RESUMEN
BACKGROUND AND PURPOSE: Granulocyte colony-stimulating factor (G-CSF; AX200; Filgrastim) is a stroke drug candidate with excellent preclinical evidence for efficacy. A previous phase IIa dose-escalation study suggested potential efficacy in humans. The present large phase IIb trial was powered to detect clinical efficacy in acute ischemic stroke patients. METHODS: G-CSF (135 µg/kg body weight intravenous over 72 hours) was tested against placebo in 328 patients in a multinational, multicenter, randomized, and placebo-controlled trial (NCT00927836; www.clinicaltrial.gov). Main inclusion criteria were ≤9-hour time window after stroke onset, infarct localization in the middle cerebral artery territory, baseline National Institutes of Health Stroke Scale score range of 6 to 22, and baseline diffusion-weighted imaging lesion size ≥15 mL. Primary and secondary end points were the modified Rankin scale score and the National Institutes of Health Stroke Scale score at day 90, respectively. Data were analyzed using a prespecified model that adjusted for age, National Institutes of Health Stroke Scale score at baseline, and initial infarct volume (diffusion-weighted imaging). RESULTS: G-CSF treatment failed to meet the primary and secondary end points of the trial. For additional end points such as mortality, Barthel index, or infarct size at day 30, G-CSF did not show efficacy either. There was, however, a trend for reduced infarct growth in the G-CSF group. G-CSF showed the expected peripheral pharmacokinetic and pharmacodynamic profiles, with a strong increase in leukocytes and monocytes. In parallel, the cytokine profile showed a significant decrease of interleukin-1. CONCLUSIONS: G-CSF, a novel and promising drug candidate with a comprehensive preclinical and clinical package, did not provide any significant benefit with respect to either clinical outcome or imaging biomarkers. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00927836.
Asunto(s)
Infarto Encefálico , Factor Estimulante de Colonias de Granulocitos , Accidente Cerebrovascular , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Infarto Encefálico/diagnóstico por imagen , Infarto Encefálico/tratamiento farmacológico , Infarto Encefálico/metabolismo , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Factor Estimulante de Colonias de Granulocitos/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/farmacocinética , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/metabolismo , Factores de TiempoRESUMEN
BACKGROUND: In patients with carotid artery disease, carotid endarterectomy (CEA) and carotid stenting (CAS) are treatment options. Controversy exists as to the relative efficacy of the 2 techniques in preventing late events. METHODS AND RESULTS: The Reduction of Atherothrombosis for Continued Health (REACH) Registry recruited > 68,000 outpatients ≥ 45 years of age with established atherothrombotic disease or ≥ 3 risk factors for atherothrombosis. Patients with CAS or CEA were chosen and followed up prospectively for the occurrence of cardiovascular events. Propensity score matching was performed to assemble a cohort of patients in whom all baseline covariates would be well balanced. Primary outcome was defined as death or stroke at the 2-year follow-up. Secondary outcome was stroke or transient ischemic attack. Tertiary outcome was a composite of death, myocardial infarction, or stroke and the individual outcomes. Of the 68 236 patients with atherothrombosis, 3412 patients (5%) had a history of carotid artery revascularization (70% asymptomatic carotid stenosis), 1025 (30%) with CAS and 2387 (70%) with CEA. Propensity score analyses matched 836 CAS patients with 836 CEA patients. At the end of 2 years of follow-up, in the propensity score-matched cohort, CAS was associated with a risk similar to CEA for the primary (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.57 to 1.26), secondary (HR, 1.20; 95% CI, 0.73 to 1.96), and tertiary (HR, 0.72; 95% CI, 0.51 to 1.01) composite outcome, death (HR, 0.63; 95% CI, 0.40 to 1.00), and stroke (HR, 1.48; 95% CI, 0.79 to 2.80). CONCLUSIONS: In a real-world cohort of patients with a history of carotid artery revascularization, CAS was comparable to CEA for late outcomes.
Asunto(s)
Enfermedades de las Arterias Carótidas/terapia , Endarterectomía Carotidea , Puntaje de Propensión , Stents , Anciano , Anciano de 80 o más Años , Enfermedades de las Arterias Carótidas/complicaciones , Trombosis de las Arterias Carótidas/etiología , Trombosis de las Arterias Carótidas/prevención & control , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Few practice-based studies have reported vascular outcome events among patients with cerebrovascular disease (CeVD). We describe 2-year vascular outcomes among symptomatic CeVD patients from the REduction of Atherothrombosis for Continued Health (REACH) Registry. METHODS: Vascular events (stroke; myocardial infarction, MI; cardiovascular death, CV death; hospitalization) were studied among symptomatic CeVD patients from a prospective cohort of stable outpatients with established atherothrombosis or ≥3 atherothrombotic risk factors. RESULTS: Of the 69,055 patients in REACH, 18,992 (28%) had symptomatic CeVD, of which outcome data were available for 18,189 patients. At 2 years, the frequency of non-fatal stroke was 5.93% (95% CI 5.22-6.64), non-fatal MI 2.21% (95% CI 1.65-2.76), CV death 4.45% (95% CI 3.66-5.22), combined vascular endpoint 11.48% (95% CI 10.46-12.49), and all deaths 7.39% (95% CI 6.34-8.42). The frequency of stroke, MI, CV death, or hospitalization for atherothrombotic events was 21.05% (95% CI 20.05-22.03). Event rates were lowest among patients with CeVD alone and highest among patients with CeVD, coronary artery disease, and peripheral artery disease. Other predictors of the primary outcome were increasing age, history of diabetes, current smoking, asymptomatic carotid stenosis, and carotid plaque. Outcomes were similar across geographical regions. CONCLUSIONS: Symptomatic CeVD patients encounter high vascular event rates despite treatment. Recurrent nonfatal stroke is more common than nonfatal MI.
Asunto(s)
Trastornos Cerebrovasculares/epidemiología , Anciano , Anciano de 80 o más Años , Asia/epidemiología , Australia/epidemiología , Trastornos Cerebrovasculares/mortalidad , Trastornos Cerebrovasculares/terapia , Distribución de Chi-Cuadrado , Europa (Continente)/epidemiología , Femenino , Hospitalización , Humanos , América Latina/epidemiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/mortalidad , América del Norte/epidemiología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Recurrencia , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/mortalidad , Factores de TiempoRESUMEN
BACKGROUND: After acute ischaemic stroke (AIS) or transient ischaemic attack (TIA), the detection of peripheral arterial disease (PAD) as a marker of generalized atherosclerosis may improve the risk stratification and prevention of future atherothrombotic events. We aimed to determine the prevalence of PAD indicated by an ankle-brachial index (ABI) of < or =0.9 in a large cohort of patients with AIS/TIA. METHODS: In this prospective, multicentre, Austrian, cross-sectional study (OECROSS), 759 patients with AIS or TIA were recruited for a systematic assessment of cardiovascular risk profiles and Doppler ultrasound at the ankle and brachial artery to calculate the ABI from systolic blood pressure readings. RESULTS: 739 patients (97.4%) had a complete ABI assessment. The mean age was 69.5 (+/- 12.1) years, and 55.8% of the patients were men. 81.6% of the patients had AIS and 18.4% had TIA. Only 6.2% of the patients had a history of PAD, but an abnormal ABI of < or =0.9 was found in 44.9%. Patients with an ABI of < or =0.9 were more likely (p < 0.05) to be older and have a history of PAD, hypertension, diabetes and congestive heart failure. An ABI of < or =0.9 was significantly associated (p < 0.0005) with a presence of carotid stenosis of >50% and an Essen Stroke Risk Score of >2, indicating a risk of > or =4% per year of stroke recurrence. DISCUSSION: A high proportion of patients with AIS/TIA have subclinical PAD, a cross-risk stroke physicians should be aware of. Large longitudinal studies are needed to elucidate whether the ABI can improve our estimation of the risk of future atherothrombotic events and help in optimizing secondary prevention.
Asunto(s)
Isquemia Encefálica/complicaciones , Enfermedades Vasculares Periféricas/complicaciones , Accidente Cerebrovascular/etiología , Anciano , Anciano de 80 o más Años , Tobillo/irrigación sanguínea , Austria/epidemiología , Presión Sanguínea , Arteria Braquial/fisiopatología , Isquemia Encefálica/epidemiología , Isquemia Encefálica/fisiopatología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/epidemiología , Enfermedades Vasculares Periféricas/fisiopatología , Prevalencia , Estudios Prospectivos , Recurrencia , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/fisiopatología , Ultrasonografía DopplerRESUMEN
BACKGROUND AND PURPOSE: Microplasmin is a recombinant truncated form of human plasmin. It has demonstrated efficacy in experimental animal models of stroke and tolerability in healthy volunteers. We tested the tolerability of microplasmin in patients with acute ischemic stroke. METHODS: In a multicenter, double-blind, randomized, placebo-controlled Phase II trial, 40 patients with ischemic stroke were treated with either placebo or active drug between 3 and 12 hours after symptom onset in a dose-finding design. Ten patients received placebo, 6 patients received a total dose of 2 mg/kg, 12 patients received a total dose of 3 mg/kg, and 12 patients received a total dose of 4 mg/kg. We studied the pharmacodynamics of microplasmin and its effect on the clinical and hemodynamic parameters of the patients. MRI was used as a surrogate marker and matrix metalloproteinases serum concentrations were used as markers of neurovascular integrity. The study was underpowered to detect clinical efficacy. RESULTS: Microplasmin induced reversible effects on markers of systemic thrombolysis and neutralized alpha(2)-antiplasmin by up to 80%. It was well tolerated with one of 30 treated patients developing a fatal symptomatic intracerebral hemorrhage. No significant effect on reperfusion rate or on clinical outcome was observed. Matrix metalloproteinase-2 levels were reduced in microplasmin-treated patients. CONCLUSIONS: Microplasmin was well tolerated and achieved neutralization of alpha(2)-antiplasmin. Further studies are warranted to determine whether microplasmin is an effective therapeutic agent for ischemic stroke.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Revascularización Cerebral/métodos , Fibrinolisina/administración & dosificación , Fibrinolíticos/administración & dosificación , Fragmentos de Péptidos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/patología , Relación Dosis-Respuesta a Droga , Femenino , Fibrinolisina/efectos adversos , Fibrinolisina/farmacocinética , Fibrinolíticos/efectos adversos , Fibrinolíticos/farmacocinética , Humanos , Inyecciones Intravenosas , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/efectos adversos , Fragmentos de Péptidos/farmacocinética , Placebos , Accidente Cerebrovascular/patología , Resultado del TratamientoRESUMEN
Neutralizing antibodies against interferon-beta are associated with a reduction of the efficacy of this drug. Continuing treatment leads to a decline or even loss of neutralizing antibodies over years. No strategies are currently available to shorten the period of neutralizing antibody positivity. The objective of this study was to investigate the effect of switching between high and low immunogenic interferon-beta products on neutralising antibody titres. Twenty-four patients treated with the subcutaneously administered interferon-beta 1b or 1a and high titres of neutralizing antibodies were included. At baseline interferon-beta therapy was interrupted for 3 months and two pulses of high dose methylprednisolone were applied. Patients were then randomized to receive either the previous interferon-beta preparation or the low immunogenic intramuscular interferon-beta 1a. The primary end-point was the change of neutralizing antibody titres 12 months after randomization. Twelve patients were switched to interferon-beta 1a intramuscularly and 12 patients remained on previous treatment. Median neutralizing antibody titres were 846 NU at baseline and 196 NU at the end of the study. The median change of neutralizing antibody titres did not differ significantly between therapy switchers and non-switchers. Baseline and final neutralizing antibody titres correlated significantly. In conclusion, neither switching nor continuous therapy with any subcutaneous interferon-beta preparation significantly changed neutralizing antibody titres.
Asunto(s)
Anticuerpos Neutralizantes/sangre , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/inmunología , Interferón beta/administración & dosificación , Interferón beta/inmunología , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Austria , Esquema de Medicación , Glucocorticoides/administración & dosificación , Humanos , Infusiones Intravenosas , Inyecciones Intramusculares , Inyecciones Subcutáneas , Interferón beta-1a , Interferon beta-1b , Imagen por Resonancia Magnética , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/inmunología , Esclerosis Múltiple Recurrente-Remitente/patología , Quimioterapia por Pulso , Recurrencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs. METHODS: The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P
Asunto(s)
Fibrinolíticos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/estadística & datos numéricos , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del Tratamiento , Actividades Cotidianas , Anciano , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/epidemiología , Comorbilidad , Grupos Diagnósticos Relacionados , Femenino , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Selección de Paciente , Pronóstico , Sistema de Registros , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/mortalidad , Terapia Trombolítica/efectos adversos , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/efectos adversosRESUMEN
BACKGROUND: Atrial fibrillation (AF) is a major risk factor (RF) for ischemic stroke. Its prevalence and prognostic impact in patients with atherothrombosis are unclear. METHODS: Risk factors, drug usage, and 1-year cardiovascular (CV) outcomes (CV death, myocardial infarction [MI], and stroke) were compared in AF and non-AF patients from the REduction of Atherothrombosis for Continued Health (REACH) Registry, an international, prospective cohort of 68,236 stable outpatients with established atherothrombosis or>or=3 atherothrombotic RFs. RESULTS: Atrial fibrillation and 1-year follow-up data are available for 63,589 patients. The prevalence of AF was, 12.5%, 13.7%, 11.5%, and 6.2% among coronary artery disease, CV disease, peripheral artery disease, and RF-only patients, respectively. Of the 6,814 patients with AF, 6.7% experienced CV death, nonfatal MI, or nonfatal stroke within a year. The annual incidence of nonfatal stroke (2.4% vs 1.6%, P<.0001) and unstable angina (6.0% vs 4.0%, P<.00001) was higher, and CV death was more than double (3.2% vs 1.4%, P<.0001), in AF versus non-AF patients. In these patients with or at high risk of atherothrombosis, most patients with AF received antiplatelet agents, but only 53.1% were treated with oral anticoagulants. Even with high CHADS2 (congestive heart failure, hypertension, aging, diabetes mellitus, and stroke) scores, anticoagulant use did not exceed (59%). The rate of bleeding requiring hospitalization was higher in AF versus non-AF patients (1.5% vs 0.8%, P<.0001), possibly related to the more frequent use of anticoagulants (53.1% vs 7.1%). CONCLUSIONS: Atrial fibrillation is common in patients with atherothrombosis, associated with more frequent fatal and nonfatal CV outcomes, and underuse of oral anticoagulants.
Asunto(s)
Aterosclerosis/complicaciones , Fibrilación Atrial/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Trombosis/complicaciones , Anciano , Femenino , Humanos , Masculino , Prevalencia , Factores de RiesgoRESUMEN
OBJECTIVE: To test the hypothesis that pre-treatment Creactive protein (CRP) predicts outcome in stroke patients undergoing intravenous thrombolysis (IVT) treatment. METHODS: We analyzed the data of 111 consecutive patients with IVT within 6 hours of stroke onset for stroke involving the middle cerebral artery territory and admission CRP < or = 6 mg/dl. RESULTS: CRP levels were consistently, yet non-significantly lower in patients with unfavourable outcome definitions. Median (range) CRP levels were 0.3 (0-5.9) mg/dl vs. 0.4 (0-5.7) mg/dl (p = 0.13) in patients dependent or dead after 3 months (modified Rankin Scale score > 2; n = 59) vs. independent patients (n = 52); 0.2 (0.1-1.5) mg/dl vs. 0.4 (0-5.9) mg/dl (p = 0.28) in patients dead after 3 months (n = 14) versus survivors (n = 97); and 0.2 (0.1-0.7) mg/dl vs. 0.4 (0-5.9) mg/dl (p = 0.09) in patients with significant neurological deterioration within 24 hours (increase in > or = 4 points on National Institute of Health Stroke scale; n = 9) vs. patients without early deterioration (n = 102). Independent predictors of dependency/death after 3 months, identified by multivariate logistic regression analyses, were baseline NIHSS score (OR = 1.31, 95 % CI 1.16-1.48, p < 0.001), time from onset to treatment (OR = 1.01, 95 % CI 1.0-1.02, p = 0.024), and presence of diabetes (OR = 8.16, 95 % CI 1.18-56.5, p = 0.033). CONCLUSION: Pre-treatment CRP clearly failed to predict outcome in stroke patients treated with IVT. Our findings contradict previously published work and highlight the need for further research on this topic.
Asunto(s)
Proteína C-Reactiva , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodos , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/administración & dosificación , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/etiología , Valor Predictivo de las Pruebas , Análisis de Regresión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
We report on 2 patients with cerebral vasculitis and stroke due to Lyme neuroborreliosis (LNB). Both patients had a prodromal stage involving headaches, and showed meningeal enhancement in addition to ischemic infarctions on brain magnetic resonance imaging and diffuse vasculitis on vascular imaging. Serological and cerebrospinal (CSF) fluid studies confirmed the diagnosis of active LNB. Ceftriaxone for 3 weeks led to an excellent recovery and improvements in the CSF examination findings. Stroke physicians should be aware of this rare presentation of LNB. A review of the current knowledge on cerebral vasculitis due to LNB is provided.
Asunto(s)
Borrelia burgdorferi , Neuroborreliosis de Lyme/complicaciones , Accidente Cerebrovascular/microbiología , Vasculitis del Sistema Nervioso Central/microbiología , Adolescente , Adulto , Anciano , Antibacterianos/uso terapéutico , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/líquido cefalorraquídeo , Borrelia burgdorferi/inmunología , Isquemia Encefálica/microbiología , Ceftriaxona/uso terapéutico , Angiografía Cerebral , Niño , Preescolar , Femenino , Cefalea/microbiología , Humanos , Neuroborreliosis de Lyme/tratamiento farmacológico , Neuroborreliosis de Lyme/patología , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/patología , Resultado del Tratamiento , Vasculitis del Sistema Nervioso Central/tratamiento farmacológico , Vasculitis del Sistema Nervioso Central/patología , Adulto JovenRESUMEN
BACKGROUND: Cerebrovascular disease (CVD) is a global public health problem. CVD patients are at high risk of recurrent stroke and other atherothrombotic events. Prevalence of risk factors, comorbidities, utilization of secondary prevention therapies and adherence to guidelines all influence the recurrent event rate. We assessed these factors in 18,992 CVD patients within a worldwide registry of stable outpatients. METHODS: The Reduction of Atherothrombosis for Continued Health Registry recruited >68,000 outpatients (44 countries). The subjects were mainly recruited by general practitioners (44%) and internists (29%) if they had symptomatic CVD, coronary artery disease, peripheral arterial disease (PAD) and/or >or=3 atherothrombotic risk factors. RESULTS: The 18,992 CVD patients suffered a stroke (53.7%), transient ischemic attack (TIA) (27.7%) or both (18.5%); 40% had symptomatic atherothrombotic disease in >or=1 additional vascular beds: 36% coronary artery disease; 10% PAD and 6% both. The prevalence of risk factors at baseline was higher in the TIA subgroup than in the stroke group: treated hypertension (83.5/82.0%; p = 0.02), body mass index >or=30 (26.7/20.8%; p < 0.0001), hypercholesterolemia (65.1/52.1%; p < 0.0001), atrial fibrillation (14.7/11.9%; p < 0.0001) and carotid artery disease (42.3/29.7%; p < 0.0001). CVD patients received antiplatelet agents (81.7%), oral anticoagulants (17.3%), lipid-lowering agents (61.2%) and antihypertensives (87.9%), but guideline treatment targets were frequently not achieved (54.5% had elevated blood pressure at baseline, while 4.5% had untreated diabetes). CONCLUSIONS: A high percentage of CVD patients have additional atherothrombotic disease manifestations. The risk profile puts CVD patients, especially the TIA subgroup, at high risk for future atherothrombotic events. Undertreatment is common worldwide and adherence to guidelines needs to be enforced.
Asunto(s)
Trastornos Cerebrovasculares/tratamiento farmacológico , Trastornos Cerebrovasculares/epidemiología , Salud Global , Sistema de Registros/estadística & datos numéricos , Anciano , Anticoagulantes/uso terapéutico , Trastornos Cerebrovasculares/prevención & control , Femenino , Guías como Asunto , Humanos , Hipercolesterolemia/epidemiología , Hipertensión/epidemiología , Arteriosclerosis Intracraneal/tratamiento farmacológico , Arteriosclerosis Intracraneal/epidemiología , Arteriosclerosis Intracraneal/prevención & control , Ataque Isquémico Transitorio/tratamiento farmacológico , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/prevención & control , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Prevención Secundaria , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & controlRESUMEN
Creutzfeldt-Jakob disease (CJD) is a subacute spongiform encephalopathy. This fatal prion disease is characterized by rapidly progressive dementia with a variety of neurological disorders. Diagnostic methods provided by nuclear medicine might be helpful for evaluation of patients with probable CJD as additional diagnostic tools to MRI and cerebro-spinal fluid evaluation. The experience with FDG-PET and brain perfusion SPECT is presented.
Asunto(s)
Encéfalo/metabolismo , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagen , Síndrome de Creutzfeldt-Jakob/metabolismo , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Diagnóstico Diferencial , Femenino , Fluorodesoxiglucosa F18/metabolismo , Humanos , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodos , Radiofármacos/metabolismo , Flujo Sanguíneo Regional , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
BACKGROUND AND PURPOSE: We report the first case of 2 intravenous thrombolysis treatments within 90 hours in a patient with early recurrent stroke. SUMMARY OF REVIEW: A 50-year-old man had improved significantly after intravenous thrombolysis for acute stroke. On the fourth day, he deteriorated dramatically because of recurrent stroke. Evidence of vessel reocclusion and profound perfusion/diffusion mismatch constituted the rationale for a second thrombolysis treatment, which resulted in vessel recanalization and significant neurologic improvement. CONCLUSIONS: The pathophysiological information obtained by multimodal magnetic resonance imaging may suit as a brain clock when repeat thrombolysis treatment is considered for early recurrent stroke.
Asunto(s)
Encéfalo/patología , Accidente Cerebrovascular/terapia , Terapia Trombolítica/métodos , Isquemia Encefálica/terapia , Humanos , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/patología , Recurrencia , Factores de TiempoRESUMEN
A 35-year-old female ingested a lethal dose of potassium cyanide in a suicide attempt. She survived following antidote therapy and intensive care. Following artificial coma she presented with an agitative state for several days followed by akinetic mutism, buccofacial and ideomotoric aphasia. Severe rigid-akinetic syndrome, dysarthria, dysphagia and generalized dystonia developed weeks later. MRI revealed lesions in the caudate and lentiform nuclei, precentral cortex, and cerebellum. SPECT by [123-I] 2 beta-carbomethoxy-3-beta-(4-iodophenyl)-Tropan on two occasions revealed progressive loss of dopamine transporter suggestive of nigral neuronal apoptosis. Striatal and frontal hypometabolism and hypoperfusion were found by FDG-PET and HMPAO SPECT.
Asunto(s)
Mutismo Acinético/inducido químicamente , Mutismo Acinético/diagnóstico , Cocaína/análogos & derivados , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Cianuro de Potasio/envenenamiento , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Distonía/inducido químicamente , Distonía/diagnóstico , Femenino , Fluorodesoxiglucosa F18 , Humanos , Intento de Suicidio , Exametazima de Tecnecio Tc 99mRESUMEN
We examined six patients with isolated venous thrombosis (n = 2), or venous thrombosis combined with sinus thrombosis (n = 4) (CVT). The clinical symptoms were non-specific (acute cephalea, paresis, epileptic seizure, progressive speech disorder). All examinations were performed on a 1.5 T system (Magnetom Symphony, Siemens, Erlangen, Germany), maximum gradient field strength 30 mT/m, minimal gradient rise time 450 micros, according to the following protocol: Transverse T2-weighted turbo spin-echo (TSE), fluid attenuated inversion recovery (FLAIR), T1-weighted spin-echo (SE), before and after administration of contrast medium, T2*-weighted conventional gradient-echo (GRE), T2*-weighted spin-echo echo planar imaging (SE EPI), both without and with diffusion weighting as well as two-dimensional (2D) venous time-of-flight (TOF) MRA. The venous thromboses were best detectable in the T2*-weighted conventional GRE sequence in all patients. In two patients, the CVT was discernible only in this sequence. The sinus thrombosis was well discernible only in the T2*-weighted GRE sequence in only one case; in the remaining cases it was detectable only with difficulty. For these cases, other sequences such as SE, diffusion-weighted, or 2D-TOF-MRA sequence were superior. The T2*-weighted conventional GRE sequence was superior to the T2*-weighted SE EPI sequence in all patients. To sum up, it can be concluded, that T2*-weighted conventional GRE sequences are possibly the best method of detection of acute cortical vein thromboses. Therefore, it seems to be of benefit to integrate a T2*-weighted conventional GRE sequence into the MR-protocol for the diagnosis of isolated cortical vein thrombosis.
Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Trombosis Intracraneal/diagnóstico , Imagen por Resonancia Magnética/métodos , Trombosis de los Senos Intracraneales/diagnóstico , Trombosis de la Vena/diagnóstico , Adulto , Anciano , Medios de Contraste , Imagen de Difusión por Resonancia Magnética/métodos , Imagen Eco-Planar/métodos , Femenino , Humanos , Aumento de la Imagen/métodos , Angiografía por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadAsunto(s)
Arteritis de Células Gigantes/complicaciones , Arteritis de Células Gigantes/tratamiento farmacológico , Insuficiencia Vertebrobasilar/complicaciones , Insuficiencia Vertebrobasilar/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Anciano de 80 o más Años , Quimioterapia Combinada , Fibrinolíticos/uso terapéutico , Arteritis de Células Gigantes/diagnóstico , Heparina/uso terapéutico , Humanos , Angiografía por Resonancia Magnética , Masculino , Metilprednisolona/uso terapéutico , Resultado del Tratamiento , Insuficiencia Vertebrobasilar/diagnósticoAsunto(s)
Proteína C-Reactiva/análisis , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Biomarcadores , Temperatura Corporal , Factores de Confusión Epidemiológicos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Infecciones/sangre , Selección de Paciente , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Proyectos de Investigación , Sensibilidad y Especificidad , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
In generalized myasthenia gravis (MG), a wide array of immunosuppressive and immunomodulating treatments is being used in clinical practice, but most drugs lack evidence from randomized controlled trials supporting their use. Furthermore, many patients develop serious side effects or do not respond sufficiently to these drugs. We report three patients with generalized MG who were treated with rituximab, a monoclonal antibody against CD20+ cells that causes prolonged B cell depletion. In all three patients, treatment with rituximab led to a sustained clinical improvement and discontinuation or reduction of prednisolone and other drugs. Rituximab was well tolerated. Therapy with rituximab was guided by the total count of peripheral B lymphocytes. Reviewing the anecdotal literature on rituximab for MG, we conclude that preliminary data on the efficacy and safety of rituximab are encouraging and that further studies in MG seem warranted.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Factores Inmunológicos/uso terapéutico , Miastenia Gravis/tratamiento farmacológico , Adulto , Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Linfocitos B/efectos de los fármacos , Quimioterapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Prednisolona/uso terapéutico , Rituximab , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Multifocal motor neuropathy (MMN) is a chronic, pure motor, asymmetric neuropathy for which intravenous immunoglobulin (IVIg) is widely regarded as first-line treatment. Rituximab is a monoclonal antibody against CD20+ cells that causes prolonged B cell depletion, a well-tolerated therapy currently explored in several immune-mediated neurologic disorders. We report three patients with MMN, who had become increasingly less responsive to IVIg but showed sustained clinical improvement following rituximab monotherapy. We provide a review of the literature on rituximab for MMN and conclude that rituximab may represent an efficacious, well-tolerated and cost-effective therapeutic option for MMN patients with declining response to IVIg.