Neuroimaging in tuberous sclerosis complex.

INTRODUCTION: Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder affecting multiple systems, due to inactivating mutations of TSC1 or TSC2 mTOR pathway genes. Neurological manifestations are observed in about 95% cases, representing the most frequent cause of morbidity and one of the most common causes of mortality. BACKGROUND: Neuroimaging is crucial for early diagnosis, monitoring, and management of these patients. While computed tomography is generally used as first-line investigation at emergency department, magnetic resonance imaging is the reference method to define central nervous system involvement and investigate subtle pathophysiological alterations in TSC patients. PURPOSE: Here, we review the state-of-the-art knowledge in TSC brain imaging, describing conventional findings and depicting the role of advanced techniques in providing new insights on the disease, also offering an overview on future perspectives of neuroimaging applications for a better understanding of disease pathophysiology.

Fourth Ventricle Outlet Obstruction and Diverticular Enlargement of Luschka Foramina in a Child with Down Syndrome.

INTRODUCTION: Hydrocephalus is not usually part of Down syndrome (DS). Fourth ventricle outlet obstruction is a rare cause of obstructive hydrocephalus, difficult to diagnose, because tetraventricular dilatation may suggest a communicant/nonobstructive hydrocephalus. CASE PRESENTATION: We describe the case of a 6-year-old boy with obstructive tetraventricular hydrocephalus, caused by Luschka and Magen-die foramina obstruction and diverticular enlargement of Luschka foramina (the so-called fourth ventricle outlet obstruction) associated with DS. He was treated with endoscopic third ventriculostomy (ETV) without complications, and a follow-up MRI revealed reduction of the ventricles, disappearance of the diverticula, and patency of the ventriculostomy. CONCLUSION: Diverticular enlargement of Luschka foramina is an important radiological finding for obstructive tetraventricular hydrocephalus. ETV is a viable option in tetraventricular obstructive hydrocephalus in DS.

Biological Pathways Involved in Tumor Angiogenesis and Bevacizumab Based Anti-Angiogenic Therapy with Special References to Ovarian Cancer.

The creation of new blood vessels from existing ones, which is a mechanism called "angiogenesis", is essential in cancer to supply cancerous growth. Moreover, the development and the progression of the tumor and its metastases are the result of an efficient vascular response. Cancer cells release and activate different angiogenic growth factors and their receptors in the tumor microenvironment to promote the angiogenic process. The most important pro-angiogenic factor is the "Vascular Endothelial Growth Factor" (VEGF) because of its mitogen activity on vascular endothelium. Bevacizumab is a monoclonal antibody that obstructs the binding of circulating vascular endothelial growth factor to its receptors and has been approved for the treatment of primary and recurrent ovarian cancer but also for many other solid tumors.

Is advanced neuroimaging for neuroradiologists? A systematic review of the scientific literature of the last decade.

INTRODUCTION: To evaluate if advanced neuroimaging research is mainly conducted by imaging specialists, we investigated the number of first authorships by radiologists and non-radiologist scientists in articles published in the field of advanced neuroimaging in the past 10 years. METHODS: Articles in the field of advanced neuroimaging identified in this retrospective bibliometric analysis were divided in four groups, depending on the imaging technique used. For all included studies, educational background of the first authors was recorded (based on available online curriculum vitae) and classified in subgroups, depending on their specialty. Finally, journal impact factors were recorded and comparatively assessed among subgroups as a metric of research quality. RESULTS: A total number of 3831 articles were included in the study. Radiologists accounted as first authors for only 12.8 % of these publications, while 56.9 % of first authors were researchers without a medical degree. Mean impact factor (IF) of journals with non-MD researchers as first authors was significantly higher than the MD subgroup (p < 10-20), while mean IF of journals with radiologists as first authors was significantly lower than articles authored by other MD specialists (p < 10-11). CONCLUSIONS: The majority of the studies in the field of advanced neuroimaging in the last decade is conducted by professional figures other than radiologists, who account for less than the 13 % of the publications. Furthermore, the mean IF value of radiologists-authored articles was the lowest among all subgroups. These results, taken together, should question the radiology community about its future role in the development of advanced neuroimaging.

Fully automated measurement of intracranial CSF and brain parenchyma volumes in pediatric hydrocephalus by segmentation of clinical MRI studies.

BACKGROUND: Brain parenchyma (BP) and intracranial cerebrospinal fluid (iCSF) volumes measured by fully automated segmentation of clinical brain MRI studies may be useful for the diagnosis and follow-up of pediatric hydrocephalus. However, previously published segmentation techniques either rely on dedicated sequences, not routinely used in clinical practice, or on spatial normalization, which has limited accuracy when severe brain distortions, such as in hydrocephalic patients, are present. PURPOSE: We developed a fully automated method to measure BP and iCSF volumes from clinical brain MRI studies of pediatric hydrocephalus patients, exploiting the complementary information contained in T2- and T1-weighted images commonly used in clinical practice. METHODS: The proposed procedure, following skull-stripping of the combined volumes, performed using a multiparametric method to obtain a reliable definition of the inner skull profile, maximizes the CSF-to-parenchyma contrast by dividing the T2w- by the T1w- volume after full-scale dynamic rescaling, thus allowing separation of iCSF and BP through a simple thresholding routine. RESULTS: Validation against manual tracing on 23 studies (four controls and 19 hydrocephalic patients) showed excellent concordance (ICC > 0.98) and spatial overlap (Dice coefficients ranging from 77.2% for iCSF to 96.8% for intracranial volume). Accuracy was comparable to the intra-operator reproducibility of manual segmentation, as measured in 14 studies processed twice by the same experienced neuroradiologist. Results of the application of the algorithm to a dataset of 63 controls and 57 hydrocephalic patients (19 with parenchymal damage), measuring volumes' changes with normal development and in hydrocephalic patients, are also reported for demonstration purposes. CONCLUSIONS: The proposed approach allows fully automated segmentation of BP and iCSF in clinical studies, also in severely distorted brains, enabling to assess age- and disease-related changes in intracranial tissue volume with an accuracy comparable to expert manual segmentation.

Removal of a thoracic intramedullary epidermoid tumor in a child.

Epidermoid cysts are rare, benign neoplasms that account for less than 1% of all intraspinal tumors. The most common localization is in the lumbar area, and one-third of the tumors are intramedullary. In this video, the authors present removal of a thoracic intramedullary epidermoid tumor in a 6-year-old boy, carrier of a 22q11 gene duplication and affected by psychomotor retardation. He presented a 1-year history of progressive gait impairment. No history of lumbar puncture or trauma was reported. The procedure was performed under neurophysiological monitoring, and it was uneventful with complete recovery of neurological function. Technical nuances are illustrated.

Atypical Clinical and Neuroradiological Findings in a Child With Bifacial Weakness With Paresthesias.

BACKGROUND: Guillain-Barré syndrome (GBS) is the broad term used to describe a number of related acute autoimmune neuropathies, which together form a continuous spectrum of variable and overlapping syndromes. Bifacial weakness with paresthesias (BFP) is a rare variant of GBS, characterized by isolated facial diplegia in the absence of ophthalmoplegia, ataxia, or limb weakness, and it is usually associated with distal limb paresthesias. CASE DESCRIPTION: An 8-year-old boy was brought to our attention; because 5 days before coming to the hospital, he noticed he could no longer smile. Bilateral facial droop and inability to close both eyes were evident along with slight paresthesias at the hands and feet and gait disturbances. He progressively developed hypophonia, dysarthria, dysphagia associated with dysmetria, and limb ataxia. Nerve conduction studies showed a demyelinating polyneuropathy. Brain and spine magnetic resonance imaging (MRI) revealed contrast enhancement of both facial nerves and cauda equina nerve roots along with a hyperintense signal of the periaqueductal gray matter, superior cerebellar peduncles, and pontine tegmentum. Because BFP is not typically associated with other cranial neuropathies or ataxia, these clinical features along with peculiar MRI findings supported the diagnosis of "BFP plus." Finally, it can be speculated that this case configures a rare overlap between BFP and the other GBS variants, such as Bickerstaff encephalitis. CONCLUSIONS: This atypical case underlines the potential role of MRI in contributing to refining the nosological classification of GBS spectrum and optimizing individual treatment, especially in children where unusual manifestations are not infrequent and neurological examination is more challenging.

Fibrodysplasia Ossificans Progressiva: A Challenging Diagnosis.

Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic condition characterized by extraskeletal bone formation. Most of the musculoskeletal characteristics of FOP are related to dysregulated chondrogenesis, with heterotopic ossification being the most typical feature. Activating mutations of activin receptor A type I (ACVR1), a bone morphogenetic protein (BMP) type I receptor, are responsible for the skeletal and nonskeletal features. The clinical phenotype is always consistent, with congenital bilateral hallux valgus malformation and early-onset heterotopic ossification occurring spontaneously or, more frequently, precipitated by trauma. Painful, recurrent soft-tissue swellings (flare-ups) precede localized heterotopic ossification that can occur at any location, typically affecting regions near the axial skeleton and later progressing to the appendicular bones. A diagnosis of FOP is suspected in a proband presenting with hallux valgus malformation, heterotopic ossification, and confirmed by the identification of a heterozygous pathogenic variant in the ACVR1/ALK2 gene. Avoiding unnecessary surgical procedures, prescribing prophylactic corticosteroids, preventing falls, and using protective headgear represent essential interventions for care management. Different classes of medications to contain acute inflammation flare-ups have been proposed, with high dose corticosteroids and nonsteroidal anti-inflammatory drugs usually utilized. Here, we report on two FOP patients, with typical clinical features summarizing the principal aspects of FOP, and we aim to provide comprehensive information outlining some unusual findings, possibly contributing to FOP's definition and management.

PARP inhibitors and epithelial ovarian cancer: Molecular mechanisms, clinical development and future prospective.

Epithelial ovarian cancer (EOC) has a poor prognosis. Since the introduction of paclitaxel as antineoplastic agent >20 years ago, only a few phase III randomized trials have shown challenging data regarding different therapeutic options for facing its aggressive clinical course and granting active therapies to patients. Different studies have shown the utility of poly(ADP-ribose) polymerase (PARP) inhibitors in women with EOC with or without BRCA mutations, both germline and somatic. Three PARP inhibitors, olaparib, rucaparib and niraparib, have been recently approved by the Food and Drug Administration for clinical use in EOC patients, though with different clinical indications and profiles of toxicity, while two other molecules, veliparib and talazoparib, are still under clinical investigation. The aim of the present paper is to evaluate the current status of PARP inhibitors in terms of molecular activity, pharmacodynamic properties and clinical applications.

Radiation-induced brain cavernomas in elderly: review of the literature and a rare case report.

Radiation-induced brain cavernomas have been mainly reported in children who underwent radiotherapy for medulloblastoma, leukemia, or low-grade glioma. Otherwise, the "de novo" appearance of a cavernoma in an elderly long-survivor patient after resection and radiotherapy of a glioblastoma is a rare event. We report the case of a 62-year-old female patient who underwent surgical resection of a right temporal glioblastoma, followed by radiation therapy of the operative field and surrounding brain and concomitant adjuvant temozolomide. Four years after the operation, a follow-up Magnetic Resonance revealed a good tumor control and a small round lesion at the superior surface of the right cerebellar hemisphere, close to the margins of the previous irradiation field. The radiological items were consistent with a cavernous angioma. Because of the small size of the malformation and the absence of related symptoms, no treatment was performed. The patient died for tumor progression 86 months after the initial operation, with unchanged cerebellar cavernoma. The occurrence of a cavernous angioma in an elderly patient after radiotherapy for brain glioblastoma is an exceptional event; the distribution of radiotherapy-induced cavernous malformations reported in current literature is presented and the mechanism of their formation is discussed.