We need a better protocols for tailoring anti-seizure medication (ASM) regimes or surgical treatment options for our children, especially the early-onset, drug-resistant epilepsies (DRE) within the DEE families - one that acts with urgency to define the best treatment available in an individualized plan based on the knowledge of the diagnosis, the types of seizures, and the values of the child and family. Yes, please let's continue in our quest for effective anti-epilepsy drugs (AED) - drugs that are aimed at changing the course of the disease based on precision medicine techniques! There are so many syndromes and consequently so many children for which this type of treatment is still so far away. Therefore, we must also try to do better with what is already in our arsenal, and we must learn to do this within a shorter timespan! This might require a pyramid shift in our clinical guidelines.
There should be an urgency associated with finding the best available ASM regime available for our DEE children as soon as we know that a child falls within this high risk category. It is unacceptable to wait 2 months to titrate up to med dose, wait 2-4 months to see if there is an effect on seizure frequency (hoping that the effect is actually due to the ASM as correlation does not prove causation), and then wait 2 months to titrate down to try another monotherapy or 2 months to titrate up on another med to once we shift to "rational polytherapy." With all the drugs at our disposal now (~30 ASM: some first line monotherapies for seizure types and syndromes, and a host of adjunct therapies), it is a combinatoric nightmare even when following the best available guidelines (many of which are woefully under-powered with evidence based studies) when time is of the essence, since we know time to control seizures often correlates with long-term prognosis of patient. Years slip by before the best, if not right, combination is found. Where is the urgency in clinic for finding the best-available option and why is our go to determinant "seizure frequency"? Seizure frequency is indeed an "endpoint" - a failed endpoint, what we need is a "start-point" that measures the risk of seizure, pre-seizure activity, or improved brain connectivity control - something that can be detected on a finer scale than seizure frequency, so that clinical decisions can be made quicker and more effectively.
One of things that stands out to me in our guidelines for care of Ring Chromosome 14 Syndrome (https://ojrd.biomedcentral.com/articles/10.1186/s13023-017-0606-4) is this statement: "This variable impairment does not appear to depend on the presence or absence of deletion or on its length, but rather on the time of onset and severity of epileptic seizures: an earlier onset is related to higher degree of disability… " As the mother of now 15 year old daughter who started having seizures at 3 months and has never gone more that 2 months without a seizure (and only twice has she achieved that), I have seen Marie trial over 15 different medications with over 30 different combinations of these, along with diet changes, along with VNS… After all of this, Marie has far fewer abilities now than when she was 3: less mobility, less communication skills, less alertness, now dependent of oxygen and GI tube, full back fusion due to neuromuscular scoliosis, and host of other comorbidities in addition to the ever present seizures. Where was the urgency during those first years as she slowly trialed one drug after another? Why are we asking parents to monitor and essentially answer questions about drug effectiveness when they are still learning to identify different seizure types? We are asking parents of babies to see subtle changes in behaviors, alertness, mobility and then evaluate side-effects while they are still getting know their child. In essence, we are asking parents to judge subtle shades of grey in determining ASM effectiveness, when they have not been trained to do so - without providing them a "light meter." But certainly if such a "light meter" exists or when it exist, it will exist in clinic first. There is too much at stake to continue with the slow pace of in-home trial and error of drugs.
What I suggest is that when a child is determined by diagnosis to fall within the high-risk category of a DEE that they be referred immediately to a rare epilepsy clinic and that an individualized best-available ASM regime be created in-clinic using our most effective to-date "light meters" (EEGs, imaging tool, ...) by trained physicians and technicians where they can rapidly, safely, and systematically trial drugs with the latest available knowledge with respect to drug safety, drug mechanism taking into account the syndrome and seizure-type(s). We need to start treating every drug trialed in our children as a N=1 drug trial while using all the tools at our disposal to measure effectiveness. Let's send the child home with some assurance that the plan in place is the best available as opposed to the current status quo which just adds another drug to mix with the idea that in 6 months the team will re-evaluate as time and abilities slip away. The long-term costs: QOL and potential of the child, family outcomes, as well as the economics of long-term care and disability are too great not to spend more time, effort, and money on the front end of the crisis as opposed to spreading out over a lifetime.