BACKGROUND AND OBJECTIVES: The Management of Myelomeningocele Study (MOMS), a randomized trial of prenatal versus postnatal repair for myelomeningocele, found that prenatal surgery resulted in reduced hindbrain herniation and need for shunt diversion at 12 months of age and better motor function at 30 months. In this study, we compared adaptive behavior and other outcomes at school age (5.9-10.3 years) between prenatal versus postnatal surgery groups. METHODS: Follow-up cohort study of 161 children enrolled in MOMS. Assessments included neuropsychological and physical evaluations. Children were evaluated at a MOMS center or at a home visit by trained blinded examiners. RESULTS: The Vineland composite score was not different between surgery groups (89.0 6 9.6 in the prenatal group versus 87.5 6 12.0 in the postnatal group; P = .35). Children in the prenatal group walked without orthotics or assistive devices more often (29% vs 11%; P = .06), had higher mean percentage scores on the Functional Rehabilitation Evaluation of Sensori-Neurologic Outcomes (92 6 9 vs 85 6 18; P , .001), lower rates of hindbrain herniation (60% vs 87%; P , .001), had fewer shunts placed for hydrocephalus (49% vs 85%; P , .001) and, among those with shunts, fewer shunt revisions (47% vs 70%; P = .02) than those in the postnatal group. Parents of children repaired prenatally reported higher mean quality of life z scores (0.15 6 0.67 vs 0.11 6 0.73; P = .008) and lower mean family impact scores (32.5 6 7.8 vs 37.0 6 8.9; P = .002). CONCLUSIONS: There was no significant difference between surgery groups in overall adaptive behavior. Long-term benefits of prenatal surgery included improved mobility and independent functioning and fewer surgeries for shunt placement and revision, with no strong evidence of improved cognitive functioning. WHAT'S KNOWN ON THIS SUBJECT: Prenatal surgery was found to reduce hydrocephalus and hindbrain herniation in infants with myelomeningocele as well as improve motor function at 30 months of age. WHAT THIS STUDY ADDS: Among school-aged children with myelomeningocele whose mothers were randomly assigned to surgery before birth versus standard postnatal repair, there were no significant differences in adaptive behavior, but motor function and quality of life were better.

Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2-relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2-56.8 ml/100 g/min; oxygen extraction fraction = 0.39-0.50) relative to controls (interquartile range cerebral blood flow = 40.8-46.3 ml/100 g/min; oxygen extraction fraction = 0.33-0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the premise that magnetic resonance imaging-based assessment of elevated oxygen extraction fraction might be a viable screening tool for evaluating stroke risk in adults with sickle cell anaemia.

Silent cerebral infarcts (SCIs) are the most commonly recognized cause of neurologic injury in patients with sickle cell anemia (SCA), identified in $20% of children. In children with SCA, SCIs are associated with an average 5 full-scale IQ point decrement, 1 poor academic performance, 2 and future overt strokes. 3 Recently, Bernaudin et al 4 reported that in children with SCA, the cumulative risk for SCI was 19.2% by age 8 years, 32.4% by age 14 years, and 39.1% by age 18 years. Very little is known about the prevalence of SCI in adults with SCA. We tested the hypothesis that the prevalence of SCI was significantly .39% in patients .18 years old with SCA.Due to the high age-dependent prevalence of SCI in children and adolescents with SCA, associated deficits in neuropsychometric performance, 5 the association of SCI with future overt stroke, 5 and the impact of these associated morbidities on health care outcomes in adults with SCA, including adherence to complex instructions associated with management of chronic illness, we elected to obtain, as part of routine clinical practice, magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) scans of the brain in adults with SCA. If SCI or cerebral vasculopathy is found via neuroimaging, we refer these adults for cognitive testing, neurology consultation, or both. We completed a retrospective chart review of adults with SCA (hemoglobin SS or hemoglobin S b zero [Sb 0 ] thalassemia) followed in the comprehensive sickle cell disease clinic, with surveillance MRI and MRA of the brain performed as part of standard-of-care assessment for SCI from 2011 to 2013. The cerebral MRIs and MRAs were rereviewed by 2 board-certified neuroradiologists for the purpose of this study. Consensus findings were recorded including presence of cerebral infarcts ($3 mm on T2-weighted images in 2 imaging planes), 6 intracerebral hemorrhage, aneurysms, 7,8 and cerebral vasculopathy 9,10 according to prior established criteria for MRI and MRA. If no neurologic concerns were reported in the medical record and the neurologic examination was normal, infarcts were judged to be silent. STATA version 13 (StataCorporation, College Station, TX) was used for all analyses. Patient characteristics were described by median and interquartile range (IQR) for continuous measures and by number and percent for categorical measures. A 2-sided P # .05 was considered statistically significant. This study was approved by the Vanderbilt University Institutional Review Board as a retrospective cohort analysis.The study population included 121 adults with SCA (hemoglobin SS or Sb 0 thalassemia) out of ;200 individuals with sickle cell disease that were followed in the clinic. Of these 121 individuals, 69 unselected adults underwent neuroimaging with brain MRI. Nine adults with SCA and overt strokes were excluded. The final study population included 60 adults with SCA and neuroimaging. Of note, a total of 52 individuals were excluded because they did not have neuroimaging, primarily because of failure...

Neurologic complications are a major cause of morbidity and mortality in sickle cell disease (SCD). In children with sickle cell anemia, routine use of transcranial Doppler screening, coupled with regular blood transfusion therapy, has decreased the prevalence of overt stroke from ∼11% to 1%. Limited evidence is available to guide acute and chronic management of individuals with SCD and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurologic deficit includes evaluation by a multidisciplinary team (a hematologist, neurologist, neuroradiologist, and transfusion medicine specialist); prompt neuro-imaging and an initial blood transfusion (simple followed immediately by an exchange transfusion or only exchange transfusion) is recommended if the hemoglobin is >4 gm/dL and <10 gm/dL. Standard therapy for secondary prevention of strokes and silent cerebral infarcts includes regular blood transfusion therapy and in selected cases, hematopoietic stem cell transplantation. A critical component of the medical care following an infarct is cognitive and physical rehabilitation. We will discuss our strategy of acute and longterm management of strokes in SCD. (Blood. 2015;125(22):3401-3410)

Cytomegalovirus (CMV) is a ubiquitous virus that usually results in asymptomatic or clinically benign infection. However, there are two groups of patients whose response to CMV infection is much more severe: those who are infected during fetal development and those who are immunocompromised. Although the manifestations of these types of infection differ, both often result in substantial neurologic sequelae. Imaging plays a key role in the diagnosis of both congenital and acquired CMV infection. Neurologic findings of congenital CMV infection include intracranial calcification, migrational abnormalities, cerebral and cerebellar volume loss, ventriculomegaly, and white matter disease. The presence of these findings in children with neurodevelopmental delays is suggestive of congenital CMV infection, even if the child was asymptomatic at birth. Certain imaging features also may indicate future neurologic deficits in symptomatic infants. Acquired CMV infection is potentially deadly in immunocompromised patients such as those infected with human immunodeficiency virus or with acquired immune deficiency syndrome and those with a history of solid organ or bone marrow transplantation. Imaging findings of acquired CMV infection often are nonspecific; however, they may indicate a need for further serologic analysis to determine if CMV infection is present. Early recognition and treatment of central nervous system CMV infection is vital for effective treatment, and familiarity with the imaging findings of this common infection is important for accurate diagnosis.