Restless legs syndrome

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Restless_legs_syndrome 

Restless legs syndrome
Other names	Willis–Ekbom disease (WED), Wittmaack–Ekbom syndrome
Sleep pattern of a person with restless legs syndrome (red) compared to a healthy sleep pattern (blue)
Specialty	Sleep medicine
Symptoms	Unpleasant feeling in the legs that briefly improves with moving them
Complications	Daytime sleepiness, low energy, irritability, sadness
Usual onset	More common with older age
Risk factors	Low iron levels, kidney failure, Parkinson's disease, diabetes mellitus, rheumatoid arthritis, pregnancy, certain medications
Diagnostic method	Based on symptoms after ruling out other possible causes
Treatment	Lifestyle changes, medication
Medication	Levodopa, dopamine agonists, gabapentin
Frequency	2.5–15% (US)

Restless legs syndrome (RLS), now known as Willis-Ekbom Disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This is often described as aching, tingling, or crawling in nature. Occasionally, arms may also be affected. The feelings generally happen when at rest and therefore can make it hard to sleep. Due to the disturbance in sleep, people with RLS may have daytime sleepiness, low energy, irritability and a depressed mood. Additionally, many have limb twitching during sleep. RLS is not the same as habitual foot tapping or leg rocking.

Risk factors for RLS include low iron levels, kidney failure, Parkinson's disease, diabetes mellitus, rheumatoid arthritis, pregnancy and celiac disease. A number of medications may also trigger the disorder including antidepressants, antipsychotics, antihistamines, and calcium channel blockers. There are two main types. One is early onset RLS which starts before age 45, runs in families and worsens over time. The other is late onset RLS which begins after age 45, starts suddenly, and does not worsen. Diagnosis is generally based on a person's symptoms after ruling out other potential causes.

Restless leg syndrome may resolve if the underlying problem is addressed. Otherwise treatment includes lifestyle changes and medication. Lifestyle changes that may help include stopping alcohol and tobacco use, and sleep hygiene. Medications used include levodopa or a dopamine agonist such as pramipexole. RLS affects an estimated 2.5–15% of the American population. Females are more commonly affected than males, and it becomes increasingly common with age.

Signs and symptoms

RLS sensations range from pain or an aching in the muscles, to "an itch you can't scratch", a "buzzing sensation", an unpleasant "tickle that won't stop", a "crawling" feeling, or limbs jerking while awake. The sensations typically begin or intensify during quiet wakefulness, such as when relaxing, reading, studying, or trying to sleep.

It is a "spectrum" disease with some people experiencing only a minor annoyance and others having major disruption of sleep and impairments in quality of life.

The sensations—and the need to move—may return immediately after ceasing movement or at a later time. RLS may start at any age, including childhood, and is a progressive disease for some, while the symptoms may remit in others. In a survey among members of the Restless Legs Syndrome Foundation, it was found that up to 45% of patients had their first symptoms before the age of 20 years.

• "An urge to move, usually due to uncomfortable sensations that occur primarily in the legs, but occasionally in the arms or elsewhere."

The sensations are unusual and unlike other common sensations. Those with RLS have a hard time describing them, using words or phrases such as uncomfortable, painful, 'antsy', electrical, creeping, itching, pins and needles, pulling, crawling, buzzing, and numbness. It is sometimes described similar to a limb 'falling asleep' or an exaggerated sense of positional awareness of the affected area. The sensation and the urge can occur in any body part; the most cited location is legs, followed by arms. Some people have little or no sensation, yet still, have a strong urge to move.

• "Motor restlessness, expressed as activity, which relieves the urge to move."

Movement usually brings immediate relief, although temporary and partial. Walking is most common; however, stretching, yoga, biking, or other physical activity may relieve the symptoms. Continuous, fast up-and-down movements of the leg, and/or rapidly moving the legs toward then away from each other, may keep sensations at bay without having to walk. Specific movements may be unique to each person.

• "Worsening of symptoms by relaxation."

Sitting or lying down (reading, plane ride, watching TV) can trigger the sensations and urge to move. Severity depends on the severity of the person's RLS, the degree of restfulness, duration of the inactivity, etc.

• "Variability over the course of the day-night cycle, with symptoms worse in the evening and early in the night."

Some experience RLS only at bedtime, while others experience it throughout the day and night. Most people experience the worst symptoms in the evening and the least in the morning.

• "Restless legs feel similar to the urge to yawn, situated in the legs or arms."

These symptoms of RLS can make sleeping difficult for many patients and a recent poll shows the presence of significant daytime difficulties resulting from this condition. These problems range from being late for work to missing work or events because of drowsiness. Patients with RLS who responded reported driving while drowsy more than patients without RLS. These daytime difficulties can translate into safety, social and economic issues for the patient and for society.

RLS may contribute to higher rates of depression and anxiety disorders in RLS patients.

Primary and secondary

RLS is categorized as either primary or secondary.

• Primary RLS is considered idiopathic or with no known cause. Primary RLS usually begins slowly, before approximately 40–45 years of age and may disappear for months or even years. It is often progressive and gets worse with age. RLS in children is often misdiagnosed as growing pains.
• Secondary RLS often has a sudden onset after age 40, and may be daily from the beginning. It is most associated with specific medical conditions or the use of certain drugs (see below).

Causes

While the cause is generally unknown, it is believed to be caused by changes in the nerve transmitter dopamine resulting in an abnormal use of iron by the brain. RLS is often due to iron deficiency (low total body iron status). Other associated conditions may include end-stage kidney disease and hemodialysis, folate deficiency, magnesium deficiency, sleep apnea, diabetes, peripheral neuropathy, Parkinson's disease, and certain autoimmune diseases, such as multiple sclerosis. RLS can worsen in pregnancy, possibly due to elevated estrogen levels. Use of alcohol, nicotine products, and caffeine may be associated with RLS. A 2014 study from the American Academy of Neurology also found that reduced leg oxygen levels were strongly associated with Restless Leg Syndrome symptom severity in untreated patients.

ADHD

An association has been observed between attention deficit hyperactivity disorder (ADHD) and RLS or periodic limb movement disorder. Both conditions appear to have links to dysfunctions related to the neurotransmitter dopamine, and common medications for both conditions among other systems, affect dopamine levels in the brain. A 2005 study suggested that up to 44% of people with ADHD had comorbid (i.e. coexisting) RLS, and up to 26% of people with RLS had confirmed ADHD or symptoms of the condition.

Medications

Certain medications may cause or worsen RLS, or cause it secondarily, including:

• certain antiemetics (antidopaminergic ones)
• certain antihistamines (especially the sedating, first generation H1 antihistamines often in over-the-counter cold medications)
• many antidepressants (both older TCAs and newer SSRIs)
• antipsychotics and certain anticonvulsants
• a rebound effect of sedative-hypnotic drugs such as a benzodiazepine withdrawal syndrome from discontinuing benzodiazepine tranquilizers or sleeping pills
• alcohol withdrawal can also cause restless legs syndrome and other movement disorders such as akathisia and parkinsonism usually associated with antipsychotics
• opioid withdrawal is associated with causing and worsening RLS

Both primary and secondary RLS can be worsened by surgery of any kind; however, back surgery or injury can be associated with causing RLS.

The cause vs. effect of certain conditions and behaviors observed in some patients (ex. excess weight, lack of exercise, depression or other mental illnesses) is not well established. Loss of sleep due to RLS could cause the conditions, or medication used to treat a condition could cause RLS.

Genetics

More than 60% of cases of RLS are familial and are inherited in an autosomal dominant fashion with variable penetrance.

Research and brain autopsies have implicated both dopaminergic system and iron insufficiency in the substantia nigra. Iron is well understood to be an essential cofactor for the formation of L-dopa, the precursor of dopamine.

Six genetic loci found by linkage are known and listed below. Other than the first one, all of the linkage loci were discovered using an autosomal dominant model of inheritance.

• The first genetic locus was discovered in one large French Canadian family and maps to chromosome 12q. This locus was discovered using an autosomal recessive inheritance model. Evidence for this locus was also found using a transmission disequilibrium test (TDT) in 12 Bavarian families.
• The second RLS locus maps to chromosome 14q and was discovered in one Italian family. Evidence for this locus was found in one French Canadian family. Also, an association study in a large sample 159 trios of European descent showed some evidence for this locus.
• This locus maps to chromosome 9p and was discovered in two unrelated American families. Evidence for this locus was also found by the TDT in a large Bavarian family, in which significant linkage to this locus was found.
• This locus maps to chromosome 20p and was discovered in a large French Canadian family with RLS.
• This locus maps to chromosome 2p and was found in three related families from population isolated in South Tyrol.
• The sixth locus is located on chromosome 16p12.1 and was discovered by Levchenko et al. in 2008.

Three genes, MEIS1, BTBD9 and MAP2K5, were found to be associated to RLS. Their role in RLS pathogenesis is still unclear. More recently, a fourth gene, PTPRD was found to be associated with RLS.

There is also some evidence that periodic limb movements in sleep (PLMS) are associated with BTBD9 on chromosome 6p21.2, MEIS1, MAP2K5/SKOR1, and PTPRD. The presence of a positive family history suggests that there may be a genetic involvement in the etiology of RLS.

Mechanism

Although it is only partly understood, pathophysiology of restless legs syndrome may involve dopamine and iron system anomalies. There is also a commonly acknowledged circadian rhythm explanatory mechanism associated with it, clinically shown simply by biomarkers of circadian rhythm, such as body temperature. The interactions between impaired neuronal iron uptake and the functions of the neuromelanin-containing and dopamine-producing cells have roles in RLS development, indicating that iron deficiency might affect the brain dopaminergic transmissions in different ways.

Medial thalamic nuclei may also have a role in RLS as part as the limbic system modulated by the dopaminergic system which may affect pain perception. Improvement of RLS symptoms occurs in people receiving low-dose dopamine agonists.

Diagnosis

There are no specific tests for RLS, but non-specific laboratory tests are used to rule out other causes such as vitamin deficiencies. Five symptoms are used to confirm the diagnosis:

• A strong urge to move the limbs, usually associated with unpleasant or uncomfortable sensations.
• It starts or worsens during inactivity or rest.
• It improves or disappears (at least temporarily) with activity.
• It worsens in the evening or night.
• These symptoms are not caused by any medical or behavioral condition.

These symptoms are not essential, like the ones above, but occur commonly in RLS patients:

• genetic component or family history with RLS
• good response to dopaminergic therapy
• periodic leg movements during day or sleep
• most strongly affected are people who are middle-aged or older
• other sleep disturbances are experienced
• decreased iron stores can be a risk factor and should be assessed

According to the International Classification of Sleep Disorders (ICSD-3), the main symptoms have to be associated with a sleep disturbance or impairment in order to support RLS diagnosis. As stated by this classification, RLS symptoms should begin or worsen when being inactive, be relieved when moving, should happen exclusively or mostly in the evening and at night, not be triggered by other medical or behavioral conditions, and should impair one's quality of life. Generally, both legs are affected, but in some cases there is an asymmetry.

Differential diagnosis

The most common conditions that should be differentiated with RLS include leg cramps, positional discomfort, local leg injury, arthritis, leg edema, venous stasis, peripheral neuropathy, radiculopathy, habitual foot tapping/leg rocking, anxiety, myalgia, and drug-induced akathisia.

Peripheral artery disease and arthritis can also cause leg pain but this usually gets worse with movement.

There are less common differential diagnostic conditions included myelopathy, myopathy, vascular or neurogenic claudication, hypotensive akathisia, orthostatic tremor, painful legs, and moving toes.

Treatment

If RLS is not linked to an underlying cause, its frequency may be reduced by lifestyle modifications such as adopting improving sleep hygiene, regular exercise, and stopping smoking. Medications used may include dopamine agonists or gabapentin in those with daily restless legs syndrome, and opioids for treatment of resistant cases.

Treatment of RLS should not be considered until possible medical causes are ruled out. Secondary RLS may be cured if precipitating medical conditions (anemia) are managed effectively.

Physical measures

Stretching the leg muscles can bring temporary relief. Walking and moving the legs, as the name "restless legs" implies, brings temporary relief. In fact, those with RLS often have an almost uncontrollable need to walk and therefore relieve the symptoms while they are moving. Unfortunately, the symptoms usually return immediately after the moving and walking ceases. A vibratory counter-stimulation device has been found to help some people with primary RLS to improve their sleep.

Iron

There is some evidence that intravenous iron supplementation moderately improves restlessness for people with RLS.

Medications

For those whose RLS disrupts or prevents sleep or regular daily activities, medication may be useful. Evidence supports the use of dopamine agonists including: pramipexole, ropinirole, rotigotine, and cabergoline. They reduce symptoms, improve sleep quality and quality of life. Levodopa is also effective. However, pergolide and cabergoline are less recommended due to their association with increased risk of valvular heart disease. Ropinirole has a faster onset with shorter duration. Rotigotine is commonly used as a transdermal patch which continuously provides stable plasma drug concentrations, resulting in its particular therapeutic effect on patients with symptoms throughout the day. One review found pramipexole to be better than ropinirole.

There are, however, issues with the use of dopamine agonists including augmentation. This is a medical condition where the drug itself causes symptoms to increase in severity and/or occur earlier in the day. Dopamine agonists may also cause rebound when symptoms increase as the drug wears off. In many cases, the longer dopamine agonists have been used the higher the risk of augmentation and rebound as well as the severity of the symptoms. Also, a recent study indicated that dopamine agonists used in restless leg syndrome can lead to an increase in compulsive gambling.

• Gabapentin or pregabalin, a non-dopaminergic treatment for moderate to severe primary RLS
• Opioids are only indicated in severe cases that do not respond to other measures due to their high rate of side effects, which may include constipation, fatigue and headache.

One possible treatment for RLS is dopamine agonists, unfortunately patients can develop dopamine dysregulation syndrome, meaning that they can experience an addictive pattern of dopamine replacement therapy. Additionally, they can exhibit some behavioral disturbances such as impulse control disorders like pathologic gambling, compulsive purchasing and compulsive eating. There are some indications that stopping the dopamine agonist treatment has an impact on the resolution or at least improvement of the impulse control disorder, even though some people can be particularly exposed to dopamine agonist withdrawal syndrome.

Benzodiazepines, such as diazepam or clonazepam, are not generally recommended, and their effectiveness is unknown. They however are sometimes still used as a second line, as add on agents. Quinine is not recommended due to its risk of serious side effects involving the blood.

Prognosis

RLS symptoms may gradually worsen with age, although more slowly for those with the idiopathic form of RLS than for people who also have an associated medical condition. Current therapies can control the disorder, minimizing symptoms and increasing periods of restful sleep. In addition, some people have remissions, periods in which symptoms decrease or disappear for days, weeks, or months, although symptoms usually eventually reappear. Being diagnosed with RLS does not indicate or foreshadow another neurological disease, such as Parkinson's disease. RLS symptoms can worsen over time when dopamine-related drugs are used for therapy, an effect called "augmentation" which may represent symptoms occurring throughout the day and affect movements of all limbs. There is no cure for RLS.

Epidemiology

RLS affects an estimated 2.5–15% of the American population. A minority (around 2.7% of the population) experience daily or severe symptoms. RLS is twice as common in women as in men, and Caucasians are more prone to RLS than people of African descent. RLS occurs in 3% of individuals from the Mediterranean or Middle Eastern regions, and in 1–5% of those from East Asia, indicating that different genetic or environmental factors, including diet, may play a role in the prevalence of this syndrome. RLS diagnosed at an older age runs a more severe course. RLS is even more common in individuals with iron deficiency, pregnancy, or end-stage kidney disease. The National Sleep Foundation's 1998 Sleep in America poll showed that up to 25 percent of pregnant women developed RLS during the third trimester. Poor general health is also linked.

There are several risk factors for RLS, including old age, family history, and uremia. The prevalence of RLS tends to increase with age, as well as its severity and longer duration of symptoms. People with uremia receiving renal dialysis have a prevalence from 20% to 57%, while those having kidney transplant improve compared to those treated with dialysis.

RLS can occur at all ages, although it typically begins in the third or fourth decade. Genome‐wide association studies have now identified 19 risk loci associated with RLS. Neurological conditions linked to RLS include Parkinson's disease, spinal cerebellar atrophy, spinal stenosis, lumbosacral radiculopathy and Charcot–Marie–Tooth disease type 2.

History

The first known medical description of RLS was by Sir Thomas Willis in 1672. Willis emphasized the sleep disruption and limb movements experienced by people with RLS. Initially published in Latin (De Anima Brutorum, 1672) but later translated to English (The London Practice of Physick, 1685), Willis wrote:

Wherefore to some, when being abed they betake themselves to sleep, presently in the arms and legs, leapings and contractions on the tendons, and so great a restlessness and tossings of other members ensue, that the diseased are no more able to sleep, than if they were in a place of the greatest torture.

The term "fidgets in the legs" has also been used as early as the early nineteenth century.

Subsequently, other descriptions of RLS were published, including those by François Boissier de Sauvages (1763), Magnus Huss (1849), Theodur Wittmaack (1861), George Miller Beard (1880), Georges Gilles de la Tourette (1898), Hermann Oppenheim (1923) and Frederick Gerard Allison (1943).^[90][92] However, it was not until almost three centuries after Willis, in 1945, that Karl-Axel Ekbom (1907–1977) provided a detailed and comprehensive report of this condition in his doctoral thesis, Restless legs: clinical study of hitherto overlooked disease. Ekbom coined the term "restless legs" and continued work on this disorder throughout his career. He described the essential diagnostic symptoms, differential diagnosis from other conditions, prevalence, relation to anemia, and common occurrence during pregnancy.

Ekbom's work was largely ignored until it was rediscovered by Arthur S. Walters and Wayne A. Hening in the 1980s. Subsequent landmark publications include 1995 and 2003 papers, which revised and updated the diagnostic criteria. Journal of Parkinsonism and RLS is the first peer-reviewed, online, open access journal dedicated to publishing research about Parkinson's disease and was founded by a Canadian neurologist Dr. Abdul Qayyum Rana.

Nomenclature

For decades the most widely used name for the disease was restless legs syndrome, and it is still the most commonly used. In 2013 the Restless Legs Syndrome Foundation renamed itself the Willis–Ekbom Disease Foundation, and it encourages the use of the name Willis–Ekbom disease; its reasons are quoted as follows:

The name Willis–Ekbom disease:

• Eliminates incorrect descriptors—the condition often involves parts of the body other than legs
• Promotes cross-cultural ease of use
• Responds to trivialization of the disease and humorous treatment in the media
• Acknowledges the first known description by Sir Thomas Willis in 1672 and the first detailed clinical description by Dr. Karl Axel Ekbom in 1945.

A point of confusion is that RLS and delusional parasitosis are entirely different conditions that have both been called "Ekbom syndrome", as both syndromes were described by the same person, Karl-Axel Ekbom. Today, calling WED/RLS "Ekbom syndrome" is outdated usage, as the unambiguous names (WED or RLS) are preferred for clarity.

Controversy

Some doctors express the view that the incidence of restless leg syndrome is exaggerated by manufacturers of drugs used to treat it. Others believe it is an underrecognized and undertreated disorder. Further, GlaxoSmithKline ran advertisements that, while not promoting off-licence use of their drug (ropinirole) for treatment of RLS, did link to the Ekbom Support Group website. That website contained statements advocating the use of ropinirole to treat RLS. The ABPI ruled against GSK in this case.

Research

Different measurements have been used to evaluate treatments in RLS. Most of them are based on subjective rating scores, such as IRLS rating scale (IRLS), Clinical Global Impression (CGI), Patient Global Impression (PGI), and Quality of life (QoL). These questionnaires provide information about the severity and progress of the disease, as well as the person's quality of life and sleep. Polysomnography (PSG) and actigraphy (both related to sleep parameters) are more objective resources that provide evidences of sleep disturbances associated with RLS symptoms.

 

Biological agent

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Biological_agent 

 

A culture of Bacillus anthracis, the causative agent of anthrax.

A biological agent (also called bio-agent, biological threat agent, biological warfare agent, biological weapon, or bioweapon) is a bacterium, virus, protozoan, parasite, fungus, chemical, or toxin that can be used purposefully as a weapon in bioterrorism or biological warfare (BW). In addition to these living or replicating pathogens, toxins and biotoxins are also included among the bio-agents. More than 1,200 different kinds of potentially weaponizable bio-agents have been described and studied to date.

Biological agents have the ability to adversely affect human health in a variety of ways, ranging from relatively mild allergic reactions to serious medical conditions, including serious injury, as well as serious or permanent disability or even death. Many of these organisms are ubiquitous in the natural environment where they are found in water, soil, plants, or animals. Bio-agents may be amenable to "weaponization" to render them easier to deploy or disseminate. Genetic modification may enhance their incapacitating or lethal properties, or render them impervious to conventional treatments or preventives. Since many bio-agents reproduce rapidly and require minimal resources for propagation, they are also a potential danger in a wide variety of occupational settings.

The 1972 Biological Weapons Convention (BWC) is an international treaty banning the development, use or stockpiling of biological weapons; as of March 2021, there were 183 States Parties to the BWC. Bio-agents are, however, widely studied for both defensive and medical research purposes under various biosafety levels and within biocontainment facilities throughout the world.

Classifications

Operational

The former US biological warfare program (1943-1969) categorized its weaponized anti-personnel bio-agents as either "lethal agents" (Bacillus anthracis, Francisella tularensis, Botulinum toxin) or "incapacitating agents" (Brucella suis, Coxiella burnetii, Venezuelan equine encephalitis virus, Staphylococcal enterotoxin B).

Legal

Since 1997, United States law has declared a list of bio-agents designated by the U.S. Department of Health and Human Services or the U.S. Department of Agriculture that have the "potential to pose a severe threat to public health and safety" to be officially defined as "select agents" and possession or transportation of them are tightly controlled as such. Select agents are divided into "HHS select agents and toxins", "USDA select agents and toxins" and "Overlap select agents and toxins".

Regulatory

The U.S. Centers for Disease Control and Prevention (CDC) breaks biological agents into three categories: Category A, Category B, and Category C. Category A agents pose the greatest threat to the U.S. Criteria for being a Category "A" agent include high rates of morbidity and mortality; ease of dissemination and communicability; ability to cause a public panic; and special action required by public health officials to respond. Category A agents include anthrax, botulism, plague, smallpox, and viral hemorrhagic fevers.

List of bio-agents of military importance

The following pathogens and toxins were weaponized by one nation or another at some time. NATO abbreviations are included where applicable.

Bacterial bio-agents

Disease	Causative Agent (Military Symbol)
Anthrax	Bacillus anthracis (N or TR)
Brucellosis (bovine)	Brucella abortus
Brucellosis (caprine)	Brucella melitensis (AM or BX)
Brucellosis (porcine)	Brucella suis (US, AB or NX)
Cholera	Vibrio cholerae (HO)
Diphtheria	Corynebacterium diphtheriae (DK)
Dysentery (bacterial)	Shigella dysenteriae, Escherichia coli (Y)
Glanders	Burkholderia mallei (LA)
Listeriosis	Listeria monocytogenes (TQ)
Melioidosis	Burkholderia pseudomallei (HI)
Plague	Yersinia pestis (LE)
Tularemia	Francisella tularensis (SR or JT)

Chlamydial bio-agents

Disease	Causative Agent (Military Symbol)
Psittacosis	Chlamydophila psittaci (SI)

Rickettsial bio-agents

Disease	Causative Agent (Military Symbol)
Q Fever	Coxiella burnetii (OU)
Rocky Mountain spotted fever	Rickettsia rickettsii (RI or UY)
Typhus (human)	Rickettsia prowazekii (YE)
Typhus (murine)	Rickettsia typhi (AV)

Viral bio-agents

Disease	Causative Agent (Military Symbol)	Comments
Equine Encephalitis (Eastern)	Eastern equine encephalitis virus (ZX)
Equine Encephalitis (Venezuelan)	Venezuelan Equine Encephalomyelitis virus (FX)
Equine Encephalitis (Western)	Western equine encephalitis virus (EV)
Japanese B encephalitis	Japanese encephalitis virus (AN)
Marburg Hemorrhagic Fever (Marburg HF)	Marburg Virus (MARV)	by the Soviet Union
Rift Valley fever	Rift Valley fever virus (FA)
Smallpox	Variola virus (ZL)
Yellow fever	Yellow fever virus (OJ or LU)

Mycotic bio-agents

Disease	Causative Agent (Military Symbol)
Coccidiomycosis	Coccidioides immitis (OC)

Biological toxins

Toxin	Source of Toxin (Military Symbol)
Abrin	Rosary pea (Abrus precatorius)
Botulinum toxins (A through G)	Clostridium botulinum bacteria or spores, and several other Clostridial species. (X or XR)
Ricin	Castor bean (Ricinus communis) (W or WA)
Saxitoxin	Various marine and brackish cyanobacteria, such as Anabaena, Aphanizomenon, Lyngbya, and Cylindrospermopsis (TZ)
Staphyloccocal enterotoxin B	Staphylococcus aureus (UC or PG)
Tetrodotoxin	Various marine bacteria, including Vibrio alginolyticus, Pseudoalteromonas tetraodonis (PP)
Trichothecene mycotoxins	Various species of fungi, including Fusarium, Trichoderma, and Stachybotrys

Biological vectors

Vector (Military Symbol)	Disease
Mosquito (Aedes aegypti) (AP)	Malaria, Dengue fever, Chikungunya, Yellow fever, other Arboviruses
Oriental flea (Xenopsylla cheopis)	Plague, Murine typhus

Simulants

Simulants are organisms or substances which mimic physical or biological properties of real biological agents, without being pathogenic. They are used to study the efficiency of various dissemination techniques or the risks caused by the use of biological agents in bioterrorism. To simulate dispersal, attachment or the penetration depth in human or animal lungs, simulants must have particle sizes, specific weight and surface properties, similar to the simulated biological agent.

The typical size of simulants (1–5 µm) enables it to enter buildings with closed windows and doors and penetrate deep into the lungs. This bears a significant health risk, even if the biological agent is normally not pathogenic.

• Bacillus globigii (historically named Bacillus subtilis in the context of bio-agent simulants) (BG, BS, or U)
• Serratia marcescens (SM or P)
• Aspergillus fumigatus mutant C-2 (AF)
• Escherichia coli (EC)
• Bacillus thuringiensis (BT)
• Erwinia herbicola (current accepted name: Pantoea agglomerans) (EH)
• Fluorescent particles such as Zinc cadmium sulfide, ZnCdS (FP)

International law

The Biological Weapons Convention

 

Main articles: Geneva Protocol and Biological Weapons Convention

While the history of biological weapons use goes back more than six centuries to the siege of Caffa in 1346, international restrictions on biological weapons began only with the 1925 Geneva Protocol, which prohibits the use but not the possession or development of chemical and biological weapons. Upon ratification of the Geneva Protocol, several countries made reservations regarding its applicability and use in retaliation. Due to these reservations, it was in practice a "no-first-use" agreement only.

The 1972 Biological Weapons Convention (BWC) supplements the Geneva Protocol by prohibiting the development, production, acquisition, transfer, stockpiling and use of biological weapons. Having entered into force on 26 March 1975, the BWC was the first multilateral disarmament treaty to ban the production of an entire category of weapons of mass destruction. As of March 2021, 183 states have become party to the treaty. The BWC is considered to have established a strong global norm against biological weapons, which is reflected in the treaty’s preamble, stating that the use of biological weapons would be "repugnant to the conscience of mankind". However, the BWC’s effectiveness has been limited due to insufficient institutional support and the absence of any formal verification regime to monitor compliance.

In 1985, the Australia Group was established, a multilateral export control regime of 43 countries aiming to prevent the proliferation of chemical and biological weapons.

In 2004, the United Nations Security Council passed Resolution 1540, which obligates all UN Member States to develop and enforce appropriate legal and regulatory measures against the proliferation of chemical, biological, radiological, and nuclear weapons and their means of delivery, in particular, to prevent the spread of weapons of mass destruction to non-state actors.

In popular culture

Main article: Biological warfare in popular culture

See also

• Biological hazard
• Biological contamination
• Laboratory Response Network
• Pulsed ultraviolet light
• Toxin

Sleep medicine

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Sleep_medicine

 

Sleep medicine

System	Respiratory system, Cardiovascular system, Nervous system
Significant diseases	Insomnia, Sleep apnoea, Narcolepsy
Significant tests	Sleep study
Specialist	Sleep medicine physician

Sleep Medicine Physician

Occupation
Names	Physician
Activity sectors	Medicine, Psychiatry
Description
Education required	Doctor of Medicine (MD) Doctor of Osteopathic Medicine (DO) Bachelor of Medicine, Bachelor of Surgery (MBBS/MBChB)

Sleep diary layout example

Sleep medicine is a medical specialty or subspecialty devoted to the diagnosis and therapy of sleep disturbances and disorders. From the middle of the 20th century, research has provided increasing knowledge and answered many questions about sleep-wake functioning. The rapidly evolving field has become a recognized medical subspecialty in some countries. Dental sleep medicine also qualifies for board certification in some countries. Properly organized, minimum 12-month, postgraduate training programs are still being defined in the United States. In some countries, the sleep researchers and the physicians who treat patients may be the same people.

The first sleep clinics in the United States were established in the 1970s by interested physicians and technicians; the study, diagnosis and treatment of obstructive sleep apnea were their first tasks. As late as 1999, virtually any American physician, with no specific training in sleep medicine, could open a sleep laboratory.

Disorders and disturbances of sleep are widespread and can have significant consequences for affected individuals as well as economic and other consequences for society. The US National Transportation Safety Board has, according to Dr. Charles Czeisler, member of the Institute of Medicine and Director of the Harvard University Medical School Division of Sleep Medicine at Brigham and Women's Hospital, discovered that the leading cause (31%) of fatal-to-the-driver heavy truck crashes is fatigue related (though rarely associated directly with sleep disorders, such as sleep apnea), with drugs and alcohol as the number two cause (29%). Sleep deprivation has also been a significant factor in dramatic accidents, such as the Exxon Valdez oil spill, the nuclear incidents at Chernobyl and Three Mile Island and the explosion of the space shuttle Challenger.

Scope and classification

Main article: Sleep disorder

Competence in sleep medicine requires an understanding of a plethora of very diverse disorders, many of which present with similar symptoms such as excessive daytime sleepiness, which, in the absence of volitional sleep deprivation, "is almost inevitably caused by an identifiable and treatable sleep disorder," such as sleep apnea, narcolepsy, idiopathic hypersomnia, Kleine-Levin syndrome, menstrual-related hypersomnia, idiopathic recurrent stupor, or circadian rhythm disturbances. Another common complaint is insomnia, a set of symptoms that can have many causes, physical and mental. Management in the varying situations differs greatly and cannot be undertaken without a correct diagnosis.

ICSD, The International Classification of Sleep Disorders, was restructured in 1990, in relation to its predecessor, to include only one code for each diagnostic entry and to classify disorders by pathophysiologic mechanism, as far as possible, rather than by primary complaint. Training in sleep medicine is multidisciplinary, and the present structure was chosen to encourage a multidisciplinary approach to diagnosis. Sleep disorders often do not fit neatly into traditional classification; differential diagnoses cross medical systems. Minor revisions and updates to the ICSD were made in 1997 and in following years. The present classification system in fact follows the groupings suggested by Nathaniel Kleitman, the "father of sleep research", in his seminal 1939 book Sleep and Wakefulness.

The revised ICSD, ICSD-R, placed the primary sleep disorders in the subgroups (1) dyssomnias, which include those that produce complaints of insomnia or excessive sleepiness, and (2) the parasomnias, which do not produce those primary complaints but intrude into or occur during sleep. A further subdivision of the dyssomnias preserves the integrity of circadian rhythm sleep disorders, as was mandated by about 200 doctors and researchers from all over the world who participated in the process between 1985–1990. The last two subgroups were (3) the medical or psychiatric sleep disorder section and (4) the proposed new disorders section. The authors found the heading "medical or psychiatric" less than ideal but better than the alternative "organic or non-organic", which seemed more likely to change in the future. Detailed reporting schemes aimed to provide data for further research. A second edition, called ICSD-2, was published in 2005.

MeSH, Medical Subject Headings, a service of the US National Library of Medicine and the National Institutes of Health, uses similar broad categories: (1) dyssomnias, including narcolepsy, apnea, and the circadian rhythm sleep disorders, (2) parasomnias, which include, among others, bruxism (tooth-grinding), sleepwalking and bedwetting, and (3) sleep disorders caused by medical or psychiatric conditions. The system used produces "trees," approaching each diagnosis from up to several angles such that each disorder may be known by several codes.

DSM-IV-TR, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, using the same diagnostic codes as the International Statistical Classification of Diseases and Related Health Problems (ICD), divides sleep disorders into three groups: (1) primary sleep disorders, both the dyssomnias and the parasomnias, presumed to result from an endogenous disturbance in sleep-wake generating or timing mechanisms, (2) those secondary to mental disorders and (3) those related to a general medical condition or substance abuse.

Recent thinking opens for a common cause for mood and sleep disorders occurring in the same patient; a 2010 review states that, in humans, "single nucleotide polymorphisms in Clock and other clock genes have been associated with depression" and that the "evidence that mood disorders are associated with disrupted or at least inappropriately timed circadian rhythms suggests that treatment strategies or drugs aimed at restoring 'normal' circadian rhythmicity may be clinically useful."

History

A 16th-century physician wrote that many laborers dozed off exhausted at the start of each night; sexual intercourse with their wives typically occurring in the watching period, after a recuperative first sleep. Anthropologists find that isolated societies without electric light sleep in a variety of patterns; seldom do they resemble our modern habit of sleeping in one single eight-hour bout. Much has been written about dream interpretation, from biblical times to Freud, but sleep itself was historically seen as a passive state of not-awake.

The concept of sleep medicine belongs to the second half of the 20th century. Due to the rapidly increasing knowledge about sleep, including the growth of the research field chronobiology from about 1960 and the discoveries of REM sleep (1952–53) and sleep apnea (first described in the medical literature in 1965), the medical importance of sleep was recognized. The medical community began paying more attention than previously to primary sleep disorders, such as sleep apnea, as well as the role and quality of sleep in other conditions. By the 1970s in the US, and in many western nations within the two following decades, clinics and laboratories devoted to the study of sleep and the treatment of its disorders had been founded. Most sleep doctors were primarily concerned with apnea; some were experts in narcolepsy. There was as yet nothing to restrict the use of the title "sleep doctor", and a need for standards arose.

Basic medical training has paid little attention to sleep problems; according to Benca in her review Diagnosis and Treatment of Chronic Insomnia (2005), most doctors are "not well trained with respect to sleep and sleep disorders," and a survey in 1990–91 of 37 American medical schools showed that sleep and sleep disorders were "covered" in less than two hours of total teaching time, on average. Benca's review cites a 2002 survey by Papp et al. of more than 500 primary care physicians who self-reported their knowledge of sleep disorders as follows: Excellent – 0%; Good – 10%, Fair – 60%; and Poor – 30%. The review of more than 50 studies indicates that both doctors and patients appear reluctant to discuss sleep complaints, in part because of perceptions that treatments for insomnia are ineffective or associated with risks, and:

Physicians may avoid exploring problems such as sleep difficulties in order to avoid having to deal with issues that could take up more than the normal allotted time for a patient.

Also, an editorial in the American College of Chest Physicians' (pulmonologists') journal CHEST in 1999 was quite concerned about the Conundrums in Sleep Medicine. The author, then chair of her organization's Sleep Section, asked "What is required to set up a sleep laboratory? Money and a building! Anyone can open a sleep laboratory, and it seems that just about everyone is." On the accreditation process for sleep laboratories, she continues: "This accreditation, however, is currently not required by most states, or more importantly, by most insurance carriers for reimbursements... There is also an American Board of Sleep Medicine (ABSM) that certifies individuals as sleep specialists. This certification presumably makes those individuals more qualified to run a sleep laboratory; however, the certification is not required to run a laboratory or to read sleep studies." Her concern at the turn of the century was:

Not all patients with hypersomnia have sleep apnea, and other diagnoses may be missed if the physician is only trained to diagnose and treat sleep apnea. Also, when a physician runs a sleep laboratory, they are "assumed" to be a sleep expert and are asked to evaluate and treat all types of sleep disorders when they are not adequately trained to do so.

In the UK, knowledge of sleep medicine and possibilities for diagnosis and treatment seem to lag. Guardian.co.uk quotes the director of the Imperial College Healthcare Sleep Centre: "One problem is that there has been relatively little training in sleep medicine in this country – certainly there is no structured training for sleep physicians." The Imperial College Healthcare site shows attention to obstructive sleep apnea syndrome (OSA) and very few other disorders, specifically not including insomnia.

Training and certification

Worldwide

The World Federation of Sleep Research & Sleep Medicine Societies (WFSRSMS) was founded in 1987. As its name implies, members are concerned with basic and clinical research as well as medicine. Member societies in the Americas are the American Academy of Sleep Medicine (AASM), publisher of the Journal of Clinical Sleep Medicine; the Sleep Research Society (SRS), publisher of SLEEP; the Canadian Sleep Society (CSS) and the Federation of Latin American Sleep Societies (FLASS). WFSRSMS promotes both sleep research and physician training and education.

Africa

The Colleges of Medicine of South Africa (CMSA) provide the well-defined specialty Diploma in Sleep Medicine of the College of Neurologists of South Africa: DSM(SA), which was first promulgated by the Health Professions Council in 2007. The newly formed South African Society of Sleep Medicine (SASSM) was launched at its inaugural congress in February 2010. The society's membership is diverse; it includes general practitioners, ENT surgeons, pulmonologists, cardiologists, endocrinologists and psychiatrists.

Asia

WFSRSMS members in Asia include the Australasian Sleep Association (ASA) of New Zealand and Australia and the Asian Sleep Research Society (ASRS), an umbrella organization for the societies of several Asian nations.

Europe

The European Sleep Research Society (ESRS) is a member of the WFSRSMS. The Assembly of National Sleep Societies (ANSS), which includes both medical and scientific organizations from 26 countries as of 2007, is a formal body of the ESRS. The ESRS has published European Accreditation Guidelines for SMCs (Sleep Medicine Centres), the first of several proposed guidelines to coordinate and promote sleep science and medicine in Europe.

United States

Polysomnography (PSG) is a multi-parametric test used as a diagnostic tool in sleep medicine.

The American Academy of Sleep Medicine (AASM), founded in 1978, administered the certification process and sleep medicine examination for doctors until 1990. Its independent daughter entity the American Board of Sleep Medicine (ABSM) was incorporated in 1991 and took over the aforementioned responsibilities. As of 2007, the ABSM ceased administering its examination, as it conceded that an examination process recognized by the American Board of Medical Specialties (ABMS) was advantageous to the field. Candidates who passed the ABSM exam in 1978–2006 retain lifetime certification as Diplomates of that organization.

The American Board of Psychiatry and Neurology (ABPN), and the corresponding boards of Internal Medicine, of Pediatrics, and of Otolaryngology (ear, nose and throat, ENT) now administer collectively the Sleep Medicine Certification exam for their members. Each board supervises the required 12 months of formal training for its candidates, while the exam is administered to all of them at the same time in the same place. For the first five years, 2007–2011, during "grandfathering", there was a "practice pathway" for ABSM certified specialists while additional, coordinated requirements were to be added after 2011. The ABPN provides information about the pathways, requirements and the exam on its website. Additionally, there are currently four boards of the American Osteopathic Association Bureau of Osteopathic Specialists that administer Sleep Medicine Certification exams. The American Osteopathic boards of Family Medicine, Internal Medicine, Neurology & Psychiatry, and Ophthalmology & Otolaryngology grant certificates of added qualification to qualified candidate physicians.

Sleep medicine is now a recognized subspecialty within anesthesiology, internal medicine, family medicine, pediatrics, otolaryngology, psychiatry and neurology in the US. Certification in Sleep Medicine by the several "Member Boards" of the ABMS shows that the specialist:

has demonstrated expertise in the diagnosis and management of clinical conditions that occur during sleep, that disturb sleep, or that are affected by disturbances in the wake–sleep cycle. This specialist is skilled in the analysis and interpretation of comprehensive polysomnography, and well-versed in emerging research and management of a sleep laboratory.

Pulmonologists, already subspecialists within internal medicine, may be accepted to sit for the board and be certified in Sleep Medicine after just a six-month fellowship, building on their knowledge of sleep-related breathing problems, rather than the usual twelve-month fellowship required of other specialists.

Sleep dentistry (bruxism, snoring and sleep apnea), while not recognized as one of the nine dental specialties, qualifies for board-certification by the American Board of Dental Sleep Medicine (ABDSM). The resulting Diplomate status is recognized by the AASM, and these dentists are organized in the Academy of Dental Sleep Medicine (USA). The qualified dentists collaborate with sleep doctors at accredited sleep centers and can provide several types of oral appliances or upper airway surgery to treat or manage sleep-related breathing disorders as well as tooth-grinding and clenching.

Laboratories for sleep-related breathing disorders are accredited by the AASM and are required to follow the Code of Medical Ethics of the American Medical Association. The new and very detailed Standards for Accreditation are available online. Sleep disorder centers, or clinics, are accredited by the same body, whether hospital-based, university-based or "freestanding"; they are required to provide testing and treatment for all sleep disorders and to have on staff a sleep specialist who has been certified by the American Board of Sleep Medicine and otherwise meet similar standards.

Diagnostic methods

Pediatric polysomnography

The taking of a thorough medical history while keeping in mind alternative diagnoses and the possibility of more than one ailment in the same patient is the first step. Symptoms for very different sleep disorders may be similar and it must be determined whether any psychiatric problems are primary or secondary.

The patient history includes previous attempts at treatment and coping and a careful medication review. Differentiation of transient from chronic disorders and primary from secondary ones influences the direction of evaluation and treatment plans.

The Epworth Sleepiness Scale (ESS), designed to give an indication of sleepiness and correlated with sleep apnea, or other questionnaires designed to measure excessive daytime sleepiness, are diagnostic tools that can be used repeatedly to measure results of treatment.

A sleep diary, also called sleep log or sleep journal, kept by a patient at home for at least two weeks, while subjective, may help determine the extent and nature of sleep disturbance and the level of alertness in the normal environment. A parallel journal kept by a parent or bed partner, if any, can also be helpful. Sleep logs can also be used for self-monitoring and in connection with behavioral and other treatment. The image at the top of this page, with nighttime in the middle and the weekend in the middle, shows a layout that can aid in noticing trends

An actigraph unit is a motion-sensing device worn on the wrist, generally for one or two weeks. It gives a gross picture of sleep-wake cycles and is often used to verify the sleep diary. It is cost-efficient when full polysomnography is not required.

Polysomnography is performed in a sleep laboratory while the patient sleeps, preferably at his or her usual sleeping time. The polysomnogram (PSG) objectively records sleep stages and respiratory events. It shows multiple channels of electroencephalogram (EEG), electrooculogram (EOG), electrocardiogram (ECG), nasal and oral airflow, abdominal, chest and leg movements and blood oxygen levels. A single part of a polysomnogram is sometimes measured at home with portable equipment, for example oximetry, which records blood oxygen levels throughout the night. Polysomnography is not routinely used in the evaluation of patients with insomnia or circadian rhythm disorders, except as needed to rule out other disorders. It will usually be a definitive test for sleep apnea.

Home Sleep Tests (HST)or Home Sleep Apnea Tests (HSAT) are types of sleep studies that can be performed in a patient's home to identify obstructive sleep apnea. These devices are increasing in utilization due to their convenience and cost effectiveness.

A Multiple Sleep Latency Test (MSLT) is often performed during the entire day after polysomnography while the electrodes and other equipment are still in place. The patient is given nap opportunities every second hour; the test measures the number of minutes it takes from the start of a daytime nap period to the first signs of sleep. It is a measure of daytime sleepiness; it also shows whether REM sleep is achieved in a short nap, a typical indication of narcolepsy.

Imaging studies may be performed if a patient is to be evaluated for neurodegenerative disease or to determine the obstruction in obstructive sleep apnea.

Sleep Questionnaires: There are some validated questionnaires in sleep medicine such as:

• Tayside children's sleep questionnaire: A ten-item questionnaire for sleep disorders in children aged between one and five years old
• Children's Sleep Habits Questionnaire
• Cleveland Adolescent Sleepiness Questionnaire (CASQ): There are 16 items to measure extreme sleepiness during the day in adolescents aged 11–17 years old.

Treatments

CPAP (positive airway pressure) machine

 

Normison (temazepam) is a benzodiazepine commonly prescribed for insomnia and other sleep disorders.

When sleep complaints are secondary to pain, other medical or psychiatric diagnoses, or substance abuse, it may be necessary to treat both the underlying cause and the sleep problems.

When the underlying cause of sleep problems is not immediately obvious, behavioral treatments are usually the first suggested. These range from patient education about sleep hygiene to cognitive behavioral therapy (CBT). Studies of both younger and older adults have compared CBT to medication and found that CBT should be considered a first-line and cost-effective intervention for chronic insomnia, not least because gains may be maintained at long-term follow-up. Sleep physicians and psychologists, at least in the US, are not in agreement about who should perform CBT nor whether sleep centers should be required to have psychologists on staff. In the UK the number of CBT-trained therapists is limited so CBT is not widely available on the NHS.

Behavioral therapies include progressive relaxation, stimulus control (to reassociate the bed with sleepiness), limiting time-in-bed to increase sleep efficiency and debunking misconceptions about sleep.

Pharmacotherapy is necessary for some conditions. Medication may be useful for acute insomnia and for some of the parasomnias. It is almost always needed, along with scheduled short naps and close follow-up, in the treatment of narcolepsy and idiopathic hypersomnia.

Chronic circadian rhythm disorders, the most common of which is delayed sleep phase disorder, may be managed by specifically-timed bright light therapy, usually in the morning, darkness therapy in the hours before bedtime, and timed oral administration of the hormone melatonin. Chronotherapy has also been prescribed for circadian rhythm disorders, though results are generally short-lived. Stimulants may also be prescribed. When these therapies are unsuccessful, counseling may be indicated to help a person adapt to and live with the condition. People with these disorders who have chosen a lifestyle in conformity with their sleeping schedules have no need of treatment, though they may need the diagnosis in order to avoid having to meet for appointments or meetings during their sleep time.

Continuous positive airway pressure (CPAP), Bilevel Continuous Positive Airway Pressure (BiPAP), or similar machines can be used nightly at home to effectively manage sleep-related breathing disorders such as apnea. In milder cases, oral appliances may be effective alternate treatments. For mild cases in obese people, weight reduction may be sufficient, but it is usually recommended as an adjunct to CPAP treatment since sustaining weight loss is difficult. In some cases, upper airway surgery, generally performed by an otolaryngologist/head & neck surgeon or occasionally an oral and maxillofacial surgeon, is indicated. The treatments prevent airway collapse, which interrupts breathing during sleep. A 2001 study published by Hans-Werner Gessmann in the Journal of Sleep Medicine and Sleep Psychology found that patients who practiced a series of electrical stimulations of suprahyoidal tongue muscles for 20 minutes a day showed a marked decline in sleep apnea symptoms after two months. Patients experienced an average of 36% fewer apnea episodes after successfully completing the treatments.

According to the National Cancer Institute (NCI), about 50% of cancer patients have trouble sleeping. Difficulty sleeping can include Restless Leg Syndrome (RLS), sleeping that is fragmented, or insomnia. Some reports show that up to 80% of patients who are undergoing cancer treatments experience some form of insomnia. One of the significant reasons for sleeping problems is stress, uncertainty, and fear. Other patients have difficulty sleeping directly due to their treatments while others experience pain that affects sleep quality. Other factors include diet and less than optimum sleeping conditions. Cancer has also been shown to be a cause of increased sleep apnea, which adds to the potential issues.

See also

• American Academy of Sleep Medicine
• Environmental noise health effects
• Polysomnographic technician
• Reversed vegetative symptoms
• Sleep study
• Sundowning (dementia)
• White noise machine