April 8, 2015
Guest blog by Deborah Wardly, MD
I have written guest blogs (Part 1 and Part 2) in the past about the link between obstructive sleep apnea (OSA) and intracranial hypertension (IH). We know that apneas can raise intracranial pressure, and that intracranial hypertension can be caused by OSA. I suspect that some of the symptoms of OSA can be explained by increases in intracranial pressure. My most recent paper discusses the idea that it may be the anatomy of the recessed jaw that (outside of respiratory factors which increase intracranial pressure) predisposes these two conditions to go hand in hand. More than likely it is the recessed jaw anatomy that also allows for temporomandibular joint dysfunction to also be present when OSA and intracranial hypertension exist in the same individual.
We have seen increasing rates of most of the chronic illnesses associated with OSA over the last 20 years, to the extent that I have wondered if the human jaw is shrinking more rapidly or has reached a critical point in its shrinkage. Along with adult human chronic disease, we have seen increases in childhood illness, not the least notable of which is autism spectrum disorder.
Interestingly, it has been noted that there are differences in the faces of the autistic children when compared to non-autistic children, and between low and high functioning autistic children. Scientists investigating this phenomenon do not appear to be aware of how facial structure reflects underlying airway patency, or what this might mean regarding an airway etiology of autism. Autistic children are described to have very prominent sleep problems. These problems are well known to pediatric sleep specialists to reflect underlying sleep disordered breathing (SDB). For example, 53% of autistic children have difficulty falling asleep, and 34% have frequent awakenings. These are signs indicating that autistic children have insomnia. Dr. Barry Krakow has eloquently demonstrated that chronic complex insomnia in adults is strongly associated with sleep disordered breathing, and it doesn’t seem likely that the cause in children is very much different.
There are a great many correlations between what is found in autistic children and what is seen in OSA, and there are also many findings in autistic children that could be explained if autistic children have mild intracranial hypertension from birth. For example, leptin, IL-6, and TNFα are elevated in OSA, and in autism. Accelerated head growth in the first year of life and favorable response to substances which decrease brain edema, as are seen in autism, might be explained by intracranial hypertension. Intracranial pressure in autistic children has never been investigated. I have collected the data available prior to 2013 and presented it in my recently published paper: “Autism, sleep disordered breathing, and intracranial hypertension: the circumstantial evidence.” If each correlation between autism and OSA, and between autism and intracranial hypertension is thought of as a “puzzle piece” in constructing the answer to the etiology of autism, then I have constructed over 90 pieces of the autism puzzle with the hypothesis presented in my paper. The ASD/OSA hypothesis is four-fold, and requires that: 1) the mother has SDB during her pregnancy, 2) the infant is born with SDB, 3) both mother and infant have variations of the methylation pathway which are then triggered by the SDB, and 4) the infant is prone to intracranial hypertension.
The idea is that the combination of SDB with the tendency for intracranial pressure to increase, leads to a pattern of increased intracranial pressure early on in development which contributes to autism, compounding the effect from repeated low oxygen levels in the mother’s womb due to maternal SDB. It is unlikely to present the same as the typical childhood case of intracranial hypertension, because it will vary depending on waxing and waning SDB symptoms. OSA can sometimes cause optic nerve (essentially brain) swelling in the presence of normal intracranial pressures while awake, therefore this process can be very subtle. This hypothesis takes into account most of the findings seen in autism, including the multiple various gene mutations seen between individuals.
I propose that it is not so much these mutations which cause autism, but it is the underlying methylation problems as triggered by OSA/SDB that leads to random mutations of genes, producing the wide variations seen. The ASD/OSA hypothesis may also account for the association of pesticides with autism development, in multiple ways. Some pesticides have been shown to affect the growth and development of the maxilla and mandible, and it has even been noted that the risk of autism from maternal organochlorine exposure during pregnancy is greatest during the 8 weeks immediately after neural tube closure—this is the embryological period when the face is forming. Surely pesticides can be directly neurotoxic, however if they are found to influence brain swelling then this may add to the brain edema that has already been determined to occur from OSA.
It has also been demonstrated that autistic brains are swollen. If children with autism tend to have recessed jaws that predispose them to not only compression of the airway with OSA, but also compression of their jugular veins preventing easy egress of cerebrospinal fluid (CSF), then this brain swelling becomes more clinically significant and may raise intracranial pressure.
Since the acceptance of my paper for publication, several articles were published which support my hypothesis. In 2013, Shen et al. at the MIND Institute published a study which demonstrated increased extra-axial fluid in infants who later developed autism. They concluded that this suggests an imbalance between CSF production and CSF drainage in these infants. Increased extra-axial fluid has also been seen in children with intracranial hypertension. In intracranial hypertension, the increased pressure is present in this extra-axial space surrounding the brain, pushing in on the brain, as opposed to in hydrocephalus where the increased pressure is present in the ventricles, pushing out on the brain. In December of 2012, Lemonnier et al. published a study demonstrating that bumetanide can be helpful in children with autism, improving autism rating scores and social functioning. Bumetanide is a loop diuretic which has also been used in children with intracranial hypertension, to reduce intracranial pressure. Diuretics are a mainstay of treatment in intracranial hypertension.
There is another piece of data which is more anecdotal at present. It has been reported that people with intracranial hypertension can have photophobia, and phonophobia: increased sensitivity to light and sound. (Dr. Park has also noted in his first book that he sees these characteristics in his SDB patients.) It does not seem to be generally acknowledged however, that most people with intracranial hypertension are significantly sensory defensive. I know this from knowing a great many of them. Almost 180 of them have compiled their symptoms on this spreadsheet.
If one believes this data, then 79% of patients with intracranial hypertension have auditory hypersensitivity, 33% of patients with intracranial hypertension have olfactory hypersensitivities, and 50% of patients with intracranial hypertension have sensitivity to proximity. These are very similar to the prevalence of these different types of sensory disorders among autistic children.
I believe that all of these correlations demand further investigation. It has never been determined that children with autism have normal intracranial pressures, and it has never been determined that the majority of autistic children do not have sleep disordered breathing. Miano et al. in 2010 stated that it is not possible to conclude how significant OSA might be in causing the insomnia in autism, because most autistic children do not get sleep studies. Add to this the difficulties encountered in diagnosing mild sleep disordered breathing at your average sleep lab, and it is likely to take a century before we figure out the answers to these questions. Given that it has been predicted that in ten years 50% of all children born will develop autism, we don’t have too much time.
It has been demonstrated that the degree of symptoms in SDB is inversely proportional to the AHI, therefore I believe that we need to start taking mild SDB very seriously and figure out how to diagnose it outside of the most elite university sleep centers. Given the amount of circumstantial evidence arguing for the ASD/OSA hypothesis, I think that autism researchers must rise to the challenge and rule it out formally before it is dismissed.
If you have a child with autism, does your child show the subtle signs of sleep disordered breathing? Can you hear his breathing when he sleeps? Does he snore sometimes? Does he wake frequently? Does he sleep with his mouth open and head extended? Is he a restless sleeper? Does he fall asleep during the day? Does he have a small lower jaw (“pixie” face)?
If you are an adult with autism, do you get headaches? Do you hear whooshing sounds in your ears? Do you have visual complaints (symptoms of intracranial hypertension)?
If you are a mother of a child with autism, do you have OSA or symptoms of sleep disordered breathing? Did you have signs of worsening SDB during your pregnancy?
August 28, 2013
Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders are two commonly described childhood conditions that are generally thought to be two different conditions. However, a recent study published in Pediatrics found that children with ADHD were 20 times more likely to exhibit traits of autism compared with children without ADHD. Numerous recent studies also report that a significant number of children with ADHD have untreated obstructive sleep apnea, and that the vast majority of children with autism have various degrees of sleep disorders.
A frightening thought is that we’re defining obstructive sleep apnea based on the average number of apneas and hypopneas you have every hour. In children, apneas are complete pauses for two or more missed breaths and hypopneas are lesser degrees of obstruction, also for two or more missed breaths. You’ll need at least one to two apneas or hypopneas per hour to receive the sleep apnea diagnosis. But what if you stop breathing 10 times every hour but your breathing pauses last only 1.5 breaths? You’ll wake up from deep to light sleep 10 times every hour, but won’t officially get the diagnosis of obstructive sleep apnea. Knowing what we already know about poor sleep quality and proper brain functioning, the above study results are not too surprising.
Do you have children with ADHD or autism? If so, do they have features of both conditions?
The Common Link Between Autism, ADHD, Bipolar, Depression, Schizophrenia: Genes or Upper Airway Anatomy?
March 3, 2013
Here’s an interesting study showing that there’s a common genetic basis to five common mental health conditions: autism, ADHD, depression, schizophrenia, and bipolar disease. In particular, single nucleotide polymorphisms (SNPs) in two genes involved in calcium-channel activity appear to play a role in all five conditions. This finding was reported in the Journal Lancet by doctors at the Massachusetts General Hospital.
I’ve written about many of these conditions as it relates to obstructive sleep apnea in the past. There have been many published studies showing how damaging lack of oxygen is to the brain, especially in young developing brains. It’s not too far fetched to imagine how brain biochemistry can be radically changed when subjected to poor sleep and hypoxia.
I mentioned in my last post that even one week of insufficient sleep has been found to affect gene expression in areas of chromatin remodeling, regulation of gene expression, and immune and stress responses. Perhaps the common mental health “gene” affects calcium channels as well as to determine the ultimate size of your jaws and upper airway.
May 7, 2012
Here’s a not-to-surprising study showing that obese women are at higher risk of having children with autism. Obese women were 67% more likely to have an autistic child, and about 2x as likely to have an child with another developmental disorder. Having gestational diabetes also raised by 2x a mother’s risk of having a baby with developmental disorders.
They also note that nearly 60% of women of childbearing age in the US is overweight and about 1/3 are obese. Obesity rates are rapidly climbing. Autism rates are also climbing, with the latest report showing 1/88 children having one of the autism spectrum disorders.
The authors mentioned every possible explanation (diabetes, high blood pressure, fluctuating glucose levels, lack of oxygen) expect for obstructive sleep apnea. I’ve written numerous times in the past about complications of obstructive sleep apnea during pregnancy. If you’re overweight or obese, you’re much more likely to have obstructive sleep apnea. One of the hallmarks of sleep apnea is hypoxia and major physiologic stress on the mother’s body. I wonder what the effect is on the developing baby’s brain? It would make sense to routinely screen for sleep apnea in all women, especially if you’re overweight or heavier.
If you were overweight during pregnancy, did your doctor screen you for obstructive sleep apnea?
August 26, 2011
A recent guest post on KevinMD’s blog points out that the rate of autism spectrum disorders (ASD) has increased 57% from 2002 to 2006. Currently, about 1 out of every 100 children born are thought to have ASD. It’s estimated that about 60 to 70% of ASD are from environmental factors, whereas 30-40% are due to genetic issues. The writer, Philip Landrigan, focuses on the possible environmental causes of autism and ADHD (attention deficit hyperactivity disorder), arguing that there are now over 80,000 synthetic chemicals that have been developed over the past 50 years. Many of these compounds have been shown to be toxic to developing brains in children. Currently 200 are toxic in adult humans, and another 1,000 are toxic in experimental models.
I have no doubt that many synthetic chemicals can be toxic to childen and adults, including some pharmaceutical products. In the world that we live in, with all the conveniences of modern life, we’re inundated to a multitude of synthetic chemicals, many of which are safe, but some are not.
However, one area that ASD and ADHD researchers almost never bring up during discussions is the fact that sleep-breathing problems are also progressing over time. Having smaller jaws and dental crowding leads to smaller airways, with leads to frequent breathing problems during sleep, with fragmented sleep. Lack of continuous, deep, efficient sleep has been shown to cause a number of biochemical, hormonal, and neurologic changes in the brain, usually for the worse. Countless times, I see children on stimulants for ADHD come off their medications after their large tonsils are taken out. Almost invariably, one or both parents of children with ASD or ADHD have major snoring or sleep apnea.
Clearly, not everyone with ADHD or ASD has sleep-breathing problems, and not all areas of obstruction are due to large tonsils. However, even if 1/3 of these children have an underlying sleep-breathing problem (some have suggested 50%), wouldn’t it make sense to routinely screen for snoring and sleep apnea in any child with ADHS or ASD?
May 25, 2011
Researchers were surprised that that rate of ADHD and autism have spiked over the last 10 years. ADHD increased 33%, whereas autism increased from 0.19% to 0.74% over the same time period. Honestly, I’m not surprised by these results. Here’s my explanation for the continued rise in these two common developmental disorders:
- There’s definitely more awareness of these two conditions (ADHD and autism), as well as more inclusive criteria for diagnosis
- Implementation of the back to sleep campaign about 20 years ago
- Worsened diet
- Environmental endocrine disruptors
- Less total sleep time
- increased incidence of allergies and food sensitivities.
There’s even evidence showing that common motor-skill milestones are often coming in delayed, since infants are not spending as much time on their tummies, even during the day. As expected, skull deformities (flat head) are much more common since the back to sleep campaign.
What does this have to do with obstructive sleep apnea? Here are 3 important reasons:
- Factors 2 to 6 all significantly increase your risk for obstructive sleep apnea, through either poor jaw development or inflammation of the upper airway.
- Obstructive sleep apnea can predispose to obesity, which narrows your airway even further
- Sleep-breathing problems begin during infancy, and the lack of deep, efficient sleep, not to mention frank hypoxia from apneas, can be detrimental to the infant’s brain development and biochemical pathways.
I realize that there are a number of other possible reasons for ADHD or autism (probably a combination of many factors), but not getting deep sleep can be a major barrier to proper brain development. Studies are definitely needed in this matter. Unfortunately, the medical/pharmaceutical industry is unlikely to change the status quo.
What do you think about this study? It is from over-reporting or more awareness, or is it for real?
November 17, 2010
I remember during M&M (morbidity and mortality) rounds as a resident, our chairman felt strongly that an error never occurs in isolation. He insisted that a bad outcome happens from a series of mistakes, oversights and lack of communication. Even in engineering or aviation, whenever something goes wrong, there’s usually a series of events that led to the final adverse outcome. The same analogy also applies with cancer.
Although vaccines were essentially exonerated by recent large-scale studies (showing that the rate of autism was no different before and after Thimerisol was removed), there are still many proponents of the vaccine theory. I think that there’s some merit to this possible connection, but not for the reasons that you may think. Let me explain.
You may remember in one of my previous posts, I described reading about a theory that proposes that since the Back to Sleep campaign for infants in the early 90s, the incidence of autism went up significantly afterwards. This campaign led to a 40% reduction in sudden infant death syndrome (SIDS). However, one of the consequences of keeping infants on their backs is to keep them in a lighter state of sleep. This can prevent proper memory consolidation and brain development.
Although it sounds like a feasible explanation, it’s going to be difficult to prove. Medically and politically, doctors are not going to retract this recommendation, even if it is found to be plausible. However, if you add to this the fact that modern jaws are smaller due to a more bottle-feeding and poor nutrition, sleeping on your back can definitely lessen your deep sleep efficiency.
In another recent post, I alluded to allergy shots aggravating obstructive sleep apnea, by increasing nasal congestion. Anything that causes inflammation in the nose or throat, including allergies, colds, migraines, reflux or weather changes, can aggravate more frequent pauses in your breathing, especially when in deep sleep.
The human voice box is unique in that it’s located below the tongue. This migration downwards begins at birth and continues until your 60 or 70s. Around 4 to 6 months, a space is created between your soft palate and your voice box, called the oropharynx. Only humans have a true oropharynx. Descent of the larynx is needed for complex speech and language. But this also predisposes humans to breathing problems, especially when on our backs. This is when the tongue and voice box falls back the most, due to gravity. When you add muscle relaxation during deep sleep, you’re more likely to stop breathing and wake up.
Not breathing at night while sleeping, from a brief second to 30 seconds or more, can be detrimental to your brain. The end extreme of this spectrum is called obstructive sleep apnea, but even multiple short episodes of breathing pauses due to upper airway obstruction can lead to various pathways that can lead to significant neurological impairment.
If you put all these mechanisms together, then it creates a situation where you can suffer serious brain damage. In most cases, you won’t be able to see any anatomic changes using traditional imaging studies, such as with a CT scan or an MRI. These are sub-radiologic changes that occur within the brain tissues itself.
Vaccines and flu shots, just like anything else that creates a mild infection, can cause swelling and inflammation in your nose and throat. If your anatomy is already predisposed, and you add additional variables such as back sleeping and bottle-feeding, then even an allergy attack could in theory cause changes in your brain that can mimic autism. Given that the total number of child immunizations has increased tremendously only adds to my argument. Not too surprisingly, there are also known reports of children who develop autism after a simple cold or flu infection.
Ultimately, it may not be the specific type of vaccine or flu shot, or even the specific materials that they’re made with, but rather the general inflammation causing properties of these immunizations that may be the trigger that tips children over the edge to progress into any of the autism spectrum disorders. I may be going out on a limb here, but in the big scheme of things, autism may even be a childhood manifestation of the same process that causes Alzheimer’s.
What’s your opinion on my thought experiment? Will you agree with me that autism has multifactorial causes and not just one trigger?
January 18, 2010
In the 1950s to 1970s, it used to be a rite of passage for young children to get their tonsils taken out. These days, we're a lot more conservative with tonsillectomy, and frequently, parents are told that their child will grow out of their tonsils. While this is true in some cases, there's a consequence to the watching and waiting option.
Your tonsils are lymphoid tissue that's part of Waldeyer's ring, which is a ring of lymphoid tissue made of the palatine tonsils (your typical tonsils), the adenoids (in the back of the nose), and the lingual tonsils (at the base of the tongue in the midline). In some children with overdeveloped lymphoid tissues, you'll see a communication between all four of these glands, forming a complete circle. These tissues are normally involved in educating your immune system, since everything you breathe or swallow has to go through this ring. As a result, it's expected that the tonsils (and adenoids) will be enlarged during the ages of 3-5.
However, with the shrinking size of modern human jaws, now there's less room for the normal-sized tonsils, which takes up relatively more space. This aggravates more frequent obstructions and arousals, leading to more inflammation from refluxed stomach contents and more swelling of the tonsils. The chronic negative pressure created from this process can prevent proper jaw enlargement, similar to what can occur with bottle-feeding. In many children, their snoring and sleep problems will prompt the parents to see an ENT for tonsillectomy. For children with mild to moderately enlarged tonsils that are not causing any symptoms, or those that are symptomatic but are told that they'll outgrow it, there can be permanent long-term consequences.
In children with huge tonsils, one of the reasons why they look so big is that the space that the tonsils sit in is too narrow. Taking out the tonsils can make a dramatic difference is most children, but there are some children that won't respond to tonsillectomy or only partially. One recent meta-analysis showed that adenotonsillectomy was helpful in about 2/3 of all children. But the remaining 1/3 still had residual symptoms or signs of obstructive sleep apnea. These are the children that have smaller jaws than the children who responded to the procedure.
In a recent Stanford University study, children who were scheduled for tonsillectomy were divided into two groups. One group underwent standard tonsillectomy, and the other under went rapid maxillary palatal expansion. The results were equivalent for both groups. When children in both groups were crossed over and given the other procedure, the overall results were additive. This just goes to show that one reason why you can have large tonsils that that your jaw is too small. Of course, everyone is on a continuum, and as usual in modern medicine, you're treated only if you are at the extreme end of the continuum.
This is pure speculation, but I wonder if the significant increase in the rate of ADHD in the 1980s and 1990s could be related to the dramatic decline in the rate of tonsillectomies. Furthermore, since the peak incidence of autism is around ages 3-4, it's interesting that this is also the time that the tonsils become enlarged in most children. If you have enlarged tonsils to begin with, any simple cold or infection (even vaccines!) can cause swelling which starts a vicious cycle, leading to a sudden increase in breathing problems and poor sleep. Sleep apnea by definition causes systemic inflammation and an increased susceptibility to form microscopic clots in the brain.
This is also the time (around age 4) when the voice box reaches its' final position below then tongue as it descends from its' original position behind the tongue. A space is created behind the tongue and between the soft palate and the epiglottis called the oropharynx, which exist only in humans, and allows for complex speech.
One last interesting phenomenon to point out is that in the early 1990s, parents were recommended to place infants on their backs, to prevent SIDs. We know that back sleeping lowers your time spent in deep sleep and leads to more frequent arousals.
All these factors taken together may be what's developed into the "perfect storm," leading to the dramatic rise in ADHD and autism in our current times. Obviously, there are many other dominant theories for ADHD and autism, but from a sleep-breathing standpoint, what I propose is something that definitely needs to be proven in clinical studies.
What do you think about all this? Please enter your responses in the comments box below.
November 5, 2009
I stumbled across this blog post, where I discovered an interesting discussion on the possible link between the sudden rise of newly diagnosed autism cases and the onset of the "back to sleep" campaign in 1992. This is when the American Academy of Pediatrics recommended that all infants up to one year old be placed on their backs while sleeping. Due to this recommendation, the rate of SIDS (sudden infant death syndrome) dropped about 40% (from 1992 to 1999). During this same time period, the rate of infants placed on their backs increased from about 10% to almost 70%. Coincidentally, the rate of autism rose sharply as well.
The person proposing this association (Thomas McCabe) has made it clear that infants, by being placed on their backs, have less efficient sleep due to more frequent obstructions and arousals. He sites numerous studies and papers showing that stomach sleeping results in much lower arousals, shorter length of breathing pauses, and lower rates of body movements and sighs. Another study showed that infants sleeping on their stomachs slept 8.3% more than back sleepers.
He cites various other papers that report developmental and neurocognitive delays in back sleepers in the first 6 months compared with stomach sleepers. Furthermore, McCabe states that back sleeping interference with deep sleep (slow wave sleep – SWS) as well as REM sleep. Both are important for memory consolidation and cognitive function. What he’s suggesting is the possibly that all at-risk infants undergo some sort of screening EEGs and place those infants highest at-risk on CPAP.
It’s a little technical, but take a look at his posts, as well as his e-book. His ideas may sound radical, but worth considering, in light of the fact that now in certain parts of NJ, about 1% of all boys have autism or some variation.
It’s important to point out that SIDS peaks at around 2-4 months. Not too surprisingly, this is also the same timeframe when the baby’s voice box descends and separates aways from the soft palate, allowing the tongue to move further back into the throat. This is when they go from obligate nose breathers to oral and nose breathers. During this transitional state, the baby has to relearn how to swallow and breathe.
Based on what I’m discovering every day about our health and sleep-breathing problems, I would’t be surprised if this hypothesis turned out to be true. Of course, more definitive research must be done to prove this hypothesis. Unfortunately, the orthodox medical profession doesn’t like to admit it was wrong, so it won’t even consider asking if there’s any merit to this possible link.
Our infants have been sleeping on their stomachs for almost all of known history. Although it’s hard to argue with the SIDS data and the significant lowering of infant deaths, but there’s something unnatural about changing our natural sleep positions all of a sudden 17 years ago.
Even my youngest son Brennan naturally rolled over onto his stomach while sleeping as soon as he was able to.
Should the medical community at least take another look at this issue? Please reply with your comments below.
January 27, 2014