Gustavo Cordeiro

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 Alemtuzumab treatment was withdrawn.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.

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.

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.

Neurosonology Accuracy for Isolated Acute Vestibular Syndromes

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.

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

ABSTRACT 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 β [S100β]), 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 S100β protein levels (OR:0.997 [CI:0.994–0.999]; P = 0.007). Advanced age was associated with poor upper limb functioning. S100β 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 S100β 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.

S100β 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 S100β 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 (S100β protein). Functional status was accessed at 48 hours and 12 weeks poststroke using the modified Rankin Scale (mRS). RESULTS S100β 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 S100β 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 S100β 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 S100β 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.

CHADS2 e CHA2DS2VASc como preditores de fonte cardioembólica em prevenção secundária cerebrovascular

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.