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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the onset of the acquired immune deficiency syndrome (AIDS) epidemic fifteen years ago, much has been learned about the effects of the human immunodeficiency virus (HIV) in the nervous system. This review summarizes the pathology findings in the central nervous system (CNS). There is now abundant evidence that HIV can infect the CNS directly, leading to a characteristic HIV encephalitis (HIVE) which occurs in 10-50 p. 100 of AIDS autopsy series. Multinucleated giant cells are the pathognomonic feature of HIVE and are found predominantly in the central white matter and deep grey matter. Evidence of productive HIV infection in the CNS is confined to cells of the microglial/macrophage lineage, from which the giant cells are almost certainly derived. These cells are known to express both CD4 and beta-chemokine receptors, which act in conjunction to permit HIV entry. Restricted infection of astrocytes has also been identified by a variety of methods. HIVE is frequently associated with white matter damage ranging from inflammatory (microglia, macrophages and sparse lymphocytes) to degenerative (myelin loss and axonal damage) pathology. Although giant cells are seen less frequently in neocortical grey matter, significant neuronal loss has been established in a number of studies. Recent investigations using markers of apoptosis, (including TUNEL, Bcl-2 and BAX), have established the presence of DNA damage in some neurons and in other cell types. Axonal damage has also been confirmed by evidence of amyloid precursor protein expression. The CNS is also vulnerable to opportunistic infections and high grade B-cell lymphomas as a result of the immune suppression of advanced HIV infection. Cytomegalovirus (CMV) infection is reported in 10-30 p. 100 of AIDS cases at autopsy, toxoplasma in 10-25 p. 100, progressive multifocal leucoencephalopathy in about 5 p. 100 and lymphomas, usually primary, in up to 10 p. 100. A wide variety of other infections has also been reported. These may coexist with HIVE and may be difficult to diagnose in life. CMV gives rise to microglial nodular encephalitis, ventriculitis, necrotising encephalitis and myelo-radiculitis. Presymptomatic HIV positive patients do not show HIVE or opportunistic infections or lymphomas in the CNS. They frequently display a low-grade T-cell infiltrate in the leptomeninges and parenchyma, particularly around vessels. This lymphocytic infiltrate has been attributed to presumed early invasion of the CNS by HIV although the exact timing of entry is uncertain. It is possible that reported abnormalities in presymptomatic cases such as gliosis, microglial activation and rising proviral load may anticipate the onset of HIVE but most studies show that significant CNS damage and HIV-related pathology is confined to patients with AIDS. HIV-related pathology in the spinal cord includes not only HIV myelitis, opportunistic infections and lymphomas, but also vacuolar myelopathy (VM) which affects predominantly the dorsolateral white matter tracts. The cause of VM is not understood and has not been unequivocally linked with HIV infection. It is noted that none of these neuropathological features (including HIVE) correlates exactly with the clinical expression of AIDS-related dementia (ARD). The exact contribution of macrophage activation and cytokine release, astrocytic infection, neuronal loss and axonal damage to the neuropsychiatric syndromes of advanced HIV infection remain to be determined. While the current understanding of the pathogenesis of HIVE and ARD is beyond the scope of this review it is axiomatic that accurate documentation of neuropathology findings will help to resolve the outstanding dilemmas relating to HIV infection of the CNS. There is considerable optimism that progress in therapeutic regimes for HIV-infected patients will succeed in eliminating the virus from the blood and from lymphoid tissue. (ABSTRACT TRUNCATED)
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PMID:The neuropathology of adult HIV infection. 993 3

Lentiviruses such as Maedi Visna virus (MVV) in sheep, and human immunodeficiency virus (HIV) in man often cause a variety of neurological syndromes in later stages of infection. Neuropathological investigations reveal damage to myelin and astrocytosis in both white and grey matter. MVV infection induces axonal damage with some areas of necrosis while neuronal loss, and synaptic damage have been reported in HIV-1 infection. It is not clear, at present, how this neurodegeneration is mediated but, as these viruses do not directly infect neurons, an indirect neurotoxic action of the viruses is indicated. Previous experiments have shown that the intra-striatal injection in rats of a synthetic peptide derived from the basic region of the MVV transactivating protein Tat causes considerable neurotoxicity 1 week post-operatively. By in vivo stereotaxic injections of the same synthetic peptide, and subsequent immunocytochemical detection of neurons, astrocytes and microglia, we show that this neurotoxicity displays a distinctive and unusual lesion profile and is evident as rapidly as 0.5 h post-operatively. Furthermore, neuroprotection studies suggest that the early effects of the MVV tat peptide may involve glutamate neurotoxicity via the N-methyl-D-aspartate (NMDA) receptors since the application of dizolcipine (MK801) reduces the volume of the lesion seen at 1 h after the injection of neurotoxic peptide, while L-NAME is ineffective. The mechanism of this early neurotoxicity is thus different from the longer term actions already described.
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PMID:Acute in vivo neurotoxicity of peptides from Maedi Visna virus transactivating protein Tat. 1036 85

We report a patient with common variable immunodeficiency (CVID) who developed an axonal sensorimotor polyneuropathy, a hitherto unreported association to our knowledge. These conditions may be linked at the pathogenetic level, since some CVID patients are prone to the development of autoimmune disease.
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PMID:Peripheral neuropathy associated with common variable immunodeficiency. 1105 46

This article addresses syndromes that clinically and/or radiologically resemble acute stroke. These syndromes generally fall into four categories. (1) Patients with acute neurological deficits with nonischemic lesions and no acute abnormality on diffusion-weighted images. These patients may have peripheral vertigo, migraines, seizures, dementia, functional disorders, amyloid angiopathy, or metabolic disorders. When these patients present, we can confidently predict that they are not undergoing infarction. (2) Patients with ischemic lesions with reversible clinical deficits. Nearly 50% of patients with transient ischemic attacks have lesions with restricted diffusion. Patients with transient global amnesia may have punctate lesions with restricted diffusion in the medial hippocampus, parahippocampal gyms, and corpus callosum. (3) Vasogenic edema syndromes that may mimic acute infarction clinically and on conventional imaging. These include eclampsia/hypertensive encephalopathy, other posterior leukoencephalopathies, human immunodeficiency virus encephalopathy, hyperperfusion syndrome following carotid endarterectomy, venous sinus thrombosis, acute demyelination, and neoplasm. These syndromes demonstrate elevated diffusion rather than the restricted diffusion associated with acute ischemic stroke. (4) Entities in which restricted diffusion may resemble acute infarction. These include pyogenic infections, herpes virus encephalitis, Creutzfeldt-Jakob disease, diffuse axonal injury, tumors with dense cell packing, and rare acute demyelinative lesions.
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PMID:Diffusion-weighted imaging as a problem-solving tool in the evaluation of patients with acute strokelike syndromes. 1114 28

Painful sensory neuropathy is a common and debilitating consequence of human immunodeficiency virus (HIV). The underlying causes of neuropathic pain are most likely not due to direct infection of the nervous system by active virus. The goal of this study was to determine whether epineural exposure to the HIV-1 envelope protein gp120 could lead to chronic painful peripheral neuropathy. Two doses of gp120 or BSA control were transiently delivered epineurally via oxidized cellulose wrapped around the rat sciatic nerve. Animals were assessed for neuropathic pain behaviors at several intervals from 1-30 days following nerve surgery. Allodynia and hyperalgesia were observed within 1-3 days following gp120 and sustained throughout the testing period. The gp120-exposed sciatic nerve exhibited early but transient pathology, notably axonal swelling and increased tumor necrosis factor alpha (TNF-alpha) within the nerve trunk. In contrast, intense astrocytic and microglial activation was observed in the spinal cord, and this gliosis persisted for at least 30 days following epineural gp120, in parallel with neuropathic pain behaviors. These findings demonstrate that limited peripheral nerve exposure to HIV protein can induce persistent painful sensory neuropathy that may be sustained and magnified by long-term spinal neuropathology.
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PMID:Peripheral nerve exposure to HIV viral envelope protein gp120 induces neuropathic pain and spinal gliosis. 1131 27

Axonal damage represented by accumulation of beta-amyloid precursor protein (beta-APP) develops in numerous central nervous system (CNS) diseases including human immunodeficiency virus (HIV) infection. To study the underlying mechanisms of axonal damage associated with HIV CNS infection, the amount of axonal beta-APP immunostaining in the corpus callosum of 24 simian immunodeficiency virus (SIV)-infected macaques and 3 control macaques was measured by computerized image analysis. The amounts of beta-APP accumulation were then compared with time post-inoculation, extent and character of CNS inflammation, and viral load in the CNS measured by the amount of immunohistochemical staining for the viral transmembrane protein gp41. Significant increases over control values were present in 10 of 24 SIV-infected animals. SIV encephalitis was present in 9 of the 10 animals with elevated beta-APP Increases in beta-APP correlated most strongly with levels of SIV gp41 in the brain (p = 0.005), but significant associations with macrophage infiltration and microglial activation (p = 0.04) and infiltration by cytotoxic lymphocytes (p = 0.05) also were identified. These data demonstrate that beta-APP accumulation in the white matter of SIV-infected macaques develops during SIV infection in close correlation with levels of viral replication and may serve as a sensitive marker of neuronal/axonal damage mediated by viral proteins.
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PMID:Accumulation of beta-amyloid precursor protein in axons correlates with CNS expression of SIV gp41. 1182 47

Peripherin is a member of the type III intermediate filament family, expressed in neurones of the peripheral nervous system of many species and in a discrete subpopulation of neurones of the central nervous system (CNS) during early development in rodents. Previous studies on rats have shown that peripherin immunoreactivity increased significantly in cell bodies of spinal motor neurones following axonal injury. Our study examined the expression of peripherin in the cerebrum of normal macaques (Macaca mulatta and Macaca fascicularis) and those with encephalitis of viral (simian immunodeficiency virus and simian virus 40) or autoimmune (experimental allergic encephalomyelitis) aetiology. Immunohistochemistry, immunoelectronmicroscopy, immunofluorescence and confocal microscopy were performed on tissue sections using antibodies against cell-specific markers and peripherin. Peripherin-positive cells were absent in the cerebrum of normal macaques of all ages examined, whereas animals with encephalitis had peripherin-positive cells associated with inflammatory infiltrates. Further evaluation revealed that these peripherin-positive cells were not neurones, but were predominantly astrocytes expressing glial fibrillary acidic protein. Our study suggests that peripherin is not neurone-specific in the CNS of macaques; peripherin is expressed in astrocytes of animals with encephalitis.
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PMID:Expression of peripherin in the brain of macaques (Macaca mulatta and Macaca fascicularis) occurs in astrocytes rather than neurones and is associated with encephalitis. 1190 26

The expression of interferon gamma (IFNgamma) increases after neural injury, and it is sustained in chronic inflammatory conditions such as multiple sclerosis and infection with human immunodeficiency virus. To understand how exposure to this proinflammatory cytokine might affect neural function, we examined its effects on cultures of neurons derived from the central and peripheral nervous systems. IFNgamma inhibits initial dendritic outgrowth in cultures of embryonic rat sympathetic and hippocampal neurons, and this inhibitory effect on process growth is associated with a decrease in the rate of synapse formation. In addition, in older cultures of sympathetic neurons, IFNgamma also selectively induces retraction of existing dendrites, ultimately leading to an 88% decrease in the size of the arbor. Dendritic retraction induced by IFNgamma represents a specific cellular response because it occurs without affecting axonal outgrowth or cell survival, and it is not observed with tumor necrosis factor alpha or other inflammatory cytokines. IFNgamma-induced dendritic retraction is associated with the phosphorylation and nuclear translocation of signal transducer and activator of transcription 1 (STAT1), and expression of a dominant-negative STAT1 construct attenuates the inhibitory effect of IFNgamma. Moreover, retrograde dendritic retraction is observed when distal axons are selectively exposed to IFNgamma. These data imply that IFNgamma-mediated STAT1 activation induces both dendritic atrophy and synaptic loss and that this occurs both at the sites of IFNgamma release and at remote loci. Regressive actions of IFNgamma on dendrites may contribute to the neuropathology of inflammatory diseases.
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PMID:Interferon gamma induces retrograde dendritic retraction and inhibits synapse formation. 1204 60

The primary target in multiple sclerosis (MS) is believed to be either myelin itself (myelinopathy) or the myelin-forming cell, the oligodendrocyte (oligodendrogliopathy). Although axonal injury occurs in MS, it is regarded as a secondary event to the myelin damage. Here, the lesion develops from myelin (outside) to the axon (inside) (Outside-In model). Recently, gray matter lesions and axonal injury in normal-appearing white matter have also been reported in MS. This raises two questions. 1) Is axonal injury exclusively secondary to myelin damage or from a direct insult to the axon or neurons (axonopathy)? (2) Is the injured axon regarded as only an end result of pathology or disease, or can axonal injury contribute to the spread of secondary damage, including demyelination? The former is raised from the fact that axonal damage has been reported in several virus infections, including human immunodeficiency virus, human T-lymphotropic virus 1, herpes simplex virus and coronavirus, which also cause demyelination. The latter possibility where axonal injury leads to other changes is raised from the rather unexpected similarity between spinal cord injury (SCI) and MS where axonal injury, oligodendrocyte apoptosis and demyelination are all present. In SCI, transection of axons leads to delayed oligodendrocyte apoptosis with secondary demyelination. Neurofilament immunostaining of spinal cord sections demonstrates that axonal injury with oligodendrocyte apoptosis also precedes demyelination in an animal model for MS, Theiler's murine encephalomyelitis virus infection. This implies that axonal injury could trigger demyelination. In this instance, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model).
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PMID:Inside-Out versus Outside-In models for virus induced demyelination: axonal damage triggering demyelination. 1250 60

Despite the high incidence of cognitive and motor impairment in acquired immunodeficiency syndrome (AIDS) patients, the mechanisms of AIDS-related central nervous system (CNS) pathology are not completely understood. Infection with simian immunodeficiency virus (SIV) in macaques provides an excellent model of AIDS, including human immunodeficiency virus (HIV)-induced CNS pathology and cognitive/behavioral impairment. Co-inoculation with two SIV strains, SIV/17E-Fr and SIV/DeltaB670, accelerates SIV CNS disease, producing SIV encephalitis in over 90% of pig-tailed macaques within 3 months. In the present study, this SIV model was employed to identify cellular and viral correlates of behavioral impairment following SIV infection. Measures of psychomotor speed (simple reaction time), fine motor control (bimanual motor task), and general motor activity (home cage movement) were all adversely affected by SIV disease. Prior to euthanasia, performance was significantly impaired in both a simple reaction time task in 6 of 12 monkeys and a bimanual motor task in 5 of 6 monkeys. All monkeys evaluated (11 of 11) showed significant reductions in spontaneous motor activity. Significant correlations were found between impaired performance on the bimanual motor test and axonal damage (accumulation of beta-amyloid precursor protein in the corpus callosum) as well as increased microglial activation and macrophage infiltration (levels of CD68 and Ham56 immunostaining). These results suggest that axonal damage is related to the behavioral impairment induced by infection with SIV. The axonal damage may result from neuroimmune responses, including microglial and macrophage activation. Therefore, axonal damage may be a morphologic manifestation of neuronal dysfunction that underlies development of behavioral impairment in HIV/SIV CNS infection.
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PMID:Central nervous system correlates of behavioral deficits following simian immunodeficiency virus infection. 1290 90


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