Incomplete partition type II in its various manifestations: isolated, in association with EVA, syndromic, and beyond; a multicentre international study.

PURPOSE: Incomplete partition type II (IP-II) is characterized by specific histological features and radiological appearance. It may occur in isolation or in association with an enlarged vestibular aqueduct (EVA). Among those with IP-II and EVA, a subset has a diagnosis of Pendred syndrome. This study aimed to explore the prevalence of isolated IP-II, IP-II with EVA, and cases with a genetic or syndromic basis in our cohort. METHODS: From a large, multicentre database of dysplastic cochleae (446 patients, 892 temporal bones), those with imaging features of IP-II were examined in detail, including whether there was a genetic or syndromic association. RESULTS: A total of 78 patients with IP-II were identified. Among these, 55 patients had bilateral IP-II and EVA (only 12 with typical Mondini triad), 8 with bilateral IP-II and normal VA, 2 with bilateral IP-II and unilateral EVA, and 13 with unilateral IP-II (9 with unilateral EVA). Among the group with bilateral IP-II and bilateral EVA in whom genetic analysis was available, 14 out of 29 (48%) had SLC26A4 mutations and a diagnosis of Pendred syndrome, 1 had a FOXI1 mutation, and a few other genetic abnormalities; none had KCNJ10 pathogenic variants. CONCLUSION: Bilateral IP-II-bilateral EVA may be seen in the context of Pendred syndrome (SLC26A4 or FOXI1 mutations) but, in the majority of our cohort, no genetic abnormalities were found, suggesting the possibility of unknown genetic associations. IP-II in isolation (without EVA) is favored to be genetic when bilateral, although the cause is often unknown.

Isolated Sixth Nerve Palsies in a Child With Familial Hemophagocytic Lymphohistiocytosis Type 2.

ABSTRACT: A previously healthy 2-year-old boy presented with a left sixth cranial nerve palsy. There was a family history of multiple sclerosis and optic neuritis. Neuroimaging showed multiple foci of T2/FLAIR hyperintense signal abnormality in both cerebral hemispheres and in the brainstem. The initial diagnosis was suspicious for demyelinating disease. However, there was no clinical improvement after a course of corticosteroids, and there was no change in his follow-up MRI. He later developed bilateral sixth nerve palsies, with esotropia addressed with bilateral medial rectus botulinum toxin injections. A brain biopsy was planned. However, his 3-month-old sister was separately admitted for fever and pancytopenia. She had markedly elevated ferritin, D-dimer, triglycerides, sIL-2R, CXCL9, and IL-18 and low fibrinogen. Her bone marrow biopsy showed hemophagocytosis. Genetic testing of both siblings revealed biallelic mutations in the PRF1 locus. The final diagnosis of familial hemophagocytic lymphohistiocytosis Type 2 was made. Both siblings underwent chemotherapy. The boy's sixth nerve palsies and MRI abnormalities resolved. Both siblings then went on to undergo bone marrow transplant.

Fetal Brain Anatomy.

"Fetal brain development has been well studied, allowing for an ample knowledge of the normal changes that occur during gestation. Imaging modalities used to evaluate the fetal central nervous system (CNS) include ultrasound and MRI. MRI is the most accurate imaging modality for parenchymal evaluation and depiction of developmental CNS anomalies. The depiction of CNS abnormalities in a fetus can only be accurately made when there is an understanding of its normal development. This article reviews the expected normal fetal brain anatomy and development during gestation. Additional anatomic structures seen on brain imaging sequences are also reviewed."

Imaging phenotype correlation with molecular and molecular pathway defects in malformations of cortical development.

The increase in understanding of molecular biology and recent advances in genetic testing have caused rapid growth in knowledge of genetic causes of malformations of cortical development. Imaging diagnosis of malformations of cortical development can be made prenatally in a large subset of fetuses based on the presence of specific deviations from the normal pattern of development, characteristic imaging features, and associated non-central-nervous-system (CNS) abnormalities. In this review the authors discuss the role of four key cell molecules/molecular pathways in corticogenesis that are frequently implicated in complex prenatally diagnosed malformations of cortical development. The authors also list the currently described genes causing defects in these molecules/molecular pathways when mutated, and the constellation of imaging findings resultant of such defects.

Pediatric Central Nervous System Imaging of Nonaccidental Trauma: Beyond Subdural Hematomas.

Infants and children under 2 years of age are at greatest risk for devastating neurologic complications following nonaccidental trauma. While a subdural hematoma (SDH) is the most common finding and is often enough to raise suspicion for abuse, no single injury is pathognomonic for abusive head trauma (AHT). Rather, the combination of imaging and physical findings and the clinical presentation help confirm the diagnosis of AHT. Familiarity with the spectrum of findings and proper identification of the imaging abnormalities is important for the radiologist to facilitate treatment and removal of the patient from the abusive environment. Injury is usually a result of shaking, which includes hyperflexion, hyperextension, and rotational forces, and less commonly impact trauma or a combination of both. Key anatomic features unique to the infant's head, neck, and spine and associated biomechanical forces are responsible for entities such as hypoxic ischemic injury, bridging vein thrombosis, SDH, parenchymal lacerations, and spinal and retinal injuries. Although the association of subpial hemorrhage with AHT has not been investigated, it warrants attention in very young infants who endure accidental or inflicted trauma. A combination of CT of the head and MRI of the brain and cervical spine aids in the accurate diagnosis, appropriate management, and subsequent protection of these patients. ©RSNA, 2018.

Pretransplant functional imaging and outcome in pediatric patients with relapsed/refractory Hodgkin lymphoma undergoing autologous transplantation.

BACKGROUND: Pretransplant functional imaging (FI), particularly a negative positron emission tomography (PET), is a strong predictor of outcome in adults with relapsed or refractory Hodgkin lymphoma (HL), but data in pediatrics are limited. METHODS: The medical records of 49 consecutive pediatric patients, who received autologous transplant at a single institution, were retrospectively analyzed. All patients had either gallium or PET scan before transplant and were conditioned with carmustine, etoposide, cytarabine, and melphalan (BEAM). Deauville scores were retrospectively assigned for patients with PET (score ≥ 4 positive). RESULTS: Of the 49 patients (median age, 16.2 years), 41 (84%) were pretransplant FI negative and eight (16%) were pretransplant FI positive, after first- to fourth-line salvage therapy, and a median of two salvage cycles. Eighteen patients (37%) received posttransplant radiation. At a median follow up of 46 months, 45 patients (92%) were alive and disease free, and there were three nonrelapse deaths and only one relapse death (Deauville score of 5). The 4-year progression-free survival (PFS) for the entire cohort was 92% (95% confidence interval [CI]: 78-97), and PFS based on pretransplant disease status was 95% (95% CI: 82-99%) in the negative FI group versus 75% (95% CI: 31-93) if positive FI (P = 0.057). CONCLUSION: Our analysis revealed outstanding outcomes for children and adolescents with relapsed/refractory HL. There were too few relapses to identify the predictive value of pretransplant metabolic status, but pediatric patients with relapsed/refractory HL and a negative pretransplant FI had excellent survival.

Metabolic, endocrine, and other genetic disorders.

Metabolic, endocrine, and genetic diseases of the brain include a very large array of disorders caused by a wide range of underlying abnormalities and involving a variety of brain structures. Often these disorders manifest as recognizable, though sometimes overlapping, patterns on neuroimaging studies that may enable a diagnosis based on imaging or may alternatively provide enough clues to direct further diagnostic evaluation. The diagnostic workup can include various biochemical laboratory or genetic studies. In this chapter, after a brief review of normal white-matter development, we will describe a variety of leukodystrophies resulting from metabolic disorders involving the brain, including mitochondrial and respiratory chain diseases. We will then describe various acidurias, urea cycle disorders, disorders related to copper and iron metabolism, and disorders of ganglioside and mucopolysaccharide metabolism. Lastly, various other hypomyelinating and dysmyelinating leukodystrophies, including vanishing white-matter disease, megalencephalic leukoencephalopathy with subcortical cysts, and oculocerebrorenal syndrome will be presented. In the following section on endocrine disorders, we will examine various disorders of the hypothalamic-pituitary axis, including developmental, inflammatory, and neoplastic diseases. Neonatal hypoglycemia will also be briefly reviewed. In the final section, we will review a few of the common genetic phakomatoses. Throughout the text, both imaging and brief clinical features of the various disorders will be discussed.

Intrarater and interrater reliability of the pediatric arteriovenous malformation compactness score in children.

OBJECT: Cerebral arteriovenous malformations (AVMs) have a higher postresection recurrence rate in children than in adults. The authors' previous study demonstrated that a diffuse AVM (low compactness score) predicts postresection recurrence. The aims of this study were to evaluate the intra- and interrater reliability of the AVM compactness score. METHODS: Angiograms of 24 patients assigned a preoperative compactness score (scale of 1-3; 1 = most diffuse, 3 = most compact) in the authors' previous study were rerated by the same pediatric neuroradiologist 9 months later. A pediatric neurosurgeon, pediatric neuroradiology fellow, and interventional radiologist blinded to each other's ratings, the original ratings, and AVM recurrence also rated each AVM's compactness. Intrarater and interrater reliability were calculated using the κ statistic. RESULTS: Of the 24 AVMs, scores by the original neuroradiologist were 1 in 6 patients, 2 in 16 patients, and 3 in 2 patients. Intrarater reliability was 1.0. The κ statistic among the 4 raters was 0.69 (95% CI 0.44-0.89), which indicates substantial reliability. The interrater reliability between the neuroradiologist and neuroradiology fellow was moderate (κ = 0.59 [95%CI 0.20-0.89]) and was substantial between the neuroradiologist and neurosurgeon (κ = 0.74 [95% CI 0.41-1.0]). The neuroradiologist and interventional radiologist had perfect agreement (κ = 1.0). CONCLUSIONS: Intrarater and interrater reliability of the AVM compactness score were excellent and substantial, respectively. These results demonstrate that the AVM compactness score is reproducible. However, the neuroradiologist and interventional radiologist had perfect agreement, which indicates that the compactness score is applied most accurately by those with extensive angiography experience.

Modified Pediatric ASPECTS Correlates with Infarct Volume in Childhood Arterial Ischemic Stroke.

BACKGROUND AND PURPOSE: Larger infarct volume as a percent of supratentorial brain volume (SBV) predicts poor outcome and hemorrhagic transformation in childhood arterial ischemic stroke (AIS). In perinatal AIS, higher scores on a modified pediatric version of the Alberta Stroke Program Early CT Score using acute MRI (modASPECTS) predict later seizure occurrence. The objectives were to establish the relationship of modASPECTS to infarct volume in perinatal and childhood AIS and to establish the interrater reliability of the score. METHODS: We performed a cross sectional study of 31 neonates and 40 children identified from a tertiary care center stroke registry with supratentorial AIS and acute MRI with diffusion weighted imaging (DWI) and T2 axial sequences. Infarct volume was expressed as a percent of SBV using computer-assisted manual segmentation tracings. ModASPECTS was performed on DWI by three independent raters. The modASPECTS were compared among raters and to infarct volume as a percent of SBV. RESULTS: ModASPECTS correlated well with infarct volume. Spearman rank correlation coefficients (ρ) for the perinatal and childhood groups were 0.76, p < 0.001 and 0.69, p < 0.001, respectively. Excluding one perinatal and two childhood subjects with multifocal punctate ischemia without large or medium sized vessel stroke, ρ for the perinatal and childhood groups were 0.87, p < 0.001 and 0.80, p < 0.001, respectively. The intraclass correlation coefficients for the three raters for the neonates and children were 0.93 [95% confidence interval (CI) 0.89-0.97, p < 0.001] and 0.94 (95% CI 0.91-0.97, p < 0.001), respectively. CONCLUSION: The modified pediatric ASPECTS on acute MRI can be used to estimate infarct volume as a percent of SBV with a high degree of validity and interrater reliability.

Pediatric high-field magnetic resonance imaging.

High-field 3 T magnetic resonance (MR) imaging provides greater signal-to-noise ratio (SNR) compared with 1.5 T systems. Various MR imaging clinical applications in children can benefit from improvements resulting from this increased SNR. High-resolution imaging of the brain, arterial spin labeling perfusion imaging, diffusion imaging, MR spectroscopy, and imaging of small anatomic parts are some areas in which these improvements can increase our clinical diagnostic capabilities. However, challenges inherent to 3 T imaging become more relevant in children. The use of 3 T imaging in children has allowed better diagnostic efficacy in neuroimaging, but certain technique modifications may be required for optimal imaging.