Lennox-Gastaut syndrome (LGS) diagnosis

My son is 40 years old. He lives with my husband and me. He was a normal 3-year-old who starting having seizures for unknown reasons. They have never been well-controlled--from several a day to, now, several a week, almost exclusively when he sleeps. He slowly but surely lost all his skills over the years and is now completely disabled. He can no longer walk, talk, feed or toilet himself. He was diagnosed with Lennox-Gesault Syndrome a few years ago based on his symptoms (not his EEG). He takes Dilantin, Celontin, and Medical Cannabis. He has tried many other meds with no improvement in seizure control and with worse side-effects. We have also tried hundreds of diets (including the ketogenic diet for a year when he was 4 years old) and alternative therapies over the years, all with no success.The cannabis makes him able to bear weight (he had lost that ability before we started it), so I can still transport him to his day program. I wonder if any readers out there have a similar situation? I know by now there is no "magic bullet." Other than his seizures, he seems in good health, pain-free, and happy.

@pamelastewart5 Im sorry your son hasnt been able to get any relief from having seizures. I too am 40 and have had epilepsy for 20 yrs. I dont have Lennox-Gesault Syndrome. I had an abnormality on my right temperol lobe, which was removed and have an abnormality on my hippocampus. Which im guessing is the reason im still having seizures. Ive had a right temperolobectomy, have been on every med made and currently on 3 different ones and medical marijuana. Still having seizures daily and they are getting a little more frequent and have started losing bladder control again. Havent had a gran mal since my brain surgery but i wonder if its only a matter of time before I do! Ive been on the keto diet, no help...I have a VNS, doesnt help. Before I had my brain surgery I was having 20 to 40 seizures a day, losing bladder control every time. My memory it feels like is dwindling away by the day. I can never remember what day it is..go in a room and dont remember what i was going to do, will start talking and my mind just goes blank in the middle of me talking to someone or i mix up my words and dont make sense at all and I feel so stupid! I dont recognize people when im out in public, ive lived here in my town for 39 yrs and dont remember how to get around to places. Scared to be alone but I have to be. Ive been wondering if anybody else my age was on the medical marijuana and it wasnt helping them either, felt like I was the only one it wasnt helping! Its good to hear you take such good care of him! Hes lucky to have you and your husband to be there with him!!! Have you tried the epidilox? I keep hearing about it and will be asking my neuro about it at my upcoming appt. Good luck to you and your son!

Hello, @pamelastewart5 - You'll notice that I have moved your message to this existing discussion, "Lennox-Gastaut syndrome (LGS) diagnosis" in the Epilepsy & Seizures group in which you've participated before. I did this so that you could talk with the members in this conversation already talking about this disease and who are familiar with what you've shared about your son previously. If you click VIEW & REPLY in the email notification, you can scroll back through the past and recent posts.

Not ever having your son's seizures well-controlled sounds very hard, and as a mom myself, I'd be discouraged after no success with diets, medications and alternative therapies.

You mentioned that medical cannabis makes him able to bear weight and wondered if other members might have similar situations. I'd like to request that @briandungan @kathyann @jakedduck1 @davesmo04 return to this conversation to offer their input on whether they have experienced ongoing lack of good seizure control and if have tried this therapy. @dawn_giacabazi @valm and @595959 may also have some thoughts for you.

You mentioned your son has tried many other meds with no improvement in seizure control and with worse side-effects. Have the phenytoin (Dilantin) and methsuximide (Celontin) had any noticeable effects? Has he experienced side effects from these medications, then, as well?

First of all, Im sorry to hear your son has LGS. That’s an awful form of Epilepsy. Below is some information from The Journal of Epilepsy Research about the results of a study for Epidiolex, the CBD medication the FDA approved last year for the treatment of Lenox Gesalut and Dravet syndrome. Sadly this medication hasn’t lived up to all the pre-release hype. It appears to be effective around 25% of the time. I don’t know the validity of the claims that Dilantin can actually worsen LGS considering how helpful it is controlling Generalized seizures.
Valproate/valproic acid seems to be the most effective first line drug with Lamactil/Lamotrigine sometimes added.
You mentioned his LGS was diagnosed from symptoms not EEG, are his EEGs always normal? If so this is very uncommon from what I understand. What kind of seizures is he having?
Is your son being followed by an Epileptologist?
I imagine since he’s having nocturnal seizures he has a seizure pillow.

EPIDIOLEX RESEARCH CONCLUSIONS

The interest in cannabis preparations in the treatment of epilepsies, particularly drug refractory childhood epilepsies, has skyrocketed in recent years. Marijuana and other cannabis products with moderate to high THC content utilized primarily for recreational purposes are generally unsuitable for this indication, not only because evidence for an anti-seizure activity of THC is equivocal and risk of seizure aggravation cannot be excluded,101 but also because THC is associated with many undesired effects, including addiction liability, psychiatric disorders, cognitive and motor impairment125–127 and, possibly, also cardiovascular toxicity.128 The maturing brain is also more vulnerable to the adverse of effects of marijuana,126,129,130 and there is evidence of THC impairing structural and functional connectivity during brain development.126,129,130 Discontinuation of THC after prolonged exposure can also lead to withdrawal manifestations131,132 and cases have been reported of seizure exacerbation after marijuana cessation in people with epilepsy.133

Compared with THC, CBD shows a better defined anticonvulsant profile in animal models considered to be predictive of efficacy against focal and generalized seizures. Moreover, CBD is largely devoid of adverse psychoactive effects, and is considered to lack the abuse liability associated with THC-containing products.134 In the last decade, this has led to an increasing use of CBD-enriched extracts as a potential treatment for epilepsy, particularly in children. Improvement in seizure control, often associated with additional benefits on sleep and behaviour, have been reported in a sizeable proportion of cases,87 but interpretation of these data is made difficult by the uncontrolled nature of the observations. Additionally, as discussed in this article, there are concerns about the quality and variability of many of the products used,98 particularly because cannabis treatment is often initiated spontaneously by patients or caregivers without adequate medical supervision.105

Evidence concerning the potential anti-seizure efficacy of cannabinoids reached a turning point in the last 12 months, with the completion of the first high-quality placebo-controlled trials of a purified oil-based liquid CBD preparation in patients with Dravet syndrome and Lennox-Gastaut syndrome. 85,86,124 The results of these studies demonstrate that, at a dosage of 20 mg/kg/day, CBD added on to pre-existing AED treatment is superior to placebo in reducing the frequency of convulsive (tonic-clonic, tonic, clonic, and atonic) seizures in patients with Dravet syndrome, and the frequency of drop seizures in patients with Lennox-Gastaut syndrome. In the latter patients, a dosage of 10 mg/kg/day treatment was also superior to placebo. Therefore there is now for the first time class 1 evidence that CBD improves seizure control when added on to other AEDs in patients with two difficult-to-treat epileptic encephalopathies. Available data, however, do not allow to conclude that CBD per se has anti-seizure activity. At least for the trial published in full,85 a majority of patients were receiving concomitant clobazam therapy, and it is unclear whether the reported seizure benefits, as well as adverse effects, were related to a direct action of CBD, or were mediated by a previously described 5-fold elevation in plasma N-desmethylclobazam levels. For the two studies in Lennox-Gastaut syndrome, the proportion of patients on concomitant clobazam therapy was not reported, but it is likely to have been significant because clobazam is a frequently used comedication in patients with this syndrome. Clarification of the independent effects of CBD would require re-assessment of trial data for the subgroup of patients not comedicated with clobazam, or the conduction of further studies after excluding such patients or, alternatively, adjusting blindly clobazam dosages to maintain unaltered concentration of N-desmethylclobazam. Additional well controlled studies are also desirable to determine the potential value of CBD in other seizure types and epilepsy syndromes, including refractory focal epilepsies.

One of the reasons for the utilization of cannabis products to have become so popular among patients and their caregivers is that these products are generally regarded as causing fewer adverse effects compared with traditional AEDs, partly out of the misperception that remedies derived from natural products are unlikely to be harmful. In a survey carried out by Epilepsia, 96% of respondents among the general public felt that there was sufficient safety evidence about cannabis products, whereas only 34% of physicians considered this to be the case.135 In fact, in the randomized controlled trials conducted to date the tolerability profile of CDB was relatively benign, with somnolence, decreased appetite and gastrointestinal symptoms being the most common treatment-emergent adverse events. Although these results are encouraging, further studies are required to evaluate the safety profile of CBD and other cannabis products in greater detail, particularly after long-term exposure and whenever these products are used in subpopulations potentially at risk. Elevations of liver enzymes have been frequently observed, especially in patients comedicated with valproate, and although they were generally reversible, close observation for signs suggestive of hepatic toxicity is advisable. Nabiximols, an oromucosal spray formulation containing approximately equal amounts of THC and CBD, has been commercially available in several countries for a number of years and has a relatively extensive safety record.68 However, the maximum approved daily CBD dose in nabiximols is considerably lower than the CBD doses used in epilepsy trials, and experience of nabiximols in pediatric age is limited because the product is not recommended for use ‘below 18 years of age due to lack of safety and efficacy data’.68 As discussed above, prolonged exposure of the immature brain to THC has been shown to cause deleterious effects on brain connectivity, and there is some evidence of prolonged recreational use of marijuana in adolescence being associated with neuropsychological decline and lower academic performance scores.136,137 There are also special concerns for risks to the offspring of mothers who use marijuana during pregnancy.138,139 Although these findings may be specific for THC and other psychoactive cannabinoids, adequate safety data for young children exposed to long-term CBD therapy are not yet available.24 Another area where limited data is available relates to the risk of rebound seizures following abrupt or rapid discontinuation of treatment. Unlike THC, CBD is not associated with the development of tolerance after repeated administration in various seizure models, and there is no evidence of a withdrawal syndrome developing after CBD discontinuation.12

These are exciting times for research in cannabinoids. After almost four millennia of their documented medical use in the treatment of seizure disorders, we are very close to obtaining conclusive evidence of their efficacy in some severe epilepsy syndromes.
Wishing you all the best,
Blessings,
Jake

@pamelastewart5
Good evening Pam,
Hope all is well with you and your family.
I wanted to talk a little about you and acknowledge your importance as a caregiver. Obviously you play an intricate part in your Sons well being. I know that responsibility can be overwhelming. As a caregiver you need to be at the “Top of your game” so to speak, all the time. Honestly, I don’t understand how you manage it. Husbands, often other children, homes to maintain, meals to prepare, errands etc. etc. Just those things can be overwhelming, they are to me. However, your important too. Too often a carers wants and needs are ignored. Carers often deal with their situation alone and can feel very isolated. I hope you get the time necessary to yourself for your needs.
Those of us who have Epilepsy many times take carers for granted and they are not properly acknowledged or told how much we need and appreciated them. I am ashamed to admit I didn’t appreciate all that I put my parents through at the time. At 15 or 16 I had a breakdown and was quite destructive. I apparently couldn’t cope with seizure after seizure, comas feeding tubes etc. I tried to make it up to them and hope I succeeded. Anyway your a very special lady and I have such admiration and respect for you. Thank you, your appreciated more than you know.
God Bless you,
Jake

Hello Everyone,
To answer some questions, my son's EEGs stayed normal for about 3-4 years after the seizures started, at age 3. Then his EEGs "slowed" and he became learning disabled and then retarded. Not until his thirties did his neurologist diagnose him as having LGS, and she based that on his symptoms rather than on his EEG. She speculates that his seizures come from deep in the brainstem, so they might not show up on an EEG. Shortly after the seizures began, he became unsteady on his feet. This increased over the years and now he cannot walk at all. They seizures seemed to affect him in many physical areas right from the beginning. For example, he started drooling. But he could still build with small Legoes and do puzzles until he was in his thirties.
He has tolerated Dilantin and Celontin (an older med) better than any others. And he has tried many meds! He had Dilantin-related gum overgrowth and surgery for that when he was in his twenties. Other than that, he has had few side-effects from these 2 drugs. They lessen the frequency and intensity but don't really control the seizures. Without any meds (we tried that when he was 7), he started going in and out of status petit mal/absence seizures. Very scary.
He is pretty happy most of the time (even before medical marijuana!). He tends to doze. He is not noisy, demanding, or combative. Everyone at his day program seems to like him because he smiles at them. My husband started helping me when he (Caleb, my son) became unable to help himself physically. Now we work together. I know I am very fortunate to have help and to be strong enough physically. So being his caretaker is not that hard. Thank you to everyone who asked about it..
We are in the process of looking into Epidiolex with our neurologist. Thank you, Leonard, for all your good info on Epidiolex. Also, I believe that you surely did make it up to your parents and that you made them feel loved and happy by doing that.
Seizures are such a drag. I wish I could make them vanish from the world! I used to fantasize about that when Caleb was younger. Wouldn't it be wonderful?

Hello, Jake,
I think I addressed Leonard instead of you in the part of my recently-posted reply when I said that I believe you made your parents feel appreciated and loved when you made it up to them. Caring enough about them to try to do that would mean so much to them--and to any parent!

Hi, Everyone, I was wondering if anyone has tried the medication SYMPAZAN? If you have, did it help and were the side-effects a problem? Thanks!

same exact thing happened to my 38 yr old daughter. I think they use LGS when they cant think of anything else. Frustrating

My daughter was diagnosed with LGS at the age of 37 after years of "guessing" from the doctors. She is one of the more high functioning even though she has 14% brain damage from the DPT shot when she was 3 months old. I feel the cocktails of meds have been worse on her than anything.