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1.
HNO ; 68(10): 763-772, 2020 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-32221628

RESUMEN

BACKGROUND: Although vestibular symptoms are amongst the most frequent reasons for seeking emergency medical help, many patients remain undiagnosed. OBJECTIVE: In this cross-sectional study, we investigated the spectrum of vertigo and dizziness in a tertiary ear, nose, and throat (ENT) emergency department (ED). Furthermore, we investigated the attendant symptoms, clinical signs, and the diagnostic tests performed. METHODS: We screened all ED reports from 01/2013 to 12/2013 for adult patients with vestibular symptoms referred to the ENT department. RESULTS: In total, we found 2596 cases with reported vestibular symptoms in the ED as a main or accompanying complaint. Of these, 286 were referred to the ENT specialist directly (n = 98) or via other major medical specialties (n = 188). Benign paroxysmal positional vertigo (BPPV) was the most frequent diagnosis in our study (n = 46, 16.1%), followed by vestibular neuritis (n = 44, 15.4%), otitis media (n = 20, 7%), and 9 patients (3.1%) had an ischemic stroke or a transient ischemic attack. In 70 (24.5%) cases, dizziness was not further specified. CONCLUSION: BPPV is the most frequent diagnosis seen in the ED; however, physicians need to document nystagmus more precisely and perform diagnostic tests systematically, in order to make an accurate diagnosis. To avoid misdiagnoses, ED physicians and ENT specialists should be able to recognize central signs in patients with an acute vestibular syndrome. Every fourth patient does not receive a definitive diagnosis. Diagnostic ED workup for patients with dizziness needs further improvement.


Asunto(s)
Vértigo Posicional Paroxístico Benigno , Mareo , Aceptación de la Atención de Salud , Faringe , Adulto , Vértigo Posicional Paroxístico Benigno/diagnóstico , Vértigo Posicional Paroxístico Benigno/etiología , Estudios Transversales , Mareo/diagnóstico , Mareo/etiología , Servicio de Urgencia en Hospital , Humanos
2.
Mol Psychiatry ; 23(2): 222-230, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-27550844

RESUMEN

Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed in brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females and 2 affected males with a de novo variant in CLCN4 (6 individuals previously unreported) and 27 affected males, 3 affected females and 15 asymptomatic female carriers from 9 families with inherited CLCN4 variants (4 families previously unreported). Intellectual disability ranged from borderline to profound. Behavioral and psychiatric disorders were common in both child- and adulthood, and included autistic features, mood disorders, obsessive-compulsive behaviors and hetero- and autoaggression. Epilepsy was common, with severity ranging from epileptic encephalopathy to well-controlled seizures. Several affected individuals showed white matter changes on cerebral neuroimaging and progressive neurological symptoms, including movement disorders and spasticity. Heterozygous females can be as severely affected as males. The variability of symptoms in females is not correlated with the X inactivation pattern studied in their blood. The mutation spectrum includes frameshift, missense and splice site variants and one single-exon deletion. All missense variants were predicted to affect CLCN4's function based on in silico tools and either segregated with the phenotype in the family or were de novo. Pathogenicity of all previously unreported missense variants was further supported by electrophysiological studies in Xenopus laevis oocytes. We compare CLCN4-related disorder with conditions related to dysfunction of other members of the CLC family.


Asunto(s)
Canales de Cloruro/genética , Síndromes Epilépticos/genética , Discapacidad Intelectual/genética , Adolescente , Adulto , Anciano , Animales , Niño , Preescolar , Canales de Cloruro/metabolismo , Epilepsia/genética , Síndromes Epilépticos/fisiopatología , Familia , Femenino , Genes Ligados a X , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Mutación de Línea Germinal , Humanos , Discapacidad Intelectual/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Oocitos , Linaje , Fenotipo , Síndrome , Sustancia Blanca/fisiopatología , Xenopus laevis
3.
Mol Psychiatry ; 21(1): 133-48, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25644381

RESUMEN

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.


Asunto(s)
Variación Genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Adulto , Animales , Células Cultivadas , Canales de Cloruro/genética , Canales de Cloruro/metabolismo , Estudios de Cohortes , Quinasas Ciclina-Dependientes/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Histona Acetiltransferasas/genética , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Ratones Noqueados , Proteínas de Microfilamentos/genética , Neuronas/metabolismo , Neuronas/patología , Proteínas Nucleares/genética , ARN Mensajero/metabolismo , Factores Asociados con la Proteína de Unión a TATA/genética , Factor de Transcripción TFIID/genética , Ubiquitina-Proteína Ligasas/genética
4.
Eur J Neurol ; 24(8): 1016-1021, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28649759

RESUMEN

BACKGROUND AND PURPOSE: Randomized controlled trials have shown that bridging endovascular therapy (EVT) after intravenous thrombolysis (IVT) therapy improves outcome in patients with stroke with large-artery anterior circulation stroke compared with IVT alone. It remains unknown whether IVT adds any benefit to EVT in these patients. The aim of this study was to assess recanalization rates and thrombus dislocation before initiation of EVT in patients receiving bridging therapy. METHODS: All patients in the Bernese stroke registry (2008-2015) in whom bridging therapy was considered were included in this analysis. Relevant recanalization before EVT, thrombus dislocation and increase in thrombus load between initial and control imaging were assessed retrospectively. RESULTS: A total of 319 patients were included. Relevant recanalization before EVT occurred in 8.8% and thrombus dislocation in 7.2% of patients before EVT. Recanalization rates were significantly higher in distal compared with large and more proximal vessel occlusions of the anterior circulation (occlusion of internal carotid artery, 5.4%; middle cerebral artery segment M1, 8.1%; middle cerebral artery segment M2, 17.6%) and in drip-and-ship patients compared with mother-ship patients. In multivariable regression analysis the occlusion site was the only independent predictor of relevant recanalization before EVT (P = 0.046). CONCLUSIONS: Relevant recanalization after IVT and prior to EVT in patients receiving bridging therapy was highly dependent on the occlusion site. These findings suggest that future randomized controlled trials should consider occlusion site and treatment paradigm to specify patients who benefit most from bridging therapy in comparison to EVT or IVT alone.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodos , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Resultado del Tratamiento
5.
Nervenarzt ; 88(6): 597-606, 2017 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-28466105

RESUMEN

Headache is one of the most frequent symptoms leading to visits at the emergency department. Here, we aim at presenting a pragmatic algorithm for headache patients at the emergency department. The basic principle is taking a detailed history of the current headache with a focus on dynamics, phenotype and trigger factors as well as a possible preexisting headache. "Red flags" should be interrogated specifically. Hypotheses of the etiology of the headache should be generated in combination with the clinical examination (vital signs, neurological exam, otorhinolaryngological and ophthalmological exams) and should be tested appropriately with imaging, laboratory, cerebral spinal fluid studies and ultrasound. Secondary headache have to be treated with a causal approach, if necessary also symptomatically. When a secondary headache can be excluded, we recommend aiming for a primary headache diagnosis with subsequent specific therapy. When a headache patient can be discharged, we recommend scheduling a follow-up appointment to understand the development of a secondary headache and its cause. In case of a primary headache, optimizing prophylaxis and acute therapy is important to prevent future emergency department visits.


Asunto(s)
Técnicas de Diagnóstico Neurológico , Servicios Médicos de Urgencia/métodos , Cefalea/diagnóstico , Cefalea/terapia , Examen Físico/métodos , Diagnóstico Diferencial , Servicio de Urgencia en Hospital/organización & administración , Cefalea/etiología , Humanos
6.
Mol Psychiatry ; 20(4): 459-71, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25070536

RESUMEN

Human mutations in PQBP1, a molecule involved in transcription and splicing, result in a reduced but architecturally normal brain. Examination of a conditional Pqbp1-knockout (cKO) mouse with microcephaly failed to reveal either abnormal centrosomes or mitotic spindles, increased neurogenesis from the neural stem progenitor cell (NSPC) pool or increased cell death in vivo. Instead, we observed an increase in the length of the cell cycle, particularly for the M phase in NSPCs. Corresponding to the developmental expression of Pqbp1, the stem cell pool in vivo was decreased at E10 and remained at a low level during neurogenesis (E15) in Pqbp1-cKO mice. The expression profiles of NSPCs derived from the cKO mouse revealed significant changes in gene groups that control the M phase, including anaphase-promoting complex genes, via aberrant transcription and RNA splicing. Exogenous Apc4, a hub protein in the network of affected genes, recovered the cell cycle, proliferation, and cell phenotypes of NSPCs caused by Pqbp1-cKO. These data reveal a mechanism of brain size control based on the simple reduction of the NSPC pool by cell cycle time elongation. Finally, we demonstrated that in utero gene therapy for Pqbp1-cKO mice by intraperitoneal injection of the PQBP1-AAV vector at E10 successfully rescued microcephaly with preserved cortical structures and improved behavioral abnormalities in Pqbp1-cKO mice, opening a new strategy for treating this intractable developmental disorder.


Asunto(s)
Terapia Genética , Microcefalia/genética , Microcefalia/terapia , Células-Madre Neurales/fisiología , Proteínas Nucleares/deficiencia , Adenoviridae/genética , Animales , Subunidad Apc4 del Ciclosoma-Complejo Promotor de la Anafase/metabolismo , Apoptosis/genética , Encéfalo/patología , Proteínas Portadoras/genética , Moléculas de Adhesión Celular/metabolismo , Ciclo Celular , Proliferación Celular , Proteínas de Unión al ADN , Modelos Animales de Enfermedad , Embrión de Mamíferos , Femenino , Humanos , Masculino , Ratones , Ratones Noqueados , Microcefalia/patología , Nestina/genética , Nestina/metabolismo , Neurogénesis , Proteínas Nucleares/genética , Sinapsinas/genética , Sinapsinas/metabolismo
8.
Eur J Neurol ; 22(5): 859-65, e61, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25712171

RESUMEN

BACKGROUND AND PURPOSE: To determine the frequency of new ischaemic or hemorrhagic brain lesions on early follow-up magnetic resonance imaging (MRI) in patients with cervical artery dissection (CAD) and to investigate the relationship with antithrombotic treatment. METHODS: This prospective observational study included consecutive CAD patients with ischaemic or non-ischaemic symptoms within the preceding 4 weeks. All patients had baseline brain MRI scans at the time of CAD diagnosis and follow-up MRI scans within 30 days thereafter. Ischaemic lesions were detected by diffusion-weighted imaging (DWI), intracerebral bleeds (ICBs) by paramagnetic-susceptible sequences. Outcome measures were any new DWI lesions or ICBs on follow-up MRI scans. Kaplan-Meier statistics and calculated odds ratios with 95% confidence intervals were used for lesion occurrence, baseline characteristics and type of antithrombotic treatment (antiplatelet versus anticoagulant). RESULTS: Sixty-eight of 74 (92%) CAD patients were eligible for analysis. Median (interquartile range) time interval between baseline and follow-up MRI scans was 5 (3-10) days. New DWI lesions occurred in 17 (25%) patients with a cumulative 30-day incidence of 41.3% (standard error 8.6%). Occurrence of new DWI lesions was associated with stroke or transient ischaemic attack at presentation [7.86 (2.01-30.93)], occlusion of the dissected vessel [4.09 (1.24-13.55)] and presence of DWI lesions on baseline MRI [6.67 (1.70-26.13)]. The type of antithrombotic treatment had no impact either on occurrence of new DWI lesions [1.00 (0.32-3.15)] or on functional 6-month outcome [1.27 (0.41-3.94)]. No new ICBs were observed. CONCLUSION: New ischaemic brain lesions occurred in a quarter of CAD patients, independently of the type of antithrombotic treatment. MRI findings could potentially serve as surrogate outcomes in pilot treatment trials.


Asunto(s)
Anticoagulantes/uso terapéutico , Disección Aórtica/epidemiología , Isquemia Encefálica/epidemiología , Hemorragia Cerebral/epidemiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Adulto , Anticoagulantes/efectos adversos , Isquemia Encefálica/inducido químicamente , Hemorragia Cerebral/inducido químicamente , Imagen de Difusión por Resonancia Magnética , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos
9.
Z Gerontol Geriatr ; 48(7): 625-32, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25990007

RESUMEN

BACKGROUND: Joint contractures are a common phenomenon in older persons and are assessed by measuring the range of motion; however, little is known about the impact of joint contractures on activities of daily living (ADL). OBJECTIVES: The aim of the study was to identify problems related to joint contracture of older persons in a geriatric setting using the international classification of functioning, disability and health (ICF) as a framework. MATERIAL AND METHODS: A cross-sectional study was conducted between February and July 2013 in nursing homes (n=11) and geriatric rehabilitation hospitals (n=3) in North Rhine-Westphalia, Germany. The study population included persons aged ≥65 years with at least one diagnosis of joint contracture. If the participant was unable to adequately answer the best informed next of kin or staff nurse acted as a proxy. A questionnaire with 124 ICF categories was completed through face-to-face interviews with the participants. RESULTS: A total of 149 participants were included in the study. The mean age was 77.6±6.9 years and 69.8% were women. Problems in climbing (94.0%), walking long distances (92.6%) and kneeling (92.6%) were most frequently identified. The most often identified facilitators in environmental factors were health services, systems and policies (93.2%), whereas the leading barrier was climate (30.3%). CONCLUSION: Joint contractures have a huge impact on functioning and social participation and particularly on personal mobility. From the nursing and rehabilitation perspective, assessments should not only measure joint mobility but also determine and quantify the consequences of contractures on ADL.


Asunto(s)
Actividades Cotidianas/psicología , Clima , Contractura/epidemiología , Contractura/psicología , Evaluación Geriátrica/estadística & datos numéricos , Calidad de Vida/psicología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Alemania/epidemiología , Hogares para Ancianos/estadística & datos numéricos , Humanos , Masculino , Casas de Salud/estadística & datos numéricos , Prevalencia , Factores de Riesgo , Perfil de Impacto de Enfermedad
11.
Eur J Neurol ; 21(12): 1493-9, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25041759

RESUMEN

BACKGROUND AND PURPOSE: Patients with prior stroke within 3 months have been mostly excluded from randomized thrombolysis trials mainly because of the fear of an increased rate of symptomatic intracerebral hemorrhage (sICH). The aim of this study was to compare baseline characteristics and clinical outcome of thrombolyzed patients who had a previous stroke within the last 3 months with those not fulfilling this criterion (comparison group). METHODS: In all, 1217 patients were included in our analysis (42.2% women, mean age 68.8 ± 14.4 years). RESULTS: Patients with previous stroke within the last 3 months (17/1.4%) had more often a basilar artery occlusion (41.2% vs. 10.8%) and less frequently a modified Rankin scale (mRS) score 0-1 prior to index stroke (88.2% vs. 97.3%) and a higher mean time lapse from symptom onset to thrombolysis (321 min vs. 262 min) than those in the comparison group. Stroke severity was not different between the two groups. Rates of sICH were 11.8% vs. 6%. None of the sICHs and only one asymptomatic intracerebral hemorrhage occurred in the region of the former infarct. At 3 months, favorable outcome (mRS ≤ 2) in patients with previous stroke within 3 months was 29.4% (vs. 48.9%) and mortality 41.2% (vs. 22.7%). CONCLUSIONS: In patients with prior stroke within the last 3 months, none of the sICHs and only one asymptomatic intracerebral hemorrhage occurred in the region of the former infarct. The high mortality was influenced by four patients, who died until discharge due to acute major index stroke. It is reasonable to include these patients in randomized clinical trials and registries to assess further their thrombolysis benefit-risk ratio.


Asunto(s)
Hemorragia Cerebral/etiología , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Anciano , Anciano de 80 o más Años , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/mortalidad , Terapia Trombolítica/mortalidad , Terapia Trombolítica/estadística & datos numéricos , Factores de Tiempo , Resultado del Tratamiento
12.
Hum Mol Genet ; 20(24): 4916-31, 2011 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-21933836

RESUMEN

The polyglutamine-binding protein 1 (PQBP1) has been linked to several X-linked intellectual disability disorders and progressive neurodegenerative diseases. While it is currently known that PQBP1 localizes in nuclear speckles and is engaged in transcription and splicing, we have now identified a cytoplasmic pool of PQBP1. Analysis of PQBP1 complexes revealed six novel interacting proteins, namely the RNA-binding proteins KSRP, SFPQ/PSF, DDX1 and Caprin-1, and two subunits of the intracellular transport-related dynactin complex, p150(Glued) and p27. PQBP1 protein complex formation is dependent on the presence of RNA. Immunofluorescence studies revealed that in primary neurons, PQBP1 co-localizes with its interaction partners in specific cytoplasmic granules, which stained positive for RNA. Our results suggest that PQBP1 plays a role in cytoplasmic mRNA metabolism. This is further supported by the partial co-localization and interaction of PQBP1 with the fragile X mental retardation protein (FMRP), which is one of the best-studied proteins found in RNA granules. In further studies, we show that arsenite-induced oxidative stress caused relocalization of PQBP1 to stress granules (SGs), where PQBP1 co-localizes with the new binding partners as well as with FMRP. Additional results indicated that the cellular distribution of PQBP1 plays a role in SG assembly. Together these data demonstrate a role for PQBP1 in the modulation of SGs and suggest its involvement in the transport of neuronal RNA granules, which are of critical importance for the development and maintenance of neuronal networks, thus illuminating a route by which PQBP1 aberrations might influence cognitive function.


Asunto(s)
Cromosomas Humanos X/genética , Gránulos Citoplasmáticos/metabolismo , Genes Ligados a X/genética , Discapacidad Intelectual/genética , Neuronas/metabolismo , Oligopéptidos/genética , ARN/metabolismo , Animales , Células Cultivadas , Complejo Dinactina , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Humanos , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Modelos Biológicos , Oligopéptidos/metabolismo , Unión Proteica , Transporte de Proteínas , Proteínas de Unión al ARN/metabolismo , Ribosomas/metabolismo , Antígeno Intracelular 1 de las Células T
13.
Eur J Neurol ; 20(7): 1017-24, e87, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23398194

RESUMEN

BACKGROUND AND PURPOSE: Endovascular therapy is used increasingly for treatment of acute symptomatic internal carotid artery (ICA) occlusion, although randomized trials are lacking. Predictors of outcome are therefore of special interest. METHODS: From 1992 to 2010 we treated 201 patients with acute ICA occlusion with intra-arterial pharmacological thrombolysis (32), endovascular mechanical therapy (78) or a combination of both (91). All data were assessed prospectively. RESULTS: There were 76/38% patients with tandem occlusions [ICA plus middle (MCA) or anterior cerebral arteries (ACA)], 18/9% without concomitant occlusions of major intracranial arteries (ICA plus branch occlusion) and 107/53% with functional ICA-T occlusions (ICA plus MCA and ACA). Median baseline National Institute of Health Stroke Scale (NIHSS) score was 17. Good recanalization (Thrombolysis in Myocardial Infarction 2-3) was achieved in (157/201) 78% patients and good reperfusion (Thrombolysis in Cerebral Infarction 2-3) in (151/182) 83%. Better recanalization rates were obtained with mechanical approaches, with/without thrombolytics (78/91 = 86% and 64/78 = 82%) compared with pharmacological thrombolysis only (15/32 = 47%; P < 0.001). Twelve patients (6%) suffered symptomatic intracranial haemorrhages. The 3-month outcome was favourable [modified Rankin score (mRS) 0-2] in 54/28% patients and moderate (mRS 0-3) in 90/46%; 60/31% patients died. Only 17/16% patients with functional ICA-T occlusions had favourable outcomes compared with 32/44% with tandem occlusions and 5/31% with ICA plus cerebral branch occlusions (P = 0.001). In multivariate analysis age [odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.93-0.98], NIHSS on admission (OR = 0.9, 95% CI = 0.83-0.98) and functional ICA-T occlusion (OR = 0.35, 95% CI = 0.16-0.77) were non-modifiable predictors, and vessel recanalization was the only modifiable predictor of outcome (OR = 9.30, 95% CI = 2.03-42.63). CONCLUSIONS: The outcome of acute symptomatic ICA occlusion is poor. However, recanalization is associated with better outcome, and recanalization rates with mechanical techniques were superior to merely pharmacological recanalization attempts.


Asunto(s)
Trombosis de las Arterias Carótidas/tratamiento farmacológico , Trombosis de las Arterias Carótidas/terapia , Arteria Carótida Interna/efectos de los fármacos , Trombolisis Mecánica , Terapia Trombolítica , Trombosis de las Arterias Carótidas/patología , Arteria Carótida Interna/patología , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reperfusión , Factores de Riesgo , Resultado del Tratamiento
14.
Eur J Neurol ; 20(6): 865-71, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23293861

RESUMEN

BACKGROUND AND PURPOSE: Intra-arterial treatment (IAT) is effective when performed within 6 h of symptom onset in selected stroke patients ('T < 6H'). Its safety and efficacy is unclear when the patient has had symptoms for more than 6 h ('T > 6H') or for an unknown time (unclear-onset stroke, UOS), or woke up with a stroke (wake-up stroke, WUS). In this study we compared the safety of IAT in these four patient groups. METHODS: Eight-hundred and fifty-nine patients treated with IAT were enrolled. The main outcome parameters were clinical outcome [excellent: modified Rankin Scale (mRS) 0 or 1; or favorable: mRS 0-2] or mortality 3 months after treatment. Further outcome parameters were the rates of vessel recanalization, and cerebral and systemic hemorrhage. RESULTS: Six-hundred and fifty-four patients were treated before (T < 6H) and 205 after 6 h or an unknown time (128 T > 6H, 55 WUS and 22 UOS). NIHSS scores were higher in UOS patients than in T < 6H patients, vertebrobasilar occlusion was more common in T > 6H and UOS patients, and middle cerebral artery occlusions less common in T > 6H than in T < 6H patients. Other baseline characteristics were similar. There was no significant difference in clinical outcome and the rate of hemorrhage in multivariable regression analysis. CONCLUSIONS: Clinical outcome of our four groups of patients was similar with no increase of hemorrhage rates in patients treated after awakening, after an unknown time or more than 6 h. Our preliminary data suggest that treatment of such patients may be performed safely. If confirmed in randomized trials, this would have major clinical implications.


Asunto(s)
Procedimientos Endovasculares/métodos , Accidente Cerebrovascular/prevención & control , Terapia Trombolítica/métodos , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Anciano , Procedimientos Endovasculares/efectos adversos , Femenino , Hemorragia/inducido químicamente , Hemorragia/diagnóstico , Hemorragia/epidemiología , Humanos , Inyecciones Intraarteriales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Activador de Plasminógeno de Tipo Uroquinasa/efectos adversos
15.
Appl Opt ; 52(18): 4103-10, 2013 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-23842150

RESUMEN

Optical simulation software based on the ray-tracing method offers easy and fast results in imaging optics. This method can also be applied in other fields of light propagation. For short distance communications, polymer optical fibers (POFs) are gradually gaining importance. This kind of fiber offers a larger core diameter, e.g., the step index POF features a core diameter of 980 µm. Consequently, POFs have a large number of modes (>3 million modes) in the visible range, and ray tracing could be used to simulate the propagation of light. This simulation method is applicable not only for the fiber itself but also for the key components of a complete POF network, e.g., couplers or other key elements of the transmission line. In this paper a demultiplexer designed and developed by means of ray tracing is presented. Compared to the classical optical design, requirements for optimal design differ particularly with regard to minimizing the insertion loss (IL). The basis of the presented key element is a WDM device using a Rowland spectrometer setup. In this approach the input fiber carries multiple wavelengths, which will be divided into multiple output fibers that transmit only one wavelength. To adapt the basic setup to POF, the guidance of light in this element has to be changed fundamentally. Here, a monolithic approach is presented with a blazed grating using an aspheric mirror to minimize most of the aberrations. In the simulations the POF is represented by an area light source, while the grating is analyzed for different orders and the highest possible efficiency. In general, the element should be designed in a way that it can be produced with a mass production technology like injection molding in order to offer a reasonable price. However, designing the elements with regard to injection molding leads to some inherent challenges. The microstructure of an optical grating and the thick-walled 3D molded parts both result in high demands on the injection molding process. This also requires complex machining of the molding tool. Therefore, different experiments are done to optimize the process parameter, find the best molding material, and find a suitable machining method for the molding tool. The paper will describe the development of the demultiplexer by means of ray-tracing simulations step by step. Also, the process steps and the realized solutions for the injection molding are described.

16.
AJNR Am J Neuroradiol ; 44(9): 1050-1056, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37500281

RESUMEN

BACKGROUND AND PURPOSE: Intra-arterial thrombolytics may be used to treat distal vessel occlusions, which cause incomplete reperfusion following mechanical thrombectomy. Because immediate reperfusion after intra-arterial thrombolytics occurs rarely, the aim of this study was to assess the delayed effect of intra-arterial thrombolytics using follow-up perfusion imaging. MATERIALS AND METHODS: We included patients from a prospective stroke registry (February 2015 to September 2022) who had undergone mechanical thrombectomy and had incomplete reperfusion (expanded TICI 2a-2c) and available 24 hour perfusion imaging. Perfusion imaging was rated as delayed reperfusion if time-sensitive perfusion maps did not show wedge-shaped delays suggestive of persisting occlusions corresponding to the post-mechanical thrombectomy angiographic deficit. Patients treated with intra-arterial thrombolytics were compared with controls using multivariable logistic regression and inverse probability of treatment weighting matching for baseline differences and factors associated with delayed reperfusion. RESULTS: The median age of the final study population (n = 459) was 74 years (interquartile range, 63-81 years), and delayed reperfusion occurred in 61% of cases. Patients treated with additional intra-arterial thrombolytics (n = 40) were younger and had worse expanded TICI scores. After matching was performed, intra-arterial thrombolytics was associated with higher rates of delayed reperfusion (adjusted OR = 2.7; 95% CI, 1.1-6.4) and lower rates of new infarction in the residually hypoperfused territory after mechanical thrombectomy (adjusted OR = 0.3; 95% CI, 0.1-0.7). No difference was found in the rates of functional independence (90-day mRS, 0-2; adjusted OR = 1.4; 95% CI, 0.4-4.1). CONCLUSIONS: Rescue intra-arterial thrombolytics is associated with delayed reperfusion of remaining vessel occlusions following incomplete mechanical thrombectomy. The value of intra-arterial thrombolytics as a potential therapy for incomplete reperfusions after mechanical thrombectomy should be assessed in the setting of randomized controlled trials.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Resultado del Tratamiento , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Fibrinolíticos/uso terapéutico , Reperfusión/métodos , Terapia Trombolítica , Isquemia Encefálica/terapia , Estudios Retrospectivos
17.
Eur Stroke J ; 8(2): 575-580, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37231695

RESUMEN

PURPOSE: There is little data on the safety and efficacy of endovascular treatment (EVT) in comparison with intravenous thrombolysis (IVT) in acute ischemic stroke due to isolated posterior cerebral artery occlusion (IPCAO). We aimed to investigate the functional and safety outcomes of stroke patients with acute IPCAO treated with EVT (with or without prior bridging IVT) compared to IVT alone. METHODS: We did a multicenter retrospective analysis of data from the Swiss Stroke Registry. The primary endpoint was overall functional outcome at 3 months in patients undergoing EVT alone or as part of bridging, compared with IVT alone (shift analysis). Safety endpoints were mortality and symptomatic intracranial hemorrhage. EVT and IVT patients were matched 1:1 using propensity scores. Differences in outcomes were examined using ordinal and logistic regression models. FINDINGS: Out of 17,968 patients, 268 met the inclusion criteria and 136 were matched by propensity scores. The overall functional outcome at 3 months was comparable between the two groups (EVT vs IVT as reference category: OR = 1.42 for higher mRS, 95% CI = 0.78-2.57, p = 0.254). The proportion of patients independent at 3 months was 63.2% in EVT and 72.1% in IVT (OR = 0.67, 95% CI = 0.32-1.37, p = 0.272). Symptomatic intracranial hemorrhages were overall rare and present only in the IVT group (IVT = 5.9% vs EVT = 0%). Mortality at 3 months was also similar between the two groups (IVT = 0% vs EVT = 1.5%). CONCLUSION: In this multicenter nested analysis, EVT and IVT in patients with acute ischemic stroke due to IPCAO were associated with similar overall good functional outcome and safety. Randomized studies are warranted.


Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Terapia Trombolítica/efectos adversos , Estudios Retrospectivos , Accidente Cerebrovascular Isquémico/etiología , Arteria Cerebral Posterior , Suiza/epidemiología , Resultado del Tratamiento , Accidente Cerebrovascular/terapia , Hemorragias Intracraneales/etiología , Sistema de Registros , Procedimientos Endovasculares/efectos adversos
18.
Nano Lett ; 11(3): 1009-13, 2011 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-21319837

RESUMEN

In this Letter, we introduce a new nanoantenna concept aimed at generating a single magnetic hot spot in the optical frequency range, thus confining and enhancing the magnetic optical field on the background of a much lower electric field. This nanoantenna, designed by applying Babinet's principle to the bowtie nanoaperture, takes the shape of a diabolo. It differs from the well-known bowtie nanoantenna in that the opposing pair of metal triangles are electrically connected through their facing tips. Thus instead of a large charge density accumulating at the air gap of the bowtie nanoantenna, leading to a large electric field, a high optical current density develops within the central "metal gap" of the diabolo nanoantenna, leading to a large magnetic field. Numerical simulation results on the first nanodiabolo geometries show a 2900-fold enhancement of the magnetic field at a wavelength of 2540 nm, confined to a 40-by-40 nm region near the center of the nanoantenna.

19.
Ther Umsch ; 69(9): 536-42, 2012 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-22923357

RESUMEN

The risk to have a stroke during childhood is at least as frequent as to suffer from a brain tumour. Unlike adults, in whom ischaemic strokes overweigh haemorrhagic strokes, ischaemic and haemorrhagic strokes are equally frequent in children, occurring with an incidence of 2 - 3/100'000 children/year. Even though the clinical presentation of arterial-ischaemic stroke in children (pedAIS) is similar to adults, time to diagnosis is longer. The delay to diagnosis is mainly explained by the low index of suspicion of both the general population and the medical personnel, a broad range of differential diagnoses, and the fact that diagnostic imaging in children often requires sedation, which is not always readily available. PedAIS is a multiple risk problem, usually occurring due to a combination of risk factors, such as infectious diseases, dehydration, trauma or an underlying condition such as congenital heart disease. Still little is known about the appropriate management of pedAIS. Supportive measures are considered to be the mainstay of therapy. The use of antithrombotic medication depends on pedAIS aetiology. In an ongoing multicenter trial, the safety and effectiveness of thrombolysis are currently being investigated. PedAIS carries an important mortality and morbidity, with neurological and neuropsychological deficits persisting in two thirds of the affected children.


Asunto(s)
Accidente Cerebrovascular/etiología , Niño , Sedación Consciente , Estudios Transversales , Diagnóstico Tardío , Diagnóstico Diferencial , Diagnóstico por Imagen , Humanos , Incidencia , Examen Neurológico , Pronóstico , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia
20.
Ther Umsch ; 69(9): 511-6, 2012 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-22923354

RESUMEN

In selected stroke patients intravenous thrombolysis and/or endovascular therapies lead to a significant reduction of long term disabilities. In case of no contraindications, patients with acute ischemic stroke, which arrive within the time window on the emergency unit, should receive thrombolysis consequently and current data indicate that patients with a severe acute ischemic stroke and a proximal cerebral arterial vessel occlusion (i. e. main stem of the arteria cerebri media, posterior, maybe also anterior, arteria carotis interna and basilaris) should preferentially be treated endovascularly, patients with a peripheral cerebral arterial vessel occlusion (i. e. main branch of the arteria cerebri media, anterior and posterior) and mild symptoms with intravenous thrombolysis.


Asunto(s)
Trastornos Cerebrovasculares/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodos , Enfermedad Aguda , Angioedema/inducido químicamente , Angiografía Cerebral , Trastornos Cerebrovasculares/diagnóstico , Contraindicaciones , Imagen de Difusión por Resonancia Magnética , Servicio de Urgencia en Hospital , Hemorragia/inducido químicamente , Humanos , Inyecciones Intraarteriales , Inyecciones Intravenosas , Accidente Cerebrovascular/diagnóstico , Terapia Trombolítica/efectos adversos
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