Today’s post
answers a question left un-answered in earlier posts about the best way to treat
the imbalance (excitatory vs inhibitory or just E/I) that exists in the
function of the key neurotransmitter GABA in many types of autism.
I first started
this blog after the pleasant shock of seeing the positive behavioral and
cognitive effect caused by Bumetanide.
This was
just copying a recent French clinical trial on humans.
Later on in
this blog we came across Professor Catterall who made two experiments in mice to
show that the same E/I imbalance could be treated using tiny doses of a drug
called Clonazepam. At doses a hundred
time higher, Clonazepam is used to treat seizures and anxiety, but at those
doses it dose have side effects.
The
mechanism is different to Bumetanide, by the effect was claimed to be the same.
Since
Bumetanide has actually been shown effective in a human trial, most readers of
this blog have this as their first choice.
I commented
that in Monty, aged 11 with ASD, there was indeed an additional positive effect
of adding clonazepam to existing bumetanide therapy. Now having several effective treatments, it
is harder to quantify the effect of new ones.
It remained
unknown what would be the effect of low
dose Clonazepam without the Bumetanide.
Since
Bumetanide is known to reduce potassium levels, albeit in a minority of cases,
to the extent that supplementation is required, it is necessary to monitor
blood levels of potassium. This is a
drawback of the therapy, although the majority of people will not actually need
supplementation. So one regular reader of
this blog has tried Clonazepam; and I assume, Maja, without Bumetanide.
Tried
Clonazepam 0.025mg in one dose, in the evening, before sleep. After whole 3
days, as you predicted, change was amazing - she become self confident, a bit
naughty, but in some joyful, playful way. Started to play more often with
friends (by report of teacher end assistant in school). They both reported that
she is different, but in good way, even she is harder to manage with (i didn't
tell them about new therapy in that time)
Started to play differently, not in pattern she's developed over the years (she has great imaginations, wich is a plus, but has stereotype of ideas in the play).
First of all, we noticed that she is capable to sense odors (she had some kind of anosmia before), than she managed to catch a rhythm to dance (that was a real wow!).
She was speaking with people in the shop (briefly, but adequately)...
There is much more...
Change is still present, but after three weeks are slightly paler . There are not so intense. I'm still overwhelmed, just wont to know if I am missing something.
Thank you Maja for sharing.
In Monty, the
effect was not this profound, but then he was already on Bumetanide, and so I was
rather expecting no effect.
So, bumetanide
and/or low-dose clonazepam for Autism?
I
suggest both, for maximum effect.
P.S. For the scientists among you
There is another drug, Diamox/Acetazolamide, that I think may also have the same effect as Bumetanide and Low dose Clonazepam. It is a so-called carbonic anhydrase inhibitor, meaning it forces the kidneys to excrete bicarbonate (HCO3-) and thus makes the blood more acidic. This has the side benefit of increasing the amount of oxygen in the blood, and hence its use off-label to prevent altitude sickness. In the brain this change in HCO3- should affect Anion exchanger 3 (AE3) and Sodium dependent anion exchanger (NDAE) which sit alongside the GABAa receptors. By reducing Cl- levels within the cell, the effect would be the same as Bumetanide, which affects the NKCC1 transporter. This might explain why Diamox, a diuretic, is also used to treat some epilepsy and periodic paralysis. Note Bumetanide is also used to treat periodic paralysis and some seizures.
This was all covered in a very complicated post:-
GABA A Receptors in Autism – How and Why to Modulate Them
If you are one of those who believe that there is mild hypoxia in some cases of autism, then you could also consider Diamox as an alternative to hyperbaric oxygen therapy.
Clonazepam has done something new, something that can not be compared with any other medicine.. I spoke with friends (doctors) before my trial. Every one of them had the same opinion: in that dose it can hurt, but it won`t work.
ReplyDeleteWell, it works.
And, I must ad, I am more comfortable to give a drug, than the supplement. Then I know what I am giving.
For the first time we have conversation like this:
- You don`t know what is dissolved into the sea water? I won`t take you to the sea again!
- Don't know... She has dysphasia....
Grammatically wrong - but cognitively brilliant! (I told her that she has dysphasia couple of months before, when she wrote her diary - trying to avoid a word "autism" )
Of course, she is not like that all the time (not at all!), but thinking in that way is developing, and now it is something what is expected.
Her sense of smell is something that surprised me. It is a clear sign of some kind of reconnection in the brain. Signals in the brain managed to pass from olfactory center to cortex to be recognised. I hope it is a beginning (from phylogenetically oldest parts of the brain). That the comprehension of language is waiting it`s turn.
Yes, Peter, Yurinex is next step (thank you). In the summer time, maybe...
P.S. I wanted to try Piracetam instead of Pantogam that I am giving her now (2x500mg), but I gave up from that. Maybe there is a synergism between the Clonazepam and Pantogam that matters? I am afraid now to change anything.
P.P.S.S. I am so sorry that my English is not better...
Thanks Maja.
DeletePrescription drugs have a big advantage over supplements in that they are reliable, as you comment. The big problem most people have is that they cannot access them.
If cognitive function is a target, I think 10mg of Atorvastatin is worth a try. You will see the effect in 24 hours. So no need to worry about long term side effects, first see if it works. In fact the common side effect of muscle pains goes away by adding back the Coenzyme Q10 that the statin has depleted. Since you use verapamil already, you do not have a risk of type 2 diabetes. So unless your daughter happens to have low cholesterol now, Atorvastatin is pretty safe for long term use. In the US it is used in kids, albeit obese ones.
Thank you, Peter. I`ll do blood tests before; have not done them in last few years. Now I am too happy to change anything.
DeleteGreat to read about such improvements. Ironically, prof. Catterall’s studies have been recently cited on one parental forum here as an example that research on mice has low chance to be repeated in humans.
ReplyDeleteInterestingly, my son started smelling things few weeks ago (in a very appropriate way). All his life he seemed like not sensing smells before. He’s never been given Clonazepam, but using Bumetanide for 5 months.
Peter, I think you are the only person in the world who can compare the effects of low dose Clonazepam and low dose Valproate, can you tell what is your experience with each one after some time has passed? Are there any clear differences i.e. with regard to cognitive function? Are you still using Valproate?
I tried to find if low dose Valproate can prevent mast cell related headaches in my son, unfortunately it did not. Maximum dose of Cromoglicate also failed, but was associated with other, unexpected improvements e.g. tics disappeared. It has been suggested that there is a common mechanism of action of cromones and NKCC transported inhibitors, including bumetanide.
I am also trying Quercetine and I agree with what Maja wrote above, that drugs are easier to deal with than supplements. You can read that Quercetine is a CYP3A4 cytochrome inhibitor and you can read that it is not. Rupatadine should not be used together with such inhibitors. Peter, I remember you mentioned Rupatadine on your blog, did you use both them together?
Once you start combining drugs it is hard to judge their effect. I am glad Maja tried Clonazepam without Bumetanide, since all I can judge is the additional effect of Clonazepam. It seems to further develop the improvements set in motion by Bumetanide. I only tried the low dose Valproate for a couple of days. The effect is visible quickly and was on top of bumetanide + low dose clonazepam. It was a hand holding, hugging effect, so it was different to Bumetanide and Bumetanide + low dose clonazepam. This seemed too much, so I stopped Valproate and Clonazepam to re-establish a baseline. Cognitive function was decreased, so I re-started the low dose Clonazepam.
DeleteI did get Rupatadine from Italy and did use it last summer. For my son the best allergy/mast cell therapy is Verapamil plus Azelastine nasal spray. If this is not enough this summer, I will add the quercetin again.
Rupatadine is also not good with higher doses of statin.
Does simple Ibuprofen have any effect on your son?
I was surprised that it did in my son. So we use it occasionally, since we have 4 wobbly teeth. But it is not pain itself that is the problem (it is the cytokines), he actually likes mild pain, he wants me to push his painful tooth.
I have found that by using the tangeretin flavonoid we hardly ever need the Ibuprofen. This product is sold as Styrinol to lower cholesterol. The PPAR gamma drugs all have side effects, but it appears that tangeretin does not They are looking for new PPAR gamma drugs, because of this problem.
The Styrinol does indeed seem to have an anti-inflammatory effect, as the studies suggested. I will be interested to see how this helps when the pollen triggers our summertime regression.
Thank you for reply. I think I will also try Clonazepam.
ReplyDeleteI gave Ibuprofen to my son for over 10 days, first started when I saw a wobbly teeth. Daily mast cell and autism symptoms did not seem to be affected by this treatment. He also had a cold then, which did not trigger his typical problem: several days of frequent flushing, fatigue, headaches etc. I am not sure if Ibuprofen prevented this, but possibly yes. Later however he developed strange, fierce aggressive behaviors, difficult for me to describe it in English, but this was something extremely unusual for him. I quit Ibuprofen, these behaviors disappeared three days later. Difficult to say, what it was, maybe unrelated. My son still communicates little about himself. From what I read, some people with mast cell disorders apparently don’t tolerate NSAIDs.
We’ve been using Rupatadine for a few months, without it his skin is itching, that’s something obviously associated. Not all antihistamines reduce itching in him. When I sent his medical records to the experienced US hospital and got mast cell activation confirmed (MCAS) they also recommended Ketotifen (not surprisingly) and increasing Cromoglicate to really high doses. The last one had unexpected good effects. Now it’s too soon to confirm, but Quercetin may be helpful for my son.
My son does not have elevated cholesterol, his triglycerides are low and I suspect mitochondrial dysfunction, that’s why I hesitate with statins. I will look into Tangeretin, thank you for sharing this idea. Also your new epigenetics post is impressive!
Hi Agnieszka,
DeleteI hope you see this since it has been a while. I just came across this organization and this 'magic lotion'. Maybe you could visit their parent forum and get more information.
http://mastokids.org/mml.html
Hi,
DeleteI read this blog every day, it changed my life. Thanks RG for “masto-lotion” suggestion, I thought they use it for rashes, but it seems that also for itching, so I’ll try it. My son used to have other mast cell related symptoms e.g. flushing, hives, but now itching is one of few visible things indicating increased mast cell activation.
Do you suspect mast cell activation in your daughter? Seizures may also be related to mast cell activation. There’s a case report of stress induced seizures in a boy with cutaneous mastocytosis; typical AED did not prevent tonic-clonic seizures in him, while he became seizure free on H1/H2 blockers:
http://www.ncbi.nlm.nih.gov/pubmed/11910271 (I have a full text if unavailable). I also remember parental reports from message boards, using Ketotifen as well.
I read your previous comments and think about catamenial epilepsy. My son suffers periodic, paroxysmal migraine-like episodes, previously suspected also of epilepsy, that used to occur exactly every 4 weeks, at times were very predictable. Of course he is a boy so this has nothing to hormonal monthly changes. He got free from this episodes for four months - the longest period in his life while not on valproate - with melatonin 10mg and low dose clonazepam. Unfortunately soon as he got back to school he started to having them back again.Now I have a common problem: “drugs stop working”.
I wandered if you tried low dose clonazepam and also as you wrote that your daughter has regressive autism, do you think it may be associated with mitochondrial dysfunction?
How is acetazolamide related to catamenial epilepsy?
Agnieszka, have you seen this? Especially scroll down to migraines. It seems valproate is contraindicated in mitochondrial disorder.
Deletehttp://www.mitoaction.org/blog/seizure-disorders-and-epilepsy
Acetazolamide has been used since the '50s at least as a weak treatment for seizures. It suppresses the activity of the carbonic anhydrase enzyme which converts carbon dioxide to bicarbonate. There are apparently fourteen of these enzymes and they are mostly concentrated in glial cells. It helps maintain Cl and K balance in the glial cells. By suppressing the activity of this enzyme, there is more carbon dioxide which stabilizes axonal membrane and inhibits the spread of electrical activity. It apparently works in a similar manner to topiramate.
DeleteApparently, it also affects gaba. Don't know how. Could not find enough information. Anyway, at the time I was looking into Diamox, I didn't know very much about gaba (thanks to this blog, I am a bit farther along now).
This is the best I could find and only when I searched for carbonic acid and seizures. There is not much you can find under acetazolamide and seizures. There is some old stuff that speculates it to be a result of increased blood acidity and its similarity to the ketogenic diet, but that has been disproved.
As you can see, I don't quite understand how it affects Cl and K in the brain, so am not able to compare to how it might be similar to bumetanide.
Have you eliminated abnormal electrical activity in your son? If you are able to sort of predict when his migraines come, or if they last more than a day, you could get him into a 24 hour Video EEG done over several days. Is that possible?
DeleteI suspected mitochondrial disorder in my daughter nine years ago, unfortunately could not find a good doctor at that time to interpret tests. I tried some supplements that did not do much. I have been trying to find Dr. Richard Kelley, but apparently he has left Kennedy Krieger and the back channel news was that he is joining Children's Hospital in Boston, but when I called there they had no information.
My daughter's cholesterol is high but that may be because she has been on a high fat diet, even before the MAD, for years. If she does not have a mito disorder, I would like to start her on statins.
I was going to start the low dose clonazepam a couple of months ago, but we got into the thyroid problem and have just started her on levothyroxine, so need to wait for a bit for this to settle down. My pharmacist is able to compound the clonazepam in .05mg capsules suspended in olive oil so I can titrate up or down to reach an optimal dose. What is the dose that has worked for you. I started verapamil more than a year ago, and then, for a year, have not been able to do much due to a bit of a family situation.
Thank you for the link. You know Agnieszka, prior to November 2013, I was one of those people who took her child's amiability and lack of sib for granted. My daughter's autism changed significantly for the worse then and it seems to be the secondary (or third or fourth) tap that Peter talks about. I do think it is due to allergies, we have had a terrible drought in California the last few years and the mean temperature across the seasons have increased. Last year, we were temporarily in a different place and I had to keep her like a bubble kid. She would fall into a seizure just stepping outside for a walk. Here, we are surrounded by trees and she has a different type of allergy. Zyrtec is not really working here and I need to find something that I can dose everyday prophylactically. Have you tried the cromolyn sodium? My daughter's only physical symptoms are occasional, maybe once a day, rubbing of her eyes, or slightly red eyes.
DeleteI just remembered something. We tried accupuncture for a while a few years ago and the chinese doctor used to give my daughter some pills called Ge Gen. She used to be very bright and focused after taking them, her face and eyes would light up. I tried them once and it was fantastic, I could literally feel the blood flow in my head. Apparently, the main ingredient is kudzu root which is well studied in headaches. It may be worth looking into. In fact, I get a lot of headaches, and I had forgotten about this, so will also try it and let you know how it goes.
Hi RG and Agnieszka
DeleteThe effect of the statin is almost the same day, so even if you had mitochondrial disease, I do not see a big risk. If the autism gets worse then you may have proved mitochondrial disease, if it gets better then mitochondrial disease is unlikely. There were statin trials in children with normal cholesterol (it was a trial for Neurofibromatosis) and there was no problem with low cholesterol being produced, it just did not seem to help the Neurofibromatosis. I use the statin plus 100mg of Coenzyme Q10. My brother with type 1 diabetes took a statin for years but had the muscle pain side effects; I told him to switch to Atorvastatin and add 100mg of Coenzyme Q10. He now has no side effects, 100mg of Coenzyme Q10 got rid of 90% of the problem and with 200mg of Coenzyme Q10 it was 100% solved. So if you add Coenzyme Q10 then you protect from damaging mitochondria.
Hi Peter,
DeleteThank you for this, great to know. We are just two weeks into the levothyroxine and at the fifth week, the endocrinologist is going to adjust dose, maybe add in T3. Do you think its ok to try the statin now or wait? Ditto question about the clonazepam as well.
Hi RG, it is best not to mix up different trials, so I would wait.
DeleteHello to both of you,
DeleteI added Coenzyme Q10 two weeks ago, following dr Kelley protocol and also it was found effective in cluster headache. Other statin toxicity risk factors have been identified and I thought that I could target them before I’ll try statin, even though they may not apply to children etc: http://www.ncbi.nlm.nih.gov/pubmed/25640999. I mean vit D deficiency in my son.
RG, last EEG of my son, done a year ago and a month after bumetanide was still with epileptiform sleep pattern, but there was a distinct change for better in wake EEG - no more theta waves as in immature brain or encephalopathy.
In 2013 I scheduled EEG predicting the time of next episode, very easy then as it happened every full moon. EEG result was as usual, but it was short, not 24h.
The only neurologist with serious interest in autism and channelopathy I found here is quite sure that these are episodes of some periodic ion channel dysfunction, the one “yet to be described in medicine”. He also advised against valproate.
I dissolve 0,5 mg clonazepam tablet in 100 ml of water and give my son 3 ml daily. I followed Peter’s recommendation how to dose it and then lowered the dose as higher seemed to increase anxiety.
Last Friday I had to pick up my son from a school trip because of crying, cold hands, headache and restlessness typical for the beginning of the "episode" and straight back home I gave him acetazolamide, it was next on my trial/error list. He did not develop full blown episode which usually lasts a week. Who knows why… I will let you know about it further.
RG,
DeleteThanks for kudzu information, I think I remember it being discussed on cluster headache message board.
I’ve been giving my son sodium cromoglicate for 1,5 year, at first suggested by allergologist for food allergy. Soon we found that its effects are beyond GI and withdrawal inevitably triggers the “migraine episode” in a day. His urinary methylhistamine turned out to be elevated during one of the episodes and this one was not triggered by cromoglicate withdrawal. He was irritable and cried then, but the only mast cell symptom were slightly red eyes. Many times I saw that behaviors were much more prominent that physical symptoms, which were slight but present.
Mast cell activation can be confirmed by lab tests and in the U.S. it’s easier than in Eastern Europe. Also some most experienced doctors in this field work in the U.S. and from what I read it’s also trial and error way how people with mast cell activation syndrome are treated. They do things like using two H1 antihistamines at one time or increasing the dose up to 4 times higher than typical.
I know that a second autism tap can be a very miserable condition, in my son I think at least partially it was related to mast cell activation.
Agnieszka, did you consider H2 agonists? It was found by chance many years ago that famotidine greatly improved a minority of cases of schizophrenia. I believe that other H2 agonists are widely used in mast cell conditions. In the US it is an OTC drug, so it must be considered
Deletepretty safe.
Many people with ASD suffer from reflux/GERD. The link seems to be mGluR5, which would connect GERD with ASD and schizophrenia.
I also have GERD sometimes, but I use a PPI drug when necessary. I think I will get some famotidine.
Agnieszka, it is interesting that you found that slightly too much "low dose" Clonazepam caused anxiety. This is now a common finding.
DeleteIt seems that the effective dose can vary from 3ml to 10 ml using the solution of 0.5mg in 100ml water. This is quite a big variation. Most people seem to be at the lower end of the range. So for anyone thinking of trying it, 5ml is probably a good place to start.
Hi Agnieszka,
DeleteThanks for the detailed information. I was looking for a mastocytosis specialist when I found a non profit masto organization here and the mastokids website. So the cromoglicate is not preventing the migraines?
It seems that migraines are also treated with AEDs and calcium channel blockers. I have heard anecdotally from a couple of doctors that untreated migraines can lead to other conditions like tinnitus, meniere's disease. For a friend of mine with migraines, her doctor tested for epileptiform activity as they are often comorbid conditions apparently. This maybe why the acetazolamide worked as it is a weak anti epileptic and modulates gaba (i don't know how).
Have you tried the verapamil? I was surprised to see how often, and in how many varied conditions, especially those that don't have good treatment options, calcium channel blockers are used. Last year, while looking at them, I found that a good number of people I know are on them, nimodipine being the one most used.
Hi Peter,
DeleteThere is a small study about famotidine in autism also and they refere to schizophrenia study you mentioned, have you seen this? http://www.ncbi.nlm.nih.gov/pubmed/11459079
I tried ranitidine 75 mg with no improvement last year. From what I read about mast cell activation syndrome, a combination of H1/H2 blocker is a first-line treatment, helpful for many. As I was told by some other doctors in my country that what I see in my son are just random findings, I consulted Mastocytosis Center at Brigham and Women’s Hospital in Boston, where people involved in MCAS diagnostic criteria work, via an on-line second-opinion service. They confirmed mast cell activation in my son, found previously unrecognized skin signs on his pictures and recommended instead of further H2 trials increasing sodium cromoglicate dose to 4x200 mg which is very high. This was associated with some enthusiastic comments from my son’s teachers about his behavior, so we continue with that dose.
In the famotidine study kids with marked stereotypies were found to be non-responders. It can be a distinct subgroup or perhaps they are just more affected, in a similar way as in bumetanide study: those less affected benefited more. I think that in severe autism there may be so many biological dysfunctions that correcting one of them may not be enough to see significant improvement. Maybe that was the case of my son with ranitidine then.
Few weeks ago I gave my son omeprazole for other reasons and soon saw the same kind of anxiety that I think it’s related to clonazepam in higher dose. If you check interactions (http://reference.medscape.com/drug-interactionchecker) you will read: “omeprazole increases levels of clonazepam by decreasing metabolism. Minor or non-significant interaction.” So I quit omeprazole, decreased clonazepam for a while and anxiety disappeared. I think low dose clonazepam has a narrow therapeutic window and in that case even “minor or non-significant interaction” may be important to see its best effect. I wonder if there's any need to modify the dose over some longer time. Have you modified the dose since you started using clonazepam?
DeleteHi RG,
DeleteI don’t know if it’s really migraine in my son. In fact some of his headaches are most similar to cluster-headaches, at least how they are described in the books. I have never meet a person with cluster headache. When I read about channelopathies like episodic ataxia for example or hypokalemic periodic paralysis, they also seem somehow familiar.
With regard to acetazolamide and GABA receptors, have you read these great posts?
http://epiphanyasd.blogspot.com/2015/05/diamox-bumetanide-ion-channels-nav14.html
http://epiphanyasd.blogspot.com/2014/09/gaba-receptors-in-autism-how-and-why-to.html (my favourite)
Thanks to Peter’s blog I used verapamil last year and saw incredible things in less than a week, one of them is complete (100%) resolution of GI symptoms that were present in my son for at least two years before. Since the 2nd day of verapamil until now.
If you think about mast cell activation disease there is a paper which I found helpful, although there is nothing about autism there:
http://www.wjgnet.com/2218-6204/pdf/v3/i1/1.pdf
It presents clinical symptoms grading scale (=when to suspect MCAD) and what labs can be done. First author is a doctor from the U.S. as are all authors of this one about treatment:
http://www.clinicaltherapeutics.com/article/S0149-2918(13)00171-9/abstract
I don’t know if open-access, but if not, I have the full text.
Nimodipine seems interesting, did you try it?
I think that slightly above the therapeutic window there definitely is some anxiety, I was also wondering if in fact the same could occur slightly below. I was away for a few days and my son had no Clonazepam. Because of the long half life it should take about three days to reach the stable level of the drug, but after two days I noticed unusual anxiety. It might be a coincidence. When I stopped Clonazepam for a couple of weeks over the summer I did notice a degree of loss of cognitive function, so I think it really does have an effect, but it is not a simple process. The other thought I had was that perhaps over time the effective dose actual decreases, rather than increases (so the opposite of tolerance).
DeleteAgnieszka, thanks for the famotidine link. I had not seem that trial. It is interesting. Once you consider autism as dynamic, both in terms of changes in the environment (weather/pollen for us and I expect diet for others) and interactions between comorbidities and indeed therapies, it is not surprising that some things work in some people, but only some of the time. Given the possible interaction between H1 and H2, not to mention H3 and H4, probably you could not expect in one trial famotidine to help everyone. I will try it, but twice, once in the pollen allergy season and once outside of it. It is becoming rather complicated.
DeleteHi Agnieszka,
DeleteThank you very much for the past posts. From the second half of last year until a couple of months ago, I had not been able to read much here and am, only now, catching up. I had no idea that Peter had written about this.
Thank you also for the mast cell paper. I really need to try some things out quickly. My daughter was off all day yesterday, raccoon eyes, low grade irritability - the verapamil, bumetanide, magnesium, zyrtec, none of them could get rid of the grumpiness completely. Could not do any class at all. Quite withdrawn. She also had two very mild seizures in the last few days. Have you tried the cinnamon? I have plenty of it at home, so thought I might try that first, while figuring out the other antihistamines.
I did not try nimodipine, I went with verapamil because, one, it is the one that is better studied for seizures, and second, Peter was already using it.
Hi,
DeleteIf I understood correctly what prof Catterall told at the end of SFARI webinar, they are about to start a clinical trial with low dose clonazepam in children with autism and epilepsy. I wonder how they will manage the dosing issue (?).
RG, I haven't tried cinnamon yet, I will for sure. My son luckily is still free from his full-blown 'episodes', but I have to wait with new trials as it turned out that he requires urgent and prolonged dental treatment. That's not a good time to check new things (and may have been a silent trigger few weeks before). Is your daughter on any "typical" antiepileptic drug now or before?
While searching for Diamox safety information I found this: "Combination Biotin Responsive Encephalopathy and Hemiplegic Migraine Disorder presenting as Autism and episodic limb dysfunction/seizures in a 10 year old girl"
http://abstracts.ashg.org/cgi-bin/2014/ashg14s.pl?author=benke&sort=ptimes&sbutton=Detail&absno=140122034&sid=707264
This is only a short conference abstract, but an interesting story about a girl whose autism much improved when those two other conditions were diagnosed and treated. Apparently Diamox was given for altitiude illness prevention on holidays and only this led later to genetic confirmation that what she suffers is migraine not seizure disorder.
I wish Prof Catterall luck with the dosing, maybe he will check this blog. He has done before.
DeleteThe abstract is interesting, in part because the girl responded to Biotin, but there was no related genetic dysfunction.
It's really interesting seeing Kudzu being mentioned here. It's also been mentioned in ASD forums regarding natural alternatives to Suramin, as it supposedly acts on some of the same receptors. I will surely try it out myself. BTW, the human Suramin trial is now under way. Keep your eyes open!
DeleteDear Agnieszka,
DeleteThank you for the paper. Very interesting. A low dose of biotin was part of my daughter's daily supplement schedule for several years. Last year, I increased the dose and found that it made her hyper and agitated, so stopped after three days.
I have not made a google account yet, so am missing posts and not able to find the one where you had mentioned that you were dealing with dental issues for your son. I just came across a parent on the mastokids forum under 'cavities' that their dentist blamed their child's cavities on prolonged antihistamine use.
I don't know what sort of dental problems your son has, but there is an orthodontist here who does a lot of work with asd kids and adults with all sorts of problems, and he has had some pretty good results. His approach is different from that of other orthodontists, in that he believes that the bite should not be offset, and he has a series of appliances he uses to first build up the back teeth, and then bring the lower jaw forward and then align the upper and lower. He is also quite familiar with microglial activation and has a lot of research to back up his orthodontic approach. He is a very nice person and I am sure would be open to talking to you if you would like. I must add here though that when I first took my daughter to him several years ago, it was helpful, but later, she would not keep the appliances in and also would not give accurate feedback during the fittings, she would just say whatever was needed to get out of there as quickly as possible.
http://tmjoakland.com/dr-dwight-jennings
Good luck,
RG
my son when he use to take ibuprofen always used to be ill with fever.What can be the cause of his fever???No one can tell me
ReplyDeleteI looked at Diamox last year, especially because it has a good record with catamenial epilepsy. Decided against it since we were going to try the Ketogenic/MAD anyway and blood acidity is a side effect of the the diet that we have to constantly watch out for.
ReplyDeleteAbout the dosing for clonazepam, if your child is sensitive to clonazepam like mine is, you might not need to give it every day. We've seen some lovely gains with clonazepam but it also makes my son really hyperactive. Now I have reduced the already tiny dose to every second day and that is working nicely. Hyperactivity is greatly reduced and we've kept the nice gains.
ReplyDeleteNina
Thanks Nina for the update.
DeleteHi what is the correct dose of clonazepam for an adolescent who is 120 lbs ? is it 0.025 mg per week . I had my compounding pharamacist make it up this way.
ReplyDeleteI would try 0.05 mg per day. It takes 3 days to reach a steady level in the bloodstream. If there is any anxiety then lower the dose slightly. The effective dose does seem to be sensitive to any other drugs being taken. Some people find 0.025mg to be enough, but they tend to be much smaller in size.
DeleteOK great I will use 0.05mg per day . I have been using lemon balm tincture 30 drops per day to help my autistic daughters panic attacks and anxiety, it works very well, I give it to her in the morning and it gets her through the school day. I have been using it for about 3 months. It has not helped her cognitive skills but the teacher noted she was more cooperative and did not get so upset when she made a mistake or was corrected. Do you have any experience with using homeopathic High tryptophan ? to increase the serotonin levels in the brain ?
DeleteHi I am a physician and I wanted to know how long before you see any changes on butenamide in the autistic persons behavior, cognition , socialiazation skills. Are the effects immediate or over several weeks. Today is the first day using it .
ReplyDeleteIt should take a couple of weeks and maybe longer. 1mg twice a day is what the researchers use. They say to try for 2 months. In our case after 10 days there were clear changes.
DeletePeter, we also started on Bumetanide and today is the third day.
ReplyDeleteI haven't seen any side effects so far and diuresis is not a problem at all for my son.
If/when I have clear behavioural changes, I'll let you know.
Thank you for your response, I will try it for 2 months. Is there any tolerance that develops to either klonopin /butenamide ?
ReplyDeleteThere is no tolerance to bumetanide. At the very low dose used for clonazepam there does no seem to be any tolerance, at the usual high doses it is very different.
DeleteHi it is the 6th day using combination of bumetanide and clonazepam. My 13yo daughter seemed almost too calm , it was unnerving; was waking up very late and was laying around and seemed in a daze/apathy. Did not seemed to be interested in anything. Her appetite is greatly reduced although she used to stress eat every 1-2 hours wanted food especially snacks. Today is the first day she seems to have perked up and is smiling. She has not allowed blood draw to check her potassium levels , I have been giving her potassium chloride since she stopped eating bananas since we started this combo.
ReplyDeleteShe urinates one hour after giving her medications just once . Did you notice any decrease in appetite?
In our case there was no effect on appetite. It might be better to trial these interventions one at a time so you know what effect is from which drug.
DeleteHi do you use NAC for your son on top of the klonopin and bumetanide ? I am going to use a slightly lower dose of klonopin with the butemanide and add a probiotic with the lactobacillus rhamnosus. Is there any benefit in using Diamox and Bumetanide together or is that overkill ? I am going to use potassium supplement bid as you do to see if it will help. Many thanks .
ReplyDeleteAsma, yes I do use NAC, 600 mg x 3 or 4 across the day. NAC seems to be very helpful in those who have oxidative stress, but has a short half-life.
DeleteBumetanide seems to be very well tolerated. Diamox may have a similar effect plus some others ones, so is worth trying, particularly in people with autism + seizures. However in our case Diamox was not well tolerated, so we just use Bumetanide.
Great thanks, I am also going to try NAC. Is there a particular brand of probiotic you use?
ReplyDeleteBiogaia Protectis works well for us. Biogaia Gastrus works well for many others. Some have a negative reaction Gastrus and some to both. Start with a small dose.
DeletePeter do you know of any studies with memantine which is used in Alzheimers? binds to NMDA receptors and blocks glutamine .
ReplyDeleteHere is a recent post:-
Deletehttps://epiphanyasd.blogspot.com/2016/07/memantine-yet-another-failed-autism.html
Many thanks you are truly a God Send, I will try this probiotics, also started my daughter on a magnesium chewable today.
ReplyDeleteHi are you Peter Smith of Balancing Brain Chemistry website/UK?
ReplyDeleteDid you try Taurine,L-Theanine supplements to increase GABA?
I am giving my daughter klonopin morning and evening with the butemanide , she is doing well. She is a little more verbal and behaviors are better controlled with klonopin bid. Today is the first day on VSL#3 . Hopefully it will help the leaky gut. Many thanks
Do you have any opinion or experience with digestive enzymes for autistic kids ? do you recommend any particular brand?
ReplyDeleteWe have never used these enzymes. Some people in the Curemark CM-AT clinical trial report a positive effect. So in some people I think there is a benefit, but how significant I cannot say. If your pancreas does not work, your doctor might prescribe Creon. I wonder if the effect of CM-AT is any greater then Creon.
DeleteHi Asma,
DeleteWe used digestive enzymes years ago when my son had severe GI issues. The quality and ingredients is really important. Most people recommend Houston brand (TriEnza with DPP IV activity). They are available in capsule, chewable and powder. They are available on Amazon and other sites: Roughly $48 for 180 doses. If you go onto the Houston website they have lots of information about DE and Autism.
Best,
Christine
Hi just wanted to let you know the progress that we have had with my 13 yo daughter. The klonopin low dose and bumetanide were working well to control her anxiety,panic and aggression,however noticed that towards the late afternoon the effect was wearing it off so I was giving her 0.02 mg in the am and 0.01 mg in the afternoon. I did not notice any cognitive improvement or any change in speech. However when I started Kirkmans liquid SupernuThera and liquid DMG and after one month of use spontaneous speech improved. She was more willing to answer questions with one to two word answers rather than shaking her head "No".
ReplyDeleteI did not get my hopes up too high , I thought OK this is better. I then started the Houston Digestive enzymes once per day in am before breakfast ( thank you to the parent that recomm. these)along with the VSL#3 at night and have noticed a " big " jump in speech ( started this Oct 31st .), now addressing me as " mom" and is asking me things" Mom tie my shoes" and other little requests. I am thrilled beyond belief !!! Also started implementing GFCF diet as much as possible. She did go through some cravings for casomorphine /BCM7 but slowly getting over it. She did not like goats milk but did buy sheep milk cheese , could not find any A2 milk over here .
Read a great book : the UnPrescription for Autism by Janet Lintala
I am ordering Liquid TMG/DMG from Kirkman Labs to up the methylation. The combination of all these agents is doing miraculous things for my daughter. I would strongly recommend other parents to try these; I started at 1/3 of the recommend doses and built up over one month. I will let you all know of further improvement. We had her IEP her teacher also noticed these improvements and also attributed it to the new supplements.
That is great. It would be good to know if it is the VSL#3 or the enzymes that made the big difference. Are GI problems an issue for your daughter?
DeletePeter,
DeleteToo much of a coincidence that at least three parents have reported improvements around 31 Oct..and on probiotics. Valentina, myself and now Asma.
I hope we are not an part of a giant experiment..ET?
Hi Asma,
DeleteIt's so encouraging for us that your daughter showed rapid improvements in communication following a nutritional and digestive protocol.
Asma, if I may ask, which of the interventions that you used had the greatest impact in your opinion or was it a cumulative effect of multiple interventions.
Also, as your daughter is thirteen, I was wondering if it was the first time you used super nu thera multivitamin mix and the DMG or even the digestive enzymes as this treatment is pretty standard and usually the first parents go for. Or was it that the same intervention did not show any impact in your earlier trials. That too happens.
In my son's case, I tried the fish oils, digestive enzymes, S. boulardi, multivitamins, minerals, amino acids and even Epsom salt baths. Everything seem to work and then stopped working. I started withdrawing these one by one and even that seemed to work.
In a child who is not cognitively stagnant, assessing effects of treatments is challenging indeed.
Wishes for your daughter
Hi Peter,
ReplyDeleteI know that a lot has been written on this blog about low dose Clonazepam and that not only Monty, but other kids on this blog have responded well.
My son's doctor was not willing to prescribe it siting worry about tolerance (I get it at higher doses, but this is such a low dose). Anyway, yesterday at my son's appointment the subject came up once again about my son's anxiety/ocd that is truly interfering in his progress and quality of life. He suggested we try a low dose (1/2 of a 25mg tab)of Zoloft (Sertraline) to see if it helps. I reluctantly filled the script as I have read horror stories about Zoloft. The only thing that was encouraging is an article I read about research being done at UC DAVIS MIND INSTITUTE under Fragile X researcher Randi Hagerman. http://www.ucdmc.ucdavis.edu/publish/news/newsroom/11139
I realize that Zoloft is an SSRI and Clonazepam is in the Benzo category, but do you think it has the capability to act in a similar fashion? Also, the kids in the study were young and my son is 12. Any thoughts by you or other readers of this blog are appreciated!
Thanks,
Christine
Hi Christine, the effect of 12mg Zoloft will not be the same as the low dose clonazepam.
DeleteDoes your doctor realize just how low dose we are talking about? It is almost no dose. The smallest available tablet where we live will last us almost 50 days. If anything, you seem to need less of it as time goes by. Even stopping taking it after a few months does nothing odd, you just lose the beneficial effect. I fear your doctor will start with Zoloft and then later Prozac etc and this is precisely the wrong way to treat autism. I would avoid all the standard psychiatric drugs, most seem to end up making things worse.
Thank you Peter.
DeleteI have already been down the Prozac and other SSRI road to no avail. Years ago I even tried the Atypicals for a very brief time as I was never comfortable with them and even at a low dose caused undesirable effects.
My son's doctor seems to have one foot planted in new research (Bumetanide, Baclofen, Memantine, Monteleukast) and the other firmly placed in the old guard (SSRI's, Atypicals, stimulants).
I'm grateful that he is open to the above mentioned newer treatments, but perplexed as to his resistance to Verapamil and low dose Clonazepam.
It seems that to GET, I have to show that I am willing to GIVE when it comes to treatment ideas.
Do you think I should give Zoloft a go and see if there is any change OR do you think it is really too risky in terms of possible setbacks. I realize that you are not giving medical advice, but I value your opinion as an extremely learned parent who understands the science behind a lot of the underlying issues within the autism spectrum.
Also we just had his second metabolic blood panel monitoring for Bumetanide and his sodium levels came back a bit high (I believe the number was 35 and the top threshold number was like 30) despite the fact that I am giving Potassium supplements and he is drinking plenty of fluids. The doctor wants me to meet with someone in the Nephrology Department to discuss and also so that they are able to meet my son to better advise. My son is taking 1mg of Bumetanide 2x/day and the Nephrologist told my son's doctor that it may be too much. From what I have read that is now the standard dose. Correct?
This is all so difficult as I just want to find something to take the edge off of my son's anxiety/ocd so that he is available to take in the world around him.
Thanks so much Peter!
Christine
Christine,
DeleteI cannot even begin to understand how difficult it might be for you but only a few days of demanding and what could be anxiety ridden behaviour in my young child had me asking my husband to take few days off as he seemed to difficult to manage alone with the schools announcing a closure for some days.
I sincerely wish that you find an intervention that works for at least taking care of your son's difficult behaviour. A stable child is on the halfway mark or even higher up on the path to progress.
Christine, it seems that you are a very conscientious parent, much more than me, but still..why not try LD clonazepam and verapamil off prescription for a few days and then decide. Who knows, either of these may work for your child and unlikely to do any harm if tried only for some days..
I know it seems so against our beliefs.
Wish you and your sons good health
Sincerely
Thank you Kritika! I appreciate your words of encouragement -- truly.
DeleteI would love to try those drugs off prescription, but I am SO afraid of quality control from on-line pharmacies. In the back of my mind I always worry that the drugs may be tampered with, adding in cheap or dangerous fillers. This may sound dramatic, but we all know how greed has leached into medical care. You hear horror stories of desperate cancer patients or autism parents being duped or even hurt by unscrupulous people/companies. If I knew of a proven/reputable on-line pharmacy, I would try it. If anyone can recommend one, I would consider it.
There is something going on with my son's GI and Psychiatric drugs. Anytime he starts a new drug that is specifically targeting the brain (SSRI, ATYPICAL, Stimulant, etc...) he gets diarrhea. I know it doesn't seem possible that it would come on that quickly, but it does. My son has been potty trained for a long time and yesterday I gave him his first dose of Zoloft (1/2 tab) and this morning he came into our room and said "a warm shower". I went to help him into the shower and realized he was covered in diarrhea. This has happened many times over the years with the introduction of new drugs. Zoloft is supposed to take weeks to work -- slowly building up in the body. Anyone know why this might be happening so quickly?
Thanks everyone!
Christine
Christine, the regular dose for bumetanide is 1mg twice a day.
DeleteIf Zoloft does not help, at least you will have kept your doctor on side; you are lucky to have someone willing to prescribe at least some of what you want.
You might want to try a low dose of Propranolol for anxiety. This drug has numerous reasons why it might be helpful in some autism. Some readers of this blog do use it. Your doctor might be happy to prescribe it. It was referred to in an earlier post.
I think anxiety means different things to different people and many biological processes can lead to some kind of anxiety. I think you might also want to consider things that enhance mood, this also varies from person to person. In our case Biogaia Protectis and the broccoli powder has a positive effect.
Christine,
DeleteI acquired burinex from an online pharmacy and had the same apprehensions..who can vouch for reliability unless you get these drugs tested. In my case my son followed the pharmacokinetic pattern of bumetanide to the t and I checked patterns of diuresis with furosemide and acetazolamide which were slightly different. Even then I am not 100% certain and S you said who knows about the base or filler used.
High sodium levels following bumetanide use might be of concern and might even interfere with the process through which bumetanide affects autistim.
Christine, since I started giving my bumetanide I intuitively felt that something is not right with his electrolyte levels, not potassium alone but sodium too..some kind of imbalance. Now after reading about your results, I am thinking of suspending my trial for some time. I am not sure about the cognitive enhancements, there has been too much of background fluctuation and potassium supplementation is making my son really uncomfortable, which might even offset whatever gains might be there.
Best of luck with the propranolol.
Hi Christine, I thought I would chime in in case it is of any help. I have noticed that periactin improves my son's mood (this is a big deal for us). It is OTC, cheap and readily available. He has histamine issues so for us this is a great drug that pulls double duty. It's always worth a try. Anxiety and OCD is so debilitating.
DeleteNina
Nina,
DeleteThank you for the periactin suggestion. In the US I believe it is a prescription. I read about it and it sounds like it has many helpful effects: weight gain (my son is skinny), improve sleep, calmness and mood. Of course there are many listed side effects too, as with any drug.
--Christine
Kritika,
DeleteI am meeting with the Nephrologist on Monday (as I had mentioned, my son's doctor wants to have him monitored since his sodium levels were on the high end). If I learn anything that I think might help you in terms of electrolytes/Bumetanide I will post.
--Christine
Peter,
DeleteThanks for the Propronolol suggestion. We tried it years ago to no avail. It may be that his body chemistry has changed and it is worth another trial. It is really tough when your child is a non-responder to so many interventions. I will put Propronolol on my list. Thanks to everyone who has made suggestions! I really appreciate it.
--Christine
Peter, I also upped the Sulforaphane to 3 capsules (v. 2) of Australian company and I think I am seeing a greater effect. I am wondering if there are also some capsules with greater potency. So Christine, you might want to up the broccoli and see if better result as well?
DeleteWe have Prop and Mirtazpine as things to consider -- those seem to me additional drugs where a little bit can do wonders.
Christine, have you checked his liver enzyme cytochrome P450 profile?? It could be with those meds he has mutations in certain pathways where they are metabolized. I would tell the doctor you do,not feel comfortable with continuing SSRI experiments until you know how these are affecting his liver. Your doctor can order the Progenity Labs saliva kit and you will have results in 7 days (I am assuming you are in the US?) I hear you on the give and take with the doctors......
ReplyDeletecontinued .... for Christine:
ReplyDeleteVerapamil greatly helped my son for what may have looked liked anxiety to some but it was really more about discomfort and also sensitivity to certain stressors (esp. if it was from a person who seemed exasperated with him). He does have some situational type anxiety moments but I think the bog driver behind that version is emotional. Still working on figuring things out. i received a recommendation to try mirtazapine and 3 weeks in that is going very well.. And as luck would have it - the enzyme pathway that clears both mirtazapine and verapamil, my son has no mutations . I wish you best of luck and hope you can give verapamil a try.
Tanya,
DeleteThank you for the recommendations. I will ask my doctor to order the Progenity labs (yes, I'm in the US -- Chicago).
Peter: my daughter had severe constipation problems as a baby , her stools were like " goat pellets" she did not want to eat anything and cried a lot which I know believe was abdominal pain upon retrospection; I remember the pediatrician looking at it and said" whats this" he was shocked. She used to drink plenty of fluids. So I really do believe in the " Leaky Gut" and release of BetaCasomorphine & and Gluteomorphine from wheat and other grains causing constipation and an Opiodbrain. Was it vaccinations that caused the leaky gut? I don't know. Now that I am giving her TriEnza before every meal and the VSL#3 before the evening meal her poopy looks so much better , no more hard stools - (sorry for the visual).I really believe the digestive enzymes with DPPIV and Probiotic have cleared the opiod brain. I dont know about your child but my child has always had an addiction to IceCream. I believe most autistic children have Bowel issues , maybe gaseous distension, abdominal pain which gets relieved with the enzymes and probiotic. This is just my opinion, I dont have any major studies to impress anyone with. All I know this regimen is working.
ReplyDeleteKritika : In response I did try the GFCF diet when my daughter was 3 yo when she was diagnosed but was impatient and gave up on it , I was expecting results like in one week, now I know better. Yes I did try Supernuthera from Kirkmans labs also at 3 yo , it tasted vile and same thing I gave up on it but did not try liquid DMG. The new Supernuthera has a green apple taste which my daughter actually likes !Upon research a lot of parents have had good results with DMG , I started with a 1/4 of the dose and built up to the 1 teaspoon. I think everything since August has had a positive cumulative effect . She is no by means conversational yet but I have peace in my home. No more smashing dishes on the ground or hitting moms face or digging nails into my skin and drawing blood or trying to run out of the house on to our busy road and has started with spontaneous speech initiated by her and answers simple questions, Who, What ,Where in a very willing manner.
The only way I know if DMG did do anything is to try TMG which is more methylation and if she improves on the TMG verbally with improved learning and speech then I will know how much this remedy helps. I am using digestive enzymes before every meal, have not been able to completely eliminate Gluten or Caseine all at once doing it gradually. We have a lot of Gluten free products in our supermarket and my daughter loves sheepsmilk cheese which apparently does not produce the BCM7 . Only time will tell. I thank God every day and I thank Peter for this wonderful blog.
By the way I am no longer giving her bumetanide it was by accident, I ran out and then the pharmacies I use did not have any for 3 days , I continued the klonopin low dose and it is still working great and just kept on forgetting to pick up the Rx for bumetanide , when I did not see any difference of her not taking it and the klonopin was fine I decided to discontinue it.
Christine: If you lived on the East coast (NY/NJ/PA )of the USA I would have been happy to help you with the Rx of klonopin, however there are such strict rules about benzos. even if you hold a CDS license. Keep trying to find a sympathetic pediatrician.
Hi Peter my 13 yo daughter was doing great 100% better at school and at home everyone was so happy. I had started juicing beets, carrots, greens to help her methylation and were doing great with VSL3 digestive enzymes ,s. boulardi. On Friday she was diagnosed with malignant osteosarcoma left distal femur we were in the hospital for 5 days , now consulting pediatric oncologist, she has a grade 4 pathological fracture . Not sure whether she will survive chemo, radiation and then needs surgery.
ReplyDeleteResearch shows gene mutations in cancer and autism - some correlation any feedback on this.
Asma, sorry to hear about this. This type of cancer is associated with a number of genes, but they are not common autism genes.
DeleteSeveral autism genes like PTEN, NF1, TSC etc are tumor suppressor genes, and you would not want to be deficient in them.
You should check with your oncologist before using any other drugs/supplements because they can interfere with his therapies. But I would certainly have the conversation about whether something can be done to improve prognosis, even if it is not standard therapy. For example statins upregulate PTEN, which would benefit some types of cancer. Ask the oncologist what is downside of taking atorvastatin to upregulate PTEN.
Expression and clinical significance of PTEN protein in osteosarcoma
http://link.springer.com/article/10.1007/s10330-008-0004-4