M.P.W.A. Houben

BACKGROUND AND PURPOSE: Recovery of oculomotor (cranial nerve [CN] III) palsy after surgery of posterior communicating artery (PcomA) aneurysms has been well documented, but recovery after coiling is poorly understood. In this study, we report the recovery after coiling of PcomA aneurysm-induced CN III palsy in 21 patients at follow-up of 1 to 7 years. MATERIALS AND METHODS: Of 135 patients with a PcomA aneurysm treated with coils between January 1997 and December 2003, there were 21 patients with initial CN III dysfunction who were selected and reevaluated. There were 2 men and 19 women with a mean age of 54.9 years. In 17 patients, CN III palsy was associated with subarachnoid hemorrhage (SAH). Timing of treatment after onset of symptoms was 1 to 3 days in 5 patients, 4 to 14 days in 13, and more than 14 days in 3. Mean size of the aneurysm was 9 mm. Initial CN III palsy was complete in 15 patients and partial in 6. Mean follow-up after coiling was 3.7 years (range, 1-7 years). RESULTS: Of 15 patients with initial complete CN III palsy, recovery was complete in 3 and partial in 10. In 2 patients, complete CN III palsy was unchanged. Of 6 patients with initial partial CN III palsy, recovery was complete in 5 and partial in 1. Initial partial CN III palsy was the only predictor of complete recovery at follow-up. CONCLUSION: PcomA aneurysm-induced CN III palsy improves or cures after coiling in most patients. Complete recovery is more likely with initial partial dysfunction of the nerve.

Rhabdoid tumour predisposition syndrome (RTPS) is a rare syndrome caused by inheritance of a mutated INI1 gene for which only two multigeneration families have been reported. To further characterise the genotype and phenotype of RTPS, we present a third family in which at least three cousins developed an atypical teratoid/rhabdoid tumour (AT/RT) at a young age. Two of these patients showed unusual long survival, and one of these developed an intracranial meningioma and a myoepithelioma of the lip in adulthood. Mutation analysis of INI1 revealed a germline G>A mutation in the donor splice site of exon 4 (c.500+1G>A) in the patients and in their unaffected fathers. This mutation prevents normal splicing and concomitantly generates a stop codon, resulting in nonsense-mediated mRNA decay. Biallelic inactivation of INI1 in the tumours, except for the meningioma, was confirmed by absence of nuclear INI1-protein staining. The myoepithelioma of one of the patients carried an identical somatic rearrangement in the NF2 gene as the AT/RT, indicating that both tumours originated from a common precursor cell. In conclusion, this study demonstrates for the first time transmission of a germline INI1-mutation in a RTPS family via nonpenetrant males, long-term survival of two members of this family with an AT/RT, and involvement of INI1 in the pathogenesis of myoepithelioma.

With traditional epidemiologic research designs, few environmental risk factors for malignant brain tumors have been revealed, and although syndromes exist where brain tumors occur frequently, these explain a small proportion of the overall incidence. In a similar way, the search for genetic causes has been thwarted by the rarity of families with multiple affected relatives, inhibiting genetic linkage, sib-pair, or even population-based association studies. Molecular genetic studies generally involve searching for candidate proto-oncogenes and tumor suppressor genes by comparing DNA from tumor material with constitutional (germline) DNA. However, it remains difficult to distinguish causative genetic aberrations from chaotic neoplastic processes, and studies so far have not yielded consistent information on the location of such causative genetic lesions. The current literature covering the molecular genetics of glioma is discussed herein and alternative approaches that can be used to identify genetic causes of glioma described.

Time trends in the incidence of glioma may reflect changes in the prevalence of environmental risk factors for glioma. We therefore investigated trends in the incidence of childhood and adult glioma in The Netherlands from 1989 to 2003. We used population-based incidence data from the Netherlands Cancer Registry. We calculated European standardised incidence rates for glioma, and stratified for age, gender and glioma subgroups. Changes in the incidence were estimated by calculating the Estimated Annual Percentage Change. Similar to other countries, the overall incidence of glioma was fairly stable in The Netherlands during the period 1989 to 2003, for both children and adults. In adult astrocytic glioma, a significantly increasing incidence of high-grade astrocytoma was balanced by simultaneous decreases of low-grade astrocytoma, astrocytoma with unknown malignancy grade and glioma of uncertain histology. Most of these time trends can be explained by improving detection and diagnostic precision. Stable incidence rates of adult and childhood glioma suggest that no major changes in environmental risk factors have occurred, which influenced the incidence of glioma in the studied period.