Related Experiment Video
Updated: Jul 14, 2025
Author Spotlight: Advancing Pediatric Epilepsy Surgery in Children Through Novel Biomarkers and Enhanced Localization
Published on: September 20, 2024
Cerebral and cerebellar pseudoatrophy associated with valproic acid. Report of three pediatric cases
M V Ordoño-Saiz1, R C Púa-Torrejón1, M Justel-Rodríguez1
1Hospital Infantil Universitario Niño Jesús, 28009 Madrid, España.
Insights
Valproic acid (VPA) can cause reversible brain pseudoatrophy in children, affecting cognitive and motor functions. This rare side effect resolves with VPA withdrawal, highlighting important diagnostic and therapeutic considerations.
Area of Science:
- Neurology
- Pediatrics
- Radiology
Background:
- Valproic acid (VPA) is a widely used antiepileptic drug.
- Cerebral and cerebellar pseudoatrophy is a rare, yet significant, adverse effect associated with VPA therapy.
Observation:
- Three pediatric cases (ages 5-9) with epilepsy on standard VPA doses presented with subacute neurological and imaging signs of cerebral/cerebellar atrophy.
- These children had normal baseline brain MRI scans prior to VPA treatment.
Findings:
- VPA-induced pseudoatrophy is distinct from other VPA-related encephalopathies (toxic, hyperammonaemic, or liver failure-related).
- Clinical manifestations in children include cognitive, motor, mood, and behavioral deterioration, potentially with worsening epilepsy.
- Radiological evidence of pseudoatrophy was observed, characterized by apparent shrinkage of brain structures.
Implications:
- Recognition of VPA-induced pseudoatrophy is crucial for accurate diagnosis and appropriate management in pediatric epilepsy.
- Complete clinical and radiological recovery is achievable through drug withdrawal, with dose reduction offering partial improvement.
- This condition underscores the importance of considering medication side effects in the differential diagnosis of neurological changes in children on VPA.
Introduction:
Cerebral and cerebellar pseudoatrophy is a rare adverse effect of valproic acid (VPA) that we need to be aware of, due to its diagnostic and therapeutic implications.
Case Report:
We report three cases of children between 5 and 9 years old, with epilepsy and previous normal brain magnetic resonance imaging, who were taking the drug at correct doses. Pseudoatrophy manifests subacutely with symptoms and images of cerebral and/or cerebellar atrophy, reversible after drug withdrawal.
Discussion And Conclusions:
This is a type of VPA-related encephalopathy, different from dose-dependent toxic encephalopathy, hyperammonaemic encephalopathy or encephalopathy related to liver failure. In children, it causes cognitive, motor, mood and behavioral deterioration, and may be accompanied by epileptic decompensation. Withdrawing the drug leads to complete clinical-radiological recovery, and reducing the dose leads to improvement.
Related Concept Videos
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
01:18Antiepileptic Drugs: GABAergic Pathway Potentiators
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for...
01:14Antiepileptic Drugs: Glutamate Antagonists
01:13Seizures: Classification
Seizures are typically classified into two main categories: focal and generalized seizures.
Focal Seizures
Focal seizures originate from specific regions of the brain. These seizures are further sub-classified into two types: