Standard and high dose ergocalciferol regimens for treatment of hypovitaminosis D in epileptic children and adolescents.

OBJECTIVES: Children with epilepsy are at increased risk of vitamin D deficiency. We aimed to compare the effect of two ergocalciferol regimens given for 90 days. METHODS: Epileptic patients aged 5-18 years who received at least one antiepileptic drug (AED) for more than 6 months and had serum 25-OHD <30 ng/mL were randomized to receive 20,000 IU/10 d (standard dose, n=41) or 60,000 IU/10 d (high dose, n=41) of oral ergocalciferol. Serum Ca, P, Mg, ALP, iPTH and urine Ca/Cr ratio were measured at baseline and after 90 days of treatment. Change in serum 25-OHD and vitamin D status after treatment was evaluated. RESULTS: The initial serum 25-OHD in the standard dose and high dose group was 19.5 ± 4.9 and 18.4 ± 4.6 ng/mL, respectively. Serum 25-OHD after treatment was significantly higher in the high dose group (39.0 ± 11.5 vs. 27.5 ± 8.6 ng/mL, p<0.05). The average increase in serum 25-OHD in the high dose and standard dose group was 20.6 ± 11.4 and 7.2 ± 7.5 ng/mL, respectively (p<0.05). Normalized serum 25-OHD was achieved in 80.5% of the high dose group compared to 36.6% of the standard dose group (p<0.05). No adverse events were found. Patients with a BMI Z-score>0 had a 2.5 times greater risk of continued hypovitaminosis D after treatment compared to those with a BMI Z-score<0 (95% CI: 1.0-5.9, p<0.05). CONCLUSIONS: Oral ergocalciferol 60,000 IU/10 d for 90 days was more effective at normalizing serum 25-OHD than 20,000 IU/10 d in epileptic children and adolescents who were receiving AEDs.

Perampanel as adjunctive therapy in drug resistant epilepsy in adolescents and children waiting for epilepsy surgery: A multicenter observational study in Thailand.

PURPOSE: To evaluate the effectiveness and tolerability of perampanel (PER) in real-world settings in patients between 1 month and 18 years of age with drug resistant epilepsy (DRE) waiting for epilepsy surgery. METHODS: In this multicenter study, patients between 1 month and 18 years of age with DRE treated with PER between January 2020 and June 2021 were selected. The study outcome was effectiveness of PER treatment reported as reduction in seizure frequency and seizure freedom rate. Effectiveness was assessed at 30, 60, 90, 120, 150 and 180 days after initiation of PER. Tolerability profiles were reported as adverse events according to the observations of the patients' family members and physician. RESULTS: Eighty-five patients treated with PER were included in the study. The mean initial dose and mean maximum dose of adjunctive PER was 2 mg/day and 5.8 mg/day, respectively. The mean seizure frequency (rate/week) was 41.3, 25.4, 18.9, 14.3, 11.2, 11.1 and 8.9 seizures at baseline, 30, 60, 90, 120, 150 and 180 days, respectively; the reduction in the mean seizure frequency at all timepoints was significant compared at the baseline (p<0.001). At 180 days, ≥75% seizure reduction was seen in 64.9% (37/57) of the patients and seizure freedom was achieved in 36.8% (21/57). Drowsiness, ataxia, and behavioral changes were the common adverse events observed, and these improved after the dose of PER was reduced. No discontinuation of PER was required due to side effects or intolerance. CONCLUSION: In real-world settings, PER is well tolerated and effective in seizure control in pediatric and adolescent patients with DRE.

Hypovitaminosis D and risk factors in pediatric epilepsy children.

BACKGROUND: Anti-seizure medication (ASM) treatment is one of the significant risk factors associated with abnormal vitamin D status in epilepsy patients. Multiple studies have shown that adult epilepsy patients can exhibit vitamin D deficiency. However, there are few reports investigating pediatric epilepsy patients. In this study, we aimed to identify risk factors related to hypovitaminosis D in pediatric epilepsy patients in Thailand. METHODS: A cross-sectional retrospective cohort study was conducted in 138 pediatric epilepsy patients who received anticonvulsants from April 2018 to January 2019. Demographic data, seizure types, puberty status, physical activity, duration, and types of anti-seizure medications were analyzed. Patients with abnormal liver function, abnormal renal function, and who received vitamin D supplements or ketogenic diet containing vitamin D were excluded. Levels of serum vitamin D (25(OH)D) were measured. RESULTS: All 138 subjects were enrolled, the age ranged from 1.04 - 19.96 years; (mean = 9.65 ± 5.09), the mean serum 25(OH) D level was 26.56 ± 9.67 ng/ml. The prevalence of vitamin D deficiency was 23.2% and insufficiency was 47.8% respectively. Two risk factors-puberty status (OR 5.43, 95% CI 1.879-15.67) and non-enzyme-inhibiting ASMs therapy (OR 3.58, 95% CI 1.117-11.46)-were significantly associated with hypovitaminosis D, as shown by multivariate analyses. CONCLUSIONS: Our study reports the high prevalence of hypovitaminosis D in pediatric epilepsy patients in Thailand despite being located in the tropical zone. These findings can guide clinicians to measure vitamin D status in pediatric epilepsy patients particularly when they reach puberty and/or are using non-enzyme-inhibiting ASMs therapy. Early detection of vitamin D status and prompt vitamin D supplementation can prevent fractures and osteoporosis later in life. TRIAL REGISTRATION: TCTR20210215005 ( http://www.clinicaltrials.in.th/ ).

Efficacy of oral perampanel in status epilepticus and acute repetitive seizures in children at a tertiary care hospital in Thailand.

Status epilepticus (SE) and acute repetitive seizure (ARS) are emergency conditions associated with significant morbidity and mortality in children. Anti-seizure medications (ASMs) need to terminate seizures to prevent brain damage and death. Common challenges that delay the management of SE and ARS in children at Phramongkutklao hospital are difficulty in accessing intravenous route for drug administration and inadequate number of intensive care units (which will be required in case of the use of adverse events to anesthetic ASMs). Oral, non-sedating ASMs could be a potential option to terminate seizures effectively in SE and ARS in children and further studies in this aspect are needed. We performed a prospective, descriptive study in children with SE or ARS < 18 years of age who had contraindication to or their seizures were refractory to the second-line ASMs after benzodiazepine and received oral perampanel. Demographic data, efficacy, and adverse effects of treatment were recorded. Fifteen patients with SE (13.3%) and acute repetitive seizure (86.6%) were enrolled. All patients received an oral perampanel loading dose and the maintenance dose depended on their body weight. The average loading and maintenance dose were 0.24 mg/kg/dose and 0.12 mg/kg/day, respectively. At 48 h after administration of loading dose of perampanel, eight of fifteen patients (53.3%) became seizure free, one patient had seizure reduction of >75% from baseline, and three patients had seizure reduction of 25-50% from baseline. No serious side effects were observed. These results indicate that oral perampanel may be potential treatment option for SE and ARS in children.

The effect of intravenous hydration strategy on plasma methotrexate clearance during intravenous high-dose methotrexate administration in pediatric oncology patients.

BACKGROUND: High-dose methotrexate (HD-MTX) is widely used as a standard chemotherapeutic agent in pediatric cancers. Most research studies have confirmed the therapeutic efficacy of HD-MTX; however, strategies to prevent side effects vary among institutions, especially in developing countries, with limited monitoring of plasma methotrexate level. OBJECTIVE: To evaluate the effect of intravenous hydration during HD-MTX administration on plasma methotrexate clearance in pediatric oncology patients. MATERIALS AND METHODS: This study retrospectively reviewed 165 courses of HD-MTX administered to children with acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma (NHL), or osteosarcoma. Demographic data of patients were collected. Adverse complications related to HD-MTX and 72-hour plasma methotrexate level were analyzed between patients receiving intravenous hydration ≥3,000 mL/m2/day and those receiving hydration <3,000 mL/m2/day. RESULTS: Among 56 HD-MTX (1.5 g/m2) courses in ALL, delayed methotrexate clearance was only found in one course administered with hydration <3,000 mL/m2/day. However, no correlation was observed between adverse complications and methotrexate levels. Of 34 HD-MTX (1.5-3 g/m2) courses in NHL, no significant correlation was observed between methotrexate levels and intravenous hydration. However, increased adverse complications were found in the course with delayed methotrexate clearance. Interestingly, among 75 HD-MTX (10-12 g/m2) courses in osteosarcoma, normal methotrexate clearance was successfully achieved in all courses administered with hydration ≥3,000 mL/m2/day compared with those administered with hydration <3,000 mL/m2/day (P=0.007). Furthermore, the courses administered with hydration <3,000 mL/m2/day and had delayed methotrexate clearance were more likely to develop adverse complications. CONCLUSION: Intravenous hydration of ≥3,000 mL/m2/day during HD-MTX administration is essentially required in osteosarcoma and can be considered as optional in ALL with HD-MTX <1.5 g/m2, especially in developing countries with limited monitoring of plasma methotrexate level.