Neurosurgical Excision of Isolated Cerebral Toxoplasmosis in an HIV Positive Patient: A Long-Term Successful Outcome

Sir, Focal cerebral involvement in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) often occurs secondary to opportunistic infections like toxoplasma, mycobacterium tuberculosis, fungi or noninfectious causes like HIV associated neurocognitive disease, and tumors including primary central nervous system lymphoma (PCNSL) and metastasis.[1] The degree of immune suppression based on the CD4 count helps to categorize the most likely cause. Most opportunistic infections and PCNSL occur when CD4 is less than 200 cells/μl. Globally, Toxoplasma gondii (toxoplasmosis) is the most common opportunistic infection to cause encephalitis or focal intracerebral lesion in patients with AIDS.[2] In the developing world, tuberculosis (TB) is the most common opportunistic infection and can occur in patients with HIV with any CD4 count. The immune status of the patient plays an important role in the way toxoplasmosis presents. It can present either as disseminated infection, encephalitis or chorioretinitis. The usual clinical manifestations are fever, headache, and hemiparesis with gait and speech abnormalities depending upon the region involved in the brain.[3] Here, we report a case of cerebral toxoplasmosis as a primary manifestation in a patient with HIV, which was surgically managed. A 52-year-old Sudanese male presented with left faciobrachial paresis of 10 days duration. He was having a history of high-grade fever lasting 10 days followed by herpes zoster infection in right thigh about 3 months prior to admission. During the evaluation, he was found to be HIV-1 seropositive with viral load of 1632500 IU/ml. He had no history of TB or contact with TB. Magnetic resonance imaging (MRI) brain revealed well-defined ring-enhancing lesion measuring 2.0 cm × 2.0 cm × 1.6 cm in the right frontal lobe [Figure 1] associated with extensive perilesional edema and lipid peak on spectroscopy. Computed tomography (CT) abdomen and CT thorax did not reveal any pathology. He was seropositive for toxoplasma with IgG titer of 3.35 IU/ml (For AxSYM, Abbott Laboratories, a positive result is defined as values of ≥3 IU/ml).[3]Figure 1: (a) Axial T1W post-contrast, (b) Sagittal T1W post-contrast, (c) Coronal T1W post-contrastCD 4 count was 186 cells/μl. In view of IgG positivity, cerebral toxoplasmosis was considered as the primary diagnosis. PCNSL was a close differential, while TB and pyogenic abscess were also considered possible. We planned to start antitoxoplasmosis therapy and assess clinical and radiological response in 2 weeks with a biopsy if the response was poor. However, the patient opted for an upfront definitive diagnosis with surgical removal of the lesion as he wanted to return to his country at the earliest. A frontoparietal craniotomy with intraoperative ultrasound-guided trans-sulcal approach and microsurgical excision of the lesion was performed [Figure 2]. Acid-Fast Bacilli (AFB) stain, Gene Xpert for TB, and bacterial and fungal stains and cultures were negative. Serum cryptococcal antigen was negative. Histopathological examination [Figure 3] of multiple gray-white soft tissue fragments altogether measuring 1.8/1/1 cm showed glial tissue with extensive areas of inflammation predominantly composed of lymphocytes and plasma cells. Clusters of macrophages surrounding areas of individual cell necrosis were positive for Vimentin and CD68. Few background lymphocytes were positive for CD45. Glial fibrillary acidic protein was positive in the adjacent glial component, and CK7 and CK20 were negative. Special stain for AFB was negative. Silver stain highlighted multiple bradyzoites encased in small cysts. Multiple basophilic dot-like parasites were noted in cysts suggestive of toxoplasmosis. Tissue polymerase chain reaction for toxoplasma was positive.Figure 2: Immediate postoperative CT showing postoperative changesFigure 3: (a) Periodic acid–Schiff (PAS) shows the bradyzoite (400 × magnification), (b) Inflammation with adjacent necrosis (H&E stain, 400 × magnification)Postoperatively, his neurological deficits resolved completely. He also received antiretroviral therapy, integrase strand transfer inhibitor-based regimens, for HIV infection with dolutegravir, abacavir, and lamivudine. He has been well on regular follow-up and repeat imaging at 1 year was within normal limits [Figure 4].Figure 4: (a) 1 year post-op MRI Axial, (b) 1 year post-op MRI Sagittal, (c) 1 year post-op MRI CoronalToxoplasmic encephalitis (TE) is a disease of the immunocompromised, presenting in 25%–50% of acquired HIV/AIDS patients who have toxoplasma antibodies. They present with fever, headache, altered mental status, cognitive impairment, seizures, and focal neurological deficits.[4] Differential diagnosis includes PCNSL, other infective etiologies including tuberculoma, pyogenic abscess, fungal CNS infections, viral infections (cytomegalovirus and herpes simplex virus), and progressive multifocal leucoencephalopathy.[2] PCNSL cannot be distinguished from toxoplasmosis solely based on neuroradiological criteria (both present as contrast-enhancing lesions with mass effect).[4] PCNSL in immunocompetent individuals are usually solitary but in immunocompromised patients, they are just as likely to be multiple as solitary. TE is known to be periventricular in 60% and an isolated lesion in the basal ganglia is favorable toward toxoplamosis.[5,6] An eccentric target sign is pathognomonic for toxoplasmosis which was not noted in our case. Our patient had a well-defined ring-enhancing solitary lesion in the right frontoparietal region, which is relatively uncommon and thus made the diagnosis difficult. Pyogenic abscess and tubercular abscess were also considered possibilities based on the MRI findings. Clinical disease with TE is uncommon in patients with CD4 counts ≥200 cells/μl with the greatest risk when the CD4 counts are <50 cells/μl.[7] In an Italian study, the probability of TE was 0.87 in toxoplasma-seropositive patients with mass effect, who were not on trimethoprim-sulfamethoxazole (TMP-SMX), whereas in patients receiving prophylaxis, the probability of TE was only 0.59 and the probability of PCNSL was 0.36; sensitivity of brain biopsy was 93%, with perioperative morbidity of 12% and mortality of 2%.[5] Biopsy diagnosis remains a challenge while dealing with tissue showing histiocytes and background lymphocytes with patchy necrosis. The differentials in such scenarios include a vanishing or regressing lymphoma particularly in the setting of presurgical steroid administration. TB and a high-grade glial neoplasm need to be kept in mind and ruled out. In our case, the AFB and gene-expert were negative. Metastasis, commonly from occult lung lesion, has to be ruled out. In the present case, a CD7 and CD20 had been done to rule out its possibility. Although a probable diagnosis can be attained by radiology and clinical presentation, a definitive diagnosis would aid appropriate therapy. Neurosurgical excision of the lesion followed by appropriate chemotherapy has helped this patient remain disease-free for more than a year. Surgical excision of toxoplasmosis has been reported rarely in literature[8-10] with a similar clinical scenario in one instance[10] and in one case status quo lymphoma[11] made the diagnosis challenging, which was proved later in autopsy. Preoperative images MRI Brain plain and contrast Figures 1–3: Preoperative MRI: Well-defined ring-enhancing lesion measuring 2.0 cm × 2.0 cm × 1.6 cm in the right frontal lobe. Axial Figure 1, Sagittal Figure 2, and Coronal sections Figure 3. Figure 4: Immediate postoperative CT showing postoperative changes. Figures 5–7: Postoperative MRI at 1-year follow-up. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.