He didn't recognize the number. They called again and left a message. Then my phone vibrated with same number. Again they called twice and left a message. I hated to disrupt the entire second row and everyone behind them, but I was pretty sure this message was important. As soon as the song ended I made my way past applauding people, apologizing as I swiped their knees and stepped on their toes.
In the lobby I retrieved the message. It was Matt's dad calling from a new cell phone number we didn't recognize, but I didn't so much hear him as I heard the shrieking. Wild, panicky shrieks came one after another; hair-raising, blood-curdling screams of terror that made me want to drop everything and fly home with superhuman-mama speed. The volume was so loud that I hurried outside, worried that the screams now echoing through the empty lobby would make their way through the double doors and into the concert hall.
I recognized those shrieks, only they were older and more violent than ever, terrifyingly so. It had been over three years since I had last heard them. I was at the same time angry with Naomi and filled with compassion for her, sorry that Matt's parents were dealing with this, and embarrassed that it had happened again. I erased the message and dialed my home only to hear the continuing cadence of panic and anger, terror and rage ringing out so loud I had to shout to be heard over the phone.
I asked them to give the phone to Naomi but she swiped and punched and kicked with such force that they couldn't get near her. I asked them to put me on speaker phone and I tried to out-shout her, "Naomi! It's Mommy! NAOMI!! Calm down and listen to me!!" But I might as well have been shouting down an erupting volcano. Naomi was gone. She wasn't in that kicking, flailing, red-faced, shrieking body anymore. I knew, because I had fought that demon before, and that girl was not my daughter.
Matt's dad was bewildered. He had asked her to come inside for bed. That was all. And she had had plenty of warning. But she had dug in her heels. It started as stubbornness and anger. She was culpable for that wrong response, but the downward spiral that followed without warning I recognized as something far beyond her control. They had had to drag her inside as the whole neighborhood looked on, and they barely got her one-hundred-pound frame in the back door before she collapsed in her violent tantrum of nuclear proportions.
I asked to talk with Matt's mom. "Try talking to her gently," I coached, "Ask her if she thinks she's having a reaction. Tell her you think she'd feel better if she had an epsom salt bath."
I couldn't say much more because it was nearly impossible to yell loud enough to be heard. I thought about driving straight home, but I knew Matt would be worried, not knowing what had happened. I'm not terribly tech savvy, and forgot I could have sent him a text message. I decided to slip back in at the next applause, and I handed Matt a written synopsis on the back of a ticket stub, "Naomi is having a horrific meltdown."
If you're not familiar with autistic meltdowns you might assume I am a lenient parent, that I encourage tantrums by not disciplining them or by giving in to them. So let me quickly say: please educate yourself. Naomi has never once been rewarded for a tantrum: quite to the opposite, we dealt very strictly with them when she was little, before we understood them. The autistic child does not tantrum to get their way. Though it may initially begin as stubbornness, it quickly escalates out of their own control. They tantrum because they must. And no, a spanking will not cure it.
I sat, bewildered and worried, through the last four songs of the concert. I watched the fingers move and heard the notes, faintly, but my mind was racing through every food Naomi had eaten that day, any new chemical exposures she may have had. We knew these meltdowns were usually caused by exposure to foods containing large amounts of phenols, a chemical found naturally in many fruits and vegetables, but in especially high doses in artificial colors and some preservatives such as sodium benzoate.
Three years ago, when Naomi's diet had been full of "fruit" snacks, yogurt, Nestle Quick, fruit loops, soda, and other dye and preservative-containing foods these violent meltdowns often happened multiple times a day. She had been plagued by terrible headaches that were only worsened by Tylenol. She had had stiff, sore joints. She had been a miserable child, overwhelmed by the world around her, in constant pain or discomfort, withdrawn into a world of her own, then suddenly lashing out with violent, unpredictable force at the tiniest of disruptions.
But we had cracked that code. We had pinpointed phenols as the culprit. We had eliminated all artificial food dyes, sodium benzoate, Tylenol (which is itself a phenol), and even some natural foods high in phenols such as red wine vinegar. And she had vastly improved. The headaches disappeared, the joint pain subsided, and the angry, violent tantrums ceased completely. The dark bags under her eyes disappeared. She slept better. Just like that she was a different child, and every medical professional I mentioned this to looked at me like I'd grown three heads. The humored me, but I knew I was right.
Then tonight it reappeared, the child who might as well have been demon possessed. What went wrong? There was nothing, nothing new that she had been exposed to. She had eaten the most bland, tried and true foods. We hadn't gone swimming (chlorine exposure causes the same symptoms), she hadn't tried a new sunscreen, a new lotion, a new deodorant, nothing.
I was at the peak of mental frustration when I looked up at that guitar player in front of me and the idea crashed into my brain like a freight train: what if she's unable to process the chemicals released by her own anger? What if the only catalyst for her meltdown was her anger itself?
When we arrived home Naomi was almost back to her normal self. After 45 minutes of flailing, wailing, and shrieking, when Matt's mother had suggested to her that she might be having a reaction, she began to calm herself. She sang songs to her pet gerbil while she calmed down. When the epsom salt bath was ready, still feeling a bit stubborn, she claimed she didn't need it. She remained a bit on-edge the rest of the evening, arguing with Grandma that she ought to be able to sleep in her dirt-smeared pants if she wanted to. But by the time for tucking-in she gave her Grandpa a hug, told him she loved him, and shed tears of remorse when I explained how her tantrum had affected our evening out.
She didn't remember much of the tantrum itself, only the anger that led up to it. She said she just felt like she had to scream, like she had to kick and fight, her body compelled her to. She didn't feel like she was in control of it at all. Looking back she felt ashamed.
More determined than ever to find answers for my daughter I have spent the last few days at my computer like a madwoman giving myself a crash course on biochemistry, the degradation pathways of catecholamines, and the three phases of liver detoxification. And I think I've found it. I'm almost sure I have.
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We know that Naomi, and many children with Autism lack the proper metabolic pathways to excrete phenols efficiently.
From Wikipedia: "Rosemary Waring a reader in human toxicology at the School of Biosciences, University of Birmingham, was the first researcher to produce scientific evidence suggestive of abnormal sulfur metabolism affecting people with autism spectrum disorders. Her findings suggest that people with autism present with consistently lower levels of circulating plasma sulfate and higher than normal levels of urinary sulfate than non-symptomatic controls (reflective of excessive 'dumping' of sulfate into the urine). Follow-up work has suggested that people with autism also present with higher than normal levels of other sulfur-related compounds, including sulfite. Waring found that most people with autism conditions have a deficiency in a key detoxification pathway involved with sulfation. The enzyme involved is phenol sulfur-transferase (PST), which is essential to the process of breaking down and removing certain toxins from the body. Waring postulates that symptoms arise from an inadequate supply of usable sulfate ions, rather than from a deficiency of the metabolic enzyme itself."
In other words, phenols must have a sulfate attached to them by certain enzymes in the liver in order to make them water soluble, and excretable by the kidneys. If the phenols aren't properly sulfated they will build up in the blood. I'm not completely sure what they do there, but I think they may want to bind with organic acids where they are able to react with them, which might conceivably affect the krebs cycle or glycolysis pathways. This is one area I would like to research more. Whatever these excess phenols are doing in the body, it isn't pretty to watch a child with phenol toxicity suffer from headaches, joint pain, dark bags under the eyes, inexplicable fevers, irritability, and irrational tantrums of nuclear proportions.
But is it possible that anger itself, and that well-known fight-or-flight response can trigger phenol toxicity? Yes, I am almost certain of it, and here's why.
The chemicals released in a fight-or-flight response are called Catecholamines. Dopamine, epinephrine (adrenaline), and norepinephrine (noradrenaline) are the three major catecholamines released in fight-or-flight, and they are all phenols. These phenols are then degraded within a few minutes by Monoamine Oxidase and Catechol-O-Methyl transferase down to other forms of phenol abbreviated MOPEG and VMA as illustrated below from Neurotransmission: The Autonomic and Somatic Motor Nervous Systems.
Ultimately, these phenols (MOPEG and VMA) need to have a sulfate added to them by enzymes in the liver in order to be excreted by the kidneys just the same way that phenols from diet do. Without adequate sulfating, these phenols will build up in the blood.
If I'm correct here (and I'm no chemist so I'll admit I might be wrong), this does not just mean that the child will suffer from excess phenols, but that build-up of these phenolic metabolites will slow down the further degradation of these catecholamines. This would mean that dopamine, epinephrine, and norepinephrine themselves would stay at extremely high levels for long periods of time in a child who is not able to excrete their degraded forms quickly and efficiently.
While these catecholamines might be degraded and excreted within a few minutes in a healthy individual, for a child with impaired sulfating, these fight-or-flight chemicals may stay at extremely high levels for forty-five minutes or an hour. If this is true, this child very literally cannot calm down.
No amount of discipline or reason will calm the child in this physiological state. They must yell, they must fight, kick, scream, thrash, and shriek as these chemicals increase their heart rate, their blood flow increases, their blood pressure rises, their energy stores are released, and their attention narrows.
Akathisia "is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless." According this Wikipedia article, "It was discovered that akathisia involves increased levels of the neurotransmitter norepinephrine, which is associated with mechanisms that regulate aggression, alertness, and arousal." And again, from this article, "Severe akathisia can become a very harrowing experience. Jack Henry Abbot (1981) describes the sensation:
...[It comes] from so deep inside you, you cannot locate the source of the pain … The muscles of your jawbone go berserk, so that you bite the inside of your mouth and your jaw locks and the pain throbs. … Your spinal column stiffens so that you can hardly move your head or your neck and sometimes your back bends like a bow and you cannot stand up. … You ache with restlessness, so you feel you have to walk, to pace. And then as soon as you start pacing, the opposite occurs to you; you must sit and rest. Back and forth, up and down you go … you cannot get relief …"
Rosemary Waring demonstrated that many children with autism lack adequate sulfating pathways. She saw that children who ingested phenols in the form of food additives suffered symptoms that some have called phenol toxicity. She suggested that limiting dietary phenol intake in these children would improve symptoms. I have found this to be true with my daughter.
Though some research has touched on the roles of catecholamines in autism, like this study which found increased levels of catecholamines circulating in the blood of people with autism, and this study which found altered patterns of excretion of catecholamines and their metabolites in autistic children, and this rather frustrating study from as recently as 2013 which concludes that "neurotransmitters might play a key role" in autism and suggests that further research is needed, I cannot find anyone who has suggested that it is the phenolic properties of catecholamines and impaired sulfation that may underlie their altered metabolism.
I propose (as I cannot see anywhere else on the internet that this has been proposed, if I am wrong, please let me know) that children who lack adequate sulfating pathways also suffer from not only phenol overload but catecholamine overload when the fight-or-flight response is activated and these chemicals are not efficiently excreted because of impaired sulfation pathways. If I am correct, this is a plausible explanation of the chemical basis for the autistic meltdown.
My experience with Naomi seems to bear this out. When sulfate is absorbed into her skin in an Epsom salt bath, the readily available sulphates make it possible for her to quickly and efficiently excrete phenols. Twenty minutes later, she emerges from her bath as a new child: no headache, no joint pain, no stomach ache; not irritable or irrational, but bright and sweet and healthy as could be. This is equally true whether she is experiencing phenol toxicity from FD&C red dye 40, or from her own fight-or-flight meltdown.
There are many more questions to ponder here: why exactly do so many children have impaired sulphation? Has something made the enzymes sluggish? Are they wasting sulphate in the urine so that it is not available for the enzymes to use?
Beyond this, I know that my daughter adversely reacts (big time) to many common drugs that are not phenols, but are processed in phase one liver detoxification through an enzyme called Cytochrome P450 3A4 (CYP3A4). I have personally witness violent meltdowns in response to:
-Midazolam (Versed)
-Fentanyl
-Dexamethasone (Decadron)
-Diazepam (Valium)
-Acetaminophen (Tylenol)
-Lidocaine
-Dextromethorphan (cough suppressant DM)
-Dexamethasone (Decadron)
-Diazepam (Valium)
-Acetaminophen (Tylenol)
-Lidocaine
-Dextromethorphan (cough suppressant DM)
All of which are processed by CYP3A4 in the liver. I don't know whether she has a genetic modification of this enzyme, or whether the Pregnane X Receptor which is supposed to cue this enzyme into action is the problem. Looking into things that downregulate PXR, which would ultimately lead to poor processing of these drugs is also fascinating, including inflammation. Let's not get into everything in our environments that could cause inflammation.
And so I have a lot left to think through, but I think I know this: my child who cannot tolerate dietary phenols also cannot tolerate the natural catecholamines released during the fight-or-flight response. Adding sulphate to her blood stream as epsom salts absorbed through her skin gives her almost immediate (within ten to twenty minutes) relief of all symptoms. I would also like to look at other ways to help her cope: dietary supplements, deescalating conflicts, calming techniques, and such, but understanding the chemical reactions are the basis for all of this, and something that is all too often overlooked in the study of autistic meltdowns, at least as far as I can see.
I need to add that Naomi is known to have both kidney and liver disease (polycystic kidneys and congenital hepatic fibrosis) that are not currently well understood in the medical world and are caused by a genetic mutation that had not yet been identified in Naomi. It is possible that her particular metabolic challenges are a result of her genetic defect and could not be applied to the autistic community as a whole, but if Dr. Waring is correct that a majority of autistic children have impaired sulfur metabolism, then I think it is reasonable to conclude that impaired catecholamine degradation may lie at the heart (or at least be a part) of the autistic meltdown.
While I am not a chemist, I did talk this through with my dad who holds a PhD in Chemistry, and he believes this is plausible. If anyone out there who has a background in biochemistry would like to challenge or confirm my musings, please do so, we could only both benefit from your insights.
