Woman has transient episodes of seeing bitemporal black spots

Trace vitreous cells and subretinal, hypopigmented lesions were noted in both eyes.

Mark E. Patron

Andre J. Witkin

A 23-year-old woman presented to the hospital with a chief complaint of two transient 5-minute episodes of left-sided arm and leg numbness over the previous 6 days. She described seeing black spots in her bilateral temporal visual fields during these episodes of numbness. On the day of presentation, she had experienced 4 minutes of expressive aphasia accompanied by shaking of her entire left upper extremity. She denied any flashes, blurriness or change in vision.

The patient’s medical and ocular histories were unremarkable, although she reported a febrile illness 6 months prior, which resolved with antibiotics. Additionally, she reported recent night sweats over the last 2 weeks. The rest of her review of systems was negative. She was born in India and had moved to the United States 2 years prior to work as a research associate, with her most recent visit to India taking place within the last year. She was sexually active only with her fiancé and reported using condoms. She denied any alcohol, tobacco or drug use.

Examination

The patient was admitted to the hospital’s neurology service, and ophthalmology was called for consultation. On examination, the patient’s best corrected visual acuity was 20/25 in both eyes. Pupillary exam was normal with no afferent pupillary defect, and extraocular movements were full in both eyes. IOP was 13 mm Hg in the right eye and 14 mm Hg in the left eye. Confrontational visual fields and anterior segment exam were within normal limits.

Figures 1a and 1b. Color fundus photographs of both eyes. Images: Cox C, Marx J

Figures 2a and 2b. Early and late fluorescein angiographs of the left eye.

Figures 3a and 3b. CT and MRI images of the patient’s head.

On dilated fundus exam, trace vitreous cells were noted in both eyes. Subretinal, hypopigmented lesions were present in both eyes, with three smaller lesions located along the arcades in the right fundus and one larger lesion inferonasal to the optic disc in the left eye (Figures 1a and 1b). There were no exudates, hemorrhages or any obvious subretinal fluid. Fluorescein angiogram showed hyperfluorescence of the smaller lesions in the right fundus, whereas it showed early blocking of the larger lesion in the left eye with later ring-like hyperfluorescence (Figures 2a and 2b). No leakage was present.

As a result of the patient’s neurological workup in the hospital, head CT and MRI scans were available at the time of initial presentation to the eye clinic. These showed numerous ring-shaped lesions with surrounding edema scattered throughout the patient’s cerebellum, corpus callosum, temporal and occipital lobes, bilateral frontal and parietal lobes, as well as her left pons, midbrain and thalamus. Slight mass effect was present on her left lateral and fourth ventricles (Figures 3a and 3b).

What is your diagnosis?

Transient visual symptoms

The differential diagnosis for a patient with transient neurological and visual symptoms, trace vitritis and subretinal hypopigmented lesions is fairly broad. General disease categories to consider should include infectious, neoplastic and inflammatory conditions. With the additional findings of ring-shaped lesions seen on CT and MRI, as well as the development of new neurological symptoms and recent night sweats, neoplastic and infectious causes are the most likely. The patient’s recent immigration from India puts her at higher risk of exposure to a variety of infectious diseases, including parasites such as neurocysticercosis or toxoplasmosis, bacterial infections such as tuberculosis, syphilis or infectious endocarditis, as well as yeast infections such as Candida.

Differential diagnosis

Neurocysticercosis, caused by ingestion of Cysticercus cellulosae, is thought to be the leading cause of adult-onset epilepsy in the Third World. Ocular disease involves mainly the posterior segment (68%), with subretinal involvement appearing as acute retinitis consisting of retinal edema and exudates, retinal detachment and/or proliferative retinopathy. Neurocysticercosis was high on our differential given the patient’s social history and suggestive brain imaging. She was suspected of having early posterior involvement without rupture of cysts into the vitreous cavity, but with a clear inflammatory reaction in the vitreous.

Toxoplasmosis, caused by ingestion of Toxoplasma gondii, was high on our differential as well. This is another disease entity that can present with ring-shaped lesions on CT and MRI scanning. Toxoplasmosis is one of the most common causes of posterior uveitis in immunocompetent patients. Typical ocular findings include a localized area of retinitis with associated vitritis. Acute, active lesions may appear white or gray-white, which would match our patient’s fundus exam. Chronic lesions, on the other hand, would appear as well-demarcated pigmented areas of chorioretinal scarring.

Tuberculosis was also a distinct possibility given the patient’s recent immigration from India. She reported night sweats 2 weeks prior to the onset of her neurological symptoms, but denied any history of respiratory symptoms. The most common manifestation of intraocular tuberculosis is one or multiple choroidal tubercles, which are lesions appearing grayish-white to yellow with indistinct borders and located in the posterior pole. These lesions can have overlying hemorrhages, retinal folds and/or exudative retinal detachments. On fluorescein angiogram, early hypofluorescence with late hyperfluorescence is typical. As with toxoplasmosis, choroidal tubercles develop into pigmented, atrophic lesions with chronic infection.

Our patient reported being monogamous with her fiancé and using condoms during intercourse. Nevertheless, syphilis should still be included in almost any differential of posterior uveitis. Chorioretinitis is common in the disease and can have a varied appearance. Often, posterior uveitis presents as yellow or gray placoid lesions located in the macula or juxtapapillary regions. As with tuberculosis, these lesions show early hypofluorescence with late hyperfluorescence on fluorescein angiogram, but may also manifest a typical “leopard spot” hypofluorescence throughout the study.

Infective endocarditis typically presents with white-centered retinal hemorrhages, or Roth’s spots, although choroidal emboli may also occur. Our patient denied any history of rheumatic fever or intravenous drug use, and her fundus lesions were not characteristic of Roth’s spots. This diagnosis was low on our differential, but given the proximity of the patient’s lesions to the retinal vasculature and the presence of multiple brain lesions, the possibility was considered.

As opposed to toxoplasmosis, Candida endophthalmitis is an infection found more commonly in immunocompromised patients. This infection most often presents with decreased vision and floaters, neither of which our patient described. Nevertheless, her fundus exam was suggestive of Candida, which can appear as multiple, white, fluffy, chorioretinal lesions with overlying vitreous inflammation. Because the immune status of the patient was unknown, this possibility was also considered.

Finally, the presence of multiple brain lesions on CT and MRI scanning could suggest a neoplastic etiology, including masquerade entities such as lymphoma or metastatic cancer. The mean age of primary central nervous system lymphoma — resulting in vitreous and retinal findings — is mid-50s. Lesions appear subretinal, elevated and creamy yellow, with possible overlying retinal pigment epithelial detachments. Findings are usually bilateral, but can also be asymmetric. Our patient was not in the typical age range for this diagnosis, nor were her lesions elevated in appearance. A diagnosis of lymphoma, therefore, was low on our differential. Metastatic disease from a primary tumor could also cause a similar appearance and should be considered.

Clinical course

Given her unremarkable physical exam, absent medical history, young age, new-onset seizures with visual symptoms, multiple ring-shaped lesions on head CT and MRI, as well as recent immigration status from India, the primary team felt that the patient should be treated for presumptive neurocysticercosis until further testing could be obtained. She was treated by the neurology service with Keppra (levetiracetam, UCB Pharma), ivermectin and dexamethasone.

During her hospitalization, the patient underwent an exhaustive panel of testing to determine the etiology of her symptoms. Lab testing included toxoplasma antibody, Lyme antibody, HIV viral load and antibody, QuantiFERON-TB Gold test for tuberculosis, hepatitis B antibodies, blood cultures and an echocardiogram. All testing was negative. The patient remained stable with no repeat seizures, and prior to the return of her neurocysticercosis and strongyloides testing, the patient was discharged. She was sent home on levetiracetam, as well as 40 mg of prednisone daily. The results of her parasitic testing returned 3 weeks later and were found to be negative.

Due to her negative results, the patient was brought back to the hospital to rule out possible metastatic cancer. She underwent full body CT scanning, revealing numerous lesions scattered throughout her lungs and kidneys, as well as a suprasternal cystic mass. This mass was biopsied, revealing acid-fast bacilli consistent with Mycobacterium tuberculosis. A repeat QuantiFERON-TB Gold test was obtained, which came back positive. Consequently, the patient was diagnosed with disseminated tuberculosis based on her biopsy and serological testing results. Steroids were discontinued, and she was started on anti-tuberculosis therapy with no repeat visual or neurological disturbances.

Discussion

As discussed above, a diagnosis of tuberculosis was considered due to the patient’s social history, recent night sweats, fundus appearance and fluorescein angiogram findings. However, based on her neurological symptoms, fundus examination and brain imaging, neurocysticercosis was the presumed diagnosis until proven otherwise by laboratory testing and further imaging. Interestingly, she reported no pulmonary symptoms prior to her presentation to our hospital, no known contact with tuberculosis or any other concerning physical symptoms. Her presenting complaints — seizures with transient visual disturbances — were atypical for a diagnosis of tuberculosis. In one case series, initial workups for lymphoma, systemic lupus erythematosus and rheumatic heart disease were pursued extensively until disseminated tuberculosis was diagnosed later. Presenting complaints in these cases were most frequently fever, followed by night sweats and abdominal pain and, finally, cough, anorexia and weight loss. Neurological symptoms were not listed as a presenting complaint in any patients included in this case series.

Tuberculosis is most commonly acquired via inhalation of droplets, but can also be spread hematogenously or by direct inoculation. If an acute infection is not recognized, subsequent dissemination via hematogenous spread may occur, potentially infecting any organ of the body. Immunocompromised individuals are at a greater risk for dissemination, as acute or latent tuberculosis can lead to silent bacteremia. Some known risk factors for reactivation of a prior tuberculosis infection include alcoholism, cardiovascular disease, blood dyscrasias, chronic obstructive pulmonary disease, congestive heart failure, gastrectomy, long-term steroid use, malnutrition and neoplasm. As mentioned in this patient’s clinical course, she was not found to be immunocompromised, which decreased our initial suspicion for possible latent tuberculosis infection.

It should be noted that given her presumptive diagnosis of neurocysticercosis, our patient was started on steroids to reduce cerebral inflammation contributing to her seizure-like activity. In light of her final diagnosis, steroids may have exacerbated her tuberculosis infection, as steroids can medically suppress a host’s immune system. Our patient may have continued to have seizures, however, if steroids were not used in the short term along with anti-epileptic therapy. Clearly, the danger of prescribing steroids for a patient with possible tuberculosis should be considered when entertaining this diagnosis. Fortunately, if disseminated tuberculosis is diagnosed early, it can be treated and even cured. We believe our patient has a fairly good prognosis because she was diagnosed at a relatively young age and has had no other major systemic complications.

References:

• Andres SC, Tan-Alora A. A case series on disseminated tuberculosis. Phil J Microbiol Infect Dis. 2001;30(1):29-35.
• Coyle CM, Tanowitz HB. Diagnosis and treatment of neurocysticercosis. Interdiscip Perspect Infect Dis. 2009;2009:180742.
• Silverman ME, Upshaw CB Jr. Extracardiac manifestations of infective endocarditis and their historical descriptions. Am J Cardiol. 2007;100(12):1802-1807.
• Yanoff M, Duker JS. Ophthalmology. Mosby; 2009:882-886, 824-825, 828-832, 807-809, 798-802.

• Catherine Cox, MD, and Jeffrey Marx, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.

• Edited by Mark E. Patron, MD, and Andre J. Witkin, MD. Drs. Patron and Witkin can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.