Corpus callosum tumor as the presenting symptom of neurofibromatosis type 1 in a patient and literature review

Introducción. La neurofibromatosis tipo 1 (NF1) es uno de los síndromes neurocutáneos más frecuentes y puede asociarse a tumores intracraneales en cualquier localización, pero excepcionalmente en el cuerpo calloso. Objetivos. Presentar un caso de NF1 que se manifiesta como un tumor de cuerpo calloso y llevar a cabo una revisión de la incidencia de tumores del cuerpo calloso en nuestra casuística y en la bibliografía. Caso clínico. Niño visto desde los 3 años con criterios diagnósticos de NF1 (sin comprobación genética), que fue estudiado por resonancia magnética (RM) y RM espectroscópica. La RM mostró objetos brillantes en la neurofibromatosis en diversas zonas cerebrales y cerebelosas, posible tumor en el tronco cerebral (parte bulbar) y tumor en la zona derecha del esplenio del cuerpo calloso. La RM espectroscópica del posible tumor del tronco mostró hallazgos compatibles con tumoración glial de bajo grado. Se siguió su evolución hasta los 19 años sin que hubieran existido cambios clínicos ni en el tamaño de los tumores en las dos localizaciones. Sólo existen seis casos publicados de tumor del cuerpo calloso en pacientes con NF1. Conclusión. Presentamos un nuevo caso de un paciente con tumor del cuerpo calloso en un paciente con NF1. Las características de la imagen y la evolución clínica van a favor del carácter benigno de este tipo de tumorIntroduction. Neurofibromatosis type 1 (NF1) is one of the most frequent neurocutaneous syndromes. NF1 can be associated with intracranial tumors in any location, but only rarely in the corpus callosum. Aims. To describe a case of NF1 presenting as a tumor of the corpus callosum and to carry out a review of the incidence of the tumors of corpus callosum in our series and in the literature. Case report. We present a child who was studied since 3 years of age because of complete NF1 clinical diagnostic criteria (without genetic study). He was studied by MR and magnetic resonance spectroscopy (MRS). MR study showed neurofibromatosis bright objects distributed over several regions of the cerebral hemispheres and cerebellum, a possible brain stem tumor (bulbar zone) and the splenium of the corpus callosum. The MRS of the brain stem tumor showed changes consistent with a low grade glial tumor. The patient was followed until 19-years of age without demonstrating any changes in the clinical features or the tumor size in both locations Only six cases of corpus callosum tumor in patients with NF1 have been published to date. Conclusions. We present a new case with tumor of the corpus callosum and NF1. The imaging characteristics and the clinical course were in favour of the benign nature of this type of tumo

Voluminous plexiform neurofibromas of the neck region in neurofibromatosis 1

Objetivo. Presentar las características clínicas, de imagen y evolutivas de una serie de pacientes con neurofibromatosis tipo 1 que desarrollaron durante la infancia neurofibromas plexiformes voluminosos en el cuello (NFPVC). Pacientes y métodos. Nueve pacientes (cinco mujeres y cuatro varones) con edades entre 3 y 15 años en el momento del diagnóstico de los tumores, que podían extenderse también a la fosa posterior y a la zona torácica superior. El diagnóstico estuvo basado fundamentalmente en la clínica, la imagen y la histología. Resultados. Un tumor era intralaríngeo y causaba problemas respiratorios. Los otros ocho casos tenían su origen en varias raíces espinales de uno o de ambos lados y podían crecer también hacia el interior de la fosa posterior y de la región torácica en algunos pacientes, y desplazaban a las estructuras anatómicas vecinas, especialmente en tres casos, todos niñas, en las que el tumor creció hasta alcanzar gran volumen, especialmente por un lado, parándose el crecimiento entre los 11 y 12 años y no volviendo a crecer más tarde. Conclusiones. Los NFPVC son tumores histológicamente benignos. La extirpación es necesaria cuando están localizados en la laringe por los problemas respiratorios que causan, pero no en los de las otras regiones, pese a que el voluminoso tamaño que alcanzan en algunos casos puede causar exagerados desplazamientos de las estructuras vecinas. El estudio de nuestra serie parece indicar que al menos los tumores extralaríngeos sólo crecen hasta los 11-12 años. Puede ser recomendable retrasar la cirugía tanto como sea posible si no existe sintomatología aguda que la haga necesariaAim. To present the clinic, imaging and evolutive characteristics of a series of patients with neurofibromatosis 1 with voluminous plexiform neurofibromas in the neck (VPNFN) during childhood. Patients and methods. Nine patients (five females and four males) who were diagnosed as VPNFN at ages between 3 and 15 years. The VPNFN widespread to the posterior fossa or the upper thoracic region in some cases. The diagnosis was based on the clinical, imaging and histological findings. Results. One of the tumors was intralaryngeal and caused respiratory difficulties. The other eight patients had the origin of the tumor in several spinal roots of one or both sides and could growth to the posterior fossa and to the upper thoracic region in some cases with displacement of the surrounding organs, especially in three patients, all girls, in whom the tumor reached a voluminous size on one side, that was observed only until 10 to 11 years when the growth ceased. Conclusions. The VPNFN are histologically benign tumors. Those located in the larynx must be removed because of the respiratory problems, but it is not necessary in cases with other locations despite the voluminous size that can reach in some patients with great displacement of the surrounding organs. The analysis of the results of our series may demonstrate that al least the extralaryngeal tumors only grow to 11-12 years of age. This possibility may make recommendable to retard the surgical treatment as much as possible in cases that it is not necessar

PHACE association with intracranial, oropharyngeal hemangiomas, and an atypical patent ductus arteriosus arising from the tortuous left subclavian artery in a premature infant

PHACE association is a rare neurocutaneous condition in which facial hemangiomas associate with a spectrum of posterior fossa malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, and eye anomalies. We reported a case of PHACE association in a premature infant showing facial, intracranial, and oropharyngeal hemangiomas with evidence of the Dandy-Walker variant and complicated cardiovascular anomalies, including a right-sided aortic arch and an atypical patent ductus arteriosus arising from a tortuous left subclavian artery. To our knowledge, intracranial hemangiomas are rare in PHACE association, and a concomitant oropharyngeal hemangioma has not been previously reported in the PHACE association literature. In infants presenting with large, plaque-like facial hemangiomas, it is important to conduct active cardiovascular and neurological evaluations. Special attention should be given to the laryngoscopic examination to search for additional hemangiomas in the airway

The 4q25 variant rs13143308T links risk of atrial fibrillation to defective calcium homoeostasis

Aims: Single nucleotide polymorphisms on chromosome 4q25 have been associated with risk of atrial fibrillation (AF) but the exiguous knowledge of the mechanistic links between these risk variants and underlying electrophysiological alterations hampers their clinical utility. Here, we tested the hypothesis that 4q25 risk variants cause alterations in the intracellular calcium homoeostasis that predispose to spontaneous electrical activity. Methods and results: Western blotting, confocal calcium imaging, and patch-clamp techniques were used to identify mechanisms linking the 4q25 risk variants rs2200733T and rs13143308T to defects in the calcium homoeostasis in human atrial myocytes. Our findings revealed that the rs13143308T variant was more frequent in patients with AF and that myocytes from carriers of this variant had a significantly higher density of calcium sparks (14.1¿±¿4.5 vs. 3.1¿±¿1.3 events/min, P¿=¿0.02), frequency of transient inward currents (ITI) (1.33¿±¿0.24 vs. 0.26¿±¿0.09 events/min, P¿<¿0.001) and incidence of spontaneous membrane depolarizations (1.22¿±¿0.26 vs. 0.56¿±¿0.17 events/min, P¿=¿0.001) than myocytes from patients with the normal rs13143308G variant. These alterations were linked to higher sarcoplasmic reticulum calcium loading (10.2¿±¿1.4 vs. 7.3¿±¿0.5¿amol/pF, P¿=¿0.01), SERCA2 expression (1.37¿±¿0.13 fold, P¿=¿0.03), and RyR2 phosphorylation at ser2808 (0.67¿±¿0.08 vs. 0.47¿±¿0.03, P¿=¿0.01) but not at ser2814 (0.28¿±¿0.14 vs. 0.31¿±¿0.14, P¿=¿0.61) in patients carrying the rs13143308T risk variant. Furthermore, the presence of a risk variant or AF independently increased the ITI frequency and the increase in the ITI frequency observed in carriers of the risk variants was exacerbated in those with AF. By contrast, the presence of a risk variant did not affect the amplitude or properties of the L-type calcium current in patients with or without AF. Conclusions: Here, we identify the 4q25 variant rs13143308T as a genetic risk marker for AF, specifically associated with excessive calcium release and spontaneous electrical activity linked to increased SERCA2 expression and RyR2 phosphorylation.Peer ReviewedPostprint (author's final draft

Sturge-Weber Syndrome

Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome, characterized by the association of facial port-wine hemangiomas in the trigeminal nerve distribution area, with vascular malformation(s) of the brain (leptomeningeal angioma) with or without glaucoma. Herein, we reported Sturge-Weber syndrome in a 50-year-old man, who presented port-wine hemangiomas and epilepsy. In this case, the patient's epilepsy episodes from his first year of life had been ignored and separated from the entity of SWS by his physicians, which led to delayed treatment. This case illustrates the importance of careful examination of patients of any age with hemangiomas in the trigeminal nerve with concomitant episodes of epilepsy. In such cases, there should be yearly neuroimaging screenings to guaranteed early interdisciplinary interventions from the time of definite diagnosis

Clinical and metabolic correlates of cerebral calcifications in Sturge–Weber syndrome

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138348/1/dmcn13433.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138348/2/dmcn13433_am.pd

MLC1 is associated with the Dystrophin-Glycoprotein Complex at astrocytic endfeet

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive cerebral white matter disease with onset in childhood, caused by mutations in the MLC1 gene. MLC1 is a protein with unknown function that is mainly expressed in the brain in astrocytic endfeet at the blood–brain and cerebrospinal fluid–brain barriers. It shares its localization at astrocytic endfeet with the dystrophin-associated glycoprotein complex (DGC). The objective of the present study was to investigate the possible association of MLC1 with the DGC. To test this hypothesis, (co)-localization of DGC-proteins and MLC1 was analyzed by immunohistochemical stainings in gliotic brain tissue from a patient with multiple sclerosis, in glioblastoma tissue and in brain tissue from an MLC patient. In control tissue, a direct protein interaction was tested by immunoprecipitation. Results revealed that MLC1 is co-localized with DGC-proteins in gliotic brain tissue. We demonstrated that both MLC1 and aquaporin-4, a member of the DGC, were redistributed in glioblastoma cells. In MLC brain tissue, we showed absence of MLC1 and altered expression of several DGC-proteins. We demonstrated a direct protein interaction between MLC1 and Kir4.1. From these results we conclude that MLC1 is associated with the DGC at astrocytic endfeet

Childhood Absence Epilepsy with Tonic-Clonic Seizures and Electroencephalogram 3–4-Hz Spike and Multispike–Slow Wave Complexes: Linkage to Chromosome 8q24

SummaryChildhood absence epilepsy (CAE), a common form of idiopathic generalized epilepsy, accounts for 5%–15% of childhood epilepsies. To map the chromosomal locus of persisting CAE, we studied the clinical and electroencephalographic traits of 78 members of a five-generation family from Bombay, India. The model-free affected–pedigree member method was used during initial screening with chromosome 6p, 8q, and 1p microsatellites, and only individuals with absence seizures and/or electroencephalogram 3–4-Hz spike– and multispike–slow wave complexes were considered to be affected. Significant P values of .00000–.02 for several markers on 8q were obtained. Two-point linkage analysis, assuming autosomal dominant inheritance with 50% penetrance, yielded a maximum LOD score (Zmax) of 3.6 for D8S502. No other locus in the genome achieved a significant Zmax. For five smaller multiplex families, summed Zmax was 2.4 for D8S537 and 1.7 for D8S1761. Haplotypes composed of the same 8q24 microsatellites segregated with affected members of the large family from India and with all five smaller families. Recombinations positioned the CAE gene in a 3.2-cM interval

Endosymbiotic bacteria nodulating a new endemic lupine Lupinus mariae-josephi from alkaline soils in Eastern Spain represent a new lineage within the Bradyrhizobium genus

Lupinus mariae-josephi is a recently described endemic Lupinus species from a small area in Eastern Spain where it thrives in soils with active lime and high pH. The L. mariae-josephi root symbionts were shown to be very slow-growing bacteria with different phenotypic and symbiotic characteristics from those of Bradyrhizobium strains nodulating other Lupinus. Their phylogenetic status was examined by multilocus sequence analyses of four housekeeping genes (16S rRNA, glnII, recA, and atpD) and showed the existence of a distinct evolutionary lineage for L. mariae-josephi that also included Bradyrhizobium jicamae. Within this lineage, the tested isolates clustered in three different sub-groups that might correspond to novel sister Bradyrhizobium species. These core gene analyses consistently showed that all the endosymbiotic bacteria isolated from other Lupinus species of the Iberian Peninsula were related to strains of the B. canariense or B. japonicum lineages and were separate from the L. mariae-josephi isolates. Phylogenetic analysis based on nodC symbiotic gene sequences showed that L. mariae-josephi bacteria also constituted a new symbiotic lineage distant from those previously defined in the genus Bradyrhizobium. In contrast, the nodC genes of isolates from other Lupinus spp. from the Iberian Peninsula were again clearly related to the B. canariense and B. japonicum bv. genistearum lineages. Speciation of L. mariae-josephi bradyrhizobia may result from the colonization of a singular habitat by their unique legume host