Neurotoxoplasmosis

Neurotoxoplasmosis is CNS infection with Toxoplasma gondii, usually reactivation of latent cysts in people with severe immunosuppression: advanced HIV (CD4 count under 100 cells/microlitre), haematopoietic stem cell transplant, solid organ transplant and haematological malignancy. It is the commonest cause of focal brain lesions in AIDS.

Pathophysiology. Bradyzoite cysts in the brain reactivate to tachyzoites, causing necrotising encephalitis and abscesses, mostly in basal ganglia and corticomedullary junction.

Subacute headache, fever, confusion, focal deficit (hemiparesis, aphasia), seizures, movement disorders (hemichorea), visual loss and falling consciousness over days to weeks.

Red flags.

• Focal deficit or seizures with CD4 count under 100 cells/microlitre.
• Falling consciousness, raised intracranial pressure or herniation signs.

MRI (preferred) or contrast CT shows multiple ring enhancing lesions with oedema in basal ganglia and grey white junction. Toxoplasma IgG is positive in most (negative IgG makes it unlikely). CSF PCR is specific but insensitive. Response to treatment within 10 to 14 days is diagnostic. Biopsy is needed for non-response, solitary lesion or negative IgG. Exclude primary CNS lymphoma, tuberculoma and cryptococcoma.

Differential diagnosis.

• Primary CNS lymphoma, tuberculoma and bacterial abscess.
• Progressive multifocal leukoencephalopathy, cryptococcoma and Chagas disease.

Start empirical treatment promptly without waiting for biopsy in an at risk patient.

Acute treatment (at least 6 weeks).

• Pyrimethamine 200 mg orally loading dose, then 50 mg daily (under 60 kg) or 75 mg daily (60 kg or more), with folinic acid 10 to 25 mg daily (up to 50 mg) to prevent marrow suppression.
• Plus sulphadiazine 1000 mg orally every 6 hours (under 60 kg) or 1500 mg every 6 hours (60 kg or more).
• Alternative: co-trimoxazole 5 mg/kg trimethoprim component IV or orally twice daily. Clindamycin 600 mg every 6 hours with pyrimethamine for sulphonamide intolerance (add pneumocystis prophylaxis).

Adjuncts. Dexamethasone 4 mg every 6 hours for mass effect only, and stop early. Levetiracetam for seizures.

Maintenance. Half dose acute regimen until CD4 count exceeds 200 cells/microlitre for 6 months.

Antiretroviral therapy. Start within 2 to 3 weeks of beginning toxoplasmosis treatment.

Monitoring. Full blood count weekly during pyrimethamine, renal function, hydration (crystalluria with sulphadiazine), and repeat MRI at 2 to 3 weeks.

Referral and escalation. Refer to infectious diseases. Refer urgently when response is poor.

Special groups. In pregnancy, treat with specialist advice (spiramycin or pyrimethamine regimen, with folinic acid), as pyrimethamine is avoided in the first trimester.