A 50 years old black male from Guinea-Bissau and living in Portugal for the past seven months presented to the emergency room complaining of persistent frontoparietal headaches for the past week. The headache was non pulsatile, associated with photo and phonophobia, nausea and anorexia, and it disturbed his sleep, leading the patient to wake up several times during the night. The headache didn't worsen with the decubitus position. He denied other symptoms, particularly in terms of the respiratory, gastrointestinal, urinary or cutaneous systems. According to his wife, he had periods of marked disorientation and apathy since 3 years ago, since the time he was diagnosed hypertension (HTA), treated with amlodipine. Other comorbidities included a probable dementia related to multi-infarctions suffered a year earlier, and had no known allergies.
At examination, the patient presented with apparent slowing of movements, associated with time and space disorientation. He was afebrile, calm, with a blood pressure of 105/78 mmHg, a heart rate of 87 beats per minute and a respiratory rate of 16 cycles per minute. The cardio-pulmonary auscultation, the abdominal inspection and palpation were all normal. He had severe xerodermia, but no other skin lesions. He had no edema and no palpable peripheral lymphadenopathy.
The neurological examination showed the patient was conscious, but uncooperative, without apparent dysarthria, preserved visual fields, isochoric and isoreactive pupils, eye movements with no limitation, without facial palsy or motor lateralization, and without ataxia or neck stiffness.
In the emergency department blood tests showed: leukocytes 5.3 x 109/L (Normal Range: 4-10 x 109/L), platelet count 213 x 109/L (NR 150-400 x 109/L), hemoglobin 14.7G/dL (NR 13-17G/dL), erythrocyte sedimentation rate of 36 mm/1st h (NR: <20 mm/1st h), creatinine 1,28 mg/dl (NR: 0.8-1.3 mg/dL), AST 40 U/L (NR: 5-30U/L), ALT 42 U/L (5-30U/L), gamma glutamyl transferase 346 U/L (NR: 6-50U/L), alkaline phosphatase 249 U/L (50-100U/L), lactate dehydrogenase 261U/L (50-150U/L). An abdominal and renal ultrasound were requested and revealed no hepatic or renal abnormalities. The CT scan of the brain initially performed revealed diffuse brain atrophy, showing multiple small nodular lesions, isodense and a ring enhancement after intravenous injection of iodinated contrast, involving the brain and the cerebellum (Fig. 1). Subsequently, a lumbar puncture was performed, and the cerebrospinal fluid (CSF) showed to be xanthochromic, with an opening pressure of 13cmH2O. CSF analysis included: glucose 52 mg/dl (NR: >60 mg/dL), protein 43 mg/dl (NR: <42 mg/dL), leukocytes <1/mm3, erythrocyte 2800/mm3; India ink test and Streptococcus pneumoniae antigen were negative.
Considered the possibility of an infectious etiology, the patient was transferred to the Infectious Diseases ward for further studies. These included: negative HIV and syphilis screening tests, immunity (IgG presence and absence of IgM) for toxoplasmosis, cytomegalovirus, Borrelia and hepatitis A virus; natural immunity to hepatitis B virus; absence of antibody for hepatitis C virus, amebiasis, hydatidosis or cysticercosis. The lymphocyte populations were normal, with lymphocyte T-CD4+ of 600 cells/mm3 (NR: >700cells/mm3) and a CD4/CD8 ratio of 2.48. Interferon gamma test (QuantiFERON TB Gold ) was strongly positive.
By the 7th day at the ward, a brain magnetic resonance was performed and it confirmed the presence of multiple nodular intra-axial lesions with intense enhancement, predominantly homogeneous, but in form of "ring" in the larger ones, and surrounding edema relatively large for their small dimensions, although with no significant mass effect. Given the characteristics of the lesions, the differential diagnosis of secondary brain (metastatic) lesions, or an infectious etiology with hematogenous spread, including tuberculosis, were considered. The lumbar puncture was repeated, with a normal cytochemical examination, as it was the adenosine deaminase (ADA). At that time, CSF was also collected for cultures and polymerase chain reaction in real time (PCR-rt) screening for mycobacteria.
By the 11th day in the ward, the liver enzymes remained elevated (AST 51U/L, ALT 54 U/L, GGT 375 U/L, alkaline phosphatase 328 U/L) and a liver biopsy was performed. Histological result of the sample revealed necrotizing granulomatous inflammation, setting the diagnostis of tuberculosis as the main one. Given these results, antituberculosis drugs (ethambutol, rifampicin, isoniazid and pyrazinamide) were initiated.
At that time, a bronchoscopy with bronchoalveolar lavage was performed, as well as CT scans of the thorax, abdomen and pelvis. These last exams revealed a mass in the posterior mediastinum with 2.6 x 2.3 cm in contact with the esophagus, multiple adenopathies above and below the diaphragm, micronodules in the lung, and an increased heterogeneous prostate. After these findings, a gastrointestinal ecoendoscopy and a prostate ultrasound were performed. The first test confirmed the presence of a retroesophageal mass and it was sent to histology and microbiological study. The direct examination (with Ziehl-Nielsen staining) was strongly positive (>10bacilis/field). On the other hand, transrectal prostatic ultrasonography showed a gland of increased dimensions (54cc) with symmetrical and regular borders, and several well-defined hypoechoic nodular formations (Fig. 2), some with internal calcifications. Given the clinical information, and after discussion with the Urology department, a tuberculous etiology was actually considered as the most likely.
Among the ongoing tests performed since the beginning of hospitalization, we highlight the negative results of mycobacterial research (cultures and PCR-rt) in CSF, blood, urine or broncho-alveolar liquid.
During his stay on the ward, the patient had a slight improvement in his cognitive functions, being able to communicate easier. Another CT scan of the brain was performed after one month of antituberculosis drugs, and it showed a change in the enhancement pattern, now more diffuse, an aspect that, combined with the absence of worsenning, favored the hypothesis of tuberculosis in opposition of neoplastic etiology.
The patient was discharged from the hospital at that time, clinically and hemodynamically stable. He remains in follow-up by the Infectious Diseases team as an outpatient, and shows improvement of his overall status, specially his cognitive functions.