We reviewed the medical records of 1,167 HIV-infected patients who were at least 16 yr old and visited the Seoul National University Hospital Infectious Disease Clinic more than once between January 1999 and December 2008. The patients with intracranial parenchymal lesions were identified from the electronic database of radiological reports. The study protocol was approved by the Institutional Review Board of Seoul National University Hospital (IRB No. H-0910-018-296).

Diagnoses of intracranial parenchymal lesions were classified as definite, presumptive, or probable. A definite diagnosis was defined as a diagnosis based on histological proof of a cerebral disorder from a brain tissue specimen obtained by stereotactic brain biopsy. Presumptive diagnostic criteria for intracranial parenchymal lesions were as follows: 1) presumptive progressive multifocal leukoencephalopathy (PML), defined as positive JC virus DNA on polymerase chain reaction (PCR) from a cerebrospinal fluid (CSF) specimen, accompanied by a typical magnetic resonance imaging (MRI) pattern (12); 2) presumptive intracranial tuberculoma or disseminated non-tuberculous mycobacteria (NTM) disease, defined as evidence of lesions with mass effect from brain imaging and microbiological confirmation of tuberculosis or NTM from CSF or extra-cerebral specimens (13); 3) presumptive Toxoplasma encephalitis, defined as recent onset of focal neurologic abnormalities consistent with intracranial disease or a reduced level of consciousness, evidence of a lesion with mass effect or contrast enhancement by brain imaging, and positive serum antibody to T. gondii (14); 4) presumptive intracranial cryptococcoma, defined as evidence of lesions with mass effect from brain imaging and microbiological confirmation of Cryptococcus neoformans from CSF specimens (15); 5) presumptive cytomegalovirus encephalitis, defined as compatible neuroradiologic findings and positive cytomegalovirus DNA on PCR from CSF specimen (16). Probable diagnoses were determined by a board-certified infection disease specialist based on clinical and neuroradiological findings; the criteria were as follows (17): 1) probable PML, defined as presence of steady progression of focal neurologic deficit with a typical MRI pattern, namely asymmetric, non-enhancing, T2-hyperintense white matter abnormalities without mass effect; 2) probable HIV encephalopathy, defined as presence of progressive cognitive impairment with diffuse, bilateral, non-enhancing white-matter hyperintense lesions on MRI, and exclusion of opportunistic central nervous system (CNS) infections by examination of CSF; 3) probable primary CNS lymphoma, defined as evidence of a lesion with mass effect from brain imaging, exclusion of opportunistic CNS infections by examination of CSF, and response to radiation and/or chemotherapy.

Continuous variables are expressed as median and interquartile range (IQR) values. Difference in the incidence of intracranial parenchymal lesions by calendar years were analyzed using the Poisson regression. Statistical analyses were performed with SPSS software (version 17.0).

We treated 1,167 HIV-infected patients between 1999 and 2008. Total follow-up duration was 4,304 person-years and median follow-up duration per person was 3.16 yr (IQR, 0.93-6.03).

One thousand and sixty seven (91.4%) of the patients were male, 442 (41.4%) of whom had the risk factor of homosexual behavior. All patients were Korean and the median age was 37 yr (IQR, 30-45). The median CD4⁺ lymphocyte count at first visit to the study hospital was 230 cells/µL (IQR, 96-360), and the median CD4⁺ lymphocyte count at nadir during follow-up was 200 cells/µL (IQR, 80-300). Of 938 patients tested for antibody against T. gondii, 41 (4.3%) were positive (Table 1).

We performed neuroradiologic studies on the 165 patients with neurological manifestation reported among the 1,167 eligible patients, and found intracranial parenchymal lesions in 40 (3.4%) of them. Thirty three (82.5%) of the intracranial parenychymal lesions were multiple lesion, and 23 (57.5%) were enhanced on contrast-enhanced MRI. The overall incidence of intracranial parenchymal lesions was 0.93 per 100 person-years, and the incidence of intracranial parenchymal lesions (per 100 person-years) declined from 2.21 in 1999 to 0.69 in 2008 (P=0.003).

Of the 40 patients with intracranial parenchymal lesions, 37 (92.5%) were male, and the median age was 41 yr (IQR, 35-48). For 19 (47.5%) of these patients, the intracranial parenchymal lesion was the initial presentation of HIV infection. The median CD4⁺ lymphocyte count at nadir during follow-up was 28 cells/µL (IQR, 10-95). At the time of the diagnosis of the intracranial parenchymal lesions, median CD4⁺ lymphocyte count was 40 cells/µL (IQR, 13-150) and in 33 (82.5%) of the patients, the CD4⁺ lymphocyte count was less than 200 cells/µL (Fig. 1).

A definite diagnosis was obtained in 12 (30%) of the 40 patients with intracranial parenchymal lesions, a presumptive diagnosis was obtained in 19 (47.5%), and a probable diagnosis was obta-ined in nine (22.5%). All of the diagnoses were included among AIDS-defining diseases. PML was diagnosed in twelve cases (30.0%), intracranial tuberculoma in seven (17.5%), primary CNS lymphoma in seven (17.5%), cerebral cryptococcoma in four (10.0%), Toxoplasma encephalitis in four (10.0%), disseminated NTM disease in three (7.5%), HIV encephalopathy in two (5.0%) patients, and CMV encephalitis in one (Table 2).

Of the 12 patients with PML, one (8.3%) died during the observation period, two (16.7%) were lost to follow-up, and nine (75.0%) were improved with antiretroviral therapy. Of the 7 patients with intracranial tuberculoma, one (14.3%) died during the observation period, and six (85.7%) were improved with anti-mycobacterial treatment. Of the 7 patients with primary CNS lymphoma, two (28.6%) died during the observation period, one (14.3%) was lost to follow-up, and four (57.1%) were improved with systemic chemotherapy and/or cranial radiation therapy. The clinical features of the patients are summarized in Table 3.