Variants in PTEN Are Associated With a Diverse Spectrum of Cortical Dysplasia.

BACKGROUND: Inactivating mutations in PTEN are among the most common causes of megalencephaly. Activating mutations in other nodes of the PI3K/AKT/MTOR signaling pathway are recognized as a frequent cause of cortical brain malformations. Only recently has PTEN been associated with cortical malformations, and analyses of their prognostic significance have been limited. METHODS: Retrospective neuroimaging analysis and detailed chart review were conducted on 20 participants identified with pathogenic or likely pathogenic mutations in PTEN and a cortical brain malformation present on brain magnetic resonance imaging. RESULTS: Neuroimaging analysis revealed four main cerebral phenotypes-hemimegalencephaly, focal cortical dysplasia, polymicrogyria (PMG), and a less severe category, termed "macrocephaly with complicated gyral pattern" (MCG). Although a high proportion of participants (90%) had neurodevelopmental findings on presentation, outcomes varied and were favorable in over half of participants. Consistent with prior work, 39% of participants had autism spectrum disorder and 19% of participants with either pure-PMG or pure-MCG phenotypes had epilepsy. Megalencephaly and systemic overgrowth were common, but other systemic features of PTEN-hamartoma tumor syndrome were absent in over one-third of participants. CONCLUSIONS: A spectrum of cortical dysplasias is present in individuals with inactivating mutations in PTEN. Future studies are needed to clarify the prognostic significance of each cerebral phenotype, but overall, we conclude that despite a high burden of neurodevelopmental disease, long-term outcomes may be favorable. Germline testing for PTEN mutations should be considered in cases of megalencephaly and cortical brain malformations even in the absence of other findings, including cognitive impairment.

Fusion of Lateral Calvarial Sutures on Volume-Rendered Computed Tomography Reconstructions in Patients With Known Craniosynostosis.

INTRODUCTION: After treating a child with familial sagittal craniosynostosis, clinocephaly, and bilateral parietomastoid/posterior squamosal suture fusion, the authors wondered if major-suture synostosis and clinocephaly were associated with abnormal fusion of minor lateral calvarial sutures. METHODS: The authors reviewed all preoperative volume-rendered head computed tomography reconstructions performed for craniosynostosis at their institution from 2010 through 2014 and determined whether the sphenoparietal, squamosal, and parietomastoid sutures were open, partially fused, or fused. The authors determined whether any sutures were abnormally fused based upon a previous study from their center, in which abnormal fusion was defined as either 1 of 3 abnormal fusion patterns or abnormally-early fusion. The authors then determined the rate of abnormal fusion of these sutures and whether abnormal fusion was associated with (1) major-suture craniosynostosis, (2) type of craniosynostosis (sutures involved; single-suture versus multisuture; syndromic versus nonsyndromic), and (3) clinocephaly. RESULTS: In 97 included children, minor lateral sutures were abnormally fused in 8, or 8.2%, which was significantly higher than in children without craniosynostosis from our earlier study. Abnormal minor lateral suture fusion was not associated with the type of single-suture synostosis or with multisuture synostosis but was associated with syndromic synostosis. Four of 8 children with abnormal minor lateral suture fusion had multisuture synostosis and 6 had syndromic synostosis. Lateral sutures were abnormally fused in 1 of 4 subjects with clinocephaly, which was not significant. CONCLUSION: Abnormal minor lateral calvarial suture fusion is significantly associated with major-suture craniosynostosis, especially syndromic synostosis.

Imaging of Macrocephaly.

Macrocephaly is a common diagnosis in the pediatric population, particularly in the infantile time period. There is a wide range of causes of macrocephaly, from benign to malignant, for which imaging plays a key role in the diagnosis and clinical guidance. Our aim is to review the distinct and prevalent neuroimaging findings in the evaluation of the macrocephalic infant.

Comparison of subdural grid and stereoelectroencephalography in a cohort of pediatric patients.

OBJECTIVE: To compare adverse events and outcomes between stereoelectroencephalography (SEEG) and subdural electrode (SDE) implantation in children. METHODS: This was a retrospective analysis of 108 patients who underwent intracranial monitoring with SEEG or SDE implantation at Children's Hospital Colorado between January 2011 and June 2019. RESULTS: There were 47 patients who underwent 53 SEEG implantations and 61 patients who underwent 64 SDE implantations, with an average age of 12.45 years (range: 1.22-19.96 years). Post-implantation imaging was performed in all SEEG implantations and 42 SDE implantations. 38 % and 88 % of SEEG and SDE implantations, respectively, had a hemorrhage of any kind (p < 0.01). Clinically significant hemorrhages did not differ between the two groups, though one death was reported in the SEEG group. No patient undergoing SEEG implantation received blood products compared to 20 % of SDE patients (p < 0.01). The rate of infection in SEEG patients was 4% compared to 33 % for SDE patients (p = 0.01). Resection was completed in 60 % of SEEG patients versus 93 % for SDE patients (p < 0.01). Rate of seizure response was not significantly different between the two groups, with 81 % and 71 % of SEEG and SDE patients, respectively, reaching Engel class I or II at 12 months (p = 0.76). SIGNIFICANCE: In pediatric patients at a single institution, SEEG is associated with less adverse effects overall yet similar rates of seizure freedom compared to SDE implantation. This includes significantly lower rates of asymptomatic hemorrhage, infection and need for blood transfusion associated with SEEG monitoring. There was no statistical difference in clinically significant hemorrhages between the two groups, although rare in both.

Fusion patterns of major calvarial sutures on volume-rendered CT reconstructions.

OBJECTIVE: Recently, the authors investigated the normal course of fusion of minor lateral calvarial sutures on "3D" volume-rendered head CT reconstructions in pediatric trauma patients. While evaluating these reconstructions, they found many more fused sagittal sutures than expected given the currently accepted prevalence of sagittal craniosynostosis. In the present study, using the same set of head CT reconstructions, they investigated the course of fusion of the sagittal as well as the lambdoid, coronal, and metopic sutures. METHODS: They reviewed all volume-rendered head CT reconstructions performed in the period from 2010 through mid-2012 at Children's Hospital Colorado for trauma patients aged 0-21 years. Each sagittal, lambdoid, coronal, or metopic suture was graded as open, partially fused, or fused. The cephalic index (CI) was calculated for subjects with fused and partially fused sagittal sutures. RESULTS: After exclusions, 331 scans were reviewed. Twenty-one subjects (6%) had fusion or partial fusion of the sagittal suture. Four of the 21 also had fusion of the medial lambdoid and/or coronal sutures. In the 17 subjects (5%) with sagittal suture fusion and no medial fusion of adjacent sutures, the mean CI was 77.6. None of the 21 subjects had been previously diagnosed with craniosynostosis. Other than in the 21 subjects already mentioned, no other sagittal or lambdoid sutures were fused at all. Nor were other coronal sutures fused medially. Coronal sutures were commonly fused inferiorly early during the 2nd decade of life, and fusion progressed superiorly and medially as subjects became older; none were completely fused by 18 years of age. Fusion of the metopic suture was first seen at 3 months of life; fusion was often not complete until after 2 years. CONCLUSIONS: The sagittal and lambdoid sutures do not usually begin to fuse before 18 years of age. However, more sagittal sutures are fused before age 18 than expected given the currently accepted prevalence of craniosynostosis. This finding is of unknown significance, but likely many of them do not need surgery. The coronal suture often begins to fuse inferiorly early in the 2nd decade of life but does not usually complete fusion before 18 years of age. The metopic suture often starts to fuse by 3 months of age, but it may not completely fuse until after 2 years of age.

The utility of magnetic resonance imaging in pediatric trauma patients suspected of having cervical spine injuries.

BACKGROUND: Pediatric cervical spine injuries (CSI) are rare but potentially devastating sequelae of blunt trauma. Existing protocols to evaluate children at risk for CSI frequently incorporate computed topography (CT) and magnetic resonance imaging (MRI); however, the clinical value of performing both remains unclear. METHODS: Single-center retrospective review of pediatric trauma patients who underwent both CT and MRI of the cervical spine between 2001 and 2015. Based on radiographic findings, CT and MRI results were grouped into one of three categories: no injury, stable injury, or unstable injury. Radiographic instability was defined by disruption of two or more contiguous spinal columns while radiographic stability was defined by any other acute cervical spine abnormality on imaging. Clinical instability was defined by the need for surgical intervention (halo or spinal fusion), with the remaining patients, including children discharged in a cervical collar, considered clinically stable. RESULTS: In total, 221 children met inclusion criteria, with a median age of 9 (interquartile range, 3-14). The Glasgow Coma Scale (GCS) score of the cohort was 9 (interquartile range, 4-15). Thirty-three (14.9%) children had clinically unstable injuries, requiring surgical intervention. Among the 160 (72.4%) children with no injury on CT, MRI identified no injury in 84 (52.5%) cases, a stable injury in 76 (47.5%) cases, and an unstable injury in none. Among the 21 children with stable injuries on CT, MRI findings were concordant in 17 (81.0%) cases. In four (19.0%) cases, a spinal column injury was identified on CT and appeared to be stable, but later deemed unstable on MRI. Forty (18.1%) patients had an unstable injury on CT with 100% MRI concordance. CONCLUSION: In pediatric trauma patients suspected of having a CSI, a normal cervical spine CT is sufficient to rule out a clinically significant CSI as no child with a normal cervical CT was found to be radiographically or clinically unstable. LEVEL OF EVIDENCE: Diagnostic Test, level III.

Feasibility and Accuracy of Fast MRI Versus CT for Traumatic Brain Injury in Young Children.

BACKGROUND: Computed tomography (CT) is commonly used for children when there is concern for traumatic brain injury (TBI) and is a significant source of ionizing radiation. Our objective was to determine the feasibility and accuracy of fast MRI (motion-tolerant MRI sequences performed without sedation) in young children. METHODS: In this prospective cohort study, we attempted fast MRI in children <6 years old who had head CT performed and were seen in the emergency department of a single, level 1 pediatric trauma center. Fast MRI sequences included 3T axial and sagittal T2 single-shot turbo spin echo, axial T1 turbo field echo, axial fluid-attenuated inversion recovery, axial gradient echo, and axial diffusion-weighted single-shot turbo spin echo planar imaging. Feasibility was assessed by completion rate and imaging time. Fast MRI accuracy was measured against CT findings of TBI, including skull fracture, intracranial hemorrhage, or parenchymal injury. RESULTS: Among 299 participants, fast MRI was available and attempted in 225 (75%) and completed in 223 (99%). Median imaging time was 59 seconds (interquartile range 52-78) for CT and 365 seconds (interquartile range 340-392) for fast MRI. TBI was identified by CT in 111 (50%) participants, including 81 skull fractures, 27 subdural hematomas, 24 subarachnoid hemorrhages, and 35 other injuries. Fast MRI identified TBI in 103 of these (sensitivity 92.8%; 95% confidence interval 86.3-96.8), missing 6 participants with isolated skull fractures and 2 with subarachnoid hemorrhage. CONCLUSIONS: Fast MRI is feasible and accurate relative to CT in clinically stable children with concern for TBI.

Infection of the spheno-occipital synchondrosis: A morbid complication following adenoidectomy.

Two 2-year-old males presented post-operatively following adenoidectomy with persistent fever and neck stiffness. After multiple office visits, both patients were admitted and found to have a widened spheno-occipital synchondrosis and other imaging findings indicative of skull base osteomyelitis. Treatment with antibiotics allowed for recovery with good long-term outcomes. Infection involving the spheno-occiptal synchondrosis is rare and its circuitous presentation of these two children no doubt led to delayed diagnosis.

Use of magnetic resonance imaging to detect occult spinal dysraphism in infants.

OBJECTIVE Cutaneous stigmata or congenital anomalies often prompt screening for occult spinal dysraphism (OSD) in asymptomatic infants. While a number of studies have examined the results of ultrasonography (US) screening, less is known about the findings when MRI is used as the primary imaging modality. The object of this study was to assess the results of MRI screening for OSD in infants. METHODS The authors undertook a retrospective review of all infants who had undergone MRI of the lumbar spine to screen for OSD over a 6-year period (September 2006-September 2012). All images had been obtained on modern MRI scanners using sequences optimized to detect OSD, which was defined as any fibrolipoma of the filum terminale (FFT), a conus medullaris ending at or below the L2-3 disc space, as well as more complex lesions such as lipomyelomeningocele (LMM). RESULTS Five hundred twenty-two patients with a mean age of 6.2 months at imaging were included in the study. Indications for imaging included isolated dimple in 235 patients (45%), asymmetrically deviated gluteal cleft in 43 (8%), symmetrically deviated (Y-shaped) gluteal cleft in 38 (7%), hemangioma in 28 (5%), other isolated cutaneous stigmata (subcutaneous lipoma, vestigial tail, hairy patch, and dysplastic skin) in 31 (6%), several of the above stigmata in 97 (18%), and congenital anomalies in 50 (10%). Twenty-three percent (122 patients) of the study population had OSD. Lesions in 19% of these 122 patients were complex OSD consisting of LMM, dermal sinus tract extending to the thecal sac, and lipomeningocele. The majority of OSD lesions (99 patients [81%]) were filar abnormalities, a group including FFT and low-lying conus. The rate of OSD ranged from 12% for patients with asymmetrically deviated gluteal crease to 55% for those with other isolated cutaneous stigmata. Isolated midline dimple was the most common indication for imaging. Among this group, 20% (46 of 235) had OSD. There was no difference in the rate of OSD based on dimple location. Those with OSD had a mean dimple position of 15 mm (SD 11.8) above the coccyx. Those without OSD had a mean dimple position of 12.2 mm (SD 19) above the coccyx (p = 0.25). CONCLUSIONS The prevalence of OSD identified with modern high-resolution MRI screening is significantly higher than that reported with US screening, particularly in patients with dimples. The majority of OSD lesions identified are FFT and low conus. The clinical significance of such lesions remains unclear.

Confidence in Assessment of Lumbar Spondylolysis Using Three-Dimensional Volumetric T2-Weighted MRI Compared With Limited Field of View, Decreased-Dose CT.

BACKGROUND: Limited z-axis-coverage computed tomography (CT) to evaluate for pediatric lumbar spondylolysis, altering the technique such that the dose to the patient is comparable or lower than radiographs, is currently used at our institution. The objective of the study was to determine whether volumetric 3-dimensional fast spin echo magnetic resonance imaging (3D MRI) can provide equal or greater diagnostic accuracy compared with limited CT in the diagnosis of pediatric lumbar spondylolysis without ionizing radiation. HYPOTHESIS: Volumetric 3D MRI can provide equal or greater diagnostic accuracy compared with low-dose CT for pediatric lumbar spondylolysis without ionizing radiation. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 2. METHODS: Three pediatric neuroradiologists evaluated 2-dimensional (2D) MRI, 2D + 3D MRI, and limited CT examinations in 42 pediatric patients who obtained imaging for low back pain and suspected spondylolysis. As there is no gold standard for the diagnosis of spondylolysis besides surgery, interobserver agreement and degree of confidence were compared to determine which modality is preferable. RESULTS: Decreased-dose CT provided a greater level of agreement than 2D MRI and 2D + 3D MRI. The kappa for rater agreement with 2D MRI, 2D + 3D MRI, and CT was 0.19, 0.32, and 1.0, respectively. All raters agreed in 31%, 40%, and 100% of cases with 2D MRI, 2D + 3D MRI, and CT. Lack of confidence was significantly lower with CT (0%) than with 2D MRI (30%) and 2D + 3D MRI (25%). CONCLUSION: For diagnosing spondylolysis, radiologist agreement and confidence trended toward improvement with the addition of a volumetric 3D MRI sequence to standard 2D MRI sequences compared with 2D MRI alone; however, agreement and confidence remain significantly greater using decreased-dose CT when compared with either MRI acquisition. CLINICAL RELEVANCE: Decreased-dose CT of the lumbar spine remains the optimal examination to confirm a high suspicion of spondylolysis, with dose essentially equivalent to radiographs. If clinical symptoms are not classic for spondylolysis, 2D MRI is still very good at detecting spondylolysis while remaining sensitive for detection of alternative diagnoses such as disc abnormalities and pars stress reaction. The data suggest that standard 2D MRI sequences should not be entirely replaced by a volumetric T2-weighted 3D sequence (despite promising features of rapid acquisition time, increased spatial resolution, and reconstruction capability).

Atypical pediatric ganglioglioma is common and associated with a less favorable clinical course.

OBJECT Ganglioglioma (GG) is commonly recognized as a low-grade tumor located in the temporal lobe, often presenting with seizures. Most are amenable to complete resection and are associated with excellent oncological outcome. The authors encountered several GGs in various locations, which seem to have a less favorable clinical course than GGs in the temporal lobe. METHODS The authors performed a single-center retrospective review of all children with a histological diagnosis of GG who were treated at Children's Hospital Colorado between 1997 and 2013. Each tumor was categorized by 2 pediatric neuroradiologists as typical or atypical based on preoperative MRI appearance. Typical lesions were cortically based, within a single cerebral lobe, well-circumscribed, and solid or mixed solid/cystic. The treatment and clinical course of each patient was analyzed. RESULTS Thirty-seven children were identified, with a median age at presentation of 8.2 years and median follow-up of 38.0 months. Eighteen tumors (48.6%) were typical and 19 (51.4%) were atypical. All typical lesions presented with seizures, whereas no atypical lesions did so. Sixteen (88.9%) typical lesions were located in the temporal lobe. In the atypical group, tumor location was variable, including 11 (57.9%) in the brainstem. Death during follow-up was statistically more common in the atypical group (31.6% vs 0%, p = 0.02). Gross-total resection (GTR) was achieved for 15 of 16 typical tumors (93.8%), compared with 3 atypical tumors (15.8%, p < 0.0001). Presentation with seizure or non-brainstem location were each associated with survival (p = 0.02 and 0.004, respectively). The presence of mutation in BRAF exon 15 did not differ between the 2 groups. CONCLUSIONS Pediatric GG with typical imaging features is associated with excellent rates of GTR and overall survival. Atypical GG is commonly encountered, less amenable to GTR, and associated with a worse outcome. This may relate to anatomical or biological characteristics and merits further investigation.

Fractionated stereotactic radiosurgery for recurrent ependymoma in children.

Outcomes for children with relapsed ependymoma are poor. Re-irradiation is a potentially viable salvage option in these patients. Data were reviewed for 12 patients (median age 5.6 years) with relapsed ependymoma who received fractionated stereotactic radiosurgery (fSRS) following maximal surgical resection from 1995 to 2012. Four patients experienced a second recurrence, including 2 in-field and 2 distant failures. Median time to second recurrence (32 months) was significantly longer than time to first recurrence (24 months) (p = 0.008). Three-year local control was 89 %, and median event free survival from fSRS was 3.4 years. Radiation necrosis was observed in 6 patients, 3 who were symptomatic. In conclusion, fSRS offers durable response with a tolerable toxicity profile in children with recurrent EPN.

Craniocervical arterial dissection in children: diagnosis and treatment.

OPINION STATEMENT: Diagnosis of craniocervical arterial dissection (CCAD) in children begins with a careful history and physical in a child with a transient ischemic attack (TIA) or arterial ischemic stroke (AIS). The extent of radiologic evaluation for suspected CCAD is based upon careful consideration of the risks associated with the best imaging techniques, weighed against the benefits of enhanced vascular imaging with better diagnostic sensitivity. Although conventional angiography (CA) and CT angiography (CTA) have a higher sensitivity than magnetic resonance angiography (MRA), they are accompanied by risks: for CA, femoral hematoma, femoral arterial pseudoaneurysm, recurrent AIS, and radiation exposure; for CTA, radiation. For children (non-neonates) with suspected CCAD, MRI with MRA is recommended as the first-line imaging study. MRI usually includes diffusion-weighted, FLAIR, and T1 images of the brain, and T1 or T2 fat-saturation axial imaging through the neck. MRA should include 3D time-of-flight MRA of the head and neck (from the aortic arch through the circle of Willis). Contrast-enhanced MRA should be highly considered in neck imaging. If MRI/MRA is equivocal, CCAD is strongly suspected but not detected on MRI/MRA (especially in the posterior circulation), or the child has recurrent events, additional imaging of the craniocervical vasculature is likely warranted. Individual clinical circumstances warrant careful, case-by-case consideration. Treatment of CCAD in children is challenging and differs for intracranial and extracranial dissections. In extracranial CCAD, we most commonly use anticoagulation for 6 weeks to 6 months in patients with TIA or AIS. Typically, unfractionated heparin is used in the acutely ill patient at heightened risk for bleeding (because of its short half-life), whereas low-molecular-weight heparin (LMWH) or warfarin are reserved for the stable patient. If the history is suspicious for dissection (head and neck trauma, recent cervical chiropractic manipulation, recent car accident, or neck pain), we consider treatment for dissection even with normal MRI/MRA. For patients with CCAD with a stroke size greater than one third to one half of the middle cerebral artery territory (or other bleeding risk factors) and extracranial CCAD, in whom there is concern about heightened risk for hemorrhagic conversion, we commonly use aspirin therapy during the acute phase. Regardless of their treatment in the initial weeks to months, we subsequently treat all patients with aspirin for 1 year after their event, and sometimes longer if they have other risk factors. Interventional techniques, such as extracranial cerebral arterial stent placement or selective occlusion, are understudied in children. Interventional techniques are typically reserved for patients who fail aggressive medical management and have recurrent TIA or AIS. The diagnosis and treatment of intracranial dissection is extraordinarily challenging in children, in whom inflammatory intracranial arteriopathies are common. When intracranial arteriopathy is clearly associated with dissection, the clinician should look for the presence of subarachnoid hemorrhage and/or dissecting aneurysm. Treatment decisions should be made by a multidisciplinary pediatric stroke team, given the lack of data in this area. Intracranial cerebral artery stent placement carries high risk and is not recommended for intracranial CCAD in children. Most importantly, we educate all children with CCAD and their parents about the paucity of evidence in the treatment of this disease, the risks of enhanced imaging techniques such as CTA or CA, and the challenges involved in weighing the risks of aggressive therapies and interventions against the costs of unclear diagnosis and potentially ineffective treatments. We also educate our patients with CCAD about the signs and symptoms of recurrence and the importance of emergent evaluation.