ABSTRACT
Leptospirosis is a zoonosis that is related to potential respiratory, renal, neurological, and cardiovascular failure. At present, antibiotics are the recommended treatment, but due to the underlying cause of the disease, they may induce the Jarisch-Herxheimer reaction (JHR) within 24 hours. At the same time, we speculate that JHR may aggravate the natural course of leptospirosis. Considering that there are few available reports on this event, we will share a case of pulmonary hemorrhagic leptospirosis, where antibiotic treatment is suspected to have triggered the JHR. This report is expected to improve clinical attention to the relationship between leptospirosis and JHR.
ABSTRACT
BACKGROUND: Infantile spasms (IS) is an age-specific and severe epileptic encephalopathy that occurs in infancy and early childhood and is usually refractory to conventional antiepileptic drugs. Adrenocorticotropic hormone (ACTH) has been the treatment of choice for IS, but ACTH use has been associated with infection and hypertension. Magnesium ion is an N-methyl-D-aspartic acid (NMDA)-noncompetitive antagonist that might inhibit NMDA activity and has antiepileptic and neuroprotective effects. OBJECTIVE: This study compared the efficacy and tolerability of ACTH + magnesium sulfate (MgSO(4)) versus ACTH monotherapy for the treatment of IS. METHODS: This 24-week, randomized, open-label follow-up study enrolled male and female infants with IS. Patients were randomly assigned to receive ACTH 25 U/d + MgSO(4) 0.25 g/kg/d, or ACTH 25 U/d only (control), intravenously for 3 weeks. Efficacy was assessed over a period of 24 weeks based on seizure frequency, EEG, and Gesell testing of psychomotor skills (subscales: language, motor, adaptive, and personal-social skills; measured using a developmental quotient [DQ] ). Tolerability was assessed by monitoring for adverse events using laboratory analysis and clinical evaluation. RESULTS: Thirty-eight infants were enrolled (23 male, 15 female; median age, 9.2 months; 19 patients per group). At 12 weeks, 14 patients (73.7%) who received ACTH + MgSO(4) and 9 patients (47.4%) in the control group were seizure free. At 24 weeks, seizure-free rates were 12 (63.2%) in the ACTH + MgSO(4) group and 10 (52.6%) in the control group. On EEG, 9 patients (47.4%) in the ACTH + MgSO(4) group achieved complete recovery (normalized EEG), 5 (26.3 %) attained partial improvement (multifocal spike wave), and 5 (26.3%) had no improvement (hypsarrhythmia or modified hypsarrhythmia). At 4 weeks, in the control group, 5 patients (26.3 %) achieved complete recovery, 6 (31.6%) achieved partial improvement, and 8 (42.1%) had no improvement. Of the 12 patients who were seizure free at 24 weeks in the ACTH + MgSO(4) group, 11 (91.7%) had complete recovery (normalized EEG); this rate was 7 of 10 (70.0%) in the control group. In the ACTH + MgSO(4) group, the change from baseline to 24 weeks in mean (SD) personal-social DQ was significant (from 48.6 [6.4] to 65.2 [7.1], respectively; P < 0.05). In the control group, the difference before and after treatment was nonsignificant (47.7 [6.0] vs 49.9 [4.4]). None of the other Gesell test findings were significant versus baseline. The most common AEs included upper respiratory tract infection and pyrexia (both, 3 [15.8%] per group); diarrhea (2 [10.5%] per group); and hypertension, insomnia, and irritability (all, 0 in the ACTH + MgSO(4) group and 2 [10.5%] in the control group). None of the between-group differences in the prevalences of AEs were significant between the 2 groups. CONCLUSIONS: In this study in infants with IS, the proportions of patients who were seizure free from 4 to 24 weeks were significantly greater in the ACTH + MgSO(4) group compared with the ACTH monotherapy group. Personal-social neurodevelopment was significantly improved from baseline in the group that received combination treatment. Both treatments were generally well tolerated. International Standard Randomized Controlled Trial no. ISRCTN 78654111.
