Apolipoprotein E genotype does not influence the risk of symptomatic hemorrhage in acute ischemic stroke.

BACKGROUND: APOE ε4 is independently associated with lobar intracranial hemorrhages (ICH). Although the ε4 allele enhances amyloid deposition in blood vessels, the ε2 allele predisposes to vasculopathic changes leading to rupture of amyloid laden vessels. Thus, ε4 and ε2 carriers might have increased susceptibility to ICH. We aimed to study the impact of the apolipoprotein E alleles in the development of symptomatic ICH (sICH). METHODS: We included 384 consecutive ischemic anterior circulation stroke patients submitted to thrombolysis between January 2014 and March 2016. Admission CT-scans were reviewed to calculate the ASPECTS. Patients were followed for up to at least 6 months post-stroke or until death. Outcome was development of sICH, defined according to the ECASS III. RESULTS: Considering APOE genotyping, three patients had ε2/ε2, four had ε2/ε4, 38 had ε2/ε3, 284 had ε3/ε3, 51 had ε3/ε4 and four had ε4/ε4. sICH was associated with sex and diabetes. In multivariate analysis, sICH was not associated with carrying one or more ε4 alleles (OR: 0.483, 95%CI = [0.059, 3.939], p = 0.497) nor with carrying one or more ε2 alleles (OR: 1.369, 95%CI = [0.278, 6.734], p = 0.699). CONCLUSION: No association was found between APOE genotype and the development of symptomatic intracranial hemorrhage.

Single Word Repetition Predicts Long-Term Outcome of Aphasia Caused by an Ischemic Stroke.

PURPOSE: Better understanding of clinical predictors of aphasia outcome is of the utmost importance, in patients' rehabilitation planning, expectation management, and further physiopathology understanding. We aimed to identify clinical predictors of long-term poststroke aphasia's outcome. METHODS: We conducted a prospective longitudinal observation study of patients with left-Middle Cerebral Artery stroke with aphasia. Patients were evaluated at baseline, day 7 and 6 months with National Institutes of Health Stroke Scale (NIHSS) and Aphasia Rapid Test Other demographic variables and vascular risk factors were collected. A linear regression was performed to identify best predictors of aphasia at 6 months. FINDINGS: We included 113 patients with a left hemisphere stroke, with 81 reaching the final evaluation. Aphasia Handicap Score at 6 months was predicted by baseline total NIHSS (ß = .077, 95%CI = [.026, .127]. P = .004), infarct volume on CT-scan (ß = .009, 95%CI = [.003, .015]. P = .003), single word repetition at baseline (ß = .188, 95%CI = [.040, .335]. P = .013), and infection during hospitalization (ß = .759, 95%CI = [.263, 1.255]. P = .003). CONCLUSIONS: Aphasia's outcome in patients with stroke is predicted by a single word repetition task at baseline. Infection during hospitalization has a negative impact on aphasia's outcome at 6 months.

Neuroimaging, serum biomarkers, and patient characteristics as predictors of upper limb functioning 12 weeks after acute stroke: an observational, prospective study.

OBJECTIVE: To evaluate the potential of neuroimaging, serum biomarkers, stroke etiology, and clinical characteristics as predictors of upper limb functioning 12 weeks after stroke. METHODS: This was a prospective, observational study of patients (18-85 years-old) hospitalized due to acute ischemic stroke in the territory of the middle cerebral artery. Patients were hospitalized at a stroke rehabilitation center, where they underwent a standardized rehabilitation program. Clinical, imagiology, laboratory (biomarkers: C-reactive protein, D-dimer, and fibrinogen, and S100 calcium binding protein ß [S100ß]), and functionality assessments were conducted four different times: within 24 hours, and at 48 hours, 3 weeks, and 12 weeks after acute stroke. RESULTS: Upper limb functioning at 12 weeks was significantly associated with Alberta Stroke Program Early CT Score (ASPECTS) score (OR:2.012 [CI:1.349-3.000]; P = 0.001) and S100ß protein levels (OR:0.997 [CI:0.994-0.999]; P = 0.007). Advanced age was associated with poor upper limb functioning. S100ß protein levels < 140.5 ng/L at 48 hours and ASPECTS scores ≥ 7.5 within 24 hours of admission predicted good hand functioning at 12 weeks. Upper limb functioning and general functioning were significantly correlated (P < 0.001), with strong negative correlations (all correlation coefficients ≤-0.586) for all comparisons. CONCLUSION: ASPECTS score ≥ 8 within 24 hours and S100ß protein < 140.5 ng/L at 48 hours predict better upper limb functioning, while advanced age predicts worse upper limb functioning 12 weeks after stroke.

[Aphasia Rapid Test: Translation, Adaptation and Validation Studies for the Portuguese Population]. / Aphasia Rapid Test: Estudos de Tradução, Adaptação e Validação para a População Portuguesa.

INTRODUCTION: Classical aphasia evaluation scales are too long to use in the context of acute stroke or as a monitoring tool. The Aphasia Rapid Test is a 26-point scale developed as a bedside assessment to rate aphasia severity in acute stroke patients in less than 3 minutes. We aimed to adapt and validate this scale for European Portuguese. MATERIAL AND METHODS: We evaluated 56 acute stroke patients in the first and in the seventh days post-stroke. In the seventh day, patients were evaluated by two independent raters, to evaluate inter-rater agreement. To study concurrent validity, the Lisbon Aphasia Examination Battery was applied to a subset of 20 patients. The predictive ability of the Aphasia Rapid Test was assessed at six months, by the aphasia subscale of the National Institutes of Health Stroke Scale. RESULTS: Translation to European Portuguese was based in the French and English versions, considering the words' utilization frequency. The Chronbach's alpha was 0.796. The concordance coefficient between the two raters was excellent (0.985). Correlation between Aphasia Rapid Test and the Lisbon Aphasia Examination Battery was strong (r = -0.958, p < 0.001). The study through Bland-Altman graphs corroborated the good inter-rater agreement and concurrent validity of the test. The Aphasia Rapid Test score in the first day is an independent predictor of long-term outcome. DISCUSSION: This study provides reliable results for European Portuguese, with adequate internal consistency, inter-rater agreement and concurrent validity. CONCLUSION: The Aphasia Rapid Test is a good tool for the evaluation and monitoring of aphasia in stroke patients.

Introdução: As baterias clássicas de caracterização de afasia são demasiado longas para serem utilizadas no contexto do acidente vascular cerebral agudo ou como ferramenta de monitorização. O Aphasia Rapid Test é uma escala de 26 pontos desenvolvida como teste de cabeceira para avaliar a gravidade da afasia num doente com acidente vascular cerebral em menos de três minutos. O objetivo do estudo é adaptar e validar a escala para o português europeu. Material e Métodos: Foram avaliados 56 doentes com acidente vascular cerebral no primeiro e sétimo dia pós-acidente vascular cerebral. Ao sétimo dia, foram avaliados por dois avaliadores independentes para avaliar o acordo interavaliadores. Para estudar a validade concorrente, a 20 doentes foi aplicada também a Bateria de Avaliação de Afasias de Lisboa. A capacidade preditiva do Aphasia Rapid Test foi avaliada aos seis meses, através do valor da subescala de afasia do National Institutes of Health Stroke Scale. Resultados: A tradução para o português europeu baseou-se nas versões francesa e inglesa, respeitando a frequência de utilização das palavras. O α de Cronbach foi de 0,796. O coeficiente de concordância entre examinadores foi excelente (0,985). A correlação entre o Aphasia Rapid Test e a Bateria de Avaliação de Afasias de Lisboa é forte (r = -0,958, p < 0,001). Os gráficos de Bland-Altman corroboram as boas concordâncias interavaliadores e validade concorrente. O Aphasia Rapid Test no primeiro dia é preditor independente do resultado a longo prazo. Discussão: Este estudo apresenta resultados confiáveis para o português europeu, com valores de consistência interna, concordância interavaliadores e validade concorrente adequados. Conclusão: O Aphasia Rapid Test é um bom instrumento para avaliação e monitorização da afasia em doentes com acidente vascular cerebral.

Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence.

Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used a functional magnetic resonance imaging block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction (n = 20, with balanced left/right lesion sites). Results Analysis of 10 right hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right hemispheric stroke. Left hemispheric stroke was, in general, characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts is novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.

S100ß Protein as a Predictor of Poststroke Functional Outcome: A Prospective Study.

BACKGROUND: Stroke is one of the leading causes of disability worldwide. Early prediction of poststroke disability using clinical models is of great interest, especially in the rehabilitation field. Although some biomarkers and neuroimaging techniques have shown potential predictive value, there are still insufficient data to support their clinical utility in predicting poststroke functional recovery. We aimed to assess the value of serum biomarkers (C-reactive protein [CRP], D-dimer, fibrinogen, and S100ß protein) in predicting medium-term (12 weeks) functional outcome in patients with acute ischemic stroke. METHODS: This is an observational, prospective study in a sample of patients hospitalized for ischemic stroke (N = 131). Peripheral blood levels of biomarkers of interest were determined at admission (CRP, D-dimer, and fibrinogen) or at 48 hours poststroke (S100ß protein). Functional status was accessed at 48 hours and 12 weeks poststroke using the modified Rankin Scale (mRS). RESULTS: S100ß protein levels measured at 48 hours were significantly associated with mRS scores at 12 weeks (odds ratio = 1.005, 95% confidence interval [CI] [1.005-1.007]; P <.001). This association was not seen for the remaining biomarkers of interest. The S100ß cutoff for poor functionality at 12 weeks was 140.5 ng/L or more (sensibility 83.8%; specificity 71.4%; area under the curve = .80, 95% CI [.722, .879]). CONCLUSIONS: S100ß levels in peripheral blood at 48 hours poststroke reflect acute stroke severity and predict functional outcome at 12 weeks with a cutoff value of 140.5 ng/dL. The value of S100ß as predictor of functional recovery after stroke should be emphasized in further clinical research and clinical practice.

Intracranial Internal Carotid Artery Wall Calcification in Ischemic Strokes Treated with Thrombolysis.

BACKGROUND: Calcifications are an important element of atherosclerotic plaques and have been used as a marker of atherosclerosis and clinical outcome predictor in different vascular territories. CT-scan, performed in the acute ischemic stroke setting, can reliably detect intracranial arterial calcifications. OBJECTIVES: To investigate the association between intracranial internal carotid artery calcification and functional outcome, symptomatic intracerebral hemorrhage (sICH), recanalization, and death. METHODS: We included 396 consecutive ischemic stroke patients submitted to recombinant tissue plasminogen activator treatment between January 2011 and September 2014. Admission CT-scans were reviewed to calculate the Total Carotid Syphon Calcification score. Patients were followed for up to at least 6 months post-stroke or until death. Outcome measures included evaluation of recanalization on the first 24 h (transcranial color coded Doppler or angio-CT), sICH, and assessment of functional outcome at 3 months after stroke (using modified Rankin scale). RESULTS: Carotid artery wall calcification did not predict sICH, recanalization or any good outcome. However, it was a statistically significant predictor of death (OR 1.102, 95% CI [1.004-1.211], p = 0.042). DISCUSSION: Intracranial carotid artery calcification does not increase the risk of thrombolysis-induced sICH. Patients with higher grade of carotid artery wall calcification may have a higher mortality rate.

Cabeça Dizpensa, corpo desvago: experimentações de um Laboratório de Sensibilidades / Lo(o)se-Head, diffuse body: experimentations with a Sensitivities Laboratory

Resumo O Laboratório de Sensibilidades da Universidade Federal de São Paulo (UNIFESP) é uma tentativa de construir experimentos abertos às alteridades, com ações em diversas superfícies que podem reverberar dentro e fora de seu lugar material. Neste artigo expomos algumas experiências que transversalizam o corpo desvago do Laboratório e suas incidências nos corpos que o compõem e decompõem. Narramos uma experimentação com uma comunidade-corpo, que se modulou em uma performance que nomeamos coletivamente de "Cabeça Dizpensa". Discutimos, dentre outras, as noções de intervenção e interferência, e um itinerário de problematizações e pequenas narrativas com ecos do laboratório.(AU)

Abstract Sensitivities Laboratory at Federal University of São Paulo (UNIFESP) is an attempt of creating experiments that are open to alterities, with actions in many different surfaces which can reverberate into and out of its material place. In this paper, we expose some experiences that transversalize the Laboratory's diffuse body and their incidences in the bodies that compose and decompose it. We report an experimentation with a community-body, which has shaped into a performance we collectively named "Lo(o)se-Head". Among others, we bring the discussion of the notions of intervention and interference, as well as an itinerary of questionings and short narratives that bring echoes from the Laboratory.(AU)

Neurosonology Accuracy for Isolated Acute Vestibular Syndromes.

OBJECTIVES: The clinical approach to acute vestibular syndromes is often complex for the physician. Neurosonology offers a noninvasive method to study the cervicocephalic circulation when a vascular etiology is suspected. We aim to evaluate the diagnostic accuracy of a vascular neurosonological exam in isolated acute vestibular syndrome. METHODS: All patients submitted to cerebrovascular ultrasound and magnetic resonance imaging during the period between 2011 and 2015 with acute isolated vestibular syndrome. Those with any clinical sign of brainstem lesion on presentation were excluded. All patients performed the neuroimaging study (brain computed tomography and magnetic resonance imaging) and neurologic surveillance. Neurosonological exam included all intra- and extracranial segments of the vertebrobasilar circulation. Positive ultrasound exam was defined as the presence of stenotic or occlusive disease in any of these segments related to the infarcted area. RESULTS: A total of 108 patients were included: 60 (53.6%) were males (mean age: 60.75 years (standard deviation, 14.17)). In 27 patients (25.0%) a cerebral ischemic lesion was found to be the cause of the vertigo. Neurosonological assessment showed a sensitivity of 40.7% (95% confidence interval (CI): 22.4; 61.2), specificity of 100% (95% CI: 95.5; 100.0), positive predictive value (PPV) of 100% (95% CI: 71.5; 100.0), and negative predictive value (NPV) of 83.5% (95% CI: 74.6; 90.3). CONCLUSIONS: Our study suggests that cerebrovascular ultrasound is a highly specific method for the diagnosis of cerebrovascular vertigo. However, its low sensitivity makes it a poor candidate for screening.

[Carotid atherosclerosis and white matter hypodensities: a controversial relationship]. / Aterosclerose Carotídea e Hipodensidades da Substância Branca: uma Relação Controversa.

INTRODUCTION: White matter hypodensities of presumed vascular origin, are recognized as an important cause of morbidity with established clinical and cognitive consequences. Nonetheless, many doubts remain on its physiopathology. Our goal is to clarify the potential role of carotid atherosclerosis and other vascular risk factors in the development of white matter hypodensities of presumed vascular origin. MATERIAL AND METHODS: We included patients that underwent CT brain scan and neurosonologic evaluation within a one-month period. Full assessment of vascular risks factors was performed. We seek to find independent associations between white matter hypodensities of presumed vascular origin, carotid intima-media thickness and vascular risk factors. RESULTS: 472 patients were included, mean age was 67.32 (SD: 14.75), 274 (58.1%) were male. The independent predictors of white matter hypodensities of presumed vascular origin were age (OR: 1.067, 95% IC: 1.049 - 1.086, p < 0.001) and hypertension (OR: 1.726, 95% IC: 1.097 - 2.715, p = 0.018). No association was found between IMT (OR: 2.613, 95% IC: 0.886 - 7.708, p = 0.082) or carotid artery stenosis (OR: 1.021, 95% IC: 0.785 - 1.328, p = 0.877) and white matter hypodensities of presumed vascular origin. DISCUSSION: Only age and hypertension proved to have an independent association with white matter hypodensities of presumed vascular origin. Carotid atherosclerosis, evaluated by IMT and the degree of carotid artery stenosis, showed no association with white matter hypodensities of presumed vascular origin. Since atherosclerosis is a systemic pathology, these results suggest that alternative mechanisms are responsible for the development of white matter hypodensities of presumed vascular origin. CONCLUSION: Age and hypertension seem to be the main factors in the development of white matter hypodensities of presumed vascular origin. No association was found between carotid atherosclerosis and white matter hypodensities of presumed vascular origin.

Introdução: As hipodensidades da substância branca de provável etiologia vascular, são uma causa importante de morbilidade, condicionando deterioração cognitiva. No entanto, numerosas dúvidas persistem quanto à sua fisiopatologia. O objectivo deste estudo é clarificar o papel da aterosclerose carotídea e outros factores de risco vascular no desenvolvimento das hipodensidades da substância branca de provável etiologia vascular.Material e Métodos: Realizou-se uma avaliação imagiológica, por tomografia computadorizada crânio-encefálica e ecografia carotídea, com menos de um mês de intervalo. Procedeu-se à recolha de informação sobre os factores de risco vascular. Determinámos associações independentes entre hipodensidades da substância branca de provável etiologia vascular, espessura da íntima média carotídea, estenose carotídea ateromatosa e factores de risco vascular.Resultados: Foram incluídos 472 doentes, idade média de 67,32 (DP: 14.75), 274 (58,1%) sexo masculino. Os preditores independentes da hipodensidades da substância branca de provável etiologia vascular foram: idade (OR: 1,067, 95% IC: 1,049 – 1,086, p < 0,001) e a hipertensão (OR: 1,726, 95% IC: 1,097 – 2,715, p = 0,018). Não foi encontrada uma associação entre a espessura da intima média carotídea (OR: 2,613, 95% IC: 0,886 – 7,708, p = 0,082) ou grau de estenose carotídea (OR: 1,021, 95% IC: 0,785 – 1,328, p = 0,877) e hipodensidades da substância branca de provável etiologia vascular.Discussão: Dos diversos factores de risco analisados, apenas a idade e hipertensão se associaram de forma independente às hipodensidades da substância branca de provável etiologia vascular. Não foi encontrada uma relação entre a aterosclerose extracraniana, expressa pela espessura do complexo intima-média ou grau de estenose, com o desenvolvimento de hipodensidades da substância branca de provável etiologia vascular. Sendo a aterosclerose um fenómeno sistémico, estes achados sugerem que as hipodensidades da substância branca de provável etiologia vascular, tenham um mecanismo alternativo ou concorrente à aterosclerose no seu desenvolvimento.Conclusão: Os dados deste estudo, sugerem que a idade e hipertensão sejam os principais factores de risco no desenvolvimento de hipodensidades da substância branca de provável etiologia vascular. Não foi encontrada uma associação independente entre a aterosclerose carotídea e as hipodensidades da substância branca de provável etiologia vascular.

Recurrence in intracranial atherosclerotic disease: a stenosis-based analysis.

BACKGROUND: Intracranial atherosclerotic disease is a common cause of stroke; its incidence and prevalence vary widely by ethnicity. The aim of our study was to analyze the recurrence rate of cerebrovascular events in patients with symptomatic and asymptomatic intracranial stenosis (IS). METHODS: We conducted a historical cohort study including all patients admitted in our hospital for stroke or transient ischemic attack (TIA) during 2011 and 2012 with information on intracranial circulation (ultrasonography and/or computed tomography angiography). We identified patients with symptomatic and asymptomatic IS and studied the recurrence of cerebrovascular events (TIA or ischemic stroke within the territory of the stenosis) for a minimum follow-up period of 6 months after the diagnosis of IS. For the recurrence rate estimation, patients with other potentially embolic diseases (in cervical arteries or heart) were excluded. We calculated the rate of recurrence of cerebrovascular events and performed Kaplan-Meier survival curves for symptomatic and asymptomatic IS. RESULTS: We investigated 1302 patients, mean age was 72.41 years (standard deviation 12.75). We identified 218 IS in 158 patients, 77 were symptomatic and 141 were asymptomatic. The recurrence rate of cerebrovascular events was 12.32 per 100 patient-years, with a mean time to recurrence of 1.73 months for symptomatic intracranial stenosis (SIS) and .88 per 100 patient-years for asymptomatic IS (P < .001). CONCLUSIONS: These results indicate a high risk of early recurrence of stroke in the territory of a SIS, highlighting the importance of its early diagnosis and aggressive treatment.

Modulation of cortical interhemispheric interactions by motor facilitation or restraint.

Cortical interhemispheric interactions in motor control are still poorly understood and it is important to clarify how these depend on inhibitory/facilitatory limb movements and motor expertise, as reflected by limb dominance. Here we addressed this problem using functional magnetic resonance imaging (fMRI) and a task involving dominant/nondominant limb mobilization in the presence/absence of contralateral limb restraint. In this way we could modulate excitation/deactivation of the contralateral hemisphere. Blocks of arm elevation were alternated with absent/present restraint of the contralateral limb in 17 participants. We found the expected activation of contralateral sensorimotor cortex and ipsilateral cerebellum during arm elevation. In addition, only the dominant arm elevation (hold period) was accompanied by deactivation of ipsilateral sensorimotor cortex, irrespective of presence/absence of contralateral restraint, although the latter increased deactivation. In contrast, the nondominant limb yielded absent deactivation and reduced area of contralateral activation upon restriction. Our results provide evidence for a difference in cortical communication during motor control (action facilitation/inhibition), depending on the "expertise" of the hemisphere that controls action (dominant versus nondominant). These results have relevant implications for the development of facilitation/inhibition strategies in neurorehabilitation, namely, in stroke, given that fMRI deactivations have recently been shown to reflect decreases in neural responses.

Different locations but common associations in subcortical hypodensities of presumed vascular origin: cross-sectional study on clinical and neurosonologic correlates.

BACKGROUND: Subcortical hypodensities of presumed vascular etiology (SHPVO) are a clinical, radiological and neuropathological syndrome with a still largely unexplained pathophysiology. Parallel to the clinical heterogeneity, there is also recognised cerebral topographical diversity with undetermined etiological implications. Our aim is to assess clinical and neurosonological predictors of SHPVO according to their location. METHODS: Cross sectional analysis of consecutive patients that underwent neurosonologic evaluation and head CT within one month, during a one year period. We excluded patients with absent temporal sonographic window, any pathology with a possible confounding effect on cerebral arterial pulsatility, atrial fibrillation and other etiologies of white matter diseases. The mean pulsatility index (PI) of both middle cerebral arteries was measured in the middle third of the M1 segment; intima media thickness was evaluated in the far wall of both common carotid arteries. SHPVO were rated by analysis of head CT in deep white matter (DWMH), periventricular white matter (PVWMH) and basal ganglia (BGH). We conducted a multivariate ordinal logistic regression model including all clinical, demographic and ultrasonographic characteristics to determine independent associations with SHPVO. RESULTS: We included 439 patients, mean age 63.47 (SD: 14.94) years, 294 (67.0%) male. The independent predictors of SHPVO were age (OR = 1.067, 95% CI: 1.047-1.088, p < 0.001 for DWMH; OR = 1.068, 95% CI: 1.049-1.088, p < 0.001 for PVWMH; OR = 1.05, 95% CI: 1.03-1.071, p < 0.001 for BGH), hypertension (OR = 1.909, 95% CI: 1.222-2.981, p = 0.004 for DWMH; OR = 1.907, 95% CI: 1.238-2.938, p = 0.003 for PVWMH; OR = 1.775, 95% CI: 1.109-2.843, p = 0.017 for BGH) and PI (OR = 17.994, 95% CI: 6.875-47.1, p < 0.001 for DWMH; OR = 5.739, 95%CI: 2.288-14.397, p < 0.001 for PVWMH; OR = 11.844, 95% CI: 4.486-31.268, p < 0.001 for BGH) for all locations of SHPVO. CONCLUSIONS: Age, hypertension and intracranial pulsatility are the main independent predictors of SHPVO across different topographic involvement and irrespective of extracranial atherosclerotic involvement.

Progressive multifocal leukoencephalopathy in a patient with chronic lymphocytic leukaemia treated with alemtuzumab.

A 69-year-old Caucasian woman with a 15-year history of refractory chronic lymphocytic B-cell leukaemia (CLL), treated with alemtuzumab in the past 10 months presented with a subacute right foot drop. Initial evaluation with a brain CT scan, lumbosacral MRI, nerve conduction studies and LP was negative. In the following months, progressive right hemibody weakness and dysarthria developed. Brain MRI showed a bilateral parasagittal frontal lesion. Alemtuzumab treatment was withdrawn. Progressive multifocal leukoencephalopathy (PML) was confirmed by PCR. Attempted antiviral therapies proved fruitless. Inexorable clinical deterioration ensued and the patient passed away 10 months after the presentation. This case report intends to call attention for PML as a potential fatal complication of severe immunosuppression, including the possible role of new monoclonal antibodies (such as alemtuzumab) in its pathogenesis.

[Atrial fibrillation in cerebrovascular disease: national neurological perspective]. / Fibrilhação Auricular na Doença Cerebrovascular: A Perspectiva Neurológica Nacional.

BACKGROUND: Cardioembolism due to atrial fibrillation assumes a dominant etiologic role in cerebrovascular diseases due to its growing incidence, high embolic risk and particular aspects of clinical events caused. Our objectives are to analyze the frequency of atrial fibrillation in patients with ischemic stroke, study the vital and functional impact of stroke due to different etiologies and evaluate antithrombotic options before and after stroke. METHODS: We conducted a retrospective study including patients admitted in a central hospital due to ischemic stroke in 2010 (at least one year of follow-up). Etiology of stroke was defined using the Trial of ORG 10172 in Acute Stroke (TOAST) classification, and functional outcome by modified Rankin scale. We performed a descriptive analysis of different stroke etiologies and antithrombotic medication in patients with atrial fibrillation. We then conducted a cohort study to evaluate the clinical impact of antithrombotic options in secondary prevention after cardioembolic stroke. RESULTS: In our population (n = 631) we found superior frequency of cardioembolism (34.5%) to that reported in the literature. Mortality, morbidity and antithrombotic options are similar to other previous series, confirming the severity of cardioembolic strokes and the underuse of vitamin K antagonists. Oral anticoagulation was effective in secondary prevention independently from post-stroke functional condition. CONCLUSIONS: Despite unequivocal recommendations, oral anticoagulation is still underused in stroke prevention. This study confirms the clinical efficacy of vitamin K antagonists in secondary prevention independently from residual functional impairment.

Introdução: A cardioembolia por fibrilhação auricular assume particular destaque etiológico nas doenças vasculares cerebrais devido à sua crescente incidência, elevado risco embólico e particularidades dos eventos clínicos causados. São objectivos deste trabalho analisar a frequência da fibrilação auricular numa população de doentes com acidente vascular cerebral isquémico observados num hospital nacional, estudar o impacto vital e funcional dos acidentes vasculares cerebrais causados por diferentes etiologias, e avaliar as opções antitrombóticas prévias e posteriores ao acidente vascular cerebral. Metodologia: Realizámos um estudo observacional retrospectivo incluindo todos os doentes internados num hospital central por acidente vascular cerebral isquémico em 2010 (pelo menos um ano de seguimento). A etiologia do acidente vascular cerebral foi definida pela classificação Trial of ORG 10172 in Acute Stroke (TOAST) modificada e o resultado funcional pela escala Rankin modificada. Realizámos análise descritiva das diferentes etiologias de acidente vascular cerebral e das prescrições antitrombóticas a doentes com fibrilhação auricular. Realizámos ainda um estudo de coorte para estudar o impacto clínico das opções antitrombóticas em prevenção secundária após acidente vascular cerebral cardioembólico. Resultados: Na nossa população (n = 631) encontramos frequência de cardioembolia (34,5%) superior à relatada na literatura. Os valores de mortalidade e morbilidade além das opções terapêuticas antitrombóticas em pré e pós-Doença Vascular Cerebral são semelhantes aos de outras séries, confirmando a gravidade dos acidentes vasculares cerebrais cardioembólicos e a subutilização dos antagonistas da vitamina K. A anticoagulação oral foi eficaz em prevenção secundária independentemente do estado funcional sequelar após acidente vascular cerebral. Conclusões: Apesar das recomendações terapêuticas inequívocas a anticoagulação oral continua a ser subutilizada em prevenção de Doença Vascular Cerebral. Confirmamos a eficácia clínica dos antagonistas da vitamina K em prevenção secundária, independentemente das limitações funcionais sequelares.

CHADS(2) and CHA(2)DS(2)VASc scores as predictors of cardioembolic sources in secondary stroke prevention.

INTRODUCTION AND OBJECTIVES: Cardioembolism is one of the most common causes of ischemic stroke, with an estimated prevalence of 20-30%, and correct diagnosis is essential given the therapeutic implications. Although stroke risk scores (CHADS2 and more recently CHA2DS2-VASc) have been validated in heterogeneous populations of patients with atrial fibrillation, their accuracy has not been ascertained for secondary stroke prevention. We set out to assess the sensitivity and specificity of the CHADS2 and CHA2DS2-VASc stroke risk scores as predictors of cardioembolic sources, documented by transesophageal echocardiography (TEE) in a population with ischemic stroke. METHODS: The CHADS2 and CHA2DS2-VASc scores were applied to all patients admitted to the stroke unit/neurology ward of a Portuguese tertiary hospital with atrial fibrillation (diagnosed previously or during or after admission) who underwent TEE between January and August 2011. The presence of a cardioembolic source was defined as the observation by TEE of spontaneous echo contrast in the left atrium and atrial appendage or thrombi in the left cardiac chambers. RESULTS: We studied 94 patients, 66.0% male, mean age 64.4 years (standard deviation 14.2). A cardioembolic source was detected in 20 patients. ROC curve analysis identified as predictors of cardioembolic source CHADS2 score ≥4 (sensitivity of 75.0%, specificity of 66.0%, p=0.014) and CHA2DS2-VASc score ≥5 (sensitivity of 83.3%, specificity of 58.0%, p=0.009). CONCLUSIONS: Both scores showed acceptable sensitivity as predictors of embolic risk in the context of secondary prevention of cardioembolic stroke. The CHA2DS2-VASc score has higher sensitivity than CHADS2 but lower specificity.