What is the management approach for a patient with Human Immunodeficiency Virus (HIV) who presents with a seizure?

Management of Seizures in HIV-Infected Patients

All HIV-infected patients presenting with new-onset seizures require immediate neuroimaging (preferably MRI with contrast within 24 hours), lumbar puncture after imaging to exclude CNS infections, and empiric treatment for toxoplasmosis if ring-enhancing lesions are present, while simultaneously initiating or optimizing antiretroviral therapy. 1

Immediate Diagnostic Evaluation

Neuroimaging - Required Before Any Other Intervention

• Obtain MRI with contrast (including diffusion-weighted imaging) within 24 hours as the preferred modality to characterize mass lesions and assess for mass effect 1
• If MRI is unavailable or contraindicated, perform urgent CT with contrast to exclude structural causes and identify alternative diagnoses 1
• Never perform lumbar puncture before neuroimaging in HIV patients with seizures, as 40% of patients have abnormal findings on imaging that could indicate mass effect 2, 1

Laboratory Studies - Essential Initial Workup

• Obtain CD4 count and HIV viral load immediately upon presentation to determine immunosuppression level and guide diagnostic workup 3
• Measure serum glucose and sodium levels, as electrolyte abnormalities are common seizure triggers 2, 4
• Check pregnancy test in women of childbearing age 2
• Consider serum cryptococcal antigen testing while awaiting imaging, as it is positive in >99% of patients with cryptococcal meningitis 2

Lumbar Puncture - Mandatory After Imaging

• Perform lumbar puncture after CT/MRI in all immunocompromised HIV patients with seizures 2
• Measure CSF opening pressure in lateral recumbent position, collect sufficient CSF (3 mL) for fungal culture, and measure cryptococcal antigen titer, glucose, protein, and cell count with differential (5 mL total) 2
• This is critical because 40% of HIV patients with new-onset seizures have acute lesions requiring specific treatment, and only 2 of 6 patients with such lesions had abnormal physical examination findings 2

Common Etiologies by CD4 Count

CD4 <50 cells/µL - Highest Risk Group

• Toxoplasmosis (most common cause of ring-enhancing lesions) 1, 5
• Cryptococcal meningitis or cryptococcomas 2, 1
• CMV encephalitis 3
• Primary CNS lymphoma 1
• Progressive multifocal leukoencephalopathy 6

CD4 50-200 cells/µL

• Tuberculosis meningitis 3
• HIV encephalopathy (direct HIV effect on brain) 2, 5
• Bacterial meningitis 3

Any CD4 Count

• HIV encephalopathy may be the single most common cause of seizures across all CD4 counts 5
• Metabolic derangements (hyponatremia, hypoglycemia) 4, 7
• Drug-related causes (antiretroviral medications, drug interactions) 8

Empiric Treatment Strategy

Immediate Antimicrobial Therapy

• Start empiric treatment for toxoplasmosis immediately in all HIV patients with ring-enhancing CNS lesions: pyrimethamine plus sulfadiazine plus leucovorin 1
• Never delay empiric anti-toxoplasmosis therapy while awaiting definitive diagnosis in HIV patients with ring-enhancing lesions 1
• For cryptococcomas ≥3 cm with mass effect, initiate 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

Antiretroviral Therapy

• Initiate or optimize antiretroviral therapy (ART) immediately, as immune reconstitution is essential for long-term disease control and improved outcomes 1
• Early initiation of highly active antiretroviral therapy (HAART) may reduce seizure incidence and frequency 7

Management of Elevated Intracranial Pressure

• Administer corticosteroids (dexamethasone 10 mg IV initially, followed by 4 mg every 6 hours) for cryptococcomas or other fungal mass lesions with significant mass effect and surrounding edema 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

Antiepileptic Drug Selection

First-Line Agent

• Use levetiracetam as the preferred long-term antiepileptic therapy due to minimal drug interactions with ART, broad spectrum activity, and favorable side effect profile 1
• This is critical because enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine) should be avoided when possible in patients on HAART due to significant drug-drug interactions 7, 8

Important Caveat About Phenytoin

• Avoid phenytoin if possible: 14% of HIV patients develop hypersensitivity reactions to phenytoin, which is substantially higher than the general population 5, 8
• The risk for AED-induced allergic skin rash is high in HIV-seropositive individuals 8

When to Initiate Antiepileptic Therapy

• Treat even a single seizure in HIV-infected patients, as many patients have multiple seizures prior to anticonvulsant administration, and seizure recurrence occurs in 63% of those with new-onset seizures 5, 7
• This differs from general seizure management guidelines because HIV-associated seizures have high recurrence rates and are poor prognostic indicators 8

Disposition and Follow-Up

Admission Criteria

• Admit patients with acute lesions requiring specific treatment (toxoplasmosis, cryptococcal infection, CNS lymphoma) 2
• Admit patients with status epilepticus or medically refractory seizures 5
• Admit patients with focal neurologic deficits, as an underlying cause is found in all such patients 5

Outpatient Management Considerations

• Patients with normal interictal neurologic examination and normal imaging may be considered for outpatient management with close follow-up, though only 2 of 24 such patients in one study had an identifiable cause 5
• However, given the high recurrence rate (63%) and potential for serious underlying pathology, a low threshold for admission is warranted 7

Critical Pitfalls to Avoid

• Never perform lumbar puncture before neuroimaging in patients with focal neurologic signs or altered mental status 1
• Never delay empiric toxoplasmosis treatment while awaiting biopsy or serology results in patients with ring-enhancing lesions 1
• Do not assume alcohol withdrawal as the cause without excluding structural and infectious etiologies first 4
• Do not use enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine) as first-line agents due to interactions with antiretroviral therapy 7, 8
• Do not withhold antiretroviral therapy due to concerns about drug interactions; immune reconstitution is essential for long-term outcomes 1

Prophylaxis Considerations

• Verify prophylaxis status for opportunistic infections based on CD4 count 3
• Ensure cotrimoxazole prophylaxis is in place, as prophylactic use may reduce seizure incidence 7
• Consider routine EEG in HIV patients to help diagnose nonconvulsive seizures early 7