Josefina F. Llena

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.

Ultrastructural and immunohistochemical studies on ballooned cortical neurons in Creutzfeldt-Jakob disease: expression of αB-crystallin, ubiquitin and stress-response protein 27

SummaryThis report concerns ultrastructural and immunohistochemical studies on ballooned neurons of ten patients with Creutzfeldt-Jakob disease (CJD). While abundant ballooned neurons and severe white matter degeneration was seen in six Japanese cases, only occasional ballooned neurons and no white matter degeneration was observed in four cases from the files of Montefiore Medical Center. Ultrastructurally, the ballooned neurons contained granule-coated fibrils of 25 to 40 nm in width and 10-nm neurofilaments. The immunohistochemical studies revealed that most ballooned neurons expressed αB-crystallin, with deposits of reaction products observed in the cytoplasm. A similar intracellular staining pattern was also seen with the antibody to phosphorylated neurofilament proteins (pNFP). Although the proportion of stained ballooned neurons was less, a positive reaction was also observed with antibodies against ubiquitin, stress-response protein 27 (srp 27) and synptophysin, but not with an antibody to srp 72. Our findings suggest that expression of pNFP and synaptophysin by ballooned neurons may reflect axonal impairment and that the presence of αB-crystallin, srp 27 and ubiquitin may be related to the degenerative processes that neurons undergo in CJD.

Modified Bielschowsky stain and immunohistochemical studies on striatal plaques in Alzheimer's disease

SummaryThe nature of senile plaques (SP) in the striatum in 14 cases of Alzheimers disease (AD) was investigated with the modified Bielschowsky stain and immunohistochemistry using antibodies to a β amyloid synthetic peptide, ubiquitin, tau protein, and paired helical filaments (PHF). Striatal SP, composed of β amyloid deposits with or without neuritic elements, were demonstrated in all AD cases examined. Compact and perivascular amyloid deposits were concentrated in the ventral striatum, including the nucleus accumbens. Many diffuse amyloid deposis in the ventral striatum contained ubiquitin-positive granular elements, presumably representing dystrophic neurites, whereas most of those in the dorsal striatum did not have such elements. On the other hand, most compact amyloid deposits in both ventral and dorsal striatum had ubiquitin immunoreactivity. Dystrophic neurites with tau or PHF immunoreactivity were detected particularly around compact amyloid deposits. Our results indicate that the ventral striatum, which is closely affiliated with the limbic system, is frequently affected by amyloid deposits with dystrophic neurites, and suggest that the ventral striatum is particularly vulnerable to AD. Furthermore, our results suggest that amyloid deposits, especially compact deposits, may induce dystrophic neurites.

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

Senile plaques (SP) in the cerebellum of 23 cases of Alzheimers 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 (βASP), 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 βASP. 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.

Paraganglioma in the cauda equina region.

SummarySome new ultrastructural observations are documented in a paraganglioma in the cauda equina region. These include the presence of nerve fibers in the tumor capsule, clear vesicles and tubulo-vesicular structures in some cytoplasmic processes in the tumor, fenestrated endothelial cells, and numerous tubular bodies in some endothelial cells.

Fine structure of a cerebellar "fibroma"

SummaryThe fine structure of an intracerebellar “fibroma” has been examined. The tumor consists of irregularly-shaped cells connected by well developed junctional complexes. Unusual, fenestrated capillaries with extremely narrow and irregular lumens are frequent. Collagen fibers are not common but the wide extracellular spaces contain large amounts of dense, granular or fibrillar material. The dense material coats the tumor cells and is apparently secreted from small vesicles found within these cells.

Glioblastoma multiforme of the cerebellum five decades after irradiation of a cerebellar tumor.

A 70-year-old woman is reported who had glioblastoma multiforme of the cerebellum 52 years after radiation therapy to a midline cerebellar tumor. Seven similar reported cases are reviewed. Dedifferentiation of astrocytoma to glioblastoma and the role of radiation therapy are discussed.

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.

Granulocytic sarcoma of the central nervous system: Inital presentation of leukemia

SummaryGranulocytic sarcoma as the presenting feature of leukemia is rare. Although it has been reported in various sites such as the retrobulbar area, mastoid region, iliac bone, and breast, this appears to be the first recorded case presenting as an intracranial tumor.

Solitary primary CNS lymphoma : long term survival following total resection

Primary non-Hodgkins 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.