An autopsied case of acute hemorrhagic leukoencephalitis

This is a clinico-pathological study of one case of acute hemorrhagic leukoencephalitis occurring in a patient with lung cancer. The main changes observed by light microscopy were in the white matter. All of these changes were the result of hemorrhage and demyelination around the venous vessels. Glial mesenchymal reactions were minimal. In view of these findings, this case supports the hypothesis that immune mechanisms play a role in the pathogenesis of neuropsychiatric symptoms during malignant illnesses. Here we will discuss the problem of differential diagnoses of acute hemorrhagic leukoencephalitis and its close morphologic similarities to perivenous encephalitis. Acute hemorrhagic leukoencephalitis and perivenous encephalitis may be a single entity of a demyelinating disease.     

Postinfectious leukoencephalitis complicating Mycoplasma pneumoniae infection

Neuropathological findings in a patient with fatal neurological complications due to infection with Mycoplasma pneumoniae were similar to those seen in postinfectious encephalitis and acute hemorrhagic leukoencephalitis. This case supports the hypothesis that immune mechanisms play a role in the pathogenesis of neurological symptoms during mycoplasmal infections.     

Computerized tomography as a diagnostic aid in acute hemorrhagic leukoencephalitis

Computerized tomography (CT) in a pathologically proven case of acute hemorrhagic leukoencephalitis (AHL) showed a mass effect and increased absorption coefficient in the right hemisphere within 18 hours of the onset of neurological symptoms. The changes corresponded to the site of white matter edema, necrosis, and petechial hemorrhages demonstrated postmortem. The early changes of CT reflect the hyperacute nature of AHL and differ from those of herpes simplex encephalitis.     

Dengue: neuropathological findings in 5 fatal cases from Brazil

Neuropathological examination of 5 patients with dengue who died of shock in Rio de Janeiro during an outbreak in summer 1987, showed nonspecific lesions (edema, vascular congestion, hemorrhagic foci and perivascular lymphocytic infiltrates). In one case with delayed marked neurological symptoms, several foci of perivenous demyelination were observed. Neurological manifestations are various and not uncommon in dengue, but their anatomical substratum is not known. An immunopathological mechanism has been postulated in some cases but has never been demonstrated morphologically. The perivenous leukoencephalitis observed in one of our cases could represent the morphological substratum of such an immunological mechanism.     

Neuropathology of two fatal cases of measles in the 1988-1989 Houston epidemic

The clinical course and autopsy findings of 2 patients with measles encephalitis that occurred during the 1988-1989 Houston epidemic are reported. A previously healthy 25-month-old boy had serologically-proved measles, hemophagocytic syndrome, and acute disseminated demyelinating encephalitis. A 19-year-old male with acute lymphocytic leukemia had proved measles pneumonia and acute hemorrhagic leukoencephalitis. These patients represent a broad spectrum of measles-induced immunopathic complications of the central nervous system.     

Acute hemorrhagic leukoencephalitis mimicking herpes simplex encephalitis: case report

Acute hemorrhagic leukoencephalitis (AHLE) is a more severe form of acute disseminated encephalomyelitis (ADEM) characterized by a fulminant clinical course and the presence of hemorrhagic necrosis of the white matter. We report the case of a 57-year-old woman who developed delirium following a respiratory infection. Magnetic resonance imaging of the brain disclosed signal abnormalities in the frontal and temporal lobes, usually found in herpes simplex encephalitis (HSE). Gram stain, India ink and acid-fast bacilli staining were all negative in CSF as was a polymerase chain reaction (PCR) for herpes simplex virus. A diagnosis of AHLE was made and the patient was treated with i.v. methylprednisolone 1g/day for 5 days. Despite treatment, the patient developed several neurological sequelae compatible with the severity of her illness.     

Treatment leading to dramatic recovery in acute hemorrhagic leukoencephalitis

The clinical course, neuroimaging, neuropathological features, and management of a 7-year-old girl with acute hemorrhagic leukoencephalitis are reported. Treatment with subtotal bifrontal craniectomies for symptoms of imminent uncal herniation followed by high-dose corticosteroid therapy was associated with dramatic clinical recovery. This report highlights the utility of aggressive intervention in acute hemorrhagic leukoencephalitis, an otherwise fatal disorder.     

Acute hemorrhagic leukoencephalitis.

We report an autopsy proven case of acute hemorrhagic leukoencephalitis. There was a very rapid evolution leading to death in less than 24 hours. CT of the brain revealed widespread hypodensities in both frontal lobes. In the cerebrospinal fluid as well as in the peripheral blood, there was a moderate leucocytosis. The literature is reviewed.     

Acute hemorrhagic leukoencephalitis. A successful recovery

A 50-year-old woman developed acute hemorrhagic leukoencephalitis approximately 7 days after the onset of a benign respiratory infection. Mycoplasmal pneumonia was suspected because of Coomb's positive hemolysis, cold agglutinins, and sensitivity to erythromycin base but was not proved. Acute hemorrhagic leukoencephalitis was demonstrated by brain biopsy 24 hours after admission. The patient recovered without lasting sequelae following reduction of increased intracranial pressure by mannitol, hyperventilation, and phenobarbital and prolonged immunosuppression by plasmapheresis, steroids, and cyclophosphamide.     

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.     

Haemorrhagic and perivenous encephalitis: a clinical-pathological review of 38 cases.

Clinical and pathological data from eight cases of acute haemorrhagic leucoencephalitis (AHL) confirm the previously documented devastating features of this disease. Data from 30 cases of perivenous encephalitis (PVE) associated with viral diseases reveal pathological changes ranging from lymphocytic cuffing of vessels to severe vasculitis similar to the vasculitis of AHL. Relatively few cases show demyelination as a prominent feature. The pathological changes are unrelated to the type of underlying disease with the exception that the pathology of 'post-rubella' encephalitis tends to be mild. Two cases of rubeola and two of mumps showed viral nodules in the cortex, raising the possibility of direct viral invasion of tissue. Allowing for species differences, these changes are analogous to the pathological features of experimental allergic encephalitis (EAE); with the various pathological changes of PVE paralleling the features of ordinary EAE, while the changes of AHL and the severe cases of PVE strongly resemble hyperacute EAE.     

Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy

HAART-induced immune restoration is beneficial for patients with AIDS-related progressive multifocal leukoencephalopathy (PML). However, in rare instances, an immune-reconstitution inflammatory syndrome (IRIS) may cause paradoxical clinical deterioration. We report the neuropathological study of an AIDS patient who presented with progressive cognitive deterioration; CD4⁺ count was 117 and the HIV viral load >10⁴; imaging showed non-enhancing lesions consistent with PML. Following initiation of HAART, CD4⁺ was 300 and HIV viral load <10³, but his neurological symptoms continued to deteriorate. Imaging revealed an increase in the size and number of lesions and enhancement of all the lesions. A stereotactic biopsy showed severe inflammatory and demyelinating lesions with marked infiltration by macrophages and T lymphocytes in the absence of a detectable infectious agent. Despite high doses of steroids, the patient died 3 months after admission. Autopsy showed two types of lesions: (1) active inflammatory PML changes with abundant JC virus, and intraparenchymal and perivascular infiltration by T lymphocytes, and (2) acute perivenous leukoencephalitis devoid of JC virus. Most lymphocytes were CD8⁺ lymphocytes; CD4⁺ lymphocytes were virtually absent. Two pathological reactions were associated with the paradoxical clinical deterioration related to dysregulation of the immune response characteristic of IRIS in PML: (1) an accentuation of JCV infection, and (2) a nonspecific acute perivenous leukoencephalitis. We suggest that both these types of lesions are due to an imbalance of CD8⁺/CD4⁺ T cells, with massive infiltration of the cerebral parenchyma by CD8⁺ cytotoxic T lymphocytes in the absence of sufficient CD4⁺ response. Better understanding of the mechanisms of the IRIS may enable prevention or cure of this severe, sometimes fatal complication of HAART.     

Neuroimaging in postinfectious demyelination and nutritional disorders of the central nervous system

The myelin sheath and oligodendrocytes in the brain may be damaged by autoimmune-mediated inflammatory processes secondary to postinfectious demyelination or nutritional and vitamin deficiency. This article describes acute disseminated encephalomyelitis, acute hemorrhagic leukoencephalitis, acute necrotizing encephalopathy, and tumefactive demyelination as well as osmotic demyelination, Wernicke encephalopathy, Marchiafava-Bignami disease, and subacute combined degeneration of the spinal cord. Although some characteristic MR imaging features allow radiologists to suggest a diagnosis, these may overlap, and images should be interpreted in light of clinical symptoms and laboratory investigations.     

Relapsed and late-onset Nipah encephalitis

An outbreak of infection with the Nipah virus, a novel paramyxovirus, occurred among pig farmers between September 1998 and June 1999 in Malaysia, involving 265 patients with 105 fatalities. This is a follow-up study 24 months after the outbreak. Twelve survivors (7.5%) of acute encephalitis had recurrent neurological disease (relapsed encephalitis). Of those who initially had acute nonencephalitic or asymptomatic infection, 10 patients (3.4%) had late-onset encephalitis. The mean interval between the first neurological episode and the time of initial infection was 8.4 months. Three patients had a second neurological episode. The onset of the relapsed or late-onset encephalitis was usually acute. Common clinical features were fever, headache, seizures, and focal neurological signs. Four of the 22 relapsed and late-onset encephalitis patients (18%) died. Magnetic resonance imaging typically showed patchy areas of confluent cortical lesions. Serial single-photon emission computed tomography showed the evolution of focal hyperperfusion to hypoperfusion in the corresponding areas. Necropsy of 2 patients showed changes of focal encephalitis with positive immunolocalization for Nipah virus antigens but no evidence of perivenous demyelination. We concluded that a unique relapsing and remitting encephalitis or late-onset encephalitis may result as a complication of persistent Nipah virus infection in the central nervous system.     

Cerebral phaeohyphomycosis caused by a dematiaceous scopulariopsis species

This report describes a rapidly fatal case of cerebral phaeohyphomycosis in a 33-year-old immunocompetent male. The infection presented as a single large lesion in the deep white matter of one temporal lobe, which was then removed surgically. Histologic features observed in the lobectomy specimen were characterized by perivascular sleeves of mononuclear cells accompanied by hemorrhages. These were reminiscent of acute hemorrhagic leukoencephalitis except for the presence of rare fungal organisms and sparse multinucleated giant cells similar to those occurring in AIDS. During the four days following surgery, a large focus of cerebritis with massive invasion of fungi developed in each centrum semiovale around the ventriculostomy sites. Fungal culture of the brain obtained at autopsy grew an organism consistent with a Scopulariopsis species.     

Value of susceptibility-weighted imaging in acute hemorrhagic leukoencephalitis

Acute hemorrhagic leukoencephalitis (AHL) is a rapidly progressive disease in the spectrum of acute disseminated encephalomyelitis. Timely accurate diagnosis is crucial but challenging clinically and radiologically. However, imaging findings of AHL are quite specific when susceptibility-weighted imaging is utilized. The purpose of this report is to present the imaging findings of autopsy-proven AHL and thus to facilitate rapid recognition and treatment.     

Fulminant acute disseminated encephalomyelitis in children

Acute disseminated encephalomyelitis (ADEM) is a typically monophasic inflammatory demyelinating disease of the central nervous system with a favorable outcome. However, 2% of ADEM involves acute hemorrhagic leukoencephalitis (AHLE), which is a fulminant and hyperacute variant of ADEM with a poor outcome and high mortality. There are limited case reports of fulminant ADEM including AHLE in children. Herein, we report two pediatric cases of fulminant ADEM. Both cases had a rapid deterioration of consciousness, repetitive seizures, and brain edema on neuroimaging, in addition to atypical neuroradiological findings on magnetic resonance imaging (MRI), a reversible splenial lesion in case 1, and bilateral frontal and occipital cortical lesions in case 2. Both cases were treated with early high-dose methyl-prednisolone and immunoglobulin, while therapeutic hypothermia was also initiated in case 2 after the patient exhibited a decerebrate posture and irregular breathing pattern. Both cases had a favorable outcome. Further case reports on pediatric fulminant ADEM are required to clarify the various clinical types, and to examine the efficacy of various treatment modalities for fulminant ADEM and AHLE in children.     

Acute hemorrhagic encephalitis (Hurst disease) associated with neuroaxonal dystrophy

Two cases that fulfil the clinical and neuropathological criteria of acute hemorrhagic encephalitis are described. Histological examination revealed additionally focal changes in the white matter characteristic for neuroaxonal dystrophy. The differences in the clinical course and morphological picture observed in both cases are discussed.     

Clinical relevance of polymerase chain reaction (PCR) assays and antigen-driven immunoblots for the diagnosis of neurological infectious diseases

Polymerase chain reaction assays are a powerful tool for detecting the presence of infectious genomes in the cerebrospinal fluid. Positive results always mean a current or pending infection of the central nervous system. Subacute (>7 days) or chronic infections induce an intrathecal humoral immune response and the appearance of oligoclonal IgG antibodies directed against the causal infectious agent. This local synthesis may be observed even in cases of severe systemic immunodeficiency. The use of polymerase chain reactions in combination with the detection of a specific intrathecal immune response should represent the most reliable strategy for the diagnosis of viral and chronic infections of the central nervous system. The authors describe their experience, using this approach, in herpetic encephalitis, acute and recurrent herpetic meningitis, varicella zoster-induced neurological diseases, cytomegalovirus encephalitis, progressive multifocal leukoencephalitis and tuberculous meningitis.     

Atypical Acute Hemorrhagic Leukoencephalitis (Hurst’s disease) Presenting with Focal Hemorrhagic Brainstem Lesion

Background  

Acute hemorrhagic leukoencephalitis (AHL; Hurst’s disease) is a rare, severe, inflammatory CNS disease that is typically diffuse, multifocal and associated with petechial hemorrhage. The objective of this study is to report the clinical, radiologic, and pathologic findings in a fatal AHL case with focal brainstem involvement and gross hemorrhage.