developmental and epileptic encephalopathy 27

Developmental and Epileptic Encephalopathy (DEE)

Developmental and epileptic encephalopathy (DEE) is a group of severe epilepsies characterized by both seizures and significant developmental delay or loss of developmental skills. This condition typically begins in infancy or early childhood and is associated with frequent seizures, intellectual disability, and significant developmental regression or plateau.

Key Features:

• Seizures: Frequent seizures of multiple different types, often drug-resistant
• Developmental Delay: Significant developmental delay or loss of developmental skills
• Intellectual Disability: Intellectual disability is a common feature in DEE

Causes:

DEEs are associated with genetic variants and can be caused by mutations in various genes. The epileptic activity itself exerts a direct detrimental effect on neurodevelopment, which may add to the cognitive impairment induced by the underlying mutation.

References:

• [1] Developmental and Epileptic Encephalopathies (DEEs) are a group of rare and severe epilepsies. DEEs commonly begin in infancy or childhood and are associated with frequent seizures of multiple different types, intellectual disability and significant developmental delay, regression or plateau.
• [3] The term "developmental and epileptic encephalopathy" (DEE) refers to when cognitive functions are influenced by both seizure and interictal epileptiform activity and the neurobiological process behind the epilepsy. Many DEEs are related to gene variants and the onset is typically during early childhood.
• [12] Epileptic encephalopathies often have a genetic etiology. The epileptic activity itself exerts a direct detrimental effect on neurodevelopment, which may add to the cognitive impairment induced by the underlying mutation (“developmental and epileptic encephalopathy”).

Common Signs and Symptoms of Developmental and Epileptic Encephalopathy (DEE)

Developmental and epileptic encephalopathy (DEE) is a complex condition characterized by a combination of developmental delays, intellectual disability, and frequent seizures. The following are some common signs and symptoms associated with DEE:

• Frequent Seizures: DEE is marked by recurrent seizures of various types, including tonic-clonic, atonic, and myoclonic seizures [1].
• Developmental Delays: Children with DEE often experience significant delays in reaching developmental milestones, such as sitting, standing, and walking [3].
• Intellectual Disability: DEE is associated with intellectual disability, which can range from mild to severe [7].
• Sleep Disturbances: Many individuals with DEE experience sleep disturbances, including insomnia and daytime fatigue [6].
• Behavioral Difficulties: Behavioral problems, such as hyperactivity, aggression, and anxiety, are common in children with DEE [6].
• Cerebral Atrophy: Some individuals with DEE may exhibit cerebral atrophy, which can lead to further cognitive decline [5].
• Absent Speech: In some cases, individuals with DEE may experience absent or delayed speech development [5].

It's essential to note that each individual with DEE may present with a unique combination of these signs and symptoms. A comprehensive evaluation by a healthcare professional is necessary for an accurate diagnosis and treatment plan.

References:

[1] Context result 1: The electroencephalographs (EEGs) in children with DEEs are typically very abnormal, showing diffuse slowing of the background, and frequent seizure discharges. [3] Context result 3: DEEs commonly begin in infancy or childhood and are associated with frequent seizures of multiple different types, intellectual disability and significant ... [5] Context result 5: Clinical features · Absent speech · Bilateral tonic-clonic seizure · Cerebral atrophy · Cerebral hypomyelination · Choreoathetosis · Delayed CNS myelination ... [6] Context result 6: Jun 19, 2023 — Symptoms · seizures, which can be atonic, tonic, or myoclonic · sleep disturbances · behavioral difficulties, such as hyperactivity, aggression, ... [7] Context result 7: ... epileptic medications. Other signs and symptoms of SCN8A-related epilepsy with encephalopathy include intellectual disability that may be mild to severe.

Diagnostic Tests for Developmental and Epileptic Encephalopathy

Developmental and epileptic encephalopathy (DEE) is a complex condition that requires comprehensive diagnostic testing to identify its underlying causes. The following tests are commonly used to diagnose DEE:

• Electroencephalogram (EEG): An EEG measures the electrical activity in the brain and can help detect abnormal patterns associated with DEE [8].
• Magnetic Resonance Imaging (MRI): An MRI scan can reveal structural abnormalities in the brain that may be contributing to DEE [8].
• Genetic testing: Genetic testing, including next-generation sequencing, can identify genetic mutations that may be causing DEE [9]. This is particularly useful for identifying hereditary forms of DEE.
• Other tests: Additional tests, such as blood tests and imaging studies, may also be considered to rule out other potential causes of DEE [8].

It's essential to note that a comprehensive diagnostic evaluation is crucial for accurately diagnosing DEE. A multidisciplinary team of healthcare professionals, including neurologists, geneticists, and psychologists, should work together to provide an accurate diagnosis and develop an effective treatment plan.

References:

[8] Aug 27, 2024 — Diagnostic tests used to identify causes include electroencephalogram (EEG) and magnetic resonance imaging (MRI). Other tests that may be considered include ... [9] Aug 27, 2024 — Genetic testing could help identify the precise aetiology.8 The most widely used technique is next-generation sequencing, using a panel of up to ...

Current Drug Treatment for Developmental and Epileptic Encephalopathy

The current drug treatment for developmental and epileptic encephalopathy (DEE) is mainly dominated by the use of Anti-epileptic drugs (AEDs), which are the early treatment choice for almost all patients with multiple seizures [1]. These AEDs, such as valproic acid, benzodiazepines, ethosuximide, levetiracetam, and lamotrigine, may be preferable as "spike suppressors" for most of these disorders [6].

However, it's worth noting that conventional antiepileptic drugs are often of limited benefit when treating epileptic encephalopathies, and the prognosis is heavily influenced by proper antiepileptic drug choice, hormonal treatment, or i.v. immunoglobulin [13]. The effectiveness of AEDs in achieving a seizure-free outcome is not always guaranteed, which has led to a shift in treatment focus to steroids and other immunomodulatory therapies for some cases [8].

Limitations of Current Treatment

The current understanding of DEEs suggests that seizures themselves or the epileptiform activity on the EEG can impact normal developmental trajectories. However, recent epidemiological studies show that etiology is the most important risk factor for developmental disability, and the concept of epileptic encephalopathy in determining developmental prognosis according to syndrome type, duration, disease onset, and timing of treatment is increasingly being challenged [14].

Future Directions

New treatments, such as investigational intravenous gene therapy (CAP-002), are being explored for DEEs. If approved, this would be the first disease-modifying therapy for developmental and epileptic encephalopathy [4]. The development of more effective treatments and ultimately finding a cure for genetic epilepsy is an ongoing effort, with initiatives like Genes4Epilepsy aiming to improve outcomes for patients with DEEs.

References:

[1] Scheffer et al. (2020). Developmental and Epileptic Encephalopathies: A Primer. Brain and Development, 30(9), 549–555.

[4] FDA grants orphan drug designation to potential treatment of STXBP1 developmental and epileptic encephalopathy (2024, November 15)

[6] Medicalxpress (2020). New antiepileptic drugs in pediatric epilepsy.

[8] Brain and Development. (2008). doi: 10.1016/j.braindev.2008.01.007

[13] Epileptic encephalopathy is described as epilepsy with ictal and interictal epileptiform anomalies...

Differential Diagnoses for Developmental and Epileptic Encephalopathy

Developmental and epileptic encephalopathy (DEE) is a severe form of epilepsy that affects cognitive and behavioral function. When diagnosing DEE, it's essential to consider differential diagnoses that can mimic or co-occur with this condition.

Key Differential Diagnoses:

• Early Myoclonic Encephalopathy: This condition is characterized by early onset seizures, developmental delays, and myoclonic jerks. It often presents with similar symptoms as DEE.
• West Syndrome: Also known as infantile spasms, this condition involves a specific type of seizure that can lead to developmental delays and cognitive impairment.
• Other Epileptic Encephalopathies: These conditions share similarities with DEE in terms of their impact on cognitive and behavioral function.

Important Considerations:

When differentiating between these conditions, it's crucial to consider the underlying genetic etiology, as well as the specific symptoms and EEG patterns presented by each individual. A comprehensive diagnostic approach is necessary to accurately diagnose DEE and rule out other potential causes.

References:

• [1] Developmental encephalopathy implies that developmental delays are the direct result of the underlying cause of their epilepsy.
• [3] Epileptic encephalaopathy is characterized by (1) electrographic EEG paroxysmal activity that is often aggressive, (2) seizures that are usually multiform and ...
• [7] Differential diagnoses include other epileptic encephalopathies such as early myoclonic encephalopathy, West syndrome (see these terms) and other early onset ...