The objectives of our study were to assess the clinical presentation, cause, treatment, outcome and predictors of mortality in patients with HIV/AIDS with neurologic complications admitted to the largest referral hospital in Ethiopia. Both sexes were equally affected unlike other studies [7
] where males outnumbered females. Majority of our patients were young (mean age 34.6 years) which is similar to other studies [7
]. There was delay at presentation (mean duration of symptoms prior to presentation was 30.6 days). The mean duration of symptoms prior to presentation for patients with cerebral toxoplasmosis (25 days) and cryptococcal meningitis (26 days) was similar to another study [2
]. Majority (66.3%) of cases were known to have HIV infection after current hospital admission. Almost all patients had advanced HIV disease at presentation (4.3% stage III and 95.7% stage IV) which is consistent with another study [8
The occurrence of seizure in cerebral toxoplasmosis in other studies [2
] was 25% and 29%, respectively, which was lower compared to our finding. In another study [12
], seizure occurred in 40% of patients with cerebral toxoplasmosis which was similar to our study. In a study [12
] the occurrence of seizure in tuberculous meningitis (28%) and cryptococcal meningitis (50%) was lower and higher, respectively, compared with findings in our study. The common neurologic disorders identified in our cases were: cerebral toxoplasmosis (36.6%), tuberculous meningitis (22.5%) and cryptococcal meningitis (22.2%), and the frequencies were similar to other studies [5
]. In contrary to our findings, tuberculous meningitis and bacterial meningitis were rare findings in patients with neurologic manifestations of HIV/AIDS in the United States [2
]. In a study from India [12
], cerebral toxoplasmosis was detected in 8.8%(5/57) which is very low compared to our finding. The number of patients with presumed diagnosis of primary CNS lymphoma was very low in our cases probably due to failure to do brain biopsy when empiric therapy for toxoplasmosis failed.
Stoke was identified in 2.3% of our patients which is low compared to a finding in another study [2
] which was 12%. The low number of patients (2%) with multiple neurologic disorders compared to 13.5% in another study [2
] probably shows the limited investigations available in our set up. Unlike other studies [2
] HIV-encephalopathy was diagnosed in only one of our patients (0.28%).
Majority of our patients (89.7%) had a CD4 count below 200/mm3 which is consistent with another study [12
]. Note that adult healthy Ethiopians have a mean absolute CD4 T-cell count of 775 cell/μL(range 366-1,235) in one study [18
]. Neuroimaging studies in our cases showed focal lesions in 56.8% which is higher when compared to 25.5% obtained in another study [2
]. The commonest (80%) cause of mass lesion on imaging studies in our patients was cerebral toxoplasmosis which is similar to other studies [1
] but contrary to a study done in South Africa [9
] where tuberculosis predominates as a cause of focal brain lesion(69%). In our study, normal neuroimaging finding and cerebral atrophy were detected in22.7% and 3.9%, respectively which is lower compared to another study [2
]. These might be explained by the limited access to neuroimaging studies and the low incidence of HIV-encephalopathy, which is the main cause of brain atrophy in HIV/AIDS patients, in our cases. A study [19
] on HIV-related neuropathology showed that the incidence of HIV-encephalopathy rises as patients survive longer after initiation of antiretroviral therapy and is the most common neurologic complications of HIV/AIDS in such set up [2
]. In a study from Nigeria [10
] which included ART naive patients only, HIV-encephalopathy was found in 12%(19/154) of cases which is higher when compared to our study. These show that history of treatment with ART alone does not explain the low incidence of HIV-encephalopathy in our patients. Our patients were highly selected group of patients with advanced disease stage in whom the neurologic symptoms might be overshadowed by overwhelming systemic illness. In addition, lack of adequate screening techniques and readily available imaging studies might contribute.
Amphotericin B was not readily available and treatment of cryptococcal meningitis was either Amphotericin B (n = 32) or oral fluconazole only (n = 45) [There was no significant difference in mortality, p-value = 0.260]. The limited availability of standard therapy might explain partly the higher case-fatality of cryptococcal meningitis (48.1%) in our cases compared to 32.4% in another study [2
]. Sulfadiazine-pyrimethamine was not available and patients with cerebral toxoplasmosis were treated with pyrimethamin-sulfadoxin. This might partly explain the higher mortality in our set up (44.1%) compared to 30.2% in patients who were treated with standard treatment [2
The overall hospital mortality was 45% which is high compared to other studies. In a study done in Nigeria [10
] which included outpatients and inpatients, an overall 6-month mortality of 45% was found. In another study from India [11
], a mortality of 34% was recorded. The in-hospital mortality of patients with neurologic manifestations of AIDS in Brazil [7
] was 32%. The case-fatality for the major neurologic disorders in our study was: tuberculous meningitis (53.8%), cryptococcal meningitis (48.1%), cerebral toxoplasmosiss (44.1%) and bacterial meningitis (33.3%). In a study done in Cambodia [15
], the case-fatality rates of tuberculous meningitis and cryptococcal meningitis was similar to our study which were 57% and 49%, respectively. In studies done in South Africa [20
] and Nigeria [10
] the case-fatality of HIV associated tuberculous meningitis was 71.8% and 77.5%, respectively, which is higher compared to our finding.
Both univariate and multivariate logistic regression analysis showed that address from Addis Ababa, altered sensorium and seizure were predictors of mortality. The unexpected relatively lower mortality of patients from outside the city of Addis Ababa might be partly explained by selection bias of cases who were relatively stable and able to travel to the city for better health care services. History of ART at admission was not found to improve mortality significantly.
This unexpected finding might be due to the relatively short period of treatment (mean 7 months, median 5 months), noncompliance (5 patients discontinued ART and of these 3 died) and only 15.6% of our cases were on ART. In patients with history of ART the common neurologic complications identified were: cerebral toxoplasmosis (n = 13), cyptococcal meningitis (n = 12), tuberculous meningitis (n = 10), bacterial meningitis (n = 9), stroke (n = 4) and others (n = 10). Further study is recommended to identify other possible reasons for the failure of ART in our patients.
There were several limitations to this study. Patients who were treated as outpatient only were not included and therefore the whole spectrum of neurologic manifestation might not be addressed. The absence of certain neurologic disorders in our study (myelopathy, peripheral neuropathy other than inflammatory demyelinating polyneurpathy, myopathy, etc.) might be partly explained by inclusion of inpatients only. Our hospital is a tertiary hospital and the chance of admitting selectively critically sick patients is high due to referral from other hospitals. The retrospective nature of the study might have caused unrecoverable missing data in some cases. There was no autopsy, biopsy, viral load and polymerase chain reaction done. CSF glucose and protein determination was done in minority of patients.
To improve care of patients with neurologic manifestations of HIV/AIDS, early diagnosis of HIV infection, patient education, starting prophylaxis when needed (e.g. INH and cotrimoxazole prophylaxis, BCG vaccination to decrease incidence of tuberculous meningitis), starting ART timely, making standard therapy for opportunistic infections readily available(e.g. sulfadiazine-pyremethamin with leucovorin and Amphotericin B), improving availability and quality of laboratory investigations and neuroimaging studies are very important.
In conclusion, most of our patients with neurologic manifestations of HIV/AIDS had advanced disease at presentations which was evidenced by: almost all were in stage IV, majority had low CD4 count and most had opportunistic CNS infections as the leading etiologies. Majority of patients were diagnosed to have HIV infection at admission and only a few patients were on ART and cotrimoxazole prophylaxis. Etiological diagnosis was difficult in some patients because of limited availability of laboratory services and lack of facilities for neuroimaging studies. Seizure and change in sensorium at presentation were independent predictors of mortality. To improve the high mortality and morbidity observed in our study, prevention of HIV infection, and when it occurs early diagnosis and appropriate prophylaxis and treatment of opportunistic infections and timely ART are recommended.