Neurology: Relationship between lysine dose reduction therapy and cognitive outcomes in patients with pyridoxine-dependent epilepsy

Pyridoxine-dependent epilepsy (PDE-ALdh7a1) is a developmental epileptic encephalopathy that improves possession seizures
with pyridoxine supplementation.
Lysine reduction adjuvant therapy reduces the accumulation of putative neurotoxic metabolites with the goal
of improving development outcomes.
A study published in Neurology explored the relationship between
lysine dose reduction therapy and cognitive outcomes.

Participants were recruited
from the International Registry of Patients with Pyridoxine-Dependent Epilepsy between August 2014 and March 2021.
The primary outcome was a standardized developmental test score
related to overall cognitive ability.
Using a mixed-effects model, the relationship between
test scores and treatment was analyzed using multivariate linear regression.
A priori hypothesis is that treatment with pyridoxine and lysine reduction therapy in early infancy leads to normal developmental outcomes
.
Sub-analyses were performed to assess associations
between cognitive outcomes and initiation of lysine-reduced treatment in the first six months of life.

There were a total of 112 test scores
from 60 participants.
On average, treatment with pyridoxine and lysine reduction therapy was associated
with a non-significant increase of 6.
9 points (95% CI -2.
7 to 16.
5) on developmental tests compared with pyridoxine alone.
For sub-analysis, a total of 14 developmental test scores are available from 8 participants
.
On average, treatment with pyridoxine and lysine reduction therapy in the first six months of life was associated
with a significant increase in developmental tests of 21.
9 points (95% CI 1.
7 to 42.
0).

Treatment with reduced pyridoxine and lysine at any age was associated with mild improvements in developmental tests, and treatment in early infancy was associated
with clinically significant increases in developmental test scores.
These results provide insight into the mechanisms of intellectual and developmental delay in PDE-ALdh7a1 and emphasize the importance of
treatment with pyridoxine and lysine dose reduction therapy in early infancy.

This study provides Category IV evidence that pyridoxine plus lysine reduction therapy was not significantly associated with an overall higher developmental test score compared with pyridoxine alone in PDE-ALDH7A1, but treatment in the first six months of life was associated
with significantly higher developmental test scores.

Source: Coughlin CR 2nd, Tseng LA, Bok LA, et al.
Association Between Lysine Reduction Therapies and Cognitive Outcomes in Patients With Pyridoxine-Dependent Epilepsy [published online ahead of].
print, 2022 Aug 25].
Neurology.
2022; 10.
1212/WNL.
0000000000201222.
doi:10.
1212/WNL.
0000000000201222