Standard of Care and the Ketogenic Diet

Treating EMAtS (Doose Syndrome) requires a specialized approach because the brain’s electrical activity is often resistant to standard epilepsy drugs. While there is no “one-size-fits-all” sequence of medications, experts have identified a set of treatments that are most likely to help and, crucially, a few that might make things worse.

Commonly Considered Medications

Doctors typically begin with one or more antiseizure medications (ASMs). While every child is different, several medications are commonly used as early-line treatments ^[1]:

• Valproate (Depakote): Often an early medication tried, valproate has a response rate of approximately 31% to 32% in large studies of EMAtS patients ^[2][3]. Families must monitor closely for adverse effects, including hepatotoxicity (liver damage), pancreatitis, low platelets, weight gain, and elevated ammonia levels.
• Clobazam (Onfi): A type of benzodiazepine that is frequently used ^[1][4]. It requires monitoring for significant sedation, respiratory effects, and behavioral changes.
• Ethosuximide (Zarontin): Primarily used if a child has frequent absence seizures (staring spells), it does not typically treat generalized tonic-clonic or drop seizures, so it is often used in combination with other medications ^[5][1].
• Levetiracetam (Keppra): While common, this drug has a lower response rate in EMAtS (~17%) and requires close monitoring, as it can sometimes cause irritability or even worsen seizures in some children ^[2][6][7]. (Note: Worsening is not universal, and changes should only be made by a clinician).

The Role of the Ketogenic Diet

In many forms of epilepsy, the ketogenic diet is a late-stage option. In EMAtS, clinicians often consider it much earlier ^[2]. This is because the diet often works when initial medications fail.

• Observational Efficacy: One large multicenter observational study found that while only 26% of children responded to their first three medications, 79% of children responded to the ketogenic diet (often defined as at least a 50% seizure reduction) ^[2]. In another study of children with drug-resistant EMAtS, approximately 54% achieved complete seizure freedom after six months on the diet ^[8].
• The Goal: The diet involves a strict, medically supervised regimen that forces the brain to burn ketones.
• Safety and Monitoring: The diet is a medical therapy, not a home remedy. It requires a neurologist and a metabolic dietitian to manage severe risks like hypoglycemia, constipation, acidosis, dyslipidemia, kidney stones, and impacts on bone health and growth ^[9][10]. Families must also plan for sick days and ensure all medications are carbohydrate-free.

Medications to Use with Caution

Some medications can cause paradoxical worsening, meaning they might actually increase the number of seizures.

• Levetiracetam: Small studies have shown that some children with EMAtS experience a significant, dose-related increase in myoclonic and atonic seizures when taking this drug ^[6].
• Sodium Channel Blockers: Drugs like carbamazepine, oxcarbazepine, and phenytoin are generally avoided in EMAtS because they can worsen generalized seizure types ^[11]. However, this is not a universal rule—if a child has a specific genetic variant (like certain SCN2A or SCN1A gain-of-function mutations), these drugs might be considered ^[12][13]. Conversely, SCN1A loss-of-function variants (associated with Dravet) commonly worsen with these drugs. Do not delay urgent seizure treatment waiting for genetic results, as only an epileptologist can safely navigate these complex choices.

A Typical Treatment Pathway

While your neurologist will tailor the plan to your child, a common clinical pathway often includes these options:

1. Early Options: Start with Valproate, Clobazam, or Ethosuximide ^[1][5].
2. Early Consideration of Diet: If medications fail to promptly control the seizures, clinicians may move to evaluate the Ketogenic Diet or its less-restrictive version, the Modified Atkins Diet ^[2][14].
3. Drug-Resistant Epilepsy Options: If two appropriate medications fail, doctors generally refer to a specialized center to consider other medications (like felbamate, which carries rare but serious black-box risks of aplastic anemia and liver failure) or palliative surgical options like Vagus Nerve Stimulation (VNS) ^[3][15]. VNS is an implanted device used selectively for drug-resistant cases; it is not a curative surgery.