The spectrum of pyridoxine dependent epilepsy across the age span: A nationwide retrospective observational study

Jamali, Ahmed; Kristensen, Erle; Tangeraas, Trine; Arntsen, Vibeke; Sikiric, Alma; Kupliauskiene, Guste; Myren‐Svelstad, Sverre; Berland, Siren; Sejersted, Yngve; Gerstner, Thorsten; Hassel, Bjørnar; Bindoff, Laurence A.; Brodtkorb, Eylert

doi:10.1016/j.eplepsyres.2023.107099

Cited by 4 publications

(21 citation statements)

References 37 publications

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“…The evolution of clinical, neurodevelopmental, and epilepsy phenotypes in adulthood has hardly been investigated so far. In a recent Dutch study investigating a young adult cohort, including 10 patients with ALDH7A1 deficiency at the age of 18 to 30 years (7 of 10 carrying a homozygous c.1279 G>C variant), good seizure control was reported [ 106 ]. Seizure breakthroughs in adult life are relatively infrequent and usually correlate with sub-optimal adherence to pyridoxine supplementation [ 106 ].…”

Section: Discussionmentioning

confidence: 99%

“…In a recent Dutch study investigating a young adult cohort, including 10 patients with ALDH7A1 deficiency at the age of 18 to 30 years (7 of 10 carrying a homozygous c.1279 G>C variant), good seizure control was reported [ 106 ]. Seizure breakthroughs in adult life are relatively infrequent and usually correlate with sub-optimal adherence to pyridoxine supplementation [ 106 ]. In the abovementioned cohort, a significant variability of cognitive functions was observed, with one patient notably attending university [ 106 ].…”

Section: Discussionmentioning

confidence: 99%

“…Seizure breakthroughs in adult life are relatively infrequent and usually correlate with sub-optimal adherence to pyridoxine supplementation [ 106 ]. In the abovementioned cohort, a significant variability of cognitive functions was observed, with one patient notably attending university [ 106 ].…”

Section: Discussionmentioning

confidence: 99%

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Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review

et al. 2023

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Background: Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects). Patients and methods: We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines. Data on demographic features, seizure semiology, EEG patterns, neuroimaging, treatment, and developmental outcomes were collected. Results: 497 published patients fulfilled the inclusion criteria. Seizure onset manifested at 59.8 ± 291.6 days (67.8% of cases in the first month of life). Clonic, tonic-clonic, and myoclonic seizures accounted for two-thirds of the cases, while epileptic spasms were observed in 7.6%. Burst-suppression/suppression-burst represented the most frequently reported specific EEG pattern (14.4%), mainly in PLPB, ALDH7A1, and PNPO deficiency. Pyridoxine was administered to 312 patients (18.5% intravenously, 76.9% orally, 4.6% not specified), and 180 also received antiseizure medications. Pyridoxine dosage ranged between 1 and 55 mg/kg/die. Complete seizure freedom was achieved in 160 patients, while a significant seizure reduction occurred in 38. PLP, lysine-restricted diet, and arginine supplementation were used in a small proportion of patients with variable efficacy. Global developmental delay was established in 30.5% of a few patients in whom neurocognitive tests were performed. Conclusions: Despite the wide variability, the most frequent hallmarks of the epilepsy phenotype in patients with vitamin B6-dependent seizures include generalized or focal motor seizure semiology and a burst suppression/suppression burst pattern in EEG.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review

et al. 2023

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“…As reported in our previous study on PDE ( 18 ), patients were identified by contacting all Norwegian, neurological, pediatric and neurohabilitation departments as well as relevant professional societies. A total of 13 Norwegian patients with PDE-ALDH7A1 aged 2 months (mo) to 55 years (y) were included.…”

Section: Methodsmentioning

confidence: 99%

“…We have recently described the phenotypic variety and the clinical course of 13 Norwegian patients with neonatal-onset PDE-ALDH7A1 ( 18 ). The aim of the present study was to explore specifically the role of EEG in the diagnosis and management of patients within this nationwide cohort spanning the age spectrum from neonates to adults.…”

Section: Introductionmentioning

confidence: 99%

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

Arntsen,

Jamali,

Sikiric

et al. 2024

Front. Neurol.

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PurposePyridoxine-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.MethodsA 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.ResultsMedian 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.ConclusionA 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.

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Genotype and phenotype features and prognostic factors of neonatal-onset pyridoxine-dependent epilepsy: A systematic review

Fang,

Yang,

Xiao

et al. 2024

Epilepsy Research

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The spectrum of pyridoxine dependent epilepsy across the age span: A nationwide retrospective observational study

Cited by 4 publications

References 37 publications

Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review

Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review

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

Genotype and phenotype features and prognostic factors of neonatal-onset pyridoxine-dependent epilepsy: A systematic review

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