Review Question - QID 221255

This patient with poorly controlled human immunodeficiency virus with subacute fevers, night sweats, and headaches as well as a cerebrospinal fluid analysis that shows elevated opening pressure, lymphocytic predominance, increased protein, and low glucose most likely has cryptococcal meningitis. This disease can be diagnosed with a cerebrospinal fluid India ink stain.

Cryptococcus neoformans is an opportunistic yeast that causes infections in immunocompromised patients such as those with HIV and a CD4+ T-cell count < 100/mm^3. The most concerning infection that it causes is meningoencephalitis, which is an indolent infection with symptoms such as fever, headache, malaise, and lethargy developing over the course of 1-3 weeks. Cerebrospinal fluid analysis commonly demonstrates a markedly elevated opening pressure (> 250-300 mm H2O), moderately elevated leukocyte count (< 50/mm^3) with a lymphocytic predominance, elevated protein, and low glucose. The diagnosis can be confirmed with an India ink stain or cerebrospinal fluid cryptococcal antigen test. Treatment involves fungicidal induction with amphotericin B and flucytosine for at least 2 weeks followed by maintenance therapy with fluconazole for several weeks to months until the CD4+ T-cell count rises. In some cases, lifelong fluconazole treatment is indicated.

Thakur and Wilson review the presentation, diagnosis, and treatment of chronic meningitis. They discuss how chronic meningitis, which lasts for more than 4 weeks, is difficult to diagnose, with no etiology identified in over 1/3 of cases. They recommend that a multidisciplinary team from fields including ophthalmology, dermatology, rheumatology, and infectious disease be involved to aid in the diagnosis of these complex clinical cases.

Figure/Illustration A is an ophthalmological exam demonstrating papilledema with changes around the macula (blue circle). These findings can be seen in patients with meningitis and elevated intracranial pressure.

Incorrect Answers:
Answer 1: Cerebrospinal fluid acid-fast stain can be used to diagnose tuberculosis meningitis, which can also present with fevers, headaches, night sweats, high opening pressure on lumbar punctures, and a lymphocytic predominant cell count on cerebrospinal fluid analysis; however, tuberculous meningitis typically causes focal neurologic deficits. Patients also often have pulmonary manifestations such as cough, hemoptysis, and lung cavitation on radiography.

Answer 2: Cerebrospinal fluid Gram stain can be used to diagnose bacterial meningitis, which would present with fevers, headaches, and a cerebrospinal fluid analysis demonstrating an elevated opening pressure, increased protein concentration, decreased glucose concentration, and a markedly increased leukocyte count (> 1,000/mm^3) with neutrophilic predominance. Bacterial meningitis typically has a more acute (days rather than weeks) and severe presentation than is seen in this patient.

Answer 4: Cerebrospinal fluid polymerase chain reaction testing for Toxoplasma gondii can diagnose neurotoxoplasmosis, which is an opportunistic infection caused by Toxoplasma gondii. Patients present with fevers, headaches, and an increased protein concentration on cerebrospinal fluid analysis; however, patients also commonly present with seizures, focal neurologic deficits, and ring-enhancing lesions on neuroimaging.

Answer 5: Cerebrospinal fluid VDRL testing can diagnose neurosyphilis, which is a late presentation of Treponema pallidum infection. Patients present with fevers, headaches, and a cerebrospinal fluid analysis that demonstrates a lymphocytic-predominant cell count and increased protein; however, neuroimaging often shows distributed areas of parenchymal enhancement or hypodensity due to ongoing inflammation and infarction. Patients have focal neurologic deficits leading to tabes dorsalis, dysesthesia, ataxia, or Argyll Robertson pupils.

Bullet Summary:
Cryptococcal meningitis presents in immunocompromised patients over the course of 1-3 weeks and can be diagnosed with an India ink stain of the cerebrospinal fluid.