**8. Diagnosis of toxoplasmic encephalitis**

Multifocal necrotizing encephalitis is the main neuropathological sign of TE in in people living with AIDS [89, 90]. However, from the start of the epidemic until more recent years, a number of publications have used the term "toxoplasma abscess" [91]. Human Immunodeficiency Virus (HIV)-related TE does not exhibit pus, contrary to the traditional definition of a brain abscess, which requires for an intraparenchymal pus accumulation. The four histological phases of the development of a brain abscess are early cerebritis, late cerebritis, early capsule formation, and late capsule formation. Pus may be seen in the latter three stages [92]. Additionally, an immunocompromised host may have a considerable delay in the progression of the phases of a brain abscess [93]. Thus, early cerebritis that more closely resembles necrotizing encephalitis is often seen in toxoplasmosis patients [92]. Although these lesions are considered abscesses in some studies, we think it is more appropriate to define "toxoplasmic encephalitis" as researchers who have worked with TE for many years.

#### **8.1 Diagnostic categories**

There are important diagnostic criteria for TE. A differential diagnosis with diseases such as tuberculous meningitis or progressive multifocal leukoencephalopathy is required at this stage. In fact, the important points at this stage are early diagnosis and direct intervention, because it should never be forgotten that the time lost in neuropathology comes back with irreparable results [94].

#### *8.1.1 Histopathology-confirmed toxoplasmic encephalitis*

To establish the diagnosis clearly and definitively by histopathological examination, it is necessary to demonstrate the presence of *T. gondii* in brain biopsy or postmortem examination. Among the most commonly used methods, the priority is stereotactic computed tomography (CT)-guided needle biopsy. *T. gondii* tachyzoites or bradyzoites from tissue cysts can be seen at the margins of lesions by hematoxylin and eosin staining methods. However, the sensitivity can be significantly increased with immunohisto/cytochemical staining. Considering these histopathological methods, a definitive diagnosis can be made easily. However, the complications of brain biopsy should not be forgotten, and it should be done if necessary to make a definitive diagnosis. It should be recommended if there is no improvement in clinical findings after antitoxoplasma treatment and no progress is detected in imaging methods [94].

#### *8.1.2 Laboratory-confirmed toxoplasmic encephalitis*

For laboratory-confirmed TE, *T. gondii* DNA from cerebrospinal fluid (CSF) or brain biopsy material must be proven by nucleic acid amplification tests. The presence of serum *T. gondii* immunoglobulin G (IgG) antibodies also contributes significantly to diagnosing TE. Therefore, these two findings should be evaluated as a whole [94].
