The objectives of this hospital-based retrospective study were to assess the clinical presentation, causes and treatment outcome of HIV-infected patients with seizure who presented to TASH which is the largest hospital in Ethiopia. The number of male (55.5%) and female were comparable (OR = 0.923, 95% CI = 0.565–2.07) which is similar to other study [3]. Unlike this study male predominance was reported in other studies [4–7, 10, 18, 19]. The mean hospital stay in days was 23.3(± 15.9) which is longer compared to other study [10] which is partly due to the advanced stage of HIV infection in most of the patients. The mean age of patients was 34 ± 8.4 years. Majority (88%) of them were below the age of 45 years which is similar to other studies [ 4–7, 10]. This might be partly due to the fact that the Ethiopian population is young [19] where 86.2% were below the age of 45 years in 2007.
Majority (69%) of the patients had primarily generalized type of seizure like in most other studies [ 4–7, 9, 11–13]. Even thought almost all patients (98.6%) had stage 4 HIV infections at presentation, in the majority (68.5%) the diagnosis of HIV infection was made after current hospital admission. Similar to other studies [4, 9], seizure occurred in patients with advanced HIV infection in these patients. The initial presenting symptom/sign was neurological in almost all patients ( 96%) patients: headache( 76%), change in mentation(76%), focal deficit(51.%), meningeal irritation signs( 37.7%) and papilledema ( 11.6%) which is consistent with other studies [5–8] in which the incidence of seizure is common in patients with neurological complications of HIV infection. Seizure as an initial manifestation was uncommon in this study (14%) similar to other studies [7, 14, 19]. In most patients, seizure was a recent onset at admission. It either started after current hospital admission (42.5%) or within 3 months prior to admission (52.5%). This indicates that most seizures were related to recent neurological complications of HIV infection.
The common causes of seizure were cerebral toxoplasmosis (46%), tuberculos meningitis (35.6%) and cryptoccocal meningitis(13.7%) which is similar to most other studies [ 6,7,9, 11–13]. Toxic-metabolic (59%) and HIV encephalopathy (22%) were the commonest causes of seizure in other studies [4, 5], respectively. HIV encephalopathy which is a common cause of seizure in developed countries [5, 9, 10, 14] was rare in this study like most other studies done in developing countries [7, 12, 13]. This may be partly explained by the fact that early and effective treatment of HIV-infection is not optimal in developing countries; hence, HIV-infected patients have a higher incidence of CNS opportunistic infections.
Status epilepticus occurred in 18% of the patients which is similar to some studies [4, 6, 14] but higher compared to other studies [7, 19]. The cause of status epilepticus was CNS infection in almost all patients which is related to the advanced stage of HIV infection and low CD4 count (mean: 77 ± 85 per mm3). The mean CD4 count in this study was lower compared to some studies [4, 5] and higher compared to other studies [ 9, 10]. The most common abnormality identified on brain imaging (done in 52%) was mass lesion (n = 43, 57%) which was due to cerebral toxoplasmosis in almost all patients. EEG and serum AED serum level was done in one patient each which indicates the limitations of diagnostic facilities in the hospital.
The AED of choice in patients with HIV infected patients is levetriracetam and where the newer AED are not available, valproic acid may be the treatment of choice [ 2 1]. In contrast to this recommendation, 94% of the patients were treated with phenytoin. Phenytoin drug reaction was not reported in these patients and was well tolerated as seen in other studies [4, 13]. In contrast to this study, phenytoin drug reaction was seen in 25% and 14% of patients in other studies [ 6, 14], respectively. Even though almost all patients were having advanced HIV infection (stage 4), only 16% were on ART during current admission which indicates early diagnosis and timely treatment of HIV infection is suboptimal in this region.
The over-all mortality was 52.7% which is higher compared to other studies [4, 7, 18] which reported mortality of 22% to 47%. Even though address from Addis Ababa ( the capital city where the hospital is found), seizure started after admission, change in mentation at initial evaluation and comatose at initial evaluation were predictors of mortality in the univariate analysis ( Table 4), only address from Addis Ababa and change in mentation at initial evaluation were independent predictors of mortality. The higher mortality in patients from Addis Ababa was unexpected finding. This might be partly due to the fact that patients who were critically ill were not able to travel to Addis Ababa from other parts of the country. Seizure as an immediate cause of death was not reported in this study and there was no relationship between status epilepticus and mortality similar to other study [4]. In contrast to this, other authors [22] reported that status epilepticus was a predictor of mortality. Unlike a study done in Zambia [18] which reported women to have a higher mortality, gender was not associated with mortality in this study.
This study had several limitations. During chart review missing information may occur. The retrospective nature of the study may cause under-ascertainment of cases. No patient with complex partial seizure was reported. Given the advanced stage of illness, patients with subtle focal seizure may be missed. Patients who were treated as outpatient only were not included in this study. With limited service of EEG, patients with non-convulsive seizure may not be identified. With limited access to brain imaging, biopsy and CSF analysis, etiological diagnosis may be difficult in some patients. Since TASH is a tertiary referral hospital, chance of selectively admitting critically ill patients is high.
To improve the high morbidity and mortality observed in patients with HIV-infection presented with seizure, prevention of HIV-infection, early diagnosis and treatment, early identification and treatment of neurological complications of HIV-infection are recommended. Improving diagnostic facilities (brain imaging, CSF analysis, EEG and biopsy) may improve treatment outcome. Replacing enzyme-inducer AEDs with non-enzyme-inducers may help improve effectiveness of ART.