What is the initial approach to treating an HIV patient with central nervous system (CNS) infection presenting with mass effect?

HIV CNS Infection with Mass Effect: Initial Treatment Approach

In HIV patients with CNS infection presenting with mass effect, immediately initiate empiric anti-toxoplasmosis therapy (pyrimethamine plus sulfadiazine) while simultaneously managing elevated intracranial pressure through serial lumbar punctures or corticosteroids, and obtain urgent neuroimaging to guide definitive diagnosis and treatment. 1, 2

Immediate Diagnostic Evaluation

Neuroimaging Priority

• MRI with contrast (including diffusion-weighted imaging) is the preferred modality and should be performed within 24 hours to characterize the mass lesion and assess for mass effect 1, 2
• If MRI is unavailable or contraindicated, obtain urgent CT with contrast to exclude structural causes of raised intracranial pressure and identify alternative diagnoses 1
• Multiple ring-enhancing lesions with surrounding edema and mass effect are characteristic of toxoplasmic encephalitis, the most common cause of CNS mass lesions in HIV patients 3

Lumbar Puncture Considerations

• Defer lumbar puncture if imaging reveals significant mass effect, obstructive hydrocephalus, or risk of herniation 1, 4
• Once safe to proceed, obtain CSF for: cryptococcal antigen, Toxoplasma PCR, bacterial culture, fungal culture, cytology, flow cytometry, and cell count with differential 1, 2
• Measure opening pressure if lumbar puncture is performed, as elevated intracranial pressure is common and requires specific management 1

Empiric Treatment Strategy

Anti-Toxoplasmosis Therapy (First-Line)

• Start empiric treatment for toxoplasmosis immediately in all HIV patients with ring-enhancing CNS lesions and mass effect, as this is the most common etiology (37.8% of HIV CNS infections) 3, 5
• Standard regimen: pyrimethamine plus sulfadiazine plus leucovorin 1, 3
• Clinical and radiographic response typically occurs within 10-14 days and serves as diagnostic confirmation 3
• If no improvement after 2 weeks of empiric therapy, proceed to brain biopsy for definitive diagnosis 3

Concurrent Antiretroviral Therapy

• Initiate or optimize antiretroviral therapy (ART) immediately, as immune reconstitution is essential for long-term disease control and improved outcomes 1, 2, 3
• ART should be fully active and managed in consultation with an HIV specialist 2

Management of Mass Effect and Elevated Intracranial Pressure

Corticosteroid Use

• For cryptococcomas or other fungal mass lesions with significant mass effect and surrounding edema, administer corticosteroids (dexamethasone 10 mg IV initially, followed by 4 mg every 6 hours) 1, 6
• For severe CNS inflammation with mass effect, consider higher doses: prednisone 0.5-1.0 mg/kg/day equivalent, with a 2-6 week taper 1
• Avoid corticosteroids in suspected toxoplasmosis until after empiric therapy is initiated, as steroids may mask therapeutic response 3

CSF Pressure Management (for Cryptococcal Disease)

• If cryptococcal meningitis is confirmed and opening pressure ≥25 cm CSF with symptoms, perform therapeutic lumbar punctures daily until pressure stabilizes 1
• Remove sufficient CSF to reduce opening pressure by 50% or to ≤20 cm CSF 1
• Consider temporary percutaneous lumbar drain or ventriculostomy for persistent elevation requiring repeated daily lumbar punctures 1
• Permanent VP shunt placement should only occur after appropriate antifungal therapy has been initiated and conservative measures have failed 1

Differential Diagnosis and Specific Treatments

Toxoplasmic Encephalitis (Most Common)

• Accounts for 12.8% of HIV CNS infections in hospitalized patients 5
• Multiple ring-enhancing lesions with mass effect on imaging 3
• Treat empirically as above; response within 2 weeks confirms diagnosis 3

Cryptococcal Meningitis/Cryptococcomas (Second Most Common)

• Accounts for 37.8% of HIV CNS infections 5
• For cryptococcomas ≥3 cm with mass effect, consider surgical debulkment in addition to medical therapy 1
• Induction therapy: amphotericin B (0.7-1 mg/kg/day IV) plus flucytosine (100 mg/kg/day orally in 4 divided doses) for at least 6 weeks 1, 2
• Consolidation: fluconazole 400-800 mg/day for 6-18 months 1

Primary CNS Lymphoma

• Less common but important consideration, especially with single lesions 1
• Treatment: rituximab plus high-dose methotrexate (3 g/m²) with concurrent ART 1, 2
• Avoid corticosteroids before tissue diagnosis if lymphoma is suspected, as they may cause lesion regression and complicate diagnosis 1

Tuberculosis

• Accounts for 35.8% of HIV CNS infections in some series 5
• Mortality rate of 16.9% among fatal CNS infections 5
• Consider empiric anti-tuberculous therapy if endemic area or suggestive clinical features 5

Seizure Management

Acute Seizure Control

• First-line: lorazepam 0.1 mg/kg IV at 2 mg/min or diazepam 0.15-0.2 mg/kg IV at 5 mg/min 2
• Second-line: levetiracetam 30 mg/kg IV at 5 mg/kg/min if seizures persist 2

Long-Term Antiepileptic Therapy

• Levetiracetam is preferred due to minimal drug interactions with ART, broad spectrum activity, and favorable side effect profile 2

Critical Pitfalls to Avoid

• Never delay empiric anti-toxoplasmosis therapy while awaiting definitive diagnosis in HIV patients with ring-enhancing lesions 3
• Do not perform lumbar puncture before neuroimaging in patients with focal neurologic signs or altered mental status 1, 4
• Failure to measure and manage elevated CSF pressure in cryptococcal disease leads to increased mortality and new neurologic deficits 1
• Do not stop treatment after 2 weeks even if clinical improvement occurs—complete induction therapy is essential 1, 3
• Ensure CD4 count is checked, as severe immunosuppression (CD4 <100 cells/μL) predicts opportunistic infections 5