Assessing the accuracy and reproducibility of computer-assisted analysis of (123) I-FP-CIT SPECT using BasGan (V2).

BACKGROUND AND PURPOSE: Over the last two decades (123) I-FP-CIT-SPECT, has been used to discriminate neurodegenerative Parkinsonian syndrome from other diseases. BasGan is a freely available software that assists (123) I-FP-CIT-SPECT evaluation by estimating semiquantitative values for each basal nucleus and compares the results to a database of healthy subjects. The aims of this study were: (1) to assess the accuracy of qualitative analysis and of semiquantitative, BasGan-assisted evaluations of (123) I-FP-CIT-SPECT; (2) to compare the accuracy of both methods when applied to "doubtful" cases; (3) to appreciate the reproducibility of the BasGan-assisted evaluations. MATERIALS AND METHODS: Seventy-eight patients were included in this 4-year follow-up study. The diagnostic cut-off for semiquantitative uptake values of each basal nucleus was determined based on ROC curves analysis. Accuracy scores were calculated for the entire population and for "doubtful" cases. Intra- and interoperator reproducibility was assessed. RESULTS: Accuracy of the software-assisted analyses was high for data from each nucleus. In "doubtful" exams accuracy was higher when using BasGan as opposed to relying solely on visual assessment. Intra- and interoperator reproducibility of the BasGan-assisted evaluations was good to excellent. CONCLUSION: BasGan-assisted evaluations of (123) I-FP-CIT-SPECT were very useful, particularly in "doubtful" cases. Multicenter studies are mandatory before routine use of BasGan.

Molecular genetic study of a metastatic oligodendroglioma.

Extracranial spread of neuroectodermal tumors is an unusual event, most frequently expected from glioblastomas and medulloblastomas. Single cases of metastatic oligodendrogliomas have been described, but no genetic data are reported. Oligodendrogliomas are characterized by distinct genetic alterations, i.e. loss of heterozygosity (LOH) of 1p and 19q; therefore, molecular genetic analysis of metastatic cases is of considerable interest. It may be instrumental in defining the distant tumor as metastatic oligodendroglioma and give clues to the genetic events associated with the highly malignant transformation. We present the case of a patient with multiple bone metastases from a cerebral oligodendroglioma. Oligodendroglioma grade II was the diagnosis both at original and second operation, performed 7 and 1 years before the extracranial dissemination. The extraneural spread presented before the local intracranial recurrence. The patient received procarbazine, lomustine, vincristine chemotherapy and radiotherapy after the second surgery. The computed tomography-guided biopsy of the bone lesions revealed tumor cells positive for GFAP, S-100 and Leu-7 and negative for cytokeratin, LCA and EMA. The genetic analysis of DNA from the original tumor, the bone metastasis and the autoptic brain tumor showed LOH of 1p; heterozygous deletion of CDKN2A/p 16 was detected as additional alteration in the metastasis and in the intracranial tumor at autopsy. TP53, MDM2 and CDKN2A/p14ARF genes were unchanged. Repeated brain surgery and extended survival may have acted as promoter of extraneural dissemination. Loss of CDKN2A most probably played an important role in the malignant progression: its involvement in metastatic potential remains to be clarified. Our data confirm that malignant transformation of oliogodendrogliomas may be undetected by histology and underscore the importance of genetic analysis. Coincidentally with intensive anticancer therapy, chemotherapy included, employed in patients with oligodendroglioma and the ensuing long survival, the frequency of metastatic oliogodendrogliomas may increase.

Keratan sulphate is a marker of differentiation of ramified microglia.

Recently we reported that the keratan sulphate epitope recognised by the monoclonal antibody 5D4 is expressed by a population of ramified microglia in adult rats. As ramified microglia is believed to differentiate from ameboid microglia during postnatal development, we studied the rat brain from birth to 90 postnatal days of life with the monoclonal antibody 5D4. Contrary to all the other microglia markers until now described, keratan sulphate is not expressed by ameboid microglia and by macrophages but appears on the surface of microglia only when the cells are differentiated and show ramified processes. The keratan sulphate positive cells become evident at different times in different central nervous system areas; the first were localised in the pyriform cortex and brainstem from the end of the second postnatal week. These observations suggest that keratan sulphate expression on microglia cells is induced by differentiation and by a resting functional state. Moreover the 5D4 monoclonal antibody showed a strong diffuse positive staining of some cortical, thalamic and white matter areas during the first two postnatal weeks. This staining was transient and it does not seem biologically correlated with the expression of the keratan sulphate on differentiated microglia.

Disappearance of the Vicia villosa-positivity from the perineuronal net containing chondroitin proteoglycan after chondroitinase digestion.

Anti-chondroitin unsulfated proteoglycan (COS-PG) 1B5 monoclonal antibody (MAb) and Vicia villosa agglutinin (VVA) recognize the same neuronal subset. Moreover, when in double immunofluorescence study the sections were digested with chondroitinase ABC (ChABC), a procedure necessary to create the epitope of 1B5 MAb, and incubated with VVA, no VVA positive neurons were detected. This finding suggests that VVA binds terminal N-acetyl-galactosamine present in the glycidic chains of COS-PG or of glycoproteins that form perineuronal molecular aggregates with COS-PG.