[Malformations of cortical development in adult patients with epilepsy: a series of 79 cases]. / Malformaciones del desarrollo cortical en pacientes adultos con epilepsia: serie de 79 casos.

INTRODUCTION: Malformations of cortical development (MCD) are an important cause of epilepsy, delayed psychomotor development or neurological deficits. AIM. To report on the long-term clinical course and differential characteristics of several groups of MCD in adults with epilepsy. PATIENTS AND METHODS: Our sample consisted of patients over 16 years of age with MCD confirmed by magnetic resonance imaging, and epilepsy. The characteristics of the epilepsy, presence of neurological deficits, intellectual disability, history of perinatal pathology and electroencephalogram recordings were analysed. The patients were classified into three groups (G) in accordance with the Barkovich classification. RESULTS: A total of 85 patients with MCD were identified from 2630 patients with epilepsy and 79 of them were finally included in the sample. Mean age: 37 years, 57% were females. Mean age at onset of the crises: 17.8 years, and 59.5% were medication resistant. The distribution of the cases according to the Barkovich classification was: G1 (alterations affecting neuronal proliferation): 59.5%; G2 (alterations affecting migration): 25.3%; and G3 (alterations affecting cortical organisation): 15.2%. Focal neurological deficit was observed in 19% and 34.2% had an intelligence quotient < 80. On analysing by groups, G3 was found to display a higher percentage of focal neurological and intelligence quotient deficits than G1 and G2 (p < 0.05). CONCLUSIONS: Patients with MCD in G3 are more likely to have neurological deficit, intellectual disability and better control over their crises than patients from G1 and G2, most of whom present refractory epilepsy.

TITLE: Malformaciones del desarrollo cortical en pacientes adultos con epilepsia: serie de 79 casos.Introduccion. Las malformaciones del desarrollo cortical (MDC) son una causa importante de epilepsia, retraso del desarrollo psicomotor o deficits neurologicos. Objetivo. Describir la evolucion clinica a largo plazo y las caracteristicas diferenciales de los distintos grupos de MDC en adultos con epilepsia. Pacientes y metodos. Pacientes mayores de 16 años con MDC confirmada por resonancia magnetica y epilepsia. Se analizaron las caracteristicas de la epilepsia, la presencia de deficits neurologicos, la discapacidad intelectual, los antecedentes de patologia perinatal y el electroencefalograma. Los pacientes se clasificaron en tres grupos (G) segun la clasificacion de Barkovich. Resultados. Se identificaron 85 pacientes con MDC de 2.630 pacientes con epilepsia, y se incluyeron 79 pacientes. Edad media: 37 años, el 57% mujeres. Edad media al inicio de las crisis: 17,8 años. El 59,5% era farmacorresistente. La distribucion de los casos segun la clasificacion de Barkovich fue: G1 (alteraciones de la proliferacion neuronal): 59,5%; G2 (alteraciones de la migracion): 25,3%; y G3 (alteraciones de la organizacion cortical): 15,2%. El 19% presentaba un deficit neurologico focal y el 34,2% tenia un cociente intelectual < 80. Al analizar por grupos, el G3 mostraba un mayor porcentaje de deficits neurologicos focales y discapacidad intelectual que el G1 y el G2 (p < 0,05). Conclusion. Los pacientes con MDC del G3 tienen mayor probabilidad de tener deficit neurologico, discapacidad intelectual y mejor control de las crisis que los pacientes del G1 y G2, que se manifiestan, predominantemente, con epilepsia farmacorresistente.

Malformaciones del desarrollo cortical en pacientes adultos con epilepsia: serie de 79 casos / Malformations of cortical development in adult patients with epilepsy: a series of 79 cases

Introducción. Las malformaciones del desarrollo cortical (MDC) son una causa importante de epilepsia, retraso del desarrollo psicomotor o déficits neurológicos. Objetivo. Describir la evolución clínica a largo plazo y las características diferenciales de los distintos grupos de MDC en adultos con epilepsia. Pacientes y métodos. Pacientes mayores de 16 años con MDC confirmada por resonancia magnética y epilepsia. Se analizaron las características de la epilepsia, la presencia de déficits neurológicos, la discapacidad intelectual, los antecedentes de patología perinatal y el electroencefalograma. Los pacientes se clasificaron en tres grupos (G) según la clasificación de Barkovich. Resultados. Se identificaron 85 pacientes con MDC de 2.630 pacientes con epilepsia, y se incluyeron 79 pacientes. Edad media: 37 años, el 57% mujeres. Edad media al inicio de las crisis: 17,8 años. El 59,5% era farmacorresistente. La distribución de los casos según la clasificación de Barkovich fue: G1 (alteraciones de la proliferación neuronal): 59,5%; G2 (alteraciones de la migración): 25,3%; y G3 (alteraciones de la organización cortical): 15,2%. El 19% presentaba un déficit neurológico focal y el 34,2% tenía un cociente intelectual < 80. Al analizar por grupos, el G3 mostraba un mayor porcentaje de déficits neurológicos focales y discapacidad intelectual que el G1 y el G2 (p < 0,05). Conclusión. Los pacientes con MDC del G3 tienen mayor probabilidad de tener déficit neurológico, discapacidad intelectual y mejor control de las crisis que los pacientes del G1 y G2, que se manifiestan, predominantemente, con epilepsia farmacorresistente (AU)

Introduction. Malformations of cortical development (MCD) are an important cause of epilepsy, delayed psychomotor development or neurological deficits. Aim. To report on the long-term clinical course and differential characteristics of several groups of MCD in adults with epilepsy. Patients and methods. Our sample consisted of patients over 16 years of age with MCD confirmed by magnetic resonance imaging, and epilepsy. The characteristics of the epilepsy, presence of neurological deficits, intellectual disability, history of perinatal pathology and electroencephalogram recordings were analysed. The patients were classified into three groups (G) in accordance with the Barkovich classification. Results. A total of 85 patients with MCD were identified from 2630 patients with epilepsy and 79 of them were finally included in the sample. Mean age: 37 years, 57% were females. Mean age at onset of the crises: 17.8 years, and 59.5% were medication resistant. The distribution of the cases according to the Barkovich classification was: G1 (alterations affecting neuronal proliferation): 59.5%; G2 (alterations affecting migration): 25.3%; and G3 (alterations affecting cortical organisation): 15.2%. Focal neurological deficit was observed in 19% and 34.2% had an intelligence quotient < 80. On analysing by groups, G3 was found to display a higher percentage of focal neurological and intelligence quotient deficits than G1 and G2 (p < 0.05). Conclusions. Patients with MCD in G3 are more likely to have neurological deficit, intellectual disability and better control over their crises than patients from G1 and G2, most of whom present refractory epilepsy (AU)

Etiología y tratamiento de la epilepsia en una serie de 1.557 pacientes / Aetiology and treatment of epilepsy in a series of 1, 557 patients

Introducción. La etiología de la epilepsia es un determinante importante del tratamiento y el pronóstico. Los avances diagnósticos y terapéuticos hacen pensar que la distribución causal, el tratamiento y el pronóstico de la población con epilepsia se hayan podido ver modificados. Objetivo. Describir la distribución sindrómica, etiológica y el tratamiento farmacológico en los pacientes con epilepsia. Pacientes y métodos. Estudio descriptivo transversal de pacientes con epilepsia atendidos de manera consecutiva en la consulta de nuestra unidad de epilepsia. Se recogieron datos demográficos, de síndrome, etiología y tratamiento farmacológico en el momento de la inclusión. Se analizaron los datos de modo conjunto y por grupos de edad. Resultados. Se incluyeron 1.557 pacientes, el 54% varones. El 73% de la muestra tenía una epilepsia focal, que era secundaria a una lesión estructural en el 56%. Las epilepsias generalizadas representaron el 20%. El 5% fue inclasificable. Por edad, la etiología vascular predominaba en prácticamente todos los grupos y su prevalencia aumentaba en relación con la edad. Los fármacos antiepilépticos más utilizados fueron ácido valproico (29%), levetiracetam (27%) y carbamacepina (20%). El 70% de las epilepsias generalizadas y el 57% de las focales seguían tratamiento en monoterapia. Conclusiones. La prevalencia por grupos de edad fue similar a la descrita en países desarrollados aunque se observó una menor prevalencia de epilepsias criptogénicas. Más del 60% de los pacientes seguía monoterapia y el ácido valproico fue el más utilizado (AU)

Introduction. The aetiology of epilepsy is an important decisive factor in its treatment and prognosis. Diagnostic and therapeutic advances suggest that the causal distribution, treatment and prognosis of the population with epilepsy may have undergone some modification. Aim. To describe the distribution of syndromes, aetiology and pharmacological treatment in patients with epilepsy. Patients and methods. We conducted a cross-sectional descriptive study of patients with epilepsy who were treated consecutively in our epilepsy department. Demographic data were collected, together with information about syndromes, aetiology and pharmacological treatment at the time of eligibility. The data were analysed jointly and by age groups Results. Altogether 1,557 patients were included, 54% of them males. Seventy-three per cent of the sample had focal epilepsy, which was secondary to a structural lesion in 56% of patients. Generalised epilepsies accounted for 20%. Five per cent were unclassifiable. By ages, vascular causation predominated in practically all the groups and its prevalence increased with age. The most commonly used antiepileptic drugs were valproic acid (29%), levetiracetam (27%) and carbamazepine (20%). Seventy per cent of the generalised epilepsies and 57% of the focal ones were on monotherapy treatment. Conclusions. The prevalence by age groups was similar to that reported in developed countries, although a lower prevalence of cryptogenic epilepsies was observed. More than 60% of patients followed monotherapy and valproic acid was the most widely used (AU)

[Aetiology and treatment of epilepsy in a series of 1,557 patients]. / Etiologia y tratamiento de la epilepsia en una serie de 1.557 pacientes.

INTRODUCTION: The aetiology of epilepsy is an important decisive factor in its treatment and prognosis. Diagnostic and therapeutic advances suggest that the causal distribution, treatment and prognosis of the population with epilepsy may have undergone some modification. AIM: To describe the distribution of syndromes, aetiology and pharmacological treatment in patients with epilepsy. PATIENTS AND METHODS: We conducted a cross-sectional descriptive study of patients with epilepsy who were treated consecutively in our epilepsy department. Demographic data were collected, together with information about syndromes, aetiology and pharmacological treatment at the time of eligibility. The data were analysed jointly and by age groups. RESULTS: Altogether 1,557 patients were included, 54% of them males. Seventy-three per cent of the sample had focal epilepsy, which was secondary to a structural lesion in 56% of patients. Generalised epilepsies accounted for 20%. Five per cent were unclassifiable. By ages, vascular causation predominated in practically all the groups and its prevalence increased with age. The most commonly used antiepileptic drugs were valproic acid (29%), levetiracetam (27%) and carbamazepine (20%). Seventy per cent of the generalised epilepsies and 57% of the focal ones were on monotherapy treatment. CONCLUSIONS: The prevalence by age groups was similar to that reported in developed countries, although a lower prevalence of cryptogenic epilepsies was observed. More than 60% of patients followed monotherapy and valproic acid was the most widely used.

TITLE: Etiologia y tratamiento de la epilepsia en una serie de 1.557 pacientes.Introduccion. La etiologia de la epilepsia es un determinante importante del tratamiento y el pronostico. Los avances diagnosticos y terapeuticos hacen pensar que la distribucion causal, el tratamiento y el pronostico de la poblacion con epilepsia se hayan podido ver modificados. Objetivo. Describir la distribucion sindromica, etiologica y el tratamiento farmacologico en los pacientes con epilepsia. Pacientes y metodos. Estudio descriptivo transversal de pacientes con epilepsia atendidos de manera consecutiva en la consulta de nuestra unidad de epilepsia. Se recogieron datos demograficos, de sindrome, etiologia y tratamiento farmacologico en el momento de la inclusion. Se analizaron los datos de modo conjunto y por grupos de edad. Resultados. Se incluyeron 1.557 pacientes, el 54% varones. El 73% de la muestra tenia una epilepsia focal, que era secundaria a una lesion estructural en el 56%. Las epilepsias generalizadas representaron el 20%. El 5% fue inclasificable. Por edad, la etiologia vascular predominaba en practicamente todos los grupos y su prevalencia aumentaba en relacion con la edad. Los farmacos antiepilepticos mas utilizados fueron acido valproico (29%), levetiracetam (27%) y carbamacepina (20%). El 70% de las epilepsias generalizadas y el 57% de las focales seguian tratamiento en monoterapia. Conclusiones. La prevalencia por grupos de edad fue similar a la descrita en paises desarrollados aunque se observo una menor prevalencia de epilepsias criptogenicas. Mas del 60% de los pacientes seguia monoterapia y el acido valproico fue el mas utilizado.

Speed of tPA-induced clot lysis predicts DWI lesion evolution in acute stroke.

BACKGROUND AND PURPOSE: We sought to evaluate the impact of the speed of recanalization on the evolution of diffusion- weighted imaging (DWI) lesions and outcome in stroke patients treated with tissue-type plasminogen activator (tPA). METHODS: We evaluated 113 consecutive stroke patients with a middle cerebral artery occlusion who were treated with intravenous tPA. All patients underwent multiparametric magnetic resonance imaging studies, including DWI and perfusion-weighted imaging before and 36 to 48 hours after administration of a tPA bolus. Patients were continuously monitored with transcranial Doppler during the first 2 hours after tPA administration. The pattern of recanalization on transcranial Doppler was defined as sudden (<1 minute), stepwise (1 to 29 minutes), or slow (>30 minutes). RESULTS: During transcranial Doppler monitoring, 13 (12.3%) patients recanalized suddenly, 32 (30.2%) recanalized in a stepwise manner, and 18 (17%) recanalized slowly. Baseline clinical and imaging parameters were similar among recanalization subgroups. At 36 to 48 hours, DWI lesion growth was significantly (P=0.001) smaller after sudden (3.23+/-10.5 cm(3)) compared with stepwise (24.9+/-37 cm(3)), slow (46.3+/-38 cm(3)), and no (51.7+/-34 cm(3)) recanalization. The slow pattern was associated with greater DWI growth (P=0.003), lesser degree of clinical improvement (P=0.021), worse 3-month outcome (P=0.032), and higher mortality (P=0.003). CONCLUSIONS: The speed of tPA-induced clot lysis predicts DWI lesion evolution and clinical outcome. Unlike sudden and stepwise patterns, slow recanalization is associated with greater DWI lesion growth and poorer short- and long-term outcomes.

Plasma S100B level after acute spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: We sought to determine plasma S100B level after acute (<24 hours) spontaneous intracerebral hemorrhage (ICH) and to study its relation with neurological outcome. METHODS: We determined S100B concentration on plasma samples from 78 ICH patients on admission. Clinical (Glasgow Coma Scale and National Institutes of Health Stroke Scale [NIHSS] scores) and radiological information (ICH and perihematomal edema volumes) were collected at baseline and follow-up visits. Early neurological deterioration, defined as the increase of >or=4 points in the NIHSS score at 48 hours, and unfavorable outcome (modified Rankin Scale >2) at 3 months were also recorded. RESULTS: The median S100B level was higher than our laboratory reference values for healthy controls (103.6 versus 48.5 pg/mL; P<0.001) and a positive correlation was observed between S100B level and baseline ICH volume (r=0.45; P<0.0001). The median S100B level was higher in patients who deteriorated early (256.8 versus 89.7 pg/mL; P=0.001) and also in patients with an unfavorable outcome (136 versus 75.9 pg/mL; P=0.003). Multivariate analysis showed baseline ICH volume as the best predictor for both early neurological deterioration (odds ratio 15; 95% CI, 2.9 to 76.3) and unfavorable outcome at 3 months (odds ratio 17; 95% CI, 2.0 to 142). CONCLUSIONS: Increased S100B level is found after acute spontaneous ICH, in association with a worse early and late evolution, and closely related to initial hematoma volume.

Tandem internal carotid artery/middle cerebral artery occlusion: an independent predictor of poor outcome after systemic thrombolysis.

BACKGROUND AND PURPOSE: Although tandem internal carotid artery/middle cerebral artery (MCA; TIM) occlusion has been associated with low recanalization rate after IV tissue plasminogen activator (tPA), its independent contribution on stroke outcome remains unknown. Moreover, whether the relative resistance to thrombolysis in tandem lesions varies depending on the location of MCA clot remains uncertain. METHODS: Two hundred and twenty-one consecutive stroke patients with an acute MCA occlusion treated with IV tPA were studied. Emergent carotid artery ultrasound and transcranial Doppler (TCD) examinations were performed in all patients before treatment. Recanalization was assessed on TCD at 2 hours of tPA bolus. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and after 24 hours. Modifed Rankin Scale score was used to assess outcome at 3 months. RESULTS: Median prebolus NIHSS score was 16 points. On TCD, 156 (71.6%) patients had a proximal and 65 (29.4%) a distal MCA occlusion. TIM occlusion was identified in 44 (19.9%) patients. Eighteen (41.9%) patients with and 123 (69.5%) without TIM lesions achieved an MCA recanalization (P=0.01). In a logistic regression model, hyperglycemia >140 mg/dL (odds ratio [OR] 3.3, 95% CI, 1.6 to 6.8) and the presence of TIM occlusion (OR 2.8, 95% CI, 1.1 to 6.9) emerged as independent predictors of absence of recanalization. However, the independent contribution of TIM lesions on poor response to thrombolysis varied depending on the location of MCA occlusion. TIM occlusion independently predicted resistance to thrombolysis in patients with proximal (OR 4.63, 95% CI, 1.79 to 11.96), but not in those with distal MCA occlusion. Patients with TIM occlusion had worse short- (P<0.0001) and long-term (P<0.0001) clinical outcome. CONCLUSIONS: TIM occlusion independently predicts poor outcome after IV thrombolysis. However, its impact varies depending on the location of MCA clot. Therefore, emergent carotid ultrasound plus TCD examinations may improve the selection of patients for more aggressive reperfusion strategies.

[Usefulness of urgent combined carotid/transcranial ultrasound testing in early prognosis of TIA patients]. / Efectividad del estudio ultrasonográfico precoz en el pronóstico a corto plazo de los pacientes con un accidente vascular cerebral isquémico transitorio.

BACKGROUND AND OBJECTIVE: Although patients with ischemic attacks (TIA) experience cardiovascular events frequently within the first 90 days after symptoms onset, strong clinical predictors of early recurrence are lacking. We investigate the value of combined carotid/transcranial ultrasound testing (UST) on the prognosis of TIA patients. PATIENTS AND METHOD: UST was performed < 24 h after symptoms onset among 311 consecutive TIA patients. Stroke recurrence, myocardial infarction, or any vascular event was recorded at 7 and 90 days of follow-up. RESULTS: A total of 20 patients suffered an stroke within 7 days of symptoms onset. During the next 90 days after index TIA, 58 (18.6%) patients experienced an endpoint: 51 cerebral ischemic events, one peripheral arterial disease, 5 myocardial infarctions and one cerebellum hemorrhage. Cox proportional hazards multivariate analyses identified the presence of intracranial stenoses (HR = 3.05; 95% CI, 1.21-7.70; p = 0.018) and carotid territory implication (HR = 15.91; 95% CI, 2.11-120.04; p = 0.007) as independent predictors of stroke within the first 7 days after index TIA. Moreover, at 90 days of follow-up, large-artery occlusive disease was an independent predictor of stroke (HR = 3.07; 95% CI, 1.76-5.38; p < 0.001). CONCLUSIONS: TIA patients with moderate to severe intracranial or extracranial stenoses have a higher risk of stroke recurrence. The routine use of UST within the first 24 h after index TIA can be useful for identifying those patients at high risk in order to plan aggressive prevention therapies.

Efectividad del estudio ultrasonográfico precoz en el pronóstico a corto plazo de los pacientes con un accidente vascular cerebral isquémico transitorio / Usefulness of urgent combined carotid/transcranial ultrasound testing in early prognosis of TIA patients

Fundamento y objetivo: Los pacientes con un accidente vascular cerebral isquémico transitorio (AIT) y estenosis tanto intracraneal como extracraneal de grado moderado a importante tienen mayor riesgo de recurrencia de ictus. Investigamos el valor de realizar un estudio ultrasonográfico (EUS) transcraneal/carotídeo precoz en el pronóstico de estos pacientes. Pacientes y método: Estudiamos de forma prospectiva a 311 pacientes con AIT atendidos en el servicio de urgencias a los que se realizó un EUS transcraneal/carotídeo dentro de las primeras 24 h. Resultados: Durante los primeros 90 días, 58 pacientes tuvieron un episodio vascular (isquemia cerebral, 51; isquemia coronaria, 5; hemorragia cerebelosa, 1, y arteriopatía periférica, 1); 20 pacientes presentaron un infarto cerebral durante la primera semana. El análisis multivariable (regresiones de Cox) identificó como predictores independientes de infarto cerebral, a los 7 días, los episodios de territorio carotídeo (razón de riesgos [RR] = 15,91; intervalo de confianza [IC] del 95%, 2,11-120,04; p = 0,007) y la presencia de estenosis intracraneal (EIC) (RR = 3,05; IC del 95%, 1,21-7,70; p = 0,018), mientras que la etiología aterotrombótica se identificó como predictor independiente para ictus isquémico a los 90 días (RR = 3,07; IC del 95%, 1,76-5,38; p < 0,001). Conclusiones: Los pacientes con AIT y estenosis intracraneal o extracraneal de grado moderado a importante tienen mayor riesgo de recurrencia de ictus. El EUS es útil para identificar a los pacientes de mayor riesgo e instaurar sin demora el tratamiento más adecuado

Background and objective: Although patients with ischemic attacks (TIA) experience cardiovascular events frequently within the first 90 days after symptoms onset, strong clinical predictors of early recurrence are lacking. We investigate the value of combined carotid/transcranial ultrasound testing (UST) on the prognosis of TIA patients. Patients and method: UST was performed < 24 h after symptoms onset among 311 consecutive TIA patients. Stroke recurrence, myocardial infarction, or any vascular event was recorded at 7 and 90 days of follow-up. Results: A total of 20 patients suffered an stroke within 7 days of symptoms onset. During the next 90 days after index TIA, 58 (18.6%) patients experienced an endpoint: 51 cerebral ischemic events, one peripheral arterial disease, 5 myocardial infarctions and one cerebellum hemorrhage. Cox proportional hazards multivariate analyses identified the presence of intracranial stenoses (HR = 3.05; 95% CI, 1.21-7.70; p = 0.018) and carotid territory implication (HR = 15.91; 95% CI, 2.11-120.04; p = 0.007) as independent predictors of stroke within the first 7 days after index TIA. Moreover, at 90 days of follow-up, large-artery occlusive disease was an independent predictor of stroke (HR = 3.07; 95% CI, 1.76-5.38; p < 0.001). Conclusions: TIA patients with moderate to severe intracranial or extracranial stenoses have a higher risk of stroke recurrence. The routine use of UST within the first 24 h after index TIA can be useful for identifying those patients at high risk in order to plan aggressive prevention therapies

Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator.

BACKGROUND AND PURPOSE: We sought to evaluate the effects of administration of microbubbles (MBs) on the beginning, speed, and degree of middle cerebral artery (MCA) recanalization during systemic thrombolysis and continuous 2-MHz pulsed-wave transcranial Doppler (TCD) monitoring. METHODS: We evaluated 111 patients with acute stroke attributable to MCA occlusion treated with intravenous tissue plasminogen activator (tPA). Thirty-eight patients were treated with tPA plus continuous 2-hour TCD monitoring plus 3 doses of 2.5 g (400 mg/mL) of galactose-based MBs given at 2, 20, and 40 minutes after tPA bolus (MB group). These patients were compared with 73 patients who were allocated to receive tPA plus continuous 2-hour TCD ultrasound (US) monitoring (tPA/US group) or tPA plus placebo monitoring (tPA group), most of whom were enrolled in a previous study of US-enhanced thrombolysis. The beginning, degree, and time to maximum completeness of recanalization during the first 2 hours of tPA bolus were recorded. RESULTS: Median prebolus National Institutes of Health Stroke Scale (NIHSS) score was 18. Eighty patients (72%) had a proximal and 31 (28%) a distal MCA occlusion on TCD. Thirty-seven patients (33%) received tPA/US, 38 (34%) received tPA/US/MB, and 36 (32%) were treated with tPA alone. Stroke severity, time to treatment, location of MCA occlusion, and presence of carotid artery disease were similar among groups. Two-hour recanalization was seen in 14 (39%), 25 (68%), and 27 patients (71%) in the tPA, tPA/US, and tPA/US/MB groups, respectively (P=0.004). Two-hour complete recanalization rate was significantly (P=0.038) higher in the tPA/US/MB group (54.5%) compared with tPA/US (40.8%) and tPA (23.9%) groups. The time to beginning of recanalization after tPA bolus was 26+/-18 minutes in the tPA/US group and 19+/-12 minutes in the tPA/US/MB group (P=0.12). Four patients (3.6%) experienced symptomatic intracranial hemorrhage: 2 (5.5%), 1 (2.7%), and 1 patient (2.6%) who received tPA only, tPA/US, and tPA/US/MB, respectively, experienced symptomatic intracranial hemorrhage. At 24 hours, 31%, 41%, and 55% of tPA, tPA/US, and tPA/US/MB improved >4 points in the NIHSS score. CONCLUSIONS: Administration of MBs induces further acceleration of US-enhanced thrombolysis in acute stroke, leading to a more complete recanalization and to a trend toward better short- and long-term outcome.

Predictors of early arterial reocclusion after tissue plasminogen activator-induced recanalization in acute ischemic stroke.

BACKGROUND AND PURPOSE: We aimed to determine clinical and hemodynamic predictors of early reocclusion (RO) in stroke patients treated with intravenous tissue plasminogen activator (tPA). METHODS: We studied 142 consecutive stroke patients with a documented middle cerebral artery (MCA) occlusion treated with intravenous tPA. All patients underwent carotid ultrasound and transcranial Doppler (TCD) examination before tPA bolus. National Institutes of Health Stroke Scale (NIHSS) scores were performed at baseline and serially for <24 hours. TCD monitoring of MCA recanalization (RE) and RO was performed during the first 2 hours after tPA bolus and repeated when clinical deterioration occurred <24 hours after documented RE in absence of intracranial hemorrhage. RESULTS: After 1 hour of tPA administration, RE occurred in 84 (61%) patients (53 partial, 31 complete). Of these, 21 (25%) patients worsened after an initial improvement and 17 (12%) of them showed RO on TCD. RO was identified at a mean time of 65+/-55 minutes after documented RE. RO was associated (P=0.034) with a lower degree of 24-hour NIHSS score improvement than sustained RE, and a higher modified Rankin scale score at 3 months (P=0.002). Age older than 75 years (P=0.012), previous antiplatelet treatment (P=0.048), baseline NIHSS score >16 points (P=0.009), higher leukocytes count (P=0.042), beginning of RE <60 minutes after tPA bolus (P=0.039), and ipsilateral severe carotid stenosis/occlusion (P=0.001) were significantly associated with RO. In a logistic regression model, NIHSS score >16 at baseline (odds ratio [OR], 7.1; 95% CI, 1.3 to 32) and severe ipsilateral carotid disease (OR, 13.3; 95% CI, 3.2 to 54) remained as independent predictors of RO. CONCLUSIONS: Stroke severity and ipsilateral severe carotid artery disease independently predict RO after tPA-induced MCA RE.

[Functional outcome after one year follow-up in cryptogenetic brain infarction and patent foramen ovale]. / Pronóstico funcional tras un año de seguimiento en pacientes con infarto cerebral de causa desconocida y foramen oval permeable.

BACKGROUND AND OBJECTIVE: The presence of patent foramen ovale (PFO) and atrioseptal aneurysm (ASA)has been described as a risk factor in cryptogenetic stroke. Patients with unknown origin stroke and PFO have less severe symptoms compared to the rest of cryptogenetic stroke patients. We evaluated the clinical situation in stroke patients with PFO and describe the factors predictive of a better outcome after a year. PATIENTS AND METHOD: 1118 patients between 18 and 70 years old were evaluated, and 223 were classified as having cryptogenetic stroke. Our protocol Included transcranial Doppler, a transesophageal echocardiography (TEE) and a cranial RM. We used the NIH Stroke Scale (NIHSS) to evaluate the clinical situation, and the modified Ranking Scale for the functional outcome. RESULTS: A total of 117 patients had all inclusion criteria. 66 (56.4%) showed a PFO. We observed a younger age, a higher percentage of females (48.4% in PFO vs. 25.5% in no-PFO) and less risk factors in PFO patients, except for migraine (24.6% in PFO vs. 5.9% in no-PFO; p = 0.01). PFO patients had less severe strokes (NIHSS: 3--median--in PFO vs. 5 in no-PFO; p = 0.010) and a lower grade of sequelae (p 0.024). Worse outcome was related to male, initial neurological evaluation (NIHSS) and presence of ASA. After a logistic regression, only the initial clinical situation (NIHSS) and the presence of ASA were associated with sequelae. CONCLUSIONS: PFO patients showed a less severe stroke and better functional outcome. The initial neurological involvement and the presence of ASA are predictive of the clinical situation after a year.

Pronóstico funcional tras un año de seguimiento en pacientes con infarto cerebral de causa desconocida y foramen oval permeable / Functional outcome after one year follow-up in cryptogenetic brain infarction and patent foramen ovale

FUNDAMENTO Y OBJETIVO: La presencia de foramen oval permeable (FOP) y aneurisma del septoauricular (ASA) se ha descrito como factor de riesgo en ictus criptogénicos. Los pacientes conictus de origen desconocido y FOP tienen una menor gravedad comparado con el resto de ictuscriptogénicos. El objetivo fue valorar la situación clínica de los ictus con FOP al cabo de 1 año,y qué factores predicen mejor pronóstico.PACIENTES Y MÉTODO: De 1.118 ictus isquémicos de pacientes entre 18 y 70 años, 223 fueronclasificados como criptogénicos. El protocolo incluía Doppler transcraneal, ecocardiogramatransesofágico (ETE) y resonancia magnética (RM) craneal. La situación clínica en fase agudase valoró mediante la escala de ictus de la NIH (National Institute of Health) y la funcional alaño mediante la escala de Rankin modificada.RESULTADOS: Cumplían todos los criterios de inclusión 117 pacientes; 66 (56,4%) tenían FOP y51 (43,2%) no. Se observó en los FOP una menor edad, un mayor porcentaje de sexo femenino(el 48,4% en los FOP frente al 25,5% en los no FOP) y menos factores de riesgo, excepto lamigraña (el 24,6% en FOP frente al 5,9% en los no FOP; p = 0,01). Los FOP presentaban menorgravedad inicial (mediana NIHSS de 3 en los FOP frente a 5 en los no FOP; p = 0,010) yun menor porcentaje de secuelas al cabo del año (p = 0,024). La peor situación funcional serelacionó con el sexo masculino, la valoración neurológica inicial (NIHSS) y la presencia deASA. Con la regresión logística sólo la gravedad neurológica inicial y la presencia de ASA seasociaban con las secuelas.CONCLUSIONES: Los pacientes con FOP presentan una menor gravedad clínica y mejor situaciónfuncional en el seguimiento. El déficit neurológico inicial y la presencia de ASA predicen la situaciónclínica al año

BACKGROUND AND OBJECTIVE: The presence of patent foramen ovale (PFO) and atrioseptalaneurysm (ASA) has been described as a risk factor in cryptogenetic stroke. Patients with unknown origin stroke and PFO have less severe symptoms compared to the rest of cryptogenetic stroke patients. We evaluated the clinical situation in stroke patients with PFO and describe the factors predictive of a better outcome after a year. PATIENTS AND METHOD: 1118 patients between 18 and 70 years old were evaluated, and 223were classified as having cryptogenetic stroke. Our protocol Included transcraneal Doppler, a transesophageal echocardiography (TEE) and a cranial RM. We used the NIH Stroke Scale (NIHSS) to evaluate the clinical situation, and the modified Ranking Scale for the functional outcome. RESULTS: A total of 117 patients had all inclusion criteria. 66 (56.4%) showed a PFO. We observed a younger age, a higher percentage of females (48.4% in PFO vs. 25.5% in no-PFO) and less risk factors in PFO patients, except for migraine (24.6% in PFO vs. 5.9% in no-PFO; p = 0.01). PFO patients had less severe strokes (NIHSS: 3 -median - in PFO vs. 5 in no-PFO; p = 0.010) and a lower grade of sequelae (p 0.024). Worse outcome was related to male, initial neurological evaluation (NIHSS) and presence of ASA. After a logistic regression, only the initial clinical situation (NIHSS) and the presence of ASA were associated with sequelae. CONCLUSIONS: PFO patients showed a less severe stroke and better functional outcome. The initial neurological involvement and the presence of ASA are predictive of the clinical situation aftera year

Impact of admission hyperglycemia on stroke outcome after thrombolysis: risk stratification in relation to time to reperfusion.

BACKGROUND AND PURPOSE: We evaluated the impact of admission hyperglycemia (HG) on stroke outcome in relation to the timing of reperfusion in patients treated with tissue plasminogen activator (tPA). METHODS: We studied 138 consecutive stroke patients with a documented middle cerebral artery (MCA) occlusion treated with intravenous tPA <3 hours of stroke onset. Serum glucose was determined at baseline before tPA administration. HG was defined as a glucose level >140 mg/dL. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hour. Transcranial Doppler monitoring of recanalization was conducted during the first 12 hour of stroke onset. mRS was used to assess outcome at 3 months. RESULTS: Median baseline NIHSS score was 17 points. At baseline, 42 (37.3%) patients were hyperglycemic and 96 (62.7%) normoglycemic. Reperfusion was achieved <3 hours of stroke onset in 32 (23%) patients, between 3 to 6 hours in 49 (36%), 6 to 12 hours in 15 (12%), and in 32 (23%) the MCA remained occluded at 12 hours. A logistic regression model revealed that baseline NIHSS score >16 points (odds ratio [OR], 3.32; 95% CI, 2.18 to 24.7; P=0.032) and admission glucose level >140 mg/dL (OR, 5.65; 95% CI, 1.97 to 16.18; P=0.002) independently predicted poor outcome (modified Rankin scale, 3 to 6) at 3 months. After adjusting by age, stroke severity, site of MCA occlusion, and degree of recanalization, the contribution of HG for poor outcome was higher as shorter the time to reperfusion. The highest odds for poor outcome related to HG corresponded to patients who recanalized <3 hour (OR, 3.1; 95% CI, 1.8 to 14.3; P=0.002), as compared with those who recanalized between 3 and 6 hours (OR, 2.1; 95% CI, 1.1 to 16; P=0.034) and between 6 to 12 hours (OR, 1.1; 95% CI, 0.7 to 21; P=0.43). Moreover, baseline glucose level was negatively correlated (r=-0.45; P=0.001) with the degree of improvement in the NIHSS score at 24 hours after early (<3 hours) but not after delayed (>3 hours) or no recanalization. CONCLUSIONS: The impact of admission HG on stroke outcome varies depending on the time to tPA-induced reperfusion. The detrimental effect of acute HG is higher after early than after delayed or no reperfusion. Ultra-early glycemic control before reperfusion may improve the efficacy of thrombolytic therapy.

Admission fibrinolytic profile is associated with symptomatic hemorrhagic transformation in stroke patients treated with tissue plasminogen activator.

BACKGROUND AND PURPOSE: Symptomatic intracranial hemorrhage (SICH) is the most feared complication after tissue plasminogen activator (tPA) stroke treatment. Endogenous fibrinolysis inhibitors play an essential role in the coagulation/fibrinolysis balance and may be involved in the bleeding process. We aim to determine the predictive value of pretreatment levels of fibrinolysis inhibitors (PAI-1, lipoprotein(a), TAFI, and homocysteine) on SICH. METHODS: Consecutive tPA-treated stroke patients with middle cerebral artery occlusion were studied. Baseline blood samples were obtained just before tPA administration and fibrinolysis inhibitors were determined. A second computed tomography (CT) scan was obtained at 24 hours or when a neurological worsening occurred to rule out SICH. RESULTS: Seventy-seven patients (40% women, age 75 years) were studied. Median admission National Institutes of Health Stroke Scale was 17 (range, 7 to 22) and mean time to treatment was 160 minutes. Six patients (7.9%) presented with a SICH. In analyses based on clinical and CT variables, no relation could be found with SICH. When laboratory data were analyzed, patients who experienced SICH showed lower baseline PAI-1 (21.7+/-3.5 ng/mL versus 31.8+/-12.1 ng/mL; P<0.01) and higher TAFI (216.7+/-78.4% versus 162.1+/-54.2%; P=0.03). Homocysteine and lipoprotein(a) were not related to SICH. The only factors associated with SICH were TAFI >180% (OR, 12.9; CI, 1.41 to 118.8; P=0.02) and PAI-1 <21.4 ng/mL (OR, 12.75; CI, 1.17 to 139.2; P=0.04). The combination of admission PAI-1 <21.4 ng/mL and TAFI >180% had a sensibility of 75% and a specificity of 97.6% (P<0.01) predicting SICH, with a positive predictive value of 75% and negative predictive value of 97.6%. CONCLUSIONS: Baseline PAI-1 and TAFI levels predict SICH after stroke tPA therapy. In the future, these biomarkers could be used to improve thrombolysis safety.

Admission fibrinolytic profile predicts clot lysis resistance in stroke patients treated with tissue plasminogen activator.

Endogenous fibrinolysis inhibitors may be involved in t-PA resistance, decreasing stroke thrombolysis benefits. We aim to determine the impact of pretreatment levels of plasminogen activator inhibitor (PAI-1), lipoprotein(a), thrombin-activatable fibrinolysis inhibitor (TAFI) and homocysteine on arterial recanalization and outcome. Forty-four consecutive patients with acute proximal middle cerebral artery occlusion were studied, including assessment of transcranial Doppler artery patency. The neurological status was determined by NIH Stroke Scale (NIHSS) and long-term outcome with modified Rankin Scale (mRS). Patients who recanalized after t-PA infusion had lower PAI-1 levels than those who remained occluded. Similarly, patients who achieved dramatic clinical recovery at 12 hours exhibited significantly lower PAI-1 levels as those independent (mRS< or =2) at third month. We observed a trend towards lower lipoprotein p(a) in patients who achieved recanalization at 1 hour, whereas no relation was found between TAFI or homo-cysteine levels and recanalization. After a regression model was applied the only independent predictor of thrombolysis resistance was baseline PAI-1>34 ng/ml, such that high PAI-1 levels interfere with tPA-induced recanalization in stroke, predicting a higher susceptibility towards clot-lysis resistance and poor out-come.

[Clinical benefit following the implementation of a specialized urgent stroke care system]. / Beneficios clínicos de la implantación de un sistema de atención especializada y urgente del ictus.

BACKGROUND AND OBJECTIVE: Several strategies as stroke teams, stroke code teams, or stroke units development have demonstrated to improve stroke care quality. The potential benefit of implementing them as a whole has not been studied. We aimed to test the clinical efficacy of a specialized and urgent stroke assistance system in a University Hospital, as well as the specific impact of each part of the system on several clinical indicators. PATIENTS AND METHOD: The implementation of the system followed three consecutive steps: stroke team and stroke code development, stroke unit creation and finally on-call stroke neurologists incorporation. Several clinical indicators to evaluate results have been selected. We compared data available before system onset (1992-1997) with data obtained during the system implementation (1998-2002). Modification in the results indicators following each of the individual steps of the system was also evaluated. RESULTS: During the five years of the system implementation, 5843 stroke patients have been prospectively studied. Admission and readmission necessities were reduced up to 34.2% and 81.8% respectively. Length of stay progressively decreased from 18 (pre-1998) to 7 days (2002). In-hospital mortality and institutionalization necessities were reduced to 50.1% and 50.5% respectively. The third step, in which on-call stroke neurologist were incorporated to the system, has demonstrated to be the most efficient in decreasing the length of stay, hospital mortality and institutionalization necessities. CONCLUSIONS: The creation of a specialized urgent stroke care system, protocol based and developed in stroke units, improves the medical assistance quality for stroke patients. Stroke neurologists on-call have a relevant role in the system working.

Temporal profile of matrix metalloproteinases and their inhibitors after spontaneous intracerebral hemorrhage: relationship to clinical and radiological outcome.

BACKGROUND AND PURPOSE: Matrix metalloproteinases (MMPs) are related to blood-brain barrier disruption, and some members of this family have been recently involved in brain bleedings. We aimed to investigate the temporal profile of MMPs and their natural inhibitors (TIMPs) after acute intracerebral hemorrhage (ICH) and to study its influence on neuroimaging and clinical outcome. METHODS: MMP-2, MMP-9, and MMP-3, as well as TIMP-1 and TIMP-2, were serially determined by enzyme-linked immunosorbent assay on admission (<12 hours), and at 24 hours, 48 hours, 7 days, and 3 months in 21 ICH patients. ICH and perihematomal edema (PE) volumes were serially measured on baseline and follow-up computed tomography (48 hours, 7 days, and 3 months), just at the time of neurological assessment. RESULTS: Deep ICH was found in 62% patients. Baseline ICH volume did not influence MMP-TIMP level. Highest levels of MMP-2 and TIMP-2 were found at baseline, for MMP-9 and TIMP-1 at 24 hours, and for MMP-3 at 24 to 48 hours. Baseline MMP-9 was positively correlated to PE volume (r=0.67, P=0.004) and, conversely, its inhibitor TIMP-1 was negatively correlated to PE (r=-0.51, P=0.04). Mortality reached 35% and MMP-3 was the only MMP/TIMP related to mortality (7.5 versus 2.4 ng/mL; P=0.035) and its most powerful baseline predictor (odds ratio = 22, confidence interval: 1.5 to 314.2). Both MMP-9 and MMP-3 correlated to the residual scar volume at 3 months (r=0.68, P=0.01 for baseline MMP-9, and r=0.86, P<0.001 for 24-hour MMP-3). CONCLUSIONS: A characteristic temporal profile of MMP/TIMP release exists in ICH. Increased MMP-9 is associated with PE, and increased MMP-3 is associated with mortality. Both molecules are related to residual cavity volume.