<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 Sexual dysfunction and can you explain it in depth? [/INST] Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction as a "persons inability to participate in a sexual relationship as they would wish". This definition is broad and is subject to many interpretations. A diagnosis of sexual dysfunction under the DSM-5 requires a person to feel extreme distress and interpersonal strain for a minimum of six months (except for substance- or medication-induced sexual dysfunction). Sexual dysfunction can have a profound impact on an individuals perceived quality of sexual life. The term sexual disorder may not only refer to physical sexual dysfunction, but to paraphilias as well; this is sometimes termed disorder of sexual preference.
A thorough sexual history and assessment of general health and other sexual problems (if any) are important when assessing sexual dysfunction, because it is usually correlated with other psychiatric issues, such as mood disorders, eating and anxiety disorders, and schizophrenia. Assessing performance anxiety, guilt, stress, and worry are integral to the optimal management of sexual dysfunction. Many of the sexual dysfunctions that are defined are based on the human sexual response cycle proposed by William H. Masters and Virginia E. Johnson, and modified by Helen Singer Kaplan.

Types
Sexual dysfunction can be classified into four categories: sexual desire disorders, arousal disorders, orgasm disorders, and pain disorders. Dysfunction among men and women are studied in the fields of andrology and gynecology respectively.

Sexual desire disorders
Sexual desire disorders or decreased libido are characterized by a lack of sexual desire, libido for sexual activity, or sexual fantasies for some time. The condition ranges from a general lack of sexual desire to a lack of sexual desire for the current partner. The condition may start after a period of normal sexual functioning, or the person may always have had an absence or a lesser intensity of sexual desire.
The causes vary considerably but include a decrease in the production of normal estrogen in women, or testosterone in both men and women. Other causes may be aging, fatigue, pregnancy, medications (such as SSRIs), or psychiatric conditions, such as depression and anxiety. While many causes of low sexual desire are cited, only a few of these have ever been the object of empirical research.

Sexual arousal disorders
Sexual arousal disorders were previously known as frigidity in women and impotence in men, though these have now been replaced with less judgmental terms. Impotence is now known as erectile dysfunction, and frigidity has been replaced with a number of terms describing specific problems that can be broken down into four categories as described by the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders: lack of desire, lack of arousal, pain during intercourse, and lack of orgasm.For both men and women, these conditions can manifest themselves as an aversion to and avoidance of sexual contact with a partner. In men, there may be partial or complete failure to attain or maintain an erection, or a lack of sexual excitement and pleasure in sexual activity.
There may be physiological origins to these disorders, such as decreased blood flow or lack of vaginal lubrication. Chronic disease and the partners relationship can also contribute to dysfunction.
Additionally, postorgasmic illness syndrome (POIS) may cause symptoms when aroused, including adrenergic-type presentation: rapid breathing, paresthesia, palpitations, headaches, aphasia, nausea, itchy eyes, fever, muscle pain and weakness, and fatigue.
From the onset of arousal, symptoms can persist for up to a week in patients.
The cause of this condition is unknown; however, it is believed to be a pathology of either the immune system or autonomic nervous systems. It is defined as a rare disease by the National Institute of Health, but the prevalence is unknown. It is not thought to be psychiatric in nature, but it may present as anxiety relating to coital activities and may be incorrectly diagnosed as such. There is no known cure or treatment.

Erectile dysfunction
Erectile dysfunction (ED), or impotence, is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis. There are various underlying causes of ED, including damage to anatomical structures, psychological causes, medical disease, and drug use. Many of these causes are medically treatable.
Psychological ED can often be treated by almost anything that the patient believes in; there is a very strong placebo effect. Physical damage can be more difficult to treat. One leading physical cause of ED is continual or severe damage taken to the nervi erigentes, which can prevent or delay erection. These nerves course beside the prostate arising from the sacral plexus and can be damaged in prostatic and colorectal surgeries.
Diseases are also common causes of erectile dysfunctional. Diseases such as cardiovascular disease, multiple sclerosis, kidney failure, vascular disease, and spinal cord injury can cause erectile dysfunction. Cardiovascular disease can decrease blood flow to penile tissues, making it difficult to develop or maintain an erection.
Due to the shame and embarrassment felt by some with erectile dysfunction, the subject was taboo for a long time and is the focus of many urban legends. Folk remedies have long been advocated, with some being advertised widely since the 1930s. The introduction of perhaps the first pharmacologically effective remedy for impotence, sildenafil (trade name Viagra), in the 1990s caused a wave of public attention, propelled in part by the newsworthiness of stories about it and heavy advertising.
It is estimated that around 30 million men in the United States and 152 million men worldwide have erectile dysfunction. However, social stigma, low health literacy, and social taboos lead to under reporting which makes an accurate prevalence rate hard to determine.
The Latin term impotentia coeundi describes the inability to insert the penis into the vagina, and has been mostly replaced by more precise terms.
ED from vascular disease is seen mainly amongst older individuals who have atherosclerosis. Vascular disease is common in individuals who smoke or have diabetes, peripheral vascular disease, or hypertension. Any time blood flow to the penis is impaired, ED can occur.
Drugs are also a cause of erectile dysfunction. Individuals who take drugs that lower blood pressure, antipsychotics, antidepressants, sedatives, narcotics, antacids, or alcohol can have problems with sexual function and loss of libido.Hormone deficiency is a relatively rare cause of erectile dysfunction. In individuals with testicular failure, as in Klinefelter syndrome, or those who have had radiation therapy, chemotherapy, or childhood exposure to the mumps virus, the testes may fail to produce testosterone. Other hormonal causes of erectile failure include brain tumors, hyperthyroidism, hypothyroidism, or adrenal gland disorders.

Orgasm disorders
Anorgasmia
Anorgasmia is classified as persistent delays or absence of orgasm following a normal sexual excitement phase in at least 75% of sexual encounters.: 368  The disorder can have physical, psychological, or pharmacological origins. SSRI antidepressants are a common pharmaceutical culprit, as they can delay orgasm or eliminate it entirely. A common physiological cause of anorgasmia is menopause; one in three women report problems obtaining an orgasm during sexual stimulation following menopause.

Premature ejaculation
Premature ejaculation is when ejaculation occurs before the partner achieves orgasm, or a mutually satisfactory length of time has passed during intercourse. There is no correct length of time for intercourse to last, but generally, premature ejaculation is thought to occur when ejaculation occurs in under two minutes from the time of the insertion of the penis. For a diagnosis, the patient must have a chronic history of premature ejaculation, poor ejaculatory control, and the problem must cause feelings of dissatisfaction as well as distress for the patient, the partner, or both.Premature ejaculation has historically been attributed to psychological causes, but newer theories suggest that premature ejaculation may have an underlying neurobiological cause that may lead to rapid ejaculation.

Post-orgasmic disorders
Post-orgasmic disorders cause symptoms shortly after orgasm or ejaculation. Post-coital tristesse (PCT) is a feeling of melancholy and anxiety after sexual intercourse that lasts for up to two hours. Sexual headaches occur in the skull and neck during sexual activity, including masturbation, arousal or orgasm.
In men, POIS causes severe muscle pain throughout the body and other symptoms immediately following ejaculation. These symptoms last for up to a week. Some doctors speculate that the frequency of POIS "in the population may be greater than has been reported in the academic literature", and that many with POIS are undiagnosed.POIS may involve adrenergic symptoms: rapid breathing, paresthesia, palpitations, headaches, aphasia, nausea, itchy eyes, fever, muscle pain and weakness, and fatigue.
The etiology of this condition is unknown; however, it is believed to be a pathology of either the immune system or autonomic nervous systems. It is defined as a rare disease by the NIH, but the prevalence is unknown. It is not thought to be psychiatric in nature, but it may present as anxiety relating to coital activities and thus may be incorrectly diagnosed as such. There is no known cure or treatment.Dhat syndrome is another condition which occurs in men: it is a culture-bound syndrome which causes anxious and dysphoric mood after sex. It is distinct from the low-mood and concentration problems (acute aphasia) seen in POIS.

Sexual pain disorders
Sexual pain disorders in women include dyspareunia (painful intercourse) and vaginismus (an involuntary spasm of the muscles of the vaginal wall that interferes with intercourse).
Dyspareunia may be caused by vaginal dryness. Poor lubrication may result from insufficient excitement and stimulation, or from hormonal changes caused by menopause, pregnancy, or breastfeeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sex.
It is unclear exactly what causes vaginismus, but it is thought that past sexual trauma (such as rape or abuse) may play a role. Another female sexual pain disorder is vulvodynia, or vulvar vestibulitis when localized to the Vulval vestibule. In this condition, women experience burning pain during sex, which seems to be related to problems with the skin in the vulvar and vaginal areas. Its cause is unknown.
In men, structural abnormalities of the penis like Peyronies disease can make sexual intercourse difficult and/or painful. The disease is characterized by thick fibrous bands in the penis that lead to excessive curvature during erection. It has an incidence estimated at 0.4–3% or more, is most common in men 40–70, and has no certain cause. Risk factors include genetics, minor trauma (potentially during cystoscopy or transurethral resection of the prostate), chronic systemic vascular diseases, smoking, and alcohol consumption.Priapism is a painful erection that occurs for several hours and occurs in the absence of sexual stimulation. This condition develops when blood is trapped in the penis and is unable to drain. If the condition is not promptly treated, it can lead to severe scarring and permanent loss of erectile function. The disorder is most common in young men and children. Individuals with sickle-cell disease and those who use certain medications can often develop this disorder.

Causes
There are many factors which may result in a person experiencing a sexual dysfunction. These may result from emotional or physical causes. Emotional factors include interpersonal or psychological problems, which include depression, sexual fears or guilt, past sexual trauma, and sexual disorders.Sexual dysfunction is especially common among people who have anxiety disorders. Ordinary anxiety can cause erectile dysfunction in men without psychiatric problems, but clinically diagnosable disorders such as panic disorder commonly cause avoidance of intercourse and premature ejaculation. Pain during intercourse is often a comorbidity of anxiety disorders among women.Physical factors that can lead to sexual dysfunctions include the use of drugs, such as alcohol, nicotine, narcotics, stimulants, antihypertensives, antihistamines, and some psychotherapeutic drugs. For women, almost any physiological change that affects the reproductive system—premenstrual syndrome, pregnancy and the postpartum period, and menopause—can have an adverse effect on libido. Back injuries may also impact sexual activity, as can problems with an enlarged prostate gland, problems with blood supply, or nerve damage (as in sexual dysfunction after spinal cord injuries). Diseases such as diabetic neuropathy, multiple sclerosis, tumors, and, rarely, tertiary syphilis may also impact activity, as can the failure of various organ systems (such as the heart and lungs), endocrine disorders (thyroid, pituitary, or adrenal gland problems), hormonal deficiencies (low testosterone, other androgens, or estrogen), and some birth defects.
In the context of heterosexual relationships, one of the main reasons for the decline in sexual activity among these couples is the male partner experiencing erectile dysfunction. This can be very distressing for the male partner, causing poor body image, and it can also be a major source of low desire for these men. In aging women, it is natural for the vagina to narrow and atrophy. If a woman does not participate in sexual activity regularly (in particular, activities involving vaginal penetration), she will not be able to immediately accommodate a penis without risking pain or injury if she decides to engage in penetrative intercourse. This can turn into a vicious cycle that often leads to female sexual dysfunction.According to Emily Wentzell, American culture has anti-aging sentiments that have caused sexual dysfunction to become "an illness that needs treatment" instead of viewing it as a natural part of the aging process. Not all cultures seek treatment; for example, a population of men living in Mexico often accept ED as a normal part of their maturing sexuality.

Post SSRI sexual dysfunction
Sexual problems are common with SSRIs, which can cause anorgasmia, erectile dysfunction, diminished libido, genital numbness, and sexual anhedonia (pleasureless orgasm).  Poor sexual function is also one of the most common reasons people stop the medication. In some cases, symptoms of sexual dysfunction may persist after discontinuation of SSRIs.: 14  This combination of symptoms is sometimes referred to as Post-SSRI Sexual Dysfunction (PSSD).

Pelvic floor dysfunction
Pelvic floor dysfunction can be an underlying cause of sexual dysfunction in both women and men, and is treatable by pelvic floor physical therapy, a type of physical therapy designed to restore the health and function of the pelvic floor and surrounding areas.

Female sexual dysfunction
Several theories have looked at female sexual dysfunction, from medical to psychological perspectives. Three social psychological theories include: the self-perception theory, the overjustification hypothesis, and the insufficient justification hypothesis:

Self-perception theory: people make attributions about their own attitudes, feelings, and behaviours by relying on their observations of external behaviours and the circumstances in which those behaviours occur
Overjustification hypothesis: when an external reward is given to a person for performing an intrinsically rewarding activity, the persons intrinsic interest will decrease
Insufficient justification: based on the classic cognitive dissonance theory (inconsistency between two cognitions or between a cognition and a behavior will create discomfort), this theory states that people will alter one of the cognitions or behaviours to restore consistency and reduce distressThe importance of how a woman perceives her behavior should not be underestimated. Many women perceive sex as a chore as opposed to a pleasurable experience, and they tend to consider themselves sexually inadequate, which in turn does not motivate them to engage in sexual activity. Several factors influence a womens perception of her sexual life. These can include race, gender, ethnicity, educational background, socioeconomic status, sexual orientation, financial resources, culture, and religion. Cultural differences are also present in how women view menopause and its impact on health, self-image, and sexuality. A study found that African American women are the most optimistic about menopausal life; Caucasian women are the most anxious, Asian women are the most inhibited about their symptoms, and Hispanic women are the most stoic.About one-third of the women experienced sexual dysfunction, which may lead to these womens loss of confidence in their sexual lives. Since these women have sexual problems, their sexual lives with their partners can become a burden without pleasure, and may eventually lose complete interest in sexual activity. Some of the women found it hard to be aroused mentally, while others had physical problems. Several factors can affect female dysfunction, such as situations in which women do not trust their sex partners, the environment where sex occurs being uncomfortable, or an inability to concentrate on the sexual activity due to a bad mood or burdens from work. Other factors include physical discomfort or difficulty in achieving arousal, which could be caused by aging or changes in the bodys condition.Sexual assault has been associated with excessive menstrual bleeding, genital burning, and painful intercourse (attributable to disease, injury, or otherwise), medically unexplained dysmenorrhea, menstrual irregularity, and lack of sexual pleasure. Physically violent assaults and those committed by strangers were most strongly related to reproductive symptoms. Multiple assaults, assaults accomplished by persuasion, spousal assault, and completed intercourse were most strongly related to sexual symptoms. Assault was occasionally associated more strongly with reproductive symptoms among women with lower income or less education, possibly because of economic stress or differences in assault circumstances. Associations with unexplained menstrual irregularity were strongest among African American women; ethnic differences in reported circumstances of assault appeared to account for these differences. Assault was associated with sexual indifference only among Latinas.

Menopause
The most prevalent of female sexual dysfunctions that have been linked to menopause include lack of desire and libido; these are predominantly associated with hormonal physiology. Specifically, the decline in serum estrogens causes these changes in sexual functioning. Androgen depletion may also play a role, but current knowledge about this is less clear. The hormonal changes that take place during the menopausal transition have been suggested to affect womens sexual response through several mechanisms, some more conclusive than others.

Aging in women
Whether or not aging directly affects womens sexual functioning during menopause is controversial. However, many studies, including Hayes and Dennersteins critical review, have demonstrated that aging has a powerful impact on sexual function and dysfunction in women, specifically in the areas of desire, sexual interest, and frequency of orgasm. In addition, Dennerstien and colleagues found that the primary predictor of sexual response throughout menopause is prior sexual functioning, which means that it is important to understand how the physiological changes in men and women can affect sexual desire. Despite the apparent negative impact that menopause can have on sexuality and sexual functioning, sexual confidence and well-being can improve with age and menopausal status. The impact that a relationship status can have on quality of life is often underestimated.
Testosterone, along with its metabolite dihydrotestosterone, is important to normal sexual function in men and women. Dihydrotestosterone is the most prevalent androgen in both men and women. Testosterone levels in women at age 60 are on average about half of what they were before the women were 40. Although this decline is gradual for most women, those who have undergone bilateral oophorectomy experience a sudden drop in testosterone levels, as the ovaries produce 40% of the bodys circulating testosterone.Sexual desire has been related to three separate components: drive, beliefs and values, and motivation. Particularly in postmenopausal women, drive fades and is no longer the initial step in a womans sexual response.

Diagnosis
List of disorders
DSM
The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders lists the following sexual dysfunctions:

Hypoactive sexual desire disorder (see also asexuality, which is not classified as a disorder)
Sexual aversion disorder (avoidance of or lack of desire for sexual intercourse)
Female sexual arousal disorder (failure of normal lubricating arousal response)
Male erectile disorder
Female orgasmic disorder (see anorgasmia)
Male orgasmic disorder (see anorgasmia)
Premature ejaculation
Dyspareunia
VaginismusAdditional DSM sexual disorders that are not sexual dysfunctions include:

Paraphilias
PTSD due to genital mutilation or childhood sexual abuse

Other sexual problems
Sexual dissatisfaction (non-specific)
Lack of sexual desire
Anorgasmia
Impotence
Sexually transmitted diseases
Delay or absence of ejaculation, despite adequate stimulation
Inability to control timing of ejaculation
Inability to relax vaginal muscles enough to allow intercourse
Inadequate vaginal lubrication preceding and during intercourse
Burning pain on the vulva or in the vagina with contact to those areas
Unhappiness or confusion related to sexual orientation
Transsexual and transgender people may have sexual problems before or after surgery.
Persistent sexual arousal syndrome
Sexual addiction
Hypersexuality
All forms of female genital cutting
Post-orgasmic diseases, such as Dhat syndrome, PCT, POIS, and sexual headacheS.

Treatment
Males
Several decades ago, the medical community believed most sexual dysfunction cases were related to psychological issues.  Although this may be true for a portion of men, the vast majority of cases have now been identified to have a physical cause or correlation. If the sexual dysfunction is deemed to have a psychological component or cause, psychotherapy can help. Situational anxiety arises from an earlier bad incident or lack of experience, and often leads to development of fear towards sexual activity and avoidance which enters a cycle of increased anxiety and desensitization of the penis. In some cases, erectile dysfunction may be due to marital disharmony. Marriage counseling sessions are recommended in this situation.
Lifestyle changes such as discontinuing tobacco smoking or substance use can also treat some types of ED. Several oral medications like Viagra, Cialis, and Levitra have become available to alleviate ED and have become first line therapy. These medications provide an easy, safe, and effective treatment solution for approximately 60% of men. In the rest, the medications may not work because of wrong diagnosis or chronic history.Another type of medication that is effective in roughly 85% of men is called intracavernous pharmacotherapy, which involves injecting a vasodilator drug directly into the penis to stimulate an erection. This method has an increased risk of priapism if used in conjunction with other treatments, and localized pain.Premature ejaculations are treated by behavioural techniques Squeeze technique and Stop Start Technique. In Squeeze technique the area between head and shaft of penis is pressed using index finger and thumb just before ejaculation. In Stop Start Technique the male partner stops having sexual intercourse just before ejaculation and waits for the sense of ejaculation to pass away. Both Techniques are repeated many times.When conservative therapies fail, are an unsatisfactory treatment option, or are contraindicated for use, the insertion of a penile implant may be selected by the patient. Technological advances have made the insertion of a penile implant a safe option for the treatment of ED, which provides the highest patient and partner satisfaction rates of all available ED treatment options.Pelvic floor physical therapy has been shown to be a valid treatment for men with sexual problems and pelvic pain.The 2020 guidelines from the American College of Physicians support the discussion of testosterone treatment in adult men with age-related low levels of testosterone who have sexual dysfunction. They recommend yearly evaluation regarding possible improvement and, if none, to discontinue testosterone; intramuscular treatments should be considered rather than transdermal treatments due to costs and since the effectiveness and harm of either method is similar. Testosterone treatment for reasons other than possible improvement of sexual dysfunction may not be recommended.

Females
In 2015, flibanserin was approved in the US to treat decreased sexual desire in women. While it is effective for some women, it has been criticized for its limited efficacy, and has many warnings and contraindications that limit its use. Women experiencing pain with intercourse are often prescribed pain relievers or desensitizing agents; others are prescribed vaginal lubricants. Many women with sexual dysfunction are also referred to a counselor or sex therapist.

Menopause
Estrogens are responsible for the maintenance of collagen, elastic fibers, and vasculature of the urogenital tract, all of which are important in maintaining vaginal structure and functional integrity; they are also important for maintaining vaginal pH and moisture levels, both of which help to keep the tissues lubricated and protected. Prolonged estrogen deficiency leads to atrophy, fibrosis, and reduced blood flow to the urogenital tract, which cause menopausal symptoms such as vaginal dryness and pain related to sexual activity and/or intercourse. It has been consistently demonstrated that women with lower sexual functioning have lower estradiol levels. Women experiencing vaginal dryness who cannot use commercial lubricants may be able to use coconut oil as an alternative.Androgen therapy for hypoactive sexual desire disorder has a small benefit but its safety is not known. It is not approved as a treatment in the United States. It is more commonly used among women who have had an oophorectomy or are in a postmenopausal state. However, like most treatments, this is also controversial. One study found that after a 24-week trial, women taking androgens had higher scores of sexual desire compared to a placebo group. As with all pharmacological drugs, there are side effects in using androgens, which include hirsutism, acne, polycythaemia, increased high-density lipoproteins, cardiovascular risks, and endometrial hyperplasia. Alternative treatments include topical estrogen creams and gels that can be applied to the vulva or vagina area to treat vaginal dryness and atrophy.

Research
In modern times, clinical study of sexual problems is usually dated back no earlier than 1970 when Masters and Johnsons Human Sexual Inadequacy was published. It was the result of over a decade of work at the Reproductive Biology Research Foundation in St. Louis, involving 790 cases. The work grew from Masters and Johnsons earlier Human Sexual Response (1966).
Prior to Masters and Johnson, the clinical approach to sexual problems was largely derived from Sigmund Freud. It was held to be psychopathology and approached with a certain pessimism regarding the chance of help or improvement. Sexual problems were merely symptoms of a deeper malaise, and the diagnostic approach was from the psychopathological viewpoint. There was little distinction between difficulties in function and variations nor between perversion and problems </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Optic nerve hypoplasia and can you explain it in depth? [/INST] Optic nerve hypoplasia (ONH) is a medical condition arising from the underdevelopment of the optic nerve(s). This condition is the most common congenital optic nerve anomaly.  The optic disc appears abnormally small, because not all the optic nerve axons have developed properly. It is often associated with endocrinopathies (hormone deficiencies), developmental delay, and brain malformations. The optic nerve, which is responsible for transmitting visual signals from the retina to the brain, has approximately 1.2 million nerve fibers in the average person. In those diagnosed with ONH, however, there are noticeably fewer nerves.

Symptoms
ONH may be found in isolation or in conjunction with myriad functional and anatomic abnormalities of the central nervous system. Nearly 80% of those affected with ONH will experience hypothalamic dysfunction and/or impaired development of the brain, regardless of MRI findings or severity of ONH.

Vision
ONH can be unilateral (in one eye) or bilateral (in both eyes), although it presents most often bilaterally (80%). Because the unilateral cases tend to have better vision, they are typically diagnosed at a later age than those with bilateral ONH. Visual acuity can range from no light perception to near-normal vision.
Children diagnosed with ONH generally present with vision problems which include nystagmus (involuntary movement of the eyes), which tends to develop at 1 to 3 months and/or strabismus (inability to align both eyes simultaneously), manifested during the first year of life.
The majority of children affected experience improvement in vision during the first few years of life, though the reason for this occurrence is unknown. There have been no reported cases of decline in vision due to ONH.

Neuroradiographic abnormalities
Estimates of cerebral malformations vary from 39% to 90% of children with ONH. Abnormalities evident via neuroradiography can include agenesis (absence) or hypoplasia of the corpus callosum, absence or incomplete development of the septum pellucidum, malformations of the pituitary gland, schizencephaly, cortical heterotopia, white matter hypoplasia, pachygyria, and holoprosencephaly. Hypoplasia of the corpus callosum, often in conjunction with other major malformations, is significantly associated with poor and delayed developmental outcome.ONH is often referred to as septo-optic dysplasia, a term that refers to agenesis of the septum pellucidum. It is now clear that the absence of the septum pellucidum does not correlate with the associated symptoms of ONH.

Hypothalamic dysfunction
Dysfunction of the hypothalamus results in loss of regulation over behavior and function of the pituitary gland (master gland). Hypopituitarism is present in 75% to 80% of patients with ONH. The anterior pituitary gland contributes to growth, metabolism, and sexual development.  The most common pituitary endocrinopathies are growth hormone (GH) deficiency (70%), hypothyroidism (43%), adrenal insufficiency (27%), and diabetes insipidus (5%).Absence of GH may often be indicated by short stature, although this is not always the case. Other indicators of GH deficiency may include hypoglycemic events (including seizures), prolonged jaundice, micropenis in boys, and delayed dentition. Testing for GH may involve blood tests (IGF-1 and IGFBP-3), growth hormone stimulation test, or bone age x-ray of the hand or wrist (or body for children younger than 2 years).
A poorly functioning pituitary gland may also cause a lack of thyroid hormone, leading to central hypothyroidism. Thyroid hormone is critical for growth and brain development, especially during the first few weeks to months of life. Children with untreated hypothyroidism are at high risk of mental retardation; thus, early detection is crucial. Central hypothyroidism can be diagnosed by a low or normal thyroid-stimulating hormone (TSH) in the presence of a low level of free T4. Free T-4 should be checked annually for at least four years.Cortisol is made in times of stress.  Approximately one-quarter of patients with ONH have adrenal insufficiency, meaning they do not produce enough cortisol on a daily basis or in stressful situations.Imbalances in sex hormone may result in a delay in sexual development (puberty) or precocious puberty. Sex hormones may be tested from birth to 6 months of age (during a mini-puberty).
Hyperprolactinemia (an excess of prolactin) often occurs in conjunction with ONH and indicates either dysfunction of the hypothalamus or a disconnect between the hypothalamus and pituitary gland. Hyperprolactinemia often correlates with development of obesity in children with ONH.The posterior pituitary gland produces anti-diuretic hormone (ADH), which controls outflow of water from the body by urine. ADH deficiency, also known as diabetes insipidus (DI), results in dehydration and high sodium levels in the body from excessive urination. Testing for DI involves blood and urine testing, including water deprivation tests, to determine ADH creation levels by the body. DI may be treated with a medication called desmopressin acetate (DDAVP).Oxytocin is also produced in the posterior pituitary gland. Though best known for its role in childbirth and lactation, oxytocin has also been found to have a role in human bonding, increase in trust, and decrease in fear.
Hypothalamic dysfunction may also result in problems with feeding, sleep, and body temperature regulation.  Feeding behaviors in children with ONH often include hyperphagia (overeating), resulting in obesity; or hypophagia (reduced food intake) with or without weight loss. Children also frequently experience aversion to specific textures of food. Disturbance of circadian sleep rhythm, resulting in abnormal sleep-wake cycles, is noted in one-third of children with ONH. This disturbance could result in behavioral problems and disruption of family life.

Development
More than 70% of children with ONH experience developmental delay, ranging from isolated focal defects to delay in all areas of development (global delay). Motor delay is most common (75%) and communication delay is least common (44%). Predictors of significantly delayed development include hypoplasia or agenesis of the corpus callosum and hypothyroidism. The absence of the septum pellucidum does not predict developmental delay. Delays may occur in unilateral (39%) as well as bilateral (78%) cases.

Cause
Genetic risks
Mutations of genes involved in transcription regulation, chromatin remodelling, α-dystroglycan glycosylation, cytoskeleton and scaffolding protein, RNA splicing, and the MAP kinase signalling pathway are currently known to cause ONH. Many transcription factors for eye development are also involved in the morphogenesis of forebrain, which may explain why ONH is commonly a part of a syndrome involving brain malformations.ONH impacts all ethnic groups, although in the United States, occurrence is lower in persons of Asian descent. To date, there have been few reports of ONH occurrence in Asian countries, although it is uncertain why this is so.

Gestational and exposure history
Although many perinatal and prenatal risk factors for ONH have been suggested, the predominant, enduring, most frequent risk factors are young maternal age and primiparity (the affected child being the first child born to the mother). Increased frequency of delivery by caesarean section and fetal/neonatal complications, preterm labor, gestational vaginal bleeding, low maternal weight gain, and weight loss during pregnancy are also associated with ONH.

Diagnosis
ONH is diagnosed by ophthalmoscopic examination. Patients with ONH exhibit an optic nerve that appears smaller than normal and different in appearance from small optic nerves caused by other eye conditions such as optic (nerve) atrophy.DM:DD ratio has proven to be a clinically useful measurement to help diagnose optic nerve hypoplasia. Where "DM" represents the distance from Disk to Macula, and "DD" represents Disc Diameter.
The mean disc diameter (DD) is (Vertical diameter of Disc+Horizontal diameter of Disc) divided by 2. The distance between the center of the disc and the macula is DM.
Interpretation:  When the ratio of DM to DD is greater than 3, ONH is suspected, and when it is greater than 4, Optic Nerve Hypoplasia is definite.

Treatment
There is no cure for ONH; however, many therapeutic interventions exist for the care of its symptoms. These may include hormone therapy for hypopituitarism,  occupational, physical, and/or speech therapy for other issues, and services of a teacher for students with blindness/visually impairment. Special attention should be paid to early development of oral motor skills and acclimation to textured foods for children with texture aversion, or who are otherwise resistant to eating.Sleep dysfunction can be ameliorated using melatonin in the evening in order to adjust a childs circadian clock.Treatment for strabismus may include patching of the better eye, which may result in improved vision in the worse eye; however, this should be reserved for cases in which the potential for vision improvement in both eyes is felt to be good. Surgery to align the eyes can be performed once children with strabismus develop equal visual acuity in both eyes, most often after the age of three </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 Ischemic optic neuropathy 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 Diabetes insipidus and can you explain it in depth? [/INST] Diabetes insipidus (DI), recently renamed to Arginine Vasopressin Deficiency (AVP-D) and Arginine Vasopressin Resistance (AVP-R), is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produced can be nearly 20 liters per day. Reduction of fluid has little effect on the concentration of the urine. Complications may include dehydration or seizures.There are four types of DI, each with a different set of causes. Central DI (CDI) is due to a lack of the hormone vasopressin (antidiuretic hormone). This can be due to injury to the hypothalamus or pituitary gland or genetics. Nephrogenic DI (NDI) occurs when the kidneys do not respond properly to vasopressin. Dipsogenic DI is a result of excessive fluid intake due to damage to the hypothalamic thirst mechanism. It occurs more often in those with certain psychiatric disorders or on certain medications. Gestational DI occurs only during pregnancy. Diagnosis is often based on urine tests, blood tests and the fluid deprivation test. Diabetes insipidus is unrelated to diabetes mellitus and the conditions have a distinct mechanism, though both can result in the production of large amounts of urine.Treatment involves drinking sufficient fluids to prevent dehydration. Other treatments depend on the type. In central and gestational DI, treatment is with desmopressin. Nephrogenic DI may be treated by addressing the underlying cause or by the use of a thiazide, aspirin or ibuprofen. The number of new cases of diabetes insipidus each year is 3 in 100,000. Central DI usually starts between the ages of 10 and 20 and occurs in males and females equally. Nephrogenic DI can begin at any age. The term "diabetes" is derived from the Greek word meaning siphon.

Signs and symptoms
Excessive urination and extreme thirst and increased fluid intake (especially for cold water and sometimes ice or ice water) are typical for DI. The symptoms of excessive urination and extreme thirst are similar to what is seen in untreated diabetes mellitus, with the distinction that the urine does not contain glucose. Blurred vision is a rarity. Signs of dehydration may also appear in some individuals, since the body cannot conserve much (if any) of the water it takes in.Extreme urination continues throughout the day and the night. In children, DI can interfere with appetite, eating, weight gain and growth, as well. They may present with fever, vomiting or diarrhea. Adults with untreated DI may remain healthy for decades as long as enough water is consumed to offset the urinary losses. However, there is a continuous risk of dehydration and loss of potassium that may lead to hypokalemia.

Cause
The several forms of diabetes insipidus are:

Central
Central (or Neurogenic) DI has many possible causes. According to the literature, the principal causes of central DI and their oft-cited approximate frequencies are as follows:

Idiopathic – 30%
Malignant or benign tumors of the brain or pituitary – 25%
Cranial surgery – 20%
Head trauma – 16%

Nephrogenic
Nephrogenic diabetes insipidus is due to the inability of the kidney to respond normally to vasopressin.

Dipsogenic
Dipsogenic DI or primary polydipsia results from excessive intake of fluids as opposed to deficiency of arginine vasopressin. It may be due to a defect or damage to the thirst mechanism, located in the hypothalamus, or due to mental illness. Treatment with desmopressin may lead to water intoxication.

Gestational
Gestational DI occurs only during pregnancy and the postpartum period. During pregnancy, women produce vasopressinase in the placenta, which breaks down antidiuretic hormone (ADH). Gestational DI is thought to occur with excessive production and/or impaired clearance of vasopressinase.Most cases of gestational DI can be treated with desmopressin (DDAVP), but not vasopressin. In rare cases, however, an abnormality in the thirst mechanism causes gestational DI, and desmopressin should not be used.Diabetes insipidus is also associated with some serious diseases of pregnancy, including pre-eclampsia, HELLP syndrome and acute fatty liver of pregnancy. These cause DI by impairing hepatic clearance of circulating vasopressinase. It is important to consider these diseases if a woman presents with diabetes insipidus in pregnancy, because their treatments require delivery of the baby before the disease will improve. Failure to treat these diseases promptly can lead to maternal or perinatal mortality.

Pathophysiology
Electrolyte and volume homeostasis is a complex mechanism that balances the bodys requirements for blood pressure and the main electrolytes sodium and potassium. In general, electrolyte regulation precedes volume regulation. When the volume is severely depleted, however, the body will retain water at the expense of deranging electrolyte levels.The regulation of urine production occurs in the hypothalamus, which produces ADH in the supraoptic and paraventricular nuclei. After synthesis, the hormone is transported in neurosecretory granules down the axon of the hypothalamic neuron to the posterior lobe of the pituitary gland, where it is stored for later release. In addition, the hypothalamus regulates the sensation of thirst in the ventromedial nucleus by sensing increases in serum osmolarity and relaying this information to the cortex.Neurogenic/central DI results from a lack of ADH; occasionally it can present with decreased thirst as regulation of thirst and ADH production occur in close proximity in the hypothalamus. It is encountered as a result of hypoxic encephalopathy, neurosurgery, autoimmunity or cancer, or sometimes without an underlying cause (idiopathic).The main effector organ for fluid homeostasis is the kidney. ADH acts by increasing water permeability in the collecting ducts and distal convoluted tubules; specifically, it acts on proteins called aquaporins and more specifically aquaporin 2 in the following cascade. When released, ADH binds to V2 G-protein coupled receptors within the distal convoluted tubules, increasing cyclic AMP, which couples with protein kinase A, stimulating translocation of the aquaporin 2 channel stored in the cytoplasm of the distal convoluted tubules and collecting ducts into the apical membrane. These transcribed channels allow water into the collecting duct cells. The increase in permeability allows for reabsorption of water into the bloodstream, thus concentrating the urine.
Nephrogenic DI results from lack of aquaporin channels in the distal collecting duct (decreased surface expression and transcription). It is seen in lithium toxicity, hypercalcemia, hypokalemia, or release of ureteral obstruction. Therefore, a lack of ADH prevents water reabsorption and the osmolarity of the blood increases. With increased osmolarity, the osmoreceptors in the hypothalamus detect this change and stimulate thirst. With increased thirst, the person now experiences a polydipsia and polyuria cycle.
Hereditary forms of diabetes insipidus account for less than 10% of the cases of diabetes insipidus seen in clinical practice.

Diagnosis
To distinguish DI from other causes of excess urination, blood glucose levels, bicarbonate levels, and calcium levels need to be tested. Measurement of blood electrolytes can reveal a high sodium level (hypernatremia as dehydration develops). Urinalysis demonstrates a dilute urine with a low specific gravity. Urine osmolarity and electrolyte levels are typically low.A fluid deprivation test is another way of distinguishing DI from other causes of excessive urination. If there is no change in fluid loss, giving desmopressin can determine if DI is caused by:

a defect in ADH production
a defect in the kidneys response to ADHThis test measures the changes in body weight, urine output, and urine composition when fluids are withheld to induce dehydration. The bodys normal response to dehydration is to conserve water by concentrating the urine. Those with DI continue to urinate large amounts of dilute urine in spite of water deprivation. In primary polydipsia, the urine osmolality should increase and stabilize at above 280 mOsm/kg with fluid restriction, while a stabilization at a lower level indicates diabetes insipidus. Stabilization in this test means, more specifically, when the increase in urine osmolality is less than 30 Osm/kg per hour for at least three hours. Sometimes measuring blood levels of ADH toward the end of this test is also necessary, but is more time-consuming to perform.To distinguish between the main forms, desmopressin stimulation is also used; desmopressin can be taken by injection, a nasal spray, or a tablet. While taking desmopressin, a person should drink fluids or water only when thirsty and not at other times, as this can lead to sudden fluid accumulation in the central nervous system. If desmopressin reduces urine output and increases urine osmolarity, the hypothalamic production of ADH is deficient, and the kidney responds normally to exogenous vasopressin (desmopressin). If the DI is due to kidney pathology, desmopressin does not change either urine output or osmolarity (since the endogenous vasopressin levels are already high).Whilst diabetes insipidus usually occurs with polydipsia, it can also rarely occur not only in the absence of polydipsia but in the presence of its opposite, adipsia (or hypodipsia). "Adipsic diabetes insipidus" is recognised as a marked absence of thirst even in response to hyperosmolality. In some cases of adipsic DI, the person may also fail to respond to desmopressin.If central DI is suspected, testing of other hormones of the pituitary, as well as magnetic resonance imaging, particularly a pituitary MRI, is necessary to discover if a disease process (such as a prolactinoma, or histiocytosis, syphilis, tuberculosis or other tumor or granuloma) is affecting pituitary function. Most people with this form have either experienced past head trauma or have stopped ADH production for an unknown reason.

Treatment
Treatment involves drinking sufficient fluids to prevent dehydration. Other treatments depend on the type. In central and gestational DI treatment is with desmopressin. Nephrogenic DI may be treated by addressing the underlying cause or the use of a thiazide, aspirin, or ibuprofen.

Central
Central DI and gestational DI respond to desmopressin which is given as intranasal or oral tablets. Carbamazepine, an anticonvulsive medication, has also had some success in this type of DI. Also, gestational DI tends to abate on its own four to six weeks following labor, though some women may develop it again in subsequent pregnancies. In dipsogenic DI, desmopressin is not usually an option.

Nephrogenic
Desmopressin will be ineffective in nephrogenic DI which is treated by reversing the underlying cause (if possible) and replacing the free water deficit. A thiazide diuretic, such as chlorthalidone or hydrochlorothiazide, can be used to create mild hypovolemia which encourages salt and water uptake in proximal tubule and thus improve nephrogenic diabetes insipidus. Amiloride has additional benefit of blocking Na uptake. Thiazide diuretics are sometimes combined with amiloride to prevent hypokalemia caused by the thiazides </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 Tabes dorsalis and can you explain it in depth? [/INST] Tabes dorsalis is a late consequence of neurosyphilis, characterized by the slow degeneration (specifically, demyelination) of the neural tracts primarily in the dorsal root ganglia of the spinal cord (nerve root). These patients have lancinating nerve root pain which is aggravated by coughing, and features of sensory ataxia with ocular involvement.

Signs and symptoms
Signs and symptoms may not appear for decades after the initial infection and include weakness, diminished reflexes, paresthesias (shooting and burning pains, pricking sensations, and formication), hypoesthesias (abnormally diminished sense of touch), tabetic gait (locomotor ataxia), progressive degeneration of the joints, loss of coordination, episodes of intense pain and disturbed sensation (including glossodynia), personality changes, urinary incontinence, dementia, deafness, visual impairment, positive Rombergs test, and impaired response to light (Argyll Robertson pupil). The skeletal musculature is hypotonic due to destruction of the sensory limb of the spindle reflex. The deep tendon reflexes are also diminished or absent; for example, the "knee jerk" or patellar reflex may be lacking (Westphals sign).  A complication of tabes dorsalis can be transient neuralgic paroxysmal pain affecting the eyes and the ophthalmic areas, previously called "Pels crises" after Dutch physician P.K. Pel </s>