Shunting effects in patients with idiopathic normal pressure hydrocephalus; correlation with cerebral and leptomeningeal biopsy findings.

Normal Pressure Hydrocephalus (NPH) is a potentially treatable syndrome with abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of the subarachnoid space have been suggested as one of the patho-anatomical substrates. However, other types of adult onset dementia, predominantly Alzheimer's disease and Vascular Dementia, may mimic the clinical NPH characteristics. The purpose of the present study was to correlate cerebral parenchymal and leptomeningeal biopsy findings to the clinical outcome after CSF shunting in a prospective group of idiopathic NPH (INPH) patients. The study comprises 27 patients with INPH, diagnosed and shunted according to generally accepted clinical, imaging and hydrodynamic criteria. In all patients a frontal leptomeningeal and brain biopsy was obtained prior to the shunt insertion. Degenerative cerebral changes, most often Alzheimer (6 cases) or vascular changes (7 cases) were described in 14 out of 27 biopsies. Arachnoid fibrosis was found in 9 of the 18 biopsies containing arachnoid tissue. Overall, nine patients (33%) improved, of whom 6 presented Alzheimer or vascular changes in their biopsies. No correlation was found between clinical outcome and the presence or absence of degenerative cerebral changes and/or arachnoid fibrosis. However, a tendency towards higher improvement rates was noted in the subgroups presenting degenerative cerebral changes or arachnoid fibrosis. The results suggest that no constant morphological element exists in the syndrome of INPH. Various aetiologies may be involved in the pathogenesis and possibly in some cases co-existing: Patients may also improve by shunting despite the presence of degenerative cerebral parenchymal changes.

Epidemiology and prognosis in children treated for intracranial tumours in Denmark 1960-1984.

A total of 911 Danish children under 15 years of age were treated for an intracranial tumour in the 25-five year period 1960-1984. All cases were followed up to the end of 1994 or to emigration or death if one of these came sooner. The mean annual incidence was 32.5 per million children with a slight increase over the 25 years. The male/female ratio was 1.15 and close to the M/F ratio for the entire Danish population of children. Of the tumours, 46% were located in the supratentorial and 54% in the infratentorial compartment, and 94% were verified histologically. In order of frequency the most common types were astrocytomas (all grades, 35%), medulloblastomas (20%), ependymomas (14%), and craniopharyngiomas (5%). Total removal of the tumour was performed in 277 and partial removal, including biopsy, in 490 children. In 57 patients a shunt operation only was performed, and 87 children did not have an operation or died before the correct diagnosis was established. Radiotherapy was administered in 55%. The outcome depended on extent of removal, radiation, location and histology of the tumour. Most (784 or 86%) of the children survived more than 1 month after diagnosis or operation, and 353 children (39% of the whole series, 47% of those alive more than 1 month after diagnosis) were alive at follow-up. Of the survivors 29% had a tumour in the supratentorial midline, 26% one in the lateral part of the supratentorial area, 31% a cerebellar tumour and 13% a IV ventricle tumour. It was possible for 66% of the survivors with supratentorial and 90% of those with infratentorial tumours to lead a normal life. The long-term prognosis was especially good for children with cerebellar and supratentorial astrocytomas and optic chiasma tumours. Children with juvenile cerebellar astrocytoma had the best prognosis: 90% were alive at the end of the follow-up period, as against 20% of those with medulloblastoma and 6% of those with glioblastoma. A comparison of the data from the present series and from a similar Danish series of intracranial tumours in 533 children seen in the years 1935-1959 shows no significant differences in location or histology, a slight increase in annual incidence, and improved survival rates during the 50 years in question.

Frontal brain and leptomeningeal biopsy specimens correlated with cerebrospinal fluid outflow resistance and B-wave activity in patients suspected of normal-pressure hydrocephalus.

OBJECTIVE: Normal-pressure hydrocephalus (NPH) is a potentially treatable syndrome with abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of the subarachnoid space has been suggested as the pathoanatomic basis. The purpose of the present study was to investigate whether meningeal fibrosis causes increased resistance to cerebrospinal fluid outflow (R(out)) and/or increased B-wave activity and whether pathological changes in the brain parenchyma after brain compliance, causing increased B-wave activity. METHODS: The study involved a group of 38 consecutively studied patients with clinical and radiological evidence of idiopathic NPH, for whom a frontal brain biopsy was obtained. For 29 patients, hydrodynamic criteria of NPH were fulfilled and a ventriculoperitoneal shunt was performed. RESULTS: Meningeal fibrosis was found in 12 of 25 biopsies containing arachnoid tissue, but no correlation with R(out) or B-waves was found. Pathological parenchymal changes, most often Alzheimer's disease (10 cases) or vascular changes (10 cases), were found in 21 biopsies, but no correlation with B-waves or R(out) was found. CONCLUSION: The results suggest that leptomeningeal fibrosis is not the only pathoanatomic basis of increased R(out) and/or B-wave activity in patients with NPH and that various degenerative changes in the parenchyma may be responsible for the altered cerebrospinal fluid dynamics characteristic of NPH.

Prognostic factors in oligodendrogliomas.

An outcome analysis was performed on 96 patients with pure cerebral oligodendrogliomas operated in the 30-year period 1962 to 1991. The most important predictive prognostic factors were youth and no neurological deficit, demonstrated as a median survival for the group younger than 20 years of 17.5 years and for the group older than 60 years of 13 months. The group without neurological deficits had a 5-years survival of 43 per cent while the group with deficits had a 5-years survival of 5 per cent. The 5-years survival for oligodendroglioma of grade II was 46 per cent and for grade III 10 per cent. We found no effect of radiotherapy on survival, neither in the whole material or in any subgroup.

Heterogeneous cerebral glucose metabolism in normal pressure hydrocephalus.

The regional cerebral metabolic rate for glucose (rCMRglu) has never been investigated in large consecutive groups of patients with normal pressure hydrocephalus (NPH), a potentially treatable form of dementia with an unpredictable outcome after shunt surgery. Using PET and 18F-2-fluorodeoxyglucose, rCMRglu was studied in 18 patients who fulfilled hydrodynamic criteria for NPH and in whom a biopsy of the frontal cortex was obtained. When compared with an age matched group of 11 healthy subjects, the patients with NPH showed a significant rCMRglu reduction in all cortical and subcortical regions of interest. Individual metabolic patterns, however, disclosed a large topographical heterogeneity. Furthermore, histopathological examination identified Alzheimer's disease or cerebrovascular disease in six cases, and no parenchymal disease or non-specific degenerative processes in the remaining 12. After separating the patients according to the histological diagnosis, the rCMRglu patterns were still heterogeneous, the abnormalities ranging from focal to diffuse in both subgroups. After shunt operation, 11 patients did not improve or worsened clinically. Six patients improved; of those, two had Alzheimer changes and two cerebrovascular changes in their biopsy. The metabolic pattern of these six patients did not differ from the rest of the NPH group. The results indicate that the NPH syndrome may be non-specifically associated with different degenerative disorders. The metabolic heterogeneity, together with the heterogeneous histopathological findings, indicate the necessity of reevaluating the pathogenesis of the NPH syndrome, and may account for the high variability in the success rate of shunt surgery series.

Histopathology and growth pattern of cystic acoustic neuromas.

In a series of 571 acoustic neuromas, 23 were identified as cystic tumors. An immunohistochemical study including nervous system-associated protein (S-100), glial fibrillary acidic protein (GFAP), neurofilament protein (NF), laminin, fibronectin, vimentin, factor VIII (von Willebrand factor)-related antigen, and the nuclear antibody Ki-67 was performed. The cyst walls contained numerous S-100-positive fibrils distributed throughout the whole extent of the walls. Laminin, fibronectin, and vimentin were predominantly located around the vessel walls, factor VIII was found inside the vessels. GFAP-positive lamellae occurred in 50% of the cases near the surface of the cyst walls. Ki-67 is an antigen associated with cell proliferation. The density of Ki-67-positive cells was found to be 36 times lower in 16 noncystic controls than in the 23 cystic neuromas, indicating that the increase in tumor size in cystic acoustic neuromas may be caused by expansion of the cysts and not by an actual increase in the growth rate of the tumor cells. The data achieved in this series may contribute to better planning of the surgical approach. Because of the risk of sudden expansion of cystic elements, a wait-and-see policy should not be applied to patients with cystic acoustic neuromas.

Subcutaneous growth of human acoustic schwannomas in athymic nude mice.

In order to develop an in vivo model for growth of acoustic schwannomas, we studied tumor specimens from 10 patients, transplanted into a subcutaneous pocket of 67 nude mice. The number of tumors which survived or grew was 63 (94%). Obvious macroscopic growth was observed in 22 (33%), status quo in 28 (42%), and regression of tumor size in 13 (19%). The tumor disappeared in 4 cases (6%). Serial implantation was not possible due to the small amount of neuroma tissue in the surviving tumors. In animals with obvious macroscopic growth, neovascularization was clearly demonstrated. The presence of Schwann cells in the implants was confirmed immunohistochemically. The proliferative activity in the original and implanted tumors was evaluated by the proliferating cell nuclear antigen (PCNA) and Ki-67 nuclear antigen stainings and showed good correlation between primary tumors and implants. This in vivo tumor model will open new opportunities to study the biology of acoustic tumors and to test different therapeutic modalities.

Histology and neuro-imaging in cystic acoustic neuromas.

Tumor configuration and attenuation on CT scan with contrast enhancement or gadolinium-DTPA-enhanced MR depends upon tumor histology. Various elements are responsible for the density on CT or MR, e.g. blood vessels, fatty tissue, connective tissue, calcium, necrotic tissue, hemorrhage and intra- or extratumoral cyst formation. In a series of 571 acoustic neuromas we found 23 cystic tumors. The diagnosis was based on neuro-imaging examination, confirmed at surgery and finally verified histologically. Eight tumors with small or large cysts were diagnosed by CT or MR scan as intratumoral, and 15 with large cysts were diagnosed as extratumoral. We found a good correlation between the histology of cystic acoustic neuromas and the CT or MR scans. The tumors were predominantly hypodense, corresponding to the cystic areas, but also iso- or hyperdense areas were observed, corresponding to other tissue types. Antoni type B tissue and xanthomatous areas were found in all 23 cases.

Brain autopsy in organic solvent syndrome.

General autopsy findings, brain weight and brain pathology were studied in 98 men and five women who had been exposed occupationally to organic solvents over several years and assessed by the Danish National Board of Industrial Injuries for chronic toxic encephalopathy. The findings were compared with a forensic control material and a hospital control material. As in the general population, the most common causes of death among the exposed workers were heart failure and other vascular diseases. Due to the composition of the material (forensic cases), the number of suicides and violent deaths was high. Atherosclerosis was the most common CNS finding, but in comparison with the two control materials, no increase in the frequency of atherosclerosis or of Alzheimer's disease was found. Brain weights of the exposed workers corresponded closely to brain weights in the control materials, after correction for body height, body weight and age. Chronic alcoholism was correlated with slightly reduced brain weight.

Localized cranial hyperostosis of meningiomas: a result of neoplastic enzymatic activity?

Cranial hyperostosis is a common secondary manifestation of intracranial meningiomas. This may occur with or without neoplastic invasion, apart or even remote from the growth. Alkaline phosphatase (AP) is one of many enzymes produced by meningiomas and is known to possess indirect ossifying properties. Meningiomatous cranial hyperostosis could possibly be mediated by a humoral mechanism. This hypothesis was tested using chemical and histochemical determination of the occurrence of the enzyme in a series of hyperostosing and non-hyperostosing meningiomas. In the hyperostosing type the content of AP was in average more than three times as high as in the non-hyperostosing type. The results thus are in favour of the induction hypothesis.

Prognostic parameters in benign astrocytomas.

To elucidate the prognosis of different types of benign astrocytomas and to ascertain whether patients with partially resected benign astrocytomas, or any subtype of these, would benefit from postoperative radiotherapy, we studied retrospectively material comprising 300 patients with benign astrocytomas treated in the period 1956 to 1991. The pilocytic type of astrocytoma was found to have an outstandingly good prognosis and should be regarded as a distinct nosological entity. For the non-pilocytic supratentorial astrocytomas, a multivariate regression analysis showed that age, tumour site, Kernohan grade and lymphocytic perivascular cuffing influenced survival. The proportion of gemistocytes increased with age. After correction for age, the proportion of gemistocytes had no significant influence on survival. It was not possible to demonstrate any influence of radiotherapy on median survival time of patients with non-pilocytic supratentorial benign astrocytomas. The study emphasizes the necessity of a prospective combined multicenter analysis of the effect of radiation on benign astrocytomas.

Histologic examination of the rat central nervous system after intrathecal administration of human beta-endorphin.

The objective of this study was to evaluate histologically the toxicity of human beta-endorphin on the rat central nervous system after intrathecal administration. Animals received a single injection of 5 micrograms (n = 9) or 50 micrograms (n = 10) on each of four consecutive days, while others received 50 micrograms (n = 8) as a single dose. The control groups received either physiologic saline (n = 10) during each of four consecutive days or had sham operations (n = 4). Tests for nociception (tail-flick latency), motor function, and reflexes (righting reflex, eye-blink reflex, and inclined plane) were performed 5, 15, 30, 60, and 120 min after injection. Both dosages produced a dose-dependent impact on these parameters. In the 50-micrograms group, there were no significant differences in analgesia between the first and the fourth doses injected. The 50-micrograms dose produced catalepsy in some animals. All changes returned to baseline within 24 h. One animal in the 50-micrograms group developed hind limb paralysis after a single injection. Histologic sections from brain, brain stem, and spinal cord were prepared. No changes in histology were found except for that in the paretic animal, which had anoxic changes in the hippocampus and other cortical areas. Human beta-endorphin produced no neurotoxicity. The effect on nociception, reflexes, and motor function confirmed the results of previous studies.

Pituitary histology in Cushing's disease.

OBJECTIVE: We assessed pituitary histology in patients with Cushing's disease. DESIGN: Systematic histological assessment of pituitary tissue removed at surgery. PATIENTS: Thirty-six consecutive patients cured from Cushing's disease by transsphenoidal neurosurgery. MEASUREMENTS: Microscopical examination of all available tissue removed at operation. RESULTS: After selective removal of tissue supposed to represent an adenoma in 25 patients this could be histologically verified in 18. In the 11 patients who had undergone a total hypophysectomy an adenoma could be demonstrated in three patients only, despite a systematic search of the entire pituitary gland. Only in 21 of the 36 cured patients (58%) could an adenoma be verified. CONCLUSIONS: Combining the present results with previous reports there is strong reason to believe that in some patients with Cushing's disease no histological lesion in the pituitary is verifiable.

Histopathology of intact and docked pigtails.

A histological examination was performed on tails from three groups of pigs, comprising 10 amputated tail tips from day-old piglets, 10 tails from undocked fattening pigs and 20 tails from docked fattening pigs. The investigation demonstrated that peripheral nerves could be traced to the tip of the tails of day-old piglets as well as of fattening pigs. In the docked fattening pigs, the peripheral nerves were unevenly distributed and showed regressive changes. In some cases traumatic neuromas were found, indicating an increased sensitivity to pain in the amputation stump. It was, surprisingly, demonstrated that widespread inflammatory reactions could be found in the apparently healthy tails of both categories of fattening pigs, presumably due to pen-mates' chewing activities.

Entrapped, non-neoplastic adenohypophysiocytes in human pituitary adenomas.

The immunoprofile of 76 human pituitary adenomas was studied with particular reference to the occurrence of entrapped, non-neoplastic pituitary cells. This phenomenon was defined as unevenly distributed, usually peripherally located cells forming less than 1% of the total cell population. The stellate contour of such passively incorporated cells departed from the more rounded shape of most principal, neoplastic cells. Thirty-six of the adenomas studied comprised one or more types of entrapped elements. According to the hormone produced, prolactin-(PRL-)cells most commonly occurred as a minor "foreign" component (seen in 23 of the adenomas), whereas growth hormone-(GH-) and adrenocorticotropic hormone-(ACTH-)cells rarely were trapped (seen in 5 and 4 of the adenomas. Entrapped follicle stimulating hormone-(FSH-), luteinizing hormone-(LH-), and thyroid-stimulating hormone-(TSH-)cells assumed an intermediate position (seen in 14, 17 and 15 of the adenomas, respectively).

Estrogen and progesterone receptors in acoustic neuromas.

Acoustic neuromas are more frequent, larger, and more vascular in women, and their growth rate increases during pregnancy. Estrogen receptors were claimed to be demonstrated in these neoplasms for the first time in 1981. Since then, numerous diverging studies, using various biochemical and histochemical methods, have been published on the contents of estrogen and progesterone receptors in acoustic neuromas. We determined the content of estrogen and progesterone receptors by means of an immunohistochemical method, using monoclonal antibodies, which has proved to be reliable, reasonably sensitive, and clinically relevant in other tissues, especially in breast carcinomas. No estrogen or progesterone receptors could be found in 18 consecutive acoustic neuromas from 7 men and 11 women, ranging in age from 26 to 73 years. The results do not support preoperative hormone treatment of acoustic neuromas.

[Plasmapheresis in the treatment of peripheral HIV neuropathy]. / Plasmaferesebehandling af perifer HIV-neuropati.

Peripheral neuropathy following HIV infection is frequently seen among HIV-positive-, ARC- and AIDS patients who often complain of debilitating paresthesias. Indirect immunofluorescence technique showed antibodies directed either to myelin and/or axons and to endothelial cells of the blood vessels within the nerve tissue. Sural nerve biopsies from five patients showed demyelination, axonal degeneration and perivascular cellular infiltration. Two of the patients had nuclear inclusions and high anti-CMV titer. Plasma exchange was undertaken on five HIV infected patients which resulted in complete disappearance of symptoms in three, incomplete remission in one and no effect in one patient. The finding of autoantibodies against different nerve tissue components, cellular infiltration, positive effect of the plasma exchange and relapse suggests that autoimmunity may play a pathogenetic role in some of the HIV infected patients with peripheral neuropathy.

Pathology of brain and eye in the acquired immune deficiency syndrome (AIDS). A comparison of lesions in a consecutive autopsy material.

During the years 1984-1987, a consecutive Danish autopsy material of 43 AIDS cases was analysed in order to investigate a possible coincidence of pathological changes in brain and eye. In the brain, nodular gliosis/encephalitis was most frequent, followed by cytomegalovirus infection, which occurred twice as frequently as toxoplasmic infection and four times as frequently as fungal infection. In the eye, cytomegalovirus infection was most frequent and the only opportunistic infection, followed by retinal gliosis and cytoid body lesion. Malignant lymphoma was present in the brain in three patients, and in the choroid in two of these. In 11 patients, no changes of the brain were found. In eight of these the eye was also without pathological findings, while three had minor changes. In 22 patients the eye was normal, but in only eight of these was the brain without changes. Eight had nodular gliosis, and four a specific infection, while multifocal leucoencephalopathy and unspecified abscess each occurred in one patient. Comparison of the three opportunistic infections--CMV, toxoplasmosis and mycosis--in the three-year period showed an overall decreasing frequency, attributed to better medical care. It is concluded that concomitance of identical pathological lesions in brain and eye is less frequent than was expected.