Low Rates of Cerebral Infarction after Hematopoietic Stem Cell Transplantation in Patients with Sickle Cell Disease at High Risk for Stroke.

Hematopoietic stem cell transplantation (HSCT) can be curative for sickle cell disease (SCD). SCD patients with cerebrovascular disease are often referred for HSCT. The objective of this study was to describe neurologic outcomes after HSCT in patients with pre-existing SCD and cerebrovascular comorbidity. Patients with SCD treated with HSCT at a single center between 1996 and 2019 were identified. Patients with cerebral ischemia and/or vasculopathy before undergoing HSCT were included. Patients with graft failure were excluded. The cohort was divided into 3 groups: symptomatic stroke, vasculopathy without symptomatic stroke, and isolated silent cerebral infarction (SCI). Magnetic resonance imaging/angiography and neurologic assessments pre- and post-HSCT were analyzed to assess outcomes. In a cohort of 44 patients, there were 25 with symptomatic infarction, 10 with vasculopathy, and 9 with isolated SCI. Post-HSCT ischemic injury (2 symptomatic strokes, 2 SCIs) was identified in 4 patients, all with previous symptomatic infarction. Within this group (n = 25), the post-HSCT incidence of subsequent symptomatic infarction was 1.6 events/100 patient-years, and SCIs occurred at a rate of 2.2 events/100 patient-years. No patient had progression of vasculopathy post-HSCT. Our data show a low incidence of new ischemic injury after successful HSCT for SCD. Patients with a history of both symptomatic stroke and vasculopathy are at greatest risk for post-HSCT ischemic injury.

Neuroimaging Findings in Normocephalic Newborns With Intrauterine Zika Virus Exposure.

BACKGROUND: Congenital Zika infection can result in a spectrum of neurological abnormalities in the newborn. Newborns exposed to Zika virus in utero often have neuroimaging as part of their clinical evaluation. METHODS: Through the Congenital Zika Program at Children's National Health System in Washington DC, we performed fetal or neonatal neuroimaging, including magnetic resonance imaging and ultrasound, on over 70 fetuses or neonates with intrauterine Zika exposure. Novel findings on neonatal brain magnetic resonance imaging were observed in two instances. RESULTS: Gadolinium-contrast magnetic resonance imaging showed enhancement of multiple cranial nerves at three days of age on one infant. Another infant underwent magnetic resonance imaging at 16 days of age and was shown to have a chronic ischemic cerebral infarction. This infant had previously normal fetal magnetic resonance imaging. CONCLUSION: Cranial nerve enhancement and cerebral infarction may be among the expanding list of neurological findings in congenital Zika infection. Postnatal brain magnetic resonance imaging should be considered for newborns exposed to Zika virus in utero.

Examination of Reticulocytosis among Chronically Transfused Children with Sickle Cell Anemia.

Sickle cell anemia (SCA) is an inherited hemolytic anemia with compensatory reticulocytosis. Recent studies have shown that increased levels of reticulocytosis during infancy are associated with increased hospitalizations for SCA sequelae as well as cerebrovascular pathologies. In this study, absolute reticulocyte counts (ARC) measured prior to transfusion were analysed among a cohort of 29 pediatric SCA patients receiving chronic transfusion therapy (CTT) for primary and secondary stroke prevention. A cross-sectional flow cytometric analysis of the reticulocyte phenotype was also performed. Mean duration of CTT was 3.1 ± 2.6 years. Fifteen subjects with magnetic resonance angiography (MRA) -vasculopathy had significantly higher mean ARC prior to initiating CTT compared to 14 subjects without MRA-vasculopathy (427.6 ± 109.0 K/µl vs. 324.8 ± 109.2 K/µl, p<0.05). No significant differences in hemoglobin or percentage sickle hemoglobin (HbS) were noted between the two groups at baseline. Reticulocyte phenotyping further demonstrated that the percentages of circulating immature [CD36(+), CD71(+)] reticulocytes positively correlated with ARC in both groups. During the first year of CTT, neither group had significant reductions in ARC. Among this group of children with SCA, cerebrovasculopathy on MRA at initiation of CTT was associated with increased reticulocytosis, which was not reduced after 12 months of transfusions.

Aspects of abuse: abusive head trauma.

Abusive Head Trauma (AHT) is a form of child physical abuse that involves inflicted injury to the brain and its associated structures. Abusive Head Trauma, colloquially called Shaken Baby Syndrome, is the most common cause of serious or fatal brain injuries in children aged 2 years and younger. The American Academy of Pediatrics recommends the term Abusive Head Trauma, as opposed to Shaken Baby Syndrome, as the former term encompasses multiple forms of inflicted head injury (inertial, contact, and hypoxic-ischemic) and a range of clinical presentations and radiologic findings and their sequelae. Children diagnosed with AHT are 5 times more likely to die compared with accidentally head-injured children, yet signs and symptoms are not always obvious, and therefore the diagnosis can be overlooked. Therefore, the American Academy of Pediatrics has tasked pediatricians with knowing how and when to begin an evaluation of children with signs and symptoms that could possibly be due to AHT. Overall, a detailed history of present illness and medical history, recognition of physical and radiological findings, and careful interpretation of retinal pathology are important aspects of formulating the differential diagnoses and increasing or decreasing the index of suspicion for AHT.

Usefulness of MRI detection of cervical spine and brain injuries in the evaluation of abusive head trauma.

BACKGROUND: In the evaluation of children younger than 3 years with intracranial hemorrhage it can be difficult to determine whether the cause of hemorrhage was traumatic, and if so, whether abusive head trauma (AHT) is a possibility. Cervical spine MRI is not a routine part of the nationally recommended imaging workup for children with suspected abusive head trauma. There is increasing evidence that spinal injuries are found at autopsy or MRI in abused children. However the prevalence of cervical spine injuries in children evaluated for abusive head trauma is unknown. We sought to determine both the incidence and the spectrum of cervical spine and brain injuries in children being evaluated for possible abusive head trauma. We also examined the relationship between cervical and brain MRI findings and selected study outcome categories. MATERIALS AND METHODS: This study is a 3-year retrospective review of children evaluated for abusive head trauma. Inclusion criteria were: children with head trauma seen at our institution between 2008 and 2010, age younger than 36 months, availability of diagnostic-quality brain and cervical spine MRI, and child abuse team involvement because abusive head trauma was a possibility. A child abuse pediatrician and pediatric radiologists, all with board certification, were involved in data collection, image interpretation and data analysis. Statistical analysis was performed using Stata v12.1. RESULTS: The study included 74 children (43 boys, 31 girls) with a mean age of 164 days (range, 20-679 days). Study outcomes were categorized as: n = 26 children with accidental head trauma, n = 38 with abusive head trauma (n = 18 presumptive AHT, n = 20 suspicious for AHT), and n = 10 with undefined head trauma. We found cervical spine injuries in 27/74 (36%) children. Most cervical spine injuries were ligamentous injuries. One child had intrathecal spinal blood and two had spinal cord edema; all three of these children had ligamentous injury. MRI signs of cervical injury did not show a statistically significant relationship with a study outcome of abusive head trauma or help discriminate between accidental and abusive head trauma. Of the 30 children with supratentorial brain injury, 16 (53%) had a bilateral hypoxic-ischemic pattern. There was a statistically significant relationship between bilateral hypoxic-ischemic brain injury pattern and abusive head trauma (P < 0.05). In addition, the majority (81%) of children with bilateral hypoxic-ischemic brain injuries had cervical injuries. CONCLUSION: Although detection of cervical spine injuries by MRI does not discriminate between accidental and abusive head trauma, it can help to distinguish a traumatic from non-traumatic intracranial subdural hemorrhage. Cervical MRI should be considered in children with acute intracranial bleeds and otherwise non-contributory history, physical examination and ophthalmological findings. There is a statistically significant relationship between diffuse hypoxic-ischemic brain injury patterns and abusive head trauma. The high incidence of cervical injuries in children with hypoxic-ischemic injuries suggests a causal relationship. Overall, increased utilization of brain and spine MRI in children being evaluated for abusive head trauma can be helpful.

White matter integrity on fractional anisotropy maps in encephalopathic neonates post hypothermia therapy with normal-appearing MR imaging.

BACKGROUND: Neonatal encephalopathy (NE) is a clinically defined neurological syndrome commonly caused by ischemia. OBJECTIVE: We investigated white matter integrity in children with NE using diffusion tensor imaging (DTI) and examined the hypothesis that white matter insults not visible on conventional MRI may have abnormal fractional anisotropy (FA) on DTI. MATERIALS AND METHODS: DTI was performed on 36 term encephalopathic neonates who had hypothermia therapy. Of these, 12 neonates had normal conventional MRI findings (NNE) and 24 neonates had abnormal MRI findings (ANE). Twelve term-equivalent premature neonates with normal clinical neuroimaging and neurological function served as the control group. RESULTS: We found significant reductions in measured FA in white matter in the ANE neonates compared to the control group. There were, however, no significant differences in measured FA in white matter between the NNE and the control group. CONCLUSION: We did not find white matter changes detectable by DTI in encephalopathic neonates post hypothermia with normal conventional MRI findings. Further studies would be required to determine whether this unexpected finding is a direct result of neuroprotective effects of hypothermia, or more sophisticated measures of FA are required to detect subtle white matter injury.

Dialysis disequilibrium syndrome occurring during continuous renal replacement therapy.

The dialysis disequilibrium syndrome (DDS) is characterized by progressive neurological symptoms and signs attributable to cerebral edema that occurs due to fluid shifts into the brain following a relatively rapid decrease in serum osmolality during hemodialysis (HD). Since continuous renal replacement therapy (CRRT) is less efficient at solute clearance than intermittent HD, it seems logical that this mode of therapy is less likely to cause DDS. This entity has not been previously reported to occur with this modality. Here, we report two cases of DDS associated with CRRT that provide insights into its pathophysiological mechanisms and suggest strategies for its prevention.

Magnetic resonance imaging in the analysis of pediatric orbital tumors: utility of diffusion-weighted imaging.

PURPOSE: To identify common radiographic features of pediatric orbital tumors by the use of magnetic resonance imaging (MRI) techniques, diffusion-weighted imaging (DWI), fat saturated T2, and pre- and postgadolinium T1. DWI is hypothesized to help identify and predict the malignancy of specific brain tumors. To our knowledge, a similar analysis in which the authors have used this combination of MRI techniques has not been performed with orbital tumors. METHODS: We performed a retrospective chart review of all patients younger than 18 years of age, each diagnosed with an orbital mass lesion, imaged by MRI from 2005 to 2008. The MR images were analyzed by use of the aforementioned techniques. RESULTS: Mass lesions identified in the chart review included rhabdomyosarcoma (n = 4), myofibroma (n = 2), hemangioma (n = 4), lymphangioma (n = 2), neurofibroma (n = 4), Langerhans histiocytosis (n = 2), and one of each of the following: giant cell tumor, meningioma, lymphoid hyperplasia of the lacrimal gland (chronic sclerosing sialadenitis), optic nerve glioma, lipodermoid, and dermoid. DWI was used to differentiate tumors into those with increased diffusion, restricted diffusion, and a mixed diffusion pattern. Capillary hemangiomas and rhabdomyosarcomas 2 tumors with potentially overlapping appearances with traditional MRI techniques had contrasting appearances with DNI. CONCLUSIONS: DWI can help to distinguish among certain pediatric orbital tumors when combined with traditional MRI techniques. This technique may thus be considered an additional tool to help, refine the differential diagnosis of orbital tumors in children.

Postoperative cerebellar mutism syndrome following treatment of medulloblastoma: neuroradiographic features and origin.

OBJECT: The origin and long-term outcome of cerebellar mutism syndrome (CMS), a postoperative syndrome of diminished speech, hypotonia, and ataxia that affects approximately 25% of patients with medulloblastoma, is poorly elucidated. The current study was undertaken to determine factors associated with development of CMS, a means to determine its severity or cause, and outcomes of patients with this syndrome. METHODS: The study included 28 children with medulloblastoma who either underwent an operation or were referred to the authors' institution soon after surgery. Eleven (39%) of these children had CMS. The preoperative, immediate postoperative, and 1-year postoperative MR images were reviewed by a neuroradiologist blinded to diagnosis of CMS. The severity of mutism and neurological and neurocognitive outcomes were examined. RESULTS: Preoperative MR images showed no differences in tumor size, hydrocephalus, or peritumoral edema in patients with and without CMS. An association with brainstem invasion was significant (p < 0.05), and there was a trend toward an association with involvement of the cerebellomedullary angle (p = 0.08). Images obtained immediately postoperatively showed cerebellar edema in 92% of all patients; there were trends for more middle and superior cerebellar peduncle edema in patients with CMS (p = 0.05 and 0.07, respectively). At 1 year postoperatively, patients with CMS showed more moderate to severe atrophy/gliosis of total cerebellum (p < 0.01), vermis (p < 0.01), and brainstem (p < 0.05). Mean IQ was 16 points lower in patients with CMS (IQ = 84.2 +/- 15.8) compared with those without CMS (IQ = 100.4 +/- 17.4), with a trend toward significance (p = 0.07). CONCLUSIONS: This study demonstrates that CMS is associated with postoperative damage to the cerebellum and brainstem, damage not predicted by immediate postoperative MR imaging, and with poorer associated functional outcome.

Reversible posterior leuko-encephalopathy in children with sickle cell disease.

Children with sickle cell disease (SCD) have high risk of neurologic morbidity and mortality, such as strokes, silent infarcts and TIA's. A retrospective review of magnetic resonance imaging and magnetic resonance angiography identified eight children with radiological and clinical characteristics of reversible posterior encephalopathy (RPLS). These patients had no evidence of previous cerebral infarcts or vasculopathy. Three have died during the 5-year follow up; one developed a stroke and one a conditional TCD. RPLS needs to be considered in the differential diagnosis of children with SCD that present with acute neurological changes, especially if they are already been hospitalized.

The cerebellar mutism syndrome and its relation to cerebellar cognitive function and the cerebellar cognitive affective disorder.

The postoperative cerebellar mutism syndrome (CMS), consisting of diminished speech output, hypotonia, ataxia, and emotional lability, occurs after surgery in up to 25% of patients with medulloblastoma and occasionally after removal of other posterior fossa tumors. Although the mutism is transient, speech rarely normalizes and the syndrome is associated with long-term adverse neurological, cognitive, and psychological sequelae. The clinical, neuroradiographic, and neuropsychological findings associated with CMS as well as possible mechanisms of injury are reviewed. Theories about the pathophysiology of CMS have evolved along with our understanding of the cerebellum as an important structure in the distributive neurocircuitry underlying complex speech, cognition, and behavior. CMS shares many similarities with the cerebellar cognitive affective syndrome, more commonly described in adults and consisting of disturbances of executive function, visuospatial skills, nonmotor language, and affect regulation. Future directions include more thorough neuropsychological characterization, functional and diffusion tensor imaging studies, and investigations into the underlying differences that may make some patients more vulnerable to CMS.

Diffusion-weighted MR imaging of early methotrexate-related neurotoxicity in children.

BACKGROUND AND PURPOSE: Methotrexate is a major cause of treatment-related acute neurotoxicity in children with hematologic malignancies. The purpose of this study was to investigate whether diffusion-weighted MR imaging (DWI) detects acute methotrexate white matter neurotoxicity in this patient population. METHODS: Six children-three female and three male-with hematologic malignancies were studied at time of onset of neurologic dysfunction during the delayed intensification or consolidation phase of therapy, when intensive intrathecal methotrexate is given. MR imaging including DWI was performed on 1.5 T MR scanners. RESULTS: DWI demonstrated abnormal restriction of motion of water in the centrum semiovale in all six patients. This finding correlated to the acute onset of hemiparesis or aphasia. Fluid-attenuated inversion recovery imaging was not positive at this time, but it was positive in all five patients in whom follow-up imaging was performed. CONCLUSION: Early detection of methotrexate white matter injury by DWI has the potential to alert the oncologist to this event and provide a technique by which treatment of neurotoxicity can be monitored.

Seizures and metabolic disease.

Seizures represent an important clinical manifestation of inborn errors of metabolism. The presence of myoclonic seizures and very early onset are clues to a metabolic disorder. Specific correlations between age of seizure onset and electroencephalogram patterns with inborn errors of metabolism are discussed. The explosion of information in neurogenetics and metabolism mandates increasing awareness of appropriate metabolic diagnostic and therapeutic strategies in the setting of certain epilepsies. Specific laboratory, imaging, and treatment considerations are included to present updated material in a field that continues to expand rapidly.

Choroid plexus carcinomas in children: MRI features and patient outcomes.

Choroid plexus carcinomas (CPC) are rare malignant intracranial neoplasms usually occurring in young children. The objectives of this study were to characterize the preoperative MRI features of CPC, determine the frequency of disseminated disease in the CNS at diagnosis, and assess patient outcomes. The preoperative cranial MR images of 11 patients with CPC were retrospectively reviewed for lesion location, lesion size, un-enhanced and enhanced MRI signal characteristics, and presence of disseminated intracranial tumor. Postoperative cranial and spinal MRI images were reviewed for residual, recurrent, and/or disseminated tumor. The study group included six male and five female patients ranging in age from 5 months to 5.3 years (median= 1.8 years). CPC were located in the lateral (n = 8), fourth (n = 1), and third (n = 1) ventricles, and foramen of Luschka (n = 1). Mean tumor size was 5.2 cm x 4.9 cm x 5.0 cm. On short-TR images, CPC had heterogeneous, predominantly intermediate signal with foci of high signal in 45% of lesions from areas of hemorrhage. On long-TR/long-TE images, solid portions of CPC typically had heterogeneous, intermediate-to-slightly-high signal. Small zones of low signal on long-TR/long-TE images were seen in 55% of the lesions secondary to areas of hemorrhage and/or calcifications. Tubular flow voids representing blood vessels were seen in 55% of the lesions. Zones of high signal comparable to CSF were seen in 64% of CPC secondary to cystic/necrotic zones. All CPC showed prominent contrast enhancement. Irregular enhancing margins suggesting subependymal invasion were seen in 73% of the lesions. Findings consistent with edema in the brain adjacent to the enhancing lesions were seen in 73% of CPC. CPC caused hydrocephalus in 82% of patients at diagnosis. Two patients died from hemorrhagic complications from surgical biopsies. Disseminated tumor in the leptomeninges was present in 45% of patients at diagnosis and was associated with a poor prognosis. The 1-year and 5-year survival probabilities were 55% and 45%, respectively. In conclusion, MRI features commonly associated with CPC include large intraventricular lesions with irregular enhancing margins; heterogeneous signal on long TR/long TE images and short-TR images; edema in adjacent brain; hydrocephalus; and presence of disseminated tumor. MRI evidence of disseminated tumor at diagnosis is associated with a poor prognosis.

Imaging of neuroblastoma and Wilms' tumor.

Neuroblastoma and Wilms' tumor are the most common noncentral nervous system solid tumors in children. Imaging plays a crucial role in the evaluation of the primary tumor and regional and metastatic disease. There is a growing body of literature supporting the use of MRI as the technique of choice for the evaluation of local and regional disease in children with suspected neuroblastoma; however, in children with suspected Wilms' tumor, MRI will likely continue to play a role as a problem-solver when the results of CT are equivocal or indeterminant.

Dose reduction fluoroscopy in pediatrics.

BACKGROUND: It is essential that we find ways to reduce radiation exposure to children and maintain image quality. OBJECTIVES: We compared radiation dose, image quality, and spatial resolution when continuous and pulse fluoroscopy with a full and half dose are applied to a phantom. The film-screen technique was compared to fluoroscopy with the digitized spot technique (fluoro grab image) in procedures such as voiding cystourethrogram (VCUG). MATERIALS AND METHODS: Using a 15.1-cm Plexiglas phantom, we obtained dosimetry in milligrays (mGy), spatial resolution in number of line pairs per millimeter (lp/mm), and threshold contrast resolution in number of visible holes. To measure total radiation dose, we calculated the average elapsed fluoroscopy time for VCUG to be approximately 3 min and estimated the average number of exposures as 10. Dosimetry was obtained for full dose and half dose continuous, for 15 pulses per second (pps), 7.5 pps, and 3.75 pps. These were also calculated with normal, magnification 1, and magnification 2 factors. RESULTS: Results of the two most relevant parameters are shown: continuous full-dose fluoroscopy, 3 min, 10 photo spots, total dose of 28.7 mGy with 2 lp/mm of resolution and a threshold contrast of 2.2%, versus 3.75 pps half-dose fluoroscopy, 3 min, grab images, total dose of 3.7 mGy with 1.9 lp/mm of resolution and a threshold contrast of 2.3%. CONCLUSION: With minimal loss of resolution there is significant dose reduction (87%) when using 3.75 pps with digitized imaging.