tag:blogger.com,1999:blog-655962722302095847.post5623109425430451792..comments2024-03-28T22:33:35.806+01:00Comments on Epiphany: End of School YearPeter Lloyd-Thomashttp://www.blogger.com/profile/10173383229834614994noreply@blogger.comBlogger31125tag:blogger.com,1999:blog-655962722302095847.post-91963414472088214832015-07-09T20:29:51.922+02:002015-07-09T20:29:51.922+02:00My son is also taking Clonidine for hyperactivity....My son is also taking Clonidine for hyperactivity. I am wondering about the possibility that it is increasing his chloride uptake, cancelling out the chloride blocking of Bumetanide. I can't find any direct literature about if Clonidine increases Chloride levels. Could you reach out to the Bumetanide researchers about this possibility?JBhttps://www.blogger.com/profile/17769827238808423873noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-31068384680727604052015-07-07T07:36:11.033+02:002015-07-07T07:36:11.033+02:00It is from feedback to me and another parent from ...It is from feedback to me and another parent from the researchers.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-83751318390925274302015-07-06T22:18:16.539+02:002015-07-06T22:18:16.539+02:00Did you learn this through your direct contact wit...Did you learn this through your direct contact with the researchers, or is this published somewhere?<br /><br />Thanks!<br />JBhttps://www.blogger.com/profile/17769827238808423873noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-75342468706825375502015-07-06T19:39:58.970+02:002015-07-06T19:39:58.970+02:00We had positive effects with 1mg once a day. The r...We had positive effects with 1mg once a day. The researchers did find that it takes longer for the effect to appear in some people, they suggest keeping going for two months. I would suggest going to 1mg twice a day and try for a longer period.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-64024841132168074152015-07-06T18:41:46.254+02:002015-07-06T18:41:46.254+02:00Hi Peter. We are on day 15 of 1mg Bumetanide. I ...Hi Peter. We are on day 15 of 1mg Bumetanide. I understand that you give Monty 2mg a day. Did it take going to the 2mg dose before you saw any positive effects? JBhttps://www.blogger.com/profile/17769827238808423873noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-61538798266034337082015-06-30T14:32:03.088+02:002015-06-30T14:32:03.088+02:00It would be very useful to match each possible dru...It would be very useful to match each possible drug with the likely effect, but it seems that the results can vary widely by each person. I found it strange that the best responders to bumetanide are supposedly the people with less severe autism. It looks to me that bumetanide's main effect is actually on cognition, so I would expect it to work best on people with more severe autism. Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-85733982182117515352015-06-30T00:41:33.104+02:002015-06-30T00:41:33.104+02:00Valentina, my e-mail is: my name.last name at gmai...Valentina, my e-mail is: my name.last name at gmail. I have movies of the upgaze in my son, so you can compare. If this happened during strep infection in your son I would at first think PANDAS, but I was told by a specialist that any tic may aggravate during infection.<br />There is also a condition called “paroxysmal tonic upward gaze”. It’s been associated with calcium channelopathy: http://www.ncbi.nlm.nih.gov/pubmed/25596066<br />They say: “Later publications demonstrated that a similar clinical picture may arise from structural brain lesions, channelopathies, neurotransmitter disorders, and epileptic seizures.”<br />I think that in my son it’s been related to oxidative stress that depletes a molecule called BH4 which is involved in neurotransmitter (dopamine) synthesis. BH4 was described by Peter:<br />http://epiphanyasd.blogspot.com/2013/07/endothelial-dysfunction-oxidative.html<br />But it’s my own idea and not supported at all by medical papers. And seems like this resolved with melatonin treatment.<br />I think that in your situation there are some important question: has your son been diagnosed with epilepsy or does he have abnormal EEG, but no seizures? And what are benefits of valproate for your son?Agnieszka Wroczyńskahttps://www.blogger.com/profile/04738535364585304041noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-54296922643873098882015-06-30T00:33:51.744+02:002015-06-30T00:33:51.744+02:00Maja, thank you for details, I learn here new thin...Maja, thank you for details, I learn here new things everyday.<br /><br />That’s a pity with Verapamil side effects, I wonder if there’s anything that could replace Verapamil in terms of its GI activity, but with no risk or less risk for these adverse events.<br /><br />Peter, this proteomics study shows clearly that you are both right with your opinion on sophisticated testing vs. “trial and error” approach. Still, it would be good to have some clinical clues and perhaps NMDAR treatment is a good example. A psychiatrist involved in a multicenter memantine trial told me once that despite this trial failed, he saw improvement in some children and when asked about good outcome indicators he said that kids with intellectual disability benefited most. It’s just the opinion of one researcher, but with more data it might be possible to find something. But I don’t know if they tried.<br /><br />I was thinking about hyperactivity and antioxidants as dr Kelley wrote “An occasional immediate sign of the effectiveness of carnitine in children with more severe, non-AMD complex I deficiencies is hyperactivity (...) hyperactivity stems from increased cerebral energy availability and, therefore, that long-term benefit from carnitine supplementation can be anticipated.” This is about carnitine, but I wonder if this can happen if you improve mitochondrial function with other treatments. Your new blog entry is very interesting and I will have to rethink what the effects of melatonin really mean for my son. Agnieszka Wroczyńskahttps://www.blogger.com/profile/04738535364585304041noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-38037120604578168352015-06-26T16:05:55.922+02:002015-06-26T16:05:55.922+02:00Agnieszka, it is such a good sighn that your son n...Agnieszka, it is such a good sighn that your son noticed you among many parents and smiled... <br />We are giving the same dose of Clonazepam (my child is ten, weight 35 kg). That is the only medicine that has "survived" two weeks trial (only lost intensity after 2 weeks). I`ve read somewhere from another parent that it seems like our kids are programed to switch "safe mode" each time they progres.<br />Sorry, there is one drug that works all the time: Verapamil. Unfortunately, my child has developed rare nus effects: gingival hyperplasia et galactorrhea (autism is making fun with me...). Verapamil was my guarantee that she will behave nicely at the school. Without it, stomach ache has come back. Now I give her Verapamil only when I expect stressful events, like test in school (she refuses to do it) ...<br />I am literally Peter`s follower... Expensive medical testing doesn't seems to do any god - today's science interpretation is foggy, and it is not guarantee for so many things. He is the first one who has the guts to try (and tell the others) all the safe stuff that can help his child.<br />This is my list:<br />• Morning: 2 caps of Carnosine (by Dr Kutcher - Carnosine Extra); 100 mg ALA; 1 caps of Krill oil<br />• After snack: 1 caps of broccoli (Super Spruit); 10mg Zn<br />• Lunch time: vitamins (50mg B1, 1 tablet of Beviplex® (contains very small doses of all B vitamins), 600 mcg of Biotin, vit C)<br />• After snack: probiotik ( Flobian® (Lactobacillus plantarum 299v) + Simethicone gtt (Espumisan® - to reduce bloating); 1 caps of Carnosine.<br />• Dinner time: Clonazepam; 150mg of tangeretine (Sytrinol - NOW); 2 caps of Krill oil<br />• Sleeping time: Mg glycinat 360mg<br /><br />My child has four indicators (measure of therapeutic benefit) :<br />- psychogenic divergent strabismus (occasional)<br />- dandruff (cradle cap), <br />- scripting (most of the time she uses it appropriately as she grows, but she lives in parallel imaginary world)<br />- digestive signs: stomach ache (gases) and aphthous stomatitis<br /><br />Her sensitivity to sounds, hyperacusis (like Superman...) is not good indicator because it doesn`t shows regularity in the time of occurrence or intensity.<br /><br />So sorry for the long post,<br />Maja<br />P.s. Next step is Yurinex …<br />majadjhttps://www.blogger.com/profile/05057299082686918549noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-31834054239897257862015-06-25T20:08:07.247+02:002015-06-25T20:08:07.247+02:00Hi Agnieszka, good that you wrote me, about my son...Hi Agnieszka, good that you wrote me, about my son´¨s blood results, 2 important things, first lymphopenia and second, sodium valproat is covering epilepsy but not mood, as it is considered a mood regulator, it has lost its function in this aspect. I realized that the upgaze wasnt an epileptic event with the days, its a kind of tic or stereotipi that appeared with his last strep thorat, i want to know your opinion about this.I sent the blood results to my argentinian neurologist and he told me to ask an interconsult with an hematologist,to find out the reaal cause of the event and treatment. and he also told me that valproat can cause lymphopenia in 10% of cases.I think this is becuase valproat causes viral infections.Also think that he has already an immune system dysfunction and valproat is fanning the flames, but its my opinion.How can i get your e mail?, I go to see de neuroligst on monday 6 july.ValentinaAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-91730149798871055452015-06-25T14:22:30.227+02:002015-06-25T14:22:30.227+02:00I have seen no negative effects of NAC, even at hi...I have seen no negative effects of NAC, even at high doses.<br /><br />A large group of researchers, like those funded by the Simons Foundation, very much believe that genetics is the key to treat autism. In the long term (50 years), I am sure they are right.<br /><br />What really matter is gene expression. The people with Down Syndrome may have no relevant genetic disorders, other than over-expression of up to 500 genes. So the genes were fine, just 50% too many copies. I imagine many things can cause over/under expression of a perfectly functional gene.<br /><br />So you would have to go to proteomics, which in effect measures gene expression. This is possible today, for example here:-<br /><br />Interaction Proteomics of Autism Spectrum Disorder- and Intellectual Disability-Associated Proteins Identifies a Novel Hap1-Tsc1 Signaling Link that Controls Neuronal mTORC1 Signaling and Pyramidal Neuron Morphogenesis<br /><br />http://dash.harvard.edu/handle/1/11181106?show=full <br /><br />It is all so complicated that you are currently better off with the “trial and error” approach; even if you are very clever in 2015, I doubt you can be clever enough.<br /><br />As in my recent post on NMDAR function, you are either going to be hypo, hyper, or just fine. There will one day be a clever test, but you can find out what you need to know by first trying an NMDAR agonist and then an NMDAR antagonist. This would be fast, cheap and safe, but also falls into “trial and error”.<br />Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-2472019377730930662015-06-25T13:13:31.296+02:002015-06-25T13:13:31.296+02:00Hi Valentina,
I read your earlier comments and see...Hi Valentina,<br />I read your earlier comments and see that our kids may have more in common than I thought. My son has also upgaze previously suspected of seizures, but it turned out not to be epileptic event, ruled out by Video-EEG. I suspect other reasons. He usually has low white blood cell count as well. Low white blood cells can be associated with Valproate use, but it’s rare for lymphocytes and depends when did your son start Valproate. 2,6 is not that bad though. If you want you can e-mail me, I can share my experience, although even after several months I haven’t explained all in my son. Agnieszka Wroczyńskahttps://www.blogger.com/profile/04738535364585304041noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-53131729695333486052015-06-25T12:36:45.849+02:002015-06-25T12:36:45.849+02:00Hi Maja and Peter, thank you both for reply!
I st...Hi Maja and Peter, thank you both for reply!<br /><br />I started with 3,5 ml a day for my son (7yo, 23 kg). In our daily notes we write if he says something exceptional and since the 4th day on Clonazepam my husband, who was unaware of new treatment, wrote several things. I can now see the same kind of affection as on low dose Valproate, other people noticed this as well. So I think it’s associated with Clonazepam. He got anxious when I increased the dose.<br /><br />I can also see like Maja that he is trying to use words to tell us something. He told me what he is afraid of and he was not able to communicate such things - feelings - in the past. He is excited for sure. He is less indifferent and this means many things: yesterday he used one of the longest sentences ever to tell his speech therapist that he is not going to sit nicely at the table any more ;-) But also noticed me among many parents watching their class performance at school and smiled to me - such thing happened for the first time in his life. All these and more happened in the last month on Clonazepam, so it is possible that such dose is enough for my son (?). He also responded to Bumetanide 2x0,5mg, which is rather low dose. <br /><br />Periodic “migraine-like” attacks are the challenge now and hyperactivity. I thought the latter could be related to Clonazepam, but it started before it, in late April. Can hyperactivity be associated with more antioxidant treatments he gets now? Or is he prone to “summer-rage”, but earlier it was not seen in all his behaviors?<br /><br />It’s great to read about your daughter Maja and her best two weeks on Clonazepam. I think that if a child is able to get better at times, then it means that it may be possible to find why and try to achieve the same for a longer time. Could you share also your other treatments?<br /><br />I didn’t think about Clonazepam in so much detailed way as Peter explained here (subunit specificity), but now I wonder if genetic testing could be helpful to point the targets for treatment? I don’t mean things like whole exome sequencing which probably gives too much data to interpret them (or maybe I’m wrong), but if one knows that there’s something about “GABRA-X”, but not sure about what subunit and there are new specific treatments in the pipeline. And we talk about things that influence such important things in the child… What do you think? OK genetics is “dark art” for me and this comment too long as usual. Thank you!Agnieszka Wroczyńskahttps://www.blogger.com/profile/04738535364585304041noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-6701964298894914322015-06-24T23:16:10.423+02:002015-06-24T23:16:10.423+02:00Yes, I give her 5ml of solution. Tried with less a...Yes, I give her 5ml of solution. Tried with less and more - no effect. First two weeks was truly amazing, after that she has maintained a stable good level till today. Tried to pull off Rivotril - just to see: less spontain, less friendly, more in fog...<br />But, those two weeks... Self Confident, with great interest in everything around her, from birds, wind, to people in the street. Learning much easier; without fear of noise; trying to communicate with other kids using WORDS, trying to explain herself... Something of that is here now, but in that intensity - not.<br />From the other hand, she was excited, prone to be dramatic if she doesn't achieve her expectations. I had the impression that her wish to talk and communicate was much bigger of her ability, so, it made her frustrate.<br />In the word - excited, not anxious...<br />Majamajadjhttps://www.blogger.com/profile/05057299082686918549noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-29039636352635711372015-06-24T18:20:40.312+02:002015-06-24T18:20:40.312+02:00It is not temporary, it is more complicated, the g...It is not temporary, it is more complicated, the great fall of lynfocites started in 2011, and has been falling until now, he has lost 2.3 million lynfocites since november 2014, in 8 months, now he has 2.6.in total.I think it is very dangerous, because his defenses are as if someone with vih. In this context, i think he needs an intensive treatment with probiotics, antibacterials and antifungus.could he have pandas?Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-81403366580567825842015-06-24T16:44:58.779+02:002015-06-24T16:44:58.779+02:00"The most common cause of temporary lymphocyt..."The most common cause of temporary lymphocytopenia/lymphopenia is a recent infection, such as the common cold."<br /><br />https://en.wikipedia.org/wiki/Lymphocytopenia<br /><br />Best to wait a couple of weeks and do the test again.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-25990805598476030952015-06-24T15:14:35.179+02:002015-06-24T15:14:35.179+02:00Peter, I need help, he has lymphopenia, no ion cha...Peter, I need help, he has lymphopenia, no ion channel dysfunction, no cases of lymphopenia and autism have been reported yet. If someone knows something i would aprecitate.valentinaAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-2018696620321630762015-06-24T12:51:50.741+02:002015-06-24T12:51:50.741+02:00I understood Maja is using 5ml a day, which is hal...I understood Maja is using 5ml a day, which is half my dose. I also noted in one post that I found that anxiety followed at a dose slightly above the effective one. I think Maja's daughter is likely a similar size to Monty, so you cannot figure out the dose just based on KG. It may be that your son has a different sub unit dysfunction, but since there is an effect from this tiny dose, it is not clear. It would be useful to know the effect on typical children, I suspect there would be no effect. So the increase in anxiety<br />may just confirm you are on the right track, but need a lower dose.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-41730612029888260182015-06-24T11:47:09.371+02:002015-06-24T11:47:09.371+02:00I’ve chosen Clonazepam to reduce E/I imbalance and...I’ve chosen Clonazepam to reduce E/I imbalance and also address Nav channels, both I think are associated with what I can see in my son. But it seems not to be so simple and I will look into this further, thanks for elaborating the details. <br /><br />Finding the right dose of Clonazepam is not that easy, all above 3 ml per day (using 0,5mg/100 ml) seems to make him prone to anxiety, so it's different that in your son or what Maja wrote here.<br /><br />OT: I would think my son has a rare medical problem, but last year he was the same kid, it was just called “mood disorder” then. There are many people with severe autism and mood disorder and now I know from other parents that headache is very common in those autistic children, who are able to tell about it. Also discussed with the other reader of your blog here, that her child seems to have some similar symptoms with “afebrile fever effect”. Agnieszka Wroczyńskahttps://www.blogger.com/profile/04738535364585304041noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-63908515575888605012015-06-23T14:38:27.566+02:002015-06-23T14:38:27.566+02:00It would make sense to be tested for CBS mutation....It would make sense to be tested for CBS mutation.<br /><br />http://ghr.nlm.nih.gov/gene/CBS<br /><br />There are 150 known mutations. If your son has one, there are known therapies; but first best to confirm if he has one. Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-83782558904542774452015-06-23T14:27:36.970+02:002015-06-23T14:27:36.970+02:00Yes, I have followed Dr Naviaux and there will be ...Yes, I have followed Dr Naviaux and there will be a post on Suramin. The strange thing is just how many therapies work in 2+ mouse models. Some of these are easier to implement. It appears that you can make the NMDAR receptor work better and rescue some autism deficits by moving zinc from a presynaptic terminal to postsynaptic sites in the brain using a drug called Clioquinol. It works on mice. Those researchers do not have Dr. Naviaux's PR skills.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-21201609199413994832015-06-23T13:00:16.365+02:002015-06-23T13:00:16.365+02:00It is all very complicated, but the GABA A recepto...It is all very complicated, but the GABA A receptor is made up of subunits; these may include 6 α subunits (GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6) and 3 β subunits(GABRB1, GABRB2, GABRB3)<br /><br />Research has linked GABRA5 and GABRA3 to migraine headaches. Other research has linked GABRA5 and GABRA3 to autism and bipolar.<br /><br />GABRB3 is linked to autism, epilepsy and migraine.<br /><br />GABRA5 is the target of Roche’s new drug to improved cognitive function in Down Sydrome. RG1662, is a selective GABAA α5 Receptor Negative Allosteric Modulator.<br /><br />Roche expect to improve the E/I imbalance with RG1662.<br /><br />Catterall’s research using low dose Clonazepam was targeting GABRA2 and GABRA3.<br /><br />So it is entirely plausible that the right dose of Clonazepam may both help your son’s headaches and improve his autism (via an increase in inhibitory GABA signaling).<br /><br /><br />Specific targeting of the GABA-A receptor α5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice<br />http://jop.sagepub.com/content/25/8/1030.short<br /><br />RG1662, a Selective GABAA α5 Receptor Negative Allosteric Modulator, Increases Gamma Power in Young Adults with Down Syndrome.<br />http://www.neurology.org/content/84/14_Supplement/P6.273<br /><br /><br />A Study of RG1662 in Adults and Adolescents With Down Syndrome<br />https://clinicaltrials.gov/ct2/show/NCT02024789<br />Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-9823961435381892142015-06-23T01:02:59.175+02:002015-06-23T01:02:59.175+02:00Also, have you ever heard of a CBS gene mutation? ...Also, have you ever heard of a CBS gene mutation? I contacted someone at Arizona State regarding their polypill (for lack of a better word, I'll plagiarize you). Anytime my son gets ANYTHING with B-12 in it, he gets off the charts aggressive. So, I asked them because that's what their polypill has in it, and they suggested he may have a CBS mutation. It sounds like it creates problems with breaking down protein and ammonia gets built up in their systems, resulting in high levels of homocysteine. He DOES have the MTHFR gene C677T mutation, and the CBS gene is part of the MTHFR (I have not had time to refresh my genetics classes, so I'm sorry my genetic references are clumsy). I am trying to decide what I think of this, and whether getting him into the CM-AT clinical trial would actually BE addressing a CBS mutation, because that's what it is supposed to do. Does a CBS mutation cause low levels of chymotrypsin or am I just really that stupid?Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-75923885182036460552015-06-23T00:56:02.503+02:002015-06-23T00:56:02.503+02:00Have you been following the Suramin research at al...Have you been following the Suramin research at all? Thoughts? Maybe a blog post about it? Dr. Naviaux seems on the right track. Clinical trial in humans just to see what it does and if they're on the right track, even though he says it can't be given long term to humans. Works on two different mouse models.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-77661899096782182015-06-23T00:35:36.946+02:002015-06-23T00:35:36.946+02:00Melatonin may also have pleiotropic effects and se...Melatonin may also have pleiotropic effects and seems to affect mast cells:<br />http://dl.tufts.edu/catalog/tufts:UA005.010.057.00001: “mast cell activation seem to be partially inhibited by incubation with melatonin”.<br /><br />I don’t know if my son has (or - hopefully - had) cluster headaches, but you are right with histamine, it has been confirmed by a lab test. I am pretty sure it’s a kind of mast cell degranulation triggered “trigeminal autonomic cephalalgia”. However it does not explain all issues: my son has other symptoms at time of these “episodes” and some are immediately relieved by liquid K+ “shots”. This would not help for mast cells, would it? You once wrote that it would be good if Ben-Ari talked to Catterall about GABA E/I balance and I think here Theoharides could talk to Gargus. To make it more complicated, during such a “week with headaches” my son’s autism core symptoms diminish: no stimming and speaks better - like in fever effect. And he has unusually high ketone bodies in urine then. <br /><br />These “episodes” happen every few weeks, so when I try something new it takes a whole month to see if it prevents them. It seems better now on melatonin 10 mg, more K+ supplementation and clonazepam. Agnieszka Wroczyńskahttps://www.blogger.com/profile/04738535364585304041noreply@blogger.com