Utility and limitations of EEG in the diagnosis and management of ALDH7A1-related pyridoxine-dependent epilepsy. A retrospective observational study

Vibeke Arntsen; Ahmed Jamali; Alma Sikiric; Erle Kristensen; Trine Tangeraas; Guste Kupliauskiene; Sigurbjörg Stefansdottir; Laurence A Bindoff; Trond Sand; Eylert Brodtkorb

doi:10.3389/fneur.2024.1355861

Utility and limitations of EEG in the diagnosis and management of ALDH7A1-related pyridoxine-dependent epilepsy. A retrospective observational study

Front Neurol. 2024 Feb 14:15:1355861. doi: 10.3389/fneur.2024.1355861. eCollection 2024.

Authors

Vibeke Arntsen^{1

2}, Ahmed Jamali³, Alma Sikiric⁴, Erle Kristensen^{5

6}, Trine Tangeraas⁷, Guste Kupliauskiene⁸, Sigurbjörg Stefansdottir⁹, Laurence A Bindoff^{6

10}, Trond Sand^{1

2}, Eylert Brodtkorb^{1

2}

Affiliations

¹ Department of Neurology and Clinical Neurophysiology, St. Olav University Hospital, Trondheim, Norway.
² Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
³ Kavli Institute for Systems Neuroscience, Center for Computational Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ Department of Neurohabilitation, Oslo University Hospital, Oslo, Norway.
⁵ Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
⁶ Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway.
⁷ Norwegian National Unit for Newborn Screening, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
⁸ Department of Paediatric and Adolescent Medicine, Stavanger University Hospital, Stavanger, Norway.
⁹ Department of Neurology and Clinical Neurophysiology, Stavanger University Hospital, Stavanger, Norway.
¹⁰ Department of Neurology, Haukeland University Hospital, Bergen, Norway.

Abstract

Purpose: Pyridoxine-dependent epilepsy due to ALDH7A1 variants (PDE-ALDH7A1) is a rare disorder, presenting typically with severe neonatal, epileptic encephalopathy. Early diagnosis is imperative to prevent uncontrolled seizures. We have explored the role of EEG in the diagnosis and management of PDE.

Methods: A total of 13 Norwegian patients with PDE-ALDH7A1 were identified, of whom five had reached adult age. Altogether 163 EEG recordings were assessed, 101 from the 1st year of life.

Results: Median age at seizure onset was 9 h (IQR 41), range 1 h-6 days. Median delay from first seizure to first pyridoxine injection was 2 days (IQR 5.5). An EEG burst suppression pattern was seen in eight patients (62%) during the first 5 days of life. Eleven patients had recordings during pyridoxine injections: in three, immediate EEG improvement correlated with seizure control, whereas in six, no change of epileptiform activity occurred. Of these six, one had prompt clinical effect, one had delayed effect (< 1 day), one had no effect, one had uncertain effect, and another had more seizures. A patient without seizures at time of pyridoxine trial remained seizure free for 6 days. Two patients with prompt clinical effect had increased paroxysmal activity, one as a conversion to burst suppression. Autonomic seizures in the form of apnoea appeared to promote respiratory distress and were documented by EEG in one patient. EEG follow-up in adult age did not show signs of progressing encephalopathy.

Conclusion: A neonatal burst suppression EEG pattern should raise the suspicion of PDE-ALDH7A1. Respiratory distress is common; isolated apnoeic seizures may contribute. EEG responses during pyridoxine trials are diverse, often with poor correlation to immediate clinical effect. Reliance on single trials may lead to under-recognition of this treatable condition. Pyridoxine should be continued until results from biomarkers and genetic testing are available.

Keywords: ALDH7A1; EEG; burst suppression; epilepsy; pyridoxine.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by a grant from the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (FFU) and the Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology.