Sporadic Central Nervous System Research Articles

Primary dural lymphoma: a comprehensive literature review and report of a case

Primary dural lymphoma (PDL) is a subtype of primary central nervous system (CNS) lymphoma (PCNSL) with only an extra-axial dural location. It accounts for less than 1% of all CNS lymphomas. PDL is a sporadic CNS tumor, and in the preoperative period, because of imaging characteristics, it is usually mimicking a meningioma. Usually, PDL is a low-grade B-cell lymphoma with a relatively good response to surgical resection with or without radiotherapy. Here we reviewed 102 case reports of PDL in the literature. Then, we present the case of our patient with PDL and explain the complexity of our treatment approach.

EASTERN EQUINE ENCEPHALITIS VIRUS INFECTION AND HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN A 5-MONTH-OLD INFANT

Eastern equine encephalitis virus infection is a rare sporadic central nervous system infection transmitted by a mosquito vector. Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease associated with the inability of an overactive immune system to effectively respond to infections. Many viruses are known to trigger primary, as well as secondary, HLH. We report a pediatric case of eastern equine encephalitis virus-associated HLH which caused severe neurologic injury and death.

Aneuploidy in the normal and diseased brain

The brain is remarkable for its complex organization and functions, which have been historically assumed to arise from cells with identical genomes. However, recent studies have shown that the brain is in fact a complex genetic mosaic of aneuploid and euploid cells. The precise function of neural aneuploidy and mosaicism are currently being examined on multiple fronts that include contributions to cellular diversity, cellular signaling and diseases of the central nervous system (CNS). Constitutive aneuploidy in genetic diseases has proven roles in brain dysfunction, as observed in Down syndrome (trisomy 21) and mosaic variegated aneuploidy. The existence of aneuploid cells within normal individuals raises the possibility that these cells might have distinct functions in the normal and diseased brain, the latter contributing to sporadic CNS disorders including cancer. Here we review what is known about neural aneuploidy, and offer speculations on its role in diseases of the brain.

Cyclin D1 Genotype and Expression in Sporadic Hemangioblastomas

Central nervous system (CNS) hemangioblastomas are highly-vascularized tumors occurring in sporadic form or as a manifestation of von Hippel-Lindau disease (VHL). The VHL protein (pVHL) regulates various target genes, one of which is the CCND1 gene, encoding cyclin D1, a protein that plays a critical role in the control of the cell cycle. Overexpression of cyclin D1 is found in many cancers. The CCND1 gene contains a common G --> A polymorphism (870G > A) that enhances alternative splicing of the gene. CCND1 genotype is associated with clinical outcome in a number of cancers although prognostic significance varies with tumor type. In VHL disease, CCND1 genotype has been suggested as a genetic modifier that influences susceptibility to hemangioblastomas. In order to analyze whether CCND1 genotype plays a role in sporadic CNS hemangioblastomas, we investigated CCND1 genotype in tumor tissue of 17 sporadic and also in five VHL-related CNS hemangioblastomas. In addition, in these tumors the extent and localization of cyclin D1 expression was investigated by immunohistochemistry. We found no deviation in CCND1 genotype distribution and allele frequencies from expected values. Also, there was no correlation between age at onset and CCND1 genotype. The expression of cyclin D1 as detected by immunohistochemistry was highly variable within and between tumors, without a clear correlation with CCND1 genotype. We conclude that, whereas variable but sometimes high cyclin D1 expression is a feature of sporadic hemangioblastomas, CCND1 genotype is unlikely to be an important genetic modifier in the oncogenesis of these tumors.

Long-term prognosis of hemangioblastomas of the central nervous system: Clinical and immunohistochemical study in relation to recurrence

The long-term prognosis and immunohistochemical findings for the expression of VEGF (vascular endothelial growth factor), p53 protein, and proliferative potential with MIB-1 were evaluated in six patients with VHL (von Hippel-Lindau) disease and seven patients with sporadic hemangioblastomas in relation to recurrent or new central nervous system (CNS) hemangioblastomas following treatment. Sporadic CNS hemangioblastomas were treated by total removal, and they demonstrated a good long-term prognosis without neurological deficits and no recurrence. However, even if total removal of the CNS hemangioblastomas in patients with VHL disease was performed initially, new lesions, consisting of small multiple hemangioblastomas, recurred in areas remote from the primary region in three of four patients during long-term follow-up. Such newly developed hemangioblastomas in patients with VHL disease could reflect the biological multipotentiality of CNS hemangioblastomas that were not detected during the initial operation. All of the hemangioblastomas displayed extensive overexpression of VEGF protein. The immunohistochemical findings for VEGF protein, p53 protein, and MIB-1 did not differ significantly between the sporadic and VHL disease-associated hemangioblastomas. In conclusion, since patients with VHL disease are at risk of developing new lesions, the management of hemangioblastomas in patients with VHL disease represents a more prolonged and difficult task.

NF2 tumor suppressor gene: a comprehensive and efficient detection of somatic mutations by denaturing HPLC and microarray-CGH.

The NF2 tumor suppressor gene, located in chromosome 22q12, is involved in the development of multiple tumors of the nervous system, either associated with neurofibromatosis 2 or sporadic ones, mainly schwannomas and meningiomas. In order to evaluate the role of the NF2 gene in sporadic central nervous system (CNS) tumors, we analyzed NF2 mutations in 26 specimens: 14 meningiomas, 4 schwannomas, 4 metastases, and 4 other histopathological types of neoplasms. Denaturing high performance liquid chromatography (denaturing HPLC) and comparative genomic hybridization on a DNA microarray (microarray- CGH) were used as scanning methods for small mutations and gross rearrangements respectively. Small mutations were identified in six out of seventeen meningiomas and schwannomas, one mutation was novel. Large deletions were detected in six meningiomas. All mutations were predicted to result in truncated protein or in the absence of a large protein domain. No NF2 mutations were found in other histopathological types of CNS tumors. These results provide additional evidence that mutations in the NF2 gene play an important role in the development of sporadic meningiomas and schwannomas. Denaturing HPLC analysis of small mutations and microarray-CGH of large deletions are complementary, fast, and efficient methods for the detection of mutations in tumor tissues.

Familial Posterior Fossa Brain Tumors of Infancy Secondary to Germline Mutation of the hSNF5 Gene

We have identified a family afflicted over multiple generations with posterior fossa tumors of infancy, including central nervous system (CNS) malignant rhabdoid tumor (a subset of primitive neuroectodermal tumors, or PNET) and choroid plexus carcinoma. Various hereditary tumor syndromes, including Li-Fraumeni syndrome, Gorlin syndrome, and Turcot syndrome, have been linked to increased risk of developing CNS PNETs and choroid plexus tumors. Malignant rhabdoid tumors of the CNS and kidney show loss of heterozygosity at chromosome 22q11. The hSNF5 gene on chromosome 22q11 has recently been identified as a candidate tumor-suppressor gene in sporadic CNS and renal malignant rhabdoid tumors. We describe a family in which both affected and some unaffected family members were found to have a germline splice-site mutation of the hSNF5 gene, leading to exclusion of exon 7 from the mature cDNA and a subsequent frameshift. Tumor tissue shows loss of the wild-type hSNF5 allele, in keeping with a tumor-suppressor gene. These findings suggest that germline mutations in hSNF5 are associated with a novel autosomal dominant syndrome with incomplete penetrance that predisposes to malignant posterior fossa brain tumors in infancy.

Neurotropic Virus Infections in Chicago, 1939-1941. Nine Gases of Lymphocytic Choriomeningitis

SummaryVirus studies were carried out on 75 patients suffering from various sporadic central nervous system infections of unknown etiology. Nine cases of lymphocytic chorio-meningitis proven by virus isolation or detection of specific antibodies are presented. The cases were clinically divisible as follows: (1) encephalomyelitic type, (2) meningeal type, and (3) an “influenzal” type without neurologic signs.,. Negative results were obtained in tests for St. Louis encephalitis and western equine encephalomyelitis.