Seizures And Sleep Apnea, Revisited

I just came across an article in the NY Times that described a condition called SUDEP (sudden unexplained death in epilepsy), where people with seizures can die in their sleep. It’s throughout to be due to loss of protective reflexes and possibly obstruction. This article brought back memories of the time I was on my neurosurgery rotation and a young woman with seizures just died in her sleep. It was a very emotional and distressing situation for everyone involved, especially when I had to tell the family about what happened. In retrospect, she probably died of SUDEP, and come to think of it, I vividly remember that she had a very narrow face.

What I found interesting was the fact that when it happens, people are usually found lying on their stomachs. References were made to SIDS (sudden infant death syndrome) and its’ many similarities. Unfortunately, it goes on to describe the typical genetic causes for this condition, without exploring the upper airway issue at all.

If you Google sleep apnea and seizures, you’ll see tons of papers and references showing a highly significant association between these two conditions. Just to review, here’s my take on this link:

Seizures are thought to develop when abnormal connections form between nerve endings in your brain, leading to a short of “short circuit.” Many of the medications that are used to control seizures essentially calm or lessen the excitability of the brain’s nerve cells. Even the newer vagal nerve stimulation technique works by enhancing the parasympathetic nervous system (which controls the vagus nerve). Anything that helps to calm or relax your nervous system can also help to prevent seizures.

Not too surprisingly, numerous recent studies have shown that untreated obstructive sleep apnea can cause brain damage in a variety of different ways, including multiple mini-strokes, major strokes, decreased brain tissue density, decreased brain volume, diminished brain functioning, and diminished reflexes. All these effects were found to occur in critical areas of of the brain, such as areas that control memory and cognition, executive functioning, breathing, autonomic nervous system control and motor movements.

I’ve also noticed that every patient that I see that has a seizure diagnosis has very narrowed upper airway anatomy, and usually can’t sleep on their backs. More often than not, parents of people who have seizures often snore heavily and likely have untreated obstructive sleep apnea. We also know that untreated obstructive sleep apnea can significantly lower your seizure thresholds, making you more susceptible to experiencing attacks.

What all this implies is that if you have an underlying sleep-breathing problem, whether or not you have obstructive sleep apnea, you’re going to be more prone to various degrees of brain disfunction and miswiring.

What do you think about my theory? Should all epilepsy patients get screened for obstructive sleep apnea? I’d like to hear your opinion.

Please note: I reserve the right to delete comments that are offensive or off-topic.

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47 thoughts on “Seizures And Sleep Apnea, Revisited

  1. Given that the association between seizure frequency and sleep apnea has been known since the early 80s (where one doctor treated a patient with sleep apnea, giving him a tracheotomy, which also stopped his seizures) and that the link between sleep and seizures has been assumed since the time of Hippocrates (literally, he wrote a book on the topic), it would appear that not testing a patient for sleep apnea (especially in the case of late onset epilepsy), or at the very least inquiring about the possibility, is irresponsible.

    When I first started having seizures (which were in my sleep), my wife suggested that it could be to do with the fact that I “gasp” in my sleep. The doctors (3 different neurologists) ruled it out – one of them because I was “not fat enough” for sleep apnea. At the time, I was unaware of all of the published research on the relationship. It was very frustrating (to say the least) to find out that my wife’s diagnosis trumped that of 3 different neurologists. After years on anti-epileptic medication (which was hell), and another few years on CPAP (which cannot be considered a long term solution), I had MMA. I have been seizure-free, with no medication, for close to 3 years (initially my seizures were one every six months, which increased to once a month, and maxed out at two in one week – all grand mal, all in my sleep).

    Why ignore the evidence? Every patient with late-onset epilepsy should be questioned about their sleeping habits and possible snoring/gasping.

    Dr Beth Malow at Vanderbilt U is undertaking a randomized controlled experiment to determine whether there is any placebo effect due to the CPAP. I am confident that she will conclusively prove the relationship – which will help to avoid other people having to have inane conversations with neurologists about the difference between “evidence” and “proof.”

  2. Mr. CAllan,

    Thanks for your candid response. Granted, not all seizures are caused by sleep apnea, but even if it’s 25% or 50%, it would make sense to at least screen for it. Questionnaires can help to find some sleep apnea, but you can be completely asymptomatic, not snore and be thin and still have significant sleep apnea. A home test is a simple procedure that any doctor can order.

    You can also have significant numbers of breathing pauses at night and not have any apnea. Something to think about.

  3. I believe they should. when i was 8 i could remember shaking a lot in my sleep and now i look back and realize i was probably having a seizure. I never had a seizure awake until the age of 10, i had a seizure in church and i was hospitalized for a few hours. In the ninth grade i had problems sleeping, i would wake up in the middle of the night with my heart racing and i had no idea why. My uncle heard me sleep and recorded my snoring so that i could hear how loud it was, when i heard it i didn’t believe that was me. the problem plagued me for a while so i eventually went for a sleep study. The results showed i had sleep apnea, a couple of months later i started using a cpap and noticed i slept much better and had more energy. Currently i haven’t been able to use my cpap because i get stuffed up at night. Although i had my adenoids removed and a turbinate reduction im still stuffy. But back to the topic i believe that anyone that has had siezure shold get tested for OSA and the people who have OSA should be aware that their at risk for a seizure.

  4. You may want to consider undergoing CPAP titration first to see if your possible siezure activity still remains while on an optimal pressure. Good luck!

  5. I believe the same. My fiance’ has unexplained seizures. No neurological concerns from any of the tests. It was automatic put on medication and anyone has refused to look further as a matter of fact because the seizures still occur they increased his mg and the seizures are closer together. He suffers from sleep apnea. I have to move him to get him to breathe. This will be something I will be looking into further. Your article makes sense.

  6. I know this is a blog for human health issues, but my pug has really bad sleep apnea and just started having seizures the last year or so. They are always while he is sleeping and they stop as soon as I can get him to wake up and start breathing again. The blanket denial of any correlation between apnea and seizures is frustrating. Even vets are unlikely to correlate the two. And why can’t they be related? Doesn’t apnea cause a lack of oxygen to the brain? Can not seizures be caused by a lack of oxygen to the brain? Anyone else see the commonality here? Evidently everyone but doctors who would rather pump us all full of chemicals than actually reveal an underlying cause and treat that instead of the symptom!!!!

  7. I believe my seizures were caused by sleep apnea. I am 31 yrs old and had my first grand-mal seizure in feb of this year. I have had every test you could think of and they all come back normal. I had a second one at the end of march. Just after the second one i demanded that my doctor do the home sleeping test. My husband said i “breath funny”. As i had every other test i wanted to see if 1: i did indeed have sleep apnea and 2: if the lack of oxygen to the brain could be a cause for my seizures. Turns out i do have mild sleep apnea, I stop breathing only 7-10 times a night, but my oxygen levels drop down to 80% and sometimes lower. I now have a cpap machine and am on carbomazipine for my seizures. I have had no problems since march. What are the chances that all other tests came out normal except the sleep test? I have had this breathing problem all my life, after 30 years of my oxygen levels dropping, it only seems natural that some sort of problem would arise from it.

  8. I have had epilepsy all my life but this is mostly under control during daytime hours
    I am at present taking 14 tablets a day for the epilepsy . A few years ago i was told
    i had apnea and was given a cpap machine wich has helped but not stoped the
    problems i have with sleeping . During the night i still take seizures wich i cannot
    help feeling are linked to the apnea as they leave me more confused than before
    and sometimes i am unable to put a sentence together for half an hour . This never
    happened when i was younger and before i had apnea . This situation is very
    frightening exhausting and alarming . I do hope someone can find an answer

  9. I am a Physician with sleep apnea. Recently at age 68 I had my first grand mal seizure. I have had several head injuries – mostly mild (falling off a horse) but one serious (automoblie accident) – I also learned that my CPAP machine has not been working well for quite some time. Both of my doctors think that this is all related but it is clearly complicated. i have also apparently had “absence” seizures for a few years (since the car accident). So it is all somehow connected but I amnot sure exactly how. I hope this wil be helpful to others.

  10. Interesting reading all this. I turn 50 in January. Had my 1st grand mal seizure about 2 years ago. Rushed to the hospital, had all the tests–no diagnosis. After having a seizure every month or so, sometimes twice in a night, and reading online, I have self diagnosed this as OSA. So I use a dental device, sleep on my back and stay alert at night, with my husband’s help and can usually avoid seizure attacks. Medication is out of the question. I drink alkaline water all day, take high quality vits and eat healthy organic vegs and fruits mostly. Have been seizure free for 8 weeks now.

  11. born in feb 1961. Never sleep walked before using cpap I was put on in feb 2012.
    6/8/12 I sleepwalked out of a semi like it was parked while wife was driving 60mph. Got concussion 3 frac ribs frac pelvic crushed rt wrist and road rash. After healing I started using cpap again in August 2012. Found I could be compliant with min 4 hrs usage for Truck driving. I was working may way up to using cpap all nite. 10/1/12 I felt disoriented that morning. I laid down without cpap to clear my head. About 5min’s later I had a seizure which lasted about 40min’s. You I can’t drive for a year after a seizure. No job no health ins. Some side effects I have found hypoxia,air embolism, bloating, change in skin color. You probably know side effects. And enormous amount of money being made from this industry. 1 case of fraud. 50 investors took for 4 million to build sleep centers. CPAP destroyed my life and was told 11/8/12 I’m to high a risk to rehire. Can’t find many post like mine. Maybe they are being deleted and passed of as other health problems. Even web site to donate cpap’s to people that need them.
    Because so many people don’t use the equipment.

  12. Yes! I as well believe seizures can develop from a sleep apnea problem. My son is 9 years old. Very recently, he had all the symptoms of a grand mal seizure upon awaking. Research is telling me that becsuse his CT, MRI, BLOOD WORK, AND EKG all concluded normal, that this must be apnea related. There has been past instances where he walks and talks in his sleep and he snores heavily. He has always had to sleep with his head propped up with a fan blowing directly on him for comfort. We go tuesday to childrens hospital seizure center for an EEG and consult with specialist. I will definately be requesting a sleep study be preformed. Thank you all for your info and comments here as it has helped me prove my therory

  13. Yes! i definately feel sleep apnea can cause seizures after our experience! I have a 9 year old son that talks in his sleep, walks in his sleep, snores, and always sleeps with his head propped up with a fan blowing directly on him all seasons of the year. Recently, I caught him seizing during his normal waking school hours. His symptoms were all those included in a grand mal seizure. His CT, MRI, blood work, and EKG all came back normal. We have an appointment tuesday with childrens seizure specialist for an EEG with imediate consultation following. I will be requesting a sleep study be our next step! Thank you all so much for this blog as it has helped me prove my thoughts about it over the last couple weeks.

  14. During my birth, my breathing was cut off momentarily, though not enough to have any immediate effects, I don’t think. At six years old, I had a seizure during my sleep, sometime in the early or mid-morning, around 6 or 7am from what I was told. I went on some medication following the event, and, after a year of no activity, was taken off of them.

    I have had trouble breathing through my mouth for the majority of my life, and it wasn’t until I was about fifteen years old that I was informed of certain treatments, though I never followed through on receiving any of them. It was when I was twenty-two and a half years old, in 2005, that I had my first seizure since when I was six. Since then, I have been experiencing clusters (always clusters) of seizures ranging in gaps of, at the shortest, six weeks apart, to, at the longest, three months apart. They almost solely occur, or begin, in the morning, either just before or just after I wake up.

    More and more I have been having trouble, and in certain cases feel like I’m in a struggle to, get a good night’s rest. I wake up 2-3 times a night to urinate, which I feel is directly related to my medications, which by common name are Kepra, Lamictal, and Vimpat, and their common effect of dehydrating the body of it’s water more quickly. Thus, I have to drink even more water and, further, urinate more. I have been told of my heavy snoring at night, and sometimes I find myself waking up at the last moment of a strong gasp for air. Both of these, I have been told or figured out on my own, are common signs of sleep apnea.

    I’m more than ready to lower the mg amounts of my medications, my first priority being the Lamictal, which can be related to insomnia and sleep disturbance.

    I am scheduled for a sleep study at the end of this month, and I hope something good will come of it. After eight years of surface searching, quick conclusions, made by my family, mostly, and too much dependence on my doctor to look more deeply, I am ready to look for myself.

  15. I have seizures in my sleep. Had my first at 56, was rushed to the hospital. All the tests can back normal. Was put on drugs by the neurologist, they all made me feel weird. I had a seizure while on one of the drugs so, we decided to stop the drugs. One of the doctors ordered a sleep study. I went to the sleep lab and started a sleep study, I had only been there a short time and they came in a put me on a cpap machine. I have OSA and still struggle with night time seizures. My dear wife took a T-shirt and made a pocket in the middle of the back and put a tennis ball in it to keep me from sleeping on my back. Last night, I removed the tennis ball because I was tired of it. At 3:00 a.m. I had a seizure while on my back. My wife heard me and tried to wake me. I don’t know if not sleeping on my back helps or not, but right now I’m trying the T-shirt with the tennis ball and of course, I faithfully use my cpap.
    I continue to search the internet for any new ideas or any new research.

  16. I have undergone surgery for RIght Frontal Meningioma 11-12 years before which might be the cause at that time for the seizure. But my seizure continued till last year when I started having parasomnia and consulted new neurologist, who established correlation of OSA with the seizure I was having. Now I am using CPAP daily and now having significant reduction on ANti-epileptic drugs and much better health and life.

    Hence I strongly recommend for sleep study for all patients undergoing nightmare or Seizures & EPilepsy…

    All the best.

  17. Hi

    I had intractable epilepsy and at the age of 30 years underwent a brain surgery and i was totally cured . it has been more than 14 years iam not taking any medicine. I was operated in 2000 , in 2004 i stopped taking medicines .
    Iam now having high BP and Sleep apnea

    will i get epilepsy again

  18. I am currently 49 years old.
    During my puberty years I was diagnosed with petite mall seizures. The symptoms started in the ninth grade, Signs were showing but I wasn’t saying anything. I didn’t really understand but I knew something wasn’t quite right. In the tenth grade my energy levels dropped and I no longer was interested in athletics. My body wanted to sleep, conversations slurred and un completed. My period stop, I became highly agitated, had the shakes, vision would turn black then I would drop to the ground. I would space out. Sometimes I would even get what was called a natural high where I would start cracking up and then fall asleep afterwards. For the first several years I was on Depakote, Tegretol. My twenties I had children and a majority of my symptoms stopped. I was no longer on meds After few years in high stress I started having symptoms. Tingles running through my arms, and still small dizzy spells of losing balance. A neurologist ran some test working with my breathing that did show abnormalities but I was no longer put on meds . He believed I was misdiagnosed with epsalepsy and I had a breathing problem.

    At this point I’ve just recently been diagnosed with mild sleep apnea and seizures only in my sleep during a 48 hour EEG no actual seizures were detected specially during the day. At night there are a few spikes which are considered abnormal. Looks like sleep apnea related.
    The problem is the trust . I don’t really know if all that I’m being told is in truth. There is the issue of the neurologist making sure that he is covering himself medically for that just in case situation. Why because of seeing possibilities is the reason my cdl is being medically blocked.
    This is very hard for me because I’m still going to through the transition and Medical off my job which I’ve been a school bus driver for 13 years.
    At this point I’m waiting for another test and have been referred to a pulmonary doctor I have to except the fact that I am the one who needed medical advice . I can honestly say I have been dealing with some symptoms for a few years on and off . I have exhausted myself with trying to fix the problem because they were enough similarities that I was concerned I was having possible seizures. I looked up diagnoses and it does match the symptoms for partial seizures. I’ve also looked up results for sleep apnea extremely similar.The doc wanted to start me on oxtellar xr (oxcarbazrpine) time release. Not taking them..can cause high suicidal risk. I am depending on Jesus for healing, and I will go all natural as much as I can. The blog is helping . I wish you all the best and me too.
    If anyone has more insight please feel free to give feed back. Again I am still in the stages of taking it all in .

  19. Female 65 yrs: I think I’m going through this, I think. I had petit mal at age of 15. A year after I had grand mal. After playing with different meds (narotin, Dilantin & phenobarbital) pheno worked! I had another seizure at 32 y but I had not slept all night & forgot to take my meds. That’s what I was told. At 55 I was put on lamictal because the epileptologist said phenobarbitol was bad on my bones. Then I had grand maps in September 2008, Feb 2009, February 2011 (3 in one day), September 2014 & February 2015. The day before yesterday I forget my night dose. I couldn’t remember the rest of the day. My husband & daughter said I didn’t make sense so they suggested I go to bed. I did.
    I got a Fitbit July 2014. Finally understand the sleep log. Over the last few months I’ve been monitoring my sleep using sensitivity setting. According to the log, I get less that 4 hrs sleep; average is 2 hrs. I pushed to get the sleep apnea test from my doctor. I have it Monday (4/13/2015).
    Since phenobarbitol worked, I want to go back to that medication. I’m hoping the sleep apnea test helps.
    What’s your thoughts? I’ll send you the results.
    Thank you!!

  20. Since I used cpap I’ve lost my job. Have found many cases of fraud. Sleep clinics double billing and not even putting people on cpap. My next step is to try hypnosis. I have had disturbed sleep since I started using cpap in Feb of 2012. Many sing the praise of cpap. I’m not one of them. I have found where research was manipulated and that researcher was banned from researching for three years. There are other ways to treat apena. A mouthpiece, has been used by air force for years, and breathing exercises, also hypnosis. Only two hours my guess is you have a lot of stress. If you believe in God a small book I’ve found helpful by Charles Calls is God’s creative power for healing. I pray you find healing.

  21. My husband had a seizure last month at the age of 55. No heart attack and no stroke, so automatically put on anti-seizure med. Then when a neuro couldn’t see him for 6 weeks, they let the medicine run out and won’t renew. This makes no sense to me. I know they are afraid of lawsuits, but come on! My husband stops breathing at night and then takes a huge breath and starts breathing again. He doesn’t believe me because he’s not a heavy man, so he doesn’t think he can have sleep apnea. We see the neuro soon, but I’m really worried. I hope doc does a variety of tests and believes me about my husbands breathing.

  22. I had my first seizure at 55 not a large man 5′-7″ and 175 lbs. The meds won’t stop the seizures. I still had a seizures while on the meds so I stopped taking them. The meds made me feel lousy. Had a sleep study done and look at the oxygen level which showed I wasn’t getting enough oxygen to the brain. I use a CPAP every night and they increased the output to try and get me more oxygen. Believe me the seizures will affect your memory over time. I have been trying to find help for ten years and have finally found a good doctor. Before they increased the output on my cpap, my seizures would last about 45 seconds. Since the increase of oxygen to my cpap the seizures may last about 15 seconds. The doctor has just had me start using an inhaler to open my airway passage in my lungs.
    It has taken a toll on me because now I have short term memory loss because of all the seizures. I know it can be very discouraging with the doctors but I hope this might help a little.

  23. Since I was diagnosed with a seizure disorder I thought I needed to do a sleep study. I know I snore heavily and it’s hard to breathe normally sometimes. Every seizure I’ve had occurred while I was sleeping. After the first one I was immediately placed on meds. Of course all the tests were done to rule of certain conditions and nothing was found. It’s almost 14 years since this all began and I’ve been on meds ever since. I have finally gotten used to taking medication…forever.

  24. Jan 29, 2016 8:59pm. How can a cpap set at 4 to 12 be safe when
    oxygen is toxic to the lungs when high F102 (>0.60). Low pressure 02 poisoning, pulmonary toxicity, or the Lorriane Smith effect. Toxicity also occurs when the (ATA) is high (1.6-4). Which is called the Paul Bert effect and is toxic to the central nervous system (CNS). I had a seizure after using cpap 1/10/12. Still have seizures. From what I’ve read the toxic effects can be perment. And hard to prove with an oddtopsy.Oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen (O
    2) at increased partial pressures. It is also known as oxygen toxicity syndrome, oxygen intoxication, and oxygen poisoning. Historically, the central nervous system condition was called the Paul Bert effect, and the pulmonary condition the Lorrain Smith effect, after the researchers who pioneered its discovery and description in the late 19th century. Severe cases can result in cell damage and death, with effects most often seen in the central nervous system, lungs and eyes. Oxygen toxicity is a concern for underwater divers, those on high concentrations of supplemental oxygen (particularly premature babies), and those undergoing hyperbaric oxygen therapy.

    The result of breathing increased partial pressures of oxygen is hyperoxia, an excess of oxygen in body tissues. The body is affected in different ways depending on the type of exposure. Central nervous system toxicity is caused by short exposure to high partial pressures of oxygen at greater than atmospheric pressure. Pulmonary and ocular toxicity result from longer exposure to increased oxygen levels at normal pressure. Symptoms may include disorientation, breathing problems, and vision changes such as myopia. Prolonged exposure to above-normal oxygen partial pressures, or shorter exposures to very high partial pressures, can cause oxidative damage to cell membranes, the collapse of the alveoli in the lungs, retinal detachment, and seizures. Oxygen toxicity is managed by reducing the exposure to increased oxygen levels. Studies show that, in the long term, a robust recovery from most types of oxygen toxicity is possible.

    Protocols for avoidance of hyperoxia exist in fields where oxygen is breathed at higher-than-normal partial pressures, including underwater diving using compressed breathing gases, hyperbaric medicine, neonatal care and human spaceflight. These protocols have resulted in the increasing rarity of seizures due to oxygen toxicity, with pulmonary and ocular damage being mainly confined to the problems of managing premature infants.

    In recent years, oxygen has become available for recreational use in oxygen bars. The US Food and Drug Administration has warned those suffering from problems such as heart or lung disease not to use oxygen bars. Scuba divers use breathing gases containing up to 100% oxygen, and should have specific training in using such gases.
    This page was last modified on 12 December 2015, at 03:48.
    Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization.

    I lost my job trying to use CPAP

  25. I cant believe I found this page. I first had a seizure when I was in year 9 in high school. I was 15 years old and I just lied down in bed and as I was dozing off I fell into a seizure I was rushed to the hospital and had a drip put in my arm but no tests just sent home the next morning and then it wasn’t until 8 years later I started having grand mal clonic tonic seizures whilst I was asleep so I had sleep studies but everything came back normal, but my doctor put me on 1 + 100mg lamictal tablets twice a day which seem to have cured me but I was still having a seizure at least 3 times a year. Anyway I believe it was the sleep apnoea because I was loosing oxygen to my brain I had another sleep study with snore Australia and I was diagnosed with OSA I would stop breathing 28 times a night on my back and only 4 times on my side so they set me up with a cpap machine and I have used it every night for 1 year and 3 months and I will never sleep without it again it has changed my life I have heaps more energy through the day, no sore throat, no bad breath, and of course no seizures since January 2013 that’s 3 years seizure free I am now in discussion with my doc about slowly reducing my medication and hopefully medication free, that’s my story so yes I believe that in some cases especially mine that seizures and sleep apnoea are connected.

  26. Wow! I am so happy to read these entries as I have always thought the seizures I was having were directly related to something in my sleep that was occurring. I am a 36 year old female who just had my first seizure in March of 2015 while sleeping. I have had two others, one in August 2015 and one in January of this year, 2016 (all while I am sleeping). All my tests come back completely normal and the doctors are still trying to put me on anti-seizure meds, which I refuse to take anymore. I took them for about 2 months after my first seizure and they made me feel crazy. I have been very frustrated that my doctors don’t want to search to find the real issue behind the seizures but instead just put me on meds. I finally asked to have a sleep study done and the test is scheduled in just a few weeks. I truly hope that this is the answer to the mystery of these nocturnal seizures I have been experiencing! Many thanks to all who have posted here.

  27. I have had seizures since I was 15…ALWAYS IN THE MORNING!!! Once I took my Phenobarbital Med on a daily basis I had an event every 8 yrs. Since 2008 my seizures took a different turn; every two years, now at 56 my seizures have become more frequent, every three months. The onlyt thing that never changes is taht it is always in the morning!!!! Now I think it is bcs I have sleep apnea which my husband said started 8 yrs ago.
    I would love to herar from you all!

  28. YES, anyone and everyone with seizure disorders should be tested for apnea. I developed epilepsy in my early 20’s. It took a few years to get it under control. But I would still have myclonic like twitch’s ( most often in the morning ), This usually happened if I had a poor nights sleep. Over exerted myself. Or was under stress. I went more than 20 years without having a grand mal. But then one of these twitch’s I had caused me to fall and break my elbow. My doctor tried switching me to a completely different medication. This resulted in my first grand mal in decades. I switched back to my old medication ( Dilantin ) And a very low dose of Kepra to control the twitch’s. Thanks to the ACA I finally had insurance and had a sleep study done. I scored a 98 on the apnea hypopnea index. Still on the meds, but no seizures or twitch’s for months now. And a LOT more energy to do things.

  29. To Crystal. I found a site about normal breathing. It explains a lot on proper balance of air and goes on to show the connection in breathing and disease. I also believe in the God aspect in life. Do drugs heal? I do go to the doctor and they tell me I’m not normal.

  30. I am 58 and had noticeable seizures since 2003. Have always been told that sleep and stress are the most significant causes of seizures, since they both lower the seizure threshold. Tried four different meds and still had seizures. Read and was told surgery was the next option. Went to the best hospital for the best surgeon in 2013, no seizures since, but still on my meds (Dilantin, Vimpat, Celexa and Ativan and CPAP). CPAP helps me sleep thru the night, but wish there was a better option… maybe exercise and a better diet. Any ideas? Thanks

  31. To LB By: Martha Garcia | Published: April 15th, 2013
    Nearly two dozen universities failed to properly warn parents that a national oxygen study may put their premature infants at risk, federal officials say.
    According to a letter (PDF) issued by the Department of Health and Human Services (DHHS) to the University of Alabama at Birmingham, the lead institution in the study, research institutions involved in the study did not offer informed consent to the parents of the premature infants.
    The study involved 1,300 premature infants between 24 to 27 weeks of gestation. Researchers evaluated the results of increased or decreased oxygen through a continuous positive airway pressure (CPAP) treatment to determine the levels of oxygen saturation and neurological effects on premature infants.

    According to the letter, the institutions involved were aware of the potential adverse affects the treatment may have on the infants, including blindness and even death. The DHHS Office of Human Research Protection says the institutions had sufficient evidence to know such treatment may cause serious consequences, but never properly informed parents participating in the study about the potential risks. The office considers the failing a violation of regulatory requirements for informed consent.

    The study took place between 2004 and 2009 and 130 infants of 654 in the low oxygen level group died, while 91 of 509 infants in the high oxygen group developed a serious eye problem, which can result in blindness.

    The study, published in the New England Journal of Medicine in 2010, was financed by the National Institutes of Health and involved 23 high profile Universities, such as Stanford, Duke and Yale.

    The consent form only mentioned risks involving abrasion of the infants skin, and claimed there was a potential benefit of decreased need for eye surgery if the infant was assigned to a certain oxygen level group.

    DHHS officials say the consent form should have highlighted that the risks of the trial were not the same as the risks of receiving standard care, so parents could make a more informed decision.

  32. I had my first seizure when I was 8 years old and it happened in my sleep! I awoke 2 days later in the hospital and was sent home with the Doctor thinking it was caused by a fever but placed me on Phenobarbital! I took the medicine for a year and was taken off and had no more seizures until I turned 18! Then I was placed on Dilantin and seizures increased until I was taking around 30 pills per day of 4 different kinds of medications!
    All of my life I have felt tired and had red eyes every day! No matter how much I slept, I still felt tired!
    It took two left temporal lobectomy surgeries and a VNS implant device to finally stop all seizures except for seizures in my sleep! I have gone 14 years since the second lobectomy with no daytime seizures!
    I still complained to the Doctors about how sleepy and tired I felt at all times so in 2004 , I had a sleep study done and it showed that I had severe sleep apnea! I tried CPAP that did not help so surgery to move my tongue forward and surgery on my throat finally stopped the sleep apnea (for a while)! I felt the best ever for about 2 years and slowly but surely I started feeling tired again! 8 years later, my Doctor told me that it could be sleep apnea again so the sleep study was performed again and I was awakening 78 times per hour which was about twice as bad as I was before surgery in 2004! I tried CPAP again and it just had to be turned as high as possible which made me have a bloated stomach every day and did not make me feel much more alert either! One of my Doctors suggested that I have a tracheotomy and I wanted that to be the LAST option so in 2014 I had a maxillomandibular advancement surgery performed at Duke university medical center that brought me from 78 awakenings per hour, down to 6 awakenings per hour! I will ALWAYS believe that due to my jaws being short, causing a small opening in my throat was what originally caused my brain damage due to a lack of enough oxygen to the brain, was what caused my brain damage from the beginning! I hope that this information helps your research on sleep apnea causing epilepsy!

  33. I started having “spells” where I would feel a tingling sensation, which would be followed by abnormal thinking. After a normal EEG, a neurologist offers me anti-epileptic medication, which I refused. About a year later, shortly after waking, I experienced my first tonic-clonic seizure at home and the second in th ER. I took Keppra for two years, had a normal EEG, and stopped Keppra until 2014, when a nocturnal tonic-clonic seizure awakened my husband. After a sleep-deprived EEG show abnormal spikes, my neurologist marked on my chart that I would need medication for life. Now, after an early 2016 diagnosis of fibromyalgia, a new neurologist recommended a sleep study. My only risk for apnea is my age, 51, but the test showed central and obstructive apneas, along with abnormal EEG activity and no deep sleep. I’m being fitted for a CPAP next Friday, and an ENT evaluation showed a deviated septum, so I’m having a sinus CT Monday. Please give me advice. I’m always tired, I always hurt, I’m always fatigued, and now I’m very scared. Please help me.

  34. Greetings in Jesus’ Name! My name is Brian Ward, a “presently disabled” minister from Mississippi that fights severe epilepsy problems… and I also have a problem with sleepwalking and memory problems. I just found out today that I have “sleep apnea”… not the news I wanted to hear but possibly the news I “needed” to hear. The seizures I have, so I have been told, are a “one of a kind” type of seizure… similar to “Complex Partial” seizures. I have been known to do things from “sleepwalking backwards”, “sleep talking while standing like I was going to the bathroom”, etc… Yes… I truly believe that “sleep studies” need to be done on individuals with epilepsy. Not saying every epileptic has sleep problems… but I sure know I do! God Bless You… and may your studies on this subject help many in years to come.

  35. You don’t want to read any of my posts as I get into fraud in the testing. I have lost my cdl do to sleepwalking out of semi while on cpap. My wife was driving about 55 at the time. I have used self hypnosis to relax. My therapist made me a tape and would make the suggestion I could breath normal. I grew up being a mouth breather. In fall the pollen would make me miserable. After having seizure using CPAP I have quit using it as I can’t drive and out of work. I can’t speak about the Deviated Septum. My step brother had that and surgery was effective for him.. I pray you find the support you need.

  36. I decided to have surgery to repair the deviated septum and swollen turbinates. I was hopeful, but it didn’t help my breathing and sleep apnea.

    I’m using BiPAP. I’m still having apnea (if the DreamStation is accurate). The pressure has been increased once. During my last visit to my sleep doctor, I asked him about the fact that every single night, there are significantly more clear apneas than obstructive apneas. He said he would have to ask the technician who fitted me for my mask (which doesn’t fit). His nurse said he would call me about the issue. That was six days ago, but he still hasn’t called me.
    My situation is complicated:
    Obstructive/central sleep apnea (treated with BiPAP, but still occurring)
    Epilepsy (changed from Keppra to lamotrigine after psychiatrist consulted with neurologist)
    Fibromyalgia (treated with gabapentin prescribed by rheumatologist)
    Anxiety associated with sleep mask use (treated with Xanax, prescribed by the sleep doctor)
    PTSD/anxiety/depression/suicidal thoughts (treated with escitalopram prescribed by psychiatrist and counseling by LCSW)
    Im not sure if some of my health problems are truly health problems or simply side effects of something else.
    I absolutely believe in the power of prayer and divine healing. In the meantime, the Lord is helping me every day to do the best I can. In December, 2015, I resigned from teaching. I truly LOVED my career AND my students. I simply had reached a breaking point. My husband, who is self-employed, has had four surgeries in less than two years, three of them after I resigned. Every month, the Lord has made a way for us to pay our bills. The December bills are in the table, and He has already made a way for us to pay some of them. I am so thankful!!!
    I welcome and appreciate any sincere advice on how to proceed!

  37. I have been diagnosed with supine OSA. I have had 7 seizures, all in my sleep, since 2009. I had one just a few days ago when I wasn’t wearing my CPAP. Also, I was taken off anti seizure med, Topamax, less than a month ago. I have had all the tests, CT scan, MI, EEG, and all come back clear. No epilepsy diagnosis, but have to wear the CPAP, and now will most likely have to go back on the Topamax. My last seizure was on my back, and obviously not enough O2 getting to my brain. Sleep test indicate levels drop as low as 80%. My question is what can be causing the drop. I’m not overweight.

  38. Dr. Park, I definitely think every patient with nocturnal seizures should be screened for apnea. It took a change of insurance and my 5th neurologist for this to be suggested to me. Hoping to take care of my obstructive and central sleep apnea…I had septoplasty and turbinate reduction…which only resulted in a larger nose and (I think, but waiting on reports) two broken teeth in the back of my mouth. I wish I had never had the procedure. Regrettably, I had not seen your article.

  39. I am a 66 year old male who had been diagnosed with JME 40 years ago. I had several grand mal seizures as a young adult and was put on anti seizure medication. I eventually weaned myself off of the meds with doctor supervision. My last seizure was at about the age of 35 and it occurred after a night of partying and very little sleep. As time passed I did continue to drink but was careful to get a good night’s sleep afterward. The seizures disappeared. I even thought of getting my pilots license and as a precaution had an EEG that revealed that I still had some unusual spikes indicative of Epilepsy. I gave up on the flying idea. By now I was running a business, had 4 children and a wonderful wife, I was fortunate why press my luck. I was still having very small, very short electrical shorts on occasion but no grand mal, or generalized seizures that is until recently. Several years ago I was diagnosed with severe sleep apnea and was told to start using a Cpap. I tried for a while but it too uncomfortable. Last January I had another grand mal seizure thought to have been provoked by codeine in cough medicine. Last Monday, March 27, I had another grand mal seizure. Both seizures occurred while I was sleeping. I also have a Thyroid problem and I am taking synthroid. I am convinced, as you seem to be, that seizures and sleep apnea have a link. There is a correlation especially for people like me who have a low threshold. I hope this helps you with your research

  40. While I was on cpap I sleep walked out of a semi. My wife was driving about 60mph at the time. You most likely look at my other comments. I’ve lost my job do to seizure during my recovery time trying to us cpap again. Have found fraud it testing. Altitude effects cpap. CO will not do testing above 5 thousand feet. Under water divers have good explanation on how oxygen effects blood stream. I have practiced mediation over 25 yrs. When do so I try now to breath into my stomach for 5 seconds then chest for 5 seconds hold for 10 seconds exhale for 10 seconds which would be one breath. Which would also fail a sleep test that is based on a 10 second pause as not breathing. During the time you hold your breath it allows your body to dump toxins. I don’t know how that can work when you are under pressure. By: Martha Garcia | Published: April 15th, 2013

    Nearly two dozen universities failed to properly warn parents that a national oxygen study may put their premature infants at risk, federal officials say.

    According to a letter (PDF) issued by the Department of Health and Human Services (DHHS) to the University of Alabama at Birmingham, the lead institution in the study, research institutions involved in the study did not offer informed consent to the parents of the premature infants.

    The study involved 1,300 premature infants between 24 to 27 weeks of gestation. Researchers evaluated the results of increased or decreased oxygen through a continuous positive airway pressure (CPAP) treatment to determine the levels of oxygen saturation and neurological effects on premature infants.

    According to the letter, the institutions involved were aware of the potential adverse affects the treatment may have on the infants, including blindness and even death. The DHHS Office of Human Research Protection says the institutions had sufficient evidence to know such treatment may cause serious consequences, but never properly informed parents participating in the study about the potential risks. The office considers the failing a violation of regulatory requirements for informed consent.

    The study took place between 2004 and 2009 and 130 infants of 654 in the low oxygen level group died, while 91 of 509 infants in the high oxygen group developed a serious eye problem, which can result in blindness.

    The study, published in the New England Journal of Medicine in 2010, was financed by the National Institutes of Health and involved 23 high profile Universities, such as Stanford, Duke and Yale.

    The consent form only mentioned risks involving abrasion of the infants skin, and claimed there was a potential benefit of decreased need for eye surgery if the infant was assigned to a certain oxygen level group.

    DHHS officials say the consent form should have highlighted that the risks of the trial were not the same as the risks of receiving standard care, so parents could make a more informed decision.

  41. AbstractOxygen (O2) is life essential but as a drug has a maximum positive biological benefit and accompanying toxicity effects. Oxygen is therapeutic for treatment of hypoxemia and hypoxia associated with many pathological processes. Pathophysiological processes are associated with increased levels of hyperoxia-induced reactive O2 species (ROS) which may readily react with surrounding biological tissues, damaging lipids, proteins, and nucleic acids. Protective antioxidant defenses can become overwhelmed with ROS leading to oxidative stress. Activated alveolar capillary endothelium is characterized by increased adhesiveness causing accumulation of cell populations such as neutrophils, which are a source of ROS. Increased levels of ROS cause hyperpermeability, coagulopathy, and collagen deposition as well as other irreversible changes occurring within the alveolar space. In hyperoxia, multiple signaling pathways determine the pulmonary cellular response: apoptosis, necrosis, or repair. Understanding the effects of O2 administration is important to prevent inadvertent alveolar damage caused by hyperoxia in patients requiring supplemental oxygenation.1. IntroductionWhen administering supplemental oxygen (O2) to treat hypoxemia associated with acute and chronic conditions, O2 toxicity by overexposure may be present. Annually, the need for supplemental O2 is projected to be around 800,000 individuals at a cost of 1.8 billion dollars [1]. Suboptimal use of O2 is reflected in prescription and treatment errors that exceed those related to antibiotics [2–4]. The alveolar epithelial and alveolar capillary endothelial cells are vulnerable targets for O2-free-radical-induced injury caused by hyperoxia. In acute lung injury (ALI) caused by hyperoxia, hyperpermeability of the pulmonary microvasculature causes flooding of the alveolus with plasma extravasations leading to pulmonary edema and abnormalities in the coagulation and fibrinolysis pathways promoting fibrin deposition [5, 6]. Type II alveolar epithelial cells are injured by O2 free radicals leading to impairment of surfactant production [7]. Thus, the maximum positive biological benefit for this life essential but toxic molecule exists along a dose-response, deficiency–toxicity continuum.2. Pathophysiology of Oxygen ToxicityHyperoxia is a state of excess supply of O2 in tissues and organs. Oxygen toxicity occurs when the partial pressure of alveolar O2 (PAO2) exceeds that which is breathed under normal conditions. With continuous exposure to supraphysiologic concentrations of O2, a state of hyperoxia develops. Under hyperoxic pathological conditions, a large influx of reactive O2 species (ROS) are produced. In intracellular and extracellular biological systems, the mass effect of ROS elevation, caused by O2 overexposure, disrupts the balance between oxidants and antioxidants, and this disruption of homeostasis can result in damage to cells and tissues [8–11]. Exposure time, atmospheric pressure, and fraction of inspired O2 (FIO2) determine the cumulative O2 dose leading to toxicity. Oxygen is toxic to the lungs when high FIO2 (>0.60) is administered over extended exposure time (≥24 hours) at normal barometric pressure (1 atmospheres absolute (ATA)). This type of exposure is referred to as low pressure O2 poisoning, pulmonary toxicity, or the Lorraine Smith effect. Oxygen exposure after approximately 12 hours leads to lung passageway congestion, pulmonary edema, and atelectasis caused by damage to the linings of the bronchi and alveoli. The formation of fluid in the lungs causes a feeling of shortness of breath combined with a burning of the throat and chest, and breathing becomes very painful [12]. The reason for this effect in the lungs but not in other tissues is that the air spaces of the lungs are directly exposed to the high O2 pressure. Oxygen is delivered to the other body tissues at almost normal partial pressure of O2 (PO2) because of the hemoglobin-O2 buffer system [13–15]. Toxicity also occurs when the ATA is high (1.6–4) and the high FIO2 exposure time is short. This type of exposure is referred to as high pressure O2 poisoning or the Paul Bert effect and is toxic to the central nervous system (CNS). Central nervous system toxicity results in seizures followed by coma in most people within 30 to 60 minutes. Seizures often occur without warning and are likely to be lethal. Other symptoms include nausea, muscle twitching, dizziness, disturbances of vision, irritability, and disorientation [13, 16–20]. Oceanic divers are more likely to experience CNS toxicity [17].Pulmonary capillary endothelial and alveolar epithelial cells are targets for ROS resulting in injury-induced lung edema, alveolar flooding, hemorrhage, and collagen, elastin, and hyaline membrane deposits [11, 21, 22]. Above a critical PAO2, the hemoglobin-O2 buffering mechanism fails and the tissue PO2 can rise to hundreds or thousands of mm Hg. At high levels of O2, protective endogenous antioxidant enzyme systems become consumed by ROS leading to cell death [16, 23]. Oxygen toxicity caused by ROS progresses in overlapping phases based on degree of severity and reversibility of injury. The phases are initiation, inflammation, proliferation, and fibrosis. Initially, there are increased ROS and depleted antioxidant levels, and the lung fails to clear itself of mucous. The inflammation phase or exudative phase is characterized by the destruction of the pulmonary lining and migration of leukocyte derived inflammatory mediators to the sites of injury. The proliferative phase is subacute and there are cellular hypertrophy, increased secretions from surfactant secreting alveolar type II cells, and increased monocytes. The final terminal phase is the fibrotic phase in which the changes to the lung are irreversible and permanent. There is collagen deposition and thickening of the pulmonary interstitial space and the lung becomes fibrotic [24–27].Clinically, progressive hypoxemia, or high O2 tension in the blood, requires increased FIO2 and assisted ventilation, which further aggravate the pathophysiological changes associated with O2 toxicity. Chest X-rays may show an alveolar interstitial pattern in an irregular distribution with evidence of a moderate loss of volume from atelectasis, however there is no clinical way of diagnosing O2 toxicity. Lung biopsy specimens may show changes consistent with O2 toxicity but the primary value of the biopsy is to exclude other causes of lung injury. Air pressure changes within the enclosed lung cavity and ventilator-induced injury may accompany and be indistinguishable from O2 toxicity. Oxygen toxicity can be minimized by keeping the PAO2 less than 80 mm Hg or the FIO2 below 0.40 to 0.50 [12]. The pulmonary cellular response to hyperoxic exposure and increased ROS is well described. Anatomically, the pulmonary epithelial surface is vulnerable to a destructive inflammatory response. This inflammation damages the alveolar capillary barrier leading to impaired gas exchange and pulmonary edema. Reactive O2 species induces pulmonary cell secretion of chemoattractants, and cytokines stimulate macrophage and monocyte mobilization and accumulation into the lungs, leading to additional ROS. The ROS leukocyte interaction further exacerbates injury. Research has shown that as these highly reduced cell layers become increasingly oxidized and levels of antioxidants fall, ROS-induced activation of multiple upstream signal transduction pathways regulates the cellular response: adaptation, repair, or cell death by apoptosis, oncosis, or necrosis [28, 29]. Mitogen-activated protein kinase (MAPK), toll-like receptor 4 (TLR4), signal transducers and activators of transcription (STAT), and nuclear factor kappa beta (NF kβ) are a few well-researched protein pathways that communicate the receptor signal to the deoxyribonucleic acid (DNA) of the cell thereby determining the cellular response. The MAPK pathway is a regulator of cell death genes, stress, and transformation and growth regulation. Mitogen-activated protein kinase activation precedes extracellular signal regulated kinase (ERK1/2), a promoter of cell proliferation. C-Jun-terminal protein kinase (JNK1/2) and p38 kinase both induce cell death and inflammation [30]. The TLR4, STAT, and nuclear regulatory factor 2 (Nrf2) pathways are associated with survival gene expression such as caspase-3 proteins and antioxidant response element (ARE) [31, 32]. The NF kβ pathway is an up-stream signal for inflammation and survival genes: anti-oxidant enzymes (AOE), Bcl-2, AKT, heme oxygenase (HO-1), and heat shock proteins (HSPs). The AKT1-4 family of signals plays an important role in glucose metabolism, cell proliferation, apoptosis, transcription, and cell migration. The Bcl-2 proteins are antiapoptotic while HO-1 and HSPs are ubiquitous stress-response proteins [33]. These signaling pathways are regulators of the pulmonary epithelial cell response to increases in ROS and hyperoxia [18, 34]. Cytokine and chemokine overexpression in response to hyperoxic stress can be protective. Tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), chemokine receptor 2 (CXCR2), interleukin 11 (IL-11), insulin and keratinocyte growth factor expression, and the beta subunit of Na, K-ATPase have been shown to attenuate death signals [35–37].3. The Formation of Free RadicalsOxygen is a requirement for cellular respiration in the metabolism of glucose and the majority of O2 consumed by the mitochondria is utilized for adenosine triphosphate (ATP) generation [38, 39]. The mitochondrial electron transport chain reduces the elemental molecular O2 to ionic O2 by the relay of electrons making O2 usable for ATP generation, during this process, oxidizing free radicals are generated [40, 41]. Toxic levels of O2 lead to the formation of additional ROS, which can impose damage to lipid membranes, proteins, and nucleic acids. Reactive O2 species mediate physiological and pathophysiological roles within the body [42]. Free radicals are a type of unstable, reactive, short-lived chemical species that have one or more unpaired electrons and may possess a net charge or be neutral. The species is termed free because the unpaired electron in the outer orbit is free to interact with surrounding molecules [42, 43]. Cells generate free radicals, or ROS, by the reduction of molecular O2 to water (H2O) (Figure 1) [44, 45]. 260482.fig.001Figure 1: Reduction of oxygen. A single-electron transfer which converts molecular oxygen to the superoxide anion, creating an unstable molecule. The decomposition of hydrogen peroxide can be a source of the hydroxyl radical; this reaction requires both superoxide and hydrogen peroxide as precursors. These steps reduce oxygen to water by the addition of four electrons, yielding three reactive oxygen species: superoxide anion, hydrogen peroxide, and hydroxyl radical.Chemically, three types of reactions lead to the formation of ROS. The one-electron reduction of molecular O2 to the superoxide anion (
    ) is catalyzed by transition metals including iron (Fe) and copper (Cu) such as

  42. The simultaneous oxidation reduction reaction of to hydrogen peroxide
    to hydrogen peroxide (H2O2) and the addition of an electron to produce the hydroxyl radical (HO●). The
    in biological membranes can act in four different modes: electron transfer, nucleophilic substitution, deprotonation, and a hydrogen atom abstraction as in
    initiated Fenton-type reaction and the decomposition of H2O2 requires
    and H2O2 as precursors and Fe and Cu presence for completion. The HO● is the most injury producing in biological systems, reacting with molecules in close proximity. These reactions are called Fenton-like reactions generating O2 and HO● when Fe II or Cu I reacts with

    The sum of reactions (3) and (4), or the Haber-Weiss reaction shown in (5) above demonstrates HO● formation by the metal-catalyzed decomposition of H2O2. The interaction between

    and H2O2 is the source of the majority of damage to biological systems due to the reactivity of continuously produced, highly toxic HO● [18, 46, 47]. These ROS-producing reactions occur endogenously involving enzymes, neutrophils, and organelles such as the mitochondria and exogenously induced by radiation, pollutants, xenobiotics, and toxins. Cellular survival and adaptation in an oxidative atmosphere are dependent upon sufficient antioxidant defenses to counteract the effects of ROS on cells and tissues [48].4. Functions and Classifications of AntioxidantsOxidant antioxidant homeostasis is highly regulated and essential for maintaining cellular and biochemical functions [49]. A change in the balance toward an increase in the oxidant over the capacity of the antioxidant defines oxidative stress and can lead to oxidative damage. Changing the balance toward an increase in the reducing power of the antioxidant can also cause damage and is defined as reductive stress [50–52]. Reduction, antioxidant and oxidation, or pro-oxidant reactions result from a gain or a loss of electrons and a loss or a gain in O2 [50, 53, 54].An antioxidant (a reductant or reducing agent) is anything that can prevent or inhibit oxidation [55–57]. Delay of oxidation can be achieved by preventing the generation or inactivating ROS [58]. Prevention, diversion, dismutation (decay), scavenging, and quenching are specialized antioxidant properties (Table 1). Antioxidant defenses may be classified as nonenzymatic and enzymatic or endogenous and dietary. Examples of nonenzymatic antioxidants are glutathione (GSH), ascorbic acid, vitamin E, beta-carotene, and uric acid. Major enzymatic antioxidants are superoxide dismutase (SOD), catalase, and GSH peroxidase which divert or dismutate ROS into harmless products. Endogenous or dietary antioxidants are based on the ability of the antioxidant to be synthesized by humans. Endogenous antioxidants are SOD, catalase, GSH peroxidase, uric acid, and bilirubin. Dietary antioxidants are ascorbic acid, vitamin E, and beta-carotene [59, 60]. Ascorbic acid, vitamin E, uric acid, bilirubin, and GSH scavenge ROS by expendable, replaceable, or recyclable substrates. Vitamin E and beta-carotene quench ROS by absorption of electrons and/or energy.tab1Table 1: Locations and properties of antioxidants.Antioxidants can be classified into four categories based on function. (1) Preventive antioxidants which suppress formation of ROS, (2) radical scavenging antioxidants which suppress chain initiation and/or break chain propagation reactions, (3) the repair and de novo antioxidants such as proteolytic enzymes and the repair enzymes of DNA, and (4) antioxidants which allow for adaptation that occurs when the signal for the production and reactions of ROS induces oxidant formation and transport [10, 61].Superoxide dismuta (I cut word off R. I.)

    to H2O2 and has three isoforms widely distributed in mammalian organisms. (1) Cytoplasmic SOD (SOD1 or Cu zinc (CuZn) SOD) is located in the cytoplasm, nucleus, and peroxisomes, (2) mitochondrial SOD (SOD2 or MnSOD) is located in the mitochondrial matrix near the electron transport chain, and (3) extracellular SOD (SOD3 or EcSOD) is found in the extracellular fluids and extracellular matrix of all human tissues especially the heart, placenta, pancreas, and lung [62–64]. The protective effects of EcSOD in the lungs are extremely important and well-established [65–68]. Catalase, one of the most potent catalysts found mostly in the peroxisome, functions to decompose H2O2 to H2O. Catalase defense from oxidant injury to lung epithelial cells exists in the cytosol or the mitochondria. Glutathione reductase is an important antioxidant enzyme for maintaining the intracellular reducing environment. This enzyme catalyzes the reduction of glutathione disulfide (GSSG) to GSH [69]. Glutathione disulfide is produced through the oxidation of GSH by ROS that arise during conditions of oxidative stress. Due to the high concentrations of GSH, GSH/GSSG is considered to be the principal redox buffer of the cell and the ratio of GSH/GSSG is viewed as a major indicator of the cellular redox status. The ratio of GSH/GSSG decreases under an oxidative stress condition [70, 71]. Tissue damage may develop when an oxidant/antioxidant imbalance occurs as a consequence of hyperoxia [72, 73]. The damaging effects of hyperoxia can lead to O2 toxicity, cell death, and can be a triggering factor in ALI [22].5. Clinical Presentation of Hyperoxic Acute Lung InjuryAcute lung injury and acute respiratory distress syndrome (ARDS) are secondarily occurring, inflammatory syndromes caused by triggers or risk factors described as direct or indirect, pulmonary or extrapulmonary. The pathological changes associated with HALI mimic the ALI triggered by other conditions such as hemorrhagic shock, reperfusion injury, pneumonia, sepsis, or paraquat inhalation [23, 33, 74, 75]. The risk of developing ALI or ARDS after inhalation injury is dependent on the toxicity and concentration of the inhaled substance [17]. For example, the cells and structure of the alveolar capillary membrane are highly susceptible to damage by toxic levels of O2 [76]. Both ALI and ARDS are the same clinical disorder, differing only in severity of hypoxemia. The ratio between arterial pressure of O2 (PaO2) and the FIO2 concentration delivered by ventilator support distinguishes the two syndromes. For ALI, the PaO2/FIO2 is ≤300 mm Hg and for ARDS, the PaO2/FIO2 is ≤200 mm Hg [74, 75, 77]. The injury to the alveolus is thought to develop when pulmonary or systemic inflammation leads to systemic release of cytokines and other proinflammatory molecules. Mast cells, which express mediators that exert effects on lung vasculature, are also increased after hyperoxic exposure [78]. Cytokine release activates alveolar macrophages and recruits neutrophils to the lungs. Subsequent activation of leukotrienes, oxidants, platelet activating factor, and protease occurs. These substances damage capillary endothelium and alveolar epithelium, disrupting the barriers between the capillaries and air spaces. Edema fluid, proteins, and cellular debris flood the air spaces and interstitium, causing disruption of surfactant, airspace collapse, ventilation-perfusion mismatch, shunting, and stiffening of the lungs with decreased compliance and pulmonary hypertension. There is no pattern to the injury; however, dependant lung areas are most frequently affected [74, 79]. Tissue examination reveals that surfactant disruption, epithelial injury, and sepsis initiate the increased expression of cytokines that sequester and activate inflammatory cells. Increased release of ROS alters normal endothelial function. Microarray analysis has revealed increased expression of genes related to oxidative stress, antiproteolytic function, and extracellular matrix repair as well as decreased surfactant proteins in ozone-induced ALI [80]. Diffuse alveolar damage results with intra-alveolar neutrophils indicating the presence of an inflammatory response in the alveoli. Red blood cells, cellular fragments, and eroded epithelial basement membranes are present with formation of hyaline membranes, indicating that serum proteins have entered and precipitated in the air spaces due to disruption of the alveolar capillary barrier. Formation of microthrombi indicates the presence of endothelial injury and activation of the coagulation cascade [81]. Acute lung injury syndrome presents within 24 to 48 hours after the direct or indirect trigger. Initially, the patient may experience dyspnea, cough, chest pain, tachypnea, tachycardia, accessory muscle use, cyanosis, mottled skin, and abnormal breath sounds (crackles, rhonchi, and wheezing). Blood gas analysis reveals progressive worsening of hypoxemia, leading to respiratory failure. Bilateral infiltrates are seen on a chest X-ray and are consistent with pulmonary edema but without the cardiac component of elevated left atrial pressure. Treatment includes mechanical ventilation, supportive care, and treatment of the underlying causes [16]. The mortality of ALI has improved over the past decade; however, it still ranges from 30% to 75% [75, 77, 82, 83] and occurs in about 86 of 100,000 individuals per year [84].6. ConclusionOxygen, often used to treat hypoxemia in the clinical setting, is itself a triggering factor in HALI given that the exposure is sufficiently concentrated and of adequate duration. The lung is a vulnerable target for oxidant-induced injury, initiating a cascade of protein signals that determine the cellular response. The alveolar epithelial and alveolar capillary endothelial surfaces are injured. Hyperpermeability, microthrombi (resulting from altered coagulation and fibrinolysis), collagen deposition, and fibrosis alter alveolar structure and function. Understanding precise mechanisms of injury and pulmonary cellular responses to hyperoxia is essential evidence for expert practice.AcknowledgmentThis project was sponsored by the TriService Nursing Research Program (TSNRP) (N08-012, HU0001-08-1-TS08). The information or content and conclusions do not necessarily represent the official position or policy of, nor should any official endorsement be inferred by, the TSNRP, the Department of Defense, or the US Government.References

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