Central nervous system lymphoma in the acquired immunodeficiency syndrome

Primary central nervous system (CNS) lymphomas were studied in fifteen autopsied patients with the acquired immunodeficiency syndrome (AIDS). Using the working formulation for non-Hodgkin's lymphomas, the tumors were classified as large cell (7 patients), mixed large and small cell (6 patients), small cleaved cell (1 patient), and unclassifiable (1 patient). The mixed lymphomas displayed unusual features characterized by a high mitotic rate and the presence of numerous medium-sized cells (5 to 10 mus), not classifiable using the working formulation. Focal T cell and lymphoplasmacytoid B cell infiltrates accompanied lymphoma cells at the periphery of and remote from solid tumor masses in 9 cases. Immunohistochemical analysis of the lymphomas suggested B cell neoplasms. All of these patients had concurrent CNS and systemic cytomegalovirus (CMV) infections. The CNS infections were of both viral (CMV, human immunodeficiency virus (HIV), varicella zoster virus (VZV), progressive multifocal leukoencephalopathy (PML) and non-viral (toxoplasmosis, candidiasis) etiology. In the general AIDS population at our institution, the autopsy incidence of CNS infections and systemic CMV was 63% and 60%, respectively. In contrast, the incidence for both these entities was 0% in otherwise healthy, non-AIDS patients with CNS lymphoma supports the hypothesis that viral infection plays a role in the pathogenesis of CNS lymphoma in the immunocompromised. Polyclonal lymphoplasmacytoid B and T cell infiltrates accompanying lymphoma may produce diagnostic difficulties on surgical biopsy. As these infiltrates were a frequent feature in this study, we caution that their recognition does not argue against the presence of CNS lymphoma.     

Central nervous system immune reconstitution disease in acquired immunodeficiency syndrome patients receiving highly active antiretroviral treatment

Highly active antiretroviral therapy (HAART)-induced immune restoration has been very beneficial for acquired immunodeficiency syndrome (AIDS) patients. In rare instances, HAART may induce a paradoxical clinical deterioration due to an immune reconstitution inflammatory syndrome (IRIS). This syndrome has been described with a wide variety of systemic infections and, in the central nervous system, with Cryptococcus neoformans infection, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy (PML). The authors have examined brain tissue in eight cases of IRIS: two autopsy cases and three biopsy cases of HIV encephalitis with IRIS and one autopsy case and two biopsy cases of PML with IRIS. All the patients presented with clinical deterioration following initiation of HAART and imaging showed contrast enhancement of the lesions. The symptoms regressed in four patients whereas the other four patients died. Neuropathological examination revealed severe inflammatory and demyelinating lesions with marked intraparenchymal and perivascular infiltration by macrophages and T lymphocytes. In some cases abundant viral proliferation was identified by immunocytochemistry or in situ hybridization, but in others the infectious agent could only be detected using PCR. T lymphocytes were predominantly CD8(+). In those cases with the more favorable course, inflammation was less severe with marked macrophage activation and a number of CD4(+) lymphocytes; in contrast, in the lethal cases inflammation was severe and mostly composed of CD8(+) cytotoxic lymphocytes. We conclude that HAART-induced paradoxical aggravation of HIV encephalitis or AIDS-related PML due to IRIS is reversible in most cases but may be lethal in others. In fatal cases, fulminant viral infection and/or acute perivenous leukoencephalitis may result from a dysregulation of the CD8(+)/CD4(+) T-cell balance.     

CNS toxoplasmosis in acquired immunodeficiency syndrome

Several distinct patterns of neurological involvement occur in epidemic acquired immune deficiency syndrome (AIDS). Two patients with this disorder had Toxoplasma gondii encephalitis, one suspected and one proved. Computed tomographic (CT) scanning showed focal lesions in both patients. Spinal fluids were remarkable for elevated protein, hypoglycorrhachia, and absence of pleocytosis. In patients with AIDS, focal CT scan findings and serum indication of past T gondii infection should prompt strong consideration of the diagnosis of CNS toxoplasmosis. The absence of specific IgM antibody or rise in IgG antibody titer to T gondii does not exclude this condition in the immune compromised host. In the patient with AIDS, CNS lesions mimicking brain abscess warrant biopsy or empiric therapy for T gondii. Early recognition and initiation of a prolonged or indefinite course of pyrimethamine plus sulfonamide therapy could reduce the mortality associated with this infection in AIDS. Computed tomographic scans, repeated frequently, appear, at present, to be the best guide to monitor the status of CNS involvement.     

Isolated central nervous system aspergillosis in the acquired immunodeficiency syndrome.

Aspergillus infection involving the central nervous system are unusual, but should be included in the differential diagnosis in patients with the acquired immunodeficiency syndrome and neurologic signs and symptoms. Of the few reported AIDS cases with central nervous system aspergillosis, the majority have had focal brain abscesses. We report an atypical case that presented as a basal meningitis with pontine infarction secondary to invasive Aspergillus sinusitis.     

Central nervous system infection in a murine retrovirus-induced immunodeficiency syndrome

Astrocyte-enriched primary glial cultures (AGC) from C57BL/6 mice were found to be highly susceptible to infection with the replication competent components of LP-BM5, consisting of the ecotropic and mink cell focus-inducing (MCF) helper murine leukemia viruses (MuLVs). The presence in infected AGC of defective LP-BM5 MuLV genome, a critical component for induction of the disease referred to as murine AIDS, was confirmed by Southern blot hybridization using a probe reactive with the p12 gag sequence of the 4.9 kb defective genome. Electron microscopic studies demonstrated C-type retrovirus particles in both astrocytes and microglial cells. In vivo studies demonstrated that the ecotropic MuLVs and the defective genome could be detected within AGC obtained form either 14-day-old mice following intraperitoneal inoculation or 7-day-old mice following intracranial inoculation. These findings suggest that: (1) the central nervous system (CNS) infection is present at an early stage in murine AIDS, (2) both astrocytes and microglial cells are possible CNS targets in which helper MuLVs replicate, and (3) these cells can harbor the defective genome that is a critical component for disease induction.     

Central nervous system Strongyloides stercoralis in acquired immunodeficiency syndrome: a report of two cases and review of the literature

Summary Hyperinfection with Strongyloides stercoralis is rare in acquired immunodeficiency syndrome (AIDS), despite endemicity in areas where infection with human immunodeficiency virus is highly prevalent. We autopsied two patients with AIDS and disseminated Strongyloides and describe their central nervous system findings. The microscopic patterns of brain infection were dissimilar in the two patients, and reflected histology in systemic viscera. In one patient, a granulomatous response accompanied filariform larvae in all locations, including granulomatous ependymitis in brain. Additionally in the brain, larvae without tissue reaction were seen. In the second patient, the absence of tissue response to larvae was body wide, and isolated parasites were found in centrum semiovale. The occurrence of these patients in a region where Strongyloides is not endemic suggests that this infection may be more prevalent in AIDS than formerly suspected.     

Aspergillus infection of the central nervous system in patients with acquired immunodeficiency syndrome

Infections of the central nervous system in patients with the acquired immunodeficiency syndrome are common. Of the many microorganisms that have been implicated, infection with Aspergillus is rare. We describe three patients with Aspergillus infection of the nervous system. Two patients had cerebral lesions due to Aspergillus flavus, and one patient had Aspergillus fumigatus infection of the spinal cord. Diagnosis of the infections was difficult, and therapy appeared to be ineffective.     

Central nervous system lymphomas and immunodeficiency

Primary lymphomas of the central nervous system (CNS) may sometimes be associated with some immunological abnormalities, including renal or cardiac transplants, some congenital and acquired immunodeficiencies, immunoinflammatory diseases and immunosuppressive treatments. A relatively high incidence of cerebral lymphomas has been particularly noticed in renal or cardiac transplantation patients and in those with acquired immune deficiency syndrome (AIDS), two conditions which are today observed with increasing frequency. The different congenital and acquired immunodeficiencies associated with cerebral lymphomas and the pathogenetic connections between the two conditions are discussed from a large review of the literature.     

Skeletal muscle toxoplasmosis in patients with acquired immunodeficiency syndrome: a clinical and pathological study.

The present article describes the clinical and pathological findings in 5 human immunodeficiency virus (HIV)-infected patients with muscle toxoplasmosis. The patients had marked lymphopenia (5/5), with less than five CD4+ cells/mm3 (3/3), when they developed fever (5/5), and multiorgan failure (5/5), including diffuse encephalitis, pneumonia, pancytopenia, and myopathy. Muscle involvement included weakness and wasting (4/5), myalgias (3/5), and high serum creatine kinase levels (3/3). Serology for toxoplasmosis showed high IgG titers in 3 patients (3/4). Anti-Toxoplasma therapy resulted in complete recovery in 2 patients. Muscle toxoplasmosis was detected by biopsy (3/5) or postmortem evaluation (2/5), and was identified using immunocytochemistry and electron microscopy. Toxoplasma cysts were detected in 0.5 to 4% of muscle fibers close to or remote from necrotic fibers and inflammatory infiltrates. Muscle fibers strongly expressed the major histocompatibility complex class I antigen (2/2) as in polymyositis. We suggest that Toxoplasma gondii should be sought by muscle biopsy in patients who have acquired immunodeficiency syndrome with fever, encephalitis, multiorgan dysfunction, and elevated serum creatine kinase levels of obscure origin.     

以中枢神经系统症状为首发表现的AIDS

目的探讨以中枢神经系统症状为首发表现的AIDS的临床特征及预后,提高对这部分患者的诊断识别能力。方法连续选择云南省德宏州盈江县人民医院的AIDS住院患者共165例,并对其中以中枢神经系统症状为首发表现的32例患者的临床资料进行回顾性分析。结果 32例患者中AIDS痴呆综合征10例,结核性脑膜炎4例,隐球菌脑膜炎5例,脑弓形虫病11例,蛛网膜下腔出血1例,脊髓损伤但性质未明确者1例。本组32例患者中1年内死亡的有26例,占81.2%。结论以中枢神经系统症状为首发表现的AIDS患者病情复杂,多合并中枢神经系统机会性感染,且进展快,预后差,死亡率高。     

Solitary midbrain toxoplasmosis and olivary hypertrophy in a patient with acquired immunodeficiency syndrome

Toxoplasmosis, one of the most common central nervous system lesions in patients with the acquired immunodeficiency syndrome (AIDS), has not been reported as a solitary lesion in the brainstem. This report describes a patient with AIDS that presented with third cranial nerve palsy and contralateral cerebellar signs, who at autopsy had a necrotic midbrain lesion due to toxoplasma. Inferior olivary hypertrophy, due to interruption of olivary afferent fibers by the lesion, in addition to subacute encephalitis and vacuolar myelopathy were other CNS findings.     

Central nervous system involvement in patients with acquired immune deficiency syndrome (AIDS)

Central nervous system involvement occurred in 28 of 121 patients with acquired immune deficiency syndrome (AIDS). The major risk factor in this AIDS population was intravenous drug abuse (64%). A neurologic symptom or disability was the principal reason for hospitalization in 16 cases (57%). Three patients had primary lymphoma of the brain and the remainder had opportunistic infections. Patients with focal neurological features usually had toxoplasmosis. Progressive headache and meningeal signs occurred with cryptococcosis. A progressive subacute dementia was probably due to cytomegalovirus. Other infections included atypical mycobacteria, candida, herpes zoster and possible progressive multifocal leukoencephalopathy.     

Central nervous system lesions in von Hippel-Lindau syndrome.

CNS manifestations were studied in 97 gene carriers of von Hippel-Lindau syndrome (HLS). Haemangioblastomas of the CNS were found in 43 patients (44%), 23 females and 20 males. The mean age at diagnosis was 39 years (12-73 years). A total of 93 haemangioblastomas were detected of which 74% were intracranial and 26% were located in the spinal cord; 75% were predominantly cystic and 25% presented as solid lesions. Multiple lesions were found in 42% of HLS-associated haemangioblastomas, but in none of 51 patients with CNS haemangioblastoma without HLS. Haemangioblastoma was the cause of death in 82% of patients with HLS. Although microsurgery has considerably improved post-operative results, multifocal tumour development and recurrence remain a serious problem in the clinical management of HLS gene carriers.     

Central nervous system involvement in the eosinophilia-myalgia syndrome.

A patient with eosinophilia-myalgia syndrome developed progressive central nervosa system involvement that did not improve despite discontinuation of L-tryptophan therapy. Neurologic impairment was manifested initially by spastic monoparesis, which was improved by treatment with methyl-prednisolone and hydroxyurea. Recurrence of weakness was accompanied by gait ataxia, dysphagia, and complaints of a gradual decline in memory and concentration. Neuropsychological testing identified a broad pattern of cognitive deficits suggestive of a subcortical dementia, and magnetic resonance imaging demonstrated multiple high-signal lesions in the white matter. Cognitive deficits appear to be underrecognized in patients with the eosinophilia-myalgia syndrome. The response of our patient's initial symptoms to corticosteroid therapy suggests a possible role for autoimmune mechanisms in the pathogenesis of central nervous system involvement in the eosinophilia-myalgia syndrome. Neuropsychological evaluation should be performed in patients with cognitive complaints to delineate the full spectrum of central nervous system impairment associated with the eosinophilia-myalgia syndrome.     

Human acquired immunodeficiency virus infection of the nervous system

Neurological manifestations of HIV infection are recognised at different phases of the evolution of the disease. During the late stages opportunistic neuro-meningeal infections and tumors develop as a result of the immuno-suppression. There exist, however, various manifestations which evolve independently of the immune state, and seem to be directly related to the virus itself. One can distinguish central neuro-meningeal syndromes and peripheral syndromes at the onset, or at later stages. Their prognostic implications are uncertain, but often severe, for example in the case of the subacute dementias which, in this setting, may lead to death in several months. There are also other manifestations which may be self limited or slowly evolving in the central and peripheral nervous systems. The neuropathological changes are known for the dementias as mentioned above, though the characteristics lesions due to HIV infection per se remain controversial. The presence of the virus in the nervous system has been established by in situ hybridization techniques, immunohistochemistry and culture. Studies on CSF have also allowed virological (cultures) and immunological studies to be carried out. The physiopathological mechanisms for the apparent neurological effects of this virus remain hypothetical. A better understanding of these mechanisms should lead to a rationalisation of therapeutic strategies, in a disorder which would seem to be an early and persisting viral infection of the nervous system.     

Progressive tumefactive inflammatory central nervous system demyelinating disease in an acquired immunodeficiency syndrome patient treated with highly active antiretroviral therapy

We report here a case of progressive tumefactive inflammatory central nervous system (CNS) demyelinating disease in a human immunodeficiency virus (HIV)-seropositive patient treated with highly active antiretroviral therapy (HAART). Biopsy revealed diffuse macrophage and perivascular T-lymphocytic infiltrates with severe demyelination and relative axonal sparing. The disease progressed in a centrifugal fashion, to involve bihemispheric cerebral white matter, with subsequent central necrotic changes and atrophy. Treatment with HAART was discontinued, and inflammatory disease was treated with subcutaneous interferon (IFN)β-1a. Massive brain edema was controlled with courses of intravenous corticosteroids. Following fulminant monophasic disease, the patient stabilized with no evidence of disease progression over long-term follow up. We propose that immune response reconstituted by HAART can unmask an autoimmune response in susceptible individuals, analogous to the enhanced immune response to the preexisting acquired immunodeficiency syndrome (AIDS) opportunistic infections. Therapeutic options are considered.     

Serologic evidence of human immunodeficiency virus infection of the central nervous system in African patients with acquired immunodeficiency syndrome

The intrathecal synthesis of antibodies to human immunodeficiency virus (HIV) was determined by 3 different immunoassays in 15 African patients with pre-acquired immunodeficiency syndrome (AIDS) and AIDS. Isoelectric focusing together with affinity-mediated immunoblot were found to be superior to enzyme-linked immunosorbent assay and Western blot in providing information not only about the antigen specificity of locally produced antibodies but also about their clonal distribution. In 9 of the subjects, HIV-specific oligoclonal bands were demonstrable with higher frequency or intensity in the cerebrospinal fluid than in the autologous serum, indicating autochthonous synthesis of HIV-related antibodies.