Cerebral toxoplasmosis typically presents in immunocompromised/advanced HIV individuals as the most common cause of focal brain lesions, characterised histologically by necrotising encephalitis with clusters of Toxoplasma gondii tachyzoites, and multiple ring-enhancing lesions predominantly at the corticomedullary junction and basal ganglia.
Description
Cerebral toxoplasmosis is a severe, often life-threatening, infection caused by the obligate intracellular protozoan parasite, Toxoplasma gondii. It predominantly manifests as a central nervous system (CNS) disease in immunocompromised patients, typically those with HIV/AIDS, where it serves as an important opportunistic infection. It is the most common cause of focal brain lesions in this population.
Pathogenesis
The infection is caused by the tachyzoite form of Toxoplasma gondii, which is capable of invading virtually all nucleated cell types in the body. After a primary infection, which is often asymptomatic, the parasite persists for life within host cells in a latent form, called bradyzoite, encapsulated within tissue cysts. In immunocompromised individuals, the bradyzoites transform back into tachyzoites, causing disease reactivation and leading to cerebral toxoplasmosis.
Subtypes
There are no recognised subtypes of cerebral toxoplasmosis.
Epidemiology, Risk Factors & Associations
- Most commonly occurs in individuals with advanced HIV infection (CD4 count <100/µL)
- Other risk factors include organ transplantation, malignancy, and conditions requiring long-term immunosuppression.
- Cats are the definitive host for Toxoplasma gondii, and exposure to cat faeces or contaminated soil is a risk factor for infection.
Clinical Features
Patients often present with:
- Focal neurological deficits
- Seizures
- Altered mental status
- Fever and headaches may also be present.
Complications
- Progressive neurological decline and death if left untreated.
- Potential for reactivation in immunosuppressed state
Pathological Features
Histopathology
- Macroscopic: Multiple, often bilateral, grey-white necrotic lesions are found throughout the brain.
- Microscopic: Characterised by necrotising encephalitis with clusters of Toxoplasma gondii tachyzoites within tissue cysts.
Serology
Positive IgG antibodies to Toxoplasma gondii.
Biochemistry
No specific biochemical markers.
Radiological Features
General Features
- Characteristically demonstrates multiple ring-enhancing lesions with surrounding oedema.
- Lesions are often located at the corticomedullary junction and basal ganglia, and are more commonly seen in the grey matter.
CT
- Non-contrast: Hypodense lesions
- Post-contrast: Ring-enhancing lesions with surrounding oedema.
MRI
- T1: Hypointense lesions
- T2/FLAIR: Hyperintense lesions with surrounding oedema.
- DWI/ADC: No restriction of diffusion.
- T1 Gad+: Ring-enhancing lesions. May demonstrated central nodular enhancement giving a target appearance.
NM
- Thallium 201 SPECT: Hypermetabolic
- F-18 FDG PET: Hypermetabolic
Grading and Staging
No specific grading and staging system for cerebral toxoplasmosis.
Diagnosis
The diagnosis is usually made based on clinical presentation, serology (presence of Toxoplasma gondii IgG antibodies), and characteristic imaging findings. Definitive diagnosis requires brain biopsy demonstrating tachyzoites.
Differential Diagnosis
- Primary CNS lymphoma: Typically shows a solitary lesion and is often associated with homogenous enhancement and minimal mass effect. Can also be solitary and located in basal ganglia and periventricular region.
- Tuberculous abscess: Tends to be located in the basal ganglia and can show ring enhancement, but often presents with meningeal involvement and other systemic symptoms of tuberculosis.
- Neurocysticercosis: Characteristically presents with multiple cystic lesions with a scolex.
- Pyogenic abscess: Can also present as a thick ring-enhancing lesion with T2 hypointense rim, central diffusion restriction. History would assist.
Management
Management typically involves a combination of antiparasitic therapy (pyrimethamine, sulfadiazine, and leucovorin), antiretroviral therapy in HIV-positive individuals, and steroids for managing cerebral oedema. Infectious disease specialists and neurologists are typically involved in the management of cerebral toxoplasmosis. Treatment may be administered empirically – lack of resolution suggests other aetiology.