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Objective: To assess adverse events (AEs) and efficacy of add-on cannabidiol (CBD) with a slower titration protocol in pediatric clinical practice. Methods: We conducted a prospective, open-label, multicenter study in seven French reference centers for rare epilepsies. Patients had slow titration to reach a target dose of 10 mg/kg/day within at least 1 month and then gradually increased to a maximum dose of 20 mg/kg/day. We analyzed AEs and efficacy at M1 (month 1), M2, and M6, comparing two sets of subgroups: Dravet syndrome (DS) vs. Lennox-Gastaut (LGS) and patients with clobazam (CLB+) vs. patients without (CLB−). Results: One hundred and twenty-five patients were enrolled (62 LGS, 48 DS, 5 Tuberous sclerosis, and 10 other etiologies). Median concomitant antiepileptic drugs (AEDs) was three (25th percentile: 3, 75th percentile: 4). Patients received a dose of 10 (10–12), 14 (10–20), and 15.5 mg/kg/day (10–20) at M1, M2, and M6, respectively. Twenty-six patients discontinued CBD, 19 due to lack of efficacy, 2 due to AEs, 4 for both, and 1 had a sudden unexpected death in epilepsy. AEs were reported in 61 patients (48.8%), mainly somnolence ( n = 26), asthenia ( n = 20), and behavior disorders ( n = 16). Abnormal transaminases (≥3 times) were reported in 11 patients receiving both valproate and clobazam. AEs were significantly higher at M2 ( p = 0.03) and increased with the number of AEDs ( p = 0.03). At M6, total seizure frequency change from baseline was −41% ± 37.5% (mean ± standard deviation), and 28 patients (37.8%) had a reduction ≥50%. AE and efficacy did not differ between DS vs. LGS and CLB+ vs. CLB– patients. Significance: A slower titration of CBD dose delivered better tolerance with comparable efficacy to previous trials. Concomitant CLB did not increase efficacy rates but in a few cases increased AEs. This slow titration scheme should help guide clinicians prescribing CBD and allow patients to benefit from its potential efficacy.

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Once continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) is started in a child, and the child is discharged home, follow-up needs to be organized with regular visits in order to check the tolerance and efficacy of the treatment. But there is a lack of validated clinical guidelines, mainly because of the heterogeneity of the ventilator servicing, the costs and health care systems among countries. Therefore, visits timing and strategies to monitor CPAP/NIV are not clearly defined. Moreover, depending on various factors such as the underlying disorder, the medical stability, the age of the child, and socioeconomic factors, follow-up usually ranges between 1 month and 3-6 months, or even 1 year following treatment initiation, with an overnight hospital stay, an outpatient visit, a home visit, via telemonitoring or telemedicine, alone or in combination. Apart from clinical evaluation, nocturnal oximetry and capnography monitoring and/or poly(somno)graphy (P(S)G) are usually carried out during the follow-up visits to monitor the delivered pressure, leaks, residual respiratory events and synchrony between the patient and the ventilator. Built-in software data of CPAP/NIV devices can be used to assess the adherence of treatment, to monitor pressure efficiency, leaks, asynchronies, and to estimate the presence of residual respiratory events under CPAP/NIV if P(S)G is not available or in alternance with P(S)G. The possibility of CPAP/NIV weaning should be assessed on a regular basis, but no criteria for the timing and procedures have been validated. Weaning timing depends on the clinical condition that justified CPAP/NIV initiation, spontaneous improvement with growth, and the possibility and efficacy of various upper airway, maxillofacial and/or neurosurgical procedures. Weaning may be allowed in case of the disappearance of nocturnal and daytime symptoms of sleep-disordered breathing (SDB) after several nights without CPAP/NIV and the objective correction of SDB on a P(S)G. But no parameters are defined. In any case, a long term follow-up is necessary to ascertain the weaning success. Large prospective studies, together with international and national guidelines, are required in order to build evidence for standardizing practice for the follow-up and weaning of CPAP/NIV in children.

Mutations in SYNGAP1 are associated with developmental delay, epilepsy, and autism spectrum disorder (ASD). Epilepsy is often drug‐resistant in this syndrome with frequent drop attacks. In a prospective study of add‐on cannabidiol (CBD), we identified three patients with SYNGAP1 mutations: two boys and one girl. Seizure onset was at 3.5, 8, and 18 months (M), respectively, with numerous atypical absences per day associated with eyelid myoclonia (2/3 patients), upper limb myoclonic jerks (2/3 patients), and drop attacks (all patients). Seizures were resistant to at least 5 antiepileptic drugs (AEDs). After CBD introduction, two patients were responders since M2 and achieve a seizure reduction of 90% and 80%, respectively, at M9 with disappearance of drop attacks. EEGs showed an improvement regarding background activity and interictal anomalies. The last patient showed a late response at M7 of treatment with an 80% decrease in seizure frequency. Caregiver in all three evaluated as much improved the status of their children. Treatment was well‐tolerated in all, and no major adverse events (AEs) were reported. CBD showed efficacy in patients with drug‐resistant epilepsy due to SYNGAP1 mutations. Other patients with rare genetic developmental and epileptic encephalopathies with drug‐resistant epilepsies might benefit from CBD.