1/9. Features of cell death in brain and liver, the target tissues of progressive neuronal degeneration of childhood with liver disease (Alpers-Huttenlocher disease).Alpers-Huttenlocher disease (AHD) is a rare encephalopathy of infancy and childhood characterized by myoclonic seizures and progressive neurological deterioration, usually associated with signs and symptoms of liver dysfunction. There is no biological marker of the disease, and ultimate diagnosis still relies on pathological examination. Features of clinical progression and pathological findings suggest AHD to be secondary to a genetically determined disorder of mitochondrial function. We report on four AHD patients and focus on their pathological features in brain, liver and muscle. liver and muscle biopsy specimens were examined using histochemical markers of the oxidative pathways, probes to immunodetect molecules of the apoptotic cascades and electron microscopy. In liver (but not in muscle) biopsy samples, activated caspases were detected by immunohistochemistry: foci of caspase-9-positive cells were seen in a child affected with chronic, progressive fibrosis. In an 18-year-old boy, who suffered from valproic acid-associated acute hepatitis, caspase-3 cells were clustered among the necrotic foci and the foamy cells. In both patients electron microscopy revealed apoptotic nuclei. Normal muscle biopsy specimens were observed in two children, 2 and 8 years-old respectively; in the 18-year-old patient cytochrome oxidase-negative fibers as well as ultrastructural findings of mitochondrial abnormalities were observed. In no patient was there biochemical evidence of impaired oxidative metabolism. Neuropathological examination of the brains of two patients (13 months and 19 years old, respectively) showed focal distribution of the lesions affecting the telencephalic cortex and, to a lesser extent, subcortical gray nuclei. Along with the necrotizing lesions, characterized by neuronal loss, neuropil microcysts and newly formed vessels, we also observed acutely shrunken neurons and features of apoptotic cell death in the cerebral cortex only. Severe neuronal loss without necrotizing features was observed in the cerebellar cortex. The presence of both anoxic and apoptotic nuclei in brain and liver, the target tissues of the disease, is consistent with the hypothesis that abnormal activation of mitochondrion-related cell death pathways might be involved in the pathogenesis of AHD.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
2/9. Progressive bulbar dysfunction caused by a predominantly venous vascular malformation of the medulla oblongata.We describe a 58-year-old patient with a rare predominantly venous vascular malformation of the medulla oblongata, which caused a progressive bulbar dysfunction consisting of hiccoughs, dysphagia, hoarseness, dysarthria, gait ataxia and dysuria over a period of 11 months. On autopsy, a large dilated vein with focal marked intimal fibroelastic thickening was present on the ventral surface of the medulla. Microscopically, moderate proliferation of capillaries and veins was observed which was confined primarily to the medulla. The veins displayed abnormal dilatation and tortuosity; prominent thickening of vessel walls was also present in the veins and capillaries. The venous abnormalities were prominent in the parenchyma of the medulla, but much less apparent in its subarachnoid space. Multifocal neuronal loss and gliosis were observed, most prominently in the inferior olives, hypoglossal, dorsal vagal and ambiguus nuclei. The histopathologic findings suggested that abnormal venous drainage within the parenchyma of the medulla was the most critical factor for the pathogenesis of this patient's neurologic symptomatology.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
3/9. optic nerve and spinal cord manifestations of malignant atrophic papulosis (Degos disease).A fatal case of malignant atrophic papulosis (Degos disease) with optic nerve and spinal cord involvement is described. magnetic resonance imaging (MRI) of the optic nerve showed abnormal signal enhancement on fat suppressed T1 weighted images after intravenous meglumine gadopentetate infusion. On T2 weighted sagittal images, a sawtooth pattern was observed over seven vertebral segments of the spinal cord. On necropsy, a severe loss of myelinated nerve fibres in the left optic nerve was seen, with thrombotic obstruction of the central retinal artery. Spongy degeneration was observed in all levels of the spinal cord, with patchy and motheaten patterns caused by thromboses and endothelial proliferation in subarachnoid vessels. Findings on MRI were consistent with findings on pathological examination.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
4/9. An autopsy case of human T lymphotropic virus type I-associated myelopathy (HAM) with a duration of 28 years.An autopsy case of human T lymphotropic virus I-associated myelopathy (HAM) of a duration of 28 years in a 61-year-old man with serological confirmation of HTLV-I infection was reported. The spinal cord was grossly atrophic. There was severe symmetrical degeneration of the lateral funiculi, particularly of the bilateral pyramidal tracts, involving all levels of the spinal cord, but anterior horn cells were relatively well preserved. In the most severely damaged middle and lower thoracic segments, the white matter degeneration also involved the anterior funiculi. In the degenerated white matter, both the myelin and axons were equally lost and had been replaced by glial scars. Marked adventitial fibrosis was commonly seen in small parenchymal vessels in both the white and gray matter. Although there was no evidence of inflammation in the spinal cord, mild lymphocytic infiltration was occasionally observed in the subarachnoid and perivascular spaces in the brain stem, cerebellum and cerebrum. This case was considered as a burnt-out case of HAM.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
5/9. Peripheral neuropathy with essential mixed cryoglobulinemia: biopsies from 5 cases.Essential mixed cryoglobulinemia, which can cause hypersensitivity vasculitis, was observed in five patients with peripheral neuropathy. Three cases presented with multifocal neuropathies and two cases with symmetrical polyneuropathy. One had cryoglobulinemia with IgM monoclonal gammopathy IgG polyclonal gammopathy, and the other four had cryoglobulinemia with polyclonal gammopathy. Biopsies showed perivascular infiltration by mononuclear cells around medium, and mainly small-sized blood vessels. This was observed in the epineurium (five cases) and muscular fragments (three cases). At ultrastructural examination two cases showed severe damage of most myelinated fibers, which presented acute stages of Wallerian-like degeneration, and the three other cases showed a less widespread destruction of myelinated fibers. Most endoneurial capillaries showed swollen endoneurial cells. Myelino-axonal degeneration of myelinated fibers is probably due mainly to the vasculitis always present in the epineurium. This damage was probably worsened by the modifications of endoneurial capillaries. These lesions and their mechanisms are quite different from those observed in cases of cryoglobulinemia with an isolated monoclonal gammopathy.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
6/9. Hypothalamic gangliocytoma. Selective appearance of neurofibrillary changes, granulovacuolar degeneration, and argentophilic bodies.A hamartomatous gangliocytoma was observed in the hypothalamus of a 54-year-old woman. The ganglion cells were atypical, highly pleomorphic and often multinucleated, and they possessed neurofibrillary changes, granulovacuolar degeneration, and argentophilic bodies. The neuronal changes were highly selective and were not found in other parts of the brain. The tumor was also characterized by the presence of angiomatous blood vessels having such degenerative changes as fibrosis and thrombosis. The angiomatous blood vessels were found only in the lesion. The ultrastructural features of the neurofibrillary changes were similar to those observed in Alzheimer's disease. Vascular alterations have been suggested to be a possible contributor to the morphogenesis of neurofibrillary changes. In this case the exact etiology of these neuronal changes remains unclear, however, the possibility of a regional vascular role is considered with respect to their morphogenesis.- - - - - - - - - - ranking = 2keywords = vessel (Clic here for more details about this article) |
7/9. Microangiopathy of vasa nervorum in dysglobulinemic neuropathy.Thickening of vessel walls resulting from endothelial proliferation was observed in the vasa nervorum of eleven patients with peripheral neuropathy associated with dysglobulinemia. Electron microscopy showed endothelial proliferation accompanied by abnormal accumulation of masses of intracytoplasmic filaments in each case. Of the eleven patients with dysglobulinemia, nine had monoclonal gammopathy and two were found to have polyclonal elevation of gamma globulin levels. Symptoms of neuropathy characteristically preceded detection of serum protein abnormalities by months to years. Nerve fiber lesions involved primarily the axon in four cases; segmental demyelination was the principal abnormality in the other seven. Both abnormalities were present to some degree in all eleven patients. Biphasic myelinopathy with uniform separation of myelin lamellae attributable to globulin deposition was observed in four cases. The microvascular changes included endothelial cytoplasmic enlargement, virtually obliterating the vessel lumen in many instances, with thickening of pericytes, in which intracytoplasmic filaments were prominent and pinocytotic vesicles numerous. No extracellular filaments were noted, and amyloid stains were negative. Possible effects of these microvascular changes include ischemia resulting from severe vascular luminal narrowing, and altered vascular permeability. Severe loss of axons in this group of neuropathies may be the result of ischemia, whereas altered vascular permeability may admit globulin into the endoneurium, where it may directly affect the myelin sheath and precipitate demyelination.- - - - - - - - - - ranking = 2keywords = vessel (Clic here for more details about this article) |
8/9. Primary familial amyloidosis with vitreous opacities. Report of an autopsy case.A 41-year-old Japanese male with a new type of primary familial amyloidosis was reported. The patient developed vitreous opacities, and later, disturbances in the gastrointestinal and nervous systems. At autopsy, amyloid was observed in the vitreous and the retinal vessels. There were extensive cerebral infarcts and heavy meningo-vascular amyloid deposition. Although the postmortem study revealed slight peripheral nerve degeneration in the lower extremities secondary to amyloid deposition, there was no clinical evidence of polyneuropathy.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |
9/9. Clinical and neuropathological study of six patients with spastic paraparesis associated with HTLV-I: an axomyelinic degeneration of the central nervous system.Between 1990 to 1994, 6 TSP/HAM patients, 3 women and 3 men with an average age of 57.1 years (39 to 76 years old), who died in the Salvador Hospital were submitted to postmortem examination. The mean time of paraparesis was 7 years (3 to 17 years), and 2 patients had pseudobulbar signs. Three cases had macroscopic atrophy of the spinal cord. Histologically, all cases had lesions in the pyramidal tracts and 4 cases showed somatotopic lesions of the Goll's tracts which followed a "dying back" ascendant and descendant distribution, respectively. In 2 cases, both of which had intellectual impairment, demyelination of the subcortical and parathalamic areas was observed without U fiber involvement. Abnormal vessels with gross thickening of the adventitia, many of them with lymphocytic cuffs, were seen everywhere, especially in the spinal cord, brain stem, midbrain and meninges, but no relation between these findings and the parenchymal lesions was observed. Also, in the cases with posterior column involvement, neuronal changes and proliferation of satellite cells in the dorsal ganglia were found. All cases showed histological sialoadenitis and none had inflammatory muscle changes. We conclude that the lesions affected the neuraxis in a systemic axial fashion as in degenerative diseases, and did not seem to be secondary to vascular or inflammatory abnormalities.- - - - - - - - - - ranking = 1keywords = vessel (Clic here for more details about this article) |