Incidence and Characteristics of Cerebellar Atrophy/Volume Loss in Children with Confirmed Diagnosis of Tuberous Sclerosis Complex.

Objectives: The goal of our study was to determine the incidence of cerebellar atrophy, assess the imaging findings in the posterior fossa and determine the incidence of hippocampal sclerosis in a cohort of pediatric patients with confirmed tuberous sclerosis complex (TSC). Material and methods: MRI studies of 98 TSC pediatric patients (mean age 7.67 years) were evaluated for cerebellar atrophy, cerebral/cerebellar tubers, white matter lesions, subependymal nodules, subependymal giant cell astrocytomas, ventriculomegaly, and hippocampal sclerosis. Clinical charts were revisited for clinical symptoms suggesting cerebellar involvement, for seizures and treatment for seizures, behavioral disorders and autism. Results: Cerebral tubers were present in 97/98 cases. In total, 97/98 had subependymal nodules, 15/98 had SEGA, 8/98 had ventriculomegaly and 4/98 had hippocampal sclerosis. Cerebellar tubers were found in 8/98 patients (8.2%), whereas cerebellar atrophy was described in 38/98 cases (38.8%). In 37/38 patients, cerebellar volume loss was mild and diffuse, and only one case presented with left hemi-atrophy. Briefly, 32/38 presented with seizures and were treated with anti-seizure drugs. In total, 8/38 (21%) presented with behavioral disorders, 10/38 had autism and 2/38 presented with seizures and behavioral disorders and autism. Conclusions: Several studies have demonstrated cerebellar involvement in patients with TSC. Cerebellar tubers differ in shape compared with cerebral tubers and are associated with cerebellar volume loss. Cerebellar atrophy may be focal and diffuse and one of the primary cerebellar manifestations of TSC, especially if a TSC2 mutation is present. Cerebellar degeneration may, however, also be secondary/acquired due to cellular damage resulting from seizure activity, the effects of anti-seizure drugs and anoxic-ischemic injury from severe seizure activity/status epilepticus. Further, prospective studies are required to identify and establish the pathogenic mechanism of cerebellar atrophy in patients with TSC.

Imaging Features of Primary Intracranial Sarcoma with DICER1 Mutation: A Multicenter Case Series.

Primary intracranial sarcoma, DICER1-mutant, is a rare, recently described entity in the fifth edition of the WHO Classification of CNS Tumors. Given the entity's rarity and recent description, imaging data on primary intracranial sarcoma, DICER1-mutant, remains scarce. In this multicenter case series, we present detailed multimodality imaging features of primary intracranial sarcoma, DICER1-mutant, with emphasis on the appearance of the entity on MR imaging. In total, 8 patients were included. In all 8 patients, the lesion demonstrated blood products on T1WI. In 7 patients, susceptibility-weighted imaging was obtained and demonstrated blood products. Primary intracranial sarcoma, DICER1-mutant, is a CNS neoplasm that primarily affects pediatric and young adult patients. In the present case series, we explore potential imaging findings that are helpful in suggesting this diagnosis. In younger patients, the presence of a cortical lesion with intralesional blood products on SWI and T1-weighted MR imaging, with or without extra-axial blood products, should prompt the inclusion of this entity in the differential diagnosis.

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.

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.

Implementation and Assessment of a Laparotomy-Assisted Three-Port Fetoscopic Spina Bifida Repair Program.

Open spina bifida (OSB) is a congenital, non-lethal malformation with multifactorial etiology. Fetal therapy can be offered under certain conditions to parents after accurate prenatal diagnostic and interdisciplinary counseling. Since the advent of prenatal OSB surgery, various modifications of the original surgical techniques have evolved, including laparotomy-assisted fetoscopic repair. After a two-year preparation time, the team at the University of Giessen and Marburg (UKGM) became the first center to provide a three-port, three-layer fetoscopic repair of OSB via a laparotomy-assisted approach in the German-speaking area. We point out that under the guidance of experienced centers and by intensive multidisciplinary preparation and training, a previously described and applied technique could be transferred to a different setting.

Introducing the "Temporal Thumb Sign" in Pediatric Patients With New-Onset Idiopathic Seizures With and Without Elevated Cerebrospinal Fluid Opening Pressure.

BACKGROUND: Temporal lobe changes, such as anterior temporal lobe meningoceles or encephaloceles, have been documented as possible epileptogenic foci in a subset of pediatric patients with seizures. In our study, we aim to analyze a different structural change in the temporal lobe, remodeling of the posterior temporal skull base by the inferior temporal gyrus called the "temporal thumb sign" (TTS), in pediatric patients presenting with new-onset seizures with or without elevated opening pressure (OP), patients presenting with confirmed diagnosis of idiopathic intracranial hypertension (IIH) without seizure presentation, and healthy controls. METHODS: Magnetic resonance imaging scans of 163 pediatric patients were studied retrospectively for the presence of TTS. We analyzed the scans of 43 patients with elevated OP and confirmed IIH, 40 patients with elevated OP and new-onset idiopathic seizures, 40 patients with normal OP and new-onset idiopathic seizures, and 40 age- and sex-matched healthy controls. RESULTS: The TTS was detected most frequently in patients with elevated OP and seizures at 72.5% compared with patients with IIH with no seizures and patients with normal OP and seizures (32.6% and 27.5%, respectively). The TTS had a frequency of 12.5% in the control group. The TTS had the highest combination of specificity and sensitivity (72.5% and 72.5%) in patients with seizures and elevated OP compared with patients with seizures and normal OP (P value < 0.001). CONCLUSIONS: Our results suggest the Kamali "temporal thumb sign" is a novel imaging feature that may be used as a sensitive and specific imaging finding associated with seizures and elevated OP in the pediatric population.

Imaging of pediatric calvarial and skull base tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee/ASPNR White Paper.

A standardized imaging protocol for pediatric oncology patients is essential for accurate and efficient imaging, while simultaneously promoting collaborative understanding of pathologies and radiologic assessment of treatment response. The objective of this article is to provide standardized pediatric imaging guidelines and parameters for evaluation of tumors of the pediatric orbit, calvarium, skull base, and temporal bone. This article was drafted based on current scientific literature as well as consensus opinions of imaging experts in collaboration with the Children's Oncology Group Diagnostic Imaging Committee, Society of Pediatric Radiology Oncology Committee, and American Society of Pediatric Neuroradiology.

Angiographic Evaluation of Cranial Venous Outflow Patterns in Patients With and Without Idiopathic Intracranial Hypertension.

BACKGROUND: Several collateral venous pathways exist to assist in cranial venous drainage in addition to the internal jugular veins. The important extrajugular networks (EJN) are often readily identified on diagnostic cerebral angiography. However, the angiographic pattern of venous drainage through collateral EJN has not been previously compared among patients with and without idiopathic intracranial hypertension (IIH). OBJECTIVE: To quantify EJN on cerebral angiography among patients both with and without IIH and to determine whether there is a different EJN venous drainage pattern in patients with IIH. METHODS: Retrospective imaging review of 100 cerebral angiograms (50 IIH and 50 non-IIH patients) and medical records from a single academic medical center was performed by 2 independent experienced neuroendovascular surgeons. Points were assigned to EJN flow from 0 to 6 using an increasing scale (with each patient's dominant internal jugular vein standardized to 5 points to serve as the internal reference). Angiography of each patient included 11 separately graded extrajugular networks for internal carotid and vertebral artery injections. RESULTS: Patients in the IIH group had statistically significant greater flow in several of the extrajugular networks. Therefore, they preferentially drained through EJN compared with the non-IIH group. Right transverse-sigmoid system was most often dominant in both groups, yet there was a significantly greater prevalence of codominant sinus pattern on posterior circulation angiograms. CONCLUSION: Patients with IIH have greater utilization of EJN compared with patients without IIH. Whether this is merely an epiphenomenon or possesses actual cause-effect relationships needs to be determined with further studies.

A descriptive neuroimaging study of retinoblastoma in children: magnetic resonance imaging features.

Purpose: Retinoblastoma (RB) is the most common intraocular malignancy of childhood. Magnetic resonance imaging (MRI) is essential for initial diagnosis, tumour extension, staging, and treatment planning of RB. Awareness of neuro-imaging findings and determining local extent are essential for early diagnosis and therapy guidance. The purpose of this study is to evaluate and to provide a detailed list of neuroimaging features of RB to improve the diagnostic work-up of children with RB. Material and methods: Retrospective review was performed among children with confirmed RB diagnosis. MRI features were identified to evaluate: 1) growth pattern; 2) intraocular extension; 3) extraocular extension; 4) central nervous system disease; 5) conventional MRI characteristics of the RB lesions; and 6) DWI and ADC characteristics. These features were compared between unilateral and bilateral RB lesions. Results: Twenty-four children (male/female: 18/6) were included in this study. The mean age at the time of diagnosis was 14.7 (11.4) months. In total, 34 RB lesions (bilateral = 18) were evaluated for the study. The most common features on MRI were: 1) endophytic RB lesion (50%); 2) subretinal haemorrhage (38%); 3) scleral involvement (3%); 4) leptomeningeal disease (12%); 5) contrast enhancement (97%); and 6) restricted diffusion (88%). The mean ADC value was 0.64 (0.15) × 10-3 mm2/s. Choroidal invasion (p = 0.05) and scleral involvement (p = 0.04) were significantly higher for bilateral RB lesions. Conclusions: Contrast enhancement and restricted diffusion are the most common neuroimaging features of RB. Choroidal invasion and scleral involvement are more frequently seen in bilateral disease.

Natural history of posterior fetal cephaloceles and incidence of progressive cephalocele herniation.

OBJECTIVE: In utero repair of fetal posterior cephaloceles (meningocele and encephalocele) is being performed based on the premise that fetal surgery prevents progressive herniation of neural tissue and brain damage during pregnancy. However, the extent to which progressive herniation occurs during pregnancy, specifically from prenatal diagnosis to after delivery, is not well known. The objective of this study was to describe the natural history of patients with fetal cephaloceles focusing on the incidence of progressive herniation. METHODS: The authors conducted a retrospective cohort study of all patients referred to their center for posterior fetal cephalocele between 2006 and 2021. All patients underwent prenatal and postnatal MRI. Progressive herniation (primary outcome) was defined as an increase in the absolute volume of neural tissue within the cephalocele of > 5% or new herniation of a critical structure into the cephalocele. Total brain and cephalocele volumes were calculated to determine herniation progression from prenatal to postnatal MRI. Information on the presence of hydrocephalus, epilepsy, and developmental delay (secondary outcomes) was collected at 1 year of age. RESULTS: Twenty patients met all study criteria. Ten patients (50%; 95% CI 0.27-0.73) demonstrated progressive herniation from prenatal to postnatal MRI. Three patients with progressive herniation were diagnosed with a meningocele prenatally and had an encephalocele postnatally. Two patients without progression had meningocele identified prenatally that regressed and became atretic by birth. Both prenatal hindbrain herniation (p = 0.03) and prenatal microcephaly (p = 0.05) were predictive of progressive herniation. The rates of hydrocephalus (44%), epilepsy (44%), and developmental delay (63%) were not associated with the occurrence of progressive herniation in this study. CONCLUSIONS: In this study, progressive herniation was not a rare event (50%). Fetal hindbrain herniation and fetal microcephaly were associated with the occurrence of progressive herniation. These results support further investigations into why progressive herniation occurs in utero and if progressive cerebral herniation in utero plays a significant role in determining clinical outcome.

Duplication of the Pituitary Gland: CT, MRI and DTI Findings and Updated Review of the Literature.

Duplication of the pituitary gland (DPG) is an extremely rare malformation. DPG is associated with a wide variety of midline and central nervous system malformations (DPG-plus syndrome). We present the computed tomography (CT), magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) findings of a rare case of DPG with associated tuberomammillary fusion resulting in a hypothalamic mass-like configuration, oropharyngeal teratoma, cleft palate, hypertelorism, duplicated/broad sella, duplication/low bifurcation of the basilar artery, and craniovertebral midline anomalies. Qualitative interpretation of DTI yielded normal white matter organization of the brain. The duplication of the prechordal plate and the rostral end of the notochordal plate/notochord is thought to be the main factor leading to a duplication of the pituitary primordium and resulting in the formation of two morphologically normal glands. The time of induction of the teratogenic influence, the extent of the prechordal plate and notochordal plate/notochord abnormalities, and the faulty interactions are believed to be the reason for the wide spectrum of associated midline abnormalities.

Pediatric tinnitus: The role of neuroimaging.

Tinnitus is defined as the perception of sound without an external source and can be categorized as either pulsatile or nonpulsatile (ie, continuous). A variety of etiologies have been reported to cause pediatric tinnitus, many with long-lasting implications due to hearing and concentration impairments. Therefore, imaging can be an essential part of the accurate and timely diagnosis of treatable etiologies. We describe neuroimaging findings in different etiologies of pediatric tinnitus. Etiologies of pulsatile tinnitus are frequently vascular in nature and include vascular loops, congenital vascular anomalies or variants, high riding jugular bulbs with or without a jugular bulb diverticulum, idiopathic intracranial hypertension, aneurysms, internal auditory canal hemangiomas, and petrous apex cephaloceles. Etiologies of continuous tinnitus frequently affect the middle/inner ear structures and include vestibular schwannomas, cholesteatomas, trauma, Chiari malformations, and labyrinthitis ossificans. CT and MR are often complementary modalities: CT is better suited to evaluate the integrity of the temporal osseous structures and MR is better suited to evaluate the vestibulocochlear nerve and to assess for the presence of any masses or malformations. Prompt diagnosis of the etiology of tinnitus in pediatric patients is important to avoid any potential long-term developmental impairments. In the approach to pediatric tinnitus, categorizing the symptoms as either pulsatile versus nonpulsatile and then being aware of the possible causes and imaging findings of either can assist both the clinician and the radiologist in making an expeditious diagnosis.

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.

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.

Prenatal diagnosis of Aicardi syndrome based on a suggestive imaging pattern: A multicenter case-series.

OBJECTIVES: To characterize a suggestive prenatal imaging pattern of Aicardi syndrome using ultrasound and MR imaging. METHODS: Based on a retrospective international series of Aicardi syndrome cases from tertiary centers encountered over a 20-year period (2000-2020), we investigated the frequencies of the imaging features in order to characterize an imaging pattern highly suggestive of the diagnosis. RESULTS: Among 20 cases included, arachnoid cysts associated with a distortion of the interhemispheric fissure were constantly encountered associated with complete or partial agenesis of the corpus callosum (19/20, 95%). This triad in the presence of other CNS disorganization, such as polymicrogyria (16/17, 94%), heterotopias (15/17, 88%), ventriculomegaly (14/20, 70%), cerebral asymmetry [14/20, 70%]) and less frequently extra-CNS anomaly (ocular anomalies [7/11, 64%], costal/vertebral segmentation defect [4/20, 20%]) represent a highly suggestive pattern of Aicardi syndrome in a female patient. CONCLUSION: Despite absence of genetic test to confirm prenatal diagnosis of AS, this combination of CNS and extra-CNS fetal findings allows delineation of a characteristic imaging pattern of AS, especially when facing dysgenesis of the corpus callosum.

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.

Fetal Brain Tumors, a Challenge in Prenatal Diagnosis, Counselling, and Therapy.

Fetal brain tumors are a rare entity with an overall guarded prognosis. About 10% of congenital brain tumors are diagnosed during fetal life. They differ from the postnatally encountered pediatric brain tumors with respect to location and tumor type. Fetal brain tumors can be benign or malignant and infiltrate or displace adjacent brain structures. Due to their high mitotic rate, they can show rapid growth. Outcome depends on age of diagnosis, size, and histological tumor type. Findings like polyhydramnios and macrocephaly encountered on routine ultrasound are frequently associated. Detailed prenatal anomaly scan and subsequent fetal magnetic resonance imaging (MRI) may identify the brain tumor and its severity. Both maternal and fetal prognosis should be included in prenatal counselling and decision making.

Neuroimaging Features of Intracranial Hypertension in Pediatric Patients With New-Onset Idiopathic Seizures, a Comparison With Patients with Confirmed Diagnosis of Idiopathic Intracranial Hypertension: A Preliminary Study.

CONCLUSION: A cutoff value of 6.0 mm for optic nerve sheath dilation may be used as a screening imaging marker to suspect elevated opening pressure with specificity of 88% in pediatric patients with new-onset idiopathic seizures.