Clinical characteristics and outcomes after new-onset seizure among Zambian children with HIV during the antiretroviral therapy era.

OBJECTIVE: This study describes clinical profiles including human immunodeficiency virus (HIV) disease history and seizure etiology among children living with HIV presenting with new-onset seizure during the era of antiretroviral therapy (ART) in Zambia. 30-day mortality and cause of death are also reported. METHODS: Children living with HIV (CLWHIV) with new-onset seizures were prospectively evaluated at one large urban teaching hospital and two non-urban healthcare facilities. Interviews with family members, review of medical records, and where needed, verbal autopsies were undertaken. Two clinicians who were not responsible for the patients' care independently reviewed all records and assigned seizure etiology and cause of death with adjudication as needed. RESULTS: From April 2016 to June 2019, 73 children (49 urban, 24 rural) were identified. Median age was 6 years (IQR 2.2-10.0) and 39 (53%) were male children. Seizures were focal in 36 (49%) and were often severe, with 37% presenting with multiple recurrent seizures in the 24 hours before admission or in status epilepticus. Although 36 (49%) were on ART at enrollment, only 7 of 36 (19%) were virally suppressed. Seizure etiologies were infectious in over half (54%), with HIV encephalitis, bacterial meningitis, and tuberculous meningitis being the most common. Metabolic causes (19%) included renal failure and hypoglycemia. Structural lesions identified on imaging accounted for 10% of etiologies and included stroke and non-accidental trauma. No etiology could be identified in 12 (16%) children, most of whom died before the completion of clinical investigations. Twenty-two (30%) children died within 30 days of the index seizure. SIGNIFICANCE: Despite widespread ART roll out in Zambia, new-onset seizure in CLWHIV occurs in the setting of advanced, active HIV disease. Seizure severity/burden is high as is early mortality. Enhanced programs to assure early ART initiation, improve adherence, and address ART failure are needed to reduce the burden of neurological injury and premature death in CLWHIV.

Relapse and outcome patterns of patients with central nervous system mixed malignant germ cell tumors treated without irradiation: Findings from the third international central nervous system (CNS) germ cell tumor (GCT) study.

OBJECTIVES: To evaluate patterns of relapse and outcome in patients newly diagnosed with CNS Mixed Malignant GCT (MMGCT) treated initially with chemotherapy alone. METHODS: A retrospective chart review was conducted using all 25 patients enrolled on the International CNS GCT Study III, with at least 7 years follow-up for all surviving patients. RESULTS: Thirteen patients at diagnosis had CNS MMGCT by pathology and tumor markers (n = 11), or tumor markers alone (n = 2). Twelve received chemotherapy alone, one additionally receiving focal irradiation prior to relapse. Six patients (46%) relapsed (mean of 30.5 months; range 6-59 months), two beyond and four within the primary site alone. Three patients relapsed early (6-23 months from diagnosis), two with alpha-fetoprotein elevations and one without tumor markers assessed; all three expired of progressive disease at 2-10 months following initial relapse. Three patients relapsed late (37-59 months) without AFP elevations, one with pathologically pure germinoma, two with mild beta-human chorionic gonadotropin elevations; these patients survive disease-free at 86+, 94+, and 126+ months following additional treatment. CONCLUSIONS: Patients with CNS MMGCT relapsing following chemotherapy alone display two distinct patterns of recurrence and outcome; patients relapsing early possess MMGCT elements and have a dismal prognosis, while patients relapsing late do so with pure germinomatous elements and have an excellent outcome. Current cooperative group studies utilizing more localized fields of irradiation should monitor closely the patterns of relapse and outcome; late recurrences with germinomatous elements might be avoided by initial use of low-dose larger field irradiation in select patients.