[Neuropathological study of 134 fetuses in HIV infected mother]. / Etude neuropathologique de 134 foetus dans un contexte d'infection maternelle par le VIH.

A neuropathological study performed in 134 foetuses from HIV infected mothers, between 16 and 35 weeks of gestation, revealed two cases of hypoxic-ischemic brain damage, related to long labor and drug abuse. Immunostains against HIV proteins were negative in all cases. Nests of migrating cells in the cerebrum and cerebellar heterotopias were found in most cases and were considered to be common findings in fetal brain. Our study clearly showed the absence of cerebral HIV infection during early pregnancy and raises the question of the frequency of vertical transmission during HIV infection. However, the evaluation of cerebral changes in infants with HIV infection should take into consideration the features of the developing brain and the existence of other adverse factors that may interfere with its development during pregnancy.

[Central nervous system infection due to varicella and zoster virus in AIDS]. / Infection du système nerveux central par le virus de la varicelle et du zona au cours du SIDA.

We have reviewed 23 cases of varicella-zoster virus infection of the central nervous system in patients with the acquired immunodeficiency syndrome, previously reported in the literature, including 11 from our own series. This allowed us to identify 5 clinico-pathological patterns which could occur simultaneously. In most cases, viral proteins or viral genome were identified using immunocytochemistry or in situ hybridization. Multifocal encephalitis involves predominantly the white matter and is likely to be due to haematogenous spread of the infection. Ventriculitis may have variable appearance according to the course of the disease. In one incipient case, the ependymal lining appeared irregular with foci of infected ependymal cells some of which protruded into the ventricular lumen; in other instances, there was acute or chronic necrosis of the ventricular wall with marked vasculitis. Acute haemorrhagic meningo-myelo-radiculitis with necrotising vasculitis may be associated with ventriculitis and results from shedding of infected ependymal cells into the ventricular lumen and secondary seeding of the cerebrospinal fluid. Focal necrotising encephalitis or myelitis usually follows cutaneous herpes zoster in the corresponding dermatoma and is considered to result from neural spread from the diseased trigeminal or dorsal root ganglion. Vasculopathy involving leptomeningeal arteries and causing cerebral infarcts is associated with meningitis in most cases. These findings are in keeping with the observation in other immunocompromised patients, that varicella-zoster virus spread to the central nervous system may follow different routes. Our study tends to show that varicella-zoster virus infection of the central nervous system is more frequent in the acquired immunodeficiency syndrome than previously suspected and suggests this diagnosis must be considered systematically in cases of encephalitis, ventriculitis, focal myelitis, acute myeloradiculitis and cerebral infarcts in these patients, since an efficient treatment is available.

Epstein-Barr virus in non-Hodgkin's lymphomas of the upper respiratory tract: association with sinonasal localization and expression of NK and/or T-cell antigens by tumour cells.

Fifty-five cases of non-Hodgkin's lymphoma (NHL) of the upper respiratory tract, comprising 27 sinonasal (SN) and 28 Waldeyer's ring (WR) NHL, were investigated for expression of Epstein-Barr virus (EBV)-encoded EBER transcripts and latent membrane protein-1 (LMP-1) by RNA in-situ hybridization (RISH) and immunohistochemistry, respectively. Thirty-two cases were B-cell tumours (10 SNHLs and 22 WRNHLs) and 23 cases expressed natural killer (NK) and/or T-cell antigens (17 SNHLs and 6 WRNHLs). EBER transcripts were detected in tumour cells in 19 lymphomas expressing NK and/or T-cell antigens (16/17 SHNHLs and 3/6 WRNHLs) but in only 2/32 B-NHLs (1/10 SNHLs and 1/22 WRNHLs). LMP-1 expression was found in tumour cells in the 19 EBER-positive tumours expressing NK and/or T-cell antigens but in none of the B-cell lymphomas. All the LMP-1-positive lymphomas expressed the CD30 molecule in tumour cells. These results indicate that in lymphomas of the upper respiratory tract, EBV is strongly associated with sinonasal localization and expression of NK and/or T-cell antigens by tumour cells. EBV can also be detected in some cases of WRNHLs expressing NK and/or T-cell antigens, whereas it is rarely found in B-cell SNHLs and WRNHLs. Furthermore, the detection of the LMP-1 protein in tumour cells in most SNHLs and some WRNHLs expressing NK and/or T-cell antigens, in view of the LMP-1 transforming potential, suggests that EBV may play a role in the pathogenesis of these lymphomas.

Isolated motor control dysfunction related to progressive multifocal leukoencephalopathy during AIDS with normal MRI.

We describe the case of a human immunodeficiency virus-infected 34-year-old man with progressive multifocal leukoencephalopathy (PML). His case displayed unusual features, including a bizarre movement disorder, predominant involvement of the subcortical U fibers on neuropathologic examination, and the absence of MRI abnormalities suggestive of PML. Anatomic-clinical correlations are discussed.

Varicella-zoster virus infection of the central nervous system in the acquired immune deficiency syndrome.

Productive varicella-zoster virus (VZV) infection of the central nervous system (CNS) was demonstrated in 11 acquired immune deficiency syndrome (AIDS) patients using immunocytochemistry and in situ hybridization. A characteristic zoster skin eruption was seen in only four cases. From our own series and 11 other cases in the literature, we identified five clinico-pathological patterns of VZV infection of the CNS in AIDS patients which could occur simultaneously. (i) Multifocal encephalitis predominantly involving the white matter, likely to be due to haematogenous spread of the infection was found in four cases. (ii) Ventriculitis was found in three cases. In two cases there was complete acute or chronic necrosis of the ventricular wall with marked vasculitis; in the third, the ependymal lining appeared irregular with foci of VZV-infected ependymal cells, some of which protruded into the ventricular lumen. (iii) Acute haemorrhagic meningo-myeloradiculitis with necrotizing vasculitis was observed in two cases. In one, this was associated with ventriculitis and was possibly due to shedding of infected ependymal cells into the ventricular lumen and secondary seeding of the CSF. (iv) Focal necrotizing myelitis was seen in one case. It followed cutaneous herpes zoster and was considered to result from neural spread from the diseased dorsal root ganglion similar to cases previously described of encephalitis limited to the visual system following VZV ophthalmicus, or bulbar encephalitis following a trigeminal zoster. (v) Vasculopathy involving leptomeningeal arteries and causing cerebral infarcts was seen in four cases, it was associated with meningitis in most cases. These findings are in keeping with the observation in non-AIDS patients that VZV spread to the CNS may follow different routes. Our study tends to show that VZV infection of the CNS occurs more frequently in AIDS than previously suspected and suggests that it must be considered as a diagnosis in cases of encephalitis, ventriculitis, focal myelitis, acute myeloradiculitis and cerebral infarcts in these patients.

Immunosuppressive effects of 1,25-dihydroxyvitamin D3 and its analogue calcipotriol on epidermal cells.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3; calcitriol) is the biologically active form of vitamin D. This hormone is a potent immunoregulatory agent. Calcipotriol is a synthetic analogue of 1,25(OH)2D3, with similar receptor binding, and comparable effects on cell proliferation and differentiation, but less potent effects on calcium metabolism. As a step towards understanding the mechanisms by which vitamin D compounds affect T-cell activation by epidermal cells (EC), we assessed the effects of 1,25(OH)2D3 and calcipotriol on the human allogeneic mixed epidermal cell-lymphocyte reaction. All experiments were performed both with 1,25(OH)2D3, and calcipotriol, with similar results. Both compounds had potent immunoinhibitory properties on this model, and enhanced the immunosuppressive effects of cyclosporin A. Using preincubation experiments, we found that pretreatment of EC with 1,25(OH)2D3 resulted in a more pronounced inhibition than preincubation of lymphoid cells. The epidermal targets of this inhibitory effect have been further investigated, using cultures with freshly isolated Langerhans cells (LC) or LC-depleted keratinocytes, separated by an immunomagnetic particle technique. Pretreatment of LC induced a 30% decrease of proliferation, compared with vehicle-treated LC. These calcitriol-pulsed LC did not decrease the proliferation induced by unmodified autologous EC. As expected, LC-depleted keratinocytes failed to stimulate allogenic lymphocytes. When added to autologous unmodified EC, however, calcitriol-pulsed keratinocytes induced an 85% decrease of proliferation, compared with vehicle-treated keratinocytes. The phenotypic expression of HLA-DR, -DQ, and -DP antigens on EC, assessed by immunoalkaline phosphatase staining, was not modified after a 2-h or 24-h pulse with 1,25(OH)2D3 or calcipotriol.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-NKH-1 antibody specifically stains unmyelinated fibres and non-myelinating Schwann cell columns in humans.

Anti-NKH-1 antibody recognizes an isoform of the neural cell adhesion molecule (N-CAM) that is involved in cell-cell interactions during embryonic stages and has been detected in skin autonomic nerves. The specificity of anti-NKH-1 antibody for human unmyelinated fibres (UF) and the distribution of the antigens recognized by this antibody at the ultrastructural level, were evaluated by immunohistochemistry and immunoelectron microscopy on nerve biopsy samples from patients with normal nerve biopsies and a variety of peripheral neuropathies. The anti-NKH-1 antibody strongly stained all unmyelinated fibres while no myelinated fibre was stained. Autonomic nerve fibres were visualized at the periphery of blood vessels. Immunoelectron microscopy showed that the antigen recognized by the antibody was located at Schwann cell-axon interfaces and in portions of joined Schwannian surfaces, i.e. along mesaxons of non-myelinating Schwann cells. Expression of NKH-1 was basically similar in normal and diseased nerves as expression of NKH-1 was similar at the level of apposed plate-like Schwann cell processes than along normal mesaxons. The extent of labelling of diseased nerves by the anti-NKH-1 antibody likely depended on the number of residual Schwann cell columns observed by light microscopy.

Epstein-Barr virus (EBV) genomes and EBV-encoded latent membrane protein (LMP) in pulmonary lymphomas occurring in nonimmunocompromised patients.

Recently, in situ hybridization (ISH) techniques have shown that Epstein-Barr virus (EBV) could be detected in tumor cells of most angiocentric T-cell non-Hodgkin's lymphomas (NHL). These studies included only a few cases of T-NHL of the lung and pulmonary B-NHL and have not been investigated. Furthermore, the expression of the EBV-encoded latent membrane protein (LMP), which is known for its oncogenic properties, has not been reported. Twelve pulmonary NHL (six angiocentric T-NHL and six B-NHL) arising in nonimmunocompromised patients were examined for the presence of EBV-EBER mRNAs and LMP with ISH and immunohistochemistry, respectively. Four cases of pulmonary lymphomas arising in immunocompromised patients were also included in the study for comparison (one T-NHL in a patient under immunosuppressive treatment and three B-NHL in AIDS patients). EBV-RNA and LMP were detected in tumor cells in two of six nonimmunocompromised angiocentric T-NHL and in the four immunocompromised NHL. The six nonimmunocompromised B-NHL were EBV negative. These results suggest that EBV is associated with some angiocentric pulmonary T-NHL arising in patients without overt immunodeficiency whereas it is absent in such patients with B-NHL. The presence of the transforming EBV-encoded LMP in tumor cells suggests that EBV may be involved in the pathogenesis of some pulmonary T-NHL.

The spectrum of vasculitis in human immunodeficiency virus-infected patients. A clinicopathologic evaluation.

OBJECTIVE: To delineate the different types of inflammatory vascular diseases (IVD) occurring in patients with human immunodeficiency virus (HIV) infection. METHODS: Muscle, nerve, or skin biopsy specimens from 148 symptomatic HIV-infected individuals were reviewed, and subgroups of vasculitis were identified using the American College of Rheumatology (ACR) 1990 clinicopathologic criteria for the classification of vasculitis. RESULTS: IVD was documented in 34 patients (23%) and included necrotizing arteritis (3 patients), non-necrotizing arteritis (1 patient), neutrophilic IVD (7 patients), mononuclear IVD (17 patients), and other small vessel inflammatory changes (6 patients). According to the ACR criteria, 11 patients could be classified as having a distinct category of vasculitis, including polyarteritis nodosa (4 patients), Henoch-Schönlein purpura (1 patient), and drug-induced hypersensitivity vasculitis (6 patients), and 23 were classified in the group "other vasculitis, type unspecified." One patient had hepatitis B virus surface antigenemia, 2 had cryoglobulinemia, and 2 were coinfected by human T lymphotropic virus type I. Cytomegalovirus inclusions and antigens were found in endothelial cells in 1 patient. HIV antigens and genome were detected in perivascular cells of 2 of the 3 patients with necrotizing arteritis; in 1, HIV-like particles were seen by electron microscopy. Immune deposits were found in small vessel walls in 5 skin biopsy samples showing small vessel vasculitis and in the muscle of the 3 patients with necrotizing arteritis. CONCLUSION: A wide range of inflammatory vascular diseases may occur in HIV-infected individuals. Vascular inflammation appears multifactorial and may result from HIV-induced immunologic abnormalities and exposure to a variety of xenoantigens, such as HIV itself, other infectious agents, and drugs.

Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus.

Recent evidence has shown that most nasal lymphomas (NL) are associated with a T-cell phenotype and are thus called nasal T-cell lymphomas (NTCL), but little information is available about the T-cell receptor (TCR) expression. The presence of Epstein-Barr virus (EBV) genome has been recently reported in NTCL in Oriental populations in which NL and EBV-associated tumors are more common and in occasional Occidental cases. This prompted us to investigate lymphoma biopsies from 7 non-Oriental patients with NTCL for the expression of natural killer (NK) and T-cell antigens, including TCR proteins, for the presence of EBV-encoded latent membrane protein (LMP) using immunohistochemistry and for the presence of EBV DNA and Epstein-Barr early region (EBER) RNA using in situ hybridization (ISH). Six cases displayed a CD3-, TCR alpha beta-, TCR gamma delta-, CD2+, CD7+, CD5-, CD4-, CD8-, CD56+ phenotype, suggesting that these tumors may be peripheral T-cell lymphomas (PTCL) with extensive loss of T-cell antigens and expression of the NK-cell (CD56) antigen or, alternatively, NK-cell neoplasias. The remaining case was a gamma delta PTCL, as shown by the CD3+, TCR gamma delta+ phenotype and the biallelic gamma and delta TCR gene rearrangements. Using ISH, EBER RNA transcripts were detected in tumor cells in all cases and EBV DNA was shown in the 6 tested cases. In all cases, tumor cells expressed LMP. These findings support the concept that NTCL constitute a distinct group of lymphomas that, in addition to their peculiar clinical features, exhibit an unusual TCR "silent" CD56+ or TCR gamma delta+ phenotype and harbor the EBV. In view of the LMP transforming potential, these data suggest that EBV may play a role in the pathogenesis of NTCL.

HIV-related demyelinating disease.

True demyelination, or at least a leukoencephalopathy with predominant involvement of myelin, may occur in many neurological complications of human immunodeficiency virus (HIV)-infection, resulting from various mechanisms which are not all well understood. These include lesions directly related to infection of the nervous tissue by HIV, opportunistic infections and lymphomas secondary to the cell-mediated immunodeficiency, and changes due to other general or systemic complications of acquired immunodeficiency syndrome (AIDS). HIV-induced pathology of the nervous system includes HIV-specific disease, due to direct infection of the nervous system by the virus. This is characterized by the presence of distinctive multinucleated giant cells and white matter changes, HIV encephalitis and HIV leukoencephalopathy, which may overlap in one third of cases. The pathogenesis of myelin destruction is unclear. Direct infection of neurons or glial cells has never been demonstrated. Indirect immunopathologic, toxic, metabolic, or vascular mechanisms secondary to infection of monocytes/macrophages are more likely. Less specific HIV-associated central nervous system (CNS) pathology including vacuolar myelopathy, and vacuolar leukoencephalopathy are characterized by numerous vacuolar myelin swellings in spinal or cerebral white matter. The exact aetiopathological relationship of these changes to HIV infection is uncertain. It seems likely that factors other than, or additional to, HIV infection play a role in their causation. Apart from these changes which usually occur at the late stages of the disease, acute perivenous inflammatory leukoencephalopathy, presenting either as acute haemorrhagic leukoencephalopathy, acute demyelinating perivenous encephalitis, or acute multiple sclerosis-like leukoencephalopathy revealing HIV-infection occur in rare cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute varicella-zoster virus ventriculitis and meningo-myelo-radiculitis in acquired immunodeficiency syndrome.

A 30-year-old AIDS patient with no history of cutaneous eruption, presented with rapidly progressive flaccid paraplegia, hypoesthesia, urinary retention, moderate psychomotor slowing and fever (39.8 degrees C), leading to death within 1 week. CD4 count was 290/mm3. Cerebrospinal fluid contained 210 white blood cells and 238 mg/100 ml protein. Neuropathology revealed HIV encephalitis and diffuse ventriculitis with Cowdry type A inclusions in the ependymal cells. Extensive necrotic and hemorrhagic changes with marked recrotizing vasculitis involved the entire spinal cord and spinal roots. Immunocytochemistry revealed numerous inclusion bodies positive for varicella-zoster virus (VZV) and negative for cytomegalovirus (CMV) and herpes simplex virus type 1 and 2, in ependymal cells, subpial glial cells, endothelial cells and Schwann cells. Electron microscopy confirmed herpes virus-like particles. In situ hybridization confirmed VZV genome in leptomeninges, brain, spinal cord and spinal roots. Comparable neuropathological findings and numerous VZV inclusion bodies were also found in the brain, spinal cord, and spinal roots of a 40-year-old AIDS patient who died from a fulminant ascending myeloradiculopathy previously reported as "necrotizing vasculitis of the nervous system". Direct infection of the brain by VZV, in AIDS patients, has been shown to cause leukoencephalitis and cerebral non-inflammatory vasculopathies. Our observations demonstrate that, in AIDS patients, VZV infection of the central nervous system may also be responsible for meningo-myelo-radiculitis possibly secondary to ventriculitis as in CMV infection. The role of VZV in the pathogenesis of some AIDS-related vasculitides seems also very likely.

[Polyglucosan body disease]. / La maladie des corps polysaccharidiques.

A 78 year-old male presented with a bilateral pyramidal syndrome, urinary incontinence and mild intellectual slowing. He died seven months after onset of the neurological signs from cerebral infarct and heart failure. Neuropathological examination showed predominant involvement of the cerebral white matter including diffuse myelin pallor, astrocytic gliosis and small necrotic foci. Polyglucosan bodies were diffuse in the cerebral cortex, white matter, brainstem, cerebellum and proximal part of the cranial nerves. In these latter, some polyglucosan bodies were found within myelinated axons but the inclusions mostly involved astrocytic processes. This case is characteristic of the polyglucosan body disease. It is compared with the autopsy and biopsy cases previously reported in the literature.

Cutaneous side effects associated with interleukin 2 administration for metastatic melanoma.

BACKGROUND: Cutaneous changes associated with recombinant interleukin 2 (r IL-2) administration are frequent but have been rarely studied in a large series. OBJECTIVE: We analyzed these clinical, microscopic, and immunologic changes. METHODS: Patients with metastatic melanoma treated with r IL-2 were studied. The eruption was scored as mild or severe. Biopsy specimens were obtained for histopathology, ultrastructural analysis, and immunophenotyping. Chi-square and t tests were used for statistics. RESULTS: Twenty-five patients were included. Eruptions were observed in 56 of 78 cycles (72%); 53 were mild with a burning pruriginous erythema, and 3 were severe with urticaria, necrotic lesions, and blisters. Regression was constant without sequelae. Pathologic changes were mild with a mononuclear cell infiltrate of activated helper T phenotype, expressing LFA-1. Keratinocytes and endothelial cells displayed intercellular adhesion molecule-1 and HLA-DR. Cells rarely expressed CD25. CONCLUSION: Administration of r IL-2 triggers non-treatment-limiting cutaneous inflammation.

Intraepidermal localization of the clone in cutaneous T-cell lymphoma.

BACKGROUND: No immunohistologic techniques are currently available to demonstrate clonality of T-cell lymphomas. Monoclonal antibodies to the variable region of the T-cell receptor (TCR) have been produced that identify minor populations of normal peripheral blood T lymphocytes. OBJECTIVE: We investigated the expression of TCR V-region genes in cutaneous lymphomas to determine whether immunostaining with these antibodies may be a simple method to detect clonal T-cell proliferations and help to distinguish benign lymphoid infiltrates from malignant lymphoma. METHODS: Cutaneous samples were obtained from 18 cutaneous T-cell lymphomas (14 mycosis fungoides, 1 Sézary syndrome, 2 pleomorphic T-cell lymphoma, and 1 large cell anaplastic lymphoma) and 8 benign lymphoid infiltrates. Frozen sections were incubated with monoclonal antibodies and stained by the alkaline phosphatase-antialkaline phosphatase technique. Staining was performed with a panel of 7 anti-TCR V-region antibodies, 6 T-cell markers, 1 anti-beta chain antibody, and 1 anti-delta chain antibody. RESULTS: Clonality could be demonstrated in 2 of 18 cutaneous lymphomas. We observed the strictly intraepidermal localization of clonal proliferation in one case of early-stage mycosis fungoides. CONCLUSION: Anti-TCR V-region antibodies may identify a strictly epidermotropic clone in early mycosis fungoides. However, the panel of antibodies currently available stains only a minority of cutaneous T-cell lymphomas. The usefulness of these antibodies as a clonotypic marker needs to be reevaluated when a larger panel of antibodies becomes available.

Varicella-zoster virus encephalitis in acquired immunodeficiency syndrome: report of four cases.

Four patients with acquired immunodeficiency syndrome, a 27-year-old female intravenous drug abuser and three males (two drug addicts aged 27 and 33 years and a 40-year-old homosexual) presented with a rapidly progressive encephalopathy. Two had generalized varicella-zoster virus skin infection, one had had a regressive thoracic zoster rash 7 months previously and one had no history of cutaneous eruption. Neuropathological examination revealed, in each case, multifocal necrotic changes with numerous, intranuclear Cowdry type A inclusion bodies in glial cells, endothelial cells, macrophages and neurons, within and around the lesions. These inclusion bodies were stained positively for varicella-zoster virus by immunocytochemistry and contained herpes virus nucleocapsids by electron microscopy. Molecular biology using the polymerase-chain-reaction method demonstrated viral genome. In one case, zoster-induced non-inflammatory vasculopathy involved medium sized leptomeningeal vessels and was associated with circumscribed areas of cortico-subcortical infarction. In another case, varicella-zoster virus encephalitis was associated with human immunodeficiency virus encephalitis and a secondary cerebral lymphoma. Multinucleated giant cells expressing human immunodeficiency virus proteins in their cytoplasm, were found in the lymphomatous deposits and in the varicella-zoster virus necrotic lesions. In these latter lesions, Cowdry type A inclusion bodies could be seen in the nuclei of some multinucleated giant cells confirming previous observations of MGCs co-infected by HIV and CMV, and supporting the hypothesis that DNA viruses interact with HIV, thus increasing its effect.

Early brain changes in HIV infection: neuropathological study of 11 HIV seropositive, non-AIDS cases.

We examined 11 brains of human immunodeficiency virus (HIV) seropositive cases who died from unnatural causes (10 intravenous drug abusers who died from heroin overdose and 1 homosexual dead from a gunshot injury); 10 brains of HIV seronegative heroin addicts who died from overdose and 1 seronegative drug abuser who died from gunshot injury served as controls. Complete postmortem examination did not show evidence of acquired immune deficiency syndrome (AIDS) or AIDS related complex. Terminal changes including nerve cell ischemia, edema and diffuse vascular congestion were observed in all cases. Perivascular pigment deposition with macrophages was a constant finding in drug addicts and was probably related to chronic intravenous injection. In contrast, cerebral vasculitis was significantly more frequent and marked in HIV seropositive cases and was often associated with lymphocytic meningitis. Granular ependymitis, myelin pallor with reactive astrocytosis and microglial proliferation were also more frequent and more severe in HIV seropositive cases. Immunocytochemistry was negative for HIV antigens. Our study further supports the view that early central nervous system changes occur in HIV infection.

[AIDS-related progressive multifocal leukoencephalopathy limited to U fibers, responsible for subacute encephalopathy with normal CT scan findings]. / Leucoencéphalopathie multifocale progressive limitée aux fibres en U au cours du SIDA, responsable d'une encéphalopathie subaiguë avec scanner normal.

A 41-year-old male homosexual with AIDS was hospitalized for temperature elevation to 40 degrees C with confusion. Neurologic evaluation found psychomotor slowing and temporospatial disorientation with no focal signs. The CD4 count was 100/mm3. CSF analysis and the CT scan were normal. Despite antiviral treatment the patient died fifteen days after admission. Gross appearance of the brain was normal. Histologic examination disclosed multiple, small foci of demyelination characteristic of progressive multifocal leukoencephalopathy. These foci were disseminated among the U fibers. In situ hybridization and immunocytochemical studies demonstrated papovavirus particles in oligodendrocytes and a few astrocytes. This case shows that papovavirus infection in AIDS patients may be responsible for a diffuse febrile encephalopathy with normal CT scan findings and a rapidly progressive course.