Adaptive, behavioral, and emotional outcomes following postoperative pediatric cerebellar mutism syndrome in survivors treated for medulloblastoma.

OBJECTIVE: Patients who experience postoperative pediatric cerebellar mutism syndrome (CMS) during treatment for medulloblastoma have long-term deficits in neurocognitive functioning; however, the consequences on functional or adaptive outcomes are unknown. The purpose of the present study was to compare adaptive, behavioral, and emotional functioning between survivors with and those without a history of CMS. METHODS: The authors examined outcomes in 45 survivors (15 with CMS and 30 without CMS). Comprehensive neuropsychological evaluations, which included parent-report measures of adaptive, behavioral, and emotional functioning, were completed at a median of 2.90 years following craniospinal irradiation. RESULTS: Adaptive functioning was significantly worse in the CMS group for practical and general adaptive skills compared with the group without CMS. Rates of impairment in practical, conceptual, and general adaptive skills in the CMS group exceeded expected rates in the general population. Despite having lower overall intellectual functioning, working memory, and processing speed, IQ and related cognitive processes were uncorrelated with adaptive outcomes in the CMS group. No significant group differences or increased rates of impairment were observed for behavioral and emotional outcomes. CONCLUSIONS: Survivors with CMS, compared with those without CMS, are rated as having significant deficits in overall or general adaptive functioning, with specific weakness in practical skills several years posttreatment. Findings from this study demonstrate the high risk for ongoing functional deficits despite acute recovery from symptoms of CMS, highlighting the need for intervention to mitigate such risk.

Advances in Imaging Modalities for Pediatric Brain and Spinal Cord Tumors.

BACKGROUND: Neuroimaging has evolved from anatomical imaging toward a multi-modality comprehensive anatomical and functional imaging in the past decades, important functional data like perfusion-weighted imaging, permeability imaging, diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI), tractography, metabolic imaging, connectomics, event-related functional imaging, resting state functional imaging, and much more is now being offered. SUMMARY: Precision diagnostics has proven to be essential for precision treatment. Many minimal invasive techniques have been developed, taking advantage of digital subtraction angiography and interventional neuroradiology. Furthermore, intraoperative CT and/or MRI and more recently MR-guided focused ultrasound have complemented the diagnostic and therapeutic armamentarium. KEY MESSAGES: In the current manuscript, we discuss standard imaging sequences including advanced techniques like DWI, DTI, susceptibility-weighted imaging, and 1H magnetic resonance spectroscopy, various perfusion weighted imaging approaches including arterial spin labeling, dynamic contrast enhanced imaging, and dynamic susceptibility contrast imaging. Pre-, intra, and postoperative surgical imaging including visualize imaging will be discussed. The value of connectomics will be presented for its value in neuro-oncology. Minimal invasive therapeutic possibilities of interventional neuroradiology and image-guided laser ablation and MR-guided high-intensity-focused ultrasound will be presented for treatment of pediatric brain and spinal cord tumors. Finally, a comprehensive review of spinal cord tumors and matching neuropathology has been included.

Diagnostic and management roles of FDG PET/CT imaging in post-transplant lympho-proliferation in pediatric heart transplantation.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of pediatric heart transplant (PHTx). 18F-FDG PET/CT has been used to differentiate early lympho-proliferation from more advanced PTLD. We report our experience with PET/CT in the management of PTLD following PHTx. METHODS: This was a retrospective study of 100 consecutive PHTx recipients at our institution between 2004 and 2018. Patients who underwent PET/CT or conventional CT scans to evaluate for PTLD or high Epstein-Barr viral load were included. RESULTS: Males, eight females. Median age at transplant was 3.5 months (IQR = 1.5-27.5). Median age at PTLD diagnosis was 13.3 years (IQR = 9.2-16.1). Median time between transplant and PTLD diagnosis was 9.5 (IQR = 4.5-15) years. Induction agents were used in 12 patients (50%): Thymoglobulin (N = 9), anti-IL2 (N = 2), and Rituximab (N = 1). Eighteen patients (75%) had PET/CT, of whom 14 had 18FDG-avid PTLD. Six had conventional CT. Nineteen patients (79.2%) had diagnostic biopsy confirmation of PTLD, and 5 (20.8%) had excisional biopsies. Two patients had Hodgkin's lymphoma; nine had monomorphic PTLD; eight had polymorphic PTLD; five were classified as other. Nine patients had monomorphic PTLD, including seven with diffuse large cell lymphoma (DLBC) and one with T cell lymphoma. The majority (16/24) had multi-site involvement at PTLD diagnosis, and PET/CT showed that 31.3% (5/16) had easily accessible subcutaneous nodes. Seventeen patients (overall survival 71%) underwent successful treatment without recurrence of PTLD. Of seven deaths (7/24, 29%), five had DLBC lymphoma, one had polymorphic PTLD and one had T-cell lymphoma. CONCLUSION: PET-CT allowed simultaneous anatomical and functional assessment of PTLD lesions, while guiding biopsy. In patients with multiple lesions, PET/CT revealed the most prominent and active lesions, improving diagnostic accuracy.

Hemostatic and Thrombotic Considerations in the Diagnosis and Management of Childhood Arterial Ischemic Stroke: A Narrative Review.

Although rare in children, arterial ischemic stroke (AIS) is associated with increased mortality and neurological morbidity. The incidence of AIS after the neonatal period is approximately 1-2/100,000/year, with an estimated mortality of 3-7%. A significant proportion of children surviving AIS experience life-long neurological deficits including hemiparesis, epilepsy, and cognitive delays. The low incidence of childhood AIS coupled with atypical clinical-presentation and lack of awareness contribute to delay in diagnosis and consequently, the early initiation of treatment. While randomized-clinical trials have demonstrated the efficacy and safety of reperfusion therapies including thrombolysis and endovascular thrombectomy in appropriately-selected adult patients, similar data for children are unavailable. Consequently, clinical decisions surrounding reperfusion therapy in childhood AIS are either extrapolated from adult data or based on local experience. The etiology of childhood AIS is multifactorial, often occurring in the setting of both acquired and congenital risk-factors including thrombophilia. While multiple studies have investigated the association of thrombophilia with incident childhood AIS, its impact on stroke recurrence and therefore duration and intensity of antithrombotic therapy is less clear. Despite these limitations, a significant progress has been made over the last decade in the management of childhood AIS. This progress can be attributed to international consortiums, and in selected cohorts to federally-funded clinical trials. In this narrative review, the authors have systematically appraised the literature and summarize the hemostatic and thrombotic considerations in the diagnosis and management of childhood AIS focusing on the evidence supporting reperfusion therapies, relevance of thrombophilia testing, and duration and drug choices for secondary-prophylaxis.

Development of a composite diffusion tensor imaging score correlating with short-term neurological status in neonatal hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal acquired brain injury. Although conventional MRI may predict neurodevelopmental outcomes, accurate prognostication remains difficult. As diffusion tensor imaging (DTI) may provide an additional diagnostic and prognostic value over conventional MRI, we aimed to develop a composite DTI (cDTI) score to relate to short-term neurological function. Sixty prospective neonates treated with therapeutic hypothermia (TH) for HIE were evaluated with DTI, with a voxel size of 1 × 1 × 2 mm. Fractional anisotropy (FA) and mean diffusivity (MD) from 100 neuroanatomical regions (FA/MD *100 = 200 DTI parameters in total) were quantified using an atlas-based image parcellation technique. A least absolute shrinkage and selection operator (LASSO) regression was applied to the DTI parameters to generate the cDTI score. Time to full oral nutrition [short-term oral feeding (STO) score] was used as a measure of short-term neurological function and was correlated with extracted DTI features. Seventeen DTI parameters were selected with LASSO and built into the final unbiased regression model. The selected factors included FA or MD values of the limbic structures, the corticospinal tract, and the frontotemporal cortices. While the cDTI score strongly correlated with the STO score (rho = 0.83, p = 2.8 × 10-16), it only weakly correlated with the Sarnat score (rho = 0.27, p = 0.035) and moderately with the NICHD-NRN neuroimaging score (rho = 0.43, p = 6.6 × 10-04). In contrast to the cDTI score, the NICHD-NRN score only moderately correlated with the STO score (rho = 0.37, p = 0.0037). Using a mixed-model analysis, interleukin-10 at admission to the NICU (p = 1.5 × 10-13) and tau protein at the end of TH/rewarming (p = 0.036) and after rewarming (p = 0.0015) were significantly associated with higher cDTI scores, suggesting that high cDTI scores were related to the intensity of the early inflammatory response and the severity of neuronal impairment after TH. In conclusion, a data-driven unbiased approach was applied to identify anatomical structures associated with some aspects of neurological function of HIE neonates after cooling and to build a cDTI score, which was correlated with the severity of short-term neurological functions.

Eosinophilic Meningitis: Eleven-Year Experience at Texas Children's Hospital.

Eosinophilic meningitis can be caused by various etiologies and is reported mostly in tropical climates. The diagnosis is rare in the continental US, presenting challenges for management. Following a case of pediatric eosinophilic meningitis, we reviewed our 11-year experience with this diagnosis at a large US children's hospital.

Cerebellar Mutism Syndrome in Pediatric Neuro-oncology: A Multidisciplinary Perspective and Call for Research Priorities.

Cerebellar mutism syndrome (CMS), also known as posterior fossa syndrome, occurs in a subset of children after posterior fossa tumor resection, most commonly medulloblastoma. Patients with this syndrome exhibit often transient, although protracted, symptoms of language impairment, emotional lability, cerebellar, and brainstem dysfunction. However, many patients experience persistent neurological deficits and lasting neurocognitive impairment. Historically, research and clinical care were hindered by inconsistent nomenclature, poorly defined diagnostic criteria, and uncertainty surrounding risk factors and etiology. Proposed diagnostic criteria include two major symptoms, language impairment and emotional lability, as proposed by the international Board of the Posterior Fossa Society in their consensus statement as well as other experts in this field. Risk factors most commonly associated with development of CMS include midline tumor location, diagnosis of medulloblastoma and specific tumor subtype, younger age at diagnosis, and preoperative language impairment. A proposed etiology of CMS includes disruption of the cerebellar outflow tracts, the cerebellar nuclei, and their efferent projections through the superior cerebellar peduncle. Treatment for CMS remains supportive. Herein, we present a comprehensive overview of CMS etiology, diagnosis, risk factors, clinical presentation, and clinical management. In addition, we identify essential multidisciplinary research priorities to advance diagnostics, prevention, and intervention efforts for patients with, or at risk for, development of CMS.

Patient-Specific Modeling Could Predict Occurrence of Pediatric Stroke.

Moyamoya disease (MMD) is a progressive steno-occlusive cerebrovascular disease leading to recurrent stroke. There is a lack of reliable biomarkers to identify unilateral stroke MMD patients who are likely to progress to bilateral disease and experience subsequent contralateral stroke(s). We hypothesized that local hemodynamics are predictive of future stroke and set out to noninvasively assess this stroke risk in pediatric MMD patients. MR and X-ray angiography imaging were utilized to reconstruct patient-specific models of the circle of Willis of six pediatric MMD patients who had previous strokes, along with a control subject. Blood flow simulations were performed by using a Navier-Stokes solver within an isogeometric analysis framework. Vascular regions with a wall shear rate (WSR) above the coagulation limit (>5,000 s-1) were identified to have a higher probability of thrombus formation, potentially leading to ischemic stroke(s). Two metrics, namely, "critical WSR coverage" and "WSR score," were derived to assess contralateral stroke risk and compared with clinical follow-up data. In two patients that suffered a contralateral stroke within 2 months of the primary stroke, critical WSR coverages exceeding 50% of vessel surface and WSR scores greater than 6× the control were present in multiple contralateral vessels. These metrics were not as clearly indicative of stroke in two additional patients with 3-5 year gaps between primary and contralateral strokes. However, a longitudinal study of one of these two cases, where a subsequent timepoint was analyzed, suggested disease stabilization on the primary stroke side and an elevated contralateral stroke risk, which was confirmed by patient outcome data. This indicates that post-stroke follow-up at regular intervals might be warranted for secondary stroke prevention. The findings of this study suggest that WSR-based metrics could be predictive of future stroke risk after an initial stroke in pediatric MMD patients. In addition, better predictions may be possible by performing patient-specific hemodynamic analysis at multiple timepoints during patient follow-up to monitor changes in the WSR-based metrics.

Radiologic and clinical outcome of isolated fourth ventricle following post-hemorrhagic hydrocephalus in children.

PURPOSE: Few studies report radiologic and clinical outcome of post-hemorrhagic isolated fourth ventricle (IFV) with focus on surgical versus conservative management in neonates and children. Our aim is to investigate differences in radiological and clinical findings of IFV between patients who had surgical intervention versus patients who were treated conservatively. METHODS: A retrospective analysis of patients diagnosed with IFV was performed. Data included demographics, clinical exam findings, surgical history, and imaging findings (dilated FV extent, supratentorial ventricle dilation, brainstem and cerebellar deformity, tectal plate elevation, basal cistern and cerebellar hemisphere effacement, posterior fossa upward/downward herniation). RESULTS: Sixty-four (30 females) patients were included. Prematurity was 94% with 90% being < 28 weeks of gestation. Mean age at first ventricular shunt was 3.6 (range 1-19); at diagnosis of IFV, post-lateral ventricular shunting was 26.2 (1-173) months. Conservatively treated patients were 87.5% versus 12.5% treated with FV shunt/endoscopic fenestration. Severe FV dilation (41%), severe deformity of brainstem (39%) and cerebellum (47%) were noted at initial diagnosis and stable findings (34%, 47%, and 52%, respectively) were seen at last follow-up imaging. FV dilation (p = 0.0001) and upward herniation (p = 0.01) showed significant differences between surgery versus conservative management. No other radiologic or clinical outcome parameters were different between two groups. CONCLUSION: Only radiologic outcome results showed stable or normal FV dilation and stable or decreased upward herniation in the surgically treated group.

Another Piece of the Puzzle of Anomalous Connectivity in Joubert's Syndrome.

We report on the conventional and diffusion tensor imaging (DTI) findings of a 2-year-old child with clinical presentation of Joubert's Syndrome (JS) and brainstem structural abnormalities as depicted by neuroimaging.Conventional magnetic resonance imaging (MRI) showed a "molar tooth" configuration of the brainstem. A band-like formation coursing in an apparent axial plane anterior to the interpeduncular fossa was noted and appeared to partially cover the interpeduncular fossa.DTI maps and three-dimensional (3D) tractography demonstrated a prominent red-encoded white matter bundle anterior to the midbrain. Probable aberrant course of the bilateral corticospinal tracts (CST) was also depicted. Absence of the decussation of the superior cerebellar peduncles and elongated thickened, horizontal superior cerebellar peduncle (SCP) reflecting the molar tooth sign were also shown.Our report and the review of the published cases suggest that DTI and tractography may be very helpful to differentiate between interpeduncular heterotopias and similarly located white matter bundles corroborating the underlying etiology of axonal guidance disorders in the complex group of ciliopathies including JS. Our case represents an important additional puzzle piece to explore the variability of these ciliopathies.

Neural correlates of cognitive behavioral therapy response in youth with negative valence disorders: A systematic review of the literature.

BACKGROUND: Cognitive-behavioral therapy (CBT) is the gold-standard psychotherapeutic treatment for pediatric negative valence disorders. However, some youths do not respond optimally to treatment, which may be due to variations in neural functioning. METHODS: We systematically reviewed functional magnetic resonance imaging studies in youths with negative valence disorders to identify pre- and post-treatment neural correlates of CBT response. RESULTS: A total of 21 studies were identified, of overall weak to moderate quality. The most consistent findings across negative valence disorders consisted of associations of treatment response with pre- and post-treatment task-based activation and/or functional connectivity within and between the prefrontal cortex, the medial temporal lobe, and other limbic regions. Associations of CBT response with baseline and/or post-treatment activity in the striatum, precentral and postcentral gyri, medial and posterior cingulate cortices, and parietal cortex, connectivity within and between the default-mode, cognitive control, salience, and frontoparietal networks, and metrics of large-scale brain network organization, were also reported, although less consistently. LIMITATIONS: The poor quality and limited number of studies and the important heterogeneity of study designs and results considerably limit the conclusions that can be drawn from this literature. CONCLUSIONS: Despite these limitations, these findings provide preliminary evidence suggesting youths presenting certain patterns of brain function may respond better to CBT, whereas others may benefit from alternative or augmented forms of treatment.

Neuroimaging Characteristics of Nasopharyngeal Carcinoma in Children.

BACKGROUND AND PURPOSE: Pediatric nasopharyngeal carcinoma (NPC) is a rare epithelial origin tumor associated with undifferentiated histology, Epstein-Barr virus (EBV) infection, and genetic risk factors. Childhood NPC is usually clinically silent, often presenting with advanced locoregional compromise, including skull base invasion and cervical lymphadenopathy, and has a better prognosis than adult NPC. This article describes computed tomography (CT) and magnetic resonance imaging (MRI) features in a cohort of 28 pediatric NPC patients. METHODS: A retrospective review was performed among children with histopathology proven NPC diagnoses between 1996 and 2019 for this study. The electronic medical records were reviewed to determine demographics, EBV serology, and World Health Organization (WHO) type. Nasopharyngeal CT and/or MRI at presentation for tumor spread as well as density and/or intensity, lymphadenopathy, postcontrast enhancement and diffusion characteristics before treatment were evaluated. RESULTS: Twenty-eight patients (21 males, 7 females) were included. The mean patient age at diagnosis was 13.3 (range 7 to 17) years. EBV was positive in 71.4% of patients. The majority of patients (78.6%) had a WHO type III tumor, unilateral fossa of Rosenmuller involvement (71.4%). Neuroimaging features were CT isodensity, T1-isointensity, T2-hyperintensity, and heterogeneous postcontrast enhancement for all patients (100%) and restricted diffusion (90%). CONCLUSIONS: Although uncommon in pediatric patients, NPC should be in the differential diagnosis of adolescents presenting with a nasopharyngeal mass. Recognizing key imaging characteristics is helpful in the diagnosis of NPC.

Characterization of Visual Pathway Abnormalities in Infants With Congenital Zika Syndrome Using Computed Tomography and Magnetic Resonance Imaging.

BACKGROUND: Severe visual impairment is present in nearly all infants with congenital Zika syndrome (CZS); however, ocular abnormalities are present only in a subset of these infants. The purpose of this study was to characterize the visual pathway abnormalities seen on computed tomography (CT) and MRI scans in infants with CZS. METHODS: Preliminary neuroimaging information was obtained from a referred sample of 105 infants with clinical and epidemiologic data consistent with CZS in the Pernambuco state of Brazil. Subjects were excluded if Zika virus infection was not confirmed by serologic or cerebrospinal fluid studies or if images were nondiagnostic. Of the 105 subjects initially screened, head CT images adequate for interpretation were available for 54, and brain MRI images adequate for interpretation were available for 20. Four patients had both CT and MRI images. Magnetic resonance imaging and CT scans from infants with CZS were systematically reviewed for globe malformations, optic nerve and chiasmal atrophy, occipital cortical volume loss, white matter abnormalities, ventriculomegaly, and calcifications. Neuroimaging findings were correlated with measures of visual function and with ocular examinations in these infants. RESULTS: Thirty-three males and 37 females were included in the analysis. The mean age of the infants at the time of neuroimaging was 16.0 weeks (range 0 days-15.5 months), and the mean gestational age at the time of birth was 38 weeks. All patients were from the Pernambuco state of Brazil. Overall, 70 of 74 (95%) scans showed occipital volume loss, whereas 9 (12%) showed optic nerve atrophy, 3 (4%) showed chiasmal atrophy, and 1 (1%) showed an ocular calcification. Sixty-two of the infants underwent ophthalmologic examinations. A total of 34 (55%) infants had at least one documented structural ocular abnormality, and 26 (42%) had at least one structural ocular abnormality documented in both eyes. Of those with available visual acuity data, all had visual impairment. Among those with visual impairment and normal eye examinations, 100% had visual pathway abnormalities on neuroimaging, including 100% with occipital cortical volume loss, 8% with optic nerve atrophy, and 8% with chiasmal atrophy. CONCLUSION: Our results suggest that cortical visual impairment related to structural abnormalities of the occipital cortex is likely an important cause of visual impairment in children with CZS with normal eye examinations.

Risk factors for pediatric cerebral sinovenous thrombosis: A case-control study with case validation.

INTRODUCTION: Cerebral sinovenous thrombosis (CSVT) represents the second most common type of venous thromboembolism (VTE) in children. Current literature includes limited evidence on risk factors for CSVT, particularly in the pediatric population. We sought to determine risk factors for CSVT in pediatric patients through a single-institutional case-control study. In addition, we evaluated thrombophilias, treatments and outcomes in CSVT among cases. METHODS: A case-control study was performed at Johns Hopkins All Children's Hospital on patients admitted from March 31, 2006 through April 1, 2018. Cases were identified using diagnostic codes and confirmed based on electronic health record (EHR) and neuroimaging review. Controls were matched in a 2:1 fashion accounting for the month and year of admission. RESULTS: A total of 60 CSVT cases and 120 controls were identified. Median (range) age was 4.8 years (0-21.3 years) for cases and 5.6 years (0-20.0 years) for controls. Factors putatively associated with CSVT in unadjusted analyses were: corticosteroid use, presence of a central venous catheter, mechanical ventilation, systemic infection, head/neck infection, head/neck trauma, and chronic inflammatory disease. In the multivariable model, head/neck infection (OR: 13.8, 95% CI: 4.87-38.7; P < 0.01), head/neck trauma (OR: 12.7, 95% CI: 2.88-56.2; P < 0.01), and mechanical ventilation (OR: 9.32, 95% CI: 2.35-36.9; P = 0.01) remained independent, statistically-significant risk factors. 61% of patients were subacutely treated with anticoagulants and of those, only two developed relevant bleeding after initiation of therapy. CONCLUSIONS: This single-institutional case-control study reveals that head/neck infection, head/neck trauma, and mechanical ventilation are independent risk factors for pediatric CSVT. These findings will be further investigated via a cooperative registry of pediatric hospital-acquired VTE, by which a risk model for pediatric CSVT will be developed and validated, in order to inform future preventive strategies in at-risk pediatric patients.

Imaging of Paranasal Sinus Infections in Children: A Review.

Paranasal sinuses (PNS) infections are common in children. They may cause common and well-known complications, but also, unusual and potentially devastating complications. Diagnosing PNS infections and complications in children requires knowledge of the unique anatomy of the nasal cavity and the PNS. In fetal life, nasal mucosa evaginations into the lateral nasal walls initiate the development of the PNS. The PNS continue to develop after birth and complete their maturation and pneumatization at different ages during childhood which makes the pattern of PNS infections determined by patient age. Complications are caused by direct spread of the infection to the orbit, face, intracranial or osseous structures or hematogenous spread of the infection to the intracranial structures. Emergent imaging studies are often necessary in the evaluation of the complications in pediatric patients when the symptoms persist for 10 days and/or if there is evidence of intracranial or orbital complications. In addition, immunocompromised children are especially vulnerable to developing unusual complications. Computed tomography (CT) is excellent for determining whether there is intraorbital extension of PNS disease. However, when the infection approaches the orbital apex, a magnetic resonance imaging (MRI) study with contrast is necessary to assess spread into the cavernous sinus and the intracranial compartment. The goal of this manuscript is to review and characterize imaging findings of PNS infections using CT and MRI allowing determination of the extent of PNS infections and their common and unusual complications in children. In addition, a summary of the development of the normal PNS is provided.

Diffusion Weighted and Diffusion Tensor MRI in Pediatric Neuroimaging Including Connectomics: Principles and Applications.

Diffusion weighted MRI (DWI) including diffusion tensor imaging (DTI) are unique imaging techniques that render qualitative and quantitative information of the central nervous system white matter (WM) ultrastructure. It uses the Brownian movement of water molecules to probe tissue microstructure. It is a noninvasive method, with superb sensitivity to the differential mobility of water molecules within various components of the brain without the necessity to inject contrast agents. By sampling the 3 dimensional shape, direction and magnitude of the water diffusion, DWI/DTI generates unique tissue contrasts that can be used to study the axonal WM organization of the central nervous system. Its application allows to study the normal and anomalous brain development including connectivity, as well as a multitude of WM diseases. This article discusses/summarizes the principles of DWI/DTI and its applications in pediatric neuroscience research.

Neurological manifestations of Erdheim-Chester Disease.

OBJECTIVE: To characterize the spectrum of neurologic involvement in Erdheim-Chester Disease (ECD), a treatable inflammatory neoplasm of histiocytes. METHODS: Sixty-two patients with ECD were prospectively enrolled in a natural history study that facilitated collection of clinical, imaging, laboratory, neurophysiologic, and pathologic data. RESULTS: Ninety-four percent of the patients had neurologic abnormalities on examination or imaging, and 22% had neurologic symptoms as the initial presentation of ECD. The most common neurologic findings were cognitive impairment, peripheral neuropathy, pyramidal tract signs, cranial nerve involvement, and cerebellar ataxia. Imaging revealed atrophy and demyelination along with focal lesions that were located throughout the nervous system, dura, and extra-axial structures. The BRAF V600E variant correlated with cerebral atrophy. Brain pathology revealed lipid-laden, phagocytic macrophages (histiocytes) accompanied by demyelination and axonal degeneration. INTERPRETATION: In patients with ECD, neurologic morbidity is common and contributes significantly to disability. Since neurologic symptoms can be the presenting feature of ECD and, given the mean delay in ECD diagnosis is 4.2 years, it is critical that neurologists consider of ECD and other histiocytosis in patients with inflammatory, infectious, or neoplastic-appearing white matter. Furthermore, given the broad spectrum of neurologic involvement, neurologists have an important role in a team of specialists treating ECD patients.

Diffusion Tensor Imaging Connectomics Reveals Preoperative Neural Connectivity Changes in Children with Postsurgical Posterior Fossa Syndrome.

BACKGROUND AND PURPOSE: Posterior fossa syndrome (PFS), characterized by loss of language and other neurological impairments within the immediate postoperative period, occurs in approximately 25% of children who undergo surgical resection of posterior fossa tumors. Diffusion tensor imaging connectomics offer promise for elucidation of pathway-level disruption in neural connectivity of patients with this disorder. We aim to determine differences in pre- and postoperative connectomics between children with PFS and children with mild or no language deficit after surgery. METHODS: Pre- and postoperative diffusion tensor imaging connectomics were applied and compared among patients with PFS, mild deficits, and intact language. RESULTS: A total of 35 patients were included in the study. Twenty-three patients with preoperative data and 24 patients with postoperative data were included in the analysis. Mean ages: PFS-8.5 years, mild-3.1 years, intact language-9.4 years (P = .02). Diagnoses included medulloblastoma (44.1%), pilocytic astrocytoma (28.6%), ependymoma (8.6%), other (11.4%), and unknown (8.6%). Five (21.7%) patients had PFS, 4 (17.4%) had mild deficits, and 14 (60.9%) had intact language. The assortativity coefficient was significantly higher in patients with PFS when compared to patients with mild deficits (P = .023). In the connectometry analyses, decreased connectivity was found involving the corpus callosum, right corticothalamic pathway, and right corticostriatal pathway in patients with PFS when compared to patients with intact language. CONCLUSIONS: Our findings revealed significant differences in preoperative neural connectivity involving the corticothalamic and other pathways among children who did, versus who did not, develop PFS postoperatively. Diffusion tensor imaging connectomics offers a unique opportunity to study the effect of the posterior fossa tumors on cerebello-cerebral networks and provide new insights into the mechanism of the structural plasticity/reorganization after surgery.