Epilepsy with myoclonic-atonic seizures is a rare childhood epilepsy that can be challenging to diagnose accurately, requiring careful evaluation of seizure patterns, brain activity, and neurological health to distinguish it from similar conditions and ensure proper care.

Introduction: Who Should Undergo Diagnostics

If your child experiences sudden falls, brief jerking movements, or episodes of staring and unresponsiveness, it is important to seek medical attention promptly. Epilepsy with myoclonic-atonic seizures, also known as EMAS or Doose syndrome, typically affects young children between 2 and 6 years of age, though it can appear as early as 6 months or as late as 8 years old^[4]. This condition usually develops in children who were previously healthy and developing normally^[3].

Parents should consider seeking diagnostic evaluation if their child shows repeated episodes of sudden muscle jerking followed by a loss of muscle tone that causes them to drop to the ground or experience head drops. These events are the hallmark of myoclonic-atonic seizures, where a brief jerk is immediately followed by a sudden loss of muscle strength^[1]. Sometimes, children may have experienced simple febrile seizures, meaning seizures during a fever, before the main symptoms of EMAS appear. About one in four children with this condition have their first seizure during a fever^[3][1].

Boys are affected more often than girls, with studies showing that males are about 2.7 to 3.1 times more likely to develop this condition than females^[3]. If you notice that your child begins to lose previously gained developmental milestones, experiences a plateau where they stop gaining new skills, or develops behavioral changes alongside seizures, these are additional signs that warrant immediate medical evaluation^[1].

It is also advisable to seek medical care if your child has multiple types of seizures. EMAS often presents with several different seizure types occurring together, including myoclonic seizures, atonic seizures, tonic-clonic seizures, and absence seizures^[1]. If you are unsure whether what you are observing is a seizure or if you have concerns about your child’s development or behavior, consulting with a healthcare provider is always the right step.

Diagnostic Methods

Diagnosing epilepsy with myoclonic-atonic seizures requires a comprehensive approach that combines several different evaluation techniques. The diagnosis is based on a careful review of the child’s medical history, observation of seizure characteristics, a complete neurological examination, and specialized testing of brain activity^[3][7].

Medical History and Seizure Observation

The diagnostic process begins with a detailed discussion about the child’s symptoms and medical background. Doctors will ask parents to describe exactly what happens during the seizures, including how long they last, what parts of the body are affected, and whether the child’s awareness or consciousness changes. This information about seizure semiology, which is the medical term for the pattern and characteristics of seizures, is crucial for accurate diagnosis^[3][7].

The doctor will want to know whether the child was developing normally before the seizures started, as most children with EMAS have typical development initially, though some may have mild delays^[1]. Information about any previous febrile seizures is also important, since about 20% of children with EMAS have had febrile seizures before the condition fully develops^[3]. The timing of when seizures occur, their frequency, and any patterns related to sleep or waking hours all provide valuable diagnostic clues.

Neurological Examination

A thorough neurological examination is an essential part of the diagnostic process. The doctor will check the child’s reflexes, muscle strength, coordination, balance, and overall neurological function. In most cases of EMAS, the neurological examination is normal, and the child’s head size is also within normal limits^[4]. This finding helps doctors distinguish EMAS from other conditions that may cause similar seizures but are associated with abnormal neurological findings.

Electroencephalogram (EEG)

The electroencephalogram, or EEG, is one of the most important diagnostic tools for EMAS. An EEG measures the electrical activity in the brain using small sensors attached to the scalp. This test is painless and provides critical information about brain wave patterns that can indicate epilepsy^[3][7].

In children with EMAS, the EEG findings can vary. At the beginning of the condition, the EEG may appear completely normal. However, as the condition progresses, the EEG typically shows a slowing of the background brain activity and generalized spike-wave discharges occurring at a rate of 2 to 3 times per second^[3][7]. These electrical patterns indicate abnormal brain activity that affects the entire brain rather than just one area.

Because myoclonic, atonic, and myoclonic-atonic seizures all can cause sudden drops or falls, it is essential to determine exactly which type of seizure is occurring. A specialized test called video-EEG with electromyogram, or EMG, is crucial for making this distinction. The EMG measures muscle activity, particularly in the deltoid muscles of the shoulders and the neck muscles. By recording both brain waves and muscle activity simultaneously on video, doctors can accurately identify whether drops are caused by myoclonic-atonic seizures or by other seizure types like tonic seizures or epileptic spasms^[3][7].

An important part of the EEG examination includes a procedure called intermittent photic stimulation at low frequencies. During this test, the child is exposed to flashing lights at various speeds while the EEG records brain activity. This test must be performed systematically to help exclude a different condition called neuronal ceroid lipofuscinosis type 2, or CLN2 disease, which can present with similar symptoms but occurs in the same age range and requires different treatment^[3][7].

Brain Imaging Studies

Brain imaging is performed to ensure that there are no structural problems in the brain that could be causing the seizures. In EMAS, brain imaging results are typically normal^[3][7]. This normal imaging finding is actually an important diagnostic feature because it helps distinguish EMAS from other epilepsy conditions that are caused by brain malformations, injuries, or other structural abnormalities.

Common imaging tests include magnetic resonance imaging, or MRI, and computed tomography, or CT scans. These tests create detailed pictures of the brain’s structure and can identify abnormalities such as tumors, scarring, or developmental malformations. When these tests show normal brain structure in a child with the characteristic seizures and EEG findings, it supports the diagnosis of EMAS.

Genetic and Metabolic Testing

Although the exact cause of EMAS is unknown in most cases, genetic factors are believed to play a role. Doctors may recommend genetic testing, especially if the clinical features suggest a specific genetic mutation or if there are concerns about differential diagnosis^[3][7].

Several genes have been identified as causes of EMAS in some children. The most common genes involved include SLC6A1, CHD2, and AP2M1. Other genes that have been reported include SLC2A1, SCN1A, SYNGAP1, KCNA2, and NEXMIF^[3]. Identifying a specific genetic cause can help with understanding the condition, predicting how it might progress, and providing information about recurrence risk for future children in the family.

Metabolic testing may also be performed to rule out metabolic disorders that can cause similar seizures. These tests typically involve blood and urine samples to check for abnormalities in how the body processes certain substances. Metabolic testing is particularly important when the differential diagnosis includes conditions like CLN2 disease^[3][7].

Distinguishing EMAS from Similar Conditions

An important part of the diagnostic process is making sure the child has EMAS rather than another similar epilepsy condition. This process is called differential diagnosis. Several conditions can look like EMAS, and distinguishing between them is crucial because they have different treatments and outcomes^[3][7].

Dravet syndrome is one condition that must be ruled out. While Dravet syndrome also causes multiple seizure types, it typically begins earlier in life and is characterized by prolonged febrile seizures that last more than 15 minutes^[3]. Myoclonic epilepsy of infancy is another similar condition, but it begins earlier than EMAS and causes only brief myoclonic seizures without the atonic component^[3].

Lennox-Gastaut syndrome can also appear similar to EMAS, but it is frequently associated with underlying structural or metabolic problems in the brain. The main seizure types in Lennox-Gastaut syndrome are tonic seizures during sleep and atypical absence seizures, which differ from the myoclonic-atonic seizures that are characteristic of EMAS^[3][7].

CLN2 disease is another critical differential diagnosis because it begins in the same age range as EMAS. However, CLN2 disease is a progressive metabolic disorder that requires different management. The systematic use of intermittent photic stimulation during EEG testing helps identify or exclude this condition^[3][7].

Diagnostics for Clinical Trial Qualification

When children with EMAS are being considered for participation in clinical trials, additional diagnostic criteria and testing may be required beyond the standard diagnostic evaluation. Clinical trials are research studies that test new treatments or approaches to managing the condition. To ensure that study results are accurate and that participants are appropriate for the trial, strict enrollment criteria must be met.

The specific diagnostic tests and criteria used for clinical trial qualification depend on the particular trial and what is being studied. However, some general principles apply to most clinical trials involving children with EMAS. First, the diagnosis of EMAS must be firmly established using the standard diagnostic methods described earlier, including documented seizure semiology, characteristic EEG findings, and normal brain imaging^[3][7].

Clinical trials typically require comprehensive documentation of the child’s seizure history, including detailed records of seizure frequency, types, and severity. Video-EEG recordings may be required to confirm the presence and characteristics of myoclonic-atonic seizures and to establish a baseline of seizure activity before any experimental treatment begins^[3][7]. This baseline information is essential for later determining whether a new treatment is effective.

Developmental and cognitive assessments are often part of the qualification process for clinical trials. These evaluations measure the child’s abilities in areas such as language, motor skills, social interaction, and learning. Because EMAS can affect development, and because some treatments being studied might aim to improve developmental outcomes, having accurate baseline measurements is crucial^[4].

Genetic testing may be required for some clinical trials, particularly those studying treatments targeted at specific genetic causes of EMAS. If a trial is investigating a treatment for children with mutations in a specific gene, such as SLC6A1 or CHD2, then confirmation of that genetic variant through laboratory testing would be necessary for enrollment^[3].

Blood tests and other laboratory evaluations are typically performed to ensure that the child is healthy enough to participate safely in the trial and to establish baseline values for various health markers. These might include blood cell counts, liver and kidney function tests, and other measurements that could be affected by experimental treatments.

Some trials may have specific inclusion or exclusion criteria related to previous treatments. For example, a trial might only accept children who have not responded to a certain number of standard medications, or it might exclude children who have tried certain treatments in the past. Documentation of all previous treatments and their outcomes is therefore an important part of the qualification process.

The timing and severity of seizures can also be qualification criteria. Some trials may require that children have a minimum frequency of seizures, such as a certain number per week or month, to be eligible. This requirement exists because if seizures are very infrequent, it becomes difficult to determine whether a treatment is working. Conversely, some trials may exclude children whose seizures are extremely frequent or severe due to safety concerns.

Behavioral and quality-of-life assessments may also be part of the qualification process, especially for trials investigating how treatments affect not just seizure frequency but also overall functioning and well-being. These evaluations might involve questionnaires completed by parents about their child’s behavior, sleep patterns, attention, and daily activities.

Throughout the qualification process for clinical trials, safety is paramount. Doctors will carefully review the child’s complete medical history, including any other health conditions, medications, or allergies, to ensure that participation in the trial would not pose unacceptable risks. Parents should feel comfortable asking questions about any aspect of the qualification process and should understand all the tests and evaluations that their child will undergo.