Immunocytochemical studies on synaptophysin in the anterior horn of lower motor neuron disease.

This report concerns the study of synaptophysin (SP) expression in the anterior horn of three cases of lower motor neuron disease (L-MND). All patients studied had anterior horn cell degeneration without neuropathological evidence of corticospinal tract degeneration. Spinal cords from six patients with no neurological disease served as controls. Immunocytochemical techniques were used. The results show that in L-MND there is decreased SP immunoreactivity of the anterior horn neuropil, but preservation of immunoreactive dots around the cell body and proximal processes, and the presence of some residual neurons in the affected gray matter that are surrounded by a dense accumulation of immunoreaction products. These findings resemble those of classical amyotrophic lateral sclerosis (ALS), indicating similarities in the distribution patterns of presynaptic terminals in the anterior horn of L-MND and classical ALS.

Modified Bielschowsky and immunocytochemical studies on cerebellar plaques in Alzheimer's disease.

Senile plaques (SP) in the cerebellum of 23 cases of Alzheimer's disease (AD), three with widespread amyloid angiopathy, were studied with a modified Bielschowsky stain and immunocytochemical methods using antibodies to a beta-amyloid synthetic peptide (beta ASP), phosphorylated neurofilament proteins, ubiquitin, tau protein, and glial fibrillary acidic protein (GFAP). The four subtypes of SP (diffuse plaques, compact plaques, perivascular plaques, and subpial fibrillar deposits) that were observed with the modified Bielschowsky stain were also stained with antibodies to beta ASP. Many cerebellar SP contained ubiquitin-positive granular elements resembling dystrophic neurites. In contrast to neuritic elements in cerebral SP in AD, ubiquitin-positive elements in cerebellar SP were not labeled with antibodies to phosphorylated neurofilament or tau proteins. Various degrees of glial reaction were observed in all subtypes of SP except diffuse plaques. The absence of phosphorylated neurofilament and tau epitopes in neuritic elements in cerebellar SP is not surprising since paired helical filaments have not been seen in the cerebellum. Nevertheless, our results suggest that cerebellar SP are frequently associated with dystrophic neurites.

Fine structure of the cerebellar cortex in Menkes Kinky-hair disease. X-chromosome-linked copper malabsorption.

The cerebellar cortices in two patients with X-chromosome-linked copper malabsorption (Menkes kinky-hair disease) were examined with both the light and electron microscope. Somatic sprouts and grotesque dendritic arborization were among the obvious light microscopical changes. At the fine structural level, the Purkinje cells were characterized by the presence of somatic spines although the surviving granule cells had already descended. Most spines were parts of synaptic complexes, but some were unattached to any presynaptic element. Similar spines were also observed on dendritic trunks. Astrocytic gliosis and nonspecific endothelial cell changes were noted.

Miller-Dieker syndrome: a disorder affecting specific pathways of neuronal migration.

A patient with the typical craniofacial features and clinical course of Miller-Dieker syndrome (MDS) was found on autopsy to have focal pachygyria rather than lissencephaly. The brainstem and cerebellum were hypoplastic, but thalami and basal ganglia were normal. We believe that MDS is a syndrome in which multiple specific pathways of neuronal migration are affected selectively, such as migration to the neocortex, migration via corpus pontobulbare, and cerebellar migration. However, another migration pathway (via corpus gangliothalamicum) is spared.

Rhabdoid transformation of tumor cells in meningiomas: a histologic indication of increased proliferative activity: report of four cases.

Four cases of meningeal tumors in adults (ages ranging from 28 to 84 years) are presented. All had the typical gross appearance of meningiomas at operation. In three tumors, areas of meningothelial or fibroblastic meningiomas showed transition to cell groups of the rhabdoid type. In the fourth case only rhabdoid cells were encountered, possibly representing a total "take-over" of a meningioma by rhabdoid elements. In the three cases with mixed pattern, the rhabdoid cells showed more anaplasia and atypism than the conventional meningiomatous elements. In case 3 this was expressed by very high MIB-1 positivity in the rhabdoid cells and absence of same in the fibroblastic meningiomatous elements. These cases (the first three with certainty, the fourth with a strong likelihood) indicate that the phenotypic changes to cells with "rhabdoid" morphology may involve meningiomas and that such change is associated with aggressive biologic and clinical behavior of the tumors showing this type of alteration.

Human immunodeficiency virus-1 infection of the nervous system: an autopsy study of 268 adult, pediatric, and fetal brains.

The central nervous system (CNS) of 221 adults and 31 infants or children with the acquired immunodeficiency syndrome (AIDS) was examined with immunocytochemistry for infectious agents and for human immunodeficiency virus-1 (HIV-1) antigen (gp41). Since the major risk factor in this population was intravenous drug abuse, there were more female and pediatric patients than in other neuropathology autopsy series. Although children had a different spectrum of pathologic changes, including less frequent opportunistic infections, women did not differ from men in terms of types or incidence of opportunistic infections, vascular disease, neoplasia, and subacute AIDS encephalitis (SAE). Subacute AIDS encephalitis was detected in 26% of adult and 48% of pediatric brains. Immunocytochemical analysis of 100 adult and 20 pediatric brains revealed gp41 immunoreactivity in 78% and 40%, respectively. Virtually all adult brains with SAE had gp41 immunoreactivity in macrophages and microglia. Even brains with no significant pathology had frequent gp41 immunoreactivity, especially in the basal ganglia. In pediatric brains, including cases with SAE, gp41 immunoreactivity was less abundant, suggesting the possibility of latent infection or viral clearance. Spinal cords with vacuolar myelopathy or corticospinal tract degeneration had only rare gp41-positive cells. Brains from 16 aborted fetuses from HIV-1-seropositive women were all negative for gp41 immunoreactivity, but 12 brains were positive for HIV-1 by the polymerase chain reaction. These results may indicate that HIV-1 infection in fetal brains is below the limits of detection of immunocytochemistry. The differences noted between adults and children suggest that adults more often have productive CNS HIV-1 infection.

Central nervous system pathology in pediatric AIDS.

Children with AIDS frequently have neurological manifestations due to complications of immunodeficiency or intrinsic effects of human immunodeficiency virus type 1 (HIV-1) on the central nervous system (CNS). The most common neurological disorders not directly related to HIV-1 infection include cerebrovascular disease and lymphoma. Global anoxic-ischemic and necrotizing encephalopathies are frequent, while CNS hemorrhages and arteriopathies are less frequent. Opportunistic CNS infections are uncommon, limited predominantly to monilial and cytomegaloviral encephalitides. Only a few cases of CNS toxoplasmosis have been reported in children. CNS lymphomas often occur in the setting of systemic polymorphous, polyclonal B-cell proliferations that have been associated with Epstein-Barr virus infection. Intrinsic effects of HIV-1 on the CNS include microcephaly, diffuse gliosis, basal ganglia mineralization, HIV encephalitis, and corticospinal tract degeneration. Although viral antigens can be detected in microglia and multinucleated cells in HIV encephalitis, most of the CNS effects of HIV-1 infection cannot be attributed to detectable levels of viral antigen, suggesting that the pediatric CNS is unusually susceptible to low-level HIV-1 infection or to systemic effects of HIV-1 infection, possibly mediated by soluble factors, including the inflammatory cytokines, interleukin-1 beta, and tumor necrosis factor-alpha, which have been shown to be increased in serum and cerebrospinal fluid of children with AIDS.

Electron microscopy of the blood-brain barrier in disease.

The anatomical site of the blood-brain barrier (BBB) is at the capillary endothelium mainly, with some contribution from astrocytes. Electron microscopic observations of endothelial cells and perivascular astrocytes comprising the BBB in brain edema and other pathological conditions are reviewed in this article. The tight junctions of cerebral endothelial cells open under several conditions such as infusion of hyperosmolar solutions. Pinocytotic vesicles increase under various pathological conditions and fenestrae appear in blood vessels of certain brain tumors and several non-neoplastic lesions. Inflammatory cells penetrate between or through endothelial cells. In long standing lesions, endothelial cells containing various tubular structures such as Weibel-Palade bodies proliferate. Other alterations include surface infoldings of endothelial cells and fluid diffusion through damaged endothelium. Astrocytic alterations include abnormal junctions between astrocytic processes in certain gliomas. In vivo and in vitro studies suggest that astrocytes maintain or develop certain functions of BBB. As the BBB is disrupted, edema fluid infiltrates the brain parenchyma. Because the white matter consists of nerve fibers without demonstrable junctions, it invades between nerve fibers. In the gray matter, expansion of the fluid is limited by complicated anatomical structures. In myelinated nerve fibers, edema fluid accumulates in five separate compartments of extracellular space.

Cerebral malaria in mice: demonstration of cytoadherence of infected red blood cells and microrheologic correlates.

To understand the microcirculatory events during cerebral malaria, we have studied the lethal strain of rodent Plasmodia, Plasmodium yoelii 17XL, originally described by Yoeli and Hargreaves in 1974. The virulence of P. yoelii 17XL is caused by intravascular sequestration of infected red blood cells (IRBCs), especially in the brain vessels and capillaries. This mouse model resembles human P. falciparum infection more closely than P. berghei ANKA infection since it shows little, if any, inflammation of the brain. In vivo microcirculatory studies on cytoadherence of IRBCs were performed using the cremaster muscle preparation, which is an easily accessible vasculature for intravital observations. Ex vivo assay of cytoadherence was carried out in the artificially perfused mesocecum preparation of the rat. The results in either preparation demonstrated cytoadherence of IRBCs that was restricted to postcapillary venules. Furthermore, the in vivo measurements showed the prevalence of cytoadherence in small-diameter (< 40 microns) venules in accordance with the local wall shear rates. The parasitized animals demonstrated significantly reduced red blood cell velocities and wall shear rates in the small-diameter postcapillary venules of the cremaster. The relationship between cytoadherence and venular wall shear rates was also reflected in the inverse correlation between the number of adhered cells and the venular diameter in the ex vivo mesocecum preparation. In the ex vivo preparation, cytoadherence of IRBCs was accompanied by a higher peripheral resistance. Transmission electron microscopy of the cremaster muscle and brain tissues showed a tight association of IRBCs with the endothelium of small venules. These observations demonstrate that cytoadherence of P. yoelii 17XL-infected mouse red blood cells is very similar to that of P. falciparum-infected cells. Thus, this model should allow a detailed analysis of the molecular mechanisms involved in the generation of cerebral malaria by cytoadherence of the infected red blood cells to the vascular endothelium.

Altered synaptophysin-immunoreactive pattern in human olivary hypertrophy.

We examined the inferior olivary nucleus from four cases of olivary hypertrophy and six control cases immunohistochemically with an anti-synaptophysin (SYP) antibody. Our study revealed the altered SYP-immunoreactive pattern in the hypertrophied olives, consisting of an increased number of SYP-immunoreactive dots on neuronal cell bodies in spite of its decreased immunoreactivity in the neuropil. Because SYP is a marker protein for presynaptic vesicles, presynaptic terminals in the inferior olivary nucleus seem to change their distribution during the course of olivary hypertrophy.

Involvement of hippocampus in Creutzfeldt-Jakob disease.

The hippocampus is generally believed to be only rarely affected in Creutzfeldt-Jakob disease. In a systematic study of the hippocampus in 6 cases of Creutzfeldt-Jakob disease, the stratum moleculare-lacunosum showed a definite spongiform change with gliosis in 5 cases. The stratum radiatum et pyramidale showed spongiform change in 3 of the 5 cases. The subiculum, presubiculum, parasubiculum and entorhinal cortex were involved in all the cases. These results suggest that involvement of the hippocampus may not be uncommon in Creutzfeldt-Jakob disease. The stratum moleculare-lacunosum seems to be the site preferentially affected. This pathology may contribute to progression of dementia in Creutzfeldt-Jakob disease.

Gangliocytic paraganglioma in cauda equina region, with biochemical and neuropathological studies. Case report.

Biochemical analysis of a nonfunctional paraganglioma in the cauda equina region demonstrates that its catecholamine content is predominantly dopamine with small amounts of noradrenaline and adrenaline. Scattered mature large neurons characterize the tumor as gangliocytic paraganglioma. Ultrastructural study shows intracytoplasmic neurosecretory granules in the neoplastic cells.

Extramedullary hemangioblastoma of the spinal cord. Case report.

A case of hemangioblastoma of the spinal cord is described in which the tumor presented in an intradural extramedullary location. The patient did not have von Hippel-Lindau's disease or metastatic seeding. It is assumed that the tumor arose in the pia, and its direction of growth was purely extramedullary.

Expression of vascular endothelial growth factor in pediatric and adult cerebral arteriovenous malformations: an immunocytochemical study.

Children and adults may differ with respect to their cerebral vasculature in both normal and pathological states. The authors have identified four pediatric patients in whom a cerebral arteriovenous malformation (AVM) recurred after surgery for removal of the AVM and in whom a normal postoperative angiogram had been obtained. This phenomenon has not been observed in adults. The propensity to regrow a cerebral AVM may reflect a less mature cerebral vasculature and a disregulated angiogenic process. Recently, attention has focused on vascular endothelial growth factor (VEGF) as a possible general mediator of angiogenesis in development and neoplasia. A retrospective immunocytochemical analysis of VEGF expression in AVM tissue was conducted to test the hypothesis that VEGF expression may be found in association with the regrowth of AVMs. The results demonstrate a high degree of astrocytic VEGF expression in four (100%) of four specimens from the initial operation in the children with recurrent AVMs as compared to one (14%) of seven nonrecurrent AVMs in the pediatric and two (25%) of eight adult specimens. All of the specimens from the first operation of the recurrent group demonstrate a clear association of cellular immunoreactivity to the abnormal blood vessels, a relationship that was not observed in the specimens from the nonrecurrent groups. These observations indicate that a humoral mechanism mediated by VEGF may play a role in AVM recurrence.

Intracerebellar "fibroma". Case report.

The authors report a unique case of intracerebellar fibroma; the tumor was well circumscribed and was treated by complete excision.

Epithelial differentiation in intraspinal meningiomas.

To investigate the epithelial features of intraspinal meningiomas, 25 intraspinal meningiomas and 25 intracranial meningiomas were examined for the presence of pseudopsammoma bodies with hematoxylin-eosin and periodic acid-Schiff staining. In addition, we investigated the expression of keratin and epithelial membrane antigen (EMA) by immunohistochemical methods. Pseudopsammoma bodies were found in 3 of 25 cases of intracranial meningiomas (12%), but no definitive pseudopsammoma bodies were observed the intraspinal meningiomas. Three cases (12%) of intraspinal meningiomas and 9 cases (36%) of intracranial meningiomas, including 3 cases with pseudopsammoma bodies, were immunoreactive for keratin. All 25 (100%) intracranial meningiomas and 20 of 25 (84%) intraspinal meningiomas were reactive for EMA. In the intraspinal meningiomas, 4 of 25 cases (16%) showed no reactivity for EMA. These findings suggest that the origin of certain cell components of meningiomas may be different according to the site of the tumor or that the nature of meningioma may be modified by the local environment.

A histopathological study of craniopharyngioma with special reference to its stroma and surrounding tissue.

The numerous pathology reports on craniopharyngioma describe the classical features of squamous epithelium and keratin. Relatively little attention has been paid to its stroma and the surrounding tissue. We focused our observation on these two areas in a retrospective study of craniopharyngiomas in 36 operative cases and 5 autopsy cases. The tumor interdigitated with the brain and pituitary gland. At the interface, the brain was markedly gliotic with Rosenthal fibers simulating pilocytic astrocytoma. The tumor stroma had reactive changes and commonly showed cyst formation and calcification.

Ganglion cyst of the odontoid process. Case report and review of the literature.

STUDY DESIGN: This case report illustrates that although it is rare, a ganglion cyst can occur intraosseously in the odontoid process. OBJECTIVES: The tissue diagnosis was established by surgical resection of the cyst membrane and evacuation of the cyst content. The patient tolerated the procedure well, and the hospital course was uneventful. SUMMARY OF BACKGROUND DATA: Synovial cyst of the spine is uncommon and is usually found in the lumbar region. Its occurrence in the cervical spine is rare, and no cases in the odontoid process, to the authors' knowledge, have been reported. METHODS: This patient was evaluated initially for neck pain, which led to radiographic studies depicting the lesion. It raised the suspicion of metastatic neoplastic process, although the search for primary source proved to be negative. A biopsy was indicated. RESULTS: Surgical findings consisted of mucoid material field cavity lined by a thin membrane. The cyst was excised, and pathologic evaluation confirmed the diagnosis of synovial cyst. CONCLUSION: The correct radiographic diagnosis of this patient was not made because of lack of experience with such lesions in this location. The authors hope that this case report helps raise the awareness of clinicians in considering this diagnosis when facing similar radiographic presentation.

Vasoformative tumor of the brain--immunohistology and ultrastructure.

A congenital vasoformative tumor in the brain of a 2-week-old boy manifested a variety of vascular spaces ranging from varices to solid cellular areas. The location of rod-shaped forms of reactivity to the immunoperoxidase stain for Factor VIII-related antigen corresponded with that of numerous Weibel-Palade bodies in the endothelial cell component of the tumor.

Solitary primary CNS lymphoma: long term survival following total resection.

Primary non-Hodgkin's CNS lymphoma is rare, constituting 0.3-1.5% of all intracranial neoplasms in patients without AIDS. In the past 10 years the incidence has tripled in this population. The role of surgery is commonly limited to obtaining adequate tissue for diagnosis. This has precluded the evaluation of total surgical resection for a surgically accessible solitary lesion. We have encountered a 36-year-old healthy white male with primary CNS lymphoma who is HIV-negative and who has survived over five years disease free after total surgical resection of his lymphoma.