N24 Awareness Day 2014: Myths and Reality

24 November 2014 at 02:07 | Posted in Circadian rhythm | Leave a comment
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Well, it’s that time of year again. The nip of Autumn is in the air, and that can mean only one thing, N24 Awareness Day. Just one year ago, the N24 community celebrated the first N24 Day, having designated November 24th as our day to spread awareness of the condition.

2014 has certainly been an eventful year for awareness of N24. In January of this year the US Food and Drug Administration approved the first drug specifically designated for the treatment of N24 in totally blind patients. In the US, advertising of medicines is permitted and Vanda has been running advertisements on television and radio talking about N24. A year ago the average person had never heard of N24. Now, if you were to ask someone (at least in the US) if they had heard of N24 there is a good chance the answer would be yes, because of the Vanda campaign.

But awareness does not necessarily mean understanding. Unfortunately as awareness has spread, so have a number of myths and misconceptions about N24.  People with N24 I have talked to tell me of the reactions that they now get which reflect these myths. It is worth addressing this issue.

2014 Icon

Myth #1: “N24 only happens to blind persons”.

Vanda’s Non-24 campaign has particularly talked about blind persons since that is the population for which the drug is approved. It is true that if you are blind your chance of having N24 increases dramatically. Over 50% of totally blind persons will have N24. It is a serious condition — many blind persons have even said it is the worst part about being blind.

But N24 also occurs in sighted persons. I am sighted myself, and so are many other people with N24 that I know. There are many research articles on the condition and it is agreed that it does occur in individuals who have sight.

In the case of blind persons, the cause of N24 is the absence of light as a zeitgeber to regulate the circadian clock.  This is not usually the issue with sighted persons.  In sighted N24 the cause is a more complex dis-regulation of the body’s circadian system and sleep wake cycle.  Although blind and sighted N24 share the same diagnostic name, the biology is quite different.

The rate of occurrence of N24 among sighted persons is much smaller than among the blind, but there are also many more sighted people overall. We don’t really have a good estimate of the total number of sighted N24s. We can put a lower bound. There are about 100 case reports in the medical literature. And online support groups number in the low hundreds. This is still a small percent of the population, but sighted N24 does exist.

Myth #2: “N24 is a disease invented by drug companies”

It is understandable that the average person, never having heard of this somewhat exotic condition, and suddenly deluged with paid advertising might think this condition was concocted for profit. One person with N24 told me her social services worker said, “Oh, N24, that’s that disease that no one really has.”

Nothing could be farther from the truth. Anyone who thinks that is the case needs to talk to the many persons who have suffered for years with this awful condition.

In my own case, I first developed N24 in 1982. I doubt I was influenced by a drug ad 30 years in the future. I was first diagnosed in 1992 at the National Institutes of Health. They didn’t just take my word for it. They conducted a 2 year study, with round-the-clock monitoring of blood chemicals via an IV line and a slew of other medical tests. This is a real condition due to a disorder of the biological clock and the regulation of the sleep-wake cycle.

There are many others who have endured this condition. You can read some personal accounts at the CSD-N web site under “personal stories”.

Bottom line: N24 is real and the suffering it causes is real.

Myth #3: “You can just take a pill and fix your N24″.

Again, this is an understandable reaction to a drug company campaign. But the reality is more complicated.

Let’s first deal with blind persons, the target population for the new drug Hetlioz. The most straightforward way to measure response to an N24 treatment is the percent who achieve entrainment. Entrainment does not mean everything is fixed, you can still have major symptoms such as debilitating exhaustion, but lack of entrainment does really mean treatment has not worked.

In the case of Hetlioz about 20% of patients achieved entrainment after 1 month of treatment. After 7 months this rose to to 59% although that figure does not include those who dropped out of the trial or whose period was not measured at 7 months. When all subjects are included, the percent of those who started the trial and achieved both entrainment and reduced symptoms at 1 or 7 months was only 28.9% (1). So success is by no means guaranteed and treatment can take a long time to achieve results.

This isn’t meant to single out Hetlioz for criticism. It may be a useful drug for some and I am glad it is available. Melatonin is also effective in many cases of blind N24. But neither is anything close to 100% successful for blind patients. The point is not that Hetlioz is an ineffective drug, because it does help a percentage of sufferers. The point is that N24 is hard to treat.

We don’t yet have data on Hetlioz in sighted N24s. The biology of sighted N24 suggests that melatonin and melatonin antagonists such as Hetlioz may be of less use than in blind subjects. The prolonged intrinsic period of some N24s may be outside the range of entrainment by melatonin-like drugs.  In practice, while some sighted N24s respond to melatonin and related drugs, most do not (2).  Whether this will be any different with Hetlioz remains to be seen.

Of course sighted N24s have some treatment options not available to totally blind persons, namely light and dark therapy. These treatments can be successful in some cases, but not all. And the light/dark regimens are complicated and time consuming. Nor does this approach correct the underlying cause of the disorder. It is a symptomatic, not a curative treatment. Even when light entrainment works patients may be left with substantial residual symptoms such as tiredness or a split sleep schedule. I am known for strongly encouraging people to try light/dark treatment, but it is not a panacea.

All of this is a far cry from popping a pill to fix the disorder.

Those are three of the myths I have heard circulating in the past year. It has changed my perspective on how to approach N24 in discussions with medical professionals and the public. In the past when I told them I had N24 (or hypernycthemeral syndrome as it used to be called) I was greeted with a blank stare or “what is that?…can you spell it?” The reaction might be skeptical. On the other hand I was dealing with a blank slate and could tell them about the condition if they were willing to listen.

Now the situation for those of us with N24 is different. The good news is, people now may have heard of the condition. The bad news is, what they think they know about the disorder may not be the truth. In the words of Mark Twain, “It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so”

With this new awareness, are we better off or not? I’m not sure. What do you think?

–posted by LivingWithN24

REFERENCES:

1. Marlene Dressman PhD. Clinical Program Efficacy. Tasimelteon, as presented to the FDA Peripheral and Central Nervous System Drugs Advisory Committee November 14, 2013 Silver Spring, MD slides CE-79 and CE-81

2.Kamei Y, Hayakawa T, Urata J, Uchiyama M, Shibui K, Kim K, Kudo Y, Okawa M. Melatonin treatment for circadian rhythm sleep disorders. Psychiatry Clin Neurosci. 2000 Jun;54(3):381-2.

68. Non-24 — Not Just a Disorder of the Blind, a guest post

24 July 2014 at 03:12 | Posted in Circadian rhythm | 4 Comments
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Perhaps I’ve “arrived”, when Healthline.com approaches me with an offer of a guest post?  I said yes, please.  So here is the article by their health-and-fitness writer Adrienne:

Adrienne

Thank you Healthline and Adrienne, for the timely article!    –D

 

 Non-24 — Not Just a Disorder of the Blind

Non-24-Hour Sleep-Wake Disorder is not a condition that a lot of people were aware of, at least until the first medication for it was approved by the U.S. Food and Drug Administration earlier this year.  The advertising for Vanda Pharmaceuticals’ new drug has brought some attention to the disorder, but since the drug is aimed at (and only approved for) those who are blind, few realize that the disorder can and does affect sighted people as well.

Non-24 in Layman’s Terms

Non-24 is a circadian rhythm sleep disorder that causes people to be unable to adjust their sleep-wake cycles to a 24 hour day.  This causes their sleep time to progress around the clock.  To put it more simply:  Each night people who have Non-24 go to sleep later than the night before, each time sleeping in the next day in accordance with the time they went to bed.  They go to bed later and later every day, eventually ending back at the same bedtime and starting the cycle all over again.  As you can imagine, this doesn’t only interfere with day-to-day responsibilities, but it can also lead to daytime sleepiness, memory issues, depression and more.

Non-24 in the Sighted 

In a majority of totally blind people, Non-24 is the result of their inability to perceive light; the lack of  light interferes with synchronization of their internal clocks to the day/night cycle in nature.  Even though the disorder goes by the same name for the sighted as it does for the blind, the causes are entirely different.  Though it’s not currently known just how many sighted people have Non-24, there are several known causes of it.

Here are some of them:

  • Changes in light sensitivity. In some sighted people, even though they are able to see well and appear to have great vision, daily light signals may not get through properly, leading to disrupted circadian rhythms.
  • Melatonin imbalance. Melatonin, a hormone, plays a part in linking sleep to the day-night cycle.  Some sighted people with Non-24 have been found to produce less melatonin than normal while others produce too much.  Problems with metabolizing melatonin properly can also impair circadian rhythm and cause Non-24.
  • Trauma and physical damage to the brain. Healthy people who suffer head injury can develop Non-24 when the injury damages the circadian and sleep centers of the brain.  This can also be the case with brain tumors, such as craniopharyngiomas.  For some it’s the brain tumor itself that causes the damage while for others it can be the effect of treatment, such as radiation.
  • Environmental factors. Sometimes it’s a sighted person’s exposure to light, or the lack of it, that can interfere with the ability to maintain a 24-hour sleep-wake cycle.  An example of this, in scientific studies in the laboratory, is being in an isolated environment without access any clues as to what time of the day it is, and not being allowed to turn lights on or off as desired.  In such studies healthy people will temporarily acquire a non-24 sleep pattern, though, of course, not the disorder.
  • Individual sleep patterns.  According to The National Organization for Rare Disorders  (NORD), a person’s need for sleep could lead to a Non-24 sleep cycle.  They give the example of a healthy person who may sleep 8 hours and stay awake for 16 while another person may need 12 hours of sleep but still be awake for the normal 16 hours, leading to a 28-hour day.  The same can happen for a person who sleeps the normal 8 hours but then requires 20 hours of awake time before sleep again is possible, also leading to a 28-hour day.

These are just some of the known or suspected causes of Non-24 in the sighted.

References

 

Adrienne is a freelance writer and author who has written extensively on all things health and fitness for more than a decade.  You can connect with Adrienne on Facebook here.

Healthline.com is funded, apparently exclusively, by advertising and they own, are owned by or are affiliated with Healthline Networks, Inc., Healthline Corp and YourDoctor.com

Their goal is to educate and empower users with relevant and responsible information in order to foster better communication between doctors and patients.

You can go to http://www.healthline.com for more information on sleep disorders and other related conditions.

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69.  Next post: –another guest post–

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67. N24 Awareness Day

24 November 2013 at 22:43 | Posted in Circadian rhythm | 6 Comments
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The online N24 community has decided to name November 24 as N24 Awareness Day.  We are encouraging bloggers and tweeters and anyone else with a platform to help spread awareness and knowledge of Non-24-Hour Sleep-Wake Disorder (N24).

The web page which links to these efforts is here (click on the N24 Day Logo):

N24 Awarenes Day Icon
This would be an appropriate time to review some events in 2013 relevant to N24.

One important advance was a paper by Kitamura et al. which measured the intrinsic circadian period in 6 patients with N24.  They compared it with two groups of individuals without a circadian disorder.  One group had an intermediate circadian preference.  The other group had an evening preference. The latter group however did not have DSPS, only a preference for being active later in the day.

Kitmura et al. found that the intrinsic period of the N24s was 24.5 hours, which was significantly longer than that of the intermediate types, but not significantly longer than that of the evening types.  The average period of the N24s was longer than that of the evening types but because of the great degree of overlap between those groups the difference was not significant.  The longest period found in an evening type subject was nearly identical to the longest period among the N24 subjects (around 24.7 hours).

These results suggest that a longer-than-average intrinsic period is a component of N24, but it is not the only causative factor.  Other factors, such as differences in phase angle between sleep and temperature rhythms, as found in several studies, may play a role.

Another paper, by An et al.  did not discuss N24 explicitly, but the results may have import for those with the condition.  They studied the effect of Vasoactive Intestinal Peptide (VIP) on shifting of circadian rhythms in mice and in cell cultures from the SCN.  They found that VIP depending on time and dose could either enhance or reduce the mutual synchronization of SCN cells.  Further, when SCN cells were less tightly synchronized together, they adapted more quickly to phase changes.  This suggests that by manipulation of VIP levels it may be possible to increase the adaptability of the SCN to phase changes.  Since N24s with a longer period need to change phase every day if they are trying to maintain a normal schedule, this approach might be of help.   It might also help people with DSPS when trying to shift to an earlier sleep phase.

–posted by LivingwithN24

REFERENCES

Kitamura S, Hida A, Enomoto M, Watanabe M, Katayose Y, Nozaki K, Aritake S, Higuchi S, Moriguchi Y, Kamei Y, Mishima K. Intrinsic circadian period of sighted patients with circadian rhythm sleep disorder, free-running type.Biol Psychiatry. 2013 Jan 1;73(1):63-9.

An S, Harang R, Meeker K, Granados-Fuentes D, Tsai CA, Mazuski C, Kim J, Doyle FJ 3rd, Petzold LR, Herzog ED. A neuropeptide speeds circadian entrainment by reducing intercellular synchrony. Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):E4355-61.

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Next post:  68.  Guest post: Non-24 — Not Just a Disorder of the Blind

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66. Blogathon: “Dear Diagnosis”

7 November 2013 at 23:34 | Posted in Circadian rhythm | 5 Comments
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Julie Flygare, the author of  Wide Awake and Dreaming: A Memoir of Narcolepsy, is hosting «Dear Diagnosis»,  a blogathon where she invites «all narcolepsy and chronic disease bloggers to write a letter to yourself on your diagnosis day.”  To date, all responses are from narcolepsy bloggers.  She needs one from another chronic disease blogger, I think. 

Dear me in April 2004,

Elation!  Finally a doctor who recognizes that you are not (just) lazy and inconsiderate.  He understands so well that he asks about things you never realized were connected to your sleep problems.  He asserts that you have a valid condition and even has a name for it:  Delayed Sleep Phase Syndrome, which in years to come will be “uprated” to Delayed Sleep Phase Disorder.

Yes, you are on a high which will last several months, in spite of the fact that the treatment he recommends doesn’t really work.  Thanking the heavens for the Internett, you will research DSPS and discover that its been known (but only to  chronobiologists, apparently) for over 20 years.  You will fill a couple of ring binders with scientific studies, learning to read and understand them along the way.

That overnight sleep study at the hospital in the early ‘90s that came up with “not narcolepsy” as a diagnosis should have rung a bell for that neurologist!  Curses on him.

It will, unfortunately, take years for you to stop blaming it all on your own lack of self-discipline and to (re)gain some self-esteem.  You will still have to make sincere apologies when you are late for work and miss appointments.

You will foolishly refuse to accept 100% disability when it is offered, going along with your GP who feels you should at least keep working part-time for social reasons.  So you’ll be 40% disabled for a while, then 60%.  Retirement age comes as a great relief.

You will actually start a blog about DSPS, partly for yourself but also in hopes of helping anyone who stumbles upon it.  You’ll hear from thankful people; it’s great to be appreciated!  You’ll find a wonderful support group, “niteowl”, online where intelligent and helpful people help each other learn.  You’ll find other fora where you can help people.  You’ll eventually start a wiki, then be a part of starting a non-profit, Circadian Sleep Disorders Network, to provide support, inform and try to spread awareness.

Your sleep specialist (yes, the same one as today)  will tell you: “Now you can hang out a sign and start taking patients.”  He’s joking, of course, but it’s a nice compliment.

In sum, your life will continue to center in large part around your sleep problems, as it always has, but increasingly in a positive way!

Best wishes,

Me in 2013

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Next post:  67.  ~coming soon~

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65. Sleep inertia

18 March 2012 at 06:54 | Posted in Circadian rhythm | 8 Comments
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Sleep inertia refers to temporary cognitive problems, low levels of alertness and vigilance, and impaired motor dexterity immediately upon awakening from an episode of sleep.  The ability to perform mental and/or physical tasks including learning is deficient for a period of time.  Executive functioning may be especially impaired; decision-making can be impaired by 50%.  Sleep inertia has been shown to be a robust, quantifiable process.

That’s the fancy way of saying that one feels groggy, slow, disoriented and a bit stupid for a while after getting up.

Normal people experience sleep inertia on abrupt awakening from a nap of more than 30 minutes and on abrupt awakening in the middle of the night.  It may last from 5 minutes to an hour or more.  The stage of sleep may be of some importance for the degree of impairment and how long it lasts.   Some degree of sleep inertia is possible even when the sleep from which a person has awoken may have fully dissipated their sleep need

“Circadian misalignment is the basis for all circadian rhythm sleep disorders. These disorders are often associated with impairments of cognitive performance that can have adverse effects on school and work performance, overall quality of life, and safety.”  [Reid et al]  Sleep inertia is common in circadian rhythm disorders and it seems to be more severe and long-lasting here than in normal people.  On top of this, people going to work or school by 9 a.m. are getting up in the middle of their biological night where sleep inertia has been shown to be 3.6 times worse than in “daytime”.

A few recent quotes from people in our support group

show that we find sleep inertia to be a major problem:

–The people I was traveling with even thought I was dead on one occasion because of my usual “coma” type sleep/difficulty waking.

–My son does that comatose thing when he is sleeping too.  NOTHING will wake him.  SO the sleep doc’s office calls and says to be sure and wake him on schedule.  I just said “Huh? That’s supposed to be funny, isn’t it?”

–I have the very deep sleep characteristic as well…  I’ve slept through fire alarms, even a jackhammer tearing up the street literally right outside my window.  […]  I’ll also apparently have limited conversations with people while still asleep, though I’ll have no recollection.  My college roommate told me I would crawl halfway down the ladder from my bunk and turn off my alarm clock with my foot, still dead asleep.

–Of course it doesn’t help that I won’t be anywhere close to alert for at least an hour after waking up if it’s morning…

–No one could understand how I could always be late for work; my bosses said “please just call and let us know if u will be late.”. What the?  There was never any recollection of turning off multiple alarms (if I did–maybe they ran out–I could never figure it out).  How could I call in my sleep? ;).  No options, if you are deaf, you can’t hear, and it’s like I was deaf or in a coma.

–I too have slept through fire alarms, normal alarms, building work in my room at one point etc.  My parents always said I could sleep through a nuclear blast :P  And I also talk in my sleep when someone’s trying to wake me up — not much though, just enough to reply “yes, I’m getting up” or something similar.

–The last time I was working regularly I had to budget at least an hour to get dressed because I could count on “losing” about 30 minutes every morning.  Just standing in the middle of the kitchen or in the shower asleep.

–Similarly, I set an alarm for three hours before class starts (takes 10-20 minutes to walk to class) because I seriously lose time when I wake up, especially if I wake up after fewer than an optimal number of hours of sleep. I don’t know if I sleep standing or not, but I definitely haze out and lose time.

–My boss can’t understand my DSPS.  And now I have an accommodation so I can work noon to 8:30 pm and still I don’t hear the alarms and often wake up half an hour before I need to be at work, thus I am often (OK, almost always) a little bit late even at noon.  I was told at work that since my supervisor was going to be on vacation, I’d need to come in to work at 8am for that week.  (I have a medical disability accommodation).  I explained it to them like this….if I was in a wheelchair, and my boss normally did something like climbing a ladder to replace lightbulbs, would you expect me to figure out a way to do that in her absence?  Would you remove a wheelchair ramp for a week for someone and expect them to crawl up a few steps for a week?

–I do wanna point out, my partner is the least DSPS person I know, he’s very average, sleeps 8 hours if allowed, but does very well on 6, works full time 9-5 without a problem. My point is, he’s normal :P  And if you set an alarm for his middle of the night, he will also be comatose-like and a total zombie even if he does manage to hear it and get up. And he’s actually fallen asleep in the shower/kitchen while getting ready for work before, when he’s had to get up at hours like 3-4am (which is very rare). So I don’t think that this type of sleep is DSPS or N24 specific .

 REFERENCES:

 Bruck D, Pisani DL.  The effects of sleep inertia on decision‐making performance.  Journal  of Sleep Research.  1999; 8: 95–103.

Matchock RL.  Circadian and sleep episode duration influences on cognitive performance following the process of awakening.  International Review of Neurobiology. 2010;93:129-51.

Achermann P, Werth E, Dijk DJ, Borbely AA.  Time course of sleep inertia after nighttime and daytime sleep episodes.  Archives italiennes de biologie. 1995 Dec;134(1):109-19.

Groeger JA, Lo JC, Burns CG, Dijk DJ.  Effects of sleep inertia after daytime naps vary with executive load and time of day.  Behavioral Neuroscience.  2011 Apr;125(2):252-60.

Reid KJ, McGee-Koch LL, Zee PC.  Cognition in circadian rhythm sleep disorders.  Progress in Brain Research. 2011;190:3-20.

Scheer FA, Shea TJ, Hilton MF, Shea SA.  An endogenous circadian rhythm in sleep inertia results in greatest cognitive impairment upon awakening during the biological night.  Journal of Biological Rhythms.  2008 Aug;23(4):353-61.

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66.  Next post:  67.  Blogathon:  “Dear Diagnosis”

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