Fetal head and neck tumors.

Imaging plays a leading role in detection and diagnosis of fetal head and neck lesions. These lesions comprise a heterogeneous group of congenital tumors and malformations. Complementary imaging modalities that can be used in prenatal medicine are ultrasound and MRI. The authors discuss imaging characteristics of fetal lesions, assessment of potential complications and pregnancy management options for the most common pathology of the fetal head and neck.

Neurologic challenges in 22q11.2 deletion syndrome.

Children with 22q11.2 deletion syndrome often come to medical attention due to signs and symptoms of neurologic dysfunction. It is imperative to understand the expected neurologic development of patients with this diagnosis in order to be alert for the potential neurologic complications, including cortical malformations, tethered cord, epilepsy, and movement disorders. We present an update of brain imaging findings from the CHOP 22q and You Center, a review of the current literature, and our current management practices for neurological issues.

N-acetylaspartate supports the energetic demands of developmental myelination via oligodendroglial aspartoacylase.

Breakdown of neuro-glial N-acetyl-aspartate (NAA) metabolism results in the failure of developmental myelination, manifest in the congenital pediatric leukodystrophy Canavan disease caused by mutations to the sole NAA catabolizing enzyme aspartoacylase. Canavan disease is a major point of focus for efforts to define NAA function, with available evidence suggesting NAA serves as an acetyl donor for fatty acid synthesis during myelination. Elevated NAA is a diagnostic hallmark of Canavan disease, which contrasts with a broad spectrum of alternative neurodegenerative contexts in which levels of NAA are inversely proportional to pathological progression. Recently generated data in the nur7 mouse model of Canavan disease suggests loss of aspartoacylase function results in compromised energetic integrity prior to oligodendrocyte death, abnormalities in myelin content, spongiform degeneration, and motor deficit. The present study utilized a next-generation "oligotropic" adeno-associated virus vector (AAV-Olig001) to quantitatively assess the impact of aspartoacylase reconstitution on developmental myelination. AAV-Olig001-aspartoacylase promoted normalization of NAA, increased bioavailable acetyl-CoA, and restored energetic balance within a window of postnatal development preceding gross histopathology and deteriorating motor function. Long-term effects included increased oligodendrocyte numbers, a global increase in myelination, reversal of vacuolation, and rescue of motor function. Effects on brain energy observed following AAV-Olig001-aspartoacylase gene therapy are shown to be consistent with a metabolic profile observed in mild cases of Canavan disease, implicating NAA in the maintenance of energetic integrity during myelination via oligodendroglial aspartoacylase.

Childhood encephalitis: relationship between diffusion abnormalities and clinical outcome.

INTRODUCTION: The impact of restricted diffusion on clinical outcome has not been well studied in childhood encephalitis. We hypothesized that the patients with lesions with restricted diffusion (LRD) would have worse clinical outcome. METHODS: We reviewed the MR studies of 83 children with encephalitis for LRD. An MRI scoring system (0-12) based on fluid-attenuated inversion recovery (FLAIR) imaging was created to evaluate the extent of imaging abnormality. Clinical outcome was graded by using Glasgow outcome scale (GOS) (1-5) in 1st and 12th month: 1 for death and five for full recovery. With respect to diffusion, the correlation between imaging score and GOS was assessed. Logistic regression analysis was used to explore the impact of diffusion and imaging score on clinical outcome. The patients were divided into three subgroups regarding imaging score: I, 0-4; II, 5-8; and III, 9-12. RESULTS: LRD was found in 28 patients. Negative significant correlation was found between imaging score and GOS in the group with LRD in both 1st month (R = -0.67, P < 0.001) and 12th month (R = -0.56, P = 0.001). Multivariate logistic regression showed that LRD (P < 0.001) and age (P = 0.026) were significant independent risk factors for unfavorable outcome in 1st month, and both LRD (P = 0.001) and imaging score (P = 0.043) were significant risk factors for unfavorable outcome in 12th month. CONCLUSIONS: Patients with LRD have a worse clinical outcome than those without LRD. In patients with LRD, those with a greater extent of abnormality have a poorer outcome.

Morphology of the foramen magnum in syndromic and non-syndromic brachycephaly.

PURPOSE: The shape and size of the foramen magnum (FM) can be altered in craniosynostoses. However, few studies have investigated these changes. In this paper, we investigate the morphology of the foramen magnum in syndromic and non-syndromic brachycephaly. METHODS: Surface area, anteroposterior (AP) diameter, and transverse diameters of the FM were measured on high-resolution CT scans in children with Crouzon (25), Pfeiffer (21), Apert (26), Saethre-Chotzen (7) syndromes, and isolated bicoronal synostosis (9) and compared to an age-matched control group (30). RESULTS: A significantly smaller FM surface area was observed in Crouzon (6.3 ± 1.7 cm(2)) and Pfeiffer (6.4 ± 2.3 cm(2)) syndromes as compared to the control group (7.4 ± 1.3 cm(2), p = 0.006 and p = .017, respectively). In comparison to the control group, no statistically significant alteration in FM surface area was noted in patients with Apert, Saethre-Chotzen, or isolated bicoronal synostosis (p = 0.37, p = 0.71, p = 0.40 respectively). The transverse diameter of FM was significantly smaller in Crouzon, Pfeiffer, and Apert syndromes compared to the control group (p = 0.005, p = 0.002, p = 0.03 respectively). In Saethre-Chotzen and isolated bicoronal synostosis, no difference in transverse diameter was demonstrated. Among all groups, only Crouzon syndrome showed reduced anteroposterior diameter as compared to controls (p = 0.005). In Pfeiffer and Apert syndromes, there was elongation of the shape of the FM with a relatively narrowed width as demonstrated in a significantly increased AP to transverse diameter ratio (p = 0.002 and p = 0.019, respectively). DISCUSSION AND CONCLUSIONS: The FM shape and area is significantly altered in fibroblast growth factor receptor (FGFR)-related brachycephaly syndromes (Crouzon, Pfeiffer, and Apert), whereas in patients with Saethre-Chotzen syndrome (TWIST-1 mutation) and isolated non-syndromic bicoronal synostosis, the shape and mean FM area was not statistically different from that of normals. This study brings to light the important role of FGFRs on FM growth and shape. TWIST-1 mutation (Saethre-Chotzen syndrome) does not appear to have an important effect in shaping the FM.

Hemizygous mutations in SNAP29 unmask autosomal recessive conditions and contribute to atypical findings in patients with 22q11.2DS.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion disorder, affecting an estimated 1 : 2000-4000 live births. Patients with 22q11.2DS have a broad spectrum of phenotypic abnormalities which generally includes congenital cardiac abnormalities, palatal anomalies, and immunodeficiency. Additional findings, such as skeletal anomalies and autoimmune disorders, can confer significant morbidity in a subset of patients. 22q11.2DS is a contiguous gene DS and over 40 genes are deleted in patients; thus deletion of several genes within this region contributes to the clinical features. Mutations outside or on the remaining 22q11.2 allele are also known to modify the phenotype. METHODS: We utilised whole exome, targeted exome and/or Sanger sequencing to examine the genome of 17 patients with 22q11.2 deletions and phenotypic features found in <10% of affected individuals. RESULTS AND CONCLUSIONS: In four unrelated patients, we identified three novel mutations in SNAP29, the gene implicated in the autosomal recessive condition cerebral dysgenesis, neuropathy, ichthyosis and keratoderma (CEDNIK). SNAP29 maps to 22q11.2 and encodes a soluble SNARE protein that is predicted to mediate vesicle fusion at the endoplasmic reticulum or Golgi membranes. This work confirms that the phenotypic variability observed in a subset of patients with 22q11.2DS is due to mutations on the non-deleted chromosome, which leads to unmasking of autosomal recessive conditions such as CEDNIK, Kousseff, and a potentially autosomal recessive form of Opitz G/BBB syndrome. Furthermore, our work implicates SNAP29 as a major modifier of variable expressivity in 22q11.2 DS patients.

Imaging of Pediatric Hearing Loss.

Temporal bone high-resolution computed tomography (HRCT) and magnetic resonance (MR) imaging are valuable tools in the evaluation of pediatric hearing loss. Computed tomography is important in the evaluation of pediatric conductive hearing loss and is the imaging modality of choice for evaluation of osseous abnormalities. MR imaging is the modality of choice for evaluation of sensorineural hearing loss. A broad spectrum of imaging findings can be seen with hearing loss in children. HRCT and MR imaging provide complementary information and are often used in conjunction in the preoperative evaluation of pediatric candidates for cochlear implantation.

3.0 T versus 1.5 T pediatric brain imaging.

This article represents a review of the authors' experience with two 3.0 T Siemens Trio Whole Body MR imaging units, with a cumulative experience of 12 months total imaging time on these scanners, over 1000 cases. The authors were able to identify and review numerous patients who had diagnostic studies both on 1.5 T and 3.0 T.

Neuroimaging evaluation of cerebral palsy.

MRI can demonstrate and differentiate the various insults and anomalies that can be responsible for cerebral palsy. Recent advances have resulted in techniques and sequences that allow prompt detection of cytotoxic edema and evaluation of brain perfusion. MRI precisely demonstrates the various patterns of injury, distinguishing insults owing to profound asphyxia, partial prolonged asphyxia, and mixed partial prolonged and profound asphyxia. Infants and children can be studied with MRI, and ultrafast MRI permits evaluation of the fetal central nervous system. In the fetus, the cause of ventriculomegaly can be determined, such as cerebrospinal fluid flow obstruction, brain malformation, or brain destruction with or without hemorrhage. Results from fetal MRI have led to better understanding of many brain abnormalities.

Risk of optic pathway glioma in children with neurofibromatosis type 1 and optic nerve tortuosity or nerve sheath thickening.

BACKGROUND/AIMS: Optic nerve tortuosity and nerve and sheath thickening are observed on MRI in some patients with neurofibromatosis type 1 (NF-1). This study aimed to determine if tortuosity and thickening are associated with the development of optic pathway glioma (OPG) and subsequent vision loss. METHODS: Children with NF-1 who underwent brain MRI between 1992 and 2005, and had at least 1 year of subsequent visual acuity (VA) follow-up, were identified retrospectively. The baseline MRI was independently reviewed by three neuroradiologists for consensus assessment. Tortuosity was identified using validated operational criteria. Optic nerve and sheath thicknesses and VA at last follow-up were directly measured. RESULTS: Of 132 evaluable children, seven (5%) had tortuosity on baseline MRI. 20 subjects (15%) ultimately developed OPG at a median of 1.9 years (range 7 months-8.0 years) following the baseline MRI. Subjects with tortuosity were significantly more likely to develop OPG than those without tortuosity (57% vs 13%, p=0.01). In subjects who developed OPG, the prevalence of tumour-related vision loss was not significantly different between those with and without baseline tortuosity (14% vs 4%, p=0.28). No difference existed between mean baseline optic nerve (2.3 vs 2.2 mm) or sheath (5.2 vs 5.4 mm) thicknesses comparing subjects who did and did not develop OPG. CONCLUSIONS: Optic nerve tortuosity at baseline is associated with OPG development among patients with NF-1, but does not predispose to aggressive OPG with associated vision loss. Neither nerve nor sheath thickening at baseline is associated with OPG development.

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.

Magnetic resonance evaluation of fetal ventriculomegaly-associated congenital malformations and lesions.

Fetal MRI provides diagnostic quality images of the brain which permit differentiation between the various etiologies of ventriculomegaly: hydrocephalus, congenital malformation, and destructive processes.

Vascular lesions of the orbit in children.

Hemangioma and venous lymphatic malformation are the two most common orbital vascular lesions occurring in the pediatric patient. MR imaging precisely delineates and characterizes these lesions and thus plays an important role in their diagnosis and management. This article discusses the characteristic clinical and imaging findings of hemangiomas and venous lymphatic malformations and the controversies regarding the origin and nomenclature of vascular lesions.

Diffusion-weighted MR imaging of subdural empyemas in children.

BACKGROUND AND PURPOSE: Subdural empyema (SDE), an infection of the subdural space, occurs most often in pediatric patients as a complication of meningitis, sinusitis, or otitis media. Diffusion-weighted imaging (DWI) has been used in the past to investigate intracerebral infections. The purpose of this study was to determine the signal intensity characteristics of SDE on DWIs as well as the corresponding apparent diffusion coefficient (ADC) maps. METHODS: MR studies of 10 patients with SDEs were retrospectively reviewed. Included were routine sequences and DWI, which consisted of an axial single-shot echo-planar spin-echo sequence (TR/TE, 4000/110) with b values of 0, 500, and 1000 s/mm(2). Signal-intensity characteristics on routine MR images and DWIs were evaluated. In seven patients, ADC values of the lesions were calculated by using two b values. Follow-up imaging study was performed in seven patients. RESULTS: In nine patients, the empyema was hyperintense on DWIs. In the remaining patient, the empyema showed mixed hyperintensity and hypointensity. ADC values were lower than those of normal cortical gray matter and much lower than those of reactive subdural effusions. In all seven patients with persistent clinical signs of infection, the empyemas were hyperintense on follow-up DWIs. CONCLUSION: SDE had high signal intensity on DWIs and low signal intensity on ADC maps, with an ADC value lower than that of the normal cortical gray matter. Diffusion MR imaging can be valuable in distinguishing SDE from effusion and in the follow-up of subdural collections.

Prenatal diagnosis of terminal myelocystocele in the fetal surgery era: case report.

OBJECTIVE AND IMPORTANCE: We report a case of a child with terminal myelocystocele (TMC). This case exemplifies the importance of performing a multidisciplinary evaluation and magnetic resonance imaging in the patient with suspected meningomyelocele when fetal surgery is being considered. CLINICAL PRESENTATION: This patient was evaluated at the Center for Fetal Diagnosis and Treatment and considered for fetal surgery to repair meningomyelocele. TECHNIQUE: A follow-up based on both ultrasound and magnetic resonance imaging was performed throughout pregnancy. CONCLUSION: Although a definitive diagnosis of TMC was not established prenatally, the patient was not offered fetal surgery, based on multiple selection criteria. We correlate the pathophysiology of TMC with the radiographic and amniocentesis findings. TMC must be considered in the differential diagnosis in a fetus with a dysraphic defect.

Endolymphatic sac tumor in a 4-year-old boy.

INTRODUCTION: Endolymphatic sac tumors (ELST) are rare, low-grade, locally aggressive papillary neoplasms. We present a case of a 4-year-old boy with an ELST, the youngest described in the literature. CASE: A boy presented with a right-sided serous otitis media and sudden-onset right facial nerve palsy. An audiogram revealed right-sided profound sensorineural hearing loss. Radiographic imaging demonstrated a 3-cm expansile lytic lesion along the posterior face of the petrous bone. INTERVENTION/RESULTS: The patient initially underwent a right transmastoid-infralabyrinthine biopsy. Pathologic examination revealed a papillary lesion suspicious for an ELST. Subsequently, a transtemporal-transcochlear approach with intra-and extradural resection of the tumor was performed. The facial nerve was dissected and transposed anteriorly and preserved. Histopathologic and immunohistochemical studies confirmed the ELST. At his 6-month follow up, there is no evidence of recurrence and the facial nerve function has returned to Grade II palsy. CONCLUSION: ELST are rare tumors of the temporal bone. This is the youngest case of ELST reported. Presentation, evaluation, and management of ELST is discussed.

Utility of magnetic resonance imaging in the evaluation of the child with central diabetes insipidus.

Because of the association of central diabetes insipidus (CDI) and occult neoplasia, magnetic resonance imaging (MRI) is an important component of the diagnostic evaluation of a child with CDI. In more than 90% of these children, MRI (T1 weighted-image, without contrast) demonstrates an absence of the normal hyperintensity of the posterior pituitary. In one third of patients, the pituitary stalk is also thickened, suggesting infiltrative disease. Of those with a thickened stalk, the etiology of the CDI remains undetermined in about 60% of patients, whereas histiocytosis and occult germinoma each account for approximately 15-20% of patients. In contrast, germinoma is infrequent (3%) in children with CDI and an MRI showing a normal infundibular stalk, though histiocytosis still accounts for 15-20% of patients. In this paper, a diagnostic approach in children with CDI is proposed.

Imaging findings of patients with metastatic neuroblastoma to the brain.

RATIONALE AND OBJECTIVES: Metastatic involvement of brain is rare in neuroblastoma (NB). We retrospectively evaluated conventional and advanced imaging and clinical findings of seven patients with secondary intra-axial brain NB metastases. MATERIALS AND METHODS: Magnetic resonance imaging and computed tomography examinations of patients with metastatic brain NB were reviewed. Recent iodine-123 metaiodobenzylguanidine ((123)I-MIBG) scans were also reviewed. A medical record review was performed for relevant clinical, laboratory, histopathologic, and genetic data. RESULTS: Mean age at the time of primary tumor diagnosis was 35 months, and all were considered high-risk NB at diagnosis. Mean time interval between diagnosis and brain involvement was 23.2 months. Extensive prior extra-central nervous system (CNS) disease was present in all patients, but concomitant extra-CNS disease at the time of brain involvement was absent in three (43%) patients. Various forms of disease, including intraparenchymal, intraventricular, and leptomeningeal lesions were detected. Most intraparenchymal lesions were supratentorial and hemorrhagic; however, hemorrhage was absent in multiple leptomeningeal nodules in one patient. Contrast enhancement of lesions was present on all contrast-enhanced studies. Restricted diffusion of lesions was present in two patients. Arterial spin labeling (ASL) perfusion in two patients also revealed increased cerebral blood flow. Recent (123)I-MIBG scans were available in four patients and showed lesions in two patients with larger metastases but failed to demonstrate lesions in another two patients with smaller lesions. CONCLUSIONS: Brain metastases of NB are often supratentorial and hemorrhagic and demonstrate contrast enhancement. Diffusion-weighted imaging can show restricted diffusion. ASL images may reveal increased perfusion. MIBG scans may not show smaller brain metastases.