Frequent Hemorrhagic Lesions in Cerebral Toxoplasmosis in AIDS Patients

Cerebral toxoplasmosis is a frequent complication in immunosuppressed patients such as AIDS (acquired immunodeficiency syndrome). Frequently, lesions are located deep in the brain which are inaccessible for biopsy making rapid diagnosis dependent on accurate interpretation of neuroimaging findings. The commonest cranial CT findings reported in toxoplasmosis are ring enhancing hypodense lesions in basal ganglia or cortical gray matter. Hemorrhage has only rarely been described and is usually seen following antitoxoplasma treatment. We reviewed the records of 11 AIDS patients with cerebral toxoplasmosis and found multiple hemorrhagic cerebral, cerebellar, or brain stem lesions in 7 of 11 patients. Six patients had hemorrhage at the time of initial clinical presentation and one developed hemorrhage following 2 weeks of antitoxoplasma treatment. We conclude that hemorrhagic lesions are frequently found on cranial MRI scans in cerebral toxoplasmosis. AIDS patients presenting with hemorrhagic cerebral lesions should be considered for a trial of presumptive antitoxoplasma treatment.     

Hemichorea-hemiballismus associated with acquired immune deficiency syndrome and cerebral toxoplasmosis

A young woman had hemichorea-hemiballismus subsequently found to be secondary to a cerebral toxoplasmosis infection complicating human immunodeficiency virus infection. This patient had the sixth reported case of acquired immune deficiency syndrome (AIDS) with hemichorea-hemiballismus, and each has been secondary to cerebral toxoplasmosis. The presence of hemichorea-hemiballismus in a young patient should suggest a diagnosis of AIDS and in particular the diagnosis of secondary cerebral toxoplasmosis. Other movement disorders that occur in AIDS are discussed.     

Prothrombotic states in HIV disease and stroke complications

Thirty to 40% of patients with acquired immunodeficiency syndrome (AIDS) have symptoms and signs of neurologic dysfunction. Radiographic and pathologic studies reveal evidence of neurologic involvement in 75% to 90% of cases of advanced-stage human immunodeficiency virus-1 (HIV) disease. Before the introduction of highly active antiretroviral therapies, AIDS dementia complex and opportunistic infections of the central nervous system were frequent causes of global cerebral dysfunction. Focal neurological deficits were most commonly due to toxoplasmosis, primary central nervous system (CNS) lymphoma, or progressive multifocal leukoencephalopathy.Thrombotic events including cerebral infarction and venous thrombosis have been reported in patients with HIV/AIDS. Various hematologic abnormalities have been described that could lead to a hypercoagulable state, including antiphospholipid antibodies; deficiencies of antithrombin III, protein C, and protein S; and increased levels of von Willebrand factor and D-dimer.In the majority of cases of cerebral infarction, there is an associated precipitating event such as opportunistic infection or malignancy. However, vasculopathy has also been described in both adults and children. Furthermore, there are reports of HIV patients with cerebral infarction in whom an HIV-related coagulopathy is identified and other cases where no explanation is found, but only a limited hematologic evaluation has been performed.     

The changing pattern of HIV neuropathology in the HAART era

Highly active antiretroviral treatment (HAART), which has been available for most AIDS patients in France since 1996, has resulted in a dramatic improvement of the progression of the disease. From the survey of our series of 343 brains with acquired immunodeficiency syndrome (AIDS) from patients who died between 1985 and 2002, we found both quantitative and qualitative changes in the pattern of human immunodeficiency virus (HIV) neuropathology. Quantitatively, despite a dramatic decrease in the number of autopsies, brain involvement remained a major cause of death. There was an overall decrease in incidence of cerebral toxoplasmosis, cytomegalovirus encephalitis (CMVE), and HIV encephalitis (HIVE), for which successful treatment is available. This contrasted with the unchanged incidence of progressive multifocal leukoencephalopathy (PML) and malignant non-Hodgkin lymphomas (MNHL). However, when looking closer at the 3 last years, the incidence of diseases affecting patients with severe immunodepression (CMVE, PML, and MNHL) decreased between 2000 and 2002, whereas infections occurring in patients with milder immunodeficiency, toxoplasmosis, varicella-zoster encephalitis (VZVE), or herpes simplex virus encephalitis (HSVE) became more frequent. In addition, we found uncommon types of brain infection such as BK virus encephalitis or general paresis. Finally, we described new variants of HIVE: severe leukoencephalopathy with intense perivascular macrophage and lymphocyte infiltration, possibly due to an exaggerated response from a newly reconstituted immune system, and chronic "burnt out" forms of HIVE as VZVE, toxoplasmosis, or PML, possibly associated with prolonged survival, in which neither inflammation nor organisms could be detected. These findings are compared with those reported in other neuropathological studies from different developed countries.     

Primäres Lymphom des zentralen Nervensystems als Neuromanifestation im AIDS-Stadium

In patients infected with human immunodeficiency virus (HIV), the risk of developing non-Hodgkin's lymphoma is over 100 times greater than with noninfected persons. Primary central nervous system lymphoma as a complication of the acquired immunodeficiency syndrome (AIDS) occurs in up to 2.4% of all cases and is strongly associated with the Epstein-Barr virus. The prognosis is very poor, with a mean survival time of 21 to 27 days without therapy and up to 119 days with radiation therapy. We describe the course of seven AIDS patients with histologically proven primary central nervous system lymphoma and present a review of clinical symptoms, diagnosis, and therapy. The main criteria for differential diagnosis from other secondary neuromanifestations such as cerebral toxoplasmosis, progressive multifocal leukoencephalopathy, abscesses, and infarctions are described.     

HIV-associated cerebral toxoplasmosis -- review and retrospective analysis of 36 patients

Highly active antiretroviral therapy (HAART) has resulted in a reduction of morbidity and mortality in HIV-associated cerebral opportunistic infection.Before HAART, up to 50% of all HIV-infected patients in Europe developed cerebral toxoplasmosis, an encephalitis caused by reactivation of Toxoplasma gondii infection.Although potent therapeutical options exist, the prognosis is still poor. We describe the course of 36 AIDS patients with cerebral toxoplasmosis and present a review of clinical signs, diagnosis, therapy, and survival times.The main criteria for differential diagnosis from other secondary neuromanifestations such as primary CNS lymphoma, progressive multifocal leukencephalopathy, abscesses, and ischemic infarctions are described. Indications and problems of stereotactic biopsy are discussed.     

CNS changes in HIV-infected patients: magnetic resonance spectroscopy

Changes that may appear in the central nervous system in the course of AIDS either result directly from HIV infection or--as is the case with opportunistic infections and some neoplasms--develop as a secondary consequence of general immunodeficiency. Neuroimaging techniques may be most useful in the differential diagnosis of these lesions. Basic principles of HIV encephalitis and progressive multifocal leukoencephalopathy differentiation in MRI scans are discussed in the paper, and diagnostic possibilities of MR imaging in some other infections (tuberculosis, toxoplasmosis, and cryptococcosis) are outlined. Special attention is paid, on the one hand, to difficulties in the differentiation between toxoplasmosis and lymphoma, and on the other hand--to the growing diagnostic utility of MR-spectroscopy in this respect.     

Weber's syndrome due to a possible solitary brainstem toxoplasmosis as a presenting sign of AIDS

We report the case of a young man, with a previous history of parenteral drug abuse, who developed a Weber's syndrome. Brain computed tomographic scan and nuclear magnetic resonance imaging showed a single ring enhancing lesion in the right mesencephalic site. After the demonstration of seropositivity for human immunodeficiency vims, a presumptive diagnosis of cerebral toxoplasmosis in an AIDS patient was made and a specific treatment was started. A partial neuroradiological and clinical improvement were obtained. Opportunistic cerebral lesions, as first manifestation of AIDS, should be always considered in subjects at risk for AIDS who present a brainstem syndrome.     

Movement disorders due to cerebral Toxoplasma gondii infection in patients with the acquired immunodeficiency syndrome (AIDS).

Hemichorea and parkinsonism are unusual manifestations of cerebral toxoplasmosis in patients with AIDS. We here describe two such cases and we reviewed extensively the literature (through computer searches using MEDLINE) for other reported instances. In our patients, unlike the other neurological symptoms, the response of the movement disorders to anti-toxoplasmosis therapy was delayed and only partial. We demonstrate that tetrabenazine is a valuable additional symptomatic treatment for choreic movements in one of our patients. We emphasize that, among patients suffering from AIDS, particularly in countries with high prevalence of toxoplasmosis, the occurrence of movement disorders should first suggest the diagnosis of cerebral toxoplasmosis.     

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.     

Stereotactic biopsy of cerebral lesions in acquired immunodeficiency syndrome

The efficacy, mortality and morbidity of CT directed stereotactic biopsy of a cerebral lesion in 32 Human Immunodeficiency Virus (HIV) infected patients between July 1991 and June 1994 who had an atypical presentation for toxoplasmosis or who were failing or intolerant of empirical antitoxoplasmosis treatment was evaluated. An histological diagnosis was able to be made in 85%: progressive multifocal leucoencephalopathy (PML) in 13, primary cerebral lymphoma in 10, toxoplasmosis in 3 and HIV encephalitis in one. Non-specific reactive changes or gliosis were seen in 5 patients. There was no mortality, and morbidity occurred in 2 patients: one intraventricular haemorrhage and one transient third nerve palsy. Correct diagnosis made by image-directed stereotactic biopsy of central nervous system (CNS) disease in acquired immunodeficiency syndrome (AIDS) patients may improve outcome, particularly in those diseases where effective treatment strategies already exist and become increasingly available in the future.     

Electroencephalography in AIDS and AIDS-related complex

EEG records from 47 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) were reviewed retrospectively to correlate EEG findings with neurologic abnormalities. Abnormal EEGs were found in 22 of 33 (67%) patients with AIDS and 5 of 14 (36%) patients with ARC. Among 27 patients with abnormal EEGs, there were 9 patients with dementia, 10 with opportunistic infections of the CNS, and 6 with no apparent neurologic disease. AIDS dementia was associated with intermittent or continuous slowing, often most prominent anteriorly. Focal slowing or sharp activity was usually found in patients who had focal CNS processes, such as cerebral toxoplasmosis and CNS lymphoma. These findings suggest the EEG can be a useful diagnostic test for evaluating patients with AIDS and ARC, particularly when these patients present with seizures, psychiatric symptoms, or cognitive dysfunction. The significance of abnormal EEGs in patients who are neurologically asymptomatic is unknown.     

Cerebral toxoplasmosis and AIDS. Clinical, neuroradiological and immunological findings in 15 patients.

Cerebral toxoplasmosis is the most common cause of focal CNS disease complicating AIDS and its incidence ranges from 3% to 40% of such patients. This opportunistic infection is generally due to reactivation of chronic toxoplasmosis as a consequence of severe immune deficiency. We present the clinical, neuroradiological and immunological findings of 15 AIDS patients with cerebral toxoplasmosis. All patients had focal neurological signs. CT-scan (13 cases) and NMR (2 cases) showed single or multiple mass lesions and edema. Serum IgG anti-Toxoplasma antibodies were positive in 14 patients; CSF specific IgG were positive in 5 out of 7 studied patients, while serum and CSF specific IgM were negative in all subjects. The intrathecal synthesis of anti-Toxoplasma antibodies were high in all 7 patients. A presumptive diagnosis of cerebral toxoplasmosis is based on the focal cerebral signs and neuroradiological findings. It is more frequently confirmed by the improvement of the clinical and neuroradiological picture during the treatment with pyrimethamine-sulphadiazine or clindamycin.     

Neurological manifestations in three German children with AIDS

We report the neurological findings in two children with AIDS and one child with lesser AIDS. The first patient developed acute encephalopathy 37 months after having received a blood transfusion from a HTLV-III positive donor. CCT showed ring-enhancement and hypodense lesions with homogenous enhancement. Autopsy revealed CNS toxoplasmosis. The second child with AIDS, born to an iv drug-addicted mother, had one seizure at four months of age, but other neurologic signs were absent. She died of pneumonia due to Pneumocystis carinii at seven months of age. Postmortem examination of the brain revealed extensive nerve cell damage in the cerebral cortex and cerebellum, probably due to terminal hypoxemia and not AIDS-related. In both children clinical features of childhood AIDS like failure to thrive, lymphadenopathy, oral thrush and chronic pulmonary infiltrates were absent. The hallmark of the third child's clinical course was a progressive loss of psychomotor abilities with onset of the neurological symptoms nine months before other signs of AIDS occurred. AIDS should be suspected or excluded in children at increased risk for AIDS presenting with either acquired atypical CNS infection or unexplained developmental regression, even in the absence of other clinical symptoms of pediatric AIDS.     

Neurotoxoplasmosis and AIDS. Cerebrospinal fluid analysis in 96 patients.

The behavior of CSF inflammatory pattern in patients with AIDS and/or toxoplasmosis of the CNS is studied in 176 patients, divided in three groups. In the first group, 96 patients with toxoplasmosis and AIDS are considered; in the second group, 50 patients with toxoplasmosis without AIDS; in the third group, 30 AIDS patients without toxoplasmosis nor any other opportunistic infection. It is possible to conclude that patients with toxoplasmosis associated to AIDS exhibit CSF inflammatory pattern similar to patients with neurotoxoplasmosis without AIDS, except in respect to gamma globulin rates for which a cumulative effect can be detected.     

Neurologic manifestations of toxoplasmosis in AIDS

Central nervous system (CNS) toxoplasmosis is the most common cause of cerebral mass lesions in AIDS patients. Toxoplasma gondii is commonly acquired through ingestion of contaminated meats resulting in latent infection. With the onset of immunosuppression, it may preferentially infect the CNS, resulting in a wide range of clinical presentations. Effective antibiotic therapy is available and capable of producing rapid remission of active infection but must be continued throughout life to prevent recurrence. Characteristic presentations and rapid therapeutic response permit presumptive diagnosis and initiation of specific antibiotics in many cases; however, appropriate clinical and radiographic monitoring to detect alternative or mixed pathologies is necessary. Unusual presentations may hinder rapid diagnosis and should be considered in AIDS patients with cryptic CNS symptoms. Despite increasing attention to primary prophylaxis, the worldwide distribution of this parasite, its potential to be the presenting illness in previously unidentified human immunodeficiency virus-infected individuals, and failures of prophylaxis are likely to make toxoplasmosis an important continuing source of neurologic morbidity in AIDS.     

Asymptomatic diffuse “encephalitic” cerebral toxoplasmosis in a woman with systemic lupus erythematosus

Classic cerebral toxoplasmosis typically presents with neurologic symptoms such as seizures and mental status changes and histological examination shows focal lesions with necrosis. However, in the diffuse “encephalitic” form, patients are asymptomatic with diffuse, inflammatory, non-necrotic lesions. Asymptomatic diffuse “encephalitic” toxoplasmosis has been reported only in four acquired immunodeficiency syndrome patients and one human immunodeficiency virus (HIV) negative patient with chronic lymphocytic leukemia. We present a 36-year-old HIV-negative woman with systemic lupus erythematosus and lupus nephritis who was on immunosuppression for 9 years after cadaveric renal transplant and died from pulmonary hemorrhage and cytomegalovirus pneumonia. Brain autopsy findings revealed multifocal microglial nodules containing Toxoplasma bradyzoites and associated astrogliosis. These nodules were prominent in the cerebellum, midbrain and medulla and also present in the cortex and thalamus. No coagulative necrosis, necrotizing abscesses, or other opportunistic infections were present. The patient had previously exhibited no neurologic symptoms and there was no clinical suspicion for toxoplasmosis. To the best of our knowledge, this is the first case of diffuse, non-necrotizing, “encephalitic” cerebral toxoplasmosis reported in a lupus patient and also the first reported female case.     

Movement disorders and AIDS

We studied seven patients with AIDS or AIDS-related complex (ARC) and movement disorders. Three had hemichorea-ballismus, two had segmental myoclonus, one had postural tremor with dystonia, and one had paroxysmal dystonia. Besides the hyperkinesias, two patients had parkinsonism, and one had cerebral Whipple's disease. In two, the movement disorder preceded other evidence of AIDS; in three others, the diagnosis of AIDS was not considered until there was a movement disorder. The movement disorders were attributed to toxoplasmosis in four patients (one confirmed at autopsy), viral encephalitis, vacuolar myelopathy, and CNS Whipple's disease.     

Pure trigeminal motor neuropathy presenting with temporo-mandibular joint dysfunction in a patient with HIV and HCV infections

Pure trigeminal motor neuropathy (PTMN) is a rarely described condition. We report the case of a 41-year-old woman infected with the human immunodeficiency virus (HIV1) and hepatitis C virus who presented with weakness of left temporalis and masseter muscles and painful left temporomandibular joint dysfunction (TMD) a few months after cerebral toxoplasmosis revealing acquired immunodeficiency syndrome (AIDS). Magnetic resonance imaging revealed severe wasting and fat replacement of the left temporalis, pterygoid and masseter muscles and showed neither abnormalities in the left motor nucleus of the trigeminal nerve nor compression of the left trigeminal nerve. Electromyographic examination gave evidence of denervation in the left temporalis, masseter and pterygoid muscles and blink reflex studies were normal, confirming the diagnosis of PTMN which was probably secondary to HIV and HCV co-infection.     

Hemichorea in acquired immunodeficiency syndrome. Toxoplasmosis abscess in the striatum]

Three HIV seropositive patients presented with cerebral toxoplasmosis which was treated by anti-infectious agents. After partial improvement, they developed hemichorea related to striatal infectious lesions. In AIDS patients with cerebral toxoplasmosis, autopsy series have reported a high incidence of basal ganglia abscesses, explaining the occurrence of involuntary movements such as hemichorea.