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Department of Neurology, Indiana University School of Medicine, Indianapolis, IndDepartment of Ophthalmology, Indiana University School of MedicineDepartment of Neurosurgery, Indiana University School of Medicine
A 35-year-old previously healthy female recently emigrated from Honduras and presented with a five-day history of sudden onset decreased vision in her right eye, pain with extraocular movements, fevers, and a 3-day history of right upper and lower extremity weakness and numbness. On exam, she was afebrile, and mental status was normal. She had no light perception in the right eye, a right relative afferent pupillary defect, right lower facial weakness, 4/5 strength of proximal and distal right upper and lower extremities, and decreased sensation in the right face, arm, and leg.
Her fundoscopic exam revealed severe optic disc edema, cotton wool spots, extensive flame-shaped peripapillary and intraretinal hemorrhages, and superior retinal pallor secondary to a branch retinal artery occlusion in the right eye (Fig. 1). The nasal periphery of the left eye retina demonstrated patchy, white lesions.
Fig. 1Right eye fundus photograph showing severe optic disc edema, cotton wool spots (white arrows), retinal hemorrhages (red arrows), and superior retinal pallor from vasculitis (blue arrows) involving the superior vascular arcade, characteristic of cytomegalovirus infection. The retinal vessels appear abnormal due to retinal vasculitis.
MRI of the brain with and without contrast showed scattered ring-enhancing lesions throughout the superficial and deep gray matter including the bilateral thalami and right globus pallidus with slight mass effect (Fig. 2), right optic nerve enhancement, and neck/parotid lymphadenopathy.
Fig. 2Magnetic resonance imaging of the brain, coronal T1-weighted post-contrast sequence. Ring-enhancing lesions (white arrows) are present within the bilateral thalami and right globus pallidus, consistent with cerebral toxoplasmosis.
Routine admission laboratory testing was remarkable for serum leukopenia (WBC, 2.8 x 109/L) and neutropenia (ANC, 1.1 x 109/L). Cerebrospinal fluid (CSF) studies revealed no pleocytosis, normal protein (320 mg/L), low glucose (1.6 mmol/L), negative VDRL, negative cytomegalovirus (CMV) PCR, negative gram stain and culture, normal ACE (0.0119 mcKat/L), and an elevated IgG index (0.99). Blood cultures, Mantoux tuberculin skin test, sputum AFB culture, fungal culture, cryptococcal antigen, and treponemal antibody testing were negative. Chest computed tomography (CT) showed no abnormalities. Western blot analysis was positive for HIV-1 with a CD4 count of 3 cells/mm3 and a viral load of 470 000 copies/mL.
Serum CMV PCR and toxoplasmosis PCR and IgG were positive. She underwent diagnostic anterior chamber paracentesis, and was treated with bilateral intravitreal ganciclovir injections, although anterior chamber CMV PCR and varicella zoster virus PCR later returned negative. She was treated with intravenous ganciclovir and oral sulfamethoxazole/trimethoprim for CMV and toxoplasmosis, respectively, as well as azithromycin for MAC prophylaxis. She was started on antiretroviral therapy with elvitegravir-cobicistat-emtricitabine-tenofovir (Genvoya). One month after presentation, her HIV viral load was 110 copies/mL, her right sided motor/sensory deficits and retinitis and optic disc edema were improving, but her right eye visual acuity remained at no light perception. The patient was subsequently lost to follow-up.
Discussion
The patient’s presentation with right eye vision loss, pain with eye movement, and right-sided weakness/numbness were initially concerning for demyelinating disease. However, her brain lesions in the gray matter were not characteristic of demyelination, and her fundus findings suggested an alternative etiology. Her subjective fevers, leukopenia, neutropenia, and recent immigration heightened awareness of infectious causes, such as dengue fever, chikungunya, zika virus, Chagas disease, toxoplasmosis, cytomegalovirus, neurocysticercosis, neurosyphilis, tuberculosis, and HIV with associated opportunistic infection.
Inflammatory, infectious, and neoplastic conditions, such as neurosarcoidosis, neurosyphilis, atypical bacterial or fungal meningitis, granulomatosis with polyangiitis, lymphoma, and opportunistic infections were also considered.
A CD4 cell count of < 200/mm3 with HIV-positive status confirmed acquired immunodeficiency syndrome (AIDS), and conferred an increased risk for central nervous system (CNS) opportunistic infection, demyelination, and malignancy, with the most common being toxoplasmosis, CNS lymphoma, progressive multifocal leukoencephalopathy (PML), HIV encephalitis, and CMV infection. These can be partially differentiated on the basis of MRI features (Table 1).
The presence of multiple ring-enhancing lesions in the bilateral thalami and right globus pallidus on brain MRI is characteristic of toxoplasmosis (Fig. 2). The patient’s optic disc edema, optic nerve enhancement on MRI, retinal vasculitis, and retinal ischemia are characteristic of CMV retinitis with optic neuritis (Fig. 1).
Table 1Differentiation of common central nervous system opportunistic infections based on brain magnetic resonance imaging findings
CMV retinitis is the most common ocular opportunistic infection in AIDS patients with a CD4 cell count of < 50/mm3, although its incidence has decreased with the use of antiretroviral therapy (ART).
Jacobson MA. Pathogenesis, clinical manifestations, and diagnosis of AIDS-related cytomegalovirus retinitis. uptodate.com. Published 2016. Accessed June 16, 2017.
Jacobson MA. Pathogenesis, clinical manifestations, and diagnosis of AIDS-related cytomegalovirus retinitis. uptodate.com. Published 2016. Accessed June 16, 2017.
Jacobson MA. Pathogenesis, clinical manifestations, and diagnosis of AIDS-related cytomegalovirus retinitis. uptodate.com. Published 2016. Accessed June 16, 2017.
A false negative anterior chamber paracentesis CMV PCR is likely in this case because of classic CMV fundus findings, positive serum CMV PCR, and her rapid response to intravitreal and intravenous ganciclovir. The patient’s ocular findings were inconsistent with toxoplasmosis, which presents with retinochoroiditis and vitreous reaction, none of which were seen in this patient.
US Department of Health and Human Services. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Morbidity and Mortality Weekly Report 2009:RR-4.
For patients with lesions near the fovea or optic nerve head, intravitreal ganciclovir or foscarnet, in addition to systemic CMV therapy, is recommended. Frequent funduscopic examinations by an ophthalmologist are needed to monitor for adequacy of response to treatment.
US Department of Health and Human Services. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Morbidity and Mortality Weekly Report 2009:RR-4.
Portions of the retina damaged by CMV do not regenerate, therefore, the goal of treatment is to prevent progression.
Like CMV, the incidence of toxoplasmosis has decreased with ART. Symptoms include fever, headache, confusion, focal neurologic deficits, as well as extracerebral manifestations such as pneumonitis and retinochoroiditis.
Stereotactic brain biopsy is the gold standard for diagnosis of brain lesions, but may cause significant morbidity. Treatment includes sulfadiazine/pyrimethamine induction therapy for six weeks followed by maintenance therapy.
US Department of Health and Human Services. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Morbidity and Mortality Weekly Report 2009:RR-4.
Clinical improvement and a reduction in lesion size are expected within two weeks of treatment commencement.
The presence of active CMV retinitis and cerebral toxoplasmosis in the same patient at the same time emphasizes the importance of a thorough evaluation in patients with opportunistic infection and that a single disease entity may not sufficiently explain a patient’s clinical presentation. Being familiar with the typical clinical presentation of each entity has the potential to decrease morbidity associated with delayed diagnosis and treatment.
Disclosure
The authors have no proprietary or commercial interest in any materials discussed in this article.
Jacobson MA. Pathogenesis, clinical manifestations, and diagnosis of AIDS-related cytomegalovirus retinitis. uptodate.com. Published 2016. Accessed June 16, 2017.
US Department of Health and Human Services. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Morbidity and Mortality Weekly Report 2009:RR-4.
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