A prospective longitudinal brain morphometry study of children with sickle cell disease.

BACKGROUND AND PURPOSE: Age-related changes in brain morphology are crucial to understanding the neurobiology of sickle cell disease. We hypothesized that the growth trajectories for total GM volume, total WM volume, and regional GM volumes are altered in children with sickle cell disease compared with controls. MATERIALS AND METHODS: We analyzed T1-weighted images of the brains of 28 children with sickle cell disease (mean baseline age, 98 months; female/male ratio, 15:13) and 28 healthy age- and sex-matched controls (mean baseline age, 99 months; female/male ratio, 16:12). The total number of MR imaging examinations was 141 (2-4 for each subject with sickle cell disease, 2-3 for each control subject). Total GM volume, total WM volume, and regional GM volumes were measured by using an automated method. We used the multilevel-model-for-change approach to model growth trajectories. RESULTS: Total GM volume in subjects with sickle cell disease decreased linearly at a rate of 411 mm(3) per month. For controls, the trajectory of total GM volume was quadratic; we did not observe a significant linear decline. For subjects with sickle cell disease, we found 35 brain structures that demonstrated age-related GM volume reduction. Total WM volume in subjects with sickle cell disease increased at a rate of 452 mm(3) per month, while the trajectory of controls was quadratic. CONCLUSIONS: There was a significant age-related decrease in total GM volume in children with sickle cell disease. The GM volume reduction was spatially distributed widely across the brain, primarily in the frontal, parietal, and occipital lobes. Total WM volume in subjects with sickle cell disease increased at a lower rate than for controls.

Correlation of prenatal and postnatal MRI findings in schizencephaly.

BACKGROUND AND PURPOSE: Schizencephaly is a rare malformation of the brain characterized by a gray matter-lined defect extending from the pial surface to the lateral ventricles. The purpose of this study was to correlate imaging findings of schizencephaly and associated anomalies on fetal and postnatal MR imaging and assess possible changes that may occur from the prenatal-to-postnatal state. MATERIALS AND METHODS: A retrospective review of subjects with schizencephaly who had both pre- and postnatal MR imaging was performed. Subject age, cleft type, number, location, and features of the defects and associated anomalies were recorded. Normalized dimensions of the defect and ipsilateral ventricle were measured and correlated to changes in the clefts between pre- and postnatal imaging. RESULTS: Ten subjects with 18 clefts (8 bilateral) were included. Most defects (83%) were open on prenatal MR imaging, but 47% of those were found to have subsequently closed on postnatal imaging. Evidence of prior hemorrhage was seen in 83%. Prenatal MR imaging detected all cases of an absent septum pellucidum but detected a fraction of gross polymicrogyria and missed all cases of optic nerve hypoplasia. The normalized ipsilateral ventricular and inner and middle width dimensions of the defects were significantly decreased at postnatal imaging (P < .05). The widths of the defects, ventricular width, and presence of hemorrhage were not predictors of closure of prenatally diagnosed open defects (P > .05). CONCLUSIONS: In our series, nearly half of prenatally open schizencephaly defects had closed on postnatal imaging. Prenatal MR imaging was only able to demonstrate some of the associated anomalies.

CT and MRI of pediatric skull lesions with fluid-fluid levels.

Fluid-fluid levels can occur whenever different fluid densities are contained within a cystic or compartmentalized lesion, usually related to the evolution of hematoma or necrosis. Review of the literature demonstrated that throughout the skeletal system, the most common etiology for fluid-fluid levels is aneurysmal bone cyst, but there are no dedicated studies of the pediatric calvaria, to our knowledge. In this report, we present clinicopathologic characteristics and CT and MR imaging of 11 patients with pediatric skull mass lesions demonstrating fluid-fluid levels. MR imaging demonstrated more fluid-fluid levels compared with CT in all cases. The etiologies of skull lesions with fluid-fluid levels were Langerhans cell histiocytosis in 4 (36.6%), aneurysmal bone cysts in 3 (27.2%), cephalohematoma in 3 (27.2%), and metastatic neuroblastoma in 1 (9%). Radiologists should be aware of the other etiologies of calvarial lesions with fluid-fluid levels in the pediatric skull.

Cerebral diffusion tensor MR tractography in tuberous sclerosis complex: correlation with neurologic severity and tract-based spatial statistical analysis.

BACKGROUND AND PURPOSE: The neurologic significance of residual cerebral white matter tracts, identified on diffusion tensor tractography, has not been well studied in tuberous sclerosis complex. We aimed to correlate the quantity of reconstructed white matter tracts with the degree of neurologic impairment of subjects with the use of DTI and determined differences in white matter integrity between patients with tuberous sclerosis complex and controls with the use of voxelwise analysis. MATERIALS AND METHODS: In this case-control study, 16 patients with tuberous sclerosis complex and 12 control subjects underwent DTI. Major white matter tracts, comprising bilateral PF and CF, were reconstructed and assessed for quantity, represented by NOP and NOF. A neurologic severity score, based on the presence of developmental disability, seizure, autism, and other neuropsychiatric disorders, was calculated for each subject. We then correlated this score with white matter quantity. Voxelwise tract-based spatial statistics was used to determine differences in FA, axial, and radial diffusivity values between the tuberous sclerosis complex group and the control subjects. RESULTS: NOP and NOF of CF, bilateral PF, and MWT in the tuberous sclerosis complex group were all significantly lower than those in the control subjects (P < .05). The neurologic severity score was moderately negatively correlated with NOF and NOP regarding CF (r = -.70; r = -.75), bilateral PF (r = -.66; r = -.68), and MWT (r = -.71; r = -.74). Tract-based spatial statistics revealed that patients with tuberous sclerosis complex showed a widespread reduction (P < .05) in FA and axial diffusivity in most cerebral white matter regions. CONCLUSIONS: Patients with tuberous sclerosis complex with reduced residual white matter were neurologically more severely affected. Tract-based spatial statistics revealed decreased FA and axial diffusivity of the cerebral white matter in the tuberous sclerosis complex group, suggesting reduced axonal integrity.

Role of diffusion MRI in diagnosis of spinal cord infarction in children.

Anterior spinal artery (ASA) infarction is a rare but well-described cause of flaccid paraparesis in adults, presenting with a high thoracic spinothalamic sensory level and preservation of dorsal column function. Careful sensory examination, demonstrating loss of spinothalamic modalities with preservation of dorsal column modalities, supports a clinical diagnosis of ASA infarction. Findings on conventional MRI of the spinal cord are often non-specific, and diffusion-weighted imaging (DWI) is not routinely performed. We describe four children with ASA infarction after minor trauma. DWI was performed in all cases and confirmed the clinical diagnosis.

Mega-corpus callosum, polymicrogyria, and psychomotor retardation: confirmation of a syndromic entity.

A mega-corpus callosum (CC) is not a common manifestation of neurological disease. Previous reports of patients with a constellation of findings including megalencephaly, perisylvian polymicrogyria, distinct facies, psychomotor retardation and mega-corpus callosum were designated as having megalencephaly, mega-corpus callosum, and complete lack of motor development [OMIM 603387; also referred to as megalencephaly-polymicrogyria-mega-corpus callosum (MEG-PMG-MegaCC)] syndrome. Three patients were initially reported with this syndrome, and a fourth was reported recently. Another case had similar findings in utero and upon autopsy. We present an additional patient who conforms to this phenotype; however, he is not megalencephalic, but has a normal head circumference in the setting of short stature. This patient is also noted to have abnormal saccades and mask-like facies. His motor function is more developed than in the other reported patients and was further improved by treatment with L-DOPA/carbidopa, which was started because of his extrapryramidal symptoms and signs which were associated with low cerebral spinal fluid (CSF) catecholamine levels.

Magnetoencephalography for pediatric epilepsy: how we do it.

Magnetoencephalography (MEG) is increasingly being used in the preoperative evaluation of pediatric patients with epilepsy. The ability to noninvasively localize ictal onset zones (IOZ) and their relationships to eloquent functional cortex allows the pediatric epilepsy team to more accurately assess the likelihood of postoperative seizure freedom, while more precisely prognosticating the potential functional deficits that may be expected from resective surgery. Confirmation of clinically suggested multifocality may result in a recommendation against resective surgery because the probability of seizure freedom will be low. Current paradigms for motor and somatosensory testing are robust. Paradigms allowing localization of those regions necessary for competent language function, though promising, are under continuous optimization. MR imaging white matter trajectory data, created from diffusion tensor imaging obtained in the same setting as the localization brain MR imaging, provide ancillary information regarding connectivity of the IOZ to sites of rapid secondary spread and the spatial relationship of the IOZ to functionally important white matter bundles, such as the corticospinal tracts. A collaborative effort between neuroradiology, neurology, neurosurgery, neuropsychology, technology, and physics ensures successful implementation of MEG within a pediatric epilepsy program.

Non-accidental brain trauma in infants: diffusion imaging, contributions to understanding the injury process.

Analysis of MRI diffusion images from 33 infants suffering from non-accidental trauma reveals five patterns of injury. These are diffuse supratentorial hypoxic ischemic, watershed hypoxic ischemic, venous infarction, diffuse axonal injury and contusion.

3T magnetic resonance arteriography in pediatric cerebrovascular disease.

Based on a series of 20 cases, eight with 1.5T and 3T MRA's, 3T MRA provides improvement over 1.5T MRA in imaging the vessels of the circle of Willis in pediatric patients with vascular disease. Dephasing artifact is reduced and laminal stenosis or occlusions become better depicted.

Acute necrotizing encephalopathy of childhood: correlation of MR findings and clinical outcome.

BACKGROUND AND PURPOSE: The clinical outcome of acute necrotizing encephalopathy of childhood (ANEC), an encephalopathy characterized by symmetrical involvement of the thalami, has historically been poor, but recent studies have reported better outcomes. By devising a MR imaging scoring system, we determined the relationship between characteristic MR findings and clinical outcome of patients with ANEC. METHODS: MR studies of 12 patients with ANEC were retrospectively reviewed. A MR imaging score was calculated for each patient according to the presence of hemorrhage, cavitation, and location of lesions. Clinical outcome of the patients was assessed, yielding outcome categories based on health state utility value. Spearman rank test was used to correlate the MR imaging score with clinical outcome of the patients. RESULTS: Statistically significant correlation (r = 0.76, P = .001) was found between the MR score and the outcome category. The thalami were involved in all 12 patients, brain stem in 10, cerebral white matter in 8, and cerebellar white matter in 4. Hemorrhage was present in 5 patients and cavitation in 4. Clinical outcome category was 1 in 2 patients, 2 in 8 patients, and 3 in 2 patients. No patients were in category 4. CONCLUSION: There is a significant and positive correlation between the clinical outcome and the MR imaging score in patients with ANEC. The relation between clinical outcome and each individual MR feature remains to be determined. Patients with ANEC may have a better clinical outcome than has been previously reported.

Primary intracranial atypical teratoid/rhabdoid tumors of infancy and childhood: MRI features and patient outcomes.

BACKGROUND AND PURPOSE: Primary atypical teratoid/rhabdoid tumors (AT/RTs) are rare malignant intracranial neoplasms, usually occurring in young children. The objectives of this study were to characterize the MR imaging features and locations of primary intracranial AT/RTs, to determine the frequency of disseminated disease in the central nervous system (CNS) at diagnosis and postoperatively, and to assess patient outcomes. METHODS: The preoperative cranial MR images of 13 patients with AT/RTs were retrospectively reviewed for evaluation of lesion location, size, MR signal intensity and enhancement characteristics, and the presence of disseminated intracranial tumor. Postoperative MR images of the head and spine for 17 patients were reviewed for the presence of locally recurrent or residual tumor and disseminated neoplasm. Imaging data were correlated with patient outcomes. RESULTS: Patients ranged in age from 4 months to 15 years (median age, 2.9 years). Primary AT/RTs were intra-axial in 94% of patients. The single primary extra-axial lesion was located in the cerebellopontine angle cistern. AT/RTs were infratentorial in 47%, supratentorial in 41%, and both infra- and supratentorial in 12%. A germ-line mutation of the hSNF5/INI1 tumor-suppressor gene was responsible for the simultaneous occurrence of an intracranial AT/RT and a malignant renal rhabdoid tumor in a 4-month-old patient. Mean tumor sizes were 3.6 x 3.8 x 3.9 cm. On short TR images, AT/RTs typically had heterogeneous intermediate signal intensity, as well as zones of low (54%), high (8%), or both low and high (31%) signal intensity from cystic and/or necrotic regions, hemorrhage, or both, respectively. On long TR/long TE images, solid portions of AT/RTs typically had heterogeneous intermediate-to-slightly-high signal intensity with additional zones of high (54%) or both high and low signal intensity (38%), secondary to cystic and/or necrotic regions, edema, prior hemorrhage, and/or calcifications. AT/RT had isointense and/or slightly hyperintense signal intensity relative to gray matter on fluid-attenuated inversion-recovery (FLAIR) and long TR/long TE images, and showed restricted diffusion. All except 1 AT/RT showed contrast enhancement. The fraction of tumor volume showing enhancement was greater than two thirds in 58%, between one third and two thirds in 33%, and less than one third in 9%. Disseminated tumor in the leptomeninges was seen with MR imaging in 24% of patients at diagnosis/initial staging and occurred in another 35% from 4 months to 2.8 years (mean, 1.1 years) after surgery and earlier imaging examinations with negative findings. The overall 1-year and 5-year survival probabilities were 71% and 28%, respectively. Patients with MR imaging evidence of disseminated leptomeningeal tumor had a median survival rate of 16 months compared with 149 months for those without disseminated tumor (P < .004, logrank test). CONCLUSION: AT/RTs are typically intra-axial lesions, which can be infra- and/or supratentorial. The unenhanced and enhanced MR imaging features of AT/RT are often variable secondary to cystic/necrotic changes, hemorrhage, and/or calcifications. Poor prognosis is associated with MR imaging evidence of disseminated leptomeningeal tumor.

Decreased expression of smooth muscle alpha-actin results in decreased contractile function of the mouse bladder.

PURPOSE: Smooth muscle alpha-actin (SMalphaA) is an important actin isoform for functional contractility in the mouse bladder. Alterations in the expression of SMalphaA have been associated with a variety of bladder pathological conditions. Recently, a SMalphaA-null mouse was generated and differences in vascular tone and contractility were observed between wild-type and SMalphaA-null mice suggesting alterations in function of vascular smooth muscle. We used SMalphaA-null mice to explore the hypothesis that SMalphaA is necessary for normal bladder function. MATERIALS AND METHODS: Reverse transcriptase polymerase chain reaction, Western blotting and immunohistochemical staining were used to confirm the absence of SMalphaA transcript and protein in the bladder of SMalphaA-null mice. In vitro bladder contractility compared between bladder rings harvested from wild-type and SMalphaA-null mice was determined by force measurement following electrical field stimulation (EFS), and exposure to chemical agonists and antagonists including KCl, carbachol, atropine and tetrodotoxin. Resulting force generation profiles for each tissue and agent were analyzed. RESULTS: There was no detectable SMalphaA transcript and protein expression in the bladder of SMalphaA-null mice. Nine wild-type and 9 SMalphaA-null mice were used in the contractility study. Bladders from SMalphaA-null mice generated significantly less force than wild-type mice in response to EFS after KCl. Similarly, bladders from SMalphaA-null mice generated less force than wild-type mice in response to pretreatment EFS, and EFS after carbachol and atropine, although the difference was not significant. Surprisingly, the bladders in SMalphaA-null mice appeared to function normally and showed no gross or histological abnormalities. CONCLUSIONS: SMalphaA appears to be necessary for the bladder to be able to generate normal levels of contractile force. No functional deficits were observed in the bladders of these animals but no stress was placed on these bladders. To our knowledge this study represents the first report to demonstrate the importance of expression of SMalphaA in force generation in the bladder.

5alpha-Androstane-3alpha,17beta-diol activates pathway that resembles the epidermal growth factor responsive pathways in stimulating human prostate cancer LNCaP cell proliferation.

5alpha-Androstane-3alpha,17beta-diol (3alpha-diol) is considered to have no androgenic effects in androgen target organs unless it is oxidized to 5alpha-dihydrotestosterone (5alpha-DHT). We used microarray and bioinformatics to identify and compare 3alpha-diol and 5alpha-DHT responsive gene in human prostate LNCaP cells. Through a procedure called 'hypervariable determination', a similar set of 30 responsive genes involving signal transduction, transcription regulation, and cell proliferation were selected in 5alpha-DHT-, 3alpha-diol-, and epidermal growth factor (EGF)-treated samples. F-means cluster and networking procedures showed that the responsive pattern of these genes was more closely related between 3alpha-diol and EGF than between 5alpha-DHT and 3alpha-diol treatments. We conclude that 3alpha-diol is capable of stimulating prostate cell proliferation by eliciting EGF-like pathway in conjunction with androgen receptor pathway.

Acute diffusion abnormalities in the hippocampus of children with new-onset seizures: the development of mesial temporal sclerosis.

We studied the role of early diffusion-weighted imaging DWI in the investigation of children with new-onset prolonged seizures which eventually result in unilateral hippocampal sclerosis (HS). We carried out MRI on five children aged 17 months to 7 years including conventional and diffusion-weighted sequences. We calculated apparent diffusion coefficients (ADC) for the affected and the normal opposite hippocampus. Follow-up examinations were performed, including DWI and ADC measurements in four. We studied four children within 3 days of the onset of prolonged psychomotor seizures and showed increased signal on T2-weighted images, and DWI, indicating restricted diffusion, throughout the affected hippocampus. The ADC were reduced by a mean of 14.4% in the head and by 15% in the body of the hippocampus. In one child examined 15 days after the onset of seizures, the ADC were the same on both sides. All five patients showed hippocampal atrophy on follow-up 2-18 months later. In the four patients in whom ADC were obtained on follow-up, they were increased by 19% in the head and 17% in the body. DWI may represent a useful adjunct to conventional MRI for identifying acute injury to the hippocampus which results in sclerosis.

Magnetic resonance imaging of carotid artery abnormalities in patients with sphenoid sinusitis.

Sphenoid sinusitis is unusual in children, but when it occurs, it can lead to serious intracranial complications. We show the value of MRI in demonstrating intracranial abnormalities due to sphenoid sinus infection, particularly those involving the internal carotid arteries and cavernous sinuses. We reviewed our imaging experience of sphenoid sinusitis and found four patients with ICA narrowing who had undergone MR evaluation including conventional and diffusion imaging. MR angiography was also performed in three patients to determine the extent of ICA narrowing. Narrowing of ICA was found in the cavernous segment in all patients and in the supraclinoid segment in three. Cerebral infarction was found in two patients. In one patient the cavernous sinus showed hyperintensity on diffusion-weighted images and hypointensity on apparent diffusion coefficient map, suggesting reduced diffusion. Although infrequent in children, sphenoid sinus infection should be considered as a possible cause of intracranial infection, particularly in teenagers. Early recognition of cavernous sinus involvement and ICA narrowing may lead to prompt treatment and hence a more favorable outcome.

Diffusion-weighted imaging in acute bacterial meningitis in infancy.

Bacterial meningitis is frequently fatal or leads to severe neurological impairment. Complications such as vasculitis, resulting in infarcts, should be anticipated and dealt with promptly. Our aim was to demonstrate the complications of meningitis by diffusion weighted imaging (DWI) in patients who deteriorated despite therapy. We studied 13 infants between the ages of 1 day and 32 months who presented with symptoms ranging from fever and vomiting to seizures, encephalopathy and coma due to bacterial meningitis, performing MRI, including DWI, 2-5 days after presentation. Multiple infarcts were found on DWI in 12 of the 13, most commonly in the frontal lobes (in 10). Global involvement was seen in four children, three of whom died; the fourth had a very poor outcome. In one case abnormalities on DWI were due to subdural empyemas. We diagnosed vasculitis in three of five patients studied with MRA. We think DWI an important part of an MRI study in infants with meningitis. Small cortical or deep white-matter infarcts due to septic vasculitis can lead to tissue damage not easily recognized on routine imaging and DWI can be used to confirm that extra-axial collections represent empyemas.

Ataxia-telangiectasia: the pattern of cerebellar atrophy on MRI.

We describe MRI of the brain in 19 patients with ataxia-telangiectasia (AT) and correlate the appearances with the degree of neurologic deficit. We examined 10 male and nine female patients; 17 were aged between 2 and 12 years (mean 8 years) but a woman and her brother were 35 and 38 years old, and had a variant of AT. Ataxia was the first recognized sign of the disease in every patient. We detected the following patterns of cerebellar atrophy: in the youngest patient, aged 2 years, the study was normal; in the five next youngest patients 3-7 years of age, the lateral cerebellum and superior vermis showed the earliest changes of atrophy; and all but one of the other patients had moderate to marked diffuse atrophy of vermis and cerebellar hemispheres. There were 12 patients aged 9 years and above; one, who was normal, was 9 years old. The five patients who at the time of examination were unable to walk all had diffuse atrophy involving both vermis and cerebellar hemispheres.

Incidental intracranial hemorrhage after uncomplicated birth: MRI before and after neonatal heart surgery.

We investigated the prevalence of intracranial hemorrhage (ICH) before and after neonatal heart surgery. We carried out pre- and postoperative MRI looking for brain lesions in 24 full-term newborns with known congenital heart disease. They underwent heart surgery with cardiopulmonary bypass (CPB), usually with deep hypothermic circulatory arrest (DHCA). The first MRI was 1-22 days after birth. There were 21 children born after uncomplicated vaginal delivery and three delivered by cesarean section (CS). ICH was seen in 13 (62%) of the vaginal delivery group but in none of the CS group. We saw subdural bleeding along the inferior surface of the tentorium in 11 (52%) and supratentorially in six (29%) of the 21 children with ICH. Small hemorrhages were present in the choroid plexus in seven (33%), in the parenchyma in one (5%) and in the occipital horn in one (5%). There were 26 foci of bleeding in these 21 patients (1.2 per patient). None was judged by formal neurologic examination to be symptomatic from the hemorrhage. Follow-up MRI after cardiac surgery was obtained in 23 children, showing 37 foci of ICH (1.6 per patient), but all appeared asymptomatic. Postoperatively, ICH had increased in 10 children (43%), was unchanged in seven (30%) and was less extensive in six (26%).

Plexiform neurofibromas in NF1: toward biologic-based therapy.

Neurofibromatosis type 1 (NF1) is one of the most common neurogenetic diseases affecting adults and children. Neurofibromas are one of the most common of the protean manifestations of NF1. Plexiform neurofibromas, which will frequently cause cosmetic abnormalities, pain, and neurologic deficits, are composed of "neoplastic" Schwann cells accompanied by other participating cellular and noncellular components. There is increasing evidence that loss of NF1 expression in neoplastic Schwann cells is associated with elevated levels of activated RAS, supporting the notion that the NF1 gene product, neurofibromin, acts as a growth regulator by inhibiting ras growth-promoting activity. In addition, there is increasing evidence that other cooperating events, which may be under cytokine modulation, are important for neurofibroma development and growth. Treatment of plexiform neurofibromas has been empiric, with surgery being the primary option for those with progressive lesions causing a major degree of morbidity. The efficacy of alternative treatment approaches, including the use of antihistamines, maturation agents, and antiangiogenic drugs, has been questionable. More recently, biologic-based therapeutic approaches, using drugs that target the molecular genetic underpinnings of plexiform neurofibromas or cytokines believed important in tumor growth, have been initiated. Evaluation of such trials is hindered by the unpredictable natural history of plexiform neurofibromas and difficulties in determining objective response in tumors that are notoriously large and irregular in shape. Innovative neuroimaging techniques and the incorporation of quality-of-life scales may be helpful in evaluation of therapeutic interventions. The ability to design more rational therapies for NF1-associated neurofibromas is heavily predicated on an improved understanding of the molecular and cellular biology of the cells involved in neurofibroma formation and growth.

Silent infarcts in children with sickle cell anemia and abnormal cerebral artery velocity.

BACKGROUND: A substantial minority of neurologically normal children with sickle cell disease have lesions consistent with cerebral infarction as seen on magnetic resonance imaging (MRI). OBJECTIVES: To determine if transfusion therapy affects the rate at which silent infarcts develop and to evaluate the contribution of MRI of the brain to stroke prediction by transcranial Doppler (TCD) ultrasonography. STUDY DESIGN: Children with elevated TCD ultrasonographic velocity were randomized to receive long-term transfusion therapy or standard care. Magnetic resonance imaging of the brain was obtained at randomization, annually, and with clinical neurologic events. The risk for new silent lesions and/or stroke was compared for each treatment arm. RESULTS: Among the 37% of subjects with silent infarcts, those receiving standard care were significantly more likely to develop new silent lesions or stroke than were those who received transfusion therapy. For subjects receiving standard care, those with lesions at baseline were significantly more likely to develop stroke or new silent lesions than those whose MRI studies showed no abnormality. CONCLUSIONS: Transfusion therapy lowers the risk for new silent infarct or stroke for children having both abnormal TCD ultrasonographic velocity and silent infarct. However, those with both abnormalities who are not provided transfusion therapy are at higher risk for developing a new silent infarct or stroke than are those whose initial MRI showed no abnormality. The finding of a silent infarct reinforces the need for TCD ultrasonographic screening and consideration of transfusion therapy if the abnormalities are seen. Similarly, elevated TCD ultrasonographic velocity warrants MRI of the brain because children with both abnormalities seem to be at increased risk for developing new silent infarct or stroke.