Do you feel your eyelids are heavy?
Are you constantly yawning?
Are your responses to questions or instructions slow, subdued or lacking commitment?
Do you fail to avoid hitting objects that you normally would?
Do you tend to drift off to a deep sleep?
Then you are dog-tired.
But why? What makes you tired? To quote F. Scott Fitzgerald, are you tired with nothing, tired with everything, tired with the world’s weight you had never chosen to bear?
What happens if humans lack sleep?
Sleep deprivation or insufficient sleep is a universal and prevalent problem in modern human society. It is pervasive across various age groups, and is regarded as a public health epidemic by the scientific community but unrecognised, under-reported or ignored by media and business hierarchies. A 2018 literature review by Chattu et al. linked sleep deprivation to a number of medical morbidities, common diseases and medical conditions, prevalent dysfunctions and disorders, and accidents.
Watson et al. (2015) recommended adults should sleep at least 7 hours per night to achieve the best health and wellbeing. Any sleep amount less than 7 hours per 24-hour period is denoted ‘short sleep duration’.
USA:
Figure 1. Age-Adjusted Prevalence of Short Sleep Duration (> 7 hours) Among Adults > 18 Years, by State, United States, 2014
- This map illustrates the age-adjusted percentage of adults who reported short sleep duration of less than 7 hours of sleep per 24-hour period, by state in the USA, 2014.
- The percentage varies considerably by state, from <30% in Colorado, South Dakota, and Minnesota to >40% in Kentucky and Hawaii.
- The highest percentages were in the southeastern United States and in states along the Appalachian Mountains.
- The lower percentages were in the Great Plains states.
- Although the Behavioural Risk Factor Surveillance System (BRFSS) provides data essential for monitoring national and state population health, their surveys have low sample sizes to generate direct survey estimates for most US counties or sub-county areas.
- Therefore, the CDC used BRFSS data to estimate short sleep duration prevalence at different geographic levels, including counties, congressional districts, and census tracts (Figures 2, 3 and 4) using a previously developed model.
- In 2014, short sleep duration ( >7 hours) was less common among respondents aged >65 years (26.3%) compared with other age groups.
- The age-adjusted prevalence of short sleep duration was higher among Native Hawaiians / Pacific Islanders (46.3%), non-Hispanic blacks (45.8%), multiracial non-Hispanic (44.3%), and American Indians / Alaska Natives (40.4%) compared with non-Hispanic whites (33.4%), Hispanics (34.5%), and Asians (37.5%).
- There was no significant difference in short sleep prevalence between American men and American women.
Figure 5. Short Sleep Duration ( >7 Hours) by Sex - Behavioural Risk Factor Surveillance System, United States, 2014
Figure 6. Short Sleep Duration ( >7 Hours) by Age - Behavioural Risk Factor Surveillance System, United States, 2014
Figure 7. Short Sleep Duration ( >7 Hours) by Race/Ethnicity - Behavioural Risk Factor Surveillance System, United States, 2014
Health Risk Factors by Sleep Duration:
Adults who were short sleepers (<7 hours per 24-hour period) were more likely to report being obese, physically inactive, and current smokers compared to people who got adequate sleep (>7 hours per 24-hour period) .Figure 8. Age-Adjusted Percentage Reporting Health Risk Factors by Sleep Duration - Behavioural Risk Factor Surveillance System, United States, 2014
- Obese = Body Mass Index > 30 kg/m2
- Physically inactive = No leisure time physical activity in the past 30 days
- Current smoker = Currently smokes cigarettes every day or some days a week.
- Excessive alcohol = Underage drinker, binge drinker, or heavy drinker.
- Underage drinker is defined as any alcohol use among those aged 18-20 years.
- Binge drinker is defined as >4 drinks for women and >5 drinks for men during a single occasion.
- Heavy drinker is defined as >8 drinks for women and >15 drinks for men per week.
Chronic Health Conditions by Sleep Duration
Adults who were short sleepers (<7 hours per 24-hour period) were more likely to report 10 chronic health conditions compared to those who achieve sufficient sleep (>7 hours per 24-hour period).Figure 9. Age-Adjusted Percentage Reporting Chronic Health Conditions by Sleep Duration - Behavioural Risk Factor Surveillance System, United States, 2014
— COPD = Chronic Obstructive Pulmonary Disease
Short Sleep Duration Among High School Students
- Sleep experts recommend adolescents sleep 8-10 hours per night. However, more than 67% of US high school students reported sleeping less than 8 hours of sleep on school nights.
- Female students are more likely to report not having the recommended amount of sleep than male students.
- Short sleep duration (<8 hours) is lowest among 9th graders and highest among 12th graders.
- Prevalence of short sleep duration also varies by race/ethnicity, with the lower prevalence among American Indian/Alaska Native students and the highest among Asian students.
Figure 10. Short Sleep Duration by Survey Year - Youth Risk Behaviour Survey, United States, 2007-2013
Figure 11. Short Sleep Duration by Sex - Youth Risk Behaviour Survey, United States, 2007-2013
Figure 12. Short Sleep Duration by Grade Level - Youth Risk Behaviour Survey, United States, 2007-2013
Figure 13. Short Sleep Duration by Race/Ethnicity - Youth Risk Behaviour Survey, United States, 2007-2013
Source: Science Advances 2016
Japan:
Daily Sleep for Japanese people by Sex - National Health and Nutrition Survey 2017
- The Japanese Ministry of Health, Labour and Welfare measured the daily average sleep (based on the previous 1-month period) for men and women in their 20s and over.
- 30.9% of respondents in their 40s, 28.4% of respondents in their 50s, and 27.6% of respondents in their 30s reported insufficient sleep or had no real sleep.
- Due to long working hours and commuting times, a large proportion of Japanese workers in the prime of life are suffering from sleep deprivation.
- 11.3% of men and 10.6% of women in their 40s slept less than 5 hours, and 37.2% of men and 41.8% of women in their 40s slept 5-6 hours.
- 44.9% of men and 51.6% of women in their 50s reported sleeping less than 5 hours of sleep a night.
- Overall, 35% of men and 33.4% of women reported sleeping 6-7 hours.
- 21.7% of men and 31.1% of women in their 70s and over reported sleeping less than 6 hours.
- In 2009, 18.4% of total respondents reported getting insufficient sleep or no sleep at all. Of those people, 27.9% were men and women in their 40s and 19.9% were those in their 50s.
- In 2017, those ratios increased by 2-8 percentage points.
- In 2018, Japan Today reported that Japanese men slept an average 6.3 hours per night, while Japanese women slept an average of 6.4 hours per night.
- In the same year, Finnish men slept an average 7.24 hours per night, both Finnish women and Belgian women slept an average 7.25 hours per night.
- As of 2018, no country’s sleep average is reported to be greater than the recommended 8 hours per night.
- In 2018, UK women slept an average 6.36 hours per night and UK men slept an average 6.28 hours per night. UK mothers aged under 40 years slept an average 6.09 hours a night (15.6 minutes less).
Figure 1. Average sleep duration per 24-hour (1440 min) night for men and women raising different numbers of children
Australia:
https://www.sleephealthfoundation.org.au/pdfs/surveys/SleepHealthFoundation-Survey.pdf
According to the Report to the Sleep Health Foundation 2016 Sleep Health Survey of Australian Adults, conducted in The Adelaide Institute for Sleep Health:
- Between 33 and 45% of Australian adults report insufficient sleep, of either duration or quality, and its daytime consequences.
- 8% of Australian adults were diagnosed with sleep apnoea, 20% with significant insomnia, and 18% with restless legs.
- Although average reported sleep time is roughly 7 hours per 24-hour period, 12% of Australian adults slept less than 5.5 hours and 8% over 9 hours.
- 76% of Australian adults who slept less than 5.5 hours reported frequent daytime impairment or sleep-related symptoms.
- 24% of Australian men and 17% of Australian women reported frequent, loud snoring and breathing pauses in sleep. Among the frequent loud snorers, 70% of them reported daytime impairment or other sleep-related symptoms.
- Among the 19% of Australians who frequently snore loudly and/or witnessed breathing pauses but don’t have prior diagnosis of OSA on a sleep study, 63% of them reported awakening unrefreshed, and 65% reported 1 or more daytime sleep-related symptoms. This suggested undiagnosed sleep apnea is prevalent in the Australian community.
How profound is the effect of the ’24/7 society’?
- 26% of all Australian adults both use the internet most or every night of the week prior to bedtime and experience frequent sleep difficulties or daytime impairments.
- 16% of all working adults work prior to their bedtime and also experience frequent sleep difficulties or daytime sleep-related symptoms.
- 23% of Australian adults report their typical weekday routine or work or home duties prevent them to achieve adequate sleep.
- Younger adults (18-34 years) sleep around 1 hour longer before non-work days compared to working days, compared to 18 minutes in older age groups.
How does sleep problems affect human performance and human society?
- A month prior to the study being conducted, 17% of Australians missed work due to sleepiness and 17% fell asleep on the job.
- 3 months prior to the study being conducted, 29% of Australian adults reported being erroneous at work due to sleepiness or sleep problems.
- Adults with sleep problems are significantly more likely to report decreased work productivity (as assessed on the Stanford Presenteeism Scale).
- 29% of Australian adults drove their car while drowsy at least once a month.
- 20% of Australian adults admitted drifting off to sleep while driving and 5% experienced a car accident 12 months prior to the study due to their sleepiness.
- The prevalence of sleep difficulties and daytime consequences in Australian society seemed to increase since 2010, with various sleep problems reported by more than adults than in 2010.
Are Australian children and adolescents getting enough sleep?
- On school days, over 95% of 6-7 year olds were meeting the recommended amount of sleep for their age group, but about 50% of 16-17 year olds were.
- Children aged 12-17 years were less likely to meet the recommended minimum hours of sleep on school nights compared to non-school nights.
- Around 80% of children misjudged the amount of sleep gained, when in fact they failed to meet the minimum sleep guidelines for their age.
- Children who don’t meet the minimum sleep guidelines were more likely to:
— Manifest symptoms of poor mental health (anxiety, depression, unhappiness)
— Be late for or absent from school
— Spend more time on homework
— Having access to the internet in the bedroom or spend more time on the internet (e.g. social media).
- 12-13 year olds who participated in sport and/or had regular bedtimes were more likely to meet minimum sleep guidelines for their age.
Figure 1. Average bedtime on school nights and non-school nights, by age and sex.
Figure 2. Average wake times on schools days and non-school days, by age and sex.
Figure 3. Average sleep duration in hours, by age
Figure 4. Proportion of children and adolescents not meeting minimum sleep guidelines on school and non-school nights, by age and sex.
What is sleep debt?
Source: https://www.sciencedirect.com/science/article/abs/pii/S1389945720302331
Also known as sleep deficit, sleep debt is defined as the cumulative effect of failing to meet the required minimum amount of sleep for one’s respectively age group.
Describe the effects of sleep debt
i. Biological
- Wang et al. (2018) identified up to 80 proteins in the brains of mice denoted as “sleep need index phosphoproteins” (SNIPPs), which become increasingly phosphorylated by the Sik3 protein during waking hours, and are dephosphorylated during sleep.
- If the Sik3 gene is inhibited, it decreases phosphorylation and SWS activity in both normal and modified mice.
- Leproult et al. (2009) stated that chronic sleep debt elicits a significant physiological impact on the human body, specifically on metabolic and endocrine functions.
ii. Physiological
- Spiegel et al. (1999) investigated the physiological effects of sleep debt by evaluating the sympathovagal balance, thyrotropic function, HPA axis activity and carbohydrate metabolism of young adult males. These subjects either slept 4 hours per night or 12 hours per night for 6 consecutive nights.
- Sleep-deprived subjects were observed to have reduced thyrotropin levels and diminished glucose and insulin responses (indicating an impairment of carbohydrate tolerance). Moreover, they demonstrated significantly higher levels of evening cortisol (the “stress” hormone) and elevated sympathetic nervous system activity compared to subjects with healthier sleep hygiene.
- Chronic sleep debt has demonstrated to be detrimental on human (neuro)physiological functioning, which negatively impacts on immune, endocrine, and metabolic function. Furthermore it increases the severity of cardiovascular and age-related illnesses over a period of time.
iii. Neurophysiological
- Motomura et al. (2013) demonstrated that accumulated and continuous short-term sleep debt increases and exacerbates psychophysiological reactions in humans to emotional stimuli.
- Researchers indicated that the amygdala associated with the expression of negative emotions such as fear, and its anatomical connections with the medial prefrontal cortex (mPFC) plays a role in subjective suppression of and the reframing and reappraisal of negative emotions.
- Moreover, sleep-deprived young Japanese men (who slept 4 hours per day) demonstrated elevated activation in the left amygdala upon perception of fearful faces but not happy faces, and an overall subjective mood deterioration.
- Minkel et al. (2012) demonstrated short-term continuous sleep debt or deprivation decreased this functional relationship between the amygdala and mPFC, manifesting in negative mood changes through intensified fear and anxiety in response to unpleasant emotional stimuli and events.
- Hence, a uninterrupted 7-hour monosleep is essential for the conventional functioning of the amygdala in regulating an individual’s mood states by decreasing negative emotional intensities and increasing reactivity to positive emotional stimuli.
iv. Obesity
- Bayon et al. (2014) found evidence of a correlation between sleep debt and/or deprivation and obesity enumerated by an increased body mass index (BMI) through various methods. They include irregularities in the hormones leptin and ghrelin that mediate appetite, increased food consumption and unhealthy diets, and a decrease in overall calories burning.
- Researchers have pointed out multimedia usage such as internet and television consumption, which associates with sleep deficit, has also correlated with obesity. They implied multimedia usage promoted unhealthy sedentary lifestyles and habits, and increased food consumption.
- Furthermore, work-related behaviours such as long working and commuting hours and inconsistent work schedules (e.g. during shift work) may contribute to obesity, due to shorter sleeping periods. Compared to adults, this may explain the solid correlation between sleep debt and obesity in children.
v. Mortality
- Ã…kerstedt et al. (2019) found a correlation between sleep duration and the risk of mortality, either on weekdays or on weekends. In people aged <65 years, a daily sleep duration of <5 hours (i.e. sleep deficit >2 hours per day) during weekends associated with a 52% higher mortality rate compared to a control group who slept the required minimum guideline of 7 hours.
- Grandner et al. (2010) implied consistent sleep debt correlated with mortality and morbidity rates, however this effect is negated when compensated with long sleep durations on weekends.
Research in sleep debt
- Researchers, such as David F. Dinges (2004) & Jim Horne (2004), are debating the validity of the concept of sleep describing a measurable phenomenon.
- Dinges et al. (1997) experimentally evinced that cumulative nocturnal sleep debt contributes to daytime sleepiness, especially on the 1st, 2nd, 6th, and 7th days of sleep restriction.
- Walker (2009) found moderate sleep deprivation had a detrimental effect on psychomotor vigilance.
- A sleep onset latency test is often used to assess sleep debt, which attempts to measure how easily a person can fall asleep.
- A 2007 suggested a saliva test for the enzyme amylase to be used as biomarker for sleep debt, since amylase activity associates the amount of sleep debt a subject accumulates.
- Kang et al. (2009) discovered crucial correlations between sleep debt, orexin, and beta amyloid, a common neuropathology of Alzheimer’s Disease.
What is sleep deprivation?
Also known as insufficient sleep or sleeplessness, sleep deprivation is defined as the condition of sleep that doesn’t meet the minimum guideline requirements according to your current age and wellbeing.
What are the physiological effects of sleep deprivation?
i. Physical
- Muscle aches
- Hand tremors
- Headaches
- Malaise
- Periorbital puffiness (Eye bags)
- Nystagmus
- Obesity
ii. Psychological & Neurological
- Depression
- Development of false memory
- Hypnagogic and hypnopompic hallucinations during sleep and waking
- Seizures
- Symptoms similar to ADHD and psychosis
- Confusion, memory loss
iii. Physiological
- Stye (Hordeolum)
- Increased blood pressure
- Increased stress hormone levels
- Increased risk of Type 2 diabetes
- Decreased immunity, increased susceptibility to illness
- Increased risk of fibromyalgia
- Irritability
- Sleep mania
iv. Behavioural
- Temper tantrums in children
- Violent behaviour
- Yawning
- Mania
https://en.wikipedia.org/wiki/Fatigue
https://en.wikipedia.org/wiki/Central_nervous_system_fatigue
https://en.wikipedia.org/wiki/Muscle_fatigue
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473877/
What is fatigue?
Also known as exhaustion, fatigue is defined as “tiredness resulting from mental or physical exertion or illness”. This definition varies depending on the context:
— Medical: A reduction in the efficiency of a muscle or organ after prolonged activity or exercise.
— Social: A reduction in one’s response to or enthusiasm for something, caused by overexposure.
— Materials: Weakness in metal or other materials caused by repeated variations of stress, i.e. metal fatigue
— Work: Menial non-military tasks performed by a soldier, occasionally as a punishment.
— Clothing: Loose clothing, typically khaki, olive drab, or camouflaged, of the sort worn by soldiers on active duty, i.e. battle fatigues.
What are the common symptoms of fatigue?
- Physical = Exhaustion, lethargy, malaise, tiredness, lassitude, weakness, eye bags (periorbital puffiness), periorbital darkness
- Impact on functioning = Decreased capacity for work, decreased quality of life, difficulty completing tasks, poor sleep quality, withdrawal from activities, debilitation
- Unpleasant emotions = Helplessness, distress, anxiety, emotional numbness, emotional lability, reactivity, impatience, vulnerability, unpleasant experience
- Decreased cognitive functions = Decreased attention, decreased concentration, decreased motivation, memory impairments, decreased mental capacity, decreased capacity for mental capacity
What causes fatigue?
- Normal fatigue is usually caused by the typical hardships of working, mental stress, overstimulation and understimulation, boredom, active recreation, and insufficient sleep.
- Acute fatigue is caused by depression, chemical triggers such as dehydration, poisoning, low blood sugar, or mineral or vitamin deficiencies.
- Prolonged fatigue persists for at least 1 month, often self-reported.
- Chronic fatigue last for at 6 consecutive months, which may be either persistent or relapsing. It is a symptom of many conditions and conditions including:
- Autoimmune diseases, such as coeliac disease, lupus, multiple sclerosis, myasthenia gravis, Sjögren’s syndrome, and spondyloarthrography.
- Blood disorders, such as anaemia and haemochromatosis
- Cancer, i.e. cancer fatigue
- Chronic fatigue syndrome (CFS)
- Drug abuse, including alcohol abuse
- Depression and other mental disorders featuring depressed mood
- Developmental disorders
- Eating disorders, which produces fatigue due to inadequate nutrition
- Endocrine disorders or metabolic disorders: diabetes mellitus, hypothyroidism, and Addison’s disease.
- Fibromyalgia
- Gulf War syndrome
- Heart failure
- HIV
- Idiopathic chronic fatigue (ICF)
- Inborn errors of metabolism such as fructose malabsorption
- Infectious diseases such as infectious mononucleosis or tuberculosis
- Irritable bowel syndrome
- Kidney diseases e.g. acute renal failure, chronic renal failure
- Leukaemia or lymphoma
- Liver failure or liver diseases e.g. Hepatitis
- Lyme disease
- Neurological disorders such as narcolepsy, Parkinson’s disease, Postural Orthostatic Tachycardia Syndrome and post-concussion syndrome
- Physical trauma and other pain-causing conditions, such as arthritis
- Sleep deprivation or sleep disorders, e.g. sleep apnoea
- Spring fever
- Stroke
- Thyroid disease such as hypothyroidism
- Uraemia, which is caused by kidney disease
- A side effect of certain medications such as lithium salts, ciprofloxacin, beta blockers and many cancer treatments including chemotherapy and radiotherapy.
- Inflammation e.g. neuroinflammation
How is fatigue diagnosed?
- Nijrolder et al. (2009) estimated about 50% of fatigued patients received a diagnosis that satisfactorily explained the fatigue after a year with the condition. They cited musculoskeletal (19.4%) and psychological problems (16.5%) as the most common cause of such fatigue, with only 8.2% of cases accounted for by definitive physical conditions.
- When a patient with fatigue seeks medical advice from a GP, the GP aims to identify and eliminate any treatable conditions. The patient’s medical history is first conferred, and any other manifesting symptoms, before the qualities of the fatigue itself is assessed.
- The patient may report identifiable patterns of the fatigue, such as experiencing exhaustion at certain times of the day, gradual increase of fatigue throughout the day, or gradual decrease of fatigue after napping.
- A diagnostic evaluation of fatigue assesses the quality of sleep, the person’s emotional state, sleep pattern and stress level, as well as the amount of sleep, and the number of times a person awakens during the night.
- Medical tests can help eliminate common causes of fatigue. They include blood tests to detect infection or anaemia, a urinalysis to detect signs of liver disease or diabetes mellitus, and other tests to check for kidney and liver function, such as a comprehensive metabolic panel.
What are the different types of fatigue?
i. Physical fatigue
https://en.wikipedia.org/wiki/Muscle_fatigue
Also known as muscle fatigue, it is defined as the reduced ability of a muscle to generate force after a stint of vigorous exercise. In addition, abnormal fatigue can be brought about by barriers to or interference with the different stages of muscle contraction.
There are 2 main causes of muscle fatigue:
1. Neural fatigue
- Nerves are involved in the control of muscle contraction, which determines the number, sequence and force of muscular contraction.
- Since most muscle movements require a force significantly less that the force generated by a muscle, nerve fatigue is rarely a problem.
- Nonetheless, during extremely powerful contractions near the upper limit of a muscle’s ability to generate force, nerve fatigue (enervation) becomes a limiting force in untrained individuals.
- After a period of maximum contraction, the peripheral nerve’s signal decreases in frequency and the force generated by the contraction diminishes, which tends to be painless.
- There often is insufficient stress on the muscles and tendons to cause delayed onset muscle soreness following the workout.
2. Metabolic fatigue
It is commonly used to define the decrease in contractile force due to the direct or indirect effects of 2 main forces:
1. Shortage of fuel (substrates) within the muscle fibre.
2. Accumulation of substance (metabolites) within the muscle fibre, which interfere either with the release of calcium (Ca2+) or with the ability of calcium to stimulate muscle contraction.(a) Substrates
- Molecules such as adenosine triphosphate (ATP), glycogen and creatine phosphate serve to power muscular contractions.
- If these substrates deplete during exercise (combined with accumulation of lactic acid), it leads to metabolic fatigue, which halts muscle contraction.
(b) Metabolites (Waste products)
Accumulation of metabolites directly or indirectly produce metabolic fatigue.
- Chloride (Cl-) = Intracellular chloride partially inhibits muscle contractions.
- Potassium (K+) = Higher levels of potassium decreases the efficiency of myocytes, leading to cramping and fatigue. It accumulates in the t-tubule system and around the muscle fibre due to action potentials. This alters the membrane potential around the muscle fibre, which reduces the release of calcium ions from the sarcoplasmic reticulum.
- Lactic acid = This metabolite is a by-product of fermentation, which increases intracellular acidity of muscles. Nonetheless, it decreases the sensitivity of contractile apparatus to calcium, as well as the increasing cytoplasmic calcium ion levels by inhibiting the chemical pump that actively transports calcium out of the cell. Lactic acid also cancels out the effect of chloride ions in the muscles, by decreasing its inhibition of contraction and isolating potassium ions to become the only restricting ion on muscle contractions. However, it’s unclear whether lactic acid decreases fatigue through elevated intracellular calcium or increases fatigue as a result from decreased sensitivity of contractile proteins to calcium ions.
- Magnesium (Mg2+)
- Reactive Oxygen species (ROS)
- Inorganic phosphate (Pi)
3. Pathology
Muscle weakness can be caused by inadequate nerve supply, neuromuscular disease (such as myasthenia gravis) or anatomical problems with the muscle itself, as well as polymyositis and other muscle disorders.
4. Molecular mechanisms
Muscle fatigue due to precise molecular changes occur in vivo with continuous exercise. Bellinger et al. (2008) observed the ryanodine receptor in skeletal muscle undergoes a conformation change during exercise, leading to calcium channels becoming “leaky” and increase in deficiency of calcium release. These “leaky” channels may contribute to muscle fatigue and decreased exercise capacity.
How does muscle fatigue affect motor performance?
- It’s known fatigue limits performance in every athlete in every sport.
- Research found voluntary force production decreases in fatigued muscles in terms of concentric, eccentric, and isometric contractions, vertical jump heights, and other field tests of lower body power.
- In addition, fatigued muscles lead to decreased throwing velocities, decreased kicking power and velocity, decreased accuracy in throwing and shooting activities, decreased endurance capacity, increased anaerobic capacity, increased anaerobic power, decreased mental concentration.
ii. Mental fatigue
https://en.wikipedia.org/wiki/Central_nervous_system_fatigue
- Mental fatigue is defined as a temporary inability to maintain optimal cognitive performance. During any cognitive activity, mental fatigue emerges gradually, depending on the individual’s cognitive ability, as well as other factors, such as sleep deprivation and overall health.
- Marcora et al. (2015) observed mental fatigue decreases physical performance in the form of somnolence, lethargy, or directed attention fatigue (or reduced level of consciousness). This compromises the performance of tasks requiring sustained concentration, such as driving vehicles long distances, hence putting the driver’s and passengers’ lives at risk.
- A 2019 study found fatigue slows down a driver’s reaction time, decreases awareness of surrounding hazards and compromises attention. Tired drivers or drivers awake for over 20 hours in a 24-hour period were evaluated to be 3 times more likely to involved in an automobile accident, which is equal to driving with a blood-alcohol concentration level of 0.08%.
What is central nervous system (CNS) fatigue?
Also known as central fatigue, it is related to changes in the synaptic concentration of neurotransmitters within the CNS that influences exercise performance and muscle function, which cannot be explained by peripheral factors that typically affect muscle function.
Which neurochemical mechanisms are involved?
i. Noradrenaline
Meeusen et al. (2006) suggested noradrenaline is involved in generating central fatigue. An NRI inhibitor called Reboxetine was observed to reduce time to fatigue and elevate subjective feelings of fatigue. The paradoxical reduction in noradrenaline caused by feedback mechanisms may account for this finding.
ii. Serotonin
- It’s known serotonin regulates arousal, behaviour, sleep, and mood, among other things in the brain. Young (1986) found serotonin levels are elevated in the brain during sustained exercise in the CNS, which augments perceptions of effect and peripheral muscle fatigue.
- This finding can be accounted for increased levels of tryptophan, the serotonin precursor, in the blood, due to increased amounts of tryptophan crossing the blood-brain barrier.
- It’s known the transport mechanism for tryptophan across the blood-brain barrier is shared with the branched chain amino acids (BCAAs), leucine, isoleucine, and valine. Therefore, these BCAAs are utilised for skeletal muscle contraction, augmenting transport of tryptophan across the blood-brain barrier.
- Newsholme et al. (1987) highlighted no component of the serotonin synthesis reaction are saturated under normal physiological conditions, which increases the production of serotonin. However, this hypothesis lacks support since the BCAAs fail to reduce the time to fatigue consistently.
iii. Dopamine
- Chaouloff et al. (1989) stated dopamine associates with arousal, motivation, muscular coordination, and endurance performance, etc.
- Bailey et al. (1993) observed dopamine levels increased after a prolonged exercise session. In addition, a reduction in dopamine levels hinders athletic performance and mental motivation. Since dopamine cannot cross the blood brain barrier, it has to be synthesised inside the brain.
- Rat experiments found exercise increased activity in the ventral tegmental area (VTA), which associates with voluntary wheel running. Since the VTA contains dopaminergic neurons that project to many areas of the brain, researchers proposed that the dopaminergic neurotransmission augments physical performance.
- Roelands & Meeusen (2010) claimed that dopamine reuptake inhibitors and noradrenaline dopamine reuptake inhibitors can increase exercise performance, especially in the heat.
iv. Acetylcholine
- It’s known cholinergic activity is needed to generate muscular force, as well as regulate arousal and temperature.
- There is debate between the researchers regarding the significance of acetylcholine’s attribution to central fatigue.
v. Cytokines
- It’s known cytokines manipulate neurotransmissions to manifest sickness behaviour, demonstrated by malaise and fatigue.
- Harrington (2016) used animal models to discover IL-1b triggers release of serotonin and increases GABA activity. Moreover, the presence of lipopolysaccharide inhibits activity of histaminergic and dopaminergic neurons.
vi. Ammonia
Wilkinson et al. (2010) suggested higher levels of ammonia changes brain function, which leads to fatigue.
How can neurochemical levels be manipulated?
i. Dopamine reuptake and release agents
- Amphetamine is a stimulant that blocks the reuptake of dopamine and noradrenaline, which delays the beginning of fatigue by increasing dopamine levels in the synaptic cleft, despite the concurrent increase in noradrenaline, in the CNS. This ultimately leads to improvements in both physical and cognitive performance.
- Researchers found collegiate athletes often use amphetamines to augment their athletic qualities hence performances. It improved muscle strength, reaction time, acceleration, anaerobic exercise performance, power output at fixed levels of perceived exertion, and endurance.
ii. Caffeine
- Caffeine is a stimulant that triggers the release of adrenaline from the adrenal medulla. Conger et al. (2011) found small doses of caffeine improves physical endurance, as well as delayed the beginning of fatigue in exercise.
- Davis et al. (2012) implied the most probable mechanism for the delay of fatigue involves blocking adenosine receptors in the CNS.
- Since adenosine is a neurotransmitter that decreases arousal and increases sleepiness, removal of it by caffeine augments rest and delays fatigue.
iii. Carbohydrates
- It’s known carbohydrates are the main source of energy in organisms for metabolism and exercise.
- Foskett et al. (2008) found consumption of carbohydrate and electrolyte solution before and during exercise improved endurance capacity. However, this finding couldn’t be accounted for by changing levels of muscle glycogen, which led to the theory that higher plasma glucose levels associated with this outcome.
- Davis & Bailey (1997) proposed the CNS is able to detect the influx of carbohydrates and decrease the perceived effort of the exercise, which augment superior endurance capacity.
iv. Branched-chain amino acids (BCAA)
- Meeusen & Watson (2007) administered BCAAs to subjects and observed its effects, which include reduction of the synthesis of serotonin and inhibition of the transport of tryptophan across the blood brain barrier. However, this led to little or no change in performance between increased BCAA intake and placebo groups.
- Blomstrand et al. (1995) observed both the carbohydrate solution and a combined carbohydrate + BCAA solution increased running times before fatigue compared to the water placebo group. Nevertheless, both interventions groups showed no significant differences in their physical performances.
- Meeusen et al. (2006) suggested the inconsistent findings with BCAA administration was a result of increased ammonia levels due to elevated BCAA oxidation.
What’s the CNS’s role in fatigue?
- To prevent peripheral muscle injury, the brain collects information from many receptors, such as osmoreceptors, to monitor dehydration, nutrition, and body temperature. After integration of relevant sensory information, the brain responds by decreasing the quantity of motor commands transmitted from the CNS. In addition, this increases the perceived effort experienced by the individual.
- Scientists theorised this signalling process exists to protect the homeostasis of the body and maintain it in a stable physiological state that achieves full recovery. Therefore, an increasingly high physical intensity perceived by the body elevates the likelihood of halting exercise through the response of fatigue.
- Enoka & Stuart (1992) found perceived effort is significantly affected by the intensity of corollary discharge from the motor cortex that influences the primary somatosensory cortex.
- Researchers theorised the CNS’s main role is to protect visceral organs from potentially dangerous core temperatures and nutritional voids, by using electrical activity and physiological responses to alert the individual about the alarming physiological conditions and enforce rest or refuelling. This prevents the individual from experiencing hyperthermia and dehydration, since they are a detriment to athletic performance.
What is chronic fatigue syndrome (CFS)?
https://en.wikipedia.org/wiki/Chronic_fatigue_syndrome
Also known as myalgic encephalomyelitis (ME), CFS is a complicated, exhausting, long-term medical condition that causes worsening symptoms after physical or mental activity. This greatly compromises an individual’s capacity to accomplish tasks that were considered routine prior to the ailment, and non-restorative sleep.
Describe the epidemiology of CFS
- Lim et al. (2020) found the global prevalence rate for CFS is 0.89%, based on the 1994 CDC diagnostic criteria.
- The CDC estimated about 836,000 to 2.5 million Americans are affected by CFS/ME, but a majority of them remain undiagnosed.
- Females are diagnosed about 1.5-2.0 times than males with CFS. A 2015 report estimated 0.5% of children suffer from CFS, and possibly many more adolescents suffering from CFS than younger children.
Describe the prognosis of CFS
- A systematic review reported the median full recovery rate of CFS was around 5% (range: 0–31%) and the median proportion of patients demonstrating improvement from symptoms during follow-up was around 39.5% (range: 8—63%).
- Studies reported CFS symptoms worsened during the period of follow-up in 5—20% of patients.
- A review by Cairns & Hotopf (2005) concluded that “irrespective of the biology of CFS, patients’ beliefs and attributions about CFS are intricately associated with the clinical presentation, the type of help sought and prognosis.
- A review by Joyce & Hotofp (1997) discovered that children have a more optimistic prognosis than adults, with 54-94% experienced recovery by follow-up compared to less than 10% of adults returning to pre-illness levels of functioning.
What are the symptoms of CFS?
The United States Centers for Disease Control and Prevention (CDC) recommended the following criteria for diagnosis:
1. Greatly lowered ability to do activities that were usual before the illness. This drop in activity level occurs along with fatigue and must last 6 months or longer.
2. Worsening of symptoms after physical or mental activity that would not have caused a problem before illness. This is known as post-exertional malaise (PEM).
3. Sleep problems
In addition, one of the following symptoms must be present:
- Problems with thinking and memory (cognitive dysfunction, or “brain fog”) - While standing or sitting upright; lightheadedness, dizziness, weakness, fainting or vision changes may occur (i.e. orthostatic intolerance).
Other common symptoms include:
- Muscle pain, joint pain without swelling or redness, and headache.
- Tender lymph nodes in the neck or armpits
- Sore throat
- Irritable bowel syndrome
- Chills and night sweats
- Allergies and sensitivities to foods, odours, chemicals, lights, or noise
- Shortness of breath
- Irregular heartbeat
i. Physical functioning
- Vanness et al. (2003) highlighted the considerable variation of functional capacity in individuals with CFS. Rose et al. (2004) reported some CFS patients lead relatively normal lives, while others are bed-ridden and unable to care for themselves.
- A 2019 CDC report stated a considerable number of CFS sufferers demonstrated decreased (complex) work, school, physical and family activities for a prolonged period of time.
- Ho-Yen & McNamara (1991) thought the severity of symptoms and disability is consistent regardless of gender, and Meeus et al. (2007) stated many CFS patients experienced disabling chronic pain.
- Anderson et al. (1997) found CFS influenced a person’s functional status and wellbeing more than major medical conditions such as multiple sclerosis, congestive heart failure, or type II diabetes mellitus.
- The CDC noted courses of remission of relapse of symptoms often occur, increasing the management of CFS. Patients who recovered for a period may overdo their activities, which can a result in worsened symptoms with a relapse of CFS.
- A 2015 Committee reported roughly 25% of CFS patients are house-bound or bed-ridden for long periods, often for decades. Furthermore, CFS associated with increased school absences. A 2018 CDC report estimated about 75% of CFS patients demonstrated incapability to work.
- Ross et al. (2004) found more than 50% of CFS sufferers were on disability benefits or temporary sick leave, and less than 20% of CFS sufferers worked full-time.
- Compared to healthy patients, CFS patients scored significantly lower on the Short Form (36) Health Survey (SF-36) quality of life questionnaire, especially in the subscales on vitality, physical functioning, general health, physical role, and social functioning. Unger et al. (2016) pointed out the subscales for “role emotional” and mental health in CFS patients were consistent with or not substantially than healthy controls.
ii. Cognitive functioning
- The negative impact of CFS on occupational and social functioning leads to cognitive dysfunction. Common cognitive symptoms of CFS are mainly caused by deficits in attention, memory, and reaction time.
- Cvejic et al. (2016) found cognitive abilities in CFS patients were below projected normal values and likely to affect day-to-day activities. Deficiencies in cognitive abilities are exhibited by increases in common mistakes, forgetting scheduled tasks, or experiencing difficulty responding when spoken to.
- CFS patients were found to have impairments in simple and complex information-processing speed, and functions requiring working memory over long time periods.
- Perceptual abilities, motor speed, language, reasoning, and intelligence were relatively unaffected.
- A poor health status report correlated with an inflated perception of the CFS patient’s own cognitive problems.
- There are inconsistencies of subjective and observed values of cognitive dysfunction reported across studies. This is mainly due to innate variations of the differences of research participants’ cognitive abilities pre and post illness onset, and the difficulties in measuring such values because of a lack of specialised tools that is able to consistently quantify the specific cognitive difficulties in CFS.
What are the causes of CFS?
The cause of CFS is currently unknown. Afari & Buchwald (2003) proposed a number of genetic, physiological, and psychological factors that combine to trigger and sustain the condition.
Unger et al. (2016) suggested CFS is a biological illness, however the biological abnormalities lack sensitivity or specificity when diagnosing the syndrome.
i. Risk factors
- All ages, ethnic groups, and income levels are susceptible to the illness.
- The CDC thought that Caucasians may be diagnosed more frequently than other races in USA, however CFS is at least as prevalent among African Americans and Hispanics.
- Dinos et al. (2009) found African Americans and Native Americans have a higher risk of CFS than Caucasians, though it excluded other more common ethnicities globally due to limited data.
- Lim et al. (2020) estimated women are diagnosed with CFS at 1.5 - 2.0 times more often than men. Nevertheless, different case definitions and diagnostic methods within datasets yielded a range of prevalence rates.
- CDC estimated women are afflicted with CFS up to 4 times more than men. Although CFS can occur regardless of age, it affects mainly those in people aged between 40 and 60 years. Moreover, CFS is less prevalent among children and adolescents than among adults.
- Van Houdenhove et al. (2010) suggested risk factors for developing CFS include psychological stress, perfectionalist personalities, allergies, childhood trauma, lower middle education, low physical fitness, old age and pre-existing psychological illness.
- Lievesley et al. (2014) suggested predisposing factors of CFS include pre-existing depressive and anxiety disorders, and high expectation of parents and family history.
ii. Viral and other infections
- Post-viral fatigue syndrome (PVFS) is occasionally used as an alternative name for CFS that occurs after viral infection.
- Eriksen (2018) found Epstein-Barr Virus (EBV) antibody activity is elevated in CFS patients compared to controls.
- Cleare (2002) stated 22% of people with EBV demonstrated chronic fatigue 6 months later, and 9% of them were diagnosed with CFS.
- Hulme et al. (2017) found risk factors for developing CFS after mononucleosis, dengue fever or the bacterial infection Q-fever include longer bed-rest during the illness, poorer pre-illness physical fitness, associating symptoms with physical illness, the need for a longer recovery time, and pre-infection distress and fatigue. Furthermore, biological factors such as CD4 and CD8 activation and liver inflammation are consistent predictors of sub-acute fatigue, but not CFS.
- Brurberg et al. (2014) found people diagnosed with ME had the worst prognosis, while those diagnosed with PVFS had the best prognosis. Reasons for these findings remains ambiguous.
Describe the pathophysiology of CFS?
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Difference between adolescents with CFS and healthy controls demonstrates less salient network activity in particular brain regions.
i. Neurological
- Carruthers et al. (2012) found a number of neurological, structural and functional abnormalities in the brains of CFS patients, such as decreased metabolism in the brainstem, decreased blood flow throughout the brain.
- Evidence suggests a relationship between autonomic nervous system dysfunction and diseases such as CFS, fibromyalgia, irritable bowel syndrome, and interstitial cystitis. However, MartÃnez-MartÃnez et al. (2014) pointed out the lack of evidence for its causation.
- Reviews of CFS literature discovered autonomic abnormalities in CFS patients, including decreased sleep efficiency, decreased slow wave sleep (SWS), and abnormal heart rate response to tilt table tests. These findings suggested the involvement of the autonomic nervous system in CFS. However, more research is needed to clear up the inconsistencies of the results.
- Neuroimaging studies have uncovered prefrontal and brainstem hypometabolism, however their sample size is rather small. More research is required to resolve the discrepancies between neuroimaging brain structure studies.
ii. Immunological
- In 2019, the CDC reported decreased Natural Killer (NK) cell activity in CFS patients, which corresponds with the severity of symptoms.
- Nijs et al. (2014) found CFS patients exhibited an abnormal response to exercise, which comprises of increased production of complement molecules, increased oxidative stress combined with decreased antioxidant response, and increased interleukin-10, and TLR4.
- Armstrong et al. (2014) implied increased cytokine levels to explain the decreased ATP production and increased lactate during exercise. However, Griffith & Zarrouf (2008) indicated the discrepancies in the specificity of cytokines.
- Meeus et al. (2009) derived similarities between cancer and CFS that concerns abnormal intracellular immunological signalling. The abnormalities found include hyperactivity of Ribonuclease L, a protein activated by IFN, and hyperactivity of NF-κB.
iii. Endocrine
- Silverman et al. (2010) found evidence of abnormalities in the hypothalamic-pituitary-adrenal axis (HPA axis) in some CFS patients, such as decreased cortisol levels, a reduction in the variation of cortisol levels throughout the day, decreased responsiveness of the HPA axis, and increased levels of serotonin.
- Studies underscored the ambiguity regarding the relationship between decreased cortisol levels of the HPA axis and a causative factor of CFS, or a secondary factor in the continuation or worsening of symptoms later onset.
- Powell et al. (2013) found most healthy adults’ cortisol awakening response elicited an increase in cortisol levels by around 50% in the first 30 mins after waking. Compared to CFS patients, this increase is significantly diminished, however methods of measuring cortisol levels can differ.
- Morris et al. (2014) proposed the role of autoimmunity in the manifestation of CFS. In a small group of CFS patients, there is evidence of increased B-cell activity and autoantibodies, perhaps due to reduced NK cell regulation of viral mimicry.
How is CFS diagnosed?
So far, no characteristic laboratory abnormalities are approved to diagnose CFS. Although physical abnormalities have been observed, no single finding is sufficiently reliable for consistent diagnosis. Studies noted blood, urine, and other physiological tests can be implemented to eliminate other conditions responsible for the observed symptoms. The CDC recommended a detailed medical history and a mental and physical examination being performed to help diagnosis.
A. Suggested diagnostic tools
- The Chalder Fatigue Scale- Multidimensional Fatigue Inventory
- Fisk Fatigue Impact Scale
- The Krupp Fatigue Severity Scale
- DePaul Symptom Questionnaire
- CDC Symptom Inventory for CFS
- Work and Social Adjustment Scale (WSAS)
- SF-36 / RAND-36
B. Definitions
(1) Centres for Disease Control and Prevention (CDC) definition (1994) = The criteria requires the presence of 4 or more symptoms beyond fatigue.
(2) The ME/CFS 2003 Canadian Clinical working definition:
- A patient with ME/CFS will meet the criteria for fatigue, post-exertional, malaise, and/or fatigue, sleep dysfunction, and pain- Have 2 or more neurological / cognitive manifestations and 1 or more symptoms from 2 of the categories of autonomic, neuroendocrine, and immune manifestations
- The illness persists for at least 6 months.
(3) The Myalgic Encephalomyelitis International Consensus Criteria (ICC) (2011):
- Based on the Canadian working definition and has an accompanying primer for clinicians.- No 6 months waiting time for diagnosis
- Requires post-exertional neuroimmune exhaustion (PENE), which is similar to post-exertional malaise.
- In addition at least 3 neurological symptoms, at least 1 immune or gastrointestinal or genitourinary symptoms, at least 1 energy metabolism or ion transportation symptom.
- Unrefreshing sleep or sleep dysfunction, headaches or other pain, problems with thinking or memory, sensory or movement symptoms.
(4) Institute of Medicine (2015):
Diagnosis requires that the patient have the following 3 symptoms:
I. A substantial decrease or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months. These symptoms persist for more than 6 months and is accompanied by fatigue (profound, new or definite onset). They are not caused by ongoing excessive exertion, and is not substantially alleviated by rest.
II. Post-exertional malaise
III. Unrefreshing sleep.
- At least 1 or the 2 following manifestations is also required:
i. Cognitive impairment
ii. Orthostatic intolerance
iii. Notes that frequency and severity of symptoms should be assessed.
Note: The diagnosis should be scrutinised if patients don’t exhibit these symptoms at least 50% of the time with moderate, substantial, or severe intensity.
C. Differential diagnosis
- Certain medical conditions can lead to chronic fatigue and need to be ruled out before a CFS diagnosis can be provided.- Hypothyroidism, anaemia, coeliac disease (occurs with gastrointestinal symptoms)
- Diabetes and certain psychiatric disorders
- Other diseases, listed by the Centres for Disease Control and Prevention, include:
- Infectious diseases: Epstein-Barr virus, influenza, HIV, tuberculosis, Lyme disease
- Neuroendocrine diseases: Thyroiditis, Addison’s disease, adrenal insufficiency, Cushing’s disease
- Haematologic diseases: Occult malignancy, lymphoma
- Rheumatologic disease: Fibromyalgia, polymyalgia rheumatica, Sjögren’s syndrome, giant-cell arteritis, polymyositis, dermatomyositis
- Psychiatric diseases: Bipolar disorder, schizophrenia, delusional disorders, dementia, anorexia/bulimia nervosa
- Neuropsychologic diseases: Obstructive sleep apnea, parkinsonism, multiple sclerosis
- Others: Nasal obstruction from allergies, sinusitis, anatomic obstruction, autoimmune diseases, some chronic illness, alcohol or substance abuse, pharmacologic side effects, heavy metal exposure and toxicity, marked body weight fluctuation
- Ehlers Danlos syndromes (EDS)
How is CFS managed?
- As of 2020, there is no approved pharmacological treatment, therapy, or cure for CFS. However, a number of pharmaceuticals have been or are being investigated.
- In 2014, the Agency for Healthcare Research and Quality stated counselling and graded exercise therapy (GET), despite its benefits, hasn’t been adequately studied for the US FDA to recommend them for all patients affected. Smith et al. (2014) expressed concern of the worsening outcomes of GET.
- The CDC proposed treatment strategies for sleep problems, pain, (depression, stress, and anxiety-induced) dizziness and lightheadedness (orthostatic intolerance), and memory and concentration problems.
- Thorough monitoring and activity management can help prevent worsening of symptoms, and counselling can help cope with the impact of CFS on quality of life. Furthermore, proper nutrition and nutritional supplements may help improve dietary health, and complementary therapies may help increase energy or decrease pain.
- The UK’s National Institute for Health and Clinical Excellence (NICE) 2007 guidelines recommended clinicians to make shared decisions between the patient and healthcare professions. In addition, it recognises the reality and impact of the condition and the symptoms.
- The NICE guidelines also include illness management aspects of diet, sleep and sleep disorders, rest, relaxation, and pacing.
- They also recommend referrals to specialist care for cognitive behavioural therapy, graded exercise therapy and activity management (pacing) programmes provided to patients with mild or moderate CFS. However, these guidelines are expected to be updated in December 2020.
i. Pacing
- Also known as activity management, pacing is an illness management strategy according to the observation that symptoms tend to worsen following mental or physical exertion, and was recommended for CFS in the 1980s.
- Symptom-contingent pacing = The self-awareness of an exacerbation of symptoms determines the decision to stop (and rest or alter an activity).
- Time-contingent pacing = This involves a set of schedule of activities that a patient determines he/she is able to complete without triggering post-exertional malaise (PEM).
- Hence, the principle behind pacing for CFS is to avoid over-exertion and an exacerbation of symptoms.
- Goudsmit et al. (2011) recommended CFS patients to rest if they exceed their activity and exercise limits.
ii. Energy envelope theory
- This management strategy was proposed in the 2011 international consensus criteria for ME, referred to using an “energy bank budget”. This theory was conceived by psychologist Leonard Jason in 1999, who also was affected by CFS.
- His research group explained energy envelope theory as a strategy for patients to stay within the ‘envelope of energy’ available to them, and refrain from exceeding. They described it subsequently decreases the post-exertional malaise “payback” caused by over-exertion, which may assist them earning moderate gains in physical functioning.
- O’Connor et al. (2019) conveyed their support for energy envelope theory as a useful management strategy, as it demonstrates to decrease symptoms and increase the level of functioning in CFS patients.
- Nevertheless, Jason et al. (2008) highlighted this theory doesn’t recommend unilaterally increasing or decreasing activity and shouldn’t be intended as a therapy or cure for CFS, despite its support by several patient groups.
- Steefel (2011) found some patient groups recommended the use of a heart rate monitor in order to increase awareness of exertion, and enable patients to remain within their aerobic threshold envelope.
iii. Exercise
Some experts recommend stretching, movement therapies, and toning exercises for pain that manifests from CFS, along with administration of pain medication. Despite its benefits in many chronic illnesses, CDC doesn’t recommend it for CFS since ME/CFS can’t tolerate such intense exercise routines.
iv. Counseling
In 2019, the CDC recommended counselling for CFS patients to manage their pain, and consulting with a professional counsellor or therapist to effectively their symptoms that continue to impact their quality of daily life.
v. Nutrition
The CDC recommended medical consultation about diet and supplements for CFS patients. If shortages are detected by medical testing, CFS patients can benefit from a balanced diet and supervised administration of nutritional support.
What are the treatments for CFS?
i. Cognitive behavioural therapy (CBT)
- A 2015 National Institutes of Health report concluded that CBT does provide moderate benefits and reduce some signs of fatigue, there is insufficient evidence this therapy significantly improves quality of life due to study limitations. Therefore it remains unclear whether CBT augments the improvment of cognitive impairments experienced by CFS patients.
- A 2008 Cochrane review concluded that CBT did improve the symptoms of CFS, but highlighted the benefits of CBT may decline upon completion of the therapy.
- Adamowicz et al. (2014) stated the lack of concrete evidence for CBT significantly improving a CFS patient’s level of physical activity. Since this finding contradicts the cognitive behavioural model of CFS, patients undergoing CBT adapts to the illness instead of recovering from it.
- In 2015, the ME Association did not recommend CBT as a primary intervention for CFS patients due to its lack of effectiveness.
ii. Graded exercise therapy (GET)
- Larun & Brunberg (2019) stated exercise therapy elicited an overall positive outcome in fatigued adults, and slight improvements in sleep. However, the long-term effects of GET are unknown, which has limited relevance to current definitions of ME/CFS.
- In 2020, Cochrane is in the process of reviewing the effects of exercise therapies on CFS in adults.
- In 2015, the ME Association doesn’t recommend GET as a primary intervention for CFS patients.
iii. Adaptive pacing therapy (APT)
- This therapy is based on the concept of a CFS patient wisely uses the limited energy in order to gradually increase it.
- The PACE trial conducted by White et al. (2011) did not demonstrate effectiveness compared to usual care or specialised medical care.
- In contrast to pacing, APT is based on the cognitive behavioural model of CFS and increasing activity levels, which may temporarily increase symptoms. A patient undergoing AFT first establishes a baseline level of activity, which can be accomplished consistently without any post-exertional malaise.
- Cox et al. (2004) stated that APT requires patients to increase their activity up to 70% of maximum capacity, and to avoid excess rest. However, Jason (2017) argued this statement is contradictory, and the limit restricts the activities CFS patients are capable of, which may lead to decreased level of functioning.
- APT was criticised by Jason and Goudsmit for its inconsistency in regards to the principles of pacing and significant differences were pointed out by the pair.
iv. Pharmacological therapy
- Rintatolimod is a double-stranded RNA drug developed to regulate an antiviral immune reaction by activating TLR-3.
- Richman et al. (2019) found that despite its improvements of symptoms in clinical trials, they weren’t maintained after discontinuation.
- In 2016, the US FDA denied commercial approval of this drug, due to deficiencies and inconsistencies in safety data in the trials. Therefore, the available evidence insufficiently demonstrate its safety or efficacy in CFS.
- Nevertheless, in 2019, rintatolimod was approved for marketing and treatment for CFS patients in Argentina. In addition, the FDA regulatory requirements were satisfied for rintatolimod exportation to the USA.
How does fatigue affect safety?
Fatigue is a major safety issue in numerous working industries, especially in transportation and logistics, which have led to several fatal accidents.
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| This graph illustrates the relationship between the number of hours driven and the percentage of crashes associated with driver fatigue. Source: Federal Motor Carrier Safety Administration |
What are the factors?
The Federal Motor Carrier Safety Administration identified 3 main factors in driver fatigue:
(1) Circadian rhythm effects
- It describes the tendency for humans to experience a normal cycle of concentration and sleepiness throughout the day. Conventionally, a person who sleeps 7-8 hours a night experience periods of fatigue in the early hours of the morning and in the early afternoon.
- Decreased attentiveness occurs during the cycle troughs and difficulty of sound sleep occurs during the cycle peaks.
- Ambient lighting (melatonin release during sleep) and an individual's pattern of regular sleeping and waking times are factors of the circadian rhythm.
- Since artificial lighting inhibits melatonin release more weakly by sunlight, it never fully displaces the day-night cycle.
- A 2008 study found shifting the circadian rhythms by more than an hour or 2 forward / backward can decrease attentiveness, which often occurs after the first night shift following a "weekend" break during which conventional sleep times were met.
- Van Dongen (2006) found non-shift workers regressing to a later schedule on the weekend experienced fatigue and drowsiness upon their return to work early on Monday morning, though the effects of sleep deprivation can vary from person to person.
(2) Sleep deprivation and cumulative fatigue effects
- This describes the inadequate sleep period (less than 7-8 hours in 24 hours) or the wakefulness period being longer than 16-17 hours, which leads to sleep deprivation.
- Sleep deprivation builds up an individual's sleep deficit, which increases the level of fatigue and fragmented daily sleep patterns.
(3) Industrial or "time-on-task" fatigue
- It describes fatigue experienced during the working period, which impairs performance on shift.
- Work performance decreases as engagement in a task increases during the shift, which is often observed in the first few hours of work.
Other potential factors that contribute to factor during transportation include:
- Endogenous factors, such as mental stress and age of the vehicle operator
- Exogenous or environmental stressors, such as the presence of non sea-level cabin pressure in-flight, vehicle noise, and vehicle vibration / acceleration (leads to sopite syndrome).
What is pilot fatigue?
- In 2013, the International Civil Aviation Organisation (ICAO) defined fatigue as "A physiological state of reduced mental or physical performance capability resulting from sleep loss or extended wakefulness, circadian rhythm, or workload.
- Caldwell & Mallis (2009) expressed concerns that fatigue placed considerable risk on the flight crew and the passengers onboard an aircraft since it increased the likelihood of pilot error.
- Pilots at risk of fatigue worked unpredictable hours, long duty periods, had disrupted circadian rhythms, and insufficient sleep. These factors combine to manifest in a deadly mix of sleep deprivation, circadian rhythm effects, and 'time-on-task' fatigue.
How does fatigue affect flight safety?
- Caldwell (2004) estimated around 4-7% of civil aviation incidents and accidents were associated with fatigued pilots. At a 2016 FAA symposium, NTSB vice chairman Robert Sumwait stated fatigue attributed to 250 deaths in air carrier accidents since 2000.
-- Slower reaction times
-- Reduced concentration on tasks leading to procedural mistakes
-- Lapses in attention
-- Inability to anticipate events
-- Higher toleration for risk
-- Forgetfulness
-- Decreased ability to make decisions
- A FFA study conducted between 1978 and 1999 discovered a disturbing trend with the prevalence of aviation accidents increasing proportionally to the amount of time the captain was on duty. It found 5.62% of aviation accidents associated with pilots who were on duty for 13+ hours, which accounted for only 1% of total pilot duty hours.
- Wilson, Caldwell & Russell (2007) found fatigued pilots demonstrated slower reaction times, and substantially more cockpit errors in simple tasks, such as reacting to warning lights and responding to automated alerts. However, sleep deprivation hardly affected the pilots' performance on tasks that required more engagement and concentration. Therefore, they concluded that fatigue impaired performance and the degree of performance impairment was determined by a function of the number of hours awake and the 'engagement' value of the task.
How prevalent was pilot fatigue?
- A study on Portuguese pilots by Reis et al. found 93% of short/medium haul pilots and 84% of long-haul pilots scored highly on the Fatigue Severity Scale (FSS). Furthermore, 96% of short/medium pilots and 92% of long-haul pilots demonstrated mental fatigue.
- A 2006 study by Jackson & Earl found 75% of short-haul pilots experienced severe levels of fatigue. Moreover, pilots who expressed concerned about their fatigue level during the flight tended to experience more fatigue whilst on duty.
- A 1997 study on German long-haul pilots by Samen, Wegmann and Vejvoda found the most prominent periods of fatigue were before and after the flight, recorded before departure, 1-hour intervals during the flight and immediately after landing.
- Moreover, an EEG study found fatigued pilots performed more microsleeps, which are alpha wave patterns that occur during wakeful relaxation often manifesting in attention loss of less than 30 seconds.
- They found the prevalence of fatigued pilots on incoming flights back to the home base was double that of those on outgoing flights. The study concluded pilots were likely to experience fatigue during the cruising stage of the flight compared to other stages such as the take-off, approach, and landing phases of the flight.
- In addition, there is a higher likelihood of fatigue during flights scheduled at night compared to at day since pilots had already been awake for 12 consecutive hours and begin their shift prior to their sleep time.
- The European Cockpit Association found only 20-30% of pilots would report unfit for duty due to fatigue. Moreover, a staggering 70-80% of fatigued pilots would not file a fatigue report or declare themselves unfit to fly because they fear disciplinary actions or stigmatisation by their employer or colleagues.
What aviation accidents were caused by pilot fatigue?
What measures have been implemented to combat pilot fatigue?
i. In-flight measures
- Cockpit naps = 40-minute naps after a long stint of wakefulness
- Taking breaks from activity
- Bunk sleeping
- In-flight rostering
- Proper cockpit lighting to inhibit the productio of melatonin
ii. Alternative measures
- Consumption of over-the-counter drugs such as Zolpidem
- Samn-Perelli checklist
- Implementation of fatigue prediction models e.g. Sleep, Activity, Fatigue, and Task Effectiveness model
- Sleep and fatigue monitoring using wrist monitors to accurately track sleep data
- Fatigue Avoidance Scheduling Tool (FAST) or Flyawake
iii. Cockpit design
- Head-up display (HUDs)
- Blinking lights on aircraft avionics
- "Keep awake" routines
How does fatigue affect driving?
- One of the major causes of motor vehicle accidents is driver fatigue, and the degree of cognitive impairment is as significant as inebriation.
How does fatigue affect driving performance?
- Fatigue is known to impair coordination, extend reaction times, impair judgment, and disrupt memory and severely affect the ability to retain information. A 2009 study identified a correlation between the hippocampal activity during sleep and driving performance.
- A 2012 report by the United States Department of Transportation found twice as many female drivers fell asleep at the wheel than male drivers.
- The Division of Sleep Medicine at Harvard Medical School found a staggering 250,000 drivers slept at the wheel every day.
- A national poll by the National Sleep Foundation revealed 54% of adult drivers felt drowsy at the wheel and 28% of adult drivers fell asleep at the wheel in the past year.
- In 2018, the National Highway Traffic Safety Administration found more than 100,000 crashes, including 6,550 deaths and 80,000 injuries annually in the USA, were attributed to driver fatigue.
-- Difficulty focusing
-- Frequent blinking
-- Heavy eyelids
-- Daydreaming
-- Disconnected thoughts
-- Difficulty remembering the previous section of road driven or missing exits and street signs
-- Frequent yawning
-- Rubbing of the eyes
-- Difficulty keeping their head up and straight
-- Drifting lanes
-- Tailgating
-- Striking a shoulder or rumble strip
-- Restlessness and irritability
- A British study found drivers who were awake for 17-18 consecutive hours demonstrated similar driving behaviours as those with blood alcohol level of 0.05%, the legal limit in many European countries.
- The Mythbusters (Grant, Tori and Kari) performed a number of trials in the episode "Tipsy vs. Tired" and have confirmed the findings that sleep deprivation is as dangerous as driving with a BAC over the legal limit (0.08 in USA).
How does fatigue affect commercial transportation and the military?
- Goodman (2012) found 20% of commercial pilots and 18% of rail operators performed serious errors on the job due to fatigue.
- The National Transportation Safety Board associated over half of truck driver deaths with fatigue, and 3-4 people are killed with every truck driver killed. Fatigued truck drivers in USA and Canada reported sleeping less than 5 hours every day.
- Peters (1999) reported approximately 9% of military vehicle crashes during Operation Desert Storm and Operation Desert Shield were attributed by sleep-deprived driving.
- Mythbusters: https://www.youtube.com/watch?v=1LN6O1cViwQ
How deadly is fatigue when driving?
- A 2017 meta-analysis by Bioulac et al. found sleep-deprived driving increased the likelihood of a motor vehicle accident by 2.5 times.
- Between 2011 and 2015, a report by the National Highway Traffic Safety Administration (NHTSA) stated 1.4% of all car crashes occurring in the USA attributed to drive fatigue, including 2% of crashes leading to serious injuries and 2.4% of crashes leading to fatalities. Owens et al. (2018) pointed out these figures based on police investigations underestimated the actual attribution of sleep-deprived driving to accidents.
- A study by the AAA Foundation between October 2010 and December 2013 found 8.8-9.5% of vehicle crashes associated with drowsiness, including 10.6-10.8% of crashes manifesting in property damage, airbag deployment, or serious injury. Nevertheless, the lack of fatalities during the study period limited the reliability of the estimated impact of drowsiness towards the likelihood of road fatality.
- A number of research groups, including the AAA Foundation, found vehicle crashes associated with fatigue were 3 times more likely to occur at night time compared to day time.
How does fatigue affect workers on ships?
Mythbusters: https://www.youtube.com/watch?v=1LN6O1cViwQ&t=691s
- A 2004 study found most ship accidents occur at night time since the human's circadian rhythm is accustomed to sleep at night. This associates with sleep deprivation, hence fatigue since ship workers have 70+ hour work weeks.
-- Food quality
-- Vibrations generated by the engine and waves
-- Noise of repair or works or engine
-- Only naps (short sleeps) due to the watch system and secondary jobs
-- Stress on board particularly when arriving into port when all hands are on deck.
What are the names of sleep disorders?
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|
Classification of sleep disorders Source: https://www.researchgate.net/figure/Classification-of-sleep-disorders_fig3_6740009 |
(A) Dyssomnia
It is a broad classification of sleeping disorders involving difficulty falling asleep, remaining asleep, and/or of excessive sleepiness.
1. Excessive daytime sleepiness (EDS)
https://en.wikipedia.org/wiki/Excessive_daytime_sleepiness
This is characterised by persistent sleepiness and lethargy, even during the day after apparently sufficient or prolonged night time sleep. They may be a broad condition that incorporates several sleep disorders where sleep hours accumulates.
What are the causes of EDS?
EDS can be caused by a number of factors and disorders. They include:— Insufficient quality or quantity of night time sleep
— Misalignments of the body’s circadian pacemaker with the environment (e.g., jet lag, shift work, or other circadian rhythm sleep disorders)
— Another underlying sleep disorder, such as narcolepsy, sleep apnoea, idiopathic hypersomnia, or restless legs syndrome
— Disorders such as clinical depression or atypical depression
— Tumours, head trauma, anaemia, kidney failure, hypothyroidism, or an injury to the CNS
— Drug abuse
— Genetic predisposition
— Vitamin deficiency, such as biotin deficiency
— Particular classes of prescription and over-the-counter medication
How is EDS diagnosed?
- The Epworth Sleepiness Scale (ESS) grades the results of a questionnaire. It produces a numerical score from zero (0) to 24 where a score of 10 or higher may indicate that the person should consult a specialist in sleep medicine for further assessment.- The Multiple Sleep Latency Test (MSLT) measures the time taken from the beginning of a daytime nap period to the first signs of sleep, called sleep latency.
- The Maintenance of Wakefulness Test (MWT) quantitatively assesses daytime sleepiness in a sleep diagnostic centre.
How is EDS treated?
- Drugs such as modafinil, Armodafinil, Xyrem (sodium oxybate) oral solution have been approved for EDS symptom treatment in the USA.
- Other drugs such as methylphenidate (Ritalin), dextroamphetamine (Dexedrine), amphetamine (Adderall), lisdexamfetamine (Vyvanse), methamphetamine (Desoxyn), and pemoline (Cylert) are decreasing in usage, since these psychostimulants elicit several adverse effects and may lead to dependency.
2. Hypersomnia
https://en.wikipedia.org/wiki/Hypersomnia
This neurological disorder involves excessive time spent sleeping or excessive sleepiness, which are caused by many factors and can cause distress and issues with functioning.
What are the symptoms?
- The main symptom of hypersomnia is excessive daytime sleepiness (EDS), or prolonged nighttime sleep, which typically occurs for at least 3 months before diagnosis.
- Another main symptom is sleep drunkenness, which is defined as the difficulty to transition from wake to sleep. Hypersomniacs often report waking with confusion, disorientation, slowness and recurrent returns to sleep, as well as irritability.
- The American Academy of Sleep Medicine found hypersomniacs often napped longer during the day, but were mainly unrefreshing.
How is hypersomnia diagnosed?
- The severity of daytime sleepiness is usually quantified by subjective scales (at least the Epworth Sleepiness Scale) and objective tests such as the multiple sleep latency test (MSLT) and Stanford sleepiness scale (SSS).
- Once the level of daytime sleepiness determined, a complete medical examination and full evaluation of potential disorders in the differential diagnosis is undertaken.
- The tools used to assess hypersomniacs include polysomnography (including EEG, EMG, ECG, muscle activity and respiratory function), MSLT, actigraphy, the maintenance of wakefulness' test (MWT), the Stanford Sleepiness Scale (SSS), and the Epworth Sleepiness Scale (ESS).
a. Primary
True primary hypersomnias include: narcolepsy (with and without cataplexy), idiopathic hypersomnia, and recurrent hypersomnias (such as Klein-Levin syndrome).
b. Primary mimics
- Prader-Willi syndrome, Norrie syndrome, Niemann-Pick disease, type C & Myotonic dystrophy - These genetic disorders are associated with primary / central hypersomnia.
- Neurological diorders that mimic the primary hypersomnias, narcolepsy and idiopathic hypersomnia include: brain tumours, stroke-provoking lesions, and dysfunctions in the thalamus, hypothalamus, or brainstem.
- Neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, or multiple system atrophy are often associated with primary hypersomnia.
- Early hydrocephalus and head trauma have been correlated with primary/central hypersomnia.
c. Secondary
- They can be secondary to disorders such as clinical depression, multiple sclerosis, encephalitis, epilepsy, or obesity, as well as a symptom of other sleep disorders such as sleep apnoea.
- It may occur as an adverse effect of certain medications, of withdrawal from some medications, or of drug / alcohol abuse.
- Upper airway resistance syndrome (UARS) is a clinical variant of sleep apnoea that is known to cause hypersomnia. Montplaisir (2001) discovered many cases of UARS involving the persistence of excessive daytime sleepiness after CPAP treatment.
- Sleep movement disorders, such as restless leg syndrome (RLS) and periodic limb movement disorder (PLMD), can cause secondary hypersomnia.
- A 2014 report stated neuromuscular diseases and spinal cord diseases often lead to sleep disturbances due to respiratory dysfunction, which causes sleep apnoea, as well as insomnia related to pain.
- Dauvilliers et al. (2006) highlighted primary hypersomnia rarely occurs in diabetes, hepatic encephalopathy, and acromegaly, but may be secondary to sleep apnoea and PLMD.
d. Post-traumatic
- Traumatic brain injury can manifest in hypersomnia with the level sleepiness associated with the severity of the injury. Watson et al. (2007) stated sleepiness persists for a year after a traumatic brain injury patients reported improvements.
e. Recurrent
- Dauvilliers & Buguet (2005) defined recurrent hypersomnias as several episodes that persist from a few days to weeks, with episodes occurring weeks or months apart from each other.
- There are types of recurrent hypersomnias: Kleine-Levin syndrome and menstrual-related hypersomnia. Kleine-Levin syndrome will be discussed in detail later down the post.
- Menstrual-related hypersomnia is characterised by episodes of excessive sleepiness correlated with the menstrual cycle, particularly the pre-menstrual phase. This type of hypersomnia doesn't show certain behavioural symptoms such as hyperphagia and hypersexuality, with hypophagia being an exception, which usually occur around 2 weeks before menstruation.
- Harris et al. (2012) suggested that hormones involved in menstruation such as prolactin and progesterone may be involved in menstrual-related hypersomnia, however the mechanism for manifesting such symptoms are unknown.
How is hypersomnia treated?
- Currently, there are no cures for chronic hypersomnia, but there are treatments that can improve patients’ quality of life, depending on the specific cause or causes of hypersomnia that are diagnosed.
- Modafinil is demonstrated to be the best pharmacological treatment against the symptoms of hypersomnia. Ivananeko et al. (2013) recommended dosage to begin at 100 mg/day and then progressively increased to 400 mg/day.
- Recommended behavioural habits include going to bed for sleeping or sexual purposes, and performing other daily activities such as eating or watching television in other locations (i.e. dining room or living room respectively).
https://www.youtube.com/watch?v=LUt42r5-5AE&ab_channel=Osmosis
https://en.wikipedia.org/wiki/Insomnia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353813/
Also known as sleeplessness, insomnia is a sleeping disorder that is characterised by sleeping difficulties such as difficulty falling asleep, or staying asleep as long as desired.
Describe the prognosis
- A survey of 1.1 million Americans conducted by Kripke et al. (2002) found the surveyors reported sleeping about 7 hours per night had the lowest mortality, those reported sleeping fewer than 6 hours or more than 8 hours had higher mortality rates. A 8.5+ hour sleep per night correlated with a 15% mortality rate increase. Those with severe insomnia slept less than 3.5 hours (for women) and 4.5 hours (for men), which also associated with a 15% mortality rate increase.
- Therefore, it is difficult to distinguish sleeplessness caused by a disorder (a premature cause of death), compared to a disorder that causes sleeplessness, and the sleeplessness causing premature death.
- Most of the mortality rate increases due to severe insomnia were disregarded after controlling for associated disorders. When sleep duration and insomnia were controlled, the increased mortality rate correlated with the increased use of sleeping pills.
- Mild to moderate insomnia correlates with increases in longevity, while severe insomnia correlates with a minimal effect on morality. Nevertheless, the reasons behind the 7.5+ hour per night sleep correlation with increased mortality remain ambiguous and require further investigation.
Describe the epidemiology
Disability-adjusted life year for insomnia per 100,000 inhabitants in 2004.
- Studies found 10-30% of adults experienced insomnia at any given point in time and up to 50% of people experienced insomnia in a given year.
- Roth (2007) reported about 6% of people experienced insomnia not caused by co-morbidities, which lasted more than a month.
- Wilson (2008) found a large proportion of insomniacs were aged 65+, compared to those younger 40, and 40% as many females having insomnia than males.
What are the signs and symptoms of insomnia?
- Waking during the night, inability to return to sleep and waking up early.
- Difficulty focusing on daily tasks, difficulty in remembering.
- Daytime sleepiness, irritability, depression or anxiety.
- Feelings of fatigue or lethargy during the day.
- Difficulty concentrating
- Irritability, aggression or impulsiveness
- Sleep onset insomnia is characterised by difficulty falling asleep at the beginning of the night, a common symptom of anxiety disorders.
- Delayed sleep phase disorder can be misdiagnosed as insomnia, since sleep onset is delayed significantly while awakening continues into daylight hours.
- Doghramji (2007) estimated 2 out of 3 patients awaken in the middle of the night, with more than 50% experiencing issues falling back to sleep after a middle-of-the-night awakening.
- Early morning awakening is defined as waking up earlier (more than 30 minutes) than desired with an inability to fall back to sleep, and before total sleep time approaches 6.5 hours.
- Examples of anxiety symptoms that can lead to insomnia include tension, compulsive worrying about the future, overstimulation, and overanalysis of past events.
- Sleep quality can be degraded due to restless legs, sleep apnoea, or major depression. Poor sleep quality associates with failure to reach stage 3 or delta sleep.
- Harvey & Tang (2012) proposed the concept of ‘sleep state misperception’ when people subjectively feel they slept inadequately despite sleeping for many hours per night and normally not experiencing significant daytime sleepiness or symptoms of sleep deprivation. Since their sleep perception is insufficient, they incorrectly think they require an abnormally long time to fall asleep, and they underestimate the amount of time they remained asleep.
What are the causes of insomnia?
- Sleep breathing disorders, such as sleep apnoea, or upper airway resistance syndrome.
- Psychoactive drugs (such as stimulants), including certain medications, herbs, caffeine, nicotine, cocaine, amphetamines, methylphenidate, aripiprazole, MDMA, modafinil, or excessive alcohol intake.
- Use of or withdrawal from alcohol and other sedatives, such as anti-anxiety and sleep drugs such as benzodiazepines.
- Use of or withdrawal from pain relievers such as opioids.
- Heart disease
- Restless legs syndrome: It can cause sleep onset insomnia due to the discomforting sensations perceived and the urge to move the legs or other body parts to relieve these sensations.
- Periodic limb movement disorder (PLMD): This occurs during sleep and causes arousals that the sleeper is unaware of.
- Pain: An injury or condition that causes pain prevents one from sleeping in a comfortable position, as well as cause awakening. e.g. chronic pain, lower back pain
- Hormone shifts e.g. those preceding menstruation and during menopause, increased levels of cortisol and adrenocorticotropic hormone
- Life events e.g. fear, stress, anxiety, emotional or mental tension, work problems, financial stress, birth of a child, and bereavement.
- Gastrointestinal issues e.g. heartburn and constipation
- Mental disorders e.g. bipolar disorder, clinical depression, generalised anxiety disorder, post traumatic stress disorder, schizophrenia, obsessive compulsive disorder, dementia, ADHD.
- Disturbances of the circadian rhythm e.g. shift work and jet lag. This compromises the ability to fall asleep at certain times of the day and excessive sleepiness at other times of the day.
- Certain neurological disorders, brain lesions, or a history of traumatic brain injury.
- Medical conditions such as hyperthyroidism
- Abuse of over-the-counter or prescription sleep aids (sedative or depressant drugs) can produce rebound insomnia.
- Poor sleep hygiene, e.g. noise or over-consumption of caffeine
- A rare genetic condition can cause a prion-based, permanent and eventually fatal form of insomnia called “fatal familial insomnia”.
- Physical exercise: Athletes commonly experience exercise-induced insomnia in the form of prolonged sleep onset latency.
- Increased exposure to the blue light from artificial sources, such as phones or computers.
- Asthma
i. Genetics
- Lind et al. (2015) estimated the heritability of insomnia varies between 38% in males to 59% in females.
- A genome-wide association study (GWAS) conducted by Hammerschlag et al. (2017) identified 3 genomic loci and 7 genes that affected the risk of insomnia, and demonstrated insomnia as highly polygenic. There was a strong positive correlation between the MEIS1 gene and insomnia severity in both females and males. Furthermore, the genetic architecture of insomnia strongly overlaps with psychiatric disorders and metabolic traits.
- Palagini et al. (2014) hypothesised a epigenetic influence on insomnia through a homeostatic process of both sleep regulation and the brain-stress response, thence affecting brain plasticity.
ii. Substance-induced
(A) Alcohol
- When people experience difficulty sleeping, they consume alcohol to induce sleep. However, scientists think it may be a cause insomnia.
- Long-term use of alcohol is correlated with a decrease in NREM stage 3 and 4 sleep as well as REM sleep suppression and fragmentation.
- Frequent oscillations between sleep stages occurs, along with awakenings due to headaches, the urge to urinate, dehydration, and excessive sweating.
- When a person stops consuming alcohol, they would experience glutamine rebound, which involves the body ameliorating glutamine production. This increase in glutamine levels stimulates the brain as the individual is attempting to sleep, preventing them from reaching the deepest levels of sleep.
- Studies found halting chronic alcohol use (alcohol withdrawal) can lead to severe insomnia with vivid dreams.
(B) Benzodiazepine
- Benzodiazepines, such as alprazolem, clonazepam, lorazepam, and diazepam, are commonly prescribed for insomnia treatment in the short-term.
- Although benzodiazepines induce sleep (i.e. inhibit NREM1 and 2), they can disrupt sleep architecture during sleep. The negative effects include decreased sleep time, delayed time to REM sleep, and decreased deep SWS.
(C) Opioid
- Opioid medications such as hydrocodone, oxycodone, and morphine are used to treat the insomnia manifested by pain due to their analgesic properties and hypnotic side-effects. They are known to disrupt sleep and decrease REM and NREM2 sleep stages.
- Although opioids can cause analgesia and sedation, dependence on such medication can lead to long-term sleep disturbances.
iii. Risk factors
- Humans aged 60 and over
- History of mental health disorder including depression, etc.
- Emotional stress
- Working late night shifts
- Travelling through different time zones
- Having chronic diseases such as diabetes, kidney disease, lung disease, Alzheimer’s, or heart disease.
- Alcohol or drug use disorders
- Gastrointestinal reflux disease
- Heavy smoking
- Work stress
Describe the mechanism of insomnia
1. Cognitive: There is a suggestion of rumination and hyperarousal contributing to the prevention of falling asleep and manifestation of an episode of insomnia.
2. Physiological:
- Increased urinary cortisol and catecholamines may increase activity of the HPA axis and arousal.
- Increased global cerebral glucose utilisation during wakefulness and NREM sleep in insomnia patients.
- Increased full body metabolism and heart rate in insomnia patients.
- The above findings suggest a dysregulation of the arousal system, cognitive system, and HPA all contribute to the development of insomnia. Nevertheless, not much is known about the association between hyperarousal and insomnia.
- There is inconsistency in findings and ambiguity regarding changing levels of neurotransmitters such as GABA. Furthermore, it is unclear if insomnia occurs due to circadian control over sleep or a wake dependent process, or dysregulation of the circadian rhythm based on core temperature.
- Although Mai & Buyesse (2008) detected increased beta activity and decreased delta wave activity in insomniacs, the cause of these findings is unknown.
- Shaver & Woods (2015) estimated around 50% of post-menopausal women experience sleep disturbances, which may be due to hormonal level alterations.
How is insomnia diagnosed?
i. Types
(1) Transient insomnia
- Lasts for less than a week
- Caused by another disorder, changes in the sleep environment, the timing of sleep, severe depression, or stress.
- Effects include sleepiness and impaired psychomotor performance
(2) Acute insomnia (Short-term or stress-related insomnia)
- Inability to consistently sleep for a period of less than a month
- Difficulty maintaining or initiating sleep or non-refreshing / poor quality sleep.
- Issues with daytime function.
(3) Chronic insomnia
- Lasts for longer than a month
- Caused by another disorder, or may be a primary disorder.
- High levels of stress hormones or changes in cytokine levels.
- Symptoms include muscular weariness, hallucinations, and/or mental fatigue.
ii. DSM-5 Criteria
Predominant complaint of dissatisfaction with sleep quantity or qualify, associated with 1 (or more) of the following symptoms:— Difficulty initiating sleep. (In children, this presents as difficulty initiating sleep without caregiver intervention.)
— Difficulty maintaining sleep, characterised by frequent awakening or problems returning to sleep after awakenings. (In children, this presents as difficulty returning to sleep without caregiver intervention.)
— Waking up in the early morning with inability to return to sleep.
— Difficulty maintaining sleep, characterised by frequent awakening or problems returning to sleep after awakenings. (In children, this presents as difficulty returning to sleep without caregiver intervention.)
— Waking up in the early morning with inability to return to sleep.
In addiction,
— The sleep disturbance causes clinically significant distress or impairment in academic, behavioural, educational, occupational, social or other important areas of functioning.— The sleep difficulty occurs at least 3 nights per week.
— The sleep difficulty is present for at least 3 months.
— The sleep difficulty occurs despite adequate opportunity for sleep.
— The insomnia is no better explained by and does not occur exclusively during the course of another sleep-wake disorder (e.g. narcolepsy).
— The insomnia is not attributable to the physiological effects of a substance (e.g. a drug of abuse, a medication).
— Coexisting mental disorders and medical conditions do not adequately explain the predominant complaint of insomnia.
iii. Diagnosis
- In medicine, insomnia is often measured using the Athens insomnia scale.
- To receive an accurate diagnosis of any sleep disorder, you should consult a qualified sleep specialist in order to plan out the most appropriate measures.
- After all other conditions are rules out, the specialist would check your comprehensive sleep history such as sleep habits, medications (prescription and non-prescription), alcohol consumption, nicotine and caffeine intake, co-morbid illnesses, and sleep environment.
- They recommend setting up a sleep diary that details your time to bed, total sleep time, time to sleep onset, number of awakenings, use of medications, time of awakening, and subjective feelings in the morning.
- Schutte-Rodin et al. (2008) stated the sleep diary can be substituted or validated by out-patient actigraphy for a week or more, using a non-invasive device that measures movement.
- Although workers complain of suffering from insomnia, it isn’t routine to use a polysomnography to screen for sleep disorders.
- The American College of Occupational and Environmental Medicine (2014) explained polysomnography may be designated for patients with symptoms in addition to insomnia, such as thick neck diameter, high-risk fullness of the flesh in the oropharynx, obesity, and sleep apnea. They suggested an alteration of the job schedule to fit in longer sleep sessions and improve sleep hygiene.
- An overnight sleep study commonly use a number of assessment tools including a polysomnogram and the multiple sleep latency test. Thorpy (2012) asserted specialists in sleep medicine are qualified to diagnose disorders within the 81 sleep disorder diagnostic categories described by the ICSD.
- Wilson et al. (2010) found approximately 50% of all diagnosed insomnia manifested with other comorbidities such as psychiatric disorders, diseases, and side-effects from medications. For instance, Luca et al. (2013) evaluated insomnia occurred in 60-80% of depressed people.
How can be insomnia be prevented?
Prevention and treatment of insomnia requires a combination of cognitive behavioural therapy, medications, and lifestyle changes.— Consistent sleeping and awakening patterns every day
— Avoiding vigorous exercise and caffeinated drinks hours prior to sleeping
— Exercise during the daytime
— Avoiding or limiting naps
— Pain treatment at bedtime
— Avoiding large meals, beverages, alcohol, and nicotine before bedtime
— Inducing sleepiness in the bedroom by turning off lights, decreasing room temperature, avoiding electrical devices such as a phone, or television.
— Maintain regular exercise
— Attempting relaxing activities before bedtime
— Using bed for sexual or sleep purposes
— Avoid checking the time
How is insomnia managed?
- Wortelboer et al. (2002) recommended rulling out medical and psychological causes of insomnia before proceeding with insomnia treatments.
- van Straten et al. (2018) advised cognitive behavioural therapy should be the first line treatment in order to achieve the most progress in treating chronic insomnia.
- Many doctors advise against prescription sleeping pills for long-term use. On the other hand, they recommend the identification and treatment of other medical conditions that may contribute to insomnia, such as breathing difficulties, depression, and chronic pain.
i. Non-medication
- Non-medication based interventions have comparable efficacy to hypnotic medication, demonstrating long-term effects. The National Prescribing Service (2010) advised the use of hypnotic medication only for short-term use since dependence with rebound withdrawal effects upon discontinuation or the development of tolerance can occur.
- Attention to sleep hygiene
- Stimulus control
- Behavioural interventions
- Sleep-restriction therapy
- Paradoxical intervention
- Patient education
- Relaxation therapy
Merrigan et al. (2013) suggested a few strategies such as:
- Journal diary
- Time restrictions on wakefulness in bed
- Relaxation techniques
- Maintenance of regular sleep schedule and a wake-up time.
Behavioural therapy also includes:
- Learning healthy sleep habits to promote sleep relaxation
- Light therapy to reduce anxiety and regular circadian rhythm
- Studies have proposed other therapies such as music, neurofeedback (NFB) and self-help therapy demonstrated effectiveness in treating insomnia and improving sleep quality.
- Lande & Gragnani (2010) implied stimulus control therapy as a treatment for patients who have conditioned themselves to associate the bed, or sleep, with a negative stimulus. Examples of environmental modifications include:
- Using the bed for sleep or sex only
- Avoidance of activities such as reading or watching television
- Waking up at the same time consistently every morning, including weekends
- Bedtime during sleepiness
- Alighting the bed and initiating an activity in a different location if sleep fails to manifest after a brief period of time after entering the bed
- Decreasing the subjective effort and energy expenditure in attempts to fall asleep
- Avoiding exposure to bright light during nighttime hours
- Elimination of daytime naps
- van Maanen et al. (2016) explained an aspect of stimulus control therapy involves restricting the amount of sleep, which aims to equal the time spent in bed with the actual sleep time. Theoretically, this helps maintain a strict sleep-wake schedule and alleviate sleep deprivation to an extent.
- If this therapy continues for 3 weeks and allows self-control of time spent on sleep and adjusting its body to a new circadian rhythm.
- Kierlin (2008) stated paradoxical intention can cognitive reframe an insomniac patient by exerting effort to stay awake. Theoretically, if patients intend to non-voluntarily go to sleep, it helps alleviate their performance anxiety that result from the will to fall asleep, and thereby reduce subjective assessment of sleep-onset latency and overestimation of sleep deficit.
— Sleep hygiene
- Sleep hygiene includes habits that lay out a solid foundation for refreshing sleep and to prevent insomnia to an extent.
Recommendations include:
-- One component of cognitive behavioural therapy for insomnia (CBT-I)
-- Reducing caffeine, nicotine, and alcohol consumption
-- Maximising the frequency and efficiency of sleep episodes
-- Minimising medication usage and daytime napping
-- Promotion of regular exercise
-- Facilitating a positive sleep environment
-- Physical exercise but not close to sleep time.
-- Creating a positive sleep environment
— Cognitive behavioural therapy
- Compared to pharmacological treatments such as benzodiazepines and non-benzodiazepines, cognitive behavioural therapy for insomnia (CBT-I) was demonstrated to be more effective in managing insomnia. It teaches patients to improve sleep habits and forget counter-productive assumptions about sleep.
- This form of therapy for insomnia is markedly accepted due to the lack of adverse effects and is recommended as a first line treatment for insomnia. The only limitation is the amount of time required to take effect and motivation to continue the therapy long-term.
— Internet interventions
- There are proposals of using the internet to overcome the limitations of CBT such as a lack of trained clinicians, delivery of treatment, poor geographical distribution of knowledgeable professionals, and cost, by providing information regarding health-care and medical intervention.
- A number of online programs delivering behaviourally-based treatments have been designed and are now up and running. Ritterband et al. (2003) found these internet interventions demonstrated structure and organisation, supported by automation or humans, delivered effective face-to-face treatment, personalisation according to the user, interaction, enhanced by graphics, audio, and video, and customised to provide follow-ups and feedback.
ii. Medications
- Insomniacs are often prescribed sleeping tablets and other sedatives, but Qaseem et al. (2016) viewed it as a second line treatment.
- Therefore, in 2019, the US FDA ordered warning labels on eszopiclone, zaleplon, and zolpidem because of reports of serious injuries resulting from abnormal sleep behaviours, such as sleep walking or sleeping behind the wheel.
- A study by Chong et al. (2013) found, between 2005 and 2010, around 4% of American adults aged 20 and over took prescription sleeping aids in the past 30 days.
- A number of over-the-counter antihistamines such as diphenhydramine or doxylamine were found to demonstrate moderate effectiveness against the symptoms of insomnia compared to prescription hypnotics.
- Nevertheless, the effectiveness of antihistamines diminishes over time, and the anti-cholinergic side-effects may act as deterrents to patients.
— Melatonin
- There is little solid evidence to support the notion that melatonin agonists, such as ramelteon, improved the symptoms of insomnia.
- However, Sánchez-Barceló et al. (2011) found melatonin agonists demonstrated effectiveness in children with autism spectrum disorders, learning disabilities, attention-deficit hyperactivity disorder (ADHD) or related neurological diseases.
— Antidepressants
- Antidepressants such as amitriptyline, doxepin, mirtazapine, and trazadone were found to help modulate sleep, as well as elicit a sedative effect when treating insomnia.
- Note that amitriptyline and doxepin both have anti-adrenergic, anti-cholinergic and anti-histaminergic effects, whereas mirtazapine's effect is mainly anti-histaminergic and trazodone's effect is mainly anti-adrenergic.
- Winokur et al. (2003) found mirtazapine decreased sleep latency, boosted sleep efficiency, and increased the total amount of sleeping time in people suffering from both depression and insomnia.
— Benzodiazepines
- Although they are the commonly prescribed hypnotic medication for insomnia, it doesn't elicit the greatest improvements on the symptoms of insomnia compared to antidepressants.
- Compared to chronic insomniacs who don't take any medications, chronic users of benzodiapezines reported worse sleep times and increased night-time awakenings. Therefore, the Drugs and Therapeutics Bulletin (2004) recommended the prescription of hypnotics for only a few days at the lowest effective dose or avoided completely wherever possible. This resulted in a decrease of benzodiazepine prescriptions by 13% in the USA.
- The side-effects of benzodiazepines include daytime fatigue, cognitive impairments, falls and fractures, hence serious injuries in vehicle accidents.
- Its effectiveness in sleep maintenance was moderate for a short period, however its efficacy dwindles in the long term with exacerbating symptoms such as benzodiazepine withdrawal syndrome upon discontinuation, physical dependence, tolerance, worsened sleep, reduced deep sleep and increased light sleep.
— Other sedatives
- Non-benzodiazepine sedative-hypnotic drugs such as eszopiclone, zaleplon, zolpidem and zopiclone demonstrate moderate effectiveness in increasing sleep time compared to benzodiazepines.
- Suvorexant was approved by the US FDA to treat the symptoms of insomnia.
Sometimes labelled as "Sleeping Beauty Syndrome", Kleine-Levin Syndrome (KLS) is a rare sleeping disorder characterised by chronic episodic hypersomnia and cognitive or mood changes, as well as hyperphagia and hypersexuality.
What are the symptoms of KLS?
Behavioural:
- Recurring episodes of hypersomnia (prolonged sleep), ranging between 15 and 21 hours a day during episodes.
- Excessive appetite (hyperphagia) and unusual cravings.
- Most male patients experience increased sexual urges (hypersexuality).
- Changes in mood and cognitive function.
- Derealisation and severe apathy
- Hallucinations or delusions
- Depression and anxiety (rarely)
- Amnesia
- Repetitive behaviours and headaches
- Child-like behaviours
- Impaired communication skills and coordination
Physiological:
- Decreased slow wave sleep at the beginning of episodes, and decreased REM sleep at the end of episodes.
- Disrupted stage 2 NREM sleep
- Withdrawn sleep-like state during the awake phase of the episode.
- Symptoms similar to those of flu or encephalitis, usually after an airway infection or a fever.
- After an infection, KLS triggers within 3 to 5 days for teenagers and fewer for children.
- Alcohol consumption, head injury, or intentional travel may precede symptoms.
- Weight gain during episodes
- Impact on mood and cognitive attention
- Long-term memory problems
- Hypoperfusion in the brain, especially in the thalamic and frontotemporal areas.
Describe the epidemiology of KLS
- So far, population-based studies of KLS have not been conducted, however Ramdurg (2010) estimated the prevalence of KLS is roughly 1 per million people.
- A 2012 study by Arnulf et al. found an association between KLS and genetic disorders in the general population, and roughly 1/3 of KLS patients experienced a form of birth difficulty. Other accompanying conditions include pre-existing psychiatric problems, neurological conditions prior to diagnosis.
Describe the prognosis of KLS
- Arnulf et al. (2012) estimated the frequency of KLS episodes range from a week long occurring twice a year to several episodes occurring in close succession, with an average of 19 episodes over the disease's duration. However, they report patients don't replicate the same symptoms in each episode.
- First experience of KLS likely occurs in childhood or adulthood, with symptoms disappearing in adulthood around 30 years old.
- The duration of disease tends to resolve spontaneously and patients are determined to have recovered if they demonstrate symptoms for 6 consecutive years.
When was KLS first reported?
- In 1815, a young man was reported to show symptoms of excessive appetite and prolonged sleep after a fever. In addition, another case in 1862 was reported to demonstrate similar symptoms, but the syndrome was still unnamed.
- In 1925, a German neurologist named Willi Kleine described 5 patients showing persistent sleepiness, and an American psychiatrist named Max Levin published a report about the cases exhibiting the same symptoms in 1935.
- In 1942, MacDonald Critchley reported the same symptoms in a number of patients in the Royal Navy during WWII, as well as irritability and depersonalisation during wakefulness. He named this condition the "Kleine-Levin Syndrome" in his 1962 publication, where he listed 4 additional characteristics such as adolescent onset, compulsive eating, hypersexuality, and spontaneous resolution.
- In 1990, Schmidt established diagnostic criteria for KLS, which was further refined by the International Classification of Sleep Disorders.
- In the early 2000s, it was categorised as a sleep disorder, particularly a type of recurrent hypersomnia.
What are the causes of KLS?
The cause of KLS is currently unknown, but a number of theories were proposed by scientists.
i. Hypothalamic or circadian dysfunction
- It is suggested the thalamus is involved in uncontrolled sleeping patterns, and patients with diencephalic-hypothalamic dysfunction experienced similar symptoms to KLS.
- The cognitive difficulties may be attributed to impairments in the temporal lobe.
- The apathy and disinhibition may be caused by dysfunction in the frontal lobe.
- Studies state the temporal and frontal lobes, and the thalamus implicated in KLS indicate a multifocal, localised encephalopathy.
ii. Other theories
- An imbalance in the serotonin and dopamine metabolism pathways, based on autopsies.
- Brown (1993) suggested androgen may block melatonin receptors, leading to cholinergic dysfunctions in KLS.
- There is a hypothesis of a genetic component in addition to environmental factors in Jews, though more evidence is required to support this theory. That genetic component may be LMOD3 on chromosome 3.
How is KLS diagnosed?
- If the patient demonstrates apathy, confusion, derealisation, frequent episodes of sheer fatigue and prolonged sleep, then they can be diagnosed with KLS.
- MRIs are required to determine whether the symptoms are exacerbated by a number of brain disorders, stroke, and multiple sclerosis, while lumbar puncture is employed to determine if encephalitis triggers KLS.
- Toxicology tests are required to distinguish KLS from substance abuse.
- EEG should be used to eliminate temporal status epilepticus as a possible cause.
- Analysis of brain lesions are useful to distinguish KLS from frontal-love syndromes and Klüver-Bucy syndrome, as well as rare cases of hypersomnia manifested by menstruation.
How can KLS be treated?
- A number of drug treatments have been recommended, however none of them were subject to randomised controlled trials.
- Stimulants, such as modafinil, alleviated the sleepiness symptom but side-effects included behavioural issues.
- de Oliveria et al. (2016) stated lithium reduced the length of sleepiness episodes and severity of KLS symptoms, and increased the gap between episodes. However, the side-effects can be detrimental to the thyroid or kidneys.
- Anti-psychotics and benzodiapines (e.g. carbamazepine) were found to alleviate psychotic and anxiety-related symptoms, respectively, however they demonstrated less efficacy than lithium but higher efficacy than some treatments in the same class.
- Caregivers are advised to reassure KLS patients and prompt them to maintain sleep hygiene, and prevent them from being in life-threatening situations, such as driving.
- Narcolepsy is a long-term neurological disorder characterised by dysfunction to sleep-wake cycle regulations.
- Although there is no data on the prevalence of narcolepsy in the world population, studies estimated as many as 200,000 Americans are affected each year, but less than 50,000 are diagnosed. In addition, an estimated 0.2 per 100,000 Israelians and 600 per 100,000 Japanese people are affected by narcolepsy.
- It can affect both men and women at any age, though symptom onset usually occurs in adolescence and young adulthood.
- Famous people known to suffer from narcolepsy include Sir Winston Churchill, Harriet Tubman, Lenny Bruce, and Jimmy Kimmel.
What are the symptoms of narcolepsy?
- Excessive daytime sleepiness (even after adequate night time sleep)
- Abnormal REM sleep
- Extreme drowsiness or tendency to fall asleep at inappropriate or undesired times and location, or persistent fatigue throughout the day.
- Inability to experience rejuvenating deep sleep due to abnormal REM regulation.
- Cataplexy = Episodic loss of muscle function that ranges from slight weakness such as limpness of the neck or knees, sagging facial muscles, knee buckling to a sheer collapse of the body, as well as aphasia. Episodes may be exacerbated by sudden emotional reactions such as laughter, anger, or fear.
- Sleep paralysis
- Hypnagogic hallucinations
- Automatic behaviours
- Night-time wakefulness
Describe the pathophysiology of narcolepsy
i. Neuronal loss
- Studies found narcoleptic brains lack neurons that produce a neuropeptide called orexin, or hypocretin, which is involved in the regulation of appetite and wakefulness, as well as other cognitive and physiological processes.
- Chow & Cao (2016) found the loss of HCRT1/OX-A neurons in type 1 narcolepsy indicated a specific autoimmune pathophysiology.
- The orexin-producing neurons are typically found at the lateral hypothalamus, reticular activating system, and the ventrolateral preoptic nucleus, which are responsible for the regulation of arousal, sleep, and transitions between these states.
- This accounts for the occurrence of REM sleep within 5 mins of falling asleep in narcoleptic patients compared to after 1 hour of slow-wave sleep in normal patients.
ii. Disturbed sleep states
- In narcoleptic patients, they experience a sudden transition from waking stage to REM sleep without any intervening NREM sleep.
- The NIH suggested that cataplexy is triggered by reflex inhibition of the motor system due to hyperpolarisation of spinal and brainstem alpha motor neurons leading to virtual atonia of skeletal muscles via an inhibitory descending reticulospinal pathway.
What are the causes of narcolepsy?
- The exact cause of narcolepsy is unknown, but a number of theories have been proposed by researchers. The theories revolved around the loss of neurons that release orexin within the lateral hypothalamus.
- Mahlious et al. (2013) found up to 10% of cases has a familial link, suggesting a genetic variant in narcolepsy. Studies also implied associations with a history of infection, diet, and toxins such as pesticides, and brain injuries caused by head trauma, brain tumours or strokes, as well as autoimmunity.
- Mahlios et al. (2013) hypothesised variants of a gene in chromosome 6 associated with the human leukocyte antigen (HLA) complex was involved in the development of narcolepsy.
- Although there was no evidence that mutations in the HLA gene didn't necessary lead to the symptoms of narcolepsy, they may increase the risk of an autoimmune response to neurons that produce orexin in the lateral hypothalamus. Example variants include HLA-DQB1*06:02 and HLA-DQA1*01:02.
- Studies have also noted polymorphisms of other genes that associate with narcolepsy such as TRAC, TNFSF4, Cathepsin H, P2RY11-DNMT1 and EIF3G.
- Sarkanen et al. (2018) established an association between GlaxoSmithKline's H1N1 flu vaccine Pandemrix and narcolepsy in both children and adults. This led to the immediate suspension of administering the Pandemrix vaccine across Finland.
How is narcolepsy diagnosed?
- The ICD-11 categorises 3 types of narcolepsy: Type 1, Type 2 and Unspecified.
- Type 1 Narcolepsy: The person must present with either cataplexy, a mean sleep latency of less than 8 minutes, and 2 or more sleep-onset REM periods, or a hypocretin-1 concentration of less than 110 pg/mL.
- Type 2 Narcolepsy: The person must present a mean sleep latency of less than 8 minutes, 2 or more sleep-onset REM periods, and a hypocretin-1 concentration of more than 110 pg/mL.
- The tests sleep specialists frequently use to diagnose narcolepsy include the Epworth Sleepiness Scale (ESS), Multiple Sleep Latency Test (MSLT) and Polysomnography (PSG).
- If MSLT results are inconclusive or difficult to interpret, orexin levels in cerebrospinal fluid can be measured with abnormally low levels serving as a reliable indicator of narcolepsy.
How can narcolepsy be treated?
- Experiments conducted by Kantor et al. (2013) have shown promising results of genetic editing of prepro-orexin transgene leading to restoration of the normal function in mice models.
- There are plans for administration of hypocretin-1 replacement therapies either intravenously, intranasally or intracisternally to begin by 2024.
- Strategies to cope with symptoms include carers and family education, sleep hygiene and medication compliance, conversations of safety issues.
- Regular medical check-ups help monitor your body's response to certain treatments, as well as assess the existence of other sleep disorders and address any psychosocial issues.
- Treatments for excessive daytime sleepiness are central nervous system stimulants, which include amphetamine, armodafinil, methylphenidate, and dextroamphetamine,
- A non-stimulant and a noradrenaline reuptake inhibitor (NRI) called atomoxetine is recommended to treat EDS if the patient is planning regular short snaps around 2 hours.
- Sodium oxybate, or sodium gamma-hydroxybutyrate (GHB) is found to treat cataplexy effectively.
- Selective serotonin reuptake inhibitors and tricyclic antidepressants such as clomipramine, imipramine, or protriptyline can treat abnormal REM sleep.
- Since venlafaxine blocks the reuptake of serotnin and noradrenline, it can manage of symptoms of cateplexy, but it carries side-effects such as sleep disruption.
- For children diagnosed with narcolepsy, improved sleep hygiene, planned naps, and physical exercise are recommended behavioural treatments.
6. Night eating syndrome (NES)
- Night eating syndrome (NES) is a type of eating disorder, characterised by a delayed circadian pattern of food intake.
- Although it shares characteristics with binge eating disorder, the amount of food consumed at night time is not necessarily significant or is evidence of a control over food intake needed.
- In 1955, Albert Stunkard originally described NES and included it in the 'other specified feeding or eating disorder' category of the DSM-5.
- Evening hyperphagia (At least 25% consumption of total daily calories after the evening meal).
- Nocturnal awakening and ingestion of food 2 or more times per week.
- Awareness of night eating (to distinguish it from parasomnia sleep-related eating disorder (SRED)
3 of 5 associated symptoms need to be present:
- Lack of appetite in the morning
- Urge to eat at night
- The belief that one must eat in order to fall back to sleep at night
- Depressed mood
- Difficulty sleeping
- Stunkard et al. (1996) stated NES affects both men and women, around 1-2% of the general population, and roughly10% of obese people.
- Wal & Vander (2012) estimated the age onset of NES is between late teenage years and late 20s, though children having NES is underreported.
- Birketvedt et al. (1999) found an association between NES and depression and low self-esteem, as well as reduced nocturnal levels of melatonin and leptin.
- There are theories that a tryptophan or serotonin-rich diet could alleviate the symptoms of NES, but studies found this barely affects serotonin levels in the brain.
- NES are found to be accompanied by a number of comorbidities such as excess weight and diabetes, as well as a number of psychiatric conditions such as depressed mood and anxiety disorders.
7. Nocturia
- The International Continence Society (ICS) defined nocturia as "the complaint that the individual is urged to wake at night at least once to void or urinate.
- The prevalence of nocturia occurs in 5-15% of 20-50 year olds, 20-30% of 50-70 year olds, and 10-50+% of 70+ year olds, which indicates symptoms of nocturia increases and/or worsens with age.
- Despite the lack of awareness by the general public, nocturia is found to elicit negative impacts on patients. Exacerbated symptoms include insomnia and sleep deprivation, thereby exhaustion, mood changes, daytime sleepiness, fatigue, impaired productivity, increased risk of accidents, and cognitive dysfunction.
- Jensen et al. (2002) found a quarter of falls experienced by elderly people occur at night time, of which a quarter occur whilst waking up to void.
What are the causes of nocturia?
i. Polyuria
It is defined as 'excessive or abnormally large production or passage of urine', sometimes referred to as 'diuresis'.
-- Global polyuria
- It is defined as the continuous excessive production of urine that isn't limited to sleep hours. It is defined as urine outputs of greater than 40 mL/kg/24 hours, which occurs in response to increased fluid intake.
- It is commonly caused by primary thirst disorders such as diabetes mellitus and diabetes insipidus (DI). The cause of central DI is reduced levels of vasopressin (antidiuretic hormone, ADH) and arginine vasopressin (AVP). Urination imbalance may lead to polydipsia or excessive thirst to prevent circulatory collapse.
- DI can be diagnosed with an overnight water deprivation test, which requires the patient to restrict fluid intake for a fixed period of time, for between 8-12 hours. If the patient shows a lowly concentrated first morning void, they are diagnosed with DI. Central DI can be treated with a synthetic replacement of ADH called desmopressin, which helps control thirst and frequent urination.
-- Nocturnal polyuria
- It refers to elevated urine production during night time with proportionally reduced urine production during day time.
- Since the 24-hour urine production is within normal limits, nocturnal polyuria is interpreted as a nocturnal polyuria index (NPI) being larger than 35% of the normal 24-hour urine volume (NUV), which can be evaluated by dividing NUV by the 24-hour volume.
-- Disruption of arginine vasopression (ADH) levels
-- Congestive heart failure
-- Nephritic syndrome
-- Liver failure
-- Lifestyle habits such as excessive night time binge drinking
-- Sleep apnoea: Obstructive sleep apnoea associates with increases in renal sodium and water excretion that is regulated by increased plasma atrial natriuretic hormone (ADH) levels.
ii. Bladder storage
- Bladder storage disorders involve the elevation of frequency of small volume voids in an individual, which associated with lower urinary tract symptoms that affect the bladder's capacity.
- Nocturnal bladder capacity (NBC) is the largest voided volume during the sleep period. Reduced NBC corresponds with decreased maximum voided volume or decreased bladder storage, which associates with:
-- Neurogenic bladder dysfunction
-- Learned voiding dysfunction
-- Anxiety disorders
-- Certain pharmacological treatments
iii. Mixed causes
- Mixed nocturia is referred to as a combination of nocturnal polyuria and reduced nocturnal bladder capacity. A study found 36% of nocturia patients demonstrated both conditions, which was more common than expected.
- It can be diagnosed by maintenance and analysis of bladder diaries reported by the patient.
How is nocturia diagnosed?
- Doctors requires the knowledge of the patient's nocturnal urine volume (NUV) prior to providing a nocturia diagnosis. NUV is defined as "the total volume of urine passed between the time the individual pass to bed with the intention of sleeping and the time of waking with the intention of rising". Note the NUV excludes the last void prior to sleeping in bed, and includes the first morning void if the urge to urinate woke the patient up.
- Other information required for diagnosis include the amount of sleep achieved, and the amount of sleep the individual intends to achieve.
- The voiding bladder diary is the main diagnostic tool for classification of the type of polyuria the patient is diagnosed with. The diary records the number of voids, timing of voids, the volume of urine voided, and the volume and time of fluid intake.
How can nocturia be managed?
i. Lifestyle changes
- Eliminating caffeine and alcohol intake, since both are diuretic compounds.
- Regulating consumption of beverages. e.g. Avoiding the consumption of fluids 3+ hours prior to bedtime.
- Compression stockings to help restrict fluid buildup in the legs, unless heart failure or contraindication is present.
- Pharmacological products that increase voiding, which decrease the 3rd spacing of fluid.
ii. Medications
- ADH replacements such as desmopressin and vasopressin
- Selective alpha-1 blockers such as alfuzosin, doxazosin, tamsulosin and terazosin, as well as 5-alpha reductase blockers such as dutasteride and tamsulosin.
- Antimuscarinic agents such as oxybutynin, tolterodine and solifenacin help treat an overactive bladder and deal with urgency incontinence but improving bladder contractility.
iii. Surgery
- Recommended if the nocturia is caused by benign prostatic hyperplasia or an overactive bladder.
-- Minimally invasive laser surgery
-- Surgical correction of the pelvic organ prolapse
-- Sacral nerve stimulation
-- Bladder augmentation
-- Detrusor muscle myectomy
8. Sleep apnea
- It is a sleep disorder characterised by pauses in breathing or intervals of shallow breathing during sleep. Each pause lasts a few seconds to a few minutes and may occur several times a night.
- This often manifests in loud snoring, as well as choking or snorting as breathing resumes. Since it disrupts normal sleep, it leads to daytime sleepiness or fatigue. In children, sleep apnoea can exacerbate hyperactivity or learning issues in school.
What are the signs and symptoms of sleep apnoea?
- Excessive daytime sleepiness (EDS)
- Impaired alertness
- Increased risk of driving accidents and work-related accidents
- Increased risk of exacerbating health problems, such as diabetes.
- Behavioural problems such as moodiness, belligerence, reduced attention, and lethargy, which may manifest in depression.
- Diabetes
What are the risk factors of sleep apnoea?
Although sleep apnoea can affect anyone regardless of age, race, or sex, the risk factors include:
- Being male
- Obesity
- Age over 40
- Large neck circumference (greater than 16-17 inches)
- Enlarged tonsils or tongue
- Narrow upper jaw
- Nasal congestion
- Allergies
- Receding chin
- Gastroesophageal reflux
- Family history of sleep apnoea
- Alcohol, sedatives and tranquilizers
- Tobacco consumption
- Heart disorders such as atrial fibrillation or atrial septal defects such as PFO
- High blood pressure
What are the different types of sleep apnoea?
a. Obstructive sleep apnoea (OSA)
- It is regarded as the most common sleep-related breathing disorder that is characterised by recurrent episodes of complete or partial obstruction of the upper airway, which results in decreased or loss of breathing during sleep.
- The ICSD-3 classified OSA as a sleep-related breathing disorder, which is subdivided into 2 types: Adult OSA and Paediatric OSA.
- When hypopneas are present, it is classified as Obstructive Sleep Apnoea-Hypopnea Syndrome. To meet the criteria of obstructive, the hypopnea must satisfy 1 or more of the following symptoms:
(1) Snoring during the event
(2) Increased oronasal flow flattening, and/or
(3) Thoraco-abdominal paradoxical respiration during the event
Describe the epidemiology of OSA
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| The prevalence of OSA (defined as either apnoea-hypopnea index (API) > 10 or 15) in various medical disorders. Compared to three population-based prevalence studies, patients with Type 2 diabetes, polycystic ovary syndrome, coronary artery disease, congestive heart failure, and stroke have a much higher prevalence of OSA. Each bar in the figure represents an individual study. Source: Epidemiology of Obstructive Sleep Apnea: a Population-based Perspective. Lee, Nagubadi, Kryger & Mokhlesi (2008) http://europepmc.org/article/PMC/2727690 |
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| Global OSA research performance (a) Density equalising map projection of the number of OSA-related publications between 1900 and 2013. This produced a distorted picture of the world map, and the sizes of the countries were determined by their total number of OSA-related publications. (b) Top 20 countries in terms of total number of OSA publications between 1900 and 2018; black: publication count from 1900 to 2013; grey: additive publication count from 2014 to 2018. (c) Distribution of the global OSA publication output between 1900 and 2018 by continent. Numbers indicate percentage of continents for the period 1900–2013/percentage for the period 1900–2018 (% 1900–2013/% 1900–2018). Antarctica with 0 publications not displayed. (d) Density equalising map projection of the OSA-related country-specific citation rate for the period 1900–2013. A distorted picture of the world map was generated, and the sizes of the countries were determined by their country-specific citation rate (only countries with ≥30 OSA-related articles). Source: Global Risk Factor Evaluation of Obstructive Sleep Apnea in Relation to Research Activity and Socioeconomic Factors. Seeger-Zybok, Klingelhöfer & Groneberg (2020) https://www.mdpi.com/1660-4601/17/18/6785/htm |
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| Global prevalence of sleep apnoea. Schematic representation of the apnoea and hypopnoea frequency per hour (apnoeahypopnoea index; AHI) worldwide. Source: Obstructive sleep apnoea syndrome. Lévy et al. (2015) https://www.semanticscholar.org/paper/Obstructive-sleep-apnoea-syndrome-L%C3%A9vy-Kohler/011dd0f204957e2805d09bcfd77b3da171c1baab/figure/2 |
A 2017 meta-analysis of numerous epidemiological studies by Senaratna et al. revealed a number of interesting findings regarding the prevalence of OSA in the general population.
- At least 5 apnoea events per hour were recorded in people aged 18 and older.
- OSA prevalence ranged between 9-38% (13-33% in men, and 6-19% in women)
- In people aged 65 and older, OSA prevalence peaked at 84% (90% in men and 78% in women).
- For at least 15 apnoea events per hour, OSA prevalence had a range of 6-17%, and roughly 49% in people aged 65 and older.
- BMI was directly proportional to OSA prevalence, where a 10% increase in BMI multiplied the OSA risk by a factor of 6 in obese people.
- Olaithe et al. (2015) stated OHS is underdiagnosed because it doesn't always feature daytime sleepiness, hence the sleep-disordered breathing may not be observed.
- Punjabi (2008) estimated the prevalence of OSA with daytime sleepiness to be approximately 3-7% in men and 2-5% in women.
- The risk of OSA increases with age, with an estimated 22-84% of individuals aged 65 years and older diagnosed with OSA. Drager et al. (2013) reported the prevalence of OSA significantly increased in recent decades due to the obesity epidemic.
- Foldvary-Schaefer & Waters (2017) found snoring and witnessed apnoea were demonstrated more by men than women, whereas insomnia was demonstrated more by women than men.
Describe the prognosis of OSA
- Franklin & Lindberg (2016) stated stroke and other cardiovascular diseases linked to OSA, as well as age over 70 years significantly increased the risk of early mortality.
- Shah et al. (2007) estimated an association between sleep apnoea and a 30% increased risk of cardiac arrest or death.
- In severe and prolonged cases, pulmonary pressure increases are transferred to the heart's right ventricle. This manifests in severe forms of congestive heart failure known as 'cor pulmonale'.
- Hypertension (increased arterial pressure) is another manifestation of OSA.
- If OSA is left untreated, the sleep deprivation and hypoxia exacerbates a number of health risks such as aortic disease (e.g. aortic aneurysm), cardiovascular disease, high blood pressure, stroke, diabetes, clinical depression, obesity, weight gain, or worse, death.
- Gagnon et al. (2014) found an association between OSA and cognitive impairment, including deficits in attention, inductive and deductive reasoning, executive functions, episodic and working memory, learning and vigilance.
- Lal et al. (2012) stated an association between OSA and a number of neuroanatomical changes such as atrophy in the hippocampus, and grey matter of the frontal and parietal lobes.
What are the signs and symptoms of OSA?
Common symptoms include:
- Daytime sleepiness
- Restless sleep
- Loud snoring (with intervals of silence followed by gasps for breath).
- Morning headaches
- Insomnia
- Decreased concentration
- Mood changes such as anxiety, depression and irritability
- Forgetfulness
- Hypertension
- Reduced sex drive
- Unexplained weight gain
- Increased urinary frequency and/or nocturia
- Frequent heartburn or gastrooesophageal reflux
- Heavy night sweats
Causes include:
- Upper respiratory function leading to nasal congestion, throat swells, or tonsillitis
- Epstein-Barr virus: Hypertrophies the lymphoid tissue during acute infection
- Acute cases of severe infectious mononucleosis
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| This is an 8-minute segment of during stage 2 sleep, during which the patient is experiencing sleep-disordered breathing. Oxygen desaturations are repeated due to severely impaired (hypopnea) or absent (apnea) airflow despite continual breathing efforts (Pepi) and the ensuing cyclical breathing pattern as the patient oscillates between sleep and arousal (downward pointing arrows). |
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| This is an expanded segment during an obstructive event. Observe the evidence of snoring on the flow tracing, quantification of the arousal threshold, and progressive increases in EMGgg activity throughout the obstructive event, although occurring, were not sufficient to restore flow without arousal in this instance. Source: Pathophysiology of Adult Obstructive Sleep Apnea. Eckert & Malhotra (2008) |
The above are polysomnographic tracings of obstructive sleep apnea from a detailed experimental study of a patient with severe disease (apnea–hypopnea index = 56 events/h).
- EMGgg = Electromyogram of the genioglossus muscle (intramuscular)
- EMGsub = EMG of the submental muscle (surface); EEG = electroencephalogram (C3–A2)
- Pepi = pressure at the level of the epiglottis; Flow = airflow measured via nasal mask and pneumotachograph
- Sa(O2) = arterial blood oxygen saturation measured via pulse oximetry at the finger
i. Adults
- Excessive daytime sleepiness
- Hypoxia result in neuroanatomical changes in the hippocampus and the right frontal cortex
- Impairments in mental manipulation of non-verbal information, executive functions and working memory.
- Possible cause of Alzheimer's Disease
- Common in adults who are in relationships: Their partner inform them of their symptoms such as loud snoring.
ii. Children
- Variable body habitus
- Failure to thrive - decreased growth
- Elevated work of breathing increases expenditure of energy at rest
- Obstruction of nose and throat leads to tastelessness and physical discomfort of eating
- Causes include obesity and adenotonsillar hypertrophy
- Narrowing of the upper airway structure due to infiltration and deposition of fat content in the anterior neck region and cervical structures.
- Increases the risk of pharyngeal collapsibility and decreases the intrathoracic volume and diaphragm excursion
- Decreased physical activity and additional weight gain (due to sedentary habits or increased food intake to overcome somnolence).
- Type I OSA features marked lymphadenoid hypertrophy without obesity
- Type II OSA involves obesity and features milder upper airway lymphadenoid hyperplasia
Describe the pathophysiology of OSA
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| (A) This is a schematic representation of the typical pathophysiological sequence that occurs in obstructive sleep apnea (OSA) (shown in grey) and the associated physiological processes that occur throughout the cycle that are either protective/restorative (outside the circle) or perpetuating (inside the circle). UA = upper airway |
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| (B) This is a schematic representation of the possible sites where each of the various pathophysiological traits would either predispose or tend to worsen OSA (inside the main circle). Note that some of the effects of these traits may be interrelated (i.e., a high loop gain may increase the ventilatory response to arousal and the propensity for cyclical breathing, and also lead to periods of decreased upper airway dilator muscle activity). Some of the potential factors that may alleviate OSA at various points throughout the typical physiological cycle (dashed arrows and ovals) are located outside the main circle. Bear in mind that some factors are theoretical and mostly untested whereas others are more proven therapies (i.e., continuous positive airway pressure [CPAP]). Source: Pathophysiology of Adult Obstructive Sleep Apnea. Eckert & Malhotra (2008) |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970937/
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| This is a road map of pathogenesis of cyclical OSA. Source: Pathophysiology of Sleep Apnea. Dempsey, Veasey, Morgan & O'Donnell (2010) |
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| Source: https://calgaryguide.ucalgary.ca/obstructive-sleep-apnea-pathogenesis-and-clinical-findings/ |
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| This map represents the exacerbations of OSA. Source: OSA Pathophysiology. Watenpaugh (2008) https://sleepconsultants.com/osa_pathophysiology.htm |
What are the risk factors of OSA?
- Obesity
- Increase in neck fat tissue, which elevates risk of respiratory obstruction during sleep
- Supine sleeping position (on the back): Gravity, loss of tongue and throat tone
- Throat lesions and enlarged tonsils (tonsillitis)
- Old age
- Muscular and neurological loss of muscle tone of the upper airway
- Precipitated by traumatic brain injury, neuromuscular disorders, or poor adherence to chemical and/or speech therapy treatments
- Muscle tone
- Higher risk of OSA in men during middle age and later, which associates with increased mass in the torso and neck.
- However, women during pregnancy and post-menopause have an increased risk of developing OSA.
- Medication and lifestyle
- Chemical irritants in cigarette smoke induces inflammation of the soft tissue of the upper airway and triggers fluid retention, both of which manifests in a narrowed upper airway. The decreases in blood nicotine levels affects an individual's sleep stability.
- Cigarette smoke irritants can trigger excess proliferation of lymphadenoid tissue in children, which leads to OSA.
- Other lifestyle factors: Consumption of alcohol, sedatives or other medications that induce sleepiness.
- Genetics
- The genetics of the pathogenesis of OSA is still unclear, however a number of syndromes have been suggested to have an association with OSA. They are Down syndrome, Prader-Willi syndrome and Beckwith-Wiedermann syndrome.
- Other syndromes that may associate with OSA include achondroplasia, Ehlers–Danlos Syndrome, Ellis–van Creveld Syndrome, Noonan Syndrome, Pierre Robin sequence/complex, and sickle cell disease.
- Congenital or acquired conditions that affect the respiratory control centre may exacerbate the symptoms of OSA.
- Other possible causes proposed include Arnold Chiari malformation, myelomeningocele and brain injuries from trauma, tumours, surgery.
- Craniofacial syndromes
- Glossoptosis
-- Posterior "normal" tongue displaced backwards by a smaller "abnormal" anterior tongue and lower way.
-- Narrower upper jaws result in narrower nasal passages and narrower throats, which leads to nasal congestion while sleeping in a supine position.
- Maxillofacial surgeries
- Craniofacial features of Down syndrome
-- de Miguel-DÃez et al. (2003) estimated around 50% of Down syndrome patients experience OSA, which prompted a number of physicians to advocate routine testing of this group.
- Cleft palate syndromes
- Post-operation complications
- OSA can manifest as a complication following a number of different types of surgeries.
- Pharyngeal flap surgery makes the flap obstruct airflow within the pharynx during sleep, which hampers effective respiration.
- Following surgery for velopalatal insufficiency, air leaks into the nasopharynx in spite of the soft palate closing the nose. The surgical procedure involves modifying the tissue from the back of the throat with the intention to partially obstruct the opening of the nasopharynx, which may manifest in OSA.
- Inflammatory factors and biomarkers
- Examples of systemic inflammatory markers implicated in OSA include C-reactive protein (CRP), NF-κB, IL-6, IL-8 IL-1a, IL-1b, IFN-γ and TNF-α. Conversely, there is a concomitant decrease of IL-10, which indicates a pro-inflammatory state in OSA.
- When NF-κB is upregulated, it increases the expression of pro-inflammatory mediators and cytokines (TNF- α, IL-6, and CRP), which results in blood vessel endothelial damage and systemic inflammation.
- Allergic rhinitis
- Nasal congestion as a result of allergic rhinitis triggers the nasal mucosa inflammatory process, which increases airway resistance. This leads to fatigue, oral breathing and sleep disruption.
- Symptoms include rhinorrhea, nasal blockage or congestion, and stuffy nose, which manifests in olfactory disorders due to a lack of odourants entering the nose during breathing.
- The inflammatory mediators of the allergic process, e.g. histamine and certain cytokines, can affect their sleep rhythm by disrupting the central nervous system. This leads to decreased REM sleep.
What are the consequences of OSA?
- There are 3 categories of consequences: physiologic, intermediate, and clinical.
- Physiologic consequences include autonomic nervous system dysregulation, hypoxia, hyperoxia or sleep fragmentation.
- Intermediate consequences include general metabolic dysfunction, oxidation of proteins and lipids or increased adiposity, pulmonary vasoconstriction and regroup inflammation.
- Clinical consequences include accidents, diabetes, cardiovascular diseases or hypertension, and pulmonary hypertension.
i. Children
- Walter & Horne (2018) found OSA affected up to 11% of children born at them, or up to 3 to 6 times more in children born pre-term.
- If untreated, OSA disrupts organs and body systems, which leads to depression, decreased quality of life, or worse, mortality.
- Dehlink & Tan (2016) stated the presence of nocturnal symptoms (e.g. gasping for breath, high energy expenditure to breath during sleep, snoring, restless sleep) correlated with daytime symptoms. They include concentration and learning difficulties, irritability, neurocognitive development impairment, diminished academic performance, and behavioural difficulties.
- Furthermore, they may exacerbate into hyperactive behaviour reminiscent of attention deficit hyperactivity disorder (ADHD), which can be alleviated with appropriate treatment of sleep-disordered breathing.
- Capdevila et al. (2008) suggested the disruption of sleep mechanisms elicit a highly adverse effect on a child's daytime functioning, as well as on the hyperactivity that manifests.
- Halbower et al. (2006) associated OSA with learning and memory deficits, which heavily contributed to significantly low childhood IQ scores.
-- Neurocognitive and behavioural consequences
- They include hyperactivity, impulsivity, aggression, cognitive deficits, impaired attention and concentration, decreased academic performance and IQ.
- Goyal et al. (2018) indicated that substandard academic performance may be a consequence of cortical and sympathetic arousals and hypoxemia, which impairs memory consolidation.
- Galland et al. (2015) asserted that OSA-related learning impairments are linked to language skills and/or executive functions.
-- Somatic and metabolic consequences
- Increased sympathetic activity and impaired cardiac cardiac autonomic control in OSA can exacerbate to cardiovascular morbidities. Further manifestations include systemic hypertension, pulmonary hypertension and blood pressure dysregulation.
- Blood pressure variability strongly correlated with the severity of the symptoms e.g. the frequency of the apnoea and hypopnea.
- Metabolic consequences of OSA include insulin resistance, altered lipidemia, liver disease, abdominal adiposity, and metabolic syndrome.
-- Nocturnal enuresis
- The causes of nocturnal enuresis in OSA may be excessive production of urine, dysfunction of the bladder and urethra, or failure to suppress the nocturnal bladder contraction due to the lack of arousal.
- Other risk factors of nocturnal enuresis in OSA include obesity and unhealthy diet, which associates with the severity of sleep-disordered breathing, hence the frequency of respiratory events per hour of sleep.
- Basha et al. (2005) found adenotonsillectomy has a 60-75% chance of resolving nocturnal enuresis, and a 80-85% chance of alleviating symptoms of nocturnal enuresis alongside other symptoms of OSA.
-- Other consequences
- Capdevila (2008) found the frequency of excessive daytime sleepiness (EDS) was reported by parents or caretakers to be 40–50% of children diagnosed with OSA.
- Other exacerbations of OSA include decreased quality of life, risk of internalising disorders such as anxiety and depression, obesity due to overeating, anhedonia, fatigue, reduced interest in daily activities.
- Studies determined a significant association between OSA and obesity and severity of depressive symptoms in children.
ii. Adults
- OSA Similarities between children and adults in terms of symptoms include snoring, blood pressure variability and morbidities. The main difference is the excessive daytime sleepiness in adults, which is rare in paediatric OSA.
-- Neurocognitive consequences
- Fulda & Schultz (2003) stated the common neurocognitive consequences related to OSA affecting adults include impairments in attention, verbal and visual delayed long-term memory, executive functions, visuospatial/constructional abilities and mental flexibility.
- Since the prefrontal cortex is involved in executive functions, OSA and other sleep disorders significantly impairs this particular brain region.
- Wallace & Bucks (2013) reported OSA patients experienced deficits in verbal memory and visuo-spatial memory, which associates with impairments of information encoding.
- Bucks, Olaithe & Eastwood (2013) suggested attention the memory deficits associated with sleep fragmentation, and deficits in global cognitive function (executive function, psychomotor function, language abilities) associated with hypoxia and/or hypercarbia manifested by the obstructive events during sleep.
-- Behavioural consequences
- Researchers associated adult OSA with personality changes, autonomic behaviour and excessive daytime sleepiness (EDS).
- Slater & Steier (2012) stated the causes of EDS include the insufficient sleep, sleep fragmentation, and disturbance of sleep quality, which may exacerbate into depressive symptoms, impairments of social life, and decreased productiveness at work.
-- Physiologic and metabolic consequences
- OSA increases the risk of cardiovascular morbidities, diabetes, hypertension, coronary artery disease and stroke.
- McNicholas (2008) suggested the synergy of OSA and obesity manifest in Type 2 diabetes, insulin resistance, hyperlipidemia and other symptoms of metabolic syndrome.
- Ashrafian et al. (2015) estimated about 58% of adult OSA cases demonstrated excess body weight, which implicates it as a risk factor for OSA.
- Reutrakul & Mokhlesi (2017) hypothesised the Type 2 diabetes associated with OSA was caused by fragmented sleep and irregular hypoxemia, which lead to dysregulated metabolism of blood glucose. They estimated 15-30% of the OSA population were also diagnosed with Type 2 diabetes.
-- Psychological consequences
- OSA associates with mood disorders and a number of psychological conditions such as depression and anxiety, which is accompanied by psychological distress due to diminished sleep quality and hypoxia.
- Garbarino et al. (2018) suggested the presence of psychological conditions may worsen the symptoms of OSA, which implicates psychopathology as either a factor or consequence of OSA.
- Some cases of OSA caused by nasal obstruction correlate with psychological issues since the balance between calcium and magnesium ions in brain cells has been disrupted.
-- Other consequences
- If left untreated, OSA can exacerbate into difficulties in social functioning, a reduced quality of life, difficulties in social functioning, occupational issues and accidents, and a significantly increased risk of vehicle accidents.
- Charopokos et al. (2018) stated an association between OSA and pain disorders such as headaches or fibromyalgia, as well as an increased pain intensity and decreased pain tolerance.
How is OSA diagnosed?
- The United States Preventative Services Task Force (2017) questioned the accuracy or clinical utility of all potential screening tools of OSA. It asserted that current evidence is inadequate for an assessment of the balance of benefits and harms of screening for OSA in asymptomatic adults.
- An apnoea is defined as decreased airflow of >90% lasting at least 10 seconds.
- A hypopnea is defined as decreased airflow of >30% lasting at least 10 seconds and correlated with a >4% reduction in pulse oxygenation, or a >3% reduction in pulse oxygenation or with an arousal.
- The Apnoea-Hypopnoea Index (AHI) measures the mean number of apnoeas and hypopnoeas per hour of sleep.
- Respiratory Disturbance Index (RDI) builds on the AHI and measures the respiratory effort-related arousals (RERAs).
-- Recurrent episodes of partial and/or complete collapse of the upper airway during sleep that lead to apnoea and/or hypopnoeas.
-- AHI > 5 episodes per hour, which results in daytime sleepiness and fatigue
-- RDI > 15 independently of the symptoms
-- Excessive daytime sleepiness
-- Tendency to fall asleep during daytime
-- Screening tools include Epworth Sleepiness Scale, STOP questionnaire, Berlin questionnaire, and STOP-BANG questionnaire.
-- Non-restorative sleep
-- Fatigue
-- Insomnia
-- Respiratory symptoms include waking with breath holding, gasping or choking
-- Snoring, breathing interruptions or both during sleep
-- Medical complications such as atrial fibrillation, coronary artery disease, heart failure, hypertension, mood disorder, cognitive impairment, stroke, or type 2 diabetes mellitus.
-- A polysomnography or home sleep apnoea test detects 5 or more predominantly obstructive respiratory events per hour of sleep
Polysomnography criteria:
-- Hypopnoea: Decrease in airflow of at least 30% for more than 10 seconds correlated with at least 4% oxygen desaturation or at least 3% oxygen desaturation or an arousal from sleep on EEG.
-- Apnoea: Complete cessation of airflow for at least 10 seconds
Home oximetry:
-- Mulgrew et al. (2007) suggested home oximetry may be sufficient and efficient in obtaining data on the likelihood of OSA than formal polysomnography.
-- However, they fail to measure apnoeic events or respiratory event-related arousals and hence unable to yield an AHI value.
How is OSA treated?
i. Physical intervention
- Continuous Positive Airway Pressire (CPAP)
- Variable positive airway pressure (VPAP)
- Nasal EPAP
- Autonomic positive airway pressure (Auto CPAP)
- Askland et al. (2020) proposed educational initiatives and supportive interventions to help improve compliance with CPAP therapy.
- Oral appliances or splints such as a mouthguard.
- Sleeping at a 30-degree elevation of the upper body
- Playing a wind instrument such as double reed instruments
- Palatal Expansion = A non-surgical orthodontic treatment that expands the volume of the nasal airway.
ii. Sleep Surgery
- A properly selected surgical intervention considers an individual's anatomy and physiology, personal preference and disease severity.
- Septoplasty = Corrects nasal septum deviation
- Tonsillectomy and/or adenoidectomy
- Uvulopalatopharyngoplasty (UPPP) or laser-assisted uvulopalatoplasty (LAUP) = Excision of parts of the soft palate and some or all of the uvula
- Turbinectomy = All or some of the turbinate bones are excised to relieve nasal obstruction.
- Laser excision or radiofrequency ablation to reduce the tongue base
- Genioglossus advancement = A small portion of the lower jaw is shifted forward in order to draw the tongue away from the back of the airway.
- Hyoid suspension
- Maxillomandibular advancement
iii. Other
- Neurostimulation = It is an upper airway stimulation system that detects respiration and administers electrical stimulation to the hypoglossal nerve. This increases muscle tone at the tongue's posterior section to prevent it from collapsing over the airway. It includes a handheld patient controller that activates before sleep and is powered by an implantable pulse generator.
- Radiofrequency ablation (RFA) = Low frequency (300 kHz to 1 MHz) radiowaves are emitted to target tissue, resulting in coagulative necrosis. Bashetty et al. (2009) found RFA is efficacious between 40 and 70 °C. It is usually administered in an outpatient setting, utilising either local anaesthetics or conscious sedation anaesthesia.
- Medications = Cannabinoids such as dronabinol, a synthetic form of THC (delta-9-tetrahydrocannabinol), was found to elicit a positive effect on the OSA symptoms. The positive effects include decreased sleep onset latency, decreased AHI and increased self-reported sleepiness. However, Ramar et al. (2018) asserted that more research was required to understand the short-term and long-term effects of these substances.
b. Central sleep apnoea (CSA)
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| This is a schematic of the several potential mechanisms that contribute to CSA/hypopnea. - The grey boxes and largest solid arrows represent the key components contributing to unstable breathing and central apnea/hypopnea during sleep. - The smaller solid arrows describe the main factors that lead to or modulate unstable breathing during sleep. - Dashed arrows indicate the potential interactive links between obstructive and central apnea/hypopnea and for hypercapnia to cause arousal. - Some arrows have been omitted to simplify the Figure. |
- Also known as Central Sleep Apnoea Syndrome (CSAS), Central Sleep Apnoea (CSA) is a sleep-related disorder characterised by decreased or lack of effort to breathe, usually for 10 to 30 seconds either intermittently or in cycles.
- It is often caused by an impairment in the body's feedback mechanisms that regulate respiration.
What are the signs and symptoms of CSA?
- Imbalance of the brain's respiratory control centres, located in the pre-Botzinger complex brain region, during sleep.
- Failure to provide signals for inhalation, leading to shortage of 1 or more cycles of breathing.
- Decreased reaction time from the neurological feedback mechanism that monitors blood carbon dioxide levels and triggers respiration. This leads to the entire respiratory system oscillating between apnoea and hyperpnoea, even after an awakening during a breathing pause.
- Halt in breathing lasts 2 minutes and then repeats.
- Lack of effort to breathe during the breathing pause
- No chest movements and no muscular struggle
- Feelings of panic exacerbated by excessive blood carbon dioxide levels
Secondary effects:
- Hypoxia and hypercapnia
- Brain damage, or worse, death
- Seizures
- Bluish or darker cast from cyanosis due to deoxygenation of blood in vessels near the skin
- In adults with coronary artery disease: Angina, arrhythmias or myocardial infarction
- Respiratory acidosis = High blood carbon dioxide levels lead to formation of carbonic acid
- Drugs that depress the central nervous system exacerbate breathing irregularities. Examples include barbiturates, benzodiazepies, opiates and alcohol.
- Sudden infant death syndrome
- Premature infants with immature brains and reflex systems are at high risk of CSA.
How is CSA diagnosed?
There are currently no official standard diagnostic criteria for CSA.
Signs observed:
- Observed breathing pauses during sleep
- Lack of abdominal and thoracic movement for 10 seconds or longer during sleep, which coincides with breathing pauses.
- Elevated carbon dioxide saturation of blood
- Low oxygen saturation of blood
- Increased heart rate (in response to both hypercapnia or hypoxia)
Symptoms observed:
- Increased frequency of gasping for breath upon awakening, manifested by hypercapnia
- Inability to voluntarily contract the diaphragm and other thoracic muscles upon awakening
Diagnosis requires an overnight sleep study (polysomnography) in a sleep laboratory for Cheyne-Stokes respiration. It measures and monitors breathing patterns, brain waves, oxygen levels, EEG, ECG and body movements.
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| A: An EEG of a patient receiving high-dose opioid medication for back pain experiencing repetitive central apneas as demonstrated by a lack of movement of respiratory effort bands (both abdominal and thoracic) with associated oxygen desaturations. B = This EGG shows significant improvement in SDB following gradual dose reduction of opioid medication Sa(O2) = Arterial oxygen saturation Source: Eckert et al. (2008). Central Sleep Apnoea - Pathophysiology and Treatment |
How is CSA treated?
- Remedē system = This implantable device functions similarly to a pacemaker by stimulating the phrenic nerve to transmit signals to the diaphragm in order to regulate breathing patterns during sleep.
- Inhalation positive airway pressure (IPAP)
- Exhalation positive airway pressure (EPAP)
- Bilevel positive airway pressure (BiPAP)
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| a, b) Expiratory groans during prolonged expiration. a) A polysomnographic segment of a 60-s epoch showing electroencephalogram (C4), left and right eye movements, snoring, oronasal airflow, thoracic and abdominal effort channels, oxygen saturation, transcutaneous carbon dioxide tension and heart rate. Note the expiratory groaning sounds and the prolonged expiration (red). b) Polysomnogram showing parts of a 60-s epoch (sleep stage 2). A typical episode of catathrenia can be seen that resembles central apnoea. Note the deep inhalation at the beginning, followed by a prolonged exhalation with groans. c, d) Findings of the fibre laryngoscopy under deep sedation (propofol). c) The examination shows the open glottis at inspiration. d) During expiration, a closure of the glottis was seen. This resulted in a “normal” phonation causing the groaning characteristic of catathrenia. Source: Ott, Hamacher & Seifert (2011). Bringing light to the sirens of light: laryngoscopy in catathrenia during sleep. https://erj.ersjournals.com/content/37/5/1288 |
- Catathrenia is a sleep-related breathing disorder characterised by end-inspiratory apnoea and expiratory groaning during sleep. It is prevalent during REM sleep, as well as NREM sleep stages.
- The term is derived from the Greek kata (below) and threnia (to lament).
- The ICSD-3 categorised catathrenia as a respiratory disorder, though critics argued it should also be categorised as a parasomnia, as was the case in ICSD-2.
Describe the epidemiology
- De Roeck identified the first case of catathrenia in 1983, but it was unfamiliar among sleep specialists and otolaryngologists due to its rarity.
- Okura & Muraki (2013) highlighted catathrenia needed to be differentiated from moaning during epileptic seizures, central sleep apnoea, sleep-related laryngospasm, snoring, and stridor.
- The actual incidence of catathrenia may be underreported due to misdiagnoses. Nonetheless, a Norwegian institution estimated the incidence to be 4 out of 1,004 (0.4%) patients that have sleep and/or wake problems over a 1-year period.
- Jaar et al. (2009) found the incidence of catathrenia to be 25 out of 15,052 (0.17%) patients with sleep and/or wake problems.
What are the signs and symptoms of catathrenia?
- Vocal sound = Short or long vocalisation of the same letter (mainly an "a", "e", "o" sound or something in between). It also has harmonics and demonstrate common and similar patterns between nights.
- Onset of groanings = Beginning in childhood, adolescence, or early adulthood. The ICSD-2 found the age of onset ranged from 5 to 36 years.
- Symptoms manifest during expiration and sound interrupted during inspiration
- Unawareness of the disorder = Noted by bed partners and entourage disturbed by the emitted sound during their sleep and concerned about the pathological meaning of the disease.
- No predisposing factors
Discrepancies:
- Sound duration = Short lasting (0.5 - 1.5 s) or long lasting (2 - 20 s, or longer). However, it is unclear if the sounds are singular long noises separated by brief expirations.
- Sound intensity = Ranges between 40 dB and 120 dB, which can be long and soft, or short and loud.
- Onset time of the noise during the night = Noise Latency after falling asleep ranged from 2 to 6 hours. In some cases, it can be as short as 3 mins.
- Correction with respiratory disorders
- Response to continuous positive airway pressure (CPAP) treatment = Little to no improvement in patients with respiratory dysrhythmia, and unsatisfactory outcomes when combined with drugs. Nevertheless, CPAP significantly improved symptoms in patients with catathrenia over a 5-year period, as well as obstructive sleep apnoea and pulmonary hypertension.
- Predominance of REM or NREM sleep
How is catathrenia managed?
- CPAP may be the most effective treatment for catathrenia since it significantly reduced the groaning sounds.
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| Ondine by John William Waterhouse (1849-1917) |
- Central hypoventilation syndrome (CHS) is a sleep-related breathing disorder that exacerbates a number of debilitating symptoms during sleep (and during wakefulness in severe cases).
- Alternative names include primary alveolar hypoventilation, alveolar hypoventilation secondary to neurologic disease, idiopathic acquired central hypoventilation syndrome, or Ondine's curse.
- It was first described by Severinghaus and Mitchell in 1962 after performing surgery to the upper cervical spinal cord and brainstem in 3 patients.
- The name Ondine's curse refers a story of Ondine and Hans, whom are characters in a 1938 play by jean Giraudoux called Ondine. The play is based on traditions that traces back through Undine (a novella of 1811) in earlier European folk tales. According to the play, Ondine tells her future husband Hans "I shall be the shoes of your feet ... I shall be the breath of your lungs." Ondine arranged a pact with her uncle, the King of the Ondines, that if Hans ever deceived her death will be inevitable for him. After their honeymoon, Han reunited with his first love Princess Bertha and Ondine broke up with Han to then be captured by a fisherman 6 months later. On Hans' wedding with Bertha, he told Ondine that "all the things my body once did by itself, it does now only by special order... A single moment of inattention and I forgot to breathe." After Ondine and Hans kiss, Hans subsequently dies.
- A majority of CCHS patients don't survive infancy if left untreated, unless they receive ventilatory support or diaphragm pacing during sleep.
What are the signs and symptoms of CCHS?
- Respiratory arrests during sleep
- Neuroblastoma (tumours of the sympathetic ganglia)
- Hirschsprung disease (Partial agenesis of the enteric nervous system)
- Dysphagia (Difficulty swallowing)
- Anomalies of the pupilla
- Darkening of skin colour due to insufficient oxygen
- Drowsiness
- Fatigue
- Headaches
- Insomnia
- Sensitivity to sedatives and narcotics
- Low oxygen concentration in red blood cells leads to hypoxia-induced pulmonary vasoconstriction and pulmonary hypertension
- Cor pulmonale (Failure of the right side of the heart)
- Associated complications include developmental delays, fainting, gastro-oesophageal reflux, learning disabilities opthalmologic issues, seizures, recurrent pnuemonia, and temperature dysregulation
What are the causes of CCHS?
- It is typically a congenital disorder, which can exacerbate from severe brain or spinal trauma or injury, or particular neurodegenerative conditions.
- Long and Allen (1984) first discovered the abnormal brainstem auditory evoked responses in an woman who recovered from CCHS. They hypothesised the woman's chronic alcoholism damaged her brainstem.
- A number of studies identified a transcription factor involved in neuronal development called PHOX2B that associated with CCHS. Lake & Heuckeroth (2013) indicated this homeobox gene played a fundamental role in the normal development of the autonomic nervous system.
How is CCHS diagnosed?
- Diagnosis usually occurs in the first months of life, since children with CCHS exacerbates life-threatening episode of apnoea with cyanosis.
- Polysomnography indicates marked hypoventilation during slow-wave sleep, or during NREM sleep stages and wakefulness in severe cases.
- CCHS patients have an elevated risk of exacerbating malignant neural crest-derived tumours, such as neuroblastoma.
- Genetic studies found a majority of cases linked to PHOX2B mutations.
How is CCHS treated?
- Tracheostomy and lifetime mechanical ventilation on a ventilator for survival purposes, but may carry a risk of infection.
- Biphasic cuirass ventilation
- Oxygen therapy
- Medicine that stimulate the respiratory system
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| Continuous video electroencephalogram monitoring at 1 month revealed bouts of spasm attacks (arrowhead) associated with a generalised high-voltage (> 300 μV) sharp wave followed by an extremely low-amplitude (< 15μV) background. Source: Hong, Hsin & Lee (2016). An Infant with Congenital Central Hypoventilation Syndrome: Transient Burst Suppression Electrroencephalogram. https://www.pediatr-neonatol.com/article/S1875-9572(16)00002-4/fulltext |
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| Pathophysiology of obesity hypoventilation syndrome (OHS): The implicated mechanisms leading to daytime hypercapnia are, potentially, the obesity-related changes in the respiratory system, central hypoventilation, obstructive sleep apnoeas and hypoventilation during sleep, mainly during rapid eye movement (REM). PEEPi = intrinsic positive end-expiratory pressure; PaO2 = Arterial oxygen tension FRC = functional residual capacity ERV = Expiratory reserve volume RV = Residual volume TLC = Total lung capacity. |
- Sometimes known as Pickwickian syndrome, obesity hypoventilation syndrome (OHS) is a condition in which severely obese people are unable to breath rapidly or deeply enough, leading to low oxygen levels and high blood carbon dioxide (CO2) levels.
- OHS was first described in 1956 by authors who reported an obese professional poker player experienced somnolence and fatigue and a tendency to fall asleep during the daytime, as well as exacerbating oedema of the legs indicating heart failure.
- They named this condition "Pickwickian syndrome" after the character Joe from Dickens' The Posthumous Papers of the Pickwick Club (1837), who was depicted to have similar symptoms. In the 1960s, further findings discovered a distinction between obstructive sleep apnoea and sleep hypoventilation.
Describe the epidemiology of OHS
- The exact prevalence of OHS is currently unknown, with many people with OHS symptoms not diagnosed. Moklesi & Tulaimat (2007) estimated about a third of people with morbid obesity (a body mass index over 40 kg/m² had elevated blood carbon dioxide levels.
- A study of obstructive sleep apnoea patients found up to 20% of them satisfied the criteria for OHS diagnosis. Furthermore, the risk of OHS is significantly higher in those who are extremely overweight, i.e. BMI of 40 kg/m² of higher.
- However, this study is based on obese Americans in which reporting rates of obesity hence OHS is higher in USA than other countries.
What are the signs and symptoms of OHS?
- Concurrent obstructive sleep apnoea: Snoring, brief episodes of apnoea during the night, interrupted sleep and excessive daytime sleepiness
- Elevated levels of carbon dioxide - Drowsiness (CO2 narcosis)
- Depression
- Hypertension
- Headaches
- Low oxygen levels - Vasoconstriction of pulmonary arteries to correct ventilation-perfusion mismatching, straining the heart's right side.
- Cor pulmonale - Right sided heart failure
- Oedema in the legs
- Ascites in abdominal cavity
- Decreased exercise tolerance
- Exertional chest pain
- Raised jugular venous pressure
- Heart murmur due to blood leaking through the tricuspid valve
- Hepatomegaly (Enlarged liver)
Describe the prognosis of OHS
- OHS associates with decreased quality of life, and increased healthcare costs due to hospital admissions including observation and treatment on intensive care units.
- OHS often coincides with asthma (18-24%), type 2 diabetes (30-32%) and heart failure (21-32%).
- The risk of death increases by 23% over 18 months and 46% over 50 months in patients with debilitating medical complications that require treatment.
Describe the mechanism of OHS
The mechanism of OHS is not well understood but a theory has been proposed.
- Breathing work increases as adipose tissue restricts the normal movement of the chest muscles and reduces the compliance of the chest wall.
- This decreases the efficient movement of the diaphragm wall and increases the fatigue of respiratory muscles.
- It disrupts air flow in and out of the lung due to excessive tissue in the head and neck area, which increases the energy expenditure for effective breathing.
- This leads to sleep-disordered breathing and insufficient removal of carbon dioxide from circulation, hence hypercapnia.
- Since carbon dioxide in aqueous solution reacts with water to produce an acid (CO2 [g] + H2O [l] --> H2CO3[aq]), it manifests in acidosis in the blood. Usually, the acidity is detected by central chemoreceptors in the brainstem, which responds by increasing the respiratory rate. However, in OHS, this respiratory response is dampened.
- Piper & Grunstein (2007) suggested a link between obesity and increased leptin levels, but ventilation is reduced in OHS instead of increased.
- Nighttime acidosis result in compensation by the kidneys with retention of the alkali bicarbonate, which normalises the acidity of the blood.
- When bicarbonate lingers in the bloodstream for extended periods, this leads to further episodes of hypercapnia, which results in relatively mild acidosis and decreased ventilatory response in a vicious circle.
- Reduced oxygen levels result in hypoxic pulmonary vasoconstruction i.e. decreasing the diameter of small blood vessels in the lung to produce an optimal distribution of blood through the lung.
- If chronic vasoconstriction occurs, it increases pressure on the pulmonary artery (pulmonary hypertension), which in turn strains the right ventricle.
- The right ventricle experiences remodelling, then distension, which decreases its capacity to remove blood from the veins. This elevated hydrostatic pressure results in oedema in the skin, liver and/or abdominal cavity.
- Hypoxia in the blood manifests the release of erthropoietin and the activation of erythropoeisis, and the production of red blood cells. This leads to polycythemia, that is, abnormally high levels of circulating red blood cells and increased levels of hematocrit.
How is OHS diagnosed?
- Body mass index over 30 km/m2
- Arterial carbon dioxide levels over 45 mmHg or 6.0 kPa
- No alternative explanation for hypoventilation, such as use of narcotics, severe obstructive or interstitial lung disease, severe chest wall disorders such as kyphoscoliosis, severe hypothyroidism, neuromuscular disease or congenital central hypoventilation syndrome.
Diagnostic Tests:
- Arterial blood gas determination: Extracting a blood sample from an artery
- Measurement of bicarbonate levels in normal (venous) blood (High = 27+ mmol/l)
- Polysomnography = Electroencephalography (Brain's electrical activity), Electrocardiography (Heart's electrical activity), Pulse oximetry (Oxygen levels)
- Blood tests to identify hypothyroidism and polycythemia
- Medical imaging of the lungs (e.g. Chest X-ray, CT/CAT Scan)
- Spirometry
Classification:
- It is classified as a sleep disordered breathing, with 2 subtypes identified depending on the nature of disordered breathing detected on tests.
- In the context of obstructive sleep apnoea, OHS patients experience 5 or more episodes of apnoea, hypopnea or respiratory-related arousals per hour (high apnoea-hypopnea index) during sleep.
- In the context of sleep hypoventilation syndrome, OHS patients experience elevated CO2 levels by 10 mmHg (1.3 kPa) after sleep.
- Roughly, 90% of OHS patients are classified in the 1st category and 10% are classified in the 2nd category.
How is OHS treated?
- Weight loss programme: Healthy diet, physical exercise, medication, weight loss surgery (bariatric surgery)
- Night time or bi-level positive airway pressure (PAP) to aid breathing
- Admission to an intensive care unit with intubation and mechanical ventilation
- Continuous positive airway pressure (CPAP) = A machine delivers a continuous positive pressure to the airways and prevent the collapse of soft tissues in the throat during breathing. It is administered through a mask on either the mouth and nose together or on the nose only (nasally). This helps relieve the symptoms of obstructive sleep apnoea and remove the excess carbon dioxide.
- Oxygen therapy
- Tracheostomy (as a last resort)
- Periodic breathing
https://en.wikipedia.org/wiki/Periodic_breathing
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| Source: Mohr et al. (2016) Clinical Associations with Immature Breathing in Preterm Infants. Part 2: Periodic Breathing https://www.researchgate.net/figure/Periodic-breathing-examples_fig1_299377404 |
- It is a bunch of breaths separated by intervals of apnoea or near-apnoea. Berry et al. (2012) defined it as 3 or more episodes of central apnoea lasting at least 4 seconds, separated by no more than 30 seconds of normal breathing.
- It tends to occur during sleep, even in healthy people, and the apnoea aspect in periodic breathing is characteristically central sleep apnoea.
- In premature and full-term infants, they pause their breathing for no more than 10 seconds at a time, followed by successive rapid, shallow breaths. Finally, normal breathing resumes without stimulation or intervention.
- Kelly et al. (1985) found 78% of healthy full-term infants experience periodic breathing in the first 2 weeks of life, which usually disappears in the first 6 months of life.
9. Sleep state misperception
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| This diagram shows a dichotomic concept of SSM. Source: Trajanovic et al. (2007) Positive sleep state misperception - A new concept of sleep misperception https://www.researchgate.net/figure/Dichotomic-concept-of-sleep-state-misperception_fig3_6530112 |
Sleep state misperception (SSM) is a sleep disorder characterised by the inaccurate perception of sleep as wakefulness, and studies suggest it often applies to those who reportedly overestimate the amount of time they slept.
How is SSM classified?
SSM is classified as a intrinsic dyssomnia with distinct pathophysiology. They can be categorised into different types:
- Short sleep (subjective insomnia complaint without objective findings), or no sleep at all (subjective total insomnia).
- Excessive daytime sleepiness (subjective sleepiness without objective findings)
- Excess sleep (subjective hypersomnia without objective findings)
How prevalent is SSM?
- As of 2008, information about the risk factors or prevention of SSM is scarce, though Kushida (2008) suggested it affected mostly young to middle-aged adults.
- Attaining knowledge about the distribution of SSM amongst the world population and by gender requires research, as it is currently unknown.
- Fernandez-Mendoza (2014) suggested SSM is prevalent among chronic insomniacs who sleep objectively more than 6 hours in the sleep lab. Chronic insomniacs with objective normal sleep function had characteristics such as depressive, anxious-ruminative traits and mediocre coping resources.
What are the symptoms of SSM?
- Appears asymptomatic despite the subjective perception of insufficient sleep, which would often be unreported.
- Significant overestimation of sleep time, often reporting half of the sleep time recoded by the polysomnogram or electroencelaphography (EEG), leading to huge discrepancies between subjective and objective reports.
- Excessive daytime sleepiness coinciding with the lack of a sleep disorder diagnosis
- Positive SSM = Longer sleep times than observed
How is SSM diagnosed?
- Polysomnography indicates typical sleep latency, a typical number of arousals and awakenings, and typical sleep duration with or without a multiple sleep latency test
- No other medical or mental or sleep disorder manifests the complaints by the patient.
- Finkbeiner (2014) proposed spectral analysis of EEG as a method to assist clinicians in discovering objective evidence for SSM.
How is SSM treated?
- Sedative hypnotics to alleviate symptoms
- Education about the typical patterns of sleep-wake cycle can alleviate anxiety
- Electroconvulsive therapy to treat those with severe depression exacerbating from the fear of insomnia diagnosis.
- Complications include dependency on prescribed hypnotics or stimulations, increased risk of depression, anxiety and substance abuse.
Does counting sheep help you sleep?
https://en.wikipedia.org/wiki/Counting_sheep
https://en.wikipedia.org/wiki/Counting_sheep
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| Mr. Bean counting sheep in Goodnight Mr. Bean episode |
- Some cultures believed counting sheep is an effective mental exercise to put oneself to sleep. It was presumed the idea behind this stereotype is to induce boredom while occupying the mind with a simple, repetitive, and rhythmic activity, which ultimately increase sleepiness.
- Although this practice is generally a stereotype, it is rarely used as a treatment for insomnia. This is often referenced by cartoons, comic strips, and other mass media, where it has become deeply engrained into popular culture's notion of sleep. The term "counting sheep" was coined in the English language as an idiomatic term for 'insomnia'.
- However, studies demonstrated counting sheep or any number of objects doesn't guarantee one to fall asleep for those struggling to sleep. Allison & Payne (2002) found subjects who imagined "a beach or a waterfall" expended more mental energy, and fell asleep quickly later, than those asked to "simply distract from thoughts, worries, and concerns". There are other complex activities that can expend as much mental energy, inducing sleepiness, such as reading books and physical exercise.
