Multiple Sclerosis and the Choroid Plexus: Emerging Concepts of Disease Immunopathophysiology.

BACKGROUND: The coexistence of multiple sclerosis and intracranial neoplasms is very rare, and whether this occurrence can be explained by a causal relationship or by coincidence remains a matter of debate. Possible roles of the choroid plexus as a site of tumor cell invasion and lymphocyte infiltration into the central nervous system have been hypothesized in recent studies. METHODS: We describe a 13-year-old boy with concurrent multiple sclerosis and choroid plexus papilloma, then review the published literature with a focus on the pathophysiologic mechanisms of neuroinflammation in multiple sclerosis and the potential role of the choroid plexus in this process. RESULTS: A growing body of evidence suggests that both physical and functional dysregulation of the choroid plexus may be a common mechanism underlying the pathophysiology of central nervous system inflammation. CONCLUSIONS: In multiple sclerosis, the choroid plexus could act as a gateway for lymphocyte entry from the peripheral blood into the central nervous system at its earlier stages. However, future studies are needed to identify whether structural alterations of the choroid plexus play a role in the pathophysiology of multiple sclerosis and to provide suitable models to determine their consequences.

c-MYC overexpression induces choroid plexus papillomas through a T-cell mediated inflammatory mechanism.

Choroid plexus tumours (CPTs) account for 2-5% of brain tumours in children. They can spread along the neuraxis and can recur after treatment. Little is known about the molecular mechanisms underlying their formation and only few high fidelity mouse models of p53-deficient malignant CPTs are available.We show here that c-MYC overexpression in the choroid plexus epithelium induces T-cell inflammation-dependent choroid plexus papillomas in a mouse model. We demonstrate that c-MYC is expressed in a substantial proportion of human choroid plexus tumours and that this subgroup of tumours is characterised by an inflammatory transcriptome and significant inflammatory infiltrates. In compound mutant mice, overexpression of c-MYC in an immunodeficient background led to a decreased incidence of CPP and reduced tumour bulk. Finally, reduced tumour size was also observed upon T-cell depletion in CPP-bearing mice. Our data raise the possibility that benign choroid plexus tumours expressing c-MYC could be amenable to medical therapy with anti-inflammatory drugs.

Papiloma de plexos coroideos / Choroid plexuses papilloma

Introducción: el papiloma de plexos coroideos es un tipo de tumor cerebral o neoplasia papilar intraventricular de origen neuroectodérmico (se deriva del epitelio de los plexos coroideos). Junto con el carcinoma de plexos coroideos, de similar origen, constituye 3-5 por ciento del total de tumores intracraneales de la infancia.Objetivo: presentar el caso de un niño con diagnóstico de papiloma de plexos coroideos con antecedente prenatal de ventriculomegalia. Presentación del caso: neonato masculino nacido en el Hospital Roberto Galindo Terán, en Cobija, Departamento de Pando (Bolivia). Nació producto de un parto distócico por cesárea a las 39 semanas, debido al antecedente prenatal de ventriculomegalia, diagnosticada en el ultrasonido transfontanelar a las 32 semanas. Se le realizó un ultrasonido craneal con transductor neonatal, en el que se observó, al nivel de los cuernos occipitales, una masa hiperecogénica lobulada en los plexos coroideos con hidrocefalia comunicante. Se le diagnosticó papiloma de plexos coroideos. Discusión: la intervención quirúrgica es el tratamiento de elección para los papilomas de plexos coroideos, puesto que, además de extirpar el tumor, en la mayoría de los casos se elimina la hidrocefalia. Los avances de las técnicas quirúrgicas aseguran la retirada o disminución de la aferencia vascular tumoral y, consecuentemente, que la tasa de mortalidad sea baja.Conclusiones: ante un neonato con antecedente prenatal de ventriculomegalia o signos y síntomas relacionados con hidrocefalia, se debe sospechar la presencia de papiloma de plexos coroideos. El diagnóstico debe ser confirmado por estudios imagenológicos(AU)

Introduction: the choroid plexus papilloma is a type of brain tumor or intraventricular papillary neoplasm of neuroectodermal origin (derived from the epithelium of the choroid plexus). Together with choroidal plexus carcinoma, of similar origin, it constitutes 3-5 percent of all childhood intracranial tumors.Objective: to present the case of a child with a diagnosis of choroid plexus papilloma with a prenatal history of ventriculomegaly.Case presentation: male newborn born in the Hospital Roberto Galindo Terán, in Cobija, Pando Department (Bolivia). He was born due to a cesarean birth at the 39th week, due to a prenatal history of ventriculomegaly, diagnosed in the transfontanellar ultrasound at 32 weeks. A cranial ultrasound was carried out with a neonatal transducer, in which a hyperechoic mass lobulated in the choroid plexuses with communicating hydrocephalus was observed at the level of the occipital horns. He was diagnosed with choroid plexus papilloma.Discussion: surgical intervention is the treatment of choice for choroid plexus papillomas, since, in addition to removing the tumor, in most cases hydrocephalus is eliminated. Advances in surgical techniques ensure the removal or reduction of tumor vascular aference and, consequently, that the mortality rate is low.Conclusions: in the presence of a neonate with a prenatal history of ventriculomegaly or signs and symptoms related to hydrocephalus, the presence of choroid plexus papilloma should be suspected. The diagnosis must be confirmed by imaging studies(AU)

Surgical treatment of choroid plexus tumors.

PURPOSE: The purpose of this study is to evaluate the results of microsurgical treatment for choroid plexus tumors (CPT) in adult patients. METHODS: From 1990 to 2008, 14 patients >18 years were treated at our institution for CPT, including seven males and seven females with a mean age of 46 years. Mean follow-up was 40 months. We reviewed the respective patients' charts, operative, and follow-up notes. Telephone interviews were performed as necessary. Neurological status was determined using the Karnofsky performance index pre- and post-operatively and at last follow-up. RESULTS: This series includes 12 plexus papillomas (CPP) and two atypical plexus papillomas (APP). Ten tumors were located in the fourth ventricle, two tumors in the cerebellopontine angle, one growth each in the third and lateral ventricle. In 12 cases, a complete tumor resection was achieved. No recurrence was observed in these cases. Two recurrent CPP were diagnosed 11 and 25 years after the initial surgery. Brain stem infiltration prevented a complete tumor removal in one case. In the other, the degree of resection after the first operation could not be ascertained. None of the patients received adjuvant chemo- or radiotherapy. In four patients (29%), a permanent ventricular-peritoneal shunt was necessary. Three patients initially presented with a Karnofsky index of 60 or below. During follow-up, three patients (21%) never improved beyond a Karnofsky index of 60. CONCLUSIONS: Surgery aiming radical excision is the key to successful treatment of CPP and APP in adults. Postoperative outcomes may be less than satisfactory in some patients.

Brain tumor animal models: importance and progress.

Recent experiments indicate that some of the genetic abnormalities found in human brain tumors can induce tumors in mice with similar histologic characteristics to their human counterparts. Such studies help unravel the biology of tumorigenesis and indicate that some of the mutations and alterations in gene expression found in human central nervous system tumors may actually contribute to the etiology of these diseases. In addition, these mouse-modeling experiments may identify essential targets for therapy and provide test animals for preclinical trials of mechanistically designed therapeutics.