Pyridoxine or pyridoxal-5-phosphate treatment for seizures in glycosylphosphatidylinositol deficiency: A cohort study

Allan Bayat*, Angel Aledo-Serrano, Antonio Gil-Nagel, Christian M. Korff, Ashley Thomas, Christian Boßelmann, Yvonne Weber, Elena Gardella, Allan M Lund, Monique G.M. de Sain-van der Velden, Rikke S. Møller

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

Aim: To investigate the short-term efficacy and safety of high-dose pyridoxine and pyridoxal 5-phosphate (P5P) in the treatment of inherited glycosylphosphatidylinositol (GPI) deficiency-associated epilepsy. Method: Participants with genetically confirmed GPI deficiency were treated with oral pyridoxine or P5P as compassionate use in an agreed-upon clinical regimen. Pyridoxine (20–30 mg/kg/day) was used for 3 months. Baseline evaluation included 4 weeks of prospective seizure data and one video electroencephalogram (EEG). Seizure frequency was captured daily. The EEG was repeated after reaching maximum dosage of pyridoxine. Pyridoxine was switched to P5P (20–30 mg/kg/day) if seizure burden was unchanged after 3 months' treatment. Another EEG was done after 3 months of P5P treatment. Primary outcome measures were reduction of seizure frequency and EEG improvements. Results: Seven participants (one female, six males; age range 5–23 year; mean age 11 years 10 months, SD 5 year 2 months) were included. The genetic causes of inherited GPI deficiency were phosphatidylinositol N-acetylglucosaminyltransferase subunit A/T/V deficiency. All had drug-resistant epilepsy and neurodevelopmental impairment. We observed more than 50% seizure frequency reduction in 2 out of 7 and less than 50% reduction in another 3 out of 7 participants. No participants reached seizure freedom. No remarkable changes in electrophysiological findings were observed in 6 out of 7 participants treated with pyridoxine or P5P when comparing the baseline and follow-up EEGs. Interpretation: We observed no long-lasting electrophysiological improvements during treatment but pyridoxine may reduce seizure frequency or burden in inherited GPI deficiency. What this paper adds: Inherited glycosylphosphatidylinositol (GPI) deficiency often causes early-onset and drug-resistant epilepsy. Vitamin B 6 is a potential disease-specific treatment; however, efficacy and safety are ill-defined. Pyridoxine may reduce seizure frequency or burden in inherited GPI deficiency. Pyridoxine and P5P could prove to be a useful treatment in some individuals with inherited GPI deficiency and epilepsy.

OriginalsprogEngelsk
TidsskriftDevelopmental Medicine and Child Neurology
Vol/bind64
Udgave nummer6
Sider (fra-til)789-798
ISSN0012-1622
DOI
StatusUdgivet - jun. 2022

Bibliografisk note

Funding Information:
The authors thank the participants and their families for their participation in this research.YW received support through the German Research Foundation (Research Unit FOR2715: We4896/4‐1) and a BMBF Treat‐ION grant (no. 01GM1907).

Publisher Copyright:
© 2022 Mac Keith Press.

Fingeraftryk

Dyk ned i forskningsemnerne om 'Pyridoxine or pyridoxal-5-phosphate treatment for seizures in glycosylphosphatidylinositol deficiency: A cohort study'. Sammen danner de et unikt fingeraftryk.

Citationsformater