What are the primary features and treatment of neuro toxoplasmosis?

Features and Treatment of Neurotoxoplasmosis

Neurotoxoplasmosis is characterized by focal neurological deficits and ring-enhancing brain lesions primarily affecting the basal ganglia and cerebral corticomedullary junction, requiring prompt treatment with pyrimethamine plus sulfadiazine and leucovorin for optimal outcomes.

Clinical Manifestations

Neurological Presentation

• Focal neurological deficits are the most common presentation, though diffuse CNS disease can also occur 1
• Fever, reduced alertness, and seizures are frequently observed 1, 2
• Stroke-like presentations can occur in HIV-infected patients 3
• Headache and changes in mental status are common but nonspecific symptoms 4

Imaging Findings

• CT scan typically shows multiple, bilateral, ring-enhancing lesions, especially in the basal ganglia and cerebral corticomedullary junction 1
• MRI is more sensitive than CT and will confirm basal ganglia lesions in the majority of patients 1
• Less common presentations include ventriculitis and hydrocephalus without focal parenchymal lesions 4

Risk Factors

• Most commonly seen in immunocompromised patients, particularly those with HIV/AIDS 2
• In HIV-infected patients, it's the most common cause of expansive brain lesions 2
• Can occur in other immunocompromised states such as post-transplant patients 5
• Rarely seen in immunocompetent individuals 6

Diagnostic Approach

Serologic Testing

• Serologic testing is the major method of diagnosis, though interpretation can be challenging 1
• Cases of Toxoplasma encephalitis have been reported in persons without Toxoplasma-specific IgG antibodies, so negative serology does not exclude the diagnosis 1
• Specialized reference laboratories capable of performing serology, isolation of organisms, and PCR can be helpful 1

Imaging Studies

• CT or MRI of the brain is essential for diagnosis 1
• F-fluoro-2-deoxyglucose-positive emission tomography can help distinguish Toxoplasma abscesses from primary CNS lymphoma, though accuracy is not high 1

Definitive Diagnosis

• Presumptive diagnosis is based on clinical symptoms, serologic evidence, and characteristic lesions on brain imaging 1
• Definitive diagnosis requires histologic or cytologic confirmation by brain biopsy 1
• Brain biopsy may show leptomeningeal inflammation, microglial nodules, gliosis, and Toxoplasma cysts 1
• Biopsy should be considered when early neurologic deterioration occurs despite empiric treatment or when patients fail to respond to anti-Toxoplasma therapy after 10-14 days 1

Treatment

First-Line Therapy

• Pyrimethamine (2 mg/kg/day for 3 days, followed by 1 mg/kg/day) plus sulfadiazine (25-50 mg/kg/dose four times daily) and leucovorin (10-25 mg/day) is the preferred treatment regimen 1, 7
• Acute therapy should be continued for 6 weeks, assuming clinical and radiological improvement 1
• Longer courses may be required for extensive disease or poor response after 6 weeks 1

Monitoring During Treatment

• Complete blood count should be performed at least weekly while on daily pyrimethamine and at least monthly while on less frequent dosing 1
• Leucovorin (folinic acid) must always be administered with pyrimethamine to minimize bone marrow suppression 1

Alternative Regimens

• Trimethoprim-sulfamethoxazole appears to have similar efficacy to pyrimethamine-based regimens and may offer practical advantages in some settings 2

Special Considerations for HIV Patients

• In HIV patients, combined antiretroviral therapy (cART) can be initiated within 2 weeks after starting anti-toxoplasma therapy 2
• Immune reconstitution inflammatory syndrome is uncommon in cerebral toxoplasmosis 2

Clinical Pitfalls and Caveats

• Failure to consider toxoplasmosis in the differential diagnosis of ring-enhancing brain lesions in immunocompromised patients can lead to delayed treatment and poor outcomes 5
• Premature discontinuation of therapy can result in relapse of neurological deficits 5
• Substitution of folic acid for folinic acid or incorrect antimicrobial agents can lead to treatment failure 5
• Serial neuroimaging is valuable for monitoring treatment response 5
• Toxoplasmosis should be considered in any HIV-infected patient with new neurological findings, even with atypical presentations 1, 2