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So during REM sleep our subconscious minds are supposed to be active, while we lie unaware with our bodies perfectly still. However, two unusual phenomena can occur during REM sleep:
A lucid dream is when a person is aware they are dreaming, and may have some control over their own actions in the dream or even the characters and the environment of the dream.
This is different from simply having a passive memory of a dream, which can sometimes happen if we awake directly from REM sleep.
when a person recognizes he or she is dreaming while in a dreaming state and often manipulates events within the dream.”Read more at: http://phys.org/news202059647.html#jCp
Sound like Inception? It should, the screenplay was inspired by the phenomenon of lucid dreaming:
Stephen LaBerge is a psychophysiologist who did research on lucid dreaming at Stanford University in the 1970s.
He found that subjects who could control their dreams had more volitional (and not random) eye movements during REM sleep.
He now runs the Lucidity Institute, which aims to train people how to achieve lucid dreaming:
Proponents of lucid dreaming claim they can control their dreams to enjoy fantasies and over come nightmares.
Click here to listen to a RadioLab podcast about Lucid Dreaming.
REM sleep behavior disorder (RBD) is in a sense the opposite of lucid dreaming. Affected patients lose the motor inhibition that is a typical feature of normal REM sleep, and regain the motor strength to “act out” their unconscious dreams. This is an uncommon disorder, and can be associated with underlying neurodegenerative disorders like Parkinson’s Disease.
Or, if you prefer the Disney interpretation of RBD:
RBD video clips courtesy of Matthew J. Davis.
So, during REM sleep our conscious minds and bodies are supposed to be switched off, while our subconscious brain performs a scandisk generating passive dreaming. If our conscious brain somehow switches on during this time we experience lucid dreaming. Of our bodies switch on, and we start unconsciously reacting to these dreams we have REM sleep behavior disorder. If both were to happen simultaneously, we’d be awake!
Posted by David Cuthbert, MSIV, Drexel University College of Medicine
Every year thousands of people flock to several world locations with one common goal in mind – to push their bodies well beyond what nature has so far intended by climbing to dangerously high altitudes.
For whatever reason this appeals to some people. Those people are eager to overcome the restrictions set by Mother Nature, despite the obvious dangers.
As a kid I loved the move Cliffhanger with Sylvester Stallone. I remember watching that film and thinking that the only real dangers associated with extreme altitude were obvious – falling (please see video clip # 1), Slyvester Stalone wanting to use you as a human sled (watch video clip #1 again), the cold, or John Lithgow going crazy and wanting to use a helicopter to kill you for money (please see video clip #2).
But apparently those aren’t the only dangers, and medical school has taught me some pretty interesting stuff.
In fact there are a whole variety of medical syndromes that can occur at high altitude that don’t involve John Lithgow, and being that this is a neurology blog, this piece will focus on the neurological high altitude medical syndromes. And in particular, will place emphasis on one terribly interesting study.
The neurological syndromes of high altitude sickness are thought to be a spectrum of illness ranging from high altitude headache (HAH), to acute mountain sickness (AMS), to the most severe – high altitude cerebral edema (HACE).
The exact pathophysiologic mechanisms leading to these conditions are still somewhat unclear but several theories have been proposed and tested – all of which related to hypoxia and elevated intracranial pressure (ICP).
It is thought that in the milder end of this spectrum (HAH) the symptoms are solely contributed from hypoxia, and as disease severity progresses, and the patient comes closer to HACE – the pathogenesis is more attributable to raised ICP.
But what I find even more interesting than just the development of these syndromes – is the fact that there is great variability between who develops them. For some people, no matter how acclimatized they are they simply cannot go to a certain altitude without great risk of HACE and subsequent death. While others require little acclimatization, and are capable to trekking to the summit of Mt. Everest without necessitating the use of supplemental oxygen. This leads one to ask, what are the factors present that allow someone this ability to tolerate high altitude?
One answer (with considerable evidence to support it) lies within their genetics. The discovery of a transcription factor called “Hypoxia Inducible Factor”, or HIF, confirmed this. HIF is a transcription factor that contributes to the regulation of several metabolic pathways, and allows both production of a higher concentration of hemoglobin, and greater sensitivity of the carotid body to hypoxia. Another older, and forgotten theory looks to further explain this increased altitude tolerance through anatomic differences.
In 1985 Ross suggested that the “random nature of cerebral mountain sickness” can be explained by “more compliant systems”. In other words, if a person has larger sized ventricles, and/or more atrophic brain, they will in turn be less susceptible to altitude sickness because the compliance will leave them better equipped to tolerate the raise intracranial pressure.
Interestingly enough, there existed someone crazy enough to test this hypothesis. Someone not only willing to hike to these ungodly altitudes, but also willing to screw a bolt in his head to measure his own intracranial pressure. This person was Brian Cummings, an avid outdoorsman, who also just so happened to be a neurosurgeon.
Cummings and a team of ten undertook an expedition to the Kishtwar region of northern India to try to put this hypothesis to the test. However the data obtained from the experiment was destroyed in a fire. Or so everyone thought! Then recently Cummings wife (Cummings has since passed away) found the data from the experiment, allowing it to have since be published.
In this experiment the “tight fit” hypothesis was tested by using 10 subjects. These subjects had computed tomographic scans of their brains to measure their ventricular size. After which a scoring system was used to measure symptomatology related to high altitude neurological syndromes while at high altitudes. Also, three lucky volunteers had their intracranial pressures measured – allowed via screwing a pressure monitor through a burr hole in their heads . This stayed in place while trekking through Northern India Himalaya’s. Cummings himself participated in the study, and also had a pressure monitor placed.
The results of the study showed that the three subjects with the smallest ventricles suffered the most from Acute Mountain Sickness, and reported the worst headaches of the group. Meanwhile patients with larger to normal sized ventricles reportedly had significantly less clinical findings related to AMS:
Regarding the intracranial pressure monitoring, of the 3 subjects to be observed, one had large ventricles, one with normal size, and one with small ventricles. The only one to experience headache, was the patient with the highest observed rise in ICP, and was also the subject with the smallest ventricles.
Therefore the results of this experiment support Ross’s “tight fit” hypothesis, and provide a potential anatomic explanation to compliment other genetic mechanisms to explain why some people are more prone to developing high altitude neurologic syndromes.
Obviously, the small study size cannot definitively explain this susceptibility, nor can it exclude other mechanisms as contributing as well. Nevertheless this experiment is considerably important to those who wish to conquer the hypoxic environment of Mother Nature’s higher altitudes.
It allows an explanation for those that are less able to adapt, and maybe even one day provide a means of testing their ability to acclimatize prior to their summit attempt. And while that very well may never happen, this study at the very least is a great story about the incredible strength of the human spirit.
Dr. Cummings showed incredibly determination while searching for answers regarding the human ability to adapt to their environment, and fortunately now his work can live on.
The term concussion is derived from the Latin word “concutere” which means “to shake violently”:
This term is used to describe a head injury associated with a temporary loss of brain function, including impaired consciousness, cognitive dysfunction and/or emotional problems.
To fully understand Concussion’s Axis of Evil, one need look no further than the brutal world of professional boxing and it’s neurological complications.
One of the most savage beatings any fighter every received occurred on July 4, 1919 in Toledo, Ohio, when 24 year old Jack Dempsey destroyed 37 year old Jess Willard to become the Heavyweight Champion of the World.
One can easily spot the effects of concussion in Willard as he sustains blow after blow to the head, and he develops unsteady gait, erratic behavior (failing to avoid punches and protect himself) and ultimately unconsciousness.
New Jersey’s own Harrison S. Martland MD (1883-1954) was the first to report in 1928 that repeated beatings of this kind could lead to a delayed permanent neurologic syndrome referred to as punch drunk syndrome.
His observations went largely unheeded.
Muhammad Ali (born as Cassius Marcellus Clay in 1942) was only 22 when he became word heavyweight champion in 1964, almost 40 years after Martland’s paper was published.
Here is with Liberace in 1964:
Almost 10 years after that performance, Prof Corsellis reported further clinical and pathological features of punch drunk syndrome in his 1973 paper “The Aftermath of Boxing”.
Here’s data from one of his cases:
By 1983, Muhammad Ali was retired from professional boxing,
Obviously, repeated head trauma, and it’s consequences, is not unique to boxing:
His brain was examined as part of an ongoing study by Boston University’s Study of Traumatic Encephalopathy.
His brain showed the same pathologic changes as the Punch Drunk boxers.
This syndrome, more commonly referred to as Chronic Traumatic Encephalopathy, is now known to have occurred as a consequence of repeated head trauma in many other sports, including soccer, hockey, horse-racing and wrestling.
SIS is said to be a rare, often fatal, traumatic brain injury that occurs when a repeat injury is sustained before symptoms of a previous head injury have resolved.
Although limited to single case reports, and disputed as a discrete syndrome in the scientific literature, SIS cases are young athletes and have become high profile in the media:
Click here to find out more about this case.
This data, as well as SIS cases, has led to a concern that the presence of ongoing concussive symptoms are a significant risk factor for further injury to occur, and that any residual symptoms should mandate restriction for further contact sport in young athletes.
Finally, it is know that concussions are under-reported by high school players.
A 2004 survey of 1500 varsity football payers in Milwaukee disclosed that although 15% had sustained a concussion during the season only 50% reported it to their coach or trainer.
Click here to find out more about the Matthew J. Morahan III Health Assessment Center for athletes at Barnabas Heath.
Posted by Saeed Tarabichi, MSIV, Drexel University College of Medicine
Even before we learned how to use paper, mankind has delegated high priority towards learning to control one of the most instinctive of natural feelings: pain. As early as 5000 BC, there are clay tablets of the Sumerians regarding the cultivation of opium as a “joy plant.”
The point I’m trying to make is that people don’t like pain. A LOT. So much, that for as long as mankind has been in civilization these past 7000 years, we have constantly tried to eliminate it from our lives. Yet even after all these amazing technological advances we have made, it’s amazing to think that we have not yet solved the problem of unnecessary pain from our lives.
At this point, you might be thinking to yourself, “What are you talking about? What about all the powerful stuff we give people in the hospital like morphine, fentanyl, oxycontin? We even have things that can take the pain away from certain areas like lidocaine!” True, there are many options for pain that we can employ today, but these options are largely used to treat two of the three cardinal types of pain that humankind can experience: Somatic (the type of pain you get from cutting yourself) and Visceral pain (organ pain- think stomach ache). The third type of pain, neuropathic (damaged nerve pain), is one that we have not fully understood, and one that we have not fully learned how to deal with.
A recent research breakthrough might suggest otherwise. A group of researchers from France have found a very interesting new potential agent to help us treat this elusive neuropathic pain. This new agent was so interesting, that it intrigued the people over at Nature magazine to publish their article about it. So what is it that has all these people excited for the next potential cure to pain?
I bet you didn’t see where that was going (unless you already scrolled through this article, you cheater, you). That is a black mamba snake. The article published in Nature magazine is titled: Black mamba venom peptides target acid-sensing ion channels to abolish pain.
Black Mamba? Isn’t that the snake from Kill Bill 2?
Now you’re probably thinking to yourself, “Well isn’t that something?” Indeed, good reader, it is something. Something extremely dangerous, enough to “kill a man in 20 minutes,” can be used in a scientifically controlled environment for the good of mankind. If the promising stuff from this article holds true, we may have found our BOTOX equivalent for pain!
So now that I’ve beefed this article up enough, I think it’s time for me to get down to the nitty gritty details on what exactly the study was:
In order to understand the paper, there are a few concepts that need to be explained first. I’ll start with the physiological basis for how neuropathic pain works. There are these sensors within our peripheral and central nervous system embedded in the walls of these nerves called Acid Sensing Ion Channels (from here on known as ASIC). They are meant to sense the acidic changes outside of the neuron, which indicates local tissue damage has been done. Once these sensors are activated, they tell your body that there is pain in a particular area.
In the past, we have known there are specific types of agents that can be used to mess with these receptors. It was actually first noted that the Texas coral snake had a toxin that activated these receptors in order to cause pain. Amiloride, in high enough doses, has been shown to block this receptor as well. Now it has been shown that the snake venom from the black mamba contains a particular type of protein that interacts with this receptor in order to shut it off in a reversible fashion.
This protein is a 3 finger protein, that interacts perfectly with the ASIC receptor to shut it off in a reversible fashion.
The new class of protein that has been discovered from the black mamba snake venom has been cleverly named “mambalgins.” Try saying that 5 times in a row.
In both rats and humans, this research study has demonstrated that the use of this mamba venom blocks only the sensory ASIC receptors. They bind to the channel when it is in its “off” mode in order to decrease the sensitivity of the receptor to protons. The end result is that the receptor does not work when it’s supposed to, and signals can never begin to generate, stopping pain at the very source.
These complicated graphs show that when you increase the concentration of the mamba toxin, you decrease the total voltage seen in a specific neuron, indicating the neuron is no longer firing.
This graph compares the effect of the mamba toxin with morphine. They measure pain here within live mice by tail and paw flick latency. What this means, is the amount of time that elapses before there is a flick of the stated body part has been immersed in 46 degree C water.
What’s most amazing about this new finding is that “The central analgesic effect of mambalgin-1 shows reduced tolerance compared with morphine, no respiratory depression and involves the ASIC2a subunit.” On the graph below, you can see another comparision of the mamba toxin with morphine to the left. On the right, you can see the effect of each of the substances on respiratory effort.
Finally, they have shown that these ASIC receptors are also found in the distant extremities. They demonstrate that injection of the paw with the mamba toxin also effects paw latency indicating that not only are ASIC receptors located centrally, but are also implicated in nociception.
So what does this all mean? Have we finally found the cure to pain? I wouldn’t go so far as to say that. While the initial data from this study looks promising, there is still a very long way to go before we can apply this study into human treatment. We need to figure out the toxic effects it can exert on the human body. We need to find the optimal dosing and best way to deliver this drug to eliminate pain. We need additional studies to further investigate the potency of the toxin with regards to pain.
While much work remains to be accomplished, this article provides us with a promising starting point. In the not too distant future, we may see it applied towards people with chronic neuropathic pain in order to drastically improve their quality of life. There may be other uses in addition to pain for the black mamba toxin.
At the end of the day, I could see this new innovation used in intrathecal pumps to deliver very small doses of the toxin for people who have chronic neuropathic pain as a result of nerve injury, similar who how baclofen is used for spasticity. It will be interesting to see what other developments come from this protein.
To close this blog post out, I leave you with a video that will hopefully allow us to look at the most negative of situations and turn it around to something positive, just like these pioneering researchers did!
The virus travels slowly along peripheral nerves from the bite to the brain, and it can be several months between the animal bite and onset of the encephalitis.
Symptoms include headache, fever, confusion and agitation, paranoia, terror, hallucinations, and delirium. There is increased salivation, but attempts to drink or swallow lead to excruciatingly painful spasms of the muscles in the throat and larynx leading to “hydrophobia” (fear of water).
The increased salivation, combined with unwillingness to swallow, leads to profuse drooling of saliva infected with virus. The encephalitis leads to increased aggressiveness, unprovoked attack and biting, and thus facilitates the spread of the virus.
Although the only confirmed cases human to human transmission of rabies have been recipients of infected donor organs, folklore has suggested transmission by sex, nursing and biting, inspiring stories about vampires, werewolves, vampires and zombies.
The similarities between rabies and werewolves needs no further explanation.
In 1998, Juan Gomez-Alonso a Spanish neurologist wrote a paper in Neurology comparing vampirism with human rabies.
The most marked similarity are caused by rabid spasms of the head and throat.
This leads to clenched teeth with retracted lips like and animal, and inability to swallow saliva with frothing at the mouth and vomiting of bloody fluid.
And the same goes for Zombies:
These creatures first made fashionable in the 1954 book I am Legend, and then featured in the more recent movies 28 Days Later and World War Z, are even said to be caused by “infections” transmitted when a human is bitten by a demented zombie.
Click here to find out more similarities between Rabies, Vampires, Werewolves and Zombies.