Sleep and Spine

//Sleep and Spine

Sleep and Spine

Sleep and Spine : the inter-relationship between physical recovery and REM sleep

This document (although some revisions and new references have been added since) was submitted to The Lancet April 17, 2007. Lancet reviews are at end of document. Re-submission to The Journal of Circadian Rhythms and Acceptance Jan 5th, 2009.

 

Manuscript:

Atonia, Gravity, and the Pulse Physics of Sleep: a New Chronobiological Hypothesis.

Sleep is a great mystery.

[1] Its function has been debated for decades. Hard work conducted by researchers, has eloquently mapped out and organized the brain wave patterns associated with the stages of sleep. But there in uncertainty with the precise function of each stage of sleep. Sleep is generally believed to to aid in physical recuperation but this has vague connotations and inherent difficulties in objectifying.

Historically, sleep research has focused on the brain and surrounding parenchyma, and not so much of the physical body (below brain). From the early work of French scientist Henri Pieron in 1913 through to the 1953 landmark discovery of rapid eye movement (REM) by Eugene Aserinsky,[2] most of the research has looked to the brain and surrounding tissues to understand sleep and its role with higher areas of neurologic processing. There was time in history when a greater understanding of muscles originated and that led out of  William C. Dement published a paper[3] in 1958 on the presence of cyclic organization in cats.  This cardinal research was a stepping stone for Michael Jouvet[4] that identified atonia (absence of muscle tone) during REM sleep.  He coined the REM state a paradoxical sleep as the brain was very active but the muscles were not at all.  And to this day,  paradoxical sleep remains enigmatic.[5]

In human sleep, atonia is experienced primarily during REM[6] but it is also found in non-REM sleep like for example, when the head dips as a seated person is falling asleep.[7] Atonia is core muscle tone loss.[8] Researchers have described this phenomenon as a total paralysis of the antigravity muscles of the body[9] and interestingly, no one knows why the core muscles shut off during sleep.  The current explanation for this complete pseudo-paralysis is believed to prevent the acting out of our dreams.[10] REM sleep is the phase of sleep where we do our dreaming. This idea evolved from observations and disturbing effects of REM sleep behavior disorder.

Here, I propose an alternative viewpoint and a new hypothesis as to why the muscles relax during sleep.  To understand this new hypothesis for atonia in sleep, it is imperative that the reader understands current concepts of spinal stability as well as joint space width in synovial joints and their diurnal variations.

To give the reader a basic understanding of spinal motion and the role of stability, Stuart McGill (Professor of Biomechanics at the University of Waterloo) states that buttressing is critical.[11]  He states the musculature act as guy wires creating a 360-degree force  to prevent the intervertebral discs from buckling during movement.

disc height loss, core muscles, sleep, recuperation

Spinal Core Muscles

These spinal forces are designed to provide a stable platform so the extremities (hip and shoulders) can do their job.  But this mechanism has a  trade-off as it causes added compression to the spinal discs.

Diurnal variations to the intervertebral discs exist with 25% of fluid being expelled over the course of the waking hours in humans. We also have see other cartilagenous structures with similar variations–like in the knee. Unfortunately, not much research has looked at quadrupeds because they do also experience REM atonia.  But we do know that significant forces are required to keep the fore-limbs and hind-limbs together to prevent spine sagging.

In upright bipedals, the forces of spinal stability significantly compress the intervertebral discs. The consequent pressures on the them are significant–when you factor in the added loads of gravity.  Researchers have seen large variations in disc heights as much as 26mm in overall height. This is most apparent with the bipedal mammal, like humans.  It is also believed to occur in quadruped mammals.

Keeping vertebrae (and other bone ends that make up synovial joints) separated from one another is important for joint health. For the spine, there are 2 forces that work against the maintenance of vertebral spacing: (1) the axial force created by the stabilizing musculature and (2) the constant force of gravity (owing to the vertical nature of the human spine, this is presumably more so in upright bipedal as compared with quadruped animals). Peripheral joints from the spine also experience the forces of stabilizing musculature.

I believe that the main reason humans and other mammals experience atonia during sleep is to relax the compressive stabilizing musculature around the intervertebral disc(s) so that more complete imbibition of the intervertebral discs can occur. This is also important in other joints including the shoulders, elbows, hands, hips, knees and feet. This atonia has a primary function to re-fill the cartilagenous structures in joints in the spine (intervertebral discs) and also in other synovial joints. This filling occurs in an tonic/atonic rhythm through the stages of sleep to aid in the recuperation loss of water that results from the loading effects of the preceding day.

 

Points of Interest

Many researchers and writers use the term antigravity muscle to identify the muscles related to atonia. This is misleading because it is physically impossible to have a muscle that can contract and unload the effects of gravity across the whole of the organism. Muscles attach to bones and if a muscle contracts, it must have a effect of pulling on the bone. The stability muscles of the spine inherently compress the spine. All muscles that contract, must also compress associated joints.

What must be understood is that it is not the muscles, per se, that keep our vertebrae apart from one another, but instead, it is the binding and swelling capacity of the highly hydrophilic proteoglycans in the intervertebral discs that perform this service. The core muscles help to stabilize the spine as a whole, preventing injurious events to weight bearing cartilaginous structures like the discs and/or facets—not to relieve joint compression.

A schematic below represents how water flows through the vertebral endplates during disc compression (during upright activity) and how horizontal decompression (during sleep) may clarify the inflow and outflow of water to these deep avascular structures.

 

sleep and spine - hydraulics compression with endplate pores

 

The valveless vertebral venous system has been investigated with respect to its role in disseminating cancer metastases.[12] But what role does the valveless system play in the hydraulic dynamics of the intervertebral disc? That is, with the absence of bilunar valves in this venous network, could there be an innate vascular/spinal function that allows sufficient backflow to the intervertebral disc, providing opportunities for the disc to imbibe water under moments of unloading for structural as well as nutritional needs? Does this anatomical venous variation help the disc access nutrients? In addition to a possible structural hydraulic role, I believe that the valveless vertebral venous system also may aid in nutritional transportation to the avascular intervertebral discs during unloading.

The net goal of recuperating lost disc height most probably involves a dynamic, pulsatile mechanism throughout the stages of sleep. Discs are deep structures without much blood supply that obtain nutrients primarily through osmotic diffusion. Non-REM and REM likely offers on/off atonic tidal pulse that not only helps recuperate lost height but also possibly provides a means of distributing nutrients to the discs and expelling byproducts.

 

The constant of gravity

Gravity can be quite harsh—the obvious example of which is an individual’s height, which gradually decreases over the course of a lifetime. In 2006, Wannamethee and associates[13] examined 4213 men and their height changes during a 20-year period. The participants were separated statistically into different groups based on how much their heights had changed. Interestingly, the authors found that risk of death was significantly higher in men who had lost 3 centimeters or more. Also, these participants were 64% more likely to die during the course of the study than those who had lost less than 1 centimeter. Not reported in this study was from where the height loss occurred. Was it due to disc height changes, remodeling of endplates or vertebrae or both, or was it due to angular changes to primary and secondary spinal curves? A relationship between changes in height and death remains to be determined, but it does appear to be related. Evidence of the deleterious effects of gravity can be seen in common conditions in humans including degenerative intervertebral discs, hips, and knees. Most often, it is these load-bearing joints that are most affected with end-stage results and lead to persons with these joints to require common unloading tools like canes or walkers.

However, gravity is absolutely essential to prevent other disorders like osteoporosis. Weight-bearing exercises are recommended in this condition to stimulate osteoblastic activity in the building of bone. Additionally, the experience of not enough loading, as occurs in microgravity environments, may lead to back pain as reported by astronauts during and after space flight;[14] this most probably is due to too much disc fluid swelling. These researchers concluded that it was very difficult to mimic the same gravitational forces on Earth in space through physical exercise—demonstrating the gravitational influence on our biomechanics.[C J1] Some space flight studies have shown alterations in sleep atonia and have suggested a possible relationship to gravity.[15]

Even if bed rest has been shown to be an ineffective treatment for nonspecific low back pain, some still like to lie down. [16] Early movement following injuries to the lower back does favor the prognosis in these conditions. It is in the delicate weighing between these 2 different physical states—loading and unloading—that is to be sought; too much of one thing appears to be not favorable. Optimal outcomes for gravity-related disorders—of quality and quantity—continue to be sought after. However, determining the best biomechanical microenvironment must include a closer look at the hydraulics and optimal nutritional hemodynamics as well as the neurophysiological correlates around the discs that occur during 24 hours and longer; at present, this has not yet been thoroughly investigated.

As research regarding human intervertebral discs and their corresponding biomechanics begins to reveal the real-time nature of the spine, we now know there is a definitive diurnal variation of the human stature.16 It has been found that we loose height over the course of 1 day by as much as 26 mm, and this is very likely due to changes in the intervertebral discs. On average, it was found that 19.3 mm of height was lost with volumetric changes of 1300 mm³ in the lumbar discs.[17] Other researchers have found in vivo diurnal variations of 16.2% in the lumbar intervertebral discs,[18] while still others, using magnetic resonance imaging (MRI), have measured a 10.6% height gain over an 8-hour recumbent rest.[19] Some may argue that just lying down for a time without the atonia that comes during REM restores any loss in disc height. This has not been definitively evaluated especially comparing healthy discs to degenerated ones.[20]

And what physiological function does atonia play? Is it neurophysiologic, hemodynamic, physical, or all of these? The physical function is the one that makes the most probable sense in this continuing complicated investigation of atonia during REM. Preloading histories and optimal diurnal recovery states have not been studied extensively.

 

What do we know about sleep, definitively?

We know few absolutes about sleep. One absolute is its mysterious capture of one third of our lifetime (that is, if we are lucky and do not have insomnia). Other things we know about sleep have come from investigations in the field of comparative biology, which have revealed that sleep quantity is negatively correlated with the size of the animal. That is, the larger the animal the less sleep that is required. If size is correlated with less sleep, then could the size (mass) of the vertebrae be either negatively or positively correlated with need for sleep? Perhaps the larger the vertebrae, the less time is required to reset mechanoreceptors and recuperate the loss to diurnal height in bipedals or length in qudrupeds, repsectively. Or could there be smaller physical diurnal variations in larger mammals? If animal size is a determinant of sleep quantity, it seems obvious that we look at what determines the fundamental mass of the mammal and what it means in pure biomechanical terms, in an attempt to understand this relationship more clearly.

We also know REM sleep has a catching up effect and most of us have experienced a longer sleep after being very tired. This curious nature of “REM debt” has brought much scientific searching. If the loss in disc height along with changes in the adjacent mechanoreceptors requires a full resetting of length for optimal recuperation, could not REM debt simply be correlated with fine adjustments in disc height, mechanoreceptor length, or both of these? And would accumulated disc compression be a function of why sleep demonstrates this catching-up phenomenon? Some researchers have seen this recovery after 63hrs of sleep deprivation in humans and believe that it is the act of sleep atonia required to recover human height loss.[21]

Interestingly, cetaceans are the only mammals in which REM is not observed.[22] This finding lends support to this new hypothesis. That is, fish are not under the same gravitational demands as are land vertebrates and do not require the same buttressing spinal mechanisms for stability. They may not require atonia to recuperate the disc height loss in the same way land vertebrates do because of their aquatic environment. With minimal axial gravitational compressive loads coupled with the horizontal and constantly moving nature of their life, the need for atonia during REM could be negligible.

Quadruped mammals are known to experience atonic sleep. Some authors might argue that the horizontal nature of quadrupeds would not require similar sleep atonia to unload similar spinal vertical creeping compression experienced by upright bipeds. However, quadrupeds are designed with buttressing mechanics around the spine similar to those of upright bipeds. Holding the fore limbs and hind limbs together must require similar compressive forces for stability to inhibit significant spinal bowing.

Diurnal variations in the height and length of quadrupeds have not been investigated thoroughly. Perhaps, the small variations are difficult to measure. Horses, for example, can sleep standing in “stay mechanisms.” Some authors have speculated that horses do not experience REM in this position but require lying down to experience REM (S McDonnell, e-mail communication, October 1, 2007).[CR2] Perhaps, because of the horizontal nature of the horse spine, they have less net diurnal length loss when compared with humans—and perhaps this is why they can remain upright during sleep and only have to experience REM occasionally. Although unknowns regarding diurnal variations in quadrupeds remain, further investigations may help define the physical aspects of recuperation during sleep.

Another interesting phenomenon that researchers have attempted to explain is the commonly observed “jerk” most often experienced when just falling asleep. Many theories have been proposed but none has been substantiated. Could this spontaneous myoclonic muscle twitch experienced during atonia [23] be a local reflex occurring at the intervertebral level? Interestingly, in 1986, some researchers believed that a peripheral mechanism was responsible for the jerk because the authors saw more myoclonic limb movements during changes in spinal position.[24] More recent research suggests a spinal generator as the cause of the propriospinal myoclonus reflex.[25], [26] If atonia during sleep creates an unloading of the buttressing effects of compression, could it also be possible that muscle spindles are stretched quickly (from the outward expansion of filling discs) when the muscles relax and that this causes a local spinal myoclonic reflex—similar to that seen with the patellar reflex? More research is needed to define the changes of muscle spindles around intervertebral discs while they lengthen and reset in sleep and what that means from a proprioceptive neurological perspective.

Another interesting finding across all species is that the quantity of REM sleep is greatest at gestation and tapers off as the organism ages. From a developmental perspective, there are many cartilaginous components of the spine during its early formation. Interestingly, endochondral bone formation is prominent early in a developing mammalian spine as the ratio of nonvascular to vascular tissues is larger. With this preponderance of avascular tissues, like that of hyaline cartilage, the possibility that more cycles of REM atonia is required for hemodynamically influenced osmotic influx to both unload and provide nutrition to the developing skeleton most likely exists. Water with its important solutes, like oxygen and glucose, must find chondrocytes. We also know that the byproducts must be expelled. Approximately 25% of sleep in the young adult is REM,[27] but interestingly, this varies with age.[28] Correspondingly, as our spinal discs age, they tend to dry out, change shape, and lose height.[29] Some authors have already seen diurnal height variations in young mammals compared with their adult counterparts.[30]

Loss of disc height is correlated with disc degeneration.[31] We know that. But what we do not know is, what are the earliest etiologic signs of degeneration? What some researchers now claim is that due to vascular changes around the disc, that disc degeneration starts as early as during the first half of the second decade of life.[32] Physical forces exerted on intervertebral discs are of great current interest in the formation of degeneration.[33] Some forms of mechanical loading have demonstrated an ability to induce highly specific metabolic responses.[34] Given this, could not a yet-to-be-determined optimal cyclic rate, that is, sleep atonia, through an active cyclic osmotic unloading mechanism, help provide relief from the effects of axial loads accumulated during the day? Height increases seen in the morning in intervertebral discs are believed to be due to imbibition. Biochemically, it is thought that height increases are due to an increase of water-bound, negatively charged, sulphated glycosaminoglycan chains [35] in the discs. With the diurnal loading recovery cycle of intervertebral discs suggested in the mechanobiology and degenerative paradigm,[36] it is proposed here that atonia during sleep aids in the drawing of water and essential solutes across endplates in and out of discs in an ebb and flow fashion.

REM Sleep Behavior Disorder is a condition absent of atonia during REM sleep. It usually affects men over the age of 50 years who eventually develop additional signs and symptoms of several neurodegenerative movement disorders.[37] Interestingly, recent ideas around REM sleep disorder suspect that its presence can be a heralding sign of Parkinson’s disease.[38] In other areas of research, the association between pain and Parkinson’s disease is just beginning with suspicions of pain itself possibly preceding Parkinson’s in some patients. [CR3] [39] Could aberrant biomechanical neurological information in ascending pathways[40], [41] be an early etiologic signal of Parkinson’s disease in those who lack atonia within the RSBD group? That is, without proper atonia (and the neurophysiological events that exist with atonia) could this lead to early musculoskeletal problems, thus leading to mechanical dysfunction and perhaps pain, thus the development of Parkinson’s disease? Is this radical or rational thinking? Ford reports that musculoskeletal disorders, may be the first sign of Parkinson’s disease.[42] Others have reported pain alterations with sleep deprivation.[43] New perspectives suggest a spinal cord influence in the augmentation of restless leg syndrome,[44] a condition that has shown to have a relationship with Parkinson’s disease.[45] With the exact role of dopamine not completely understood at the spinal level;[46] there remains the possibility that the spinal cord and associated physiological structures may significantly influence the understanding of these related disorders.

New research on the mechanics of soft tissue deformation is beginning to reveal the harmful effects of sustained postures, demonstrating that in lumbar intervertebral discs, this mechanobiological creep happens more quickly when compared with cyclic patterns.[47] Could resting tremors in Parkinson’s disease be a favorable intention to physiologically help with mechanical joint problems in this disease? Interestingly, in Parkinson’s disease, tremors frequently surface on the side of the body in which pain is most prominent.[48]

Understanding what happens physically to those who experience RSBD may be challenging to researchers, as these persons usually perform some form of “exercise movement,” frequently through violent behaviors, as opposed to lying still during sleep. This may cloud the attempt to define fine measurements of height changes in these subjects. Movement in general is probably favorable to discs and surrounding tissues, if not injurious, both for individuals with the disorder and for their bed partners.

Fibromyalgia is a chronic condition of unknown etiology characterized by widespread pain, persistent fatigue, nonrestorative sleep, and generalized morning stiffness.[49] But what eludes investigators of the disease is the definition of “nonrestorative sleep.” What is it? If these patients do not achieve optimal sleep, what is going on in the muscles related to sleep? Is it possible that these patients are not experiencing the full range—from atonia to tonia—during sleep? Pain in this disease is not effectively treated with peripheral pharmaceuticals like nonsteroidal anti-inflammatory medications,[50] perhaps because of sensory-motor central nervous processing problem.[51] Are these muscles not achieving proper spindle length gain during sleep compared with muscles in persons without fibromyalgia? There are many questions to be answered but one thing we do know is that fibromyalgia is linked to poor sleep. We also know that muscle problems in this disease are typically bilateral.[52] If Fibromyalgia includes muscle problems, then, to find solutions to this disabling disease, we must look closely at the mechanobiology of the attachments for these muscles, and what “nonrestorative” sleep means physically.

Cataplexy and narcolepsy are other interesting phenomena that include spontaneous atonia similar to REM. Curiously, laughing has been found to stimulate the onset of these disorders.[53] It also has been reported that the deeper the emotional laughter, the more probable the catalyst is in many cases. From a biomechanical perspective, laughter increases intra-abdominal pressures. With more emotion, the more forceful is the laugh and in turn, the greater the possible rise in intra-discal pressures. Could changes in mechanoreceptor length during trigger a manifestation of the disease? An interesting study revealed that lateral, recumbent laughing increases intra-discal pressures.[54]

“So what,” one might ask. Well, if we begin to understand the underlying mechanisms of “why we sleep” and start to define what it means to truly recuperate, many doors in medicine will open up. Often, drugs with unclear specific mechanisms of action are prescribed for sleep-related disorders. If we begin to understand “why” patients respond to pharmaceutical interventions by understanding more clearly “where” the interventions are working, we can begin to focus on the underlying mechanisms of diseases known to be associated with sleep like fibromyalgia, Parkinson’s disease, Alzheimer’s disease, insomnia, restless leg syndrome, sleep obstructive apnea, narcolepsy, cataplexy, and osteoarthritis—while helping direct pharmaceutical interventions where needed. What about osteoarthritic degeneration? Is this a normal part of aging, or is it directly related to time and the forces of gravity that we encounter over a lifetime? Osteoarthritis is a huge economic burden worldwide, and if we can begin to understand the forces involved, we might be able to help the aging process of the spine and other related joints.

This perspective is purely physical in nature—looking at water, nutrients, and the body’s deep desire to undo the diurnal effects of gravity in a way that creates a pulsatile nutritional net influx to our discs (and possibly other joints). This hypothesis should not be considered exclusive but inclusive in understanding the complexities of sleep. If we are searching for a single answer to the question, Why do we sleep? we may be searching for a long time. Looking at the multifactorial demands on each specialized mammalian system must include looking at time-gravity if we want to understand why a third of our lives is spent under this strange unloaded physiological state.

The testing methodology of whether net disc height restoration occurs specifically during sleep’s atonia will require the use of imaging modalities. It is suggested that new, upright MRI technology be coupled with recumbent MRI to help discern the influence of atonia on spinal tissues. These technologies, along with sensitive spatial mapping tools like computer-aided design applications, should allow us to begin to observe the diurnal intervertebral disc changes during sleep and possibly begin to measure finer changes through time. Determining changes in intervertebral discs across time and sleep should help us begin to understand the physics of the wake/sleep cycle of the spine. Specifically, if height or volume changes in spinal discs could be measured for decompression rates across all stages of sleep, would one see a trend for disc height recuperation in atonia? With the greatest diurnal changes occurring in the lumbar discs, this should be the first place of investigation. Additional tools like highly sensitive digital stadiometers also should help reveal more clues to this ongoing investigation.

The goal of this article is to stimulate spine research during sleep. Since the discovery that atonia occurs during REM sleep, researchers have been looking to the brain and surrounding parenchyma for the reasons “why we sleep” with much progress in the neuromechanisms around the reticular formation. Still, our understanding of sleep is limited. Perhaps we should be looking closely at the diurnal behavior of the mechanical structures that help hold the brain up–the intervertebral discs. Limiting our search to top-down mechanisms may not allow us to step back and look at the physical interaction with gravity. Vertebral approximation is not a favorable situation in the spine [55] and simplistically, it seems reasonable to think that there should be an innate biological mechanism to allow intervertebral discs to decompress, obtain nutrients, and reset fine mechanoreceptor length, to prepare physically for the next day. Unfolding the full wake/sleep story on these biological tissues should begin to provide us with real measures into concepts of REM debt, for example, in hopes that the underlying physical mechanisms of recovery in sleep be more clearly understood. The curious nature of sleep’s atonia may not be as complex as once thought. Perhaps we have not been looking at the right structures for answers. Future long-term studies using polysomnography and simultaneous measures of height are required to substantiate or refute the hypothesis proposed in this article.

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Lancet Response from Reviewers

Dear Jerome,

At the first editorial meeting, a few weeks ago, there was a small majority [of 1!] in favour of continuing with your manuscript.

Opinions were polarised and feelings intense. At the most recent meeting, there were 2 in favour, 2 lukewarm, and about 5 against.

Sadly, in science the threshold is always high for papers that challenge conventional perspectives, or those that approach subjects in ways that are not customary.

I think your paper’s chances on appeal are not very high, but it is difficult to tell at this stage. If you could answer all the points concisely, clearly, and convincingly, your chances would at least be reasonable. I should add that it is unlikely that the process would take another 5 months. Appealing would take 1-2 weeks, and, if successful, your paper would probably go out for one more set of reviews. These would be easier to obtain than before, as we have a good idea of whom to approach, and would be likely to be written more quickly than before, as the reviewers would have seen the first version.

With all best wishes,

Yours sincerely,

Dear *****,

Thank you for the opportunity. A hypothesis paper, as requested, needs to be streamlined and condensed. I feel this request limited my ability to provide more supporting evidence to a topic that deserves a larger arena.

All the comments and questions below have explanations and I am uncertain as how to proceed and whether your team would reject again.

Could you at least tell me how many editors were in favour vs. were not?

Again I thank you for the opportunity and will decide where to go from here,

Jerome

—– Original Message —–

From: “The Lancet Peer Review Team” <eesTheLancet@lancet.com>

To: <drfryer@shaw.ca>

Sent: Friday, September 14, 2007 7:26 AM

Subject: Your submission to The Lancet

> Manuscript reference number: THELANCET-D-07-02591

> Title: Is the purpose of atonia in REM sleep to help restore the

> diurnal intervertebral disc height loss?

>

> Dear Jerome,

>

> I’m terribly sorry to tell you that, at the editorial meeting

> yesterday, we decided not to accept your manuscript; though not

without some debate.

> The reviewers’ comments and some editorial points are below. I hope

> you find these comments helpful.

>

> Your paper may be received favourably by the journal Medical

> Hypotheses, particularly if you can answer the points below. You also,

> of course, have the option to appeal to us. To appeal, you would send

> me an email answering the points below, with your manuscript amended

accordingly.

>

> With all best wishes,

> Yours sincerely,

>*******

>

> ____________________________

>

> Senior Editor

> The Lancet

> 32 Jamestown Road

> London NW1 7BY

>

> Reviewer #1 [SPINAL MECHANICS]: In some ways I am sympathetic to the

> authors idea yet in others it is far fetched. I am very familiar with

> the issue having performed substantial work in the area. The height of

> discs are dependant upon the previous loading history and it has been

> found that simply laying in bed for more than 8 hours causes the disc

> to continue swelling eventually to a level that induces disc stresses

> – this is probably not good. So the idea that REM sleep is needed to

> unload the discs and increase their height is far fetched in my

> opinion. Perhaps the solution is to perform the experiment and solve

> the issue rather than simply propose the notion.

>

>

>

> Reviewer #2 [SLEEP MEDICINE]: The paper provides light relief and some

> interesting provocative thinking – it is an excellent hypothesis

> potentially rebuffing established thinking in sleep medicine. The last

> line of the article should read something along the following lines

> “further long term studies using Polysomnography and sequential

> measures of height are required to substantiate or refute the

> hypothesis proposed in this article”

>

>

>

>

> Reviewer #3 [SPINAL MECHANICS]: This manuscript presents a very

> interesting and thought provoking hypothesis that atonia in REM sleep

> helps to restore the diurnal intervertebral disc height loss.

> Overall, this hypothesis is reasonable. However, the author should

> consider the following points, which are presented from a one-sided

point of view.

>

> 1) Atonia during REM sleep may have many functions, only one of which

> could be the restoration of disc height. Thus, the presented

> hypothesis does not need to be “an alternative” or exclusive (page 1,

> bottom and the last sentence of the article (no page numbers)).

>

> 2) The issue of height loss was described in a much too bleak point of

> view. Much of the height loss comes from the change in the vertebral

> height due to micro-fractures of trabeculi and increasing kyphosis

> with age. I believe that a more important issue pertaining to the

> presented hypothesis is the nutrient transport to the disc via fluid

> flow in and out of the disc (diurnal changes). Therefore, both

> periods of spine loading and trunk muscle atonia are necessary to

maintain adequate disc health.

> If only the issue of disc height was important, microgravity or bed

> rest environments would have been ideal for a healthy disc, which we

> know is not true.

>

> Minor issues:

>

> 3) Last sentence in the abstract: Try “Methods to test this

> hypothesis are introduced”.

>

> 4) Figures are not referred to in the text.

>

> 5) Reference #9 is missing.

>

> 6) Just a question for the author’s consideration: Do horses and cows

> also experience REM sleep atonia while standing?

>

>

>

>

> Reviewer #4 [SLEEP MEDICINE, ESP REM SLEEP]: This is an interesting

> article that presents the hypothesis that the characteristic REM sleep

> muscle atonia relaxes the stabilizing musculature around the

> intervertebral discs to allow imbibition of the intervertrebal discs.

> The authors should address the following points.

> -It is known that no-REM sleep is also a ssociated with a dramatic

> decrease of the muescular tone compared with wakefulness. When a

> person is sitting in a chair and suddenly falls asleep the head

> usually drops due to a decrease of the cervical paraspinal muscles.

> The title of the article should refer to SLEEP instead of REM-SLEEP.

> – Since the hypothesis concerns animal physiology the authors should

> discuss how the imbibition of the intervertebral discs may be affected

> when a subject sufferes from a REM sleep disorder (REM sleep behavior

> disorder which is characterized by lack of REM sleep atonia, and

> narcolepsy which is characterized by high REM sleep pressure) from

> bone and disc diseases (intervertebral disk prolapse, spondylosis,

> dwarfism) or from a muscular disease (Duchenne muscular dystrophy,

> severe polyneuropathies).

> – Concerning the hypothesis, the authors should mention and discuss

> some seminal papers by Jerome Siegel who cites the different amounts

> of REM sleep across the animal species. The term vertebrate,therefore,

> should be changed to mammals

> – Does body position (supine,lateral) during sleep has an effect on

> the proposed hypothesis?

> – Does the level of the intervertrebal disc (cervical, thoiracic and

> lumbar) has an impact on the proposed hypothesis?

> – References concerning sleep features need to be up-dated

>

> EDITORS

> 1. How will this paper be of clinical use?

> 2. [From the editor who disliked the paper the most]: “Basically the

> paper says that sleep restores intervertebral discs. That is well

> documented. It is well known that morning height is more than evening

> height – the effect supposedly of gravity. This paper adds nothing

> that is biologically sustainable.”

> 3. How will this paper interest and aid readers of the Lancet?

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