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PubMed2003

Opportunistic infections of the CNS in patients with AIDS: diagnosis and management.

The CNS is the second most commonly affected organ in patients with AIDS. Many opportunistic infections may involve the brain, but the four most frequent conditions are toxoplasmosis, progressive multifocal leukoencephalopathy (PML), cryptococcosis and cytomegalovirus infection. Although the incidence of these infections among patients with AIDS has decreased in the past years as a consequence of the introduction of highly active antiretroviral therapy (HAART), they remain a major cause of morbidity and mortality in this patient group. This article summarises the clinical manifestations, diagnostic procedures and management strategies for these four conditions. The clinical manifestations are nonspecific and depend on the type and location of the lesions. In clinical practice, the diagnosis of these entities is made with noninvasive methods. Imaging studies, especially magnetic resonance imaging, are very useful for the diagnosis of toxoplasmic encephalitis and PML, although their usefulness for the diagnosis of cryptococcal meningitis and cytomegalovirus infections is lower. The presence of multiple ring-enhancing lesions with surrounding oedema and mass effect is characteristic of toxoplasmosis. The response to antitoxoplasmic therapy, which is usually observed within the first 2 weeks, is also used for diagnostic purposes. Molecular methods applied to the CSF are essential for the diagnosis of PML and cytomegalovirus infections. In addition, the quantification of viral DNA of both JC virus (the causative agent of PML) and cytomegalovirus has prognostic implications and may serve to evaluate the response to therapy. Cryptococcosis may be easily diagnosed by CSF stains and cultures, as well as by the detection of the cryptococcal capsular polysaccharide antigen in the blood and, especially, the CSF. Effective treatments are available for toxoplasmosis and cryptococcosis, although adverse effects are common and some patients may not respond to therapy. In contrast, there is no specific treatment for PML, and the efficacy of anticytomegalovirus therapy is poor and the toxicity significant. HAART has improved the outcome of patients with AIDS who have infections of the CNS, and the initiation of this therapy is mandatory for all patients with such infections, particularly in those conditions for which effective therapy is not available. Lifelong secondary prophylaxis with agents for the opportunistic infections was necessary before the HAART era because the risk of recurrence was very high if only induction therapy was administered. However, today, the discontinuation of secondary prophylaxis in patients treated with HAART who have stably reached a certain immune reconstitution is possible.

AIDS-Related Opportunistic Infections↗
PubMed2000

The HHV6 paradox: ubiquitous commensal or insidious pathogen? A two-step in situ PCR approach.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) and multiple sclerosis (MS) are demyelinative diseases of the central nervous system (CNS). PML occurs mostly in individuals with AIDS-impaired immunity and is thought to be caused by JC polyoma virus (JCV). In MS a neurotrophic virus trigger is suspected, but the precise etiology remains unknown. Human herpesvirus 6 (HHV6) is a ubiquitous, commensal and usually benign beta-herpesvirus. Some researchers have found evidence for HHV6 infection in MS plaques and sera. We recently demonstrated a high frequency of cells containing HHV6 genome in PML lesions, as well as co-infection of oligodendrocytes by JCV and HHV6. This suggests that HHV6 may be a co-factor in the etiology of PML, and raises questions about its role in other demyelinative diseases. OBJECTIVES: To determine the prevalence and cellular localization of HHV6, JCV and HIV-1 infected cells in PML, MS, AIDS and control CNS tissues, and their potential relationship with disease. STUDY DESIGN: An unconventional, sensitive two-step in situ polymerase chain reaction (ISPCR) procedure was used to amplify and detect HHV6, JCV and HIV-1 genomic DNAs in formalin fixed, paraffin-embedded archival CNS tissues. HHV6, JCV and HIV-1 gene expression was detected by ICC for HHV6 p41 and gp101, JCV large T, and HIV-1 p24 gag and NEF proteins. RESULTS: A high frequency of HHV6 genome was consistently detected in both PML and MS white matter lesional cells; a peri-lesional concentration was notable. HHV6 was found mainly in oligodendrocytes, but neurons were also infected. HHV6 was present in larger amounts than JCV in PML lesions, while more HIV-1 than HHV6 was present in AIDS. Variable amounts of HHV6 genome were detected in normal, AIDS and other control brains; the frequency of infected cells tended to increase with patient age. CONCLUSIONS: High concentrations of HHV6 genome in association with PML and MS lesions, open the possibility that HHV6 activation may play a role in the pathogenesis of these demyelinative diseases.

AIDS Dementia Complex↗
PubMed1995

[Clinical and paraclinical diagnosis of AIDS neurologic lesions].

Seventy to eighty percent of HIV-infected patients exhibit neurological disorders at an advanced stage of the disease. In almost 90% of cases anatomical examination of brains shows histological lesions. Even when often reversible neurological disorders occur during the HIV primary infection, most of the manifestations of central nervous system (CNS) damage remains the prerogative of severe immunodepression. The principal CNS lesions associated with HIV infection are presented here with the clinical and biological elements that lead to the diagnosis. Cerebral toxoplasmosis holds a privileged place in these manifestations since it responds to an efficient curative and prophylactic treatment with a well-codified medical care based on the test treatment. Biological data, therefore, only have a contributing value. HIV encephalopathy is frequent, but the dementia syndrome is less frequent than the finding of associated imaging and pathological anatomy: atrophy and lesions of the white matter. Thus, the dementia complex is an elimination diagnosis. Cryptococcosis must be systematically considered, not only in patients with meningeal symptoms and headaches, but also with those with isolated fever. The demonstration of cryptococcus and cryptococcic antigen in the CSF has an almost absolute diagnostic value; imaging plays a very small diagnostic role, looking for an exceptional cryptococcoma. Multifocal progressive leukoencephalopathy benefits from the accuracy of MRI, and the diagnosis is usually based on clinical data, MRI and evidence of the virus in the CSF by PCR, even though the only mean of obtaining full proof is, in theory, stereotaxic biopsy. Primary cerebral lymphoma is the diagnostic alternative to toxoplasmosis.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗
PubMed1988

Human immunodeficiency virus and papovavirus infections in acquired immunodeficiency syndrome: an ultrastructural study of three cases.

A wide variety of neurologic conditions associated with the acquired immunodeficiency syndrome (AIDS) have been attributed to human immunodeficiency virus (HIV) infection of the central nervous system (CNS). Tissue samples from the brains of three patients with AIDS, diagnosed as having CNS toxoplasmosis on the basis of computed tomographic scans of the head, were studied by transmission electron microscopy. In two, HIV particles were observed budding from, in close association with, and in cytoplasmic vacuoles of mononuclear and multinucleated macrophages, but no other cell types. The patient with the greatest number of HIV particles also had large amounts of papovavirus (progressive multifocal leukoencephalopathy) in the nuclei of oligodendroglial cells and in the cytoplasm of astrocytes. These astrocytes often had atypical features at the light microscopic level. Following an initial biopsy that showed only HIV, primary CNS lymphoma was diagnosed by needle biopsy and confirmed at autopsy in a second case. A diagnosis of progressive multifocal leukoencephalopathy was rendered by transmission electron microscopy in a third case, but no HIV was detected. Toxoplasmosis was not confirmed in any of the three cases. Diagnosis of CNS lesions in patients with AIDS should not rely exclusively on radiography but include biopsy for both light and transmission electron microscopy. Transmission electron microscopy can be employed to reveal HIV and papovavirus infections not discernible at the light microscopic level and should be used as a diagnostic tool in HIV-related infections.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Natalizumab induction and maintenance therapy for Crohn's disease.

BACKGROUND: Natalizumab, a humanized monoclonal antibody against alpha4 integrin, inhibits leukocyte adhesion and migration into inflamed tissue. METHODS: We conducted two controlled trials to evaluate natalizumab as induction and maintenance therapy in patients with active Crohn's disease. In the first trial, 905 patients were randomly assigned to receive 300 mg of natalizumab or placebo at weeks 0, 4, and 8. The primary outcome was response, defined by a decrease in the Crohn's Disease Activity Index (CDAI) score of at least 70 points, at week 10. In the second trial, 339 patients who had a response to natalizumab in the first trial were randomly reassigned to receive 300 mg of natalizumab or placebo every four weeks through week 56. The primary outcome was a sustained response through week 36. A secondary outcome in both trials was disease remission (a CDAI score of less than 150). RESULTS: In the first trial, the natalizumab and placebo groups had similar rates of response (56 percent and 49 percent, respectively; P=0.05) and remission (37 percent and 30 percent, respectively; P=0.12) at 10 weeks. Continuing natalizumab in the second trial resulted in higher rates of sustained response (61 percent vs. 28 percent, P<0.001) and remission (44 percent vs. 26 percent, P=0.003) through week 36 than did switching to placebo. Serious adverse events occurred in 7 percent of each group in the first trial and in 10 percent of the placebo group and 8 percent of the natalizumab group in the second trial. In an open-label extension study, a patient treated with natalizumab died from progressive multifocal leukoencephalopathy, associated with the JC virus, a human polyomavirus. CONCLUSIONS: Induction therapy with natalizumab for Crohn's disease resulted in small, nonsignificant improvements in response and remission rates. Patients who had a response had significantly increased rates of sustained response and remission if natalizumab was continued every four weeks. The benefit of natalizumab will need to be weighed against the risk of serious adverse events, including progressive multifocal leukoencephalopathy. (ClinicalTrials.gov numbers, NCT00032786 and NCT00032799.)

Adult↗
PubMed1977

Polyclonal gammopathies associated with chronic diseases in nonhuman primates.

Serum samples collected from clinically healthy rhesus macaques (Macaca mulatta) were compared with serums from animals diagnosed as having malignant lymphoma, atypical tuberculosis, progressive multifocal leukoencephalopathy, or more than 1 of these. Electrophoretic analyses of serum proteins (in grams per deciliter) indicated that mean values in a clinically normal group were as follows--total protein, 8.30; albumin, 4.07; alpha-globulin, 0.85; beta-globulin, 2.23; and gamma-globulin, 1.15. In macaques with malignant lymphoma, mean values were--total protein, 7.60; albumin, 2.72; alpha-globulin, 0.91; beta-globulin, 1.71; and gamma-globulin, 2.23. In macaques with atypical tuberculosis, these values were 8.47, 2.92, 0.84, 2.18, and 2.52, respectively, and those with progressive multifocal leukoencephalopathy, 9.06, 4.01, 6.71, 2.42, and 1.93. Where multiple serum samples were available from 1 macaque for analysis, gamma-globulin values were increased before clinical disease was apparent. Evaluation of serums from macaques may be used as a means of detecting preclinical lymphoproliferative disease.

Animals↗
PubMed1992

Stereotactic brain biopsy in AIDS.

In the hope of finding a treatable condition, the need for rapid diagnosis in HIV-seropositive patients with brain lesions is apparent. In order to evaluate the efficacy of stereotactic brain biopsy in AIDS patients, we retrospectively studied 25 HIV-infected patients undergoing stereotactic biopsy. Brain lesions were identified with gadolinium-enhanced MRI and/or contrast CT. Brain biopsy was performed using the system of Riechert. From 8 up to 15 small tissue samples from one or two targets were obtained in every patient. The biopsy material was examined cytologically, histologically (including electron microscopy), immunohistochemically and, in part, by animal test and polymerase chain reaction (PCR). A definite diagnosis was achieved in 92%. Diagnosis included primary central nervous system lymphoma (PCNSL) (10), toxoplasmosis (10), progressive multifocal leukoencephalopathy (2) and one case of co-existing toxoplasmosis and cytomegalovirus infection. Two biopsies were non-diagnostic. All PCNSLs showed polymorphic B-cell populations of high malignancy; accurate classification according to the Kiel classification was not possible. In 3 lymphomas Epstein-Barr nuclear antigen (EBNA) 2-mRNA could be detected by PCR and confirmed immunohistochemically by EBNA 2 expression. In 6 cases autopsy confirmed the biopsy diagnosis. Conventional histology was not sufficiently decisive for toxoplasmosis and progressive multifocal leukoencephalopathy, so that immunohistochemistry and animal tests became very important for a final diagnosis. With the help of different morphological and molecular biological techniques stereotactic brain biopsy appears to be an effective method in the diagnosis of HIV-associated brain lesions. In view of the marked radio- and chemosensitivity of PCNSLs it is mandatory to establish an early and accurate histological diagnosis for adequate treatment.

Acquired Immunodeficiency Syndrome↗
PubMed2000

AIDS-related focal brain lesions in the era of highly active antiretroviral therapy.

OBJECTIVE: To compare the years since the introduction of highly active antiretroviral therapy (HAART) with the pre-HAART era for trends in the proportions of HIV-related focal brain lesion-causing disorders. METHODS: A prospective, single-center study of all consecutive HIV-infected patients with a neurologic presentation and focal brain lesions observed between January 1991 and December 1998 was undertaken. RESULTS: The major diagnoses in the 281 patients were toxoplasmic encephalitis (36.4%), primary CNS lymphoma (26.7%), progressive multifocal leukoencephalopathy (18.2%), and focal HIV encephalopathy (5.0%). During the HAART period, patients were less likely to be male, contracted HIV more often through heterosexual exposure, had fewer previous AIDS-defining events, received antiToxoplasma prophylaxis less frequently, had a CD4+ lymphocyte count 2.5 times higher, and had diagnosis based more often on PCR assays from CSF, reducing the need for brain biopsy and enhancing the likelihood of in vivo diagnosis. Using all patients hospitalized per year as reference population, the risk of focal brain lesions strongly increased during the pre-HAART period and declined significantly during the HAART years. In the HAART period a relevant decline of primary CNS lymphoma was found (OR for 1998, 0.25; p for trend = 0.03) and the effect of progressive calendar year was confirmed on multivariable analysis (OR, 0.52; 95% CI, 0.28 to 0.97). The frequency of toxoplasmic encephalitis decreased during the pre-HAART era and was stable afterwards. For progressive multifocal leukoencephalopathy, a slight increase was seen over time. Focal white matter lesions without enhancement or mass effect increased between 1991 and 1998. CONCLUSIONS: During the HAART era, AIDS-related primary CNS lymphoma showed a strong decline, toxoplasmic encephalitis remained stable, and progressive multifocal leukoencephalopathy showed a slight increase. Focal white matter lesions without mass effect or contrast enhancement became the most frequently seen focal brain lesion. For differential diagnosis, PCR-based assays from CSF led to a shift from brain biopsy toward a minimally invasive approach with an augmented likelihood of in vivo diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Differential distribution of the JC virus receptor-type sialic acid in normal human tissues.

JC virus (JCV), a member of the polyomavirus family, causes a demyelinating disease of the central nervous system (CNS) in humans known as progressive multifocal leukoencephalopathy. Although glial cells are the principal target of JCV productive infection in progressive multifocal leukoencephalopathy patients, little is known regarding the site of JCV persistence and the mechanisms by which the virus spreads to the CNS to cause disease. Previous work has demonstrated the presence of replicating JCV DNA in B lymphocytes from peripheral blood, tonsil, and spleen and it has been hypothesized that lymphocytes may be one site of JCV persistence. Detection of viral gene products in renal tubules and excretion of JC virions in the urine suggests JCV persistence in the kidney. A respiratory route of viral transmission has also been hypothesized implicating the lung as another possible site of persistent JCV infection. Earlier studies from our laboratory have shown that terminal alpha 2,6-linked sialic acid is a critical component of the JCV receptor. In this report we examined the tissue distribution of this JCV receptor-type sialic acid in a panel of normal human tissues. Our results demonstrate that in normal brain JCV receptor-type sialic acids are expressed on oligodendrocytes and astrocytes, but not on cortical neurons. The receptor-type sialic acid is also more highly expressed on B lymphocytes than on T lymphocytes in normal human spleen and tonsil. In addition, both the kidney and lung express abundant levels of alpha 2-6-linked sialic acids. Our data show a striking correlation between the expression of the JCV receptor-type sialic acid on cells and their susceptibility to infection by the virus. These findings also support the hypothesis of JCV persistence in lymphoid tissue and B-cell-facilitated viral dissemination to the CNS.

Astrocytes↗
PubMed2002

p53 in nonneoplastic central nervous system lesions: an immunohistochemical and genetic sequencing study.

OBJECTIVE: Immunostaining for p53 commonly is considered a marker of neoplasia. Previous studies of nonneoplastic processes have yielded conflicting results. METHODS: To test the assumption that p53 immunoreactivity indicates neoplasia, we examined 60 formalin-fixed, paraffin-embedded biopsies of nonneoplastic central nervous system lesions, including gliosis (n = 12), infarction (n = 9), demyelinating disease (n = 23), progressive multifocal leukoencephalopathy (n = 11), and herpes simplex virus encephalitis (n = 5). Diffuse astrocytomas (n = 50) of World Health Organization Grades 2 to 4 also were studied, as were six control autopsy brains. The avidin-biotin-peroxidase complex method was used with commercially available monoclonal antisera to both p53 (clone DO7; Dako, Carpinteria, CA) and mdm2 (Dako), a protein known to stabilize p53. Two samples of each nonneoplastic lesion also were subjected to deoxyribonucleic acid isolation, amplification, and sequencing of exons 5 to 8 of TP53. RESULTS: Although it was low level in most instances, p53 immunoreactivity was noted in all but normal control samples. In reactive lesions, staining was largely observed in astrocytes and histiocytes. Scant oligodendroglia also were labeled in demyelinating disease. The progressive multifocal leukoencephalopathy samples revealed exceptionally strong staining in astrocytes and infected oligodendrocytes. Staining also was noted in occasional endothelial cells and neurons, and in rare lymphocytes. Immunoreactivity for mdm2, studied only in nonneoplastic lesions, was moderate to strong in all cases and limited to reactive astrocytes and histiocytes. No TP53 mutations were noted in the nonneoplastic lesions studied. To some extent, all astrocytomas exhibited p53 immunopositivity, particularly high-grade lesions. CONCLUSION: p53 immunoreactivity is not limited to astrocytomas, but it can be observed in lesions that often are mistaken for glioma. No TP53 mutations accompany p53 expression in nonneoplastic lesions, and mdm2 may be responsible for persistence of p53 expression in these processes.

Astrocytoma↗
PubMed2003

JC virus leukoencephalopathy complicating Wegener's granulomatosis.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain caused by the JC virus. It occurs in association with immunodepression due, for instance, to a hematological malignancy, HIV infection, or immunosuppressive therapy for an organ transplant or systemic disease. We describe the fourth reported case of PML in a patient receiving immunosuppressants for Wegener's granulomatosis. A 71-year-old woman receiving azathioprine and glucocorticoid therapy experienced onset of right-sided hemiplegia within a few days, became comatose, and died within a few days. MRI of the brain showed a subcortical lesion in the left parietal lobe generating low signal on T1 images and high signal on T2 images. The initial diagnosis was cerebral vasculitis. However, the postmortem examination showed PML. The diagnosis of PML rests on JC virus detection in the cerebrospinal fluid by PCR assay and on demonstration in a brain biopsy of the typical histological pattern with presence of the JC virus within the demyelinated lesions. No specific or effective treatments are available. Immunosuppressant drugs should be discontinued if possible.

Aged↗
PubMed2006

Immune reconstitution inflammatory syndrome in the CNS of HIV-infected patients.

OBJECTIVE: To describe challenges in diagnosis and management of patients with clinical syndromes of immune reconstitution inflammatory syndrome (IRIS) involving the CNS. METHODS: The authors describe three patients with clinically distinct neurologic manifestations of IRIS with HIV infection who presented as diagnostic and therapeutic challenges. RESULTS: One patient with cryptococcal meningitis developed acute cerebellitis with mass effect and brainstem compression. Corticosteroid therapy was associated with complete resolution of the cerebellar lesion but the patient developed VZV encephalitis. Another patient with progressive multifocal leukoencephalopathy developed subacute progression of focal neurologic deficits associated with contrast enhancing lesions on brain MRI. This patient had spontaneous resolution of the lesion but was left with residual deficits. One patient developed a progressive dementing syndrome and deterioration over several months resulting in coma during combination antiretroviral therapy. A brain biopsy in this latter patient showed massive infiltration of T lymphocytes predominantly of the CD8 subtype. This patient had a significant improvement with corticosteroids and change in antiretroviral regimen although she was left with residual cognitive impairment. CONCLUSIONS: Immune reconstitution inflammatory syndrome should be suspected in patients who show clinical or radiologic deterioration following initiation of antiretroviral therapy accompanied with improvement in CD4 cell count and viral load. Some patients may respond to a brief course of treatment with corticosteroids.

AIDS-Related Opportunistic Infections↗
PubMed2005

Detection of JC virus DNA sequences and expression of viral T antigen and agnoprotein in esophageal carcinoma.

BACKGROUND: The human polyomavirus JC virus (JCV) causes progressive multifocal leukoencephalopathy. Subclinical infection with JCV occurs in 85-90% of the population worldwide. The virus usually remains latent but can reactivate under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy. JCV is oncogenic in experimental animals and is associated with human brain tumors. JCV is found in normal mucosa of the gastrointestinal tract, and some colon carcinomas express the oncogenic JCV T-antigen protein. The objective of this study was to examine the presence of JCV DNA sequences and JCV protein expression in normal and malignant human esophageal tissues. METHODS: The authors examined the presence of JCV DNA sequences and protein expression in normal and malignant human esophageal tissues. Seventy well characterized biopsy specimens from patients with a spectrum of esophageal disorders were studied by immunohistochemistry, and 18 specimens were analyzed further by polymerase chain reaction amplification. RESULTS: JC viral DNA was isolated from 11 of 13 normal esophageal biopsy specimens (85%) and from 5 of 5 esophageal carcinomas (100%). Using immunohistochemistry, JCV T antigen was detected in 10 of 19 carcinomas (53%), agnoprotein was detected in 8 carcinomas (42%), p53 tumor suppressor was detected in 11 carcinomas (58%), and beta-catenin was detected in 4 carcinomas (21%). Zero of 51 normal, benign, and premalignant esophageal samples expressed viral proteins. Laser-capture microdissection verified the presence and specificity of JCV DNA sequences. beta-Catenin and p53 were colocalized with JCV T-antigen in the nuclei of neoplastic cells. CONCLUSIONS: The results provide evidence for infection of gastrointestinal tract cells by JCV and suggest a potential role of JCV in the development of upper digestive tract carcinomas.

Adult↗
PubMed1990

Acquired immunodeficiency syndrome: correlation of radiologic and pathologic findings in the brain.

The appearance on magnetic resonance (MR) and computed tomographic (CT) images of specific central nervous system disorders associated with acquired immunodeficiency syndrome in 12 cases was correlated with autopsy findings. There were three cases of human immunodeficiency virus (HIV) encephalopathy; three, primary lymphoma; three, toxoplasmosis; one, cryptococcosis; one, cytomegalovirus infection; and one, progressive multifocal leukoencephalopathy. MR imaging demonstrated the various cranial lesions more clearly than did CT. On the basis of MR imaging characteristics, HIV encephalopathy could be distinguished from other lesions, particularly progressive multifocal leukoencephalopathy. Basal ganglia were the most common sites of involvement in opportunistic infections and primary lymphoma. Reliable distinguishing features among lesions of the basal ganglia were not found, except for cryptococcal lesions, which had a unique appearance.

AIDS Dementia Complex↗
PubMed2003

Correlation between cidofovir-associated uveitis and failing immunorestoration during HAART.

In order to elucidate the factors related to the development of cidofovir-associated uveitis in AIDS patients receiving highly active antiretroviral therapy, the characteristics of 17 AIDS patients with Cytomegalovirus retinitis ( n=10) or progressive multifocal leukoencephalopathy ( n=7) treated with intravenous cidofovir were evaluated. Six cases of cidofovir-associated uveitis occurred among the patients with retinitis. No cases were detected among the patients with progressive multifocal leukoencephalopathy. Stepwise linear regression analysis revealed a significantly higher HIV-viremia level ( P=0.01) and a significantly lower CD4+ cell count ( P=0.009) among cases at the time of uveitis onset in comparison with patients who did not develop uveitis. Thus, cidofovir-associated uveitis seems to occur more frequently in AIDS patients with retinitis in whom highly active antiretroviral therapy fails to restore immunity.

Acquired Immunodeficiency Syndrome↗
PubMed1977

Neuromuscular syndromes associated with malignant disease.

Malignant disorders may produce neuromuscular syndromes in a variety of ways, for some of which it is still difficult to determine the exact pathophysiology. In the myopathic and neuropathic disorders, one possible explanation is that they are due to a virus such as is found in the rare "progressive multifocal leukoencephalopathy". This is seen in association with the malignant lymphomas and with other conditions such as sarcoidosis where immune responses may be altered by either the disease or the treatment. No viral material has been found in the nonmetastatic neurological disorders apart from progressive multifocal leukoencephalopathy. An alternative theory is that there may be an autoimmune process, the nervous system sharing some antigenic determinant with the neoplasm (Urich, 1967). The prognosis in the paraneoplastic neurological disorders is usually poor. As well as the direct threat to life posed by the malignant disease, when the neurological disorder is due to destruction of neurones (for instance cerebellar degeneration or sensory neuronopathy) recovery of function is impossible. Spontaneous remissions have been recorded in cases of proximal muscle weakness and sensorimotor neuropathy, but it is difficult to know whether the remissions have been truly spontaneous or related to treatment (excision of the neoplasm or administration of steroids). Further immunological and virological studies will probably reveal the answers to some of the outstanding problems. In the meantime the clinician must continue to investigate patients with muscular weakness for evidence of an occult neoplasm, and to repeat investigations if no other cause for the neurological disorder is found. Also, in patients with known malignant disease, apart from trying to differentiate forms of neuromyopathy from the effects of metastases the various metabolic disorders must be considered because the therapeutic possibilities are a little more promising in the paraneoplastic endocrine disorders. Ross (1975) wisely said that "cancer has replaced syphilis as the great imitator".

Cachexia↗
PubMed1992

Lack of JC viral genomic sequences in multiple sclerosis brain tissue by polymerase chain reaction.

With DNA extracted from brain specimens from 19 multiple sclerosis, 5 progressive multifocal leukoencephalopathy, 1 Alzheimer's disease, and 8 nonneurological control subjects, polymerase chain reaction was performed using nested sets of primer pairs amplifying segments of the large T and VP1 antigen-encoding sequences of JC virus. Both sequences were detected in each of the 5 brain specimens of progressive multifocal leukoencephalopathy but in none of the 19 multiple sclerosis, 1 Alzheimer's disease, or the 8 control brain specimens.

Base Sequence↗