Jamary Oliveira-Filho

Fever in subarachnoid hemorrhage: Relationship to vasospasm and outcome

Objective: To investigate the causes of fever in subarachnoid hemorrhage (SAH) and examine its relationship to outcome. Background: Fever adversely affects outcome in stroke. Patients with SAH are at risk for cerebral ischemia due to vasospasm (VSP). In these patients, fever may be both caused by, and potentiate, VSP-mediated brain injury. Methods: The authors prospectively studied patients admitted to a neurologic intensive care unit with nontraumatic SAH, documenting Hunt–Hess grade, Fisher group, Glasgow Coma Score, bacterial culture data, daily transcranial Doppler mean velocities, and maximum daily temperatures. Patients were classified as febrile (temperature above 38.3 °C for at least 2 consecutive days) or afebrile (no fever or isolated episodes of temperature above 38.3 °C). VSP was verified by either transcranial Doppler or angiographic criteria. Rankin scale scores on discharge were dichotomized into good (0 to 2) or poor (3 to 6) outcomes. Results: Ninety-two consecutive patients were studied. Thirty-eight patients were classified as febrile. No source for infection was found in 10 of 38 (26%) patients. In a multivariate analysis, three variables independently predicted fever occurrence: ventriculostomy (OR, 8.5 [CI, 2.4 to 29.7]), symptomatic VSP (OR, 5.0 [CI, 1.03 to 24.5]), and older age (OR, 1.75 per 10 years [CI, 1.02 to 3.0]). Poor outcome was related to fever (OR, 1.4 per each day febrile [CI, 1.1 to 1.88]), older age (OR, 1.64 per 10 years [CI, 1.04 to 2.58]), and intubation (OR, 21.8 [CI, 5.6 to 84.5]). Conclusion: Fever in SAH is associated with vasospasm and poor outcome independently of hemorrhage severity or presence of infection.

Detrimental effect of blood pressure reduction in the first 24 hours of acute stroke onset.

Background: High blood pressure, although the main modifiable risk factor for stroke, may have a beneficial effect in maintaining brain perfusion after acute ischemia. The authors assessed the effects of blood pressure variation in the first 24 hours of stroke onset. Methods: The authors prospectively studied consecutive patients admitted in the first 24 hours after stroke onset. Patients were classified according to the NIH Stroke Scale (NIHSS) and Oxfordshire Stroke Classification Scale (OSCS). Stroke etiology was defined according to Trial of ORG 10172 in Acute Stroke Treatment classification. After 3 months, outcome was assessed using Rankin and Barthel scales, with poor outcome defined as Rankin score > 2 or Barthel score < 70. Results: A total of 115 patients were admitted between January 2001 and October 2002. Median NIHSS was 4.5; main stroke etiology was cardioembolism (30%). After 3 months, 44 (39%) patients had a poor outcome. Predictors of poor outcome in univariable analyses (p < 0.05) were as follows: total anterior circulation classification on OSCS, nonlacunar stroke etiology, older age, higher NIHSS score, lack of antiplatelet use, higher body temperature, lower diastolic blood pressure on admission, and a larger degree of systolic blood pressure reduction. In the multivariable analysis, remaining predictors of poor outcome included the following: NIHSS score (OR = 1.55 per 1 point increase; 95% CI = 1.28 to 1.87; p < 0.001) and degree of systolic blood pressure reduction in the first 24 hours (OR = 1.89 per 10% decrease; 95% CI = 1.02 to 3.52; p = 0.047). Conclusion: Blood pressure reduction in the first 24 hours of stroke onset is independently associated with poor outcome after 3 months.

Diffusion-weighted imaging identifies a subset of lacunar infarction associated with embolic source

BACKGROUND AND PURPOSEnSmall infarcts in the territory of penetrator arteries were described as causing a number of distinct clinical syndromes. The vascular pathophysiology underlying such infarcts is difficult to ascertain without careful pathological study. However, the occurrence of multiple, small infarcts, linked closely in time but dispersed widely in the brain, raises the possibility of an embolic mechanism. The current study determines the frequency and clinical characteristics of patients with well-defined lacunar syndromes and the diffusion-weighted imaging (DWI) evidence of multiple acute lesions.nnnMETHODSnSixty-two consecutive patients who presented to the emergency room with a clinically well-defined lacunar syndrome were studied by DWI within the first 3 days of admission.nnnRESULTSnDWI showed multiple regions of increased signal intensity in 10 patients (16%). A hemispheric or brain stem lesion in a penetrator territory that accounted for the clinical syndrome (index lesion) was found in all. DWI-hyperintense lesions other than the index lesion (subsidiary infarctions) were punctate and lay within leptomeningeal artery territories in the majority. As opposed to patients with a single lacunar infarction, patients with a subsidiary infarction more frequently (P<0.05) harbored an identifiable cause of stroke.nnnCONCLUSIONSnAlmost 1 of every 6 patients presenting with a classic lacunar syndrome has multiple infarctions demonstrated on DWI. This DWI finding usually indicates an identifiable cause of stroke and therefore may influence clinical decisions regarding the extent of etiologic investigations and treatment for secondary prevention.

‘Footprints’ of Transient Ischemic Attacks: A Diffusion-Weighted MRI Study

Objective: Diffusion-weighted imaging (DWI) conveys temporal as well as anatomic information about brain infarction, and is therefore well suited to identify ischemic injury that has occurred simultaneously, or closely linked in time, with a transient ischemic attack (TIA). We aimed to determine the proportion and clinical characteristics of patients with TIA who harbor infarction(s) on DWI. Methods: Using T2-weighted imaging (T2-WI), fast fluid attenuated inversion recovery (FLAIR), and DWI, we studied 57 consecutive patients presenting with acute focal neurologic symptoms lasting less than 24 h. Results: A hyperintense DWI lesion was identified in a vascular territory appropriate to the symptoms in 27 patients (47%). Lesions judged to be clinically appropriate on T2-WI and FLAIR overlapped with a DWI lesion in 41 and 48% of patients, respectively. Independent predictors of infarction on DWI were previous nonstereotypic TIAs, presentation with motor symptoms, and identified stroke mechanism. Conclusion: DWI establishes that recent infarction occurs in almost half of patients with the clinical syndrome of TIA and this subgroup is more likely to harbor an underlying cardiac or cerebrovascular abnormality.

Validation of the National Institutes of Health Stroke Scale, Modified Rankin Scale and Barthel Index in Brazil: The Role of Cultural Adaptation and Structured Interviewing

Background: We aimed to validate three widely used scales in stroke research in a multiethnic Brazilian population. Methods: The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) were translated, culturally adapted and applied by two independent investigators. The mRS was applied with or without a previously validated structured interview. Interobserver agreement (kappa statistics) and intraclass correlation coefficients were calculated. Results: 84 patients underwent mRS (56 with and 28 without a structured interview), 57 BI and 62 NIHSS scoring. Intraclass correlation coefficient was 0.902 for NIHSS and 0.967 for BI. For BI, interobserver agreement was good (kappa = 0.70). For mRS, the structured interview improved interobserver agreement (kappa = 0.34 without a structured interview; 0.75 with a structured interview). Conclusion: The NIHSS, BI and mRS show good validity when translated and culturally adapted. Using a structured interview for the mRS improves interobserver concordance rates.

Cerebral amyloid angiopathy with and without hemorrhage Evidence for different disease phenotypes

Objective: To gain insight into different cerebral amyloid angiopathy (CAA) phenotypes and mechanisms, we investigated cortical superficial siderosis (CSS), a new imaging marker of the disease, and its relation with APOE genotype in patients with pathologically proven CAA, who presented with and without intracerebral hemorrhage (ICH). Methods: MRI scans of 105 patients with CAA pathologic confirmation and MRI were analyzed for CSS (focal, ≤3 sulci; disseminates, ≥4 sulci) and other imaging markers. We compared pathologic, imaging, and APOE genotype data between subjects with vs without ICH, and investigated associations between CSS and APOE genotype. Results: Our cohort consisted of 54 patients with CAA with symptomatic lobar ICH and 51 without ICH. APOE genotype was available in 53 patients. More than 90% of pathology samples in both groups had neuritic plaques, whereas neurofibrillary tangles were more commonly present in the patients without ICH (87% vs 42%, p < 0.0001). There was a trend for patients with CAA with ICH to more commonly have APOE ε2 (48.7% vs 21.4%, p = 0.075), whereas patients without ICH were more likely to be APOE ε4 carriers (85.7% vs 53.9%, p = 0.035). Disseminated CSS was considerably commoner in patients with ICH (33.3% vs 5.9%, p < 0.0001). In logistic regression, disseminated CSS was associated with APOE ε2 (but not APOE ε4) (odds ratio 5.83; 95% confidence interval 1.49–22.82, p = 0.011). Conclusions: This neuropathologically defined CAA cohort suggests that CSS and APOE ε2 are related to the hemorrhagic expression of the disease; APOE ε4 is enriched in nonhemorrhagic CAA. Our study emphasizes the concept of different CAA phenotypes, suggesting divergent pathophysiologic mechanisms.

Interrelationship of superficial siderosis and microbleeds in cerebral amyloid angiopathy.

Objective: We sought to explore the mechanisms leading to cerebral amyloid angiopathy (CAA)-related cortical superficial siderosis (cSS) by examining its neuroimaging and genetic association with cerebral microbleeds (CMBs). Methods: MRI scans of 84 subjects with probable or definite CAA participating in a longitudinal research study were graded for cSS presence and severity (focal, restricted to ≤3 sulci vs disseminated, ≥4 sulci), and CMB count. APOE ε variants were directly genotyped. We performed cross-sectional analysis comparing CMB counts and APOE ε2 and ε4 allele frequency between subjects with no, focal, or disseminated cSS. Results: cSS was present in 48% (n = 40) of the population. APOE ε2 was overrepresented among participants with focal (odds ratio [OR] 7.0, 95% confidence interval [CI] 1.7–29.3, p = 0.008) and disseminated (OR 11.5, 95% CI 2.8–46.2, p = 0.001) cSS relative to individuals without cSS. CMB counts decreased with increasing severity of cSS (median: 41, 38, and 15 for no cSS, focal cSS, and disseminated cSS, respectively, p = 0.09). The highest CMB count tertile was associated with APOE ε4 (OR 3.0, 95% CI 1.4–6.6, p = 0.006) relative to the lowest tertile. Conclusions: Among individuals with advanced CAA, cSS tends to occur in individuals with relatively lower CMB counts and with a distinct pattern of APOE genotypes. These results suggest that CAA-related cSS and CMBs may arise from distinct vasculopathic mechanisms.

Total Magnetic Resonance Imaging Burden of Small Vessel Disease in Cerebral Amyloid Angiopathy: An Imaging-Pathologic Study of Concept Validation

IMPORTANCEnCerebral amyloid angiopathy (CAA) is characteristically associated with magnetic resonance imaging (MRI) biomarkers of small vessel brain injury, including strictly lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities. Although these neuroimaging markers reflect distinct pathophysiologic aspects in CAA, no studies to date have combined these structural imaging features to gauge total brain small vessel disease burden in CAA.nnnOBJECTIVESnTo investigate whether a composite score can be developed to capture the total brain MRI burden of small vessel disease in CAA and to explore whether this score contributes independent and complementary information about CAA severity, defined as intracerebral hemorrhage during life or bleeding-related neuropathologic changes.nnnDESIGN, SETTING, AND PARTICIPANTSnThis retrospective, cross-sectional study examined a single-center neuropathologic CAA cohort of eligible patients from the Massachusetts General Hospital from January 1, 1997, through December 31, 2012. Data analysis was performed from January 2, 2015, to January 9, 2016. Patients with pathologic evidence of CAA (ie, any presence of CAA from routinely collected brain biopsy specimen, biopsy specimen at hematoma evacuation, or autopsy) and available brain MRI sequences of adequate quality, including T2-weighted, T2*-weighted gradient-recalled echo, and/or susceptibility-weighted imaging and fluid-attenuated inversion recovery sequences, were considered for the study.nnnMAIN OUTCOMES AND MEASURESnBrain MRIs were rated for lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities. All 4 MRI lesions were incorporated into a prespecified ordinal total small vessel disease score, ranging from 0 to 6 points. Associations with severity of CAA-associated vasculopathic changes (fibrinoid necrosis and concentric splitting of the wall), clinical presentation, number of intracerebral hemorrhages, and other imaging markers not included in the score were explored using logistic and ordinal regression.nnnRESULTSnIn total, 105 patients with pathologically defined CAA were included: 52 with autopsies, 22 with brain biopsy specimens, and 31 with pathologic samples from hematoma evacuations. The mean (range) age of the patients was 73 (71-74) years, and 55 (52.4%) were women. In multivariable ordinal regression analysis, severity of CAA-associated vasculopathic changes (odds ratio, 2.40; 95% CI, 1.06-5.45; Pu2009=u2009.04) and CAA presentation with symptomatic intracerebral hemorrhage (odds ratio, 2.23; 95% CI, 1.07-4.64; Pu2009=u2009.03) were independently associated with the total MRI small vessel disease score. The score was associated with small, acute, diffusion-weighted imaging lesions and posterior white matter hyperintensities in adjusted analyses.nnnCONCLUSIONS AND RELEVANCEnThis study provides evidence of concept validity of a total MRI small vessel disease score in CAA. After further validation, this approach can be potentially used in prospective clinical studies.

Guidelines for acute ischemic stroke treatment - Part I

Executive Committee: Charles André, Aroldo Luiz Bacellar, Daniel da Cruz Bezerra, Roberto Campos, João José Freitas de Carvalho, Gabriel Rodrigues de Freitas, Roberto de Magalhães Carneiro de Oliveira, Sebastião Eurico Melo de Souza, Soraia Ramos Cabette Fábio, Eli Faria Evaristo, Jefferson Gomes Fernandes, Maurício Friedrich, Marcia Maiumi Fukujima, Rubens José Gagliardi, Sérgio Roberto Haussen, Maria Clinete Sampaio Lacativa, Bernardo Liberato, Alexandre L. Longo, Sheila Cristina Ouriques Martins, Ayrton Roberto Massaro, Cesar Minelli, Carla Heloísa Cabral Moro, Jorge El-Kadum Noujaim, Edison Matos Nóvak, Jamary Oliveira-Filho, Octávio Marques Pontes-Neto, César Noronha Raffin, Bruno Castelo Branco Rodrigues, José Ibiapina Siqueira-Neto, Elza Dias Tosta, Raul Valiente, Leonardo Vedolim, Marcelo Gabriel Veja, Leonardo Vedolin, Fábio Iuji Yamamoto, Viviane Flumignan Zétola. Correspondence: Jamary Oliveira-Filho; Rua Reitor Miguel Calmon s/n; Instituto de Ciências da Saúde / sala 455; 40110-100 Salvador BA Brasil; E-mail: jamaryof@ufba.br Conflict of interest: There is no conflict of interest to declare. Received 18 February 2012; Received in final form 22 February 2012; Accepted 29 February 2012 Guidelines for acute ischemic stroke treatment – Part I

Guidelines for acute ischemic stroke treatment: part II: stroke treatment

The second part of these Guidelines covers the topics of antiplatelet, anticoagulant, and statin therapy in acute ischemic stroke, reperfusion therapy, and classification of Stroke Centers. Information on the classes and levels of evidence used in this guideline is provided in Part I. A translated version of the Guidelines is available from the Brazilian Stroke Society website (www.sbdcv.com.br).