<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 Asperger syndrome and can you explain it in depth? [/INST] Asperger syndrome (AS), also known as Aspergers, was the name of a neurodevelopmental disorder no longer recognised as a diagnosis in itself, having been merged into autism spectrum disorder (ASD). It was characterized by significant difficulties in social interaction and nonverbal communication, along with restricted and repetitive patterns of behaviour and interests. It was said to differ from other diagnoses that were merged into ASD by relatively unimpaired language and intelligence. The syndrome was named after the Austrian pediatrician Hans Asperger, who, in 1944, described children in his care who struggled to form friendships, did not understand others gestures or feelings, engaged in one-sided conversations about their favourite interests, and were clumsy.The exact cause of Aspergers is poorly understood. While it has high heritability, the underlying genetics have not been determined conclusively. Environmental factors are also believed to play a role. Brain imaging has not identified a common underlying condition.In 1994, the diagnosis of Aspergers was included in the fourth edition (DSM-IV) of the American Diagnostic and Statistical Manual of Mental Disorders; with the publication of DSM-5 in 2013 the diagnosis was removed, and the symptoms are now included within autism spectrum disorder along with classic autism and pervasive developmental disorder not otherwise specified (PDD-NOS). It was similarly merged into autism spectrum disorder in the International Classification of Diseases (ICD-11) as of 2021.There is no single treatment, and the UKs National Health Service (NHS) guidelines suggest that treatment of any form of autism should not be a goal, since autism is not a disease that can be removed or cured. According to the Royal College of Psychiatrists, while co-occurring conditions might require treatment, management of autism itself is chiefly about the provision of the education, training and social support/care required to improve the persons ability to function in the everyday world. The effectiveness of particular interventions for autism is supported by only limited data. Interventions may include social skills training, cognitive behavioral therapy, physical therapy, speech therapy, parent training, and medications for associated problems, such as mood or anxiety. Autistic characteristics tend to become less obvious in adulthood, but social and communication difficulties usually persist.Some autistic people,  as well as a number of researchers, have advocated a shift in attitudes toward the view that autism spectrum disorder is a difference, rather than a disease that must be treated or cured. Critics have bemoaned the entrenchment of some of these groups opinions.In 2015, Aspergers was estimated to affect 37.2 million people globally, or about 0.5% of the population. The exact percentage of people affected is not firmly established. Autism spectrum disorder is diagnosed in males more often than females, and females are typically diagnosed at a later age. The modern conception of Asperger syndrome came into existence in 1981, and went through a period of popularization. It became a standardized diagnosis in the 1990s, and was retired as a diagnosis in 2013. Many questions and controversies about the condition remain.

Classification
The extent of the overlap between Asperger syndrome and high-functioning autism (HFA – autism unaccompanied by intellectual disability) is unclear. The ASD classification is to some extent an artifact of how autism was discovered, and may not reflect the true nature of the spectrum; methodological problems have beset Asperger syndrome as a valid diagnosis from the outset. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published in May 2013, Asperger syndrome, as a separate diagnosis, was eliminated and folded into autism spectrum disorder. Like the diagnosis of Asperger syndrome, the change was controversial and thus Asperger syndrome was subsequently not removed from the WHOs ICD-10; however, it was removed from the ICD-11.The World Health Organization (WHO) previously defined Asperger syndrome (AS) as one of the autism spectrum disorders (ASD) or pervasive developmental disorders (PDD), which are a spectrum of psychological conditions that are characterized by abnormalities of social interaction and communication that pervade the individuals functioning, and by restricted and repetitive interests and behavior. Like other neurodevelopment disorders, ASD begins in infancy or childhood, has a steady course without remission or relapse, and has impairments that result from maturation-related changes in various systems of the brain. ASD, in turn, is a subset of the broader autism phenotype, which describes individuals who may not have ASD but do have autistic-like traits, such as social deficits.

Characteristics
As a pervasive developmental disorder, Asperger syndrome is distinguished by a pattern of symptoms rather than a single symptom. It is characterized by qualitative impairment in social interaction, by stereotyped and restricted patterns of behavior, activities, and interests, and by no clinically significant delay in cognitive development or general delay in language. Intense preoccupation with a narrow subject, one-sided verbosity, restricted prosody, and physical clumsiness are typical of the condition, but are not required for diagnosis. Suicidal behavior appears to occur at rates similar to those without ASD.

Social interaction
A lack of demonstrated empathy affects aspects of social relatability for persons with Asperger syndrome. Individuals with Asperger syndrome experience difficulties in basic elements of social interaction, which may include a failure to develop friendships or to seek shared enjoyments or achievements with others (e.g., showing others objects of interest); a lack of social or emotional reciprocity (social "games" give-and-take mechanic); and impaired nonverbal behaviors in areas such as eye contact, facial expression, posture, and gesture.People with Asperger syndrome may not be as withdrawn around others, compared with those with other forms of autism; they approach others, even if awkwardly. For example, a person with Asperger syndrome may engage in a one-sided, long-winded speech about a favorite topic, while misunderstanding or not recognizing the listeners feelings or reactions, such as a wish to change the topic of talk or end the interaction. This social awkwardness has been called "active but odd". Such failures to react appropriately to social interaction may appear as disregard for other peoples feelings and may come across as rude or insensitive. However, not all individuals with Asperger syndrome will approach others. Some may even display selective mutism, not speaking at all to most people and excessively to specific others. Some may choose only to talk to people they like.The cognitive ability of children with AS often allows them to articulate social norms in a laboratory context, where they may be able to show a theoretical understanding of other peoples emotions; however, they typically have difficulty acting on this knowledge in fluid, real-life situations. People with AS may analyze and distill their observations of social interaction into rigid behavioral guidelines and apply these rules in awkward ways, such as forced eye contact, resulting in a demeanor that appears rigid or socially naïve. Childhood desire for companionship can become numbed through a history of failed social encounters.

Violent or criminal behavior
The hypothesis that individuals with AS are predisposed to violent or criminal behavior has been investigated but is not supported by data. More evidence suggests that children diagnosed with Asperger syndrome are more likely to be victims, rather than offenders.A 2008 review found that an overwhelming number of reported violent criminals with Asperger syndrome also had other coexisting psychotic psychiatric disorders such as schizoaffective disorder. This coexistence of psychotic disorders is referred to as comorbid disorders. Comorbid disorders can be completely independent of one another or can have overlap in symptoms and how they express themselves.

Empathy
People with an Asperger profile might not be recognized for their empathetic qualities, due to variation in the ways empathy is felt and expressed. Some people feel deep empathy, but do not outwardly communicate these sentiments through facial expressions or language. Some people come to empathy through intellectual processes, using logic and reasoning to arrive at the feelings. It is also important to keep in mind that many people with Asperger profiles have been bullied or excluded by peers in the past and might therefore be guarded around people, which could appear as lack of empathy. People with Asperger profiles can be and are extremely caring individuals; in fact, it is particularly common for those with the profile to feel and exhibit deep concern for human welfare, animal rights, environmental protection, and other global and humanitarian causes.Evidence suggests that in the "double empathy problem model, autistic people have a unique interaction style which is significantly more readable by other autistic people, compared to non-autistic people."

Restricted and repetitive interests and behavior
People with Asperger syndrome can display behavior, interests, and activities that are restricted and repetitive and are sometimes abnormally intense or focused. They may stick to inflexible routines, move in stereotyped and repetitive ways, preoccupy themselves with parts of objects, or engage in compulsive behaviors like lining objects up to form patterns.The pursuit of specific and narrow areas of interest is one of the most striking among possible features of AS. Individuals with AS may collect volumes of detailed information on a relatively narrow topic such as weather data or star names without necessarily having a genuine understanding of the broader topic. For example, a child might memorize camera model numbers while caring little about photography. This behavior is usually apparent by age five or six. Although these special interests may change from time to time, they typically become more unusual and narrowly focused and often dominate social interaction so much that the entire family may become immersed. Because narrow topics often capture the interest of children, this symptom may go unrecognized.Stereotyped and repetitive motor behaviors are a core part of the diagnosis of AS and other ASDs. They include hand movements such as flapping or twisting, and complex whole-body movements. These are typically repeated in longer bursts and look more voluntary or ritualistic than tics, which are usually faster, less rhythmical, and less often symmetrical. However, in addition to this, various studies have reported a consistent comorbidity between AS and Tourette syndrome in the range of 8–20%, with one figure as high as 80% for tics of some kind or another,  for which several explanations have been put forward, including common genetic factors and dopamine, glutamate, or serotonin abnormalities.According to the Adult Asperger Assessment (AAA) diagnostic test, a lack of interest in fiction and a positive preference towards non-fiction is common among adults with AS.

Speech and language
Although individuals with Asperger syndrome acquire language skills without significant general delay and their speech typically lacks significant abnormalities, language acquisition and use is often atypical. Abnormalities include verbosity; abrupt transitions; literal interpretations and miscomprehension of nuance; use of metaphor meaningful only to the speaker; auditory perception deficits; unusually pedantic, formal, or idiosyncratic speech; and oddities in loudness, pitch, intonation, prosody, and rhythm. Echolalia has also been observed in individuals with AS.Three aspects of communication patterns are of clinical interest: poor prosody, tangential and circumstantial speech, and marked verbosity. Although inflection and intonation may be less rigid or monotonic than in classic autism, people with AS often have a limited range of intonation: speech may be unusually fast, jerky, or loud. Speech may convey a sense of incoherence; the conversational style often includes monologues about topics that bore the listener, fails to provide context for comments, or fails to suppress internal thoughts. Individuals with AS may fail to detect whether the listener is interested or engaged in the conversation. The speakers conclusion or point may never be made, and attempts by the listener to elaborate on the speechs content or logic, or to shift to related topics, are often unsuccessful.Children with AS may have a sophisticated vocabulary at a young age and such children have often been colloquially called "little professors" but have difficulty understanding figurative language and tend to use language literally. Children with AS appear to have particular weaknesses in areas of nonliteral language that include humor, irony, teasing, and sarcasm. Although individuals with AS usually understand the cognitive basis of humor, they seem to lack understanding of the intent of humor to share the enjoyment with others. Despite strong evidence of impaired humor appreciation, anecdotal reports of humor in individuals with AS seem to challenge some psychological theories of AS and autism.

Motor and sensory perception
Individuals with Asperger syndrome may have signs or symptoms that are independent of the diagnosis but can affect the individual or the family. These include differences in perception and problems with motor skills, sleep, and emotions.
Individuals with AS often have excellent auditory and visual perception. Children with ASD often demonstrate enhanced perception of small changes in patterns such as arrangements of objects or well-known images; typically this is domain-specific and involves processing of fine-grained features. Conversely, compared with individuals with high-functioning autism, individuals with AS have deficits in some tasks involving visual-spatial perception, auditory perception, or visual memory. Many accounts of individuals with AS and ASD report other unusual sensory and perceptual skills and experiences. They may be unusually sensitive or insensitive to sound, light, and other stimuli; these sensory responses are found in other developmental disorders and are not specific to AS or to ASD. There is little support for increased fight-or-flight response or failure of habituation in autism; there is more evidence of decreased responsiveness to sensory stimuli, although several studies show no differences.Hans Aspergers initial accounts and other diagnostic schemes include descriptions of physical clumsiness. Children with AS may be delayed in acquiring skills requiring dexterity, such as riding a bicycle or opening a jar, and may seem to move awkwardly or feel "uncomfortable in their own skin". They may be poorly coordinated or have an odd or bouncy gait or posture, poor handwriting, or problems with motor coordination. They may show problems with proprioception (sensation of body position) on measures of developmental coordination disorder (motor planning disorder), balance, tandem gait, and finger-thumb apposition. There is no evidence that these motor skills problems differentiate AS from other high-functioning ASDs.Children with AS are more likely to have sleep problems, including difficulty in falling asleep, frequent nocturnal awakenings, and early morning awakenings. AS is also associated with high levels of alexithymia, which is difficulty in identifying and describing ones emotions. Although AS, lower sleep quality, and alexithymia are associated with each other, their causal relationship is unclear.

Causes
Hans Asperger described common traits among his patients family members, especially fathers, and research supports this observation and suggests a genetic contribution to Asperger syndrome. Although no specific genetic factor has yet been identified, multiple factors are believed to play a role in the expression of autism, given the variability in symptoms seen in children. Evidence for a genetic link is that AS tends to run in families where more family members have limited behavioral symptoms similar to AS (for example, some problems with social interaction, or with language and reading skills). Most behavioral genetic research suggests that all autism spectrum disorders have shared genetic mechanisms, but AS may have a stronger genetic component than autism. There may be shared genes in which particular alleles make an individual vulnerable, and varying combinations result in differing severity and symptoms in each person with AS.A few ASD cases have been linked to exposure to teratogens (agents that cause birth defects) during the first eight weeks from conception. Although this does not exclude the possibility that ASD can be initiated or affected later, it is strong evidence that ASD arises very early in development. Many environmental factors have been hypothesized to act after birth, but none has been confirmed by scientific investigation.

Mechanism
Asperger syndrome appears to result from developmental factors that affect many or all functional brain systems, as opposed to localized effects.Although the specific underpinnings of AS or factors that distinguish it from other ASDs are unknown, and no clear pathology common to individuals with AS has emerged, it is still possible that ASs mechanism is separate from other ASDs.Neuroanatomical studies and the associations with teratogens strongly suggest that the mechanism includes alteration of brain development soon after conception. Abnormal fetal development may affect the final structure and connectivity of the brain, resulting in altered neural circuits controlling thought and behavior. Several theories of mechanism are available; none are likely to provide a complete explanation.

General-processing theories
One general-processing theory is weak central coherence theory, which hypothesizes that a limited ability to see the big picture underlies the central disturbance in ASD. A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and perceptual operations in autistic individuals.

Mirror neuron system (MNS) theory
The mirror neuron system (MNS) theory hypothesizes that alterations to the development of the MNS interfere with imitation and lead to Aspergers core feature of social impairment. One study found that activation is delayed in the core circuit for imitation in individuals with AS. This theory maps well to social cognition theories like the theory of mind, which hypothesizes that autistic behavior arises from impairments in ascribing mental states to oneself and others; or hyper-systemizing, which hypothesizes that autistic individuals can systematize internal operation to handle internal events but are less effective at empathizing when handling events generated by other agents.

Diagnosis
Standard diagnostic criteria require impairment in social interaction and repetitive and stereotyped patterns of behavior, activities, and interests, without significant delay in language or cognitive development. Unlike the international standard, the DSM-IV-TR criteria also required significant impairment in day-to-day functioning; DSM-5 eliminated AS as a separate diagnosis in 2013, and folded it into the umbrella of autism spectrum disorders. Other sets of diagnostic criteria have been proposed by Szatmari et al. and by Gillberg and Gillberg.Diagnosis is most commonly made between the ages of four and eleven. A comprehensive assessment involves a multidisciplinary team that observes across multiple settings, and includes neurological and genetic assessment as well as tests for cognition, psychomotor function, verbal and nonverbal strengths and weaknesses, style of learning, and skills for independent living. The "gold standard" in diagnosing ASDs combines clinical judgment with the Autism Diagnostic Interview-Revised (ADI-R), a semistructured parent interview; and the Autism Diagnostic Observation Schedule (ADOS), a conversation and play-based interview with the child. Delayed or mistaken diagnosis can be traumatic for individuals and families; for example, misdiagnosis can lead to medications that worsen behavior.Underdiagnosis and overdiagnosis may be problems. The cost and difficulty of screening and assessment can delay diagnosis. Conversely, the increasing popularity of drug treatment options and the expansion of benefits has motivated providers to overdiagnose ASD. There are indications AS has been diagnosed more frequently in recent years, partly as a residual diagnosis for children of normal intelligence who are not autistic but have social difficulties.There are questions about the external validity of the AS diagnosis. That is, it is unclear whether there is a practical benefit in distinguishing AS from HFA and from PDD-NOS; different screening tools render different diagnoses depending in the same person.

Differential diagnosis
Many children with AS are initially misdiagnosed with attention deficit hyperactivity disorder (ADHD). Diagnosing adults is more challenging, as standard diagnostic criteria are designed for children and the expression of AS changes with age. Adult diagnosis requires painstaking clinical examination and thorough medical history gained from both the individual and other people who know the person, focusing on childhood behavior.Conditions that must be considered in a differential diagnosis along with ADHD include other ASDs, the schizophrenia spectrum, personality disorders, obsessive–compulsive disorder, major depressive disorder, semantic pragmatic disorder, nonverbal learning disorder, social anxiety disorder, Tourette syndrome, stereotypic movement disorder, bipolar disorder, social-cognitive deficits due to brain damage from alcohol use disorder, and obsessive–compulsive personality disorder (OCPD).

Screening
Parents of children with Asperger syndrome can typically trace differences in their childrens development to as early as 30 months of age. Developmental screening during a routine check-up by a general practitioner or pediatrician may identify signs that warrant further investigation. The United States Preventive Services Task Force in 2016 found it was unclear if screening was beneficial or harmful among children in whom there are no concerns.Different screening instruments are used to diagnose AS, including the Asperger Syndrome Diagnostic Scale (ASDS); Autism Spectrum Screening Questionnaire (ASSQ); Childhood Autism Spectrum Test (CAST), previously called the Childhood Asperger Syndrome Test; Gilliam Aspergers disorder scale (GADS); Krug Aspergers Disorder Index (KADI); and the autism-spectrum quotient (AQ), with versions for children, adolescents, and adults. None have been shown to reliably differentiate between AS and other ASDs.

Management
Asperger syndrome treatment attempts to manage distressing symptoms and to teach age-appropriate social, communication, and vocational skills that are not naturally acquired during development, with intervention tailored to the needs of the individual based on multidisciplinary assessment. Although progress has been made, data supporting the efficacy of particular interventions are limited.

Therapies
Managing AS ideally involves multiple therapies that address core symptoms of the disorder. While most professionals agree that the earlier the intervention, the better, there is no treatment combination that is recommended above others. AS treatment resembles that of other high-functioning ASDs, except that it takes into account the linguistic capabilities, verbal strengths, and nonverbal vulnerabilities of individuals with AS. A typical program generally includes:
Applied behavior analysis (ABA) procedures, including positive behavior support (PBS)—or training and support of parents and school faculty in behavior management strategies to use in the home and school, and social skills training for more effective interpersonal interactions;
Cognitive behavioral therapy to improve stress management relating to anxiety or explosive emotions and to help reduce obsessive interests and repetitive routines;
Medication for coexisting conditions such as major depressive disorder and anxiety disorders;
Occupational or physical therapy to assist with poor sensory processing and motor coordination; and,
Social communication intervention, which is specialized speech therapy to help with the pragmatics and give-and-take of normal conversation.Of the many studies on behavior-based early intervention programs, most are case reports of up to five participants and typically examine a few problem behaviors such as self-injury, aggression, noncompliance, stereotypies, or spontaneous language; unintended side effects are largely ignored. Despite the popularity of social skills training, its effectiveness is not firmly established. A randomized controlled study of a model for training parents in problem behaviors in their children with AS showed that parents attending a one-day workshop or six individual lessons reported fewer behavioral problems, while parents receiving the individual lessons reported less intense behavioral problems in their AS children. Vocational training is important to teach job interview etiquette and workplace behavior to older children and adults with AS, and organization software and personal data assistants can improve the work and life management of people with AS.

Medications
No medications directly treat the core symptoms of AS. Although research into the efficacy of pharmaceutical intervention for AS is limited, it is essential to diagnose and treat comorbid conditions. Deficits in self-identifying emotions or in observing effects of ones behavior on others can make it difficult for individuals with AS to see why medication may be appropriate. Medication can be effective in combination with behavioral interventions and environmental accommodations in treating comorbid symptoms such as anxiety disorders, major depressive disorder, inattention, and aggression. The atypical antipsychotic medications risperidone, olanzapine and aripiprazole have been shown to reduce the associated symptoms of AS; risperidone can reduce repetitive and self-injurious behaviors, aggressive outbursts, and impulsivity, and improve stereotypical patterns of behavior and social relatedness. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, fluvoxamine, and sertraline have been effective in treating restricted and repetitive interests and behaviors, while stimulant medication, such as methylphenidate, can reduce inattention.Care must be taken with medications, as side effects may be more common and harder to evaluate in individuals with AS, and tests of drugs effectiveness against comorbid conditions routinely exclude individuals from the autism spectrum. Abnormalities in metabolism, cardiac conduction times, and an increased risk of type 2 diabetes have been raised as concerns with antipsychotic medications, along with serious long-term neurological side effects. SSRIs can lead to manifestations of behavioral activation such as increased impulsivity, aggression, and sleep disturbance. Weight gain and fatigue are commonly reported side effects of risperidone, which may also lead to increased risk for extrapyramidal symptoms such as restlessness and dystonia and increased serum prolactin levels. Sedation and weight gain are more common with olanzapine, which has also been linked with diabetes. Sedative side-effects in school-age children have ramifications for classroom learning. Individuals with AS may be unable to identify and communicate their internal moods and emotions or to tolerate side effects that for most people would not be problematic.

Prognosis
There is some evidence that children with AS may see a lessening of symptoms; up to 20% of children may no longer meet the diagnostic criteria as adults, although social and communication difficulties may persist. As of 2006, no studies addressing the long-term outcome of individuals with Asperger syndrome are available and there are no systematic long-term follow-up studies of children with AS. Individuals with AS appear to have normal life expectancy, but have an increased prevalence of comorbid psychiatric conditions, such as major depressive disorder and anxiety disorders that may significantly affect prognosis. Although social impairment may be lifelong, the outcome is generally more positive than with individuals with lower-functioning autism spectrum disorders; for example, ASD symptoms are more likely to diminish with time in children with AS or HFA. Most students with AS and HFA have average mathematical ability and test slightly worse in mathematics than in general intelligence. However, mathematicians are at least three times more likely to have autism-spectrum traits than the general population, and are more likely to have family members with autism.Although many attend regular education classes, some children with AS may attend special education classes such as separate classroom and resource room because of their social and behavioral difficulties. Adolescents with AS may exhibit ongoing difficulty with self-care or organization, and disturbances in social and romantic relationships. Despite high cognitive potential, most young adults with AS remain at home, yet some do marry and work independently. The "different-ness" adolescents experience can be traumatic. Anxiety may stem from preoccupation over possible violations of routines and rituals, from being placed in a situation without a clear schedule or expectations, or from concern with failing in social encounters; the resulting stress may manifest as inattention, withdrawal, reliance on obsessions, hyperactivity, or aggressive or oppositional behavior. Depression is often the result of chronic frustration from repeated failure to engage others socially, and mood disorders requiring treatment may develop. Clinical experience suggests the rate of suicide may be higher among those with AS, but this has not been confirmed by systematic empirical studies.Education of families is critical in developing strategies for understanding strengths and weaknesses; helping the family to cope improves outcomes in children. Prognosis may be improved by diagnosis at a younger age that allows for early interventions, while interventions in adulthood are valuable but less beneficial. There are legal implications for individuals with AS as they run the risk of exploitation by others and may be unable to comprehend the societal implications of their actions.

Epidemiology
Frequency estimates vary enormously. In 2015, it was estimated that 37.2 million people globally are affected. A 2003 review of epidemiological studies of children found autism rates ranging from 0.03 to 4.84 per 1,000, with the ratio of autism to Asperger syndrome ranging from 1.5:1 to 16:1; combining the geometric mean ratio of 5:1 with a conservative prevalence estimate for autism of 1.3 per 1,000 suggests indirectly that the prevalence of AS might be around 0.26 per 1,000. Part of the variance in estimates arises from differences in diagnostic criteria. For example, a relatively small 2007 study of 5,484 eight-year-old children in Finland found 2.9 children per 1,000 met the ICD-10 criteria for an AS diagnosis, 2.7 per 1,000 for Gillberg and Gillberg criteria, 2.5 for DSM-IV, 1.6 for Szatmari et al., and 4.3 per 1,000 for the union of the four criteria. Boys seem to be more likely to have AS than girls; estimates of the sex ratio range from 1.6:1 to 4:1, using the Gillberg and Gillberg criteria. Females with autism spectrum disorders may be underdiagnosed.

Comorbidities
Anxiety disorders and major depressive disorder are the most common conditions seen at the same time; comorbidity of these in persons with AS is estimated at 65%. Reports have associated AS with medical conditions such as aminoaciduria and ligamentous laxity, but these have been case reports or small studies and no factors have been associated with AS across studies. One study of males with AS found an increased rate of epilepsy and a high rate (51%) of nonverbal learning disorder. AS is associated with tics, Tourette syndrome and bipolar disorder. The repetitive behaviors of AS have many similarities with the symptoms of obsessive–compulsive disorder and obsessive–compulsive personality disorder, and 26% of a sample of young adults with AS were found to meet the criteria for schizoid personality disorder (which is characterised by severe social seclusion and emotional detachment), more than any other personality disorder in the sample. However many of these studies are based on clinical samples or lack standardized measures; nonetheless, comorbid conditions are relatively common.

History
Named after the Austrian pediatrician Hans Asperger (1906–1980), Asperger syndrome is a relatively new diagnosis in the field of autism, though a syndrome like it was described as early as 1925 by Soviet child psychiatrist Grunya Sukhareva (1891–1981), leading some of those diagnosed with Aspergers Syndrome to instead refer to their condition as Sukharevas Syndrome, in opposition to Hans Aspergers association with Nazism. As a child, Asperger appears to have exhibited some features of the very condition named after him, such as remoteness and talent in language. In 1944, Asperger described four children in his practice who had difficulty in integrating themselves socially and showing empathy towards peers. They also lacked nonverbal communication skills and were physically clumsy. Asperger described this "autistic psychopathy" as social isolation. Fifty years later, several standardizations of AS as a medical diagnosis were tentatively proposed, many of which diverge significantly from Aspergers original work.Unlike todays AS, autistic psychopathy could be found in people of all levels of intelligence, including those with intellectual disability. Asperger defended the value of so-called "high-functioning" autistic individuals, writing: "We are convinced, then, that autistic people have their place in the organism of the social community. They fulfill their role well, perhaps better than anyone else could, and we are talking of people who as children had the greatest difficulties and caused untold worries to their care-givers." Asperger also believed some would be capable of exceptional achievement and original thought later in life.Aspergers paper was published during World War II and in German, so it was not widely read elsewhere. Lorna Wing used the term Asperger syndrome in 1976, and popularized it to the English-speaking medical community in her February 1981 publication of case studies of children showing the symptoms described by Asperger, and Uta Frith translated his paper to English in 1991. Sets of diagnostic criteria were outlined by Gillberg and Gillberg in 1989 and by Szatmari et al. in the same year. In 1992, AS became a standard diagnosis when it was included in the tenth edition of the World Health Organizations diagnostic manual, International Classification of Diseases (ICD-10). It was added to the fourth edition of the American Psychiatric Associations diagnostic reference, Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), published in 1994.Hundreds of books, articles, and websites now describe AS and prevalence estimates have increased dramatically for ASD, with AS recognized as an important subgroup. Whether it should be seen as distinct from high-functioning autism is a fundamental issue requiring further study, and there are questions about the empirical validation of the DSM-IV and ICD-10 criteria. In 2013, DSM-5 eliminated AS as a separate diagnosis, folding it into the autism spectrum on a severity scale.

Society and culture
People identifying with Asperger syndrome may refer to themselves in casual conversation as aspies (a term first used in print in the Boston Globe in 1998). Some autistic people have advocated a shift in perception of autism spectrum disorders as complex syndromes rather than diseases that must be cured. Proponents of this view reject the notion that there is an "ideal" brain configuration and that any deviation from the norm is pathological; they promote tolerance for what they call neurodiversity. These views are the basis for the autistic rights and autistic pride movements. There is a contrast between the attitude of adults with self-identified AS, who typically do not want to be cured and are proud of their identity; and parents of children with AS, who typically seek assistance and a cure for their children.Some researchers have argued that AS can be viewed as a different cognitive style, not a disorder, and that it should be removed from the standard Diagnostic and Statistical Manual, much as homosexuality was removed. In a 2002 paper, Simon Baron-Cohen wrote of those with AS: "In the social world, there is no great benefit to a precise eye for detail, but in the worlds of maths, computing, cataloging, music, linguistics, engineering, and science, such an eye for detail can lead to success rather than failure." Baron-Cohen cited two reasons why it might still be useful to consider AS to be a disability: to ensure provision for legally required special support, and to recognize emotional difficulties from reduced empathy. Baron-Cohen argues that the genes for Aspergers combination of abilities have operated throughout recent human evolution and have made remarkable contributions to human history.By contrast, Pier Jaarsma and Welin wrote in 2011 that the "broad version of the neurodiversity claim, covering low-functioning as well as high-functioning autism, is problematic. Only a narrow conception of neurodiversity, referring exclusively to high-functioning autists, is reasonable." They say that "higher functioning" individuals with autism may "not [be] benefited with such a psychiatric defect-based diagnosis ... some of them are being harmed by it, because of the disrespect the diagnosis displays for their natural way of being", but "think that it is still reasonable to include other categories of autism in the psychiatric diagnostics. The narrow conception of the neurodiversity claim should be accepted but the broader claim should not." Jonathan Mitchell, an autistic author and blogger who advocates a cure for autism, has described autism as having "prevented me from making a living or ever having a girlfriend. Its given me bad fine motor coordination problems where I can hardly write. I have an impaired ability to relate to people </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 Supravalvular aortic stenosis 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 Hereditary nonpolyposis colorectal cancer and can you explain it in depth? [/INST] Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. The increased risk for these cancers is due to inherited mutations that impair DNA mismatch repair. It is a type of cancer syndrome. Because patients with Lynch syndrome can have polyps, the term HNPCC has fallen out of favor.

Signs and symptoms
Risk of cancer
Lifetime risk and mean age at diagnosis for Lynch syndrome associated cancers

In addition to the types of cancer found in the chart above, it is understood that Lynch syndrome also contributes to an increased risk of small bowel cancer, pancreatic cancer, ureter/renal pelvis cancer, biliary tract cancer, brain cancer, and sebaceous neoplasms. Increased risk of prostate cancer and breast cancer has also been associated with Lynch syndrome, although this relationship is not entirely understood.Two-thirds of colon cancers occur in the proximal colon and common signs and symptoms include blood in the stool, diarrhea or constipation, and unintended weight loss. The mean age of colorectal cancer diagnosis is 44 for members of families that meet the Amsterdam criteria. The average age of diagnosis of endometrial cancer is about 46 years. Among women with HNPCC who have both colon and endometrial cancer, about half present first with endometrial cancer, making endometrial cancer the most common sentinel cancer in Lynch syndrome. The most common symptom of endometrial cancer is abnormal vaginal bleeding. In HNPCC, the mean age of diagnosis of gastric cancer is 56 years of age with intestinal-type adenocarcinoma being the most commonly reported pathology. HNPCC-associated ovarian cancers have an average age of diagnosis of 42.5 years-old; approximately 30% are diagnosed before age 40.Significant variation in the rate of cancer has been found depending on the mutation involved. Up to the age of 75 years the risks of different cancers by the mutations are in the table below.

Genetics
HNPCC is inherited in an autosomal dominant fashion. The hallmark of HNPCC is defective DNA mismatch repair, which causes an elevated rate of single nucleotide changes and microsatellite instability, also known as MSI-H (the H is "high"). MSI is identifiable in cancer specimens in the pathology laboratory. Most cases result in changes in the lengths of dinucleotide repeats of the nucleobases cytosine and adenine (sequence: CACACACACA...).The 4 main genes involved in HNPCC normally encode for proteins that form dimers to function:

MLH1 protein dimerizes with PMS2 protein to form MutLα, which coordinates the binding of other proteins involved with mismatch repair like DNA helicase, single-stranded-DNA binding-protein (RPA), and DNA polymerases.
MSH2 protein dimerizes with MSH6 protein, which identifies mismatches via a sliding clamp model, a protein for scanning for errors.The impairment of either gene for the protein dimer impairs the protein function. These 4 genes are involved in error correction (mismatch repair), so dysfunction of the genes can lead to the inability to fix DNA replication errors and cause HNPCC. HNPCC is known to be associated with other mutations in genes involved in the DNA mismatch repair pathway:

People with MSH6 mutations are more likely to be Amsterdam criteria II-negative. The presentation with MSH6 is slightly different from with MLH1 and MSH2, and the term "MSH6 syndrome" has been used to describe this condition. In one study, the Bethesda guidelines were more sensitive than the Amsterdam Criteria in detecting it.Up to 39% of families with mutations in an HNPCC gene do not meet the Amsterdam criteria. Therefore, families found to have a deleterious mutation in an HNPCC gene should be considered to have HNPCC regardless of the extent of the family history. This also means that the Amsterdam criteria fail to identify many people who are at risk for Lynch syndrome. Improving the criteria for screening is an active area of research, as detailed in the Screening Strategies section of this article.
Most people with HNPCC inherit the condition from a parent. However, due to incomplete penetrance, variable age of cancer diagnosis, cancer risk reduction, or early death, not all people with an HNPCC gene mutation have a parent who had cancer. Some people develop HNPCC de-novo in a new generation, without inheriting the gene. These people are often only identified after developing an early-life colon cancer. Parents with HNPCC have a 50% chance of passing the genetic mutation on to each child. It is also important to note, that deleterious mutation in one of MMR genes alone is not sufficient to cause cancer, but that rather further mutations in other tumour suppressor genes need to occur.

Diagnosis
A diagnosis of Lynch syndrome is applied to people with a germline DNA mutation in one of the MMR genes (MLH1, MSH2, MSH6, and PMS2) or the EPCAM gene, identified by genetic testing. Candidates for germline genetic testing can be identified by clinical criteria such as the Amsterdam Clinical Criteria and Bethesda Guidelines, or through tumor analysis by immunohistochemistry(IHC), or microsatellite instability (MSI) testing. In the US, professional societies recommend testing every colon cancer for MSI or IHC as screening for Lynch syndrome, but this is not always performed because of cost and resource limitations. Genetic testing is commercially available and consists of a blood test.

Immunohistochemistry
Immunohistochemistry (IHC) is a method that can be used to detect abnormal mismatch repair (MMR) protein expression in tumours that are associated with Lynch syndrome. While it is not diagnostic of a Lynch syndrome, it can play a role in identifying people who should have germline testing. Two methods of implementation of IHC testing includes age-based testing and universal testing for all people. Currently, there is no widespread agreement regarding which screening method should be used. Age-based testing for IHC has been suggested in part due to cost-benefit analyses, whereas universal testing for all people with colorectal cancer ensures people with Lynch Syndrome are not missed. To address the costs, researchers are trying to predict MSI or IHC directly from the way the tumor looks under the microscope, without doing any molecular testing.

Microsatellite Instability
Mutations in DNA mismatch repair systems can lead to difficulty transmitting regions within the DNA which contain repeating patterns of two or three nucleotides (microsatellites), otherwise known as microsatellite instability (MSI). MSI is identified through DNA extraction from both a tumor tissue sample and a normal tissue sample followed by PCR analysis of microsatellite regions. MSI analysis can be used to identify people who may have Lynch syndrome and direct them for further testing.

Classification
Three major groups of MSI-H (microsatellite instability – MSI) cancers can be recognized by histopathological criteria:
right-sided poorly differentiated cancers
right-sided mucinous cancers
adenocarcinomas in any location showing any measurable level of intraepithelial lymphocyte (TIL)The histopathological criteria are not sensitive enough to detect MSI from histology but researchers are trying to use artificial intelligence to predict MSI from histology.In addition, HNPCC can be divided into Lynch syndrome I (familial colon cancer) and Lynch syndrome II (HNPCC associated with other cancers of the gastrointestinal tract or reproductive system).

Prevention
After reporting a null finding from their randomized controlled trial of aspirin (acetylsalicylic acid – ASA) to prevent the colorectal neoplasia of Lynch syndrome, Burn and colleagues have reported new data, representing a longer follow-up period than reported in the initial NEJM paper. These new data demonstrate a reduced incidence in people with Lynch syndrome who were exposed to at least four years of high-dose aspirin, with a satisfactory risk profile. These results have been widely covered in the media; future studies will look at modifying (lowering) the dose (to reduce risk associated with the high dosage of ASA).

Screening
Genetic counseling and genetic testing are recommended for families that meet the Amsterdam criteria, preferably before the onset of colon cancer.
Colon cancer
Colonoscopies are recommended as a preventative method of surveillance for individuals who have Lynch syndrome, or LS-associated genes. Specifically, it is recommended that colonoscopies begin at ages 20–25 for MLH1 and MSH2 mutation carriers and 35 years for MSH6 and PMS2 mutation carriers. Colonoscopic surveillance should then be performed at a 1-2 year interval for Lynch Syndrome patients.Endometrial/Ovarian cancer
A transvaginal ultrasound with or without endometrial biopsy is recommended annually for ovarian and endometrial cancer screening. For women with Lynch syndrome, a yearly CA-125 blood test can be used to screen for ovarian cancer, however there is limited data on the efficacy of this test in reducing mortality.Other cancers
There are also strategies for detecting other cancers early or reducing the chances of developing them that people with Lynch syndrome can discuss with their doctor, however their effectiveness is not clear. These options include:

Upper endoscopies to detect stomach and small bowel cancer every 3–5 years, starting at age 30 at the earliest (preferably in a research setting)
Annual urinalysis to detect bladder cancer, starting at age 30 at the earliest (preferably in a research setting)
Annual physical and neurological exams to detect cancer in the central nervous system (brain or spinal cord), starting at age 25 at the earliest

Amsterdam criteria
The following are the Amsterdam criteria in identifying high-risk candidates for molecular genetic testing:Amsterdam I Criteria (all bullet points must be fulfilled): The Amsterdam I criteria were published in 1990; however, were felt to be insufficiently sensitive.

Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two
Two successive affected generations
One or more colon cancers diagnosed under age 50 years
Familial adenomatous polyposis (FAP) has been excludedThe Amsterdam II criteria were developed in 1999 and improved the diagnostic sensitivity for Lynch syndrome by including cancers of the endometrium, small bowel, ureter and renal pelvis.Amsterdam Criteria II (all bullet points must be fulfilled):

Three or more family members with HNPCC-related cancers, one of whom is a first-degree relative of the other two
Two successive affected generations
One or more of the HNPCC-related cancers diagnosed under age 50 years
Familial adenomatous polyposis (FAP) has been excludedThe Bethesda criteria were developed in 1997 and later updated in 2004 by the National Cancer Institute to identify persons requiring further testing for Lynch syndrome through MSI. In contrast to the Amsterdam Criteria, the Revised Bethesda Guidelines use pathological data in addition to clinical information to help health care providers identify persons at high risk.Revised Bethesda Guidelines
If a person meets any 1 of 5 criteria the tumour(s) from the person should be tested for MSI:1. Colorectal cancer diagnosed before age 50
2. Presence of synchronous or metachronous colorectal or other Lynch syndrome associated cancers (e.g. cancers of endometrium, ovary, stomach, small bowel, pancreas, biliary tract, ureter, renal pelvis, brain, sebaceous glands, keratoacanthomas)
3. Colorectal cancer with MSI-high pathology in a person who is younger than 60 years of age
4. Colorectal cancer diagnosed in a person with one or more first-degree relative with colorectal cancer or Lynch syndrome associated tumour diagnosed under age 50
5. Person with colorectal cancer and two or more first- or second-degree relatives with colorectal cancer or Lynch syndrome associated cancer diagnosed at any age.It is important to note that these clinical criteria can be difficult to use in practice and clinical criteria used alone misses between 12 and 68 percent of Lynch syndrome cases.

Surgery
Prophylactic hysterectomy and salpingo-oophorectomy (removal of the uterus, Fallopian tubes, and ovaries to prevent cancer from developing) can be performed before ovarian or endometrial cancer develops.

Treatment
Surgery remains the front-line therapy for HNPCC. Patients with Lynch syndrome who develop colorectal cancer may be treated with either a partial colectomy or total colectomy with ileorectal anastomosis. Due to increased risk of colorectal cancer following partial colectomy and similar quality of life after both surgeries, a total colectomy may be a preferred treatment for HNPCC, especially in younger patients.There is an ongoing controversy over the benefit of 5-fluorouracil-based adjuvant therapies for HNPCC-related colorectal tumours, particularly those in stages I and II.
Anti-PD-1 antibody therapy can be effective.Checkpoint blockade with anti-PD-1 therapy is now preferred first line therapy for advanced Microsatellite-Instability–High colorectal cancer.

Epidemiology
Though the exact prevalence of Lynch syndrome-causing mutations in the general population remain unknown, recent studies estimate the prevalence to be 1 in 279 individuals, or 0.35%. Certain populations are known to have a higher prevalence of founder mutations, including, but not limited to, French Canadians, Icelanders, African Americans, and Ashkenazi Jews. Lynch syndrome-causing mutations are found in approximately 3% of all diagnosed colorectal cancers, and 1.8% of all diagnosed endometrial cancers. The average age of diagnosis of cancer in patients with this syndrome is 44 years old, as compared to 64 years old in people without the syndrome.

Terminology
Henry T. Lynch, Professor of Medicine at Creighton University Medical Center, characterized the syndrome in 1966. In his earlier work, he described the disease entity as "cancer family syndrome." The term "Lynch syndrome" was coined in 1984 by other authors; Lynch named the condition HNPCC in 1985. Since then the two terms have been used interchangeably, until later advances in the understanding of the genetics of the disease led to the term HNPCC falling out of favor.Other sources reserve the term "Lynch syndrome" when there is a known DNA mismatch repair defect, and use the term "familial colorectal cancer type X" when the Amsterdam criteria are met but there is no known DNA mismatch repair defect </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 Portal hypertensive gastropathy and can you explain it in depth? [/INST] Portal hypertensive gastropathy refers to changes in the mucosa of the stomach in patients with portal hypertension; by far the most common cause of this is cirrhosis of the liver.  These changes in the mucosa include friability of the mucosa and the presence of ectatic  blood vessels at the surface.  Patients with portal hypertensive gastropathy may experience bleeding from the stomach, which may uncommonly manifest itself in vomiting blood or melena; however, portal hypertension may cause several other more common sources of upper gastrointestinal bleeding, such as esophageal varices and gastric varices.  On endoscopic evaluation of the stomach, this condition shows a characteristic mosaic or "snake-skin" appearance to the mucosa of the stomach.

Signs and symptoms
Most patients with portal hypertensive gastropathy have either a stable or improving course in the appearance of the gastropathy on endoscopy.  However, according to retrospective data, roughly one in seven patients with portal hypertensive gastropathy will develop bleeding (either acute or chronic) attributable to the gastropathy.  Patients with chronic bleeding will usually come to the attention of the medical system because of anemia.
The diagnosis of portal hypertensive gastropathy is usually made on endoscopy.  The usual appearance of portal hypertensive gastropathy on endoscopy is a mosaic-like or reticular pattern in the mucosa.  Red spots may or may not be present.  The pattern is usually seen throughout the stomach.  A similar pattern can be seen with a related condition called gastric antral vascular ectasia (GAVE), or watermelon stomach.  However, in GAVE, the ectatic blood vessels are more commonly found in the antrum or lower part of the stomach.

Pathogenesis
Several studies have found that patients with portal hypertension develop increased blood flow to the stomach.   The physiological findings that correlate with worsening portal hypertensive gastropathy include an increased portal venous pressure gradient and decreased hepatic blood flow.  Biopsies of the stomach in patients with portal hypertensive gastropathy show ectatic (or dilated) blood vessels, evidence of bleeding by means of red blood cells in the lamina propria, and edema in the stomach wall.

Treatment
Medications
Several treatment options have been developed for portal hypertensive gastropathy.  The first is the use of beta-blockers, which reduce portal pressures </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 Potassium-aggravated myotonia and can you explain it in depth? [/INST] Potassium-aggravated myotonia is a rare genetic disorder that affects skeletal muscle. Beginning in childhood or adolescence, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Myotonia causes muscle stiffness, often painful, that worsens after exercise and may be aggravated by eating potassium-rich foods such as bananas and potatoes. Stiffness occurs in skeletal muscles throughout the body. Potassium-aggravated myotonia ranges in severity from mild episodes of muscle stiffness to severe, disabling disease with frequent attacks. Potassium-aggravated myotonia may, in some cases, also cause paradoxical myotonia, in which myotonia becomes more severe at the time of movement instead of after movement has ceased. Unlike some other forms of myotonia, potassium-aggravated myotonia is not associated with episodes of muscle weakness.Mutations in the SCN4A gene cause potassium-aggravated myotonia </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 Dermatitis and can you explain it in depth? [/INST] Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved can vary from small to covering the entire body. Dermatitis is often called eczema, and the difference between those terms is not standardized.
The exact cause of the condition is often unclear. Cases may involve a combination of  allergy and poor venous return. The type of dermatitis is generally determined by the persons history and the location of the rash. For example, irritant dermatitis often occurs on the hands of those who frequently get them wet. Allergic contact dermatitis occurs upon exposure to an allergen, causing a hypersensitivity reaction in the skin.Prevention of atopic dermatitis is typically with essential fatty acids, and may be treated with moisturizers and steroid creams. The steroid creams should generally be of mid- to high strength and used for less than two weeks at a time, as side effects can occur. Antibiotics may be required if there are signs of skin infection. Contact dermatitis is typically treated by avoiding the allergen or irritant. Antihistamines may help with sleep and decrease nighttime scratching.Dermatitis was estimated to affect 245 million people globally in 2015, or 3.34% of the world population. Atopic dermatitis is the most common type and generally starts in childhood. In the United States, it affects about 10–30% of people. Contact dermatitis is twice as common in females as males. Allergic contact dermatitis affects about 7% of people at some point in their lives. Irritant contact dermatitis is common, especially among people with certain occupations; exact rates are unclear.

Types
Dermatitis includes:
Atopic dermatitis
Allergic contact dermatitis
Irritant contact dermatitis
Seborrhoeic dermatitis
Stasis dermatitis

Signs and symptoms
Dermatitis symptoms vary with all different forms of the condition. Although every type of dermatitis has different symptoms, there are certain signs that are common for all of them, including redness of the skin, swelling, itching and skin lesions with sometimes oozing and scarring. Also, the area of the skin on which the symptoms appear tends to be different with every type of dermatitis, whether on the neck, wrist, forearm, thigh or ankle. Although the location may vary, the primary symptom of this condition is itchy skin. More rarely, it may appear on the genital area, such as the vulva or scrotum. Symptoms of this type of dermatitis may be very intense and may come and go. Irritant contact dermatitis is usually more painful than itchy.
Although the symptoms of atopic dermatitis vary from person to person, the most common symptoms are dry, itchy, red skin. Typical affected skin areas include the folds of the arms, the back of the knees, wrists, face and hands. Perioral dermatitis refers to a red bumpy rash around the mouth.Dermatitis herpetiformis symptoms include itching, stinging and a burning sensation. Papules and vesicles are commonly present. The small red bumps experienced in this type of dermatitis are usually about 1 cm in size, red in color and may be found symmetrically grouped or distributed on the upper or lower back, buttocks, elbows, knees, neck, shoulders and scalp.
The symptoms of seborrhoeic dermatitis, on the other hand, tend to appear gradually, from dry or greasy scaling of the scalp (dandruff) to scaling of facial areas, sometimes with itching, but without hair loss.  In newborns, the condition causes a thick and yellowish scalp rash, often accompanied by a diaper rash. In severe cases, symptoms may appear along the hairline, behind the ears, on the eyebrows, on the bridge of the nose, around the nose, on the chest, and on the upper back.

Complications
People with eczema should not receive the smallpox vaccination due to risk of developing eczema vaccinatum, a potentially severe and sometimes fatal complication.
Other major health risks for people with dermatitis are viral and bacterial infections because atopic dermatitis patients have deficiencies in their proteins and lipids that have barrier functions along with defects in dendritic cells and as a result are unable to keep foreign invaders out leading to recurring infections. If left untreated, these infections may be life-threatening, so skin barrier improvement (such as daily moisturizing to minimize transepidermal water loss) and anti-inflammatory therapy are recommended as preventative measures.

Cause
The cause of dermatitis is unknown but is presumed to be a combination of genetic and environmental factors.

Environmental
The hygiene hypothesis postulates that the cause of asthma, eczema, and other allergic diseases is an unusually clean environment in childhood which leads to an insufficient human microbiota. It is supported by epidemiologic studies for asthma. The hypothesis states that exposure to bacteria and other immune system modulators is important during development, and missing out on this exposure increases the risk for asthma and allergy. One systematic review of literature on eczema found that urban areas have an increased prevalence of eczema compared to rural areas.
While it has been suggested that eczema may sometimes be an allergic reaction to the excrement from house dust mites, with up to 5% of people showing antibodies to the mites, the overall role this plays awaits further corroboration.

Malnutrition
Essential fatty acid deficiency results in a dermatitis similar to that seen in zinc or biotin deficiency.

Genetic
A number of genes have been associated with eczema, one of which is filaggrin. Genome-wide studies found three new genetic variants associated with eczema: OVOL1, ACTL9 and IL4-KIF3A.Eczema occurs about three times more frequently in individuals with celiac disease and about two times more frequently in relatives of those with celiac disease, potentially indicating a genetic link between the conditions.

Prevention
Exclusive breastfeeding of infants during at least the first few months may decrease the risk. There is no good evidence that a mothers diet during pregnancy or breastfeeding affects the risk, nor is there evidence that delayed introduction of certain foods is useful. There is tentative evidence that probiotics in infancy may reduce rates but it is insufficient to recommend its use. There is moderate certainty evidence that the use of skin care interventions such as emollients within the first year of life of an infants life is not effective in preventing eczema. In fact, it may increase the risk of skin infection and of unwanted effects such as allergic reaction to certain moisturizers and a stinging sensation.

Healthy diet
There has not been adequate evaluation of changing the diet to reduce eczema. There is some evidence that infants with an established egg allergy may have a reduction in symptoms if eggs are eliminated from their diets. Benefits have not been shown for other elimination diets, though the studies are small and poorly executed. Establishing that there is a food allergy before dietary change could avoid unnecessary lifestyle changes.

Fatty acids
Oils with fatty acids that has been studied to prevent dermatitis includes:
Corn oil: Linoleic acid (LA)
Fish oil: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
Hemp seed oil: Linoleic acid (LA), and alpha-Linolenic acid (ALA)In the 1950s Arild Hansen showed that in humans: infants fed skimmed milk developed the essential fatty acid deficiency. It was characterized by an increased food intake, poor growth, and a scaly dermatitis, and was cured by the administration of corn oil.

Management
There is no known cure for some types of dermatitis, with treatment aiming to control symptoms by reducing inflammation and relieving itching. Contact dermatitis is treated by avoiding what is causing it.

Lifestyle
Bathing once or more a day is recommended, usually for five to ten minutes in warm water. Soaps should be avoided, as they tend to strip the skin of natural oils and lead to excessive dryness. The American Academy of Dermatology suggests using a controlled amount of bleach diluted in a bath to help with atopic dermatitis.People can wear clothing designed to manage the itching, scratching and peeling.House dust mite reduction and avoidance measures have been studied in low quality trials and have not shown evidence of improving eczema.

Moisturizers
Low-quality evidence indicates that moisturizing agents (emollients) may reduce eczema severity and lead to fewer flares. In children, oil–based formulations appear to be better, and water–based formulations are not recommended. It is unclear if moisturizers that contain ceramides are more or less effective than others. Products that contain dyes, perfumes, or peanuts should not be used. Occlusive dressings at night may be useful.Some moisturizers or barrier creams may reduce irritation in occupational irritant hand dermatitis, a skin disease that can affect people in jobs that regularly come into contact with water, detergents, chemicals or other irritants. Some emollients may reduce the number of flares in people with dermatitis.

Medications
Corticosteroids
If symptoms are well controlled with moisturizers, steroids may only be required when flares occur. Corticosteroids are effective in controlling and suppressing symptoms in most cases. Once daily use is generally enough. For mild-moderate eczema a weak steroid may be used (e.g., hydrocortisone), while in more severe cases a higher-potency steroid (e.g., clobetasol propionate) may be used. In severe cases, oral or injectable corticosteroids may be used. While these usually bring about rapid improvements, they have greater side effects.
Long term use of topical steroids may result in skin atrophy, stria, telangiectasia. Their use on delicate skin (face or groin) is therefore typically with caution. They are, however, generally well tolerated. Red burning skin, where the skin turns red upon stopping steroid use, has been reported among adults who use topical steroids at least daily for more than a year.

Antihistamines
There is little evidence supporting the use of antihistamine medications for the relief of dermatitis. Sedative antihistamines, such as diphenhydramine, may be useful in those who are unable to sleep due to eczema. Second generation antihistamines have minimal evidence of benefit. Of the second generation antihistamines studied, fexofenadine is the only one to show evidence of improvement in itching with minimal side effects.

Immunosuppressants
Topical immunosuppressants like pimecrolimus and tacrolimus may be better in the short term and appear equal to steroids after a year of use. Their use is reasonable in those who do not respond to or are not tolerant of steroids. Treatments are typically recommended for short or fixed periods of time rather than indefinitely. Tacrolimus 0.1% has generally proved more effective than pimecrolimus, and equal in effect to mid-potency topical steroids. There is no link to increased risk of cancer from topical use of 1% pimecrolimus cream.When eczema is severe and does not respond to other forms of treatment, systemic immunosuppressants are sometimes used. Immunosuppressants can cause significant side effects and some require regular blood tests. The most commonly used are ciclosporin, azathioprine, and methotrexate.
Dupilumab is a new medication that improves eczema lesions, especially moderate to severe eczema. Dupilumab, a monoclonal antibody, suppresses inflammation by targeting the interleukin-4 receptor.

Others
In September 2021, ruxolitinib cream (Opzelura) was approved by the U.S. Food and Drug Administration (FDA) for the topical treatment of mild to moderate atopic dermatitis. It is a topical Janus kinase inhibitor.

Light therapy
Narrowband UVB
Atopic dermatitis (AD) may be treated with narrowband UVB, which increases 25-hydroxyvitamin D3 in persons in individuals with AD.Light therapy using heliotherapy, balneophototherapy, psoralen plus UVA (PUVA), light has tentative support but the quality of the evidence is not very good compared with narrowband UVB, and UVA1. However, UVB is more effective than UVA1 for treatment of atopical dermatitis.Overexposure to ultraviolet light carries its own risks, particularly that of skin cancer.

Alternative medicine
Topical
Limited evidence suggests that acupuncture may reduce itching in those affected by atopic dermatitis.Chiropractic spinal manipulation lacks evidence to support its use for dermatitis. There is little evidence supporting the use of psychological treatments. While dilute bleach baths have been used for infected dermatitis there is little evidence for this practice.

Supplements
Sulfur: There is currently no scientific evidence for the claim that sulfur treatment relieves eczema.
Chinese herbs: It is unclear whether Chinese herbs help or harm. Dietary supplements are commonly used by people with eczema.
Neither evening primrose oil nor borage seed oil taken orally have been shown to be effective. Both are associated with gastrointestinal upset.
Probiotics are likely to make little to no difference in symptoms.

Pathophysiology
Eczema can be characterized by spongiosis which allows inflammatory mediators to accumulate. Different dendritic cells sub types, such as Langerhans cells, inflammatory dendritic epidermal cells and plasmacytoid dendritic cells have a role to play.

Diagnosis
Diagnosis of eczema is based mostly on the history and physical examination. In uncertain cases, skin biopsy may be taken for a histopathologic diagnosis of dermatitis. Those with eczema may be especially prone to misdiagnosis of food allergies.Patch tests are used in the diagnosis of allergic contact dermatitis.

Classification
The term eczema refers to a set of clinical characteristics. Classification of the underlying diseases has been haphazard with numerous different classification systems, and many synonyms being used to describe the same condition.A type of dermatitis may be described by location (e.g., hand eczema), by specific appearance (eczema craquele or discoid) or by possible cause (varicose eczema). Further adding to the confusion, many sources use the term eczema interchangeably for the most common type: atopic dermatitis.The European Academy of Allergology and Clinical Immunology (EAACI) published a position paper in 2001, which simplifies the nomenclature of allergy-related diseases, including atopic and allergic contact eczemas. Non-allergic eczemas are not affected by this proposal.

Histopathologic classification
By histopathology, superficial dermatitis (in the epidermis, papillary dermis, and superficial vascular plexus) can basically be classified into either of the following groups:
Vesiculobullous lesions
Pustular dermatosis
Non vesicullobullous, non-pustularWith epidermal changes
Without epidermal changes. These characteristically have a superficial perivascular inflammatory infiltrate and can be classified by type of cell infiltrate:Lymphocytic (most common)
Lymphoeosinophilic
Lymphoplasmacytic
Mast cell
Lymphohistiocytic
Neutrophilic

Terminology
There are several types of dermatitis including atopic dermatitis, contact dermatitis, stasis dermatitis and seborrhoeic dermatitis. Many authors use the terms dermatitis and eczema synonymously, and various dictionaries that treat the terms as differentiable nonetheless do not provide explicit criteria for differentiating them, as the aspects of inflammation, pruritus, and either exogenous or endogenous provoking agent all can apply to either term, and thus autoimmune components are not excluded from either.
Others use the term eczema to specifically mean atopic dermatitis. Atopic dermatitis is also known as atopic eczema. In some languages, dermatitis and eczema mean the same thing, while in other languages dermatitis implies an acute condition and eczema a chronic one.

Common types
Diagnosis of types may be indicated by codes defined according to International Statistical Classification of Diseases and Related Health Problems (ICD).

Atopic
Atopic dermatitis is an allergic disease believed to have a hereditary component and often runs in families whose members have asthma. Itchy rash is particularly noticeable on the head and scalp, neck, inside of elbows, behind knees, and buttocks. It is very common in developed countries and rising. Irritant contact dermatitis is sometimes misdiagnosed as atopic dermatitis. Stress can cause atopic dermatitis to worsen.

Contact
Contact dermatitis is of two types: allergic (resulting from a delayed reaction to an allergen, such as poison ivy, nickel, or Balsam of Peru), and irritant (resulting from direct reaction to a detergent, such as sodium lauryl sulfate, for example).
Some substances act both as allergen and irritants (wet cement, for example). Other substances cause a problem after sunlight exposure, bringing on phototoxic dermatitis. About three-quarters of cases of contact eczema are of the irritant type, which is the most common occupational skin disease. Contact eczema is curable, provided the offending substance can be avoided and its traces removed from ones environment. (ICD-10 L23; L24; L56.1; L56.0)

Seborrhoeic
Seborrhoeic dermatitis or seborrheic dermatitis is a condition sometimes classified as a form of eczema that is closely related to dandruff. It causes dry or greasy peeling of the scalp, eyebrows, and face, and sometimes trunk. In newborns, it causes a thick, yellow, crusty scalp rash called cradle cap, which seems related to lack of biotin and is often curable. (ICD-10 L21; L21.0)

Less common types
Dyshidrosis
Dyshidrosis (dyshidrotic eczema, pompholyx, vesicular palmoplantar dermatitis) only occurs on palms, soles, and sides of fingers and toes. Tiny opaque bumps called vesicles, thickening, and cracks are accompanied by itching, which gets worse at night. A common type of hand eczema, it worsens in warm weather. (ICD-10 L30.1)

Discoid
Discoid eczema (nummular eczema, exudative eczema, microbial eczema) is characterized by round spots of oozing or dry rash, with clear boundaries, often on lower legs. It is usually worse in winter. The cause is unknown, and the condition tends to come and go. (ICD-10 L30.0)

Venous
Venous eczema (gravitational eczema, stasis dermatitis, varicose eczema) occurs in people with impaired circulation, varicose veins, and edema, and is particularly common in the ankle area of people over 50. There is redness, scaling, darkening of the skin, and itching. The disorder predisposes to leg ulcers. (ICD-10 I83.1)

Herpetiformis
Dermatitis herpetiformis (Duhrings disease) causes an intensely itchy and typically symmetrical rash on arms, thighs, knees, and back. It is directly related to celiac disease, can often be put into remission with an appropriate diet, and tends to get worse at night. (ICD-10 L13.0)

Neurodermatitis
Neurodermatitis (lichen simplex chronicus, localized scratch dermatitis) is an itchy area of thickened, pigmented eczema patch that results from habitual rubbing and scratching. Usually, there is only one spot. Often curable through behaviour modification and anti-inflammatory medication. Prurigo nodularis is a related disorder showing multiple lumps. (ICD-10 L28.0; L28.1)

Autoeczematization
Autoeczematization (id reaction, auto sensitization) is an eczematous reaction to an infection with parasites, fungi, bacteria, or viruses. It is completely curable with the clearance of the original infection that caused it. The appearance varies depending on the cause. It always occurs some distance away from the original infection. (ICD-10 L30.2)

Viral
There are eczemas overlaid by viral infections (eczema herpeticum or vaccinatum), and eczemas resulting from underlying disease (e.g., lymphoma).
Eczemas originating from ingestion of medications, foods, and chemicals, have not yet been clearly systematized. Other rare eczematous disorders exist in addition to those listed here.

Prognosis
Most cases are well managed with topical treatments and ultraviolet light. About 2% of cases are not. In more than 60% of young children, the condition subsides by adolescence.

Epidemiology
Globally dermatitis affected approximately 230 million people as of 2010 (3.5% of the population). Dermatitis is most commonly seen in infancy, with female predominance of eczema presentations occurring during the reproductive period of 15–49 years. In the UK about 20% of children have the condition, while in the United States about 10% are affected.Although little data on the rates of eczema over time exists prior to the 1940s, the rate of eczema has been found to have increased substantially in the latter half of the 20th century, with eczema in school-aged children being found to increase between the late 1940s and 2000. In the developed world there has been rise in the rate of eczema over time.  The incidence and lifetime prevalence of eczema in England has been seen to increase in recent times.Dermatitis affected about 10% of U.S </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 Macropsia and can you explain it in depth? [/INST] Macropsia is a neurological condition affecting human visual perception, in which objects within an affected section of the visual field appear larger than normal, causing the person to feel smaller than they actually are. Macropsia, along with its opposite condition, micropsia, can be categorized under dysmetropsia. Macropsia is related to other conditions dealing with visual perception, such as aniseikonia and Alice in Wonderland Syndrome (AIWS, also known as Todds syndrome).  Macropsia has a wide range of causes, from prescription and illicit drugs, to migraines and (rarely) complex partial epilepsy, and to different retinal conditions, such as epiretinal membrane. Physiologically, retinal macropsia results from the compression of cones in the eye. It is the compression of receptor distribution that results in greater stimulation and thus a larger perceived image of an object.

Signs and symptoms
The most obvious symptom of macropsia is the presence of exceptionally enlarged objects throughout the visual field. For example, a young girl might see her sisters books as the same size as her sister. Stemming from this symptom, someone with macropsia may feel undersized in relation to his or her surrounding environment. Patients with macropsia have also noted the cessation of auditory function prior to the onset of visual hallucination, indicating possible seizure either before or after the hallucination. A buzzing sound in the ears has also been reported immediately before macropsia development. Some patients claim that symptoms may be eased if an attempt is made to physically touch the object which appears enormous in size. It is important to note, however, that patients typically remain lucid and alert throughout episodes, being able to recount specific details. A person with macropsia may have no psychiatric conditions. Symptoms caused chemically by drugs such as cannabis, magic mushrooms, or cocaine tend to dissipate after the chemical compound has been excreted from the body. Those who acquire macropsia as a symptom of a virus usually experience complete recovery and restoration of normal vision.Dysmetropsia in one eye, a case of aniseikonia, can present with symptoms such as headaches, asthenopia, reading difficulties, depth perception problems, or double vision. The visual distortion can cause uncorrelated images to stimulate corresponding retinal regions simultaneously impairing fusion of the images. Without suppression of one of the images symptoms from mild poor stereopsis, binocular diplopia and intolerable rivalry can occur.

Psychological effects
There are a broad range of psychological and emotional effects that a person with macropsia may experience. One competing theory has radically stated that macropsia may be an entirely psychological pathological phenomenon without any structural defect or definite cause. They may be in an irritable or angry state, or in contrast, a euphoric state. There is evidence that those who experience Alice in Wonderland Syndrome and associated macropsia are able to recount their experiences with thorough detail. There may be no evidence of psychiatric disturbance and, as a result, no psychiatric therapy may be required. Psychological conditions often arise from macropsia, but the general consensus is that they do not cause macropsia. Those affected may experience extreme anxiety both during and after episodes as a result of the overwhelming nature of his or her distorted visual field. Due to the fear and anxiety associated with the condition, those who have previously had an episode hesitate to recount the episode, although retain the ability to do so. Psychologically, a person with macropsia may feel separation and dissociation from the outside world and even from immediate family. This feeling of dissociation has mostly been noted in child or adolescent patients. The patient may feel that he or she must unfairly contend with hostile and aggressive forces due to the gigantic nature of the surrounding environment. The defense against said forces is usually expressed verbally. The patient may falsely present an outgoing or flamboyant persona, while remaining fearful of people internally. He or she, in an attempt to balance the size distortion, may try to make others feel small in size through insult or hostile behavior. The psychological impact of macropsia on long-time people who have had the condition since childhood may be greater and lead to severe ego-deficiencies. An alternative interpretation of the condition is that macropsia is a response to biophysiological contraction and has no psychological roots. Thus, when a patient reaches for an enlarged object, he or she is overcoming that physiological contraction. However, this theory has been under much scrutiny.

Causes
Structural defects
In cases where macropsia affects one eye resulting in differences in the way the two eyes perceive the size or shape of images, the condition is known as aniseikonia. Aniseikonia is known to be associated with certain retinal conditions. Epiretinal membrane has been found to cause metamorphopsia and aniseikonia. Vitreomacular traction caused by the excessive adhesion of vitreous fluid to the retina is related to aniseikonia due to the separation and compression of photoreceptor cells. Macular edema and surgical re-attachment for macula-off rhegmatogenous retinal detachment can also cause an increased separation of macular photoreceptor cells resulting in dysmetropsia. Retinoschisis is another eye disease that has been shown to cause aniseikonia.There is evidence that a lesion appearing in the posterior area of the ventral occipitotemporal visual pathway can cause macropsia. This lesion can be due to an ischemic cell death after an acute posterior cerebral infarction.

Medications
The most prevalent research on prescription drugs with side effects of macropsia deals with zolpidem and citalopram. Zolpidem is a drug prescribed for insomnia, and although it has proven beneficial effects, there have been numerous reported cases of adverse perceptual reactions. One of these cases discusses an anorexic womans episode of macropsia, which occurred twenty minutes after taking 10 mg zolpidem. The same woman later had two more episodes of zolpidem-induced macropsia, after taking 5 mg and 2.5 mg zolpidem, respective to each episode. The intensity of the macropsia episodes decreased with the decreasing amount of zolpidem administered; it is implied in the article that the level of intensity was based on the patients accounts of her macropsia episodes, and that no external diagnosis was used. Hoyler points out notable similarities among the different reported cases of zolpidem-induced disorganization. The similarities were that all the cases were reported by women, the disorganization and agitation followed the first administration of zolpidem, and once zolpidem was discontinued, there were no lasting residual effects. It is believed that zolpidem-related macropsia is more prevalent in women because plasma zolpidem concentration is 40% higher in women, a concentration that further increases in anorexic women.Citalopram-induced macropsia is similar to zolpidem-induced macropsia since both types have been observed in relatively few cases, and neither of the drugs side effects can be supported by experimental evidence. Citalopram is an antidepressant that inhibits serotonin reuptake. The first case of macropsia thought to be induced by citalopram involves a woman who experienced macropsia after her first administration of 10 mg citalopram. Just as with zolpidem, after the immediate discontinuation of citalopram, there were no further episodes of macropsia.

Illicit drugs
There are suggestions that visual distortions, such as macropsia, can be associated with cocaine use. Episodes of temporary drug-induced macropsia subside as the chemicals leave the body.

Migraine
Past research has linked macropsia to migraine. One of these studies was conducted on Japanese adolescents who reported visual episodic illusions with macropsia and showed that illusions are three times more likely to occur in association with migraine. The illusions were most prevalent among girls between the ages of 16 and 18. It is unlikely that macropsia in Japanese adolescents could be due to epileptic seizure since only 0.3% of Japanese adolescents have epilepsy. No evidence of drugs was found, which eliminates the possibility of the macropsia in the adolescents being drug-induced. It is also unlikely for macropsia in adolescent children to be associated with a serious disease. It is usually the macropsia or other visual disturbance which precedes the painful migrainous headaches. The episodes of macropsia can occur as part of the aura in a migraine. These episodes are often brief, lasting only a few minutes. Adolescents who are deemed to have multiple distortions per episode, such as slow motion vision and macropsia, are even more likely to be people with migraine. The macropsia episodes associated with migraine are typically equivalent to the duration of the aura, which can range from moments to 15 minutes. Non-migrainous headaches are not known to be associated with episodic illusions. Even in the absence of a migraine, a fever or a hypnogogic state can provoke visual illusions, which one might claim to be macropsia. A person with macropsia may fail to see the connection between the migraine and the macropsia, since the conditions may not elicit symptoms at the same time. The pathophysiology of the condition is not fully understood, but the timing of some episodic occurrences with the headaches suggests that there is a connection between macropsia and the vasoconstrictive phase of a migraine. The differences in visual phenomena, such as macropsia with slow motion versus macropsia without slow motion, may result from different areas of the brain being affected by migraine.

Epilepsy
Macropsia may present itself as a symptom of both frontal lobe epilepsy and temporal lobe epilepsy, which may actually help in the diagnosis of those diseases. Children who experience nocturnal hallucinations accompanied by macropsia may seek medical care for panic attack disorders and instead are diagnosed with forms of epilepsy. Epilepsy patients may have no memory of the seizure, but can remember the hallucinations and aura which proceed the attack. Electroencephalography, or EEG imaging, can then be utilized while the patient experiences the episode. It may be subsequently concluded that the EEG is congruent with temporal or frontal lobe seizure. Anxiety and headaches accompany the episodes of visual distortion associated with epilepsy. While Valproic acid has been used to treat this type of seizure, anti-seizure medications appropriate for focal-onset seizures, like oxcarbazapine, have also been used successfully in the treatment of epilepsy-related macropsia.

Hypoglycaemia
Endogenous hypoglycaemia can result in number of visual disturbances and sometimes macropsia. This kind of hypoglycaemia is defined as having an abnormally low blood-sugar level due to anything other than the exogenous administration of insulin. Macropsia has been observed in experimental hypoglycaemia and in patients receiving insulin therapy.

Viruses
Patients with both Epstein-Barr virus and infectious mononucleosis have cited an increase in the sizes of perceived objects, coinciding with other symptoms of Alice in Wonderland Syndrome. Additionally, it has been observed that Epstein-Barr patients who cite hallucinations display abnormal MRI scans. The MRI may show swelling of the cerebral cortex, transient T2 prolongation, and transient lesions. Unlike in MRIs, no abnormalities have been reported in CT scans. It is thus recommended that an Epstein-Barr patient who cites visual hallucinations have an MRI scan. Macropsia may appear either before the onset, or after the resolution, of all clinical symptoms associated with the illness. The duration of the disturbances have been shown to range between two weeks and seven months. Almost all patients with macropsia due to infectious mononucleosis make full recoveries. Patients with Coxsackievirus B1 have reported numerous symptoms of Alice in Wonderland Syndrome, the most common of which being macropsia and micropsia.

Pathophysiology
Macropsia may be a result of optical magnification differences between the eyes, retinal receptor distribution, or the cortical processing of the sampled image. The current hypothesis for the occurrence of dysmetropsia is due to the stretching or compression of the retina leading to the displacement of receptors. Macropsia arises from a compressed receptor distribution leading to a larger perceived image size and conversely, micropsia results from stretching of the retina leading to a more sparse receptor distribution that gives a smaller perceived image size. In the case of macropsia, the greater density of photoreceptor cells leads to greater stimulation making the object seem larger. In some cases, the effects of macropsia have been shown to be field dependent, in that the degree of visual distortion is related to the visual field angle. Non-uniform stretching or compression of the receptor distribution could explain the field dependency of the macropsia. If the compression forces were closer to the fovea the resulting compression would cause a greater amount of macropsia at lower field angles with little effect at higher field angles where the receptor distribution is not as compressed. Alterations in receptor distribution can be the result of epiretinal membrane, neuroretina detachment and/or re-attachment, or retinoschisis. Macropsia caused by surgical re-attachment of macula-off rhegmatogenous retinal detachment is not symmetrical around the fovea, resulting in differences size changes in the horizontal and vertical meridians. Asymmetry has also been observed with retinoschisis, in which macropsia generally results in the vertical direction while micropsia presents in the horizontal direction.

Diagnosis
Macropsia is generally diagnosed once a patient complains of the characteristic symptoms, such as disproportionally large objects in their visual field. The Amsler Grid test can be used to diagnose macropsia, along with other visual maladies depending on the subjective disturbance reported by the patient after looking at the Amsler Grid. Outward bulging of the lines on an Amsler Grid is consistent with patients experiencing macropsisa. The New Aniseikonia Test (NAT) can quantify the degree of macropsia or micropsia independently in the vertical and horizontal meridians. The test consists of red and green semicircles on a black background with a white round fixation target. The size of the red semicircle is held constant while the green semicircle is varied in size in 1% increments. The patient wears a pair of red/green goggles so that one eye is tested at a time, and the patient attempts to determine when the semicircles are the same size. This is termed the reversal threshold and the size difference between the semicircles is reported as the degree of aniseikonia. A positive value indicates that the object was perceived bigger and thus corresponds to macropsia, and conversely a negative value indicates micropsia. The Aniseikonia Inspector contains an aniseikonia test based on the same principles as the NAT, but the test is run on a computer screen, it is based on a forced choice method, and it can measure the size difference as a function of the size of the objects </s>