Sex-Related Differences in Clinical Features, Neuroimaging, and Long-Term Prognosis After Transient Ischemic Attack.

BACKGROUND AND PURPOSE: Differences in sex in the incidence, presentation, and outcome of events after ischemic stroke have been studied in depth. In contrast, only limited data are available after transient ischemic attack (TIA). We aim to assess sex-related differences in the presentation, cause, neuroimaging features, and predictors of long-term prognosis in patients with TIA. METHODS: We carried out a prospective cohort study of consecutive patients with TIA from January 2006 to June 2010. Nondefinitive TIA events were defined by the presence of isolated atypical symptoms. The risk of stroke recurrence (SR) and composite of major vascular events were stratified by sex after a median follow-up time of 6.5 (interquartile range, 5.0-9.6) years. RESULTS: Among the 723 patients studied, 302 (41.8%) were female and 79 (10.9%) suffered a nondefinitive TIA event. Vascular territory diffusion-weighted imaging patterns (odds ratio, 1.61 [95% CI, 0.94-2.77]), and nondefinitive TIA events (odds ratio, 2.66 [95% CI, 1.55-4.59]) were associated with women, whereas active smoking (odds ratio, 0.30 [95% CI, 0.15-0.58]) and large artery atherosclerosis causes (odds ratio, 0.50 [95% CI, 0.29-0.83]) were related to men. The risk of SR was similar in both sexes (12.6% [95% CI, 8.9-16.3] for women versus 14.3% [95% CI, 11.0-17.6] for men). In contrast, the risk of major vascular events was significantly lower in women than in men (17.5% [95% CI, 13.2-21.8] versus 23.8% [95% CI, 19.7-27.9]). In both sexes, after adjusting for age, large artery atherosclerosis was associated with SR (hazard ratio, 3.22 [95% CI, 1.42-7.24] and hazard ratio, 2.00 [95% CI, 1.14-3.51]). In a Kaplan-Meier analysis, females with positive diffusion-weighted imaging (P=0.014) and definitive TIA (log-rank test P=0.022) had a significantly higher risk of SR. CONCLUSIONS: Despite similar risks of SR, there were sex-related differences in baseline characteristics, presenting symptoms, patterns of acute ischemic lesions, cause, and outcomes. These findings encourage further research into optimal preventive strategies that take into account these differences.

Risk-benefit assessment of treatment of epileptic women of childbearing age with valproic acid.

AIM: Valproic acid (VPA) is a widely used anti-epileptic drug (AED) of demonstrated efficacy. However, its teratogenic effects have resulted in many regulatory agencies recommending that it should not be administered to women of childbearing age unless they are taking contraceptives. The aim of this study was to determine the willingness of candidate patients to change their treatment and to monitor the evolution of their attitude. METHODS: We identified patients aged between 15 and 45 years old who had been diagnosed with epilepsy and were being treated with VPA. A shared decision-making visit was arranged, during which variables related to their epilepsy were recorded. The patients were informed about the teratogenic effects of VPA and the risks/benefits of a change in treatment. The patient, or legal guardian, then freely chose the course of treatment that they wished to follow. On a follow-up visit, six months later, seizure control and tolerance to the chosen treatment were recorded. The variables related to each patient's willingness to their change treatment were analysed. RESULTS: A total of 60 patients, with a median age of 32.7 years, were included in the study. Of these, 25 (41.7%) suffered some form of intellectual disability. Only one (1.7%) had poor seizure control. After the initial visit, 41 patients (68%) opted to continue with the VPA treatment, six opted to stop receiving VPA, and 13 decided to switch to another AED. The median age of the patients who opted to change treatment was significantly lower than that of those who opted to continue with the VPA treatment (29.1 vs. 34.4, p = 0.024). The absence of intellectual disability (p = 0.047) and a length of treatment of less than five years (0.016) were both significantly associated with the decision to change treatment. Of the 19 patients who changed treatment, nine (47%) returned to the initial treatment with VPA. CONCLUSIONS: Despite being informed of the teratogenic risk associated with VPA, a significant number of patients and legal guardians opted to continue with this treatment; the reasons given for this were the low possibility of pregnancy and the risk of breakthrough seizures. In almost half the cases studied, the pharmacological alternatives to VPA were poorly tolerated and did not provide a good level of seizure control.

Flutter diafragmático como síntoma conversivo: un caso de trastorno de la interfaz neurologíapsiquiatría / Diaphragmatic flutter as conversion symptom: a case report of a neurology-psychiatry-interface disorder

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Metabolomics predicts stroke recurrence after transient ischemic attack.

OBJECTIVE: To discover, by using metabolomics, novel candidate biomarkers for stroke recurrence (SR) with a higher prediction power than present ones. METHODS: Metabolomic analysis was performed by liquid chromatography coupled to mass spectrometry in plasma samples from an initial cohort of 131 TIA patients recruited <24 hours after the onset of symptoms. Pattern analysis and metabolomic profiling, performed by multivariate statistics, disclosed specific SR and large-artery atherosclerosis (LAA) biomarkers. The use of these methods in an independent cohort (162 subjects) confirmed the results obtained in the first cohort. RESULTS: Metabolomics analyses could predict SR using pattern recognition methods. Low concentrations of a specific lysophosphatidylcholine (LysoPC[16:0]) were significantly associated with SR. Moreover, LysoPC(20:4) also arose as a potential SR biomarker, increasing the prediction power of age, blood pressure, clinical features, duration of symptoms, and diabetes scale (ABCD2) and LAA. Individuals who present early (<3 months) recurrence have a specific metabolomic pattern, differing from non-SR and late SR subjects. Finally, a potential LAA biomarker, LysoPC(22:6), was also described. CONCLUSIONS: The use of metabolomics in SR biomarker research improves the predictive power of conventional predictors such as ABCD2 and LAA. Moreover, pattern recognition methods allow us to discriminate not only SR patients but also early and late SR cases.

Contribution of high-b-value diffusion-weighted imaging in determination of brain ischemia in transient ischemic attack patients.

BACKGROUND AND PURPOSE: High-b-value diffusion-weighted imaging (DWI) (b = 2,000 and b = 3,000 second/mm(2)) offers theoretical advantages over DWI examinations at b = 1,000 second/mm(2) for detection of acute ischemic stroke. The purpose of this study was to determine whether high-b-value DWI are better than b = 1,000 images in TIA patients. METHODS: We compared DWI obtained with 3 different b-values (1,000, 2,000, and 3,000 second/mm(2)) and fluid-attenuated inversion recovery (FLAIR) sequences in 75 consecutive TIA patients. DWI examinations were performed within 3.25 ± 1.5 days after the onset of symptoms. Presence of ischemic lesion, volume, lesion conspicuity, and lesion distinction were determined. RESULTS: A total of 40 (53.3%) patients revealed ischemic acute lesions with b = 1,000 while 34 (45.3%) were positive on FLAIR. High-b-value DWI did not increase the sensitivity for the detection of acute brain ischemia. The median lesion value increased as the b-value did: .17 mL (interquartile range [IQR] .12-.78) at b = 1,000; .19 mL (IQR .13-1.00) at b = 2,000; .29 mL (IQR .14-1.02) at b = 3,000; and .12 mL (IQR .04-.62 mL) on FLAIR (P < .001). As b-value increased, we observed hyperintensities in white matter that could erroneously be considered as acute ischemia. CONCLUSION: High-b-value DWI did not improve the conspicuity and distinction of the ischemic lesions.

Higher carotid intima media thickness predicts extracranial vascular events and not stroke recurrence among transient ischemic attack patients.

BACKGROUND: Increased common carotid artery intima-media thickness has been associated with an increased risk of vascular ischemic events. We investigated the relationship between common carotid artery intima-media thickness and extracranial vascular events (coronary heart disease and peripheral arterial disease) or stroke recurrence in a cohort of transient ischemic attack patients from the REGITELL registry. METHODS: High-resolution B-mode ultrasonographic measurements of the common carotid artery intima-media thickness were performed in a series of 283 consecutive transient ischemic attack patients. Clinical, neuroimaging, ultrasonographic, and etiological data were collected. Patients were followed prospectively for six-months or more. Extracranial vascular events and stroke recurrence were recorded. RESULTS: Fifteen extracranial vascular events (12 coronary heart disease and three peripheral arterial disease) and 29 recurrent strokes occurred during a median follow-up period of 12.3 months. Patients who experienced extracranial vascular events had significantly (P < 0.001) higher common carotid artery intima-media thickness values (1.087 (standard deviation 0.189) mm) than subjects who were free of extracranial vascular events (0.887 (standard deviation 0.195) mm). Nevertheless, common carotid artery intima-media thickness was not found to correlate with stroke recurrence. Cox proportional hazards multivariate analyses identified hypercholesterolemia (hazard ratio 6.87, 95% confidence interval: 1.93-24.39, P = 0.003) and common carotid artery intima-media thickness > 0.939 mm (hazard ratio 8.90, 95% confidence interval: 2.00-39.49, P = 0.004) as independent predictors of extracranial vascular events after transient ischemic attack. Almost one of every three patients with hypercholesterolemia and high common carotid artery intima-media thickness had extracranial vascular events. CONCLUSIONS: An elevated common carotid artery intima-media thickness value was associated with a higher long-term risk of extracranial vascular events but no with stroke recurrence. Hypercholesterolemia was the main risk factor for extracranial vascular events. The combination of hypercholesterolemia and common carotid artery intima-media thickness > 0.939 mm justify the establishment of aggressive therapies and the study of subclinical coronary heart disease and peripheral arterial disease.

Validación de las escalas ABCDI y ABCD2I en el registro de pacientes con ataque isquémico transitorio de Lleida (REGITELL) / Validation of the ABCDI and ABCD2I scales in the registry of patients with transient ischemic attacks from Lleida (REGITELL) Spain

Fundamento y objetivo: Recientemente se ha descrito una escala clinicorradiológica (ABCDI) de riesgo de recurrencia tras un ataque isquémico transitorio. Validamos esta escala en una cohorte de pacientes prospectivos (REGITELL). Pacientes y método: Se estudió a 310 pacientes con ataques isquémicos transitorios consecutivos. Se cuantificaron escalas clínicas (ABCD y ABCD2) y escalas clinicorradiológicas (ABCDI y ABCD2I). Las escalas clinicorradiológicas se calcularon sumando a su homónima clínica un punto por la presencia de lesiones isquémicas cerebrales en la tomografía computarizada (TC) craneal. Se estableció su relación con el riesgo de recurrencia a los 7 y a los 90 días y con la presencia de etiología ateromatosa (EA). Resultados: Durante la primera semana de seguimiento, 18 pacientes (5,8%) presentaron una recurrencia, mientras que a los 90 días esta ocurrió en 24 pacientes (7,7%). El estudio multivariante (regresión de Cox) identificó la recurrencia de los episodios transitorios (razón de riesgos [RR]: 2,92; intervalo de confianza [IC] del 95%: 1,11–7,64; p=0,029) y la EA (RR: 3,13; IC del 95%: 1,17–8,36; p=0,023) como predictores independientes de nuevos ictus a los 7 días, y solo la EA a los 3 meses (RR: 3,33; IC del 95%: 1,42–7,77; p=0,006). Los predictores (regresión logística) de EA fueron la recurrencia en los episodios (odds ratio: 3,12; IC del 95%: 1,58–6,14; p=0,001) y la presencia de lesiones isquémicas en la TC craneal (odds ratio: 2,69; IC del 95%: 1,38–5,28; p=0,004).Conclusiones: Las escalas clinicorradiológicas ABCDI y ABCD2I no son útiles en nuestra población. El riesgo de recurrencia no se puede establecer únicamente con variables clínicas o radiológicas mediante TC craneal (AU)

Background and objectives: A new radiological-clinical score (ABCDI) has been recently described to predict the risk of stroke recurrence after a transient ischemic attack (TIA). We validated this score in a cohort of patients with TIA (REGITELL). Patients and methods: We studied 310 consecutive patients with TIA. Clinical scales (ABCD and ABCD2) and radiological-clinical scales (ABCDI and ABCD2I) were quantified. Radiological clinical scales were calculated by adding one point for the presence of ischemic brain injury in CT scan to its eponymous clinical score. We established its relationship with the risk of recurrence at 7 and 90 days, and the presence of an atheromatous etiology (AE). Results: During the first week of follow-up, 18 (5.8%) patients suffered a recurrence, whereas 24 (7.7%) had a recurrence at 90 days. The multivariate study (Cox regression) identified the recurrence of episodes (hazard ratio [HR] 2.92, 95% CI 1.11 to 7.64, p=0.029) and AE (HR 3.13 95% CI: 1.17 to 8.36, p=0.023) as independent predictors of new stroke at 7 days and only AE for stroke at three months (RR 3.33, 95% CI: 1,42–7,77, p=0.006). The predictors (logistic regression) of AE were recurrence of episodes (odds ratio [OR] 3.12, 95% CI 1.58–6.14, p=0.001) and presence of ischemic lesions on CT scan (OR 2.69, 1.38–5.28, p=0.004).conclusions: The ABCDI and ABCD2I scales are not useful in our population. The risk of recurrence after a TIA cannot only be established by clinical scores or CT scan findings (AU)

[Validation of the ABCDI and ABCD2I scales in the registry of patients with transient ischemic attacks from Lleida (REGITELL) Spain]. / Validación de las escalas ABCDI y ABCD2I en el registro de pacientes con ataque isquémico transitorio de Lleida (REGITELL).

BACKGROUND AND OBJECTIVES: A new radiological-clinical score (ABCDI) has been recently described to predict the risk of stroke recurrence after a transient ischemic attack (TIA). We validated this score in a cohort of patients with TIA (REGITELL). PATIENTS AND METHODS: We studied 310 consecutive patients with TIA. Clinical scales (ABCD and ABCD2) and radiological-clinical scales (ABCDI and ABCD2I) were quantified. Radiological clinical scales were calculated by adding one point for the presence of ischemic brain injury in CT scan to its eponymous clinical score. We established its relationship with the risk of recurrence at 7 and 90 days, and the presence of an atheromatous etiology (AE). RESULTS: During the first week of follow-up, 18 (5.8%) patients suffered a recurrence, whereas 24 (7.7%) had a recurrence at 90 days. The multivariate study (Cox regression) identified the recurrence of episodes (hazard ratio [HR] 2.92, 95% CI 1.11 to 7.64, p=0.029) and AE (HR 3.13 95% CI: 1.17 to 8.36, p=0.023) as independent predictors of new stroke at 7 days and only AE for stroke at three months (RR 3.33, 95% CI: 1,42-7,77, p=0.006). The predictors (logistic regression) of AE were recurrence of episodes (odds ratio [OR] 3.12, 95% CI 1.58-6.14, p=0.001) and presence of ischemic lesions on CT scan (OR 2.69, 1.38-5.28, p=0.004). CONCLUSIONS: The ABCDI and ABCD2I scales are not useful in our population. The risk of recurrence after a TIA cannot only be established by clinical scores or CT scan findings.

Implicaciones diagnósticas del perfil de recurrencia tras un ataque isquémico transitorio / Diagnostic lessons of recurrence pattern after transient ischemic attacks

Introducción: El ataque isquémico transitorio (AIT) es una situación de alto riesgo. Los autores se proponen estudiar las implicaciones diagnósticas del perfil de recurrencia a los 7 y a los 90 días. Pacientes y método: Se estudió de forma consecutiva a una cohorte de 210 pacientes con AIT reciente. Se recogieron datos sobre los estudios ultrasonográfico, de neuroimagen y cardiológico. Resultados: Se obtuvo el seguimiento a 90 días en 209 casos y a 7 días en 210 casos. A los 90 días, 14 pacientes (6,7%; intervalo de confianza [IC] del 95%: 3,3 a 10,1) tuvieron un infarto isquémico cerebral (IIC), 9 pacientes (4,3%; IC del 95%: 1,5 a 7,1) tuvieron un AIT y 6 pacientes (2,9%; IC del 95%: 0,6 a 5,1) tuvieron un episodio de cardiopatía isquémica, mientras que 13 de los 210 pacientes (6,2%; IC del 95%: 2,8 a 9,6) con seguimiento mínimo de 7 días tuvieron un IIC. La presencia de estenosis intracraneal (razón de riesgos [RR] de 23,29; IC del 95%: 5,80 a 93,47; p<0,001) fue predictor independiente del IIC a los 7 días, mientras que la etiología aterotrombótica (RR de 7,16; IC del 95%: 3,01 a 17,04; p<0,001) lo fue de ictus a los 90 días. Se llegó a un nuevo diagnóstico de fibrilación auricular en 21 sujetos (10,0%), mayoritariamente mediante electrocardiograma basal (62%). Se observaron lesiones agudas en difusión (DF) en 81 (44,5%) de los 182 pacientes y se observaron lesiones crónicas en 110 pacientes (60,4%) mediante resonancia magnética craneal frente a 56 (26,7%) sobre 210 pacientes con tomografía computarizada craneal. Conclusión: El perfil de recurrencia tan precoz justifica la realización de estudios ultrasonográficos en las primeras horas tras el AIT. El estudio del valor predictivo de la DF sólo puede plantearse si se realiza de forma muy inmediata, mientras que el rendimiento de las exploraciones cardiológicas es bajo (AU)

Background and objective: Early stroke recurrence risk alter a transient ischemic attack (TIA) is high. We studied the diagnostic implications of the recurrence pattern after TIA. Methods: 210 consecutive TIA patients were studied. Ultrasonographic (US), neuroimaging and cardiologic data were collected. Results: At 90 day follow-up, 14 patients (6.7%; 95% CI: 3.3–10.1) among 209 suffered an ischemic infarction (II), 9 (4.3%; 1.5–7.1) a TIA and 6 (2.9%; 0.6–5.1) a cardiac ischemic event. Moreover, 13 patients (6.2%; 2.8–9.6) among 210 with a seven-day follow-up had an II. Multivariate analyses only identified the presence of intracranial stenoses (HR, 23.29; 95% CI, 3.49 to 23.57; p<0.018) as independent predictors of stroke within the first 7 days, and large-artery occlusive disease (HR, 9.07; CI, 3.49 to 23.57; p<0.001) as a predictor of stroke recurrence at 90 day follow-up. A new diagnosis of atrial fibrillation was observed in 21 subjects (10.0%), and it was documented in the baseline ECG in 62% cases. Acute diffusion abnormalities were identified in 81 (44,5%) of 182 patients, and chronic ischemic lesions were observed in 110 (60.4%) on MRI vs 56 (26.7%) among 210 on CT scan. Conclusion: Due to very early recurrence, the routine use of ultrasonography within the first hours after an index TIA will be useful to identify those patients at high risk. The prognostic usefulness of diffusion-weighted studies will be only achieved if it is performed early. Routine noninvasive cardiac rhythm monitoring has a low detection rate (AU)

[Diagnostic lessons of recurrence pattern after transient ischemic attacks]. / Implicaciones diagnósticas del perfil de recurrencia tras un ataque isquémico transitorio.

BACKGROUND AND OBJECTIVE: Early stroke recurrence risk alter a transient ischemic attack (TIA) is high. We studied the diagnostic implications of the recurrence pattern after TIA. METHODS: 210 consecutive TIA patients were studied. Ultrasonographic (US), neuroimaging and cardiologic data were collected. RESULTS: At 90 day follow-up, 14 patients (6.7%; 95% CI: 3.3-10.1) among 209 suffered an ischemic infarction (II), 9 (4.3%; 1.5-7.1) a TIA and 6 (2.9%; 0.6-5.1) a cardiac ischemic event. Moreover, 13 patients (6.2%; 2.8-9.6) among 210 with a seven-day follow-up had an II. Multivariate analyses only identified the presence of intracranial stenoses (HR, 23.29; 95% CI, 3.49 to 23.57; p<0.018) as independent predictors of stroke within the first 7 days, and large-artery occlusive disease (HR, 9.07; CI, 3.49 to 23.57; p<0.001) as a predictor of stroke recurrence at 90 day follow-up. A new diagnosis of atrial fibrillation was observed in 21 subjects (10.0%), and it was documented in the baseline ECG in 62% cases. Acute diffusion abnormalities were identified in 81 (44,5%) of 182 patients, and chronic ischemic lesions were observed in 110 (60.4%) on MRI vs 56 (26.7%) among 210 on CT scan. CONCLUSION: Due to very early recurrence, the routine use of ultrasonography within the first hours after an index TIA will be useful to identify those patients at high risk. The prognostic usefulness of diffusion-weighted studies will be only achieved if it is performed early. Routine noninvasive cardiac rhythm monitoring has a low detection rate.

The California, ABCD, and unified ABCD2 risk scores and the presence of acute ischemic lesions on diffusion-weighted imaging in TIA patients.

BACKGROUND AND PURPOSE: Some clinical models, like California ABCD and unified ABCD2 scores, are now available to predict the early risk of stroke after a TIA. Despite the transitivity of symptoms, DWI identified an area of acute brain ischemia in almost half of patients. It would be interesting to know how the presence of DWI abnormalities relates to clinical risk scores to plan other prognostic variables or to recommend the performance of DWI. METHODS: We prospectively studied 135 consecutive TIA patients visited by the neurologists in our institution. All patients underwent DWI (3.8+/-1.7 days after symptoms onset). Clinical risk scores (California, ABCD, and ABCD2) were calculated prospectively for each patient. The identification of acute ischemic lesions (positive DWI) was related to the presence of clinical features and clinical risk scores. RESULTS: DWI were positive in 67 (49.6%) patients. After Bonferroni adjustment, elevated ABCD, ABCD2, and California scores were not associated with a positive DWI. However, some clinical symptoms such as facial palsy and motor weakness were associated with a positive DWI (P<0.001). The logistic regression model identified only facial palsy as an independent predictor of acute ischemic lesions (odds ratio 6.26, 95% CI 2.49 to 15.71, P<0.001). CONCLUSIONS: Clinical symptoms such as motor impairment, but not clinical risk scores, were associated with a positive DWI. Performing a DWI may add prognostic information to clinical risk scales as a predictor of stroke recurrence after TIA in future large studies.