Sickle cell disease (SCD) is the most common cause of ischemic and hemorrhagic stroke in children and without treatment has a very high rate of recurrence. Acute neurological symptoms and signs are common in SCD at any age, and, as well as stroke, include transient ischaemic attack, headaches, seizures, and coma. An altered mental status with or without reduced level of consciousness, headache, seizures, visual loss, or focal signs can occur spontaneously, but also in numerous contexts, such as infection, acute chest syndrome (ACS), and acute anaemia. Nearly 50 years ago, it was clear from conventional cerebral angiography studies that the large extracranial and intracranial vessels were abnormal in patients with SCD and neurologic deficits, although the pathophysiology is not fully understood from human studies or laboratory models. Transcranial Doppler ultrasound has been used successfully to predict stroke risk in children, although those with abnormal time averaged maximum mean velocity >200 cm/sec may have very high blood flow or arterial stenosis.
Although there are relatively few studies with matched controls, silent cerebral infarction on MRI is found in a high proportion of patients with SCD without clinical symptoms, sometimes starting as early as the 6th month of life, steadily accumulating with age, and predicting overt stroke. Meta-analyses have shown that typically siblings, children, and adults with SCD have cognitive difficulties over a wide range of domains, compared with matched controls. This includes processing speed and executive function.
Until recently, therapeutic options for preventing stroke or improving cognitive performance in SCD were limited to regular blood transfusion, hydroxyurea, or stem cell transplantation.
This Research Topic aims to investigate the following areas in the SCD field:
1. Although there are relatively few studies, the incidence of stroke is high in adults with SCD of all genotypes and it is an important cause of death. It is not currently clear if stroke risk in adults can be predicted from transcranial or extracranial Doppler.
2. Much of the available epidemiological data on acute events comes from studies before the advent of cross-sectional neuroimaging, e.g., CT, MRI, PET, or from countries where this is not available. The gap in knowledge and dissemination means that clinical events presenting with seizures, headache, or altered mental status are commonly misdiagnosed, sometimes leading to avoidable death or disability.
3. For prediction of neurological events, there are relatively few large or longitudinal studies of the use of intracranial or extracranial MR angiography, or of quantitative MR techniques, such as measures of focal or global blood flow or perfusion, oxygen extraction, or venous anatomy.
4. The relative importance of socioeconomic factors influencing cognition, silent cerebral infarction, white and grey matter atrophy, or microstructural injury and other disease-related factors, such as anemia and oxygen desaturation, remains unclear. However, quantitative neuroimaging methods in patients with SCD and animal models are likely to shed light in this area.
5. Several new options for treatment of SCD and prevention of complications are emerging but to date, there are few studies with neuroimaging or cognitive endpoints.
Areas of interest include, but are not limited to the following:
• Clinico-radiological correlation in series of adults and children with acute neurological symptoms and signs
• Prediction of acute neurological symptoms
• Associations with cognitive difficulties in children and adults with SCD
• Quantitative neuroimaging techniques shedding light on the neurological phenotype
• The effects of treatment on prevention of SCD complications, such as acute neurological events and cognitive difficulties, with neuroimaging endpoints
Topic Editor, Fenella Kirkham, received financial support from Global Blood Therapeutics, Inc. (GMT). The other Topic Editors declare no competing interests with regard to the Research Topic subject.
Sickle cell disease (SCD) is the most common cause of ischemic and hemorrhagic stroke in children and without treatment has a very high rate of recurrence. Acute neurological symptoms and signs are common in SCD at any age, and, as well as stroke, include transient ischaemic attack, headaches, seizures, and coma. An altered mental status with or without reduced level of consciousness, headache, seizures, visual loss, or focal signs can occur spontaneously, but also in numerous contexts, such as infection, acute chest syndrome (ACS), and acute anaemia. Nearly 50 years ago, it was clear from conventional cerebral angiography studies that the large extracranial and intracranial vessels were abnormal in patients with SCD and neurologic deficits, although the pathophysiology is not fully understood from human studies or laboratory models. Transcranial Doppler ultrasound has been used successfully to predict stroke risk in children, although those with abnormal time averaged maximum mean velocity >200 cm/sec may have very high blood flow or arterial stenosis.
Although there are relatively few studies with matched controls, silent cerebral infarction on MRI is found in a high proportion of patients with SCD without clinical symptoms, sometimes starting as early as the 6th month of life, steadily accumulating with age, and predicting overt stroke. Meta-analyses have shown that typically siblings, children, and adults with SCD have cognitive difficulties over a wide range of domains, compared with matched controls. This includes processing speed and executive function.
Until recently, therapeutic options for preventing stroke or improving cognitive performance in SCD were limited to regular blood transfusion, hydroxyurea, or stem cell transplantation.
This Research Topic aims to investigate the following areas in the SCD field:
1. Although there are relatively few studies, the incidence of stroke is high in adults with SCD of all genotypes and it is an important cause of death. It is not currently clear if stroke risk in adults can be predicted from transcranial or extracranial Doppler.
2. Much of the available epidemiological data on acute events comes from studies before the advent of cross-sectional neuroimaging, e.g., CT, MRI, PET, or from countries where this is not available. The gap in knowledge and dissemination means that clinical events presenting with seizures, headache, or altered mental status are commonly misdiagnosed, sometimes leading to avoidable death or disability.
3. For prediction of neurological events, there are relatively few large or longitudinal studies of the use of intracranial or extracranial MR angiography, or of quantitative MR techniques, such as measures of focal or global blood flow or perfusion, oxygen extraction, or venous anatomy.
4. The relative importance of socioeconomic factors influencing cognition, silent cerebral infarction, white and grey matter atrophy, or microstructural injury and other disease-related factors, such as anemia and oxygen desaturation, remains unclear. However, quantitative neuroimaging methods in patients with SCD and animal models are likely to shed light in this area.
5. Several new options for treatment of SCD and prevention of complications are emerging but to date, there are few studies with neuroimaging or cognitive endpoints.
Areas of interest include, but are not limited to the following:
• Clinico-radiological correlation in series of adults and children with acute neurological symptoms and signs
• Prediction of acute neurological symptoms
• Associations with cognitive difficulties in children and adults with SCD
• Quantitative neuroimaging techniques shedding light on the neurological phenotype
• The effects of treatment on prevention of SCD complications, such as acute neurological events and cognitive difficulties, with neuroimaging endpoints
Topic Editor, Fenella Kirkham, received financial support from Global Blood Therapeutics, Inc. (GMT). The other Topic Editors declare no competing interests with regard to the Research Topic subject.