RASopathies for Radiologists.

RASopathies are a heterogeneous group of genetic syndromes caused by germline mutations in a group of genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) signaling pathway. RASopathies include neurofibromatosis type 1, Legius syndrome, Noonan syndrome, Costello syndrome, cardiofaciocutaneous syndrome, central conducting lymphatic anomaly, and capillary malformation-arteriovenous malformation syndrome. These disorders are grouped together as RASopathies based on our current understanding of the Ras/MAPK pathway. Abnormal activation of the Ras/MAPK pathway plays a major role in development of RASopathies. The individual disorders of RASopathies are rare, but collectively they are the most common genetic condition (one in 1000 newborns). Activation or dysregulation of the common Ras/MAPK pathway gives rise to overlapping clinical features of RASopathies, involving the cardiovascular, lymphatic, musculoskeletal, cutaneous, and central nervous systems. At the same time, there is much phenotypic variability in this group of disorders. Benign and malignant tumors are associated with certain disorders. Recently, many institutions have established multidisciplinary RASopathy clinics to address unique therapeutic challenges for patients with RASopathies. Medications developed for Ras/MAPK pathway-related cancer treatment may also control the clinical symptoms due to an abnormal Ras/MAPK pathway in RASopathies. Therefore, radiologists need to be aware of the concept of RASopathies to participate in multidisciplinary care. As with the clinical manifestations, imaging features of RASopathies are overlapping and at the same time diverse. As an introduction to the concept of RASopathies, the authors present major representative RASopathies, with emphasis on their imaging similarities and differences. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Successful Treatment for Hepatoblastoma in Trisomy 18: A Case Report.

Children with trisomy 18 tend to develop hepatoblastoma. Since the introduction of appropriate management for organ malfunction, individuals with trisomy 18 have come to have a longer life expectancy. However, the predisposition to hepatoblastoma becomes a significant issue for the quality of a case. Here, we present a rare multifocal hepatoblastoma involving predominantly Couinaud segments 5 and 7 in a 10-month-old boy with trisomy 18. Though the first-line cisplatin monotherapy resulted in unsatisfactory tumor shrinkage, the second-line neoadjuvant chemotherapy administrating irinotecan and vincristine gave rise to significant tumor reduction in volume, leading to the completion of partial resection of the liver without the microscopic residual disease. The patient has been free from recurrence for 44 months. Because anatomical right hepatectomy can cause circulatory instability, including acute onset of pulmonary hypertension in trisomy 18 patients, physicians should balance treatment benefits and potential adverse effects. Our successful experience utilizing a combination of efficacious and less cardiotoxic neoadjuvant chemotherapy followed by the partial hepatectomy encourages physicians to treat a patient with trisomy 18 and tackle hepatoblastoma with a genetic background.

Clinical and neuroimaging review of monogenic cerebral small vessel disease from the prenatal to adolescent developmental stage.

Cerebral small vessel disease (cSVD) refers to a group of pathological processes with various etiologies affecting the small vessels of the brain. Most cases are sporadic, with age-related and hypertension-related sSVD and cerebral amyloid angiopathy being the most prevalent forms. Monogenic cSVD accounts for up to 5% of causes of stroke. Several causative genes have been identified. Sporadic cSVD has been widely studied whereas monogenic cSVD is still poorly characterized and understood. The majority of cases of both the sporadic and monogenic types, including cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), typically have their onset in adulthood. Types of cSVD with infantile and childhood onset are rare, and their diagnosis is often challenging. The present review discusses the clinical and neuroimaging findings of monogenic cSVD from the prenatal to adolescent period of development. Early diagnosis is crucial to enabling timely interventions and family counseling.

Pediatric Ribs at Chest Radiography: Normal Variants and Abnormalities.

Normal variants and abnormalities of the ribs are frequently encountered on chest radiographs. Accurate identification of normal variants is crucial to avoid unnecessary investigations. A meticulous evaluation of rib abnormalities can provide valuable insights into the patient's symptoms, and even when no osseous condition is suspected, rib abnormalities may offer critical clues to underlying conditions. Rib abnormalities are associated with various conditions, including benign tumors, malignant tumors, infectious and inflammatory conditions, vascular abnormalities, metabolic disorders, nonaccidental injuries, malformation syndromes, and bone dysplasias. Abnormalities of the ribs are classified into three groups based on their radiographic patterns: focal, multifocal, and diffuse changes. Focal lesions are further subdivided into nonaggressive lesions, aggressive lesions, and infectious and inflammatory disorders. Radiologists should be aware of individual disorders of the pediatric ribs, including their imaging findings, relevant clinical information, and underlying pathogenesis. Differential diagnoses are addressed as appropriate. Since chest radiographs can suffice for diagnosis in certain cases, the authors emphasize a pattern recognition approach to radiographic interpretation. However, additional cross-sectional imaging may be necessary for focal lesions such as tumors or inflammatory conditions. Awareness of disease-specific imaging findings helps ascertain the nature of the lesion and directs appropriate management. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Infantile Hypoxic Encephalopathy Mimicking Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion (AESD) Identified as an Episode of Brief Resolved Unexplained Event (BRUE).

Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) is characterized by biphasic seizures following febrile viral infections and delayed reduced diffusion of the cerebral white matter on magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) (bright tree appearance, BTA). However, hypoxic encephalopathy with biphasic seizures and AESD-mimicking imaging findings has not been reported. We report a case of hypoxic encephalopathy due to suffocation with concomitant biphasic seizures and BTA, mimicking AESD. On day 1, a healthy 5-month-old girl was found face down with decreased breathing and a deteriorating consciousness level, suggesting a brief resolved unexplained event (BRUE). Electroencephalography (EEG) revealed periodic epileptic discharges, suggesting possible nonconvulsive status epilepticus. Despite improvements in consciousness level and EEG abnormalities on day 2, her consciousness level deteriorated again with generalized tonic-clonic seizures on day 3, and a head MRI-DWI revealed restricted diffusion predominantly in the subcortical areas, suggesting BTA. Treatment for acute encephalopathy resolved the clinical seizures and EEG abnormalities. Persistence of abnormal EEG, reflecting abnormal excitation and accumulation of neurotoxic substances caused by hypoxia, may have contributed to the development of AESD-like findings. As hypoxic encephalopathy causes AESD-like biphasic seizures, monitoring consciousness level, seizure occurrence, and EEG abnormalities even after acute symptoms have temporarily improved following hypoxia is essential.

Imaging findings of juvenile idiopathic arthritis and autoinflammatory diseases in children.

Juvenile idiopathic arthritis (JIA) is a collective term for pediatric inflammatory arthritis of unknown etiology, which presents diverse clinical and imaging findings. The pathogenesis is complex; however, most cases stem from an autoimmune mechanism. Herein we provide a short review of imaging findings of JIA. Imaging assessment begins with plain radiography demonstrating joint swelling, periarticular osteopenia, and juxtaarticular bone erosion. Bone erosion occurs later in JIA. Instead, aberrant epimetaphyseal growth often gives the first clue to the diagnosis. US and MRI can demonstrate the details of the synovium, cartilage, and subchondral bone. JIA is subdivided into oligoarthritis, polyarthritis (rheumatoid factor-negative and positive), psoriatic arthritis, enthesitis-related arthritis, and systemic JIA. Awareness of the different clinical characteristics, pathogenic background, and prognosis of each subtype facilitates a more advanced, imaging-based diagnosis. Unlike the other types, systemic JIA is an autoinflammatory disease accompanied by inflammatory cytokinemia and systemic symptoms stemming from aberrant activation of the innate immunity. Other autoinflammatory diseases, both monogenic (e.g., NOMID/CINCA) and multifactorial (e.g., CRMO), are also discussed.

Neuroimaging findings of inborn errors of metabolism: urea cycle disorders, aminoacidopathies, and organic acidopathies.

Although there are many types of inborn errors of metabolism (IEMs) affecting the central nervous system, also referred to as neurometabolic disorders, individual cases are rare, and their diagnosis is often challenging. However, early diagnosis is mandatory to initiate therapy and prevent permanent long-term neurological impairment or death. The clinical course of IEMs is very diverse, with some diseases progressing to acute encephalopathy following infection or fasting while others lead to subacute or slowly progressive encephalopathy. The diagnosis of IEMs relies on biochemical and genetic tests, but neuroimaging studies also provide important clues to the correct diagnosis and enable the conditions to be distinguished from other, more common causes of encephalopathy, such as hypoxia-ischemia. Proton magnetic resonance spectroscopy (1H-MRS) is a powerful, non-invasive method of assessing neurological abnormalities at the microscopic level and can measure in vivo brain metabolites. The present review discusses neuroimaging findings, including those of 1H-MRS, of IEMs focusing on intoxication disorders such as urea cycle disorders, aminoacidopathies, and organic acidopathies, which can result in acute life-threatening metabolic decompensation or crisis.

Sinus pericranii associated with syntelencephaly: a case report.

BACKGROUND: Sinus pericranii is a rare cranial venous malformation resulting in a subcutaneous mass due to abnormal communication between intracranial and subperiosteal/interperiosteal veins. To date, to the best of our knowledge, there are no reports of sinus pericranii associated with syntelencephaly, a subtype of lobar holoprosencephaly. We herein report a case of sinus pericranii associated with syntelencephaly. This report can provide us better understanding of the etiology of sinus pericranii, the potential risks, and the treatment options for these patients. CASE PRESENTATION: A 2-year-4-month old female patient who received the diagnosis of syntelencephaly as a neonate presented with a subcutaneous mass in the parietal region. The mass was soft, nonpulsatile, 3 × 2 cm in size, and showed enlargement in the lying position. Color cranial Doppler ultrasound, head magnetic resonance imaging (MRI), and cerebral angiography revealed a dilated vessel passing through the parietal bone and forming a communication between the superior sagittal sinus and scalp veins. Based on these findings, sinus pericranii was diagnosed. The head MRI also showed coronal craniosynostosis, a tight posterior fossa. At age 2 years and 7 months, the patient underwent a transection of the sinus pericranii and the mass resolved without any complications or recurrences for more than 2.5 years to date. CONCLUSION: Sinus pericranii is a rare cranial and venous malformation sometimes accompanied by brain malformations or craniosynostosis that may become more apparent as the brain and skull develop. Since this condition can be complicated by intracranial hemorrhage and sinus thrombosis, early detection is necessary to determine the treatment options. Physicians should be alert to the possibility of this condition if they observe a soft cranial mass that appears to decrease in size in the sitting position and bulge in the lying position.

Syndromic vascular malformations related to the PIK3CA and RAS pathways: A clinical and imaging review.

Vascular malformations are a complex and diverse group of disorders. They may enlarge with time, impair quality of life, and even be fatal. While many are sporadic, others are part of inherited syndromes; several gene mutations responsible for vascular anomalies have been identified. The PI3K/AKT/mTOR and RAS/MEK/ERK cascades have been extensively studied, and new molecular agents targeting these cascades are being developed. Diagnostic imaging findings are increasingly used to guide genetic testing, and in some cases, pathognomonic imaging characteristics can lead to a specific diagnosis. We review each of the representative syndromes associated with PIK3CA and RAS cascades, with updates of the latest in clinical and imaging information.

Symptomatic enophthalmos due to sphenoid wing dysplasia appearing over 12 years in a patient with neurofibromatosis type 1: a case report and literature review.

Sphenoid wing dysplasia (SWD) is a common orbital complication of neurofibromatosis type 1 (NF1). However, enophthalmos associated with SWD is extremely rare, and details of its natural history are unclear. We present the case of a 14-year-old boy with an early childhood diagnosis of NF1 presenting with left blepharophimosis and enophthalmos for several months. Imaging demonstrated enlargement of the left lateral SWD, progression of the posteromedial deviation of the orbital contents, and sphenoid/ethmoid sinus deformation due to left temporal lobe compression over 12 years. Two characteristic changes were revealed on imaging: enlargement of the middle cranial fossa and deformation of the sphenoid/ethmoid sinuses. The orbital contents were compressed by the intracranial pressure of the temporal lobe and were displaced posteromedially into the space created by the deformed sphenoid/ethmoid sinuses. Because orbital symptoms can gradually become apparent over years with the progression of SWD and skeletal growth, long-term follow-up of orbital symptoms is recommended in patients with NF1.

BCG osteomyelitis: tips for diagnosis.

OBJECTIVE: To report the clinical and imaging characteristics of BCG-osteomyelitis, and compare them with those of pyogenic osteomyelitis. MATERIALS AND METHODS: Clinical and imaging findings were retrospectively evaluated in 14 children with BCG osteomyelitis, including 3 with Mendelian susceptibility to mycobacterial diseases (MSMD), and in 40 children with pyogenic osteomyelitis, using Fisher exact and Mann-Whitney U tests. RESULTS: BCG-osteomyelitis was an indolent inflammatory disease of young children (mean age 15.5 months). Immunocompetent patients came to medical attention over months after vaccination, while patients with MSMD much earlier (the average time lapse: 13.7 vs. 5.0 months). The former manifested with a slowly progressive, painless mass with only mildly increased acute-phase reactants, while the latter started with lymphadenitis with significant inflammatory reactions and later developed osteomyelitis. These clinical scenarios contrasted with acute febrile illness in pyogenic osteomyelitis. The imaging findings were identical in both immunocompetent and MSMD groups; however, the former showed monoostotic involvement, while the latter polyostotic affliction. The typical imaging finding of BCG-osteomyelitis comprises a large intraosseous abscess with modest reactive edema commonly associated with transphyseal extension from the metaphysis to the epiphysis, contrasting with the manifestation of pyogenic osteomyelitis; size of abscess (p=0.028), pattern of abscess extension (p<0.001), and extent of surrounding edema (p<0.001). CONCLUSIONS: BCG-osteomyelitis should be suspected in children under 2 years of age with insidious osteomyelitis, accompanied with characteristic imaging findings. Polyostotic BCG osteomyelitis is highly suggestive of MSMD. Awareness of the distinctive features of BCG-osteomyelitis enables the early diagnosis and timely therapeutic intervention.

Multisystem Imaging Manifestations of Kawasaki Disease.

Kawasaki disease (KD) is a common pediatric vasculitis syndrome involving medium- and small-sized arteries that is especially prevalent in early childhood (ie, age 6 months to 5 years). The diagnosis of KD is made on the basis of clinical features, such as fever, characteristic mucocutaneous changes, and nonsuppurative cervical lymphadenopathy. However, early diagnosis is often challenging because many children with KD present with atypical symptoms. The most serious complication of KD is coronary artery aneurysm caused by coronary arteritis. Prompt intravenous immunoglobulin therapy reduces the risk of cardiac morbidity. In addition, the systemic extension of KD-related vasculitis during the acute phase causes a variety of multisystem manifestations, including encephalopathy, stroke, retropharyngeal edema, pericarditis, myocarditis, KD shock syndrome, pulmonary lesions, intestinal pseudo-obstruction, gallbladder hydrops, arthritis, and myositis. These complications tend to be more common in affected children with atypical presentation. Radiologists can play an important role in the timely identification of diverse KD-associated morbidities and thus may contribute to the early diagnosis of atypical KD. Online supplemental material is available for this article. ©RSNA, 2021.

A novel case of congenital hepatic arterio-veno-portal shunts with umbilical vein aneurysm.

A term male infant presented with congenital hepatic arterio-veno-portal shunts. A mass-like lesion in the left lobe of the liver received blood supply from not only the umbilical vein, but also the hepatic and inferior intrahepatic arteries, communicating with the hepatic and portal veins in a complicated manner, with an umbilical vein aneurysm. The blood flow of the arterio-veno-portal shunts spontaneously and gradually declined from the neonatal period to six years of age. Although mild high-output cardiac failure had developed, no life-threatening events or health problems originating from portosystemic shunts, such as pulmonary artery hypertension and hepatopulmonary syndrome, were observed. However, this report shows that scrupulous follow-up to identify pulmonary artery hypertension and hepatopulmonary syndrome should be continued because complete resolution of the arterio-veno-portal shunts was not obtained in this case.

Short-term outcomes in infants with mild neonatal encephalopathy: a retrospective, observational study.

BACKGROUND: Neonatal encephalopathy due to acute perinatal asphyxia is a major cause of perinatal brain damage. Moderate to severe neonatal encephalopathy is associated with high mortality and morbidity rates. However, the neurodevelopmental outcomes in neonates with mild neonatal encephalopathy are unclear. The primary aim of this single-center observational study was to assess the short-term outcomes in term neonates with mild neonatal encephalopathy due to perinatal asphyxia. A secondary aim was to identify predictors of poor prognosis by identifying the characteristics of these infants according to their short-term outcomes. METHODS: We retrospectively investigated all infants with perinatal asphyxia at Tokyo Metropolitan Children's Medical Center from January 2014 to December 2019. An abnormal short-term outcome was defined as any one of the following: seizures or abnormal electroencephalography, abnormal brain magnetic resonance imaging obtained within the first 4 weeks of life, and abnormal neurological examination findings at discharge. RESULTS: In total, 110 term infants with perinatal asphyxia during the study period were screened and 61 were diagnosed with mild neonatal encephalopathy. Eleven (18 %) of these infants had an abnormal short-term outcome. The median Thompson score at admission was significantly higher in infants with abnormal short-term outcomes than in those with normal short-term outcomes (5 [interquartile range, 4-5.5] vs. 2 [interquartile range, 1-3], p < 0.01). Receiver operating characteristic curve analysis showed that a cutoff value of 4 had high sensitivity and specificity (90.9 and 83.0 %, respectively) for prediction of an abnormal short-term outcome. CONCLUSIONS: 18 % of infants with mild encephalopathy had an abnormal short-term outcome, such as abnormal brain magnetic resonance imaging findings. The Thompson score at admission may be a useful predictor of an abnormal short-term outcome in infants with mild neonatal encephalopathy.

Enterovirus D68 respiratory infection in a children's hospital in Japan in 2015.

BACKGROUND: Outbreaks of enterovirus D68 (EV-D68) respiratory infections in children were reported globally in 2014. In Japan, there was an EV-D68 outbreak in the autumn of 2015 (September-October). The aim of this study was to compare EV-D68-specific polymerase chain reaction (PCR)-positive and EV-D68-specific PCR-negative patients. METHODS: Pediatric patients admitted for any respiratory symptoms between September and October 2015 were enrolled. Nasopharyngeal swabs were tested for multiplex respiratory virus PCR and EV-D68-specific reverse transcription-PCR. EV-D68-specific PCR-positive and -negative patients were compared regarding demographic data and clinical information. RESULTS: A nasopharyngeal swab was obtained from 76 of 165 patients admitted with respiratory symptoms during the study period. EV-D68 was detected in 40 samples (52.6%). Median age in the EV-D68-specific PCR-positive and -negative groups was 3.0 years (IQR, 5.5 years) and 3.0 years (IQR, 4.0 years), respectively. The rates of coinfection in the two groups were 32.5% and 47.2%, respectively. There was no significant difference in the history of asthma or recurrent wheezing, length of hospitalization, or pediatric intensive care unit admission rate between the groups. The median days between symptom onset and admission was significantly lower for the EV-D68-positive group (3.0 days vs 5.0 days, P = 0.001). EV-D68 was identified as clade B on phylogenetic analysis. No cases of acute flaccid myelitis were encountered. CONCLUSIONS: More than half of the samples from the children admitted with respiratory symptoms were positive for EV-D68-specific PCR during the outbreak. Asthma history was not associated with the risk of developing severe respiratory infection.

Ultrasonographic study of intestinal Doppler blood flow in infantile non-IgE-mediated gastrointestinal food allergy.

BACKGROUND: Although non-IgE-mediated gastrointestinal food allergy has increased rapidly in Japan, a small number of reports has evaluated B-mode and Doppler ultrasonographic findings in the acute phase of infantile gastrointestinal milk allergy. The aim of the present study was to compare the diagnostic utility of ultrasonographic findings and laboratory allergic data in non-IgE-mediated infantile gastrointestinal milk allergy. METHODS: Sixteen cases of active non-IgE-mediated infantile gastrointestinal milk allergy, diagnosed by food elimination tests and oral food challenge tests (OFCTs) (group A), 15 cases of acute viral gastroenteritis (AGE) (group B), and 15 controls (group C) were enrolled. 1) B-mode abdominal ultrasound findings, 2) laboratory allergic data including eosinophil counts (Eos), serum IgE, and the antigen-specific lymphocyte proliferation test (ALPT) against milk protein, and 3) vessel density (VD) indirectly quantified by gastrointestinal Doppler flow at jejunum, ileum, and sigmoid colonic mucosae were evaluated and compared among the groups. RESULTS: In the small intestine, wall thickening, dilation, mesenteric thickening, and poor peristalsis were found in 100%, 62.5%, 93.7%, and 100%, respectively, in group A. Eos, IgE, ALPT, and VD were positive in 25.0%, 0%, 87.5%, and 100%, respectively, in group A. Small intestinal VD was significantly greater in group A than in groups B (jejunum p < .001; ileum p < .001) and C (jejunum p < .001; ileum p < .001), with no significant differences between groups B and C (jejunum: p = .74; ileum: p = .73). CONCLUSIONS: Abdominal Doppler ultrasonography and small intestinal VD at symptomatic state can support the diagnosis and evaluation of non-IgE-mediated infantile gastrointestinal milk allergy with symptoms of vomiting, diarrhea, and failure to thrive.

Pediatric oncologic emergencies: Clinical and imaging review for pediatricians.

Children with cancer are at increased risk of life-threatening emergencies, either from the cancer itself or related to the cancer treatment. These conditions need to be assessed and treated as early as possible to minimize morbidity and mortality. Cardiothoracic emergencies encompass a variety of pathologies, including pericardial effusion and cardiac tamponade, massive hemoptysis, superior vena cava syndrome, pulmonary embolism, and pneumonia. Abdominal emergencies include bowel obstruction, intussusception, perforation, tumor rupture, intestinal graft-versus-host disease, acute pancreatitis, neutropenic colitis, and obstructive uropathy. Radiology plays a vital role in the diagnosis of these emergencies. We here review the clinical features and imaging in pediatric patients with oncologic emergencies, including a review of recently published studies. Key radiological images are presented to highlight the radiological approach to diagnosis. Pediatricians, pediatric surgeons, and pediatric radiologists need to work together to arrive at the correct diagnosis and to ensure prompt and appropriate treatment strategies.