<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Angina and can you explain it in depth? [/INST] Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease.Angina is typically the result of obstruction or spasm of the arteries that supply blood to the heart muscle. The main mechanism of coronary artery obstruction is atherosclerosis as part of coronary artery disease. Other causes of angina include abnormal heart rhythms, heart failure and, less commonly, anemia. The term derives from the Latin angere ("to strangle") and pectus ("chest"), and can therefore be translated as "a strangling feeling in the chest".
The severity of angina pain does not always match the degree of oxygen deprivation to the heart or the risk of a myocardial infarction (heart attack). Some people may experience severe pain even though there is little or no risk of a heart attack. Others may have a heart attack and experience little or no pain. In some cases, angina can be quite severe. Worsening angina attacks, sudden-onset angina at rest, and angina lasting more than 15 minutes are symptoms of unstable angina (usually grouped with similar conditions as the acute coronary syndrome). As these may precede a heart attack, they require urgent medical attention and are, in general, treated similarly to myocardial infarction.In the early 20th century, severe angina was seen as a sign of impending death.  However, modern medical therapies have improved the outlook substantially. Middle-age patients who experience moderate to severe angina (grading by classes II, III, and IV) have a five-year survival rate of approximately 92%.

Classification
Stable angina
Also known as effort angina, this refers to the classic type of angina related to myocardial ischemia. A typical presentation of stable angina is that of chest discomfort and associated symptoms precipitated by some activity (running, walking, etc.) with minimal or non-existent symptoms at rest or after administration of sublingual nitroglycerin. Symptoms typically abate several minutes after activity and recur when activity resumes. In this way, stable angina may be thought of as being similar to intermittent claudication symptoms. Other recognized precipitants of stable angina include cold weather, heavy meals, and emotional stress.

Unstable angina
Unstable angina (UA) (also "crescendo angina"; this is a form of acute coronary syndrome) is defined as angina pectoris that changes or worsens.It has at least one of these three features:

it occurs at rest (or with minimal exertion), usually lasting more than 10 minutes
it is severe and of new-onset (i.e., within the prior 4–6 weeks)
it occurs with a crescendo pattern (i.e., distinctly more severe, prolonged, or frequent than before).UA may occur unpredictably at rest, which may be a serious indicator of an impending heart attack. What differentiates stable angina from unstable angina (other than symptoms) is the pathophysiology of the atherosclerosis. The pathophysiology of unstable angina is the reduction of coronary flow due to transient platelet aggregation on apparently normal endothelium, coronary artery spasms, or coronary thrombosis. The process starts with atherosclerosis, progresses through inflammation to yield an active unstable plaque, which undergoes thrombosis and results in acute myocardial ischemia, which, if not reversed, results in cell necrosis (infarction). Studies show that 64% of all unstable anginas occur between 22:00 and 08:00 when patients are at rest.In stable angina, the developing atheroma is protected with a fibrous cap. This cap may rupture in unstable angina, allowing blood clots to precipitate and further decrease the area of the coronary vessels lumen. This explains why, in many cases, unstable angina develops independently of activity.

Microvascular angina
Microvascular angina, also known as cardiac syndrome X, is characterized by angina-like chest pain, in the context of normal epicardial coronary arteries (the largest vessels on the surface of the heart, prior to significant branching) on angiography. The original definition of cardiac syndrome X also mandated that ischemic changes on exercise (despite normal coronary arteries) were displayed, as shown on cardiac stress tests. The primary cause of microvascular angina is unknown, but factors apparently involved are endothelial dysfunction and reduced flow (perhaps due to spasm) in the tiny "resistance" blood vessels of the heart. Since microvascular angina is not characterized by major arterial blockages, it is harder to recognize and diagnose. Microvascular angina was previously considered a rather benign condition, but more recent data has changed this attitude. Studies, including the Womens Ischemia Syndrome Evaluation (WISE), suggest that microvascular angina is part of the pathophysiology of ischemic heart disease, perhaps explaining the higher rates of angina in women than in men, as well as their predilection towards ischemia and acute coronary syndromes in the absence of obstructive coronary artery disease.

Signs and symptoms
Angina pectoris can be quite painful, but many patients with angina complain of chest discomfort rather than actual pain: the discomfort is usually described as a pressure, heaviness, tightness, squeezing, burning, or choking sensation. Apart from chest discomfort, anginal pains may also be experienced in the epigastrium (upper central abdomen), back, neck area, jaw, or shoulders. This is explained by the concept of referred pain and is because the spinal level that receives visceral sensation from the heart simultaneously receives cutaneous sensation from parts of the skin specified by that spinal nerves dermatome, without an ability to discriminate the two. Typical locations for referred pain are arms (often inner left arm), shoulders, and neck into the jaw. Angina is typically precipitated by exertion or emotional stress. It is exacerbated by having a full stomach and by cold temperatures. Pain may be accompanied by breathlessness, sweating, and nausea in some cases. In this case, the pulse rate and the blood pressure increases. Chest pain lasting only a few seconds is normally not angina (such as precordial catch syndrome).
Myocardial ischemia comes about when the myocardium (the heart muscle) receives insufficient blood and oxygen to function normally either because of increased oxygen demand by the myocardium or because of decreased supply to the myocardium. This inadequate perfusion of blood and the resulting reduced delivery of oxygen and nutrients are directly correlated to blocked or narrowed blood vessels.
Some experience "autonomic symptoms" (related to increased activity of the autonomic nervous system) such as nausea, vomiting, and pallor.
Major risk factors for angina include cigarette smoking, diabetes, high cholesterol, high blood pressure, sedentary lifestyle, and family history of premature heart disease.
A variant form of angina—Prinzmetals angina—occurs in patients with normal coronary arteries or insignificant atherosclerosis. It is believed caused by spasms of the artery. It occurs more in younger women.Coital angina, also known as angina damour, is angina subsequent to sexual intercourse.  It is generally rare, except in patients with severe coronary artery disease.

Cause
Major risk factors
Routine counseling of adults by physicians to advise them to improve their diet and increase their physical activity has, in general, been found to induce only small changes in actual behavior. Therefore, as of 2012, The U.S. Preventive Services Task Force does not recommend routine lifestyle counseling of all patients without known cardiovascular disease, hypertension, hyperlipidemia, or diabetes, and instead recommends selectively counseling only those patients who seem most ready to make lifestyle changes and using available time with other patients to explore other types of intervention that would be more likely to have a preventative impact.
Conditions that exacerbate or provoke angina
One study found that smokers with coronary artery disease had a significantly increased level of sympathetic nerve activity when compared to those without. This is in addition to increases in blood pressure, heart rate, and peripheral vascular resistance associated with nicotine, which may lead to recurrent angina attacks. In addition, the Centers for Disease Control and Prevention (CDC) reports that the risk of CHD (Coronary heart disease), stroke, and PVD (Peripheral vascular disease) is reduced within 1–2 years of smoking cessation. In another study, it was found that, after one year, the prevalence of angina in smoking men under 60 after an initial attack was 40% less in those having quit smoking compared to those that continued.  Studies have found that there are short-term and long-term benefits to smoking cessation.

Other medical problems
Esophageal disorders
Gastroesophageal reflux disease (GERD)
Hyperthyroidism
Hypoxemia
Profound anemia
Uncontrolled hypertension

Other cardiac problems
Bradyarrhythmia
Hypertrophic cardiomyopathy
Tachyarrhythmia
Valvular heart diseaseMyocardial ischemia can result from:

a reduction of blood flow to the heart that can be caused by stenosis, spasm, or acute occlusion (by an embolus) of the hearts arteries.
resistance of the blood vessels. This can be caused by narrowing of the blood vessels; a decrease in radius. Blood flow is proportional to the radius of the artery to the fourth power.
reduced oxygen-carrying capacity of the blood, due to several factors such as a decrease in oxygen tension and hemoglobin concentration. This decreases the ability of hemoglobin to carry oxygen to myocardial tissue.Atherosclerosis is the most common cause of stenosis (narrowing of the blood vessels) of the hearts arteries and, hence, angina pectoris. Some people with chest pain have normal or minimal narrowing of heart arteries; in these patients, vasospasm is a more likely cause for the pain, sometimes in the context of Prinzmetals angina and syndrome X.
Myocardial ischemia also can be the result of factors affecting blood composition, such as the reduced oxygen-carrying capacity of blood, as seen with severe anemia (low number of red blood cells), or long-term smoking.

Pathophysiology
Angina results when there is an imbalance between the hearts oxygen demand and supply. This imbalance can result from an increase in demand (e.g., during exercise) without a proportional increase in supply (e.g., due to obstruction or atherosclerosis of the coronary arteries).
However, the pathophysiology of angina in females varies significantly as compared to males. Non-obstructive coronary disease is more common in females.

Diagnosis
Angina should be suspected in people presenting tight, dull, or heavy chest discomfort that is:
Retrosternal or left-sided, radiating to the left arm, neck, jaw, or back.
Associated with exertion or emotional stress and relieved within several minutes by rest.
Precipitated by cold weather or a meal.Some people present with atypical symptoms, including breathlessness, nausea, or epigastric discomfort, or burning. These atypical symptoms are particularly likely in older people, women, and those with diabetes.Anginal pain is not usually sharp or stabbing or influenced by respiration. Antacids and simple analgesics do not usually relieve the pain. If chest discomfort (of whatever site) is precipitated by exertion, relieved by rest, and relieved by glyceryl trinitrate, the likelihood of angina is increased.In angina patients momentarily not feeling any chest pain, an electrocardiogram (ECG) is typically normal unless there have been other cardiac problems in the past. During periods of pain, depression, or elevation of the ST segment may be observed. To elicit these changes, an exercise ECG test ("treadmill test") may be performed, during which the patient exercises to his/her maximum ability before fatigue, breathlessness, or pain intervenes; if characteristic ECG changes are documented (typically more than 1 mm of flat or downsloping ST depression), the test is considered diagnostic for angina. Even constant monitoring of the blood pressure and the pulse rate can lead to some conclusions regarding angina. The exercise test is also useful in looking for other markers of myocardial ischemia: blood pressure response (or lack thereof, in particular, a drop in systolic blood pressure), dysrhythmia, and chronotropic response. Other alternatives to a standard exercise test include a thallium scintigram or sestamibi scintigram (in patients unable to exercise enough for the treadmill tests, e.g., due to asthma or arthritis or in whom the ECG is too abnormal at rest) or stress echocardiography.
In patients in whom such noninvasive testing is diagnostic, a coronary angiogram is typically performed to identify the nature of the coronary lesion, and whether this would be a candidate for angioplasty, coronary artery bypass graft (CABG), treatment only with medication, or other treatments. In hospitalized patients with unstable angina (or the newer term of "high-risk acute coronary syndromes"), those with resting ischaemic ECG changes or those with raised cardiac enzymes such as troponin may undergo coronary angiography directly.

Treatment
Angina pectoris occurs as a result of coronary blood flow insufficiency in the face of increased oxygen demand. The principal goal in the prevention and relief of angina is to limit the oxygen requirement of the heart so it can meet the inadequate oxygen supply derived through the blood supplied from the stenosed or constricted arteries. The main goals of treatment in angina pectoris are relief of symptoms, slowing progression of the disease, and reduction of future events, especially heart attacks and death. Beta blockers (e.g., carvedilol, metoprolol, propranolol) have a large body of evidence in morbidity and mortality benefits (fewer symptoms, less disability, and longer life) and short-acting nitroglycerin medications have been used since 1879 for symptomatic relief of angina. There are differing course of treatments for the patient depending on the type of angina the patient has. However, this second can provide a brief overview of the types of medications provided for angina and the purpose by which they are prescribed.
Beta blockers, specifically B1 adrenergic blockers without intrinsic sympathomimetic activity are the most preferred for the angina treatment out of B1 selective and non-selective as well as B1 ISA agents. B1 blockers are cardioselective blocking agents such as Nevibolol, Atenolol, Metoprolol and Bisoprolol, which result in blocking cAMP in the heart muscle cells. The cAMP which plays a vital role in phosphorylating the ryanodine receptor and LTCC will usually increase Ca+2 levels in the heart muscle cells, which will then result in contraction is blocked. Therefore, B1 blockade decreases the HR and contraction of the heart muscle, making it need less oxygen demand.  An important thing to note is that the B1 cardioselective blockers are cardioselective and not cardio specific. This means that if the beta-adrenergic antagonist is prescribed in higher doses, it can lose the selectivity aspect and begin causing hypertension from B2 adrenergic stimulation of smooth muscle cells.  This is why in therapy for patients with angina, the vasodilatory organonitrates complement the use of B-blockers when prescribed the use of angina. The preference for Beta-1 cardioselective blockers is for B1 cardioselective blockers without instrinsic sympathetic activity. Beta blockers with intrinsic sympathetic activity will still do the beta blockade of the heart muscle cells and have a decreased ionotrophic and chronotropic effect, but this effect will be to a lesser extent than if the beta blocker did not have the instrinsic sympathetic activity. A common beta-blocker with ISA prescribed for the treatment of angina is Acebutolol.
Non-selective beta-adrenergic antagonists will yield the same action on B1 receptors, however will also act on B2 receptors. These medications, such as Propranolol and Nadolol, act on B1 receptors on smooth muscle cells as well. B1 blockade occurs in the smooth muscle cells. Specifically cAMP is responsible for inhibiting Myosin Light Kinase, the enzyme responsible for acting on Actin-Myosin. The inhibition of B1 will result in decreased levels of cAMP which will lead to increased levels of  Myosin Light Chain Kinase in the smooth muscle cells, the enzyme responsible for acting on Actin-Myosin and leading to contraction of the smooth muscle cell. This increased contraction of the smooth muscle cell from B1 blockade is not desirable since it explains the hypertension that may arise with patients taking that medication.
Calcium channel blockers act to decrease the hearts workload, and thus its requirement for oxygen by blocking the calcium channels of the heart muscle cell. With decreased intracellular calcium, the calcium-troponin complex does not form in the heart muscle cell and it does not contract, therefore reducing the need for oxygen.
The other class of medication that can be used to treat angina are the organic nitrates. Organic nitrates are used extensively to treat angina. They improve coronary blood flow of the coronary arteries (arteries which supply blood to the heart muscle) by reversing and preventing vasospasm, which increases the blood flow to the heart, improving perfusion and oxygen delivery to the heart associated with the pain of angina. These drugs also reduce systemic vascular resistance, of both veins and arteries but the veins to a greater extent. The decrease in the resistance of the arteries and veins decreases the myocardial oxygen demand, which also reduces myocardial oxygen demand.  Nitroglycerin is a potent vasodilator that decreases myocardial oxygen demand by decreasing the hearts workload. Nitroglycerin should not be given if certain inhibitors such as sildenafil, tadalafil, or vardenafil have been taken within the previous 12 hours as the combination of the two could cause a serious drop in blood pressure.
Treatments for angina are balloon angioplasty, in which the balloon is inserted at the end of a catheter and inflated to widen the arterial lumen. Stents to maintain the arterial widening are often used at the same time. Coronary bypass surgery involves bypassing constricted arteries with venous grafts. This is much more invasive than angioplasty.
Calcium channel blockers (such as nifedipine (Adalat) and amlodipine), isosorbide mononitrate and nicorandil are vasodilators commonly used in chronic stable angina. A new therapeutic class, called If inhibitor, has recently been made available: Ivabradine provides heart rate reduction without affecting contractility leading to major anti-ischemic and antianginal efficacy. ACE inhibitors are also vasodilators with both symptomatic and prognostic benefit. Statins are the most frequently used lipid/cholesterol modifiers, which probably also stabilize existing atheromatous plaque. Low-dose aspirin decreases the risk of heart attack in patients with chronic stable angina, and was part of standard treatment. However, in patients without established cardiovascular disease, the increase in hemorrhagic stroke and gastrointestinal bleeding offsets any benefits and it is no longer advised unless the risk of myocardial infarction is very high.Exercise is also a very good long-term treatment for the angina (but only particular regimens – gentle and sustained exercise rather than intense short bursts), probably working by complex mechanisms such as improving blood pressure and promoting coronary artery collateralisation.
Though sometimes used by patients, evidence does not support the use of traditional Chinese herbal products (THCP) for angina.Identifying and treating risk factors for further coronary heart disease is a priority in patients with angina. This means testing for elevated cholesterol and other fats in the blood, diabetes and hypertension (high blood pressure), and encouraging smoking cessation and weight optimization.
The calcium channel blocker nifedipine prolongs cardiovascular event- and procedure-free survival in patients with coronary artery disease. New overt heart failures were reduced by 29% compared to placebo; however, the mortality rate difference between the two groups was statistically insignificant.

Microvascular angina in women
Women with myocardial ischemia often have either no or atypical symptoms, such as palpitations, anxiety, weakness, and fatigue. Additionally, many women with angina are found to have cardiac ischemia, yet no evidence of obstructive coronary artery disease on cardiac catheterization. Evidence is accumulating that nearly half of women with myocardial ischemia have coronary microvascular disease, a condition often called microvascular angina (MVA). Small intramyocardial arterioles constrict in MVA causing ischemic pain that is less predictable than with typical epicardial coronary artery disease (CAD). The pathophysiology is complex and still being elucidated, but there is strong evidence that endothelial dysfunction, decreased endogenous vasodilators, inflammation, changes in adipokines, and platelet activation are contributing factors. The diagnosis of MVA may require catheterization during which there is an assessment of the microcirculatory response to adenosine or acetylcholine and measurement of coronary and fractional flow reserve. New techniques include positron emission tomography (PET) scanning, cardiac magnetic resonance imaging (MRI), and transthoracic Doppler echocardiography. Managing MVA can be challenging, for example, women with this condition have less coronary microvascular dilation in response to nitrates than do those without MVA. Women with MVA often have traditional risk factors for CAD such as obesity, dyslipidemia, diabetes, and hypertension. Aggressive interventions to reduce modifiable risk factors are an important component of management, especially smoking cessation, exercise, and diabetes management </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Madelungs deformity and can you explain it in depth? [/INST] Madelungs deformity is usually characterized by malformed wrists and wrist bones and is often associated with Léri-Weill dyschondrosteosis. It can be bilateral (in both wrists) or just in the one wrist.
It has only been recognized within the past hundred years. Named after Otto Wilhelm Madelung (1846–1926), a German surgeon, who described it in detail, it was noted by others. Guillaume Dupuytren mentioned it in 1834, Auguste Nélaton in 1847, and Joseph-François Malgaigne in 1855.

Signs and symptoms
It is a congenital subluxation or dislocation of the ulnas distal end, due to malformation of the bones. Sometimes, minor abnormalities of other bone structures, often caused by disease or injury, such as a fracture of the distal end of the radius with upward displacement of the distal fragment. The deformity varies in degree from a slight protrusion of the lower end of the ulna, to complete dislocation of the inferior radio-ulnar joint with marked ulnar deviation of the hand. Severe deformities are associated with congenital absence or hypoplasia of the radius.The male:female rate of this disorder is 1:4. The incidence is unknown, and there is no described racial predominance. Even though Madelungs Deformity is considered a congenital disorder, symptoms sometimes arent seen until adulthood. In most cases, symptoms find their onset during midchildhood. At this age, the relatively slower growth of the ulnar and palmar part of the radius, leads to an increasingly progressive deformity. Pain and deformity are the main symptoms patients present with. Typical clinical presentation consists of a short forearm, anterior-ulnar bow of the radius and a forward subluxation of the hand on the forearm. As mentioned before, the severity of the disorder varies greatly, which also leads to a spectrum of presentation.

Genetics
Leri-Weill dyschondrosteosis is a pseudoautosomal dominant disorder which occurs more frequently in females and is due to a mutation,  deletion or duplication of the SHOX gene. The SHOX gene plays a particularly important role in the growth and maturation of bones in the arms and legs. The SHOX gene is located within band Xp22.3 of the pseudoautosomal region of the X chromosome, which escapes X-inactivation. Homozygous SHOX gene mutations result in Langer mesomelic dysplasia.

Pathogenesis
Madelung deformity of the wrist is caused by a growth disturbance in the inferior volar part of the epiphysial growth plate in the distal radius, resulting in a volar placed slope of the lunate facet and scaphoid facet. This produces volar translation of the hand and wrist. The ulna continues growing straight, resulting in a dorsally prominent distal ulna. It occurs predominantly in adolescent females, who present with pain, decreased range of motion, and deformity. It often has a genetic cause and is associated with mesomelic dwarfism and a mutation on the X chromosome. Attempts can be made to treat the deformity surgically by addressing the deforming bone and fibrous bands called "Vickers ligament". This is an abnormal ligament formed between the Lunate bone of the wrist and the radius and is found in 91% of cases of Madelungs deformity.

Diagnosis
Diagnosis is normally confirmed by X-rays.

Treatment
Non-surgical
First options for treatment are conservative, using hot or cold packs, rest and NSAIDs at first. If no improvement is made, a splint or brace can be used to keep the deviated arm straight. When none of the conservative treatments work surgical intervention is designated.

Surgical
Pediatrics
Physiolysis
Purpose of the treatment is the removal of the epiphysis that causes the abnormal growth of the wrist. This is done by making a small incision at the volar-radial side. This approach passes the Flexor pollicis longus and Palmaris longus and leaves the Median nerve and Radial artery protected. Then the Pronator quadratus muscle is found and detached from the radius.  Here a cut into the bone will find the abnormal epiphysis. When the epiphysis is clearly defined more bone is removed so the radius is in its normal position and prevents a new bone bar from forming. This is the end of the physiolisis. This is always combined with a Vickers Ligament release.Dome osteotomy
Purpose of this treatment option is to straighten the abnormal radius. To do this, an 8 cm incision is made from the wrist crease at the palmair radial side. The approach is made passing the Flexor carpi radialis with detachment of the Pronator quadratus muscle from the radius. Now the Vickers ligament release is done. After this the periosteum is elevated and a crescent-shaped osteotomy, concave at the end, is marked on the bone. Now the radius is cut dome shaped and straightened. The distal end of the radius stays attached to the ulna. The dome shape of the osteotomy allows adequate bony contact for stability and a subperiosteal void for rapid healing.Vickers Ligament Release
This ligament causes the wrist to deform even more. The purpose of this release is to release the tension and leave the wrist straight in further growth. In both physiolysis and dome osteotomy there should be a clear view of the abnormal.

Adults
Ulna reduction
Adults with Madelung’s deformity may suffer from ulnar-sided wrist pain. Madelungs Deformity is usually treated by treating the distal radial deformity. However, if patients have a positive ulnar variance and focal wrist pathology, it’s possible to treat with an isolated ulnar-shortening osteotomy. In these patients the radial deformity is not treated.The ulna is approached from the subcutaneous border. A plate is attached to the distal end of the ulna, to plan the osteotomy. An oblique segment is removed from the ulna, after which the distal radial-ulnar joint is freed, making sure structures stay attached to the styloid process. After this, the freed distal end is reattached to the proximal ulna with the formerly mentioned plate.Total DRUJ replacement
An alternative treatment for patients with ulnar-sided wristpain is a total replacement of the distal radial-ulnar joint </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Left atrial enlargement and can you explain it in depth? [/INST] Left atrial enlargement (LAE) or left atrial dilation refers to enlargement of the left atrium (LA) of the heart, and is a form of cardiomegaly.

Signs and symptoms
Left atrial enlargement can be mild, moderate or severe depending on the extent of the underlying condition. Although other factors may contribute, left atrium size has been found to be a predictor of mortality due to both cardiovascular issues as well as all-cause mortality. Research suggests that left atrium size as measured by an echo-cardiograph may be linked to cardiovascular disease. However, studies that have found LAE to be a predictor for mortality recognize the need for more standardized left atrium measurements than those found in an echo-cardiogram.

Causes
In the general population, obesity appears to be the most important risk factor for LAE. LAE has been found to be correlated to body size, independent of obesity, meaning that LAE is more common in people with a naturally large body size </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Coma and can you explain it in depth? [/INST] A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhibit a complete absence of wakefulness and are unable to consciously feel, speak or move. Comas can be derived by natural causes, or can be medically induced.Clinically, a coma can be defined as the inability consistently to follow a one-step command. It can also be defined as a score of ≤ 8 on the Glasgow Coma Scale (GCS) lasting ≥ 6 hours. For a patient to maintain consciousness, the components of wakefulness and awareness must be maintained. Wakefulness describes the quantitative degree of consciousness, whereas awareness relates to the qualitative aspects of the functions mediated by the cortex, including cognitive abilities such as attention, sensory perception, explicit memory, language, the execution of tasks, temporal and spatial orientation and reality judgment. From a neurological perspective, consciousness is maintained by the activation of the cerebral cortex—the gray matter that forms the outer layer of the brain—and by the reticular activating system (RAS), a structure located within the brainstem.

Etymology
The term coma, from the Greek κῶμα koma, meaning deep sleep, had already been used in the Hippocratic corpus (Epidemica) and later by Galen (second century AD). Subsequently, it was hardly used in the known literature up to the middle of the 17th century. The term is found again in Thomas Willis (1621–1675) influential De anima brutorum (1672), where lethargy (pathological sleep), coma (heavy sleeping), carus (deprivation of the senses) and apoplexy (into which carus could turn and which he localized in the white matter) are mentioned. The term carus is also derived from Greek, where it can be found in the roots of several words meaning soporific or sleepy. It can still be found in the root of the term carotid. Thomas Sydenham (1624–89) mentioned the term coma in several cases of fever (Sydenham, 1685).

Signs and symptoms
General symptoms of a person in a comatose state are:

Inability to voluntarily open the eyes
A non-existent sleep-wake cycle
Lack of response to physical (painful) or verbal stimuli
Depressed brainstem reflexes, such as pupils not responding to light
Irregular breathing
Scores between 3 and 8 on the Glasgow Coma Scale

Causes
Many types of problems can cause a coma. Forty percent of comatose states result from drug poisoning. Certain drug use under certain conditions can damage or weaken the synaptic functioning in the ascending reticular activating system (ARAS) and keep the system from properly functioning to arouse the brain. Secondary effects of drugs, which include abnormal heart rate and blood pressure, as well as abnormal breathing and sweating, may also indirectly harm the functioning of the ARAS and lead to a coma. Given that drug poisoning is the cause for a large portion of patients in a coma, hospitals first test all comatose patients by observing pupil size and eye movement, through the vestibular-ocular reflex. (See Diagnosis below.)The second most common cause of coma, which makes up about 25% of cases, is lack of oxygen, generally resulting from cardiac arrest. The Central Nervous System (CNS) requires a great deal of oxygen for its neurons. Oxygen deprivation in the brain, also known as hypoxia, causes sodium and calcium from outside of the neurons to decrease and intracellular calcium to increase, which harms neuron communication. Lack of oxygen in the brain also causes ATP exhaustion and cellular breakdown from cytoskeleton damage and nitric oxide production.Twenty percent of comatose states result from the side effects of a stroke. During a stroke, blood flow to part of the brain is restricted or blocked. An ischemic stroke, brain hemorrhage, or tumor may cause restriction of blood flow. Lack of blood to cells in the brain prevents oxygen from getting to the neurons, and consequently causes cells to become disrupted and die. As brain cells die, brain tissue continues to deteriorate, which may affect the functioning of the ARAS.The remaining 15% of comatose cases result from trauma, excessive blood loss, malnutrition, hypothermia, hyperthermia, hyperammonemia, abnormal glucose levels, and many other biological disorders. Furthermore, studies show that 1 out of 8 patients with traumatic brain injury experience a comatose state.

Pathophysiology
Injury to either or both of the cerebral cortex or the reticular activating system (RAS) is sufficient to cause a person to enter coma.The cerebral cortex is the outer layer of neural tissue of the cerebrum of the brain. The cerebral cortex is composed of gray matter which consists of the nuclei of neurons, whereas the inner portion of the cerebrum is composed of white matter and is composed of the axons of neuron. White matter is responsible for perception, relay of the sensory input via the thalamic pathway, and many other neurological functions, including complex thinking.
The RAS, on the other hand, is a more primitive structure in the brainstem which includes the reticular formation (RF). The RAS has two tracts, the ascending and descending tract. The ascending tract, or ascending reticular activating system (ARAS), is made up of a system of acetylcholine-producing neurons, and works to arouse and wake up the brain. Arousal of the brain begins from the RF, through the thalamus, and then finally to the cerebral cortex. Any impairment in ARAS functioning, a neuronal dysfunction, along the arousal pathway stated directly above, prevents the body from being aware of its surroundings. Without the arousal and consciousness centers, the body cannot awaken, remaining in a comatose state.The severity and mode of onset of coma depends on the underlying cause. There are two main subdivisions of a coma: structural and diffuse neuronal. A structural cause, for example, is brought upon by a mechanical force that brings about cellular damage, such as physical pressure or a blockage in neural transmission. While a diffuse cause is limited to aberrations of cellular function, that fall under a metabolic or toxic subgroup. Toxin-induced comas are caused by extrinsic substances, whereas metabolic-induced comas are caused by intrinsic processes, such as body thermoregulation or ionic imbalances(e.g. sodium). For instance, severe hypoglycemia (low blood sugar) or hypercapnia (increased carbon dioxide levels in the blood) are examples of a metabolic diffuse neuronal dysfunction. Hypoglycemia or hypercapnia initially cause mild agitation and confusion, but progress to obtundation, stupor, and finally, complete unconsciousness. In contrast, coma resulting from a severe traumatic brain injury or subarachnoid hemorrhage can be instantaneous. The mode of onset may therefore be indicative of the underlying cause.Structural and diffuse causes of coma are not isolated from one another, as one can lead to the other in some situations. For instance, coma induced by a diffuse metabolic process, such as hypoglycemia, can result in a structural coma if it is not resolved. Another example is if cerebral edema, a diffuse dysfunction, leads to ischemia of the brainstem, a structural issue, due to the blockage of the circulation in the brain.

Diagnosis
Although diagnosis of coma is simple, investigating the underlying cause of onset can be rather challenging. As such, after gaining stabilization of the patients airways, breathing and circulation (the basic ABCs) various diagnostic tests, such as physical examinations and imaging tools (CT scan, MRI, etc.) are employed to access the underlying cause of the coma.When an unconscious person enters a hospital, the hospital utilizes a series of diagnostic steps to identify the cause of unconsciousness. According to Young, the following steps should be taken when dealing with a patient possibly in a coma:

Perform a general examination and medical history check
Make sure the patient is in an actual comatose state and is not in a locked-in state or experiencing psychogenic unresponsiveness. Patients with locked-in syndrome present with voluntary movement of their eyes, whereas patients with psychogenic comas demonstrate active resistance to passive opening of the eyelids, with the eyelids closing abruptly and completely when the lifted upper eyelid is released (rather than slowly, asymmetrically and incompletely as seen in comas due to organic causes).
Find the site of the brain that may be causing coma (e.g., brainstem, back of brain...) and assess the severity of the coma with the Glasgow Coma Scale
Take blood work to see if drugs were involved or if it was a result of hypoventilation/hyperventilation
Check for levels of serum glucose, calcium, sodium, potassium, magnesium, phosphate, urea, and creatinine
Perform brain scans to observe any abnormal brain functioning using either CT or MRI scans
Continue to monitor brain waves and identify seizures of patient using EEGs

Initial evaluation
In the initial assessment of coma, it is common to gauge the level of consciousness on the AVPU (alert, vocal stimuli, painful stimuli, unresponsive) scale by spontaneously exhibiting actions and, assessing the patients response to vocal and painful stimuli. More elaborate scales, such as the Glasgow Coma Scale, quantify an individuals reactions such as eye opening, movement and verbal response in order to indicate their extent of brain injury. The patients score can vary from a score of 3 (indicating severe brain injury and death) to 15 (indicating mild or no brain injury).In those with deep unconsciousness, there is a risk of asphyxiation as the control over the muscles in the face and throat is diminished. As a result, those presenting to a hospital with coma are typically assessed for this risk ("airway management"). If the risk of asphyxiation is deemed high, doctors may use various devices (such as an oropharyngeal airway, nasopharyngeal airway or endotracheal tube) to safeguard the airway.

Imaging and testing
Imaging basically encompasses computed tomography (CAT or CT) scan of the brain, or MRI for example, and is performed to identify specific causes of the coma, such as hemorrhage in the brain or herniation of the brain structures. Special tests such as an EEG can also show a lot about the activity level of the cortex such as semantic processing, presence of seizures, and are important available tools not only for the assessment of the cortical activity but also for predicting the likelihood of the patients awakening. The autonomous responses such as the skin conductance response may also provide further insight on the patients emotional processing.In the treatment of traumatic brain injury (TBI), there are 4 examination methods that have proved useful: skull x-ray, angiography, computed tomography (CT), and magnetic resonance imaging (MRI). The skull x-ray can detect linear fractures, impression fractures (expression fractures) and burst fractures. Angiography is used on rare occasions for TBIs i.e. when there is suspicion of an aneurysm, carotid sinus fistula, traumatic vascular occlusion, and vascular dissection. A CT can detect changes in density between the brain tissue and hemorrhages like subdural and intracerebral hemorrhages. MRIs are not the first choice in emergencies because of the long scanning times and because fractures cannot be detected as well as CT. MRIs are used for the imaging of soft tissues and lesions in the posterior fossa which cannot be found with the use of CT.

Body movements
Assessment of the brainstem and cortical function through special reflex tests such as the oculocephalic reflex test (dolls eyes test), oculovestibular reflex test (cold caloric test), corneal reflex, and the gag reflex. Reflexes are a good indicator of what cranial nerves are still intact and functioning and is an important part of the physical exam. Due to the unconscious status of the patient, only a limited number of the nerves can be assessed. These include the cranial nerves number 2 (CN II), number 3 (CN III), number 5 (CN V), number 7 (CN VII), and cranial nerves 9 and 10 (CN IX, CN X).

Assessment of posture and physique is the next step. It involves general observation about the patients positioning. There are often two stereotypical postures seen in comatose patients. Decorticate posturing is a stereotypical posturing in which the patient has arms flexed at the elbow, and arms adducted toward the body, with both legs extended. Decerebrate posturing is a stereotypical posturing in which the legs are similarly extended (stretched), but the arms are also stretched (extended at the elbow). The posturing is critical since it indicates where the damage is in the central nervous system. A decorticate posturing indicates a lesion (a point of damage) at or above the red nucleus, whereas a decerebrate posturing indicates a lesion at or below the red nucleus. In other words, a decorticate lesion is closer to the cortex, as opposed to a decerebrate posturing which indicates that the lesion is closer to the brainstem.

Pupil size
Pupil assessment is often a critical portion of a comatose examination, as it can give information as to the cause of the coma; the following table is a technical, medical guideline for common pupil findings and their possible interpretations:

Severity
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.

Treatment
Treatment for people in a coma will depend on the severity and cause of the comatose state. Upon admittance to an emergency department, coma patients will usually be placed in an Intensive Care Unit (ICU) immediately, where maintenance of the patients respiration and circulation become a first priority. Stability of their respiration and circulation is sustained through the use of intubation, ventilation, administration of intravenous fluids or blood and other supportive care as needed.

Continued care
Once a patient is stable and no longer in immediate danger, there may be a shift of priority from stabilizing the patient to maintaining the state of their physical wellbeing. Moving patients every 2–3 hours by turning them side to side is crucial to avoiding bed sores as a result of being confined to a bed. Moving patients through the use of physical therapy also aids in preventing atelectasis, contractures or other orthopedic deformities which would interfere with a coma patients recovery.Pneumonia is also common in coma patients due to their inability to swallow which can then lead to aspiration. A coma patients lack of a gag reflex and use of a feeding tube can result in food, drink or other solid organic matter being lodged within their lower respiratory tract (from the trachea to the lungs). This trapping of matter in their lower respiratory tract can ultimately lead to infection, resulting in aspiration pneumonia.Coma patients may also deal with restlessness or seizures. As such, soft cloth restraints may be used to prevent them from pulling on tubes or dressings and side rails on the bed should be kept up to prevent patients from falling.

Caregivers
Coma has a wide variety of emotional reactions from the family members of the affected patients, as well as the primary care givers taking care of the patients. Research has shown that the severity of injury causing coma was found to have no significant impact compared to how much time has passed since the injury occurred. Common reactions, such as desperation, anger, frustration, and denial are possible. The focus of the patient care should be on creating an amicable relationship with the family members or dependents of a comatose patient as well as creating a rapport with the medical staff. Although there is heavy importance of a primary care taker, secondary care takers can play a supporting role to temporarily relieve the primary care takers burden of tasks.

Prognosis
Comas can last from several days to, in particularly extreme cases, years. Some patients eventually 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; and in some cases may remain in vegetative state for years or even decades (the longest recorded period is 42 years).Predicted chances of recovery will differ depending on which techniques were used to measure the patients severity of neurological damage. Predictions of recovery are based on statistical rates, expressed as the level of chance the person has of recovering. Time is the best general predictor of a chance of recovery. For example, 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 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; similarly, a milder coma does not indicate a higher chance of recovery. 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.

Recovery
People may emerge from a coma with a combination of physical, intellectual, and psychological difficulties that need special attention. It is common for coma patients to awaken in a profound state of confusion and experience dysarthria, the inability to articulate any speech. Recovery is usually gradual. In the first days, the patient may only awaken for a few minutes, with increased duration of wakefulness as their recovery progresses, and they may eventually recover full awareness. That said, some patients may never progress beyond very basic responses.There are reports of people coming out of a 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 man with brain-damage and 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 with a traumatic brain injury. His injuries left him in a minimally conscious state, a condition akin to a coma but characterized by occasional, but brief, evidence of environmental and self-awareness that coma patients lack.

Society and culture
Research by Dr. Eelco Wijdicks on the depiction of comas in movies was published in Neurology in May 2006. Dr. Wijdicks studied 30 films (made between 1970 and 2004) that portrayed actors in prolonged comas, and he concluded that only two films accurately depicted the state of a coma patient and the agony of waiting for a patient to awaken: Reversal of Fortune (1990) and The Dreamlife of Angels (1998). The remaining 28 were criticized for portraying miraculous awakenings with no lasting side effects, unrealistic depictions of treatments and equipment required, and comatose patients remaining muscular and tanned.

Bioethics
A person in a coma is said to be in an  unconscious state. Perspectives on personhood, identity and consciousness come into play when discussing the metaphysical and bioethical views on comas.
It has been argued that unawareness should be just as ethically relevant and important as a state of awareness and that there should be metaphysical support of unawareness as a state.In the ethical discussions about disorders of consciousness (DOCs), two abilities are usually considered as central: experiencing well-being and having interest. Well-being can broadly be understood as the positive effect related to what makes life good (according to specific standards) for the individual in question. The only condition for well-being broadly considered is the ability to experience its ‘positiveness’. That said, because experiencing positiveness is a basic emotional process with phylogenetic roots, it is likely to occur at a completely unaware level and therefore, introduces the idea of an unconscious well-being. As such, the ability of having interests, is crucial for describing two abilities which those with comas are deficient in. Having an interest in a certain domain can be understood as having a stake in something that can affect what makes our life good in that domain </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Carcinoid and can you explain it in depth? [/INST] A carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) are associated with carcinoid syndrome.
Carcinoid tumors are the most common malignant tumor of the appendix, but they are most commonly associated with the small intestine, and they can also be found in the rectum and stomach. They are known to grow in the liver, but this finding is usually a manifestation of metastatic disease from a primary carcinoid occurring elsewhere in the body. They have a very slow growth rate compared to most malignant tumors. The median age at diagnosis for all patients with neuroendocrine tumors is 63 years.

Signs and symptoms
While most carcinoids are asymptomatic through the natural life and are discovered only upon surgery for unrelated reasons (so-called coincidental carcinoids), all carcinoids are considered to have malignant potential.
About 10% of carcinoids secrete excessive levels of a range of hormones, most notably serotonin (5-HT), causing:

Flushing (serotonin itself does not cause flushing). Potential causes of flushing in carcinoid syndrome include bradykinins, prostaglandins, tachykinins, substance P, and/or histamine, diarrhea, and heart problems. Because of serotonins growth-promoting effect on cardiac myocytes, a serotonin-secreting carcinoid tumour may cause a tricuspid valve disease syndrome, due to the proliferation of myocytes onto the valve.
Diarrhea
Wheezing
Abdominal cramping
Peripheral edemaThe outflow of serotonin can cause a depletion of tryptophan leading to niacin deficiency. Niacin deficiency, also known as pellagra, is associated with dermatitis, dementia, and diarrhea.
This constellation of symptoms is called carcinoid syndrome or (if acute) carcinoid crisis. Occasionally, haemorrhage or the effects of tumor bulk are the presenting symptoms. The most common originating site of carcinoid is the small bowel, particularly the ileum; carcinoid tumors are the most common malignancy of the appendix. Carcinoid tumors may rarely arise from the ovary or thymus.They are most commonly found in the midgut at the level of the ileum or in the appendix. The next most commonly affected area is the respiratory tract, with 28% of all cases—per PAN-SEER data (1973–1999). The rectum is also a common site.

Gastrointestinal
Carcinoid tumors are apudomas that arise from the enterochromaffin cells throughout the gut. Over two-thirds of carcinoid tumors are found in the gastrointestinal tract.

Lung
Carcinoid tumors are also found in the lungs.

Other sites and metastases
Metastasis of carcinoid can lead to carcinoid syndrome. This is due to the over-production of many substances, including serotonin, which are released into the systemic circulation, and which can lead to symptoms of cutaneous flushing, diarrhea, bronchoconstriction, and right-sided cardiac valve disease. It is estimated that less than 6% of carcinoid patients will develop carcinoid syndrome, and of these, 50% will have cardiac involvement.

Goblet cell carcinoid
This is considered to be a hybrid between an exocrine and endocrine tumor derived from crypt cells of the appendix. Histologically, it forms clusters of goblet cells containing mucin with a minor admixture of Paneth cells and endocrine cells. The growth pattern is distinctive: typically producing a concentric band of tumor nests interspersed among the muscle and stroma of the appendiceal wall extending up the shaft of the appendix. This makes the lesion difficult to suspect grossly and difficult to measure. Small tumor nests may be camouflaged amongst the muscle or in periappendiceal fat; cytokeratin preparations best demonstrate the tumor cells; mucin stains are also helpful in identifying them. They behave in a more aggressive manner than do classical appendiceal carcinoids. Spread is usually to regional lymph nodes, peritoneum, and particularly the ovary. They do not produce sufficient hormonal substances to cause carcinoid or other endocrine syndromes. In fact, they more closely resemble exocrine than endocrine tumors. The term crypt cell carcinoma has been used for them, and though perhaps more accurate than considering them carcinoids, has not been a successful competitor.

Cause
Carcinoid syndrome involves multiple tumors in one out of five males. The incidence of gastric carcinoids is increased in achlorhydria, Hashimotos thyroiditis, and pernicious anemia.

Treatment
Surgery, if feasible, is the only curative therapy. If the tumor has metastasized (most commonly, to the liver) and is considered incurable, there are some promising treatment modalities, such as radiolabeled octreotide (e.g </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Combined hyperlipidemia and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Anal fistula and can you explain it in depth? [/INST] Anal fistula is a chronic abnormal communication between the epithelialised surface of the anal canal and usually the perianal skin. An anal fistula can be described as a narrow tunnel with its internal opening in the anal canal and its external opening in the skin near the anus. Anal fistulae commonly occur in people with a history of anal abscesses. They can form when anal abscesses do not heal properly.Anal fistulae originate from the anal glands, which are located between the internal and external anal sphincter and drain into the anal canal. If the outlet of these glands becomes blocked, an abscess can form which can eventually extend to the skin surface. The tract formed by this process is a fistula.Abscesses can recur if the fistula seals over, allowing the accumulation of pus. It can then extend to the surface again – repeating the process.Anal fistulae per se do not generally harm, but can be very painful, and can be irritating because of the drainage of pus (it is also possible for formed stools to be passed through the fistula). Additionally, recurrent abscesses may lead to significant short term morbidity from pain and, importantly, create a starting point for systemic infection.Treatment, in the form of surgery, is considered essential to allow drainage and prevent infection. Repair of the fistula itself is considered an elective procedure which many patients opt for due to the discomfort and inconvenience associated with an actively draining fistula.

Signs and symptoms
Anal fistulae can present with the following symptoms:
skin maceration
pus, serous fluid and/or (rarely) feces discharge — can be bloody or purulent
pruritus ani — itching
depending on presence and severity of infection:pain
swelling
tenderness
fever
unpleasant odorThick discharge, which keeps the area wet

Diagnosis
Diagnosis is by examination, either in an outpatient setting or under anaesthesia (referred to as EUA or Examination Under Anaesthesia). The fistula may be explored by using a fistula probe (a narrow instrument). In this way, it may be possible to find both openings. The examination can be an anoscopy. Diagnosis may be aided by performing a fistulogram, proctoscopy and/or sigmoidoscopy.
Possible findings:

The opening of the fistula onto the skin may be observed
The area may be painful on examination
There may be redness
An area of induration may be felt; thickening due to chronic infection
A discharge may be seen

Classification
Parks classification: This was done by Parks et al. from the UK in 1976, before MRI or endoanal ultrasound was available. It classified the fistula in four grades:
St James University Hospital Classification: This was done by Morris et al. in the year 2000. This classification was improvement over Parks classification as it was based on MRI studies. It classified the fistula in five grades.
Garg classification: This was done by Pankaj Garg in 2017. This classification is improvement over both Parks and St James University Hospital Classification. This was based on MRI studies and operative findings in 440 patients. It classified the fistula in five grades. The grades of this classification correlate quite well with the severity of the disease. Grade I & II are simpler fistulas and can be managed by Fistulotomy whereas Grade III-V are complex fistulas in which fistulotomy should be not be done. They should be managed by Fistula experts. Unlike Parks and St James University Hospital Classification, this correlation is quite accurate with Gargs classification. Therefore this new classification is useful to both surgeons and radiologists.

Types
Depending on their relationship with the internal and external sphincter muscles, fistulae are classified into five types:

Extrasphincteric fistulae begin at the rectum or sigmoid colon and proceed downward, through the levator ani muscle and open into the skin surrounding the anus. Note that this type does not arise from the dentate line (where the anal glands are located). Causes of this type could be from a rectal, pelvic or supralevator origin, usually secondary to Crohns disease or an inflammatory process such as appendiceal or diverticular abscesses.
Suprasphincteric fistulae begin between the internal and external sphincter muscles, extend above and cross the puborectalis muscle, proceed downward between the puborectalis and levator ani muscles, and open an inch or more away from the anus.
Transphincteric fistulae begin between the internal and external sphincter muscles or behind the anus, cross the external sphincter muscle and open an inch or more away from the anus. These may take a U shape and form multiple external openings. This is sometimes termed a horseshoe fistula.
Intersphincteric fistulae begin between the internal and external sphincter muscles, pass through the internal sphincter muscle, and open very close to the anus.
Submucosal fistulae pass superficially beneath the submucosa and do not cross either sphincter muscle.

Differential diagnosis
Other conditions in which infected perianal "holes" or openings may include pilonidal cyst.

Treatment
There are several stages to treating an anal fistula:
Definitive treatment of A fistula aims to stop it recurring.  Treatment depends on where the fistula lies, and which parts of the internal and external anal sphincters it crosses.

Lay-open of fistula-in-ano – this option involves an operation to cut the fistula open. Once the fistula has been laid open it will be packed on a daily basis for a short period of time to ensure that the wound heals from the inside out. This option leaves behind a scar, and depending on the position of the fistula in relation to the sphincter muscle, can cause problems with incontinence.  This option is not suitable for fistulae that cross the entire internal and external anal sphincter.
Cutting seton – if the fistula is in a high position and it passes through a significant portion of the sphincter muscle, a cutting seton (from the Latin seta, "bristle") may be used. This involves inserting a thin tube through the fistula tract and tying the ends together outside of the body. The seton is tightened over time, gradually cutting through the sphincter muscle and healing as it goes. This option minimizes scarring but can cause incontinence in a small number of cases, mainly of flatus. Once the fistula tract is in a low enough position it may be laid open to speed up the process, or the seton can remain in place until the fistula is completely cured.  This was the traditional modality used by physicians in Ancient Egypt and formally codified by Hippocrates, who used horsehair and linen.
Seton stitch –  a length of suture material looped through the fistula which keeps it open and allows pus to drain out. In this situation, the seton is referred to as a draining seton. The stitch is placed close to the ano-rectal ring – which encourages healing and makes further surgery easy.
Fistulotomy – till anorectal ring
Colostomy – to allow healing
Fibrin glue injection is a method explored in recent years, with variable success. It involves injecting the fistula with a biodegradable glue which should, in theory, close the fistula from the inside out, and let it heal naturally. This method is perhaps best tried before all others since, if successful, it avoids the risk of incontinence, and creates minimal stress for the patient.
Fistula plug involves plugging the fistula with a device made from small intestinal submucosa. The fistula plug is positioned from the inside of the anus with suture. According to some sources, the success rate with this method is as high as 80%. As opposed to the staged operations, which may require multiple hospitalizations, the fistula plug procedure requires hospitalization for only about 24 hours. Currently, there are two different anal fistula plugs cleared by the FDA for treating ano-rectal fistulae in the United States. This treatment option does not carry any risk of bowel incontinence. In the systematic review published by Dr Pankaj Garg, the success rate of the fistula plug is 65–75%.
Endorectal advancement flap is a procedure in which the internal opening of the fistula is identified and a flap of mucosal tissue is cut around the opening.  The flap is lifted to expose the fistula, which is then cleaned and the internal opening is sewn shut.  After cutting the end of the flap on which the internal opening was, the flap is pulled down over the sewn internal opening and sutured in place.  The external opening is cleaned and sutured.  Success rates are variable and high recurrence rates are directly related to previous attempts to correct the fistula.
LIFT Technique is a novel modified approach through the intersphincteric plane for the treatment of fistula-in-ano, known as LIFT (ligation of intersphincteric fistula tract) procedure. LIFT procedure is based on secure closure of the internal opening and removal of infected cryptoglandular tissue through the intersphincteric approach. Essential steps of the procedure include, incision at the intersphincteric groove, identification of the intersphincteric tract, ligation of intersphincteric tract close to the internal opening and removal of intersphincteric tract, scraping out all granulation tissue in the rest of the fistulous tract, and suturing of the defect at the external sphincter muscle. The procedure was developed by Thai colorectal surgeon, Arun Rojanasakul, The first reports of preliminary healing result from the procedure were 94% in 2007. Additional ligation of the intersphincteric fistula tract did not improve the outcome after endorectal advancement flap.
Fistula clip closure (OTSC Proctology) is a recent surgical development, which involves the closure of the internal fistula opening with a superelastic clip made of nitinol (OTSC). During surgery, the fistula tract is debrided with a special fistula brush and the clip is transanally applied with the aid of a preloaded clip applicator. The surgical principle of this technique relies on the dynamic compression and permanent closure of the internal fistula opening by the superelastic clip. Consequently, the fistula tract dries out and heals instead of being kept open by continuous feeding with stool and fecal organisms. This minimally-invasive sphincter-preserving technique has been developed and clinically implemented by the German surgeon Ruediger Prosst. First clinical data of the clip closure technique demonstrate a success rate of 90% for previously untreated fistulae and a success rate of 70% for recurrent fistulae.
VAAFT is a surgical kit for treating anal fistulae. The system comprises:
A video telescope (fistuloscope) to allow surgeons to see inside the fistula tract.
A unipolar electrode for diathermy of the internal tract. This is connected to a high frequency generator.
A fistula brush and forceps for cleaning the tract and clearing any granulation tissue.The VAAFT procedure is done in 2 phases, diagnostic and operative </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Phakomatosis pigmentokeratotica and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Ameboma and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Psychogenic alopecia and can you explain it in depth? [/INST] Psychogenic alopecia, also called over-grooming or psychological baldness, is a compulsive behavior that affects domestic cats. Generally, psychogenic alopecia does not lead to serious health consequences or a decreased lifespan.

Causes
Grooming is a natural behavior for cats. Cats spend 5–25% of their waking hours grooming. Grooming becomes excessive when it takes precedence over other activities or no longer seems functional. Excessive grooming, which can lead to hair loss, skin wounds, and ulceration, can result from chronic stress or develop in cats who already exhibit nervous temperaments. Even when the source of stress is resolved or removed, excessive grooming may continue. There may be some genetic basis for the behavior, and it predominantly affects purebred cats of oriental breeds, but can develop in any feline. Female cats appear more susceptible. Environmental factors suspected of causing over-grooming include flea allergy, boredom, food allergy, dust or pollen causing an allergic reaction, constipation and urinary tract infection caused by avoidance of a dirty litter tray, dermatitis, and anxiety caused by inconsistent meal times. Deprivation of sunlight could be the part of the problem for indoors only cats.

Symptoms
Areas affected are those the cat can access most easily, including the abdomen, legs, flank, and chest.
Baldness, usually beginning with the abdomen.
Obvious over-grooming (although some cats may only engage in the behavior in the absence of owners).
Redness, rashes, pus, scabs on the bald area or areas traumatized by over-grooming.
A highly irritable cat may even cut its face with the claw of its hind foot if over-zealously scratching the back of its head.

Treatment
The cat should be taken to a veterinarian. The most suspected cause of skin problems in cats will be fleas. Other causes of over-grooming are not as easily ascertained </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Lipedema and can you explain it in depth? [/INST] Lipedema is a condition that is almost exclusively found in women and results in enlargement of both legs due to deposits of fat under the skin. Women of any weight may develop lipedema and the fat associated with lipedema is resistant to traditional weight-loss methods. There is no cure and typically it gets worse over time, pain may be present, and patients bruise easily. Over time mobility may be reduced, and due to reduced quality of life, patients often experience depression. In severe cases the trunk and upper body may be involved. Lipedema is commonly misdiagnosed and is now becoming known as lipoalgia due to there being no oedema.The cause is unknown but is believed to involve genetics and hormonal factors. It often runs in families; having a family member with the condition is a risk factor for developing it. Other conditions that may present similarly include lipohypertrophy, chronic venous insufficiency, and lymphedema. It is estimated to affect up to 11% of women. Onset is typically during puberty, pregnancy, or menopause.The fat associated with lipedema is shown to be resistant to weight loss methods; however, unlike other fat, lipedema is not associated with increased risks of diabetes or cardiovascular disease. Physiotherapy may help to preserve mobility for a little longer than would otherwise be the case. Exercise, only as much as the patient is able to do without causing damage to the joints, may help with overall fitness but will not prevent progression of the disease. Compression stockings can help with pain and make walking easier. Regularly moisturising with emollients protects the skin and prevents it from drying out. Liposuction to remove the fat can help if the symptoms are particularly severe. While surgery can remove fat tissue it can also damage lymphatic vessels. Treatment does not typically result in complete resolution.

Presentation
Associated conditions
Depression and anxiety are very common for a variety of reasons, particularly the fact that diagnosis usually takes a long time and patients have received much advice on diet and exercise in the meantime, neither of which are effective treatment for the lipedema although they may help associated conditions. Joint pain, arthritis, dry skin, fungal infections, cellulitis and slow wound healing are also associated with lipedema.

Diagnosis
Differential diagnosis
Lipedema stages
Lipedema is classified by stage:
Stage 1: Normal skin surface with enlarged hypodermis (lipedema fat).
Stage 2: Uneven skin with indentations in fat and larger hypodermal masses (lipomas).
Stage 3: Bulky extrusions of skin and fat cause large deformations especially on the thighs and around the knees. These large extrusions of tissue drastically inhibit mobility.

Similar conditions
Lipedema is often underdiagnosed due to the difficulty in differentiating it from lymphedema, obesity, or other edemas.

Lipo-lymphedema
Lipo-lymphedema, a secondary lymphedema, is associated with both lipedema and obesity (which occur together in the majority of cases), most often lipedema stages 2 and 3.

Dercums disease
Lipedema / Dercums disease differentiation – these conditions may co-exist. Dercums disease is a syndrome of painful growths in subcutaneous fat. Unlike lipedema, which occurs primarily in the trunk and legs, the fatty growths can occur anywhere on the body.

Treatment
A number of treatments may be useful including physiotherapy and light exercise which does not put undue stress on the lymphatic system </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Post-traumatic epilepsy and can you explain it in depth? [/INST] Post-traumatic epilepsy (PTE) is a form of acquired epilepsy that results from brain damage caused by physical trauma to the brain (traumatic brain injury, abbreviated TBI). A person with PTE experiences repeated post-traumatic seizures (PTS, seizures that result from TBI) more than a week after the initial injury. PTE is estimated to constitute 5% of all cases of epilepsy and over 20% of cases of acquired epilepsy (in which seizures are caused by an identifiable organic brain condition).It is not known who will develop epilepsy after TBI and who will not. However, the likelihood that a person will develop PTE is influenced by the severity and type of injury; for example penetrating injuries and those that involve bleeding within the brain confer a higher risk. The onset of PTE can occur within a short time of the physical trauma that causes it, or months or years after. People with head trauma may remain at a higher risk for post-traumatic seizures than the general population even decades after the injury. PTE may be caused by several biochemical processes that occur in the brain after trauma, including overexcitation of brain cells and damage to brain tissues by free radicals.Diagnostic measures include electroencephalography (EEG) and brain imaging techniques such as magnetic resonance imaging, but these are not totally reliable. Antiepileptic drugs do not prevent the development of PTE after head injury, but may be used to treat the condition if it does occur. When medication does not work to control the seizures, surgery may be needed. Modern surgical techniques for PTE have their roots in the 19th century, but trepanation (cutting the skull to make a hole) may have been used for the condition in ancient cultures.

Classification
Seizures may occur after traumatic brain injury; these are known as post-traumatic seizures (PTS). However, not everyone who has post-traumatic seizures will continue to have post-traumatic epilepsy, because the latter is a chronic condition. However, the terms PTS and PTE are used interchangeably in medical literature. Seizures due to post-traumatic epilepsy are differentiated from non-epileptic post-traumatic seizures based on their cause and timing after the trauma.
A person with PTE has late seizures, those occurring more than a week after the initial trauma. Late seizures are considered to be unprovoked, while early seizures (those occurring within a week of trauma) are thought to result from direct effects of the injury. A provoked seizure is one that results from an exceptional, nonrecurring cause such as the immediate effects of trauma rather than a defect in the brain; it is not an indication of epilepsy. Thus for a diagnosis of PTE, seizures must be unprovoked.
Disagreement exists about whether to define PTE as the occurrence of one or more late, unprovoked seizures, or whether the condition should only be diagnosed in people with two or more. Medical sources usually consider PTE to be present if even one unprovoked seizure occurs, but more recently it has become accepted to restrict the definition of all types of epilepsy to include only conditions in which more than one occur. Requiring more than one seizure for a diagnosis of PTE is more in line with the modern definition of epilepsy, but it eliminates people for whom seizures are controlled by medication after the first seizure.As with other forms of epilepsy, seizure types in PTE may be partial (affecting only part of one hemisphere of the brain) or generalized (affecting both hemispheres and associated with loss of consciousness). In about a third of cases, people with PTE have partial seizures; these may be simple or complex. In simple partial seizures, level of consciousness is not altered, while in complex partial seizures consciousness is impaired. When generalized seizures occur, they may start out as partial seizures and then spread to become generalized.

Causes
It is not clear why some patients develop PTE while others with very similar injuries do not. However, possible risk factors have been identified, including severity and type of injury, presence of early seizures, and genetic factors.

Genetics
Genetics may play a role in the risk that a person will develop PTE; people with the ApoE-ε4 allele may be at higher risk for PTE. The haptoglobin Hp2-2 allele may be another genetic risk factor, possibly because it binds hemoglobin poorly and thus allows more iron to escape and damage tissues. However, most studies have found that having family members with epilepsy does not significantly increase the risk of PTS, suggesting that genetics are not a strong risk factor.

Severity of trauma
The more severe the brain trauma is, the more likely a person is to have late PTE. Evidence suggests that mild head injuries do not confer an increased risk of developing PTE, while more severe types do. In simple mild TBI, the risk for PTE is about 1.5 times that of the uninjured population. By some estimates, as many as half of individuals with severe brain trauma experience PTE; other estimates place the risk at 5% for all TBI patients and 15–20% for severe TBI. One study found that the 30-year risk of developing PTE was 2.1% for mild TBI, 4.2% for moderate, and 16.7% for severe injuries, as shown in the chart at right.

Nature of trauma
The nature of the head trauma also influences the risk of PTE. People who have depressed skull fractures, penetrating head trauma, early PTS, and intracerebral and subdural haematomas due to the TBI are especially likely to have PTE, which occurs in more than 30% of people with any one of these findings. About 50% of patients with penetrating head trauma develop PTE, and missile injuries and loss of brain volume are associated with an especially high likelihood of developing the condition. Injuries that occur in military settings carry higher-than-usual risk for PTE, probably because they more commonly involve penetrating brain injury and brain damage over a more widespread area. Intracranial hematomas, in which blood accumulates inside the skull, are one of the most important risk factors for PTE. Subdural hematoma confers a higher risk of PTE than does epidural hematoma, possibly because it causes more damage to brain tissue. Repeated intracranial surgery confers a high risk for late PTE, possibly because people who need more surgery are more likely to have factors associated with worse brain trauma such as large hematomas or cerebral swelling. In addition, the chances of developing PTE differ by the location of the brain lesion: brain contusion that occurs on in one or the other of the frontal lobes has been found to carry a 20% PTE risk, while a contusion in one of the parietal lobes carries a 19% risk and one in a temporal lobe carries a 16% chance. When contusions occur in both hemispheres, the risk is 26% for the frontal lobes, 66% for the parietal, and 31% for the temporal.

Post-traumatic seizures
The risk that a person will develop PTE is heightened but not 100% if PTS occur. Because many of the risk factors for both PTE and early PTS are the same, it is unknown whether the occurrence of PTS is a risk factor in and of itself. However, even independent of other common risk factors, early PTS have been found to increase the risk of PTE to over 25% in most studies. A person who has one late seizure is at even greater risk for having another than one who has early PTS; epilepsy occurs in 80% of people who have a late seizure. Status epilepticus, a continuous seizure or multiple seizures in rapid succession, is especially strongly correlated with the development of PTE; status seizures occur in 6% of all TBIs but are associated with PTE 42% of the time, and quickly halting a status seizure reduces chances of PTE development.

Pathophysiology
For unknown reasons, trauma can cause changes in the brain that lead to epilepsy. There are a number of proposed mechanisms by which TBI causes PTE, more than one of which may be present in a given person. In the period between a brain injury and onset of epilepsy, brain cells may form new synapses and axons, undergo apoptosis or necrosis, and experience altered gene expression. In addition, damage to particularly vulnerable areas of the cortex such as the hippocampus may give rise to PTE.Blood that gathers in the brain after an injury may damage brain tissue and thereby cause epilepsy. Products that result from the breakdown of hemoglobin from blood may be toxic to brain tissue. The "iron hypothesis" holds that PTE is due to damage by oxygen free radicals, the formation of which is catalyzed by iron from blood. Animal experiments using rats have shown that epileptic seizures can be produced by injecting iron into the brain. Iron catalyzes the formation of hydroxyl radicals by the Haber-Weiss reaction; such free radicals damage brain cells by peroxidizing lipids in their membranes. The iron from blood also reduces the activity of an enzyme called nitric oxide synthase, another factor thought to contribute to PTE.After TBI, abnormalities exist in the release of neurotransmitters, chemicals used by brain cells to communicate with each other; these abnormalities may play a role in the development of PTE. TBI may lead to the excessive release of glutamate and other excitatory neurotransmitters (those that stimulate brain cells and increase the likelihood that they will fire). This excessive glutamate release can lead to excitotoxicity, damage to brain cells through overactivation of the biochemical receptors that bind and respond to excitatory neurotransmitters. Overactivation of glutamate receptors damages neurons; for example it leads to the formation of free radicals. Excitotoxicity is a possible factor in the development of PTE; it may lead to the formation of a chronic epileptogenic focus. An epileptic focus is the part of the brain from which epileptic discharges originate.In addition to chemical changes in cells, structural changes that lead to epilepsy may occur in the brain. Seizures that occur shortly after TBI can reorganize neural networks and cause seizures to occur repeatedly and spontaneously later on. The kindling hypothesis suggests that new neural connections are formed in the brain and cause an increase in excitability. The word kindling is a metaphor: the way the brains response to stimuli increases over repeated exposures is similar to the way small burning twigs can produce a large fire. This reorganization of neural networks may make them more excitable. Neurons that are in a hyperexcitable state due to trauma may create an epileptic focus in the brain that leads to seizures. In addition, an increase in neurons excitability may accompany loss of inhibitory neurons that normally serve to reduce the likelihood that other neurons will fire; these changes may also produce PTE.

Diagnosis
To be diagnosed with PTE, a person must have a history of head trauma and no history of seizures prior to the injury. Witnessing a seizure is the most effective way to diagnose PTE. Electroencephalography (EEG) is a tool used to diagnose a seizure disorder, but a large portion of people with PTE may not have the abnormal "epileptiform" EEG findings indicative of epilepsy. In one study, about a fifth of people who had normal EEGs three months after an injury later developed PTE. However, while EEG is not useful for predicting who will develop PTE, it can be useful to localize the epileptic focus, to determine severity, and to predict whether a person will have more seizures if they stop taking antiepileptic medications.Magnetic resonance imaging (MRI) is performed in people with PTE, and CT scanning can be used to detect brain lesions if MRI is unavailable. However, it is frequently not possible to detect the epileptic focus using neuroimaging.For a diagnosis of PTE, seizures must not be attributable to another obvious cause. Seizures that occur after head injury are not necessarily due to epilepsy or even to the head trauma. Like anyone else, TBI survivors may have seizures due to factors including imbalances of fluid or electrolytes, epilepsy from other causes, hypoxia (insufficient oxygen), and ischemia (insufficient blood flow to the brain). Withdrawal from alcohol is another potential cause of seizures. Thus these factors must be ruled out as causes of seizures in people with head injury before a diagnosis of PTE can be made.

Prevention
Prevention of PTE involves preventing brain trauma in general; protective measures include bicycle helmets and child safety seats. No specific treatment exists to prevent the development of epilepsy after TBI occurs. In the past, antiepileptic drugs were used with the intent of preventing the development of PTE. However, while antiepileptic drugs can prevent early PTS, clinical studies have failed to show that prophylactic use of antiepileptic drugs prevents the development of PTE. Why antiepileptic drugs in clinical trials have failed to stop PTE from developing is not clear, but several explanations have been offered. The drugs may simply not be capable of preventing epilepsy, or the drug trials may have been set up in a way that did not allow a benefit of the drugs to be found (e.g. drugs may have been given too late or in inadequate doses). Animal studies have similarly failed to show much protective effect of the most commonly used seizure medications in PTE trials, such as phenytoin and carbamazepine. Antiepileptic drugs are recommended to prevent late seizures only for people in whom PTE has already been diagnosed, not as a preventative measure. On the basis of the aforementioned studies, no treatment is widely accepted to prevent the development of epilepsy. However, it has been proposed that a narrow window of about one hour after TBI may exist during which administration of antiepileptics could prevent epileptogenesis (the development of epilepsy).Corticosteroids have also been investigated for the prevention of PTE, but clinical trials revealed that the drugs did not reduce late PTS and were actually linked to an increase in the number of early PTS.

Treatment
Antiepileptic drugs may be given to prevent further seizures; these drugs eliminate seizures for about 35% of people with PTE. However, antiepileptics only prevent seizures while they are being taken; they do not reduce the occurrence once the patient stops taking the drugs. Medication may be stopped after seizures have been controlled for two years. PTE is commonly difficult to treat with drug therapy, and antiepileptic drugs may be associated with side effects. The antiepileptics carbamazepine and valproate are the most common drugs used to treat PTE; phenytoin may also be used but may increase risk of cognitive side effects such as impaired thinking. Other drugs commonly used to treat PTE include clonazepam, phenobarbitol, primidone, gabapentin, and ethosuximide. Among antiepileptic drugs tested for seizure prevention after TBI (phenytoin, sodium valproate, carbamazepine, phenobarbital), no evidence from randomized controlled trials has shown superiority of one over another.People whose PTE does not respond to medication may undergo surgery to remove the epileptogenic focus, the part of the brain that is causing the seizures. However surgery for PTE may be more difficult than it is for epilepsy due to other causes, and is less likely to be helpful in PTE than in other forms of epilepsy. It can be particularly difficult in PTE to localize the epileptic focus, in part because TBI may affect diffuse areas of the brain. Difficulty locating the seizure focus is seen as a deterrent to surgery. However, for people with sclerosis in the mesial temporal lobe (in the inner aspect of the temporal lobe), who comprise about one third of people with intractable PTE, surgery is likely to have good outcome. When there are multiple epileptic foci or the focus cannot be localized, and drug therapy is not effective, vagus nerve stimulation is another option for treating PTE.People with PTE have follow-up visits, in which health care providers monitor neurological and neuropsychological function and assess the efficacy and side effects of medications. As with other types of epilepsy, individuals with PTE are advised to exercise caution when performing activities for which seizures could be particularly risky, such as rock climbing.

Prognosis
The prognosis for epilepsy due to trauma is worse than that for epilepsy of undetermined cause. People with PTE are thought to have shorter life expectancies than people with brain injury who do not have seizures. Compared to people with similar structural brain injuries but without PTE, people with PTE take longer to recover from the injury, have more cognitive and motor problems, and perform worse at everyday tasks. This finding may suggest that PTE is an indicator of a more severe brain injury, rather than a complication that itself worsens outcome. PTE has also been found to be associated with worse social and functional outcomes but not to worsen patients rehabilitation or ability to return to work. However, people with PTE may have trouble finding employment if they admit to having seizures, especially if their work involves operating heavy machinery.The period of time between an injury and development of epilepsy varies, and it is not uncommon for an injury to be followed by a latent period with no recurrent seizures. The longer a person goes without developing seizures, the lower the chances are that epilepsy will develop. At least 80–90% of people with PTE have their first seizure within two years of the TBI. People with no seizures within three years of the injury have only a 5% chance of developing epilepsy. However, one study found that head trauma survivors are at an increased risk for PTE as many as 10 years after moderate TBI and over 20 years after severe TBI. Since head trauma is fairly common and epilepsy can occur late after the injury, it can be difficult to determine whether a case of epilepsy resulted from head trauma in the past or whether the trauma was incidental.The question of how long a person with PTE remains at higher risk for seizures than the general population is controversial. About half of PTE cases go into remission, but cases that occur later may have a smaller chance of doing so.

Epidemiology
Studies have found that the incidence of PTE ranges between 1.9 and more than 30% of those with TBI, varying by severity of injury and by the amount of time after TBI for which the studies followed subjects.Brain trauma is one of the strongest predisposing factors for epilepsy development, and is an especially important factor in young adults. Young adults, who are at the highest risk for head injury, also have the highest rate of PTE, which is the largest cause of new-onset epilepsy cases in young people. Children have a lower risk for developing epilepsy; 10% of children with severe TBI and 16–20% of similarly injured adults develop PTE. Being older than 65 is also a predictive factor in the development of epilepsy after brain trauma. One study found PTE to be more common in male TBI survivors than in females.

History
Records of PTE exist from as early as 3000 BC. Trepanation, in which a hole is cut in the skull, may have been used to treat PTE in ancient cultures. In the early 19th century, the surgeons Baron Larrey and WC Wells each reported having performed the operation for PTE. The French-educated American surgeon Benjamin Winslow Dudley (1785–1870) performed six trepanations for PTE between the years of 1819 and 1832 in Kentucky and had good results despite the unavailability of antisepsis. The surgery involved opening the skull at the site of injury, debriding injured tissue, and sometimes draining blood or fluid from under the dura mater. Dudleys work was the largest series of its kind that had been done up to that point, and it encouraged other surgeons to use trepanation for post-traumatic seizures. His reports on the operations came before it was accepted that surgery to relieve excess pressure within the skull was effective in treating epilepsy, but it helped set the stage for trepanation for PTE to become common practice. The procedure became more accepted in the late 19th century once antisepsis was available and cerebral localization was a familiar concept. However, in 1890, the prominent German physician Ernest von Bergmann criticized the procedure; he questioned its efficacy (except in particular circumstances) and suggested that operations had been declared successful too soon after the procedures to know whether they would confer a long-term benefit. The late 19th century saw the advent of intracranial surgery, operating on brain lesions believed to be causing seizures, a step beyond cranial surgery which involved just the skull and meninges. By 1893, at least 42 intracranial operations had been performed for PTE in the US, with limited success.Surgery was the standard treatment for PTE until the years following World War II, when the condition received more attention as soldiers who had survived head trauma developed it. The increased need for drugs to treat PTE led to trials with antiepileptics; these early trials suggested that the drugs could prevent epileptogenesis (the development of epilepsy). It was still thought that antiepileptic drugs could prevent epileptogeneis in the 1970s; in 1973, 60% of physicians surveyed used them to prevent PTE. However, the clinical trials which had supported a protective effect of antiepileptics were uncontrolled; in later, controlled trials the drugs failed to demonstrate an antiepileptogenic effect. Studies did show that antiepileptics prevented seizures occurring within a week after injury, and in 1995 the task force of the Brain Trauma Foundation published a recommendation suggesting their use to protect against seizures early after trauma </s>