Cerebrospinal Fluid Hyaluronan and Neurofibromatosis Type 2.

Neurofibromatosis type 2 (NF-2) is associated with mainly three types of recurrent benign tumors restricted to the central nervous system: schwannoma, meningioma and ependymoma. The absence of the protein NF2/Merlin causes an uninterrupted cell proliferation cascade originating from an abnormal interaction between an extracellular mucopolysaccharide, hyaluronan (HA), and schwann cell surface CD44 receptor, which has been identified as one of the central causative factors for schwannoma. Most tumors in NF-2 have a predilection to originate from either arachnoid cap cells or schwann cells of the cisternal portion of nerve rootlets that share a continuous exposure to cerebrospinal fluid (CSF). We hypothesize that the CSF HA may play a role in tumorigenesis in NF-2. In a prospective analysis over a period of one year, the levels of medium to low molecular weight HA (LMW HA) was estimated in the CSF of three subjects with central schwannomas and compared against that of age-sex matched controls, using Cetyltrimethylammonium bromide coupled turbidimetric assay and found to be seventeen-fold higher in the schwannoma subjects compared to the controls. HA was observed to be actively secreted by cultured schwannoma cells isolated from tumor tissues commensurate with their proliferation rate. On cell viability index analysis to compare the cell proliferation of astrocytoma cells with LMW HA vs. oligomeric HA (OHA), we found a decrease in cell proliferation of up to 30% with OHA. The study provides initial evidence that CSF HA may have a central role in the tumorigenesis of schwannoma in NF-2.

Genotype-phenotype analysis of von Hippel-Lindau syndrome in fifteen Indian families.

The general prevalence of the familial multi-organ tumor disorder, von Hippel-Lindau syndrome (VHL), was estimated to be 1 in 25-40,000 in western studies two decades back. Few studies were done in Indian sub-continent, amidst a surge in clinical reports on VHL specific manifestations. The syndrome is correlated with mutations of the gene VHL (located in Chr 3p25.3). We aimed to conduct a prospective case series describing phenotypic and genotypic characteristics in Indian population. The VHL-specific clinical and radiological features were collected from patients and family members. Genotypic changes such as deletion/duplication or point mutation in the VHL locus were identified using sequencing and MLPA. Thirty-one subjects, from fifteen families with diagnosed VHL, were included in the study. Multicystic pancreas was found in 71% (22/31), CNS hemangioblastoma in 68% (21/31), renal cell carcinoma and retinal angiomas in 23% (7/31) each, pheochromocytoma in 9.7% (3/31) of the population and endolymphatic sac tumor in one subject. Four families (9 subjects) had full length deletion of VHL, three families (4 subjects) had a deletion of exon 3, eight families (18 subjects) had different exonic, splice-site and intronic point mutations and one subject had a de novo in-frame indel in exon 1. Multicystic pancreas and CNS hemangioblastomas were the most common manifestations in our population. The phenotypic expression patterns in terms of tumorigenesis, tissue tropism and penetrance in comparison to the genotypic features were found to be different from previous correlative studies.

Temporal fossa arachnoid cyst presenting with bilateral subdural hematoma following trauma: two case reports.

INTRODUCTION: Intracranial arachnoid cysts are considered to be congenital malformations with a predilection for the temporal fossa. They are often asymptomatic but can sometimes be symptomatic due to enlargement or hemorrhage. There are multiple case reports of arachnoid cysts becoming symptomatic with hemorrhagic complications following head trauma. In such cases, the bleeding is often confined to the side ipsilateral to the arachnoid cyst. Occurrence of contralateral subdural hematomas in patients with temporal fossa arachnoid cysts has rarely been observed and is reported less frequently in the medical literature. CASE PRESENTATION: We report two cases of people (a 23-year-old man and a 41-year-old man) with temporal fossa arachnoid cysts complicated by a subdural hematoma following head injury. Both patients developed a subdural hematoma contralateral to the side of a temporal fossa arachnoid cyst. It is likely that lack of adequate intracranial cushioning in the presence of an intracranial arachnoid cyst may result in injury not only to ipsilateral but also to contralateral bridging veins, following head trauma. CONCLUSION: It is important to identify and report such rare complications with intracranial arachnoid cysts, so that asymptomatic patients with an intracranial arachnoid cyst can be counseled about such possibilities following head trauma.