Hemichorea-hemiballismus associated with a case of cerebral toxoplasmosis in a hematopoietic stem cell transplant recipient.

Due to their immunocompromised state, recipients of hematopoietic stem cell transplants (HSCTs) are at a higher risk of opportunistic infections, such as that of toxoplasmosis. Toxoplasmosis is a rare but mortal infection that can cause severe neurological symptoms, including confusion. In immunosuppressed individuals, such as those with acquired immunodeficiency syndrome (AIDS), toxoplasmosis can cause movement disorders, including hemichorea-hemiballismus. We present the case of a 54-year-old Caucasian male with a history of hypertension and JAK-2-negative primary myelofibrosis who underwent an allogeneic peripheral blood stem cell transplant from a related donor. After the development of acute changes in mental status, left-sided weakness, and left-sided hemichorea-hemiballismus post-transplant, the patient was readmitted to the hospital. Subsequent testing included an magnetic resonance imaging (MRI) of the brain, which revealed multiple ring-enhancing lesions around the thalami and basal ganglia, as well as a cerebrospinal fluid tap that tested positive for toxoplasmosis. The patient was initially treated with intravenous clindamycin and oral pyrimethamine with leucovorin. The completion of treatment improved the patient's mental status but did not improve his hemichorea-hemiballismus. This case illustrates an uncommon complication associated with central nervous system (CNS) toxoplasmosis in stem cell transplant recipients. Due to its rarity, cerebral toxoplasmosis in immunocompromised patients often remains undetected, particularly in HSCT patients who are immunosuppressed to improve engraftment. Neurological and neuropsychiatric symptoms due to toxoplasmosis may be misidentified as psychiatric morbidities, delaying appropriate treatment. Polymerase chain reaction (PCR) assays offer methods that are sensitive and specific to detecting toxoplasmosis and provide opportunities for early intervention.

[Cerebral toxoplasmosis developed after unrelated bone marrow transplantation for acute myeloid leukemia].

A 16-year-old boy received an unrelated bone marrow transplant while in second remission of acute myeloid leukemia. He suffered from severe oral mucosal complications and had difficulty taking oral drugs such as sulfamethoxazole/trimethoprim (ST). Engraftment was obtained on transplant day 35, and blurred vision and headache appeared around transplant day 60. Funduscopy revealed retinal hemorrhage and macular edema, and an MRI scan of the head revealed a nodular lesion in the left putamen. Toxoplasma gondii was detected by CSF PCR, and cerebral toxoplasmosis was diagnosed. Following therapy with ST and clindamycin, the patient was administered pyrimethamine, sulfadiazine, and leucovorin. Symptoms improved promptly, and CSF PCR was negative 45 days after the start of treatment. Since the prevalence of toxoplasma antibodies increases with age, it is crucial to avoid toxoplasma reactivation by ST after hematopoietic cell transplantation in postpubescent patients.

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.

Blastic plasmacytoid dendritic cell neoplasm and cerebral toxoplasmosis: a case report.

BACKGROUND: The present case contributes to the limited literature on central nervous system involvement of blastic plasmacytoid dendritic cell neoplasm (BPDCN).  CASE PRESENTATION : A 63-year-old male presented to the department of neurology with a three-day history of rapidly progressing headache, fatigue, and confusion. Physical examination revealed multiple bruise-like skin lesions. Initial laboratory workup raised suspicion of acute leukemia, and a brain computer tomography identified several hyperdense processes. A bone marrow biopsy gave the diagnosis BPDCN, a rare and aggressive hematologic malignancy derived from plasmacytoid dendritic cells with a poor prognosis. Lumbar puncture showed not only signs of BPDCN, but also cerebral toxoplasmosis, thus providing a differential diagnosis. Despite intensive systemic and intrathecal chemotherapy, the patient died 25 days later due to multi-organ failure. DISCUSSION: The exact incidence of BPDCN is unknown and perhaps underestimated but may account for 0.5 - 1% of all hematological malignancies. The median age at onset is 60 to 70 years, and most patients are men. Cutaneous lesions are the most frequent clinical manifestation at diagnosis. Other symptoms present at time of diagnosis or during disease progression include lymphadenopathy, splenomegaly and cytopenia caused by bone marrow involvement. Although the majority of BPDCN patients have no symptoms or signs of central nervous system involvement, plasmacytoid dendritic cells have been detected in the cerebrospinal fluid in more than 50%. CONCLUSIONS: This case highlights the importance of considering hematological malignancies as a differential diagnosis in patients developing acute neurological symptoms and raises suspicion of a possible association between toxoplasmosis and hematological malignancies.

Central nervous system aspergillosis misdiagnosed as Toxoplasma gondii encephalitis in a patient with AIDS: a case report.

BACKGROUND: Patients with acquired immunodeficiency syndrome (AIDS) tend to suffer from several central nervous system (CNS) infections due to hypoimmunity. However, CNS aspergillosis (CNSAG) is extremely rare and difficult to diagnose. Thus, it is easily misdiagnosed. CASE PRESENTATION: We reported a 47-year-old male AIDS patient with ghosting vision and anhidrosis on the left head and face. He was accordingly diagnosed with Toxoplasma gondii encephalitis (TE) at other hospitals, for which he received regular anti-Toxoplasma gondii and anti-human immunodeficiency virus (anti-HIV) treatment. Then, the patient was transferred to our hospital due to a lack of any improvement with the prescribed treatment. The patient's neurological examination revealed no abnormalities at admission, only a slight change in the cerebrospinal fluid. His cranial magnetic resonance imaging (MRI) revealed multiple abnormal signals in the brain parenchyma, and his blood was positive for Toxoplasma gondii IgG antibody. The initial diagnosis at our hospital was also TE. Considering the poor efficacy of anti-TE treatment, cerebrospinal fluid metagenomics next-generation sequencing (mNGS) was performed, but no pathogenic bacteria were detected. However, Aspergillus fumigatus was detected in the cerebrospinal fluid via targeted next-generation sequencing (tNGS) and bronchoalveolar alveolar lavage fluid via mNGS. The diagnosis was accordingly revised to CNSAG combined with his other clinical manifestations. After administering voriconazole antifungal therapy, the patient's symptoms were relieved, with improved absorption of the intracranial lesions. CONCLUSIONS: The present case experience indicates the need for clinicians to strengthen their understanding of CNSAG. Moreover, for patients with diagnostic difficulties, early mNGS and tNGS (using biological samples with only a few pathogens) are helpful for early diagnosis and treatment, potentially allowing patients to achieve favorable outcomes.

Cerebral toxoplasmosis complicating lymphoplasmacytic lymphoma in partial remission.

Toxoplasma gondii can develop toxoplasmic encephalitis (TE) in immunodeficient conditions such as AIDS and after organ transplantation. While some cases of TE with malignant lymphoma were reported, these cases occurred immediately after chemotherapy or when their diseases were active. Here we report the first Case of TE that occurred in patient who was in partial remission (PR) of lymphoplasmacytic lymphoma (LPL) for two years. A 76-year-old man was referred to our institute because of disturbance of consciousness, right arm weakness and paresthesia. A computed tomography (CT) scan detected multiple nodules in his brain. Magnetic resonance imaging (MRI) of the head detected multiple gadolinium-enhancing parenchymal lesions with hyperintense signals on T2-and diffusion-weighted images, located in both cerebral and cerebellar hemispheres. Blood test and cerebrospinal fluid (CSF) findings were unremarkable. His rapidly deteriorating consciousness precluded a chance of brain biopsy. Considering the limited efficacy of antimicrobials and the imaging findings that could be compatible with the diagnosis of malignant lymphoma, we suspected central nerve system (CNS) recurrence of LPL. Although chemotherapy was initiated, he died of respiratory failure just after chemotherapy. A pathological autopsy showed his cause of death was TE. To our knowledge, this is the first case of TE in long-term PR of malignant lymphoma. TE should be suspected when patients with malignant lymphoma present unexplained neurologic symptoms regardless of their treatment efficacy of lymphoma. (226/250 words).

Delayed Cerebral Toxoplasmosis in a Kidney Transplant Patient: a Case Report.

Cerebral toxoplasmosis is often life-threatening in an immunocompromised patient due to delayed diagnosis and treatment. Several differential diagnoses could be possible only with preoperative brain images of cerebral toxoplasmosis which show multiple rim-enhancing lesions. Due to the rarity of cerebral toxoplasmosis cases in Korea, the diagnosis and treatment are often delayed. This paper concerns a male patient whose cerebral toxoplasmosis was activated 21 years post kidney transplantation. Brain open biopsy was decided to make an exact diagnosis. Cerebral toxoplasmosis was confirmed by immunohistochemistry and PCR analyses of the tissue samples. Although cerebral toxoplasmosis was under control with medication, the patient did not recover clinically and died due to sepsis and recurrent gastrointestinal bleeding.

Detection and treatment of cerebral toxoplasmosis in an aplastic pediatric post-allogeneic hematopoietic cell transplant patient: a case report.

BACKGROUND: Cerebral toxoplasmosis infection presents with non-specific neurologic symptoms in immunocompromised patients. With lack of measurable adaptive immune responses and reluctance to sample affected brain tissue, expedient diagnosis to guide directed treatment is often delayed. CASE PRESENTATION: We describe the use of cerebrospinal fluid polymerase chain reaction and plasma cell-free DNA technologies to supplement neuroimaging in the diagnosis of cerebral toxoplasmosis in an immunocompromised pediatric patient following allogeneic hematopoietic cell transplantation for idiopathic severe aplastic anemia. Successful cerebral toxoplasmosis treatment included antibiotic therapy for 1 year following restoration of cellular immunity with an allogeneic stem cell boost. CONCLUSIONS: Plasma cell-free DNA technology provides a non-invasive method of rapid diagnosis, improving the likelihood of survival from often lethal opportunistic infection in a high risk, immunocompromised patient population.

Spinal cord toxoplasmosis in a young immunocompetent patient.

We report a case of spinal cord toxoplasmosis occurring as a primary infection in a 31-year-old immunocompetent man. Exhaustive immunologic and genetic investigations did not identify any immunodeficiency. The causative agent was a typical type 2 strain. In cases of spinal cord lesions, toxoplasmosis should be considered, even in an immunocompetent patient.

[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.

Combination of Clindamycin and Azithromycin as Alternative Treatment for Toxoplasma gondii Encephalitis.

Current standard therapies for toxoplasmic encephalitis often cause severe adverse events. A 57-year-old HIV-positive man in Japan who had toxoplasmic encephalitis but was intolerant to trimethoprim/sulfamethoxazole, pyrimethamine, sulfadiazine, and atovaquone was successfully treated with the combination of clindamycin and azithromycin. This drug combination can be an alternative treatment for this condition.

Disseminated toxoplasmosis with atypical symptoms which developed with exacerbation of systemic lupus erythematosus.

Toxoplasma is a common parasite worldwide that mainly affects the brain, lungs and eyes. Although toxoplasmic encephalitis is a lethal disease without treatment, past case reports show most patients with systemic lupus erythematosus who developed toxoplasmic encephalitis were misdiagnosed and treated as neuropsychiatric systemic lupus erythematosus, which led to unfavorable outcomes. We herein describe a case of disseminated toxoplasmosis affecting all the above organs with atypical symptoms, which developed with exacerbation of systemic lupus erythematosus. She had initially manifested with retinochoroiditis without vitritis, mild cognitive impairment and an isolated lung mass. These are completely different from the classic symptoms of toxoplasmosis that have been reported in patients with HIV infection and/or those after hematopoietic transplantation. Our case, together with previously reported cases, suggests the manifestation of toxoplasmosis that develops in systemic lupus erythematosus patients can be different from that seen in conventional cases and varies between individual patients. Our case highlights both the difficulty in and the importance of diagnosing toxoplasmosis in patients with systemic lupus erythematosus and provides helpful information to identify this rare, devastating, yet treatable disease.

Parasitic Infections of the Nervous System.

Parasitic infections of the central nervous system are much more common than suspected, although most infections are asymptomatic. For example, parasites like the ubiquitous protozoa Toxoplasma gondii or the nematode larvae Toxocara canis infect significant proportions of the human population. Other parasitic infections such as malaria and neurocysticercosis are widespread in developing countries and become major causes of neurological morbidity in these regions as well in immigrants and travelers. This article reviews parasitic pathogens causing neurological morbidity and mortality, including an extensive list of less common parasitic infections of the human nervous system.

Toxoplasmic encephalitis of basal ganglia with tumor-like features proven by pathogen-specific polymerase chain reaction and direct DNA sequencing.

We report a case of a young female patient who developed progressive neurological dysfunction with a ring-enhancing tumor-like nodule on brain magnetic resonance imaging. Urgent surgery was performed to remove the mass in the left basal ganglia. Pathological findings showed that the necrotic brain areas were accompanied by congestion, edema, discrete hemorrhage, and intestinal and perivascular lymphohistiocytic infiltration. Immunohistochemical staining results showed that Toxoplasma gondii (T. gondii) immunoreactivity was detected in both cysts and tachyzoites in these areas. The glycerol-3-phosphate dehydrogenase gene (B1) of T. gondii was amplified by sequence-specific polymerase chain reaction (PCR) and the PCR products were bi-directional Sanger sequenced. A 195 bp consensus sequence of the gene B1 was found to be 98% identical to a reference T. gondii sequence (GenBank accession No. kx270373). The final diagnosis was toxoplasmic encephalitis in the left basal ganglia. This report suggests that PCR and bi-directional DNA sequencing of T. gondii gene might be the most convenient and rapid tools for accurate diagnosis of toxoplasmic encephalitis .

[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.

Early detection of Toxoplasma gondii infection by using a interferon gamma release assay: A review.

Antibody-based serological tests are currently the most common diagnostic methods for detection of Toxoplasma gondii; however, these tests bear several limitations. Recently, Interferon-gamma release assay (IGRA), a T-cell-based test, was introduced as an in vitro test for detection of T. gondii infection. Few studies have investigated the potential role of cell immunity in diagnosis of toxoplasmosis. IGRA accurately distinguished infected from uninfected individuals, showing strong lymphocyte activation after in vitro stimulation with T. gondii antigens, even during the first days of life. IGRA is an easy-operation and low-cost method to measure cell mediated immunity against T. gondii. The results of this review underline the importance of evaluating cellular immunity to establish an early diagnosis particularly for congenital toxoplasmosis. Therefore, ELISA-based IGRA holds the potential to become a useful diagnostic tool for early detection of T. gondii infection.

Respiratory Tract Infection Caused by Fonsecaea monophora After Kidney Transplantation.

Fonsecaea spp. are melanized fungi which cause most cases of chromoblastomycosis. The taxonomy of this genus has been revised, now encompassing four species, with different pathogenic potential: F. pedrosoi, F. nubica, F. pugnacius, and F. monophora. The latter two species present wider clinical spectrum and have been associated with cases of visceral infection, most often affecting the brain. To our knowledge, this is the first report of proven case of F. monophora respiratory tract infection. A Brazilian 57-year-old-female patient underwent kidney transplantation on January 12, 2013. On the fourth postoperative month, the patient presented with fever, productive cough, and pleuritic pain in the right hemithorax. A thoracic CT scan showed a subpleural 2.2-cm nodular lesion in the right lung lower lobe, with other smaller nodules (0.5-0.7 cm) scattered in both lungs. Bronchoscopy revealed a grayish plaque on the right bronchus which was biopsied. Microscopic examination demonstrated invasion of bronchial mucosa by pigmented hyphae. Culture from the bronchial biopsy and bronchoalveolar lavage samples yielded a melanized mold, which was eventually identified as F. monophora. She started treatment with voriconazole (400 mg q.12h on the first day, followed by 200 mg q.12h). After 4 weeks of therapy, voriconazole dose was escalated to 200 mg q.8h and associated with amphotericin B (deoxycolate 1 mg/kg/day) because of a suspected dissemination to the brain. The patient eventually died of sepsis 8 weeks after the start of antifungal therapy. In conclusion, F. monophora may cause respiratory tract infection in solid organ transplant recipients.

Molecular detection of Toxoplasma gondii in snakes.

Toxoplasma gondii, an obligate intracellular protozoan parasite, is responsible for one of the most common zoonotic parasitic diseases in almost all warm-blooded vertebrates worldwide, and it is estimated that about one-third of the world human population is chronically infected with this parasite. Little is known about the circulation of T. gondii in snakes and this study for the first time aimed to evaluate the infection rates of snakes by this parasite by PCR methods. The brain of 68 Snakes, that were collected between May 2012 and September 2015 and died after the hold in captivity, under which they were kept for taking poisons, were examined for the presence of this parasite. DNA was extracted and Nested-PCR method was carried out with two of pairs of primers to detect the 344 bp fragment of T. gondii GRA6 gene. Five positive nested-PCR products were directly sequenced in the forward and reverse directions by Sequetech Company (Mountain View, CA). T. gondii GRA6 gene were detected from 55 (80.88%) of 68 snakes brains. Sequencing of the GRA6 gene revealed 98-100% of similarity with T. gondii sequences deposited in GenBank. To our knowledge, this is the first study of molecular detection of T. gondii in snakes and our findings show a higher frequency of this organism among them.