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Nunez FJ, Mohieldin AM, Pan AY, Palecek SP, Zennadi R, Ramchandran R, Rarick KR, Nauli SM. Sickle cell mice exhibit elevated plasma bilirubin and altered intracranial cerebral blood velocities that are exacerbated by hypoxia-reoxygenation. J Cereb Blood Flow Metab 2025:271678X251338961. [PMID: 40370318 DOI: 10.1177/0271678x251338961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/16/2025]
Abstract
Sickle cell disease (SCD) is a genetic disorder characterized by sickle red blood cells (RBCs). Sickle RBCs cause cerebral vasculopathies including vaso-occlusive events, leading to ischemia-reperfusion injury and hypoxic tissue environment. To date, the physiological blood flow velocities in cerebral vessels of preclinical SCD models has not been evaluated under hypoxic-reoxygenation. In our study, we used transcranial ultrasound techniques to measure abnormal blood flow velocities in the internal carotid (ICA) and middle cerebral arteries (MCA) of transgenic sickle cell mice (SS) challenged with hypoxia-reoxygenation. Our study showed that SS mice that underwent hypoxic stress exhibited lower relative mean velocities in the MCA compared to wildtype mice (AA) (0.67 ± 0.18 vs. 0.95 ± 0.15; p < 0.05). Comparison of the Lindegaard ratio between normoxia and hypoxia in SS mice suggested that the MCA underwent vasodilation (0.67 ± 0.18 vs. 0.95 ± 0.15; p < 0.05). Bilirubin, a potential biomarker for cerebral vasculopathies in SCD, was higher in SS than AA mice (0.56 ± 0.28 vs. 0.05 ± 0.07 mg/dL; p < 0.05). Correlation analyses revealed a significant association between bilirubin levels and blood velocities of MCA (r = -0.9377, p = 0.0002) and ICA (r = 0.8203, p = 0.0068), especially in hypoxic conditions of SS mice. We propose that the reactivity of cerebral vessels in SS mice is correlated with the elevated plasma bilirubin level.
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Affiliation(s)
- Francisco J Nunez
- Department of Pharmaceutical Sciences, School of Pharmacy, Chapman University, Irvine, CA, USA
| | - Ashraf M Mohieldin
- College of Graduate Studies, Master Program of Pharmaceutical Science, California Northstate University, Elk Grove, CA, USA
| | - Amy Y Pan
- Division of Quantitative Health Sciences, Department of Pediatrics, CRI, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Sean P Palecek
- Department of Chemical and Biological Engineering, College of Engineering, University of Wisconsin-Madison, Madison, WI, USA
| | - Rahima Zennadi
- Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Ramani Ramchandran
- Developmental Vascular Biology Program, Division of Neonatology, Department of Pediatrics, Children's Research Institute (CRI), Medical College of Wisconsin, Milwaukee, WI, USA
| | - Kevin R Rarick
- Division of Critical Care, Department of Pediatrics, CRI, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Surya M Nauli
- Department of Pharmaceutical Sciences, School of Pharmacy, Chapman University, Irvine, CA, USA
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Franco E, Nimura C, McGann PT. Fostering a healthier generation of children with sickle cell disease through advancements in care. Pediatr Res 2025; 97:1280-1289. [PMID: 39271903 DOI: 10.1038/s41390-024-03566-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 08/12/2024] [Accepted: 08/21/2024] [Indexed: 09/15/2024]
Abstract
Sickle cell disease (SCD) is an inherited disorder of hemoglobin that affects tens of millions of individuals worldwide. Without preventive and disease-modifying therapy, SCD results in many acute and chronic complications impacting both quality and length of life. We are currently in a new generation of SCD care in high resource settings due to recent advancements in care. Universal newborn screening (NBS) for SCD with associated parental education and preventive care significantly improved mortality rates. Beginning in the 1990s, hydroxyurea emerged as a promising pharmacologic treatment for SCD due to its ability to increase the amount of fetal hemoglobin. It is now the mainstay of treatment, with strong recommendations to begin as early as the first year of life with the goal of reducing most short- and long-term complications and allowing for a normalized quality of life. More recently, gene therapy has come to the forefront in SCD and brings the hope of a cure for many patients. In 2023, the FDA approved two cell-based gene therapies for patients with SCD. The future is bright for patients with SCD, and the current generation of affected children will expectantly be able to grow up free of suffering and severe, frequent pain.
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Affiliation(s)
- Emily Franco
- Alpert Medical School of Brown University, Providence, RI, USA
- Brown University Health Sickle Cell Center, Providence, RI, USA
| | - Clare Nimura
- Alpert Medical School of Brown University, Providence, RI, USA
- Brown University Health Sickle Cell Center, Providence, RI, USA
| | - Patrick T McGann
- Alpert Medical School of Brown University, Providence, RI, USA.
- Brown University Health Sickle Cell Center, Providence, RI, USA.
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AIUM Practice Parameter for the Performance of Transcranial Doppler Ultrasound. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2023; 42:E36-E44. [PMID: 37132485 DOI: 10.1002/jum.16234] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 04/04/2023] [Indexed: 05/04/2023]
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Modebe E, Nonyelu C, Duru A, Ezenwosu O, Chukwu B, Madu A, Ezekekwu C, Aneke J, Izuka M, Nri-Ezedi C, Nnachi O, Eze A, Ajuba I, Okwummuo E, Chilaka J, Onodugo C, Fidelis-Ewa U, Agwu O, Anigbogu I, Muoghalu E, Okoye H, Efobi C, Ejiofor O, Ugwu N, Maduka C, Iloanusi N, Ugwu A, Okocha C, Ulasi T, Okpala I. Cerebral artery conditional blood velocity in sickle cell disease: a multicentre study and evidence for active treatment. Arch Dis Child 2023; 108:440-444. [PMID: 36737235 DOI: 10.1136/archdischild-2022-325106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 01/19/2023] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To obtain multicentre data on the prevalence of normal, high or conditional (intermediate) blood velocity in the cerebral arteries among children with sickle cell disease (SCD) in Nigeria. DESIGN A prospective observational study in five tertiary healthcare institutions. By transcranial Doppler (TCD) ultrasonography, cerebral artery peak systolic blood velocity (PSV) was determined in 193 children with SCD and time averaged mean of the maximum blood velocity (TAMMV) in a different cohort of 115 children. This design was to make the findings relevant to hospitals with TCD equipment that measure either PSV or TAMMV. SETTING Nigeria. PARTICIPANTS 308 children (126 girls, 182 boys; age 2-16 years). MAIN OUTCOME MEASURES Percentage of children with SCD who have normal, high or intermediate (often termed conditional) PSV or TAMMV. RESULTS In the cohort of 193 children, PSV was normal in 150 (77.7%), high in 7 (3.6%) and conditional in 36 (18.7%). In the cohort of 115 children, TAMMV was normal in 96 (84%), high in 7 (6%) and conditional in 12 (10%). There were no significant differences in gender or age distribution between the PSV and TAMMV cohorts. Altogether, cerebral artery blood velocity was normal in 246/308 children (80%), high in 14 (4.5%) and conditional in 48 (15.5%). CONCLUSION Since conditional blood velocity in cerebral arteries can progress to high values and predispose to stroke, the proportion of children with SCD who are affected (15.5%) raises the question of whether regular monitoring and proactive intervention ought to be the standard of care.
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Affiliation(s)
- Emmanuel Modebe
- Department of Radiation Medicine, University of Nigeria Teaching Hospital, Ituku Ozalla, Nigeria
| | - Charles Nonyelu
- Department of Haematology and Immunology, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria
| | - Augustine Duru
- Department of Haematology and Immunology, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria
| | - Osita Ezenwosu
- Department of Paediatrics, University of Nigeria Teaching Hospital, Ituku Ozalla, Nigeria
| | - Barth Chukwu
- Department of Paediatrics, University of Nigeria Teaching Hospital, Ituku Ozalla, Nigeria
| | - Anazoeze Madu
- Department of Haematology and Immunology, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria
| | - Chinedu Ezekekwu
- Department of Haematology and Immunology, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria
| | - John Aneke
- Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra, Nigeria
| | - Mildred Izuka
- Department of Paediatrics, Federal Medical Centre, Umuahia, Nigeria
| | - Chisom Nri-Ezedi
- Department of Paediatrics, Nnamdi Azikiwe University, Nnewi, Nigeria
| | - Oluomachi Nnachi
- Department of Haematology, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Nigeria
| | - Alozie Eze
- Department of Haematology, Federal Medical Centre, Umuahia, Nigeria
| | - Ifeoma Ajuba
- Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra, Nigeria
| | - Emeka Okwummuo
- Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra, Nigeria
| | - Jane Chilaka
- Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra, Nigeria
| | - Chinenye Onodugo
- Department of Pharmacy, University of Nigeria Teaching Hospital, Ituku Ozalla, Nigeria
| | - Uwaoma Fidelis-Ewa
- Department of Haematology and Immunology, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria
- Department of Pharmacy, University of Nigeria Teaching Hospital, Ituku Ozalla, Nigeria
| | - Obineche Agwu
- Department of Haematology, Federal Medical Centre, Umuahia, Nigeria
| | - Ikechukwu Anigbogu
- Department of Haematology and Immunology, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria
| | - Ebele Muoghalu
- Department of Haematology and Immunology, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria
| | - Helen Okoye
- Department of Haematology and Immunology, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria
| | - Chilota Efobi
- Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra, Nigeria
| | - Obiora Ejiofor
- Department of Paediatrics, Chukwuemeka Odumegwu-Ojukwu University Teaching Hospital, Amaku, Nigeria
| | - Ngozi Ugwu
- Department of Haematology and Immunology, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria
| | - Collins Maduka
- Department of Haematology, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Nigeria
- Department of Haematology, Federal Medical Centre, Umuahia, Nigeria
| | - Nneka Iloanusi
- Department of Radiation Medicine, University of Nigeria Teaching Hospital, Ituku Ozalla, Nigeria
| | - Angela Ugwu
- Department of Radiation Medicine, University of Nigeria Teaching Hospital, Ituku Ozalla, Nigeria
| | - Chide Okocha
- Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra, Nigeria
| | - Thomas Ulasi
- Department of Paediatrics, Nnamdi Azikiwe University, Nnewi, Nigeria
| | - Iheanyi Okpala
- Department of Haematology and Immunology, University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria
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Imaging of Suspected Stroke in Children, From the AJR Special Series on Emergency Radiology. AJR Am J Roentgenol 2023; 220:330-342. [PMID: 36043606 DOI: 10.2214/ajr.22.27816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Pediatric stroke encompasses different causes, clinical presentations, and associated conditions across ages. Although it is relatively uncommon, pediatric stroke presents with poor short- and long-term outcomes in many cases. Because of a wide range of overlapping presenting symptoms between pediatric stroke and other more common conditions, such as migraine and seizures, stroke diagnosis can be challenging or delayed in children. When combined with a comprehensive medical history and physical examination, neuroimaging plays a crucial role in diagnosing stroke and differentiating stroke mimics. This review highlights the current neuroimaging workup for diagnosing pediatric stroke in the emergency department, describes advantages and disadvantages of different imaging modalities, highlights disorders that predispose children to infarct or hemorrhage, and presents an overview of stroke mimics. Key differences in the initial approach to suspected stroke between children and adults are also discussed.
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Mandalaneni K, Venkatapathappa P, Koshy S, Walcott-Bedeau G, Singh V. Transcranial Doppler Ultrasonography-Related Research in the Caribbean Region. Cureus 2023; 15:e35147. [PMID: 36949970 PMCID: PMC10027575 DOI: 10.7759/cureus.35147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/18/2023] [Indexed: 02/20/2023] Open
Abstract
Transcranial Doppler (TCD) ultrasonography is a non-invasive ultrasound technique that uses high-frequency sound waves to measure blood flow velocities in the cerebral vasculature. This review analyzes TCD research in the Caribbean region using a bibliometric analysis of 29 articles from PubMed. The articles were analyzed using Microsoft Excel 2016 and the VOSviewer software (Van Eck and Waltman, Leiden University, Centre for Science and Technology Studies (CWTS), www.vosviewer.com) and characterized various aspects of TCD research, including countries, research themes, authorship, journals, affiliations, and keywords. The majority of the 29 publications came from Cuba (38%), followed by the French West Indies (22%) and Jamaica (20%). Most TCD research focused on sickle cell disease (SCD), accounting for 45% of the studies, followed by 21% of articles on vasospasm and subarachnoid hemorrhage. The use of TCD in brain death and neuro-intensive care was also explored, constituting 17% of the studies. Alternative TCD-monitored treatment options for SCD, such as stem cell transplantation and hydroxyurea, were also frequently investigated. The most productive institutions were Hospital Clínico-Quirúrgico Hermanos Ameijeiras in Havana, Cuba, the Sickle Cell Unit at the University of West Indies (UWI) Mona in Jamaica, the Medical-Surgical Research Center (CIMEQ) in Havana, Cuba, and the SCD Reference Center in Guadeloupe and Martinique in the French West Indies. TCD has been identified as a cost-effective tool for real-time monitoring of cerebral blood flow in many clinical settings, including stroke and SCD, which are prevalent in the Caribbean. Although there is an increase in the trend of using TCD for neuromonitoring in the Caribbean, gaps still exist. Capacity-building initiatives, such as training programs for healthcare providers and the development of local TCD research networks, can improve access to TCD in resource-constrained settings to treat and neuromonitor patients cost-effectively.
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Affiliation(s)
- Kesava Mandalaneni
- Department of Neuroscience, St. George's University School of Medicine, St. George's, GRD
| | | | - Sarah Koshy
- Department of Neuroscience, St. George's University School of Medicine, St. George's, GRD
| | | | - Vajinder Singh
- Department of Pathology, St. George's University School of Medicine, St. George's, GRD
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Mozaffarzadeh M, Verschuur DJE, Verweij MD, de Jong N, Renaud G. Accelerated 2-D Real-Time Refraction-Corrected Transcranial Ultrasound Imaging. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2022; 69:2599-2610. [PMID: 35797321 DOI: 10.1109/tuffc.2022.3189600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
In a recent study, we proposed a technique to correct aberration caused by the skull and reconstruct a transcranial B-mode image with a refraction-corrected synthetic aperture imaging (SAI) scheme. Given a sound speed map, the arrival times were calculated using a fast marching technique (FMT), which solves the Eikonal equation and, therefore, is computationally expensive for real-time imaging. In this article, we introduce a two-point ray tracing method, based on Fermat's principle, for fast calculation of the travel times in the presence of a layered aberrator in front of the ultrasound probe. The ray tracing method along with the reconstruction technique is implemented on a graphical processing unite (GPU). The point spread function (PSF) in a wire phantom image reconstructed with the FMT and the GPU implementation was studied with numerical synthetic data and experiments with a bone-mimicking plate and a sagittally cut human skull. The numerical analysis showed that the error on travel times is less than 10% of the ultrasound temporal period at 2.5 MHz. As a result, the lateral resolution was not significantly degraded compared with images reconstructed with FMT-calculated travel times. The results using the synthetic, bone-mimicking plate, and skull dataset showed that the GPU implementation causes a lateral/axial localization error of 0.10/0.20, 0.15/0.13, and 0.26/0.32 mm compared with a reference measurement (no aberrator in front of the ultrasound probe), respectively. For an imaging depth of 70 mm, the proposed GPU implementation allows reconstructing 19 frames/s with full synthetic aperture (96 transmission events) and 32 frames/s with multiangle plane wave imaging schemes (with 11 steering angles) for a pixel size of [Formula: see text]. Finally, refraction-corrected power Doppler imaging is demonstrated with a string phantom and a bone-mimicking plate placed between the probe and the moving string. The proposed approach achieves a suitable frame rate for clinical scanning while maintaining the image quality.
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Gajjar B, Sharma S, Khan E, Sharma P, Jain P, Goel V, Neral A, Patel J, Parmar M, Sharma K, Sharma VK, Sharma AK. Cerebral hemodynamics in children with sickle cell disease in India: An observational cohort study. Medicine (Baltimore) 2022; 101:e29882. [PMID: 35801747 PMCID: PMC9259145 DOI: 10.1097/md.0000000000029882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
India has the second highest number of cases of sickle cell disease (SCD) and affects the most socioeconomically disadvantaged communities living in a horizontal belt from Gujarat to Odisha state. Despite high prevalence, information about cerebral hemodynamics among children with SCD in India remains scarcely described. We performed transcranial Doppler (TCD) to assess cerebral hemodynamics among Indian children with SCD and evaluated their association with clinical and hematological parameters. Children aged 3-18years, diagnosed with SCD living in Raipur in Chhattisgarh and Ahmedabad in Gujarat state were recruited. TCD was performed to obtain flow velocities from middle cerebral (MCA), intracranial internal carotid (ICA) and basilar artery. Associations were evaluated between timed-average-mean-maximum velocities (TAMMV) and various clinical and hematological parameters. Our prospective study included 62 consecutive children with known SCD. Mean ± SD age of the study population was 9.8 ± 3.9 years and 31 (50%) were male. Mean ± SD hemoglobin was 8.64 ± 1.34 Gm/dL while the mean HbSS ± SD was 70.25 ± 15.27%. While 6 (9.6%) children had suffered from stroke during previous 2 years, 7 (11%) demonstrated abnormal TAMMV. Higher HbSS level along with history of iron chelation therapy, blood transfusion and/or stroke showed a trend towards having higher TAMMV. Stroke and cerebral hemodynamic alterations are common among Indian children with SCD. Larger studies with detailed neuroimaging and genetic evaluations are needed for better understanding, characterization, risk stratification as well as optimization of the timing of blood transfusion to reduce physical disabilities among Indian children with SCD.
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Affiliation(s)
- Bhakti Gajjar
- Department of Neurology, Zydus Hospital, Ahmedabad, Gujarat, India
| | - Sanjay Sharma
- Department of Neurology, Zydus Hospital, Ahmedabad, Gujarat, India
- Department of Neurology, Ramkrishna Care Hospitals, Raipur, Chhattisgarh, India
| | - Erum Khan
- BJ Medical College, Ahmedabad, Gujarat, India
| | | | - Pawan Jain
- Department of Pediatrics, Ramkrishna Care Hospitals, Raipur, Chhattisgarh, India
| | - Vikas Goel
- Department of Hematology, Ramkrishna Care Hospitals, Raipur, Chhattisgarh, India
| | | | | | - Mamta Parmar
- Department of Neurology, Zydus Hospital, Ahmedabad, Gujarat, India
| | - Kanika Sharma
- Department of Neurology, Zydus Hospital, Ahmedabad, Gujarat, India
| | - Vijay K. Sharma
- YLL School of Medicine, National University of Singapore and Division of Neurology, National University Hospital, Singapore
- *Correspondence: Vijay K. Sharma, Yong Loo Lin School of Medicine, National University of Singapore, Level 10, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228 (e-mail: )
| | - Arvind K. Sharma
- Department of Neurology, Zydus Hospital, Ahmedabad, Gujarat, India
- BJ Medical College, Ahmedabad, Gujarat, India
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Shen J, Miao X, Vu C, Xu B, González-Zacarías C, Nederveen AJ, Wood JC. Anemia Increases Oxygen Extraction Fraction in Deep Brain Structures but Not in the Cerebral Cortex. Front Physiol 2022; 13:896006. [PMID: 35784894 PMCID: PMC9248375 DOI: 10.3389/fphys.2022.896006] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 05/19/2022] [Indexed: 01/26/2023] Open
Abstract
Sickle cell disease (SCD) is caused by a single amino acid mutation in hemoglobin, causing chronic anemia and neurovascular complications. However, the effects of chronic anemia on oxygen extraction fraction (OEF), especially in deep brain structures, are less well understood. Conflicting OEF values have been reported in SCD patients, but have largely attributed to different measurement techniques, faulty calibration, and different locations of measurement. Thus, in this study, we investigated the reliability and agreement of two susceptibility-based methods, quantitative susceptibility mapping (QSM) and complex image summation around a spherical or a cylindrical object (CISSCO), for OEF measurements in internal cerebral vein (ICV), reflecting oxygen saturation in deep brain structures. Both methods revealed that SCD patients and non-sickle anemia patients (ACTL) have increased OEF in ICV (42.6% ± 5.6% and 30.5% ± 3.6% in SCD by CISSCO and QSM respectively, 37.0% ± 4.1% and 28.5% ± 2.3% in ACTL) compared with controls (33.0% ± 2.3% and 26.8% ± 1.8%). OEF in ICV varied reciprocally with hematocrit (r 2 = 0.92, 0.53) and oxygen content (r 2 = 0.86, 0.53) respectively. However, an opposite relationship was observed for OEF measurements in sagittal sinus (SS) with the widely used T2-based oximetry, T2-Relaxation-Under-Spin-Tagging (TRUST), in the same cohorts (31.2% ± 6.6% in SCD, 33.3% ± 5.9% in ACTL and 36.8% ± 5.6% in CTL). Importantly, we demonstrated that hemoglobin F and other fast moving hemoglobins decreased OEF by TRUST and explained group differences in sagittal sinus OEF between anemic and control subjects. These data demonstrate that anemia causes deep brain hypoxia in anemia subjects with concomitant preservation of cortical oxygenation, as well as the key interaction of the hemoglobin dissociation curve and cortical oxygen extraction.
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Affiliation(s)
- Jian Shen
- Biomedical Engineering, University of Southern California, Los Angeles, Los Angeles, CA, United States
| | - Xin Miao
- Siemens, Boston, MA, United States
| | - Chau Vu
- Biomedical Engineering, University of Southern California, Los Angeles, Los Angeles, CA, United States
| | - Botian Xu
- Biomedical Engineering, University of Southern California, Los Angeles, Los Angeles, CA, United States
| | - Clio González-Zacarías
- Neuroscience Graduate Program, University of Southern California, Los Angeles, Los Angeles, CA, United States
| | - Aart J. Nederveen
- Amsterdam UMC, Radiology and Nuclear Medicine, University of Amsterdam, Amsterdam, Netherlands
| | - John C. Wood
- Biomedical Engineering, University of Southern California, Los Angeles, Los Angeles, CA, United States,Department of Pediatrics and Radiology, Children’s Hospital Los Angeles, Los Angeles, CA, United States,*Correspondence: John C. Wood,
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10
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Schatz J, Reinman L, Bills SE, Johnston JD. Sociodemographic and Biomedical Correlates of Developmental Delay in 2- and 4-Year-Olds with Sickle Cell Disease. J Dev Behav Pediatr 2022; 43:224-232. [PMID: 34570066 PMCID: PMC8942869 DOI: 10.1097/dbp.0000000000001011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 08/12/2021] [Indexed: 11/25/2022]
Abstract
BACKGROUND Developmental delay occurs frequently in sickle cell disease (SCD). Psychosocial and biomedical factors contribute to delays, but most studies have not examined the timing of risk factors and developmental delay. We examined sociodemographic and biomedical factors to evaluate whether risks of developmental delay differed across 2 developmental periods. METHODS We examined Ages and Stages Questionnaire, second edition (ASQ-2), outcomes in 2-year-olds (n = 100) and 4-year-olds (n = 101) with SCD. ASQ-2 data were obtained from routine developmental screenings administered as part of health care between 2009 and 2016 at a single hematology clinic. Medical record reviews were used to identify sociodemographic and biomedical factors associated with positive screenings for developmental delay. RESULTS Two-year-olds with positive ASQ-2 screenings (n = 32; 32%) were less likely to have private health insurance or to have been in formal daycare and more likely to have a severe SCD genotype. Four-year-olds with positive screenings (n = 40; 40%) were more likely to have a severe SCD genotype or an abnormal transcranial Doppler ultrasound (TCD) examination indicating high stroke risk. The strength of the association between positive screenings and insurance status, severe genotypes, and TCD examinations differed across the 2 age groups. Domain-level outcomes on the ASQ-2 also differed across the 2 age groups. CONCLUSION The cross-sectional data indicate biomedical and psychosocial risks are related to developmental delay, but the association with specific risk factors differs across age.
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Affiliation(s)
- Jeffrey Schatz
- Department of Psychology, University of South Carolina, Columbia, SC
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Intharakham K, Panerai RB, Robinson TG. The scalability of common paradigms for assessment of cognitive function: A functional transcranial Doppler study. PLoS One 2022; 17:e0266048. [PMID: 35344567 PMCID: PMC8959162 DOI: 10.1371/journal.pone.0266048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 03/12/2022] [Indexed: 11/18/2022] Open
Abstract
Cognitive paradigms induce changes in cerebral blood flow (CBF) associated with increased metabolic demand, namely neurovascular coupling (NVC). We tested the hypothesis that the effect of complexity and duration of cognitive paradigms will either enhance or inhibit the NVC response. Bilateral CBF velocity (CBFV) in the middle cerebral arteries (MCAs) via transcranial Doppler ultrasound (TCD), blood pressure (BP), electrocardiogram (ECG) and end-tidal CO2 (EtCO2) of 16 healthy participants (aged 21–71 years) were simultaneously recorded at rest and during randomized paradigms of different complexities (naming words beginning with P-,R-,V- words and serial subtractions of 100–2,100–7,1000–17), and durations (5s, 30s and 60s). CBFV responses were population mean normalized from a 30-s baseline period prior to task initiation. A significant increase in bilateral CBFV response was observed at the start of all paradigms and provided a similar pattern in most responses, irrespective of complexity or duration. Although significant inter-hemispherical differences were found during performance of R-word and all serial subtraction paradigms, no lateralisation was observed in more complex naming word tasks. Also, the effect of duration was manifested at late stages of 100–7, but not for other paradigms. CBFV responses could not distinguish different levels of complexity or duration with a single presentation of the cognitive paradigm. Further studies of the ordinal scalability of the NVC response are needed with more advanced modelling techniques, or different types of neural stimulation.
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Affiliation(s)
- Kannakorn Intharakham
- Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom
- * E-mail:
| | - Ronney B. Panerai
- Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom
- NIHR Leicester Biomedical Research Centre, British Heart Foundation Cardiovascular Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Thompson G. Robinson
- Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom
- NIHR Leicester Biomedical Research Centre, British Heart Foundation Cardiovascular Research Centre, Glenfield Hospital, Leicester, United Kingdom
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12
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Adanho CSA, Yahouédéhou SCMA, Santana SS, Vieira C, Santiago RP, de Santana JM, Pitanga TN, Aleluia MM, Maffili VV, Leite IPR, Zanette DL, Lyra IM, Goncalves MS. Association of laboratory markers and cerebral blood flow among sickle cell anemia children. Front Pediatr 2022; 10:914466. [PMID: 36090571 PMCID: PMC9458965 DOI: 10.3389/fped.2022.914466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 08/10/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Stroke is one of the highest complications of sickle-cell anemia (SCA). The Transcranial Doppler (TCD) has been adopted worldwide as a gold standard method for detecting alterations in the blood velocity in cerebral arteries. In this study, we investigated the association between laboratory parameters and increased cerebral blood flow velocity in Brazilian SCA pediatric patients. METHODS The study included 159 pediatric patients with SCA, submitted to TCD velocity screening, and the time-averaged maximum mean velocity (TAMMV) was determined in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and distal intracranial internal carotid artery (ICA). We compared cerebral blood flow in patients stratified by the following: TCD1-defined as normal, with TAMMV inferior to 170 cm/s; TCD2-conditional, with TAMMV above 170 cm/s, but less than 199 cm/s; TCD3-altered, with TAMMV greater than or equal to 200 cm/s. RESULTS TAMMV was negatively correlated with age and weight (p < 0.05). Moreover, TAMMV was associated or correlated with reductions in HbF, RBC, hemoglobin, hematocrit, HDL, and haptoglobin and, increases in MCV, MCH, RDW, reticulocytes, WBC, lymphocytes, monocytes, eosinophils, total and indirect bilirubin, LDH, AST, ALT, glucose, ferritin, and AAT (p < 0.05). CONCLUSION The current study highlights the importance of the investigation of hemolytic and inflammatory biomarkers for monitoring the clinical outcome of SCA pediatric patients, to avoid acute or chronic stroke. Moreover, glucose and HDL-C appear useful for predicting higher TAMMV.
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Affiliation(s)
- Corynne Stéphanie Ahouéfa Adanho
- Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, Bahia, Brazil.,Laboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Sètondji Cocou Modeste Alexandre Yahouédéhou
- Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, Bahia, Brazil.,Laboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Sânzio Silva Santana
- Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, Bahia, Brazil.,Faculdade de Biomedicina, Universidade Católica do Salvador, Salvador, Bahia, Brazil
| | - Camilo Vieira
- Ambulatório Pediátrico de Doença Cerebrovascular, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Rayra Pereira Santiago
- Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, Bahia, Brazil.,Laboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Jeanne Machado de Santana
- Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, Bahia, Brazil
| | - Thassila Nogueira Pitanga
- Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, Bahia, Brazil.,Faculdade de Biomedicina, Universidade Católica do Salvador, Salvador, Bahia, Brazil
| | | | - Vítor Valério Maffili
- Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, Bahia, Brazil
| | - Ivana Paula Ribeiro Leite
- Serviço de Pediatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Dalila Luciola Zanette
- Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, Bahia, Brazil
| | - Isa Menezes Lyra
- Serviço de Pediatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.,Ambulatório, Fundação de Hematologia e Hemoterapia da Bahia, Salvador, Bahia, Brazil.,Curso de Medicina, Escola de Ciências da Saúde e Bem-Estar, Universidade Salvador, Salvador, Bahia, Brazil
| | - Marilda Souza Goncalves
- Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, Bahia, Brazil.,Laboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Bahia, Brazil
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13
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Prevalence and risk factors of cognitive impairment in children with sickle cell disease in Egypt. Int J Hematol 2021; 115:399-405. [PMID: 34792734 DOI: 10.1007/s12185-021-03260-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 11/05/2021] [Accepted: 11/07/2021] [Indexed: 10/19/2022]
Abstract
Little is known about cognitive impairment in patients with sickle cell disease in Africa. This study aimed to assess cognitive impairment and identify possible risk factors in patients with sickle cell disease in Egypt. This study was conducted at Cairo University Children Hospital. Patients with sickle cell disease, between ages of 6-20 years were enrolled. Cognitive ability was tested using the Stanford Binet intelligence quotient (IQ) test, fourth edition. Transcranial Doppler, magnetic resonance imaging and magnetic resonance angiography of the brain were performed within a week of the IQ test. Among the 40 enrolled patients, 55% had a Full Scale IQ at least 1 standard deviation below the mean, and 27.5% had an IQ 2 standard deviations below the mean. High lactate dehydrogenase was significantly associated with low IQ (p = 0.004). In univariate analyses, IQ was significantly correlated with older age (p = 0.025), high lactate dehydrogenase (p = 0.008) and older age at the start of hydroxyurea (p = 0.025). Impaired cognition is prevalent among sickle cell disease patients. Early initiation of hydroxyurea therapy, which should also reduce hemolysis and lactate dehydrogenase, may be a simple measure to preserve mental abilities in these patients.
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14
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Champlin G, Hwang SN, Heitzer A, Ding J, Jacola L, Estepp JH, Wang W, Ataga KI, Owens CL, Newman J, King AA, Davis R, Kang G, Hankins JS. Progression of central nervous system disease from pediatric to young adulthood in sickle cell anemia. Exp Biol Med (Maywood) 2021; 246:2473-2479. [PMID: 34407676 DOI: 10.1177/15353702211035778] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Silent cerebral infarcts and arteriopathy are common and progressive in individuals with sickle cell anemia. However, most data describing brain lesions in sickle cell anemia are cross-sectional or derive from pediatric cohorts with short follow-up. We investigated the progression of silent cerebral infarct and cerebral vessel stenosis on brain MRI and MRA, respectively, by describing the incidence of new or worsening lesions over a period of up to 25 years among young adults with sickle cell anemia and explored risk factors for progression. Forty-four adults with sickle cell anemia (HbSS or HbSβ0thalassemia), exposed to chronic transfusions (n = 12) or hydroxyurea (n = 32), median age 19.2 years (range 18.0-31.5), received a screening brain MRI/MRA and their results were compared with a clinical exam performed during childhood and adolescence. We used exact log-rank test to compare MRI and MRA progression among any two groups. The hazard ratio (HR) and 95% confidence interval (CI) were calculated from Cox regression analyses. Progression of MRI and MRA occurred in 12 (27%) and 4 (9%) young adults, respectively, relative to their pediatric exams. MRI progression risk was high among participants with abnormal pediatric exams (HR: 11.6, 95% CI: 2.5-54.7) and conditional or abnormal transcranial Doppler ultrasound velocities (HR: 3.9, 95% CI: 1.0-15.1). Among individuals treated with hydroxyurea, high fetal hemoglobin measured in childhood was associated with lower hazard of MRI progression (HR: 0.86, 95% CI: 0.76-0.98). MRA progression occurred more frequently among those with prior stroke (HR: 8.6, 95% CI: 1.2-64), abnormal pediatric exam (P = 0.00084), and elevated transcranial Doppler ultrasound velocities (P = 0.004). Brain MRI/MRA imaging in pediatrics can identify high-risk patients for CNS disease progression in young adulthood, prompting consideration for early aggressive treatments.
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Affiliation(s)
- Grace Champlin
- Department of Clinical Education and Training, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Scott N Hwang
- Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Andrew Heitzer
- Department of Psychology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Juan Ding
- Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Lisa Jacola
- Department of Psychology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Jeremie H Estepp
- Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.,Global Medicine, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Winfred Wang
- Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Kenneth I Ataga
- University of Tennessee Health Science Center (UTHSC), Center for Sickle Cell Disease, Memphis, TN 38163, USA.,Methodist University Comprehensive Sickle Cell Center, Memphis, TN 38104, USA
| | - Curtis L Owens
- Methodist University Comprehensive Sickle Cell Center, Memphis, TN 38104, USA
| | - Justin Newman
- Memphis Radiological Professional Corporation, Memphis, TN 38138, USA
| | - Allison A King
- Washington University School of Medicine, St. Louis, MO 63130, USA
| | - Robert Davis
- Center in Biomedical Informatics at UTHSC, Memphis, TN 38163, USA
| | - Guolian Kang
- Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - Jane S Hankins
- Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
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15
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Edjlali M, Gobin‐Metteil M, Mélé N, Maïer B, Habibi A, Kauv P, Hosseini H, Mas J, Oppenheim C, Galactéros F, Bartolucci P, Calvet D. Transcranial color-coded duplex sonography reliably identifies intracranial vasculopathy in adult patients with sickle cell disease. Am J Hematol 2021; 96:961-967. [PMID: 33971039 DOI: 10.1002/ajh.26215] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 04/28/2021] [Accepted: 05/01/2021] [Indexed: 11/08/2022]
Abstract
In order to prevent stroke, screening for disease-related intracranial vasculopathy using Doppler ultrasound is recommended in sickle-cell disease (SCD) children. How to screen such vasculopathy in adults remains largely unknown. The objective of this study was to assess whether transcranial color-coded duplex sonography (TCCD) is sensitive and specific enough to identify SCD adult patients with vasculopathy, compared with magnetic resonance angiography (MRA). Sickle cell disease adults followed in referral centers at high risk of vasculopathy were included in this study. Transcranial color-coded duplex sonography examination and 3-D time-of-flight MRA were performed on the same day. On MRA, vasculopathy was defined by the presence of at least one ≥50% arterial stenosis. On TCCD, vasculopathy was defined by a time-averaged mean of the maximum velocity (TAMx) stenotic/prestenotic ratio ≥ 3, an occlusion, or a Moyamoya pattern. Vasculopathy was also considered as present when TAMx ratio could not be calculated because of the presence of severe cervical lesions. Among 80 included patients, quality of MRA was insufficient in three patients. Among the 38 patients with vasculopathy on MRA, 37 had a vasculopathy according to TCCD criteria: TAMx ratio ≥ 3 or intracranial occlusion in 33 patients and cervical lesion in four patients. A Moyamoya pattern was identified with TCCD in all 17 patients with Moyamoya on MRA. Sensitivity and specificity of TCCD to identify patients with ≥50% vasculopathy on MRA were (n = 37/38) 97% and (n = 28/34) 82%, respectively. Positive and negative predictive values were (n = 37/43) 86% and (n = 28/29) 97%, respectively. Note, TCCD may be used to identify SCD adult patients with vasculopathy.
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Affiliation(s)
- Myriam Edjlali
- Service d'Imagerie, GHU Paris Psychiatrie et Neurosciences (Sainte‐Anne) Université de Paris Paris France
- INSERM 1266 Institut de Psychiatrie et Neurosciences de Paris ‐ FHU Neurovasc—Paris Sorbonne Paris France
| | - Marie‐Pierre Gobin‐Metteil
- Service d'Imagerie, GHU Paris Psychiatrie et Neurosciences (Sainte‐Anne) Université de Paris Paris France
- INSERM 1266 Institut de Psychiatrie et Neurosciences de Paris ‐ FHU Neurovasc—Paris Sorbonne Paris France
| | - Nicolas Mélé
- INSERM 1266 Institut de Psychiatrie et Neurosciences de Paris ‐ FHU Neurovasc—Paris Sorbonne Paris France
- Service de Neurologie et Unité Neurovasculaire, GHU Paris Psychiatrie et Neurosciences (Sainte‐Anne) Université de Paris Paris France
| | - Benjamin Maïer
- INSERM 1266 Institut de Psychiatrie et Neurosciences de Paris ‐ FHU Neurovasc—Paris Sorbonne Paris France
- Service de Neurologie et Unité Neurovasculaire, GHU Paris Psychiatrie et Neurosciences (Sainte‐Anne) Université de Paris Paris France
| | - Anoosha Habibi
- Sickle Cell Referral Center, Médecine Interne, Hôpital Henri‐Mondor, UPEC Créteil France
- INSERM U955, team 2, Laboratoire d'Excellence GRex Créteil France
| | - Paul Kauv
- Department of Imaging Henri‐Mondor Hospital, UPEC, Assistance Publique‐Hopitaux de Paris, Creteil Créteil France
| | - Hassan Hosseini
- Department of Neurology Henri‐Mondor Hospital, UPEC, Assistance Publique‐Hopitaux de Paris, Creteil Créteil France
| | - Jean‐Louis Mas
- INSERM 1266 Institut de Psychiatrie et Neurosciences de Paris ‐ FHU Neurovasc—Paris Sorbonne Paris France
- Service de Neurologie et Unité Neurovasculaire, GHU Paris Psychiatrie et Neurosciences (Sainte‐Anne) Université de Paris Paris France
| | - Catherine Oppenheim
- Service d'Imagerie, GHU Paris Psychiatrie et Neurosciences (Sainte‐Anne) Université de Paris Paris France
- INSERM 1266 Institut de Psychiatrie et Neurosciences de Paris ‐ FHU Neurovasc—Paris Sorbonne Paris France
| | - Frédéric Galactéros
- Sickle Cell Referral Center, Médecine Interne, Hôpital Henri‐Mondor, UPEC Créteil France
- INSERM U955, team 2, Laboratoire d'Excellence GRex Créteil France
| | - Pablo Bartolucci
- Sickle Cell Referral Center, Médecine Interne, Hôpital Henri‐Mondor, UPEC Créteil France
- INSERM U955, team 2, Laboratoire d'Excellence GRex Créteil France
| | - David Calvet
- INSERM 1266 Institut de Psychiatrie et Neurosciences de Paris ‐ FHU Neurovasc—Paris Sorbonne Paris France
- Service de Neurologie et Unité Neurovasculaire, GHU Paris Psychiatrie et Neurosciences (Sainte‐Anne) Université de Paris Paris France
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16
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Sabarense AP, Silva CM, Muniz MBDSR, Viana MB. Follow-up of children with sickle cell anemia screened with transcranial Doppler and enrolled in a primary prevention program of ischemic stroke. Hematol Transfus Cell Ther 2021; 44:478-484. [PMID: 34210619 PMCID: PMC9605893 DOI: 10.1016/j.htct.2021.05.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 05/08/2021] [Accepted: 05/17/2021] [Indexed: 12/03/2022] Open
Abstract
Background Stroke is a serious complication of sickle cell anemia (SCA). The transcranial Doppler (TCD) is the risk-screening tool for ischemic strokes. The objective of the study was to describe the clinical progression of children with SCA who presented with high risk for stroke by TCD or relevant changes by magnetic resonance angiography (MRA) and underwent the regular transfusion program (RTP) and/or hydroxyurea (HU) treatment between 2007 and 2018. Method This was a neonatal retrospective/prospective cohort study with children born between 1999 and 2014 with the homozygotic form (HbSS) or Sβ0-thalassemia who underwent TCD at least once. Results Of the 718 children screened during this period, 675 had HbSS and 43 Sβ0-thalassemia. In 54 children (7.5%), all with HbSS, a high-risk TCD (n = 45) or, when the TCD was inconclusive, an MRA with cerebral vasculopathy (n = 9) was used for detection. Of these, 51 started the RTP and the families of three refused treatment. Of the 43 children with a high-risk TCD who initiated the RTP, 29 (67.4%) reverted to low risk. In 18 of them (62%), HU was started at the maximum tolerated dose (MTD) before transfusion discontinuation. None of these 29 patients had a stroke. Eight children (18.6%) maintained a high-risk TCD, even using the RTP/HU and two had a stroke. Conclusions The TCD was confirmed as a viable tool for tracking patients with a risk for stroke. The RTP was effective in preventing the primary event. New strategies are necessary to prevent stroke using HU and new drugs, in addition to bone marrow transplantation.
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Affiliation(s)
| | | | | | - Marcos Borato Viana
- Faculdade de Medicina da Universidade Federal de Minas Gerais (FM UFMG), Belo Horizonte, MG, Brazil; Núcleo de Ações e Pesquisa em Apoio Diagnóstico da Universidade Federal de Minas Gerais (Nupad UFMG), Belo Horizonte, MG, Brazil.
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17
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Ojewunmi OO, Adeyemo TA, Oyetunji AI, Benn Y, Ekpo MG, Iwalokun BA. Association of alpha-thalassemia and Glucose-6-Phosphate Dehydrogenase deficiency with transcranial Doppler ultrasonography in Nigerian children with sickle cell anemia. J Clin Lab Anal 2021; 35:e23802. [PMID: 33938598 PMCID: PMC8183942 DOI: 10.1002/jcla.23802] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 03/28/2021] [Accepted: 04/06/2021] [Indexed: 12/01/2022] Open
Abstract
Background Stroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler Ultrasonography (TCD). The evidence on the role of alpha‐thalassemia and glucose‐6‐phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is conflicting. Thus, this study investigated the association of alpha‐thalassemia and G6PD(A−) variant with abnormal TCD velocities among Nigerian children with SCA. Methods One hundred and forty‐one children with SCA were recruited: 72 children presented with normal TCD (defined as the time‐averaged mean of the maximum velocity: < 170 cm/s) and 69 children with abnormal TCD (TAMMV ≥ 200 cm/s). Alpha‐thalassemia (the α‐3.7 globin gene deletion) was determined by multiplex gap‐PCR, while G6PD polymorphisms (202G > A and 376A > G) were genotyped using restriction fragment length polymorphism—polymerase chain reaction. Results The frequency of α‐thalassemia trait in the children with normal TCD was higher than those with abnormal TCD: 38/72 (52.8%) [α‐/ α α: 41.7%, α ‐/ α ‐: 11.1%] versus 21/69 (30.4%) [α‐/ α α: 27.5%, α ‐/ α ‐: 2.9%], and the odds of abnormal TCD were reduced in the presence of the α‐thalassemia trait [Odds Ratio: 0.39, 95% confidence interval: 0.20–0.78, p = 0.007]. However, the frequencies of G6PDA− variant in children with abnormal and normal TCD were similar (11.6% vs. 15.3%, p = 0.522). Conclusion Our study reveals the protective role of α‐thalassemia against the risk of abnormal TCD in Nigerian children with SCA.
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Affiliation(s)
- Oyesola Oyewole Ojewunmi
- Sickle Cell Foundation Nigeria, Surulere, Lagos, Nigeria.,School of Cancer and Pharmaceutical Sciences, King's College London, London, UK
| | - Titilope Adenike Adeyemo
- Department of Haematology & Blood Transfusion, College of Medicine, University of Lagos, Lagos, Nigeria
| | | | - Yewande Benn
- Sickle Cell Foundation Nigeria, Surulere, Lagos, Nigeria
| | | | - Bamidele Abiodun Iwalokun
- Department of Molecular Biology and Biotechnology, Nigerian Institute of Medical Research, Lagos, Nigeria
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18
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Ogu UO, Badamosi NU, Camacho PE, Freire AX, Adams-Graves P. Management of Sickle Cell Disease Complications Beyond Acute Chest Syndrome. J Blood Med 2021; 12:101-114. [PMID: 33658881 PMCID: PMC7920619 DOI: 10.2147/jbm.s291394] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 02/07/2021] [Indexed: 12/14/2022] Open
Abstract
Sickle cell disease results in numerous complications that can lead to significant morbidity and mortality. Amongst them, acute chest syndrome is the leading cause of mortality. As a result, most providers are in tune with this complication and well versed with management. As sickle cell patients now live longer, they face a multitude of other complications that if left unattended, can lead to significant morbidity and mortality as well. It is critical to look beyond acute chest syndrome and adopt a more comprehensive approach to the management of the sickle cell patient.
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Affiliation(s)
- Ugochi O Ogu
- Center for Sickle Cell Disease, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Nnenna U Badamosi
- Division of Pediatric Hematology and Oncology, Medical College of Georgia, Augusta, GA, USA
| | - Pamela E Camacho
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Amado X Freire
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Patricia Adams-Graves
- Center for Sickle Cell Disease, University of Tennessee Health Science Center, Memphis, TN, USA
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19
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Wali Y, Kini V, Yassin MA. Distribution of sickle cell disease and assessment of risk factors based on transcranial Doppler values in the Gulf region. ACTA ACUST UNITED AC 2020; 25:55-62. [PMID: 31983291 DOI: 10.1080/16078454.2020.1714113] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Background/Objective: Stroke is a potentially fatal complication of sickle cell disease (SCD). Transcranial Doppler (TCD) is useful at identifying increased risk of stroke in children with SCD and vasospasm after subarachnoid hemorrhage. The main aim of this study was to determine the proportion of patients with SCD in the Gulf region who are at a high risk of stroke, as determined by TCD.Methods: This multicenter (Oman, Qatar, and UAE), descriptive, cross-sectional study in patients (aged 2-16 years) with SCD included a baseline visit, 1 follow-up visit for patients with conditional TCD, and 3-year retrospective data analysis for all patients.Results: Of the 410 eligible patients (Oman, 86.5%; Qatar, 8.2%; UAE, 5.1%), most had a TCD finding (left side, 91.7%; right side, 92.0%) of normal velocity (<155 cm/s) at baseline. For 6 of 7 patients with conditional velocity (155-179 cm/s) and 1 patient with high velocity (≥180 cm/s), baseline TCD results were not confirmed at follow-up. As per bivariate linear regression, age, race, transfusion type, and transfusion frequency were significant predictors of the TCD velocities. Multivariate logistic regressions revealed that TCD velocities were significantly correlated with sex, race, and type of transfusion. No patients reported any adverse events at follow-up. No deaths occurred during the study.Discussion/Conclusions: The study results show that far fewer patients with SCD in the Gulf have abnormal TCD findings than the internationally reported. Larger studies are needed to identify the factors underlying this observation.
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Affiliation(s)
- Yasser Wali
- Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman.,Alexandria University Children's Hospital, Alexandria, Egypt
| | | | - Mohamed A Yassin
- Department of Medicine, College of Medicine, Qatar University, Doha, Qatar
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20
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Evaluation of oxidative stress-related genetic variants for predicting stroke in patients with sickle cell anemia. J Neurol Sci 2020; 414:116839. [PMID: 32344219 DOI: 10.1016/j.jns.2020.116839] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Revised: 03/29/2020] [Accepted: 04/14/2020] [Indexed: 01/29/2023]
Abstract
Overt stroke in adults with sickle cell anemia (SCA) continues to be a major cause of morbidity and mortality, while no evidence-based strategy for prevention has been reached so far. Although transcranial Doppler ultrasonography represents the most important tool for identifying young patients with SCA at risk of primary stroke, strategies for stroke prediction in adulthood remain challenging. Emerging data suggest that oxidative stress may exert a pivotal role in the pathogenesis of ischemic brain injury. Combining these pieces of evidences with the well-known genetic contribution to the development of stroke in SCA, we hypothesized that genetic variants related to the biology of oxidative stress could be used to identify adult patients at higher risk of stroke. Overall, 499 unrelated patients with SCA aged >18 years were genotyped for SOD2 Val16Ala (rs4880), GPX3 T-568C (rs8177404), GPX3 T-518C (rs8177406), GPX3 T-65C (rs8177412), and CAT01 C-262 T (rs1001179) polymorphisms, along with α-thalassemia status and β-globin gene haplotypes. Of these, only the SOD2 Val16Ala polymorphism was associated with stroke. SOD2 Val16Ala polymorphism was independently associated with risk of stroke (odds ratio: 1.98; 95% confidence interval [CI]: 1.18-3.32; P = .009) and with the long-term cumulative incidence of stroke (hazard ratio: 2.24, 95% CI: 1.3-3.9; P = .004). In summary, we provide evidence that oxidative stress-related genetic variants, in particular, the SOD2 Val16Ala polymorphism, may represent a simple and inexpensive alternative for identifying patients at risk of stroke.
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21
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Robertson RL, Palasis S, Rivkin MJ, Pruthi S, Bartel TB, Desai NK, Kadom N, Kulkarni AV, Lam HFS, Maheshwari M, Milla SS, Mirsky DM, Myseros JS, Partap S, Radhakrishnan R, Soares BP, Trout AT, Udayasankar UK, Whitehead MT, Karmazyn B. ACR Appropriateness Criteria® Cerebrovascular Disease-Child. J Am Coll Radiol 2020; 17:S36-S54. [PMID: 32370977 DOI: 10.1016/j.jacr.2020.01.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 01/30/2020] [Indexed: 10/24/2022]
Abstract
Stroke is an uncommon but an important and under-recognized cause of morbidity and mortality in children. Strokes may be due to either brain ischemia or intracranial hemorrhage. Common symptoms of pediatric acute stroke include headache, vomiting, focal weakness, numbness, visual disturbance, seizures, and altered consciousness. Most children presenting with an acute neurologic deficit do not have an acute stroke, but have symptoms due to stroke mimics which include complicated migraine, seizures with postictal paralysis, and Bell palsy. Because of frequency of stroke mimics, in children and the common lack of specificity in symptoms, the diagnosis of a true stroke may be delayed. There are a relatively large number of potential causes of stroke mimic and true stroke. Consequently, imaging plays a critical role in the assessment of children with possible stroke and especially in children who present with acute onset of stroke symptoms. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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Affiliation(s)
| | - Susan Palasis
- Panel Chair, Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia
| | - Michael J Rivkin
- Boston Children's Hospital, Boston, Massachusetts; American Academy of Neurology
| | - Sumit Pruthi
- Panel Vice Chair, Vanderbilt Children's Hospital, Nashville, Tennessee
| | | | | | - Nadja Kadom
- Emory University and Children's of Atlanta (Egleston), Atlanta, Georgia
| | - Abhaya V Kulkarni
- Hospital for Sick Children, Toronto, Ontario, Canada; Neurosurgery expert
| | - H F Samuel Lam
- Sutter Medical Center, Sacramento, California; American College of Emergency Physicians
| | | | - Sarah S Milla
- Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia
| | | | - John S Myseros
- Children's National Health System, Washington, District of Columbia; Neurosurgery expert
| | - Sonia Partap
- Stanford University, Stanford, California; American Academy of Pediatrics
| | | | - Bruno P Soares
- The University of Vermont Medical Center, Burlington, Vermont
| | - Andrew T Trout
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | | | | | - Boaz Karmazyn
- Specialty Chair, Riley Hospital for Children Indiana University, Indianapolis, Indiana
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22
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Jordan LC, Kassim AA, Wilkerson KL, Lee CA, Waddle SL, Donahue MJ. Using novel magnetic resonance imaging methods to predict stroke risk in individuals with sickle cell anemia. Hematol Oncol Stem Cell Ther 2020; 13:76-84. [PMID: 32192979 DOI: 10.1016/j.hemonc.2019.12.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 12/11/2019] [Indexed: 11/28/2022] Open
Abstract
Sickle cell anemia (SCA) is a well-characterized monogenetic disorder with a high prevalence of cerebral vasculopathy, silent cerebral infarcts, and strokes. A significant mechanism for cerebral infarction in SCA is hemodynamic imbalance. To compensate for reduced oxygen-carrying capacity due to anemia, individuals with SCA have chronically elevated cerebral blood flow to maintain viable oxygen delivery to the brain tissue. Often the oxygen extraction fraction (ratio of oxygen consumed to oxygen delivered) is increased in more severely affected individuals. Subsequently, cerebrovascular reserve capacity, the ability of arterioles to dilate and further increase the cerebral blood volume and flow, will be reduced. These hemodynamic profiles have been associated with prior cerebral infarcts and increased evidence of disease severity. These cerebral hemodynamic parameters can be assessed noninvasively with noncontrast magnetic resonance imaging (MRI) of the brain utilizing specific MRI methods. This review focuses on using advanced neuroimaging methods to assess stroke risk in individuals with SCA, and such methods may be utilized before and after bone marrow or hematopoietic stem cell transplant to assess cerebral hemodynamic response. This manuscript is part of the Proceeding of The European Group for Blood and Marrow Transplantation (EBMT) Congress on Sickle Cell Disease, 16th-17 May 2019, Regensburg, Germany.
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Affiliation(s)
- Lori C Jordan
- Pediatrics-Division of Pediatric Neurology, Vanderbilt University Medical Center, Nashville, TN, USA; Neurology, Vanderbilt University Medical Center, Nashville, TN, USA; Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Adetola A Kassim
- Medicine-Division of Hematology/Stem Cell Transplantation, Vanderbilt-Meharry Sickle Cell Center for Excellence, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Karina L Wilkerson
- Medicine-Division of Hematology/Stem Cell Transplantation, Vanderbilt-Meharry Sickle Cell Center for Excellence, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Chelsea A Lee
- Pediatrics-Division of Pediatric Neurology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Spencer L Waddle
- Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Manus J Donahue
- Neurology, Vanderbilt University Medical Center, Nashville, TN, USA; Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA; Psychiatry, Vanderbilt University Medical Center, Nashville, TN, USA; Physics and Astronomy, Vanderbilt University, Nashville, TN, USA
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23
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Abd-Allah F, Eltagui M, Aboulfotooh AM, Kishk NA, Farrag MA, Mohammed SA, Shamloul RM, El-Jaafary S, Said F, Ibrahim A, Elghamrawy M. Factors associated with abnormal cerebral blood flow in Egyptian children with sickle cell disease. CLINICAL AND TRANSLATIONAL NEUROSCIENCE 2020. [DOI: 10.1177/2514183x20911351] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Background: Transcranial Doppler (TCD) is a well-established tool for cerebrovascular assessment. Estimating the flow velocity across the intracranial arteries helps to identify children with sickle cell anaemia who are at risk for stroke. Objective: Our aim is to correlate TCD findings with clinical condition in children with sickle cell disease (SCD) to determine the value of TCD assessment as a predictive tool for stroke in SCD and to identify any association of TCD findings with disease severity, transfusion therapy and treatment administered. Methods: Eighty-five paediatric SCD patients aged from 3 years to 18 years of both genders who were followed up at the Hematology Clinic of New Children’s Hospital at Cairo University were included in this cross-sectional observational study. All our participants underwent routine laboratory investigations and TCD assessments. Results: Oof the 85 patients, two patients (2.3%) died before completing the TCD study and eventually 83 patients were included in the analysis. Seventeen (20.5%) patients had abnormal TCD findings, seven (8.4%) patients showed high-risk findings and 10 (12.1%) patients had conditional flow pattern. Logistic linear regression analysis confirmed that annual frequency of blood transfusion and hydroxyurea (HU) dose were associated with a decreased risk of abnormal TCD findings. Conclusion: The current study demonstrates that our TCD data reproduce the findings of other studies and that it is very likely the results from large trials are applicable for Egyptian children. The annual frequency of blood transfusion and HU dose were associated with a decreased frequency of abnormal TCD findings.
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Affiliation(s)
- Foad Abd-Allah
- Neurovascular Unit, Department of Neurology, Cairo University, Giza, Egypt
| | - Mona Eltagui
- Pediatric Hematology and BMT Unit, Department of Pediatrics, Cairo University, Giza, Egypt
| | | | - Nirmeen Adel Kishk
- Neurovascular Unit, Department of Neurology, Cairo University, Giza, Egypt
| | | | | | | | - Shaimaa El-Jaafary
- Neurovascular Unit, Department of Neurology, Cairo University, Giza, Egypt
| | - Fadwa Said
- Department of Clinical and Chemical Pathology, Cairo University, Giza, Egypt
| | - Ahmed Ibrahim
- Department of Pediatrics, Jaber Al Ahmed Hospital, Kuwait
| | - Mona Elghamrawy
- Pediatric Hematology and BMT Unit, Department of Pediatrics, Cairo University, Giza, Egypt
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Identification of Pulse Onset on Cerebral Blood Flow Velocity Waveforms: A Comparative Study. BIOMED RESEARCH INTERNATIONAL 2019; 2019:3252178. [PMID: 31355255 PMCID: PMC6634067 DOI: 10.1155/2019/3252178] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 06/02/2019] [Accepted: 06/18/2019] [Indexed: 11/17/2022]
Abstract
The low cost, simple, noninvasive, and continuous measurement of cerebral blood flow velocity (CBFV) by transcranial Doppler is becoming a common clinical tool for the assessment of cerebral hemodynamics. CBFV monitoring can also help with noninvasive estimation of intracranial pressure and evaluation of mild traumatic brain injury. Reliable CBFV waveform analysis depends heavily on its accurate beat-to-beat delineation. However, CBFV is inherently contaminated with various types of noise/artifacts and has a wide range of possible pathological waveform morphologies. Thus, pulse onset detection is in general a challenging task for CBFV signal. In this paper, we conducted a comprehensive comparative analysis of three popular pulse onset detection methods using a large annotated dataset of 92,794 CBFV pulses—collected from 108 subarachnoid hemorrhage patients admitted to UCLA Medical Center. We compared these methods not only in terms of their accuracy and computational complexity, but also for their sensitivity to the selection of their parameters' values. The results of this comprehensive study revealed that using optimal values of the parameters obtained from sensitivity analysis, one method can achieve the highest accuracy for CBFV pulse onset detection with true positive rate (TPR) of 97.06% and positive predictivity value (PPV) of 96.48%, when error threshold is set to just less than 10 ms. We conclude that the high accuracy and low computational complexity of this method (average running time of 4ms/pulse) makes it a reliable algorithm for CBFV pulse onset detection.
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25
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Jalaleddini K, Canac N, Thorpe SG, O'Brien MJ, Ranjbaran M, Delay B, Dorn AY, Scalzo F, Thibeault CM, Wilk SJ, Hamilton RB. Objective Assessment of Beat Quality in Transcranial Doppler Measurement of Blood Flow Velocity in Cerebral Arteries. IEEE Trans Biomed Eng 2019; 67:883-892. [PMID: 31217091 DOI: 10.1109/tbme.2019.2923146] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
OBJECTIVE Transcranial Doppler (TCD) ultrasonography measures pulsatile cerebral blood flow velocity in the arteries and veins of the head and neck. Similar to other real-time measurement modalities, especially in healthcare, the identification of high-quality signals is essential for clinical interpretation. Our goal is to identify poor quality beats and remove them prior to further analysis of the TCD signal. METHODS We selected objective features for this purpose including Euclidean distance between individual and average beat waveforms, cross-correlation between individual and average beat waveforms, ratio of the high-frequency power to the total beat power, beat length, and variance of the diastolic portion of the beat waveform. We developed an iterative outlier detection algorithm to identify and remove the beats that are different from others in a recording. Finally, we tested the algorithm on a dataset consisting of more than 15 h of TCD data recorded from 48 stroke and 34 in-hospital control subjects. RESULTS We assessed the performance of the algorithm in the improvement of estimation of clinically important TCD parameters by comparing them to that of manual beat annotation. The results show that there is a strong correlation between the two, that demonstrates the algorithm has successfully recovered the clinically important features. We obtained significant improvement in estimating the TCD parameters using the algorithm accepted beats compared to using all beats. SIGNIFICANCE Our algorithm provides a valuable tool to clinicians for automated detection of the reliable portion of the data. Moreover, it can be used as a pre-processing tool to improve the data quality for automated diagnosis of pathologic beat waveforms using machine learning.
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26
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Montrief T, Alerhand S, Jewell C, Scott J. Incorporation of Transcranial Doppler into the ED for the neurocritical care patient. Am J Emerg Med 2019; 37:1144-1152. [PMID: 30894296 DOI: 10.1016/j.ajem.2019.03.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 02/05/2019] [Accepted: 03/04/2019] [Indexed: 01/03/2023] Open
Abstract
INTRODUCTION In the catastrophic neurologic emergency, a complete neurological exam is not always possible or feasible given the time-sensitive nature of the underlying disease process, or if emergent airway management is indicated. As the neurologic exam may be limited in some patients, the emergency physician is reliant on the assessment of brainstem structures to determine neurological function. Physicians thus routinely depend on advanced imaging modalities to further investigate for potential catastrophic diagnoses. Acquiring these tests introduces the risks of transport as well as delays in managing time-sensitive neurologic processes. A more immediate, non-invasive bedside approach complementing these modalities has evolved: Transcranial Doppler (TCD). OBJECTIVE This narrative review will provide a description of scenarios in which TCD may be applicable. It will summarize the sonographic findings and associated underlying pathophysiology in such neurocritical care patients. An illustrated tutorial, along with pearls and pitfalls, is provided. DISCUSSION Although there are numerous formalized TCD protocols utilizing four views (transtemporal, submandibular, suboccipital, and transorbital), point-of-care TCD is best accomplished through the transtemporal window. The core applications include the evaluation of midline shift, vasospasm after subarachnoid hemorrhage, acute ischemic stroke, and elevated intracranial pressure. An illustrative tutorial is provided. CONCLUSIONS With the wide dissemination of bedside ultrasound within the emergency department, there is a unique opportunity for the emergency physician to utilize TCD for a variety of conditions. While barriers to training exist, emergency physician performance of limited point-of-care TCD is feasible and may provide rapid and reliable clinical information with high temporal resolution.
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Affiliation(s)
- Tim Montrief
- Department of Emergency Medicine, Jackson Memorial Health System, Miami, FL 33136, USA.
| | - Stephen Alerhand
- Department of Emergency Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
| | - Corlin Jewell
- Berbee Walsh Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
| | - Jeffery Scott
- Department of Emergency Medicine, Jackson Memorial Health System, Miami, FL 33136, USA
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27
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Ismail A, Yusuf AA, Kuliya-Gwarzo A, Ahmed SG, Tabari AM, Abubakar SA. Correlating transcranial arterial Doppler velocities with haematologic parameters and haemolytic indices of Nigerian children with sickle cell anaemia. ULTRASOUND : JOURNAL OF THE BRITISH MEDICAL ULTRASOUND SOCIETY 2019; 27:101-110. [PMID: 31037094 DOI: 10.1177/1742271x19836264] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Accepted: 02/12/2019] [Indexed: 11/17/2022]
Abstract
Introduction Cerebral vasculopathy, elevated transcranial Doppler velocities and stroke are linked to excessive intravascular haemolysis in sickle cell anaemia. This study determined the prevalence and pattern of abnormal blood flow velocities in children with sickle cell anaemia from Northern Nigeria using transcranial Doppler and to correlate transcranial Doppler velocities with haematological and biochemical markers of haemolysis. Methods Full blood count, reticulocyte count, fetal haemoglobin and some selected biochemical markers of haemolysis of 100 children with sickle cell anaemia were determined at steady state. The time-averaged mean of maximal velocities in four major intracranial blood vessels was measured using non-imaging transcranial Doppler, which were then classified according to the stroke prevention in sickle cell disease trial protocol. A simple linear correlation between time-averaged mean of maximal velocities in the four major intracranial vessels as the dependent variable and haematological and biochemical markers of haemolysis as independent variables was also determined at the significance level of 0.05. Results Abnormal transcranial Doppler velocities, classified as high risk, were found in 3% of the studied patients; 11% had intermediate risk while 84% had standard risk. Most high velocities were detected in the middle cerebral artery. The time-averaged mean of maximal velocities of middle cerebral artery positively correlated with total white blood cell count, absolute neutrophil count, platelet count, reticulocyte count, serum lactate dehydrogenase and total bilirubin, while it was negatively correlated with haematocrit and fetal haemoglobin levels. Conclusion Our study showed low prevalence of abnormal transcranial Doppler velocities and low prevalence is unrelated to low markers of haemolysis in our study population.
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Affiliation(s)
- Anas Ismail
- Department of Radiology, Aminu Kano Teaching Hospital (AKTH), Bayero University, Kano, Nigeria
| | - Aminu Abba Yusuf
- Department of Haematology and Blood Transfusion, Aminu Kano Teaching Hospital (AKTH), Bayero University, Kano, Nigeria
| | - Aisha Kuliya-Gwarzo
- Department of Haematology and Blood Transfusion, Aminu Kano Teaching Hospital (AKTH), Bayero University, Kano, Nigeria
| | - Sagir Gumel Ahmed
- Department of Haematology and Blood Transfusion, Aminu Kano Teaching Hospital (AKTH), Bayero University, Kano, Nigeria
| | - Abdulkadir Musa Tabari
- Department of Radiology, Aminu Kano Teaching Hospital (AKTH), Bayero University, Kano, Nigeria
| | - Shehi Ali Abubakar
- Department of Radiology, Aminu Kano Teaching Hospital (AKTH), Bayero University, Kano, Nigeria
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28
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Juttukonda MR, Donahue MJ. Neuroimaging of vascular reserve in patients with cerebrovascular diseases. Neuroimage 2019; 187:192-208. [PMID: 29031532 PMCID: PMC5897191 DOI: 10.1016/j.neuroimage.2017.10.015] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Revised: 10/01/2017] [Accepted: 10/07/2017] [Indexed: 12/21/2022] Open
Abstract
Cerebrovascular reactivity, defined broadly as the ability of brain parenchyma to adjust cerebral blood flow in response to altered metabolic demand or a vasoactive stimulus, is being measured with increasing frequency and may have a use for portending new or recurrent stroke risk in patients with cerebrovascular disease. The purpose of this review is to outline (i) the physiological basis of variations in cerebrovascular reactivity, (ii) available approaches for measuring cerebrovascular reactivity in research and clinical settings, and (iii) clinically-relevant cerebrovascular reactivity findings in the context of patients with cerebrovascular disease, including atherosclerotic arterial steno-occlusion, non-atherosclerotic arterial steno-occlusion, anemia, and aging. Literature references summarizing safety considerations for these procedures and future directions for standardizing protocols and post-processing procedures across centers are presented in the specific context of major unmet needs in the setting of cerebrovascular disease.
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Affiliation(s)
- Meher R Juttukonda
- Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Manus J Donahue
- Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Physics and Astronomy, Vanderbilt University, Nashville, TN, USA.
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29
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Adekile A, Hassan M, Asbeutah A, Al-Hinai M, Trad O, Farhan N. Transcranial Doppler Ultrasound in Peninsular Arab Patients With Sickle Cell Disease. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2019; 38:165-172. [PMID: 29732592 DOI: 10.1002/jum.14680] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Revised: 04/07/2018] [Accepted: 04/10/2018] [Indexed: 06/08/2023]
Abstract
OBJECTIVES Transcranial Doppler ultrasound is used to identify patients with sickle cell disease (SCD) at risk for stroke. We performed transcranial Doppler studies in patients from 4 countries in the Arabian Peninsula (Kuwait, Oman, Iraq, and United Arab Emirates) to document the prevalence of abnormal transcranial Doppler findings. METHODS The patients were recruited from outpatient clinics and studied in a steady state. Transcranial Doppler examinations were performed with standard equipment by experienced operators. The time-averaged maximum mean velocity (TAMMV) was documented in the arteries of the circle of Willis. The hemoglobin (Hb) genotype was confirmed, and the fetal Hb level and complete blood counts were determined. RESULTS There were 415 patients in the study, aged 2 to 18 years (mean ± SD, 8.6 ± 3.5 years). None of the patients had an abnormal TAMMV (ie, > 200 cm/s), whereas only 13 (3.1%), all from Iraq, had conditional values (170-200 cm/s) in the right middle cerebral artery and 7 (1.7%) in the left middle cerebral artery. There were no consistent TAMMV differences among male and female patients or in patients with different Hb genotypes (sickle cell anemia, sickle cell β0- thalassemia, and sickle D). The use of hydroxyurea was associated with a lower TAMMV, whereas a blood transfusion history had no influence. Total hemoglobin, reticulocyte count, serum bilirubin, and fetal Hb values showed varying degrees of association with the TAMMV in the different vessels. CONCLUSIONS This study has demonstrated the rarity of abnormal transcranial Doppler findings among Peninsular Arab patients with SCD. The guidelines for transcranial Doppler screening in this population need further studies and recommendations.
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Affiliation(s)
- Adekunle Adekile
- Department of Pediatrics, Faculty of Medicine, Kuwait University, Safat, Kuwait
| | - Meaad Hassan
- Department of Pediatrics, College of Medicine, University of Basra, Basra, Iraq
| | - Akram Asbeutah
- Department of Radiologic Sciences, Faculty of Allied Health Sciences, Kuwait University, Safat, Kuwait
| | - Mohamed Al-Hinai
- Department of Pediatric Hematology-Oncology, Royal Hospital, Muscat, Oman
| | - Omar Trad
- Department of Pediatric Oncology, Tawam Hospital, Al Ain, United Arab Emirates
| | - Nayef Farhan
- Department of Pediatrics, Basra Specialty Hospital, Basra, Iraq
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30
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Rankine-Mullings AE, Morrison-Levy N, Soares D, Aldred K, King L, Ali S, Knight-Madden JM, Wisdom-Phipps M, Adams RJ, Ware RE, Reid M. Transcranial Doppler velocity among Jamaican children with sickle cell anaemia: determining the significance of haematological values and nutrition. Br J Haematol 2018; 181:242-251. [PMID: 29504121 DOI: 10.1111/bjh.15162] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 01/03/2018] [Indexed: 11/29/2022]
Affiliation(s)
- Angela E. Rankine-Mullings
- Sickle Cell Unit; Caribbean Institute for Health Research; University of the West Indies; Kingston Jamaica
| | - Nadine Morrison-Levy
- Sickle Cell Unit; Caribbean Institute for Health Research; University of the West Indies; Kingston Jamaica
| | - Deanne Soares
- Tropical Metabolism Research Unit; Caribbean Institute for Health Research Institute; University of the West Indies; Kingston Jamaica
| | - Karen Aldred
- Sickle Cell Unit; Caribbean Institute for Health Research; University of the West Indies; Kingston Jamaica
| | - Lesley King
- Sickle Cell Unit; Caribbean Institute for Health Research; University of the West Indies; Kingston Jamaica
| | - Susanna Ali
- Sickle Cell Unit; Caribbean Institute for Health Research; University of the West Indies; Kingston Jamaica
| | - Jennifer M. Knight-Madden
- Sickle Cell Unit; Caribbean Institute for Health Research; University of the West Indies; Kingston Jamaica
| | - Margaret Wisdom-Phipps
- Sickle Cell Unit; Caribbean Institute for Health Research; University of the West Indies; Kingston Jamaica
| | - Robert J. Adams
- Neurology; College of Medicine; Medical University of South Carolina; Charleston SC USA
| | - Russell E. Ware
- Cincinnati Children's Hospital Medical Centre; Cincinnati OH USA
| | - Marvin Reid
- Tropical Metabolism Research Unit; Caribbean Institute for Health Research Institute; University of the West Indies; Kingston Jamaica
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31
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Comorbid obstructive sleep apnea and increased risk for sickle cell disease morbidity. Sleep Breath 2018; 22:797-804. [DOI: 10.1007/s11325-018-1630-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Revised: 01/09/2018] [Accepted: 01/11/2018] [Indexed: 01/19/2023]
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Kanavaki A, Spengos K, Moraki M, Delaporta P, Kariyannis C, Papassotiriou I, Kattamis A. Serum Levels of S100b and NSE Proteins in Patients with Non-Transfusion-Dependent Thalassemia as Biomarkers of Brain Ischemia and Cerebral Vasculopathy. Int J Mol Sci 2017; 18:ijms18122724. [PMID: 29244749 PMCID: PMC5751325 DOI: 10.3390/ijms18122724] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2017] [Revised: 12/07/2017] [Accepted: 12/08/2017] [Indexed: 11/16/2022] Open
Abstract
Patients with non-transfusion-dependent thalassemia (NTDT) are at risk of developing brain ischemia. Transcranial Doppler (TCD) has been established as a useful screening tool of cerebrovascular disease in patients with sickle cell disease. Proteins neuron specific enolase (NSE) and S100B are biomarkers that reflect CNS injury. The purpose of this study is to evaluate cerebral vessel vasculopathy and brain damage in NTDT patients using non-invasive methods as TCD and measurement serum levels of NSE and S100B. We included in our study 30 patients with NTDT, aged between 8 and 62 years old (mean: 29.4, median: 32) who presented in our Unit for regular follow-up. We performed in all patients a non-imaging TCD examination and have measured serum S100, NSE and lactate dehydrogenase (LDH) levels. We investigated the possible correlation between TCD results and S100B, NSE and LDH levels as well as between NSE-LDH and S100B-LDH levels by regression analysis. We found a statistically significant relationship for both NSE, S100B with LDH. We also found a statistically significant relationship for S100B and time-averaged mean velocity (TAMV)/peak velocity of left middle cerebral artery (MCA), NSE and pulsatility index (PI)/resistive index (RI) of the left posterior cerebral artery (PCA). TCD results correlated with biomarkers for brain ischemia. This finding enhances the role of TCD as a screening tool for brain ischemia in patients with NTDT.
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Affiliation(s)
- Aikaterini Kanavaki
- First Department of Pediatrics, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.M.); (P.D.); (A.K.)
- Correspondence: ; Tel.: +30-21-0618-4000
| | - Konstantinos Spengos
- First Department of Neurology, “Eginition” Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece;
| | - Maria Moraki
- First Department of Pediatrics, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.M.); (P.D.); (A.K.)
| | - Polyxeni Delaporta
- First Department of Pediatrics, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.M.); (P.D.); (A.K.)
| | - Catherine Kariyannis
- Department of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, Goudi, 11527 Athens, Greece; (C.K.); (I.P.)
| | - Ioannis Papassotiriou
- Department of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, Goudi, 11527 Athens, Greece; (C.K.); (I.P.)
| | - Antonis Kattamis
- First Department of Pediatrics, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.M.); (P.D.); (A.K.)
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Sun YY, Lee J, Huang H, Wagner MB, Joiner CH, Archer DR, Kuan CY. Sickle Mice Are Sensitive to Hypoxia/Ischemia-Induced Stroke but Respond to Tissue-Type Plasminogen Activator Treatment. Stroke 2017; 48:3347-3355. [PMID: 29127268 PMCID: PMC5726594 DOI: 10.1161/strokeaha.117.018334] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Revised: 10/04/2017] [Accepted: 10/06/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND PURPOSE The effects of lytic stroke therapy in patients with sickle cell anemia are unknown, although a recent study suggested that coexistent sickle cell anemia does not increase the risk of cerebral hemorrhage. This finding calls for systemic analysis of the effects of thrombolytic stroke therapy, first in humanized sickle mice, and then in patients. There is also a need for additional predictive markers of sickle cell anemia-associated vasculopathy. METHODS We used Doppler ultrasound to examine the carotid artery of Townes sickle mice tested their responses to repetitive mild hypoxia-ischemia- and transient hypoxia-ischemia-induced stroke at 3 or 6 months of age, respectively. We also examined the effects of tPA (tissue-type plasminogen activator) treatment in transient hypoxia-ischemia-injured sickle mice. RESULTS Three-month-old sickle cell (SS) mice showed elevated resistive index in the carotid artery and higher sensitivity to repetitive mild hypoxia-ischemia-induced cerebral infarct. Six-month-old SS mice showed greater resistive index and increased flow velocity without obstructive vasculopathy in the carotid artery. Instead, the cerebral vascular wall in SS mice showed ectopic expression of PAI-1 (plasminogen activator inhibitor-1) and P-selectin, suggesting a proadhesive and prothrombotic propensity. Indeed, SS mice showed enhanced leukocyte and platelet adherence to the cerebral vascular wall, broader fibrin deposition, and higher mortality after transient hypoxia-ischemia. Yet, post-transient hypoxia-ischemia treatment with tPA reduced thrombosis and mortality in SS mice. CONCLUSIONS Sickle mice are sensitive to hypoxia/ischemia-induced cerebral infarct but benefit from thrombolytic treatment. An increased resistive index in carotid arteries may be an early marker of sickle cell vasculopathy.
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Affiliation(s)
- Yu-Yo Sun
- From the Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (Y.-Y.S., J.L., H.H., C.-Y.K., C.H.J., D.R.A., M.B.W.); Center for Neurodegenerative Diseases (Y.-Y.S., J.L., H.H., C.-Y.K.); Aflac Cancer and Blood Disorders Center, Atlanta, GA (C.H.J., D.R.A.); Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (M.B.W.); and Children's Healthcare of Atlanta, GA (M.B.W.)
| | - Jolly Lee
- From the Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (Y.-Y.S., J.L., H.H., C.-Y.K., C.H.J., D.R.A., M.B.W.); Center for Neurodegenerative Diseases (Y.-Y.S., J.L., H.H., C.-Y.K.); Aflac Cancer and Blood Disorders Center, Atlanta, GA (C.H.J., D.R.A.); Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (M.B.W.); and Children's Healthcare of Atlanta, GA (M.B.W.)
| | - Henry Huang
- From the Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (Y.-Y.S., J.L., H.H., C.-Y.K., C.H.J., D.R.A., M.B.W.); Center for Neurodegenerative Diseases (Y.-Y.S., J.L., H.H., C.-Y.K.); Aflac Cancer and Blood Disorders Center, Atlanta, GA (C.H.J., D.R.A.); Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (M.B.W.); and Children's Healthcare of Atlanta, GA (M.B.W.)
| | - Mary B Wagner
- From the Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (Y.-Y.S., J.L., H.H., C.-Y.K., C.H.J., D.R.A., M.B.W.); Center for Neurodegenerative Diseases (Y.-Y.S., J.L., H.H., C.-Y.K.); Aflac Cancer and Blood Disorders Center, Atlanta, GA (C.H.J., D.R.A.); Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (M.B.W.); and Children's Healthcare of Atlanta, GA (M.B.W.)
| | - Clinton H Joiner
- From the Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (Y.-Y.S., J.L., H.H., C.-Y.K., C.H.J., D.R.A., M.B.W.); Center for Neurodegenerative Diseases (Y.-Y.S., J.L., H.H., C.-Y.K.); Aflac Cancer and Blood Disorders Center, Atlanta, GA (C.H.J., D.R.A.); Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (M.B.W.); and Children's Healthcare of Atlanta, GA (M.B.W.)
| | - David R Archer
- From the Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (Y.-Y.S., J.L., H.H., C.-Y.K., C.H.J., D.R.A., M.B.W.); Center for Neurodegenerative Diseases (Y.-Y.S., J.L., H.H., C.-Y.K.); Aflac Cancer and Blood Disorders Center, Atlanta, GA (C.H.J., D.R.A.); Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (M.B.W.); and Children's Healthcare of Atlanta, GA (M.B.W.)
| | - Chia-Yi Kuan
- From the Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (Y.-Y.S., J.L., H.H., C.-Y.K., C.H.J., D.R.A., M.B.W.); Center for Neurodegenerative Diseases (Y.-Y.S., J.L., H.H., C.-Y.K.); Aflac Cancer and Blood Disorders Center, Atlanta, GA (C.H.J., D.R.A.); Children's Heart Research and Outcomes Center, Emory University School of Medicine, Atlanta, GA (M.B.W.); and Children's Healthcare of Atlanta, GA (M.B.W.).
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McKiernan S, Selmes C. Transcranial colour-coded duplex of the intracranial large arteries. SONOGRAPHY 2017. [DOI: 10.1002/sono.12124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Adegoke SA, Macedo-Campos RDS, Braga JAP, Figueiredo MS, Silva GS. Changes in Transcranial Doppler Flow Velocities in Children with Sickle Cell Disease: The Impact of Hydroxyurea Therapy. J Stroke Cerebrovasc Dis 2017; 27:425-431. [PMID: 29056404 DOI: 10.1016/j.jstrokecerebrovasdis.2017.09.020] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Revised: 07/30/2017] [Accepted: 09/17/2017] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Hydroxyurea (HU) was recently described as a substitute for chronic transfusion for children with sickle cell disease (SCD) and abnormal transcranial Doppler (TCD) velocities who have received at least 1 year of transfusions. However, the role of HU in reverting elevated TCD velocities in patients not treated with transfusion is still debatable. The objective of the study was to examine whether HU influences the progression of TCD velocities in children with SCD. PATIENTS AND METHODS Children with SCD with at least 2 TCDs not less than 6 months apart were evaluated over 51 months. Time-averaged maximum mean (TAMM) velocities for the initial and the last transcranial Doppler examinations were noted and differences compared between HU and HU-naive groups. RESULTS Overall, 68.8% of the HU-group with elevated TCD velocities compared with 40.0% of the HU-naive experienced TCD reversal (P = .047). A higher proportion of the HU-naive group, 7 (14.3%) versus 9.8% of the HU group experienced TCD conversion. Those with initial conditional velocities in the HU-group experienced a significant reduction in TAMM velocities (from 176.8 ± 5.3 to 162.7 ± 13.9 cm/s, difference of 14.1 cm/s; P = .001) unlike those in the HU-naive group (176.3 ± 5.3 to 170.0 ± 18.6 cm/s, difference of 6.3 cm/s; P = .148). The change in the TAMM velocities was also significantly higher among the HU-group (14.1 ± 12.4 cm/s versus 6.3 ± 18.5 cm/s, P = .015). CONCLUSION Our data suggest a beneficial role of HU in TCD velocity reduction in patients not treated with chronic transfusions, particularly among those with initial conditional TCD velocities.
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Affiliation(s)
- Samuel Ademola Adegoke
- Haematology and Blood Transfusion Division, Universidade Federal de São Paulo, São Paulo, Brazil; Department of Pediatrics and Child Health, Obafemi Awolowo University, Ile-Ife, Nigeria.
| | | | | | - Maria Stella Figueiredo
- Haematology and Blood Transfusion Division, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Gisele Sampaio Silva
- Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil; Programa Integrado de Neurologia, Hospital Israelita Albert Einstein, São Paulo, Brazil
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Developmental Screening in Pediatric Sickle Cell Disease: Disease-Related Risk and Screening Outcomes in 4 Year Olds. J Dev Behav Pediatr 2017; 38:654-662. [PMID: 28816916 PMCID: PMC5617784 DOI: 10.1097/dbp.0000000000000486] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Studies of early child development in sickle cell disease (SCD) have found modest associations between disease-related risks and developmental status in infants and toddlers, but such associations are evident by early elementary school. We screened 4-year-old children with SCD using 2 screening strategies to assess if biomedical risk factors for neurologic disease are related to developmental screening outcomes at this intermediate age. METHODS Seventy-seven 4-year-old children with SCD (M = 4.5 yrs, SD = 0.3 yrs) completed developmental screenings at routine hematology visits using child testing (Fluharty Preschool Speech and Language Screenings Test, 2nd edition) and parent-report (Ages and Stages Questionnaire, 2nd edition) procedures. Genotype and other biomedical variables were coded from medical records. RESULTS Children with higher-risk SCD genotypes (n = 52) showed lower performance than children with lower-risk genotypes (n = 25) on a measure related to neurologic disease risk in older children (syntactic processing); genotype risk was also related to rates of positive screenings on parent-reported developmental milestones (52% positive screenings in high-risk genotypes vs 12% in low-risk genotypes). Screening outcomes were also related to transcranial Doppler ultrasound findings assessing cerebral blood flow. CONCLUSION Developmental screening at age 4 may be a useful target age for identifying preschoolers with sickle cell-related neurodevelopmental concerns. Parent report of developmental milestones and behavioral testing each may have a role in screening for children in need of follow-up services to address potential neurodevelopmental effects from SCD.
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Greenwood S, Deane C, Rees OL, Freedman B, Kumar S, Ben Ramadan N, Wilkinson S, Marais G, Lord J, Chakravorty S, Height SE, Gardner K, Rees DC. The significance of inadequate transcranial Doppler studies in children with sickle cell disease. PLoS One 2017; 12:e0181681. [PMID: 28742875 PMCID: PMC5526506 DOI: 10.1371/journal.pone.0181681] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Accepted: 07/05/2017] [Indexed: 12/22/2022] Open
Abstract
Sickle cell disease (SCD) is a common cause of cerebrovascular disease in childhood. Primary stroke prevention is effective using transcranial Doppler (TCD) scans to measure intracranial blood velocities, and regular blood transfusions or hydroxycarbamide when these are abnormal. Inadequate TCD scans occur when it is not possible to measure velocities in all the main arteries. We have investigated the prevalence and significance of this in a retrospective audit of 3915 TCD scans in 1191 children, performed between 2008 and 2015. 79% scans were normal, 6.4% conditional, 2.8% abnormal and 12% inadequate. 21.6% of 1191 patients had an inadequate scan at least once. The median age of first inadequate scan was 3.3 years (0.7-19.4), with a U-shaped frequency distribution with age: 28% aged 2-3 years, 3.5% age 10 years, 25% age 16 years. In young children reduced compliance was the main reason for inadequate TCDs, whereas in older children it was due to a poor temporal ultrasound window. The prevalence of inadequate TCD was 8% in the main Vascular Laboratory at King's College Hospital and significantly higher at 16% in the outreach clinics (P<0.0001), probably due to the use of a portable ultrasound machine. Inadequate TCD scans were not associated with underlying cerebrovascular disease.
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Affiliation(s)
- Simon Greenwood
- Vascular Laboratory, King’s College Hospital, London, United Kingdom
| | - Colin Deane
- Vascular Laboratory, King’s College Hospital, London, United Kingdom
| | | | - Ben Freedman
- Vascular Laboratory, King’s College Hospital, London, United Kingdom
| | - Suresh Kumar
- Department of Paediatrics, Darent Valley Hospital, Dartford, Kent, United Kingdom
| | - Naser Ben Ramadan
- Department of Paediatrics, Medway Maritime Hospital, Gillingham, Kent, United Kingdom
| | - Sarah Wilkinson
- Department of Paediatrics, Lewisham and Greenwich NHS Trust, London, United Kingdom
| | - Grant Marais
- Department of Paediatrics, Croydon University Hospital, London, United Kingdom
| | - Julie Lord
- Department of Paediatrics, Lewisham and Greenwich NHS Trust, London, United Kingdom
| | - Subarna Chakravorty
- Department of Paediatric Haematology, King’s College Hospital, London, United Kingdom
| | - Susan E. Height
- Department of Paediatric Haematology, King’s College Hospital, London, United Kingdom
| | - Kate Gardner
- Department of Paediatric Haematology, King’s College Hospital, London, United Kingdom
| | - David C. Rees
- Department of Paediatric Haematology, King’s College Hospital, London, United Kingdom
- * E-mail:
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Vieira C, de Oliveira CNC, de Figueiredo LAB, Santiago RP, Adanho CSA, Santana SS, Burak CL, Lyra IM, Goncalves MS. Transcranial Doppler in hemoglobin SC disease. Pediatr Blood Cancer 2017; 64. [PMID: 27957790 DOI: 10.1002/pbc.26342] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Revised: 10/05/2016] [Accepted: 10/06/2016] [Indexed: 11/07/2022]
Abstract
BACKGROUND Stroke is a severe clinical disorder in sickle cell disease (SCD), and few studies have evaluated transcranial Doppler (TCD) flow velocities in hemoglobin SC disease (HbSC). The guidelines for stroke risk are based on evaluations in sickle cell anemia (SCA) or HbS/β thalassemia. PROCEDURE In this study, we compare cerebral blood flow in patients with SCD stratified by genotypes. A total of 1,664 pediatric patients with SCD underwent TCD velocity screening, and the time-averaged maximum mean velocity (TAMM) was determined in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and distal intracranial internal carotid artery (ICA). RESULTS Abnormal velocities were not identified in the ACA; therefore, we only use ICA and MCA velocities. TAMM from the left and right in the ICA and MCA was 134.3 ± 32.0 and 134.4 ± 32.6 cm/s in patients with SCA, and 105.2 ± 20.6 and 104.7 ± 20.0 cm/s in the patients with HbSC, respectively. Mean TAMM between right and left ICA/MCA was 134.5 ± 30.5 cm/s in the SCA group, and 104.9 ± 19.3 cm/s in the HbSC group. Notably, our data show that TCD velocities were significantly lower among the patients with HbSC compared to SCA. TAMM was negatively correlated with hemoglobin and hematocrit in both genotypes. CONCLUSION These results suggest that a different cut-off value for abnormal TCD velocities could be considered for patients with HbSC. Additional studies are warranted to determine the actual risk of stroke in HbSC genotype associated with this possible TCD risk value.
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Affiliation(s)
- Camilo Vieira
- Ambulatório Pediátrico de Doença Cerebrovascular, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Bahia, Brazil.,Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Bahia, Brazil
| | | | | | - Rayra Pereira Santiago
- Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Bahia, Brazil.,Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal da Bahia, Bahia, Brazil
| | - Corynne Stephanie Ahouefa Adanho
- Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Bahia, Brazil.,Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal da Bahia, Bahia, Brazil
| | - Sanzio Silva Santana
- Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Bahia, Brazil.,Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal da Bahia, Bahia, Brazil
| | - Caroline Lang Burak
- Departamento de Hematologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Bahia, Brazil
| | - Isa Menezes Lyra
- Departamento de Hematologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Bahia, Brazil
| | - Marilda Souza Goncalves
- Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Bahia, Brazil.,Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal da Bahia, Bahia, Brazil
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Ferrão TDO, Martins-Filho PR, Aragão C, Santana M, Nascimento A, Cardoso T, Cipolotti R. Doppler velocimetry of the orbital arteries in patients with sickle cell anemia: relationship with biomarkers of hemolysis. Radiol Bras 2017; 50:103-108. [PMID: 28428653 PMCID: PMC5397001 DOI: 10.1590/0100-3984.2015.0180] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
Objective To investigate orbital vascular resistance by Doppler velocimetry in patients
with steady-state sickle cell anemia, as well as to characterize its
relationship with biomarkers of hemolysis. Materials and Methods This was a cross-sectional study of two groups: 71 outpatients with sickle
cell anemia; and 32 age- and gendermatched, healthy subjects (control
group). All participants underwent Doppler velocimetry of the orbital
arteries and laboratory tests. Results All biochemical laboratory markers were abnormal in the sickle cell anemia
patients (p < 0.0001 vs. controls). In the patient
group, Doppler velocimetry revealed increased flow velocities in the
ophthalmic artery and reduced flow velocities in the central retinal artery,
as well as high values for the resistance index (RI) and pulsatility index
(PI) in both arteries (p < 0.0001 vs. controls).
Biomarkers of hemolysis were found to correlate significantly with the RI
and PI indices. In the ophthalmic artery, the reticulocyte count showed a
moderate direct correlation with RI and with PI. In the central retinal
artery, hemoglobin showed a strong inverse correlation with RI and with
PI. Conclusion Orbital vascular resistance, as evaluated by Doppler velocimetry, is elevated
in patients with steady-state sickle cell anemia and shows a significant
correlation with biomarkers of hemolysis.
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Affiliation(s)
- Thiago de Oliveira Ferrão
- PhD, Radiologist, Assistant Professor in the Department of Medicine at the Universidade Federal de Sergipe (UFS), Aracaju, SE, Brazil
| | - Paulo Ricardo Martins-Filho
- PhD, Adjunct Professor in the Graduate Program in Health Sciences and Head of the Laboratory of Investigative Pathology at the Universidade Federal de Sergipe (UFS), Aracaju, SE, Brazil
| | - Cleverton Aragão
- Medical Student at the Universidade Federal de Sergipe (UFS), Aracaju, SE, Brazil
| | - Marlyson Santana
- Medical Student at the Universidade Federal de Sergipe (UFS), Aracaju, SE, Brazil
| | - Allan Nascimento
- Medical Student at the Universidade Federal de Sergipe (UFS), Aracaju, SE, Brazil
| | - Thayane Cardoso
- Medical Student at the Universidade Federal de Sergipe (UFS), Aracaju, SE, Brazil
| | - Rosana Cipolotti
- PhD, Pediatric Oncologist/Hematologist, Associate Professor in the Department of Medicine at the Universidade Federal de Sergipe (UFS), Aracaju, SE, Brazil
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Thein MS, Igbineweka NE, Thein SL. Sickle cell disease in the older adult. Pathology 2017; 49:1-9. [PMID: 27914684 PMCID: PMC10757825 DOI: 10.1016/j.pathol.2016.10.002] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Revised: 10/12/2016] [Accepted: 10/20/2016] [Indexed: 01/14/2023]
Abstract
Sickle cell disease (SCD) is an inherited haemoglobin disorder, associated with recurrent painful episodes, ongoing haemolytic anaemia and progressive multi-organ damage. Until the early 1990s, survival beyond the fourth decade for a patient with SCD was considered unusual and prompted case reports. Nowadays, in countries with developed health care systems, more than 90 percent of newborns with SCD survive into adulthood. Nevertheless, their life expectancy is still shortened by more than two decades compared to the general population. With an increasing life expectancy, SCD has now evolved into a debilitating disorder with substantial morbidity resulting from ongoing sickle cell vasculopathy and multi-organ damage. Limited data on health care issues of older adults with SCD poses multiple challenges to patients, their families and health care providers. In this review, we will address and discuss acute and chronic complications of SCD with a special focus on the older adult.
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Affiliation(s)
- Mya S Thein
- Sickle Cell Branch, National Heart Lung and Blood Institute, National Institute of Health, Bethesda, MD, USA
| | - Norris E Igbineweka
- Department of Haematology, Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom
| | - Swee Lay Thein
- Sickle Cell Branch, National Heart Lung and Blood Institute, National Institute of Health, Bethesda, MD, USA.
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Rodrigues DLG, Adegoke SA, Campos RDSM, Braga JAP, Figueiredo MS, Silva GS. Patients with sickle cell disease are frequently excluded from the benefits of transcranial doppler screening for the risk of stroke despite extensive and compelling evidence. ARQUIVOS DE NEURO-PSIQUIATRIA 2017; 75:15-19. [DOI: 10.1590/0004-282x20160175] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Accepted: 09/01/2016] [Indexed: 11/22/2022]
Abstract
ABSTRACT Transcranial doppler (TCD) is a strategic component of primary stroke prevention in children with sickle cell disease (SCD). This study was conducted to examine the TCD characteristics of children with SCD in nine different medical centers in Brazil. Methods: Transcranial doppler was performed in accordance with the Stroke Prevention Trial in Sickle Cell Anemia Protocol. Results: Of the 396 patients, 69.5% had homozygous SS hemoglobin. The TCD result was abnormal in 4.8%, conditional in 12.6%, inadequate in 4.3% and abnormally low in 1% of patients. The highest mean flow velocities were 121±23.83cm/s and 124±27.21cm/s in the left and right middle cerebral artery respectively. A total of 28.8% patients (mean age 9.19±5.92 years) were evaluated with TCD for the first time. Conclusions: The SCD patients were evaluated with TCD at an older age, representing an important missed opportunity for stroke prevention. Since TCD screening in patients with SCD is important to detect those at high risk for stroke, it is recommended that this screening should be made more readily available.
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Affiliation(s)
| | | | | | | | | | - Gisele Sampaio Silva
- Universidade Federal de São Paulo, Brasil; Hospital Israelita Albert Einstein, Brasil
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Transcranial Doppler in the evaluation of infants treated with retrograde ventriculosinus shunt. Childs Nerv Syst 2016; 32:2133-2142. [PMID: 27638718 DOI: 10.1007/s00381-016-3237-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2016] [Accepted: 08/30/2016] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Hydrocephalus is a prevalent condition among infants. Retrograde ventriculosinus shunt (RVSS) proposes a feasible option to treat hydrocephalus according to the principles presented by El-Shafei. In this essay, we analyze nuances and application of transcranial Doppler (TCD) in patients submitted to RVSS. METHODS We consecutively enrolled patients diagnosed with hydrocephalus after surgical repair of myelomeningocele from January 2010 to January 2012, users of Hospital das Clinicas, University of Sao Paulo. They were treated with RVSS. Patients enrolled to the study were consecutively evaluated in an outpatient basis with TCD in preoperative, immediate postoperative period, and late postoperative period (1 year). RESULTS Except for patient 3, there was an increase in mean flow velocity, decreased pulsatility index, and decreased resistance index in all vessels analyzed. DISCUSSION In our sample, transcranial Doppler could be used as a diagnostic and follow-up tool to evaluate hemodynamics and hydrodynamics in the preoperative and postoperative phases of RVSS. It was technically feasible in all patients, had close relation with other clinical and image parameters, and was sensitive to identify system malfunction.
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Transcranial Doppler Screening in a Regional Care Network for Sickle Cell Disease in the United Kingdom. J Pediatr Hematol Oncol 2016; 38:517-24. [PMID: 27379529 DOI: 10.1097/mph.0000000000000633] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The risk of stroke in children screened with transcranial Doppler ultrasound in the United Kingdom is not known. We evaluated a clinician-led program using a risk assessment modified from the STOP protocol. High-risk classification included abnormal velocities in the anterior cerebral artery, and single abnormal scan if initial velocity >220 cm/s (high abnormal) or if preceded by at least 2 conditional scans. In total, 1653 scans were performed in 542 children, followed for 2235 patient-years. Fifty-eight (10.7%) high-risk subjects were identified, including 18 (31%) with high abnormal, and 15 (26%) with previous conditional scans. In 2 (3%), abnormal velocity was restricted to the anterior cerebral artery. The estimated proportion of children at high risk, scanned before 6 years of age was >20%. There were 4 cases of acute ischemic stroke (AIS) and 2 of acute hemorrhagic stroke. The incidence of all stroke, AIS, and acute hemorrhagic stroke were 0.27, 0.18, and 0.09 per 100 patient-years, respectively. The proportion of children at high risk is higher than most previous estimates, partly as a result of our modified risk assessment. About 2 children per 1000 screened with transcranial Doppler ultrasound progress to AIS.
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Geard A, Pule GD, Chelo D, Bitoungui VJN, Wonkam A. Genetics of Sickle Cell-Associated Cardiovascular Disease: An Expert Review with Lessons Learned in Africa. OMICS : A JOURNAL OF INTEGRATIVE BIOLOGY 2016; 20:581-592. [PMID: 27726639 PMCID: PMC5067873 DOI: 10.1089/omi.2016.0125] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Sickle cell disease (SCD) vastly impacts the African continent and is associated with cardiovascular diseases. Stroke, kidney disease, and pulmonary hypertension are considered as proxies of severity in SCD with several genomic loci implicated in their heritability. The present expert review examined the current data on epidemiology and genetic risk factors of stroke, pulmonary hypertension, and kidney disease associated with SCD, as indexed in PubMed® and Google Scholar®. Studies collectively show that stroke and kidney disease each affect ∼10% of SCD patients, with pulmonary hypertension displaying a higher prevalence of 30% among adults with SCD. There is some evidence that these epidemiology figures may be an underestimate in SCD patients living in Africa. A modest number of publications have identified genetic factors involved in pathways regulating inflammation, coagulation, cell adhesion, heme degradation, α-globin and γ-globin production, and others, which contribute to the development risk of targeted cardiovascular phenotypes. However, in most cases, these studies have not been validated across populations. There is therefore an urgent need for large-scale genome-wide association, whole-exome and whole-genome studies, and multiomics research on cardiovascular diseases associated with SCD, particularly in Africa, to allow for proportional investment of global research funding on diseases that greatly impact the African continent. Ultimately, this will cultivate socially responsible research investments and identification of at-risk individuals with improved preventive medicine, which should be a cornerstone of global precision medicine.
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Affiliation(s)
- Amy Geard
- Division of Human Genetics, Departments of Medicine and Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Gift D. Pule
- Division of Human Genetics, Departments of Medicine and Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - David Chelo
- Department of Paediatrics, Faculty of Medicine and Biomedical Sciences, University of Yaoundé, Yaoundé, Cameroon
| | | | - Ambroise Wonkam
- Division of Human Genetics, Departments of Medicine and Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
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Abstract
Assessing intracranial pressure (ICP) remains a cornerstone in neurosurgical care. Invasive techniques for monitoring ICP remain the gold standard. The need for a reliable, safe and reproducible technique to non-invasively assess ICP in the context of early screening and in the neurocritical care environment is obvious. Numerous techniques have been described with several novel advances. While none of the currently available techniques appear independently accurate enough to quantify raised ICP, there is some promising work being undertaken.
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D'Andrea A, Conte M, Cavallaro M, Scarafile R, Riegler L, Cocchia R, Pezzullo E, Carbone A, Natale F, Santoro G, Caso P, Russo MG, Bossone E, Calabrò R. Transcranial Doppler ultrasonography: From methodology to major clinical applications. World J Cardiol 2016; 8:383-400. [PMID: 27468332 PMCID: PMC4958690 DOI: 10.4330/wjc.v8.i7.383] [Citation(s) in RCA: 78] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2016] [Revised: 04/29/2016] [Accepted: 05/17/2016] [Indexed: 02/06/2023] Open
Abstract
Non-invasive Doppler ultrasonographic study of cerebral arteries [transcranial Doppler (TCD)] has been extensively applied on both outpatient and inpatient settings. It is performed placing a low-frequency (≤ 2 MHz) transducer on the scalp of the patient over specific acoustic windows, in order to visualize the intracranial arterial vessels and to evaluate the cerebral blood flow velocity and its alteration in many different conditions. Nowadays the most widespread indication for TCD in outpatient setting is the research of right to left shunting, responsable of so called "paradoxical embolism", most often due to patency of foramen ovale which is responsable of the majority of cryptogenic strokes occuring in patients younger than 55 years old. TCD also allows to classify the grade of severity of such shunts using the so called "microembolic signal grading score". In addition TCD has found many useful applications in neurocritical care practice. It is useful on both adults and children for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoidal haemorrhage (caused by aneurysm rupture or traumatic injury), traumatic brain injury, brain stem death. It is used also to evaluate cerebral hemodynamic changes after stroke. It also allows to investigate cerebral pressure autoregulation and for the clinical evaluation of cerebral autoregulatory reserve.
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Affiliation(s)
- Antonello D'Andrea
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Marianna Conte
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Massimo Cavallaro
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Raffaella Scarafile
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Lucia Riegler
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Rosangela Cocchia
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Enrica Pezzullo
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Andreina Carbone
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Francesco Natale
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Giuseppe Santoro
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Pio Caso
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Maria Giovanna Russo
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Eduardo Bossone
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
| | - Raffaele Calabrò
- Antonello D'Andrea, Marianna Conte, Massimo Cavallaro, Raffaella Scarafile, Lucia Riegler, Rosangela Cocchia, Enrica Pezzullo, Andreina Carbone, Francesco Natale, Giuseppe Santoro, Pio Caso, Maria Giovanna Russo, Raffaele Calabrò, Integrated Diagnostic Cardiology, Second University of Naples, AORN "dei Colli", Monaldi Hospital, 80121 Naples, Italy
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Crosby LE, Joffe NE, Davis B, Quinn CT, Shook L, Morgan D, Simmons K, Kalinyak KA. Implementation of a Process for Initial Transcranial Doppler Ultrasonography in Children With Sickle Cell Anemia. Am J Prev Med 2016; 51:S10-6. [PMID: 27320459 PMCID: PMC4924807 DOI: 10.1016/j.amepre.2016.01.021] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Revised: 01/13/2016] [Accepted: 01/22/2016] [Indexed: 11/27/2022]
Abstract
Stroke, a devastating complication of sickle cell anemia (SCA), can cause irreversible brain injury with physical and cognitive deficits. Transcranial Doppler ultrasonography (TCD) is a non-invasive tool for identifying children with SCA at highest risk of stroke. National guidelines recommend that TCD screening begin at age 2 years, yet there is research to suggest less than half of young children undergo screening. The purpose of this project was to use quality improvement methods to improve the proportion of patients aged 24-27 months who successfully completed their initial TCD from 25% to 75% by December 31, 2013. Quality improvement methods (e.g., process mapping, simplified failure mode effect analysis, and plan-do-study-act cycles) were used to develop and test processes for identifying eligible patients, scheduling TCDs, preparing children and families for the first TCD, and monitoring outcomes (i.e., TCD protocol). Progress was tracked using a report of eligible patients and a chart showing the age in months for the first successful TCD (population metric). As of December 2013, 100% of eligible patients successfully completed their initial TCD screen; this improvement was maintained for the next 20 months. In November 2014, a Welch's one-way ANOVA was conducted. Results showed a statistically significant difference between the average age of first TCD for eligible patients born in 2009 and eligible patients born during the intervention period (2010-2013; F[1,11.712]=16.03, p=0.002). Use of quality improvement methods to implement a TCD protocol was associated with improved TCD screening rates in young children with SCA.
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Affiliation(s)
- Lori E Crosby
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; College of Medicine, University of Cincinnati, Cincinnati, Ohio.
| | - Naomi E Joffe
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; College of Medicine, University of Cincinnati, Cincinnati, Ohio
| | - Blair Davis
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Charles T Quinn
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; College of Medicine, University of Cincinnati, Cincinnati, Ohio
| | - Lisa Shook
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; College of Medicine, University of Cincinnati, Cincinnati, Ohio
| | - Darice Morgan
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Kenya Simmons
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Karen A Kalinyak
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; College of Medicine, University of Cincinnati, Cincinnati, Ohio
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Long-term treatment follow-up of children with sickle cell disease monitored with abnormal transcranial Doppler velocities. Blood 2016; 127:1814-22. [DOI: 10.1182/blood-2015-10-675231] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Accepted: 01/29/2016] [Indexed: 11/20/2022] Open
Abstract
Key PointsChildren with normalized TCD on transfusions were safely switched to hydroxyurea treatment, but trimestrial Doppler follow-up is required. Allogeneic transplant allowed the safe stop of transfusions in all patients, even in those with abnormal velocities before transplant.
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Abnormal transcranial Doppler cerebral blood flow velocity and blood pressure profiles in children with syndromic craniosynostosis and papilledema. J Craniomaxillofac Surg 2016; 44:465-70. [PMID: 26857754 DOI: 10.1016/j.jcms.2016.01.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Revised: 12/09/2015] [Accepted: 01/04/2016] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE Children with syndromic craniosynostosis are at risk of intracranial hypertension. This study aims to examine patient profiles of transcranial Doppler (TCD) cerebral blood flow velocity (CBFv) and systemic blood pressure (BP) in subjects with and without papilledema at the time of surgery, and subsequent effect of cranial vault expansion. METHODS Prospective study of patients treated at a national referral center. Patients underwent TCD of the middle cerebral artery 1 day before and 3 weeks after surgery. Measurements included mean CBFv, peak systolic velocity, and end diastolic velocity; age-corrected resistive index (RI) was calculated. Systemic BP was recorded. Papilledema was used to indicate intracranial hypertension. RESULTS Twelve patients (mean age 3.1 years, range 0.4-9.5) underwent TCD; 6 subjects had papilledema. Pre-operatively, patients with papilledema, in comparison to those without, had higher TCD values, RI, and BP (all p = 0.04); post-operatively, the distinction regarding BP remained (p = 0.04). There is a significant effect of time following vault surgery with a decrease in RI (p < 0.01). CONCLUSION Patients with syndromic craniosynostosis who have papilledema have a different TCD profile with raised BP. Vault surgery results in increased CBFv and decrease in RI, however the associated systemic BP response to intracranial hypertension remained at short-term follow-up.
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D'Andrea A, Conte M, Scarafile R, Riegler L, Cocchia R, Pezzullo E, Cavallaro M, Carbone A, Natale F, Russo MG, Gregorio G, Calabrò R. Transcranial Doppler Ultrasound: Physical Principles and Principal Applications in Neurocritical Care Unit. J Cardiovasc Echogr 2016; 26:28-41. [PMID: 28465958 PMCID: PMC5224659 DOI: 10.4103/2211-4122.183746] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Transcranial Doppler (TCD) ultrasonography is a noninvasive ultrasound study, which has been extensively applied on both outpatient and inpatient settings. It involves the use of a low-frequency (≤2 MHz) transducer, placed on the scalp, to insonate the basal cerebral arteries through relatively thin bone windows and to measure the cerebral blood flow velocity and its alteration in many different conditions. In neurointensive care setting, TCD is useful for both adults and children for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, and brain stem death. It also allows to investigate the cerebrovascular autoregulation in setting of carotid disease and syncope. In this review, we will describe physical principles underlying TCD, flow indices most frequently used in clinical practice and critical care applications in Neurocritical Unit care.
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Affiliation(s)
- Antonello D'Andrea
- Department of Cardiology, Integrated Diagnostic Cardiology, Second University of Neaples, Monaldi Hospital, Neaples, Italy
| | - Marianna Conte
- Department of Cardiology, Integrated Diagnostic Cardiology, Second University of Neaples, Monaldi Hospital, Neaples, Italy
| | - Raffaella Scarafile
- Department of Cardiology, Integrated Diagnostic Cardiology, Second University of Neaples, Monaldi Hospital, Neaples, Italy
| | - Lucia Riegler
- Department of Cardiology, Integrated Diagnostic Cardiology, Second University of Neaples, Monaldi Hospital, Neaples, Italy
| | - Rosangela Cocchia
- Department of Cardiology, Integrated Diagnostic Cardiology, Second University of Neaples, Monaldi Hospital, Neaples, Italy
| | - Enrica Pezzullo
- Department of Cardiology, Integrated Diagnostic Cardiology, Second University of Neaples, Monaldi Hospital, Neaples, Italy
| | - Massimo Cavallaro
- Department of Cardiology, Integrated Diagnostic Cardiology, Second University of Neaples, Monaldi Hospital, Neaples, Italy
| | - Andreina Carbone
- Department of Cardiology, Integrated Diagnostic Cardiology, Second University of Neaples, Monaldi Hospital, Neaples, Italy
| | - Francesco Natale
- Department of Cardiology, Integrated Diagnostic Cardiology, Second University of Neaples, Monaldi Hospital, Neaples, Italy
| | - Maria Giovanna Russo
- Department of Cardiology, Integrated Diagnostic Cardiology, Second University of Neaples, Monaldi Hospital, Neaples, Italy
| | - Giovanni Gregorio
- Department of Cardiology, San Luca Hospital, Vallo della Lucania, Salerno, Italy
| | - Raffaele Calabrò
- Department of Cardiology, Integrated Diagnostic Cardiology, Second University of Neaples, Monaldi Hospital, Neaples, Italy
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