The first case of eosinophilia–myalgia syndrome was reported to the Centers for Disease Control and Prevention (CDC) in November 1989, although some cases had occurred as early as 2–3 years before this. In total, more than 1,500 cases of EMS were reported to the CDC, as well as at least 37 EMS-associated deaths. After preliminary investigation revealed that the outbreak was linked to intake of tryptophan, the U.S. Food and Drug Administration (FDA) recalled tryptophan supplements in 1989 and banned most public sales in 1990, with other countries following suit.

Subsequent epidemiological studies suggested that EMS was linked to specific batches of L-tryptophan supplied by a single large Japanese manufacturer, Showa Denko. It eventually became clear that recent batches of Showa Denko's L-tryptophan were contaminated by trace impurities, which were subsequently thought to be responsible for the 1989 EMS outbreak. While a total of 60 trace contaminants were eventually identified, only 6 of them were associated with EMS. The compound EBT (1,1'-ethylidene-bis-L-tryptophan, also known as "Peak E") was the only contaminant identifiable by initial analysis, but further analysis revealed PAA (3-(phenylamino)-L-alanine, also known as "UV-5"), and peak 200 (2[3-indolyl-methyl]-L-tryptophan). Two of the remaining uncharacterized peaks associated with EMS have been labeled "UV-28" and "peak AAA", with peak AAA being "the contaminant most significantly associated with EMS". The specific impurity or impurities responsible for the toxic effects was never firmly established. EBT has been frequently implicated as the culprit, but there is no statistically significant association between EBT levels and EMS.

As most research has focused on attempts to associate individual contaminants with EMS, there is a lack of detailed research on other possible contributing factors. Tryptophan itself has been implicated as a potentially major contributory factor in EMS. While critics of this theory have argued that this hypothesis fails to explain the near-absent reports of EMS prior to and following the EMS outbreak, this fails to take into account the sudden rapid increase in tryptophan's usage immediately prior to the 1989 outbreak, and ignores the strong influence of the EMS outbreak's legacy and the extended FDA ban on later usage of tryptophan. Crucially, this also ignores the existence of a number of cases of EMS that developed both prior to and after the primary epidemic, including at least one case where the tryptophan was tested and found to lack the contaminants found in the contaminated lots of Showa Denko's tryptophan, as well as cases with other supplements inducing EMS, and even a case of EMS induced by excessive dietary L-tryptophan intake via overconsumption of cashew nuts. A major Canadian analysis located a number of patients that met the CDC criteria for EMS but had never been exposed to tryptophan, which "brings causal interpretations of earlier studies into question". Other research highlighted numerous major flaws in many of the epidemiological studies on the association of tryptophan with EMS, which cast serious doubt on the validity of their results. As the FDA concluded, "other brands of L-tryptophan, or L-tryptophan itself, regardless of the levels or presence of impurities, could not be eliminated as causal or contributing to the development of EMS". Even animal studies have suggested that tryptophan itself "when ingested by susceptible individuals either alone or in combination with some other component in the product, results in the pathological features in EMS".

At the time of the outbreak, Showa Denko had recently made alterations to its manufacturing procedures that were thought to be linked to the possible origin of the contaminants detected in the affected lots of tryptophan. A key change was the reduction of the amount of activated charcoal used to purify each batch from >20 kg to 10 kg. A portion of the contaminated batches had also bypassed another filtration step that used reverse-osmosis to remove certain impurities. Additionally, the bacterial culture used to synthesize tryptophan was a strain of "Bacillus amyloliquefaciens" had been genetically engineered to increase tryptophan production. Although the prior four generations of the genetically engineered strain had been used without incident, the fifth generation used for the contaminated batches was thought to be a possible source of the impurities that were detected. This has been misused to argue that the genetic engineering itself was the primary cause of the contamination, a stance that was heavily criticized for overlooking the other known non-GMO causes of contamination, as well as for its use by anti-GMO activists as a way to threaten the development of biotechnology with false information. The reduction in the amount of activated carbon used and the introduction of the fifth generation "Bacillus amyloliquefaciens" strain were both associated with the development of EMS, but due to the high overlap of these changes, the precise independent contribution of each change could not be determined (although the bypass of the reverse-osmosis filtration for certain lots was determined to be not significantly associated with the contaminated lots of tryptophan). While Showa Denko claimed a purity of 99.6%, it was noted that "the quantities of the known EMS associated contaminants, EBT and PAA, were remarkably small, of the order of 0.01%, and could easily escape detection".

The dexamethasone suppression test involves administering dexamethasone, a synthetic glucocorticoid, to the horse, and measuring its serum cortisol levels before and 19–24 hours after injection. In a normal horse, dexamethasone administration results in negative feedback to the pituitary, resulting in decreased ACTH production from the pars distalis and, therefore, decreased synthesis of cortisol at the level of the adrenal gland. A horse with PPID, which has an overactive pars intermedia not regulated by glucocorticoid levels, does not suppress ACTH production and, therefore, cortisol levels remain high. False negatives can occur in early disease. Additionally, dexamethasone administration may increase the risk of laminitis in horses already prone to the disease. For these reasons, the dexamethasone suppression test is currently not recommended for PPID testing.

Due to the strong link between PPID and insulin resistance, testing is recommended for all horses suspected or confirmed to be suffering from PPID. There are two tests commonly used for insulin resistance: the oral sugar test and fasting insulin blood concentration.

The fasting insulin concentration involves giving a horse a single flake of hay at 10 pm the night before testing, with blood being drawn the following morning. Both insulin and glucose blood levels are measured. Hyperinsulinemia suggests insulin resistance, but normal or low fasting insulin does not rule out PPID. This test is easy to perform, but is less sensitive than the oral sugar test. It is best used in cases where risks of laminitis make the oral sugar test potentially unsafe.

The oral sugar test also requires giving the horse only a single flake of hay at 10pm the night before the test. The following morning, karo corn syrup is given orally, and glucose and insulin levels are measured at 60 and 90 minutes after administration. Normal or excessively high insulin levels are diagnostic. However, equivocal test results require retesting at a later date, or performing a different test. A similar test is available outside the US, in areas where corn-syrup products are less readily available, where horses are given a morning meal of chaff with dextrose powder, and blood insulin levels are measured 2 hours later.

Other imaging tools have been used to show mechanical deviations in laminitis cases include computed tomography, as well as MRI, which also provides some physiologic information. Nuclear scintigraphy may also be useful in certain situations. Ultrasonography has been explored as a way to quantify changes in bloodflow to the foot.

Radiographs are an important part of evaluating the laminitic horse. They not only allow the practitioner to determine the severity of the episode, which does not always correlate with degree of pain, but also to gauge improvement and response to treatment. Several measurements are made to predict severity. Additionally, radiographs also allow the visualization and evaluation of the hoof capsule, and can help detect the presence of a lamellar wedge or seromas. The lateral view provides the majority of the information regarding degree of rotation, sole depth, dorsal hoof wall thickness, and vertical deviation. A 65-degree dorsopalmar view is useful in the case of chronic laminitis to evaluate the rim of the coffin bone for pathology.

- Radiographic measurements

Several radiographic measurements, made on the lateral view, allow for objective evaluation of the episode.

1. "Coronary extensor distance (CE)": the vertical distance from the level of the proximal coronary band to the extensor process of P3. It is often used to compare progression of the disease over time, rather than as a stand-alone value. A rapidly increasing CE value can indicate distal displacement (sinking) of the coffin bone, while a more gradual increase in CE can occur with foot collapse. Normal values range from 0–30 mm, with most horses >12–15 mm.

2. "Sole depth (SD)": the distance from the tip of P3 to the ground.

3. "Digital breakover (DB)": distance from the tip of P3 to the breakover of the hoof (dorsal toe).

4. "Palmar angle (PA)": the angle between a line perpendicular to the ground, and a line at the angle of the palmar surface of P3.

5. "Horn:lamellar distance (HL)": the measurement from the most superficial aspect of the dorsal hoof wall to the face of P3. 2 distances are compared: a proximal measurement made just distal to the extensor process of P3, and a distal measurement made toward the tip of P3. These two values should be similar. In cases of rotation, the distal measurement will be higher than the proximal. In cases of distal displacement, both values will increase, but may remain equal. Therefore, it is ideal to have baseline radiographs for horses, especially for those at high-risk for laminitis, to compare to should laminitis ever be suspected. Normal HL values vary by breed and age:

- Weanlings will have a greater proximal HL compared to distal HL

- Yearlings will have approximately equal proximal and distal HL

- Thoroughbreds are usually 17mm proximally, and 19mm distally

- Standardbreds have been shown to have a similar proximal and distal HL, around 16 mm at 2 years old, and 20 mm at 4 years old

- Warmbloods have similar proximal and distal values, up to 20 mm each

- HL tends to increase with age, up to 17 mm in most light breeds, or higher, especially in very old animals

- Venograms

Venograms can help determine the prognosis for the animal, particularly in horses where the degree of pain does not match the radiographic changes. In venography, a contrast agent, visible on radiographs, is injected into the palmar digital vein to delineate the vasculature of the foot. The venogram can assess the severity and location of tissue compromise and monitor effectiveness of the current therapy. Compression of veins within the hoof will be seen as sections that do not contain contrast material. Poor or improper blood flow to different regions of the hoof help determine the severity of the laminitic episode. Venography is especially useful for early detection of support limb laminitis, as changes will be seen on venograph (and MRI) within 1–2 weeks, whereas clinical signs and radiographic changes do not manifest until 4–6 weeks.

Horses undergoing venography have plain radiographs taken beforehand to allow for comparison. The feet are blocked to allow the sedated horse to stand comfortably during the procedure. Prior to injection, a tourniquet is placed around the fetlock to help keep the contrast material within the foot during radiography. Diffusion of contrast may make some areas appear hypoperfused, falsely increasing the apparent severity of the laminitic episode. After injection of the contrast material, films are taken within 45 seconds to avoid artifact caused by diffusion. Evaluation of blood supply to several areas of the foot allows the practitioner to distinguish mild, moderate, and severe compromise of the hoof, chronic laminitis, and sinking.

Smith (2015) conducted a study that looked into specific biological markers that correlate to Moyamoya disease. Some of the categories of these biomarkers include phenotypes - conditions commonly related to Moyamoya, radiographical markers for the diagnosis of Moyamoya, and proteins as well as cellular changes that occur in cases of Moyamoya.

Similar to Moyamoya Disease, there are conditions that are closely associated with Moyamoya Syndrome. Some of the more common medical conditions that are closely associated with Moyamoya Syndrome include trisomy 21 (Down's Syndrome), sickle cell disease, and neurofibromatosis type 1. There is also evidence that identifies hyperthyroidism and congenital dwarfing syndromes as two of the more loosely associated syndromes that correlate with the possibility of being diagnosed with Moyamoya Disease later in life.

There is also research that has shown that certain radiographic biomarkers that lead to the diagnosis of Moyamoya Disease have been identified. The specific radiographic markers are now considered an acceptable key component to Moyamoya Disease and have been added to the INternational Classification of Diseases (ICD). These biomarkers of Moyamoya are "stenosis of the distal ICA's up to and including the bifurcation, along with segments of the proximal ACA and MCA...dilated basal collateral vessels must be present" Some other common findings that have not been added to the classification index of those with Moyamoya Disease which are found using radiography involve very distinct changes in the vessels of the brain. These changes include newly formed vessels made to compensate for another change noted, ischemia and cerebrovascular reserve, both found on MRI. Functional changes include evidence of ischemia in vessels of the brain (ICA, ACA, MCA, specifically). It is important to also note that the radiographic biomarkers, in order to be classified as Moyamoya Disease, all findings must be bilateral. If this is not the case and the findings are unilateral, it is diagnosed as Moyamoya Syndrome.

There are also several protein biomarkers that have been linked to the Moyamoya Disease diagnosis. Although the sample size of the studies performed are small due to the rarity of the disease, the findings are indicative of a correlation between the disease and several specific protein biomarkers. Other studies have confirmed the correlation of Moyamoya and adhesion molecule 1 (ICAM-1) being increased as compared to normal vascular function counterparts Furthermore, it has been concluded that the localization of inflammatory cells suggests that the inflammation stimulus iteself may be responsible for the proliferation and occlusion in the ICA, ACA, and MCA found in those with Moyamoya Disease.

Given the constant threat of bioterrorist related events, there is an urgent need to develop pulmonary protective and reparative agents that can be used by first responders in a mass casualty setting. Use in such a setting would require administration via a convenient route for e.g. intramuscular via epipens. Other feasible routes of administration could be inhalation and perhaps to a lesser extent oral – swallowing can be difficult in many forms of injury especially if accompanied by secretions or if victim is nauseous. A number of in vitro and in vivo models lend themselves to preclinical evaluation of novel pulmonary therapies.

The diagnosis of moyamoya is suggested by CT, MRI, or angiogram results. Contrast-enhanced T1-weighted images are better than FLAIR images for depicting the leptomeningeal ivy sign in moyamoya disease. MRI and MRA should be performed for the diagnosis and follow-up of moyamoya disease. Diffusion-weighted imaging can also be used for following the clinical course of children with moyamoya disease, in whom new focal deficits are highly suspicious of new infarcts.

Proliferation of smooth muscle cells in the walls of the Moyamoya affected arteries has been found to be representative of the disease. A study of six autopsies of six patients who died from Moyamoya disease lead to the finding that there is evidence that supports the theory that there is a thickening, or proliferation, of the innermost layer of the vessels affected by Moyamoya. These vessels are the ACA (anterior cerebral artery), MCA (middle cerebral artery), and ICA (internal carotid artery). The occlusion of the ICA results in concomitant diminution of the "puff-of-smoke" collaterals, as they are supplied by the ICA.

Often nuclear medicine studies such as SPECT (single photon emission computerized tomography) are used to demonstrate the decreased blood and oxygen supply to areas of the brain involved with moyamoya disease. Conventional angiography provided the conclusive diagnosis of moyamoya disease in most cases and should be performed before any surgical considerations.

Dr. Darren B. Orbach, MD, PhD explains how the disease progresses as well as the role angiography plays in detecting the progression of Moyamoya in a short video

Specific pretreatments, drugs to prevent chemically induced lung injuries due to respiratory airway toxins, are not available. Analgesic medications, oxygen, humidification, and ventilator support currently constitute standard therapy. In fact, mechanical ventilation remains the therapeutic mainstay for acute inhalation injury. The cornerstone of treatment is to keep the PaO2 > 60 mmHg (8.0 kPa), without causing injury to the lungs with excessive O2 or volutrauma. Pressure control ventilation is more versatile than volume control, although breaths should be volume limited, to prevent stretch injury to the alveoli. Positive end-expiratory pressure (PEEP) is used in mechanically ventilated patients with ARDS to improve oxygenation. Hemorrhaging, signifying substantial damage to the lining of the airways and lungs, can occur with exposure to highly corrosive chemicals and may require additional medical interventions. Corticosteroids are sometimes administered, and bronchodilators to treat bronchospasms. Drugs that reduce the inflammatory response, promote healing of tissues, and prevent the onset of pulmonary edema or secondary inflammation may be used following severe injury to prevent chronic scarring and airway narrowing.

Although current treatments can be administered in a controlled hospital setting, many hospitals are ill-suited for a situation involving mass casualties among civilians. Inexpensive positive-pressure devices that can be used easily in a mass casualty situation, and drugs to prevent inflammation and pulmonary edema are needed. Several drugs that have been approved by the FDA for other indications hold promise for treating chemically induced pulmonary edema. These include β2-agonists, dopamine, insulin, allopurinol, and non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen. Ibuprofen is particularly appealing because it has an established safety record and can be easily administered as an initial intervention. Inhaled and systemic forms of β2-agonists used in the treatment of asthma and other commonly used medications, such as insulin, dopamine, and allopurinol have also been effective in reducing pulmonary edema in animal models but require further study. A recent study documented in the "AANA Journal" discussed the use of volatile anesthetic agents, such as sevoflurane, to be used as a bronchodilator that lowered peak airway pressures and improved oxygenation. Other promising drugs in earlier stages of development act at various steps in the complex molecular pathways underlying pulmonary edema. Some of these potential drugs target the inflammatory response or the specific site(s) of injury. Others modulate the activity of ion channels that control fluid transport across lung membranes or target surfactant, a substance that lines the air sacs in the lungs and prevents them from collapsing. Mechanistic information based on toxicology, biochemistry, and physiology may be instrumental in determining new targets for therapy. Mechanistic studies may also aid in the development of new diagnostic approaches. Some chemicals generate metabolic byproducts that could be used for diagnosis, but detection of these byproducts may not be possible until many hours after initial exposure. Additional research must be directed at developing sensitive and specific tests to identify individuals quickly after they have been exposed to varying levels of chemicals toxic to the respiratory tract.

Currently there are no clinically approved agents that can reduce pulmonary and airway cell dropout and avert the transition to pulmonary and /or airway fibrosis.

A recent study by Salcido et al. (2010) ascertained rearrest in all initial and rearrest rhythms treated by any level of Emergency Medical Service (EMS), finding a rearrest rate of 36% and a lower but not significantly different rate of survival to hospital discharge in cases with rearrest compared to those without rearrest.

Current research seeks to predict the event of rearrest after patients have already achieved ROSC. Biosignals, such as electrocardiogram (ECG), have the potential to predict the onset of rearrest and are currently being investigated to preemptively warn health care providers that rearrest could be imminent.

A stronger pulse detector would also contribute to lowering the rate of rearrest. If the resuscitator could accurately know when the patient has achieved ROSC, there would be less instances of chest compressions being provided when a native pulse is present.

Cardiac arrest is synonymous with clinical death.

A cardiac arrest is usually diagnosed clinically by the absence of a pulse. In many cases lack of carotid pulse is the gold standard for diagnosing cardiac arrest, as lack of a pulse (particularly in the peripheral pulses) may result from other conditions (e.g. shock), or simply an error on the part of the rescuer. Nonetheless, studies have shown that rescuers often make a mistake when checking the carotid pulse in an emergency, whether they are healthcare professionals or lay persons.

Owing to the inaccuracy in this method of diagnosis, some bodies such as the European Resuscitation Council (ERC) have de-emphasised its importance. The Resuscitation Council (UK), in line with the ERC's recommendations and those of the American Heart Association,

have suggested that the technique should be used only by healthcare professionals with specific training and expertise, and even then that it should be viewed in conjunction with other indicators such as agonal respiration.

Various other methods for detecting circulation have been proposed. Guidelines following the 2000 International Liaison Committee on Resuscitation (ILCOR) recommendations were for rescuers to look for "signs of circulation", but not specifically the pulse. These signs included coughing, gasping, colour, twitching and movement. However, in face of evidence that these guidelines were ineffective, the current recommendation of ILCOR is that cardiac arrest should be diagnosed in all casualties who are unconscious and not breathing normally. Another method is to use molecular autopsy or postmortem molecular testing which uses a set of molecular techniques to find the ion channels that are cardiac defective.

Comas can last from several days to several weeks. In more severe cases a coma may last for over five weeks, while some have lasted as long as several years. After this time, some patients gradually come out of the coma, some progress to a vegetative state, and others die. Some patients who have entered a vegetative state go on to regain a degree of awareness. Others remain in a vegetative state for years or even decades (the longest recorded period being 42 years).

The outcome for coma and vegetative state depends on the cause, location, severity and extent of neurological damage. A deeper coma alone does not necessarily mean a slimmer chance of recovery, because some people in deep coma recover well while others in a so-called milder coma sometimes fail to improve.

People may emerge from a coma with a combination of physical, intellectual, and psychological difficulties that need special attention. Recovery usually occurs gradually—patients acquire more and more ability to respond. Some patients never progress beyond very basic responses, but many recover full awareness. Regaining consciousness is not instant: in the first days, patients are only awake for a few minutes, and duration of time awake gradually increases. This is unlike the situation in many movies where people who awake from comas are instantly able to continue their normal lives. In reality, the coma patient awakes sometimes in a profound state of confusion, not knowing how they got there and sometimes suffering from dysarthria, the inability to articulate any speech, and with many other disabilities.

Predicted chances of recovery are variable owing to different techniques used to measure the extent of neurological damage. All the predictions are based on statistical rates with some level of chance for recovery present: a person with a low chance of recovery may still awaken. Time is the best general predictor of a chance of recovery: after four months of coma caused by brain damage, the chance of partial recovery is less than 15%, and the chance of full recovery is very low.

The most common cause of death for a person in a vegetative state is secondary infection such as pneumonia, which can occur in patients who lie still for extended periods.

There are reports of patients coming out of coma after long periods of time. After 19 years in a minimally conscious state, Terry Wallis spontaneously began speaking and regained awareness of his surroundings.

A brain-damaged man, trapped in a coma-like state for six years, was brought back to consciousness in 2003 by doctors who planted electrodes deep inside his brain. The method, called deep brain stimulation (DBS) successfully roused communication, complex movement and eating ability in the 38-year-old American man who suffered a traumatic brain injury. His injuries left him in a minimally conscious state (MCS), a condition akin to a coma but characterized by occasional, but brief, evidence of environmental and self-awareness that coma patients lack.

Comas lasting seconds to minutes result in post-traumatic amnesia (PTA) that lasts hours to days; recovery plateau occurs over days to weeks.

Comas that last hours to days result in PTA lasting days to weeks; recovery plateau occurs over months.

Comas lasting weeks result in PTA that lasts months; recovery plateau occurs over months to years.

A coma can be classified as (1) supratentorial (above Tentorium cerebelli), (2) infratentorial (below Tentorium cerebelli), (3) metabolic or (4) diffused. This classification is merely dependent on the position of the original damage that caused the coma, and does not correlate with severity or the prognosis.

The severity of coma impairment however is categorized into several levels. Patients may or may not progress through these levels. In the first level, the brain responsiveness lessens, normal reflexes are lost, the patient no longer responds to pain and cannot hear.

The Rancho Los Amigos Scale is a complex scale that has eight separate levels, and is often used in the first few weeks or months of coma while the patient is under closer observation, and when shifts between levels are more frequent.

Clinicians classify cardiac arrest into "shockable" versus "non–shockable", as determined by the ECG rhythm. This refers to whether a particular class of cardiac dysrhythmia is treatable using defibrillation. The two "shockable" rhythms are ventricular fibrillation and pulseless ventricular tachycardia while the two "non–shockable" rhythms are asystole and pulseless electrical activity.