<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 Non-celiac gluten sensitivity and can you explain it in depth? [/INST] Non-celiac gluten sensitivity (NCGS) or gluten sensitivity is "a clinical entity induced by the ingestion of gluten leading to intestinal and/or extraintestinal symptoms that improve once the gluten-containing foodstuff is removed from the diet, and celiac disease and wheat allergy have been excluded".NCGS is included in the spectrum of gluten-related disorders. The definition and diagnostic criteria of non-celiac gluten sensitivity were debated and established by three consensus conferences. However, as of 2019, there remained much debate in the scientific community as to whether or not NCGS was a distinct clinical disorder.The pathogenesis of NCGS is not well understood, but the activation of the innate immune system, the direct cytotoxic effects of gluten and probably other wheat components, are implicated. There is evidence that not only gliadin (the main cytotoxic antigen of gluten), but also other proteins named ATIs which are present in gluten-containing cereals (wheat, rye, barley, and their derivatives) may have a role in the development of symptoms. ATIs are potent activators of the innate immune system. FODMAPs, especially fructans, are present in small amounts in gluten-containing grains and have been identified as a possible cause of some gastrointestinal symptoms in NCGS patients. As of 2019, reviews have concluded that although FODMAPs may play a role in NCGS, they explain only certain gastrointestinal symptoms, such as bloating, but not the extra-digestive symptoms that people with NCGS may develop, such as neurological disorders, fibromyalgia, psychological disturbances, and dermatitis.For these reasons, NCGS is a controversial clinical condition and some authors still question it.  It has been suggested that "non-celiac wheat sensitivity" is a more appropriate term, without forgetting  that other gluten-containing cereals are implicated in the development of symptoms.NCGS is the most common syndrome of gluten-related disorders with prevalence rates between 0.5%–13% in the general population. As no biomarker for diagnosing this condition is available, its diagnosis is made by exclusion of other gluten-related disorders such as celiac disease and wheat allergy. Many people have not been diagnosed following strict criteria, and there is a "fad component" to the recent rise in popularity of the gluten-free diet, leading to debate surrounding the evidence for this condition and its relationship to celiac disease and irritable bowel syndrome. People with NCGS are often unrecognized by specialists and lack adequate medical care and treatment. They often have a long history of health complaints and unsuccessful consultations with physicians, and thus many resort to a gluten-free diet and a self-diagnosis of gluten sensitivity.

Signs and symptoms
Reported symptoms of NCGS are similar to those of celiac disease, with most patients reporting both gastrointestinal and non-gastrointestinal symptoms. In the "classical" presentation of NCGS, gastrointestinal symptoms are similar to those of irritable bowel syndrome, and are also not distinguishable from those of wheat allergy, but there is a different interval between exposure to wheat and onset of symptoms. Wheat allergy has a fast onset (from minutes to hours) after the consumption of food containing wheat and can be anaphylaxic.

Gastrointestinal
Gastrointestinal symptoms may include any of the following: abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), nausea, aerophagia, flatulence, gastroesophageal reflux disease, and aphthous stomatitis.

Extraintestinal
NCGS can cause a wide range of extraintestinal symptoms, which can be the only manifestation of NCGS in absence of gastrointestinal symptoms. These include any of the following: headache, migraine, "foggy mind", fatigue, fibromyalgia, joint and muscle pain, leg or arm numbness, tingling of the extremities, dermatitis (eczema or skin rash), atopic disorders such as asthma, rhinitis, other allergies, depression, anxiety, iron-deficiency anemia, folate deficiency, or autoimmune diseases.

NCGS is also linked to a wide spectrum of neurological and psychiatric disorders, including  ataxia, schizophrenia, epilepsy, peripheral neuropathy, encephalopathy, vascular dementia, eating disorders, autism, attention deficit hyperactivity disorder (ADHD), hallucinations (so-called "gluten psychosis"),  and various movement disorders (restless legs syndrome, chorea, parkinsonism, Tourette syndrome, palatal tremor,  myoclonus, dystonia, opsoclonus myoclonus syndrome, paroxysms, dyskinesia, myorhythmia, myokymia).Above 20% of people with NCGS have IgE-mediated allergy to one or more inhalants, foods, or metals, among which most common are mites, graminaceae, parietaria, cat or dog hair, shellfish, and nickel.  Approximately 35% of patients suffer other food intolerances, mainly lactose intolerance.

Causes
The pathogenesis of NCGS is not yet well understood, but the activation of the innate immune system, the direct cytotoxic effects of gluten, and probably the cytotoxicity of other wheat molecules are implicated. Besides gluten, other components in wheat, rye, barley, and their derivatives, including amylasetrypsin inhibitors (ATIs) and FODMAPs, may  cause symptoms.

Gluten
It was hypothesized that gluten, as occurs in celiac disease, is the cause of NCGS. In addition to its ability to elicit abnormal responses of the immune system, in vitro studies on cell cultures showed that gluten is cytotoxic and causes direct intestinal damage. Gluten and gliadin promote cell apoptosis (a form of programmed cell death) and reduce the synthesis of nucleic acids (DNA and RNA) and proteins, leading to a reduction in the viability of cells. Gluten alters cellular morphology and motility, cytoskeleton organization, oxidative balance and intercellular contact (tight junction proteins).

Other proteins
Some people may have a reaction to other proteins (α-amylase/trypsin inhibitors [ATIs]) present in gluten-containing cereals that are able to inhibit amylase and trypsin. They have been identified as the possible activator of the innate immune system in celiac disease and NCGS.ATIs are part of the plants natural defence against insects and may  cause toll-like receptor 4 (TLR4)-mediated intestinal inflammation in humans. These TLR4-stimulating activities of ATIs are limited to gluten-containing cereals (wheat, rye, barley, and derivatives) and may induce innate immunity in people with celiac disease or NCGS. ATIs resist proteolytic digestion. ATIs are about 2%–4% of the total protein in modern wheat and are present in commercial gluten. A 2017 study in mice demonstrated that ATIs exacerbate preexisting inflammation and may also worsen it at extraintestinal sites. This may explain why there is an increase of inflammation in people with preexisting diseases upon ingestion of ATI-containing grains.Modern wheat cultivation, by breeding for high ATI content, may play a role in the onset and course of disorders such as celiac disease and gluten sensitivity. However, it has been questioned whether there is sufficient empirical evidence to support this claim, because as of 2018 we lack studies that directly compare modern wheat versus ancient cultivars with low ATI content (such as einkorn wheat) in people with NCGS.Wheat germ agglutinin is also considered to be a possible trigger of NCGS-like symptoms.

FODMAPs
FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) that are present in gluten-containing grains (mainly fructans) have been identified as a possible cause of gastrointestinal symptoms in people with NCGS, in place of, or in addition to, gluten.The amount of fructans in gluten-containing cereals is relatively small and their role has been controversial. In rye they account for 3.6%–6.6% of dry matter, 0.7%–2.9% in wheat, and barley contains only trace amounts. They are only minor sources of FODMAPs when eaten in the usual standard amounts in the daily diet. Wheat and rye may comprise a major source of fructans when consumed in large amounts. They may cause mild wheat intolerance at most, limited to certain gastrointestinal symptoms, such as bloating, but do not justify the NCGS extradigestive symptoms. A 2018 review concluded that although fructan intolerance may play a role in NCGS, it only explains some gastrointestinal symptoms, but not the extradigestive symptoms that people with NCGS may develop, such as neurological disorders, fibromyalgia, psychological disturbances, and dermatitis. FODMAPs cause digestive symptoms when the person is hypersensitive to luminal distension. A 2019 review concluded that wheat fructans can cause certain IBS-like symptoms, such as bloating, but are unlikely to cause immune activation or extra-digestive symptoms. Many people with NCGS report resolution of their symptoms after removing gluten-containing cereals while continue to eat fruits and vegetables with high FODMAPs content.

Diagnosis
Absence of reliable biomarkers and the fact that some people do not have digestive symptoms make the recognition and diagnosis of non-celiac gluten sensitivity (NCGS) difficult.Diagnosis is generally performed only by exclusion criteria. NCGS diagnostic recommendations have been established by several consensus conferences. Exclusion of celiac disease and wheat allergy is important because these two conditions also appear in people who experience symptoms similar to those of NCGS, which improve with a gluten withdrawal and worsen after gluten consumption.The onset of NCGS symptoms may be delayed hours to a few days after gluten ingestion, whereas in celiac disease it can take days to weeks. Wheat allergy has a fast onset (from minutes to hours) after the consumption of food containing wheat and can lead to anaphylaxis.The presence of related extraintestinal manifestations has been suggested to be a feature of NCGS. When symptoms are limited to gastrointestinal effects, there may be an overlap with wheat allergy, irritable bowel syndrome (IBS), and (less likely) intolerance to FODMAPs.Proposed criteria for a diagnosis of NCGS suggest an improvement of gastrointestinal symptoms and extra-intestinal manifestations higher than 30% with a gluten-free diet (GFD), assessed through a rating scale, is needed to make a clinical diagnosis of NCGS. To exclude a placebo effect, a double-blind placebo-controlled gluten challenge is a useful tool, although it is expensive and complicated for routine clinical use, and so is usually performed in research studies.These suggestions were incorporated in the Salerno expert consensus on diagnostic criteria for NCGS. These recommend assessment of the response to a 6-week trial of a gluten-free diet using a defined rating scale (Step 1), followed by a double-blind, placebo-controlled challenge of gluten (or placebo) for a week of each (Step 2).  A variation of greater than 30% in the main symptoms when challenged by gluten or placebo is needed for a positive result. Further research on possible biomarkers was also identified.

Differential diagnosis
Examinations evaluating celiac disease and wheat allergy should be performed before patients remove gluten from their diet. It is critical to make a clear distinction between celiac disease and NCGS.

Celiac disease
The main goal in diagnosing NCGS is to exclude celiac disease. NCGS and celiac disease cannot be separated in diagnosis because many gastrointestinal and non-gastrointestinal symptoms are similar in both diseases, and there are people with celiac disease having negative serology (absence of specific celiac disease antibodies in serum) or without villus atrophy. There is no test capable of eliminating a diagnosis of a celiac disease, but such a diagnosis is unlikely without confirming HLA-DQ2 and/or HLA-DQ8 haplotypes.The prevalence of undiagnosed celiac disease has increased fourfold during the past half-century, with most cases remaining unrecognized, undiagnosed and untreated, leaving celiac patients with the risk of long-term complications. Some people with NCGS may indeed have celiac disease. A 2015 systematic review found that 20% of people with NCGS presenting with HLA-DQ2 and/or HLA-DQ8 haplotypes, negative serology, and normal histology or duodenal lymphocytosis had celiac disease.The presence of autoimmune symptoms in people with NCGS suggests the possibility of undiagnosed celiac disease. Autoimmune diseases typically associated with celiac disease are diabetes mellitus type 1, thyroiditis, gluten ataxia, psoriasis, vitiligo, autoimmune hepatitis, dermatitis herpetiformis, primary sclerosing cholangitis, and others.To evaluate the possible presence of celiac disease, specific serology and duodenal biopsies are required while the person is still on a diet that includes gluten.

Serological markers
Serological CD markers (IgA tissue transglutaminase [tTGA], IgA endomysial [EmA] and IgG deamidated gliadin peptide [DGP] antibodies) are always negative in those with NCGS; in addition to specific IgA autoantibody levels, it is necessary to determine total IgA levels. IgG tTGA antibodies should be checked in selective IgA deficiency, which can be associated with celiac disease and occurs in as many as one in 40 celiac patients.Nevertheless, the absence of serological markers does not certainly exclude celiac disease. In those with celiac disease before diagnosis (on a gluten-containing diet), celiac disease serological markers are not always present. As the age of diagnosis increases, these antibody titers decrease, and may be low or even negative in older children and adults. The absence of celiac disease-specific antibodies is more common in patients without villous atrophy who only have duodenal lymphocytosis (Marsh 1 lesions) and who respond to a gluten-free diet with histological and symptomatic improvement.

Duodenal biopsies
According to the diagnostic criteria established by the consensus conferences (2011 and 2013), it is necessary to perform duodenal biopsies to exclude celiac disease in symptomatic people with negative specific celiac disease antibodies. Because of the patchiness of the celiac disease lesions, four or more biopsies are taken from the second and third parts of the duodenum, and at least one from the duodenal bulb. Even in the same biopsy fragments, different degrees of pathology may exist.Duodenal biopsies in people with NCGS are always almost normal – an essential parameter for diagnosis of NCGS, although is generally accepted that a subgroup of people with NGCS may have an increased number of duodenal intraepithelial lymphocytes (IELs) ( ≥25/100 enterocytes), which represent Marsh I lesions. Nevertheless, Marsh I is considered compatible with celiac disease and the most frequent cause of these findings, especially in people positive for HLA DQ2 and/or DQ8 haplotypes, is celiac disease, with a prevalence of 16-43%.In people with duodenal lymphocytosis – following guidelines from the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) – a high count of celiac disease cells (or CD/CD3 ratio) in immunohistochemical assessment of biopsies, or the presence of IgA anti-TG2 and/or anti-endomysial intestinal deposits, might be specific markers for celiac disease. Catassi and Fasano proposed in 2010 that in patients without celiac disease antibodies, either lymphocytic infiltration associated with IgA subepithelial deposits or a histological response to a gluten-free diet, could support a diagnosis of celiac disease.

Wheat allergy
The clinical presentation may be sufficient in most cases to distinguish a wheat allergy from other entities. It is excluded when there are normal levels of serum IgE antibodies to gluten proteins and wheat fractions, and no skin reaction to prick tests for wheat allergy. Nevertheless, these tests are not always completely reliable.If an allergic reaction can not be clearly identified, the diagnosis should be confirmed by food provocation tests, ideally performed in a double-blinded and placebo-controlled manner. Delayed allergic reactions may occur with these type of tests, which have to be negative over time, but there are no international consensus statements on diagnosing delayed wheat/food-related symptoms. Usually, reactions that appear between two hours and five days after the oral challenge are considered delayed. Mucosal challenge followed by confocal endomicroscopy is a complementary diagnostic technique, but this technology is not yet generally available and remains experimental.

Other tests
Evaluating the presence of antigliadin antibodies (AGA) can be a useful complementary diagnostic test. Up to 50% NCGS patients may have elevated AGA IgG antibodies, but rarely AGA IgA antibodies (only 7% of the cases). In these patients, unlike in those with celiac disease, the IgG AGA became undetectable within six months of following a gluten-free diet.

People already on a gluten-free diet
Many people remove gluten from their diet after a long history of health complaints and unsuccessful consultations with numerous physicians, who simply consider them to be suffering from irritable bowel syndrome, and some may eliminate gluten before seeking medical attention. This fact can diminish the CD serological markers titers and may attenuate the inflammatory changes found in the duodenal biopsies. In these cases, patients should be tested for the presence of HLA-DQ2/DQ8 genetic markers because a negative HLA-DQ2 and HLA-DQ8 result has a high negative predictive value for celiac disease. If these markers are positive, it is advisable to undertake a gluten challenge under medical supervision, followed by serology and duodenal biopsies. However, gluten challenge protocols have significant limitations, because a symptomatic relapse generally precedes the onset of a serological and histological relapse, and therefore becomes unacceptable for many patients. Gluten challenge is also discouraged before the age of five and during pubertal growth.It remains unclear what daily intake of gluten is adequate and how long the gluten challenge should last. Some protocols recommend eating a maximum of 10 g of gluten per day for six weeks. Nevertheless, recent studies have shown that a two-week challenge of 3 g of gluten per day may induce histological and serological abnormalities in most adults with proven celiac disease. This new proposed protocol has shown higher tolerability and compliance. It has been calculated that its application in secondary-care gastrointestinal practice would identify celiac disease in 7% of patients referred for suspected NCGS, while the remaining 93% would be confirmed as NCGS; this is not yet universally adopted.For people on a gluten-free diet who are unable to perform an oral gluten challenge, an alternative to identify possible celiac disease is an in vitro gliadin challenge of small bowel biopsies, but this test is only available at selected specialized tertiary-care centers.

Treatment
After exclusion of celiac disease and wheat allergy, the subsequent step for diagnosis and treatment of NCGS is to start a strict gluten-free diet (GFD) to assess if symptoms improve or resolve completely. This may occur within days to weeks of starting a GFD, but improvement may also be due to a non-specific, placebo response. The recovery of the nervous system is slow and sometimes incomplete.Recommendations may resemble those for celiac disease, for the diet to be strict and maintained, with no transgression. The degree of gluten cross contamination tolerated by people with NCGS is not clear but there is some evidence that they can present with symptoms even after consumption of small amounts. Sporadic accidental contaminations with gluten can reactivate movement disorders. A part of people with gluten-related neuropathy or ataxia appears not to be able to tolerate even the traces of gluten allowed in most foods labeled as "gluten-free".Whereas celiac disease requires adherence to a strict lifelong gluten-free diet, it is not yet known whether NCGS is a permanent or a transient condition. The results of a 2017 study suggest that NCGS may be a chronic disorder, as is the case with celiac disease. A trial of gluten reintroduction to observe any reaction after one to two years of strict gluten-free diet might be performed.A strict gluten-free diet is effective in most of the neurological disorders associated with NCGS, ameliorating or even resolving the symptoms. It should be started as soon as possible to improve the prognosis. The death of neurons in the cerebellum in ataxia is the result of gluten exposure and is irreversible. Early treatment with a strict gluten-free diet can improve ataxia symptoms and prevent its progression. When dementia has progressed to an advanced degree, the diet has no beneficial effect. Cortical myoclonus appears to be treatment-resistant on both gluten-free diet and immunosuppression.

Persistent symptoms
Approximately one third of presumed NCGS patients continue to have symptoms, despite gluten withdrawal. Apart from a possible diagnostic error, there are multiple possible explanations.One reason is poor compliance with gluten withdrawal, whether voluntary and/or involuntary.  There may be ingestion of gluten, in the form of cross contamination or food containing hidden sources.  In some cases, the amelioration of gastrointestinal symptoms with a gluten-free diet is only partial, and these patients could significantly improve with the addition of a low-FODMAP diet.A subgroup may not improve when eating commercially available gluten-free products, as these can be rich in preservatives and additives such as sulfites, glutamates, nitrates and benzoates, which can also have a role in triggering functional gastrointestinal symptoms.  Furthermore, people with NCGS may often present with IgE-mediated allergies to one or more foods. It has been estimated that around 35% suffer other food intolerances, mainly lactose intolerance.

History
The subject of "food intolerance", including gluten sensitivity and elimination diets, was discussed in 1976.Patients with symptoms including abdominal pain and diarrhea, which improved on gluten withdrawal, and who did not have celiac disease were initially described in 1976 and 1978 with the first series in 1980.  Debate regarding the existence of a specific condition has continued since then, but the three consensus conferences held since 2010 produced consistent definitions of NCGS and its diagnostic criteria.

Society and culture
NCGS has been a topic of popular interest. Gluten has been named "the new diet villain". The gluten-free diet has become popular in the United States and other countries. Clinicians worldwide have been challenged by an increasing number of people who do not have celiac disease nor wheat allergy, with digestive or extra-digestive symptoms which improved after removing wheat / gluten from the diet. Many of these persons began a gluten-free diet on their own, without having been previously evaluated. Another reason that contributed to this trend was the publication of several books that demonize gluten and point to it as a cause of type 2 diabetes, weight gain and obesity, and a broad list of conditions ranging from depression and anxiety to arthritis and autism. The book that has had the most impact is Grain Brain: The Surprising Truth about Wheat, Carbs, and Sugar – Your Brains Silent Killers, by the American neurologist David Perlmutter, published in September 2013. Another book that has had great impact is Wheat Belly: Lose the Wheat, Lose the Weight, and Find Your Path Back to Health, by cardiologist William Davis. The gluten-free diet has been advocated and followed by many celebrities to lose weight, such as Miley Cyrus and Gwyneth Paltrow, and some elite athletes to improve performance.Estimates suggest that in 2014, 30% of people in the US and Australia were consuming gluten-free foods, with estimates that by 2016 approximately 100 million Americans would consume gluten-free products. Data from a 2015 Nielsen survey of 30,000 adults in 60 countries around the world showed that 21% of people prefer to buy gluten-free foods, with interest highest among younger generations. Another school of thought suggests that many people may be unnecessarily avoiding gluten when they do not need to.Debate around NCGS as a genuine clinical condition can be heightened because often patients are self diagnosed, or a diagnosis is made by alternative health practitioners. Many people who are making a gluten-free diet did not previously exclude celiac disease or, when they are fully evaluated, other alternative diagnoses can be found such as fructose intolerance or small intestinal bacterial overgrowth, or a better response to a low-FODMAP diet obtained.

Research
There are many open questions on gluten sensitivity, emphasized in one review that "it is still to be clarified whether this disorder is permanent or transient and whether it is linked to autoimmunity" </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 Omphalocele and can you explain it in depth? [/INST] Omphalocele or omphalocoele also called exomphalos, is a rare abdominal wall defect. Beginning at the 6th week of development, rapid elongation of the gut and increased liver size reduces intra abdominal space, which pushes intestinal loops out of the abdominal cavity. Around 10th week, the intestine returns to the abdominal cavity and the process is completed by the 12th week. Persistence of intestine or the presence of other abdominal viscera (e.g. stomach, liver) in the umbilical cord results in an omphalocele.
Omphalocele occurs in 1 in 4,000 births and is associated with a high rate of mortality (25%) and severe malformations, such as cardiac anomalies (50%), neural tube defect (40%), exstrophy of the bladder and Beckwith–Wiedemann syndrome. Approximately 15% of live-born infants with omphalocele have chromosomal abnormalities. About 30% of infants with an omphalocele have other congenital abnormalities.

Signs and symptoms
The sac, which is formed from an outpouching of the peritoneum, protrudes in the midline, through the umbilicus (navel).It is normal for the intestines to protrude from the abdomen, into the umbilical cord, until about the tenth week of pregnancy, after which they return to inside the fetal abdomen. The omphalocele can be mild, with only a small loop of intestines present outside the abdomen, or severe, containing most of the abdominal organs. In severe cases surgical treatment is made more difficult because the infants abdomen is abnormally small, having had no need to expand to accommodate the developing organs.
Larger omphaloceles are associated with a higher risk of cardiac defects.

Complications
Complications may occur prenatally, during birth, management, treatment or after surgery. Both prenatally and during birth, the exomphalos can rupture. During birth there may be trauma to the liver for giant omphaloceles. During management exomphalos can act as a metabolic drain affecting nitrogen balance which can lead to failure to thrive, as well as hypothermia. Use of a non-absorbent patch during surgery can lead to wound sepsis post-surgery. Herniation from the patch is also a possibility. Intestinal dysfunction for a few weeks after the surgery is common, therefore parenteral feeding is continued post-surgery, however prolonged use of this may lead to hepatomegaly and cholestasis. If intestinal dysfunction persists it can lead to intestinal necrosis. Intestinal atresia can occur, which is where the mucosa and submucosa of the intestine form a web that obstructs the lumen which leads to malabsorption. Obstruction of the bowel can occur which results in short bowel syndrome. For the first few years of life there is a high incidence of gastroesophageal reflux which can be complicated by oesophagitis.Post-surgery the umbilicus (navel) is deficient or abnormally placed that causes dislike amongst many patients. Umbilical reconstruction can be difficult due to scar tissue and lack of extra skin for surgical use, though this can be overcome by using tissue expanders below the skin and umbilicoplasty.Ultimately, prognosis depends on the size of the defect and whether associated abnormalities are present or complications develop. Mortalities and morbidities still occur, with the mortality rate for large omphaloceles with associated abnormalities being higher. Most surviving omphalocele infants have no-long-term problems and grow up to be normal individuals.

Causes
Omphalocele is caused by malrotation of the bowels while returning to the abdomen during development. Some cases of omphalocele are believed to be due to an underlying genetic disorder, such as Edwards syndrome (trisomy 18) or Patau syndrome (trisomy 13).
Beckwith–Wiedemann syndrome is also associated with omphaloceles.

Pathophysiology
Exomphalos is caused by a failure of the ventral body wall to form and close the naturally occurring umbilical hernia that occurs during embryonic folding which is a process of embryogenesis. The normal process of embryogenesis is that at 2 weeks gestation the human embryo is a flat disc that consists of three layers, the outer ectoderm and inner endoderm separated by a middle layer called the mesoderm. The ectoderm gives rise to skin and the CNS, the mesoderm gives rise to muscle and the endoderm gives rise to organs. The focus areas for exomphalos are that the ectoderm will form the umbilical ring, the mesoderm will form the abdominal muscles and the endoderm will form the gut. After the disc becomes tri-layered, it undergoes growth and folding to transform it from disc to cylinder shaped. The layer of ectoderm and mesoderm in the dorsal axis grow ventrally to meet at the midline. Simultaneously, the cephalic (head) and caudal (tail) ends of these layers of the disc fold ventrally to meet the lateral folds in the center. The meeting of both axis at the center form the umbilical ring. Meanwhile, the endoderm migrates to the center of this cylinder.By the fourth week of gestation the umbilical ring is formed. During the 6th week the midgut rapidly grows from the endoderm which causes a herniation of the gut through the umbilical ring. The gut rotates as it re-enters the abdominal cavity which allows for the small intestine and colon to migrate to their correct anatomical position by the end of the 10th week of development. This process fails to occur normally in cases of exomphalos, resulting in abdominal contents protruding from the umbilical ring.Gut contents fail to return to the abdomen due to a fault in myogenesis (muscle formation and migration during embryogenesis). During embryogenesis the mesoderm that forms muscle divides into several somites that migrate dorso-ventrally towards the midline. The somites develop three parts that are sclerotome which will form bone, dermatome which will form skin of the back and myotome which will form muscle. The somites that remain close to the neural tube at the back of the body have epaxial myotome, whilst the somites that migrate to the midline have hypaxial myotome. The hypaxial myotome forms the abdominal muscles. The myotome cells will give rise to myoblasts (embryonic progenitor cells) which will align to form myotubules and then muscle fibers. Consequently, the myotome will become three muscle sheets that form the layers of abdominal wall muscles. The muscle of concern for exomphalos is the rectus abdominis. In the disease the muscle undergoes normal differentiation but fails to expand ventro-medially and narrow the umbilical ring which causes the natural umbilical hernia that occurs at 6 weeks of gestation to remain external to the body.The location of the folding defect in the embryo determines the ultimate position of the exomphalos. A cephalic folding defect results in an epigastric exomphalos that is positioned high up on the abdomen which can be seen in the chromosomal defect pentalogy of Cantrell. Lateral folding defects result in a typical exomphalos that is positioned in the middle of the abdomen. A caudal folding defect results in a hypogastric exomphalos that is positioned on the lower abdomen.

Genetics
The genes that cause exomphalos are controversial and subject to research. Exomphalos is greatly associated with chromosomal defects and thus these are being explored to pinpoint the genetic cause of the disease. Studies in mice have indicated that mutations in the fibroblast growth factor receptors 1 and 2 (Fgfr1, Fgfr2) cause exomphalos. Fibroblast growth factor (FBGF) encourages the migration of myotubules during myogenesis. When FBGF runs out myoblasts stop migrating, cease division and differentiate into myotubules that form muscle fibers. Mutations in homeobox genes such as Alx4, that direct the formation of body structures during early embryonic development cause exomphalos in mice. Mutations in the Insulin like growth factor-2 gene (IGF2) and its associated receptor gene IGF2R cause high levels of IGF-2 protein in humans which leads to exomphalos in the associated disease Beckwith Wiedemann syndrome (BWS).  IFG2R is responsible for degradation of excess IGF-2 protein. BWS disease is caused by a mutation in chromosome 11 at the locus where the IGF2 gene resides. Observance of the inheritance patterns of the associated anomalies through pedigrees show that exomphalos can be the result of autosomal dominant, autosomal recessive and X-linked inheritance.

Environmental factors
It is not well known if actions of the mother could predispose or cause the disease. Alcohol use during the first trimester, heavy smoking, use of certain medications like the selective serotonin-reuptake inhibitors and methimazole (anti-thyroid drug) during pregnancy, maternal febrile illness, IVF, parental consanguinity and obesity elevate the risk of a woman giving birth to a baby with exomphalos. Preventive methods that could be utilised by mothers include ingestion of a preconception multivitamin and supplementation with folic acid. Termination of pregnancy may be considered if a large exomphalos with associated congenital abnormalities is confirmed during prenatal diagnosis.

Diagnosis
Related conditions
Gastroschisis is a similar birth defect, but in gastroschisis the umbilical cord is not involved and the intestinal protrusion is usually to the right of the midline. Parts of organs may be free in the amniotic fluid and not enclosed in a membranous (peritoneal) sac. Gastroschisis is less frequently associated with other defects than omphalocele.Omphaloceles occurs more frequently with increased maternal age. Other related syndromes are Shprintzen Goldberg, pentalogy of Cantrell, Beckwith–Wiedemann and OEIS complex (omphalocele, exstrophy of the cloaca, imperforate anus, spinal defects).After surgery a child with omphalocele will have some degree of intestinal malrotation. Due to intestinal malrotation 4.4% of children with omphalocele will experience a midgut volvulus in the days, months, or years after surgery. Parents of children with omphalocele should seek immediate medical attention if their child displays signs and symptoms of an intestinal obstruction at any point in their childhood to avoid the possibility of bowel necrosis or death.Some experts differentiate exomphalos and omphalocele as 2 related conditions, one worse than the other; in this sense, exomphalos involves a stronger covering of the hernia (with fascia and skin), whereas omphalocele involves a weaker covering of only a thin membrane. Others consider the terms synonymous names for any degree of herniation and covering.

Screening
An omphalocele is often detected through AFP screening or a detailed fetal ultrasound. Genetic counseling and genetic testing such as amniocentesis are usually offered during the pregnancy.

Management
There is no treatment that is required prenatally unless there is a rupture of the exomphalos within the mother. An intact exomphalos can be delivered safely vaginally and C-sections are also acceptable if obstetrical reasons require it. There appears to be no advantage for delivery by C-section unless it is for a giant exomphalos that contains most of the liver. In this case vaginal delivery may result in dystocia (inability of the baby to exit the pelvis during birth) and liver damage. Immediately after birth a nasogastric tube is required to decompress the intestines and an endotracheal intubation is needed to support respiration. The exomphalos sac is kept warm and covered with a moist saline gauze and plastic transparent bowel bag to prevent fluid loss. The neonate also requires fluid, vitamin K and antibiotic administration intravenously.   After management strategies are applied, a baby with an intact sac is medically stable and does not require urgent surgery. This time is used to assess the newborn to rule out associated anomalies prior to surgical closure of the defect. Studies show there is no significant difference in survival between immediate or delayed closure.Surgery can be performed directly for small omphaloceles, which will require a short stay in the nursery department, or in a staged manner for large omphaloceles, which will require several weeks stay. Staged closure requires a temporary artificial holding sac (a silo) to be placed over the abdominal organs and sutured to the abdominal wall. This can be made of non-adhesive dressing. The silo is gradually reduced in size at least once daily until all of the viscera have been returned to the abdominal cavity. This is repeated for several days to a week until surgical closure of the fascia/skin can be done </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 Spasm of accommodation and can you explain it in depth? [/INST] A spasm of accommodation (also known as a ciliary spasm, an accommodation, or accommodative spasm) is a condition in which the ciliary muscle of the eye remains in a constant state of contraction. Normal accommodation allows the eye to "accommodate" for near-vision. However, in a state of perpetual contraction, the ciliary muscle cannot relax when viewing distant objects. This causes vision to blur when attempting to view objects from a distance. This may cause pseudomyopia or latent hyperopia.
Although antimuscarinic drops (homoatropine 5%) can be applied topically to relax the muscle, this leaves the individual without any accommodation and, depending on refractive error, unable to see well at near distances.  Also, excessive pupil dilation may occur as an unwanted side effect. This dilation may pose a problem since a larger pupil is less efficient at focusing light (see pupil, aperture, and optical aberration for more.)
Patients who have accommodative spasm may benefit from being given glasses or contacts that account for the problem or by using vision therapy techniques to regain control of the accommodative system.
Possible clinical findings include:

Normal Amplitude of accommodation
Normal Near point of convergence
Reduced Negative relative accommodation
Difficulty clearing plus on facility testing

Treatments
Cycloplegic Eye Drops (Dilation)
Spasm of accommodation is frequently resistant to treatment. However, some patients do find relief through the use of daily eye dilation with cycloplegic drops. One side effect of cycloplegic drops is that they often have BAK as a preservative ingredient, which, with daily use, can erode the tear shield:

At each administration of an eye drop containing benzalkonium chloride, its detergent effect disrupts the lipid layer of the tear film. This cannot be regenerated and can no longer protect the aqueous layer of the tear film, which evaporates easily. In these circumstances, the cornea is exposed and eye dryness occurs. In addition, benzalkonium chloride has a cellular toxicity on caliciform cells, entailing a reduction in the amount of mucin, an additional reason for disrupting the tear film.
In fact, none of the cycloplegic drops used to treat Spasm of Accommodation in the United States are available without BAK. This unfortunately makes treatment much more difficult as the side effect of dry eyes and corneal damage can occur. France, Australia, Canada, and the United Kingdom do have limited availability of BAK-free eye drops available in unidose, and they must be imported to the United States with a physicians letter to the FDA enclosed with the imported prescription.
Due to the high potential of tear shield damage with long-term use and the associated dry eye condition caused by cycloplegic eye drops with BAK (preservative), many physicians do not recommend cycloplegic eye drops </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 Nasal polyp and can you explain it in depth? [/INST] Nasal polyps (NP) are noncancerous growths within the nose or sinuses. Symptoms include trouble breathing through the nose, loss of smell, decreased taste, post nasal drip, and a runny nose. The growths are sac-like, movable, and nontender, though face pain may occasionally occur. They typically occur in both nostrils in those who are affected. Complications may include sinusitis and broadening of the nose.The exact cause is unclear. They may be related to chronic inflammation of the lining of the sinuses. They occur more commonly among people who have allergies, cystic fibrosis, aspirin sensitivity, or certain infections. The polyp itself represents an overgrowth of the mucous membranes. Diagnosis may be accomplished by looking up the nose. A CT scan may be used to determine the number of polyps and help plan surgery.Treatment is typically with steroids, often in the form of a nasal spray. If this is not effective, surgery may be considered. The condition often recurs following surgery; thus, continued use of a steroid nasal spray is often recommended. Antihistamines may help with symptoms but do not change the underlying disease. Antibiotics are not required for treatment unless an infection occurs.About 4% of people currently have nasal polyps while up to 40% of people develop them at some point in their life. They most often occur after the age of 20 and are more frequent in males than females. Nasal polyps have been described since the time of the Ancient Egyptians.

Signs and symptoms
Symptoms of polyps include nasal congestion, sinusitis, loss of smell, thick nasal discharge, facial pressure, nasal speech, and mouth breathing. Recurrent sinusitis can result from polyps. Long-term, nasal polyps can cause destruction of the nasal bones and widening of the nose.As polyps grow larger, they eventually prolapse into the nasal cavity, resulting in symptoms. The most prominent symptoms of nasal polyps is blockage of the nasal passage. People with nasal polyps due to aspirin intolerance often have symptoms known as Samters triad, which consists of asthma worse with aspirin, a skin rash caused by aspirin, and chronic nasal polyps.

Causes
The exact cause of nasal polyps is unclear. They are, however, commonly associated with conditions that cause long term inflammation of the sinuses. This includes chronic rhinosinusitis, asthma, aspirin sensitivity, and cystic fibrosis.Various additional diseases associated with polyp formation include:

Chronic rhinosinusitis is a common medical condition characterized by symptoms of sinus inflammation lasting at least 12 weeks. The cause is unknown and the role of microorganisms remains unclear. It can be classified as either with or without nasal polyposis.Cystic fibrosis (CF) is the most common cause of nasal polyps in children. Therefore, any child under 12 to 20 years old with nasal polyps should be tested for CF. Half of people with CF will experience extensive polyps leading to nasal obstruction and requiring aggressive management.

Pathophysiology
The true cause of nasal polyps is unknown, but they are thought to be due to recurrent infection or inflammation. Polyps arise from the lining of the sinuses. Nasal mucosa, particularly in the region of middle meatus becomes swollen due to collection of extracellular fluid. This extracellular fluid collection causes polyp formation and protrusion into the nasal cavity or sinuses. Polyps which are sessile in the beginning become pedunculated due to gravity.In people with nasal polyps due to aspirin or NSAID sensitivity, the underlying mechanism is due to disorders in the metabolism of arachidonic acid. Exposure to cycloxygenase inhibitors such as aspirin and NSAIDs leads to shunting of products through the lipoxygenase pathway leading to an increased production of products that cause inflammation. In the airway, these inflammatory products lead to symptoms of asthma such as wheezing as well as nasal polyp formation.

Diagnosis
Nasal polyps can be seen on physical examination inside of the nose and are often detected during the evaluation of symptoms. On examination, a polyp will appear as a visible mass in the nostril. Some polyps may be seen with anterior rhinoscopy (looking in the nose with a nasal speculum and a light), but frequently, they are farther back in the nose and must be seen by nasal endoscopy. Nasal endoscopy involves passing a small, rigid camera with a light source into the nose. An image is projected onto a screen in the office so the doctor can examine the nasal passages and sinuses in greater detail. The procedure is not generally painful, but the person can be given a spray decongestant and local anesthetic to minimize discomfort.Attempts have been made to develop scoring systems to determine the severity of nasal polyps. Proposed staging systems take into account the extent of polyps seen on endoscopic exam and the number of sinuses affected on CT imaging. This staging system is only partially validated, but in the future, may be useful for communicating the severity of disease, assessing treatment response, and planning treatment.

Types
There are two primary types of nasal polyps: ethmoidal and antrochoanal. Ethmoidal polyps arise from the ethmoid sinuses and extend through the middle meatus into the nasal cavity. Antrochoanal polyps usually arise in the maxillary sinus and extend into the nasopharynx and represent only 4–6% of all nasal polyps.However, antrochoanal polyps are more common in children comprising one-third of all polyps in this population. Ethmoidal polyps are usually smaller and multiple while antrochoanal polyps are usually single and larger.

CT scan
CT scan can show the full extent of the polyp, which may not be fully appreciated with physical examination alone. Imaging is also required for planning surgical treatment. On a CT scan, a nasal polyp generally has an attenuation of 10–18 Hounsfield units, which is similar to that of mucus. Nasal polyps may have calcification.

Histology
On histologic examination, nasal polyps consist of hyperplastic edematous (excess fluid) connective tissue with some seromucous glands and cells representing inflammation (mostly neutrophils and eosinophils). Polyps have virtually no neurons. Therefore, the tissue that makes up the polyp does not have any tissue sensation and the polyp itself will not be painful. In early stages, the surface of the nasal polyp is covered by normal respiratory epithelium, but later it undergoes metaplastic change to squamous type epithelium with the constant irritation and inflammation. The submucosa shows large intercellular spaces filled with serous fluid.

Differential diagnosis
Other disorders can mimic the appearance of nasal polyps and should be considered if a mass is seen on exam. Examples include encephalocele, glioma, inverted papilloma, and cancer. Early biopsy is recommended for unilateral nasal polyps to rule out more serious conditions such as cancer, inverted papilloma, or fungal sinusitis.

Treatment
The first line of treatment for nasal polyps is topical steroids. Steroids decrease the inflammation of the sinus mucosa to decrease the size of the polyps and improve symptoms. Topical preparations are preferred in the form of a nasal spray but are often ineffective for people with many polyps. Steroids by mouth often provide drastic symptom relief, but should not be taken for long periods of time due to their side effects. Because steroids only shrink the size and swelling of the polyp, people often have recurrence of symptoms once the steroids are stopped. Decongestants do not shrink the polyps, but can decrease swelling and provide some relief. Antibiotics are only recommended if the person has a co-occurring bacterial infection.In people with nasal polyps caused by aspirin or NSAIDs, avoidance of these medications will help with symptoms. Aspirin desensitization has also been shown to be beneficial.

Surgery
Endoscopic sinus surgery, advocated and popularized by Professor Stammberger, is often very effective for most people, providing rapid symptom relief. Endoscopic sinus surgery is minimally-invasive and is done entirely through the nostril with the help of a camera. Surgery should be considered for those with complete nasal obstruction, uncontrolled runny nose, nasal deformity caused by polyps or continued symptoms despite medical management. Surgery serves to remove the polyps as well as the surrounding inflamed mucosa, open obstructed nasal passages, and clear the sinuses. This not only removes the obstruction caused by the polyps themselves, but allows medications such as saline irrigations and topical steroids to become more effective. It has been suggested that one of the main objectives in sinus surgery for polyps is to allow delivery of the steroids into those areas of the sinuses where polyps develop, namely, the ethmoid sinuses </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 Peripheral T-cell lymphoma 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 Confusional arousals and can you explain it in depth? [/INST] Confusional arousals are classified as “partial awakenings in which the state of consciousness remains impaired for several minutes without any accompanying major behavioural disorders or severe autonomic responses”. Complete or partial amnesia of the episodes may be present.

Signs and symptoms
Confusional arousals are accompanied by mental confusion and disorientation, relative lack of response to environmental stimuli, and difficulty of awakening the subject. Vocalisation accompanied with coherent speech is common. Patients may appear upset, and some of them become aggressive or agitated. As well as for children, attempting to awaken or console an adult patient may increase agitation. Confusional arousals can occur during or following an arousal of deep sleep (see slow-wave sleep) and upon an attempt of awakening the subject from sleep in the morning.In children, confusional arousals can often be reproduced artificially by awakening the child during deep sleep. However, it doesn’t have any clinical significance without deeper investigation. Children living an episode of confusional arousal typically sit up in bed, whimper, cry, moan, and may utter words like “no” or “go away”. They remain distressed and inconsolable despite all parental efforts. Paradoxically, parental efforts can rather increase agitation of the child. The onset of symptoms is usually within 2 and 3 hours of sleep onset (at the time of transition from slow-wave sleep to a lighter sleep stage) and those events can last from 10 to 30 minutes. Patients generally wake up without any recollection of the event. It is necessary to distinguish confusional arousals in adults from children.

Neurological symptomatology
Confusional arousals are associated with behavioural awakening with persistent slow-wave electroencephalographic activity (see slow-wave sleep) during Non-rapid eye movement sleep (NREM). It suggests that sensorimotor network is activated while non sensorimotor areas are still "asleep". The altered state of consciousness may be explained by a hypersynchronous delta activity (see delta wave) in network involving the frontoparietal cortices (suggesting to be "asleep"), and higher frequency activities in sensorimotor, orbitofrontal, and temporal lateral cortices (suggesting an "awakening").

Sleep-related violence and abnormal sexual behaviours
Confusional arousals have often been linked to sleep-related violence (self-injury or injury to the bed partner). The latter highlights important medical and legal issues when such behaviours are suspected and purported to have caused a criminal offense. The first documented case of homicide as a result of confusional arousal was reported in medieval times by the case of the Silesian woodcutter Bernard Schedmaizig. Sleep-related abnormal sexual behaviours (also called sexsomnia or sleep sex) are mainly classified as confusional arousals and more rarely associated to sleepwalking (also known as somnambulism). Even if sleep-related violence may occur during an episode of confusional arousal, it remains extremely rare and there are no specific predisposition to aggression during these episodes.

Distinction between sleepwalking and night terrors
Violent behaviours in confusional arousals slightly differ from those in sleepwalking or night terrors. Above all, during an episode of confusional arousal the patient never leaves the bed unlike sleepwalking. A bed partner or parent who tries to calm or restrain the patient by grabbing him or her may trigger a violent reaction as with sleepwalkers. In case of a confusional arousal triggered by an attempt of awakening the patient, violent behaviours may occur almost spontaneously. Unlike confusional arousals and sleep walking, patients experiencing night terrors seem to react to some type of frightening image. Therefore, the violent reaction may occur if another individual is encountered or is in proximity.

Classification
International Classification of Sleep Disorders (ICSD)
According to the 2nd edition of the International Classification of Sleep Disorders (ICSD-2), confusional arousals are classified in NREM parasomnias embedded in the non-epileptic paroxysmal motor events during sleep, which include (1) Parasomnia, (2) Sleep-related movement disorders and (3) Isolated symptoms, apparently normal variants and unresolved issues. NREM parasomnias (or disorders of arousal) also include sleep terrors (see night terror) and sleepwalking. Confusional arousals are characterised by more or less complex movements without leaving bed with whimpering, sitting up in bed and some articulation without walking or terror. In comparison of other arousal parasomnias the age onset of sleep walking is generally between 5 and 10 years whereas confusional arousals and sleep terror may occur 3 years earlier. Sleep terrors are mainly characterised by screaming, agitation, flushed face, sweating and only share the inconsolability with confusional arousals. The current 3rd edition of the International Classification of Sleep Disorders (ICSD-3) added the sleep-related eating disorders in the disorders of arousal from NREM sleep.

Diagnostic and Statistical Manual of Mental Disorders (DSM)
Confusional arousals are at the time not considered as a disorder in the current 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). This absence may be explained by the fact that confusional arousals have been understudied by the scientific community.

Diagnosis
The evaluation "should include a comprehensive medical history, a physical, neurological, and developmental examination, and a detailed description of the nocturnal events, sleep-wake schedules, and daytime behaviour”. However, the episodes have a long duration and a low rate of same-night recurrence. Even if amnesia usually follows episodes of confusional arousal, it is not a distinct trait related to severity.A video-polysomnography (see polysomnography) might be required if life history is untypical. In case of suspicion parents are encouraged to use infrared camera to record the behaviour of their child during sleep. Association of video recordings of nocturnal episodes with historical features is an important tool for both understanding and correctly diagnosing the disorder differently from other episodes of parasomnia. Confusional arousals as well as arousal parasomnias in general must be distinguished from epileptic seizure on the basis of clinical and electroencephalographic features (see electroencephalography).

Management
Children mostly outgrow the condition by late adolescence if not sooner </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 General paresis of the insane and can you explain it in depth? [/INST] General paresis, also known as general paralysis of the insane (GPI), paralytic dementia, or syphilitic paresis is a severe neuropsychiatric disorder, classified as an organic mental disorder and is caused by late-stage syphilis and the chronic meningoencephalitis and cerebral atrophy that are associated with this late stage of the disease when left untreated. GPI differs from mere paresis, as mere paresis can result from multiple other causes and usually does not affect cognitive function. Degenerative changes caused by GPI are associated primarily with the frontal and temporal lobar cortex.  The disease affects approximately 7% of individuals infected with syphilis, and is far more common in third world countries where fewer options for timely treatment are available. It is more common among men.
GPI was originally considered to be a type of madness due to a dissolute character, when first identified in the early 19th century. The conditions connection with syphilis was discovered in the late 1880s.  Progressively, with the discovery of organic arsenicals such as Salvarsan and Neosalvarsan (1910s), the development of pyrotherapy (1920s), and the widespread availability and use of penicillin in the treatment of syphilis (1940s), the condition was rendered avoidable and curable.  Prior to this, GPI was inevitably fatal, and it accounted for as much as 25% of the primary diagnoses for residents in public psychiatric hospitals.

Signs and symptoms
Symptoms of the disease first appear from 10 to 30 years after infection. Incipient GPI is usually manifested by neurasthenic difficulties, such as fatigue, headaches, insomnia, dizziness, etc. As the disease progresses, mental deterioration and personality changes occur. Typical symptoms include loss of social inhibitions, asocial behavior, gradual impairment of judgment, concentration and short-term memory, euphoria, mania, depression, or apathy. Subtle shivering, minor defects in speech and Argyll Robertson pupil may become noticeable.
Delusions, common as the illness progresses, tend to be poorly systematized and absurd. They can be grandiose, melancholic, or paranoid. These delusions include ideas of great wealth, immortality, thousands of lovers, unfathomable power, apocalypsis, nihilism, self-guilt, self-blame, or bizarre hypochondriacal complaints. Later, the patient experiences dysarthria, intention tremors, hyperreflexia, myoclonic jerks, confusion, seizures and severe muscular deterioration. Eventually, the paretic dies bedridden, cachectic and completely disoriented, frequently in a state of status epilepticus.

Diagnosis
The diagnosis could be differentiated from other known psychoses and dementias by a characteristic abnormality in eye pupil reflexes (Argyll Robertson pupil), and, eventually, the development of muscular reflex abnormalities, seizures, memory impairment (dementia) and other signs of relatively pervasive neurocerebral deterioration. Definitive diagnosis is based on the analysis of cerebrospinal fluid and tests for syphilis.

Prognosis
Although there were recorded cases of remission of the symptoms, especially if they had not passed beyond the stage of psychosis, these individuals almost invariably experienced relapse within a few months to a few years. Otherwise, the patient was seldom able to return home because of the complexity, severity and unmanageability of the evolving symptom picture. Eventually, the patient would become completely incapacitated, bed ridden, and would die, the process taking about three to five years on average.

History
While retrospective studies have found earlier instances of what may have been the same disorder, the first clearly identified examples of paresis among the insane were described in Paris after the Napoleonic Wars. General paresis of the insane was first described as a distinct disease in 1822 by Antoine Laurent Jesse Bayle </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 Complex regional pain syndrome and can you explain it in depth? [/INST] Complex regional pain syndrome (CRPS) is any of several painful conditions that are characterized by a continuing (spontaneous and/or evoked) regional pain that is seemingly disproportionate in time or degree to the usual course of any known trauma or other lesion. Usually starting in a limb, it manifests as extreme pain, swelling, limited range of motion, and changes to the skin and bones. It may initially affect one limb and then spread throughout the body; 35% of affected people report symptoms throughout their whole bodies. Two types exist: reflex sympathetic dystrophy (RSD) and causalgia. Having both types is possible.

Classification
The classification system in use by the International Association for the Study of Pain (IASP) divides CRPS into two types. It is recognised that people may exhibit both types of CRPS.

Signs and symptoms
Clinical features of CRPS have been found to be inflammation resulting from the release of certain proinflammatory chemical signals from the nerves, sensitized nerve receptors that send pain signals to the brain, dysfunction of the local blood vessels ability to constrict and dilate appropriately, and maladaptive neuroplasticity.The signs and symptoms of CRPS usually manifest near the injury site. The most common symptoms are extreme pain, including burning, stabbing, grinding, and throbbing. The pain is out of proportion to the severity of the initial injury. Moving or touching the limb is often intolerable. With diagnosis of either CRPS types I or II, patients may develop burning pain and allodynia.  Both syndromes are also characterized by autonomic dysfunction, which presents with temperature changes (usually localized, but can be global), cyanosis, and/or edema.The patient may also experience localized swelling; extreme sensitivity to nonpainful stimuli such as wind, water, noise, and vibrations; extreme sensitivity to touch (by themselves, other people, and even light clothing or bedding/blankets); abnormally increased sweating (or absent sweating); changes in skin temperature (alternating between overly warm and cold); changes in skin colouring (from white and mottled to bright red or reddish-violet); changes in skin texture (waxy, shiny, thin, tight skin); softening and thinning of bones; joint tenderness or stiffness; changes in nails and hair (delayed or increased growth, brittle nails/hair that easily break); muscle spasms; muscle loss (atrophy); tremors; dystonia; allodynia; hyperalgesia; and decreased/restricted ability and painful movement of affected body part. Drop attacks (falls), almost fainting, and fainting spells are infrequently reported, as are visual problems.The symptoms of CRPS vary in severity and duration. Since CRPS is a systemic problem, potentially any organ can be affected. Symptoms may change over time, and they can vary from person to person. The more dynamic symptoms, especially vascular aspects (edema, temperature) and location of pain, can change numerous times a day.Previously, CRPS was considered to have three stages however more recent studies suggest people affected by CRPS do not progress through sequential stages and the staging system is no longer in wide use. Growing evidence instead points towards distinct sub-types of CRPS.

Cause
Complex regional pain syndrome is uncommon, and its cause is not clearly understood. CRPS typically develops after an injury, surgery, heart attack, or stroke. Investigators estimate that 2–5% of those with peripheral nerve injury, and 13-70% of those with hemiplegia (paralysis of one side of the body) will develop CRPS. In addition, some studies have indicated that cigarette smoking was strikingly present in patients and is statistically linked to RSD. This may be involved in its pathology by enhancing sympathetic activity, vasoconstriction, or by some other unknown neurotransmitter-related mechanism. This hypothesis was based on a retrospective analysis of 53 patients with RSD, which showed that 68% of patients and only 37% of controls were smokers. The results are preliminary and are limited by their retrospective nature. 7% of people who have CRPS in one limb later develop it in another limb.

Pathophysiology
Inflammation and alteration of pain perception in the central nervous system are proposed to play important roles. The persistent pain and the perception of nonpainful stimuli as painful are thought to be caused by inflammatory molecules (IL-1, IL2, TNF-alpha) and neuropeptides (substance P) released from peripheral nerves. This release may be caused by inappropriate cross-talk between sensory and motor fibers at the affected site. CRPS is not a psychological illness, yet pain can cause psychological problems, such as anxiety and depression. Often, impaired social and occupational function occur.Complex regional pain syndrome is a multifactorial disorder with clinical features of neurogenic inflammation (swelling in the central nervous system), nociceptive sensitisation (which causes extreme sensitivity or allodynia), vasomotor dysfunction (blood flow problems which cause swelling and discolouration) and maladaptive neuroplasticity (where the brain changes and adapts with constant pain signals); CRPS is the result of an "aberrant [inappropriate] response to tissue injury". The "underlying neuronal matrix" of CRPS is seen to involve cognitive and motor as well as nociceptive processing; pinprick stimulation of a CRPS affected limb was painful (mechanical hyperalgesia) and showed a "significantly increased activation" of not just the S1 cortex (contralateral), S2 (bilateral) areas, and insula (bilateral) but also the associative-somatosensory cortices (contralateral), frontal cortices, and parts of the anterior cingulate cortex. In contrast to previous thoughts reflected in the name RSD, it appears that there is reduced sympathetic nervous system outflow, at least in the affected region (although there may be sympatho-afferent coupling). Wind-up (the increased sensation of pain with time) and central nervous system (CNS) sensitization are key neurologic processes that appear to be involved in the induction and maintenance of CRPS.Compelling evidence shows that the N-methyl-D-aspartate (NMDA) receptor has significant involvement in the CNS sensitization process. It is also hypothesized that elevated CNS glutamate levels promote wind-up and CNS sensitization. In addition, there exists experimental evidence demonstrating the presence of NMDA receptors in peripheral nerves. Because immunological functions can modulate CNS physiology, a variety of immune processes have also been hypothesized to contribute to the initial development and maintenance of peripheral and central sensitization. Furthermore, trauma-related cytokine release, exaggerated neurogenic inflammation, sympathetic afferent coupling, adrenoreceptor pathology, glial cell activation, cortical reorganisation, and oxidative damage (e.g., by free radicals) are all factors which have been implicated in the pathophysiology of CRPS. In addition, autoantibodies are present in a wide number of CRPS patients and IgG has been recognized as one of the causes of hypersensitivity that stimulates A and C nociceptors, attributing to the inflammation.The mechanisms leading to reduced bone mineral density (up to overt osteoporosis) are still unknown. Potential explanations include a dysbalance of the activities of sympathetic and parasympathetic autonomic nervous system and mild secondary hyperparathyroidism. However, the trigger of secondary hyperparathyroidism has not yet been identified.In summary, the pathophysiology of complex regional pain syndrome has not yet been defined;  CRPS, with its variable manifestations, could be the result of multiple pathophysiological processes.

Diagnosis
Diagnosis is primarily based on clinical findings. The original diagnostic criteria for CRPS adopted by the International Association for the Study of Pain (IASP) in 1994 have now been superseded in both clinical practice and research by the "Budapest Criteria" which were created in 2003 and have been found to be more sensitive and specific. They have since been adopted by the IASP. The criteria require there to be pain as well as a history and clinical evidence of Sensory, Vasomotor, Sudomotor and Motor or Trophic changes. It is also stated that it is a diagnosis of exclusion.To make a clinical diagnosis all four of the following criteria must be met:
Continuing pain, which is disproportionate to any inciting event
Must report at least one symptom in three of the four following categories..
Sensory: Reports of hyperesthesia
Vasomotor: Reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry
Sudomotor/Edema: Reports of edema and/or sweating changes and/or sweating asymmetry
Motor/Trophic: Reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)
Must display at least one sign at time of evaluation in two or more of the following categories
Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or temperature sensation and/or deep somatic pressure and/or joint movement)
Vasomotor: Evidence of temperature asymmetry (>1 °C) and/or skin color changes and/or asymmetry
Sudomotor/Edema: Evidence of edema and/or sweating changes and/or sweating asymmetry
Motor/Trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)
There is no other diagnosis that better explains the signs and symptoms

Diagnostic adjuncts
No specific test is available for CRPS, which is diagnosed primarily through observation of the symptoms. However, thermography, sweat testing, X-rays, electrodiagnostics, and sympathetic blocks can be used to build up a picture of the disorder. Diagnosis is complicated by the fact that some patients improve without treatment. A delay in diagnosis and/or treatment for this syndrome can result in severe physical and psychological problems. Early recognition and prompt treatment provide the greatest opportunity for recovery.

Thermography
Presently, established empirical evidence suggests against thermographys efficacy as a reliable tool for diagnosing CRPS. Although CRPS may, in some cases, lead to measurably altered blood flow throughout an affected region, many other factors can also contribute to an altered thermographic reading, including the patients smoking habits, use of certain skin lotions, recent physical activity, and prior history of trauma to the region. Also, not all patients diagnosed with CRPS demonstrate such "vasomotor instability" — particularly those in the later stages of the disease. Thus, thermography alone cannot be used as conclusive evidence for—or against—a diagnosis of CRPS and must be interpreted in light of the patients larger medical history and prior diagnostic studies.In order to minimise the confounding influence of external factors, patients undergoing infrared thermographic testing must conform to special restrictions regarding the use of certain vasoconstrictors (namely, nicotine and caffeine), skin lotions, physical therapy, and other diagnostic procedures in the days prior to testing. Patients may also be required to discontinue certain pain medications and sympathetic blockers. After a patient arrives at a thermographic laboratory, he or she is allowed to reach thermal equilibrium in a 16–20 °C, draft-free, steady-state room wearing a loose fitting cotton hospital gown for approximately twenty minutes. A technician then takes infrared images of both the patients affected and unaffected limbs, as well as reference images of other parts of the patients body, including his or her face, upper back, and lower back. After capturing a set of baseline images, some labs further require the patient to undergo cold-water autonomic-functional-stress-testing to evaluate the function of their autonomic nervous systems peripheral vasoconstrictor reflex. This is performed by placing a patients unaffected limb in a cold water bath (approximately 20 °C) for five minutes while collecting images. In a normal, intact, functioning autonomic nervous system, a patients affected extremity will become colder. Conversely, warming of an affected extremity may indicate a disruption of the bodys normal thermoregulatory vasoconstrictor function, which may sometimes indicate underlying CRPS.

Radiography
Scintigraphy, plain radiographs, and magnetic resonance imaging  may all be useful diagnostically. Patchy osteoporosis (post-traumatic osteoporosis), which may be due to disuse of the affected extremity, can be detected through X-ray imagery as early as two weeks after the onset of CRPS. A bone scan of the affected limb may detect these changes even sooner and can almost confirm the disease. Bone densitometry can also be used to detect changes in bone mineral density. It can also be used to monitor the results of treatment since bone densitometry parameters improve with treatment.

Ultrasound
Ultrasound-based osteodensitometry (ultrasonometry) may be potential future radiation-free technique to identify reduced bone mineral density in CRPS. Additionally, this method promises to quantify the bone architecture in the periphery of affected limbs. This method is still under experimental development.

Electrodiagnostic testing
Electromyography (EMG) and nerve conduction studies (NCS) are important ancillary tests in CRPS because they are among the most reliable methods of detecting nerve injury. They can be used as one of the primary methods to distinguish between CRPS types I and II, which differ based on evidence of actual nerve damage. EMG and NCS are also among the best tests for ruling in or out alternative diagnoses. CRPS is a "diagnosis of exclusion", which requires that no other diagnosis can explain the patients symptoms. This is very important to emphasise because patients otherwise can be given a wrong diagnosis of CRPS when they actually have a treatable condition that better accounts for their symptoms. An example is severe carpal tunnel syndrome (CTS), which can often present in a very similar way to CRPS. Unlike CRPS, CTS can often be corrected with surgery to alleviate the pain and avoid permanent nerve damage and malformation.Both EMG and NCS involve some measure of discomfort. EMG involves the use of a tiny needle inserted into specific muscles to test the associated muscle and nerve function. Both EMG and NCS involve very mild shocks that in normal patients are comparable to a rubber band snapping on the skin. Although these tests can be very useful in CRPS, thorough informed consent must be obtained prior to the procedure, particularly in patients experiencing severe allodynia. In spite of the utility of the test, these patients may wish to decline the procedure to avoid discomfort.

Classification
Type I, formerly known as reflex sympathetic dystrophy (RSD), Sudecks atrophy, or algoneurodystrophy, does not exhibit demonstrable nerve lesions. As the vast majority of patients diagnosed with CRPS have this type, it is most commonly referred to in medical literature as type I.
Type II, formerly known as causalgia, has evidence of obvious nerve damage. Despite evidence of nerve injury, the cause or the mechanisms of CRPS type II are as unknown, as the mechanisms of type I.Patients are frequently classified into two groups based upon temperature: "warm" or "hot" CRPS in one group and "cold" CRPS in the other group. The majority of patients (about 70%) have the "hot" type, which is said to be an acute form of CRPS. Cold CRPS is said to be indicative of a more chronic CRPS and is associated with poorer McGill Pain Questionnaire scores, increased central nervous system involvement, and a higher prevalence of dystonia. Prognosis is not favourable for cold CRPS patients; longitudinal studies suggest these patients have "poorer clinical pain outcomes and show persistent signs of central sensitisation correlating with disease progression".

Prevention
Vitamin C may be useful in prevention of the syndrome following fracture of the forearm or foot and ankle.

Treatment
Treatment of CRPS often involves a number of modalities.

Therapy
Physical and occupational therapy have low-quality evidence to support their use. Physical therapy interventions may include transcutaneous electrical nerve stimulation, progressive weight bearing, graded tactile desensitization, massage, and contrast bath therapy. In a retrospective cohort (unblinded, non-randomised and with intention-to-treat) of fifty patients diagnosed with CRPS, the subjective pain and body perception scores of patients decreased after engagement with a two-week multidisciplinary rehabilitation programme. The authors call for randomised controlled trials to probe the true value of multidisciplinary programs for CRPS patients.

Mirror box therapy
Mirror box therapy uses a mirror box, or a stand-alone mirror, to create a reflection of the normal limb such that the patient thinks they are looking at the affected limb. Movement of this reflected normal limb is then performed so that it looks to the patient as though they are performing movement with the affected limb. Mirror box therapy appears to be beneficial at least in early CRPS. However, beneficial effects of mirror therapy in the long term is still unproven.

Graded motor imagery
Graded motor imagery appears to be useful for people with CRPS-1. Graded motor imagery is a sequential process that consists of (a) laterality reconstruction, (b) motor imagery, and (c) mirror therapy.Transcutaneous Electrical Nerve Stimulation (TENS)
Transcutaneous Electrical Nerve Stimulation (TENS) is a therapy that uses low voltage electrical signals to provide pain relief through electrodes that are placed on the surface of the skin.  Evidence supports its use in treating pain and edema associated with CRPS although it does not seem to increase functional ability in CRPS patients.

Medications
Tentative evidence supports the use of bisphosphonates, calcitonin, and ketamine. Nerve blocks with guanethidine appear to be harmful. Evidence for sympathetic nerve blocks generally is insufficient to support their use. Intramuscular botulinum injections may benefit people with symptoms localized to one extremity.

Ketamine
Ketamine, a dissociative anesthetic, appears promising as a treatment for CRPS. It may be used in low doses if other treatments have not worked. No benefit on either function or depression, however, has been seen.

Bisphosphonate treatment
As of 2013, high-quality evidence supports the use of bisphosphonates (either orally or via IV infusion) in the treatment of CRPS. Bisphosphonates inhibit osteoclasts which are cells involved in the resorption of bone. Bone remodeling, via osteoclast activity in resorption of bone, is thought to sometimes be hyperactive in CRPS. It is hypothesized that bone resorption causes acidification of the intercellular milieu and this activates nerves involved in nociception that densely innervate bone causing pain; therefore inhibiting bone resorption and remodeling is thought to help with regards to pain in CRPS.  CRPS involving high levels of bone resorption, as seen on bone scan, is more likely to respond to bisphosphonate therapy.

Opioids
Opioids such as oxycodone, morphine, hydrocodone, and fentanyl have a controversial place in treatment of CRPS. These drugs must be prescribed and monitored under close supervision of a physician, as these drugs will lead to physical dependence and can lead to addiction. Thus far, no long-term studies of oral opioid use in treating neuropathic pain, including CRPS, have been performed. The consensus among experts is that opioids should not be a first line therapy and should only be considered after all other modalities (non-opioid medications, physical therapy, and procedures) have been trialed.

Surgery
Spinal cord stimulators
Spinal cord stimulator appears to be an effective therapy in the management of patients with CRPS type I (level A evidence) and type II (level D evidence). While they improve pain and quality of life, evidence is unclear regarding effects on mental health and general functioning.Dorsal root ganglion stimulation is type of neurostimulation that is effective in the management of focal neuropathic pain.  The FDA approved its use in February 2016.  The ACCURATE Study demonstrated superiority of dorsal root ganglion stimulation over spinal (dorsal column) stimulation in the management of CRPS and causalgia.

Sympathectomy
Surgical, chemical, or radiofrequency sympathectomy — interruption of the affected portion of the sympathetic nervous system — can be used as a last resort in patients with impending tissue loss, edema, recurrent infection, or ischemic necrosis. However,  little evidence supports these permanent interventions to alter the pain symptoms of the affected patients, and in addition to the normal risks of surgery, such as bleeding and infection, sympathectomy has several specific risks, such as adverse changes in how nerves function.

Amputation
No randomized study in medical literature has studied the response with amputation of patients who have failed the above-mentioned therapies and who continue to be miserable. Nonetheless,  on average, about half of the patients will have resolution of their pain, while half will develop phantom limb pain and/or pain at the amputation site. As in any other chronic pain syndrome, the brain likely becomes chronically stimulated with pain, and late amputation may not work as well as it might be expected. In a survey of 15 patients with CRPS type 1, 11 responded that their lives were better after amputation. Since this is the ultimate treatment of a painful extremity, it should be left as a last resort.

Prognosis
The prognosis in CRPS is improved with early and aggressive treatment; with the risk of chronic, debilitating pain being reduced with the early treatment. If treatment is delayed, however, the disorder can quickly spread to the entire limb, and changes in bone, nerve, and muscle may become irreversible. The prognosis is worse with the chronic "cold" form of CRPS and with CRPS affecting the upper extremities. Disuse of the limb after an injury or psychological distress related to an injury are also associated with a poorer prognosis in CRPS. Some cases of CRPS may resolve spontaneously (with 74% of patients undergoing complete resolution of symptoms (often spontaneously) in a population based study in Minnesota), but others may develop chronic pain for many years. Once one is diagnosed with CRPS, should it go into remission, the likelihood of it resurfacing after going into remission is significant. Taking precautions and seeking immediate treatment upon any injury is important.

Epidemiology
CRPS can occur at any age, with the average age at diagnosis being 42. It affects both men and women; however, CRPS is three times more frequent in females than males.CRPS affects both adults and children, and the number of reported CRPS cases among adolescents and young adults has been increasing, with a recent observational study finding an incidence of 1.16/100,000 among children in Scotland.

History
The condition currently known as CRPS was originally described during the American Civil War by Silas Weir Mitchell, who is sometimes also credited with inventing the name "causalgia". However, this term was actually coined by Mitchells friend Robley Dunglison from the Greek words for heat and for pain. Contrary to what is commonly accepted, it emerges that these causalgias were certainly major by the importance of the vasomotor and sudomotor symptoms but stemmed from minor neurological lesions. In the 1940s, the term reflex sympathetic dystrophy came into use to describe this condition, based on the theory that sympathetic hyperactivity was involved in the pathophysiology. In 1959, Noordenbos observed in causalgia patients that "the damage of the nerve is always partial." Misuse of the terms, as well as doubts about the underlying pathophysiology, led to calls for better nomenclature </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 Horners syndrome and can you explain it in depth? [/INST] Horners syndrome, also known as oculosympathetic paresis, is a combination of symptoms that arises when a group of nerves known as the sympathetic trunk is damaged. The signs and symptoms occur on the same side (ipsilateral) as it is a lesion of the sympathetic trunk. It is characterized by miosis (a constricted pupil), partial ptosis (a weak, droopy eyelid), apparent anhidrosis (decreased sweating), with apparent enophthalmos (inset eyeball).The nerves of the sympathetic trunk arise from the spinal cord in the chest, and from there ascend to the neck and face. The nerves are part of the sympathetic nervous system, a division of the autonomic (or involuntary) nervous system. Once the syndrome has been recognized, medical imaging and response to particular eye drops may be required to identify the location of the problem and the underlying cause.

Signs and symptoms
Signs that are found in people with Horners syndrome on the affected side of the face include the following:

ptosis (drooping of the upper eyelid)
anhidrosis (decreased sweating)
miosis (constriction of the pupil)
Enophthalmos (sinking of the eyeball into the face)
inability to completely close or open the eyelid
facial flushing
headaches
loss of ciliospinal reflex
bloodshot conjunctiva, depending on the site of lesion.
unilateral straight hair (in congenital Horners syndrome); the hair on the affected side may be straight in some cases.
heterochromia iridum (in congenital Horners syndrome)Interruption of sympathetic pathways leads to several implications. It inactivates the dilator muscle and thereby produces miosis. It inactivates the superior tarsal muscle which produces ptosis. It reduces sweat secretion in the face. Patients may have apparent enophthalmos (affected eye looks to be slightly sunken in) but this is not always the case. The ptosis from inactivation of the superior tarsal muscle causes the eye to appear sunken in, but when actually measured, enophthalmos is not present. The phenomenon of enophthalmos is seen in Horners syndrome in cats, rats, and dogs.Sometimes there is flushing on the affected side of the face due to dilation of blood vessels under the skin.  The pupils light reflex is maintained as this is controlled via the parasympathetic nervous system.In children, Horners syndrome sometimes leads to heterochromia, a difference in eye color between the two eyes. This happens because a lack of sympathetic stimulation in childhood interferes with melanin pigmentation of the melanocytes in the superficial stroma of the iris.In veterinary medicine, signs can include partial closure of the third eyelid, or nictitating membrane.

Causes
Horners syndrome is usually acquired as a result of disease, but may also be congenital (inborn, associated with heterochromatic iris) or iatrogenic (caused by medical treatment). In rare cases, Horners syndrome may be the result of repeated, minor head trauma, such as being hit with a soccer ball.  Although most causes are relatively benign, Horners syndrome may reflect serious disease in the neck or chest (such as a Pancoast tumor (tumor in the apex of the lung) or thyrocervical venous dilatation).Causes can be divided according to the presence and location of anhidrosis:
Central (anhidrosis of face, arm and trunk)
Syringomyelia
Multiple sclerosis
Encephalitis
Brain tumors
Lateral medullary syndrome
Preganglionic (anhidrosis of face)
Cervical rib traction on stellate ganglion
Thyroid carcinoma
Thyroidectomy
Goiter
Bronchogenic carcinoma of the superior fissure (Pancoast tumor) on apex of lung
Klumpke paralysis
Trauma - base of neck, usually blunt trauma, sometimes surgery.
As a complication of tube thoracostomy
Thoracic aortic aneurysm
Postganglionic (no anhidrosis)
Cluster headache - combination termed Hortons headache
An episode of Horners syndrome may occur during a migraine attack and be relieved afterwards
Carotid artery dissection/carotid artery aneurysm/trauma
Cavernous sinus thrombosis
Middle ear infection
Sympathectomy
Nerve blocks, such as cervical plexus block, stellate ganglion or interscalene block

Pathophysiology
Horner syndrome is due to a deficiency of sympathetic activity.
The site of lesion to the sympathetic outflow is on the ipsilateral side of the symptoms.
The following are examples of conditions that cause the clinical appearance of Horners syndrome:
First-order neuron disorder: Central lesions that involve the hypothalamospinal tract (e.g. transection of the cervical spinal cord).
Second-order neuron disorder: Preganglionic lesions (e.g. compression of the sympathetic chain by a lung tumor) that releases acetylcholine.
Third-order neuron disorder: Postganglionic lesions at the level of the internal carotid artery (e.g. a tumor in the cavernous sinus or a carotid artery dissection) that releases norepinephrine.
Partial Horners syndrome: In case of a third-neuron disorder, anhidrosis is limited to the middle part of the forehead or can be absent, resulting in a partial Horners syndrome.If patients have impaired sweating above the waist affecting only one side of the body, and they  do not have clinically apparent Horners syndrome, then their lesions are just below the stellate ganglion in the sympathetic chain.

Diagnosis
Three tests are useful in confirming the presence and severity of Horner syndrome:

Cocaine drop test: Cocaine eyedrops block the reuptake of post-ganglionic norepinephrine resulting in the dilation of a normal pupil from retention of norepinephrine in the synapse. However, in Horners syndrome the lack of norepinephrine in the synaptic cleft causes mydriatic failure.  A more recently introduced approach that is more dependable and obviates the difficulties in obtaining cocaine is to apply the alpha-agonist apraclonidine to both eyes and observe the increased mydriatic effect (due to hypersensitivity) on the affected side of Horner syndrome (the opposite effect to what the cocaine test would produce in the presence of Horners).
Paredrine test: This test helps to localize the cause of the miosis. If the third order neuron (the last of three neurons in the pathway which ultimately discharges norepinephrine into the synaptic cleft) is intact, then the amphetamine causes neurotransmitter vesicle release, thus releasing norepinephrine into the synaptic cleft and resulting in robust mydriasis of the affected pupil </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 Cutaneous amoebiasis 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 Ehrlichiosis ewingii infection and can you explain it in depth? [/INST]  </s>