The Link Between Global Developmental Delay and Seizures
There is a significant bidirectional relationship between global developmental delay (GDD) and seizures, with seizures being both a potential cause and consequence of developmental delays in children. 1, 2, 3
Epidemiological Association
- Children with neurodevelopmental disorders (NDDs) exhibit a high prevalence of seizures 3
- Epilepsy occurs in 5-46% of children with autism spectrum disorders, with epileptiform abnormalities found in up to 60% 1
- In a recent study, 30.5% of children with seizures had global developmental delay 3
- Seizures in the neonatal period are associated with subsequent developmental delay and cerebral palsy 4
Underlying Mechanisms
Shared Genetic Factors
- Several genetic syndromes and mutations are associated with both seizures and developmental delays:
Neurobiological Mechanisms
- Both seizures and developmental delays may represent disorders of synaptic plasticity with imbalances in excitation and inhibition 1
- Seizures in childhood can alter brain development at the cellular and molecular level through:
- Disruption of excitatory and inhibitory neurotransmitter systems (GABA and glutamate)
- Impaired neuronal membrane integrity
- Altered neuromodulatory pathways affecting synaptic plasticity and memory formation 1
Bidirectional Relationship
Seizures Contributing to Developmental Delay
- Perioperative seizures in children with congenital heart disease are linked to worse neurodevelopmental outcomes and neurological abnormalities 1
- Seizures can further injure a vulnerable neural system, facilitating aberrant cognitive and social development 1
- Nonconvulsive status epilepticus can present primarily as global developmental delay, with resolution of delays after appropriate seizure treatment 2
Developmental Delay as Risk Factor for Seizures
- Children with global developmental delay are at higher risk for developing seizures 3
- In self-limited familial epilepsy, global developmental delay was associated with:
- Older age at last seizure
- Longer epilepsy duration
- Higher number of anti-seizure medications 6
Clinical Implications
Screening and Evaluation
- EEG should be recommended in any infant who manifests neurodevelopmental delay to rule out nonconvulsive status epilepticus 2
- Children with seizures should undergo developmental screening using standardized tools like Parents' Evaluation of Developmental Status (PEDS) or Ages and Stages Questionnaire (ASQ) 7
- Brain MRI with appropriate sequences is the preferred neuroimaging modality for evaluating children with both microcephaly and global developmental delay 7
Management Considerations
- Early identification and treatment of seizures may improve developmental outcomes 1, 2
- Scheduled reassessments should be performed at regular intervals (12-24 months after initial evaluation, 3-5 years of age, and 11-12 years of age) to monitor developmental progress 7
- A multidisciplinary approach involving pediatric neurology, developmental pediatrics, medical genetics, and various therapies is essential for children with both conditions 7
Prognostic Factors
- Predictors of poor neurodevelopmental outcomes after neonatal seizures include:
- Seizure type
- Early seizure onset
- Abnormal EEG background findings
- Low 5-minute Apgar scores 4
- In children with epilepsy, higher seizure frequency and longer epilepsy duration are associated with greater risk of developmental delay 6
Important Caveats
- Not all children with seizures develop developmental delays, and not all children with developmental delays have seizures
- The relationship varies based on seizure type, frequency, duration, and underlying etiology
- Early intervention for either condition may positively impact outcomes for the other
- Genetic testing should be considered in children presenting with both conditions, as identifying specific mutations may guide treatment and prognosis 7, 5