<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 Toxic shock syndrome and can you explain it in depth? [/INST] Toxic shock syndrome (TSS) is a condition caused by bacterial toxins. Symptoms may include fever, rash, skin peeling, and low blood pressure. There may also be symptoms related to the specific underlying infection such as mastitis, osteomyelitis, necrotising fasciitis, or pneumonia.TSS is typically caused by bacteria of the Streptococcus pyogenes or Staphylococcus aureus type, though others may also be involved. Streptococcal toxic shock syndrome is sometimes referred to as toxic-shock-like syndrome (TSLS). The underlying mechanism involves the production of superantigens during an invasive streptococcus infection or a localized staphylococcus infection. Risk factors for the staphylococcal type include the use of very absorbent tampons, and skin lesions in young children characterized by fever, low blood pressure, rash, vomiting and/or diarrhea, and multiorgan failure. Diagnosis is typically based on symptoms.Treatment includes intravenous fluids, antibiotics, incision and drainage of any abscesses, and possibly intravenous immunoglobulin. The need for rapid removal of infected tissue via surgery in those with a streptococcal cause, while commonly recommended, is poorly supported by the evidence. Some recommend delaying surgical debridement. The overall risk of death is about 50% in streptococcal disease, and 5% in staphylococcal disease. Death may occur within 2 days.In the United States, streptococcal TSS occurs in about 3 per 100,000 per year, and staphylococcal TSS in about 0.5 per 100,000 per year. The condition is more common in the developing world. It was first described in 1927. Due to the association with very absorbent tampons, these products were removed from sale.

Signs and symptoms
Symptoms of toxic shock syndrome (TSS) vary depending on the underlying cause. TSS resulting from infection with the bacterium Staphylococcus aureus typically manifests in otherwise healthy individuals via signs and symptoms including high fever, accompanied by low blood pressure, malaise and confusion, which can rapidly progress to stupor, coma, and multiple organ failure. The characteristic rash, often seen early in the course of illness, resembles a sunburn (conversely, streptococcal TSS will rarely involve a sunburn-like rash), and can involve any region of the body including the lips, mouth, eyes, palms and soles of the feet. In patients who survive, the rash desquamates (peels off) after 10–21 days.STSS caused by the bacterium Streptococcus pyogenes, or TSLS, typically presents in people with pre-existing skin infections with the bacteria. These individuals often experience severe pain at the site of the skin infection, followed by rapid progression of symptoms as described above for TSS.

Pathophysiology
In both TSS (caused by S. aureus) and TSLS (caused by S. pyogenes), disease progression stems from a superantigen toxin. The toxin in S. aureus infections is TSS Toxin-1, or TSST-1. The TSST-1 is secreted as a single polypeptide chain. The gene encoding toxic shock syndrome toxin is carried by a mobile genetic element of S. aureus in the SaPI family of pathogenicity islands. The toxin causes the non-specific binding of MHC II, on professional antigen presenting cells, with T-cell receptors, on T cells.
In typical T-cell recognition, an antigen is taken up by an antigen-presenting cell, processed, expressed on the cell surface in complex with class II major histocompatibility complex (MHC) in a groove formed by the alpha and beta chains of class II MHC, and recognized by an antigen-specific T-cell receptor. This results in polyclonal T-cell activation. Superantigens do not require processing by antigen-presenting cells but instead, interact directly with the invariant region of the class II MHC molecule. In patients with TSS, up to 20% of the bodys T-cells can be activated at one time. This polyclonal T-cell population causes a cytokine storm, followed by a multisystem disease.

Risk factors
A few possible causes of toxic shock syndrome are:
Cuts or open wounds on the skin
Surgical wounds
Viral infections (e.g. Chicken Pox)
Contraceptive sponges
History of a recent birth, miscarriage, or abortion
Using super-absorbent tampons
Previously having TSS

Diagnosis
For staphylococcal toxic shock syndrome, the diagnosis is based upon CDC criteria defined in 2011, as follows:
Body temperature > 38.9 °C (102.02 °F)
Systolic blood pressure < 90 mmHg
Diffuse macular erythroderma
Desquamation (especially of the palms and soles) 1–2 weeks after onset
Involvement of three or more organ systems:
Gastrointestinal (vomiting, diarrhea)
Muscular: severe myalgia or creatine phosphokinase level at least twice the upper limit of normal for laboratory
Mucous membrane hyperemia (vaginal, oral, conjunctival)
Kidney failure (serum creatinine > 2 times normal)
Liver inflammation (bilirubin, AST, or ALT > 2 times normal)
Low platelet count (platelet count < 100,000 / mm3)
Central nervous system involvement (confusion without any focal neurological findings)
Negative results of:
Blood, throat, and CSF cultures for other bacteria (besides S. aureus)
Negative serology for Rickettsia infection, leptospirosis, and measlesCases are classified as confirmed or probable as follows:

Confirmed: All six of the criteria above are met (unless the patient dies before desquamation can occur)
Probable: Five of the six criteria above are met

Treatment
The severity of this disease frequently warrants hospitalization. Admission to the intensive care unit is often necessary for supportive care (for aggressive fluid management, ventilation, renal replacement therapy and inotropic support), particularly in the case of multiple organ failure. Treatment includes removal or draining of the source of infection—often a tampon—and draining of abscesses. Outcomes are poorer in patients who do not have the source of infection removed.Antibiotic treatment should cover both S. pyogenes and S. aureus. This may include a combination of cephalosporins, penicillins or vancomycin. The addition of clindamycin or gentamicin reduces toxin production and mortality.
In some cases doctors will prescribe other treatments such as blood pressure medications (to stabilize blood pressure if it is too low), dialysis, oxygen mask (to stabilize oxygen levels), and sometimes a ventilator. These will sometimes be used to help treat side affects of contracting TSS.

Prognosis
With proper treatment, people usually recover in two to three weeks. The condition can, however, be fatal within hours. TSS has a mortality rate of 30%–70%. Children who are affected by TSS tend to recover easier than adults do.

Complications
Amputation of fingers, toes, and sometimes limbs
Death
Liver or Kidney failure
Heart problems
Respiratory distress
Septic shock
Other abnormalities may occur depending on the case

Prevention
During menstruation:
Use pads at night instead of tampons
Try to keep up with changing a tampon every 4 to 8 hours
Use low absorbent tampons
Follow directions when using vaginal contraceptives (sponges or diaphragms)
Make sure to maintain good hygiene during a menstrual cycleFor anyone:
Keep open wounds clean
Watch wounds and cuts for signs of infection (e.g. pus, redness, and warm to touch)
Keep personal items personal (e.g.towels, sheets, razors)
Wash clothing and bedding in hot water

Epidemiology
Staphylococcal toxic shock syndrome is rare and the number of reported cases has declined significantly since the 1980s. Patrick Schlievert, who published a study on it in 2004, determined incidence at three to four out of 100,000 tampon users per year; the information supplied by manufacturers of sanitary products such as Tampax and Stayfree puts it at one to 17 of every 100,000 menstruating females per year.TSS was considered a sporadic disease that occurred in immunocompromised people. It was not a more well-known disease until the 1980s, when high-absorbency tampons were in use by menstruating women.  Due to the idea of the tampons having a high absorbency this led women to believe that they could leave a tampon in for several hours. Doing this allowed the bacteria to grow and infect women. This resulted in a spike of cases of TSS.Philip M. Tierno Jr. helped determine that tampons were behind TSS cases in the early 1980s. Tierno blames the introduction of higher-absorbency tampons in 1978. A study by Tierno also determined that all-cotton tampons were less likely to produce the conditions in which TSS can grow; this was done using a direct comparison of 20 brands of tampons including conventional cotton/rayon tampons and 100% organic cotton tampons from Natracare. In fact, Dr Tierno goes as far to state, "The bottom line is that you can get TSS with synthetic tampons, but not with an all-cotton tampon."A rise in reported cases occurred in the early 2000s: eight deaths from the syndrome in California in 2002 after three successive years of four deaths per year, and Schlieverts study found cases in part of Minnesota more than tripled from 2000 to 2003. Schlievert considers earlier onset of menstruation to be a cause of the rise; others, such as Philip M. Tierno and Bruce A. Hanna, blame new high-absorbency tampons introduced in 1999 and manufacturers discontinuing warnings not to leave tampons in overnight.TSS is more common during the winter and spring and occurs most often in the young and old.Toxic shock syndrome is commonly known to be an issue for females who menstruate. TSS although can occur in people of all ages and genders.  Around fifty percent of Toxic Shock Syndrome cases are in non menstruating cases. TSS in these cases can be caused by skin wounds, surgical sites, nasal packing, and burns.

History
Initial description
The term "toxic shock syndrome" was first used in 1978 by a Denver pediatrician, James K. Todd, to describe the staphylococcal illness in three boys and four girls aged 8–17 years. Even though S. aureus was isolated from mucosal sites in the patients, bacteria could not be isolated from the blood, cerebrospinal fluid, or urine, raising suspicion that a toxin was involved. The authors of the study noted reports of similar staphylococcal illnesses had appeared occasionally as far back as 1927, but the authors at the time failed to consider the possibility of a connection between toxic shock syndrome and tampon use, as three of the girls who were menstruating when the illness developed were using tampons. Many cases of TSS occurred after tampons were left in after they should have been removed.

Rely tampons
Following controversial test marketing in Rochester, New York, and Fort Wayne, Indiana, in August 1978, Procter and Gamble introduced superabsorbent Rely tampons to the United States market in response to womens demands for tampons that could contain an entire menstrual flow without leaking or replacement. Rely used carboxymethylcellulose (CMC) and compressed beads of polyester for absorption. This tampon design could absorb nearly 20 times its own weight in fluid. Further, the tampon would "blossom" into a cup shape in the vagina to hold menstrual fluids without leakage.In January 1980, epidemiologists in Wisconsin and Minnesota reported the appearance of TSS, mostly in those menstruating, to the CDC. S. aureus was successfully cultured from most of the subjects. The Toxic Shock Syndrome Task Force was created and investigated the epidemic as the number of reported cases rose throughout the summer of 1980. In September 1980, CDC reported users of Rely were at increased risk for developing TSS.On 22 September 1980, Procter and Gamble recalled Rely following release of the CDC report. As part of the voluntary recall, Procter and Gamble entered into a consent agreement with the FDA "providing for a program for notification to consumers and retrieval of the product from the market". However, it was clear to other investigators that Rely was not the only culprit. Other regions of the United States saw increases in menstrual TSS before Rely was introduced.It was shown later that higher absorbency of tampons was associated with an increased risk for TSS, regardless of the chemical composition or the brand of the tampon. The sole exception was Rely, for which the risk for TSS was still higher when corrected for its absorbency. The ability of carboxymethylcellulose to filter the S. aureus toxin that causes TSS may account for the increased risk associated with Rely.

Notable cases
Clive Barker, fully recovered, contracted the syndrome after visiting the dentist.
Lana Coc-Kroft, fully recovered, contracted the syndrome due to group A streptococcal infection.
Jim Henson, d. 1990, contracted the syndrome due to group A streptococcal infection and subsequently died from it.
Nan C. Robertson, d. 2009, the 1983 winner of the Pulitzer Prize for Feature Writing for her medically detailed account of her struggle with toxic shock syndrome, a cover story for The New York Times Magazine which at that time became the most widely syndicated article in Times history.
Barbara Robison, lead vocalist for the psychedelic rock band the Peanut Butter Conspiracy, was performing in Butte, Montana on April 6, 1988; during the concert, she fell ill and was transported to a hospital </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 Biliary dyskinesia and can you explain it in depth? [/INST] Biliary dyskinesia is a disorder of some component of biliary part of the digestive system in which bile cannot physically move in the proper direction through the tubular biliary tract. It most commonly involves abnormal biliary tract peristalsis muscular coordination within the gallbladder in response to dietary stimulation of that organ to squirt the liquid bile through the common bile duct into the duodenum. Ineffective peristaltic contraction of that structure produces postprandial (after meals) right upper abdominal pain (cholecystodynia) and almost no other problem. When the dyskinesia is localized at the biliary outlet into the duodenum just as increased tonus of that outlet sphincter of Oddi, the backed-up bile can cause pancreatic injury with abdominal pain more toward the upper left side. In general, biliary dyskinesia is the disturbance in the coordination of peristaltic contraction of the biliary ducts, and/or reduction in the speed of emptying of the biliary tree into the duodenum.

Mechanism
Normally, the downstream gallbladder stores and concentrates the bile which originates in liver hepatocyte cells and is released into the microscopic component of the biliary system by the liver. Through aggregating tubules of increasing diameter, the bile leaves the liver and reaches the upstream (proximal) component of the common bile duct. Apparently, the common bile duct beyond (distal to) the gallbladder tends to normally have a greater tone so that the bile backs up into the gallbladder </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 Maturity-onset diabetes of the young and can you explain it in depth? [/INST] Maturity-onset diabetes of the young (MODY) refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production. MODY is often referred to as monogenic diabetes to distinguish it from the more common types of diabetes (especially type 1 and type 2), which involve more complex combinations of causes involving multiple genes and environmental factors. MODY 2 and MODY 3 are the most common forms.Robert Tattersall and Stefan Fajans initially identified the phenomenon known as maturity onset diabetes of the young in a classic study published in the journal Diabetes in 1975.

Signs and symptoms
MODY is the final diagnosis in 1%–2% of people initially diagnosed with diabetes. The prevalence is 70–110 per million people. 50% of first-degree relatives will inherit the same mutation, giving them a greater than 95% lifetime risk of developing MODY themselves. For this reason, correct diagnosis of this condition is important. Typically patients present with a strong family history of diabetes (any type) and the onset of symptoms is in the second to fifth decade.
There are two general types of clinical presentation.

Some forms of MODY produce significant hyperglycemia and the typical signs and symptoms of diabetes: increased thirst and urination (polydipsia and polyuria).
In contrast, many people with MODY have no signs or symptoms and are diagnosed either by accident, when a high glucose is discovered during testing for other reasons, or screening of relatives of a person discovered to have diabetes. Discovery of mild hyperglycemia during a routine glucose tolerance test for pregnancy is particularly characteristic.MODY cases may make up as many as 5% of presumed type 1 and type 2 diabetes cases in a large clinic population. While the goals of diabetes management are the same no matter what type, there are two primary advantages of confirming a diagnosis of MODY.

Insulin may not be necessary and it may be possible to switch a person from insulin injections to oral agents without loss of glycemic control.
It may prompt screening of relatives and so help identify other cases in family members.As it occurs infrequently, many cases of MODY are initially assumed to be more common forms of diabetes: type 1 if the patient is young and not overweight, type 2 if the patient is overweight, or gestational diabetes if the patient is pregnant. Standard diabetes treatments (insulin for type 1 and gestational diabetes, and oral hypoglycemic agents for type 2) are often initiated before the doctor suspects a more unusual form of diabetes.

Genetics
Some sources make a distinction between two forms of monogenetic diabetes: MODY and neonatal diabetes. However, they have much in common and are often studied together.

Heterozygous
MODY is inherited in an autosomal dominant fashion, and most patients therefore have other members of the family with diabetes; penetrance differs between the types (from 40% to 90%).

Homozygous
By definition, the forms of MODY are autosomal dominant, requiring only one abnormal gene to produce the disease; the severity of the disease is moderated by the presence of a second, normal allele which presumably functions normally. However, conditions involving people carrying two abnormal alleles have been identified. Unsurprisingly, combined (homozygous) defects of these genes are much rarer and much more severe in their effects.

MODY2: Homozygous glucokinase deficiency causes severe congenital insulin deficiency resulting in persistent neonatal diabetes mellitus. About 6 cases have been reported worldwide. All have required insulin treatment from shortly after birth. The condition does not seem to improve with age.
MODY4: Homozygous IPF1 results in failure of the pancreas to form. Congenital absence of the pancreas, termed pancreatic agenesis, involves deficiency of both endocrine and exocrine functions of the pancreas.Homozygous mutations in the other forms have not yet been described. Those mutations for which a homozygous form has not been described may be extremely rare, may result in clinical problems not yet recognized as connected to the monogenic disorder, or may be lethal for a fetus and not result in a viable child.

Pathophysiology
The recognised forms of MODY are all due to ineffective insulin production or release by pancreatic beta cells. Several of the defects are mutations of transcription factor genes. One form is due to mutations of the glucokinase gene. For each form of MODY, multiple specific mutations involving different amino acid substitutions have been discovered. In some cases, there are significant differences in the activity of the mutant gene product that contribute to variations in the clinical features of the diabetes (such as degree of insulin deficiency or age of onset).

Diagnosis
The following characteristics suggest the possibility of a diagnosis of MODY in hyperglycemic and diabetic patients:
Mild to moderate hyperglycemia (typically 130–250 mg/dL, or 7–14 mmol/L) discovered before 30 years of age. However, anyone under 50 can develop MODY.
A first-degree relative with a similar degree of diabetes.
Absence of positive antibodies or other autoimmunity (e.g., thyroiditis) in patient and family. However, Urbanova et al. found that about one quarter of Central European MODY patients are positive for islet cell autoantibodies (GABA and IA2A). Their expression is transient but highly prevalent. The autoantibodies were found in patients with delayed diabetes onset, and in times of insufficient diabetes control. The islet cell autoantibodies are absent in MODY in at least some populations (Japanese, Britons).
Persistence of a low insulin requirement (e.g., less than 0.5 u/kg/day) past the usual "honeymoon" period.
Absence of obesity (although overweight or obese people can get MODY) or other problems associated with type 2 diabetes or metabolic syndrome (e.g., hypertension, hyperlipidemia, polycystic ovary syndrome).
Insulin resistance very rarely happens.
Cystic kidney disease in patient or close relatives.
Non-transient neonatal diabetes, or apparent type 1 diabetes with onset before six months of age.
Liver adenoma or hepatocellular carcinoma in MODY type 3
Renal cysts, rudimentary or bicornuate uterus, vaginal aplasia, absence of the vas deferens, epidymal cysts in MODY type 5The diagnosis of MODY is confirmed by specific gene testing available through commercial laboratories.

Classification
Common or well-established forms of MODY (1% of MODY or greater) - HNF1A-(MODY3), HNF4A-(MODY1) and GCK-(MODY2), HNF1B-(MODY5), ABCC8-(MODY12), KCNJ11-(MODY13), INS-(MODY10)
Rare forms of MODY (Few families described but reasonable generic evidence for causing MODY) - NEUROD1-(MODY6), IPF1/PDX1-(MODY4), CEL-(MODY8), WSF1 and RFX6
Genes reported as causal for MODY but evidence not compelling - BLK-(MODY11), PAX4-(MODY9) and KLF11-(MODY7), APPL1-(MODY14), NKX6-1

Treatment
In some forms of MODY, standard treatment is appropriate, though exceptions occur:

In MODY2, oral agents are relatively ineffective, however most patients are managed conservatively through diet and exercise.
In MODY1 and MODY3, sulfonylureas are usually very effective, delaying the need for insulin treatment.
Sulfonylureas are effective in the KATP channel forms of neonatal-onset diabetes. The mouse model of MODY diabetes suggested that the reduced clearance of sulfonylureas stands behind their therapeutic success in human MODY patients, but Urbanova et al </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 Syringofibroadenoma and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Encephalitis lethargica and can you explain it in depth? [/INST] Encephalitis lethargica is an atypical form of encephalitis. Also known as "sleeping sickness" or "sleepy sickness" (distinct from tsetse fly-transmitted sleeping sickness), it was first described in 1917 by the neurologist Constantin von Economo and the pathologist Jean-René Cruchet. The disease attacks the brain, leaving some victims in a statue-like condition, speechless and motionless. Between 1915 and 1926, an epidemic of encephalitis lethargica spread around the world. The exact number of people infected is unknown, but it is estimated that more than one million people contracted the disease during the epidemic, which directly caused more than 500,000 deaths. Most of those who survived never returned to their pre-morbid vigour.

In the words of the famed neurologist and writer Oliver Sacks: They would be conscious and aware – yet not fully awake; they would sit motionless and speechless all day in their chairs, totally lacking energy, impetus, initiative, motive, appetite, affect or desire; they registered what went on about them without active attention, and with profound indifference. They neither conveyed nor felt the feeling of life; they were as insubstantial as ghosts, and as passive as zombies.No recurrence of the epidemic has since been reported, though isolated cases continue to occur.

Signs and symptoms
Encephalitis lethargica is characterized by high fever, sore throat, headache, lethargy, double vision, delayed physical and mental response, sleep inversion and catatonia. In severe cases, patients may enter a coma-like state (akinetic mutism). Patients may also experience abnormal eye movements ("oculogyric crises"), Parkinsonism, upper body weakness, muscular pains, tremors, neck rigidity, and behavioral changes including psychosis. Klazomania (a vocal tic) is sometimes present.

Cause
The causes of encephalitis lethargica are uncertain. Some studies have explored its origins in an autoimmune response, and, separately or in relation to an immune response, links to pathologies of infectious disease—viral and bacterial, such as in the case of influenza, where a link with encephalitis is clear. Postencephalitic Parkinsonism was clearly documented to have followed an outbreak of encephalitis lethargica following the 1918 influenza pandemic; evidence for viral causation of the Parkinsons symptoms is circumstantial (epidemiologic, and finding influenza antigens in encephalitis lethargica patients), while evidence arguing against this cause is of the negative sort (for example, lack of viral RNA in postencephalitic Parkinsonian brain material). In reviewing the relationship between influenza and encephalitis lethargica (EL), McCall and coworkers conclude, as of 2008, that "the case against influenza [is] less decisive than currently perceived… there is little direct evidence supporting influenza in the etiology of EL," and that "[a]lmost 100 years after the EL epidemic, its etiology remains enigmatic." Hence, while opinions on the relationship of encephalitis lethargica to influenza remain divided, the preponderance of literature appears skeptical.The German neurologist Felix Stern, who examined hundreds of encephalitis lethargica patients during the 1920s, noted that their encephalitis lethargica typically evolved over time. The early symptoms would be dominated by sleepiness or wakefulness. A second symptom would lead to an oculogyric crisis. The third symptom would be recovery, followed by a Parkinson-like syndrome. If patients of Stern followed this course of disease, he diagnosed them with encephalitis lethargica. Stern suspected encephalitis lethargica to be close to poliomyelitis, without evidence. Nevertheless, he experimented with the convalescent serum of survivors of the first acute syndrome. He vaccinated patients with early-stage symptoms, telling them that it might be successful. Stern is author of the definitive 1920s book, Die Epidemische Encephalitis.In 2010, in a substantial Oxford University Press compendium reviewing the historic and contemporary views on EL, its editor, Joel Vilensky, of the Indiana University School of Medicine, quotes another researcher, writing in 1930, who states, "we must confess that etiology is still obscure, the causative agent still unknown, the pathological riddle still unsolved…", and goes on to offer the following conclusion, as of that publication date:

Does the present volume solve the "riddle" of EL, which… has been referred to as the greatest medical mystery of the 20th century? Unfortunately, no: but inroads are certainly made here pertaining to diagnosis, pathology, and even treatment."
Subsequent to publication of this compendium, an enterovirus was discovered in encephalitis lethargica cases from the epidemic. In 2012, Oliver Sacks, the author of the book Awakenings, about institutionalized survivors, acknowledged this virus as the probable cause of the disease. Other sources have suggested Streptococcus pneumoniae as a cause.

Diagnosis
There have been several proposed diagnostic criteria for encephalitis lethargica. One, which has been widely accepted, includes an acute or subacute encephalitic illness where all other known causes of encephalitis have been excluded. Another diagnostic criterion, suggested more recently, says that the diagnosis of encephalitis lethargica "may be considered if the patients condition cannot be attributed to any other known neurological condition and that they show the following signs: influenza-like signs; hypersomnolence (hypersomnia), wakeability, ophthalmoplegia (paralysis of the muscles that control the movement of the eye), and psychiatric changes."

Treatment
Modern treatment approaches to encephalitis lethargica include immunomodulating therapies, and treatments to remediate specific symptoms.There is little evidence so far of a consistent effective treatment for the initial stages, though some patients given steroids have seen improvement. The disease becomes progressive, with evidence of brain damage similar to that of Parkinsons disease.Treatment is then symptomatic. L-DOPA (Levodopa) and other anti-Parkinson drugs often produce dramatic responses; however, most people given L-DOPA experience improvements that are short lived.

History
Occurrences
Retrospective diagnosis tentatively suggests various historical outbreaks of encephalitis lethargica:

In 1580, Europe was swept by a serious febrile and lethargic illness that led to Parkinsonism and other neurological sequelae.
In 1673–1675, a similar serious epidemic occurred in London, which Thomas Sydenham described as "febris comatosa".
In 1695, a 20-year-old woman in Germany experienced oculogyric crises, Parkinsonism, diplopia, strabismus, and other symptoms following an attack of somnolent brain fever, as described by Albrecht of Hildesheim.
In 1712–1713, a severe epidemic of Schlafkrankheit (sleep sickness) occurred in Tübingen, Germany, followed in many cases by persistent slowness of movement and lack of initiative (aboulia).
Between 1750 and 1800, France and Germany experienced minor epidemics of "coma somnolentum" with features of Parkinsonism, including hyperkinetic hiccup, myoclonus, chorea, and tics.
Between 1848 and 1882, Paris-based neurologist Jean-Martin Charcot documented many isolated cases of juvenile Parkinsonism, associated with diplopia, oculogyria, tachypnoea, retropulsion, and obsessional disorders, which were almost certainly post-encephalitic in origin.
In 1890 in Italy, following the influenza epidemic of 1889–1890, a severe epidemic of somnolent illnesses (nicknamed the "Nona") appeared. For the few survivors of the Nona, Parkinsonism and other sequelae developed in almost all cases.
Between 1915 and 1926, a world-wide encephalitis lethargica pandemic occurred, impacting nearly 5 million people and killing an estimated 1.6 million people.

Pandemic of 1915–1926
In the winter of 1916–1917, a "new" illness suddenly appeared in Vienna and other cities, and rapidly spread world-wide over the next three years. Earlier reports appeared throughout Europe as early as the winter of 1915–1916, but communication about the disease was slow and chaotic, given the varied manifestation of symptoms and difficulties disseminating information in wartime. Until Constantin von Economo identified a unique pattern of damage among the brains of deceased patients and introduced the unifying name encephalitis lethargica, reports of the protean disease came in under a range of names: botulism, toxic ophthalmoplegia, epidemic stupor, epidemic lethargic encephalitis, acute polioencephalitis, Heine-Medin disease, bulbar paralysis, hystero-epilepsy, acute dementia, and sometimes just "an obscure disease with cerebral symptoms." Just 10 days before von Economos breakthrough in Vienna, Jean-René Cruchet described 40 cases of "subacute encephalomyelitis" in France.The number of people infected during the ten years of the pandemic is unknown, but it is estimated that more than 1 million people contracted the disease, which directly caused more than 500,000 deaths. Encephalitis lethargica assumed its most virulent form between October 1918 and January 1919. The pandemic disappeared in 1927, as abruptly and mysteriously as it first appeared. The great encephalitis pandemic coincided with the 1918 influenza pandemic, and it is likely that the influenza virus potentiated the effects of the causative agent of the encephalitis or lowered resistance to it in a catastrophic way.

Aftermath
Many surviving patients of the 1915–1926 pandemic seemed to make a complete recovery and return to their normal lives. However, the majority of survivors subsequently developed neurological or psychiatric disorders, often after years or decades of seemingly perfect health. Post-encephalitic syndromes varied widely: sometimes they proceeded rapidly, leading to profound disability or death; sometimes very slowly; sometimes they progressed to a certain point and then stayed at this point for years or decades; and sometimes, following their initial onslaught, they remitted and disappeared. Postencephalitic Parkinsonism is perhaps the most widely recognized of such syndromes.

Notable cases
Notable cases include:

Muriel "Kit" Richardson (née Hewitt), first wife of actor Sir Ralph Richardson, died of the condition in October 1942, having first shown symptoms in 1927–28.
There is speculation that Adolf Hitler may have had encephalitis lethargica when he was a young adult (in addition to the more substantial case for Parkinsonism in his later years).
Mervyn Peake (1911–1968), author of the Gormenghast books, began his decline towards death which was initially attributed to encephalitis lethargica with Parkinsons disease–like symptoms, although others have later suggested his decline in health and eventual death may have been due to Lewy body dementia.
Those described in the book Awakenings by the British neurologist Oliver Sacks.
Jane Norton Grew Morgan, wife of J. P. Morgan Jr., died of encephalitis lethargica in 1925. At the time, doctors attributed her encephalitis to having contracted influenza during the 1918 pandemic.

References
Further reading
Crosby, Molly Caldwell (2010). Asleep: The Forgotten Epidemic that Remains One of Medicines Greatest Mysteries. New York: Penguin/Berkley. – Describes the history of the disease, and the epidemic of the 1920s.
Reid, A.H.; McCall, S.; Henry, J.M.; Taubenberger, J.K. (2001). "Experimenting on the Past: The Enigma of von Economos Encephalitis Lethargica". J. Neuropathol. Exp. Neurol. 60 (7): 663–670. doi:10.1093/jnen/60.7.663. PMID 11444794.
Sacks, Oliver (1990). Awakenings. Vintage Books. ISBN 978-0-375-70405-5. OCLC 21910570.
Sacks O (1983). "The origin of Awakenings". Br. Med. J. (Clin. Res. Ed.). 287 (6409): 1968–1969. doi:10.1136/bmj.287.6409.1968. PMC 1550182. PMID 6418286.
Vilensky, J.A.; Foley, P.; Gilman, S. (2007) </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 Phaeohyphomycosis and can you explain it in depth? [/INST] Phaeohyphomycosis is a diverse group of fungal infections, caused by dematiaceous fungi whose morphologic characteristics in tissue include hyphae, yeast-like cells, or a combination of these.: 324  It can be associated an array of melanistic filamentous fungi including Alternaria species, Exophiala jeanselmei, and Rhinocladiella mackenziei.The term “phaeohyphomycosis” was introduced to determine infections caused by dematiaceous (pigmented) filamentous fungi which contain melanin in their cell walls. Phaeohyphomycosis is an uncommon infection, but the number of cases reported has been increasing in recent years. Fungal melanin is thought to be a virulence factor. The outcome of antifungal treatment is poor, and mortality is almost 80%. Phaeohyphomycosis has been attributed to more than 100 species and 60 genera of fungi over the past several decades. The pathogens are considered opportunistic. Almost all cases of widely disseminated infection have occurred in immunosuppressed people.

Clinical signs of phaeohyphomycosis
Wildlife
Phaeohyphomycosis is found throughout the animal kingdom. From molluscs to humans, different strains of this fungus affect animals differently, based on how severely the fungus has infected the animal. The clinical signs depend on the species of animal that is infected as well as the strain of fungus it is infected with. This disease is usually found more often in stressed animals after removal from their habitat.

Invertebrates
Invertebrates, such as crabs and mollusks, show a variety of clinical signs.
Crabs had increasingly weak motor control, especially in legs and claws, and were lethargic. They had poor balance and tetany, or muscle spasms, in the claws. Finally, they had tissue necrosis, which caused deterioration of the epidermis, connective tissue, heart, hepatopancreas, nervous system, and gills. In severe cases, there was congestion of hemal sinuses, two principal empty areas along the digestive tube and vessels. Mass amounts of yeast-like cells compressed nerve fibers and the gill lamellae were destroyed.
Mollusks clinical signs vary from scattered spots of brownish discoloration on the mantle tissues to general deterioration of mussel condition. In severe cases, there were black-bodied mussels with a distinct odor and black yeast-cells infected the connective tissues around the gonads and the digestive tract.

Cold-blooded vertebrates
Cold-blooded vertebrates exhibited an assortment of clinical signs.
Amphibians showed signs of anorexia. Ulcers or nodules in the skin were found, as well as swelling and lesions of internal organs, including the spleen, liver, and kidney. In extreme cases, neurological disorders and multifocal dermatitis (swelling caused by irritation of the fungus) occurred.
Fish demonstrated signs of lethargy and disoriented swimming. There were ulcerative lesions, multiple dark foci in the gills, and non-ulcerative dermal masses found. In critical cases, some fish showed a variety of inflammatory responses including the formation of microabscesses. Lesions in the brain and kidneys were also found. These fish had abnormal swimming behavior, bulging eyes, and abdominal swelling.

Warm-blooded vertebrates
From birds to equines, Phaeohyphomycosis persists and has a massive range of clinical signs throughout differing species. Poultry and wild birds had neurological disorders and a loss of movement control. They experienced severe torticollis, which are severe muscle spasms that compromise the bird’s ability to hold up its head. The birds exhibited a loss of balance due to the rigidity of their legs.
Cats showed signs of difficulty breathing due to excessive swelling of the nose. There were also lesions found throughout the body, including the brain. Common lesions include ulcerated cutaneous nodules of the digits, pinnae, nasal planum, and nasal/paranasal tissues.In extreme cases dogs exhibited vision impairment and had deep infections in the nasal cavity, kidneys, and the cerebellum. In dogs, brain infections were found similar to infections that were found in humans. Other clinical signs were lesions, abscesses, and severe inflammation throughout the dog’s body.
Ruminants and equines were affected the same way from Phaeohyphomycosis. They showed respiratory distress through constant coughing and a fever. They demonstrated signs of anorexia, lethargy, and hypothermia. There was inflammation, hair loss, scaling, and damage to their cerebellum.

Humans
Human’s clinical signs consisted of swelling and eye infections. There were nodules underneath the skin, abscesses or cysts, and lesions running throughout the body. There were papules, plaques and granulomatous damages on the body. In extreme cases there were deep infections within the eyes, bones, heart and central nervous system.

Treatment
Extensive treatments have been used on domestic animals more than on wild animals, probably because infected domestic animals are easier to identify and treat than infected wildlife. Treatment plans and management vary across taxa because this disease tends to affect each species differently. Antifungal drugs are the first line of defense to kill the agents causing phaeohyphomycosis, but despite the significant progress made in the last two decades and a 30% increase in available antifungal drugs since 2000, many drugs are not effective against black fungi. Diseases caused by black fungi are hard to treat because the fungi are very difficult to kill. This high resilience may be contributed to the presence of melanin in their cell walls, as well as the greater similarity to host cells which are both eukaryotes than other pathogens such as bacteria or viruses. Current antifungal agents the fungi are not resistant to are posaconazole, voriconazole, and azole isavuconazole.In 2006, a free-living Eastern box turtle, Terrapene carolina carolina, was found with a form of phaeohyphomycosis and was brought in the Wildlife Center of Virginia. Its symptom was swelling of the right hindfoot; it was diagnosed as having chromomycosis by histopathology. The center provided a series of antimicrobial treatments and a one-month course of 1 mg itraconazole, administered orally once a day. The eastern box turtle was euthanized due to further complications and the caretakers’ belief that the turtle would not be able to survive if placed back in the wild.
A recent case of a form of phaeohyphomycosis infection was found in a dog in 2011. The Journal of the American Veterinary Medical Association published a case study in which researchers successfully managed an intracranial phaeohyphomycotic fungal granuloma in a one-year-old male Boxer dog. Veterinarians of the Department of Veterinary Clinical Sciences at Tufts University surgically removed the granuloma in the right cerebral hemisphere. The patient was treated with fluconazole for 4 months, and was followed with voriconazole for 10 months. Both are medications used to treat fungal infections. Based on magnetic resonance imaging and cerebrospinal fluid (CSF) analysis 8 months after the surgery, the male Boxer’s outcome was considered excellent.
Emphasis has been placed on how to manage this disease through careful management practices including: proper handling, preventing crowding situation with animals, and transportation. Both the animals and the environment should be treated thoroughly to hinder the spread and control the fungal infection. This is especially important since humans can also contract this disease.

Research projects and implications
Phaeohyphomycosis is a disease caused by this fungus </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 Birth weight and can you explain it in depth? [/INST] Birth weight is the body weight of a baby at its birth. The average birth weight in babies of European descent is 3.5 kilograms (7.7 lb), with the normative range between 2.5 and 4.5 kilograms (5.5 and 9.9 lb). On average, babies of South Asian and Chinese descent weigh about 3.26 kilograms (7.2 lb). As far as low birth weight prevalence rates changing over time, there has been a slight decrease from 7.9% (1970) to 6.8% (1980), then a slight increase to 8.3% (2006), to the current levels of 8.2% (2016). The prevalence of low birth weights has trended slightly upward from 2012 to the present.There have been numerous studies that have attempted, with varying degrees of success, to show links between birth weight and later-life conditions, including diabetes, obesity, tobacco smoking, and intelligence. Low birth weight is associated with neonatal infection and infant mortality.

Abnormalities
A low birth weight can be caused either by a preterm birth (low gestational age at birth) or of the infant being small for gestational age (slow prenatal growth rate), or a combination of both. Potential causes of low birth weight can also be cause by health issues in the person giving birth, genetic factors, or problems in the placenta.
A very large birth weight is usually caused by the infant having been large for gestational age. Infants that are large for gestational age have been associated with significantly higher rates of neonatal morbidity.

Determinants
Genetics
There are two genetic loci that have been strongly linked to birth weight, ADCY5 and CCNL1, as well four that show some evidence (CDKAL1, HHEX-IDE, GCK, and TCF7L2).  The heritability of birth weight ranges from 25 to 40%. There is a complex relationship between a babys genes and the maternal environment that the child is developing in. Foetal genes influence how the fetus grows in utero, and the maternal genes influence how the environment affects the growing fetus.

Maternal health
The health of the mother during the pregnancy can affect birth weight.  A pre-existing disease or acquired disease in pregnancy is sometimes associated with decreased birth weight. For example, celiac disease confers an odds ratio of low birth weight of approximately 1.8. Certain medications (e.g. for high blood pressure or epilepsy) can put a mother at a higher risk for delivering a low birth weight baby. Women younger than 15 or older than 35 are at a higher risk to have a low-birth weight baby. Multiple births, where a mother has more than one child at one time, can also be a determinant in birth weight as each baby is likely to be outside the AGA (appropriate for gestational age). Multiple births put children at a higher rate to have low birth weight (56.6%) compared to children born in a single birth ( 6.2%). Low birth weight can also vary by maternal age. In 2008 the rate of low birth weight was the highest in babies born to women younger than 15 years old (12.4%). Women aged 40–54 had a rate of low birth weight at 11.8 percent. The lowest rates of low birth weight happened among babies whose mothers were between the ages of 25–29 years (4.4%) and 30–34 years (7.6%).

Stress
Stressful events have been demonstrated to produce significant effects on birth weight. Those mothers who have stressful events during pregnancy, especially during the first and second trimester, are at higher risk to deliver low-birth weight babies. Researchers furthered this study and found that maternal stressful events that occur prior to conception have a negative impact on birth weight as well, and can result in a higher risk for preterm and lower birth weight babies. Women who experienced abuse (physical, sexual, or emotional) during pregnancy are also at increased risk of delivering a low-birth weight baby. For example, in a study completed by Witt et al., those women who experienced a stressful event (i.e. death of close family member, infertility issues, separation from partner) prior to conception had 38% more of a chance to have a very low birth weight baby compared to those who had not experienced a stressful life event. The theory is that stress can impact a baby based on two different mechanisms: neuroendocrine pathway or immune/inflammatory pathway. Stress causes the body to produce stress hormones called glucocorticoids that can suppress the immune system., as well as raises levels of placental corticotropin-releasing hormone (CRH) which can lead to preterm labor. These findings can pose evidence for future prevention efforts for low birth weight babies. One way to decrease rates of low birth weight and premature delivery is to focus on the health of women prior to conception through reproductive education, screening and counseling regarding mental health issues and stress, and access to primary care.

Racial stress
Non-Hispanic Blacks have the highest infant mortality rate in the United States (11.4 deaths per 1,000 live births compared to the national average of 5.9 deaths per 1,000 live births). Subsequently,  there has been growing research supporting the idea of racial discrimination as a risk factor for low birth weight. In one study by Collins et al., evidence suggested that African American mothers who experienced high levels of racial discrimination were at significantly higher risk of delivering a very low-birth weight baby compared to African American mothers who had not experienced racial discrimination. Black infants (13.2%) are more likely to have low birth weight compared to Asian and Pacific Islander (8.1%), American Indian and Alaska Native (7.6%), Non-Hispanic White (7.0%), and Hispanic Infants (7.1%).

Environmental factors
Environmental factors, including exposure of the mother to secondhand smoke can be a factor in determining the birth weight of child. In 2014, 13% of children exposed to smoke were born with low birth weight compared with 7.5% of those children born to nonsmokers.  Children born to mothers who smoked or were exposed to secondhand smoke are more likely to develop health problems earlier in life such as neurodevelopmental delays. When mothers actively smoke during pregnancy, their child is at a higher risk of being born with a low birth weight. Smoking can also be a stress management tool used by expecting mothers. There is some support for lower socioeconomic status of the parents being a determinant of low birth weight, but there is conflicting evidence, as socioeconomic status is tied to many other factors.

Neonatal care
Most babies admitted to the NICU are born before 37 weeks of pregnancy or have low birth weight which is less than 5.5 pounds (2.5 kg). They could also have a medical condition that requires special care. In the United States nearly half a million babies are born preterm. Because of this, many of these babies also have low birth weights. There are four levels of care in the neonatal care units. Intensive Care, High Dependency Care, Low Dependency, and Transitional Care are the four levels:
Intensive Care: For babies with serious problems. This includes babies born three months early and have extremely low birth weight.
High Dependency Care: For babies with less serious problem, but who still may not to be looked after or babies that are recovering from a critical illness.
Low Dependency Care: For babies that do not need a continuous supervision.
Transitional Care: For babies that still need medical treatment, but are well enough to be called for at their mothers bedside.

Influence on the first few years of life
Children born with an abnormally low birth weight can have significant problems within the first few years of life. They may have trouble gaining weight, obtaining adequate nutrition, and supporting a strong immune system. They also have higher risks for mortality, behavior problems, and mental deficiencies. Low birth weight babies are more likely to develop the following conditions after birth compared to normal birth weight babies:
Breathing problems (infant respiratory distress syndrome)
Bleeding in the brain (intraventricular hemorrhage)
Patent ductus arteriosus (PDA)
Necrotizing enterocolitis
Retinopathy of prematurity
Jaundice
InfectionsThat said, the effects of low birth weight on a childs first few years of life are often intertwined with other maternal, environmental, and genetic factors and most effects of low birth weight are only slightly negatively significant on a childs life when these factors are controlled for. When these factors are controlled, the only significant effect low birth weight has on a childs development is physical growth in the early years and the likelihood of being underweight compared to normal birth weight babies.

Influence on adult life
Studies have been conducted to investigate how a persons birth weight can influence aspects of their future life. This includes theorised links with obesity, diabetes and intelligence.

Obesity and diabetes
A baby born small or large for gestational age (either of the two extremes) is thought to have an increased risk of obesity in later life, but it was also shown that this relationship is fully explained by maternal weight. Middle aged adults with low birth weight present with a higher chance of obesity and diabetes. Children that are born under six pounds were 1.27 times more likely to develop diabetes compared to babies born at a healthy weight over six pounds.
Growth hormone (GH) therapy at a certain dose induced catch-up of lean body mass (LBM). However percentage body fat decreased in the GH-treated subjects. Bone mineral density SDS measured by DEXA increased significantly in the GH-treated group compared to the untreated subjects, though there is much debate over whether or not SGA (small for gestational age) is significantly adverse to children to warrant inducing catch-up.
Babies that have a low birth weight are thought to have an increased risk of developing type 2 diabetes in later life. Low birth weight is linked with increase rates of obesity, insulin resistance, and type 2 diabetes and it is shown that children with the low birth weights have increased leptin levels after they catch up growth during childhood. Adiponectin levels are positively related with birth weight and BMI in babies with an increase of risk of type 2 diabetes. The leptin and adiponection mechanisms are still being studied when involving low birth weight.

Around the world
There is much variation regarding birth weight within continents, countries, and cities.  Even though over 20 million babies are born each year with low birth weight, it is hard to know the exact number as more than half of babies born in the world are not weighed at birth. The babys weight is an indicator of the mother and babys health. In 2013, 22 million newborns had low birth weight, around 16 percent of all babies globally. Data on low birth weight is adjusted to account for under reporting. South Asia has the highest rate of babies not weighed at birth with 66 percent, but also have the highest low birth weight at 28 percent worldwide. West and Central Africa and least developed countries are next with 14 percent low birth weight worldwide.More than 96.5% of low birth weight babies are born in developing countries around the world. Because low birth weight babies can require more extensive care, it places a financial burden on communities.

Prevention
The World Health Organization (WHO) recently announced an initiative to have a thirty percent reduction in low birth weight worldwide. This is public health priority, as birth weight can have short and long term effects. WHO estimates that worldwide, 15-20 % of all births each year are considered low birth weight, which is about 20 million births.The start of prenatal care is very important to help prevent low birth weight and early medical problems </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 Heerfordt syndrome and can you explain it in depth? [/INST] Heerfordt syndrome  is a rare manifestation of sarcoidosis. The symptoms include inflammation of the eye (uveitis), swelling of the parotid gland, chronic fever, and in some cases, palsy of the facial nerves.

Causes
The exact cause of Heerfordt syndrome has not yet been definitively determined. Of those patients who have been diagnosed with Heerfordt syndrome, 15% have a close relative who also has the syndrome. One possible explanation is that the syndrome results from a combination of an environmental agent and a hereditary predisposition. Mycobacterium and Propionibacteria species have both been suggested as the environmental agent, though the evidence for this is inconclusive.

Diagnosis
In patients that have already been diagnosed with sarcoidosis, Heerfordt syndrome can be inferred from the major symptoms of the syndrome, which include parotitis, fever, facial nerve palsy and anterior uveitis. In cases of parotitis, ultrasound-guided biopsy is used to exclude the possibility of lymphoma </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 Campomelic dysplasia and can you explain it in depth? [/INST] Campomelic dysplasia (CMD) is a genetic disorder characterized by bowing of the long bones and many other skeletal and extraskeletal features.
It can be lethal in the neonatal period due to respiratory insufficiency, but the severity of the disease is variable, and a significant proportion of patients survive into adulthood.
The name is derived from the Greek roots campo (or campto), meaning bent, and melia, meaning limb. An unusual aspect of the disease is that up to two-thirds of affected 46,XY genotypic males display a range of disorders of sexual development (DSD) and genital ambiguities or may even develop as normal phenotypic females as in complete 46 XY sex reversal. An atypical form of the disease with absence of bowed limbs is called, prosaically, acampomelic campomelic dysplasia (ACD) and is found in about 10% of patients, particularly those surviving the neonatal period.

Signs and symptoms
While the definitive presentation of the disease is a patient having bowed lower limbs and sex reversal in 46,XY males, there are other clinical criteria that can be used, absent these characteristics, to make the diagnosis </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 Ovarian remnant syndrome and can you explain it in depth? [/INST] Ovarian remnant syndrome is a condition that occurs when ovarian tissue is left behind following oophorectomy, causing development of a pelvic mass, pelvic pain, and occasionally dyspareunia. Ovarian remnant syndrome (ORS) is characterized by the presence of residual ovarian tissue after a woman has had surgery to remove one ovary or both ovaries (oophorectomy).

Signs and symptoms
If ovarian hormones are present after the ovaries are removed can be a sign that ovarian tissue still remains. Signs and symptoms may include pelvic pain, a pelvic mass, or the absence of menopause after oophorectomy. Factors may include pelvic adhesions (limiting ability to see the ovary or causing it to adhere to other tissues); anatomic variations; bleeding during surgery; or poor surgical technique. Treatment is indicated for people with symptoms and typically involves surgery to remove the residual tissue. Therapy for those who refuse surgery, cannot have surgery, or do not have a pelvic mass may include hormonal therapy to suppress ovarian function.Some women have symptoms consistent with endometriosis, including difficult or painful intercourse; urinary symptoms; or bowel symptoms. It is likely that some women with ORS dont have any symptoms, but the rate of this is unknown. In most cases, symptoms occur within the first five years of the oophorectomy, although there are reports of ORS presenting 20 years after the initial surgery.

Cause
The cause of ORS is the unintentional retention of ovarian tissue after the procedure to remove the ovaries. If a woman is receiving hormone replacement therapy, distinguishing from other disease process may be difficult. Other confounding conditions contributing to ORS are thick and profuse pelvic adhesions, inflammation, bleeding after surgery (peri-operative bleeding), and ovaries which are retroperitoneal, can all contribute to the unintentional preservation of ovarian fragments.

Risks
The risk of ovarian remnant (ORS) is increased by incomplete removal of the ovary at the time of oophorectomy. Surgical factors that contribute to incomplete removal include those that limit surgical exposure of the ovary, or compromise surgical technique. Factors may include:

adhesions – these can limit visualization of the ovary and may also cause it to adhere to surrounding tissues. Adhesions are often present due to preexisting conditions and/or prior surgeries. In the majority of cases reported since 2007, endometriosis was the most common indication for the initial oophorectomy in patients who subsequently had ORS. Endometriosis increases the risk for functional ovarian tissue being embedded into adjacent structures, making complete excision of tissue challenging.
Anatomic variations - unusual location of ovarian tissue, for example
Intraoperative bleeding
Poor surgical technique – this may include failure to obtain adequate exposure or restore adequate anatomy, or imprecise choice of incision siteOvarian remnant (ORS) may first be considered in women who have undergone oophorectomy and have suggestive symptoms, the presence of a mass, or evidence of persistent ovarian function (by symptoms or laboratory testing). A history of oophorectomy is required, by definition, to make the diagnosis. Notes regarding the indication for the procedure and the procedure itself should be reviewed and may include prior abdominal or pelvic surgery, endometriosis, and/or poor surgical visualization. If ORS is possible, pelvic should be performed to evaluate for a pelvic mass.[1]

Diagnosis
Surgical exploration and confirmation of possible ovarian tissue is required for the definitive diagnosis of ORS, and treatment by excision of the remnant ovarian tissue may be performed during the same procedure </s>