By: Catherine Joachin
What are infantile epilepsy syndromes?
Infantile-onset epilepsy syndromes refer to seizure disorders with symptoms appearing from birth to within 1 year of life. These conditions are identified by similarities in seizure types, electroencephalographic results and developmental history (NYU Langone Health, 2024). They include infantile spasms, Dravet syndrome, Ohtahara syndrome, myoclonic epilepsies of infancy and benign familial/non-familial infantile epilepsy.
Infantile spasms
Infantile spasms, also called West syndrome, are a rare type of seizure that develops in infants aged 3 to 12 months old (Johns Hopkins Medicine, 2021). Approximately 1 in 2,000 to 4,000 infants are affected by this condition (Cleveland Clinic, 2022).
Infantile spasms are characterized by a sudden jerking movement followed by stiffening. Infants who experience these spasms may sling their arms out and bend their bodies forward (Johns Hopkins Medicine, 2021). These seizures only last a few seconds and can be difficult to notice. As a result, they can be mistaken for colic or normal startle reflex (Moro reflex), where babies reflexively move their heads toward the origin of a loud sound or sudden movement (Cleveland Clinic, 2022; Johns Hopkins Medicine; 2021). Identifying subtle signs such as eyes rolling up, chin movements, grimacing, head nodding, and belly tensioning up may help prevent misdiagnosis (Cleveland Clinic, 2022). Infantile spasms typically resolve by age 4 or 5; however, children may later develop other types of seizures or epileptic disorders (Cleveland Clinic, 2022).
Infantile spasms are associated with developmental regression, irregular brain electrical activity (hypsarrhythmia), and cognitive impairments (Children’s Hospital of Philadelphia, n.d.). Babies with this condition are also at risk of developing intractable epilepsy, intellectual disability, and autism (Boston Children’s Hospital, n.d.).
Dravet syndrome
Previously known as severe myoclonic epilepsy of infancy (SMEI), Dravet syndrome is a genetic disorder that affects 1 in 15,700 to 40,000 babies in the U.S. (Cleveland Clinic, 2022). It is marked by prolonged, treatment-resistant seizures and enduring cognitive developmental issues (UCSF Benioff Children’s Hospital, n.d.).
Dravet syndrome seizures typically begin within the first year of life and involve sudden muscle jerking (myoclonus) (Cleveland Clinic, 2022). People with this condition may experience other types of seizures, including atypical absence seizures, atonic seizures, focal seizures, non-convulsive status epilepticus, and tonic-clonic seizures (Cincinnati Children’s Hospital, n.d.). Seizures usually occur in clusters and can be triggered by infections, illness, changes in body temperature, photosensitivity, stress, excitement, and certain medications (Cincinnati Children’s Hospital, n.d.).
Other symptoms associated with this condition include:
- Speech and language impairments
- Poor coordination (abnormal ungait, crouched posture)
- Dysautonomia
- Behavioral and emotional issues
- Growth and nutrition problems
- Difficulty sleeping
- Features of autism spectrum disorder
(Cleveland Clinic, 2022)
Ohtahara syndrome
Ohtahara syndrome, also known as early infantile epileptic encephalopathy (EIEE), is a rare neurological condition in which seizures and signs of developmental regression appear within the first three months of life (National Institute of Neurological Disorders and Stroke, 2023). These seizures are mainly tonic; however, infants may experience partial and myoclonic seizures as well (NINDS, 2023.). Some children with Ohtahara syndrome die in infancy, while others go on to develop neurological problems and other forms of epilepsy (NYU Langone Health, 2024). Symptoms to look out for include upward eye gaze, dilated pupils, and altered breathing (NINDS, 2023).
Myoclonic epilepsy of infancy
This condition is characterized by rapid myoclonic seizures featuring head nodding, blinking, upward eye rolling, and spontaneous muscle jerks (Balasundaram & Anilkumar, 2023). It is an early, self-limiting form of possibly genetic idiopathic generalized epilepsy, from which variants such as photosensitive myoclonic epilepsy in infancy and familial infantile mycologic epilepsy are derived (Balasundaram & Anilkumar, 2023).
Benign familial neonatal seizures
These seizures can appear in infants as young as 3 days old (NYU Langone Health, 2024). They are brief (1 to 2 minutes long), recurrent, and tend to resolve without treatment by 4 months of age (NYU Langone Health, 2024). Benign familial neonatal seizures involve generalized tonic-clonic seizures, which cause convulsions, muscle rigidity, and loss of consciousness (NYU Langone Health, 2024). Benign non-familial infantile seizures share the same features and EEG electrical patterns as their familial counterparts but are not associated with a family history of epilepsy (Gaily et al., 2016).
Causes
Several conditions can lead to the development of infantile epileptic syndromes, including severe brain damage, genetic mutations (such as the SCN1A mutation associated with Dravet syndrome), metabolic disorders, and congenital brain structure defects (Children’s Hospital of Philadelphia, n.d.). In some cases, the cause remains unclear.
Diagnosis and Treatment
Infantile epilepsies can be diagnosed with the help of electroencephalogram (EEG) and magnetic resonance imaging (MRI) screenings; however, diagnosis may be delayed as test results may not detect abnormal brain activity when seizures first appear, as is the case in Dravet syndrome (Cleveland Clinic, 2022). Furthermore, the underlying cause behind these seizures can be investigated with the help of neuroimaging technology, blood tests, and genetic testing (Children’s Hospital of Philadelphia, n.d.).
Treatment for these syndromes typically includes a combination of therapy, anticonvulsant medication, or dietary changes (ketogenic diet). Some forms of infantile seizures go away with time, whereas others require lifelong treatment and management.
In terms of medication, adrenocorticotropic hormone (ACTH) therapy is the first-line treatment for West syndrome (Cleveland Clinic, 2022). Certain drugs (e.g., Stiripentol, Cannabidiol, and Fenfluramine HCI) can help manage Dravet syndrome seizure activity, while others (e.g., phenytoin, carbamazepine and fosphenytoin) may worsen it (Cleveland Clinic, 2022). Finally, corticosteroids, occupational therapy, vagus nerve stimulation, and, in cases involving focal brain lesions, epileptic surgery may be envisioned as treatment routes (Cleveland Clinic, 2022; NINDS, 2023).
Research
Population-based information is scarce on the incidence and prognosis of infantile epilepsy syndromes, which explains the disparity in information between the aforementioned conditions (Gaily et al., 2016). Furthermore, while research into infantile epileptic syndromes mentions epilepsy of infancy with migrating focal seizures (EIMFS), generalized epilepsy with febrile seizures plus (GEFS+) and hemiconvulsion-hemiplegia epilepsy (HHE), all three of which are uncommon, early-onset seizure disorders associated with developmental delays and epileptiform EEG findings, few recent articles provide detailed descriptions of these conditions (Korff & Nordli, 2006).
Conclusion
Infancy epilepsy syndromes are a constellation of seizure disorders defined by their age of onset, seizure type(s), distinct brain wave patterns, and history of developmental regression (NYU Langone Health, 2024).
References:
Balasundaram, P., & Anilkumar, A. C. (2023) Myoclonic Epilepsy of Infancy. National Library of Medicine. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK570566/
Boston Children’s Hospital (n.d.). Infantile Spasms. Boston Children’s Hospital. Retrieved from: https://www.childrenshospital.org/conditions/infantile-spasms
Children’s Hospital of Philadelphia (n.d.). Dravet Syndrome. Children’s Hospital of Philadelphia. Retrieved from: https://www.chop.edu/conditions-diseases/dravet-syndrome
Children’s Hospital of Pittsburgh (n.d.). Types of Epilepsy Syndromes. UPMC Children’s Hospital of Pittsburgh. Retrieved from: https://www.chp.edu/our-services/brain/neurology/epilepsy/types/syndromes
Cleveland Clinic (2022). Dravet Syndrome. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/diseases/22517-dravet-syndrome
Cleveland Clinic (2022). Infantile Spasms. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/diseases/22494-infantile-spasms
Gaily, E., Lommi, M., Lapatto, R., & Lehesjoki, A. (2016). Incidence and outcome of epilepsy syndromes with onset in the first year of life: A retrospective population‐based study. Epilepsia (Copenhagen), 57(10), 1594–1601. https://doi.org/10.1111/epi.13514
Johns Hopkins Medicine. (2021). Epilepsy Syndromes in Children. Johns Hopkins Medicine. Retrieved: https://www.hopkinsmedicine.org/health/conditions-and-diseases/epilepsy/epilepsy-syndromes-in-children.
Korff, C. M., & Nordli, D. R. (2006). Epilepsy Syndromes in Infancy. Pediatric Neurology, 34(4), 253–263. https://doi.org/10.1016/j.pediatrneurol.2005.08.005
National Institute of Neurological Disorders and Stroke (2023). Ohtahara Syndrome. National Institute of Health. Retrieved from: https://www.ninds.nih.gov/health-information/disorders/ohtahara-syndrome
NYU Langone Health (2024). Types of Epilepsy & Seizure Disorders in Children. NYU Langone Health. Retrieved from: https://nyulangone.org/conditions/epilepsy-seizure-disorders-in-children/types
UCSF Benioff Children’s Hospital. Dravet Syndrome. (n.d.). ucsfbenioffchildrens.org. Retrieved from: https://www.ucsfbenioffchildrens.org/conditions/dravet-syndrome
