A 20-year-old, non-Hispanic Black, cis-gender male with a history of iron deficiency anemia presented with several weeks of intermittent headache and mild fever. While the fever resolved, the headache became constant, and over the following month, he developed a worsened peripheral vision with mild photophobia, left upper extremity weakness, expressive aphasia, and difficulty in walking due to the loss of balance. Since the age of 15, he had experienced recurrent, painful oral and scrotal ulcers that would last for several days at a time. He was sexually active but had not been tested for sexually transmitted infections.
Vital signs were unremarkable. On physical examination, he had left lower facial droop, weakness of his left wrist and fingers, and hyperreflexia of the left lower extremity. A scrotal ulcer was present. On ophthalmologic exam, he had decreased vision in the left homonymous inferior quadrantanopia, bilateral posterior uveitis, chorioretinal scarring, and a single white retinal lesion suspicious for infectious or metastatic disease. On admission, he was found to have CD4 lymphocytopenia (163,000 cells/mcL).
Computerized tomography (CT) of the brain was obtained which showed a heterogenous region with surrounding vasogenic edema centered in the right thalamus and gangliocapsular region (involving the entire right basal ganglia, including the putamen, globus pallidus, and caudate, as well as the posterior aspects of the internal and external capsule). There was a 3-mm leftward midline shift; a mass effect on the Foramen of Monro, right lateral ventricle, and third ventricle; and dilation of the bilateral lateral ventricles. The CT scan also demonstrated a partial effacement of the basal cisterns.
Given the concern for an infectious or neoplastic process or central venous infarct sequelae, contrast-enhanced magnetic resonance imaging (MRI) of the brain was obtained. On MRI, abnormalities were also found involving the right midbrain, with further extension into the pons with mixed regions of T1 isointense and hypointense dense regions and with predominantly T2 and fluid-attenuated inversion recovery (FLAIR) hyperintense lesions. Additionally, there were multiple ring-enhancing lesions in the right thalamic region (with the largest measurement of 9 mm) and midbrain (with the largest measurement of 7 mm), with a surrounding T2 hyperintense region attributable to edema (Figure 1). At this point, additional differential diagnoses were considered, including neurocysticercosis, autoimmune encephalitis, vasculitis, and multiple sclerosis among others.
CT angiography (CTA) of the head and neck with and without contrast showed no large branch arterial occlusion, high-grade stenosis, arteriovenous malformation, or aneurysm.
Due to concerns for autoimmune etiologies, edema, and mass effects, the patient was started on dexamethasone, while the workup was ongoing. Given concerns for an infectious process (brain mass suspicious for brain abscess, in a sexually active person with CD4 lymphopenia), he was also started on broad-spectrum antibiotics.
Right-sided stereotactic needle biopsy with stealth navigation was performed, and a representative brain tissue sample showed only polymorphonuclear cells on the frozen specimen; therefore, no further neurosurgical intervention was performed. The brain tissue sample histopathology showed parenchymal and perivascular mixed inflammation and reactive gliosis with no evidence of malignancy or inflammation. Infectious studies of the brain tissue biopsy, including cultures (bacterial, fungal, and mycobacterial) and stains (Grocott's methenamine silver, periodic acid:Schiff, and gram stains), were all negative. Most parenchymal and vascular lymphocytes stained positive for CD3, with a subset of these positive for CD8 as well. Immunohistochemistry of the brain tissue also revealed rare CD20+ perivascular cells, numerous CD68+ histiocytes (some of which are microglia), and a Ki67 nuclear proliferation index of 2-3% (Figure 2).
Given the concern for malignancy, a CT scan of the chest, abdomen, and pelvis was completed, but the results were completely unremarkable for any disease process. Other infectious workups included blood cultures and fungal (histoplasmosis and cryptococcus), parasitic (toxoplasmosis and echinococcosis), bacterial (syphilis and tuberculosis), and viral (human immunodeficiency virus, cytomegalovirus, herpes simplex virus, hepatitis B, and hepatitis C) studies, which were all negative.
Further studies revealed that he had mildly elevated antinucleotide antibody titers (1:40:speckled), an erythrocyte sedimentation rate (ESR) of 69 mm/hr (normal range, 0-10), and C-reactive protein (CRP) of 1.3 mg/dl (normal range: <1). He had an elevated total serum protein of 8.3 gm/dL (normal range, 6.3-8.2), a normal serum albumin of 4 gm/dL, an elevated serum globulin of 4.3 gm/dl (normal range, 2-3.5), elevated immunoglobulin (Ig) G of 1830 mg/dl (normal range, 700-1600), and IgA of 534 mg/dl (normal range: 70-400). IgM was within normal limits.
An MRI of the brain after 5 days of high-dose methylprednisolone (1 g daily) and antibiotics showed an improvement in ring-enhancing lesions of the right thalamus, midbrain, and pons with a less mass effect. His neurological symptoms also improved significantly after several days of treatment. Given the negative infectious workup, antibiotics were discontinued after day 7 of admission. Neuro-Behcet's syndrome was diagnosed, given the patient's history, workup, clinical, and radiographic improvement after steroids and absence of alternate diagnostic etiologies. The pathergy test was negative. Genetic testing for HLA-B51 was collected but not resulted. The patient responded well to high-dose steroids and continued on an oral prednisone taper and azathioprine therapy after discharge. A 2-year follow-up brain MRI later showed no new or enhancing lesions (Figure 3) although the patient continued to have minimal residual deficits in mobility and vision.