Surgery, Gastroenterology and Oncology

Toxoplasma gondii is a parasitic infection widespread worldwide, being the prerogative of AIDS patients. We present a case of reactivated T. gondii in a 30-year-old, HIV-positive patient who presented with secondary partial and generalized seizures, hepatitis C virus infection, hematological abnormalities. MRI examination identifies a 14/12 mm left paramedian cortico-subcortical lesion with intense peripheral contrast uptake and associated edema. The importance of cerebral radiographic examination in HIV patients is discussed in this paper.

Toxoplasma gondii is one of the most common parasitic infections worldwide (1). It is a ubiquitous intracellular protozoan and one of the main causes of diseases focusing on the central nervous system in AIDS, this being a late complication of the disease, the treatment decision of the disease being empirical in most cases with a reserved prognosis (2). This infection is due to the reactivation of the parasite Toxoplasma gondii and is predilected in immuno-suppressed patients or with immunodeficiency syndrome whose CD4 cell count is below 200 elements (2).

The brain, myocardium, skeletal muscles and last but not least the retina are the main target organs infested by this parasite.

CASE REPORT

In this sense, we will present a case of cerebral toxoplasmosis in an immunocompromised patient, detected from an imaging point of view.

A 30-year-old patient known as a carrier of the HIV virus serologically confirmed in 2013, currently with antiviral treatment, compliant but also known in the antecedents with an expansive left parietal intracranial process with secondary epilepsy with association of partial seizures on the right side and secondary generalization (June 2016), with multiple associated comorbidities – hepatitis C virus, inguinal herpes-zoster and anemia with thrombocytopenia – admitted for tonic-clonic convulsions at the level of the right hemisphere with secondary generalization and myoclonus on the right side of the body, headache, vertigo, nausea and alteration of the general condition by approx. 3 days ago.

From the point of view of the objective clinical examination, upon admission the patient presents an altered general condition, pale skin, BP=100/60 mmHg, AV=90 beats per minute, supple abdomen, mobile with breathing, painless spontaneously and on palpation, muscular system with myoclonus at the level of the right calf and right foot and without signs of meningeal irritation. The laboratory analyzes show the following: Hb=9.8g/dl, Leu=2080/mmc, Platelets=273000/mmc, CD4+ lymphocytes=197, and the serology for toxoplasmosis is IgG-positive (83 IU/ml) and, respectively, IgM positive (113 IU/ml). Ocular exam showed  focal vasculitis could be seen near posterior pole oedema. Periphlebitis and retinal hemorrhages were also present with vitritis some degree of perivascular retinal inflammation. RT-PCR molecular examination using specific DNA primers and commercial purification methods, revealed the possibility of amplification of the B1 gene for T. gondii, therefore the result being the confirmation of the infection.

RESULTS

The decision was made to perform an MRI examination which described the following changes compared to the last examination when the patient was discharged in a stable condition: thus the significant dimensional progression of the expansive lesion present at the previous exploration, at the left paramedian parietal cortico-subcortical level, which currently presents maximum axial diameters of approximately 14/12 mm, cranio-caudal extension of 22 mm, has an inhomogeneous structure in T1 hyposignal, T2/FLAIR hypersignal and shows intense, predominantly peripheral uptake of contrast material.

The injury causes the appearance of a large area of edema at the level of the adjacent white matter, in significant dimensional progression compared to the previous examination. In conclusion, the patient presents a tumor-compatible lesion located in the left paramedian cortico-subcortical parietal that appears in significant dimensional progression, with associated edema that also has a projection area in significant progression, which in the context of the patient's pathological antecedents may suggest a toxoplasmosis reactivation.

Following the MRI examination and the IgG serology results, the decision was made to administer Biseptol in a dose of 3 tablets every 6 hours daily, and upon discharge the patient was in a stable, afebrile, hemo-dynamically and respiratoryly compensated state, but with the recommendation of to present himself once a month for a clinical-neurological and imaging check-up.

At the check-up performed one month after the episode, the patient presents with a favorable evolution, and the MRI examination describes a clearly improved appearance, with marked dimensional regression of the confluent gadophilic lesions located at the left paramedian parietal cortico-subcortical level, currently measuring approx. 15 mm maximum cranio-caudal diameter, approx. 7mm transverse and antero-posterior diameter approximately 9 mm. The gadophilia of the lesion appears clearly reduced compared to the previous exploration. Marked limitation of the perilesional edema, of which only a small left paramedian parietal beach of approx. 18 mm maximum transverse diameter, without residual mass effect on the left lateral ventricle. Important regression of the beach with water diffusion restriction from the left parietal level, currently highlighting a small predominantly cortical area with discrete subcortical extension in DWI hypersignal, hypersignal on the ADC map, with edematous appearance, of approx. 18 mm maximum axial diameter.

As a result of the radiological examination performed and the results obtained, the therapeutic decision was made to start the treatment with trimethoprim 10 mg/kg/day and sulfmethoxazole 50 mg/kg/day divided into two doses, for 2 weeks, with favorable clinical results and radiological, with the reduction of the anti-T.gondii IgM antibody titer to 26 IU/ml and, respectively, IgG to 40 IU/ml.

Figure 1- Axial T2 sequences one month apart, before and after the therapeutic test

Figure 2 – Coronal FLAIR sequences one month apart, before and after the therapeutic trial

Figure 3 – 3d T1 sequences in the coronal plane one month apart, before and after the therapeutic trial

Figure 4- DWI sequences in the axial plane one month apart, before and after the therapeutic trial

Figure 5 - ADC sequences in the axial plane one month apart, before and after the therapeutic trial

Figure 6 - Coronal T1 sequences with contrast administration

DISCUSSIONS

The positive laboratory diagnosis for the existence of Toxoplasma Gondii activation is made either by serological tests, most frequently by PCR, or by the detection and histological diagnosis of the parasite and its antigens on histoarchived tissue (3). On the other hand, less commonly used methods can be used to diagnose this infection, such as: identification of the parasite antigen in the blood and antigenemia, skin tests for parasitosis, but also the specific antigen transformation test of lymphocytes (3,4).

However, in many cases the diagnosis is supported on the basis of the therapeutic evidence following imaging investigations. Thus, with the suspicion of the existence of tissue toxoplasmic lesions, an antiparasitic treatment is resorted to, observing the reduction or even the disappearance of the lesions from an imaging point of view, thus supporting the continuation of the treatment (3). Seroepidemiological studies have revealed toxoplasmic infection in 15-68% of HIV patients, claiming that 10-25% of patients diagnosed with AIDS manifest (25% in Europe) and subsequently develop toxoplasmic encephalitis, sometimes as the first manifestation of infection HIV (2).

On a contrast-enhanced CT or MRI examination, cerebral toxoplasmosis is often visualized as multiple nodular or ring-enhancing lesions with associated vasogenic edema, often out of proportion to lesion size and outcome. The most common location of these lesions are the basal ganglia and the frontal and parietal lobes. On the other hand, on CT examinations, primary CNS lymphoma usually presents isoattenuating or hyper-attenuating mass lesions due to high cellularity. After contrast administration, CT or MRI of these lesions may show homogeneous round or oval contrast enhancement and a variable extent of edema in a multifocal or periventricular distribution. The reported coexistence of neurotoxoplasmosis and Cryptococcus neoformans meningitis can be difficult to detect on the basis of CT and MRI examination, in the main secondary lesions of the two pathogenic money being intricate and similar, the differentiation being made only on a clinical basis and sometimes by puncture brain biopsy with histological evidence of C. neoformans (5). The differential diagnosis of herpetic encephalitis and neurotoxoplasmosis can easily be made by CT, but early diagnosis is difficult, being even with a "normal" scan which, however, should not discourage the diagnosis, contrast enhancement being less frequent in the first week of illness. If abnormalities are present, they usually consist of subtle decreased density in the anterior and medial parts of the temporal lobe and the insula of Reil (insular cortex); at the same time, if they are scanned later in the course of the disease, the changes may become more obvious and may even evolve into hemorrhage. After therapy, in herpetic encephalitis, a nonhomogeneous low-level improvement can be observed (6). In progressive multifocal leukoencephalopathy (PML), asymmetric focal areas of low attenuation involving the periventricular and subcortical white matter are typically seen, which is in contrast to the more symmetrical hypoattenuation seen in HIV encephalopathy, and from an MRI imaging perspective, found multifocal, asymmetric periventricular and subcortical involvement with insignificant mass effect or enhancement 10 and subcortical U fibers being usually involved with a predilection for the parieto-occipital regions. In fact, even though involvement of subcortical U fibers is an important feature of multiple sclerosis lesions, typically with the lesion showing a peripheral border demarcated along the subcortical U fibers and an indistinct and ill-defined inner border, the corpus callosum may be involved. Considering the evolutionary stages in which neuro-toxoplasmosis can be captured from an imaging point of view, it is necessary to take into account the possibility of acquiring the non-focal aspect of T. gondii secondary lesions, the main characteristic to follow in order to make a differential diagnosis with the elements of other etiopathogenesis, especially primary CNS lymphoma in the context of HIV, the distribution of hemorrhagic lesional elements, especially micro-hemorrhages in the focus, remains the characteristic and helpful element in differentiating neurotoxoplasmosis from other pathologies in immunocompromised patients (7).

As useful paraclinical investigations we find tomography and nuclear magnetic resonance with or without contrast substance. On the MRI examination, a sign "in the target" can be described on the T2 sequences showing alternating concentric areas in hypo or hypersignal (8). Spectro-NMR usually shows an increase in the curve of lactate, lipids, but also a decrease in choline together with that of N-acetylaspartate.

Note the increase in the lactate-lipid curve that is characteristic of this type of pathology (9).

CONCLUSIONS

 In conclusion, brain lesions in immunocompromised patients can have a similar pattern, and differential diagnosis is difficult and delays treatment. Biopsies are difficult to perform and present significant risks, sometimes life-threatening. Thus, modern MRI and spectro-RM imaging together with biological samples can guide the diagnosis and thus the patient can receive an appropriate treatment that cures or stops the progression of the disease.

Conflict of interest

All authors declare that they have no conflict of interest.

Funding

No funding sources.

Ethical statement

Written informed consent was obtained from the patient of this case report.

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