<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 Prolactinoma and can you explain it in depth? [/INST] A prolactinoma is a benign tumor (adenoma) of the pituitary gland that produces the hormone prolactin. It is the most common type of functioning pituitary tumor. Symptoms of prolactinoma are due to abnormally high levels of prolactin in the blood (hyperprolactinemia), or due to pressure of the tumor on surrounding tissues. Based on size, a prolactinoma can be classified as a microprolactinoma (<10 mm diameter) or a macroprolactinoma (>10 mm diameter).

Signs and symptoms
The symptoms due to a prolactinoma are broadly divided into those that are caused by increased prolactin levels or mass effect.
Those that are caused by increased prolactin levels are:
Amenorrhea (disappearance of ovulation periods)
Galactorrhea (Milk production; infrequent in men)
Loss of axillary and pubic hair
Hypogonadism (Reduced function of the gonads.)
Gynecomastia (an increase in male breast size)
Erectile dysfunction (in males)Those that are caused by mass effect are:

Headaches
Vision Changes-visual field deficits, blurred vision, decreased visual acuity
Cranial nerve palsies-especially with invasive tumors or with pituitary apoplexy
Seizures, Hydrocephalus, Unilateral exophthalmos are rare presentations
Hypopituitarism
Pituitary apoplexy is a medical emergency because of spontaneous hemorrhage into the pituitary tumor and presents with severe headaches, vision changes, and acute panhypopituitarism.

Causes
The cause of pituitary tumors remains unknown. Though most pituitary tumors are sporadic, some genetic syndromes include increased risk for pituitary adenomas including Multiple endocrine neoplasia type 1 (caused by a mutation in the MEN1 gene) and Familial isolated pituitary adenoma (FIPA).
The majority of moderately raised prolactin levels (up to 5000 mIU/L) are not due to microprolactinomas but other causes. The effects of some prescription drugs are the most common. Other causes are other pituitary tumours and normal pregnancy and breastfeeding. This is discussed more under hyperprolactinaemia.The xenoestrogenic chemical Bisphenol-A has been shown to lead to hyperprolactinaemia and growth of prolactin-producing pituitary cells. The increasing and prolonged exposure of Bisphenol-A from childhood on, may contribute to the growth of a Prolactinoma.

Diagnosis
A doctor will test for prolactin blood levels in women with unexplained milk secretion (galactorrhea) or irregular menses or infertility, and in men with impaired sexual function and, in rare cases, milk secretion. If prolactin is high, a doctor will test thyroid function and ask first about other conditions and medications known to raise prolactin secretion. The doctor will also request a magnetic resonance imaging (MRI), which is the most sensitive test for detecting pituitary tumors and determining their size. MRI scans may be repeated periodically to assess tumor progression and the effects of therapy. Computed Tomography (CT scan) also gives an image of the pituitary, but it is less sensitive than the MRI.In addition to assessing the size of the pituitary tumor, doctors also look for damage to surrounding tissues and perform tests to assess whether production of other pituitary hormones is normal. Depending on the size of the tumor, the doctor may request an eye exam with measurement of visual fields.

Treatments
The goal of treatment is to return prolactin secretion to normal, reduce tumor size, correct any visual abnormalities, and restore normal pituitary function. As mentioned above, the impact of stress should be ruled out before the diagnosis of prolactinoma is given.  Exercise can significantly reduce stress and, thereby, prolactin levels.  In the case of very large tumors, only partial reduction of the prolactin levels may be possible.

Medications
Dopamine is the chemical that normally inhibits prolactin secretion, so clinicians may treat prolactinoma with drugs that act like dopamine such as bromocriptine and cabergoline. This type of drug is called a dopamine agonist. These drugs shrink the tumor and return prolactin levels to normal in approximately 80% of patients. Both bromocriptine and cabergoline have been approved by the Food and Drug Administration for the treatment of hyperprolactinemia. Bromocriptine is associated with side-effects such as nausea and dizziness and hypotension in patients with already low blood pressure readings. To avoid these side-effects, it is important for bromocriptine treatment to start slowly.Bromocriptine treatment should not be interrupted without consulting a qualified endocrinologist. Prolactin levels often rise again in most people when the drug is discontinued. In some, however, prolactin levels remain normal, so the doctor may suggest reducing or discontinuing treatment every two years on a trial basis. Recent studies have shown increased success in remission of prolactin levels after discontinuation, in patients having been treated for at least 2 years prior to cessation of bromocriptine treatment.Cabergoline is also associated with side effects such as nausea and dizziness, but these may be less common and less severe than with bromocriptine. However, people with low blood pressure should use caution when starting cabergoline treatment, as the long half-life of the drug (4–7 days) may inadvertently affect their ability to keep their blood pressure within normal limits, creating intense discomfort, dizziness, and even fainting upon standing and walking until the single first dose clears from their system. As with bromocriptine therapy, side effects may be avoided or minimized if treatment is started slowly. If a patients prolactin level remains normal for 6 months, a doctor may consider stopping treatment. Cabergoline should not be interrupted without consulting a qualified endocrinologist.Other dopamine agonists that have been used less commonly to suppress prolactin include dihydroergocryptine, ergoloid, lisuride, metergoline, pergolide, quinagolide, and terguride.

Surgery
Surgery should be considered if medical therapy cannot be tolerated or if it fails to reduce prolactin levels, restore normal reproduction and pituitary function, and reduce tumor size.  If medical therapy is only partially successful, this therapy should continue, possibly combined with surgery or radiation treatment.The results of surgery depend a great deal on tumor size and prolactin level.  The higher the prolactin level the lower the chance of normalizing serum prolactin.  In the best medical centers, surgery corrects prolactin levels in 80% of patients with a serum prolactin less than 250 ng/ml. Even in patients with large tumors that cannot be completely removed, drug therapy may be able to return serum prolactin to the normal range after surgery.  Depending on the size of the tumor and how much of it is removed, studies show that 20 to 50% will recur, usually within five years.

Prognosis
People with microprolactinoma generally have an excellent prognosis.  In 95% of cases, the tumor will not show any signs of growth after a 4 to 6-year period.Macroprolactinomas often require more aggressive treatment otherwise they may continue to grow.  There is no way to reliably predict the rate of growth, as it is different for every individual.  Regular monitoring by a specialist to detect any major changes in the tumor is recommended.

Osteoporosis risk
Hyperprolactinemia can cause reduced estrogen production in women and reduced testosterone production in men.  Although estrogen/testosterone production may be restored after treatment for hyperprolactinemia, even a year or two without estrogen/testosterone can compromise bone strength, and patients should protect themselves from osteoporosis by increasing exercise and calcium intake through diet or supplementation, and by avoiding smoking. Patients may want to have bone density measurements to assess the effect of estrogen/testosterone deficiency on bone density. They may also want to discuss testosterone/estrogen replacement therapy with their physician.

Pregnancy and oral birth control
If a woman has one or more small prolactinoma, there is no reason that she cannot conceive and have a normal pregnancy after successful medical therapy. The pituitary enlarges and prolactin production increases during normal pregnancy in women without pituitary disorders. Women with prolactin-secreting tumors may experience further pituitary enlargement and must be closely monitored during pregnancy. However, damage to the pituitary or eye nerves occurs in less than one percent of pregnant women with prolactinoma. In women with large tumors, the risk of damage to the pituitary or eye nerves is greater, and some doctors consider it as high as 25%. If a woman has completed a successful pregnancy, the chances of her completing further successful pregnancies are extremely high.A woman with a prolactinoma should discuss her plans to conceive with her physician, so she can be carefully evaluated prior to becoming pregnant. This evaluation will include a magnetic resonance imaging (MRI) scan to assess the size of the tumor and an eye examination with measurement of visual fields. As soon as a patient is pregnant, her doctor will usually advise that she stop taking bromocriptine or cabergoline, the common treatments for prolactinoma. Most endocrinologists see patients every two months throughout the pregnancy. The patient should consult her endocrinologist promptly if she develops symptoms — in particular, headaches, visual changes, nausea, vomiting, excessive thirst or urination, or extreme lethargy. Bromocriptine or cabergoline treatment may be renewed and additional treatment may be required if the patient develops symptoms from growth of the tumor during pregnancy.At one time, oral contraceptives were thought to contribute to the development of prolactinomas. However, this is no longer thought to be true. Patients with prolactinoma treated with bromocriptine or cabergoline may also take oral contraceptives. Likewise, post-menopausal estrogen replacement is safe in patients with prolactinoma treated with medical therapy or surgery.

Epidemiology
Autopsy studies indicate that 6-25% of the U. S. population have small pituitary tumors </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 Benign paroxysmal positional vertigo and can you explain it in depth? [/INST] Benign paroxysmal positional vertigo (BPPV) is a disorder arising from a problem in the inner ear. Symptoms are repeated, brief periods of vertigo with movement, characterized by a spinning sensation upon changes in the position of the head. This can occur with turning in bed or changing position. Each episode of vertigo typically lasts less than one minute. Nausea is commonly associated. BPPV is one of the most common causes of vertigo.BPPV is a type of balance disorder along with labyrinthitis and Ménières disease. It can result from a head injury or simply occur among those who are older. Often, a specific cause is not identified. When found, the underlying mechanism typically involves a small calcified otolith moving around loose in the inner ear. Diagnosis is typically made when the Dix–Hallpike test results in nystagmus (a specific movement pattern of the eyes) and other possible causes have been ruled out. In typical cases, medical imaging is not needed.BPPV is easily treated with a number of simple movements such as the Epley maneuver ( in case of diagonal/rotational nystagmus ), the Lempert maneuver ( in case of horizontal nystagmus ), the deep head hanging maneuver ( in case of vertical nystagmus ) or sometimes the less effective Brandt–Daroff exercises. Medications, including antihistamines such as meclizine, may be used to help with nausea. There is tentative evidence that betahistine may help with vertigo, but its use is not generally needed. BPPV is not a serious medical condition, but may present serious risks of injury through falling or other spatial disorientation-induced accidents.
When untreated, it might resolve in days to months; however, it may recur in some people. One can needlessly suffer from BPPV for years despite there being a simple an very effective cure. Short-term self-resolution of BPPV is unlikely because the effective cure maneuvers induce strong vertigo which the patient will naturally resist and not accidentally perform.
The first medical description of the condition occurred in 1921 by Róbert Bárány. Approximately 2.4% of people are affected at some point in time. Among those who live until their 80s, 10% have been affected. BPPV affects females twice as often as males. Onset is typically in people between the ages of 50 and 70.

Signs and symptoms
Symptoms:

Paroxysmal—appears suddenly, and in episodes of short duration: lasts only seconds to minutes
Positional—is induced by a change in position, even slight
Vertigo—a spinning dizziness, which must have a rotational component
Torsional nystagmus—a diagnostic symptom where the top of the eye rotates toward the affected ear in a beating or twitching fashion, which has a latency and can be fatigued (vertigo should lessen with deliberate repetition of the provoking maneuver): nystagmus should only last for 30 seconds to one minute
Pre-syncope—(feeling faint) or syncope (fainting) is unusual, but possible
Visual disturbance—due to associated nystagmus, making it difficult to read or see during an attack
Nausea—is often associated
Vomiting—is common, depending on the strength of vertigo itself and the causes for this illnessMany people will report a history of vertigo as a result of fast head movements. Many are also capable of describing the exact head movements that provoke their vertigo. Purely horizontal nystagmus and symptoms of vertigo lasting more than one minute can also indicate BPPV occurring in the horizontal semicircular canal.
The spinning sensation experienced from BPPV is usually triggered by movement of the head, will have a sudden onset, and can last anywhere from a few seconds to several minutes. The most common movements people report triggering a spinning sensation are tilting their heads upward in order to look at something and when rolling over in bed.People with BPPV do not experience other neurological deficits such as numbness or weakness. If those symptoms are present, a more serious etiology, such as posterior circulation stroke or ischemia, must be considered.
The most significant symptom is nystagmus as it is essential to determine the kind of nystagmus ( horizontal, vertical, or diagonal ) to select the correct cure maneuver.

Cause
Within the labyrinth of the inner ear lie collections of calcium crystals known as otoconia or otoliths. In people with BPPV, the otoconia are dislodged from their usual position within the utricle, and over time, migrate into one of the three semicircular canals (the posterior canal is most commonly affected due to its anatomical position). When the head is reoriented relative to gravity, the gravity-dependent movement of the heavier otoconial debris (colloquially "ear rocks") within the affected semicircular canal causes abnormal (pathological) endolymph fluid displacement and a resultant sensation of vertigo. This more common condition is known as canalithiasis. There is a direct link between the kind of nystagmus and which of the three semicircular canals is affected. With horizontal nystagmus ( left-right eye movement ) the horizontal ( also called lateral ) canal is affected, with vertical nystagmus ( up-down eye movement ) the superior ( also called anterior ) canal is affected, and with diagonal nystagmus ( diagonal or rotational eye movement ) the posterior canal is affected. Diagonal eye movement is easily confused with horizontal movement. This is important since it might result in selecting a wrong and thus ineffective cure maneuver.
In rare cases, the crystals themselves can adhere to a semicircular canal cupula, rendering it heavier than the surrounding endolymph. Upon reorientation of the head relative to gravity, the cupula is weighted down by the dense particles, thereby inducing an immediate and sustained excitation of semicircular canal afferent nerves. This condition is termed cupulolithiasis.There is evidence in the dental literature that malleting of an osteotome during closed sinus floor elevation, otherwise known as osteotome sinus elevation or lift, transmits percussive and vibratory forces capable of detaching otoliths from their normal location and thereby leading to the symptoms of BPPV.BPPV can be triggered by any action that stimulates the posterior semi-circular canal including:
Looking up or down
Following head injury
Sudden head movement
Rolling over in bed
Tilting the headBPPV may be made worse by any number of modifiers which may vary among individuals:
Changes in barometric pressure – people may feel increased symptoms up to two days before rain or snow
Lack of sleep (required amounts of sleep may vary widely)
StressAn episode of BPPV may be triggered by dehydration, such as that caused by diarrhea. For this reason, it commonly occurs in people with post-operative diarrhea induced by post-operative antibiotics.BPPV is one of the most common vestibular disorders in people presenting with dizziness; a migraine is implicated in idiopathic cases. Proposed mechanisms linking the two are genetic factors and vascular damage to the labyrinth.Although BPPV can occur at any age, it is most often seen in people older than the age of 60. Besides aging, there are no major risk factors known for BPPV, although previous episodes of head trauma, or the inner ear infection labyrinthitis, may predispose to the future development of BPPV.

Mechanism
The inside of the ear is composed of an organ called the vestibular labyrinth. The vestibular labyrinth includes three semicircular canals, which contain fluids and fine hairlike sensors that act as a monitor to the rotations of the head. An important structure in the inner ear includes the otolith organs that contain crystals that are sensitive to gravity. These crystals are responsible for sensitivity to head positions, and can also be dislocated, causing them to lodge inside one of the semicircular canals, which causes dizziness.

Diagnosis
The condition is diagnosed by the persons history, and by performing the Dix–Hallpike test or the roll test, or both. The patient can also be asked to induce vertigo by performing a movement that the patient knows to induce vertigo. The eyes of the patient can then easily be observed for which kind ( horizontal, vertical, or diagonal ) of nystagmus is present, to determine which semicircular canal ( horizontal, superior, or posterior ) is affected.
The Dix–Hallpike test is a common test performed by examiners to determine whether the posterior semicircular canal is involved. It involves a reorientation of the head to align the posterior semicircular canal (at its entrance to the ampulla) with the direction of gravity. This test will reproduce vertigo and nystagmus characteristic of posterior canal BPPV.When performing the Dix–Hallpike test, people are lowered quickly to a supine position, with the neck extended by the person performing the maneuver. For some people, this maneuver may not be indicated, and a modification may be needed that also targets the posterior semicircular canal. Such people include those who are too anxious about eliciting the uncomfortable symptoms of vertigo, and those who may not have the range of motion necessary to comfortably be in a supine position. The modification involves the person moving from a seated position to side-lying without their head extending off the examination table, such as with Dix–Hallpike. The head is rotated 45 degrees away from the side being tested, and the eyes are examined for nystagmus. A positive test is indicated by the patient report of a reproduction of vertigo and clinician observation of nystagmus. Both the Dix–Hallpike and the side-lying testing position have yielded similar results, and as such the side-lying position can be used if the Dix–Hallpike cannot be performed easily.The roll test can determine whether the horizontal semicircular canal is involved. The roll test requires the person to be in a supine position with their head in 30° of cervical flexion. Then the examiner quickly rotates the head 90° to the left side, and checks for vertigo and nystagmus. This is followed by gently bringing the head back to the starting position. The examiner then quickly rotates the head 90° to the right side and checks again for vertigo and nystagmus. In this roll test, the person may experience vertigo and nystagmus on both sides, but rotating toward the affected side will trigger a more intense vertigo. Similarly, when the head is rotated toward the affected side, the nystagmus will beat toward the ground and be more intense.As mentioned above, both the Dix–Hallpike and roll test provoke the signs and symptoms in subjects with archetypal BPPV. The signs and symptoms people with BPPV experience are typically a short-lived vertigo and observed nystagmus. In some people, although rarely, vertigo can persist for years. Assessment of BPPV is best done by a medical health professional skilled in the management of dizziness disorders, commonly a physiotherapist, audiologist, or other physician.The nystagmus associated with BPPV has several important characteristics that differentiate it from other types of nystagmus.

Latency of onset: there is a 5–10 second delay prior to onset of nystagmus
Nystagmus lasts for 5–60 seconds
Positional: the nystagmus occurs only in certain positions
Repeated stimulation, including via Dix–Hallpike maneuvers, cause the nystagmus to fatigue or disappear temporarily
Rotatory/torsional component is present, or (in the case of lateral canal involvement) the nystagmus beats in either a geotropic (toward the ground) or ageotropic (away from the ground) fashion
Visual fixation suppresses nystagmus due to BPPVAlthough rare, CNS disorders can sometimes present as BPPV. A practitioner should be aware that if a person whose symptoms are consistent with BPPV, but does not show improvement or resolution after undergoing different particle repositioning maneuvers — detailed in the Treatment section below — need to have a detailed neurological assessment and imaging performed to help identify the pathological condition.

Differential diagnosis
Vertigo, a distinct process sometimes confused with the broader term, dizziness, accounts for about six million clinic visits in the United States every year; between 17 and 42% of these people are eventually diagnosed with BPPV.
Other causes of vertigo include:

Motion sickness/motion intolerance: a disjunction between visual stimulation, vestibular stimulation, and/or proprioception
Visual exposure to nearby moving objects (examples of optokinetic stimuli include passing cars and falling snow)
Other diseases: (labyrinthitis, Ménières disease, and migraine, etc.)

Treatment
Repositioning maneuvers
A number of maneuvers have been found to be effective including the Epley maneuver, the Semont maneuver, and to a lesser degree Brandt–Daroff exercises. Both the Epley and the Semont maneuvers are equally effective. None of these maneuvers addresses the presence of the particles (otoconia); rather it changes their location. The maneuvers aim to move these particles from some locations in the inner ear that cause symptoms such as vertigo and reposition them to where they do not cause these problems. These maneuvers are easily performed at home and online resources are available to patients. The Epley maneuver is the most popular of the maneuvers because it is designed to address particles in the posterior semicircular canal, the most common cause of BPPV. This might give the wrong impression that the Epley maneuver is the cure for all BPPV. Misdiagnosing which semicircular canal is affected, typically by confusing horizontal and diagonal nystagmus, or simply ignoring the identification of the affected canal, results regularly in no cure. Using the appropriate maneuver for the affected canal is essential. The maneuvers are uncomfortable for the patient as they induce strong vertigo and the patient might resist performing them. If the maneuver is not uncomfortable then most likely the wrong maneuver has been selected by a misdiagnosis of the affected semicircular canal. All the maneuvers consist of a series of steps in which the head is held in a specific position, typically for 30 to 60 seconds until nystagmus stops. Movement from one position to the position of the next step has to be done fluently to give the particles enough momentum to move. A position has to be held until nystagmus has completely resided, which indicates that the particles have stopped moving, before one proceeds to the next step.

Epley maneuver
The Epley maneuver employs gravity to move the calcium crystal build-up from the posterior semicercular canal ( resulting in diagonal nystagmus ) that causes the condition. This maneuver can be performed during a clinic visit by health professionals, or taught to people to perform at home, or both. Postural restriction after the Epley maneuver increases its effect somewhat.When practiced at home, the Epley maneuver is more effective than the Semont maneuver. The most effective repositioning treatment for posterior canal BPPV is the therapist-performed Epley combined with home-practiced Epley maneuvers. Devices such as the DizzyFIX can help users conduct the Epley maneuver at home, and are available for the treatment of BPPV.

Lempert maneuver or Roll maneuver
For the lateral (horizontal) canal, resulting in horizontal nystagmus, the Lempert maneuver has been used for productive results. It is unusual for the lateral canal to respond to the canalith repositioning procedure used for the posterior canal BPPV. Treatment is therefore geared toward moving the canalith from the lateral canal into the vestibule.The roll maneuver or its variations are used, and involve rolling the person 360 degrees in a series of steps to reposition the particles. This maneuver is generally performed by a trained clinician who begins seated at the head of the examination table with the person supine There are four stages, each a minute apart, and at the third position the horizontal canal is oriented in a vertical position with the persons neck flexed and on forearm and elbows. When all four stages are completed, the head roll test is repeated, and if negative, treatment ceases.

Deep head hanging maneuver
For the superior ( also called anterior ) semicircular canal, resulting in vertical nystagmus, the Deep head hanging maneuver is used. The patient lays down on their back on a bed with their head overhanging the bed.
In the first step the head is turned as backward (hanging) as possible. In the following step, the patient remains lying but lifts their head with the chin close to the chest. In the last step, the patient sits upright with the head in the normal position. Before going to the next step, one has to wait until the nystagmus fully resides ( typical 30 to 60 seconds ) and progression from one step to the next has to happen in a fluid movement.

Semont maneuver
The Semont maneuver has a cure rate of 90.3%. It is performed as follows:

The person is seated on a treatment table with their legs hanging off the side of the table. The therapist then turns the persons head 45 degrees toward the unaffected side.
The therapist then quickly tilts the person so they are lying on the affected side. The head position is maintained, so their head is turned up 45 degrees. This position is maintained for 3 minutes. The purpose is to allow the debris to move to the apex of the semicircular duct.
The person is then quickly moved so they are lying on the unaffected side with their head in the same position (now facing downward 45 degrees). This position is also held for 3 minutes. The purpose of this position is to allow the debris to move toward the exit of the semicircular duct.
Finally, the person is slowly brought back to an upright seated position. The debris should then fall into the utricle of the canal and the symptoms of vertigo should decrease or end completely.Some people will only need one treatment, but others may need multiple treatments, depending on the severity of their BPPV. In the Semont maneuver, as with the Epley maneuver, people are able to achieve canalith repositioning by themselves.

Brandt–Daroff exercises
The Brandt–Daroff exercises may be prescribed by the clinician as a home treatment method, usually in conjunction with particle-repositioning maneuvers or in lieu of the particle-repositioning maneuver. The exercise is a form of habituation exercise, designed to allow the person to become accustomed to the position that causes the vertigo symptoms </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 Hiatal hernia and can you explain it in depth? [/INST] A hiatal hernia or hiatus hernia is a type of hernia in which abdominal organs (typically the stomach) slip through the diaphragm into the middle compartment of the chest. This may result in gastroesophageal reflux disease (GERD) or laryngopharyngeal reflux (LPR) with symptoms such as a taste of acid in the back of the mouth or heartburn. Other symptoms may include trouble swallowing and chest pains. Complications may include iron deficiency anemia, volvulus, or bowel obstruction.The most common risk factors are obesity and older age. Other risk factors include major trauma, scoliosis, and certain types of surgery. There are two main types: sliding hernia, in which the body of the stomach moves up; and paraesophageal hernia, in which an abdominal organ moves beside the esophagus. The diagnosis may be confirmed with endoscopy or medical imaging. Endoscopy is typically only required when concerning symptoms are present, symptoms are resistant to treatment, or the person is over 50 years of age.Symptoms from a hiatal hernia may be improved by changes such as raising the head of the bed, weight loss, and adjusting eating habits. Medications that reduce gastric acid such as H2 blockers or proton pump inhibitors may also help with the symptoms. If the condition does not improve with medications, a surgery to carry out a laparoscopic fundoplication may be an option. Between 10% and 80% of people in the United States are affected.

Signs and symptoms
Hiatal hernia has often been called the "great mimic" because its symptoms can resemble many disorders. Among them, a person with a hiatal hernia can experience dull pains in the chest, shortness of breath (caused by the hernias effect on the diaphragm), heart palpitations (due to irritation of the vagus nerve), and swallowed food "balling up" and causing discomfort in the lower esophagus until it passes on to the stomach.  In addition, hiatal hernias often result in heartburn but may also cause chest pain or pain with eating.In most cases however, a hiatal hernia does not cause any symptoms. The pain and discomfort that a patient experiences is due to the reflux of gastric acid, air, or bile. While there are several causes of acid reflux, it occurs more frequently in the presence of hiatal hernia.
In newborns, the presence of Bochdalek hernia can be recognised from symptoms such as difficulty breathing fast respiration, increased heart rate.

Causes
The following are potential causes of a hiatal hernia.
Increased pressure within the abdomen caused by:
Heavy lifting or bending over
Frequent or hard coughing
Hard sneezing
Violent vomiting
Straining during defecation (i.e., the Valsalva maneuver)Obesity and age-related changes to the diaphragm are also general risk factors.

Diagnosis
The diagnosis of a hiatal hernia is typically made through an upper GI series, endoscopy, high resolution manometry, esophageal pH monitoring, and computed tomography (CT). Barium swallow as in upper GI series allows the size, location, stricture, stenosis of oesophagus to be seen. Besides, it can also evaluate the oesophageal movements. Endoscopy can analyse the eosophageal internal surface for erosions, ulcers, and tumours. Meanwhile, manometry can determine the integrity of esophageal movements, and the presence of esophageal achalasia. pH testings allows the quantitative analysis of acid reflux episodes. CT scan is useful in diagnosing complications of hiatal hernia such as gastric volvulus, perforation, pneumoperitoneum, and pneumomediastinum.

Classification
Four types of esophageal hiatal hernia are identified:Type I: A type I hernia, also known as a sliding hiatal hernia, occurs when part of the stomach slides up through the hiatal opening in the diaphragm. There is a widening of the muscular hiatal tunnel and circumferential laxity of the phrenoesophageal ligament, allowing a portion of the gastric cardia to herniate upward into the posterior mediastinum. The clinical significance of type I hernias is in their association with reflux disease. Sliding hernias are the most common type and account for 95% of all hiatal hernias. (C)
Type II: A type II hernia, also known as a paraesophageal or rolling hernia, occurs when the fundus and greater curvature of the stomach roll up through the diaphragm, forming a pocket alongside the esophagus. It results from a localized defect in the phrenoesophageal ligament while the gastroesophageal junction remains fixed to the pre aortic fascia and the median arcuate ligament. The gastric fundus then serves as the leading point of herniation. Although type II hernias are associated with reflux disease, their primary clinical significance lies in the potential for mechanical complications. (D)
Type III: Type III hernias have elements of both types I and II hernias. With progressive enlargement of the hernia through the hiatus, the phrenoesophageal ligament stretches, displacing the gastroesophageal junction above the diaphragm, thereby adding a sliding element to the type II hernia.
Type IV: Type IV hiatus hernia is associated with a large defect in the phrenoesophageal ligament, allowing other organs, such as colon, spleen, pancreas and small intestine to enter the hernia sac.
The end stage of type I and type II hernias occurs when the whole stomach migrates up into the chest by rotating 180° around its longitudinal axis, with the cardia and pylorus as fixed points. In this situation the abnormality is usually referred to as an intrathoracic stomach.

Treatment
In the great majority of cases, people experience no significant discomfort, and no treatment is required. People with symptoms should elevate the head of their beds and avoid lying down directly after meals. If the condition has been brought on by stress, stress reduction techniques may be prescribed, or if overweight, weight loss may be indicated.

Medications
Antisecretory drugs such as proton pump inhibitors and H2 receptor blockers can be used to reduce acid secretion. Medications that reduce the lower esophageal sphincter (LES) pressure should be avoided.

Procedures
There is tentative evidence from non-controlled trials that oral neuromuscular training may improve symptoms. This has been approved by the UK National Health Service (NHS) for supply on prescription from 1 May 2022.

Surgery
In some unusual instances, as when the hiatal hernia is unusually large, or is of the paraesophageal type, it may cause esophageal stricture or severe discomfort. About 5% of hiatal hernias are paraesophageal. If symptoms from such a hernia are severe for example if chronic acid reflux threatens to severely injure the esophagus or is causing Barretts esophagus, surgery is sometimes recommended </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 Medullary sponge kidney and can you explain it in depth? [/INST] Medullary sponge kidney is a congenital disorder of the kidneys characterized by cystic dilatation of the collecting tubules in one or both kidneys. Individuals with medullary sponge kidney are at increased risk for kidney stones and urinary tract infection (UTI). Patients with MSK typically pass twice as many stones per year as do other stone formers without MSK. While having a low morbidity rate, as many as 10% of patients with MSK have an increased risk of morbidity associated with frequent stones and UTIs. While many patients report increased chronic kidney pain, the source of the pain, when a UTI or blockage is not present, is unclear at this time. Renal colic (flank and back pain) is present in 55% of patients. Women with MSK experience more stones, UTIs, and complications than men. MSK was previously believed not to be hereditary but there is more evidence coming forth that may indicate otherwise.

Signs and symptoms
Most cases are asymptomatic or are discovered during an investigation of blood in the urine. Symptomatic patients typically present as middle-aged adults with renal colic, kidney stones, nephrocalcinosis and/or recurrent urinary tract infections; however, MSK also may affect children very rarely. In addition to the typical clinical phenotype of recurrent stone disease, other clinical profiles have now been recognized, that is, an indolent, almost asymptomatic MSK, and a rare form characterized by intractable pain.

Complications
Complications associated with medullary sponge kidney include the following:

Kidney stones
Urinary tract infection (UTI)
Blood in the urine
Distal renal tubular acidosis (Type 1 RTA)
Chronic kidney disease (rarely)
Marked chronic pain

Cause
In recent studies, insight has been obtained on the genetic basis of this disease, supporting the hypothesis that MSK is due to a disruption at the ureteric bud-metanephric mesenchyme interface. This explains why so many tubular defects coexist in this disease, and particularly a distal tubular acidification defect of which the highly prevalent metabolic bone disease is one very important consequence. In addition to the typical clinical phenotype of recurrent stone disease, other clinical profiles have now been recognized, that is, an indolent, almost asymptomatic MSK, and a rare form characterized by intractable, excruciating pain. It was previously believed that most cases of medullary sponge kidney were sporadic; however, recent studies show familial clustering of MSK is common and has an autosomal dominant inheritance, a reduced penetrance, and variable expressivity.  Other theories suggest that dilatation of a collecting duct may occur, caused by occlusion by uric acid during fetal life or resulting from tubular obstruction due to calcium oxalate calculi secondary to infantile hypercalciuria.A rare, autosomal recessive form is associated with Caroli disease.

Diagnosis
Classically, MSK is seen as hyperechoic papillae with clusters of small stones on ultrasound examination of the kidney or with an abdominal x-ray. The irregular (ectatic) collecting ducts are often seen in MSK, which are sometimes described as having a "paintbrush-like" appearance, are best seen on intravenous urography. However, IV urography has been largely replaced by contrast-enhanced, high-resolution helical CT with digital reconstruction.

Treatment
Often, aggressive treatment is unnecessary for people with MSK disease that does not cause any symptoms (asymptomatic) </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 HELLP syndrome and can you explain it in depth? [/INST] HELLP syndrome is a complication of pregnancy; the acronym stands for hemolysis, elevated liver enzymes, and low platelet count. It usually begins during the last three months of pregnancy or shortly after childbirth. Symptoms may include feeling tired, retaining fluid, headache, nausea, upper right abdominal pain, blurry vision, nosebleeds, and seizures. Complications may include disseminated intravascular coagulation, placental abruption, and kidney failure.The cause is unknown. The condition occurs in association with pre-eclampsia or eclampsia. Other risk factors include previously having the syndrome and a mother older than 25 years. The underlying mechanism may involve abnormal placental development. Diagnosis is generally based on blood tests finding signs of red blood cell breakdown (lactate dehydrogenase greater than 600 U/L), an aspartate transaminase greater than 70 U/L, and platelets less than 100×109/l. If not all the criteria are present, the condition is incomplete.Treatment generally involves delivery of the baby as soon as possible. This is particularly true if the pregnancy is beyond 34 weeks of gestation. Medications may be used to decrease blood pressure and blood transfusions may be required.HELLP syndrome occurs in about 0.7% of pregnancies and affects about 15% of women with eclampsia or severe pre-eclampsia. Death of the mother is uncommon (< 1%). Outcomes in the babies are generally related to how premature they are at birth. The syndrome was first named in 1982 by American gynaecologist Louis Weinstein.

Signs and symptoms
The first signs of HELLP usually start appearing midway through the third trimester, though the signs can appear in earlier and later stages. Symptoms vary in severity and between individuals and are commonly mistaken with normal pregnancy symptoms, especially if they are not severe.HELLP syndrome patients experience general discomfort followed by severe epigastric pain or right upper abdominal quadrant pain, accompanied by nausea, vomiting, backache, anaemia, and hypertension. Some patients may also have a headache and visual issues. These symptoms may also become more severe at night. As the condition progresses and worsens, a spontaneous hematoma occurs following the rupture of the liver capsule, which occurs more frequently in the right lobe. The presence of any combinations of these symptoms, subcapsular liver hematoma in particular, warrants an immediate check-up due to the high morbidity and mortality rates of this condition.

Risk factors
Elevated body mass index and metabolic disorders, as well as antiphospholipid syndrome, significantly increase the risk of HELLP syndrome in all female patients. Females who have had or are related to a female with previous HELLP syndrome complications tend to be at a higher risk in all their subsequent pregnancies.The risk of HELLP syndrome is not conclusively associated with a specific genetic variation, but likely a combination of genetic variations, such as FAS gene, VEGF gene, glucocorticoid receptor gene and the tol-like receptor gene, increase the risk.

Pathophysiology
The pathophysiology is still unclear and an exact cause is yet to be found. However, it shares a common mechanism, which is endothelial cell injury, with other conditions, such as acute kidney injury and thrombotic thrombocytopenic purpura. Increasing the understanding of HELLP syndromes pathophysiology will enhance diagnostic accuracy, especially in the early stages. This will lead to advancements in the prevention, management, and treatment of the condition, which will increase the likelihood of both maternal and fetal survival and recovery.

Inflammation and coagulation
As a result of endothelial cell injury, a cascade of pathological reactions manifests and become increasingly severe and even fatal as signs and symptoms progress. Following endothelial injury, vasospasms and platelet activation occur alongside the decreased release of the endothelium-derived relaxing factor and increased the release of von Willebrand factor (vWF), leading to general activation of the coagulation cascade and inflammation. Placental components, such as inflammatory cytokines and syncytiotrophoblast particles interact with the maternal immune system and endothelial cells, further promoting coagulation and inflammation. These interactions also elevate leukocyte numbers and interleukin concentrations, as well as increase complement activity.

Low platelet count
vWF degradation in HELLP syndrome is inhibited due to decreased levels of degrading proteins, leading to an increased exposure of platelets to vWF. As a result, thrombotic microangiopathies develop and lead to thrombocytopenia.

Blood breakdown
As a result of the high number of angiopathies, the erythrocytes fragment as they pass through the blood vessels with damaged endothelium and large fibrin networks, leading to macroangiopathic haemolytic anaemia. As a consequence of hemolysis, lactic acid dehydrogenase (LDH) and hemoglobin are released, with the latter binding to serum bilirubin or haptoglobin.

Liver
During the coagulation cascade, fibrin is deposited in the liver and leads to hepatic sinusoidal obstruction and vascular congestion, which increase intrahepatic pressure. Placenta-derived FasL (CD95L), which is toxic to human hepatocytes, leads to hepatocyte apoptosis and necrosis by inducing the expression of TNFα and results in the release of liver enzymes. Hepatic damages are worsened by the disrupted portal and total hepatic blood flow that result as a consequence of the microangiopathies. Collectively, widespread endothelial dysfunction and hepatocellular damage result in global hepatic dysfunction often leading to liver necrosis, haemorrhages, and capsular rupture.

Diagnosis
Early and accurate diagnosis, which relies on laboratory tests and imaging exams, is essential for treatment and management and significantly reduces the morbidity rate. However, diagnosis of the syndrome is challenging, especially due to the variability in the signs and symptoms and the lack of consensus amongst healthcare professionals. Similarities to other conditions, as well as normal pregnancy features, commonly lead to misdiagnosed cases or more often, delayed diagnosis.There is a general consensus regarding the main three diagnostic criteria of HELLP syndrome, which include hepatic dysfunction, thrombocytopenia and microangiopathic haemolytic anaemia in patients suspected to have preeclampsia.
A blood smear will often exhibit abnormalities, such as schistocytes, bur cells, and helmet cells, which indicate erythrocyte damage.
Thrombocytopenia, which is the earliest coagulopathy present in all HELLP syndrome patients, is indicated by low platelet count (below 100 x 109 L-1) or by testing the levels of fibrin metabolites and antithrombin III.
Elevated serum levels of certain proteins, in particular, LDH, alanine transaminase (ALT) and aspartate transaminase (AST), are indicative of hepatic dysfunction. Extremely high serum levels of these proteins, specifically LDH levels > 1,400 IU/L, AST levels > 150 IU/L and ALT levels > 100 IU/L, significantly elevate the risk of maternal mortality.A number of other, but less conclusive, clinical diagnostic criteria are also used in diagnosis alongside the main clinical diagnostic criteria for HELLP syndrome.

De novo manifestation of hypertension with systolic pressure and diastolic pressure above 160mmHg and 110 mmHg, respectively.
Proteinuria, leucocytosis and elevated uric acid concentrations > 7.8 mg.
Decreased serum haptoglobin and haemoglobin levels.
Increased serum bilirubin levels and visual disturbances.Imaging tests, such as ultrasound, tomography or magnetic resonance imaging (MRI), are instrumental in the correct diagnosis of HELLP syndrome in patients with suspected liver dysfunction. Unurgent cases must undergo MRI, but laboratory tests, such as glucose determination, are more encouraged in mild cases of HELLP syndrome.

Classification
A classification system, which was developed in Mississippi, measures the severity of the syndrome using the lowest observed platelet count in the patients alongside the appearance of the other two main clinical criteria. Class I is the most severe, with a relatively high risk of morbidity and mortality, compared to the other two classes.
Class I HELLP syndrome is characterised by a platelet count below 50,000/µL.
Class II HELLP syndrome is characterised by a platelet count of 50,000-100,000/µL.
Class III HELLP syndrome is characterised by a platelet count of 100,000-150,000/µL.Another classification system, introduced in Memphis, categorises HELLP syndrome based on its expression.

Partial expression of the condition is characterised by the manifestation of one or two of the main diagnostic criteria.
The complete expression of the condition is characterised by the manifestation of all three main diagnostic criteria.

Treatment
The only current recommended and most effective treatment is delivery of the baby, as the signs and symptoms diminish and gradually disappear following the delivery of the placenta </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 Tension headache and can you explain it in depth? [/INST] Tension headache, also known as stress headache, or tension-type headache (TTH), is the most common type of primary headache. The pain can radiate from the lower back of the head, the neck, eyes or other muscle groups in the body typically affecting both sides of the head. Tension-type headaches account for nearly 90% of all headaches.
Pain medications, such as paracetamol and ibuprofen, are effective for the treatment of tension headache. Tricyclic antidepressants appear to be useful for prevention. Evidence is poor for SSRIs, propranolol and muscle relaxants.As of 2016, tension headaches affect about 1.89 billion people and are more common in women than men (23% to 18% respectively).

Signs and symptoms
According to the third edition of the International Classification of Headache Disorders, the attacks must meet the following criteria:

A duration of between 30 minutes and 7 days.
At least two of the following four characteristics:
bilateral location
pressing or tightening (non-pulsating) quality
mild or moderate intensity
not aggravated by routine physical activity such as walking or climbing stairs
Both of the following:
no nausea or vomiting
no more than one of photophobia (sensitivity to bright light) or phonophobia (sensitivity to loud sounds)Tension-type headaches may be accompanied by tenderness of the scalp on manual pressure during an attack.

Risk factors
Various precipitating factors may cause tension-type headaches in susceptible individuals:
Anxiety
Stress
Sleep problems
Young age
Poor health

Mechanism
Although the musculature of the head and neck and psychological factors such as stress may play a role in the overall pathophysiology of TTH, neither is currently believed to be the sole cause of the development of TTH. The pathologic basis of TTH is most likely derived from a combination of personal factors, environmental factors, and alteration of both peripheral and central pain pathways. Peripheral pain pathways receive pain signals from pericranial (around the head) myofascial tissue (protective tissue of muscles) and alteration of this pathway likely underlies episodic tension-type headache (ETTH). In addition to these myofascial tissue pain signals, pericranial muscle tenderness, inflammation, and muscle ischemia have been postulated in headache literature to be causal factors in the peripheral pathophysiology of TTH. However, multiple studies have failed to illustrate evidence for a pathologic role of either ischemia or inflammation within the muscles. Pericranial tenderness is also not likely a peripheral causal factor for TTH, but may instead act to trigger a chronic pain cycle in which the peripheral pain response is transformed over time into a centralized pain response. It is then these prolonged alterations in the peripheral pain pathways that lead to increased excitability of the central nervous system pain pathways, resulting in the transition of episodic tension-type headache into chronic tension type headache (CTTH). Specifically, the hyperexcitability occurs in central nociceptive neurons (the trigeminal spinal nucleus, thalamus, and cerebral cortex) resulting in central sensitization, which manifests clinically as allodynia and hyperalgesia of CTTH. Additionally, CTTH patients exhibit decreased thermal and pain thresholds which further bolsters support for central sensitization occurring in CTTH.The alterations in physiology that lead to overall process of central sensitization involve changes at the level of neural tracts, neurotransmitters and their receptors, the neural synapse, and the post-synaptic membrane. Evidence suggests dysfunction in supraspinal descending inhibitory pain pathways may contribute to the pathogenesis of central sensitization in CTTH.

Neurotransmitters
Specific neuronal receptors and neurotransmitters thought to be most involved include NMDA and AMPA receptors, glutamate, serotonin (5-HT), β-endorphin, and nitric oxide (NO). Of the neurotransmitters, NO plays a major role in central pain pathways and likely contributes to the process of central sensitization. Briefly, the enzyme nitric oxide synthase (NOS) forms NO which ultimately results in vasodilatation and activation of central nervous system pain pathways. Serotonin may also be of significant importance and involved in malfunctioning pain filter located in the brain stem. The view is that the brain misinterprets information—for example from the temporal muscle or other muscles—and interprets this signal as pain. Evidence for this theory comes from the fact that chronic tension-type headaches may be successfully treated with certain antidepressants such as nortriptyline. However, the analgesic effect of nortriptyline, as well as amitriptyline in chronic tension-type headache, is not solely due to serotonin reuptake inhibition, and likely other mechanisms are involved.

Synapses
Regarding synaptic level changes, homosynaptic facilitation and heterosynaptic facilitation are both likely to be involved in central sensitization. Homosynaptic facilitation occurs when synapses normally involved in pain pathways undergo changes involving receptors on the post-synaptic membrane as well as the molecular pathways activated upon synaptic transmission. Lower pain thresholds of CTTH result from this homosynaptic facilitation. In contrast, heterosynaptic facilitation occurs when synapses not normally involved in pain pathways become involved. Once this occurs innocuous signals are interpreted as painful signals. Allodynia and hyperalgesia of CTTH represent this heterosynaptic facilitation clinically.

Stress
In the literature, stress is mentioned as a factor and may be implicated via the adrenal axis. This ultimately results in downstream activation of NMDA receptor activation, NFκB activation, and upregulation of iNOS with subsequent production of NO leading to pain as described above.

Diagnosis
With TTH, the physical exam is expected to be normal with perhaps the exception of either pericranial tenderness upon palpation of the cranial muscles, or presence of either photophobia or phonophobia.

Classification
The International Headache Societys most current classification system for headache disorders is the International Classification of Headache Disorders 3rd edition (ICHD-3) as of 2018. This classification system separates tension-type headache (TTH) into two main groups: episodic (ETTH) and chronic (CTTH). CTTH is defined as fifteen days or more per month with headache for greater than three months, or one-hundred eighty days or more, with headache per year. ETTH is less than fifteen days per month with headache or less than one-hundred eighty days with headache per year. However, ETTH is further sub-divided into frequent and infrequent TTH. Frequent TTH is defined as ten or more episodes of headache over the course of one to fourteen days per month for greater than three months, or at least twelve days per year, but less than one-hundred eighty days per year. Infrequent TTH is defined as ten or more episodes of headache for less than one day per month or less than twelve days per year. Furthermore, all sub-classes of TTH can be classified as having presence or absence of pericranial tenderness, which is tenderness of the muscles of the head. Probable TTH is utilized for patients with some characteristics, but not all characteristics of a given sub-type of TTH.

Differential diagnosis
Extensive testing is not needed as TTH is diagnosed by history and physical. However, if symptoms indicative of a more serious diagnosis are present, a contrast enhanced MRI may be utilized. Furthermore, giant cell arteritis should be considered in those 50 years of age and beyond. Screening for giant cell arteritis involves the blood tests of erythrocyte sedimentation rate (ESR) and c-reactive protein.
Migraine
Oromandibular dysfunction
Sinus disease
Eye disease
Cervical spine disease
Infection in immunocompromised
Intracranial mass
Idiopathic intracranial hypertension
Medication overuse headache
Secondary headache (headache due to other disorder)
Giant cell arteritis ( ≥50 years of age)
Dermatochalasis

Prevention
Lifestyle
Good posture might prevent headaches if there is neck pain.Drinking alcohol can make headaches more likely or severe.Drinking water and avoiding dehydration helps in preventing tension headache.People who have jaw clenching might develop headaches, and getting treatment from a dentist might prevent those headaches.Using stress management and relaxing often makes headaches less likely.Biofeedback techniques may also help.

Medications
People who have 15 or more headaches in a month may be treated with certain types of daily antidepressants which act to prevent continued tension headaches from occurring. In those who are predisposed to tension type headaches the first-line preventative treatment is amitriptyline, whereas mirtazapine and venlafaxine are second-line treatment options. Tricyclic antidepressants appear to be useful for prevention. Tricyclic antidepressants have been found to be more effective than SSRIs but have greater side effects. Evidence is poor for the use of SSRIs, propranolol, and muscle relaxants for prevention of tension headaches.

Treatment
Treatment for a current tension headache is to drink water and confirm that there is no dehydration. If symptoms do not resolve within an hour for a person who has had water, then stress reduction might resolve the issue.

Exercise
Evidence supports simple neck and shoulder exercises in managing ETTH and CTTH for headaches associated with neck pain. Exercises include stretching, strengthening and range of motion exercises. CTTH can also benefit from combined therapy from stress therapy, exercises and postural correction.

Medications
Episodic
Over-the-counter drugs, like paracetamol, or NSAIDs (ibuprofen, aspirin, naproxen, ketoprofen), can be effective but tend to only be helpful as a treatment for a few times in a week at most. For those with gastrointestinal problems (ulcers and bleeding), acetaminophen is the better choice over aspirin, though both provide roughly equivalent pain relief. It is important to note that large daily doses of paracetamol should be avoided as it may cause liver damage especially in those that consume 3 or more drinks/day and those with pre-existing liver disease.  Ibuprofen, one of the NSAIDs listed above, is a common choice for pain relief but may also lead to gastrointestinal discomfort.Analgesic/caffeine combinations are popular such as the aspirin-caffeine combination or the aspirin, paracetamol and caffeine combinations. Frequent use (daily or skipping just one day in between use for 7–10 days) of any of the above analgesics may, however, lead to medication overuse headache.Analgesic/sedative combinations are widely used (e.g., analgesic/antihistamine combinations, analgesic/barbiturate combinations such as Fiorinal).Muscle relaxants are typically used for and are helpful with acute post-traumatic TTH rather than ETTH. Opioid medications are not utilized to treat ETTH. Botulinum toxin does not appear to be helpful.

Chronic
Classes of medications involved in treatment of CTTH include tricyclic antidepressants (TCAs), SSRIs, benzodiazepine (Clonazepam in small evening dose), and muscle relaxants. The most commonly utilized TCA is amitriptyline due to the postulated role in decreasing central sensitization and analgesic relief. Another popular TCA used is Doxepine. SSRIs may also be utilized for management of CTTH. For patients with concurrent muscle spasm and CTTH, the muscle relaxant Tizanidine can be a helpful option.These medications however, are not effective if concurrent overuse of over the counter medications or other analgesics is occurring. Stopping overuse must occur prior to proceeding with other forms of treatment.

Manual therapy
Current evidence for acupuncture is slight </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 Ehlers–Danlos syndromes and can you explain it in depth? [/INST] Ehlers–Danlos syndromes (EDS) are a group of 13 genetic connective-tissue disorders in the current classification, with a 14th type discovered in 2018. Symptoms include loose joints, joint pain, stretchy velvety skin, and abnormal scar formation. These may be noticed at birth or in early childhood. Complications may include aortic dissection, joint dislocations, scoliosis, chronic pain, or early osteoarthritis.EDS occurs due to variations of more than 19 genes that are present at birth. The specific gene affected determines the type of EDS. Some cases result from a new variation occurring during early development, while others are inherited in an autosomal dominant or recessive manner. Typically, these variations result in defects in the structure or processing of the protein collagen.Diagnosis is often based on symptoms and confirmed by genetic testing or skin biopsy, but people may initially be misdiagnosed with hypochondriasis, depression, or chronic fatigue syndrome.No cure is known and treatment is supportive in nature. Physical therapy and bracing may help strengthen muscles and support joints. Some forms of EDS result in a normal life expectancy, but those that affect blood vessels generally decrease it.The hypermobile type of EDS (hEDS) affects at least one in 5,000 people globally; other types occur at lower frequencies. The prognosis depends on the specific disorder. Excess mobility was first described by Hippocrates in 400 BC. The syndromes are named after two physicians, Edvard Ehlers and Henri-Alexandre Danlos, who described them at the turn of the 20th century.

Types
In 2017, 13 subtypes of EDS were classified using specific diagnostic criteria. According to the Ehlers–Danlos Society, the syndromes can also be grouped by the symptoms determined by specific gene mutations. Group A disorders are those that affect primary collagen structure and processing. Group B disorders affect collagen folding and crosslinking. Group C are disorders of structure and function of myomatrix. Group D disorders are those that affect glycosaminoglycan biosynthesis. Group E disorders are characterized by defects in the complement pathway. Group F are disorders of intracellular processes, and Group G is considered to be unresolved forms of EDS.

Hypermobile EDS
Hypermobile EDS (hEDS, formerly categorized as type 3) is mainly characterized by hypermobility that affects both large and small joints. It may lead to frequent joint subluxations (partial dislocations) and dislocations. In general, people with this variant have skin that is soft, smooth, and velvety and bruises easily, and may have chronic muscle and/or bone pain. It affects the skin less than other forms. It has no available genetic test. hEDS is the most common of the 19 types of connective tissue disorders. Since no genetic test exists, providers have to diagnose hEDS based on what they know about the condition and the patients physical attributes. Other than the general signs, attributes can include faulty connective tissues throughout the body, musculoskeletal issues, and family history. Along with these general signs and side effects, patients can have trouble healing.Women who are pregnant should be warned about things such as pre-labor rupture of membranes, drop in blood pressure with anesthesia, precipitate birth (very fast, active labor), malposition of bleeding, and more. New mothers with hEDS should pay extra attention to taking care of their babies. Mothers may have trouble taking care of babies because of the risk of dropping a baby due to weak connective tissue in arms and legs, falling, postpartum depression (more than the general population), and healing from the birthing process.

Genetics of Hypermobile EDS
While 12 of the 13 subtypes of EDS have genetic variations that can be tested for by genetic testing, there is no known genetic cause of hEDS. Despite the unknown gene, hEDS appears to follow an autosomal dominant pattern of inheritance. This means that in order to be affected, a person needs a mutation in only one copy of the responsible gene in each cell. This mutation can be inherited from a parent or a de novo (new) mutation. A person with hEDS has a 50% chance of passing their mutated gene on to their children.Recently, several labs and research initiatives have been attempting to uncover a potential hEDS gene. In 2018, the Ehlers–Danlos Society began the Hypermobile Ehlers–Danlos Genetic Evaluation (HEDGE) study. The ongoing study has screened over 1,000 people who have been diagnosed with hEDS by the 2017 criteria to evaluate their genome for a common mutation. To date, 200 people with hEDS have had whole genome sequencing, and 500 have had whole exome sequencing; this study aims to increase those numbers significantly.Promising outcomes of this increased screening have been reported by the Norris Lab, led by Russell Norris, in the Department of Regenerative Medicine and Cell Biology at Medical University of South Carolina. Using CRISPR Cas-9 mediated genome editing on mouse models of the disease, the lab has recently identified a "very strong candidate gene" for hEDS. This finding, and a greater understanding of cardiac complications associated with the majority of EDS subtypes, has led to the development of multiple druggable pathways involved in aortic and mitral valve diseases. While this candidate gene has not been publicly identified, the Norris lab has conducted several studies involving small population genome sequencing and come up with a working list of possible hEDS genes. A mutation in COL3A1 in a single family with autosomal dominant hEDS phenotype was found to cause reduced collagen secretion and an over-modification of collagen. In 35 families, copy number alterations in TPSAB1, encoding alpha-tryptase, were associated with increased basal serum tryptase levels, associated with autonomic dysfunction, gastrointestinal disorders, allergic and cutaneous symptoms, and connective tissue abnormalities, all concurrent with hEDS phenotype. Lastly, Tenascin X, an extracellular matrix protein important for collagen mutation encoded by the TNXB gene, has been associated with hEDS in patients with Tenascin X deficiency.
Another way the Norris lab is attempting to find this gene is by looking at genes involved in the formation of the aorta and mitral valves, as these valves are often prolapsed or malformed as a symptom of EDS. Because hEDS is such a complex, multi-organ disease, focusing on one hallmark trait has proven successful. One gene found this way is DZIP1, which regulates cardiac valve development in mammals through a Cby1-beta-catenin mechanism. Mutations at this gene affect the beta-catenin cascade involved in development, causing malformation of the extra-cellular matrix, resulting in loss of collagen. A lack of collagen here is both consistent with hEDS and explains the "floppy" mitral and aortic valve heart defects. A second genetic study specific to mitral valve prolapse focused on the PDGF signaling pathway, which is involved in growth factor ligands and receptor isoforms. Mutations in this pathway affect the ability to localize cilia in various cell types, including cardiac cells. With the resulting ciliopathies, structures such as the cardiac outflow tract, heart tube assembly, and cardiac fusion are limited and/or damaged.

Classical EDS
Classical EDS (formerly categorized as type 1) is characterized by extremely elastic skin that is fragile and bruises easily and hypermobility of the joints. Molluscoid pseudotumors (calcified hematomas that occur over pressure points) and spheroids (cysts that contain fat occurring over forearms and shins) are also often seen. A side complication of the hyperelasticity presented in many EDS cases makes wounds closing on their own more difficult. Sometimes, motor development is delayed and hypotonia occurs. The variation causing this type of EDS is in the genes COL5A2, COL5A1, and less frequently COL1A1. It involves the skin more than hEDS. In classical EDS, large variation in symptom presentation is seen. Because of this variance, EDS has often been underdiagnosed. Without genetic testing, healthcare professionals may be able to provide a provisional diagnosis based on careful examination of the mouth, skin, and bones, as well as by neurological assessment. The hyperelasticity of EDS patients skin can be difficult to use in diagnosis because there is no good standardized way to measure and assess the elasticity, but hyperelasticity is still a good indicator of EDS, along with other symptoms.A good way to begin the diagnosis process is looking at family history. EDS is an autosomal dominant condition, so is often inherited from parents. Genetic testing remains the most reliable way to diagnose EDS. No cure for type 1 EDS has been found, but a course of non-weight-bearing exercise can help with muscular tension, which can help correct some EDS symptoms. Anti-inflammatory drugs and lifestyle changes can help with joint pain. Lifestyle choices should also be made with children who have EDS to try to prevent wounds to the skin. Protective garments can help with this. In a wound, deep stitches are often used and left in place for longer than normal.

Vascular EDS
Vascular EDS (formerly categorized as type 4) is identified by skin that is thin, translucent, extremely fragile, and bruises easily. It is also characterized by fragile blood vessels and organs that can easily rupture. Affected people are frequently short, and have thin scalp hair. It also has characteristic facial features, including large eyes, an undersized chin, sunken cheeks, a thin nose and lips, and ears without lobes. Joint hypermobility is present, but generally confined to the small joints (fingers, toes). Other common features include club foot, tendon and/or muscle rupture, acrogeria (premature aging of the skin of the hands and feet), early-onset varicose veins, pneumothorax (collapse of a lung), the recession of the gums, and a decreased amount of fat under the skin. It can be caused by the variations in the COL3A1 gene. Rarely, COL1A1 variations can also cause it.

Kyphoscoliosis EDS
Kyphoscoliosis EDS (formerly categorized as type 6) is associated with severe hypotonia at birth, delayed motor development, progressive scoliosis (present from birth), and scleral fragility. People may also have easy bruising, fragile arteries that are prone to rupture, unusually small corneas, and osteopenia (low bone density). Other common features include a "marfanoid habitus" characterized by long, slender fingers (arachnodactyly), unusually long limbs, and a sunken chest (pectus excavatum) or protruding chest (pectus carinatum). It can be caused by variations in the gene PLOD1, or rarely, in the FKBP14 gene.

Arthrochalasia EDS
Arthrochalasia EDS (formerly categorized as types 7A and B) is characterized by severe joint hypermobility and congenital hip dislocation. Other common features include fragile, elastic skin with easy bruising, hypotonia, kyphoscoliosis (kyphosis and scoliosis), and mild osteopenia. Type-I collagen is usually affected. It is very rare, with about 30 cases reported. It is more severe than the hypermobility type. Variations in the genes COL1A1 and COL1A2 cause it.

Dermatosparaxis EDS
Dermatosparaxis EDS (formerly categorized as type 7C) is associated with extremely fragile skin leading to severe bruising and scarring; saggy, redundant skin, especially on the face; hypermobility ranging from mild to serious; and hernias. Variations in the ADAMTS2 gene cause it. It is extremely rare, with around 11 cases reported.

Brittle-cornea syndrome
Brittle-cornea syndrome is characterized by the progressive thinning of the cornea, early-onset progressive keratoglobus or keratoconus, nearsightedness, hearing loss, and blue sclerae. Classic symptoms, such as hypermobile joints and hyperelastic skin, are also seen often. It has two types. Type 1 occurs due to variations in the ZNF469 gene. Type 2 is due to variations in the PRDM5 gene.

Classical-like EDS
Classical-like EDS is characterized by skin hyperextensibility with velvety skin texture and absence of atrophic scarring, generalized joint hypermobility with or without recurrent dislocations (most often shoulder and ankle), and easily bruised skin or spontaneous ecchymoses (discolorations of the skin resulting from bleeding underneath). It can be caused by variations in the TNXB gene.

Spondylodysplastic EDS
Spondylodysplastic EDS is characterized by short stature (progressive in childhood), muscle hypotonia (ranging from severe congenital to mild later-onset), and bowing of limbs. It can be caused by variations in both copies of the B4GALT7 gene. Other cases can be caused by variations in the B3GALT6 gene. People with variations in this gene can have kyphoscoliosis, tapered fingers, osteoporosis, aortic aneurysms, and problems with the lungs. Other cases can be caused by the SLC39A13 gene. Those with variations in this gene have protuberant eyes, wrinkled palms of the hands, tapering fingers, and distal joint hypermobility.

Musculocontractural EDS
Musculocontractural EDS is characterized by congenital multiple contractures, characteristically adduction-flexion contractures and/or talipes equinovarus (clubfoot), characteristic craniofacial features, which are evident at birth or in early infancy, and skin features such as skin hyperextensibility, bruising, skin fragility with atrophic scars, and increased palmar wrinkling. It can be caused by variations in the CHST14 gene. Some other cases can be caused by variations in the DSE gene.

Myopathic EDS
Myopathic EDS (mEDS) is characterized by three major criteria: congenital muscle hypotonia and/or muscle atrophy that improves with age, proximal joint contractures of the knee, hip, and elbow, and hypermobility of distal joints (ankles, wrists, feet, and hands). Four minor criteria may also contribute to a diagnosis of mEDS. This disorder can be inherited through either an autosomal dominant or an autosomal recessive pattern. Molecular testing must be completed to verify that mutations in the COL12A1 gene are present; if not, other collagen-type myopathies should be considered.

Periodontal EDS
Periodontal EDS (pEDS) is an autosomal-dominant disorder characterized by four major criteria of severe and intractable periodontitis of early-onset (childhood or adolescence), lack of attached gingiva, pretibial plaques, and family history of a first-degree relative who meets clinical criteria. Eight minor criteria may also contribute to the diagnosis of pEDS. Molecular testing may reveal mutations in C1R or C1S genes affecting the C1r protein.

Cardiac-valvular EDS
Cardiac-valvular EDS (cvEDS) is characterized by three major criteria: severe progressive cardiac-valvular problems (affecting aortic and mitral valves), skin problems such as hyperextensibility, atrophic scarring, thin skin, and easy bruising, and joint hypermobility (generalized or restricted to small joints). Four minor criteria may aid in diagnosis of cvEDS. cvEDS is an autosomal recessive disorder, inherited through variation in both alleles of the gene COL1A2.

Signs and symptoms
This group of disorders affects connective tissues across the body, with symptoms most typically present in the joints, skin, and blood vessels. However, as connective tissue is found throughout the body, EDS may result in an array of unexpected impacts with any degree of severity, and the condition is not limited to joints, skin, and blood vessels. Effects may range from mildly loose joints to life-threatening cardiovascular complications. Due to the diversity of subtypes within the EDS family, symptoms may vary widely between individuals diagnosed with EDS.

Musculoskeletal
Musculoskeletal symptoms include hyperflexible joints that are unstable and prone to sprain, dislocation, subluxation, and hyperextension. There can be an early onset of advanced osteoarthritis, chronic degenerative joint disease, swan-neck deformity of the fingers, and Boutonniere deformity of the fingers. Tearing of tendons or muscles may occur. Deformities of the spine, such as scoliosis (curvature of the spine), kyphosis (a thoracic hump), tethered spinal cord syndrome, craniocervical instability, and occipitoatlantoaxial hypermobility may also be present. There can also be myalgia (muscle pain) and arthralgia (joint pain), which may be severe and disabling. Trendelenburgs sign is often seen, which means that when standing on one leg, the pelvis drops on the other side. Osgood–Schlatter disease, a painful lump on the knee, is common as well. In infants, walking can be delayed (beyond 18 months of age), and bottom-shuffling instead of crawling occurs.

Skin
The weak connective tissue causes abnormal skin. This may present as stretchy or in other types simply be velvet soft. In all types, some increased fragility occurs, but the degree varies depending on the underlying subtype. The skin may tear and bruise easily, and may heal with abnormal atrophic scars; atrophic scars that look like cigarette paper are a sign seen including in those whose skin might appear otherwise normal. In some subtypes, though not the hypermobile subtype, redundant skin folds occur, especially on the eyelids. Redundant skin folds are areas of excess skin lying in folds.Other skin symptoms include molluscoid pseudotumors, especially on pressure points, petechiae, subcutaneous spheroids, livedo reticularis, and piezogenic papules are less common. In vascular EDS, skin can also be thin and translucent. In dermatosparaxis EDS, the skin is extremely fragile and saggy.

Cardiovascular
Thoracic outlet syndrome
Arterial rupture
Valvular heart disease, such as mitral valve prolapse, creates an increased risk for infective endocarditis during surgery. This may progress to a life-threatening degree. Heart conduction abnormalities have been found in those with hypermobility form of EDS.
Dilation and/or rupture (aneurysm) of ascending aorta
Cardiovascular autonomic dysfunction such as postural orthostatic tachycardia syndrome
Raynauds phenomenon
Varicose veins
Heart murmur
Heart conduction abnormalities

Other manifestations
Hiatal hernia
Gastroesophageal reflux
Poor gastrointestinal motility
Dysautonomia
Gorlins sign (touch tongue to nose)
Anal prolapse
Flat feet
Tracheobronchomalacia / tracheal collapse
Collapsed lung (spontaneous pneumothorax)
Nerve disorders (carpal tunnel syndrome, acroparesthesia, neuropathy, including small fiber neuropathy)
Insensitivity to local anesthetics
Arnold–Chiari malformation
Platelet aggregation failure (platelets do not clump together properly)
Mast cell disorders (including mast cell activation syndrome and mastocytosis)
Pregnancy complications: increased pain, mild to moderate peripartum bleeding, cervical insufficiency, uterine tearing, or premature rupture of membranes
Hearing loss may occur in some types
Eye: Nearsightedness, retinal tearing and retinal detachment, keratoconus, blue sclera, dry eye, Sjogrens syndrome, lens subluxation, angioid streaks, epicanthal folds, strabismus, corneal scarring, brittle cornea syndrome, cataracts, carotid-cavernous sinus fistulas, macular degeneration
Craniocervical instability: caused by trauma(s) to the head and neck areas such as concussion and whiplash. Ligaments in neck are unable to heal properly, so the neck structure does not have the ability to support the skull, which can then sink into the brain stem, blocking the flow of cerebrospinal fluid, leading to issues related to the autonomic nervous system failing to work properly.
Osteoporosis and osteopenia are associated with EDS and symptomatic joint hypermobility
There is some evidence that EDS may be associated with greater than expected frequencies of neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD) and other learning, communication and motor issues, including autism spectrum conditions and Tourette syndrome.

Because it is often undiagnosed or misdiagnosed in childhood, some instances of EDS have been mischaracterized as child abuse. The pain may also be misdiagnosed as a behavior disorder or Munchausen by proxy.The pain associated with EDS ranges from mild to debilitating.

Causes
Every type of EDS except the hypermobile type (which affects the vast majority of people with EDS) can be positively tied to specific genetic variation.
Variations in these genes can cause EDS:
Collagen primary structure and collagen processing: ADAMTS2, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2
Collagen folding and collagen cross-linking: PLOD1, FKBP14
Structure and function of myomatrix: TNXB, COL12A1
Glycosaminoglycan biosynthesis: B4GALT7, B3GALT6, CHST14, DSE
Complement pathway: C1R, C1S
Intracellular processes: SLC39A13, ZNF469, PRDM5Variations in these genes usually alter the structure, production, or processing of collagen or proteins that interact with collagen. Collagen provides structure and strength to connective tissue. A defect in collagen can weaken connective tissue in the skin, bones, blood vessels, and organs, resulting in the features of the disorder. Inheritance patterns depend on the specific syndrome.
Most forms of EDS are inherited in an autosomal dominant pattern, which means only one of the two copies of the gene in question must be altered to cause a disorder. A few are inherited in an autosomal recessive pattern, which means both copies of the gene must be altered for a person to be affected. It can also be an individual (de novo or "sporadic") variation. Sporadic variations occur without any inheritance.

Diagnosis
A diagnosis can be made by an evaluation of medical history and clinical observation. The Beighton criteria are widely used to assess the degree of joint hypermobility. DNA and biochemical studies can help identify affected people. Diagnostic tests include collagen gene-variant testing, collagen typing via skin biopsy, echocardiogram, and lysyl hydroxylase or oxidase activity, but these tests are not able to confirm all cases, especially in instances of an unmapped variation, so clinical evaluation remains important. If multiple members of a family are affected, prenatal diagnosis may be possible using a DNA information technique known as a linkage study. Knowledge about EDS among all kinds of practitioners is poor. Research is ongoing to identify genetic markers for all types.

Differential diagnosis
Several disorders share some characteristics with EDS. For example, in cutis laxa, the skin is loose, hanging, and wrinkled. In EDS, the skin can be pulled away from the body, but is elastic and returns to normal when let go. In Marfan syndrome, the joints are very mobile and similar cardiovascular complications occur. People with EDS tend to have a "marfanoid" appearance (e.g., tall, skinny, long arms and legs, "spidery" fingers), but physical appearance and features in several types of EDS also have characteristics including short stature, large eyes, and the appearance of a small mouth and chin, due to a small palate. The palate can have a high arch, causing dental crowding. Blood vessels can sometimes be easily seen through translucent skin, especially on the chest. The genetic connective tissue disorder Loeys–Dietz syndrome also has symptoms that overlap with EDS.In the past, Menkes disease, a copper metabolism disorder, was thought to be a form of EDS. People are commonly misdiagnosed with fibromyalgia, bleeding disorders, or other disorders that can mimic EDS symptoms. Because of these similar disorders and complications that can arise from an unmonitored case of EDS, a correct diagnosis is important. Pseudoxanthoma elasticum is worth consideration in diagnosis.

Management
No cure for Ehlers–Danlos syndromes is known, and treatment is supportive. Close monitoring of the cardiovascular system, physiotherapy, occupational therapy, and orthopedic instruments (e.g., wheelchairs, bracing, casting) may be helpful. This can help stabilize the joints and prevent injury. Orthopedic instruments are helpful for the prevention of further joint damage, especially for long distances. People should avoid activities that cause the joint to lock or overextend.A physician may prescribe casting to stabilize joints. Physicians may refer a person to an orthotist for orthotic treatment (bracing). Physicians may also consult a physical and/or occupational therapist to help strengthen muscles and to teach people how to properly use and preserve their joints.Aquatic therapy promotes muscular development and coordination. With manual therapy, the joint is gently mobilized within the range of motion and/or manipulations. If conservative therapy is not helpful, surgical joint repair may be necessary. Medication to decrease pain or manage cardiac, digestive, or other related conditions may be prescribed. To decrease bruising and improve wound healing, some people have responded to vitamin C. Medical care workers often take special precautions because of the sheer number of complications that tend to arise in people with EDS. In vascular EDS, signs of chest or abdominal pain are considered trauma situations.Cannabinoids and medical marijuana have shown some efficacy in reducing pain levels.In general, medical intervention is limited to symptomatic therapy. Before pregnancy, people with EDS should have genetic counseling and familiarize themselves with the risks pregnancy poses. Children with EDS should be given information about the disorder so they can understand why they should avoid contact sports and other physically stressful activities. Children should be taught that they should not demonstrate the unusual positions they can maintain due to loose joints, as this may cause early degeneration of the joints. Emotional support along with behavioral and psychological therapy can be useful. Support groups can be immensely helpful for people dealing with major lifestyle changes and poor health. Family members, teachers, and friends should be informed about EDS so they can accept and assist the child.

Pain management
Successful treatment of chronic pain in EDS requires a multidisciplinary team. The ways to manage pain can be to modify pain management techniques used in the normal population. Chronic pain has two types. The first type is nociceptive, which is caused by an injury sustained to tissues. The second type is neuropathic pain, caused by abnormal signals by the nervous system. In most cases, the pain is an unequal mix of the two. Physiotherapy (exercise rehabilitation) can be helpful, especially stabilizing the core and the joints. Stretching exercises must be reduced to slow and gentle stretching to reduce the risks of dislocations or subluxations. Usable methods may include posture reeducation, muscle release, joint mobilization, trunk stabilization, and manual therapy for overworked muscles. Cognitive behavioural therapy is used in all chronic pain patients, especially those who have severe, chronic, life-controlling pain that is unresponsive to treatment. It had not been checked for efficiency in clinical trials. The state of pain management with EDS is considered insufficient.

Medications
Nonsteroidal anti-inflammatory drugs (NSAIDs) may help if the pain is caused by inflammation. But long-term use of NSAIDs is often a risk factor for gastrointestinal, renal, and blood-related side effects. It can worsen symptoms of mast cell activation syndrome, a disease that may be associated with EDS. Acetaminophen can be used to avoid the bleeding-related side effects of NSAIDs.Opioids have shown efficiency in some EDS cases for the management of both acute and chronic pain.112
Lidocaine can be applied topically after subluxations and painful gums. It can also be injected into painful areas in the case of musculoskeletal pain.If the pain is neuropathic in origin, tricyclic antidepressants in low doses, anticonvulsants, and selective norepinephrine reuptake inhibitors can be used.

Dislocation and subluxation management
When a dislocation or subluxation does occur, muscle spasms and stress tend to occur, increasing pain and reducing the chances of the dislocation/subluxation naturally relieving. Methods to support a joint after such an incident include usage of a sling to hold the joint in place and allow it to relax. Orthopedic casts are not advised as there could be pain if unrelaxed muscles are still trying to spasm out against the cast. Other solutions to promote relaxation are heat, gentle massaging, and mental distractions.

Surgery
The instability of joints, leading to subluxations and joint pain, often requires surgical intervention in people with EDS. Instability of almost all joints can happen, but appears most often in the lower and upper extremities, with the wrist, fingers, shoulder, knee, hip, and ankle being most common.Common surgical procedures are joint debridement, tendon replacements, capsulorrhaphy, and arthroplasty. After surgery, the degree of stabilization, pain reduction, and peoples satisfaction can improve, but surgery does not guarantee an optimal result; affected peoples and surgeons report being dissatisfied with the results. The consensus is that conservative treatment is more effective than surgery, particularly since people have extra risks of surgical complications due to the disease. Three basic surgical problems arise due to EDS – the strength of the tissues is decreased, which makes the tissue less suitable for surgery; the fragility of the blood vessels can cause problems during surgery; and wound healing is often delayed or incomplete. If considering surgical intervention, seeking care from a surgeon with extensive knowledge and experience in treating people with EDS and joint hypermobility issues would be prudent.Local anesthetics, arterial catheters, and central venous catheters cause a higher risk of bruise formation in people with EDS. Some people with EDS also show a resistance to local anaesthetics. Resistance to lidocaine and bupivacaine is not uncommon, and mepivacaine tends to work better in people with EDS. Special recommendations for anesthesia are given for people with EDS. Detailed recommendations for anesthesia and perioperative care of people with EDS should be used to improve safety.Surgery in people with EDS requires careful tissue handling and a longer immobilization afterward.

Prognosis
The outcome for individuals with EDS depends on the specific type of EDS they have. Symptoms vary in severity, even in the same disorder, and the frequency of complications varies. Some people have negligible symptoms, while others are severely restricted in daily life. Extreme joint instability, chronic musculoskeletal pain, degenerative joint disease, frequent injuries, and spinal deformities may limit mobility. Severe spinal deformities may affect breathing. In the case of extreme joint instability, dislocations may result from simple tasks such as rolling over in bed or turning a doorknob. Secondary conditions such as autonomic dysfunction or cardiovascular problems, occurring in any type, can affect prognosis and quality of life. Severe mobility-related disability is seen more often in hEDS than in classical EDS or vascular EDS.Although all types of EDS are potentially life-threatening, most people have a normal lifespan. Those with blood vessel fragility, though, have a high risk of fatal complications, including spontaneous arterial rupture, which is the most common cause of sudden death. The median life expectancy in the population with vascular EDS is 48 years.

Complications
Vascular
Pseudoaneurysm
Vascular lesions (nature is disputed) due to tears in the lining of the arteries or deterioration of congenitally thin and fragile tissue
Enlarged arteries

Gastrointestinal
A 50% risk of colonic perforation exists.

Obstetric
Pregnancy increases the likelihood of uterine rupture.
Maternal mortality is around 12%.
Uterine hemorrhage can occur during the postpartum recovery.

Epidemiology
Ehlers–Danlos syndromes are estimated to occur in about one in 5,000 births worldwide. Initially, prevalence estimates ranged from one in 250,000 to 500,000 people, but these were soon found to be low, as medical professionals became more adept at diagnosis. EDS may be far more common than the currently accepted estimate due to the wide range of severities with which the disorder presents.The prevalence of the disorders differs dramatically. The most common is hypermobile EDS, followed by classical EDS. The others are very rare. For example, fewer than 10 infants and children with dermatosparaxis EDS have been described worldwide.
Some types of EDS are more common in Ashkenazi Jews. For example, the chance of being a carrier for dermatosparaxis EDS is one in 2,000 in the general population but one in 248 among Ashkenazi Jews.

History
Until 1997, the classification system for EDS included 10 specific types and acknowledged that other extremely rare types existed. At this time, the classification system underwent an overhaul and was reduced to six major types using descriptive titles. Genetic specialists recognize that other types of this condition exist, but have only been documented in single families. Except for hypermobility (type 3), the most common type of all 10 types, some of the specific variations involved have been identified, and they can be precisely identified by genetic testing; this is valuable due to a great deal of variation in individual cases. Negative genetic test results, though, do not rule out the diagnosis, since not all of the variations have been discovered; therefore, the clinical presentation is very important.Forms of EDS in this category may present with soft, mildly stretchable skin, shortened bones, chronic diarrhea, joint hypermobility and dislocation, bladder rupture, or poor wound healing. Inheritance patterns in this group include X-linked recessive, autosomal dominant, and autosomal recessive. Examples of types of related syndromes other than those above reported in the medical literature include:
305200: type 5
130080: type 8 – unspecified gene, locus 12p13
225310: type 10 – unspecified gene, locus 2q34
608763: Beasley–Cohen type
130070: progeroid form – B4GALT7
130090: type unspecified
601776: D4ST1-deficient Ehlers–Danlos syndrome (adducted thumb-clubfoot syndrome) CHST14

Society and culture
EDS may have contributed to the virtuoso violinist Niccolò Paganinis skill, as he was able to play wider fingerings than a typical violinist.Many sideshow performers have EDS </s>