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Epilepsy with myoclonic-atonic seizures – Treatment

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Epilepsy with myoclonic-atonic seizures, also known as Doose syndrome, is a rare childhood epilepsy that requires specialized treatment approaches to control frequent seizures and support a child’s development through challenging phases of the condition.

Understanding Treatment Goals in Childhood Myoclonic-Atonic Epilepsy

When a child is diagnosed with epilepsy with myoclonic-atonic seizures, the main goals of treatment focus on controlling the different types of seizures they experience, preventing falls and injuries, and supporting their development during what doctors call the “stormy phase” of active seizures. This rare form of childhood epilepsy, which affects only 1% to 2% of all children with epilepsy, typically begins between ages 2 and 6 years and can involve multiple seizure types occurring throughout the day.[1]

Treatment choices depend heavily on the specific seizure types a child is having, how frequently seizures occur, and how the condition is affecting their development and daily life. Most children experience periods when seizures become very frequent and multiple seizure types appear, making treatment particularly important during these intense phases. The medical approach needs to be tailored to each child because the condition can vary significantly from one patient to another, with some children responding well to certain medications while others may need different treatment strategies.[3]

Healthcare teams aim not only to reduce seizures but also to minimize developmental setbacks that often accompany active seizure periods. Many children experience regression in skills or fail to gain new abilities when seizures are frequent. Medical guidelines approved by neurological societies provide recommendations for treatment, though ongoing research continues to explore new therapeutic options that might work better for children who don’t respond to currently available medications.[1]

Standard Treatment Approaches

The foundation of treatment for epilepsy with myoclonic-atonic seizures relies on antiseizure medications, which are drugs designed to reduce abnormal electrical activity in the brain. These medications work by various mechanisms to prevent or reduce the frequency and severity of seizures. However, it’s important to understand that finding the right medication or combination of medications can take time, as seizures in this condition are often initially resistant to treatment.[4]

Several specific antiseizure medications have been used in children with this condition, though no large systematic studies have been completed that definitively show which medications work best. A systematic review conducted for medical guidelines found no studies that met criteria for determining the most effective antiseizure therapies specifically for epilepsy with myoclonic-atonic seizures, highlighting the need for more research in this area.[6]

⚠️ Important
Despite the lack of large controlled studies, doctors use clinical experience and smaller studies to guide treatment decisions. Approximately two-thirds of children with this condition eventually achieve seizure freedom, typically within three years of seizure onset, though the journey to finding effective treatment can be challenging during the initial phases.

Treatment duration varies considerably depending on how each child responds. Some children may need medications for several years, while others might continue treatment into adolescence or beyond if seizures persist. Doctors typically start with one medication and may adjust the dose or add additional medications if seizures continue. The goal is to use the lowest effective dose that controls seizures while minimizing unwanted effects.[4]

Side effects from antiseizure medications can vary depending on which medication is used. Common side effects may include drowsiness, changes in behavior or mood, difficulty with coordination, or problems with attention and learning. These effects need to be carefully balanced against the benefits of seizure control, as uncontrolled seizures themselves can significantly impact a child’s development and safety. Regular monitoring by the medical team helps ensure that any concerning side effects are identified and addressed promptly.

In addition to medications, treatment includes practical safety measures to prevent injuries from falls during seizures. Since myoclonic-atonic seizures cause sudden drops or head movements, protective measures such as helmets may be recommended during periods of frequent seizures. Families also receive education about recognizing different seizure types and knowing when to seek emergency medical care, such as when a seizure lasts longer than usual or when multiple seizures occur close together without recovery in between.[1]

Emerging Treatments Being Studied in Clinical Trials

While standard antiseizure medications form the backbone of treatment, researchers continue to investigate new therapeutic approaches for epilepsy with myoclonic-atonic seizures. The fact that seizures in this condition can be difficult to control with existing medications drives the search for more effective treatments. Clinical trials represent an important avenue for developing and testing new therapies that might work better for children who don’t respond adequately to current options.

Understanding the genetic basis of the condition has opened new research directions. Scientists have identified several genes that can cause epilepsy with myoclonic-atonic seizures, including SLC6A1, CHD2, and AP2M1 as the most common genetic causes, along with other genes such as SLC2A1, SCN1A, SYNGAP1, KCNA2, and NEXMIF. This genetic knowledge helps researchers develop treatments that target the specific molecular pathways affected by these genetic changes, though most cases still don’t have an identified genetic cause and are thought to involve multiple genes working together.[3]

Research into epilepsy with myoclonic-atonic seizures faces particular challenges because the condition is rare, making it difficult to recruit large numbers of patients for clinical trials. Additionally, because the condition primarily affects young children and has a variable course, with many children eventually achieving seizure freedom, designing studies that can clearly show whether a treatment is effective requires careful planning. Researchers must consider factors such as the natural tendency for the condition to improve over time and the multiple seizure types that need to be assessed.

Clinical trials for childhood epilepsy conditions like this typically progress through different phases. Phase I trials focus primarily on safety, testing new treatments in small groups to understand how the body processes the drug and what side effects might occur. Phase II trials expand to larger groups and begin assessing whether the treatment appears to reduce seizures effectively, while Phase III trials compare the new treatment against standard approaches or placebo to definitively determine effectiveness. Because this condition is rare, many studies occur at specialized epilepsy centers that have experience treating children with difficult-to-control seizures.

The location of clinical trials can vary, with research centers in the United States, Europe, and other regions conducting studies on childhood epilepsy conditions. Eligibility for clinical trials typically depends on factors such as the child’s age, specific seizure types, previous medications tried, and overall health status. Families interested in clinical trials often work with their child’s neurologist to determine if any appropriate studies are available and whether their child might be eligible to participate.

⚠️ Important
Participation in clinical trials is entirely voluntary and involves careful consideration of potential benefits and risks. Families receive detailed information about what the trial involves, and they can withdraw at any time. Clinical trials are carefully monitored to protect participants’ safety while advancing medical knowledge about this rare condition.

Monitoring and Diagnostic Approaches

Accurate diagnosis forms the foundation for appropriate treatment. Doctors rely heavily on electroencephalogram or EEG testing, which measures electrical activity in the brain. This test helps identify the abnormal brain wave patterns characteristic of epilepsy with myoclonic-atonic seizures. At the beginning of the condition, the EEG might appear normal, but as the condition develops, it typically shows slowing of background brain activity and generalized spike-wave discharges occurring at a frequency of 2 to 3 cycles per second.[3]

Because different seizure types in this condition can look similar on the outside, specialized EEG testing called video-EEG monitoring proves particularly valuable. This combines video recording with EEG monitoring and electromyogram or EMG recording from muscles, allowing doctors to see exactly what happens during a seizure while simultaneously recording brain and muscle electrical activity. This helps distinguish myoclonic-atonic seizures from other seizure types such as tonic seizures or epileptic spasms, which might need different treatment approaches.[3]

Brain imaging such as magnetic resonance imaging or MRI is typically performed to ensure there are no structural brain abnormalities causing the seizures. In epilepsy with myoclonic-atonic seizures, neuroimaging typically appears normal, which is one feature that helps distinguish this condition from other forms of childhood epilepsy that might have visible brain changes.[3]

Genetic and metabolic testing plays an increasingly important role, particularly when doctors want to rule out other conditions that might look similar or when clinical features suggest a specific genetic cause. Special EEG testing using intermittent photic stimulation at low frequencies should be systematically performed to exclude a condition called neuronal ceroid lipofuscinosis type 2, also known as CLN2 disease, which can present with similar features but has different treatment implications and prognosis.[3]

Most Common Treatment Methods

  • Antiseizure Medications
    • Primary treatment approach using drugs that reduce abnormal brain electrical activity
    • May involve single medications or combinations depending on seizure control
    • Dosing adjusted based on response and side effects
    • Treatment typically continued for extended periods, often years
  • EEG Monitoring
    • Standard EEG to identify abnormal brain wave patterns characteristic of the condition
    • Video-EEG with EMG to distinguish different seizure types
    • Helps guide treatment decisions and monitor response to therapy
    • Special EEG protocols to rule out similar-appearing conditions
  • Genetic Testing
    • Testing for known genes associated with the condition including SLC6A1, CHD2, AP2M1, and others
    • Helps identify specific genetic causes when present
    • May guide treatment choices in genetically-defined cases
    • Important for family counseling and understanding recurrence risks
  • Safety Interventions
    • Protective headgear during periods of frequent drop seizures
    • Environmental modifications to reduce injury risk from falls
    • Education for families on seizure recognition and first aid
    • Plans for managing prolonged seizures or clusters of seizures

Ongoing Clinical Trials on Epilepsy with myoclonic-atonic seizures

References

https://www.childneurologyfoundation.org/disorder/epilepsy-with-myoclonic-atonic-seizures-doose-syndrome/

https://www.epilepsy.org.uk/info/syndromes/epilepsy-with-myoclonic-atonic-seizures-doose-syndrome

https://www.orpha.net/en/disease/detail/1942

https://www.epilepsydiagnosis.org/syndrome/epilepsy-myoclonic-atonic-overview.html

https://rarediseases.info.nih.gov/?gard_id=0016108

https://www.ncbi.nlm.nih.gov/books/NBK581164/

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Epilepsy with myoclonic-atonic seizures:

FAQ

What age do children typically develop epilepsy with myoclonic-atonic seizures?

The condition typically begins between 2 and 6 years of age, with the peak onset occurring around 3 to 4 years. The age range can extend from 6 months to 8 years in some cases. Most children have completely normal development before their first seizure, though a small percentage may have mild developmental delays even before seizures begin.

What does the “stormy phase” mean in this type of epilepsy?

The “stormy phase” refers to a period when seizures become very frequent and multiple different seizure types appear together. During this phase, children often experience developmental setbacks, behavioral changes, sleep problems, coordination difficulties, and executive function problems. This phase can be particularly challenging for families, but understanding that it’s a recognized part of the condition’s course can help with management and realistic expectations.

Do children outgrow epilepsy with myoclonic-atonic seizures?

Approximately two-thirds of children achieve seizure freedom, usually within 3 years of epilepsy onset. However, the remaining one-third continue to have seizures and may have ongoing developmental challenges. Factors that suggest a poorer outcome include the presence of tonic seizures, recurring nonconvulsive status epilepticus, and slower background activity on EEG testing.

Is genetic testing important for this condition?

Genetic testing has become increasingly important as researchers have identified several genes that can cause this condition. The most common genetic causes include mutations in SLC6A1, CHD2, and AP2M1 genes, though many other genes have been identified. However, most cases still don’t have an identified single genetic cause and are thought to involve multiple genetic factors working together. Testing can be particularly useful when clinical features suggest a specific genetic cause or for family planning purposes.

What’s the difference between this condition and other childhood epilepsies?

Epilepsy with myoclonic-atonic seizures is distinguished from other childhood epilepsies by several features. It differs from Dravet syndrome, which starts earlier and involves prolonged febrile seizures. Myoclonic epilepsy of infancy occurs earlier and involves only brief myoclonic seizures as a single seizure type. Lennox-Gastaut syndrome frequently has structural or metabolic causes and involves tonic seizures during sleep and atypical absences as main seizure types, whereas epilepsy with myoclonic-atonic seizures typically has normal brain imaging.

🎯 Key Takeaways

  • • Epilepsy with myoclonic-atonic seizures is rare, causing only 1-2% of all childhood epilepsy cases, but requires specialized treatment approaches due to multiple seizure types.
  • • The “stormy phase” with frequent seizures and developmental setbacks is a recognized part of the condition’s natural course, though it can be particularly challenging for families.
  • • About two-thirds of children eventually achieve seizure freedom within 3 years, showing that the condition can improve significantly over time despite initial difficulties.
  • • Boys are affected approximately 3 times more often than girls, making gender one of the most notable risk factors for this condition.
  • • Genetic causes have been identified in some cases, with SLC6A1, CHD2, and AP2M1 being the most common genes involved, though most cases remain unexplained genetically.
  • • Video-EEG monitoring with muscle recording is essential for accurate diagnosis because different seizure types can appear similar without specialized testing.
  • • Large systematic studies on the best treatments are lacking, highlighting the need for more research and the importance of clinical trials in this rare condition.
  • • Brain imaging typically appears normal in this condition, which helps distinguish it from other epilepsy syndromes with visible brain abnormalities.

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