Unexpected Diagnosis of Cerebral Toxoplasmosis by 16S and D2 Large-Subunit Ribosomal DNA PCR and Sequencing.

The protozoan parasite Toxoplasma gondii causes severe opportunistic infections. Here, we report an unexpected diagnosis of cerebral toxoplasmosis. T. gondii was diagnosed by 16S and D2 large-subunit (LSU) ribosomal DNA (rDNA) sequencing of a cerebral biopsy specimen and confirmed by T. gondii-specific PCR and immunohistochemistry. The patient was later diagnosed with HIV/AIDS.

Cerebral toxoplasmosis in Acquired Immunodeficiency Syndrome (AIDS) patients also provides unifying pathophysiologic hypotheses for Holmes tremor.

BACKGROUND: Holmes tremor is a rare symptomatic movement disorder. Currently suggested pathophysiological mechanisms of the disease are mostly derived from stroke cases. Although rare, cerebral toxoplasmosis may strengthen the pathophysiologic mechanism of disease. CASE PRESENTATION: A case of Holmes tremor secondary to cerebral toxoplasmosis in an AIDS patient is presented. A relevant literature search was performed, using pubmed and several entries for Holmes tremor as labelled in the literature. The unifying feature of our case and those of the literature is the involvement of either the cerebello-thalamo-cortical and/or the dentato-rubro-olivary pathways. The abscess or the extension of surrounding edema beyond these two circuits may account for the superimposed dysfunction of the nigrostriatal system in some but not all cases. The short delay observed in our observation and the dramatic response to treatment may indirectly support the secondary neuronal degeneration theory in the mechanism of Holmes tremor. CONCLUSION: Cases of cerebral toxoplasmosis in AIDS patients also provide arguments for the role of the thalamo-cortical and/or the dentato-rubro-olivary pathways dysfunction in the pathogenesis of Holmes tremor. Involvement of the nigro-striatal pathway may not be crucial in the development of this syndrome. Our case also brings additional indirect arguments for the role of secondary neuronal degeneration in the mechanism of Holmes tremor.

[Female patient with organic psychosyndrome and neurological focal signs after immunosuppressant therapy]. / Patientin mit organischem Psychosyndrom und neurologischen Herdzeichen unter Immunsuppression.

Cerebral toxoplasmosis nearly exclusively affects immunodeficient or immunocompromised patients. Mostly, it is a reactivation of latent toxoplasmosis. The pathogens, persisting in the reticuloendothelial system of heart and skeletal muscle cells, are causing a multifocal necrotizing encephalitis. The characteristic clinical features are organic psychosyndrome and focal neurological signs such as monoparesis, hemiparesis, aphasia, or seizures. Here we describe a 56-years-old patient who developed cerebral toxoplasmosis after receiving stem-cell transplantation treatment for acute myeloic leukemia, and we discuss the clinical features, differential diagnoses and therapeutic strategies.

Late-Onset Cerebral Toxoplasmosis After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND Toxoplasmosis is an uncommon but potentially fatal complication following allogeneic hematopoietic stem cell transplantation (HCT). Post-transplant toxoplasmosis is often a reactivation of prior infection and typically occurs within the first 6 months of transplant. Herein, we report that cerebral toxoplasmosis may occur 22 months after allogeneic hematopoietic stem cell transplantation. CASE REPORT We describe a case of cerebral toxoplasmosis that occurred 22 months after an allogeneic HCT while the patient was on aerosolized pentamidine for Pneumocystis jiroveci pneumonia (PCP) prophylaxis. The disease was only diagnosed after brain biopsy because of atypical MRI appearance of the cerebral lesion and negative Toxoplasma gondii IgG antibody test result in the cerebrospinal fluid (CSF). The patient received pyrimethamine and sulfadiazine treatment, with dramatic improvement after several months. The patient is alive 2 years after infection diagnosis, with no evidence of disease and is off Toxoplasma prophylaxis. CONCLUSIONS Cerebral toxoplasmosis can occur late after allogeneic HCT while patients are on immunosuppression therapy, with atypical features on imaging studies and negative Toxoplasma gondii IgG antibody test result in the CSF. Pre-transplant serologic screening for T. gondii antibodies in allogeneic transplant candidates is warranted. Brain biopsy can be a helpful diagnostic tool for cerebral lesions.

Extensive brain masses and cavitary lung lesions associated with toxoplasmosis and acquired immunodeficiency syndrome.

Toxoplasmosis is an important cause of enhancing brain lesions in patients with acquired immunodeficiency syndrome (AIDS), and it is typically associated with low CD4-lymphocyte counts. Extensive toxoplasma encephalitis when the CD4-lymphocyte count is above 100 cells/µl is unusual. Cavitary lung lesions are also not typically associated with toxoplasmosis. Here, we present a case of toxoplasmosis associated with extensive brain masses and cavitary lung lesions, both of which improved with directed toxoplasmosis therapy, in an AIDS patient with a CD4 cell count of 120 cells/µl.

Spinal cord toxoplasmosis in human immunodeficiency virus infection/acquired immunodeficiency syndrome.

Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.

Early biopsy versus empiric treatment with delayed biopsy of non-responders in suspected HIV-associated cerebral toxoplasmosis: a decision analysis.

OBJECTIVE: To construct and evaluate a decision analytic model of proposed management strategies for HIV-infected patients presenting with cerebral mass lesions, radiographically compatible with toxoplasmosis, lymphoma, or other etiologies, assuming knowledge of Toxoplasma antibody status in serum. METHODS: Using decision analysis, we evaluated two management strategies, for patients found to be either Toxoplasma-seropositive or -negative, for whom an initial choice was made for early brain biopsy (EB) or for empiric therapy with delayed biopsy (ETDB) of non-responders. The outcome to be optimized was the percentage of patients alive at 12 months. Model variables included predictive value of toxoplasmosis serology, probabilities of treatment response and death within 14-21 days conditional on correct diagnosis, probability of operative death, probabilities of non-diagnostic brain biopsy conditional both on correct diagnosis and prior treatment. RESULTS: One and two-way sensitivity analyses, by Toxoplasma serostatus, led to the following conclusions (1) for Toxoplasma-seropositive patients, ETDB gives nearly equivalent outcomes to EB of all patients; (2) for Toxoplasma-seronegative patients, although both strategies have equivalent outcomes under baseline assumptions, EB is preferred if there are even small survival advantages for early versus delayed diagnosis of lymphoma or other conditions, or if risk of death within 14-21 days of ET exceeds 10% when correct diagnosis is not toxoplasmosis. CONCLUSION: Under plausible assumptions, Toxoplasma-seronegative patients will benefit from an early biopsy strategy.

Treatment regimens for patients with toxoplasmic encephalitis.

Toxoplasma gondii is an obligate intracellular parasitic protozoan that infects a variety of warm-blooded animals, including humans. Infection is usually asymptomatic in immunocompetent individuals but may be devastating in immunocompromised individuals such as those with acquired immunodeficiency syndrome (AIDS). Clinical manifestations of infection in immunocompromised patients include the development of encephalitis. It has been estimated that approximately 30% of patients with AIDS who are latently infected will eventually develop toxoplasmic encephalitis. The most common regimen used to treat toxoplasmic encephalitis is a combination of pyrimethamine 50 to 100 mg/d and sulfadiazine 4 to 8 g/d, with or without folinic acid 10 mg/d. This regimen, however, commonly leads to adverse effects or relapses. Other pharmacologic approaches include the use of clindamycin rather than sulfadiazine, the macrolide antibiotics, atovaquone, 5-fluorouracil, trimethoprim/sulfamethoxazole, minocycline or doxycycline, trimetrexate with folinic acid, dapsone, rifabutin, pentamidine, and diclazuril. None of these alternative regimens has been proven to be more effective than the standard pharmacologic therapy. An evolving approach is the use of immunotherapy, such as interleukin-2, -6, and -12; interferon-gamma; and alpha-tumor necrosis factor. Restoring a competent immune system may be the only cure for toxoplasmosis and other opportunistic infections.

Neurocysticercosis and acquired cerebral toxoplasmosis in children.

Neurocysticercosis, prevalent wherever pigs are raised in the presence of poor sanitation, is the most common identifiable cause of new-onset epilepsy throughout the developing world. As immigration patterns have changed, children with neurocysticercosis are seen throughout the United States. Acute cysticercosis, the most common manifestation in children, reflects the host response to the dying parasite. Children typically present with seizures and have an excellent prognosis. Neuroimaging demonstrates a single ring or nodular enhancing lesion surrounded by edema. Short-term anticonvulsant therapy is indicated, but treatment with antiparasitic agents is not required. Other forms, such as active cysts (intact organism), intraventricular or subarachnoid racemous cysticercosis, and cysticercal meningoencephalitis, are less common manifestations of parasitic infection. Toxoplasmosis, caused by the parasite Toxoplasma gondii, can be acquired by ingestion of infected undercooked meat or from oocytes shed in cat feces. Acquired cerebral toxoplasmosis, due to primary or reactivated infections, rarely occurs in immunocompetent children. In children who are immunodeficient as the result of AIDS, chemotherapy, tissue transplantation, or congenital immunodeficiency, toxoplasmosis may be difficult to distinguish from cerebral lymphoma. A variety of techniques, including neuroimaging, Thallium-201 SPECT, polymerase chain reaction analysis of CSF, and special histological methods, may be used to diagnose acquired toxoplasmosis. Antiparasitic therapy, using pyrimethamine and sulfadiazine, and serial neuroimaging often enable clinicians to differentiate toxoplasmosis from other central nervous system lesions. Toxoplasmosis may respond to other antimicrobials, including macrolide antibiotics, dapsone, clinidamycin, and atovaquone. Suppressive treatment is generally required for life in immunodeficient patients. Immunodeficient children with acquired toxoplasmosis have high rates of mortality and neurological sequelae.

HIV-1-related neurologic disorders. Neurosurgical implications.

It has become important for clinicians to increase their understanding of the breadth, mechanism, and neurosurgical implications of viral illnesses of the central nervous system. These needs can now be more safely and accurately addressed using stereotactic neurosurgical techniques. This article provides an introduction to these disease and identifies the neurosurgical issues that may be raised in their diagnosis and treatment.

A case of cerebral toxoplasmosis.

A histopathologically proven case of cerebral toxoplasmosis in a young HIV positive patient has been presented. The clinical problems in management are highlighted.

[Cerebral toxoplasmosis in a hospital environment in Lomé (Togo)]. / Toxoplasmose cérébrale en milieu hospitalier a Lomé (Togo).

The authors report the clinical, serological and neuroradiological results of a study about 23 cases of cerebral toxoplasmosis in the Teaching Hospital of Lome. Response to antitoxoplasmic treatment was rapidly favourable with all patients. Cerebral toxoplasmosis was the inaugural manifestation of AIDS in 20 of the 23 patients.

[Toxoplasmosis in AIDS]. / Toxoplasmose au cours du SIDA.

Toxoplasmosis is one of the major opportunistic infections observed in France in 15 to 37 percent of HIV-infected patients. Its main manifestation is encephalitis. Other, less frequent manifestations are chorioretinitis, pneumonia or disseminated toxoplasmosis. The conventional treatment is a combination of pyrimethamine 50-75 mg/day and sulfadiazine 6-8 g/day. Acute therapy should be pursued for at least 3 weeks or until optimal response is achieved, i.e. 6 to 8 weeks in most cases. The pyrimethamine-clindamycin combination in doses of at least 2.4 g/day is a possible alternative. Other drugs are being studied, but there is still a need for new drugs active against the parasite, that could be used in humans. In HIV-infected patients treatment should be maintained lifelong to prevent relapses. Maintenance regimens use the same drugs as acute therapy but in lower doses. The main field of research is primary prophylaxis of toxoplasmosis in HIV-infected patients.

Usefulness of stereotactic biopsy and neuroimaging in management of HIV-1 Clade C associated focal brain lesions with special focus on cerebral toxoplasmosis.

BACKGROUND: Focal brain lesions (FBL) in HIV/AIDS frequently pose a diagnostic dilemma as the etiology varies from infective (tuberculoma, toxoplasmosis and tuberculous abscesses) to neoplastic lesions like lymphoma. For determining etiology, advanced neuroimaging techniques, serological and molecular biological tests have been evolved with varying sensitivities/specificities. Stereotactic biopsy (STB) of the lesions is reserved for lesions unresponsive to appropriate therapy. OBJECTIVE AND METHODS: In this study, the diagnostic yield of neuroimaging [cranial CT (n=25), MRI (n=24), and Th201/99Tc SPECT scan (n=18)] is compared with histopathological diagnosis obtained by STB (n=21) or autopsy (n=4) in 25 HIV-1 subtype C seropositive individuals with FBL identified by neuroimaging with special reference to cerebral toxoplasmosis in an eighteen month study period (2006-2007). RESULTS AND CONCLUSION: Cerebral toxoplasmosis was the most frequent cause of FBL (21/25, 84%), followed by one case each of tuberculoma, progressive multifocal leukoencephalopathy (PML), primary central nervous system lymphoma (PCNSL) and measles inclusion body encephalitis (MIBE), the last two diagnosed at autopsy. Of the 21 cases of cerebral toxoplasmosis, definitive diagnosis with histopathological confirmation was available in 14/21 (66.6%), with indirect evidence suggesting probable toxoplasmosis in seven, all of whom responded to antitoxoplasma therapy. CT and MRI had comparable specificities (75%), while MRI had marginally higher sensitivity (85% versus 80.9%) in detecting multiple lesions. The positive predictive value of both CT and MRI was identical (94.4%), suggesting that CT maybe a cost effective screening tool in resource restricted settings, for evaluating FBL. Sensitivity of 99Tc SPECT scan for diagnosing inflammatory lesions was 75% but failed to differentiate PCNSL from toxoplasmosis. This study is the first of its kind from India analyzing FBL with specific focus on cerebral toxoplasmosis in the setting of HIV-1 subtype C.

Neurotoxoplasmose em paciente imunocompetente: relato de caso / Neurotoxoplasmosis in an Immunocompetent Patient: Case Report

A toxoplasmose é uma doença causada pelo protozoário Toxoplasma gondii e é a principal causa de lesão com efeito de massa no sistema nervoso central (SNC) em pacientes imunodeprimidos, causando sintomas neurológicos significativos. Em pacientes imunocompetentes, a evolução clínica da toxoplasmose é habitualmente benigna e a infecção é, na maioria das vezes, assintomática. O diagnóstico da neurotoxoplasmose é presuntivo, baseado nos achados de tomografia computadorizada (TC) ou de ressonância magnética (RM), e emcasos inconclusivos, pode-se utilizar a biópsia cerebral estereotáxica. O paciente relatado apresentava lesões sugestivas de neurotoxoplasmose na RM de encéfalo, porém era imunocompetente, e a sorologia para neurotoxoplasmose era negativa para o IgM. Foi submetido então a biópsia estereotáxica como extensão de propedêutica. O presente trabalho visa, a partir do relato de um caso raro, discutir sobre as formas de diagnóstico e tratamento de uma infecção em paciente previamente sadio, cuja evolução foi benigna devido ao diagnóstico e tratamento precoces.

Toxoplasmosis is a disease caused by the protozoan Toxoplasma Gondii and is the leading cause of injury with mass effect on the central nervous system (CNS) in immunocompromised patients, that causes significant neurological symptoms. In immunocompetent patients, the clinical course of toxoplasmosis is usually benign and the infection is most often asymptomatic. The presumptive diagnosis of toxoplasmosis is based on findings of computed tomography (CT) or magnetic resonance imaging (MRI), and inconclusive cases, can use stereotactic brain biopsy . The reported patient had lesions suggestive of cerebral toxoplasmosis in brain MRI, but was immunocompetent and toxoplasmosis serology was negative for IgM. The, he underwent a stereotactic biopsy as an extension of workup. The present work aims, from a rare case description, discuss ways of diagnosing and treating an infection in a previously healthy patient whose evolution was benign diagnosis because early treatment.