Glial swelling with eosinophilia in human post-mortem brains: a change indicative of plasma extravasation.

Swollen, intensely eosinophilic glial cells are often observed in the vicinity of hemorrhagic lesions in post-mortem human brains. We sought to determine the nature of this change. Thirty adult human brains removed at autopsy and three surgical specimens were obtained 6h to 60 days following a hemorrhagic event. They were subjected to a battery of histochemical and immunohistochemical stains. The swollen cells, which were observed in the majority of autopsy specimens in which hemorrhage had occurred within the previous 9 days, stained intensely red with Masson stain and were immunoreactive for IgG, IgM, IgA, and fibrinogen. Some were also immunoreactive for glial fibrillary acidic protein, particularly in subpial and subependymal areas, if the lesions were more than 3 days old. In white matter some of the cells were immunoreactive for CNPase. There was no labeling with markers for macrophage/microglial cells. The absence of DNA fragment detection by TUNEL suggests that the cells were not dying. Mild glial cytoplasmic eosinophilia without swelling was observed in surgical specimens. No eosinophilic swollen glia were seen in perfusion-fixed rat brains with experimental intracerebral hemorrhage, although they were seen in rat brains that were not promptly fixed. We conclude that human macroglia, including astrocytes and oligodendrocytes, ingest plasma proteins that have been released into brain parenchyma. This likely represents a homeostatic mechanism that maintains the composition of the extracellular environment. If the tissue is not promptly fixed the cells become more swollen and eosinophilic.

Injury of the tunica media in fatal rupture of the vertebral artery.

The histologic findings in seven cases of traumatic basal subarachnoid hemorrhage from rupture of a vertebral artery are reported. In all cases, blows to the head or neck resulted in minor injury to the cranial or cervical soft tissues but the ipsilateral intracranial segment of the vertebral artery was the site of a longitudinal transmural tear. In addition to rupture, the arterial wall proximal and distal to the site of rupture showed evidence of distortional injury of the tunica media. These traumatic lesions appeared as patchy anuclear regions of the media with distinctive pallor of smooth muscle staining. We propose that the forces which cause vertebral artery rupture stretch the artery along its long axis, thereby distorting the artery leading to this characteristic histologic change.

Syrinx extending from conus medullaris to basal ganglia: a clinical, radiological, and pathological correlation.

A 41-year-old woman with a history of birth injury to the brachial plexus suffered several delayed episodes of neurological deterioration. Magnetic resonance imaging studies revealed a syrinx extending from the conus medullaris into the brainstem and rostrally into both internal capsules. She died of an acute exacerbation of chronic respiratory failure. Autopsy demonstrated syringomyelia and syringobulbia with cavity extension bilaterally along the corticospinal tracts into the internal capsules. Islands of glial tissue in the subarachnoid space around the medulla caused obstruction of the subarachnoid space at the foramen magnum. These were probably the result of birth injury to the cerebellum. A detailed clinico-pathological correlation is provided to explain her neurological deficits. The pathogenesis of syrinx formation is discussed in terms of a late manifestation of birth trauma.

Neuroendocrine tumor (paraganglioma) of the cauda equina: MR and pathologic findings.

The MR and pathologic features of a case with neuroendocrine tumor (paraganglioma) of the cauda equina are presented. MR showed the tumor to be hyperintense on postcontrast examination and also showed serpiginous flow voids suggesting vessels capping the tumor. A neuroendocrine tumor should be considered in the differential diagnosis of tumors in this location.

Rosenthal fibers producing a granular cell appearance in a glioblastoma.

In this report we describe a glioblastoma multiforme with focal granular cell change. In most astroglial tumors with granular cells, the granular appearance is due to the presence of periodic acid-Schiff-positive, membrane-bound cellular debris. In the present case the granular appearance was due to the presence of many small Rosenthal fibers, which were immunoreactive for glial fibrillary acidic protein, vimentin, ubiquitin, and heat-shock protein 27, but not for alpha-B crystallin. The ultrastructural characteristics are described. These findings demonstrate that granulofilamentous inclusions with the appearance of Rosenthal fibers in glial tumors are a structurally heterogeneous feature.

Fracture of temporal bone with exsanguination: pathology and mechanism.

Eight cases of basal skull fracture with transverse fracture of the petrous temporal bone with medial extension to the internal carotid artery and lateral extension of the structures of the middle ear are described. Injuries in all cases were due to major blunt impact to the head usually occurring in a motor vehicle accident. General autopsy revealed major blood loss without any obvious external or internal site of hemorrhage suggesting that exsanguination was a complication of the head injury. The internal carotid arteries at the most medial extension of the fractures were lacerated or transected in all cases. In selected cases, the cervical internal carotid arteries were perfused and perfusate escaped rapidly from the ear(s) with the majority of fluid bypassing the cerebral venous system. Magnetic resonance image reconstruction of sequential sections of the fractured base of the skull confirmed the laceration of the internal carotid arteries and disruption of the middle ear. Based on this evidence, we propose that some displaced fractures of the base of the skull produce carotid-middle ear continuities which act as arterial shunts, resulting in rapid fatal exsanguination through the ear.

Lesions of the tunica media in traumatic rupture of vertebral arteries: histologic and biochemical studies.

Discontinuous non-circumferential lesions of tunica media were observed in four cases of traumatic rupture of the vertebral artery. We hypothesize that these lesions were due to mechanical disruption of smooth muscle cells and the liberation of catabolic enzymes with subsequent degradation of the arterial media. To test this hypothesis, healthy vertebral arteries were incubated with crude extracts of bovine smooth muscle cytosol in attempt to reproduce the histological changes of the arterial media in traumatized vertebral arteries. We observed cytosol-induced degradation of tunica media, characterized by pallor of staining with the Masson's Trichrome method, which was due to catabolic enzyme activity that was effectively inhibited by heat inactivation of the cytosol. The cytosol-induced tinctorial changes were similar to the lesions of the tunica media in naturally-occurring cases of traumatic vertebral artery rupture. We conclude that although vertebral arteries can be ruptured by physical distortion alone, associated lesions of the tunica media are due to in situ trauma-associated release of heat-labile catabolic enzymes.

Aging produces a specific pattern of striatal dopamine loss: implications for the etiology of idiopathic Parkinson's disease.

To examine the possible causal contribution of normal or accelerated aging to the neurodegenerative process of Parkinson's disease, we measured the influence of aging on subregional striatal dopamine and homovanillic acid levels in postmortem brain of 23 neurologically and psychiatrically normal human subjects 14-92 years old. We observed a significant decline in striatal dopamine levels and increase in the homovanillic acid/dopamine molar ratios with increasing age. The dopamine loss, on average, was of the same magnitude in the caudate nucleus and the putamen (-60% in the 84-year-old group as compared with the 22-year-old group), with the caudal component of both nuclei being more affected than the rostral subdivisions. The level of subregional dopamine metabolism, as measured by the homovanillic acid/dopamine ratio, in our young individuals (mean age, 22 years) was found to be inversely correlated to the degree of subregional dopamine loss suffered by the individuals in the older age groups. We conclude the following: (a) Striatal subdivisions with physiologically higher dopamine metabolism are not at a greater risk of suffering dopamine neuronal damage with advancing age, as would seem to be implied by the oxidative stress hypothesis; thus, formation of dopamine-derived oxy radicals in the human striatum appears unlikely to be a primary factor responsible for the age-related striatal dopamine loss. (b) The regional and subregional pattern of striatal dopamine loss in normal aging differs substantially from the pattern typically observed in idiopathic Parkinson's disease; therefore, the cause of idiopathic Parkinson's disease cannot be primarily an age-dependent neurodegenerative process.

Pneumocephalus following treatment of esthesioneuroblastoma.

The course of a patient with an olfactory neuroblastoma treated with conventional doses of chemotherapeutic agents and radiotherapy is presented. The patient survived 34 months after tumour necrosis with resultant pneumocephalus requiring surgical intervention.

Post-herpetic neuralgia: further post-mortem studies of cases with and without pain.

The pathological features associated with post-herpetic neuralgia require further study. We report here 5 cases, 3 with severe post-herpetic neuralgia (PHN) and 2 with no persistent pain. The findings of dorsal horn atrophy and cell, axon and myelin loss with fibrosis in the sensory ganglion were found only in patients with persistent pain. Marked loss of myelin and axons in the nerve and/or sensory root were found in cases with and without pain. Some evidence is presented for a more generalized subacute or chronic inflammatory process which may explain the clinical features of some patients. Further studies will be necessary to fully describe the morbid anatomy of this disorder.

Glycerophosphoethanolamine concentration is elevated in brain of patients with dominantly inherited olivopontocerebellar atrophy.

We measured the concentration of glycerophosphoethanolamine (GPEA), a membrane breakdown product, in autopsied brain of 10 patients with dominantly inherited olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder. As compared with the controls, mean GPEA levels were significantly elevated by 37-69% in 11 of the 15 brain areas examined, including extracerebellar brain regions in which no neuronal cell loss could be detected by semiquantitative estimation. Our data suggest the possibility of altered membrane phospholipid metabolism in OPCA which could be a contributing factor in the neuronal cell death.

The mechanism of embolic watershed infarction: experimental studies.

The mechanism for the preferential distribution of emboli to cerebral arterial borderzone regions, known to cause some watershed infarcts was studied. We hypothesized that emboli of a specific size range are selectively directed to the arterial borderzones due to the tendency of emboli to bypass the small arterial branches which emerge proximal to major borderzones. To test this hypothesis we perfused the brains of cadavers with suspensions of 90-210 microns glass microspheres and chemically extracted the particles from various arterial territories and a watershed zone. Particles in the 150-210 microns size range were found to be preferentially distributed to the watershed zone whereas particles less than 150 microns in size were randomly dispersed in leptomeningeal arteries of all vascular regions. To assess the role of branch size on the concentration of emboli at bifurcations, we perfused artificial analogs of evenly and unevenly branching bifurcations with suspensions of 90-150 microns and 150-210 microns particles. Branching cylinders with symmetrical branches contained the same concentration of particles, independent of particle size. In contrast, when one branch was one-quarter the size of the other, the concentration of 150-210 microns particles in the asymmetric branch was approximately 65% of the main trunk. Particles 90-150 microns in size were evenly distributed despite variation in branch size. These results indicate that emboli, of a limited range of size, may be selectively propagated to the distal ramifications of subarachnoid arteries located in the watershed zone rather than diverging into small calibre branches which arise along the way.

Immunohistochemistry of ecchordosis physaliphora and chordoma.

Immunohistochemical stains for cytokeratins, vimentin, epithelial membrane antigen, carcinoembryonic antigen and S-100 were performed on nine ecchordoses and 10 chordomas. 100% of the ecchordoses were positive for cytokeratin, vimentin and epithelial membrane antigen. 78% were S-100 positive. 100% of the chordomas stained positively for cytokeratin, vimentin and S-100 and 90% were positive for epithelial membrane antigen. No ecchordosis or chordoma was carcinoembryonic-antigen positive. These findings are interesting for two reasons. First, the similar staining properties of chordoma and ecchordosis physaliphora support the embryologic hypothesis of their common origin from the fetal notochord. Second, they indicate that when an ecchordosis causes symptoms prompting surgical resection, differentiation of the lesion from chordoma with routine immunohistochemistry would not be helpful.

[3H]vesamicol binding in human brain cholinergic deficiency disorders.

We measured the binding of the vesicular acetylcholine transport blocker [3H]vesamicol (2-[4-phenylpiperidino] cyclohexanol; AH-5183) to autopsied frontal cortex and amygdala of patients from 4 disorders having a marked brain cholinergic reduction, namely Alzheimer's disease, Parkinson's disease with dementia, dominantly inherited olivopontocerebellar atrophy and Down's syndrome. Although mean activity of the specific cholinergic marker enzyme choline acetyltransferase (ChAT) was markedly reduced by about 60% in frontal cortex in the 4 patient groups and by 80% or greater in amygdala of the Alzheimer's and Down's syndrome patients, [3H]vesamicol binding density was, on average, either normal or only slightly reduced as compared with the controls. This discrepancy suggests that in human brain [3H]vesamicol binding is either not preferentially localized to cholinergic nerve endings or, in these cholinergic deficiency syndromes, a substantial proportion of the vesamicol binding sites persist on cholinergic nerve terminals despite loss of ChAT activity.

Histopathological features of congenital fundus lesions in familial adenomatous polyposis.

We report the light and electron microscopic findings for two lesions from two patients who died of complications of familial adenomatous polyposis. In the first case microscopy of a small (100 to 200 mu), uniformly dark lesion (the commonest type seen in this condition) showed enlarged retinal pigment epithelial cells with an increased number of pigment granules. This is consistent with the term "hypertrophy of the retinal pigment epithelium", currently used to describe these lesions. In the second case we sectioned a larger (1000 to 1500 mu), oval, grey lesion from the posterior pole. The pigment epithelium was normal, but between it and outer retina was an unusual choristoma consisting largely of myelinated axons and astrocytes.

Cerebrospinal fluid fistula secondary to ecchordosis physaliphora.

A patient with a large ecchordosis physaliphora extending from the sphenoid sinus into the subarachnoid space of the prepontine cistern and resulting in a cerebrospinal fluid fistula is described. Ecchordoses are most commonly asymptomatic and found only incidently at autopsy. This case report adds to the scant literature on symptomatic ecchordoses. The previously reported cases of symptomatic ecchordoses and intradural chordomas are briefly reviewed. Differentiation of chordoma and symptomatic ecchordosis may be difficult; however, the intradural location and relatively benign behavior of the latter are useful points. A discussion concerning the remnants of the notochord which persist in the adult and their role in the genesis of chordoma and ecchordosis physaliphora is also provided.

"Anemone" cell (villiform) tumor of the brain.

At age 31, the patient developed hydrocephalus secondary to a brain lesion that had been present for 12 years. A ventriculoperitoneal shunt was performed, but a stereotactic biopsy did not establish a definitive diagnosis at that time. At age 34 the patient experienced spontaneous intratumoral and ventricular hemorrhage, which prompted radical surgical resection of the lesion. Histologic and immunocytochemical findings established a diagnosis of ependymoma; review of the ultrastructure of the tumor from the biopsy performed when the patient was 31 years old revealed the characteristics of an "anemone" cell neoplasm.

Phrenic involvement in Charcot-Marie-Tooth disease. A pathologic documentation.

A 69-year-old woman diagnosed as having Charcot-Marie-Tooth disease (CMT) for 30 years' duration died of respiratory failure secondary to diaphragmatic weakness. At autopsy, identical neuropathic changes were found in phrenic and other affected somatic peripheral nerves. We conclude that the phrenic nerve may be involved by the neuropathy of at least some forms of CMT.