Leucovorin & hyperactivity

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heartnbutterfly
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Joined: Tue Apr 25, 2017 8:46 pm

Leucovorin & hyperactivity

Postby heartnbutterfly » Wed May 03, 2017 8:04 am

Hi,
I'm brand new here, & I registered because I did a search online for the link between hyperactivity & leucovorin use in children & this was the only place I could find any information. It was a very old thread that started in 2012, so I thought I should maybe start a new one?

I have a 6 year old daughter with 2 genetic abnormalities - xxx syndrome & 15q11.2 microdeletion. Both come with speech & language delays & issues, & the 15q11.2 increases the risk of autism, ADHD, & other problems. She has not been diagnosed, but she does show some signs of Autism - infrequent eye contact, lining objects up, loves patterns, & odd gesturing with her hands. She was evaluated by a child psychologist last Summer & she said she didn't feel that she was on the spectrum. I have not ruled the possibility of ASD out because she does show some symptoms. She's also followed by a neurologist. She has Childhood Apraxia of Speech, as well as expressive & receptive speech delays. She has struggled with school this year, & I am holding her back in kindergarten. She is still not fully potty trained, & has accidents.

Her geneticist wanted to try her out on leucovorin & see if it would help increase brain function & speech. He told me not to tell anyone, & to just sit back & watch & wait. She started it on Feb 10, & I noticed that within about an hour of taking it she would become very tired. At about mid-dose she would start bouncing off the walls. To be clear, this child has NEVER posed a behavior problem! Perfect strangers would approach me in stores to ask if she was always so well behaved. She would stay right by my side, & always did as told. In March she had her check up, & was all over the room, flipping the light switch off & on, & the pediatrician (who hadn't seen her in a year) said that she had ADHD. She had an appointment with her neurologist a couple of weeks later, & was EXTREMELY chatty, but still difficult to understand, & very busy - getting into everything in the office. She couldn't sit still. About 2 weeks ago we saw a GI Dr, & this Dr wrote in bold writing in her notes HYPERACTIVE!

It has been since Feb 10 & I have had zero feedback from her teachers, so I finally broke down & told them that we'd given it a try & asked if they'd seen any changes. I also asked them if she was showing signs of ADHD. Her 2 teachers & para said that she is the best behaved child in the class, & that she's acting no differently than any other kindergarten student. They have noticed more talking, but she's still difficult to understand. They've also noticed an increase in hand gesturing.

She has other symptoms that started since taking it:
Stomach aches
Extremely thirsty
Headaches daily (never had them before)
Grumpy (normally happy)
VERY hyperactive at times
Other times lethargic. She has slept from 4:30 pm - 6:45 am more than once.

I've spoken to the pharmacist who said that she hadn't heard of these symptoms, but to report them to her Dr. She said he'd probably want to either lower the dose or stop them. I sent the geneticist a message about it & he said that he had never heard of any of these symptoms, but it didn't mean that it wasn't affecting her that way, to stop them, & to let him know how she was doing. Thurs or Fri of last week was her last dose. I don't know how long it takes to leave their system, but my husband & I have seen a HUGE change already. Her speech therapist yesterday noticed a slight improvement.

Are these symptoms unusual? Have any of your children experienced them? If so why do Dr's seem to be unaware? I asked both the pediatrician & neurologist when they made the ADHD comment & they flat out said no, that leucovorin was just folic acid & was not known to cause these symptoms.

Is there any literature or research studies floating around in cyberspace that shows a connection to hyperactivity or any of the other symptoms?

Thank you!!!!!

FatherOf2
Posts: 1675
Joined: Mon Mar 11, 2013 1:37 am

Re: Leucovorin & hyperactivity

Postby FatherOf2 » Wed May 03, 2017 9:33 am

My son also had hyperactivity while on Leucovorin, but also developed irritability, which was gone after termination of treatment. The doctor said just wait a couple of weeks and hyperactivity will reduce. It did, but increased irritability is a showstopper. I still give Leucovorin every now and then, but not as high dose as doctor recommended, 5mg 1x/day instead of 10mg 2x/day, which would make my son too hyper. While my son talks more on Leucovorin, it is not a social talk towards others but self-talk, which I don't like.

Mossy
Posts: 16
Joined: Wed May 03, 2017 5:12 am

Re: Leucovorin & hyperactivity

Postby Mossy » Wed May 03, 2017 4:14 pm

Leucovorin leaves the system pretty quickly.

I don't know about xxx syndrome but 15q11.2 microdeletion I've come across with respect to broader Angelman and Prader–Willi. IANAD (I am not a doctor) but I would suggest that your daughter may already have enough folate in her system and thus perhaps be overloaded by the Luecovorin as she has no issues processing it. This means you can get build ups elsewhere in the methylation pathway and overmethylate, for example in Methionine or Glutamate, which would lead to hyperactivity. Have you done folate antibody tests or are there any issues with her MTHFR genes?

A classical tell of ASD for most subtypes is the hyperactivity as there is a GABA-Glutamate imbalance (too much glutamate, not enough gaba or misfunctioning GABA A receptors being excitatory).

Given your daughter sounds pretty calm I would suggest perhaps trying a different tack? Given Apraxia a safe approach would be fish oil perhaps, SPEAK supplement, or Equazen DHA/GLA ratios.

heartnbutterfly
Posts: 3
Joined: Tue Apr 25, 2017 8:46 pm

Re: Leucovorin & hyperactivity

Postby heartnbutterfly » Fri May 05, 2017 9:04 am

Thank you both so much for your answers! Funny that you mentioned self talk, because she does a lot of that too! It seems as though she is holding conversations with herself - not even a imaginary friend or just playing with toys.

She has calmed down dramatically in my husband & my estimation. The next 24 hrs will be a test for us. We are about to check into the hospital for a 24 hr EEG, which means being mostly confined to the bed, with some movement around the room. I'm staying with her, so I will be certain to ask the medical staff to put in their notes that they saw no signs of hyperactivity if she behaves normally. We suspect absence seizures, but she also has jerky arm & leg movements with facial grimacing & vocalizations. The 2 sleep deprived EEG' she's had previously didn't catch anything, so we are hoping she will have these seizure like behaviors during the next 24 hrs. Oddly, the jerky movements have decreased quite a lot since stopping the Leukovorin.

Mossy; she doesn't have Angelman or Prader–Willi. Her 15q affects the bp1-bp2 section. Apparently it affects 5 different genes, but I only just learned that this week - it was news to me. I am going to read up on the fish oil supplements & other things that you suggested.

Do either of you know of any documentation online about hyperactivity & leukovorin? Are there any research studies about it that I can present her Dr's with?

Thank you so much!

heartnbutterfly
Posts: 3
Joined: Tue Apr 25, 2017 8:46 pm

Re: Leucovorin & hyperactivity

Postby heartnbutterfly » Fri May 05, 2017 9:07 am

Mossy; I forgot to answer your question. There has been no folate testing & I don't know about her MTHFR genes. Is this something that the geneticist should have ordered before putting her on the Leukovorin?

Mossy
Posts: 16
Joined: Wed May 03, 2017 5:12 am

Re: Leucovorin & hyperactivity

Postby Mossy » Fri May 05, 2017 11:35 am

Yes the logic behind supllemtantation is that the child is not processing folate correctly so needs a different form for their methylation pathways, often indicated by mthfr mutation or excess folate antibodies. If there are no issues with that part or the pathway it can cause overload in another part of the pathway that maybe is broken, e.g. Creating more glutamate but maybe the glutamate clean up process is broken.

FatherOf2
Posts: 1675
Joined: Mon Mar 11, 2013 1:37 am

Re: Leucovorin & hyperactivity

Postby FatherOf2 » Fri May 05, 2017 11:56 am

I agree with Mossy. Here is the link to an artcle https://metabolichealing.com/glutamate-excitotoxicity-the-brain-the-nervous-system-nutritional-solutions/ Folate can cause excess glutamate, which can lead to hyperactivity or even seizures. I am also convinced that exciting NMDA receptors through excess glutamate leads to self talk. This is based on my observations that blocking NMDA receptors by Namenda or reducing glutamate release by Lamictal redirected self talk to social talk in my son. What you really want is to convert excess glutamate to GABA because that would address social and sensory issues. My son has a GAD mutation that reduces that conversion. There is no easy way to fix it. Aspiegene, who was on this forum a few months ago, had a life long issue with that conversion process and the only thing that worked was anti-anxiety and anti-seizure drug Clonazepam. Look up his posts.

By the way, besides Namenda, another drug that redirected self talk to social talk was Galantamine. But it too caused hyperactivity while Namenda didn't. I think nicotinic acetylcholine receptors help with more social behaviors.
Last edited by FatherOf2 on Fri May 05, 2017 4:11 pm, edited 1 time in total.

Mossy
Posts: 16
Joined: Wed May 03, 2017 5:12 am

Re: Leucovorin & hyperactivity

Postby Mossy » Fri May 05, 2017 2:23 pm

Galantamine combined with Namenda is a potent combination and helped with our son (Galantamine OTC Galantamind, Namenda from ceretropic).

Currently low dose nicotine patches (3mg) have a similar social effect..

For glutamate conversion a treatment undergoing increasing analysis is using n-acetyl cysteine (NAC).

However, in this case it doesn't seem like an Gaba/Glutamate imbalance is at the core of the issues but rather it is focused on apraxia and speech versus behavioural problems like stimming and self-injurious behaviours.

One interesting intervention may be broccoli sprouts (!), which contain Sulforaphane if you get the right type: https://www.autismspeaks.org/blog/2014/ ... -need-know this can increase socialisation

What worked for kicking off speech for us was a supplement called Cytoflora, which is lyased bacteria of various types for the gut. Note this has alcohol as 20% of volume, but they have an alcohol-free kids version called NDF Shine, which is also more reasonably priced

FatherOf2
Posts: 1675
Joined: Mon Mar 11, 2013 1:37 am

Re: Leucovorin & hyperactivity

Postby FatherOf2 » Fri May 05, 2017 4:03 pm

Mossy wrote:Galantamine combined with Namenda is a potent combination and helped with our son (Galantamine OTC Galantamind, Namenda from ceretropic).

Currently low dose nicotine patches (3mg) have a similar social effect..

For glutamate conversion a treatment undergoing increasing analysis is using n-acetyl cysteine (NAC).

However, in this case it doesn't seem like an Gaba/Glutamate imbalance is at the core of the issues but rather it is focused on apraxia and speech versus behavioural problems like stimming and self-injurious behaviours.

One interesting intervention may be broccoli sprouts (!), which contain Sulforaphane if you get the right type: https://www.autismspeaks.org/blog/2014/ ... -need-know this can increase socialisation

What worked for kicking off speech for us was a supplement called Cytoflora, which is lyased bacteria of various types for the gut. Note this has alcohol as 20% of volume, but they have an alcohol-free kids version called NDF Shine, which is also more reasonably priced

Mossy, how old is your son? Does he have self-injurious behaviors and tantrums? Have you done genetic testing?

Mossy
Posts: 16
Joined: Wed May 03, 2017 5:12 am

Re: Leucovorin & hyperactivity

Postby Mossy » Fri May 05, 2017 5:21 pm

Our son is 8, he has just developed SIB in recent months along with tantrums, seems to be quite common in 7-9 year range.

Nicotine patches seem to have calmed things down for now after we reintroduced them this week, back to his usual, happy self and have seen improved speech.

Waiting on results of his genetic testing, already have ours but tough to get enough of his saliva (!) so we had to get blood.

Our main issues are apraxia and visual stimming. Only namenda seemed to slow stimming (not stop) but on off cycle now so he doesn't build up tolerance. A tough nut to crack.

FatherOf2
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Joined: Mon Mar 11, 2013 1:37 am

Re: Leucovorin & hyperactivity

Postby FatherOf2 » Fri May 05, 2017 5:27 pm

Mine is 8 too. I am surprised that yours has developed SIB only in recent months. Mine has developed it at 2.5yo, and it was due to DMG. It stayed for a few years. It would get better than worse again depending on supplements. Is stopped only after we started Trileptal last April. The neurologist who prescribed it said that he is prescribing it not because my son had abnormal EEG, but because of SIB. EEG has normalized too. Have you tested EEG?

Mossy
Posts: 16
Joined: Wed May 03, 2017 5:12 am

Re: Leucovorin & hyperactivity

Postby Mossy » Fri May 05, 2017 6:18 pm

Nope not tested EEG yet, just MRI and hearing. This is the deucedly difficult part, lots of different ASD profiles that could be caused by all sorts of subtle differences so you kinda have to mix and match, particularly as you can only approximate neurotransmitters really through a lumbar puncture (!)

The SIB is only when super frustrated and angry at not getting something he wants versus spontaneous and is punching his chin, that seems a normal(ish) reaction versus something that would show up on an EEG. Still we will get one sometime this year to round out our test suite.

Trileptal looks like it acts in a similar way to verapamil wrt SIB?

FatherOf2
Posts: 1675
Joined: Mon Mar 11, 2013 1:37 am

Re: Leucovorin & hyperactivity

Postby FatherOf2 » Fri May 05, 2017 8:02 pm

I am not sure about similarity between Trileptal and Verapamil. Both have some calcium channel blocking activity. I haven't tried Verapamil. My son had SIBs (hitting his forehead with his fist) when frustrated or when too much pressure was put on him. Someone here said that this reaction often is due to abnormal EEG in frontal cortex or something like that. My son is taking a minimum dose of Trileptal (150mg 2x/day) and that seems to be effective without any side effects so far. Interestingly, his alpha rhythm became normal too whereas before it was very weak, which is typical in autistic children (see video from Dr. Kevin Murphy about MRT, who son is also autistic: https://www.youtube.com/watch?v=RuUcXPs-u2o).


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