Risk factors for silent cerebral infarcts in subcortical white matter and basal ganglia

BACKGROUND AND PURPOSE: The purpose of this study was to clarify whether the relevant risk factors for silent cerebral infarcts (SCIs) in subcortical white matter (WM) are different from those in the basal ganglia (BG). METHODS: Subjects of this study were 219 adults without a history of stroke or transient ischemic attack and without any abnormality on a neurological examination who consecutively visited the neurology service in our hospital between January 1994 and November 1997 requesting medical evaluation for possible cerebrovascular diseases. Subjects included 141 men and 78 women ranging in age from 33 to 83 years (mean+/-SD, 63.2+/-9.5 years). We performed brain MRIs and cervical/cranial MR angiographies on all subjects. In this study, SCI was defined as a focal lesion >5 mm in diameter that was prolonged on both T2-weighted and proton density images. RESULTS: SCIs in the WM and/or BG were detected in 88 (40.2%) of the 219 subjects. No SCI >15 mm was observed in this series. Fifty of the subjects had SCIs only in the WM, 32 subjects had SCIs in both the WM and BG, and 6 subjects had SCIs only in the BG. Thus, 82 (93.2%) of 88 subjects with SCIs had lesions in the WM. Most subjects with SCIs in the BG also had SCIs in the WM. Multiple logistic regression analyses revealed that age, female sex, and hypertension were significant and independent predictors of SCIs in the WM, and that age, a history of ischemic heart disease, and carotid artery stenosis were significant and independent predictors of SCIs in the BG. CONCLUSIONS: The present study indicated that the relevant risk factors for SCIs in the WM and those for SCI in the BG were different. Our results suggest that SCIs are prone to first appear in the WM in association with aging and hypertension, and the additional appearance of SCIs in the BG predicts a progression of generalized atherosclerosis that is manifested in the carotid and coronary arteries.     

Cognitive and academic problems associated with childhood cancers and sickle cell disease.

Childhood cancers and sickle cell disease represent some of the most complex medical conditions of childhood, impacting development in all domains. The influence of these conditions on cognitive functioning and academic achievement has particular relevance for the school psychologist, who is poised to promote the positive adaptation of children with these chronic illnesses in the school setting. This article provides a review of the research related to cognitive aspects of pediatric cancer and sickle cell disease. Based on that literature, science-based practice recommendations of relevance to the school psychologist are offered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Splenic sepsis in sickle cell disease

We describe two patients with sickle cell disease (SCD) who developed infections situated in the spleen. One patient had a splenic abscess and there was strong clinical evidence for an infected splenic infarct in the second patient. SCD predisposes to splenic infection because of functional hyposplenism, defective phagocyte function and splenic infarction. Splenic infections can occur in patients who might be considered to have an absent spleen and the diagnosis of splenic abscess should be considered in individuals with SCD who present with fever and abdominal pain.     

Neonatal screening for sickle cell disease in the Consorci Sanitari de Mataro. Rationale and first results]

A total of 62 ears of patients with typical Meniere's disease was examined by the furosemide test to detect endolymphatic hydrops. In 95% of the normal control group, the per cent change in the maximum velocity of the slow phase of caloric nystagmus (MVS) after injection of furosemide was under 10%. Therefore, a positive furosemide test was defined as a change in MVS of more than 10%. Thirty-five (56%) of the 62 ears with typical Meniere's disease showed a positive furosemide test. When the affected ears were divided into two groups according to vestibular symptoms, only 11 (38%) of 29 inactive ears were positive while 24 (73%) of 33 active ears were positive. There was a significant difference in the positive rate of the furosemide test between the ears with clinically inactive and active vestibular disease. The per cent canal paresis (CP%) was determined to assess canal excitability and a CP%> 25% was defined as canal paresis. There was no significant difference in the furosemide test positive rate between ears with canal paresis and ears with a normal CP%, although the former tended to show a greater MVS change. The response to the furosemide test showed no relationship to the results of pure tone audiometry. In conclusion, the furosemide test appears to indicate the vestibular status in various stages of Meniere's disease.     

Mechanisms of stroke in sickle cell disease: sickle erythrocytes decrease cerebral blood flow in rats after nitric oxide synthase inhibition

The etiology of stroke in sickle cell disease is unclear, but may involve abnormal red blood cell (RBC) adhesion to the vascular endothelium and altered vasomotor tone regulation. Therefore, we examined both the adhesion of sickle (SS)-RBCs to cerebral microvessels and the effect of SS-RBCs on cerebral blood flow when the nitric oxide (NO) pathway was inhibited. The effect of SS-RBCs was studied in the rat cerebral microcirculation using either a cranial window for direct visualization of infused RBCs or laser Doppler flowmetry (LDF) to measure RBC flow. When fluorescently labeled human RBCs were infused into rats, SS-RBCs had increased adhesion to rat cerebral microvessels compared with control AA-RBCs (P = .01). Next, washed SS-RBCs or AA-RBCs were infused into rats prepared with LDF probes after pretreatment (40 mg/kg intravenously) with the NO synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), or the control isomer, D-NAME. In 9 rats treated with systemic L-NAME and SS-RBCs, 5 of 9 experienced a significant decrease in LDF and died within 30 minutes after the RBC infusion (P = .0012). In contrast, all control groups completed the experiment with stable LDF and hemodynamics. Four rats received a localized superfusion of L-NAME (1 mmol/L) through the cranial window followed by infusion of SS-RBCs. Total cessation of flow in all observed cerebral microvessels occurred in 3 of 4 rats within 15 minutes after infusion of SS-RBCs. We conclude that the NO pathway is critical in maintaining cerebral blood flow in the presence of SS-RBCs in this rat model. In addition, the enhanced adhesion of SS-RBCs to rat brain microvessels may contribute to cerebral vaso-occlusion either directly, by disrupting blood flow, or indirectly, by disturbing the vascular endothelium.     

Orbital compression syndrome in sickle cell disease

BACKGROUND: Orbital complications are an uncommonly reported finding in sickle cell disease. METHODS: The authors review the reported orbital manifestations of sickle cell disease and discuss a patient with hemoglobin sickle beta(0) thalassemia in whom rapidly progressive bilateral orbital compression developed. RESULTS: Computed tomography of the orbits in a patient with fever, headache, orbital swelling, and optic nerve dysfunction displayed bilateral superior subperiosteal cystic masses. Surgical exploration showed bilateral liquefied hematomas, which were evacuated. Recovery was complete 13 days after surgery. A mild recurrence 14 months later resolved with conservative treatment. The literature contains 11 reports of 16 young patients with sickle cell disease (15 sickle cell disease [Hb SS] and 1 hemoglobin sickle cell disease [Hb SC]) with rapidly developing findings ranging from frontal headache, fever, and eyelid edema to bilateral complete orbital compression syndrome. Including our patient, 60% had orbital hemorrhage on computed tomography. Ten of 12 patients tested were found to have orbital bone marrow infarctions. Sixteen of 17 patients had complete recovery; 13 were treated conservatively and 4 surgically. Only 2 of 17 had recurrence. CONCLUSIONS: Orbital complications in sickle cell disease are unusual manifestations in which a vaso-occlusive process in the marrow space around the orbit results in frontal headache, fever, eyelid edema, and often orbital compression syndrome. Subperiosteal hematomas are common and appear to result from bone marrow infarctions. Appropriate management requires a thorough evaluation to exclude other hemorrhagic, infectious or neoplastic processes, as well as vigilant ophthalmic monitoring. Supportive care is effective, unless optic nerve dysfunction or large hematomas are present, which would indicate that surgical evacuation is warranted to prevent loss of vision and to speed recovery.     

Plasma and red cell lipids in sickle cell disease

Lipids, in particular phospholipids, are essential components of membrane systems, and the measurement of phospholipids and cholesterol in plasma and tissues is helpful in diagnosis. Phospholipids represent about 60 to 70% of total red cell (RBC) lipids, while about 25% is free cholesterol. Lipids in RBC are present in a dynamic state of equilibrium, and the RBC have the capacity for rapid exchange of lipids with plasma in several ways. The present study examined the cholesterol and phospholipid levels of plasma and erythrocytes in male patients with sickle cell anemia and in healthy male individuals of comparable age. This was performed with a view to detecting possible differences that might be related to some of the RBC abnormalities which accompany the disease. The results show that plasma lipids are significantly reduced in patients with sickle cell anemia and that RBC cholesterol was higher in sickle cell patients than in normal subjects.     

Acute normovolemic red cell exchange for cardiopulmonary bypass in sickle cell disease

A patient with sickle cell disease (hematocrit, 28.5%; hemoglobin S fraction, 79%), required mitral valve repair. Partial red cell removal and blood component sequestration with an autotransfusion device before cardiopulmonary bypass initially decreased the sickle red cell mass. This was followed by an acute one-volume whole blood exchange transfusion performed upon the initiation of cardiopulmonary bypass, resulting in a further reduction. Both techniques yielded fresh autologous plasma for use; sequestration yielded a platelet-pheresis product. Adequate postbypass hemostasis was demonstrated.     

Psychosocial aspects of sickle cell disease

The study described in this article deals with sickle cell patients in Jamaica whose illness is accompanied by leg ulceration, a common complication of sickle cell disease. After exploring the disease's psychological, social, and economic effects, the authors suggest various ways for social workers to help sickle cell patients.     

Analysis of IMP-SPECT in cerebral infarcts

We performed single photon emission computed tomography with N-isopropyl[123I]-p-iodoamphetamine in 22 normal volunteers (mean age, 68.3 +/- 9.5 years) and 190 patients with unilateral cerebral infarcts (66.1 +/- 11.4 years). We then compared visual and semiquantitative assessment of the left/right ratio of the early images. Cerebral blood flow in the patients with cerebral infarcts was compared with data from normal volunteers. An abnormal left/right ratio was recognized in 110 of 136 (81%) patients in whom X-ray computed tomography (CT) showed an abnormality, while visual inspection revealed abnormalities in only 99 (73%). In 54 patients no abnormality on CT, an abnormal left/right ratio was found in 28 (52%), and visual abnormalities in only 9 (17%). Altogether, the left/right ratio was abnormal in 138 of 190 (73%) patients, and abnormalities were detected visually in 108 (57%). Of 95 patients, 56 (59%) showed markedly larger lesions using the left/right ratio method than with the visual method.     

Platelet activation in patients with sickle cell disease

Vascular occlusion and vasculopathy underlie much of the morbidity in patients with sickle cell anaemia. Platelets may play a role in this vasculopathy. Samples from 43 patients with sickle cell disease (SCD) were examined for evidence of platelet activation using fluorescent-labelled monoclonal antibodies and flow cytometry. There was increased expression of activation-dependent antigens on the platelets from patients with SCD compared to those from both Caucasian and African-American controls. In addition, SCD patients had increased levels of platelet microparticles. Platelets are activated in patients with sickle cell disease. The contribution of platelet activation to sickle cell pathophysiology is under active investigation in our laboratories.     

Accuracy of pulse oximetry in sickle cell disease

Pulmonary complications and hypoxemia are common in sickle cell disease (SCD) and may exacerbate microvascular occlusive phenomena. Thus, detecting hypoxemia is of particular importance in SCD. To assess the accuracy of pulse oximetry in the diagnosis of hypoxemia in SCD, we compared 22 pulse oximetric measurements of arterial oxygen saturation (SpO2) in adult patients with SCD and acute vasoocclusive crisis with simultaneously drawn arterial saturation (SaO2 = oxyhemoglobin divided by oxyhemoglobin plus reduced hemoglobin) measured by co-oximetry. We accepted SpO2 readings only if they were stable and characterized by strong and regular photoplethysmographic waves on the oximeter screen. To assess the position of these patients' oxyhemoglobin dissociation curves, we plotted arterial and venous oxygen saturation (SaO2 and SvO2 ) against oxygen tension. We found right-shifted oxyhemoglobin dissociation curves, with pH-corrected p50s ranging from 28 to 38 mm Hg. Pulse oximetry slightly overestimated oxyhemoglobin percentage (by an average of 3.4 percentage points), but it almost always accurately estimated SaO2 (underestimating on average by 1.1 percentage points). The error in SpO2 was never enough to classify a hypoxemic patient erroneously as normoxemic or a normoxemic patient as hypoxemic. We conclude that, as long as strong and regular photoplethysmographic waves are present, pulse oximeters can be relied upon not to misdiagnose either hypoxemia or normoxemia in SCD.     

Knockout-transgenic mouse model of sickle cell disease

When transgenic mice that expressed human sickle hemoglobin were mated with mice having knockout mutations of the mouse alpha- and beta-globin genes, animals were produced that synthesized only human hemoglobin in adult red blood cells. Similar to many human patients with sickle cell disease, the mice developed a severe hemolytic anemia and extensive organ pathology. Numerous sickled erythrocytes were observed in peripheral blood. Although chronically anemic, most animals survived for 2 to 9 months and were fertile. Drug and genetic therapies can now be tested in this mouse model of sickle cell disease.