Olfactory neuroblastoma with spinal metastasis--a problem in diagnosis.

The olfactory neuroblastoma or esthesioneuroblastoma is a rare neuroectodermal tumor originating from the olfactory neuroepithelium, which can metastasis via cerebrospinal fluid pathways. In the present case of an extensive nasal malignancy with cervical lymph node metastases in a 75-year old woman, its difficult histology alternatively led to a diagnosis of anaplastic carcinoma and non-Hodgkin lymphoma. The patient died from complications following spread of the tumor to the spinal cord and cauda equina. Review of the literature shows that this tumor is notorious for its chameleonic character. In view of its clearly demonstrated malignancy an aggressive therapeutic approach is advocated.

Early transient accumulation of methotrexate in the cerebrospinal fluid of rabbits after treatment with methotrexate and roentgen rays.

Concomitant application of intrathecal methotrexate (MTX) and cranial irradiation has been described as being able to cause brain abnormalities in patients with leukemia. In the investigation presented, rabbits were treated once weekly for 6 weeks with intraventricular MTX and irradiation. Cerebrospinal fluid (CSF) sampled at various time points after each treatment contained for the samples obtained 4 hours after treatment increasing amounts of MTX. This indicated a retardation in MTX clearance from the CSF. Such a retardation might contribute to the generation of brain abnormalities, although no data have as yet been obtained to prove this suggestion.

Progressive poliodystrophy (Alpers' disease) with a defect in cytochrome aa3 in muscle: a report of two unrelated patients.

We present two unrelated patients, a boy and a girl, with a progressive neurologic disorder, characterized by psychomotor retardation, seizures and paresis, the illness being exacerbated during stressful periods. Lactate levels in serum and cerebrospinal fluid were elevated in both patients. Histopathologic studies of muscle tissue revealed mitochondrial abnormalities in the boy; in the girl, slight neuronal degeneration was observed. A cerebral biopsy in the girl showed abnormalities compatible with progressive poliodystrophy. Autopsy in the boy demonstrated progressive poliodystrophy. Biochemical studies in muscle tissue showed a defect of cytochrome aa3 in both patients, connected with a defect of cytochrome b in the girl. The association of defective pyruvate metabolism and progressive poliodystrophy is discussed.

Experiences with recurring ventricular catheter obstructions.

Seven cases are presented of recurrent ventricular catheter obstruction, an infrequent but serious problem in the management of hydrocephalus. Plugging of the catheter was caused by detritus rather than by choroid plexus. A retrospective analysis of 214 shunt revisions indicated that obstruction both by detritus and by choroid plexus were incidental phenomena in the great majority of the cases - the former type occurring mainly within the first month, the latter between 3 and 6 months after operation. It is suggested that the ultimate cause of recurrent catheter obstruction by detritus may be destruction or ablation of the ependymal lining of the ventricles (e.g. by an inflammatory process), which easily provides debris to the catheter. In 4 of the cases insertion of the catheter into the opposite ventricle prevented further recurrence, when reinsertion into the same ventricle had been ineffective. In one case, with scarcely dilated ventricles, external decompression was helpful. In patients with compartmentalisation of the ventricles (substantiated in one of our patients) one might consider removal of the septa via craniotomy before the insertion of the catheter.

Iatrogenic damage to the central nervous system in malignant systemic disease.

The various ways in which the central nervous system can become affected in the course of malignant systemic disease are discussed, with particular emphasis on iatrogenic damage. Examples of presumably iatrogenic damage are presented. It is suggested that minor alterations may be much more frequent than is assumed at present. The need for systematic investigation is stressed--with a view on assessing the frequency of such damage and on unravelling the aetiology and pathogenesis of the lesions.

A peculiar brain scan pattern in necrotizing leukoencephalopathy after treatment for CNS-leukaemia.

Two patients with CNS-leukaemia who developed a leukoencephalopathy after cranial irradiation and methotrexate administration are described. Conventional brain scanning with 99m TC-pertechnetate showed a peculiar pattern which suggested the presence of radio-activity within enlarged ventricles, but were later interpreted as accumulation in the periventricular white matter. The brainscan pattern correlated well with the neuropathological findings in the case where autopsy was performed. This brain scan pattern is for unknown reasons only rarely mentioned in literature. It seems a useful tool in diagnostic procedures in similar patients.

Intracranial malignant lymphomas. A morphologic and immunocytologic study of twenty cases.

Fifteen primary intracranial reticulum cell sarcomas and five cases with an additional solitary extracranial tumor mass have been studied. For comparison, seven extracranial malignant non-Hodgkin lymphomas and normal lymphoid tissue were included. The methods used on formalin-fixed paraffin-embedded tissue sections were an immunoperoxidase technique for the demonstration of intracellular immunoglobulins, microglial staining, Gomori's reticulin, methylgreen-pyronin, Giemsa, diastase resistant PAS, Mallory's PTAH and H&E. Electron microscopy was performed in one primary brain tumor. According to histopathologic criteria all tumors could be classified as malignant non-Hodgkin lymphomas, predominantly of the pleomorphic immunocytic or of the immunoblastic type; follicular lymphomas were notably absent. In all cases intracellular immunoglobulins were demonstrable in tumor cells and in a majority of the tumors these were monoclonal. Thus, all malignant lymphomas proved to be of B cell origin with demonstrable cytoplasmic immunoglobulin production. Based on the microglial staining more than half of the malignant lymphomas could also be classified as microgliomas. As a comparable staining was present in non-Hodgkin lymphomas outside the CNS, microglioma characteristics are not associated with intracranial growth.

Glial fibrillary acidic protein in human gliomas.

The presence of GFA protein, an astrocyte specific antigen, was investigated in surgical biopsies of ninety-five gliomas using an immunoperoxidase detection method. In some cases electron microscopy was added and also in one tumour immunoelectron microscopy. The results were correlated with the histological classification and grading of the tumours. In astrocytomas, the number of GFA positive cells decreased with increasing malignancy. Some malignant oligodendrogliomas surprisingly showed GFA in oligodendroglial and gemistocytic tumour cells. Thus, transition from oligodendroglial into astrocytic tumour cells seems to occur. In the mixed astrocytoma/oligodendrogliomas, theoli godendroglioma areas were negative. Subependymomas were strongly GFA positive, whereas ependymomas and medulloblastomas were negative. The presence or absence of GFA seems to contribute a 'hard' criterion for classifying gliomas and may be helpful in grading them according to the degree of malignancy.

Cerebral metastasis without known primary tumour: a retrospective study.

A retrospective study was made of 19 patients who underwent operation for an intracerebral metastasis of an unknown primary tumour. Most patients survived for a few months only, with 2 remarkable ecceptions. In only 8 of them, the primary tumour became manifest in the further course of the illness.

Temporary cell cycle arrest in neural and extraneural developing rat tissues after exposure to methyl--and ethylnitrosourea.

8 days old rats were exposed to 20 or 100 mg/kg b.w. of either Methylnitrosourea (MNU) or Ethylnitrosourea (ENU), followed by injection of 10 muCi/g b.w. of (3H-methyl)-Thymidine. After a 100 mg dose of MNU or ENU in both neural and extraneural tissues a total inhibition of S-phase radioactivity is observed that lasts longer for MNU than for ENU. Moreover reappearance of S-phase cells in the neural tissues is later (36-48 h) than in the extraneural tissues (24-36 h) for both drugs. In both neural and extraneural tissues reappearance of S-phase cells is consistently found to occur about 12 h earlier than recurrence of M-phase cells. After a 20 mg dose of MNU or ENU in both neural and extraneural tissues a clear decrease in S-phase radioactivity is found after a 6 h' interval only. There are only slight differences between the various tissues and drugs. In developing rat tissues there is obviously a trend for both mitotic activity and S-phase radioactivity to decrease with increasing single doses of MNU or ENU. Our results point to an arrest in or before entering the S-phase of the cells involved. The more pronounced cytotoxic activity of MNU as compared to ENU is discussed. Recurrence of DNA synthesis and re-entrance of damaged cells into their cycle prior to the elimination of altered bases from DNA might be of importance for the problem of oncogenesis.

Dark neurons: a significant artifact: the influence of the maturational state of neurons on the occurrence of the phenomenon.

In cerebella of young rats, killed by decapitation, dark Purkinje cells were readily observed in animals from 16 days of age onward. In younger animals (from 0-12 days of age) these dark neurons were never observed. The author agrees with Cammermeyer and others that dark neurons are an avoidable artifact. The findings presented suggest, however, that the possibility of the occurrence of this type of artifact depends on the maturational state of the neurons concerned.

Studies on ectopic granule cells in the cerebellar cortex. III. An investigation into the restoration of the external granular layer after partial destruction.

In order to strengthen a hypothesis concerning the occurrence of ectopic granule cells, one of the assumptions made was tested systematically. The reaction of the EGL to partial destruction by various single doses by hydroxyurea at various ages was followed. Under all conditions examined, re-population of the EGL takes place--rapidly after lower doses, slowly after high doses of HU. The phenomena observed are discussed with a view on the hypothesis mentioned. Re-population is beneficial, but may itself be a major pathogenetic factor in certain developmental malformations by upsetting the "time-schedule". The results are also of potential interest for an analysis of the regulation of normal cerebellar morphogenesis.