Can you think of any situation when, let’s say, you were talking to someone and suddenly that person would glance at you with boredom and their eyes seemed to slowly close as if they were on the verge of nodding off? This sort of situations can be very annoying and it would be a lie to say that you didn’t feel mad or at least slightly pissed off when they happened. You probably either ignored them or chose a more aggressive approach, in order to ‘wake’ them up.
But what if instead of just a very rude or uneducated person you would have to deal with someone who suffers from narcolepsy? Not only the person you would supposedly talk to is actually asleep, but waking them up is very likely to trigger unwanted behaviours.
As odd as it sounds, there are people in this world who can fall asleep instantaneously, without any previous warning, in the middle of doing anything ranging from reading and talking to cooking and driving. These people are called ‘narcoleptics’.
So what is narcolepsy?
Narcolepsy or the so-called syndrome of excessive sleepiness is a chronic neurological disorder that affects less than one percent of the population, therefore it is considered a relatively rare disease. Due to the multiple causes that lead to this disorder, narcolepsy has been considered either an autoimmune or a neurodegenerative disease. Often it is hard to be identified and wrong diagnosis is given, such as epilepsy (because cataplexy could resemble epileptic seizures) or schizophrenia (due to visual and sometimes auditory hallucinations).
The most common symptoms of narcolepsy are: sleep disturbance, cataplexy (muscle weakness), excessive daytime sleepiness, sleep paralysis, hypnagogic hallucinations and abnormal rapid eye movement (REM) – in narcoleptics REM occurs extremely fast (within a few minutes), whereas normally it should manifest after one hour and a half. Nevertheless, patients who suffer from narcolepsy have also experienced increased appetite, automatic behaviour, sleep apnoea and memory problems (this is not due to cortical dysfunction, but to impaired attention).
Except for cataplexy, sleep paralysis and hypnogogic hallucinations, reduced attention and disorientation after waking from daytime naps are also common. Moreover, patients could suffer from aggressive behaviour, with temper outburst and irritability especially if woken up and they might also deny their condition.
Interestingly enough, despite the fact that narcoleptics have trouble with being awake during the day, they would often experience insomnia during the night. Their sleep deficiency can be accentuated by some forms of medical treatment.
It has been demonstrated that many factors are involved in the initiation and development of narcolepsy; these range from genetic factors, including the human leukocyte antigen DQ and DR (HLA-DQ and -DR) genes and polymorphism of certain type of genes (for instance tumour necrosis factor alpha or monoamine oxidase genes, both located on chromosome 6) to environmental factors (head trauma and various infections, such as the infection with Streptococcus pyogenes). HLA genes code for the HLA complex called antigens, proteins with an essential role in the immune functions and usually associated with autoimmune diseases.
In addition, latest discoveries have shown a decrease in levels of hypocretin-1 and -2 (also known as orexin-A and-B) in the cerebrospinal fluid and hypothalamus could account for the trigger of narcolepsy. Deficiencies of this neuropeptide might produce changes in monoamine oxidases, enzymes with an important role in the degradation of amine neurotransmitters, such as serotonin and dopamine. Low levels of dopamine dramatically influence the development of some psychiatric and neurodegenerative disorders (ADHD and Parkinson’s disease, respectively) including narcolepsy.
Given the fact that the decrease of hypocretin tone plays an important role in the production of narcolepsy, an efficient solution would involve the increase in the concentration of these peptides. One way of achieving this is by intracerebroventricular administration of hypocretin-1 peptide, which appears to reduce the frequency of cataplexy and stimulate arousal in mice. Another even more efficient and less invasive method is represented by the intranasal administration, hence the neuropeptides being directly delivered to the central nervous system.
Serotonin was also discovered to have significant role in wakefulness and REM regulation, hence decrease levels of serotonin (5-HT) might induce narcolepsy. Therefore, medicines that could increase the levels of serotonin in narcoleptic humans might be a solution for this disease.
Most of the patients diagnosed with narcolepsy are recommended pharmaceutical treatments, which usually consist of the intake of certain doses of stimulants. Nevertheless, taking into consideration the side effects of these drugs and the limited adherence of the patients to the medications, alternative methods have been discovered. One of them is represented by behavioural and psychological approaches, for instance regularly scheduled naps during the day and daily exercises (but avoidance of activities that increase body temperature).
Since treatment involving cognitive stimulants is the most wide-spread, a lot of drugs are used in order to cure narcolepsy. A very common example is represented by amphetamines (such as Ritalin), which are known to increase levels of dopamine in the brain, reduce daytime sleepiness and inhibit the monoamine oxidases. Also Mazindol, Modafil and Selegiline are used as treatment for narcolepsy, as they reduce cataplexy and inhibit the monoamine oxidases. The amino acid L-tyrosine stimulates the production of noradrenaline and dopamine, therefore it also represents a solution (although more tests of its effects are required).
Some very important drawbacks that should be considered when using pharmaceutical stimulants in treating narcolepsy, and any disorder that affects the nervous system in general, are the possible adverse effects and the chances of dependence, abuse and tolerance. Although serious addiction problems haven’t been registered, high dosages increase the risk. According to some studies, 30-40% of narcoleptic patients using medicines have developed tolerance, therefore 1-2 days per week of no medication is recommended.
The most common adverse effects of the psychostimulants are headaches, insomnia, anorexia, irritability, heart palpitation. Patients must acknowledge that these drugs cannot be taken as brain enhancers and they must also be aware of the side effects and possible risk of addiction before deciding to undergo a medicine-based treatment.
I hope you enjoyed reading this article 🙂 It is actually highly based on an essay I had to write in my first year of university and therefore I am going to add the literature I used at the time in order to gather information.
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Image edited by Isuru Priyaranga