**4. Clinical features**

Toxoplasmic encephalitis (TE) is the most common cause of focal brain lesion (FBL) in HIV/AIDS individuals with profound immune deficiency. Clinical presentations of TE depended on the location, number and size of the lesions. It may present with generalized cerebral dysfunction or focal signs and symptoms of the central nervous system (CNS) or with psychiatric abnormalities (Table 3). The majority of patients present with a combination of generalized and focal CNS abnormalities (Table 1) such as headache, fever, alteration of consciousness, confusion, cognitive impairment, hemiparesis, facial nerve palsy and convulsion (Berger et al, 1987; Ragnaud et al, 1993; Wainstein et al, 1993, Sukthana et al, 2000; Anrinori et al, 2004; Nissapatorn et al, 2004b; Chankrachang, 2004; Miro et al; 2006; Hoffmann et al, 2007; Ho et al, 2008). Headache was a more frequent symptom than fever ranging from 47% to 100%, while fever was found 45.6% to 64.5%. However, Ragnaud and

Toxoplasmic Encephalitis 295

Toxoplasmosis of the spinal cord is a rare manifestation and is usually associated with multiple lesions in the brain. Sites of involvement include the cervical, thoracic and lumbar spine. Few cases did not have brain lesions showing myelitis and myelopathic symptoms including a sensory level deficit, paraparesis, incontinence and changes in the deep tendon reflexes (Vyas, & Ebright, 1996; Kung et al, 2011). Kung and colleagues (2011) reported the first case of toxoplasmosis with myelitis in the absence of encephalitis and the diagnosis can be made pre-mortem by muscle biopsy showing multiple *Toxoplasma* bradyzoites and tachyzoites. Ajzenberg et al (2009) found a significantly higher TE occurrence in patients with AIDS than in patients whose immunosuppression was due to other causes than HIV infection (75% v.s. 27,8%). Patients with TE had a better outcome than those whose infection was non-cerebral, whereas pulmonary involvement was more frequently associated with

There are no obvious or non-specific clinical manifestations of toxoplasmosis in competent hosts which are unique to the disease. Most of the time, infections are overlooked. Thus, it is not straightforward to diagnose. Serological testing in such patient is the main identifying evidence of specific antibody. In TE reactivation, clinical features are more helpful than

Centre for Disease Control and Prevention (CDC), the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America recommend that making a definitive diagnosis of TE requires 1) compatible clinical features; 2) single or multiple mass lesions by computerized tomography (CT), magnetic resonance imaging (MRI), or other radiographic testing; and 3) the most important is detection of the organism in a clinical sample. This requires a brain biopsy performed by a stereotactic CT-guided needle biopsy. Organisms are demonstrable with hematoxylin and eosin stains and immunohistochemistry staining by experienced laboratories might increase sensitivity (CDC 2009). However, these are always impracticable due to patients' conditions. For clinically suspected TE cases, CDC criteria should be applied for a presumptive diagnosis i.e. 1) the recent onset of a focal neurological abnormality that is consistent with intracranial disease or reduced consciousness; 2) evidence from brain imaging of a lesion with mass effect and ring enhanced appearance after injection of a contrast medium; and 3) positive serum antibody to *T. gondii* or successful response to anti-toxoplasmic treatment (Sukthana, 2006). By using these presumptive diagnostic criteria, the positive predictive value is achievable in

On brain imaging, most of TE lesions occur in the basal ganglia, thalamus and corticomedullary junction (Lee et al, 2009). MRI is more sensitive than CT, Weenink and colleagues reported a TE patient who showed a normal contrast-enhanced CT scan, but MRI revealed clear abnormalities in the basal ganglia (Weenink et al, 2009). TE usually appears as multiple nodular or ring enhanced lesions with edema and mass effect. However, 14% of cases showing a solitary lesion which need to be differentiated from CNS lymphoma that more commonly presented as a single mass than toxoplasmosis (Legrand et al, 2010). Several techniques such as a diffusion weighted imaging; single-photon emission CT (SPECT) and positron-emission tomography (PET) could provide a more precise diagnosis (Sukthana, 2006; Legrand et al, 2010). Weighted MRI shows a peripheral hyperintensity of

death.

**5. Diagnosis** 

serological testing in term of diagnostic criteria.

approximately 80% (Cohn et al, 1989; Katlama, 1992; Luft et al, 1993).

colleagues (1993) demonstrated that fever was more sensitive than headache when used as diagnostic criteria (92% v. s. 41%sensitivity).

TE has an insidious onset presenting initially by non-focal features such as headache, lethargy, cognitive impairment or confusion followed by focal neurological deficits which develop over a period of days to weeks (up to 4-6 weeks). The common focal neurological deficits are hemiparesis, ataxia and cranial nerve palsies (Mariuz & Steigbigel, 2001; Chankrachang, 2004). Convulsion was found to be the initial manifestations in 14%-39% of TE cases (Nissapatorn et al, 2004b; Chankrachang, 2004).



Neuropsychiatric abnormalities occasionally dominate the clinical picture (Mariuz & Steigbigel, 2001). Thus the diagnosis will be missed if those were not borne in mind. Meningeal involvement is rare, so that meningeal irritation is unusual on physical examination. However, nearly half of Thai TE patients had positive neck stiffness (Chankrachang, 2004; Mootsikapun et al, 2004). Diffuse form, without focal deficit, of TE showed rapidly progressive generalized cerebral dysfunction which was usually fatal. In such cases, histological study revealed numerous diffuse microglial nodules with *T. gondii*  tachyzoites and cysts, hence brain CT scans were negative (Mariuz & Steigbigel, 2001).

colleagues (1993) demonstrated that fever was more sensitive than headache when used as

TE has an insidious onset presenting initially by non-focal features such as headache, lethargy, cognitive impairment or confusion followed by focal neurological deficits which develop over a period of days to weeks (up to 4-6 weeks). The common focal neurological deficits are hemiparesis, ataxia and cranial nerve palsies (Mariuz & Steigbigel, 2001; Chankrachang, 2004). Convulsion was found to be the initial manifestations in 14%-39% of

**Neurological manifestations Clinical presentations** 

**Generalized CNS dysfunction** Alteration of consciousness

**Focal neurological deficits** Hemiparesis, hemiplegia

**Psychiatric abnormalities** Dementia

Confusion

Headache

Convulsion

Papilledema

Anxiety Psychosis

Table 3. Neurological manifestations and clinical presentations of toxoplasmic encephalitis Neuropsychiatric abnormalities occasionally dominate the clinical picture (Mariuz & Steigbigel, 2001). Thus the diagnosis will be missed if those were not borne in mind. Meningeal involvement is rare, so that meningeal irritation is unusual on physical examination. However, nearly half of Thai TE patients had positive neck stiffness (Chankrachang, 2004; Mootsikapun et al, 2004). Diffuse form, without focal deficit, of TE showed rapidly progressive generalized cerebral dysfunction which was usually fatal. In such cases, histological study revealed numerous diffuse microglial nodules with *T. gondii*  tachyzoites and cysts, hence brain CT scans were negative (Mariuz & Steigbigel, 2001).

Fever

Cognitive impairment

Cranial nerves deficit

Hemisensory deficit

Personality changes

Dysphasia, Aphasia, Dysarthria

Stiffness of neck

Coma

diagnostic criteria (92% v. s. 41%sensitivity).

TE cases (Nissapatorn et al, 2004b; Chankrachang, 2004).

Toxoplasmosis of the spinal cord is a rare manifestation and is usually associated with multiple lesions in the brain. Sites of involvement include the cervical, thoracic and lumbar spine. Few cases did not have brain lesions showing myelitis and myelopathic symptoms including a sensory level deficit, paraparesis, incontinence and changes in the deep tendon reflexes (Vyas, & Ebright, 1996; Kung et al, 2011). Kung and colleagues (2011) reported the first case of toxoplasmosis with myelitis in the absence of encephalitis and the diagnosis can be made pre-mortem by muscle biopsy showing multiple *Toxoplasma* bradyzoites and tachyzoites. Ajzenberg et al (2009) found a significantly higher TE occurrence in patients with AIDS than in patients whose immunosuppression was due to other causes than HIV infection (75% v.s. 27,8%). Patients with TE had a better outcome than those whose infection was non-cerebral, whereas pulmonary involvement was more frequently associated with death.
