A Comprehensive Examination of Clinical Characteristics and Determinants of Long-Term Outcomes in Pediatric Cerebral Sinus Venous Thrombosis.

BACKGROUND: To analyze the clinical and neuroimaging features, risk factors, treatment choices, and long-term clinical outcomes in children with cerebral sinus venous thrombosis (CSVT). METHODS: This is a retrospective cohort study of children diagnosed with CSVT between 2002 and 2018 at Texas Children's Hospital. RESULTS: A total of 183 children (male: 62.3%) with CSVT were included. The average presenting age was 7.7 years (S.D.: 5.6). The mean follow-up duration was 33.7 months (S.D.: 38.6). The most common presenting clinical feature was headache (36.6%). Head and neck infections other than meningitis (36.6%) were the most common risk factors. Prevalent neurological examination findings included motor deficit (21.3%) and altered mental status (AMS, 20.2%). Neuroimaging features included hemorrhagic infarction (19.6%), ischemic infarction (8.2%), and intracranial hemorrhage without infarction (5.5%). The most common site of thrombosis was the superior sagittal sinus (37.2%), with 78.2% of patients demonstrating involvement of multiple sinuses. Treatment of choice was low-molecular-weight heparin in 69.4% of patients. Factors associated with worse clinical outcomes included head and neck infections, malignancy (other than hematologic), cardiac disease, and recent surgery; seizure and dehydration on initial presentation; motor abnormalities and AMS on initial examination; ischemic infarct only; and involvement of vein of Trolard on neuroimaging. Thrombus condition on repeat imaging, receiving any anticoagulant/antithrombotic treatment, treatment duration, or follow-up duration was not associated with severity of long-term outcome. CONCLUSIONS: CSVT may lead to unfavorable long-term outcomes in a remarkable portion of pediatric patients. Thus, a high index of suspicion and early and appropriate management of pediatric CSVT is imperative.

Expanded clinical phenotype and untargeted metabolomics analysis in RARS2-related mitochondrial disorder: a case report.

BACKGROUND: RARS2-related mitochondrial disorder is an autosomal recessive mitochondrial encephalopathy caused by biallelic pathogenic variants in the gene encoding the mitochondrial arginyl-transfer RNA synthetase 2 (RARS2, MIM *611524, NM_020320.5). RARS2 catalyzes the transfer of L-arginine to its cognate tRNA during the translation of mitochondrially-encoded proteins. The classical presentation of RARS2-related mitochondrial disorder includes pontocerebellar hypoplasia (PCH), progressive microcephaly, profound developmental delay, feeding difficulties, and hypotonia. Most patients also develop severe epilepsy by three months of age, which consists of focal or generalized seizures that frequently become pharmacoresistant and lead to developmental and epileptic encephalopathy (DEE). CASE PRESENTATION: Here, we describe a six-year-old boy with developmental delay, hypotonia, and failure to thrive who developed an early-onset DEE consistent with Lennox-Gastaut Syndrome (LGS), which has not previously been observed in this disorder. He had dysmorphic features including bilateral macrotia, overriding second toes, a depressed nasal bridge, retrognathia, and downslanting palpebral fissures, and he did not demonstrate progressive microcephaly. Whole genome sequencing identified two variants in RARS2, c.36 + 1G > T, a previously unpublished variant that is predicted to affect splicing and is, therefore, likely pathogenic and c.419 T > G (p.Phe140Cys), a known pathogenic variant. He exhibited significant, progressive generalized brain atrophy and ex vacuo dilation of the supratentorial ventricular system on brain MRI and did not demonstrate PCH. Treatment with a ketogenic diet (KD) reduced seizure frequency and enabled him to make developmental progress. Plasma untargeted metabolomics analysis showed increased levels of lysophospholipid and sphingomyelin-related metabolites. CONCLUSIONS: Our work expands the clinical spectrum of RARS2-related mitochondrial disorder, demonstrating that patients can present with dysmorphic features and an absence of progressive microcephaly, which can help guide the diagnosis of this condition. Our case highlights the importance of appropriate seizure phenotyping in this condition and indicates that patients can develop LGS, for which a KD may be a viable therapeutic option. Our work further suggests that analytes of phospholipid metabolism may serve as biomarkers of mitochondrial dysfunction.

Prognostic Significance of Central Skull Base Remodeling in Chiari II Malformation.

BACKGROUND AND PURPOSE: Outward convexity of the basiocciput and posterior atlanto-occipital membrane are common in patients with Chiari II malformation associated with an open neural tube defect. We aimed to determine if the severity of these findings correlated with the need for future hydrocephalus treatment. MATERIALS AND METHODS: A retrospective chart and imaging review identified patients who underwent open neural tube defect repair at a quaternary care pediatric hospital from July 2014 through September 2022. Patients were classified by the need for hydrocephalus treatment and whether they received prenatal or postnatal neural tube defect repair. Measurements of imaging parameters related to posterior fossa maldevelopment and skull base remodeling were performed. RESULTS: Compared with 65 patients who did not require hydrocephalus treatment, 74 patients who required treatment demonstrated statistically significantly greater mean basiocciput convexity (P < .001). While the mean basiocciput length in the hydrocephalus treatment group was smaller (P < .001), the ratio of basiocciput convexity to length was larger (P < .001). Notably, 100% of patients with a basiocciput convexity of ≥4 mm required hydrocephalus treatment. The mean posterior atlanto-occipital membrane convexity was significantly greater for patients who required hydrocephalus treatment in the postnatal group (P = .02), but not the prenatal group (P = .09). CONCLUSIONS: Pediatric patients with Chiari II malformation who ultimately required surgical hydrocephalus treatment had greater outward convexity of the basiocciput but had greater posterior atlanto-occipital membrane outward convexity only if the repair was performed postnatally. Together these measurements may be useful in predicting the need for hydrocephalus treatment.

Heteroplasmic pathogenic m.12315G>A variant in MT-TL2 presenting with MELAS syndrome and depletion of nitric oxide donors.

The MT-TL2 m.12315G>A pathogenic variant has previously been reported in five individuals with mild clinical phenotypes. Herein we report the case of a 5-year-old child with heteroplasmy for this variant who developed neurological regression and stroke-like episodes similar to those observed in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Biochemical evaluation revealed depletion of arginine on plasma amino acid analysis and low z-scores for citrulline on untargeted plasma metabolomics analysis. These findings suggested that decreased availability of nitric oxide may have contributed to the stroke-like episodes. The use of intravenous arginine during stroke-like episodes and daily enteral L-citrulline supplementation normalized her biochemical values of arginine and citrulline. Untargeted plasma metabolomics showed the absence of nicotinamide and 1-methylnicotinamide, and plasma total glutathione levels were low; thus, nicotinamide riboside and N-acetylcysteine therapies were initiated. This report expands the phenotype associated with the rare mitochondrial variant MT-TL2 m.12315G>A to include neurological regression and a MELAS-like phenotype. Individuals with this variant should undergo in-depth biochemical analysis to include untargeted plasma metabolomics, plasma amino acids, and glutathione levels to help guide a targeted approach to treatment.

Pediatric and adult meningeal, parenchymal, and spinal tuberculosis: A neuroimaging review.

Neurotuberculosis is defined as a tuberculous infection of the meninges, brain parenchyma, vessels, cranial and spinal nerves, spinal cord, skull, and spine that can occur either in a localized or in a diffuse form. It is a heterogeneous disease characterized by many imaging appearances and it has been defined as "the great mimicker" due to similarities with many other conditions. The diagnosis of central nervous system (CNS) tuberculosis (TB) is based on clinical presentation, neuroimaging findings, laboratory and microbiological findings, and comprehensive evaluation of the response to anti-TB drug treatment. However, the absence of specific symptoms, the wide spectrum of neurological manifestations, the myriad of imaging findings, possible inconclusive laboratory results, and the paradoxical reaction to treatment make the diagnosis often challenging and difficult, potentially delaying adequate treatment with possible devastating short-term and long-term neurologic sequelae. Familiarity with the imaging characteristics helps in accurate diagnosis and may prevent or limit significantly morbidity and mortality. The goal of this review is to provide a comprehensive up-to-date overview of the conventional and advanced imaging features of CNS TB for radiologists, neuroradiologists, and pediatric radiologists. We discuss the most typical neurotuberculosis imaging findings and their differential diagnosis in children and adults with the goal to provide a global overview of this entity.

Circulating tumor DNA sequencing of pediatric solid and brain tumor patients: An institutional feasibility study.

The potential of circulating tumor DNA (ctDNA) analysis to serve as a real-time "liquid biopsy" for children with central nervous system (CNS) and non-CNS solid tumors remains to be fully elucidated. We conducted a study to investigate the feasibility and potential clinical utility of ctDNA sequencing in pediatric patients enrolled on an institutional clinical genomics trial. A total of 240 patients had tumor DNA profiling performed during the study period. Plasma samples were collected at study enrollment from 217 patients and then longitudinally from a subset of patients. Successful cell-free DNA extraction and quantification occurred in 216 of 217 (99.5%) of these initial samples. Twenty-four patients were identified whose tumors harbored 30 unique variants that were potentially detectable on a commercially-available ctDNA panel. Twenty of these 30 mutations (67%) were successfully detected by next-generation sequencing in the ctDNA from at least one plasma sample. The rate of ctDNA mutation detection was higher in patients with non-CNS solid tumors (7/9, 78%) compared to those with CNS tumors (9/15, 60%). A higher ctDNA mutation detection rate was also observed in patients with metastatic disease (9/10, 90%) compared to non-metastatic disease (7/14, 50%), although tumor-specific variants were detected in a few patients in the absence of radiographic evidence of disease. This study illustrates the feasibility of incorporating longitudinal ctDNA analysis into the management of relapsed or refractory patients with childhood CNS or non-CNS solid tumors.

Quantitative assessment of cerebrospinal fluid flow and volume in enlargement of the subarachnoid spaces of infancy using MRI.

BACKGROUND: The etiology of enlarged subarachnoid spaces of infancy is unknown; however, there is radiologic similarity with normal pressure hydrocephalus. Adults with normal pressure hydrocephalus have been shown to have altered cerebrospinal (CSF) flow through the cerebral aqueduct. OBJECTIVE: To explore potential similarity between enlarged subarachnoid spaces of infancy and normal pressure hydrocephalus, we compared MRI-measured CSF flow through the cerebral aqueduct in infants with enlarged subarachnoid spaces of infancy to infants with normal brain MRIs. MATERIALS AND METHODS: This was an IRB approved retrospective study. Clinical brain MRI examinations including axial T2 imaging and phase contrast through the aqueduct were reviewed for infants with enlarged subarachnoid spaces of infancy and for infants with a qualitatively normal brain MRI. The brain and CSF volumes were segmented using a semi-automatic technique (Analyze 12.0) and CSF flow parameters were measured (cvi42, 5.14). All data was assessed for significant differences while controlling for age and sex using analysis of covariance (ANCOVA). RESULTS: Twenty-two patients with enlarged subarachnoid spaces (mean age 9.0 months, 19 males) and 15 patients with normal brain MRI (mean age 18.9 months, 8 females) were included. Volumes of the subarachnoid space (P < 0.001), lateral (P < 0.001), and third ventricles (P < 0.001) were significantly larger in infants with enlarged subarachnoid spaces of infancy. Aqueductal stroke volume significantly increased with age (P = 0.005), regardless of group. CONCLUSION: CSF volumes were significantly larger in infants with enlarged subarachnoid spaces of infancy versus infants with a normal MRI; however, there was no significant difference in CSF flow parameters between the two groups.

Arterial Spin Labeling Changes Parallel Asymmetric Perisylvian and Perirolandic Symptoms in 3 Pediatric Cases of Anti-NMDAR Encephalitis.

BACKGROUND AND OBJECTIVES: Anti-NMDA receptor autoimmune encephalitis (NMDAR AE) is an autoantibody-mediated disorder characterized by seizures, neuropsychiatric symptoms, movement disorder, and focal neurologic deficits. Conventionally defined broadly as an inflammatory brain disease, the heterotopic localization is rarely discussed in children. Imaging findings are often nonspecific, and there are no early biomarkers of disease other than the presence of anti-NMDAR antibodies. METHODS: We conducted a retrospective analysis of our pediatric NMDAR AE cases (as determined by either positive serum or CSF antibodies or both) at Texas Children's Hospital between 2020-2021 and extracted medical record data of those patients who had arterial spin labeling (ASL) as part of their imaging workup for encephalitis. The ASL findings were described in the context of their symptoms and disease courses. RESULTS: We identified 3 children on our inpatient floor, intensive care unit (ICU), and emergency department (ED) settings who were diagnosed with NMDAR AE and had ASL performed as part of their focal neurologic symptom workup. All 3 patients presented with focal neurologic deficits, expressive aphasia, and focal seizures before the onset of other well-characterized NMDAR AE symptoms. Their initial MRI revealed no diffusion abnormalities but uncovered asymmetric and predominantly unilateral multifocal hyperperfusion of perisylvian/perirolandic regions on ASL that correlated with focal EEG abnormalities and their focal examination findings. All 3 patients were treated with first-line and second-line therapies, and their symptoms improved. DISCUSSION: We found that ASL may be a suitable early imaging biomarker to highlight perfusion changes corresponding to the functional localization of NMDAR AE in pediatric patients. We briefly highlight the neuroanatomic parallels between working models of schizophrenia, chronic NMDAR antagonist administration (ketamine abuse), and NMDAR AE affecting primarily language centers. The regional specificity seen in NMDAR hypofunction may make ASL a reasonable early and specific biomarker of NMDAR AE disease activity. Future studies are necessary to evaluate regional changes in those patients who present with primarily psychiatric phenotypes rather than classical focal neurologic deficits.

Treatment of Langerhans cell histiocytosis with subcutaneous cytarabine.

Patients with Langerhans cell histiocytosis (LCH) have been effectively treated with intravenous cytarabine. Intravenous or subcutaneous cytarabine infusions have been effective for leukemia patients, and pharmacokinetic studies have shown very similar blood levels of the drug with either route. We present three LCH patients treated with subcutaneous cytarabine either because intravenous access could not be maintained or due to patient refusal. One patient with pulmonary and skin LCH had a complete response. Another patient had a partial response of pulmonary and cutaneous lesions, but progressive bone disease. The third patient was treated for LCH-related cerebellar changes eight years after the diagnosis of isolated diabetes insipidus, with stable brain MRI for 5 years post-treatment. Subcutaneous cytarabine administration provides an alternative for patients with LCH in whom vascular access is not possible or practical, such as in some resource-limited circumstances.

Intracranial hemangioma-associated cranial nerve VII palsy treated with propranolol in an infant with possible PHACE syndrome.

A 2-week-old infant with a large vascular birthmark involving her right face presented with right-sided facial paralysis. MRI of the brain revealed multiple intracranial hemangiomas, and the hemangioma within the right temporal bone impinged on the facial nerve, which resulted in paralysis. Cranial nerve palsies are a rare neurological manifestation of PHACE syndrome. We report successful treatment of the facial nerve palsy with oral propranolol.

Neuroimaging in cerebellar ataxia in childhood: A review.

Ataxia is one of the most common pediatric movement disorders and can be caused by a large number of congenital and acquired diseases affecting the cerebellum or the vestibular or sensory system. It is mainly characterized by gait abnormalities, dysmetria, intention tremor, dysdiadochokinesia, dysarthria, and nystagmus. In young children, ataxia may manifest as the inability or refusal to walk. The diagnostic approach begins with a careful clinical history including the temporal evolution of ataxia and the inquiry of additional symptoms, is followed by a meticulous physical examination, and, depending on the results, is complemented by laboratory assays, electroencephalography, nerve conduction velocity, lumbar puncture, toxicology screening, genetic testing, and neuroimaging. Neuroimaging plays a pivotal role in either providing the final diagnosis, narrowing the differential diagnosis, or planning targeted further workup. In this review, we will focus on the most common form of ataxia in childhood, cerebellar ataxia (CA). We will discuss and summarize the neuroimaging findings of either the most common or the most important causes of CA in childhood or present causes of pediatric CA with pathognomonic findings on MRI. The various pediatric CAs will be categorized and presented according to (a) the cause of ataxia (acquired/disruptive vs. inherited/genetic) and (b) the temporal evolution of symptoms (acute/subacute, chronic, progressive, nonprogressive, and recurrent). In addition, several illustrative cases with their key imaging findings will be presented.

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.

Clinical Profile and Long-Term Outcomes in Pediatric Cavernous Sinus Thrombosis.

BACKGROUND: Pediatric cavernous sinus thrombosis (CST) is a rare condition with limited data regarding its clinical characteristics and long-term outcomes. The objective of this study was to describe the clinical and radiologic features, diagnostic evaluation, management, and long-term prognosis and to identify clinical variables associated with long-term outcomes in pediatric CST. METHODS: A retrospective chart review of patients younger than 18 years diagnosed with a CST between 2004 and 2018 at a single center was conducted. RESULTS: We identified 16 (M:F = 10:6) children with CST with a mean age of 7.6 years (10 days to 15 years) and average follow-up duration of 29 months (3 weeks to 144 months). The most common symptom and examination finding at presentation was eyelid swelling (n = 8). Six patients had bilateral CST. The most common etiologies were sinusitis (n = 5) and orbital cellulitis (n = 5). Treatments included antibiotics (n = 14), anticoagulation (n = 11), and surgery (n = 5). Only one patient died due to intracranial complications. Twelve patients had a normal examination at follow-up. None of the clinical variables including age (P = 0.14), gender (P = 0.09), use of antibiotics (P = 1.00) or anticoagulation (P = 1.00), surgery (P = 0.28), parenchymal abnormalities (P = 0.30), additional cerebral venous thrombosis (P = 0.28), and early versus late commencing of anticoagulation (P = 1.00) were significant when comparing patients with full/partial resolution versus those with no resolution of thrombosis on follow-up neuroimaging. CONCLUSIONS: Our study is one of the largest cohorts with the longest follow-up data for the pediatric CST. Most of our patients had favorable outcomes at follow-up. We found no statistical difference between clinical variables when comparing patients with full/partial resolution versus those with no resolution of thrombosis on follow-up neuroimaging.

Neuroimaging of primary mitochondrial disorders in children: A review.

Mitochondrial disorders represent a diverse and complex group of entities typified by defective energy metabolism. The mitochondrial oxidative phosphorylation system is typically impaired, which is the predominant source of energy production. Because mitochondria are present in nearly all organs, multiple systems may be affected including the central nervous system, skeletal muscles, kidneys, and liver. In particular, those organs that are metabolically active with high energy demands are explicitly vulnerable. Initial diagnostic work up relies on a detailed evaluation of clinical symptoms including physical examination as well as a comprehensive review of the evolution of symptoms over time, relation to possible "triggering" events (eg, fever, infection), blood workup, and family history. High-end neuroimaging plays a pivotal role in establishing diagnosis, narrowing differential diagnosis, monitoring disease progression, and predicting prognosis. The pattern and characteristics of the neuroimaging findings are often highly suggestive of a mitochondrial disorder; unfortunately, in many cases the wide variability of involved metabolic processes prevents a more specific subclassification. Consequently, additional diagnostic steps including muscle biopsy, metabolic workup, and genetic tests are necessary. In the current manuscript, basic concepts of energy production, genetics, and inheritance patterns are reviewed. In addition, the imaging findings of several illustrative mitochondrial disorders are presented to familiarize the involved physicians with pediatric mitochondrial disorders. In addition, the significance of spinal cord imaging and the value of "reversed image-based discovery" for the recognition and correct (re-)classification of mitochondrial disorders is discussed.

Gadolinium is not necessary for surveillance MR imaging in children with chiasmatic-hypothalamic low-grade glioma.

BACKGROUND: Patients with chiasmatic-hypothalamic low-grade glioma (CHLGG) have frequent MRIs with gadolinium-based contrast agents (GBCA) for disease monitoring. Cumulative gadolinium deposition in the brains of children is a potential concern. The purpose of this study is to evaluate whether MRI with GBCA is necessary for determining radiographic tumor progression in children with CHLGG. METHODS: Children who were treated for progressive CHLGG from 2005 to 2019 at Texas Children's Cancer Center were identified. Pre- and post-contrast MRI sequences were separately reviewed by one neuroradiologist who was blinded to the clinical course. Three dimensional measurements and tumor characteristics were evaluated. Radiographic progression was defined as a 25% increase in size (product of two largest dimensions) compared with baseline or best response after initiation of therapy. RESULTS: A total of 28 patients with progressive CHLGG were identified with a total of 683 MRIs with GBCA reviewed (mean 24 MRIs/patient; range, 11-43 MRIs). Radiographic progression was observed 92 times, 91 (99%) on noncontrast and 90 (98%) on contrast imaging. Sixty-seven progressions necessitating management changes were identified in all (100%) noncontrast sequences and 66 (99%) contrast sequences. Tumor growth > 2 mm in any dimension was identified in 184/187 (98%) noncontrast and 181/187 (97%) with contrast imaging. Metastatic tumors were better visualized on contrast imaging in 4/7 (57%). CONCLUSION: MRI without GBCA effectively identifies patients with progressive disease. When imaging children with CHLGG, eliminating GBCA should be considered unless monitoring patients with metastatic disease.

Clinical Profile and Long-Term Outcome in Neonatal Cerebral Sinus Venous Thrombosis.

BACKGROUND: Neonatal cerebral sinus venous thrombosis (CSVT) causes high morbidity and mortality. Factors associated with either favorable or unfavorable long-term outcomes have not been clearly established. This study aimed to determine the factors involved in long-term neurological outcomes in patients with neonatal CSVT. METHODS: This was a retrospective cohort study of patients with neonatal CSVT at a single institution. Clinical factors associated with long-term neurological outcomes were examined. RESULTS: A total of 67 patients met study inclusion criteria for radiologically confirmed neonatal CSVT. The mean patient follow-up duration was four years (range one week to 16 years, median six years). We observed a favorable neurological outcome defined by a pediatric stroke outcome measures (PSOM) score of 0 to 0.5 in 26 (53%) of osurviving patients at follow-up. An unfavorable neurological outcome as defined by PSOM score >0.5 was observed in 23 survivors (47%). Death was reported in 18 (27%) patients, of which 10 patients died due to direct complications of CSVT. Congential heart disease and genetic disease were associated with significantly increased odds for all-cause death. Cardiorespiratory failure and altered mental status during the initial neurological examination were significantly associated with increased odds of death due to CSVT. Among surviving patients, higher PSOM scores were associated with premature birth (i.e., gestational age < 37 weeks), traumatic birth, site of thrombosis in the straight sinus, site of thrombosis in the internal cerebral veins, and hemorrhagic infarct. In contrast, lower PSOM scores were associated with a normal neurological examination at presentation, thrombosis in only superficial sinuses, and hemorrhage without infarct. There was no statistically significant association between the type and duration of CSVT treatment. CONCLUSIONS: The major factors influencing outcome of neonates following CSVT included comorbid medical conditions, abnormal neurological examination at presentation, location of venous thrombosis, and type of cerebral injury. These results can help guide further studies in neonatal CSVT aiming to decrease morbidity and mortality with the goal of improving long-term neurological outcomes.

Acute Strokelike Presentation and Long-term Evolution of Diffusion Restriction Pattern in Ethylmalonic Encephalopathy.

Ethylmalonic encephalopathy is a rare autosomal recessive mitochondrial disorder caused by pathogenic biallelic variants in the ETHE1 gene. The phenotype of this disease has been attributed to deficiency in the mitochondrial sulfur dioxygenase leading to many downstream effects. Ethylmalonic encephalopathy classically presents with developmental regression, petechiae, acrocyanosis, and chronic diarrhea. The neurologic phenotype includes hypotonia, spastic diplegia, ataxia, and developmental delay. As more patients with this condition are described, the neurologic phenotype continues to expand. Although strokelike episodes or metabolic strokes have been studied in other mitochondrial disorders, they have not been thoroughly reported in this disorder. Herein, we describe 3 patients with ethylmalonic encephalopathy who presented clinically with strokelike episodes and strokelike abnormalities on brain magnetic resonance imaging in the setting of acute illness, and the long-term sequelae with evolution into cystic changes in one of these subjects.

Image segmentation of plexiform neurofibromas from a deep neural network using multiple b-value diffusion data.

We assessed the accuracy of semi-automated tumor volume maps of plexiform neurofibroma (PN) generated by a deep neural network, compared to manual segmentation using diffusion weighted imaging (DWI) data. NF1 Patients were recruited from a phase II clinical trial for the treatment of PN. Multiple b-value DWI was imaged over the largest PN. All DWI datasets were registered and intensity normalized prior to segmentation with a multi-spectral neural network classifier (MSNN). Manual volumes of PN were performed on 3D-T2 images registered to diffusion images and compared to MSNN volumes with the Sørensen-Dice coefficient. Intravoxel incoherent motion (IVIM) parameters were calculated from resulting volumes. 35 MRI scans were included from 14 subjects. Sørensen-Dice coefficient between the semi-automated and manual segmentation was 0.77 ± 0.016. Perfusion fraction (f) was significantly higher for tumor versus normal tissue (0.47 ± 0.42 vs. 0.30 ± 0.22, p = 0.02), similarly, true diffusion (D) was significantly higher for PN tumor versus normal (0.0018 ± 0.0003 vs. 0.0012 ± 0.0002, p < 0.0001). By contrast, the pseudodiffusion coefficient (D*) was significantly lower for PN tumor versus normal (0.024 ± 0.01 vs. 0.031 ± 0.005, p < 0.0001). Volumes generated by a neural network from multiple diffusion data on PNs demonstrated good correlation with manual volumes. IVIM analysis of multiple b-value diffusion data demonstrates significant differences between PN and normal tissue.

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.

Preoperative computed tomography perfusion in pediatric moyamoya disease: a single-institution experience.

OBJECTIVE: Moyamoya disease is a progressive occlusive arteriopathy for which surgical revascularization is indicated. In this retrospective study, the authors investigated the use of preoperative CT perfusion with the aim of establishing pathological data references. METHODS: The authors reviewed the medical records of children with moyamoya disease treated surgically at one institution between 2016 and 2019. Preoperative CT perfusion studies were used to quantify mean transit time (MTT), cerebral blood volume (CBV), cerebral blood flow (CBF), and time to peak (TTP) for the anterior, middle, and posterior cerebral artery vascular territories for each patient. CT perfusion parameter ratios (diseased/healthy hemispheres) and absolute differences were compared between diseased and normal vascular territories (defined by catheter angiography studies). Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for CT perfusion parameters for severe angiographic moyamoya were calculated. RESULTS: Nine children (89% female) had preoperative CT perfusion data; 5 of them had evidence of unilateral hemispheric disease and 4 had bilateral disease. The mean age at revascularization was 77 months (range 40-144 months). The etiology of disease was neurofibromatosis type 1 (3 patients), Down syndrome (2), primary moyamoya disease (2), cerebral proliferative angiopathy (1), and sickle cell disease (1). Five patients had undergone unilateral revascularization. Among these patients, pathological vascular territories demonstrated increased MTT in 66% of samples, increased TTP in 66%, decreased CBF in 47%, and increased CBV in 87%. Severe moyamoya (Suzuki stage ≥ 4) had diseased/healthy ratios ≥ 1 for MTT in 78% of cases, for TTP in 89%, for CBF in 67%, and for CBV in 89%. The MTT and TTP region of interest ratio ≥ 1 demonstrated 89% sensitivity, 67% specificity, 80% PPV, and 80% NPV for the prediction of severe angiographic moyamoya disease. CONCLUSIONS: Pathological hemispheres in these children with moyamoya disease demonstrated increased MTT, TTP, and CBV and decreased CBF. The authors' results suggest that preoperative CT perfusion may, with high sensitivity, be useful in deciphering perfusion mismatch in brain tissue in children with moyamoya disease. More severe angiographic disease displays a more distinct correlation, allowing surgeons to recognize when to intervene in these patients.