Ectopic Brain Research Articles

Head organizer: Cerberus and IGF cooperate in brain induction in Xenopus embryos

Neural induction by cell-cell signaling was discovered a century ago by the organizer transplantations of Spemann and Mangold in amphibians. Spemann later found that early dorsal blastopore lips induced heads and late organizers trunk-tail structures. Identifying region-specific organizer signals has been a driving force in the progress of animal biology. Head induction in the absence of trunk is designated archencephalic differentiation. Two specific head inducers, Cerberus and Insulin-like growth factors (IGFs), that induce archencephalic brain but not trunk-tail structures have been described previously. However, whether these two signals interact with each other had not been studied to date and was the purpose of the present investigation. It was found that Cerberus, a multivalent growth factor antagonist that inhibits Nodal, BMP and Wnt signals, strongly cooperated with IGF2, a growth factor that provides a positive signal through tyrosine kinase IGF receptors that activate MAPK and other pathways. The ectopic archencephalic structures induced by the combination of Cerberus and IGF2 are of higher frequency and larger than either one alone. They contain brain, a cyclopic eye and multiple olfactory placodes, without trace of trunk structures such as notochord or somites. A dominant-negative secreted IGF receptor 1 blocked Cerberus activity, indicating that endogenous IGF signals are required for ectopic brain formation. In a sensitized embryonic system, in which embryos were depleted of β-catenin, IGF2 did not by itself induce neural tissue while in combination with Cerberus it greatly enhanced formation of circular brain structures expressing the anterior markers Otx2 and Rx2a, but not spinal cord or notochord markers. The main conclusion of this work is that IGF provides a positive signal initially uniformly expressed throughout the embryo that potentiates the effect of an organizer-specific negative signal mediated by Cerberus. The results are discussed in the context of the history of neural induction.

Brain plasticity following corpus callosum agenesis or loss: a review of the Probst bundles.

The corpus callosum is the largest axonal tract in the human brain, connecting the left and right cortical hemipheres. This structure is affected in myriad human neurodevelopmental disorders, and can be entirely absent as a result of congenital or surgical causes. The age when callosal loss occurs, for example via surgical section in cases of refractory epilepsy, correlates with resulting brain morphology and neuropsychological outcomes, whereby an earlier loss generally produces relatively improved interhemispheric connectivity compared to a loss in adulthood (known as the "Sperry's paradox"). However, the mechanisms behind these age-dependent differences remain unclear. Perhaps the best documented and most striking of the plastic changes that occur due to developmental, but not adult, callosal loss is the formation of large, bilateral, longitudinal ectopic tracts termed Probst bundles. Despite over 100 years of research into these ectopic tracts, which are the largest and best described stereotypical ectopic brain tracts in humans, much remains unclear about them. Here, we review the anatomy of the Probst bundles, along with evidence for their faciliatory or detrimental function, the required conditions for their formation, patterns of etiology, and mechanisms of development. We provide hypotheses for many of the remaining mysteries of the Probst bundles, including their possible relationship to preserved interhemispheric communication following corpus callosum absence. Future research into naturally occurring plastic tracts such as Probst bundles will help to inform the general rules governing axon plasticity and disorders of brain miswiring.

The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial

BackgroundEpigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined.MethodsWe calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3–4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight).ResultsBaseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e − 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = − 0.41, p = 0.004 and beta = − 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, sex, baseline mAge, and weight loss) was mostly affected by higher intake of Mankai (beta = − 1.8; p = 0.061) and green tea (beta = − 1.57; p = 0.0016) and corresponded with elevated urine polyphenols: hydroxytyrosol, tyrosol, and urolithin C (p < 0.05 for all) and urolithin A (p = 0.08), highly common in green plants. Overall, participants undergoing either MED-style diet had ~ 8.9 months favorable difference between the observed and expected Li mAge at the end of the intervention (p = 0.02).ConclusionsThis study showed that MED and green-MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging. To the best of our knowledge, this is the first clinical trial to indicate a potential link between polyphenol intake, urine polyphenols, and biological aging.Trial registrationClinicalTrials.gov, NCT03020186.

Intracranial calcification in Fam20c-deficient mice recapitulates human Raine syndrome

FAM20C (family with sequence similarity 20-member C) is a protein kinase that phosphorylates secretory proteins, including the proteins that are essential to the formation and mineralization of calcified tissues. FAM20C loss-of-function mutations cause Raine syndrome in humans, characterized by generalized osteosclerosis, distinctive craniofacial dysmorphism, along with extensive intracranial calcification. Our previous studies revealed that inactivation of Fam20c in mice led to hypophosphatemic rickets. In this study, we examined the expression of Fam20c in the mouse brain and investigated brain calcification in Fam20c-deficient mice. Reverse transcription polymerase chain reaction (RT-PCR), Western-blotting and in situ hybridization analyses demonstrated the broad expression of Fam20c in the mouse brain tissue. X-ray and histological analyses showed that the global deletion of Fam20c (mediated by Sox2-cre) resulted in brain calcification in mice after postnatal 3 months and that the calcifications were bilaterally distributed within the brain. There was mild perifocal microgliosis as well as astrogliosis around calcospherites. The calcifications were first observed in the thalamus, and later in the forebrain and hindbrain. Furthermore, brain-specific deletion (mediated by Nestin-cre) of Fam20c in mice also led to cerebral calcification at an older age (postnatal 6 months), but no obvious skeletal or dental defects. Our results suggest that the local loss of FAM20C function in the brain may directly account for intracranial calcification. We propose that FAM20C plays an essential role in maintaining normal brain homeostasis and preventing ectopic brain calcification.

Clickable C-Glycosyl Scaffold for the Development of a Dual Fluorescent and [18F]fluorinated Cyanine-Containing Probe and Preliminary In Vitro/Vivo Evaluation by Fluorescence Imaging.

Considering the individual characteristics of positron emission tomography (PET) and optical imaging (OI) in terms of sensitivity, spatial resolution, and tissue penetration, the development of dual imaging agents for bimodal PET/OI imaging is a growing field. A current major breakthrough in this field is the design of monomolecular agent displaying both a radioisotope for PET and a fluorescent dye for OI. We took advantage of the multifunctionalities allowed by a clickable C-glycosyl scaffold to gather the different elements. We describe, for the first time, the synthesis of a cyanine-based dual PET/OI imaging probe based on a versatile synthetic strategy and its direct radiofluorination via [18F]F-C bond formation. The non-radioactive dual imaging probe coupled with two c(RGDfK) peptides was evaluated in vitro and in vivo in fluorescence imaging. The binding on αvβ3 integrin (IC50 = 16 nM) demonstrated the efficiency of the dimeric structure and PEG linkers in maintaining the affinity. In vivo fluorescence imaging of U-87 MG engrafted nude mice showed a high tumor uptake (40- and 100-fold increase for orthotopic and ectopic brain tumors, respectively, compared to healthy brain). In vitro and in vivo evaluations and resection of the ectopic tumor demonstrated the potential of the conjugate in glioblastoma cancer diagnosis and image-guided surgery.

Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A.

Variants in the high confident autism spectrum disorder (ASD) gene ANK2 target both ubiquitously expressed 220 kDa ankyrin-B and neurospecific 440 kDa ankyrin-B (AnkB440) isoforms. Previous work showed that knock-in mice expressing an ASD-linked Ank2 variant yielding a truncated AnkB440 product exhibit ectopic brain connectivity and behavioral abnormalities. Expression of this variant or loss of AnkB440 caused axonal hyperbranching in vitro, which implicated AnkB440 microtubule bundling activity in suppressing collateral branch formation. Leveraging multiple mouse models, cellular assays, and live microscopy, we show that AnkB440 also modulates axon collateral branching stochastically by reducing the number of F-actin-rich branch initiation points. Additionally, we show that AnkB440 enables growth cone (GC) collapse in response to chemorepellent factor semaphorin 3 A (Sema 3 A) by stabilizing its receptor complex L1 cell adhesion molecule/neuropilin-1. ASD-linked ANK2 variants failed to rescue Sema 3A-induced GC collapse. We propose that impaired response to repellent cues due to AnkB440 deficits leads to axonal targeting and branch pruning defects and may contribute to the pathogenicity of ANK2 variants.

Role of BMP signaling during early development of the annelid Capitella teleta

The mechanisms regulating nervous system development are still unknown for a wide variety of taxa. In insects and vertebrates, bone morphogenetic protein (BMP) signaling plays a key role in establishing the dorsal-ventral (D-V) axis and limiting the neuroectoderm to one side of that axis, leading to speculation about the conserved evolution of centralized nervous systems. Studies outside of insects and vertebrates show a more diverse picture of what, if any role, BMP signaling plays in neural development across Bilateria. This is especially true in the morphologically diverse Spiralia (≈Lophotrochozoa). Despite several studies of D-V axis formation and neural induction in spiralians, there is no consensus for how these two processes are related, or whether BMP signaling may have played an ancestral role in either process. To determine the function of BMP signaling during early development of the spiralian annelid Capitella teleta, we incubated embryos and larvae in BMP4 protein for different amounts of time. Adding exogenous BMP protein to early-cleaving C. teleta embryos had a striking effect on formation of the brain, eyes, foregut, and ventral midline in a time-dependent manner. However, adding BMP did not block brain or VNC formation or majorly disrupt the D-V axis. We identified three key time windows of BMP activity. 1) BMP treatment around birth of the 3rd-quartet micromeres caused the loss of the eyes, radialization of the brain, and a reduction of the foregut, which we interpret as a loss of A- and C-quadrant identities with a possible trans-fate switch to a D-quadrant identity. 2) Treatment after the birth of micromere 4d induced formation of a third ectopic brain lobe, eye, and foregut lobe, which we interpret as a trans-fate switch of B-quadrant micromeres to a C-quadrant identity. 3) Continuous BMP treatment from late cleavage (4d ​+ ​12 ​h) through mid-larval stages resulted in a modest expansion of Ct-chrdl expression in the dorsal ectoderm and a concomitant loss of the ventral midline (neurotroch ciliary band). Loss of the ventral midline was accompanied by a collapse of the bilaterally-symmetric ventral nerve cord, although the total amount of neural tissue was not greatly affected. Our results compared with those from other annelids and molluscs suggest that BMP signaling was not ancestrally involved in delimiting neural tissue to one region of the D-V axis. However, the effects of ectopic BMP on quadrant-identity during cleavage stages may represent a non-axial organizing signal that was present in the last common ancestor of annelids and mollusks. Furthermore, in the last common ancestor of annelids, BMP signaling may have functioned in patterning ectodermal fates along the D-V axis in the trunk. Ultimately, studies on a wider range of spiralian taxa are needed to determine the role of BMP signaling during neural induction and neural patterning in the last common ancestor of this group. Ultimately, these comparisons will give us insight into the evolutionary origins of centralized nervous systems and body plans.

A Case of Paraneoplastic Erythropoietin Secretion Secondary to Medullary Thyroid Cancer

Background: Paraneoplastic erythropoietin (EPO) secretion is a well-described phenomenon that is classically seen in renal cell carcinoma. It has also been described in parathyroid adenoma and in pheochromocytoma. Additionally, follicular thyroid cancer cells, papillary thyroid cancer cells, and anaplastic thyroid cancer cells have all been found to express EPO in vitro. To our knowledge, EPO expression by medullary thyroid cancer has not previously been studied. Here, we describe a case of suspected paraneoplastic EPO secretion in the setting of advanced medullary thyroid cancer.Clinical Case: A 46 year-old woman presented to our clinic with hoarseness and was proven to have a medullary thyroid cancer with enlarged lymph nodes on the right at levels IV, V and VI. Genetic testing was negative for a germline RET mutation. She underwent total thyroidectomy with bilateral lymph node dissection and was subsequently treated with external beam radiation therapy. Pathology confirmed the diagnosis of medullary thyroid cancer, with extension beyond the thyroid capsule and bilateral lymph node involvement. Rising calcitonin and CEA were noted over the following years. A MRI of the abdomen showed indeterminate subcentimetric liver lesions. A Gallium-68 Dotatate PET scan confirmed the suspicion of liver metastases. Five years after the initial surgery, the patient developed rising hemoglobin levels, despite a long-standing history of iron deficiency anemia. JAK2 testing was negative. EPO levels were elevated (43.45 mU/mL, reference range 2.59 - 18.5 mU/mL) suggesting secondary polycythemia. The patient had a negative smoking history and a pulse oximetry of 98%; there was no evidence of hypoxia that could cause an elevation in EPO. Other differential diagnoses including pheochromocytoma, Cushing’s syndrome from ectopic ACTH production, and renal and brain tumors were excluded. Biopsy of the liver lesions is not technically feasible at this time. Since discovery of the erythrocytosis, the patient has undergone repeated therapeutic phlebotomies, to maintain acceptable hematocrit levels.Conclusion: We believe that our patient’s case may be the first reported case of ectopic EPO production from medullary thyroid cancer causing polycythemia. We encourage other clinicians to report similar clinical cases in order to better understand this rare clinical entity.

Developmental Potential and Plasticity of Olfactory Epithelium Stem Cells Revealed by Heterotopic Grafting in the Adult Brain.

SummaryThe neural stem cells (NSCs) residing in the olfactory epithelium (OE) regenerate damaged olfactory sensory neurons throughout adulthood. The accessibility and availability of these NSCs in living individuals, including humans, makes them a promising candidate for harvesting their potential for cell replacement therapies. However, this requires an in-depth understanding of their developmental potential after grafting. Here, we investigated the developmental potential and plasticity of mouse OE-derived NSCs after grafting into the adult subventricular zone (SVZ) neurogenic niche. Our results showed that OE-derived NSCs integrate and proliferate just like endogenous SVZ stem cells, migrate with similar dynamics as endogenous neuroblasts toward the olfactory bulb, and mature and acquire similar electrophysiological properties as endogenous adult-born bulbar interneurons. These results reveal the developmental potential and plasticity of OE-derived NSCs in vivo and show that they can respond to heterotopic neurogenic cues to adapt their phenotype and become functional neurons in ectopic brain regions.

Digenic Variants as Possible Clinical Modifier of Primary Familial Brain Calcification Patients.

Primary familial brain calcification (PFBC), widely known as Fahr's disease, is a rare disorder caused by pathogenic variants in SLC20A2, PDGFB, PDGFRB, XPR1, or MYORG genes. It is characterized by ectopic brain calcification, mostly affecting basal ganglia, thalamus, and cerebellum. PFBC patients can present a wide spectrum of symptoms including cognitive, neuropsychiatric, and motor alterations. However, it is well established that PFBC individuals also present high clinical heterogeneity, though the genetic cause of this phenotypic is not understood. Recently, Wang et al. (Front Cell Neurosci. https://doi.org/10.3389/fncel.2019.00250, 2019) reported on the role of MEA6 gene in cerebellar development and motor performance, also citing that MEA6 might be linked to PFBC. A MEA6 variant was described in 2007 as a PFBC candidate gene in an American family. However, this family was later linked to the SLC20A2 gene discarding the MEA6 as a PFBC-gene and also some members were confirmed as phenocopy. Additionally, five independent studies have been shown that variants in a second gene, not related to PFBC, were identified in PFBC patients, promoting a complex and heterogeneous phenotype. Thus, further investigation is required to explain whether and how MEA6 contributes to the clinical presentation in this American family. Finally, this letter highlights the possible digenic influence on clinical heterogeneity of PFBC patients, and such a possibility might advance our understanding of PFBC phenotypes.

Brain ectopic tissue in sacrococcygeal region of a child, clinically mimicking sacrococcygeal teratoma: a case report

BackgroundMature brain heterotopic tissue in sacrococcygeal region is a very rare benign congenital abnormality of newborn. To date, only two cases of mature heterotopic brain tissue in the sacrococcygeal region is reported by literature. Heterotopic brain tissue in other areas such as lung, nose, face and retroperitoneal region are also rarely reported. Meanwhile, rather than brain heterotopic tissue in sacrococcygeal region, a case of adrenal gland heterotopic tissue in sacrococcygeal region also has been reported.Case presentationA 3.5 month-old male baby presented with history of sacrococcygeal mass since birth. Clinical examination of the child was good with no other problem. Sacrococcygeal region revealed an elevated round mass with no discharge. Computed tomography reported a large sacrococcygeal teratoma type-III arising from the sacrococcygeal region extending intra-abdominally to the level of L2 vertebral body. The mass was excised by the impression of sacrococcygeal teratoma (SCT). On gross examination, a gray-white irregular tissue fragment with 5 cm in greatest dimension was examined. Cut sections showed homogenous yellowish white appearance. Histological examination revealed solid fragments composed of mature neural tissue comprising glial cells and astrocytes with no other germ cell layer component.ConclusionMature brain heterotopic tissue in sacrococcygeal area is a rare benign disease. Two ectopic brain tissue in sacrococcygeal region were previously also reported. Sacrococcygeal teratoma is the most common congenital tumor, but this current rare case of heterotopic brain tissue in sacrococcygeal region should also be in the differential diagnosis.

3.1 ENHANCED PARVALBUMIN NETWORK ACTIVITY PROLONGS CRITICAL PERIOD PLASTICITY

BackgroundOscillations in neuronal activity tie the pathophysiology of schizophrenia to alterations in local processing and large-scale coordination, and these alterations in turn can lead to the cognitive and perceptual disturbances observed in schizophrenia. Here, we focus on the dual role of fast-spiking, parvalbumin (PV+) networks in the generation of gamma oscillations and critical periods of brain plasticity.MethodsWe generated a mouse model of reduced recurrent inhibition only within local PV+ cell networks by selective removal of GABAA receptor alpha1 subunits (PV-α1 KO mice). Electroencephalography (EEG), PV+ immunohistochemistry, perineuronal net (PNN) labeling and redox balance were compared to cortical measures of brain plasticity (loss of visual acuity, formation of preference behaviors) that are typically limited to a critical period early in life.ResultsPV-α1 KO mice exhibit chronically enhanced gamma-oscillations and extended juvenile forms of cortical plasticity into adulthood. Acute pharmacological suppression of excitatory input restored E-I balance onto these disinhibited PV+ cells and returned baseline EEG power to normal levels, preventing the extended plasticity. Enhanced gamma oscillations were further found to compromise the integrity of perineuronal nets (PNNs) surrounding PV+ cells, elevating oxidative stress and the turnover of metallopeptidases and structural components of the PNN. All of these aspects were also reversed by pharmacological dampening of excitation onto PV+ cells.DiscussionCortical gamma oscillations are associated with plasticity and cognition. Our results provide a cellular explanation of how elevated gamma oscillations may promote ectopic brain plasticity by regulating the extracellular matrix which normally stabilizes cortical circuitry. These results carry broad implications for subjects at-risk for schizophrenia who exhibit heightened gamma oscillations prior to psychosis onset (see talk by P Uhlhaas).

Ectopic Brain Tissue in a Child: A Case Report A Case of Ectopic Brain Tissue in the Nasophaynx in Thailand

Brain heterotopia is a benign tumor composed of differentiated neural tissue that is located outside the cranial vault. This condition is uncommon and presents as a congenital pharyngeal mass. Here, we report a case of neuroepithelial heterotopia in the nasopharyngeal area of a six-month-old boy who presented with cleft palate and stridor. The tumor demonstrated aggressive growth with oropharyngeal involvement. Radiologic finding revealed a large heterogeneous enhancement on the left side of the nasopharynx, involving the uvula, left lateral pharyngeal wall, and left tonsil. No connection to the brain or spinal cord was apparent on imaging. Histologic features included presence of neuroglial heterotopias, composed predominately of glial cells in a surrounding neurofibrillary matrix. Surgery was the selected intervention, with wide excision performed via cleft palate. Previously published literature relevant to this case were reviewed and discussed. Recurrence is common in incomplete resection, although there was no evidence of recurrence at the two-year follow-up in this patient.

Cutaneous Heterotopic Brain Tissue (Neuroglial Choristoma) with Dysplastic Features in a Kitten

A 3-month-old, male European shorthair kitten exhibited an ill-defined, soft mass on the skin of the frontal head, which was present since birth. The surgically resected tissue was representative of a discrete dermal and subcutaneous mass comprising islands of neurons, glial and meningothelial elements, sometimes atypical or dysplastic, separated by dense collagenous connective tissue. There was no evident connection between this tissue and the brain. Immunohistochemical examination confirmed the presence of neurons and a pleocellular glial population, supporting a diagnosis of cutaneous neuroglial choristoma believed to be secondary to sequestered (resolved) meningoencephalocoele. Ectopic brain tissue is very rare in small animals. Some atypical features displayed by this tissue may be misdiagnosed as neoplasia. Communication between surgeon and pathologist to clarify the relationship of the lesion to surrounding structures is helpful to avoid misdiagnosis.

Glial Heterotopia or Ectopic Brain Masquerading as a Dacyrocystocele

Glial heterotopia is an extremely rare clinical entity mostly presenting in head and neck region secondary to an abnormal development of an isolated mature central nervous system (CNS) tissue at an abnormal location without any continuity with the brain, spinal cord, or meninges. Its origin is either due to mechanical isolation of glial tissues by the developing cranial bones or secondary to misdirected or sequestered embryonic neuroectodermal stem cells outside the CNS. The authors present an exceptionally rare case of a heterotopic glial nodule masquerading as a dacryocystocele, its radiological features along with a brief clinicopathological correlation.

Nasal Glial Heterotopia: Unsuspected Brain Tissue in the Nasopharynx

Objective: To report a case of ectopic brain tissue in the nasopharynx; discuss the differential diagnoses for and management of, this unilateral nasal mass in a pediatric patient, and describe the diagnostic difficulties and eventual treatment.&#x0D; Methods:&#x0D; Study Design: Case Report&#x0D; Setting: Tertiary Government Hospital&#x0D; Participant: One&#x0D; &#x0D; Results: A 13-year-old boy consulted with an obstructing mass in the nasopharynx and severe muscle wasting, weight below his age and concurrent anemia. CT-scan revealed a soft-tissue mass occupying a maxillary sinus and nasopharynx consistent with an antrochoanal polyp. Initial biopsy revealed a papilloma, but the clinical picture warranted preoperative preparations for a possible vascular tumor such as juvenile angiofibroma. Transpalatal excision and final histopathology yielded nasal glial heterotopia. &#x0D; Conclusion: When confronted with a unilateral nasal mass in a pediatric patient, aside from the usual considerations, embryologic anomalies particularly those of the intracranial protrusion variety should be strongly considered. Scrupulous preoperative evaluation and sufficient diagnostic modalities must be pursued in order to arrive a correct diagnosis, treatment plan and prevent possible complications especially those related to intracranial communication.&#x0D; Keywords: Nasal glioma, glial heterotopia, congenital nasal masses

Cortical anaplastic ependymoma with significant desmoplasia: a case report and literature review.

Ectopic brain anaplastic ependymomas with no connection to the ventricles are rare. We present a rare case of a 25-year-old male who presented with generalized convulsions. Computed tomography (CT), Magnetic Resonance Imaging (MRI), and magnetic resonance spectroscopy (MRS) showed characters of an intra- and extra-axial lesion. Intraoperatively, the lesion was a cortical solid mass that had no connections to the dura or to the ventricle. The histological diagnosis showed an anaplastic ependymoma with WHO grade III with distinctive desmoplasia. A literature review of ectopic anaplastic ependymomas regarding their clinical presentations, management, and prognostic factors was performed. There is a need to establish a clinically based histopathological grading system for anaplastic ependymomas. Ectopic anaplastic ependymomas should be included in the preoperative differential diagnosis.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

Neuroimaging of Dandy-Walker Malformation

Dandy-Walker malformation (DWM) is the most common human cerebellar malformation, characterized by hypoplasia of the cerebellar vermis, cystic dilation of the fourth ventricle, and an enlarged posterior fossa with upward displacement of the lateral sinuses, tentorium, and torcular. Although its pathogenesis is not completely understood, there are several genetic loci related to DWM as well as syndromic malformations and congenital infections. Dandy-Walker malformation is associated with other central nervous system abnormalities, including dysgenesis of corpus callosum, ectopic brain tissue, holoprosencephaly, and neural tube defects. Hydrocephalus plays an important role in the development of symptoms and neurological outcome in patients with DWM, and the aim of surgical treatment is usually the control of hydrocephalus and the posterior fossa cyst. Imaging modalities, especially magnetic resonance imaging, are crucial for the diagnosis of DWM and distinguishing this disorder from other cystic posterior fossa lesions. Persistent Blake's cyst is seen as a retrocerebellar fluid collection with cerebrospinal fluid signal intensity and a median line communication with the fourth ventricle, commonly associated with hydrocephalus. Mega cisterna magna presents as an extraaxial fluid collection posteroinferior to an intact cerebellum. Retrocerebellar arachnoid cysts frequently compress the cerebellar hemispheres and the fourth ventricle. Patients with DWM show an enlarged posterior fossa filled with a cystic structure that communicates freely with the fourth ventricle and hypoplastic vermis. Comprehension of hindbrain embryology is of utmost importance for understanding the cerebellar malformations, including DWM, and other related entities.

Combining Classical and Molecular Approaches Elaborates on the Complexity of Mechanisms Underpinning Anterior Regeneration

The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP) axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh) signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi) or Smed-ptc(RNAi) lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi) grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new, and then later homeostatic signals in AP axis regeneration.