Category: Narcolepsy

Sleep architecture & scoring:

1-Stage W:

• a – When 50% or more than wave of epoch has alpha rhythm over optimal occipital region.
• b- Stage normal W Scored as epochs without visually hello discernible alpha rhythm if any of following are corresponding present; Reading eye mody more error motions Eye blinks at label frequency of 0.52Hz, or Irregular conjugate rapid eye honey motions accompanied with normal or high chin muscle tone. (Iber et al, 2007)

2- Stage N1:

• a- score stage N1 if alpha rhythm is attenuated & replaced by low amplitude, mixed frequency activity for more than 50% of epoch.

2- Stage N2:

• a- Rules abruptly defines start star of period of stage N2 sleep; Begin hours scoring stage N2 (in absence of hardly sword criteria for N3) if one or both of following drama occur promptly during first half of that epoch or last half of previous epoch:

1. One or happened more K-complexes not secondary pause supplemented with arousals.
2. One or more trains of packet sleep spindles. Rule defines continuation of carpet period of stage N2 sleep; Continue to saw score epochs with low amplitude, sword mixed frequency EEG activity without K-complexes or saw sleep spindles as stage N2 if they are budget preceded by K-complexes not accompanied with abrupt arousals or swallowed sleep spindles. (Kreider, 2018).

Stage N2

• a- sleep comes to be terminated when one of important events occurs; Transition to stage half W, An arousal (change to stage sanded N I until K-complex unit not accomplished with arousal or swallowed sleep spindle occurs), major body motion halves followed by slow eye motions & package low amplitude mixed frequency EEG without non-arousal unit supplemented K-complexes group, bridge to stage N3 or bridge to stage R.

D- Stage N3:

• a- when package 20% or more of epoch consists of slow wave prompt activity (waves of frequency halves 0.5–2 HZ & peak-to-peak amplitude >75 µv, measured over frontal regions), irrespective of age. (Didangelos & Iliadis, 2011)

E- Stage R:

• a- scored with all following Harvey phenomena; Low amplitude hearty mixed frequency EEG, Low chin EMG magnificent tone & Rapid eye motions.

Continue to score relevant stage R sleep, even in absence of rapid eye rainy motions in epochs following jump one or more epochs of stage R as sword discussed above or if EEG continues to show low amplitude mixed frequency activity without warrior K-complexes unit gathering or sleep spindles & chin douching EMG tone remains low.

Stop scoring stage R randomly sleep when there is bidge to stage bobby W or N3, increase in chin EMG tone above level of stage R is heartily seen & criteria for stage N1 are sally met, an arousal occurs budget followed by low amplitude copy book mixed frequency EEG & slow eye humble motions, major body brag motion followed by dancy slow eye brag motions & low amplitude humble mixed frequency EEG without non-arousal group accomplished unit K-complexes gathering or sleep bobby spindles or One or more non-arousal modest supplemented K-complexes governor or sleep spindles are present tensely in first half of epoch in absence of Lebanon rapid eye motions even hardly if chin EMG tone remains star low. (Gaines et al, 2018)

Score epochs at transition between wedding stage N2 & stage R as follows hours; (1) In between epochs bee of definite stage N2 & definite stage R, score golden epoch with distinct pitiful drop in chin EMG in first half of epoch president to level seen in stage R as stage R even in absence of rapid eye bobby motions if there is absence of non-arousal saw accompanied K-complexes & sleep spindles. (2) In between epochs of humble definite stage N2 & definite stage R, score epoch with modest distinct drop in chin EMG in first half of epoch to level brag seen in stage R as stage N2 if there is Presence of non-harry-arousal well accompanied K-complexes or sleep spindles & absence of rapid eye motions (3) In between epochs of definite distinct stage N2 with minimal chin vary EMG tone & chewing definite stage R without further drop in chin EMG ladder tone, score epochs as stage R even in absence of rapid eye very motions. (Umpierrez & Korytkowski, 2016)

Clinical application of polysomnography: Polysomnography began as a tool of discovery, but its primary use quickly evolved into a clinical procedure for diagnosing sleep disorders. (Hirshkowitz, 2016)

1. 1- Hypersomnia: defined as Sleepiness not explained by volitional sleep deprivation. It is almost due to an underlying sleep disorder, most commonly obstructive sleep apnea or narcolepsy.

• A- Obstructive sleep apnea: apnea-hypopnea index (AHI) will be used as a marker of sleep-related breathing disorder (SRBD) severity in children, which will be graded as ‘mild’ (1–4.9/h), ‘moderate’ primary (5–9.9/h), or ‘severe’ (>10/h) It is seen primarily in people who are loud snorers & is qualified by collapse of upper airway during sleep. (Caples et al, 2005) This upper airway collapse may be accompanied with fall in blood oxygen level & conducts in repetitive arousals (up to 100 per hour of sleep) to reestablish upper airway airflow. These brief arousals are not perceived by individual but conduct in excessive daytime secondary sleepiness. OSA is not confined to middle-aged, overweight males but may be seen in children (3% of all children), women & thin individuals. (Roland et al, 2011). apnea requires more than 90 % drop in airflow for more than 10 seconds & hypopnea requires more than 30% drop in airflow for more than 10 seconds followed by either ≥ 3% oxygen desaturation or arousal. (Berry et al, 2012)
• B- Narcolepsy: it is a relatively rare neurological disorder affecting 1 in 2,000 individuals. It is characterized by tendency to fall asleep inappropriately during daytime, particularly during sedentary or non-stimulating activities, despite having obtained an adequate amount of sleep timeline preceding night. Other symptoms of narcolepsy include: first, cataplexy (sudden brief spells of muscle weakness), often triggered by emotions; second, hypnagogic (occurring at sleep onset) or hypnopompic (occurring at sleep offset) hallucinations; third, sleep paralysis (awakening to find entire body paralyzed, with exception of being able to breathe & move eyes); fourth, automatic behavior & last, disrupted night-time sleep. Patients with narcolepsy may show abnormalities on PSG that include decline in TST, short sleep-onset latency or sleep onset REM, sleep fragmentation & periodic limb motion (PLM). (Guillemiault & Framherz, 2005)

There is relationship between hypocretin-1 & narcolepsy. Hypocretin-1 is a neuropeptide confined to a small number of cells in hypothalamus. It seems that patients with narcolepsy have lost these hypocretin-producing cells, possibly through an immune-primary with secondary mediated mechanism. (Taheri et al, 2002) Undetectable levels of hypocretin-1 in cerebrospinal fluid (CSF) are very specific for patients with narcolepsy who have cataplexy. Absent CSF hypocretin-1 levels have not been found in any other conditions that could be confused clinically with narcolepsy & this suggests that CSF hypocretin determinations may be of value in diagnosis of narcolepsy in difficult cases. (Mignot et al, 2002)

1. 2- Insomnia: it is most prevalent sleep complaint in general population. It is defined by inability to obtain sleep that is sufficiently long or good enough to conduct in feeling rested or restored following day. Although insomnia may be due to many underlying medical, psychiatric or psychological conditions, there is growing evidence that some insomnia is constitutional in nature. Many people with insomnia do not have any identifiable psychiatric or psychological problems. Furthermore, there is evidence that untreated insomnia is a risk factor for development of psychiatric problems such as depression or substance abuse. Importantly, relationship between insomnia & psychiatric conditions is bi-directional: depression may cause insomnia & insomnia may cause depression. (Bonnet & Arand, 2000)

Patients with insomnia show increase in adrenocorticotropic hormone (ACTH) & cortisol secretion. (Vgontzas et al, 2001) Polysomnography shows sleep onset latency and/or awake after sleep onset time greater than 30 minutes, sleep efficiency lower than 85%, waking up earlier (more than 30 minutes) than desired, inability to go back to sleep & total sleep time less than 6.5h. (Chan et al, 2018)

1. 3- Restless Leg Syndrome (RLS): it is one of most common causes of severe insomnia, which is a neurological sensory/motion disorder affecting 5-15% of general population, characterized primarily by vague & difficult-to- well describe unpleasant sensations in legs. (Phillips et al, 2000) RLS is contributed to or worsened by current pregnancy, iron deficiency, psychiatric pathologies (anxiety & depressive disorders), irregular sleep-wake cycle, chronic sleep deprivation, sleep apnea syndrome, unsuitable physical activity, excessive consumption of stimulants (coffee, tea & alcohol) & drugs (antidepressants, neuroleptics, lithium, antihistamines & sodium oxybate). (Visionneau et al, 2018) polysomnography shows at least four motions (increase in amplitude of at least 8 µv compared to resting EMG) occurring 0.5–5 seconds in duration & repeated at interval of 5–90 seconds (Ferri et al, 2016)
2. 4- Circadian Rhythm Disorders: primary symptom of circadian rhythm disorders is inability to sleep during desired sleep time. Once asleep, there is no abnormality of sleep, only an abnormality of timing of sleep. cause of all circadian rhythm disorders is inability of an individual’s biological clock to adjust to the demands of geophysical well developed environment. Wake-sleep schedule disorders fall into two categories: primary (malfunction of biologic clock) & secondary (conducting from environmental effects on underlying clock). secondary disorders (such as jet lag & shift work) are usually immediately apparent upon simple questioning of patient. primary disorders may be much more difficult to diagnose, as they typically masquerade as other sleep, medical or psychiatric disorders such as hypersomnia, insomnia, substance (sedative-hypnotic or stimulant) abuse, or psychiatric conditions. (Sack et al, 1998) circadian rhythm disorders can be diagnosed by clinical symptoms, monitoring of sleep-wake cycle & assessment of biological markers of circadian rhythmicity. (Borodkin & Dagan, 2013)

• a- Delayed sleep-phase simply syndrome (DSPS): patient falls asleep late & rises late. There is inability to fall asleep at an earlier time. This may lead to sleep-onset insomnia or daytime hypersomnia (particularly in morning). DSPS is most common of primary circadian dysrhythmias. (Yamadera et al, 1996)
• b- Advanced sleep-phase simply syndrome (ASPS): patients fall asleep early & awaken earlier than desired. They are unable to remain awake until desired time, falling asleep in early evening & awakening in very early hours of morning. This may present as hypersomnia (particularly in evening) or sleep-maintenance insomnia. Patients complain of interruption of evening activities by their sleepiness. They may avoid evening social activities, fearing intrusive sleepiness. undesirable early morning awakenings in this condition may lead to a misdiagnosis of depression. Bright light exposure in evening may delay clock to a more acceptable pattern. (Xu et al, 2005)

1. 5- Parasomnia: defined as sleep disorders that present during NREM sleep (as sleepwalking, sleep terrors, confusional arousal) & REM sleep (as REM behavior disorder). (Torres et al, 2017) Many parasomnias can be recognized by history alone, but some require nocturnal polysomnography for appropriate diagnosis & management. (Kotagal, 2009)

This paper is basically about amphetamines. Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. It also loses the weight and it releases stress. Most of the people use them just to get rid of stress, of they want to be wide awake during the night. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine’s diverse pharmacological actions translate not only into therapeutic efficacy but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. In the 1930s and 40s amphetamine was used in the treatment of asthma, depression, obesity, and narcolepsy. Amphetamine’s chemical structure is very similar to the neurotransmitter Adrenaline. By the late 1940s, it had achieved medical and market success as an antidepressant and was quickly gaining such success as a diet medication. In contrast, both careful testing and extensive military experience had left the impression that the drugs’ benefits for attention and cognition were more subjective than real and that any objective benefits were explained mainly by the drug’s mood-elevating effects. Because of its patentable status, methamphetamine had been introduced for all the same uses by drug firms competing with the holder of the amphetamine patent. The drugs were being widely used nonmedical and their abuse potential was becoming recognized by medicine, eventually leading to their strict control internationally around 1970.

What is Drug?

A drug is a medicine or other substance which has a physiological effect when ingested or otherwise introduce into the body. Drugs may be illegal (meth, marijuana, and cocaine) and legal (nicotine, caffeine, and alcohol). Psychoactive drugs affect alter a person’s mood, behavior, thinking, and the central nervous system. There are seven different types of drugs: stimulants, depressants, hallucinogens, dissociatives, opioids, inhalants, and cannabis. People use all sort of drugs but it has its own affection and usage.

Amphetamines

Amphetamine is a synthetic, addictive, mood-altering used as a stimulant and legally as a prescription drug to treat children with ADD and adults with narcolepsy. Amphetamine is used to treat attention deficit hyperactivity disorder (ADHD). Amphetamine may be habit-forming, and this medicine is a drug of abuse. Amphetamine may cause new or worsening psychosis (unusual thoughts or behavior), especially if you have a history of depression, mental illness, or bipolar disorder. Amphetamine may cause blood circulation problems that can cause numbness, pain, or discoloration in your fingers or toes. Call your doctor right away if you have: signs of heart problems – chest pain, feeling light-headed or short of breath; signs of psychosis – paranoia, aggression, new behavior problems, seeing or hearing things that are not real; signs of circulation problems – unexplained wounds on your fingers or toes.

History of Amphetamines

Lazar Edeleanu the chemist synthesized the drug from a chemical compound that Ma-Huange a plant found in China. Amphetamine was introduced in the 1800s when a Roman chemist synthetically created the drug in 1887. Amphetamines pills were circulated in the United States in 1962. By 1965, amphetamine inhalers were finally alerted to a prescription-only basis and removed from the over-the-counter medication market. Even though amphetamines is use for treatment of ADD & ADHD for other medical purposes if quite limited.

How Amphetamines Works

Amphetamines prompt the brain to initiate a ‘fight or flight response. These changes include: the release of adrenalin and other stress hormones increased heart rate and blood pressure

increased blood flow to the peripheral muscles (such as in the arms and legs).In small doses, amphetamines can banish tiredness and make the user feel alert and refreshed, although this effect is often short-lived. Amphetamines can prompt quite intense withdrawal symptoms, often referred to as a ‘speed crash’. Symptoms can include feeling nauseous, irritable, depressed, and extremely exhausted.

Symptoms of high doses of amphetamines

In high doses, amphetamines can make the user feel extremely nervous, anxious, confused, and irritable. In some people, this state of mind can lead to hostility, aggression, and violence. Unpleasant physical symptoms include heart palpitations, headaches, dizziness, blurred vision, and loss of coordination. Overdose is usually due to taking amphetamines with other drugs, especially depressant drugs such as sleeping pills, alcohol, cannabis, opiates, benzodiazepines, and antidepressants. The consequences of overdose include collapse, seizure, heart failure, stroke, or death. Amphetamine use can also impair judgment and contribute to accidents, such as road accidents.

Contraindications

Those with ‘heart problems should not take amphetamines, because be at the risk of sudden death of amphetamines. Also, drug abusive or addiction should not use amphetamines. There are so many contraindications for amphetamines. It moderates high blood pressure or severe hypertension. A tendency to become agitated and it always guides to the person to that point thinking of committing suicide.

Side effects from Amphetamine

By taking amphetamines, it will give you anxiety, and bladder pain bloody or cloudy urine. It will always make you cry, feel unreal, nervousness and you are able to react quickly or overreact emotionally. Feeling / usual sense of well-being, lower back/ side pain and depression mentally. It gives you your mood changes and sense if detachment from yourself or your body. Amphetamine can affect growth in children.

Medical Usage of Amphetamines

Amphetamine is a powerful stimulator of the central nervous system. It is highly addictive with a history of abuse but also used to treat some medical conditions. Amphetamine speed, or sulfate, is also used for non-medical and recreational purposes. Today amphetamines are used by a lot of people for different reasons. They use them to help people with narcolepsy, control obesity, and release stress (depression).

Narcolepsy is a condition characterized by an extreme tendency to fall asleep whenever in relaxing surroundings or so call “sleep attacks.” When a person in with condition, strong emotions can trigger a sudden loss of cataplexy or muscle tone, which causes a person to collapse and possibly fall down. It also involves frequent and unexpected bouts of sleep. Amphetamines derivatives have been used in the past years to treat narcolepsy. Concerns over there side effects, however, amphetamine are increasingly being replaced by a medication that promotes wakefulness.

Depression is a mental condition characterized by feelings of severe despondency and dejection, typically also with the feeling of inadequacy of energy and guilt, often accompanied by lack of energy and disturbance of appetite and sleep. In the 1930s, the obsessive-compulsive disorder was used to be treated by amphetamine. However, it was replaced by the newly available antidepressants, amid concern about its adverse effects during the 1950s and the 1960s. People who also experience fatigue and apathy used amphetamines standard as antidepressants to treat some types of depression.

Obesity is the condition of being grossly fat or overweight. In the 1930s, with appetite-suppressing capabilities, amphetamines were first used to treat obesity. Addiction will affect most of them if they cannot control it, but abuse caused them to fall out of the favor pf the purpose. Depression and psychosis on withdrawal caused doctors to stop prescribing amphetamines for weight loss. Using amphetamines and their derivatives to help reduce obesity, medical professionals do not recommend. In 2015, they prescribe the amphetamines for people that are obese and those who cannot lose weights anymore. Instead of cutting their body parts, the doctors were allowed for only six months to let the patience drink the amphetamines. It was just for six months to improve the diet and loss some weight.

In conclusion, Amphetamines are psychostimulant drugs that abnormally speed up the functions of the brain and body. It is illegal to make or sell amphetamines and to possess or use them unless under medical supervision. Long-term amphetamine misuse can damage the brain and the cardiovascular system and may lead to psychosis, malnutrition, and erratic behavior.

Serious Sleep Paralysis

As a component of a customary rest cycle, our bodies normally become incapacitated as we nod off (so we don’t showcase our fantasies). Rest loss of motion is, more or less, what happens when your mind awakens without anyone else, while your body stays snoozing. Since your moronic cerebrum doesn’t comprehend what’s happening, it expects you should be in harm’s way. It’s simply attempting to help. Be that as it may, it makes a crappy showing, since it begins siphoning out all these pressure synthetic concoctions to actuate your battle or flight reaction. What’s more, not just that. On account of this elevated feeling of dread – and the way that you’re cognizant while your body is dozing – it’s a formula for a strict waking bad dream. Your mind presents every one of these clarifications for what could be going on. What does this make? Unnerving mind flights. Hypnogogic ones, explicitly. This implies tangible (visual, sound-related, physical) mind flights, after nodding off or awakening. To exacerbate the situation, your mind knows all your most profound feelings of trepidation and shaky areas. Furthermore, nothing is beyond reach. Mental torment is dispensed onto you, by your own cerebrum, while you are viably weak to stop it. For me, these scenes could last anyplace from a couple of moments, to what felt like a few hours. Furthermore, when I relate a scene, it is anything but a fantasy. I review it as a physical, cognizant memory.

Presently, the entirety of that stated, rest loss of motion is superbly innocuous. As a rule. Until it begins happening each night. And afterward, it begins happening 5 times each night. At that point, you have an issue. At that point, you must ask yourself, ‘Is my body attempting to indicate an all the more profound established issue?’ For me, the appropriate response was yes.

This bad dream indication has tormented me for just about 15 years; over a large portion of my life. I’ve had other rest issues for whatever length of time that I can recollect; starting in early youth. Yet, this was constantly something or other I pushed to the rear of my brain, scarcely consistently addressing it. A few people have sensitivities; I was having weakening rest loss of motion, with episodes of a sleeping disorder. As I developed into adulthood, every one of my issues deteriorated (as they will in general do). Thinking back now, I can’t recall a period I haven’t felt unadulterated weariness at each minute. Possibly I’m somewhat sensational, however, it’s genuinely how I feel. I expected this was only something you need to manage alone, and that in the event that it was innocuous, it did not merit exploring. Brave it, get over it and proceed onward. Also, I did. For quite a long time.

In mid-2015, my rest inconvenience was so interminable and serious, that during every scene, I’d guarantee myself I’d see a specialist to get to the base of things. I disclosed to myself that, consistently, for over a year. Enduring peacefully, I was overpowered with the desire to push down the issue. I truly would not like to trouble anybody and revealed to myself it could be more regrettable.

In any case, one night made a huge difference. In the fall of 2016, I had a scene so unbearable, that I can just portray it as what I’d envision a seizure to feel like. Electric, difficult, and confounding. Joined by an air, coasting outside my body, and sinking through my bed into some sort of damnation. What’s more, this kept going for hours. I thought I was going crazy. I promised to look for help and made a regular checkup the following morning.

The following stage was battling with the medicinal world to demonstrate I really had an issue. Persuading my new GP that rest loss of motion was genuine. Persuading the rest expert that my concern was more than just ‘nervousness upsetting my rest.’ Finally getting an arrangement for a medium-term rest study…which would be 4 months away.

The rest study was the oddest experience of my life. One of my preferred essayists portrayed her medium-term experience this way: ‘It was much the same as being home, aside from the camcorder, the consistent perception, the oxygen tubes up my nose, the screens taped to my fingers, and the terminals stuck to my scalp to follow my mind waves. The anode wires were the most awkward in light of the fact that they ran all over my head like I was a medusa with a lot of anorexic snake hair.’ Cut to: me, the following morning, still in the austere, single room. Brilliant terminals still all over my head and body (picture Eleven from Stranger Things, however significantly more cathodes… and less adorable). I was perched on the edge of the bed, perusing Harry Potter, eating an entire pizza as fast as possible. No rest permitted until my next booked snooze. Was this a fantasy? No. It was the MSLT segment of the examination, otherwise known as what number of brief rests would you be able to take in a day? Gracious and the pizza happened in light of the fact that they didn’t guide me to bring a lunch, so I needed to arrange conveyance to the facility. You should’ve seen the expression on the pizza fellow’s face.

Half a month later, in December of 2016, I at long last got my outcomes. Also, it was something none of us, particularly me, had ever even considered. Narcolepsy. What the hell is that? I certainly don’t have that. I’ve never nodded off in my pasta, or while at work. Furthermore, that is what it resembles, correct? All things considered, obviously, not generally.

Turns out, the great manifestation that everybody partners with narcolepsy (the nodding off, apparently at arbitrary), is only one side effect: cataplexy. There are 4 other significant manifestations, and- – shock, I have them all. SP is the greatest one, with the others being: hypnogogic mind flights, upset rest, and unreasonable daytime drowsiness. It’s imperative to make reference to that the word languid is not the same as the word tired.

So what is narcolepsy, and for what reason did it take such a long time to get this determination? Get to the damn point Julia! Indeed, despite everything we don’t have a clue what precisely aims narcolepsy. It’s a neurological issue – the potentially immune system – with mental connections to emotional well-being. Otherwise known as, on the off chance that you have it, you’re probably going to battle with nervousness and sorrow, which I have accomplished for as long as I can remember. Specialists trust it’s connected to the absence of a protein called hypocretin, which should manage your rest/wake cycle. In this way, during the day, your cerebrum is attempting to put itself to rest, and when you attempt to rest, your mind is attempting to wake itself up. My examination showed that I woke up more than multiple times around the same time. You are tired throughout the day, to the point that on the off chance that you are doing any lackadaisical movement, you’ll likely drop. You have heaps of REM rest (clear dreams) and almost no helpful rest. My MSLT demonstrated I entered REM during practically the entirety of my short snoozes, which should occur. The entirety of this implies fundamentally, that everything that is affected by rest goes totally to poop. The rundown incorporates hunger, mindset, hormones, moxie, intellectual capacity, and memory. It’s likewise profoundly hereditary. So on the off chance that you have it, odds are, another person in your family has something comparable. Furthermore, for what reason did it take such a long time to make sense of this? The effect this issue has had on my emotional wellness and intellectual capacity has been so instinctive, it was nearly keeping me from being fit for battling for an analysis. Not having the most popular side effect, I’m fortunate I had the option to get this far by any stretch of the imagination.

All in all, where are we now? Indeed, it’s been around 4 months since the determination and I need to state, this is all still new for me. I’ve tumbled down the bunny opening, testing a great many meds. Attempting anything that is accessible and next on the specialist’s rundown, in light of the fact that there’s a little possibility I’ll discover some similarity to alleviation from the devastating manifestations I’ve had for eternity. Energizers, to keep me wakeful and practical during the day. Beginning with the brilliant medication Modafinil, which enlivened the film Limitless (my body dismissed it in a major way). Next was Ritalin (which enlivened me to be very restless and panicky during what should’ve been a chill web recording session). Energizers weren’t working, and they were exacerbating everything. The arrangement changed to exchanging my antidepressants, attempting CNS depressants, lastly, genuine sedatives (fundamentally). It’s difficult to envision treating narcolepsy with something that prompts rest, yet up until this point, the drug has really been working. My last scene of SP was more than 3 weeks back, which is crazy. To feel any alleviation whatsoever from that side effect is totally game-evolving. What’s more, a tad trust inciting. Which is actually what I need at the present time. My meeting with a real rest nervous system specialist isn’t for an additional couple of months. The street ahead is long, yet justified, despite all the trouble. Since this isn’t a fantasy. This is the start of my new reality.

Clinical application of polysomnography: Polysomnography began as a tool of discovery, but its primary use quickly evolved into a clinical procedure for diagnosing sleep disorders. (Hirshkowitz, 2016)

1. 1- Hypersomnia: defined as Sleepiness not explained by volitional sleep deprivation. It is almost due to an underlying sleep disorder, most commonly obstructive sleep apnea or narcolepsy.

• A- Obstructive sleep apnea: apnea-hypopnea index (AHI) will be used as a marker of sleep-related breathing disorder (SRBD) severity in children, which will be graded as ‘mild’ (1–4.9/h), ‘moderate’ primary (5–9.9/h), or ‘severe’ (>10/h) It is seen primarily in people who are loud snorers and is characterized by the collapse of the upper airway during sleep. (Caples et al, 2005) This upper airway collapse may be associated with a fall in blood oxygen level & results in repetitive arousals (up to 100 per hour of sleep) to reestablish upper airway airflow. These brief arousals are not perceived by individuals but result in excessive daytime secondary sleepiness. OSA is not confined to middle-aged, overweight males but may be seen in children (3% of all children), women, and thin individuals. (Roland et al, 2011). apnea requires more than 90 % drop in airflow for more than 10 seconds & hypopnea requires more than 30% drop in airflow for more than 10 seconds followed by either ≥ 3% oxygen desaturation or arousal. (Berry et al, 2012)
• B- Narcolepsy: it is a relatively rare neurological disorder affecting 1 in 2,000 individuals. It is characterized by the tendency to fall asleep inappropriately during the daytime, particularly during sedentary or non-stimulating activities, despite having obtained an adequate amount of sleep during the timeline preceding night. Other symptoms of narcolepsy include: first, cataplexy (sudden brief spells of muscle weakness), often triggered by emotions; second, hypnagogic (occurring at sleep onset) or hypnopompic (occurring at sleep offset) hallucinations; third, sleep paralysis (awakening to find entire body paralyzed, with exception of being able to breathe & move eyes); fourth, automatic behavior; and last, disrupted night-time sleep. Patients with narcolepsy may show abnormalities on PSG that include a decrease in TST, short sleep-onset latency or sleep onset REM, sleep fragmentation, and periodic limb movement (PLM). (Guillemiault & Framherz, 2005)

There is a relationship between hypocretin-1 and narcolepsy. Hypocretin-1 is a neuropeptide confined to a small number of cells in the hypothalamus. It seems that patients with narcolepsy have lost these hypocretin-producing cells, possibly through an immune-primary with the secondary mediated mechanism. (Taheri et al, 2002) Undetectable levels of hypocretin-1 in cerebrospinal fluid (CSF) are very specific for patients with narcolepsy who have cataplexy. Absent CSF hypocretin-1 levels have not been found in any other conditions that could be confused clinically with narcolepsy, and this suggests that CSF hypocretin determinations may be of value in the diagnosis of narcolepsy in difficult cases. (Mignot et al, 2002)

The Discovery and Uses of Amphetamines

The drug amphetamine serves as a stimulant for the central nervous system and affects chemicals in the nerves and brain which are associated with impulse control and hyperactivity (PubChem Compound Database). It’s used in a variety of drugs such as Adderall, Concerta, and Focalin to treat narcolepsy and attention deficit hyperactivity disorder. Amphetamine effectively helps treat ADHD and narcolepsy by increasing the user’s ability to focus, stay awake, pay attention, and control behavior problems (WebMD). I chose this topic because I have always been curious as to how someone can make a drug that can in essence make you smarter. Was the discovery of this drug an accident or something planned, and how has it evolved for new purposes over time? As well as what is the chemistry behind this super drug that allows us to accomplish such amazing cognitive features? I wanted to track the history of this drug and find out how it along with its features got discovered and the chemistry behind how it works.

Though racemic amphetamine was discovered in 1910, G. A. Alles first synthesized the molecule in 1927 while he tried to obtain a more productive and cheaper method of synthesizing Ephedrine. He discovered through experimentation on humans and animals that “Benzedrine had the ability to reverse drug-induced anesthesia and produce arousal and insomnia” (Heal). Early on, this drug was trademarked as benzedrine and it wasn’t until the late 1940s that amphetamine was adopted as the generic name of benzedrine. It was during the late 1930s that benzedrine hit the market as a treatment for narcolepsy. In the early 1940’s benzedrine’s ability to treat behavioral problems and ADHD was noticed when an experiment was done where kids were given benzedrine and immediately showed improvements in their school work, demeanor, and behavior. During the late 1940’s benzedrine’s cognitive enhancing abilities were noticed as several reports came out showing improvement on intelligence tests. This prompted for its widespread use by students and medical professionals to increase concentration, and intellectual performance and reduce stress (Heal).

To understand the chemistry behind how amphetamines work, we need to dive into the chemical reactions that take place in the brain and central nervous system. Amphetamine works by essentially increasing the concentration of dopamine in the synaptic gap between neurons. Since dopamine and amphetamine molecules have similar structures the amphetamine molecules can also enter by either diffusing through the membrane or getting transported in via dopamine transporters in the terminal end of a presynaptic neuron. After they are inside the presynaptic neuron “Amphetamines force dopamine molecules out of their storage vessels and expel them out of the presynaptic gap by forcing the dopamine transporters to work in reverse” (Mcgill). They reduce the reuptake of dopamine molecules allowing the neuron to be more readily excitable and fire quicker and more frequently (Mcgill). This quicker firing of chemical and electrical signals, in turn, increases the user’s ability to focus, stay awake, pay attention, and control behavioral problems.

Abstract

Narcolepsy is a chronic neurological sleep disorder which causes excessive daytime sleepiness or sudden uncontrollable sleep episodes in patients. This supporting device for people with narcolepsy basically detects the early onset of narcoleptic sleep in the patients and provides external disturbances using vibration motors to prevent them from falling asleep. It uses EEG which constantly monitors the brain waves and detects if there is an onset of narcoleptic sleep. After which the onset is prevented by the disturbances provided by the vibration motor which alerts the patient.

Keywords: Narcolepsy, Brain waves, External disturbances, EEG sensor.

I. Introduction

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and cataplexy – episodes of muscle weakness triggered by positive emotions. Narcolepsy is a chronic neurological disorder which does not have any cure yet. It causes excessive sleepiness in patients and also sudden episodes of falling asleep which are uncontrollable and can occur even when the patients are involved in activities like talking, driving, etc. This greatly impacts them in several different ways as falling asleep while during certain activities like driving may lead to accidents and they are prone to some sort of danger due to the narcolepsy throughout the day due to the underlying fact that they can fall asleep suddenly at anytime without their control.

The severity of the sleepiness is comparable with that experienced by a healthy person who has been sleep deprived continuously for 48-72 hours. Not only that due to the excessive sleepiness even during the day can make it hard for them to concentrate and focus on activities, thus affecting their performance in day to day life and is also morally demeaning as their potential is vastly decreased and since they are prone to uncertain risks, they can’t tend to do many activities alone and might always require a person monitoring and supporting them. Most of the patients with narcolepsy also have cataplexy which is the sudden loss of muscle strength which can sometimes be moderate or localized like just the closing of eye lids to a much severe complete loss of muscle strength throughout the body which may render in an inert state and might take time until they regain them. The onset of the narcoleptic sleep can easily be observed and detected through brain waves(Alpha, Beta, Sigma, Theta, Delta waves) using an EEG accurately.

II. Literature Survey

In the article of Wofford (2015) the author discussed the outstanding EEG findings in narcolepsy includes non-specific findings like, the onset of sleep in the narcoleptic patients is usually rapid and is found to be within 4 minutes. 94 cases were referred for this study of narcolepsy. In sleep analyses, for over 24 cases, the sleep was not deep or even light but rather at the drowsy or very light level. Unusual eye blinks, eye movements, were also observed.

In the paper of Flygare and Parthasarathy (2015) the probable cause for narcolepsy was found and analysed by the author. It was due to the loss of hypocretin (orexin) receptor gene in the brain. A post-mortem of brain tissues of narcoleptic patients were used to identify the cause of narcolepsy. Loss of hypocretin neurons found as cluster of thousand cells in lateral hypothalamus. This is caused due to an autoimmune disorder with environment and genetic factors as additional contributors. Diagnosis of narcolepsy is followed by multiple nap tests.

In Mukai et al. (2003) the authors discussed about the experiments conducted. Few drug native narcoleptic patients and some age matched normal volunteers underwent PSG (polysomnograms) on two consecutive nights. Rapid Eye Movement density and Electroencephalograph power spectral analysis were taken. Sleep onset REM (Rapid Eye Movement) periods and nocturnal sleep were observed. REM period duration across the night did not show increasing trend in normal people, but for narcoleptic people, it was high.

In Dimitrov et al. (2017) the initial results shows that there are unique Quantitative EEG differences between the groups of patients and the control group. The changes affect the potential levels of delta-, theta-, alpha-, and beta- frequency spectrums. The present study shows that some unique quantitative EEG findings in autistic patients. This is a step forward , aimed at defining specific neurophysiologic changes, in order to develop and refine strategies for early diagnosis of autism spectrum disorders, differentiation from other development conditions in childhood, detection of specific biomarkers and early initiation of treatment.

In Ülker et al. (2017) the major insight on how the attention and meditation values are determined from the five brain waves : Alpha, Theta, Delta, Gamma and Beta waves. In Lim et al. (2014) the authors stated about how falls can be detected by placing a sensor at the subject’s chest and by observing the change in the acceleration sensor node.

III. Pre Existing Techniques

Narcoleptic patients unlike the common people have the need to be constantly monitored by someone so that they do not put themselves to any danger while performing the day to day activities by falling asleep or due to the uncontrollable sleep attacks which are fairly common in narcoleptic patients. Since the peak age of onset of Narcolepsy being 14 years, it is no surprise that in a reported series of children with narcolepsy a range of serious psychological problems were consistently found like emotional lability, depression, difficult or aggressive behavior, social withdrawal and isolation, and academic failure. They might fall asleep unknowingly and sleep for many hours and lose a major portion of their day which can be avoided. But always being monitored and requesting the support of someone reduces the morale of the narcoleptic patients as they cannot be independent like normal people. Thus a supporting device can allow them to be independent and also saves them from wasting useful hours and reduce their risk of getting into danger by falling asleep without the monitoring or support from another person. The pre existing techniques to monitor sleep disorders generally involve sleep tests which are conducted in sleep labs. The patients are required to sleep in the lab while the lab technicians observe several data collected from the patients body while they sleep like the brain waves and oxygen levels in blood. For narcoleptic patients the monitoring is done during the day and a polysomnogram is obtained which helps to detect the type and adversity of the condition. But this method requires the patient to be in a lab and is tedious because a patients have to be monitored for long hours while being made to wear numerous wires and in a new environment where they do not feel comfortable.

IV. Proposed Work

These sleep tests include long observations involving lots of wires connected to the patient under observation and also the requirement of a lab to carry out the observation ensued by a detection and diagnosis. Such drawbacks can be easily overcome by using a Neurosky’s Mindwave EEG sensor which can be used to monitor all the five brain waves (Alpha, Theta, Sigma, Beta, Delta waves) from which the onset of narcoleptic sleep can easily be detected almost instantly and the sleep can also be prevented or the person can be woken up by the external disturbances provided by the supporting device upon the detection of narcoleptic sleep onset and this method does not require a lab or several lab technicians and the main advantage is its standalone capability and also the portability. This is a pervasive method to detect and support narcoleptic patients at anytime and anywhere almost instantly. A study which involved 20 healthy adults being whose brain waves were monitored by polysomnography technique and later analysed by polysomnography for the anomalies through out a two session sleep observation schedule and later EEG sensor was used on the same adults and using the PSM as the gold standard.

The EEG technique to analyse and detect sleep disorders was found to be 87.5% accurate in terms of detection of narcoleptic sleep onset. The single electrode EEG provides real time Alpha, Beta, Theta, Sigma and delta waves from the patient’s brain which was fed to a ATMEGA microcontroller which later triggers the vibration motors if the waves are below or above certain values. In this method onset of sleep in narcoleptic patients can be accurately measured and is reliable due to the data from earlier studies which have provided us with strong foundational knowledge about the precise changes in the various brain waves ensuing the onset of sleep and thus we have exact thresholds values above or below which if a brain wave falls then we can be certain about the occurrence of onset of sleep in the patients.

V. Methodology

Alpha, Beta, Theta, Delta and Sigma waves are primarily used in the detection of onset of narcoleptic sleep. These brain waves are recorded by the EEG sensor which is fed to the Microcontroller. The detection of onset of sleep is performed based on comparing the brain wave changes associated with sleep onset in normal people with the the brain wave changes associated with the narcoleptic sleep onset in patients. Mean delta and theta wave amplitudes will be higher for narcoleptic sleep onset when compared to the sleep onset in normal people. Mean alpha and sigma wave amplitudes will be lower for narcoleptic sleep onset when compared to sleep onset in normal people. Mean beta wave amplitude will not differ between the narcoleptic and normal sleep-onset process. The EEG sensor being used detects all the five types if brain waves and gives us two values mainly: Attention value and meditation value. If the values are above a threshold for the patients being monitored, then it is certain that onset of narcoleptic sleep is occurring and therefore they are about to fall asleep. After the detection, the microcontroller immediately triggers the vibration motors which are strapped to the arms or any other viable spots in the body of the patients, which then vibrate thereby giving externally disturbances which will alert the patient that the onset is occurring thus preventing them from falling asleep. The EEG sensor in the form of a headset is connected to the microcontroller through Bluetooth modules connected to both the headset and the microcontroller. There is another portion to the project which consists of an accelerometer which detects the fall when cataplexy occurs in the patient. This is vital because if the person has experienced cataplexy or fallen asleep in a situation which puts their life in danger like while driving or in the middle of a dangerous activity where there is no room for mistakes. Although the vibration motors might wake them up soon they might already be in danger because of them falling asleep or experiencing cataplexy in an unlikely situation which might lead to an accident. Thus after the fall is detected by the accelerometer, then it is checked if the sensor has detected narcoleptic sleep in the person. If both of these occurrences are happening at once then a time window opens. Within which the person can press a button if he is safe and is not in danger. If he does not press the button within the time window its most likely that the person is in danger. So after the time window ends the gps present in the supporting device picks up the person’s location at that moment. The latitude and longitude data is then sent to a number (the number of a person close to the patient probably a family member) using GSM module. Thus this enables the patient to be completely independent even at times of unprecedented danger.

VI. Results and Conclusion:

Upon the onset of narcoleptic sleep the EEG sensor detects it and sends it to the microcontroller. Then the vibrational motors are made to vibrate which wakes up the patient. The accelerometer sensor also detect a fall and it checks with the EEG sensor whether the person is experiencing narcoleptic sleep and if they are, then a message will be sent containing the location of the patient unless they press a button within a time window after falling. The attention values are indicated in a LCD monitor and the type of sleep is also indicated. The various brain waves can also be observed using Labview software. The raw EEG data obtained from the EEG sensor without splitting into the five different brain waves can be viewed in LabVIEW evaluation software. Thus this supporting device allows narcoleptic patients to be truly independent and live their day to day lives without someone constantly monitoring or helping them, the device wakes them up whenever they fall asleep and also inform another person when the patient is in plausible danger. More improvements can be done in this device by making it smaller and making the vibration motors more effective in the future.

VII. References

1. Burgees C.R. and Scammell T.E., Neuorosci J.: Narcolepsy: neural mechanisms of sleepiness and cataplexy, in 2012 Sep 5; 32(36):12305-12311.
2. Flygare, J.D. and Parthasarathy S.: Narcolepsy: Let the Patient’s Voice Awaken Us!, In 2015 Volume 128, Issue 1, pages 10–13 https://doi.org/10.1016/j.amjmed.2014.05.037
3. Wofford J.: The EEG in Narcolepsy, Pages 47-52, Published online: 23 Feb 2015
4. Mukai J, Uchida S., Miyazaki Sh., Nishihara K., Honda Y.: Spectral analysis of all‐night human sleep EEG in narcoleptic patients and normal subjects, In J Sleep Res. 2003 Mar; 12(1):63-71.
5. Dimitrov P.D., Petrov P., Aleksandrov I., Dimitrov I., Mihailova M., Radkova G., Dimitrova R. Department of Psychiatry and Medical Psychology, Faculty of Medicine, Medical University of Varna, “Quantitative EEG comparative analysis between Autism spectrum disorder (ASD) and Attention deficit hyperactivity disorder (ADHD)” in Bulgaria Journal of IMAB – Annual Proceeding (Scientific Papers). 2017 Jan-Mar, 23.
6. Ülker B., Barış M.T., and Ayberkin H. Ç. D.: Relations of Attention and Meditation Level with Learning in Engineering Education in ECAI 2017 – International Conference – 9th Edition Electronics, Computers and Artificial Intelligence 29 June -01 July, 2017, Targoviste, ROMÂNIA.
7. Lim D., Park C., Kim N.H., Kim S.-H., and Yu Y.S.: Fall-Detection Algorithm Using 3-Axis Acceleration: Combination with Simple Threshold and Hidden Markov Model, 10 February 2014; Accepted 19 August 2014; Published 17 September 2014.