CEREBRAL TOXOPLASMOSIS IN THE COURSE OF HIV INFECTION - CASE STUDY.

OBJECTIVE: Aim: To the aim of our study is to draw attention to the need to take into account HIV infection and its complications, such as CNS toxoplasmosis, in the differential diagnosis of people presenting with impaired consciousness. We analyzed our patient's medical records and available statistical data on HIV infection, as well as literature on nervous system involvement in the course of AIDS. PATIENTS AND METHODS: Materials and Methods: In our paper, we present the case of a 43-year-old male who was admitted to a neurological ward due to impaired consciousness. Diagnostic imaging and laboratory tests were conducted, and patient was diagnosed with toxoplasmosis in the course of AIDS. CONCLUSION: Conclusions: HIV infection is a global public health problem. In the absence or ineffectiveness of treatment, it leads to profound immunodeficiency and, consequently, opportunistic infections. One of them is the reactivation of the latent Toxoplasma gondii infection. It is the most common cause of extensive cerebral lesions in patients infected with the HIV virus. In these cases, MRI reveals numerous scattered ring-enhancing lesions. The symptoms are non-specific: headaches, impaired consciousness, convulsions, behavioral changes, and focal neurological deficits. The onset of neurological symptoms may be the first clinically relevant manifestation of AIDS. It is key to diagnose such patients as soon as possible and treat them accordingly.

Imaging in Differentiating Cerebral Toxoplasmosis and Primary CNS Lymphoma With Special Focus on FDG PET/CT.

OBJECTIVE. The purpose of this article is to present a brief review of literature evaluating different imaging modalities with special focus on 18F-FDG PET/CT in differentiating cerebral toxoplasmosis and primary CNS lymphoma. CONCLUSION. Differentiating cerebral toxoplasmosis and primary CNS lymphoma is crucial in the care of patients with HIV infection. Delayed diagnosis can lead to considerable morbidity and mortality. The reference standard for diagnosis is biopsy and histopathologic examination. Biopsy has disadvantages due to its invasive nature and associated complications. Noninvasive imaging can be an alternative to biopsy for differentiation of toxoplasmosis and primary CNS lymphoma. Despite advances in MRI techniques, prophylaxis of opportunistic infection, and treatment of HIV infection, clinical situations continue to arise in which the diagnosis is not clear. In these instances, molecular imaging can be helpful.

Desensitization to trimethoprim-sulfamethoxazole in a toxoplasmic encephalitis patient who was intolerant to conventional treatments.

Toxoplasma gondii is an obligate intracellular protozoan that causes toxoplasmic encephalitis (TE) in immunocompromised patients. We describe a case of a 29-year-old Japanese man presenting with headache and vomiting. He had previously been diagnosed with human immunodeficiency virus infection. Magnetic resonance imaging identified some nodules in his brain. We suspected TE and began treatment successively with parenteral trimethoprim-sulfamethoxazole (TMP/SMX) plus clindamycin. After that, we switched to pyrimethamine plus sulfadiazine (PMT/SDZ) because these drugs are the first-line treatment for TE. Because the patient experienced nausea and vomiting, PMT/SDZ was replaced with TMP/SMX, atovaquone, and clindamycin. However, the patient could not tolerate them owing to their adverse reactions. Thus, we attempted oral desensitization to TMP/SMX to treat his TE. We began desensitization with 0.4/2 mg of TMP/SMX. The patient experienced morbilliform rash and elevated aminotransferase levels. Therefore, we administered a glycyrrhizin and an antihistamine and continued the last tolerable dose until these symptoms improved. After 37 days, we achieved desensitization to 160/800 mg of TMP/SMX, and the patient's symptoms improved. After using nested-polymerase chain reaction to identify T. gondii DNA in his frozen cerebrospinal fluid, which was collected at admission, his diagnosis was confirmed as TE. This might be the first case to attempt desensitization to TMP/SMX to treat TE.

[Neurological symptoms in a patient on anti-TNF therapy, methotrexate and prednisolone for rheumatoid arthritis]. / Neurologische Symptome bei einer Patientin unter TNF-α-Inhibitor, Methotrexat und Prednisolon bei rheumatoider Arthritis.

A 78-year-old woman with rheumatoid arthritis on TNF-α inhibitor, methotrexate and prednisolone presented with severe but unspecific symptoms such as leg weakness, shivering, bifrontal headache, nausea and staggering. The broad range of differential diagnoses lead to intricate and time-consuming diagnostic procedures. Serology, magnetic resonance imaging and microbiological investigations represent important steps to make the final diagnosis of cerebral toxoplasmosis. Both diagnostic approach and therapy require close cooperation of different disciplines. Therapies of rheumatoid arthritis as well as of toxoplasmosis are based on a long-term treatment and could be associated with numerous harmful side effects. Continuous monitoring and permanent adjustment of therapy regimes are therefore mandatory.

[IMPROVEMENT OF ETIOLOGICAL DIAGNOSIS OF THE CEREBRAL TOXOPLASMOSIS IN HIV-INFECTED PERSONS].

The objective of the study was to determine the diagnostic value of the parallel detection of the avidity index of the IgG to Toxoplasma gondii in the blood and cerebrospinal fluid by a three-step solid-phase enzyme immunoassay using T. gondii antigen, protein dissociating agent and monoclonal antibodies against human IgG at HIV-infected individuals with a focal damage of the brain. The results of the study showed that conducting of the enzyme-linked immunosorbent assay by a direct and dissociated method makes it possible to detect specific intrathecal and serum immunoglobulins, which is proposed in terms of improving diagnosis of cerebral toxoplasmosis in HIV-infected individuals. The high informative ability of the test system for detecting the avidity index of IgG antibodies to T. gondii allows the possibility to apply it in the algorithm for diagnosing an etiological factor of neuroinfection in HIV-infected individuals.

Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets.

BACKGROUND: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed. CASE PRESENTATION: A 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4+ T cells and higher percentage of activated CD4+ T cells at HAART initiation. The percentage of memory CD4+ T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8+ T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset. CONCLUSION: Although both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.

Disseminated toxoplasmosis after hematopoietic stem cell transplantation showing unusual magnetic resonance images.

We herein report a patient who had disseminated toxoplasmosis after hematopoietic stem cell transplantation showing atypical clinical presentation and neuroimaging. Parkinsonism symptoms such as muscle rigidity, bradykinesia, tremor, and postural instability were initial manifestations. Magnetic resonance imaging showed diffuse symmetrical lesions of bilateral basal ganglia lacking ringed enhancement. Post-mortem analysis revealed multiple tachyzoites of Toxoplasma gondii in the basal ganglia, mid brain, cerebellum, and cardiac muscle.

Multiple Ring-Enhancing Brain Lesions: Fulminant Diffuse Cerebral Toxoplasmosis or Cerebral Metastases?

ABSTRACT: In this case report, we describe a 76-year-old woman, presenting with dizziness for the past 2 months, without other focal neurological signs. A magnetic resonance imaging of the brain was ordered by her GP. The MRI demonstrated multiple ring-enhancing lesions, both supratentorial and infratentorial. Lumbar puncture showed normal findings, in particular a normal cell count and culture. Because of the radiologic appearance, initially thought to be suggestive of cerebral abscesses, antibiotics were started. However, further workup revealed a new diagnosis of a stage IV (metastatic) small cell lung carcinoma, making diffuse brain metastases more likely. The patient was transferred to oncology/pneumology, where she was started on whole-brain radiotherapy, after which systemic therapy would start. However, because of further clinical deterioration, she was admitted at the palliative ward, where she died only 3 months after the initial presentation. In this case report, we emphasize the importance of keeping a broad differential diagnosis and briefly review the various possible pathologies causing ring-enhancing lesions.

Toxoplasmic encephalitis with high 201Tl uptake and retention mimicking malignant lymphoma in a patient with human immunodeficiency virus infection.

Various opportunistic infections develop during immunodeficiency due to human immunodeficiency virus (HIV) infection. The treatment options for malignant lymphoma (ML) and toxoplasmic encephalitis (TE) are completely different; therefore, their discrimination is critical. A 25-year-old female of foreign nationality had been experiencing headaches for several weeks and suddenly developed convulsions. Brain computed tomography revealed multiple intracranial lesions; therefore, the patient was referred to the neurosurgery department. Brain magnetic resonance imaging (MRI) revealed multiple masses with surrounding edema, accompanied by enhanced contrast. The largest mass (2 cm) in the left occipital lobe exhibited ringed contrast enhancement. Her blood test results showed a CD4 count of 40/µL, positive HIV Ag/Ab, HIV-RNA level of 56 × 104 copies/mL, positive anti-Toxoplasma IgG (63 IU/mL), and negative anti-Toxoplasma IgM. 201Tl- single photon emission computed tomography (201Tl-SPECT) revealed abnormal accumulation only in the tumor in the left occipital lobe (early T/N ratio, 3.034; delayed T/N ratio, 2.738; retention index, 0.9), which was suspected to be a ML. Both tumors, with or without high accumulation of 201Tl, were subjected to craniotomy biopsy. Pathological examination revealed infiltration of small lymphocytes with a necrotic background. The patient was diagnosed with TE based on a positive result of a tissue polymerase chain reaction test for Toxoplasma gondii. Two weeks after sulfamethoxazole and trimethoprim combination therapy, MRI imaging showed dramatic improvement in multiple brain tumors. This case is atypical because ML was ruled out despite high 201Tl-SPECT uptake and retention. Careful diagnosis through pathological examination and DNA testing is important.

Differentiation of Acquired Immune Deficiency Syndrome Related Primary Central Nervous System Lymphoma from Cerebral toxoplasmosis with Use of Susceptibility-Weighted Imaging and Contrast Enhanced 3D-T1WI.

BACKGROUND: We aimed to investigate whether susceptibility-weighted imaging (SWI) and contrast-enhanced 3D-T1WI can differentiate Acquired Immune Deficiency Syndrome-Related Primary Central Nervous System Lymphoma (AR-PCNSL) from cerebral toxoplasmosis. METHODS: This was a prospective cohort study. 20 AIDS patients were divided into AR-PCNSL group (13 cases) and cerebral toxoplasmosis group (7 cases) based on pathology results. We analyzed the appearance of lesions on SWI and enhanced 3D T1WI and ROC curves in the diagnosis of AR-PCNSL and cerebral toxoplasmosis. RESULTS: Cerebral toxoplasmosis was more likely to show annular enhancement (p = 0.002) and complete smooth ring enhancement (p = 0.002). It was also more likely to present a complete, smooth low signal intensity rim (LSIR) (p = 0.002) and an incomplete, smooth LSIR (p = 0.019) on SWI. AR-PCNSL was more likely to present an incomplete, irregular LSIR (p < 0.001) and irregular central low signal intensity (CLSI) (p<0.001) on SWI. The areas under the ROC curve of the SWI-ILSS grade and enhanced volume on 3D-T1WI were 0.872 and 0.862, respectively. CONCLUSION: A higher SWI-ILSS grade and larger 3D-T1WI volume enhancement were diagnostic for AR-PCNSL. SWI and CE 3D-T1WI were useful in the differential diagnosis of AR-PCNSL and cerebral toxoplasmosis.

Cerebral toxoplasmosis with multiple hemorrhage lesions in an HIV infected patient: A case report and literature review.

A 47-year-old man was admitted to a hospital for disturbance of consciousness. He was diagnosed with multiple hemorrhagic brain abscesses in bilateral hemispheres with human immunodeficiency virus (HIV) infection, and was transferred to our hospital for further examination and treatment. On admission, although he could respond to pain stimuli, he could not talk or communicate. His laboratory data on admission revealed CD4-positive T cell count of 67 cells/µL, and HIV1-RNA viral load of 5.6 × 105 copies/mL. Both the serum IgG Toxoplasma gondii antibody and the cerebrospinal fluid polymerase chain reaction for Toxoplasma gondii DNA were positive. He was diagnosed with cerebral toxoplasmosis and HIV infection. His level of consciousness worsened, and the number of hemorrhagic lesions had increased in both hemispheres and the left thalamus on the computed tomography scan following two weeks of antitoxoplasma therapy. These newly discovered hemorrhagic lesions revealed in the CT had been found as the high intensity signal regions of initial fluid-attenuated inversion recovery magnetic resonance imaging. After five weeks of treatment, the hemorrhagic lesions gradually improved along with the patient's consciousness. Antiretroviral therapy was initiated six weeks following antitoxoplama therapy with reassurance that immune reconstitution inflammatory syndrome did not occur. After approximately four months of antitoxoplasma therapy, the patient was discharged into a group home with residual left hemiparesis on maintenance antitoxoplasma and antiretroviral therapy. Clinicians should recognize the delay of clinical and radiological improvement for hemorrhagic cerebral toxoplasmosis and patiently continue the antitoxoplasma therapy.

Multiple Reactivations of Viral Infections Followed by Cerebral Toxoplasmosis After Allogeneic Hematopoietic Stem Cell Transplantation in an Adolescent With Ph(+) Acute Lymphoblastic Leukemia: A Case Report.

After allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially from an unrelated donor, infectious complications are frequent and severe, sometimes with fatal outcomes. Despite using highly sensitive molecular techniques for close monitoring in the early post-transplant period for early diagnosis, not every viral infection or reactivation can be detected adequately early, even with highly sensitive methods. Particularly after toxic and deeply immunosuppressive treatment, multiple infections or reactivations, uncommon infections, or infections in unusual locations can occur. Here, we present a case of multiple viral infections or reactivations and cerebral toxoplasmosis in a 17-year-old youth with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) treated with allo-HSCT who suffered multiple viral infections followed by cerebral toxoplasmosis.

Hemichorea-Hemiballismus as a Presentation of Cerebritis from Intracranial Toxoplasmosis and Tuberculosis.

Background: There is limited literature documenting hemichorea-hemiballism (HCHB) resulting from co-infection of toxoplasmosis and tuberculosis (TB) in acquired immunodeficiency syndrome (AIDS). Toxoplasmic abscess is the most common cause while TB is a rare etiology. Case Description: We describe a 24-year-old male with AIDS-related HCHB as the presentation of cerebritis on the right subthalamic nucleus and cerebral peduncle from intracranial toxoplasma and TB co-infection. Antimicrobials and symptomatic therapy were given. Marked improvement was seen on follow-up. Discussion: HCHB may be the initial presentation of intracranial involvement of this co-infection in the setting of AIDS and is potentially reversible with timely management. Highlights: Hemichorea-hemiballismus (HCHB) may be an initial presentation of intracranial involvement of concomitant toxoplasmosis and tuberculosis causing focal cerebritis in the contralateral subthalamic nucleus and cerebral peduncle, particularly in the setting of human immunodeficiency virus infection.Acquired immunodeficiency syndrome-related HCHB is potentially reversible with timely diagnosis and treatment.

Multimodal Medical Image Fusion Based on Multiple Latent Low-Rank Representation.

A multimodal medical image fusion algorithm based on multiple latent low-rank representation is proposed to improve imaging quality by solving fuzzy details and enhancing the display of lesions. Firstly, the proposed method decomposes the source image repeatedly using latent low-rank representation to obtain several saliency parts and one low-rank part. Secondly, the VGG-19 network identifies the low-rank part's features and generates the weight maps. Then, the fused low-rank part can be obtained by making the Hadamard product of the weight maps and the source images. Thirdly, the fused saliency parts can be obtained by selecting the max value. Finally, the fused saliency parts and low-rank part are superimposed to obtain the fused image. Experimental results show that the proposed method is superior to the traditional multimodal medical image fusion algorithms in the subjective evaluation and objective indexes.

Neurotoxoplasmosis mimicking intracranial tuberculoma.

Neurotoxoplasmosis is a major cause of morbidity and mortality, especially in immunocompromised patients. Definitive diagnosis is invasive and difficult thereby requiring a therapeutic trial. We herein report a case of an 11-year-old boy who presented with a tuberculoma on computerized tomography (CT) brain and did not show any clinical improvement on anti-tuberculous drugs. Subsequently, reviewing the CT scans and with supportive serology, a diagnosis of neurotoxoplasmosis was considered. A trial of antitoxoplasmosis therapy was given to which the child fully responded in two weeks. Three weeks later, his magnetic resonance imaging showed complete resolution of the lesion. This report provides an insight into the significance of therapeutic trial in neurotoxoplasmosis.

Unexpected neurologic complications following a novel lymphoma treatment 'expected' to give rise to neurologic toxicity.

Chimeric antigen receptor (CAR) T-cell therapy is a novel and promising form of cellular immunotherapy using genetically engineered, tumour-specific autologous T cells. CD19-specific CAR T-cells have been shown to be very effective as a treatment for relapsed/refractory B-cell acute lymphoblastic leukaemia and aggressive B-cell non-Hodgkin's lymphoma. ICANS (immune effector cell-associated neurotoxicity syndrome) is one of the most frequently occurring toxicities of CAR T-cell treatment. We describe two cases of patients with neurologic symptoms following CAR T-cell infusion who were suspected to have ICANS, but in fact had cerebral toxoplasmosis and venous sinus thrombosis respectively. The focus on CRS and ICANS after CAR T-cell infusion may lead to less vigilance to the 'normal' threats faced by intensively pretreated patients with lymphoma such as infections and thrombosis. Both cases underscore the importance of a broad and thorough examination of patients if they experience neurologic symptoms after CAR T-cell treatment.

Severe disseminated acute toxoplasmosis in an adult immunocompetent patient from the Colombian Pacific

We present the case of a 72-year-old immunocompetent patient from Chocó, Colombia, with a 12-day course of fever, headache, progressive neurological deterioration, and rapid evolution to multiorgan failure and death. In the histopathological study of tissues obtained at necropsy, tissue cysts morphologically suggestive of being bradyzoites of Toxoplasma gondii were identified and confirmed by immunohistochemistry in heart, brain, and striated muscle.