Pediatric schwannomatosis, a rare but distinct form of neurofibromatosis.

Schwannomatosis is the third major form of neurofibromatosis, distinct from neurofibromatosis type 2 (NF2) and type 1 (NF1). This condition is rare with a variable phenotypic presentation and complex molecular and genetic findings. In this case, a previously healthy teenager was found to have multiple spinal lesions and an enhancing right parotid mass on MRI. On extensive further work-up, this patient met the existing clinical criteria for schwannomatosis. This case report aims to review the clinical features and current diagnostic criteria for schwannomatosis and compare it to NF1 and NF2. Special emphasis will be placed on imaging features that should prompt the radiologist to suggest this rare diagnosis.

Comparison of radiation dose estimates, image noise, and scan duration in pediatric body imaging for volumetric and helical modes on 320-detector CT and helical mode on 64-detector CT.

BACKGROUND: Advanced multidetector CT systems facilitate volumetric image acquisition, which offers theoretic dose savings over helical acquisition with shorter scan times. OBJECTIVE: Compare effective dose (ED), scan duration and image noise using 320- and 64-detector CT scanners in various acquisition modes for clinical chest, abdomen and pelvis protocols. MATERIALS AND METHODS: ED and scan durations were determined for 64-detector helical, 160-detector helical and volume modes under chest, abdomen and pelvis protocols on 320-detector CT with adaptive collimation and 64-detector helical mode on 64-detector CT without adaptive collimation in a phantom representing a 5-year-old child. Noise was measured as standard deviation of Hounsfield units. RESULTS: Compared to 64-detector helical CT, all acquisition modes on 320-detector CT resulted in lower ED and scan durations. Dose savings were greater for chest (27-46%) than abdomen/pelvis (18-28%) and chest/abdomen/pelvis imaging (8-14%). Noise was similar across scanning modes, although some protocols on 320-detector CT produced slightly higher noise. CONCLUSION: Dose savings can be achieved for chest, abdomen/pelvis and chest/abdomen/pelvis examinations on 320-detector CT compared to helical acquisition on 64-detector CT, with shorter scan durations. Although noise differences between some modes reached statistical significance, this is of doubtful diagnostic significance and will be studied further in a clinical setting.

Radiation dose estimation for prospective and retrospective ECG-gated cardiac CT angiography in infants and small children using a 320-MDCT volume scanner.

OBJECTIVE: The purpose of this study is to determine patient dose estimates for clinical pediatric cardiac-gated CT angiography (CTA) protocols on a 320-MDCT volume scanner. MATERIALS AND METHODS: Organ doses were measured using 20 metal oxide semiconductor field effect transistor (MOSFET) dosimeters. Radiation dose was estimated for volumetrically acquired clinical pediatric prospectively and retrospectively ECG-gated cardiac CTA protocols in 5-year-old and 1-year-old anthropomorphic phantoms on a 320-MDCT scanner. Simulated heart rates of 60 beats/min (5-year-old phantom) and 120 beats/min (1- and 5-year-old phantoms) were used. Effective doses (EDs) were calculated using average measured organ doses and International Commission on Radiological Protection 103 tissue-weighting factors. Dose-length product (DLP) was recorded for each examination and was used to develop dose conversion factors for pediatric cardiac examinations acquired with volume scan mode. DLP was also used to estimate ED according to recently published dose conversion factors for pediatric helical chest examinations. Repeated measures and paired Student t test analyses were performed. RESULTS: For the 5-year-old phantom, at 60 beats/min, EDs ranged from 1.2 mSv for a prospectively gated examination to 4.5 mSv for a retrospectively gated examination. For the 5-year-old phantom, at 120 beats/min, EDs ranged from 3.0 mSv for a prospectively gated examination to 4.9 mSv for a retrospectively gated examination. For the 1-year-old phantom, at 120 beats/min, EDs ranged from 2.7 mSv for a prospectively gated examination to 4.5 mSv for a retrospectively gated examination. CONCLUSION: EDs for 320-MDCT volumetrically acquired ECG-gated pediatric cardiac CTA are lower than those published for conventional 16- and 64-MDCT scanners.

Morphometric differences in the Heschl's gyrus of hearing impaired and normal hearing infants.

This study investigates the morphometry of Heschl's gyrus and its included primary auditory cortex (PAC) in hearing impaired (HI) and normal hearing (NH) infants. Fourty-two infants, age 8-19 months, with NH (n = 26) or hearing impairment (n = 16) were studied using high-resolution 3D magnetic resonance imaging. Gray matter (GM) and white matter (WM) volumes were obtained using software for automatic brain imaging segmentation to estimate the volume of each tissue within manually defined regions for the anterior portion of Heschl's gyrus (aHG) in each individual subject, transformed to an infant brain template space. Interactions among group (HI, NH), tissue type (GM, WM), and hemisphere (left, right) were examined using analysis of variance. Whole-brain voxel-based morphometry was utilized to explore volume differences between groups across the entire brain. The HI group showed increased GM and decreased WM in aHG compared with the NH group; likely effects of auditory deprivation. The HI group did not exhibit their typical L > R asymmetry pattern that the NH group showed. Increased GM in aHG in HI infants may represent abnormal cortical development in PAC as seen in animal models of sensory deprivation. Lower WM volume is consistent with studies with deaf adults.

Comparison of standard, prone and cine MRI in the evaluation of tethered cord.

BACKGROUND: Tethered cord syndrome (TCS) is defined by abnormal traction on the spinal cord that confines its movement. Surgical cord release usually stops neurological deterioration; therefore, early and accurate neuroradiological diagnosis is important. Supine MRI is the imaging modality of choice, but prone MRI and cine MRI can demonstrate cord movement. OBJECTIVE: We compared the diagnostic accuracies of standard MRI, prone MRI and cine MRI in patients with clinical suspicion of TCS and evaluated inter-reader reliability for MR imaging. MATERIALS AND METHODS: Children who underwent MRI for suspicion of TCS were retrospectively identified. Supine, prone and cine MRI studies were re-read by two pediatric neuroradiologists. Conus level, filum appearance and cord movement were documented. RESULTS: Thirteen of 49 children had tethered cord documented at surgery. Conus level had the highest diagnostic accuracy (sensitivity 69-77%, specificity 94%, positive predictive value 82-83%, negative predictive value 89-92%, correct diagnosis 88-90%) and highest between-reader concordance (98%). Prone and cine MRI did not add to the accuracy of the supine imaging. CONCLUSION: Conus level provides the highest diagnostic accuracy and inter-reader reliability in TCS. Until a larger series is evaluated, it remains questionable whether prone or cine MRI provides enough additional diagnostic information to warrant routine use.

Sleep-related respiratory abnormalities and arousal pattern in achondroplasia during early infancy.

OBJECTIVE: To assess sleep-disordered breathing (SDB), sleep architecture, and arousal pattern in infants with achondroplasia and to evaluate the relationship between foramen magnum size and the severity of SDB. STUDY DESIGN: A retrospective review of polysomnographic recordings and medical records was performed in infants with achondroplasia and in aged-matched control subjects. All studies were re-scored with the emphasis on respiratory events, sleep state, and arousals. In addition, the neuroimaging study of the brain (magnetic resonance imaging) was reviewed to evaluate foramen magnum diameters and to assess their relationship to SDB. RESULTS: Twenty-four infants met the criteria for entry into analysis, 12 infants with achondroplasia (A) and 12 control infants (C). There was no significant difference in age or sex. Infants with achondroplasia had a significant increase in total respiratory disturbance index (RDI; A, 13.9 +/- 10.8 versus C, 2.0 +/- 0.9; P < .05). However, there was no significant difference in percentages of active sleep, quiet sleep, or sleep efficiency. Analysis of arousals demonstrated that infants with achondroplasia had a significant decrease in both spontaneous arousal index (A, 10.5 +/- 3.5/hr versus C, 18.6 +/- 2.7; P < .0001) and respiratory arousals (A, 10.3% +/- 6.3% versus C, 27.5 +/- 9.5%; P < .0001). Evaluation of foramen magnum dimensions demonstrated smaller foramen magnum size, but there were no significant correlations between anteroposterior or transverse diameters and RDI. CONCLUSION: Infants with achondroplasia have significant SDB during early infancy. SDB in infants with achondroplasia is not associated with alteration in sleep architecture, possibly because of attenuation of the arousal response. We speculate that the concomitant increased apneic events and decreased arousal response will lead to vulnerability in these infants and may underlie the pathophysiologic mechanism of sudden unexpected death in this population.

Decreased brain volume in adults with childhood lead exposure.

BACKGROUND: Although environmental lead exposure is associated with significant deficits in cognition, executive functions, social behaviors, and motor abilities, the neuroanatomical basis for these impairments remains poorly understood. In this study, we examined the relationship between childhood lead exposure and adult brain volume using magnetic resonance imaging (MRI). We also explored how volume changes correlate with historic neuropsychological assessments. METHODS AND FINDINGS: Volumetric analyses of whole brain MRI data revealed significant decreases in brain volume associated with childhood blood lead concentrations. Using conservative, minimum contiguous cluster size and statistical criteria (700 voxels, unadjusted p < 0.001), approximately 1.2% of the total gray matter was significantly and inversely associated with mean childhood blood lead concentration. The most affected regions included frontal gray matter, specifically the anterior cingulate cortex (ACC). Areas of lead-associated gray matter volume loss were much larger and more significant in men than women. We found that fine motor factor scores positively correlated with gray matter volume in the cerebellar hemispheres; adding blood lead concentrations as a variable to the model attenuated this correlation. CONCLUSIONS: Childhood lead exposure is associated with region-specific reductions in adult gray matter volume. Affected regions include the portions of the prefrontal cortex and ACC responsible for executive functions, mood regulation, and decision-making. These neuroanatomical findings were more pronounced for males, suggesting that lead-related atrophic changes have a disparate impact across sexes. This analysis suggests that adverse cognitive and behavioral outcomes may be related to lead's effect on brain development producing persistent alterations in structure. Using a simple model, we found that blood lead concentration mediates brain volume and fine motor function.

Interstitial deletion of 13q associated with polymicrogyria.

Interstitial deletion of the long arm of chromosome 13 is a rare condition characterized by multiple clinical findings. We report a male dizygotic twin with an interstitial deletion of 13q and failure to thrive, hypotonia, polymicrogyria, bilateral foci of retinoblastoma, hearing loss, bilateral inguinal hernias, submucous cleft palate, and dysmorphic features including a triangular shaped face, broad forehead, small chin, prominent eyes, downslanting palpebral fissures, and a downturned mouth. Chromosome analysis showed an interstitial deletion of chromosome 13 which was confirmed by fluorescence in situ hybridization analysis to include the Rb locus, but spare the 13q subtelomeric region. The karyotype was 46,XY,del(13)(q14.1q31.2).ish del(13)(RB1-,D13S327+) de novo. Breakpoints were further characterized by SNP-based microarray. Retinoblastoma tumors are a well-known complication of deletion of the retinoblastoma susceptibility gene, located at chromosome 13q14.2. Growth retardation is another common feature that has been described in other patients with a deletion of 13q. Additionally, this patient had brain findings on MRI consistent with bilateral polymicrogyria with predominance of the frontal lobes, as well as prominent infratentorial and supratentorial vasculature. There are a variety of polymicrogyria syndromes that are distinguished by the cortical location of the abnormal folding. Several of the subtypes have known genetic loci associated with them. To our knowledge, this is the only report of polymicrogyria in association with a deletion of chromosome 13.

Magnetic resonance imaging findings in children with a first recognized seizure.

This study characterized structural abnormalities associated with onset of seizures in children, using magnetic resonance imaging and a standardized classification system in a large prospective cohort. Two hundred eighty-one children aged 6-14 years completed magnetic resonance imaging within 6 months of their first recognized seizure. Most examinations were performed with a standardized, dedicated seizure protocol; all were scored using a standard scoring system. At least one magnetic resonance imaging abnormality was identified in 87 of 281 (31%) children with a first recognized seizure. Two or more abnormalities were identified in 34 (12%). The commonest abnormalities were ventricular enlargement (51%), leukomalacia/gliosis (23%), gray-matter lesions such as heterotopias and cortical dysplasia (12%), volume loss (12%), other white-matter lesions (9%), and encephalomalacia (6%). Abnormalities defined as significant, or potentially related to seizures, occurred in 40 (14%). Temporal lobe and hippocampal abnormalities were detected at a higher frequency than in previous studies (13/87). Magnetic resonance imaging and a standardized, reliable, valid scoring system demonstrated a higher rate of abnormal findings than previously reported, including findings formerly considered incidental. Practice parameters may need revision, to expand the definition of significant abnormalities and support wider use of magnetic resonance imaging in children with newly diagnosed seizures.

Magnetic resonance imaging (MRI) and electroencephalographic (EEG) findings in a cohort of normal children with newly diagnosed seizures.

In the initial assessment of children with new-onset seizures, the suggestion that electroencephalography (EEG) should be standard and that magnetic resonance imaging (MRI) should be optional has been questioned. The purposes of this study were to (1) describe the frequency of EEG and MRI abnormalities and (2) explore relationships between MRI and EEG findings to determine their relevance in the assessment of children with new-onset seizures who are otherwise developing normally. As part of an ongoing, prospective study of children with new-onset seizures, we studied 181 children (90 girls and 91 boys). Children were entered into the study within 3 months of their first-recognized seizure. The association between EEG and MRI abnormalities was explored using a chi-square test. Abnormal MRI findings were found in 32.6% (n = 59) of the sample. The EEG and MRI results agreed with respect to classification into normal or abnormal in 37% (n = 67). Of the 50 children with a normal EEG, however, 21 (42%) were found to have an abnormal MRI. We found an unexpectedly high frequency of imaging abnormalities in our sample of otherwise normal children, although the significance of these findings is not clear. Follow-up of these patients will help us interpret the importance of the abnormalities. Despite our relatively small sample, however, our findings indicate that a normal EEG does not reliably predict a normal MRI in children with first seizures.

Supratentorial tuber location and autism in tuberous sclerosis complex.

The high rate of autism in tuberous sclerosis complex provides an opportunity to study the pathogenesis of autism. This study investigated the relationship between a DSM-IV diagnosis of autism and tuber location in a sample of 50 individuals with tuberous sclerosis complex. Chi-square analyses revealed no differences between individuals with autism (n = 15) and those without autism (n = 35) on the occurrence of tubers in the right or left frontal, occipital, parietal, or temporal regions. There were no differences between the two groups in the occurrence of tubers in subcortical or cortical regions. In the largest sample to date, these results fail to support the hypothesis that supratentorial tuber location is a marker for autism.

Comparison of radiation dose estimates and scan performance in pediatric high-resolution thoracic CT for volumetric 320-detector row, helical 64-detector row, and noncontiguous axial scan acquisitions.

RATIONALE AND OBJECTIVES: Efforts to decrease radiation exposure during pediatric high-resolution thoracic computed tomography (HRCT), while maintaining diagnostic image quality, are imperative. The objective of this investigation was to compare organ doses and scan performance for pediatric HRCT using volume, helical, and noncontiguous axial acquisitions. MATERIALS AND METHODS: Thoracic organ doses were measured using 20 metal oxide semiconductor field-effect transistor dosimeters. Mean and median organ doses and scan durations were determined and compared for three acquisition modes in a 5-year-old anthropomorphic phantom using similar clinical pediatric scan parameters. Image noise was measured and compared in identical regions within the thorax. RESULTS: There was a significantly lower dose in lung (1.8 vs 2.7 mGy, P < .02) and thymus (2.3 vs 2.7 mGy, P < .02) between volume and noncontiguous axial modes and in lung (1.8 vs 2.3 mGy, P < .02), breast (1.8 vs 2.6 mGy, P < .02), and thymus (2.3 vs 2.4 mGy, P < .02) between volume and helical modes. There was a significantly lower median image noise for volume compared to helical and axial modes in lung (55.6 vs 79.3 and 70.7) and soft tissue (76.0 vs 111.3 and 89.9). Scan times for volume, helical, and noncontiguous axial acquisitions were 0.35, 3.9, and 24.5 seconds, respectively. CONCLUSION: Volumetric HRCT provides an opportunity for thoracic organ dose and image noise reduction, at significantly faster scanning speeds, which may benefit pediatric patients undergoing surveillance studies for diffuse lung disease.

Proton magnetic resonance spectroscopy in adults with childhood lead exposure.

BACKGROUND: Childhood lead exposure adversely affects neurodevelopment. However, few studies have examined changes in human brain metabolism that may underlie known adverse cognitive and behavioral outcomes. OBJECTIVE: We examined the association between mean childhood blood lead levels and in vivo brain metabolite concentrations as adults, determined by proton magnetic resonance spectroscopy (MRS) in a birth cohort with documented low-to-moderate lead exposure. METHODS: Adult participants from the Cincinnati Lead Study [n = 159; mean age (± SD), 20.8 ± 0.9 years] completed a quantitative, short-echo proton MRS protocol evaluating seven regions to determine brain concentrations of N-acetyl aspartate (NAA), creatine and phosphocreatine (Cr), cholines (Cho), myo-inositol, and a composite of glutamate and glutamine (GLX). Correlation and multiple linear regression analyses were conducted. RESULTS: Mean childhood blood lead levels were associated with regionally specific brain metabolite concentrations adjusted for age at imaging and Full-Scale intelligence quotient. Adjusted analyses estimated for a unit (micrograms per deciliter) increase in mean childhood blood lead concentrations, a decrease of NAA and Cr concentration levels in the basal ganglia, a decrease of NAA and a decrease of Cho concentration levels in the cerebellar hemisphere, a decrease of GLX concentration levels in vermis, a decrease of Cho and a decrease of GLX concentration levels in parietal white matter, and a decrease of Cho concentration levels in frontal white matter. CONCLUSIONS: Gray-matter NAA reductions associated with increasing childhood blood lead levels suggest that sustained childhood lead exposure produces an irreversible pattern of neuronal dysfunction, whereas associated white-matter choline declines indicate a permanent alteration to myelin architecture.

Neurologic outcome in neonatal temporal lobe hemorrhagic venous infarcts.

Consequences of neonatal cerebral venous infarct can be severe. However, we have identified a series of neonates with unilateral temporal lobe infarcts, suspected to be secondary to superficial cortical venous thrombosis, who have had relatively normal outcomes. Medical records were reviewed retrospectively. History, relevant studies, and outcomes for 7 patients are described. Most patients presented with neonatal seizures. Neuroimaging showed unilateral temporal lobe hemorrhage and surrounding ischemic change, which was initially attributed to thrombosis of the vein of Labbe; however, magnetic resonance venogram findings suggest that thrombosis of other superficial temporal lobe veins may also be involved. Seizure control was achieved in all cases. Development and neurologic examination at follow-up were usually normal. We conclude that neonatal temporal lobe hemorrhagic infarct secondary to suspected superficial temporal venous thrombosis appears to have a good clinical outcome. This is surprising, given the dramatic imaging and clinical presentations.

Altered myelination and axonal integrity in adults with childhood lead exposure: a diffusion tensor imaging study.

Childhood lead exposure is associated with adverse cognitive, neurobehavioral and motor outcomes, suggesting altered brain structure and function. The purpose of this work was to assess the long-term impact of childhood lead exposure on white matter integrity in young adults. We hypothesized that childhood lead exposure would alter adult white matter architecture via deficits in axonal integrity and myelin organization. Adults (22.9+/-1.5 years, range 20.0-26.1 years) from the Cincinnati Lead Study were recruited to undergo a study employing diffusion tensor imaging (DTI). The anatomic regions of association between water diffusion characteristics in white matter and mean childhood blood lead level were determined for 91 participants (52 female). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on an exploratory voxel-wise basis. In adjusted analyses, mean childhood blood lead levels were associated with decreased FA throughout white matter. Regions of the corona radiata demonstrated highly significant lead-associated decreases in FA and AD and increases in MD and RD. The genu, body, and splenium of the corpus callosum demonstrated highly significant lead-associated decreases in RD, smaller and less significant decreases in MD, and small areas with increases in AD. The results of this analysis suggest multiple insults appear as distinct patterns of white matter diffusion abnormalities in the adult brain. Neurotoxic insults from the significant lead burden the participants experienced throughout childhood affect neural elements differently and may be related to the developmental stage of myelination at periods of exposure. This study indicates that childhood lead exposure is associated with a significant and persistent impact on white matter microstructure as quantified with diffusivity changes suggestive of altered myelination and axonal integrity.

The association of MRI findings and neuropsychological functioning after the first recognized seizure.

PURPOSE: To explore relationships between MRI abnormalities of the brain and neuropsychological functioning in children who were evaluated following their first recognized seizure. METHODS: Subjects were children aged 6 to 14 years with a first recognized seizure within the past 3 months who participated in a larger prospective study of child adaptation. The 249 children with neuropsychological testing and neuroimaging were studied. Children underwent neuropsychological examination an average of 2.8 months and MRI examination an average of 1.3 months after the first recognized seizure. On factor analysis four factors were found for neuropsychological function: LANG = Language, PS = Processing Speed, EC = Executive/ Construction, VMEM = Verbal Memory and Learning. For analysis, structural abnormalities found on MRI were classified as significant (yes/no) based on whether they were presumed to be related to the seizure condition. RESULTS: On MRI, 34 (14%) had structural abnormalities that were judged to be significant in that they were possibly related to their seizures. Children with significant abnormalities had significantly lower estimated IQ scores and significantly lower language, processing speed, executive/constructional ability, and verbal memory and learning factor scores than did children without significant abnormalities. CONCLUSIONS: Children who have structural brain abnormalities at onset have slightly lower cognitive functioning overall, and all neuropsychological domains seemed to be affected relatively equally. This pattern was apparent even when we restricted the analysis to children with intellectual functioning in the broadly normal range.

Partial absence of the posterior semicircular canal in Alagille syndrome: CT findings.

We report a case of bilateral partial absence of the posterior semicircular canals (with normal lateral semicircular canals) imaged with CT in a patient with Alagille syndrome. Similar histologic findings have been reported in the pathology literature. This association has been previously reported only for Waardenburg syndrome in the imaging literature. We review the imaging findings and embryology of the semicircular canals, and suggest that this abnormality is specific to patients with Alagille or Waardenburg syndrome.

The impact of early childhood lead exposure on brain organization: a functional magnetic resonance imaging study of language function.

OBJECTIVES: The purpose of this work was to assess the long-term impact of childhood lead exposure on the neurosubstrate of language function and brain organization. METHODS: Young adults from the Cincinnati Lead Study were recruited to undergo functional magnetic resonance image scanning while performing a verb generation task. These subjects have been followed from birth through early childhood with extensive documentation of lead exposure, neuropsychology, and behavior. Forty-two subjects provided useful imaging data. The locale, strength, and the correlation between brain language activation and childhood blood lead concentration were studied. RESULTS: After adjusting for potential confounders, the activation in left frontal cortex, adjacent to Broca's area, and left middle temporal gyrus, including Wernicke's area, were found to be significantly associated with diminished activation in subjects with higher mean childhood blood lead levels, whereas the compensatory activation in the right hemisphere homolog of Wernicke's area was enhanced in subjects with higher blood lead levels. CONCLUSION: This study indicates that childhood lead exposure has a significant and persistent impact on brain reorganization associated with language function.

Methylsulfonylmethane observed by in vivo proton magnetic resonance spectroscopy in a 5-year-old child with developmental disorder: effects of dietary supplementation.

Proton magnetic resonance spectroscopy (MRS) revealed a distinct resonance at 3.15 ppm in the brain of a 5-year-old male diagnosed with autism. The resonance assignment is attributable to ingestion of methylsulfonylmethane (MSM) as a dietary supplement. Glucosamine with MSM is marketed as a source of dietary sulfur and treatment of joint pain. Recognition of this chemical on brain proton MRS as an exogenous compound is necessary to avoid confusion as a pathologic metabolite of pediatric metabolic disease.

Magnetic resonance spectroscopy in a 9-day-old heterozygous female child with creatine transporter deficiency.

An X-linked creatine deficiency syndrome caused by mutations in the creatine transporter gene SLC6A8/CRTR mapped to Xq28 has recently been described. Essential in the recognition of this disorder is the absence of creatine on proton magnetic resonance spectroscopy (MRS) examination. A 9-day-old heterozygous female child with this syndrome demonstrated a significant reduction of creatine on proton MRS. She is a carrier of the R514X nonsense mutation.