Fernando Góngora-Rivera

Autopsy Prevalence of Intracranial Atherosclerosis in Patients With Fatal Stroke

Background and Purpose— The objective of this study was to determine the prevalence of intracranial plaques and stenoses and their causal role in patients with fatal stroke. Intracranial atherosclerosis is considered to be a rare condition with a severe prognosis. However, disease prevalence may be underestimated due to lack of appropriate diagnostic procedures. Methods— We performed a systematic analysis of intra- and extracranial arteries, the aortic arch, and the heart in 339 consecutive autopsies of patients with stroke. Clinical history, risk factors, imaging data, and general autopsy reports were analyzed. Patients with brain hemorrhage (n=80) were used as control subjects. Results— Intracranial plaques and stenoses occurred in 62.2% (95% CI, 56.3 to 68.1) and 43.2% (95% CI, 37.2 to 49.3) of patients with brain infarction, respectively, compared with 48.8% (P<0.05) and 17.5% (P<0.001) of patients with brain hemorrhage, respectively. In the 43% of patients with brain infarction with at least one intracranial plaque-inducing luminal stenosis graded >30%, the stenosis was considered to be causal in 5.8% of cases (n=15) because of superimposed clot on ulcerated plaques; 27% of these patients had stenoses graded 30% to 75%. In multivariate analyses, diabetes and male sex were significantly associated with intracranial plaques and stenosis. History of myocardial infarction was significantly associated with intracranial plaques and previous stroke was associated with intracranial stenosis. Conclusions— Intracranial plaques and stenoses are highly prevalent in fatal stroke, and stenoses graded 30% to 75% may be causal. New arterial wall imaging techniques should be used to reevaluate the frequency and role of intracranial artery plaques in living patients with stroke.

Autopsy prevalence of coronary atherosclerosis in patients with fatal stroke.

Background and Purpose— Myocardial infarction (MI) is the leading cause of long-term mortality in patients with stroke, yet the prevalence of coronary atherosclerosis in these individuals is unknown. The objective of the study was to establish the prevalence of coronary atherosclerosis and MI after fatal stroke. Methods— Using an autopsy data bank, we studied the prevalence of coronary plaques and coronary stenoses >50% and pathologic evidence of MI in 803 consecutive autopsies of neurologic patients. Results— Coronary plaques, coronary stenoses, and MI were present in 72.4%, 37.5%, and 40.8%, respectively, of the 341 patients with stroke and in 26.8%, 10.1%, and 12.8%, respectively, of the 462 patients with other neurologic diseases (P<0.001). Two-thirds of cases of MI were clinically silent and found at autopsy. Compared with other neurologic diseases, and after adjusting for age, gender, and heart weight, the odds ratios (95% confidence intervals) of the presence of coronary plaques, coronary stenosis, and MI in stroke patients were 3.81 (2.66 to 5.46), 2.80 (1.85 to 4.25), and 2.34 (1.58 to 3.46), respectively. The frequency of coronary atherosclerosis and MI was similar between stroke subtypes. The prevalence of coronary plaques, coronary stenosis, and MI was 79.0%, 42.9%, and 46.0%, respectively, in the presence of plaques in any segment of the extracranial and intracranial brain arteries, and 50.8%, 17.9%, and 23.9%, respectively, in the absence of plaques (adjusted P<0.01). Coronary atherosclerosis was also related to the severity of atherosclerosis in any segment of the cerebral arteries (adjusted probability value for linear trend <.005). Conclusions— Coronary atherosclerosis and MI are highly prevalent in patients who died from a stroke regardless of the etiology. They are more frequent when atherosclerosis is present in the carotid and cerebral arteries. They are also common in stroke patients with no evidence of carotid or cerebral atherosclerosis.

Prevalence of Coronary Atherosclerosis in Patients With Cerebral Infarction

Background and Purpose— There is an overlap between stroke and coronary heart disease, but the exact prevalence of coronary artery disease in patients with nonfatal cerebral infarction is unclear, particularly when there is no known history of coronary heart disease. Methods— We consecutively enrolled 405 patients presenting with acute cerebral infarction documented by neuroimaging who underwent carotid and femoral artery, thoracic, and abdominal aorta ultrasound examinations. Of the 342 patients with no known coronary heart disease, 315 underwent coronary angiography a median of 8 days (interquartile range, 6–11) after stroke onset. Results— Coronary plaques on angiography, regardless of stenosis severity, were present in 61.9% of patients (95% confidence interval [CI], 56.5–67.3) and coronary stenoses ≥50% were found in 25.7% (95% CI, 20.9–30.5). The overall prevalence of coronary plaque increased with the number of arterial territories (carotid or femoral arteries) involved, with an adjusted odds ratio of coronary artery disease of 1.25 (95% CI, 0.58–2.71) for presence of plaque in 1 territory, and 4.31 (95% CI, 1.92–9.68) for presence of plaque in both territories, compared with no plaque in either territory. The presence of plaque in both femoral and carotid arteries had an age- and sex-adjusted positive predictive value of 84% for presence of coronary plaque and a negative predictive value of 44%. Conclusions— There is a high burden of silent coronary artery disease in patients with nonfatal cerebral infarction and no known coronary heart disease, even in the absence of systemic atherosclerosis. The prevalence is even higher in patients with evidence of carotid and/or femoral plaque.

Predictors for malignant middle cerebral artery infarctions A postmortem analysis

Background: Early detection of malignant infarction of the middle cerebral artery (MI-MCA) is important because of possible treatment by hemicraniectomy. Objective: To investigate the anatomic and vascular predictors of MI-MCA. Method: The authors evaluated 192 consecutive autopsies of patients with nonlacunar cerebral infarction affecting the MCA territory. MI-MCA was defined by an infarct with temporal or central brain herniation and brain swelling. The autopsy protocol included a systematic analysis of intracranial arteries (including the bony segments of carotid and vertebral arteries and the circle of Willis), extracranial arteries, the aortic arch, and the heart. Results: A total of 45 patients with MI-MCA were identified. Their median (range) survival time was 6 (0 to 20) days as compared with 18 (0 to 2,040) days for non-MI-MCA patients. Compared with non-MI-MCA, MI-MCA cases more frequently involved the superficial and deep MCA territory and were more frequently associated with anterior cerebral and anterior choroidal artery territory infarcts. Hemorrhagic transformation, Duret hemorrhages, carotid occlusion, and ipsilateral abnormalities of the circle of Willis were also more frequent (p < 0.05). Multivariable analysis showed that younger age, female sex, absence of stroke history, higher heart weight, carotid artery occlusion, and abnormal circle of Willis ipsilaterally were all independently associated with MI-MCA (p < 0.03). Conclusions: Typical pathologic pattern for development of malignant infarction of the middle cerebral artery is a carotid occlusion with abnormal ipsilateral circle of Willis in a young patient who had a first-ever large hemispheric stroke including the superficial territory with possibly a slight predominance of female sex.

Albendazole trial at 15 or 30 mg/kg/day for subarachnoid and intraventricular cysticercosis

Thirty-six patients with subarachnoid and intraventricular cysticercosis were randomly assigned to receive albendazole at 15 or 30 mg/kg/day plus dexamethasone for 8 days. Results favored a higher dose, with larger cyst reduction on MRI at 90 and 180 days and higher albendazole sulfoxide levels in plasma. An albendazole course at 30 mg/kg/day combined with corticosteroids is safe and more effective than the usual dose. A single treatment was insufficient in intraventricular and giant cysts.

Placebo-Controlled Trial of High-Dose Atorvastatin in Patients With Severe Cerebral Small Vessel Disease

BACKGROUND AND PURPOSE Uncontrolled studies have shown that statins can improve cerebral vasoreactivity (CVR) in patients with mild small vessel disease. We sought to determine whether high-dose atorvastatin increases CVR compared with placebo in patients with severe small vessel disease. METHODS Ninety-four adults with recent lacunar stroke were randomly allocated in a double-blind manner to 80 mg of atorvastatin daily or matching placebo after stratification for hypertensive and diabetic status. The primary end point was change in CVR after 3 months of treatment. Secondary outcomes were changes in brachial and carotid artery endothelial-dependent vasodilations. RESULTS At baseline, all patients had a severely impaired CVR (mean, 12.1%; 95% CI, 9.5-14.7) and carotid (mean, -0.25%; 95% CI, -1.17-0.67) and brachial artery (mean, 2.72%; 95% CI, 1.39-4.05) endothelial function. Despite reductions of 55% in low-density lipoprotein cholesterol and of 30% in high-sensitivity C-reactive protein in the active arm compared to placebo, atorvastatin 80 mg per day did not improve CVR or endothelial dysfunction of carotid and brachial arteries. CONCLUSIONS We found no positive effect of 3-month treatment with atorvastatin on severe cerebral microvasculature endothelial dysfunction in patients with lacunar stroke.

Autopsy Prevalence of Proximal Extracranial Atherosclerosis in Patients With Fatal Stroke

Background and Purpose— Extracranial atherosclerosis, proximal to the carotid bifurcation and V3 segment of the vertebral artery, is considered to be an infrequent condition with a benign prognosis. However, its prevalence may be underestimated due to lack of data. We aimed to determine the prevalence of proximal extracranial plaques and stenosis in the common carotid artery, innominate and subclavian arteries, and proximal vertebral artery. Methods— We performed a systematic analysis of intra- and extracranial arteries, the aortic arch, and the heart in 339 consecutive autopsies of patients with stroke; 259 patients had brain infarction; 80 patients had brain hemorrhage and were used as control subjects. Clinical history, risk factors, imaging data, and general autopsy reports were analyzed. Results— Proximal extracranial plaques and stenosis were present in the arteries of 46.9% and 19.8% of patients, respectively, without a significant difference between brain infarction and brain hemorrhage groups. Proximal extracranial atherosclerosis occurred more frequently in the proximal vertebral artery than in other arteries (stenosis prevalence 12.7% versus 5.3% in the common carotid artery) and in patients with posterior circulation brain infarction (except for the posterior cerebral artery territory). More specifically, atherosclerosis in the proximal vertebral artery was significantly associated with posterior circulation brain infarction (age- and sex-adjusted OR, 2.31; 95% CI, 1.28 to 4.17 for plaques and 2.10; 95% CI, 1.01 to 4.38 for stenosis) using patients with isolated anterior circulation infarctions as control subjects. Conclusions— Proximal extracranial atherosclerosis was frequent and was significantly associated with brainstem infarcts. These findings support the importance of a systematic workup, including the evaluation of proximal extracranial atherosclerotic lesions.

Circulating Markers of Endothelial Dysfunction and Platelet Activation in Patients with Severe Symptomatic Cerebral Small Vessel Disease

Background: Small deep infarcts (SDI), also called lacunar infarcts, resulting from the occlusion of deep branch arteries, account for 25% of ischemic strokes. The physiopathology of the disease remains largely unknown. However, evidence about the role of endothelial dysfunction has emerged. Whereas chronic platelet activation is of major importance in acute thrombosis of large atherosclerotic arteries, its role in SDI remains unclear. Frequently associated risk factors are hypertension and diabetes mellitus. The aim of this study was to determine platelet and endothelial activation in patients with recent SDI in comparison to population-based control subjects matched for age, sex and vascular risk factors. Methods: Platelet activation markers (activated glycoprotein IIb/IIIa, P-selectin and platelet microparticles), shear-induced platelet aggregation (SIPA) studied in the SIPAgreg device at 4,000 s-1, endothelial activation markers [including von Willebrand factor (vWF) antigen and homocysteine] and high-sensitivity C-reactive protein (hsCRP) were measured in 74 consecutive patients with recent SDI, in whom detectable large artery atherosclerosis or cardiac embolism had been ruled out. Blood samples were collected 1 and 3 months after symptom onset. These factors were also measured in 74 population-based controls with no stroke history and matched for age, sex, hypertension and diabetes. Results: One month after symptom onset, the patients had similar levels of platelet activation to matched controls (p > 0.40 for all comparisons). In contrast, endothelial activation parameters were increased in patients in comparison to controls (vWF: p = 0.002 and homocysteinemia/creatinemia: p = 0.025). The level of hsCRP was slightly increased in patients compared to controls (p = 0.059). At 3 months, we observed a significant decrease in vWF and hsCRP levels in patients (median change in vWF = 10%, p = 0.004; median change in hsCRP = 0.4 mg/l, p = 0.02). Homocysteine levels and all platelet parameters remained unchanged at this time compared to at 1 month. Conclusions: Our results confirm that chronic platelet activation, when compared to controls matched for age, sex and vascular risk factors, did not seem to play a central role in the pathophysiology of lacunar stroke. In contrast, we found markers of endothelial dysfunction, the role of which in the occurrence of lacunar infarction has still to be clarified in further studies.

Coronary Artery Disease and Risk of Major Vascular Events After Cerebral Infarction

Background and Purpose— The impact of asymptomatic coronary artery disease on the risk of major vascular events in patients with cerebral infarction is unknown. Methods— Four hundred five patients with acute cerebral infarction underwent carotid, femoral artery, thoracic, and abdominal aorta ultrasound examination. Of 342 patients with no known coronary heart disease, 315 underwent coronary angiography. We evaluated the 2-year risk of major vascular events (myocardial infarction, resuscitation after cardiac arrest, hospitalization for unstable angina or heart failure, stroke, or major peripheral arterial disease events) in patients with known coronary heart disease (n=63), and in the no known coronary heart disease group (n=315) as a function of coronary angiographic status (n=315). Results— At 2 years, the estimated risk of major vascular events was 11.0% (95% confidence interval, 8.2–14.7). According to baseline coronary angiography, estimated risk was 3.4% in patients with no coronary artery disease (n=120), 8.0% with asymptomatic coronary artery stenosis <50% (n=113), 16.2% with asymptomatic coronary artery stenosis ≥50% (n=81), and 24.1% with known coronary heart disease (P<0.0001). Using no coronary artery disease as the reference, the age- and sex-adjusted hazard ratio (95% confidence interval) of vascular events was 2.10 (0.63–6.96) for asymptomatic coronary stenosis <50%, 4.36 (1.35–14.12) for asymptomatic coronary stenosis ≥50%, and 6.86 (2.15–21.31) for known coronary artery disease. Conclusions— In patients with nonfatal cerebral infarction, presence and extent of asymptomatic stenoses on coronary angiography are strong predictors of major vascular events within 2 years.

The clinical spectrum of neurological manifestations in AIDS patients in Mexico

BACKGROUND Neurological complications may be present clinically in up to 39% of patients infected with HIV or AIDS. Some reports have shown different profiles of neurological illness related to geographic variations and the population studied. METHODS This retrospective study describes the neurological manifestations of patients with AIDS seen between 1990 and 1998 at a single neurological referral hospital in Mexico City. RESULTS One hundred forty-nine patients were included, 133 males (89%) and 16 females (10.7%). The average age was 33.8 years (9 to 75 years). Upon admission, only 50 patients (33.6%) were known to be seropositive to HIV-1. In 75 patients (50.3%), the neurological illness was definitory of AIDS and also was its first recognized clinical manifestation. The most common infection problems were brain toxoplasmosis (32.2%), meningeal cryptococcosis (21.5%), tuberculosis (8.7%), and AIDS-dementia complex (8.7%). There were eight (5.4%) cases of ischemic cerebrovascular disease and four (2. 7%) neoplasms. Two primary brain lymphomas and single cases of astrocytoma and oligodendroglioma, progressive multifocal leukoencephalopathy (PML), aseptic meningitis, acute encephalitis, transverse myelitis, myopathy, and cranial neuropathy were also seen. CONCLUSION In comparison with other studies of neurological complications of AIDS, opportunistic infections amenable to treatment in our population were more common. A high case fatality rate was observed, as was a large proportion of patients in whom the neurological illness was the first manifestation of HIV infection or AIDS due to denied, unknown, or unrecognized risk factors for HIV infection.