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RATIONALE: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data are lacking to address this question. AIMS: The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO. METHODS: This study is the randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. STUDY OUTCOMES: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best-corrected visual acuity of the Logarithm of the Minimum Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomography/angiography, ultrasound and magnetic resonance imaging (MRI) biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha = 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. DISCUSSION: By enrolling patients within 4.5 h of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may translate to CRAO with its similar pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.
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Fibrinolíticos , Recuperación de la Función , Oclusión de la Arteria Retiniana , Activador de Tejido Plasminógeno , Humanos , Oclusión de la Arteria Retiniana/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Tejido Plasminógeno/administración & dosificación , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Método Doble Ciego , Recuperación de la Función/efectos de los fármacos , Reperfusión/métodos , Resultado del Tratamiento , Administración Intravenosa , Agudeza Visual/efectos de los fármacos , Agudeza Visual/fisiología , Masculino , Ensayos Clínicos Fase III como Asunto , Femenino , Terapia Trombolítica/métodos , Persona de Mediana EdadRESUMEN
BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants. CONCLUSIONS: In participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks. (Funded by the European Union Horizon 2020 program; FAIRPARK-II ClinicalTrials.gov number, NCT02655315.).
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Antiparkinsonianos , Deferiprona , Quelantes del Hierro , Hierro , Enfermedad de Parkinson , Sustancia Negra , Humanos , Deferiprona/administración & dosificación , Deferiprona/efectos adversos , Deferiprona/farmacología , Deferiprona/uso terapéutico , Hierro/análisis , Hierro/metabolismo , Levodopa/uso terapéutico , Neutropenia/inducido químicamente , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Quelantes del Hierro/administración & dosificación , Quelantes del Hierro/efectos adversos , Quelantes del Hierro/farmacología , Quelantes del Hierro/uso terapéutico , Sustancia Negra/química , Sustancia Negra/diagnóstico por imagen , Sustancia Negra/efectos de los fármacos , Sustancia Negra/metabolismo , Progresión de la Enfermedad , Método Doble Ciego , Administración Oral , Encéfalo/diagnóstico por imagen , Química Encefálica , Dopaminérgicos/administración & dosificación , Dopaminérgicos/efectos adversos , Dopaminérgicos/farmacología , Dopaminérgicos/uso terapéutico , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/efectos adversos , Antiparkinsonianos/farmacología , Antiparkinsonianos/uso terapéuticoRESUMEN
Background: Despite antiretroviral therapy, cognitive dysfunction seems to remain a major issue for people living with human immunodeficiency virus (PLWH). Previous studies showed a correlation between the width of the third ventricle (WTV) and neurocognitive disorders in PLWH. Patients and methods: We investigated prevalence and correlation of neuropsychological disorders using WTV as a brain atrophy marker examined by transcranial sonography and MRI in PLWH and healthy age- and gender-matched controls. We used Becks Depression Inventory (BDI) for depression screening, the questionnaires Fatigue Severity Scale (FSS) for fatigue and Short-Form-36 (SF36) for quality of life (QoL) evaluation and Consortium to establish a registry for Alzheimer's disease (CERAD-PLUS) as neuropsychological test battery. Results: 52 PLWH (47 males) and 28 non-infected controls (23 males) with a median age of 52 years (24-78 years) and 51 years (22-79) were analyzed. WTV correlated significantly with age (p < 0.01) but showed no significantly difference in PLWH (median = 3.4 mm) compared to healthy controls (median = 2.8 mm) (p = 0.085). PLWH had both significantly higher BDI-Scores (p = 0.005) and FSS-Scores (p = 0.012). Controls reported higher QoL (SF-36) with significant differences in most items. However, the overall cognitive performance (CERAD total score) showed no significant difference. The WTV of all subjects correlated with neurocognitive performance measured as CERAD total score (p = 0.009) and trail making tests A (p < 0.001) and B (p = 0.018). There was no correlation between the scores of BDI, FSS, SF-36, and CERAD-PLUS items and WTV. Conclusion: WTV is considered as a predictor of cognitive deficits in neurodegenerative diseases. Nevertheless, we found no significant difference in WTV or overall cognitive performance between PLWH and controls. PLWH suffer more often from depression and fatigue and report reduced QoL when compared to healthy controls.
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BACKGROUND: The prehospital identification of stroke patients with large-vessel occlusion (LVO), that should be immediately transported to a thrombectomy capable centre is an unsolved problem. Our aim was to determine whether implementation of a state-wide standard operating procedure (SOP) using the Los Angeles Motor Scale (LAMS) is feasible and enables correct triage of stroke patients to hospitals offering (comprehensive stroke centres, CSCs) or not offering (primary stroke centres, PSCs) thrombectomy. METHODS: Prospective study involving all patients with suspected acute stroke treated in a 4-month period in a state-wide network of all stroke-treating hospitals (eight PSCs and two CSCs). Primary endpoint was accuracy of the triage SOP in correctly transferring patients to CSCs or PSCs. Additional endpoints included the number of secondary transfers, the accuracy of the LAMS for detection of LVO, apart from stroke management metrics. RESULTS: In 1123 patients, use of a triage SOP based on the LAMS allowed triage decisions according to LVO status with a sensitivity of 69.2% (95% confidence interval (95%-CI): 59.0-79.5%) and a specificity of 84.9% (95%-CI: 82.6-87.3%). This was more favourable than the conventional approach of transferring every patient to the nearest stroke-treating hospital, as determined by geocoding for each patient (sensitivity, 17.9% (95%-CI: 9.4-26.5%); specificity, 100% (95%-CI: 100-100%)). Secondary transfers were required for 14 of the 78 (17.9%) LVO patients. Regarding the score itself, LAMS detected LVO with a sensitivity of 67.5% (95%-CI: 57.1-78.0%) and a specificity of 83.5% (95%-CI: 81.0-86.0%). CONCLUSIONS: State-wide implementation of a triage SOP requesting use of the LAMS tool is feasible and improves triage decision-making in acute stroke regarding the most appropriate target hospital.
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BACKGROUND: Spinal cord injuries are frequently associated with severe clinical-neurological deficits. These are evident with specific symptoms and syndromes. Hereby, a thorough knowledge of spinal neuroanatomy is essential. METHODS: Spinal anatomy, examination procedures and classical spinal syndromes are presented. RESULTS: Important spinal syndromes comprise the dorsal cord syndrome, spinothalamic tract syndrome, pyramidal tract syndrome, central cord syndrome, transversal and Brown-Séquard syndrome as well as combined syndromes. CONCLUSION: Clinical examination allows assessment and anatomical classification of spinal syndromes and targeted examination of the spinal cord using additional diagnostic methods.
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Síndrome de Brown-Séquard , Traumatismos de la Médula Espinal , Humanos , Médula Espinal/diagnóstico por imagen , Columna VertebralRESUMEN
Cardiac dysautonomia is a potentially life-threatening complication of Guillain-Barré syndrome (GBS). Proper and prompt recognition of patients at risk and subsequent intensive care unit (ICU) monitoring are mandatory to prevent fatal outcome. Eyeball pressure testing (EP) has been suggested as an easy applicable bedside test for vagal overreactivity in GBS and thus identifying patients at risk. Yet, there is only sparse follow-up data concerning the course of EP findings in GBS. We report a 25 years-old male patient with GBS who underwent consecutive EP (n = 11) during his ICU stay over a period of 11 weeks. The series of tests performed in this patient (and corresponding clinical events) show that EP data might represent an approximation of vagal dysfunction and vagal recovery in GBS. Interestingly, we observed a much longer duration of pathological EP compared to a previous report. The tenacious cardiac dysautonomia in this patient necessitated long-term application of a transvenous temporary pacemaker.
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Systemic BCGitis and autoimmune diseases are possible adverse events of intravesical Bacille Calmette-Guérin-(BCG)-instillations in the treatment of urothelioma cancer. We present the case of an 83-years-old male patient with rapid progressive symptoms of dementia up to mutism as well as tonic seizures. Immune-mediated cerebral small vessel disease was diagnosed and retraced to former instillations of BCG. Intense immunosuppressive treatment was performed and clinical restoration was achieved within several months. While cerebral vasculitis due to BCGitis has already been described before, this is to our knowledge the first case report to illustrate an immune-mediated small vessel disease after BCG-instillations. This should be considered in patients with rapidly progressive dementia-like symptoms treated with BCG, as an immunosuppressive treatment can be highly effective even at severe clinical stages.
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BACKGROUND: The spread of the novel coronavirus SARS-CoV-2 and the guidance from authorities for social distancing and media reporting lead to significant uncertainty in Germany. Concerns have been expressed regarding the underdiagnosing of harmful diseases. We explored the rates of emergency presentations for acute coronary syndrome (ACS) and acute cerebrovascular events (ACVE) before and after spread of SARS-CoV-2. METHODS: We analyzed all-cause visits at a tertiary university emergency department and admissions for ACS and ACVE before (calendar weeks 1-9, 2020) and after (calendar weeks 10-16, 2020) the first coronavirus disease (COVID-19) case in the region of the Saarland, Germany. The data were compared with the same period of the previous year. RESULTS: In 2020 an average of 346 patients per week presented at the emergency department whereas in 2019 an average of 400 patients presented up to calendar week 16 (p = 0.018; whole year 2019 = 395 patients per week). After the first COVID-19 diagnosis in the region, emergency department visit volume decreased by 30% compared with the same period in 2019 (p = 0.0012). Admissions due to ACS decreased by 41% (p = 0.0023 for all; Δ - 71% (p = 0.007) for unstable angina, Δ - 25% (p = 0.42) for myocardial infarction with ST-elevation and Δ - 17% (p = 0.28) without ST-elevation) compared with the same period in 2019 and decreased from 142 patients in calendar weeks 1-9 to 62 patients in calendar weeks 10-16. ACVE decreased numerically by 20% [p = 0.25 for all; transient ischemic attack: Δ - 32% (p = 0.18), ischemic stroke: Δ - 23% (p = 0.48), intracerebral haemorrhage: Δ + 57% (p = 0.4)]. There was no significant change in ACVE per week (p = 0.7) comparing calendar weeks 1-9 (213 patients) and weeks 10-16 (147 patients). Testing of 3756 samples was performed to detect 58 SARS-CoV-2 positive patients (prevalence 1,54%, thereof one patient with myocardial and two with cerebral ischemia) up to calendar week 16 in 2020. CONCLUSIONS: The COVID-19 pandemic was associated with a significant decrease in all-cause admission and admissions due to cardiovascular events in the emergency department. Regarding acute cerebrovascular events there was a numerical decrease but no significant difference.
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COVID-19 , Servicio de Cardiología en Hospital/tendencias , Trastornos Cerebrovasculares/terapia , Servicio de Urgencia en Hospital/tendencias , Cardiopatías/terapia , Admisión del Paciente/tendencias , COVID-19/epidemiología , Trastornos Cerebrovasculares/diagnóstico , Trastornos Cerebrovasculares/epidemiología , Alemania/epidemiología , Accesibilidad a los Servicios de Salud/tendencias , Cardiopatías/diagnóstico , Cardiopatías/epidemiología , Humanos , Aceptación de la Atención de Salud , Prevalencia , Factores de TiempoRESUMEN
INTRODUCTION: To assess the value of optic nerve sheath diameter (ONSD) measurements at different time points to predict the malignant evolution in middle cerebral artery (MCA) infarction and to investigate the relationship between ONSD and infarct volume on follow-up computed tomography (CT). METHODS: In a single-center prospective observational study, we recruited patients with MCA infarction and age- and sex-matched controls. Clinical characteristics including NationaI Institutes of Health Stroke Scale (NIHSS) and ONSD measurement were assessed during the first five days after symptom onset. Volumetric analysis of the infarction was performed by a neuroradiologist, who was blinded to results of ONSD measurement and clinical examinations, based on CT scans. RESULTS: We enrolled 29 patients with MCA infarction, including 10 with malignant MCA (mMCA) infarction and 14 controls. Mean ONSD on admission was already larger in patients who had developed an mMCA (5.99 ± 0.32 mm) compared to patients with MCA infarction (4.98 ± 0.53 mm; P = 0.003), and to control patients (4.57 ± 0.29 mm; P < 0.001). Correlation was observed between the ONSD mean value bilateral measures per individual and volumetric evaluation of cerebral infarction in the CT scan after one day (r = 0.623; P = 0.002). An ONSD value of 5.6 mm predicted an mMCA with a sensitivity of 100% and specificity of 90% yielding a positive predictive value of 83% and negative predictive value of 100%. CONCLUSIONS: ONSD measurement might be accurate for the noninvasive detection of increased ICP and for the recognition of patients being likely to develop mMCA.
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Infarto de la Arteria Cerebral Media , Hipertensión Intracraneal , Humanos , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Presión Intracraneal , Nervio Óptico/diagnóstico por imagen , Estudios Prospectivos , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
BACKGROUND AND PURPOSE: Endovascular treatment represents a well-established therapeutic option in patients with vertebral artery origin (VAO) stenosis. Our aim was to determine which factors affect short- and long-term restenosis rates after endovascular VAO therapy. METHODS: We conducted a single center analysis of 52 patients (36 men; age 64⯱ 9.54 years) who underwent 55 endovascular procedures (27 balloon-assisted angioplasty [BAA], 28 stent-assisted angioplasty [SAA]) between 2005-2015. We collected data on patients clinical characteristics, medication and post-interventional follow-up visits. RESULTS: Overall, 15 of 55 vessels (27%) showed ≥70% restenosis at 1 year (short-term follow-up) and 18 after a mean follow-up of 52.9⯱ 31.8 months (long-term). BMIâ¯≥ 25â¯kg/m2 was associated with ≥70% restenosis in short-term (Pâ¯= 0.014) and long-term (Pâ¯= 0.003) follow-up. Other risk factors, namely, hypertension, ischemic heart disease, smoking, diabetes mellitus, hypercholesterolemia, atrial fibrillation, CRP (>5â¯mg/l) or pre-treatment antiplatelet administration, statin intake and platelet count, were not associated with restenosis risk in the entire cohort or in patients in the BAA group (all Pâ¯> 0.05). BMI (Pâ¯= 0.003) and ischemic heart disease (Pâ¯= 0.041) were, in turn, associated with restenosis risk in the long-term follow-up in the SAA group. Patients undergoing BAA developed less frequently (Pâ¯= 0.032) restenosis (18%) during long-term follow-up as compared to patients treated by stenting (46%). CONCLUSION: BMIâ¯≥ 25â¯kg/m2 increases the odds for ≥70% restenosis of VAO while ischemic heart disease represents an additional risk factor in stented patients. Further studies are required to established therapeutic strategies lowering the restenosis rates in overweight individuals after VAO therapy, especially ones undergoing stenting.
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Angioplastia de Balón/métodos , Procedimientos Endovasculares/métodos , Stents , Insuficiencia Vertebrobasilar/terapia , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/complicaciones , Recurrencia , Factores de Riesgo , Resultado del Tratamiento , Insuficiencia Vertebrobasilar/complicacionesRESUMEN
INTRODUCTION: Cognitive impairment and dementia are common in PD; however, no stable marker of cognitive dysfunction is available. Transcranial sonography can evaluate global and focal brain atrophy and has been widely used in the differential diagnosis of parkinsonism. METHODS: 225 consecutive PD patients were recruited in a two-center cross sectional study and underwent a standardized sonographic protocol assessing the third ventricle's width and substantia nigra hyperechogenicity. All subjects were evaluated with an extensive motor and cognitive battery. RESULTS: 222 PD patients were included and classified as PD with normal cognition (PDNC; nâ¯=â¯130), mild cognitive impairment (PD-MCI; nâ¯=â¯61) and dementia (PDD; nâ¯=â¯31). Ventricular width correlated strongly with cognitive performance in all cognitive domains (pâ¯<â¯0.001) while SN size did not. PDD patients had significantly wider ventricles than PD patients without dementia (pâ¯<â¯0.001) while differences between PD-MCI and PDNC or PDD were less strong (pâ¯<â¯0.05). There were no group differences in SN size. ROC analyses resulted in age-related cut-offs of third ventricular diameter for the prediction of PDD (6.0 and 7.5 mm for subjects < and ≥70 years of age, respectively). These cut-offs significantly differentiated PDD from PDNC (p < 0.001) and from all patients without dementia (PDNC + PD-MCI; p < 0.001). CONCLUSIONS: The third ventricular diameter correlated with cognitive performance in all domains and was able to differentiate PDD patients from those without dementia. Longitudinal studies are warranted to evaluate whether transcranial sonography could identify PD patients at risk for a rapid cognitive decline.
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Disfunción Cognitiva/diagnóstico por imagen , Demencia/diagnóstico por imagen , Enfermedad de Parkinson/complicaciones , Tercer Ventrículo/diagnóstico por imagen , Anciano , Disfunción Cognitiva/etiología , Estudios Transversales , Demencia/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Ultrasonografía Doppler TranscranealRESUMEN
BACKGROUND AND PURPOSE: Optic nerve sheath diameter (ONSD) is used for the estimation of intracranial pressure (ICP). But there are still doubts about the quality of the images and the lateral resolution. Our aim is to investigate the system suitability and best lateral resolution of different ultrasound systems for acoustic ONSD measurement. METHODS: First, we calculated the theoretically lateral imaging resolution at increasing frequencies: 6.6, 10, and 15 MHz using two different ultrasound systems. Second, we created two phantoms consisting of copper wires or polyvinylchloride (PVC) strips and tested the best lateral resolution at different frequencies with the two ultrasound systems. Using the same ultrasound systems, we evaluated the anatomy of optic nerve at increasing transmission frequencies. Finally, the two probes were tested in two patients with different neurological conditions affected by an increase of ICP. RESULTS: Theoretical resolutions were .63, .43, and .41 mm, respectively, with a frequency of 6.6, 10, and 15 MHz. We found a similar lateral resolution in both phantoms: copper wire; .56 mm at 6.6 MHz, .46 mm at 10 MHz, and .44 mm at 15 MHz; and PVC strips .6 mm at 6.6 MHz, .47 mm at 10 MHz, and .40 mm at 15 MHz in accordance with experimental resolution. The ONSD thickening could be clearly displayed at frequencies higher than 7.5 MHz using the two linear probes and the two patients with an increase of ICP showed thickening of ONSD. CONCLUSION: According to our study, both systems are suitable for ultrasound OSND measurement.
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Hipertensión Intracraneal/diagnóstico por imagen , Presión Intracraneal/fisiología , Nervio Óptico/diagnóstico por imagen , Ultrasonografía , Acústica , Humanos , Hipertensión Intracraneal/fisiopatología , Fantasmas de ImagenRESUMEN
BACKGROUND AND PURPOSE: A new generation of carotid artery stents that uses a second micromesh layer to reduce embolic events during carotid artery stenting has recently been introduced. The purpose of this study was to compare acute occlusion rates of these new dual-layer stents with those of single-layer stents in the setting of emergency carotid artery stenting with intracranial mechanical thrombectomy in acute ischemic stroke. METHODS: Consecutive patients with acute tandem (intra- and extracranial) lesions of the anterior circulation who were endovascularly treated at our institution were identified from our registry of neuroendovascular interventions. Clinical, angiographic, and neuroimaging data were analyzed. End points included acute occlusions of the carotid stents (within 72 hours after stenting) and symptomatic intracerebral hemorrhage. RESULTS: Forty-seven patients were included. Dual-layer stents (n=20) had a significantly higher rate of acute occlusions than single-layer stents (n=27; 45% versus 3.7%; P=0.001; odds ratio, 21.3; 95% confidence interval, 2.4-188.4). There were no significant differences in the rates of patients who had any antiplatelet or dual antiplatelet medication before admission, in the rates of postinterventional symptomatic intracerebral hemorrhage, the mean National Institutes of Health Stroke Scale scores at admission, or the modified Rankin Scale scores at discharge. CONCLUSIONS: The recently introduced dual-layer stents have a higher risk of acute occlusion compared with single-layer stents in the treatment of acute stroke.
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Isquemia Encefálica/cirugía , Estenosis Carotídea/diagnóstico , Tratamiento de Urgencia/efectos adversos , Procedimientos Endovasculares/efectos adversos , Stents/efectos adversos , Accidente Cerebrovascular/cirugía , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico , Estenosis Carotídea/etiología , Tratamiento de Urgencia/métodos , Procedimientos Endovasculares/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico , Trombectomía/efectos adversos , Trombectomía/métodos , Resultado del TratamientoAsunto(s)
Enfermedad de Parkinson/psicología , Anciano , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Pruebas Neuropsicológicas , Oportunidad Relativa , Enfermedad de Parkinson/diagnóstico , Síntomas Prodrómicos , Estudios Prospectivos , Escalas de Valoración PsiquiátricaRESUMEN
A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson's disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies.
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BACKGROUND: Enormous effort is being put into the identification and characterization of symptoms that may be used as predictive and progression markers in Parkinson's disease (PD). An impressive number of PD patients and individuals at risk for or in the prodromal stage of PD are currently followed in longitudinal studies; however, there does not exist an overview on the kind of markers evaluated and the assessments used. METHODS: Information on the design, sample size, evaluated markers and assessments of 21 studies of the Joint Programme - Neurodegenerative Disease Research BioLoC-PD working group were collected by questionnaire. The studies were classified into at risk/prodromal or clinical PD cohorts. The assessments were grouped into quantitative assessments, investigator-rated assessments, investigator interviews, patient-rated questionnaires and caregiver-rated questionnaires. RESULTS: Compilation of these data revealed an interesting consensus on evaluated markers, but there was an enormous variability of assessments. Furthermore, there is a remarkable similarity in the markers assessed and evaluation methods applied in the risk/prodromal and clinical PD cohorts. CONCLUSIONS: The inventory of the longitudinal cohorts that are part of the BioLoC-PD consortium reveals that there is a growing consensus on the markers that should be assessed in longitudinal cohort studies in PD. However, controversy still exists on the specific type of assessment. To allow comparison of data and common analyses it will be essential to harmonize scales and assessment outcomes.
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Enfermedad de Parkinson/diagnóstico , Proyectos de Investigación , Biomarcadores , Progresión de la Enfermedad , Europa (Continente) , Humanos , Estudios Longitudinales , Síntomas ProdrómicosRESUMEN
BACKGROUND: Decompressive hemicraniectomy (DHC) after space-occupying strokes among patients older than 60 years has been shown to reduce mortality rates but at the cost of severe disability. There is an ongoing debate about what could be considered an acceptable outcome for these patients. Data about retrospective consent to the procedure after lengthy time periods are lacking. METHODS: This study included 79 consecutive patients who underwent DHC during a 7.75-year period. Surviving patients were assessed for functional and psychological outcome, quality of life (QoL) and retrospective consent for the procedure. Patients younger than 60 years were compared with older patients. RESULTS: Of our 79 patients, 44 were younger than 60 years (median 50 years, interquartile range (IQR) 19-59 years) and 35 were older (median 68 years, interquartile range 60-87 years). The 30-day mortality rate was higher for the older group, but the difference was not statistically significant. Functional outcome was significantly better in the younger group: 31% of the patients in this group vs. 10% in the older group had a modified Rankin Scale score of 0-3 (p = 0.046). The mean National Institutes of Health Stroke Scale score was 17 ± 14 for the younger group and 29 ± 15 for the older group (p = 0.002). On the 36-Item Short Form Health Survey, with the exception of the item 'General health', the older group reported higher values for all items, with statistically significant differences between the 2 groups on the items 'Role limitation emotional' (p = 0.0007) and 'Vitality' (p = 0.02). In the younger group, 29% of patients retrospectively declined consent for DHC opposed to 0% of patients in the older group (p = 0.07). CONCLUSIONS: Despite impaired functional outcome after DHC, indicators of QoL and retrospective consent are higher for patients older than 60 years over the long term. This finding should be taken into account by those who counsel patients and caregivers with regard to this serious procedure.
Asunto(s)
Daño Encefálico Crónico/etiología , Edema Encefálico/cirugía , Craniectomía Descompresiva , Consentimiento Informado , Aceptación de la Atención de Salud , Complicaciones Posoperatorias/etiología , Accidente Cerebrovascular/complicaciones , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Daño Encefálico Crónico/epidemiología , Daño Encefálico Crónico/parasitología , Edema Encefálico/etiología , Bases de Datos Factuales , Craniectomía Descompresiva/psicología , Ajuste Emocional , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Complicaciones Posoperatorias/epidemiología , Calidad de Vida , Recuperación de la Función , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/mortalidad , Sobrevivientes/psicología , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
There is evidence that nigrostriatal pathology may at least partly underlie mild Parkinsonian signs. We evaluated whether an increase in the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) could be predicted by the presence of risk and prodromal markers for neurodegenerative diseases in elderly individuals without those diseases. Therefore, we analyzed the UPDRS-III score and various risk and prodromal markers known to antecede neurodegenerative diseases in a population-based cohort comprising 807 individuals free of neurodegenerative diseases at baseline. After 5 years, eight persons (1.0 %) were diagnosed with Parkinson's Disease (PD). Of those, seven (87.5 %) had motor worsening ≥3 points on the UPDRS-III from baseline to follow-up, one had two points increase. Of the 788 people without PD, 568 (72.1 %) showed no increase in the UPDRS-III scale, 220 (27.9 %) had ≥1 point increase and out of these 104 (13.2 %) had an increase of ≥3 points in the UPDRS-III score after 5 years. We identified an age >60 years (relative risk, RR = 1.7; confidence interval, CI 1.3-2.1) and the occurrence of ≥2 risk factors (RR = 1.5; CI 1.2-1.9) as possible predictors of motor progression. After 5 years, individuals with an increase in the UPDRS-III score had more often a one-sided reduced arm swing (p < 0.001) and identified less odors in the Sniffin' sticks test (p < 0.041) than persons with stable motor performance. Our data support the assumption that progression of Parkinsonian signs assessed by the UPDRS-III parallels the development of prodromal markers for neurodegenerative diseases in the elderly population.