DD, a 45 year-old male, presented to the Mulago Hospital with complaints of a 2 1/2 month history of recurrent fevers, a one month history of cough and "not speaking", and a 3 day history of "failure to walk" and "urinary incontinence". Due to his aphasia, his history was obtained from his wife. He was generally healthy and this was his first admission to the hospital. For the first month of his fevers, he received treatment for malaria at various private clinics. However, the persistent fevers and lack of improvement despite treatment with antimalarial drugs prompted his wife to urge him to get tested from HIV. An HIV test was done at Mulago hospital one month prior to admission. Upon finding out that he was HIV+, he refused to share this information with his wife. However, after repeated pleas, he revealed his status and never spoke from that moment on. He refused to feed, became withdrawn, and kept himself isolated during the one month before admission. Three days prior to admission, he stopped walking due to lower limb weakness, developed urinary incontinence and constipation, all of which prompted his wife to bring him to the Mulago Hospital casualty department on the 6th of September.
On presentation, the physical exam was difficult to interpret because of DD's psychiatric presentation. He appeared to be mildly wasted, was fully conscious with a GCS of 15/15, with intact comprehension but with expressive aphasia. He had oral candidiasis, his neck was "stiff", Kernig's sign was negative, and papilledema was not assessed. The power in his right and left upper limb were 5/5 and 4/5 respectively and 3/5 in both lower limbs. The tone and reflexes were normal in the upper limbs. There was hypertonia and hyperreflexia (3+) in both lower limbs. Toes were down-going bilaterally and the remainder of the physical exam was unremarkable. He was diagnosed with depression and subjective paraparesis with a differential diagnosis of organic brain syndrome secondary to opportunistic infections associated with HIV (TBM, toxoplasmosis, CM, ABM, encephalitis). To rule out organic brain syndrome, a lumbar puncture was done and results revealed clear and colourless CSF that was under moderate pressure, a white blood cell count <5 cells/mm3, protein of 80 mg/dL, and Gram stain, India ink, ZN, VDRL, TPHA, and culture were all negative. The LP was therefore undiagnostic with only mild protein elevation. His CBC revealed lymphocytopenia corresponding to immunosuppression associated with HIV/AIDS. Chest x-ray and liver function tests were normal. The working diagnosis remained depression and he was treated with Fluoxetine (20 mg po QD).
On the 4th day of admission, weakness progressed and became right-sided hemiparesis. Toxoplasmosis titers were done on the same day and came back negative (IgG 4.1 ng/ml [>5 ng/ml being positive], IgM index 0.37 [>0.96 being positive]). On the 7th day of admission, weakness further progressed and became right-sided hemiplegia. A CT scan of the head was done on the same day and revealed a nodular, ring-enhancing lesion in the anterior part of the left basal ganglia with brain edema and moderately raised intracranial pressure. There was a mid-line shift of 0.5 mm to the right with lateral ventricle compression on the left. The findings were suggestive of an inflammatory process with abscess formation and a high suspicion of toxoplasmosis. The diagnosis post-CT scan was cerebral toxoplasmosis with differential diagnoses of primary CNS lymphoma and bacterial abscess (mycotic aneurysm, tuberculoma, metastatic lesion less likely). The patient was started on high dose Septrin (1920 mg po q6h) for toxoplasmosis and 2 days of high dose IV steroids (8 mg dexamethasone q8h) followed by oral prednisolone (40 mg QD) for brain edema. After four days of anti-toxoplasmosis and steroid treatment, the patient remained in hospital and the wife reported slight improvement. However, the patient remained aphasic with right-sided weakness.
The case would be challenging in any setting. Firstly, it illustrates the difficulty associated with acceptance of serostatus due to stigmatization associated with being HIV positive. HIV status challenges relationships. In this case, the husband feared revealing his status to his wife for fear of his wife leaving him alone with his illness. The impact of HIV infection on the disruption of families through separation, divorce, and widowhood has been examined among women in the Rakai district, Uganda. The research results revealed that family dissolution is more common among HIV-infected women and that infected women in HIV-discordant couples (where only one partner is positive) are especially vulnerable to separation or divorce. It is very likely that DD was facing similar fears, especially because his wife was HIV negative.
The case also demonstrates challenges in diagnosis of psychiatric illness versus an organic process. The patient's depressive state on admission was diagnosed as a psychiatric illness and would have been overlooked as such had further investigations not been performed. Finally, the fact that a CT scan revealed a brain lesion is only somewhat helpful. The fact that anti-toxoplasmosis antibody titers were negative [they are positive in most patients either before or at time of diagnosis in part because the tests used for measuring anti-toxoplasmosis antibody titers have a high sensitivity and thus are positive in most of suspected cases, being negative in <3-6% of patients with toxoplasmosis ] and the CT scan revealed a single lesion [toxoplasmosis usually presents with multiple ring-enhancing lesions ] questions the value of toxoplasmosis treatment. There is, however, one report of anti-Toxoplasma antibody negative cases with pathologically proven disease (in 22% of patients) and single enhancing lesions on CT (in 27% of patients), providing further evidence of the complexity of diagnosing CNS infections in any setting, irrespective of available diagnostic modalities. It is important to note that if the patient's lesion is a primary CNS lymphoma, treatment in a resource-poor setting is limited (see discussion for challenges in differentiating toxoplasmosis and primary CNS lymphoma). At the time of this report, the patient remains in the hospital awaiting response to treatment.