemia (Odds ratio (OR): 2.4, 95%CI: 1.4-4.0), diabetes (OR: 2.2, 95%CI: 1.2-3.9), obesity (OR: 5.4, 95%CI: 2.5-11.8) and, psychosocial factors (OR: 5.3, 95%CI: 3.2-8.9). When adding the VRFs that were overrepresented in INPH, although not independently (physical inactivity and hypertension), these six VRFs accounted for 24% of the INPH cases in the elderly population (population attributable risk %: 24). Depression was overrepresented in shunted INPH patients compared to the controls (46% vs. 13%, p&lt;0.001) and the main predictor for low QoL was a coexisting depression (p&lt;0.001). In conclusion, the results of the INPH-CRasH study are consistent with a vascular pathophysiological component of INPH and indicate that INPH may be subgroup of vascular dementia. In clinical care and research, a complete risk factor analysis as well as screening for depression and a measurement for quality of life should be included in the work-up of INPH patients. The effect of targeted interventions against modifiable VRFs and anti-depressant treatment in INPH patients should be evaluated. / Idiopatisk normaltryckshydrocefalus (INPH, från engelskans ”idiopathic normal pressure hydrocephalus”) är en neurokirurgiskt behandlingsbar demens. Behandlingen är att operera in en shunt som dränerar cerebrospinalvätska från ventriklarna. Det har föreslagits att INPH skulle kunna orsakas av liknande patofysiologiska mekanismer som vid cerebrovaskulär sjukdom, men den vaskulära riskfaktorprofilen hos INPH-patienter har aldrig undersökts i en modern epidemiologisk studie. De kognitiva symtomen vid INPH påminner om symtomen vid depression, men prevalensen av depression hos INPH-patienter är okänd. Få studier undersöker hur shuntning påverkar livskvalitet och ingen studie har undersökt hur komorbiditet påverkar livskvaliteten vid INPH. Syftet med den här avhandlingen var att undersöka den vaskulära riskfaktorprofilen hos INPH-patienter samt att utforska hypotesen att INPH skulle kunna vara en undergrupp till vaskulär demens. Ytterligare ett syfte med avhandlingen var att undersöka hur många INPH-patienter som har depression samt undersöka hur shunting och komorbiditet påverkar livskvalitet vid INPH. I den första kohorten undersöktes kliniska och radiologiska fynd som tydde på INPH hos de patienter som blivit diagnostiserade med en TIA (från engelskans: transient ischemic attack) 2006-2008 på Norrlands Universitetssjukhus i Umeå. I den andra kohorten undersöktes konsekutivt shuntade INPH-patienter 2008-2010 från fem av sex neurokirurgiska kliniker i Sverige. De patienter som inkluderades i studien (n=176, ålder: 60-85 år, ej dementa) jämfördes med köns- och åldersmatchade kontroller från normalpopulationen (n=368, samma inklusionskriterier som för INPH-patienterna). De riskfaktorer som undersöktes var: hypertension, hyperlipidemi, diabetes, fetma, psykosociala faktorer (stress och depression), rökning, alkohol, fysisk aktivitet och diet. Även kardiovaskulära och cerebrovaskulära sjukdomar undersöktes, liksom perifer vaskulär sjukdom samt livskvalitet. Datainsamling skedde genom frågeformulär, kliniska undersökningar, mätningar, EKG och blodprov. I den första kohorten hade 4% av TIA-patienterna kliniskt och radiologiskt verifierad INPH. I den andra kohorten var vaskulära riskfaktorer överrepresenterade hos INPH-patienterna jämfört med iv normalpopulationen. Hyperlipidemi (OR: 2.4, 95%CI: 1.4-4.0), diabetes (OR: 2.2, 95%CI: 1.2-3.9), fetma (OR: 5.4, 95%CI: 2.5-11.8) och psykosociala faktorer (OR: 5.3, 95%CI: 3.2-8.9) var associerade med INPH oberoende av kön, ålder och de andra riskfaktorerna. Hypertension och fysisk inaktivitet var också associerade med INPH, dock inte oberoende av övriga riskfaktorer. Sammanlagd PAR% (från engelskans: population attributable risk %) för de här sex riskfaktorerna var 24%. INPH-patienterna hade depression i högre utsträckning än kontrollerna (46% vs. 13%, p&lt;0.001), och depression var den viktigaste prediktorn för låg livskvalitet. Resultaten tyder på att vaskulär sjukdom och vaskulära riskfaktorer är involverade i den patofysiologiska mekanismen vid INPH. INPH kan vara en undergrupp till vaskulär demens. En fullständig riskfaktoranalys och screening för depression bör ingå i den preoperativa utvärderingen såväl som i forskning på INPH-patienter, och ett mått på livskvalitet bör införas. Effekten av riktade insatser mot såväl vaskulära riskfaktorer som depression vid INPH bör utvärderas.

INTRODUÇÃO: Pacientes com suboclusão da carótida com sinal do barbante podem ser incorretamente classificados como portadores de oclusão total, por meio de exames não invasivos. A história natural e o tratamento desta condição são controversos na literatura médica. OBJETIVOS: 1. Avaliar a evolução, em longo prazo, de pacientes com suboclusão carotídea com sinal do barbante assintomáticos, quando submetidos a tratamento clínico exclusivo; 2. Avaliar os resultados imediatos e em longo prazo do tratamento intervencionista de pacientes com suboclusão carotídea com sinal do barbante sintomáticos. MÉTODOS: Foram inclusos 195 pacientes que apresentavam ultrassonografia Doppler convencional prévia com oclusão completa de, pelo menos, uma das carótidas internas, totalizando 204 carótidas ocluídas (9 oclusões bilaterais). Após a realização de angiotomografia computadorizada e ultrassonografia com contraste de microbolhas, 46 pacientes (46 carótidas) apresentavam, na realidade, placas suboclusivas com fluxo filiforme na carótida interna, sendo acompanhados prospectivamente. Desses, 22 eram assintomáticos e foram tratados clinicamente; e 24 eram sintomáticos e foram submetidos à tentativa de angioplastia com implante de stent. O seguimento foi executado com consultas periódicas e ultrassonografia Doppler realizadas com 14 dias, 3 meses, 6 meses e, posteriormente, a cada 12 meses, após a intervenção. Angiotomografia computadorizada era realizada em até 2 meses após o procedimento. RESULTADOS: O seguimento médio foi de 63,9 meses. Os pacientes assintomáticos tiveram sobrevida cumulativa de 81,8%, sem quaisquer eventos neurológicos em 60 meses. Os pacientes sintomáticos tiveram taxa de sucesso no implante de stent de 79,1% (19 de 24). Não houve isquemia miocárdica ou morte em até 30 dias após a cirurgia. Um dos pacientes com sucesso no implante do stent apresentou paresia de membro superior com recuperação em 3 meses, portanto, a taxa de desfecho primário (acidente vascular cerebral, infarto agudo do miocárdio e morte), foi 4,2%. A taxa de perviedade para os procedimentos com sucesso foi de 89,4%, em 60 meses. Os pacientes sintomáticos com sucesso na angioplastia tiveram taxa de sobrevida livre de eventos neurológicos de 84,2%, em 60 meses, com sobrevida total de 89,4% nesse período. Todos os 5 pacientes sintomáticos nos quais a angioplastia não foi factível evoluíram com eventos neurológicos no acompanhamento, com sobrevida de 40,0%, em 60 meses. CONCLUSÕES: 1. Pacientes com suboclusão carotídea com sinal do barbante assintomáticos são favorecidos, em longo prazo, pelo tratamento medicamentoso exclusivo. 2. Pacientes com suboclusão carotídea com sinal do barbante sintomáticos beneficiam-se, em longo prazo, da angioplastia com implante de stent / INTRODUCTION: Patients with carotid near-occlusion with string sign may be incorrectly classified as total occlusion through non-invasive tests. The natural history and treatment of such condition are controversial in medical literature. OBJECTIVES: 1. Monitor the natural long-term outcome of asymptomatic patients with carotid near-occlusion with string sign treated medically; 2. Evaluate the short and long-term results of interventional treatment in symptomatic patients with carotid near-occlusion with string sign. METHODS: 195 patients, who had previous Doppler ultrasound with complete occlusion of at least one internal carotid, were included. 9 had bilateral occlusion, totaling 204 occluded arteries. After conducting computed tomography angiography and contrast-enhanced ultrasound, 46 patients (46 carotid arteries) had near-occlusion with string sign and were prospectively analyzed. Asymptomatic patients (22) received best medical therapy while symptomatic individuals (24) were referred to carotid artery stenting. After the procedure follow-up was made with clinical surveillance and Doppler ultrasound performed at 14 days, 3 months, 6 months and then every 12 months thereafter. A computed tomographic angiography was performed within 2 months. RESULTS: Mean follow-up was of 63.9 months. Asymptomatic patients had a cumulative survival rate of 81.8%, in 60 months, without any neurologic events. Symptomatic patients had intraoperative success rate of 79.1% (19/24 procedures). No intraoperative or 30-day events of myocardial infarction or death occurred. One of the successful carotid artery stenting patients evolved with a mild upper limb monoparesis, with total recovery in 3 months. The rate of primary end point (stroke, myocardial infarction or death) was 4.2%. Cumulative patency rate for the 19 successful procedures was 89.4%, in 60 months. Symptomatic individuals with successful angioplasty had a neurologic event-free survival rate of 84.2%, in 60 months, with overall survival rate of 89.4%, in the same period. All 5 symptomatic patients to whom string angioplasty procedure was not feasible evolved with neurological events, with a cumulative survival rate of 40.0%, in 60 months. CONCLUSIONS: 1. Asymptomatic patients with carotid near-occlusion with string sign evolve well with best medical therapy in long-term follow-up; 2. Symptomatic patients with carotid near-occlusion with string sign have good outcomes with carotid artery stenting in long-term follow-up

Ischämietoleranz bezeichnet das Phänomen, dass ein kurzer ischämischer, metabolischer oder physikalischer Stimulus das Gehirn paradoxerweise "resistent" macht gegenüber einer darauffolgenden, längerdauernden Ischämie. In einer retrospektiven Studie versuchten wir die Hypothese zu untermauern, dass transiente ischämische Attacken (als kurzdauernde ischämische Stimuli) vor einem Infarkt (prodromale TIAs) protektiv sind gegen eine nachfolgende zerebrale Ischämie. Es zeigte sich dabei, dass Patienten mit prodromalen TIAs ein geringeres Defizit und einen günstigeren Verlauf zeigten und im CT seltener Infarktfrühzeichen hatten. Somit könnten transiente ischämische Attacken, vor einem Schlaganfall, analog zu der Situation am Herzen und wie in zahlreichen in vivo Modellen gezeigt, ein klinisches Korrelat zur hypoxischen Präkonditionierung darstellen. Im experimentellen Teil der vorliegenden Arbeit wird gezeigt, dass sich hypoxische Präkonditionierung in vitro in neuronalen Kulturen modellieren lässt. Eine kurzzeitige Sauerstoff-Glucose-Deprivation (OGD) 1-3 Tage vor einer längeren OGD führt zu einem signifikanten Schutz von Neuronen, bis zu 90%. Hypoxietoleranz kann auch durch andere metabolische Stimuli, wie Inhibition von Atmungskettenenzymen durch 3-NPA im gleichen Zeitrahmen simuliert werden. Eine genaue Kenntnis der endogenen Neuroprotektion durch Ischämietoleranz könnte in Zukunft helfen, den Schaden durch ischämische Infarkte und ischämische Enzephalopathien zu minimieren. / Ischemic tolerance is a phenomenon where a brief episode of ischemia renders the brain resistant against a subsequent, longerlasting ischemic event. In a retrospective study we tested the hypothesis that transient ischemic attacks (as brief ischemic stimuli) before cerebral ischemia (prodromal TIA's) may have a protective effect. Here we show that patients with prodromal TIA's have less severe neurologic impairment, a better clinical course and have less early infarct signs. Therefore we siggest that TIA's, before stroke could represent a clinical correlate to hypoxic preconditioning, as shown in the heart. Experimentally we were able to model hypoxic preconditioning in vitro using neuronal cultures. Brief oxygen-glucose deprivation (OGD) 1-3 days before longer lasting OGD protects neurons, up to 90%. Hypoxic tolerance was also simulated by metabolic stimuli like inhibition of the respiratory chain by 3-NPA. Increasing knowledge of this endogenous neuroprotection by ischemic tolerance might help to minimize neuronal damage following ischemic strokes and hypoxic encephalopathy.

INTRODUÇÃO: Pacientes com suboclusão da carótida com sinal do barbante podem ser incorretamente classificados como portadores de oclusão total, por meio de exames não invasivos. A história natural e o tratamento desta condição são controversos na literatura médica. OBJETIVOS: 1. Avaliar a evolução, em longo prazo, de pacientes com suboclusão carotídea com sinal do barbante assintomáticos, quando submetidos a tratamento clínico exclusivo; 2. Avaliar os resultados imediatos e em longo prazo do tratamento intervencionista de pacientes com suboclusão carotídea com sinal do barbante sintomáticos. MÉTODOS: Foram inclusos 195 pacientes que apresentavam ultrassonografia Doppler convencional prévia com oclusão completa de, pelo menos, uma das carótidas internas, totalizando 204 carótidas ocluídas (9 oclusões bilaterais). Após a realização de angiotomografia computadorizada e ultrassonografia com contraste de microbolhas, 46 pacientes (46 carótidas) apresentavam, na realidade, placas suboclusivas com fluxo filiforme na carótida interna, sendo acompanhados prospectivamente. Desses, 22 eram assintomáticos e foram tratados clinicamente; e 24 eram sintomáticos e foram submetidos à tentativa de angioplastia com implante de stent. O seguimento foi executado com consultas periódicas e ultrassonografia Doppler realizadas com 14 dias, 3 meses, 6 meses e, posteriormente, a cada 12 meses, após a intervenção. Angiotomografia computadorizada era realizada em até 2 meses após o procedimento. RESULTADOS: O seguimento médio foi de 63,9 meses. Os pacientes assintomáticos tiveram sobrevida cumulativa de 81,8%, sem quaisquer eventos neurológicos em 60 meses. Os pacientes sintomáticos tiveram taxa de sucesso no implante de stent de 79,1% (19 de 24). Não houve isquemia miocárdica ou morte em até 30 dias após a cirurgia. Um dos pacientes com sucesso no implante do stent apresentou paresia de membro superior com recuperação em 3 meses, portanto, a taxa de desfecho primário (acidente vascular cerebral, infarto agudo do miocárdio e morte), foi 4,2%. A taxa de perviedade para os procedimentos com sucesso foi de 89,4%, em 60 meses. Os pacientes sintomáticos com sucesso na angioplastia tiveram taxa de sobrevida livre de eventos neurológicos de 84,2%, em 60 meses, com sobrevida total de 89,4% nesse período. Todos os 5 pacientes sintomáticos nos quais a angioplastia não foi factível evoluíram com eventos neurológicos no acompanhamento, com sobrevida de 40,0%, em 60 meses. CONCLUSÕES: 1. Pacientes com suboclusão carotídea com sinal do barbante assintomáticos são favorecidos, em longo prazo, pelo tratamento medicamentoso exclusivo. 2. Pacientes com suboclusão carotídea com sinal do barbante sintomáticos beneficiam-se, em longo prazo, da angioplastia com implante de stent / INTRODUCTION: Patients with carotid near-occlusion with string sign may be incorrectly classified as total occlusion through non-invasive tests. The natural history and treatment of such condition are controversial in medical literature. OBJECTIVES: 1. Monitor the natural long-term outcome of asymptomatic patients with carotid near-occlusion with string sign treated medically; 2. Evaluate the short and long-term results of interventional treatment in symptomatic patients with carotid near-occlusion with string sign. METHODS: 195 patients, who had previous Doppler ultrasound with complete occlusion of at least one internal carotid, were included. 9 had bilateral occlusion, totaling 204 occluded arteries. After conducting computed tomography angiography and contrast-enhanced ultrasound, 46 patients (46 carotid arteries) had near-occlusion with string sign and were prospectively analyzed. Asymptomatic patients (22) received best medical therapy while symptomatic individuals (24) were referred to carotid artery stenting. After the procedure follow-up was made with clinical surveillance and Doppler ultrasound performed at 14 days, 3 months, 6 months and then every 12 months thereafter. A computed tomographic angiography was performed within 2 months. RESULTS: Mean follow-up was of 63.9 months. Asymptomatic patients had a cumulative survival rate of 81.8%, in 60 months, without any neurologic events. Symptomatic patients had intraoperative success rate of 79.1% (19/24 procedures). No intraoperative or 30-day events of myocardial infarction or death occurred. One of the successful carotid artery stenting patients evolved with a mild upper limb monoparesis, with total recovery in 3 months. The rate of primary end point (stroke, myocardial infarction or death) was 4.2%. Cumulative patency rate for the 19 successful procedures was 89.4%, in 60 months. Symptomatic individuals with successful angioplasty had a neurologic event-free survival rate of 84.2%, in 60 months, with overall survival rate of 89.4%, in the same period. All 5 symptomatic patients to whom string angioplasty procedure was not feasible evolved with neurological events, with a cumulative survival rate of 40.0%, in 60 months. CONCLUSIONS: 1. Asymptomatic patients with carotid near-occlusion with string sign evolve well with best medical therapy in long-term follow-up; 2. Symptomatic patients with carotid near-occlusion with string sign have good outcomes with carotid artery stenting in long-term follow-up

Sammenfatning Baggrund og formål: Apopleksisygdommen er ansvarlig for flest tilfælde af invalidering blandt voksne i eget hjem. I Danmark alene lever godt 50.000 mennesker med følgerne efter apopleksi. En følge kan være reduceret evne til at kommunikere, afasi. Forebyggelse kan reducere antallet af nye tilfælde og følgerne efter sygdommen. Livskvalitet ved kronisk sygdom har voksende bevågenhed. Rehabilitering medvirker til at patienten kan blive fysisk, psykisk og socialt fungerende på et niveau, men sygdommens indvirken på oplevelsen af helbredsrelateret livskvalitet er i Danmark ikke undersøgt med sygdomsspecifikke instrumenter. Patienter med afasi udelukkes som regel fra undersøgelser, der kræver intakt tale og forståelse. Afhandlingens overordnede mål er at tilvejebringe et instrument, som kan anvendes til at måle helbredsrelateret livskvalitet efter apopleksi inkl. afasi. Metode og materiale: Afhandlingen har en kvantitativ tilgang. Et nordamerikansk instrument, Stroke Specific Quality of Life Scale, version 2.0, SSQOL © (copyright Linda S. Williams), er blevet oversat og kulturelt bearbejdet til dansk i overensstemmelse med anerkendt systematik i studie I. Instrumentet dækker med 49 items 12 domæner med fysisk, socialt og mentalt fokus samt 13 items, der dækker en vurdering af domænerne og livskvaliteten sammenlignet med før apopleksien. Instrumentets psykometriske egenskaber er blevet testet ved hjælp af tre studiepopulationer rekrutteret dels retrospektivt, dels konsekutivt. I studie II blev reliabilitet og validitet undersøgt, og i studie III responsivitet og sensitivitet. Afprøvningerne er foretaget med referenceformularer som eksterne kriterier i form af etablerede generiske skalaer. I studie IV er afprøvet en proxy-version tiltænkt patienter, som er ude af stand til selv at udfylde skemaet eller som ikke er i stand til at kommunikere tilstrækkeligt. Afprøvningen blev udført af en nærtstående udpeget af patienten. I studie V blev en gruppe let ramte patienter beskrevet, og variabler med betydningsfuld sammenhæng med oplevelsen af forringet helbredsrelateret livskvalitet blev undersøgt. Data er blevet testet ved hjælp af gennemsnit og standarddeviationer, median og range, proportioner, korrelationer og logistisk regression. Resultater: Den danske version af SSQOL, SSQOL-DK, har god face- og indholdsvaliditet. Det udfyldes på 10-20 minutter. Stabilitet, undersøgt med test-retest metode, viste korrelationer i området rs 0.65-0.99. Intern konsistens undersøgt med Cronbach’s alfa viste værdier i områderne 0.81-0.94 i studie II, 0.75-0.96 i studie III og 0.64-0.87 i studie V. Der blev set en ceiling effekt, 24-52%, men beskeden floor effekt. Begrebsvaliditet viste moderat delte varianser med de eksterne kriterier, r2 0.03-0.62. Konvergent validitet var (r) &gt; 0.40 med undtagelse af et enkelt item. SSQOL-DK var i stand til at klassificere retning af ændring i livskvalitet over tid i overensstemmelse med eksterne kriterier i 43-58 % af tilfældene. Proxy-versionen viste god overensstemmelse mellem patient- og proxy data. I en gruppe af let ramte patienter med apopleksi og transcerebral iskæmi, TCI, et år efter sygdommen vurderede 57 % deres livskvalitet som uændret i forhold til før apopleksien. Det mandlige køn (OR 3.77), erhvervsaktivitet (OR 2.84), og lavere scores på domænerne Mood og Work ved tre måneder var covariater, som var signifikant relateret til sandsynligheden for at vurdere livskvaliteten forringet efter sygdommen. Konklusion: Der foreligger nu et dansksproget instrument, SSQOL-DK, som har demonstreret tilfredsstillende reliabilitet og validitet, og som kan anvendes på gruppeniveau til dansktalende patienter med let til moderat apopleksi. Apopleksipatienten med større kommunikationsproblemer har dog stadig begrænsede muligheder med dette instrument, idet de foreliggende resultater fra proxy-afprøvningen fordrer yderligere undersøgelse af datas validitet / Abstract Background and aim: Stroke is most frequently the cause of adult disability. In Denmark more than 50.000 people suffer from the sequels of stroke. One of them may be aphasia, i.e. reduced ability to communicate. Primary and secondary prevention may reduce the incidence and the severity of stroke. The interest in quality of life with a chronic disease is increasing. Rehabilitation efforts are targeted for physical, mental and social function but the impact on health related quality of life after stroke has not been studied with stroke specific instruments. Aphasic patients are normally excluded from studies where communicative skills are required. The aim of this thesis is to develop an instrument suitable for measuring health related quality of life after stroke. Methods and material: The design of the thesis is quantitative. In study I Stroke Specific Quality of Life Scale, version 2.0, SSQOL © (copyright Linda S. Williams), an American instrument recently developed, was translated and culturally adapted to Danish according to established guidelines. With 49 items SSQOL covers 12 domains comprising physical and mental issues. Thirteen items covers an appraisal of each domain compared to pre stroke status and overall quality of life. Psychometric properties was examined by studying three samples of stroke survivors. Study II and III examined reliability, validity and responsiveness. Established generic scales were used as external criteria. Study IV tested a proxy-version meant for stroke patients with language impairment or patients who are unable to fill in a questionnaire. The patients chose the proxies. Study V provided health related quality of life in a group of mildly affected patients after stroke or transient ischemic attack, TIA. Significant covariates with deteriorated health related quality of life were studied. Data were analyzed with mean and standard deviations, median and range, proportions correlations and logistic regression. Results: The Danish version of SSQOL, SSQOL-DK, showed good face- and content validity. It can be completed in less than 25 minutes. Test-retest showed correlations rs 0.65-0.99. Internal consistency showed Cronbach’s alpha from 0.81-0.94 in study II, 0.75-0.96 in study III and 0.64-0.87 in study V. Ceiling effect was 24-52%, floor-effect was modest. Construct validity showed shared variance with external criteria, r2 0.03-0.62. Convergent validity showed (r) &gt;0.40 for 48 out of 49 items. SSQOL-DK classified direction of change in over all quality of life concordantly from 43-58% with external criteria. The agreement between patient- and proxy data was good. Fifty seven (57) percent of mildly affected patients after stroke or TIA rated their overall quality of life unchanged one year after stroke compared to pre stroke status. In the regression model male sex OR 3.77), working outside home (OR 2.84), and less than 5.00 (maximum score) on the domains Mood and Work/productivity at three months were significant predictors for rating over all quality of life deteriorated at 12 months. Conclusion: The SSQOL-DK has demonstrated satisfactory reliability and validity and can be used on group level measuring health related quality of life among Danish survivors after mild to moderate stroke and TIA. Stroke survivors with severe communication problems are still limited as validity of the proxy data should be further tested

Il est reconnu que les survivants d’accident vasculaire cérébral (AVC) présentent un important déconditionnement physique ainsi qu’une grande prévalence de comorbidités cardiovasculaires qui augmente considérablement le risque de subir un autre événement cardiovasculaire. En prévention secondaire, mis à part le traitement pharmacologique, il existe actuellement très peu de prise en charge de ces facteurs de risque lors de la phase de retour en communauté des patients. Pourtant, les lignes directrices recommandent l’activité physique de type aérobie comme moyen efficace de prévention cardiovasculaire. Par ailleurs, il existe de plus en plus de données probantes suggérant que l’entraînement par intervalles à haute intensité (HIIT) représenterait une forme d’exercice efficace pour améliorer la capacité cardiorespiratoire et le profil de santé chez différentes populations symptomatiques. La littérature demeure, toutefois, limitée quant à l’utilisation de cette méthode post-AVC. L’objectif général de cette thèse était de développer et d’évaluer un programme d’exercice incluant le HIIT en combinaison avec l’entraînement continu à intensité moyenne (MICT) pour les personnes ayant vécu un AVC ischémique ou une ischémie cérébrale transitoire (ICT) en prévention secondaire dans la phase chronique de la maladie. Les différentes étapes de cette recherche ont permis la rédaction de quatre articles scientifiques. Premièrement, la faisabilité et l’acceptabilité du protocole d’exercice élaboré incluant le HIIT ont été évaluées de façon favorable à la suite d’une intervention de trois mois. Cette première étude aura permis d’optimiser notre protocole pour développer les étapes subséquentes. En second lieu, l’efficacité du protocole lors d’une intervention de six mois a été évaluée dans une étude contrôlée randomisée en démontrant notamment une amélioration de la capacité cardiorespiratoire ainsi que des marqueurs d’anxiété et de dépression qui persistaient six mois après l’arrêt du programme supervisé comparativement à un groupe contrôle. Cette deuxième étude a également permis de comparer notre programme combiné contenant du HIIT à un programme d’activité physique standard comprenant seulement du MICT, sans toutefois démontrer aucune supériorité du protocole expérimental sur les variables cliniques mesurées. En troisième lieu, les réponses aiguës de la mesure ambulatoire de la pression artérielle à la suite d’un entraînement HIIT et à un iv entraînement MICT ont démontré un effet hypotenseur perdurant jusqu’à huit heures post-exercice, lequel était comparable pour les deux types d’entraînement. Finalement, une quatrième étude qualitative a permis de mettre en lumière une acceptabilité favorable des participants au programme comprenant du HIIT en plus de permettre de comprendre leur expérience afin de bonifier et d’optimiser des recherches futures. Cette thèse a contribué à l’avancement des connaissances en lien avec l’utilisation de la méthode HIIT chez les victimes d’AVC ischémique ou d’ICT dans la phase de réintégration et de maintien en communauté du continuum de soins post-AVC. Cette recherche a démontré un effet favorable sur des variables cliniques en plus d’avoir mis de l’avant l’acceptabilité positive du projet par les participants. Toutefois, les résultats ne supportent pas de supériorité d’inclure la méthode HIIT par rapport à l’utilisation du MICT seulement. Cette thèse soutient donc que l’ajout du HIIT pourrait être une alternative efficace dans un objectif de prévention secondaire en phase chronique de l’AVC ischémique et de l’ICT. Ce qui importe réellement est de rendre l’activité physique aérobie accessible, faisable et acceptable pour améliorer la santé et la qualité de vie des survivants d’AVC. / Stroke survivors have significant physical deconditioning and a high prevalence of cardiovascular comorbidities that significantly increase the risk of another cardiovascular event. In secondary prevention, apart from pharmacological treatment, there is currently little management of these risk factors during the phase of community reintegration. However, guidelines recommend aerobic exercise as an effective method of cardiovascular protection. In addition, there is growing evidence to suggest that high-intensity interval training (HIIT) is an effective form of exercise for improving cardiorespiratory fitness and health profile in different symptomatic populations. However, the literature remains limited on the use of this method post-stroke. The overall objective of this thesis was to develop et evaluate a realistic physical activity program including a combination of HIIT and moderate intensity continuous training (MICT) for people with ischemic stroke or transient ischemic attack (TIA) for secondary prevention in the chronic phase of the disease, thus addressing a clinical need. The different steps of this research led to the writing of four scientific articles. First, the feasibility and acceptability of the protocol developed were favorably evaluated following a three-month intervention. This first study allowed us to optimize our protocol to develop the subsequent steps. Secondly, the effectiveness of our protocol during a sixmonth intervention was evaluated in a randomized controlled study by demonstrating an improvement in cardiorespiratory capacity as well as markers of anxiety and depression that persisted six months after the program supervision was stopped compared to a control group. This second study also compared our program containing HIIT to a standard physical activity program with MICT without, however, showing any superiority of our combinated protocol on our variables. Third, the acute responses of ambulatory blood pressure measurement following HIIT training and MICT training demonstrated a hypotensive effect lasting up to eight hours post-exercise that was comparable for both types of intervention. Finally, a fourth qualitative study revealed a favorable acceptability of the participants to the combined program including HIIT and allowed us to understand their experience in order to improve and optimize future research. This thesis has contributed to the advancement of knowledge related to the use of HIIT post-stroke or TIA. Our research has demonstrated a positive effect on clinical variables and has highlighted the positive acceptability of the project by the participants. However, our results do not support a superiority of including the HIIT method over the use of MICT alone. This thesis therefore argues that the addition of HIIT could be an effective alternative in a secondary prevention goal in the chronic phase of ischemic stroke and TIA, but what really matters is making aerobic physical activity accessible to improve the health and quality of life of stroke survivors.