Trends in comorbid sickle cell disease among stroke patients

BackgroundVisuospatial skills including spatial navigation are known to be impaired in Huntington's disease. Spatial navigation comprises two navigational frameworks, allocentric and egocentric. Several studies have associated the allocentric navigation with the hippocampus and the egocentric navigation with the striatum. The striatum is predominantly impaired from the early stages of Huntington's disease.ObjectiveTo find whether spatial navigation impairment is present in the early stages of Huntington's disease and to test the hypothesis that the egocentric navigation is predominantly affected compared to the allocentric navigation.MethodsIn nineteen patients with Huntington's disease the egocentric and the allocentric navigation skills were tested using the Blue Velvet Arena, a human analog of Morris Water Maze, and compared to nineteen age and gender-matched healthy controls. Cognitive functions, with emphasis on the executive functions, were also assessed.ResultsThe spatial navigation skills deteriorated with the increasing motor impairment in Huntington's disease. These changes only became apparent in patients with moderate functional impairment. No difference between the egocentric and the allocentric skills was seen.DiscussionSpatial navigation deficit is not an early marker of the cognitive dysfunction in Huntington's disease. We speculate that the striatal circuitry that is known to degenerate early in the course of Huntington's disease is not directly associated with the spatial navigation.     

Electroencephalography hyperventilation and stroke in children with sickle cell disease.

A recent study and report in which hyperventilation was used during electroencephalography (EEG) in 6 children with sickle cell disease (SCD) and seizures, without serious complication, prompted a cautionary response regarding the potential risks attending the practice of EEG hyperventilation in SCD patients. Earlier reports of neurological impairment and stroke precipitated by the routine use of hyperventilation in children with SCD are reviewed, the mechanism and management of vascular infarction following hyperventilation are discussed, and readers are reminded of the AEEGS guidelines and contraindications to routine hyperventilation, which include SCD and trait and cerebrovascular disorders. The frequent nonobservance of these guideline recommendations among neurologists, and the need to more widely inform practitioners of the risks of hyperventilation in SCD are discussed.     

Cerebral infarction in sickle cell trait

Sickle cell disease is known to predispose patients to the risk of cerebral infarction. However, only scattered reports exist of the neurological sequelae of the sickle cell trait. Only 8 cases are reported in the English literature, in some of which the sickle cell trait was not documented by hemoglobin electrophoresis. This report describes 2 men, age 35 and 24 years, who developed acute cerebral infarction. Investigation revealed no apparent cause for the lesion other than the sickle cell trait.     

Current concepts in the management of stroke in children with sickle cell disease

Stroke is the most significant complication of sickle cell disease (SCD) in children with the potential for major morbidity and mortality. The recent two decades have witnessed tremendous advancements in understanding the pathophysiology of stroke, risk stratification of children and the role of timely preventative interventions. The aetiopathogenesis, types of stroke and specific risk factors are reviewed here with special emphasis on the role of transcranial Doppler ultrasonogram in the early identification of at-risk children. Published studies on primary and secondary prevention of stroke in children with SCD are analysed with respect to the levels of evidence, in favour of preventative and therapeutic strategies. The roles of the neurologist and the neurosurgeon are highlighted.     

Therapy insight: stroke risk and its management in patients with sickle cell disease

Children with sickle cell disease, a chronic hemolytic anemia, present with a wide variety of neurological syndromes, including ischemic and hemorrhagic stroke, transient ischemic attacks, 'soft neurological signs', seizures, headache, coma, visual loss, altered mental status, cognitive difficulties, and covert or 'silent' infarction. Those with ischemic stroke usually have stenosis or occlusion of the distal internal carotid and proximal middle cerebral arteries. Indefinite transfusion prevents recurrence in most patients who have had a stroke, and can prevent first stroke in those with high transcranial Doppler velocities. High white cell count, low hemoglobin and oxyhemoglobin desaturation predict neurological complications. Other risk factors for overt ischemic stroke include hypertension, previous transient ischemic attack, covert infarction and chest crisis. For hemorrhagic stroke, aneurysms are common in adults but not children, who often present with hypertension after transfusion or corticosteroids. Seizures are particularly common in patients with cerebrovascular disease and covert infarction; the latter is also associated with hyposplenism and infrequent pain. Factors associated with cognitive difficulties include thrombocytosis, infarction, large-vessel disease, and perfusion abnormality on neuroimaging. As well as investigating the role of genes and the possibility that hydroxyurea or blood pressure control reduce neurological complications, we should explore the modifiable effects of poor nutrition, chronic infection, hemolysis and oxyhemoglobin desaturation on stroke risk.     

Long-term stroke risk in children with sickle cell disease screened with transcranial doppler

Stroke is an important complication of sickle cell disease. Stroke prediction is clinically important because it offers the possibility of primary prevention. In 1992, transcranial Doppler (TCD) evidence of elevated intracranial internal carotid or middle cerebral artery velocity was demonstrated to be associated strongly with an increased risk of ischemic stroke. This study extends the original study and includes 125 more children, longer follow-up, and intracranial hemorrhage in the stroke-risk model. Elevated time averaged mean maximum blood flow velocity, especially when velocity is 200 cm/sec or greater by TCD, was associated strongly with stroke risk. The cases not predicted by TCD point to the need for more information on the optimal timing of TCD surveillance for stroke risk.     

Characteristics and outcomes of stroke hospitalizations in patients with sickle cell disease and moyamoya syndrome

Objectives: Stroke is the leading cause of death in patients with Sickle cell disease (SCD). Here, we detail the burden of Moyamoya syndrome (MMS) as a cause of stroke in patients with SCD.Materials and Methods: A review of SCD-related hospital discharges was conducted utilizing the National Inpatient Sample. Rates of stroke hospitalization, risk factors, procedures, and outcomes were compared between patients with SCD-MMS and SCD alone. Univariate analyses including T-test, Wilcoxon Rank-Sum test, Chi-square were performed to compare risk factors and outcomes. Multivariable regression was used to identify predictors of stroke unique to each population.Results: Stroke occurred in 9.8% of SCD-MMS hospitalizations versus 0.5% of those involving patients with SCD alone (OR = 20.71, p < 0.001). Patients with SCD-MMS developed stroke at younger ages and with fewer comorbidities compared to those with SCD alone. Stroke hospitalizations in SCD-MMS involved a greater number of procedures (90.5% vs. 79.3%, p = 0.007), but were more likely to result in favorable discharge (58.5% vs. 44.2%, p = 0.005). The presence of anemia during hospitalization was a significant risk factor for stroke in both cohorts. Long-term antiplatelet use was protective against stroke (OR = 0.42, p = 0.008) only in the SCD-MMS cohort.Conclusions: MMS confers a 20-fold increased risk of stroke among patients with SCD and appears to be an important cause of recurrent stroke in this population. Anemia is one of the most significant risk factors for stroke, while antiplatelet use appears to confer a protective benefit.     

Stroke in sickle cell disease

Stroke is a major cause of morbidity in sickle cell disease (SCD), especially in children. Both ischemic and hemorrhagic strokes may be encountered, and subclinical stroke is a common finding in children with SCD. In the majority of cases, infarctions are associated with occlusive thrombi involving the large arteries supplying the anterior cerebral circulation. A distinct form of intimal hyperplasia involving the large intracranial arteries is characteristically associated with SCD. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) demonstrated the success of chronic transfusion therapy for primary stroke prevention in children identified to be at risk on screening. As a result of this landmark study, it is now recommended that transcranial Doppler be used to screen for stroke risk in all children with SCD between the ages of 2 and 16. Questions still remain about the mechanism of benefit of transfusion therapy and the optimal duration of therapy. Hydroxyurea and bone marrow transplantation continue to be evaluated as alternative therapies for stroke prevention. Recent paradigms suggest that activation of the coagulation and inflammatory systems in SCD may contribute to the pathophysiology of certain vaso-occlusive complications, although it is not known what role (if any) they may play in stroke.     

Stroke and sickle cell disease

Sickle cell disease has evolved from an illness of abnormal red blood cells to a multisystemic molecular disease. It attacks at an early age, with stroke being one of the most feared complications. Sickle hemoglobinopathy is inherited in a Mendelian fashion, with a 25% chance of inheriting the disease if both parents are heterozygous. The polymerization of red blood cells in harsher environments, such as hypoxia, acidosis, or dehydration, is the basic change that can promote subsequent systemic diseased states. Stroke in sickle cell patients is fairly common, with an incidence ranging between 4% and 8%. The most common stroke is ischemic, but hemorrhagic stroke can be seen in up to 2% of patients, particularly in early adulthood. Several risk factors increase the likelihood for stroke. Evaluating the middle cerebral and internal carotid arteries with transcranial Doppler has emerged as a very accessible marker of stroke risk (using time-averaged mean velocities above 200 cm/sec). Stroke presentation follows usual clinical patterns, but it can be confused in the presence of other illnesses such as pain crises or pain treatments. Clinical diagnosis relies on many of the usual modalities used in stroke evaluation, with particular importance for those that allow full-vessel visualization (magnetic resonance angiography, angiography). The pathophysiology of endothelial proliferation manifests itself in both small and large vessels. Other hematologic abnormalities, perhaps with hypercoagulable states, might compound the risk of stroke. Intracranial hemorrhage etiology may occur, especially in older patients. The landmark STOP trial has established periodic transfusion as a clear primary prevention method to reduce the incidence of stroke in patients at risk. There are still many unanswered questions, but this first century of sickle cell disease knowledge has brought hope for a long-term cure of this life-threatening disease.     

Trials in sickle cell disease

Children with sickle cell disease are at risk of developing neurologic complications, including stroke, transient ischemic attack, seizures, coma, and a progressive reduction in cognitive function. Transcranial Doppler ultrasound, magnetic resonance imaging, and overnight pulse oximetry appear to predict, making prevention an achievable goal so that there is now a focus on randomized controlled trials. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) reported a reduction in the number of overt clinical strokes experienced by those children with critically high transcranial Doppler velocities (>200 centimeters per second) who were chronically transfused. Two additional Phase III studies and two pilot trials have been funded. STOP II focused on whether it is safe to discontinue blood in prophylactically transfused children when their velocities had remained normal for at least 30 months. The Silent Infarct Transfusion trial is designed to determine whether children with sickle cell anemia and silent cerebral infarcts, approximately 20% of the population, will have a decrease in the progressive neurologic complications after receiving regular blood transfusion therapy. Pilot safety and feasibility trials of low-dose aspirin and overnight respiratory support are also beginning. The collaboration provides an infrastructure for future clinical trials in this vulnerable group of children.     

The epidemiology of stroke in sickle cell patients in Yaounde, Cameroon

BACKGROUND AND PURPOSE: Stroke, a severe and recurrent but preventable complication of sickle cell disease (SCD), has not been well studied in Cameroon. To obtain baseline data towards the development of a national stroke prevention programme in SCD, we studied a sample of sickle cell patients with the aim of determining stroke prevalence, clinical presentation and management practices. PATIENTS AND METHODS: Homozygous sickle cell patients in two centres in Yaounde were screened for stroke, in a cross-sectional study. Stroke was diagnosed clinically and confirmed where possible with brain computerized tomography. The National Institutes of Health Stroke Score (NIHSS) and modified Rankin scale (mRS) were used to assess stroke severity. Management practices were noted from patient charts. RESULTS: One hundred and twenty patients aged 7 months to 35 years (mean age 13.49+/-8.79 years) were included. Eight cases of stroke (mean age 16.6+/-11.2 years) were identified, giving a stroke prevalence of 6.67%. Cerebral infarction was thrice as common as cerebral hemorrhage and clinical presentation was classical. Cerebral infarction was more frequent in patients aged below 20 years and hemorrhage in those above 20 (p=0.11). The annual recurrence rate was 25%. Missed diagnosis rate by attending physician was 25%. The NIHSS and mRS showed high stroke severity. Stroke management practices were insufficient and no patient received any form of stroke prophylaxis. CONCLUSION: Stroke prevalence and presentation in sickle cell patients in Yaounde is similar to that observed in developed countries, but the wide management gap calls for rapid action. Our situation is ideal for the study of the natural history of stroke in sickle cell disease.     

Preliminary study of working memory in children with stroke related to sickle cell disease

The verbal working memory abilities of children with stroke related to sickle cell disease (SCD) (n = 20) were compared to those of control children with SCD who had no history of stroke (n = 11). Memory span for one-, two-, and three-syllable words was assessed. For children with anterior infarcts, overall span was comparable to that of controls, but the typical effect of word length on span was reduced. For children with diffuse infarcts, overall span was reduced in comparison to that of controls, but the typical effect of word length on span was observed. For children with posterior infarcts, overall span was comparable to that of controls and the typical effect of word length on span was observed. These results provide preliminary evidence that patterns of working memory performance may vary across children with infarcts affecting different regions of the brain.     

Subarachnoid hemorrhage in sickle cell disease

Subarachnoid hemorrhage occurs in 1%–2% of patients with neurological complications from sickle cell disease. The authors report a case of subarachnoid hemorrhage in a 13-year-old black girl with sickle cell disease. Computed tomography of the brain demonstrated diffuse subarachnoid hemorrhage in the right sylvian fissure and the right frontoparietal cortical region. Angiography revealed no evidence of aneurysm but multiple stenosis and/or occlusions of the distal branches of the anterior and middle cerebral arteries bilaterally. Rupture of leptomeningeal collateral vessels is a possible cause of subarachnoid hemorrhage in our patient.     

Depression and sickle cell disease.

Depressive symptoms are very common in patients with a chronic medical illness such as sickle cell disease (SCD). Clinicians may fail to recognize depression in such patients when, as in SCD, the two conditions have many overlapping symptoms. Based on a Medline database search, we review papers addressing the relationship between depression and SCD. Data regarding this relationship are conflicting. We provide recommendations for improving the treatment of patients with SCD and depression.     

Stroke prevention and treatment in sickle cell disease

While the problem of stroke in the patients with sickle cell disease (SCD) has been known for more than 75 years, adequate preventive and treatment strategies are just now being tested. Recent data on prevalence and incidence have been obtained from the Cooperative Study of Sickle Cell Disease of more than 4000 patients with SCD observed in 23 US clinical centers over a 10-year period.1 The overall age-specific incidence of first stroke in SCD (homozygous sickle cell anemia) is low (0.13%) at ages younger than 24 months, increasing to just over 1% at ages 2 to 5 years, with only a slight decrement to 0.79% at ages 6 to 9 years. The risk of brain infarction declines until a second peak is seen at ages older than 50 years, when the incidence again increases to nearly 1.3%. Although intracranial hemorrhage does occur in young children with SCD, the risk is low compared with older children and adults. The Cooperative Study of Sickle Cell Disease reported risk factors for infarction to be prior transient ischemic attack, low steady-state hemoglobin values, and rate and recency of episodes of acute chest syndrome, as well as elevated systolic blood pressure. Risk factors for intracranial hemorrhage included low steady-state hemoglobin values and a high leukocyte count. The burden of cerebrovascular disease is even higher if subclinical magnetic resonance imaging (MRI) lesions, presumed to be ischemic, are included. The prevalence of such lesions is more than 22% in patients with SCD, and most of these patients have not reported symptoms, although specialized neuropsychological testing shows lower scores in children with silent lesions on MRI scans. Patients with a history of clinical stroke typically have infarcts in the cortex and deep white matter, whereas silent infarcts tend to be more limited to deep white matter. Common infarction patterns are characterized by wedge-shaped lesions of large-vessel territories; border zone infarctions, particularly of the middle and cerebral artery watershed region; and small punctate lesions of the deep white matter. Fat embolism to the brain and venous thromboses are encountered rarely.