The collection and processing of human brain tissue for research.

To further understand the neuroanatomy, neurochemistry and neuropathology of the normal and diseased human brain, it is essential to have access to human brain tissue where the biological and chemical nature of the tissue is optimally preserved. We have established a human brain bank where brain tissue is optimally processed and stored in order to provide a resource to facilitate neuroscience research of the human brain in health and disease. A donor programme has been established in consultation with the community to provide for the post-mortem donation of brain tissue to the brain bank. We are using this resource of human brain tissue to further investigate the basis of normal neuronal functioning in the human brain as well as the mechanisms of neuronal dysfunction and degeneration in neurodegenerative diseases. We have established a protocol for the preservation of post-mortem adult human brain tissue firstly by snap-freezing unfixed brain tissue and secondly by chemical fixation and then storage of this tissue at -80 degrees C in a human brain bank. Several research techniques such as receptor autoradiography, DNA and RNA analysis, are carried out on the unfixed tissue and immunohistochemical and histological analysis is carried out on the fixed human tissue. Comparison of tissue from normal control cases and from cases with neurodegenerative disorders is carried out in order to document the changes that occur in the brain in these disorders and to further investigate the underlying pathogenesis of these devastating neurological diseases.

Leptomeningeal infiltration as the presenting manifestation of a malignant glioma.

Infiltration of the leptomeninges by a malignant glioma typically occurs with recurrent supratentorial tumors, but patients may present with leptomeningeal gliomatosis before the primary tumor is diagnosed. This report describes two patients who presented with headache and signs of multifocal neurological disease. One of the patients had neurofibromatosis type I. In both patients the cerebrospinal fluid examination showed a mild pleocytosis, but malignant cells were not detected. The diagnosis of leptomeningeal gliomatosis was not confirmed until autopsy, but in retrospect imaging showed a small, asymptomatic primary tumor in both patients. Leptomeningeal gliomatosis should be considered in the differential diagnosis of chronic meningitis, if the patient is afebrile and if there are multifocal neurological signs, even when a primary tumor is not obvious.

Establishment of primary human meningiomas as subcutaneous xenografts in mice.

Meningiomas are the most frequently occurring benign central nervous system tumours. We determined whether a subcutaneous animal model of meningioma was feasible by implanting fresh meningioma tissue from six patients into 60 athymic (nude) mice, either as tissue blocks (38 mice) or as cell suspensions (22 mice). The tumour take-rates were 74% (block) and 50% (suspension), and the xenografts retained the original tumour grade and subtype morphology by light microscopy. Comparison of cell proliferation markers in xenografts and original tumours gave similar immunohistochemical score rates for Ki-67, but not for PCNA. With the exception of one atypical tumour surgical specimen, all tumours lacked p53 immunopositivity. Transmission electron microscopy of sections of tumour xenografts revealed ultrastructural features, including desmosomes and desmosome-like structures, characteristic of well-differentiated meningiomas. The xenografts grew progressively with a volume increase of more than 10-fold over 6-11 months and an apparent doubling time of 16 weeks. This study demonstrates the utility of the subcutaneous meningioma xenograft as a model for further biological and therapeutic studies.

Childhood cancer in New Zealand 1990 to 1993.

An epidemiological study of childhood cancer in New Zealand identified 409 children aged 0 to 14 years with malignant neoplasms newly diagnosed between 1990 and 1993 inclusive. The original microscopic material on which the diagnoses were based was reviewed in 398 cases and the neoplasms were allocated into the 12 major groupings and 48 further subcategories of the International Classification of Childhood Cancer (ICCC). The pathology reviewers agreed with group and subcategory classification of the confirmed cancers in all but one case of acute leukemia and three cancers of the central nervous system. Changes were also made in the FAB classification of three cases of acute non-lymphocytic leukemia and in the further subcategorisation of three Hodgkin's lymphomas and ten astrocytomas. The results show a high level of diagnostic accuracy for confirmed childhood neoplasms in that time period. Nine of 15 cases of malignant melanoma notified to the study were not confirmed for various reasons, which included a change in the pathological diagnosis in four cases. Compared with Victoria (Australia), New Zealand has a high incidence rate of lymphomas in boys and an unusual female preponderance of Wilms' tumor cases.

Loss of A1 adenosine receptors in human temporal lobe epilepsy.

Using quantitative receptor autoradiographic methods we have examined A1 adenosine receptors, adenosine uptake sites, benzodiazepine receptors, NMDA, AMPA, and kainic acid receptors in temporal lobes removed from patients suffering from complex partial seizures and in normal control post-mortem temporal cortex. Binding to A1 adenosine receptors and NMDA receptors was reduced in epileptic temporal cortex, while the other neurochemical parameters were unchanged. The reason for this A1 receptor loss is unclear as it occurred in both idiopathic and symptomatic cases and thus may be a consequence rather than an initial cause of seizures. However, because adenosine is a powerful anticonvulsant substance, loss of anticonvulsant A1 receptors may contribute to the human epileptic condition. It is also possible that the observed differences in A1 binding are due to autopsy vs. biopsy changes in the levels of A1 adenosine receptors.

Leptomeningeal and brain biopsy in chronic meningitis.

BACKGROUND: The cause is not found in one third of patients presenting with chronic meningitis. Biopsy of the leptomeninges and brain is often recommended in these patients, but the value of a biopsy is uncertain. AIMS: To review the results of leptomeningeal and brain biopsies and their effect on diagnosis and management in patients with chronic meningitis, if the diagnosis was uncertain after clinical assessment, lumbar puncture and radiological investigations. METHODS: The clinical features, investigations and the results of leptomeningeal and brain biopsies were reviewed retrospectively in 25 patients presenting with chronic meningitis between 1967 and 1990. RESULTS: The biopsy identified the cause of the chronic meningitis in five patients (neoplastic meningitis in three, tuberculous meningitis in one, granulomatous angiitis in one). In 17 patients the biopsy was abnormal but it did not identify the cause (non-granulomatous lymphocytic meningitis in eight, granulomatous meningitis in two, non-specific abnormalities in seven). In two patients the biopsy was normal and in one patient the tissue was used only for culture. The results of the biopsy led to a beneficial change in treatment in two patients but did not influence management in the other patients. CONCLUSIONS: A leptomeningeal and brain biopsy was of limited practical value in diagnosis and management in most patients with chronic meningitis.

A fatal case of ovarian hyperstimulation syndrome with cerebral infarction.

The ovarian hyperstimulation syndrome (OHSS) as a cause of death in infertile patients involved in in vitro fertilization is an extremely rare phenomenon. Reported here are the clinical and pathological feature of just such a case together with a discussion of the pathophysiology thought to be involved.

Diagnostic markers demonstrating successful culture of human meningioma cells.

The light microscopic and ultrastructural features of cultured meningioma cells were compared with those of surgically resected specimens. Meningioma cells normally show variable degrees of epithelial or mesenchymal differentiation. In cultured cells, well formed psammoma bodies and whorls were seen by light microscopy and specialised intercellular junctions were observed by electron microscopy. Cytogenetic analysis was also shown to be a useful diagnostic marker to differentiate cultured meningioma from contaminant proliferating fibroblastic and endothelial cells. These methods have demonstrated that the cells cultured from operative samples were predominantly meningioma cells. The ability to reproducibly cultivate populations of meningioma cells should facilitate in vitro assessment of potential adjunctive treatment modalities.

Brain biopsy in the management of focal encephalitis.

The value of a brain biopsy in diagnosis and management of suspected herpes simplex encephalitis was studied in 29 patients (16 prospectively and 13 retrospectively). The biopsy showed herpes simplex encephalitis in eight, culture-negative encephalitis in 14, and was normal in three patients. It provided an alternative diagnosis in four patients, for two of whom curative treatment was available. The biopsy was complicated by a fatal intracranial haemorrhage in one patient. The low yield of alternative diagnoses suggests that a brain biopsy is not justified in the routine investigation of focal encephalitis.

The acromegalic rosary.

Palpable enlargement of the costochondral junctions on the anterolateral chest wall was detected in 26 of 27 patients with acromegaly. In a further study three doctors wearing eyemasks examined a further 13 acromegalic patients and 12 control subjects; costochondral enlargement was detected with a sensitivity of 77% and specificity of 86%. It was not found in normal subjects in the absence of previous chest injury. The presence and extent of costochondral enlargement was unrelated to the duration of active or cured acromegaly, the initial or present growth hormone concentrations, or other clinical features of growth hormone excess. Costochondral enlargement is a common clinical sign in acromegaly and can serve as a biological marker of previous or current growth hormone excess.

Adrenoleukodystrophy: manifestations of a protean disorder: report of a recently identified kindred.

Adrenoleukodystrophy is an inherited metabolic disorder resulting in accumulation of fatty acids in body tissues, principally the central nervous system. We report a recently identified kindred with this disease to highlight the varied clinical manifestations and recent advances in diagnosis and treatment.

An antineuronal autoantibody in paraneoplastic opsoclonus.

Sera from 7 patients with paraneoplastic opsoclonus were examined for antineuronal autoantibodies. An antibody against neuronal nuclei was found in serum from a patient with breast cancer, opsoclonus, and ataxia. This antibody recognized 53- to 61-kDa and 79- to 84-kDa antigens in immunoblots of neurons. Antineuronal antibodies were not found in other patients with paraneoplastic opsoclonus.

Unusual scalp recorded somatosensory evoked potentials after removal of a large intraventricular meningioma.

Very unusual scalp recorded SEPs were seen in a case after removal of a large intraventricular meningioma. One day before death (ten days after surgery) when the patient was moribund, SEPs from the clinically and radiologically affected hemisphere in which a hematoma and thalamic infarct were found, had a normal latency and were decreased in amplitude. SEPs from the clinically and radiologically nonaffected hemisphere, where only minimal findings were seen, had an abnormally short latency (16.9 msec) and the CCT was only 3.1 msec. We do not offer any logical explanation of these unusual SEP findings from both hemispheres shortly before death.

Opsoclonus, myoclonus, ataxia, and encephalopathy in adults with cancer: a distinct paraneoplastic syndrome.

The clinical and pathological findings in 4 adults with cancer and opsoclonus were compared with those of 15 other patients described elsewhere. The clinical syndrome of paraneoplastic opsoclonus is characterized by the acute onset of opsoclonus and truncal ataxia, often accompanied by encephalopathy, myoclonus and a cerebrospinal fluid pleocytosis. Unlike most other paraneoplastic syndromes, the course is often remitting and relapsing. Neuropathological examination in 3 of our patients showed lymphocytic cuffing of occasional blood vessels throughout the central nervous system, associated with a mild, diffuse proliferation of microglia in 1 patient. Apart from a mild, patchy loss of Purkinje cells in 1 patient, there was no loss of neurons from the cerebellum, brainstem, cerebral hemispheres, or spinal cord. These patients differ from those with the more common paraneoplastic cerebellar degeneration by the predominance of truncal over limb ataxia, the presence of myoclonus, the absence of severe dysarthria, a tendency for remission, and the preservation of Purkinje cells.

Transition from alpha to theta pattern coma in fatal cerebral anoxia.

A transition of alpha to theta pattern coma is documented in a case of fatal cerebral anoxia after a cardiac arrest. The patient was a 35-year-old woman who suffered a cardiac arrest due to myocardial ischaemia and ventricular tachycardia. Altogether 6 EEGs showing progressive deterioration were performed during the 11 days of survival. There was histopathological evidence of extensive ischaemic damage involving cerebral and cerebellar cortex, basal ganglia and brainstem structures. Although closed chest cardiopulmonary resuscitation was begun with minimal delay after cardiac arrest, the outcome may reflect the increasingly documented failure of this type of resuscitation to provide adequate organ perfusion during cardiac arrest.

Deaths from trauma in Auckland: a one year study.

We report a one year prospective study of all deaths from trauma in the Auckland region. Data was collected on the circumstances of death from coroner's, police and hospital records. All cases had autopsies and the injuries were scored using the abbreviated injury scale (AIS) system. The group of 236 had a median age of 27 years and 73% were under the age of 45. Seventy-two percent were male. Blunt trauma, predominantly the result of road crashes, accounted for 89% of the fatalities. Most deaths occurred at the site of injury and only 37% survived to reach hospital. Cases were audited if death occurred without a critical or unsurvivable injury. Thirteen cases were considered to be potentially salvageable if medical treatment had been optimal. The implications for the organisation of prehospital and inhospital trauma care are discussed.

"Theta pattern coma" occurring in younger adults.

Since our previous report, where "theta pattern coma" was described in 2 elderly patients as an EEG pattern with a grave prognosis, we have had the opportunity to see another 9 affected patients. In this article, 3 men with a mean age of 36 years who died after cardiorespiratory arrest presented a "theta coma pattern." The EEG activity was initially reactive to and attenuated by external stimulation in 2, but prior to death the pattern became arreactive. This article shows that "theta pattern coma" is not an age related phenomenon as previously considered. So far, 11 patients with this type of EEG abnormality have been seen in our department; all have died, and all were over 30 years of age. An expanded definition of "theta pattern coma" is given in the discussion. The pathophysiological mechanisms involved in generation of this abnormality are not known. This abnormality, when seen in the unconscious patient, should be classified as a grade 4 abnormality on the EEG coma scale and should be differentiated from rather diffuse theta activity in coma. The prognostic significance of "theta pattern coma" appears to be similar to that of "alpha pattern coma."

A familial syndrome of cardiac myxomas, myxoid neurofibromata, cutaneous pigmented lesions, and endocrine abnormalities.

A family syndrome of cardiac myxomas, myxoid neurofibromata, cutaneous pigmented lesions, and endocrine abnormalities is described. Three cases from a family of four are presented. All had cutaneous pigmented lesions. The mother had left and right atrial myxomata, her daughter a left ventricular myxoma, subcutaneous myxoid neurofibromata, and mammary fibroadenosis, and her son has no evidence of cardiac myxoma. Elevated circulating levels of insulin-like growth factors in the one family member tested raises the possibility of abnormal stimulation of somatic growth and may be linked to development of soft tissue neoplasms in these patients.