<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 High-grade prostatic intraepithelial neoplasia and can you explain it in depth? [/INST] High-grade prostatic intraepithelial neoplasia (HGPIN) is an abnormality of prostatic glands and believed to precede the development of prostate adenocarcinoma (the most common form of prostate cancer).It may be referred to simply as prostatic intraepithelial neoplasia (PIN). It is considered to be a pre-malignancy, or carcinoma in situ, of the prostatic glands.

Signs and symptoms
HGPIN in isolation is asymptomatic.  It is typically discovered in prostate biopsies taken to rule-out prostate cancer and very frequently seen in prostates removed for prostate cancer.

Relation to prostate cancer
There are several reasons why PIN is the most likely prostate cancer precursor. PIN is more common in men with prostate cancer. High grade PIN can be found in 85 to 100% of radical prostatectomy specimens, nearby or even in connection with prostate cancer. It tends to occur in the peripheral zone of the prostate. With age, it becomes increasingly multifocal, like prostate cancer. Molecular analysis has shown that high grade PIN and prostate cancer share many genetic abnormalities.The risk for men with high grade PIN of being diagnosed with prostate cancer after repeat biopsy has decreased since the introduction of biopsies at more than six locations (traditional sextant biopsies).

Histology
HGPIN typically has one of four different histologic patterns:
tufted,
micropapillary,
cribriform and,
flat.Its cytologic features are that of prostatic adenocarcinoma:

presence of nucleoli,
increased nuclear-to-cytoplasmic ratio and,
increased nuclear size.Microscopically, PIN is a collection of irregular, atypical epithelial cells. The architecture of the glands and ducts remains normal. The epithelial cells proliferate and crowding results in a pseudo-multilayer appearance. They remain fully contained within a prostate acinus (the berry-shaped termination of a gland, where the secretion is produced) or duct. The latter can be demonstrated with special staining techniques (immunohistochemistry for cytokeratins) to identify the basal cells forming the supporting layer of the acinus. In prostate cancer, the abnormal cells spread beyond the boundaries of the acinus and form clusters without basal cells. In HGPIN, the basal cell layer is disrupted but present. PIN is primarily found in the peripheral zone of the prostate (75-80%), rarely in the transition zone (10-15%) and very rarely in the central zone (5%), a distribution that parallels the zonal distribution for prostate carcinoma.Because it is thought to be a premalignant state, PIN is often considered the prostate equivalent of what is called carcinoma in situ (localized cancer) in other organs. However, PIN differs from carcinoma in situ in that it may remain unchanged or even spontaneously regress.Several architectural variants of PIN have been described, and many cases have multiple patterns </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 Ventilator-associated lung injury and can you explain it in depth? [/INST] Ventilator-associated lung injury (VALI) is an acute lung injury that develops during mechanical ventilation and is termed ventilator-induced lung injury (VILI) if it can be proven that the mechanical ventilation caused the acute lung injury. In contrast, ventilator-associated lung injury (VALI) exists if the cause cannot be proven. VALI is the appropriate term in most situations because it is virtually impossible to prove what actually caused the lung injury in the hospital.

Cause
It is generally regarded, based on animal models and human studies, that volutrauma is the most harmful aspect of mechanical ventilation. This may be regarded as the over-stretching of the airways and alveoli.During mechanical ventilation, the flow of gas into the lung will take the path of least resistance. Areas of the lung that are collapsed (atelectasis) or filled with secretions will be underinflated, while those areas that are relatively normal will be overinflated. These areas will become overdistended and injured. This may be reduced by using smaller tidal volumes.During positive pressure ventilation, atelectatic regions will inflate, however, the alveoli will be unstable and will collapse during the expiratory phase of the breath (atelectotrauma) </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 Lentigo maligna melanoma and can you explain it in depth? [/INST] Lentigo maligna melanoma is a melanoma that has evolved from a lentigo maligna,: 695  as seen as a lentigo maligna with melanoma cells invading below the boundaries of the epidermis. They are usually found on chronically sun damaged skin such as the face and the forearms of the elderly.
Lentigo maligna is the non-invasive skin growth that some pathologists consider to be a melanoma-in-situ.  A few pathologists do not consider lentigo maligna to be a melanoma at all, but a precursor to melanomas.  Once a lentigo maligna becomes a lentigo maligna melanoma, it is treated as if it were an invasive melanoma.

Presentation
An invasive tumor arising from a classical lentigo maligna.  Usually a darkly pigmented raised papule or nodule, arising from a patch of irregularly pigmented flat brown to dark brown lesion of sun exposed skin of the face or arms in an elderly patient.

Diagnosis
The first problem is difficulty. As lentigo malignas often present on severely sun damaged skin, it is frequently found amongst numerous pigmented lesions – thin seborrheic keratoses, lentigo senilis, lentigines. It is difficult to distinguish these lesions with the naked eye alone, and even with some difficulty using dermatoscopy. As the lentigo maligna is often very large, it often merges with, or encompasses other skin tumors – such as lentigines, melanocytic nevi, and seborrheic keratosis.
The second difficulty   is the biopsy technique </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 Chronic actinic dermatitis and can you explain it in depth? [/INST] Chronic actinic dermatitis is a condition where a subjects skin becomes inflamed due to a reaction to sunlight or artificial light. Patients often have other related conditions of the skin that cause dermatitis in response to a variety of stimuli (e.g., flowers, sunscreens, cosmetics, etc.).

Symptoms
Once affected, the symptoms may not show for several days </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 Terson syndrome 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 Acute abdomen and can you explain it in depth? [/INST] An acute abdomen refers to a sudden, severe abdominal pain. It is in many cases a medical emergency, requiring urgent and specific diagnosis. Several causes need immediate surgical treatment.

Differential diagnosis
The differential diagnosis of acute abdomen includes:
Acute appendicitis
Acute peptic ulcer and its complications
Acute cholecystitis
Acute pancreatitis
Acute intestinal ischemia (see section below)
Acute diverticulitis
Ectopic pregnancy with tubal rupture
Ovarian torsion
Acute peritonitis (including hollow viscus perforation)
Acute ureteric colic
Bowel volvulus
Bowel obstruction
Acute pyelonephritis
Adrenal crisis
Biliary colic
Abdominal aortic aneurysm
Familial Mediterranean fever
Hemoperitoneum
Ruptured spleen
Kidney stone
Sickle cell anaemia
Carcinoid

Peritonitis
Acute abdomen is occasionally used synonymously with peritonitis. While this is not entirely incorrect, peritonitis is the more specific term, referring to inflammation of the peritoneum. It manifests on physical examination as rebound tenderness, or pain upon removal of pressure more than on application of pressure to the abdomen. Peritonitis may result from several of the above diseases, notably appendicitis and pancreatitis. While rebound tenderness is commonly associated with peritonitis, the most specific finding is rigidity.

Ischemic acute abdomen
Vascular disorders are more likely to affect the small bowel than the large bowel </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 Pityriasis amiantacea and can you explain it in depth? [/INST] Pityriasis amiantacea is an eczematous condition of the scalp in which thick tenaciously adherent scale infiltrates and surrounds the base of a group of scalp hairs. It does not result in scarring or alopecia.: 647 Pityriasis amiantacea was first described by Alibert in 1832 </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 Vaginal yeast infection and can you explain it in depth? [/INST] Vaginal yeast infection, also known as candidal vulvovaginitis and vaginal thrush, is excessive growth of yeast in the vagina that results in irritation. The most common symptom is vaginal itching, which may be severe. Other symptoms include burning with urination, a thick, white vaginal discharge that typically does not smell bad, pain during  sex, and redness around the vagina. Symptoms often worsen just before a womans period.
Vaginal yeast infections are due to excessive growth of Candida. These yeast are normally present in the vagina in small numbers. Vaginal yeast infections are typically caused by the yeast species Candida albicans. Candida albicans is a common fungus often harbored in the mouth, digestive tract, or vagina without causing adverse symptoms. The causes of excessive Candida growth are not well understood, but some predisposing factors have been identified.
It is not classified as a sexually transmitted infection; however, it may occur more often in those who are frequently sexually active. Risk factors include taking antibiotics, pregnancy, diabetes, and HIV/AIDS. Tight clothing, type of underwear, and personal hygiene do not appear to be factors. Diagnosis is by testing a sample of vaginal discharge. As symptoms are similar to that of the sexually transmitted infections, chlamydia and gonorrhea, testing may be recommended.
Treatment is with an antifungal medication. This may be either as a cream such as clotrimazole or with oral medications such as fluconazole. Despite the lack of evidence, wearing cotton underwear and loose fitting clothing is often recommended as a preventive measure. Avoiding douching and scented hygiene products is also recommended.  Probiotics have not been found to be useful for active infections.
Around 75% of women have at least one vaginal yeast infection at some point in their lives, while nearly half have at least two. Around 5% have more than three infections in a single year. It is the second most common cause of vaginal inflammation after bacterial vaginosis.

Signs and symptoms
The symptoms of vaginal thrush include vulval itching, vulval soreness and irritation, pain or discomfort during sexual intercourse (superficial dyspareunia), pain or discomfort during urination (dysuria) and vaginal discharge, which is usually odourless. Although the vaginal discharge associated with yeast infection is often described as thick and lumpy, like paper paste or cottage cheese, it can also be thin and watery, or thick and of uniform texture. In one study, women with vaginal yeast infection were no more likely to describe their discharge as cottage-cheese like than women without.As well as the above symptoms of thrush, vulvovaginal inflammation can also be present. The signs of vulvovaginal inflammation include erythema (redness) of the vagina and vulva, vaginal fissuring (cracked skin), edema (swelling from a build-up of fluid), also in severe cases, satellite lesions (sores in the surrounding area). This is rare, but may indicate the presence of another fungal condition, or the herpes simplex virus (the virus that causes genital herpes).Vaginal candidiasis can very rarely cause congenital candidiasis in newborns.

Causes
Medications
Infection occurs in about 30% of women who are taking a course of antibiotics by mouth. Broad-spectrum antibiotics kill healthy bacteria in the vagina, such as Lactobacillus. These bacteria normally help to limit yeast colonization.Oral contraceptive use is also associated with increased risk of vaginal thrush.

Pregnancy
In pregnancy, higher levels of estrogen make a woman more likely to develop a yeast infection. During pregnancy, the Candida fungus is more common, and recurrent infection is also more likely. There is tentative evidence that treatment of asymptomatic candidal vulvovaginitis in pregnancy reduces the risk of preterm birth.

Lifestyle
While infections may occur without sex, a high frequency of intercourse increases the risk. Personal hygiene methods or tight-fitting clothing, such as tights and thong underwear, do not appear to increase the risk.

Diseases
Those with poorly controlled diabetes have increased rates of infection while those with well controlled diabetes do not. The risk of developing thrush is also increased when there is poor immune function, as with HIV/AIDS, or in those receiving chemotherapy.

Diet
A diet high in sugar may increase the risk of vaginal thrush; in some women, reducing sugar intake seems to reduce the risk of reoccurring vaginal thrush.

Species of yeast responsible
While Candida albicans is the most common yeast species associated with vaginal thrush, infection by other types of yeast can produce similar symptoms. A Hungarian study of 370 patients with confirmed vaginal yeast infections identified the following types of infection:
Candida albicans: 85.7%
Non-albicans Candida (8 species): 13.2%
Saccharomyces cerevisiae: 0.8%
Candida albicans and Candida glabrata: 0.3%Non-albicans Candida are often found in complicated cases of vaginal thrush in which the first line of treatment is ineffective. These cases are more likely in those who are immunocompromised.

Diagnosis
Vulvovaginal candidosis is the presence of Candida in addition to vaginal inflammation. The presence of yeast is typically diagnosed in one of three ways: vaginal wet mount microscopy, microbial culture, and antigen tests. The results may be described as being either uncomplicated or complicated.

Uncomplicated
Uncomplicated thrush is when there are less than four episodes in a year, the symptoms are mild or moderate, it is likely caused by Candida albicans, and there are no significant host factors such as poor immune function.

Complicated
Complicated thrush is four or more episodes of thrush in a year or when severe symptoms of vulvovaginal inflammation are experienced. It is also complicated if coupled with pregnancy, poorly controlled diabetes, poor immune function, or the thrush is not caused by Candida albicans.

Recurrent
About 5-8% of the reproductive age female population will have four or more episodes of symptomatic Candida infection per year; this condition is called recurrent vulvovaginal candidiasis (RVVC). Because vaginal and gut colonization with Candida is commonly seen in people with no recurrent symptoms, recurrent symptomatic infections are not simply due to the presence of Candida organisms. There is some support for the theory that RVVC results from an especially intense inflammatory reaction to colonization. Candida antigens can be presented to antigen-presenting cells, which may trigger cytokine production and activate lymphocytes and neutrophils that then cause inflammation and edema.

Treatment
The following treatments are typically recommended:

Intravaginal (vaginal suppository): butoconazole, clotrimazole, miconazole, nystatin, tioconazole, terconazole. Candidal vulvovaginitis in pregnancy should be treated with intravaginal clotrimazole or nystatin for at least 7 days. All are more or less equally effective.
By mouth: ibrexafungerp, fluconazole as a single dose. For severe disease another dose after 3 days may be used.Short-course topical formulations (i.e., single dose and regimens of 1–3 days) effectively treat uncomplicated candidal vulvovaginitis. The topically applied azole drugs are more effective than nystatin. Treatment with azoles results in relief of symptoms and negative cultures in 80–90% of patients who complete therapy.The creams and suppositories in this regimen are oil-based and might weaken latex condoms and diaphragms. Treatment for vagina thrush using antifungal medication is ineffective in up to 20% of cases. Treatment for thrush is considered to have failed if the symptoms do not clear within 7–14 days. There are a number of reasons for treatment failure. For example, if the infection is a different kind, such as bacterial vaginosis (the most common cause of abnormal vaginal discharge), rather than thrush.

Recurrent
For infrequent recurrences, the simplest and most cost-effective management is self-diagnosis and early initiation of topical therapy. However, women whose condition has previously been diagnosed with candidal vulvovaginitis are not necessarily more likely to be able to diagnose themselves; therefore, any woman whose symptoms persist after using an over the counter preparation, or who has a recurrence of symptoms within two months, should be evaluated with office-based testing. Unnecessary or inappropriate use of topical preparations is common and can lead to a delay in the treatment of other causes of vulvovaginitis, which can result in worse outcomes.When there are more than four recurrent episodes of candidal vulvovaginitis per year, a longer initial treatment course is recommended, such as orally administered fluconazole followed by a second and third dose 3 and 6 days later, respectively.Other treatments after more than four episodes per year, may include ten days of either oral or topical treatment followed by fluconazole orally once per week for six months. About 10-15% of recurrent candidal vulvovaginitis cases are due to non-Candida albicans species </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 Genodermatosis and can you explain it in depth? [/INST] Genodermatosis is a hereditary skin disease with three inherited modes including single gene inheritance, multiple gene inheritance and chromosome inheritance. There are many different types of genodermatosis, the prevalence of genodermatosis ranges from 1 per 6000 people to 1 per 500,000 people. Genodermatosis has influence on the texture, color and structure of skin cuticle and connective tissue, specific lesion site and clinical manifestations on the body vary depending on the type. In the spite of the variety and complexity of genodermatosis, there are still some common methods that can help people diagnose. After diagnosis, different types of genodermatosis require different levels of therapy including interventions, nursing interventions and treatments. Among that, research of therapy for some new, complex and rare types are still in the developing stage. The impact of genodermatosis not only can be seen in body but also can be seen in all aspects of patients life, including but not limited to psychological, family life, economic conditions and social activities. Accordingly, the patients need treatment, support and help in these areas.

Hereditary modes
Genodermatosis is inherited in three modes: single gene inheritance, multiple gene inheritance and chromosome inheritance.

Single gene (monogenic)
Single-gene inheritance of genodermatosis refers to the inheritance of a skin disease caused by one genetic abnormality and single gene heredity is divided into four kinds mainly.

Autosomal dominant inheritance
The first kind is autosomal dominant inheritance, in this kind of inheritance, patients can be of any sex and their genodermatosis are often inherited from one of the parents. Cases of skin disease that may be inherited in this kind of mode include epidermolysis bullosa simplex (EBS), acute intermittent porphyria, white sponge nevus, ichthyosis, epidermolytic palmoplantar keratoderma, hereditary benign intraepithelial dyskeratosis and so on.

Autosomal recessive inheritance
The second kind is autosomal recessive inheritance, in this kind of inheritance, patients can be of any sex and inbreeding tends to lead to this inheritance. Cases of skin disease that may be inherited in this kind of mode include epidermolysis bullosa, xeroderma pigmentosum, acrodermatitis enteropathica, ichthyosis and so on.

X-linked dominant inheritance
The third kind is X-linked dominant inheritance, in this kind of inheritance, patients can be of any sex. Male patients can pass the disease on to their sons and the chances of female patients passing it to their daughters or sons are almost equal. Cases of skin disease that may be inherited in this kind of mode include incontinentia pigmenti, focal dermal hypoplasia and so on.

X-linked recessive inheritance
The last kind is X-linked recessive inheritance, in this kind of inheritance, patients can be of any sex and the prevalence in men is higher than that in women. Male patients cannot pass the disease on to their sons. Cases of skin disease that may be inherited in this kind of mode include fabry disease, anhidrotic ectodermal dysplasia, dyskeratosis congenita and so on.

Multiple gene (polygenic)
Multiple-gene inheritance of genodermatosis refers to the inheritance of a skin disease caused by multiple genetic abnormalities. Cases of skin disease that may be inherited in this mode include vitiligo, psoriasis, pemphigus vulgaris, systemic lupus erythematosus and so on.

Chromosome
Chromosome inheritance of genodermatosis refers to the inheritance of a skin disease caused by chromosome abnormality.
The same disease can be inherited in different modes. For instance, epidermolysis bullosa can be inherited in the mode of autosomal dominant or in the mode of autosomal recessive.

Types
Genodermatosis has many types, many of which are rare.

Common types
Ichthyosis
Ichthyosis refers mainly to ichthyosis vulgaris, a common genodermatosis, people with this disease have a fishy, dry skin, which usually appears in early childhood and may disappear in adulthood. The prevalence of ichthyosis vulgaris is high, affecting almost 1 per 250 people. There are also rare types of ichthyosis, such as epidermolytic hyperkeratosis, harlequin ichthyosis and so on.

Rare types
Michelin tyre baby syndrome
Michelin tyre baby syndrome is a rare genodermatosis that occurs at birth, the skin of the patients is stacked symmetrically in layers like the image of the Michelin tyres mascot, which is also how this disease got its name.

Epidermolysis bullosa
Epidermolysis bullosa is a rare type of genodermatosis, people with this disease have blisters on their skin and this disease is never completely cured for a lifetime. Epidermolysis bullosa is mainly subdivided into four types: dystrophic epidermolysis bullosa, epidermolysis bullosa simplex, junctional epidermolysis bullosa and kindler syndrome. Almost 1 in 50,000 people has epidermolysis bullosa.

Pachyonychia congenita
Pachyonychia congenita is a rare type of genodermatosis, its clinical manifestations are abnormal enlargement of fingernails or toenails, excessive or poor palmoplantar keratinization, excessive sweating in the palmar or the plantar. Between 5000 and 10000 people in the world have pachyonychia congenita.

Epidermolytic palmoplantar keratoderma
Epidermolytic palmoplantar keratoderma often appears at birth and it is almost impossible to be cured completely. The clinical manifestations of this disease include excessive palmoplantar keratinization, the palmar or plantar become yellow divergently with around the edges or abnormally excessive sweating and clinical manifestation appear in a symmetrical form on the body.

Hereditary benign intraepithelial dyskeratosis
Hereditary benign intraepithelial dyskeratosis is a rare type of genodermatosis that may occur in infancy and early childhood, its symptoms often appear in the patients eyes and mouths. The patients eyes appear red due to the dilatation of superficial vessels and appearance of conjunctival plaques in their eyes, patients may have variable-size, thick, soft and white plaques in their mouth. Spring is an acute episode of symptoms, such as itching, erythema, photophobia and so on.

Epidermolytic hyperkeratosis
Epidermolytic hyperkeratosis is a rare genodermatosis which is also referred to as disorder of cornification type 3 and bullous congenital ichthyosiform erthroderma, affecting almost 1 per 200,000 - 300,000 people. They also stated that its clinical manifestations often begin at birth with large rashes all over the body, and the patients skin will be so sensitive that even mild wounds can cause blisters and peeling. Potential complications of this disease include electrolyte disturbances, sepsis and so on.

Hidrotic ectodermal dysplasia
Hidrotic ectodermal dysplasia is a rare genodermatosis which is also known as Clouston syndrome. The patients nails may be too thick, too brittle, too bent or have different colors, their hair also appear mottled, sparse and other abnormalities. These symptoms often begin when the patient is an infant.

Diagnostic methods
Genodermatosis is often rare and varied, but diagnostic methods have some commonalities, the diagnosis of rare genodermatosis is basically divided into six steps: 1. Each genodermatosis has different clinical manifestations. People can observe the special features and changes of the skin to judge whether they are sick or not. Features will be different in different age groups, so it is necessary to observe and record the special features of the skin in each age group; 2. Genodermatosis is a hereditary disease, knowing as much as possible about a detailed and complete family history helps in screening and diagnosis; 3. People can do a detailed physical examination to observe the special features and manifestations of other organs besides skin. It can help to narrow down the disease and make a definitive diagnosis; 4. People can carry out laboratory tests such as skin biopsies with high-tech and precise scientific instruments to have further results; 5. Different genodermatosis and their clinical manifestations may be caused by abnormalities in the same gene, and abnormalities in different genes may also lead to the same clinical manifestations. In order to have a definitive diagnosis or identify complex and specific types of genodermatosis, genotype–phenotype correlation needs attention; 6. If the above five steps fails to help people who suspected of having a genodermatosis to obtain the diagnosis result, they should keep all their information such as the diagnosis record and the clinical manifestations at different stages, and continue to record the changes of the body, waiting with a positive attitude, the future medicine may give the answer.

Therapy
The therapy of genodermatosis not only needs to take care of patients skin, reduce their pain and prevent complications, but also needs to carry out mental support for patients and their families.

Prevention and care
Different types of genodermatosis require different kinds of prevention and care.

Ichthyosis
There is no radical therapeutic method for ichthyosis, but some care can ease the symptoms. To prevent skin thickening and hydrate skin, patients can apply a cream containing alpha hydroxy acids and patients can also be treated with antibiotics for subsequent infections.

Epidermolysis bullosa
For epidermolysis bullosa, daily care is important. When treating a wound, keep it clean and reduce friction, the bandages and dressing used must be non-sticky and gentle, and the patient should wear loose clothing to avoid damaging the wound.

Epidermolytic hyperkeratosis
The treatment of Epidermolytic hyperkeratosis is mainly control and alleviate symptoms, and good nursing can reduce the incidence of complications like electrolyte disturbances and sepsis. To improve the look and feeling of the skin, patients can apply a cream containing alpha hydroxy acids, glycerol and urea, and if necessary, patients can use antibiotics to control secondary infections.

Pachyonychia congenita
There is no radical therapeutic method for pachyonychia congenita, but some care can ease the symptoms. Patients can polish and trim thickened nails, some of them can use retinoids to relieve symptoms but it may increase pain.

Neurofibromatosis type I
Selumetinib and trametinib have been shown to reduce and control tumor growth in people with neurofibromatosis type I, reducing the likelihood of malignant lesions.

Therapeutic methods
There are some new and developing genetic therapies available in genodermatosis.In the case of X-linked hypohidrotic ectodermal dysplasia, unborn babies diagnosed with this disease can be treated in their mothers womb. Providing regulatory proteins in the womb during a critical period of infant growth may help correct the development of babies sweat glands.Ustekinumab is a biologic therapy that can be used in a variety of genodermatosis such as congenital ichthyosis, psoriasis, deficiency of interleukin-36 receptor antagonist (DITRA) and so on.A new topical method could treat skin abnormalities in rare inherited lipid metabolic diseases </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 Athetosis and can you explain it in depth? [/INST] Athetosis is a symptom characterized by slow, involuntary, convoluted, writhing movements of the fingers, hands, toes, and feet and in some cases, arms, legs, neck and tongue. Movements typical of athetosis are sometimes called athetoid movements. Lesions to the brain are most often the direct cause of the symptoms, particularly to the
corpus striatum.  This symptom does not occur alone and is often accompanied by the symptoms of cerebral palsy, as it is often a result of this physical disability.  Treatments for athetosis are not very effective, and in most cases are simply aimed at managing the uncontrollable movement, rather than the cause itself.

Signs and symptoms
Athetosis can vary from mild to severe motor dysfunction; it is generally characterized by unbalanced, involuntary movements of muscle and a difficulty maintaining a symmetrical posture. The associated motor dysfunction can be restricted to a part of the body or present throughout the body, depending on the individual and the severity of the symptom. One of the pronounced signs can be observed in the extremities in particular, as the writhing, convoluted movement of the digits. Athetosis can appear as early as 18 months from birth with first signs including difficulty feeding, hypotonia, spasm, and involuntary writhing movements of the hands, feet, and face, which progressively worsen through adolescence and at times of emotional distress. Athetosis is caused by lesions in several brain areas such as the hippocampus and the motor thalamus, as well as the corpus striatum; therefore children during the developmental age could possibly suffer from severe communication deficits such as speech impairment, hearing loss, and failed or delayed acquirement of sitting balance, although most people with athetosis have normal or near-normal intelligence.

Causes
Athetosis is a symptom primarily caused by the marbling, or degeneration of the basal ganglia. This degeneration is most commonly caused by complications at birth or by Huntingtons disease, in addition to rare cases in which the damage may also arise later in life due to stroke or trauma. The two complications of particular interest are intranatal asphyxia and neonatal jaundice.

Asphyxia
Asphyxia directly causes basal ganglia damage due to lack of oxygen and therefore, insufficient nutrient supply. The lesions caused by asphyxia are most prominent on the caudate nucleus and the putamen. However, a less-studied consequence of the resulting hypoxia is its effect on the concentrations of the neurotransmitter dopamine within the synapses of neurons in the basal ganglia. Hypoxia leads to an increase in the extracellular dopamine levels and therefore, an increase in the activity of the dopaminergic neurons. Furthermore, this increase in extracellular concentration is not caused by an increase in the neurotransmitter synthesis, but instead on inhibiting its reuptake back into the neurons and glial cells. Therefore, there is an increased dopaminergic effect as dopamine remains in the synapse at higher concentrations leading to additional post-synaptic response. As a result, the uncontrollable writhing motions witnessed with athetosis deal with the over-activity of synapses within the basal ganglia.

Neonatal jaundice
Neonatal jaundice is the other chief complication that leads to the basal ganglia damage associated with this condition. Jaundice is caused by hyperbilirubinemia, or abnormally high levels of bilirubin in the blood. Bilirubin is usually bound to albumin immediately and sent to the liver. However, in neonatal jaundice, the concentration of bilirubin overwhelms that of albumin and some of the bilirubin remains unconjugated and can enter the brain through the blood–brain barrier. Normally bilirubin would not be able to diffuse across the blood–brain barrier, but in infants, the barrier is immature and has higher permeability. Bilirubin is toxic as it prevents the phosphorylation of many proteins, including synapsin I which binds vesicles in the presynaptic terminal. Therefore, it directly inhibits the exocytosis of neurotransmitters and severely hinders the synapses it affects. In autopsies of children who suffered from neonatal jaundice, chronic changes of neuronal loss, gliosis and demyelination were observed in the basal ganglia and more specifically within the globus pallidus.

Thalamic stroke
Another study was done where the onset of athetoid movement followed a thalamic stroke. The thalamus is part of a pathway that is involved with the cortical feedback loop in which signals from the cortex are relayed through the striatum, pallidus and thalamus before making it back to the cortex. The striatum receives excitatory inputs from the cortex and inhibits the pallidum. By doing so it frees the thalamus from pallidal inhibition allowing the thalamus to send excitatory outputs to the cortex. Therefore, the lesions to the thalamus or any other part of this feedback loop can result in movement disorders as they can alter the reactivity of one towards the other.  Also, in a case of people with thalamic stroke, a majority suffered severe sensory deficits and ataxia. It is proposed that this loss of proprioception and the ensuing loss of synergic stabilization may also lead to abnormal movements, such as those dealt with in athetosis.

Fahrs syndrome
Treatments
There are several different treatment approaches to dealing with athetosis.  The most common methods are the use of drugs, surgical intervention, and retraining movements of the afflicted person.  It is suggested that training a person to relearn movements can be helpful in select situations.  Though, generally, this type of treatment will not work, in certain cases it can be found to be very helpful in treating the symptom of athetosis.Drugs can also be used in the treatment of athetosis, however their collective effectiveness is not very convincing.  There is not a single drug that is a standard among treatment.  Many different medicines can be used, including:

Artane
Cogentin
Curare, though not practical due to respiratory paralysis
Tetrabenazine
Haloperidol
Thiopropazate
DiazepamMost instances of drug use where the symptoms seem to be lessened tend to be in more mild cases of athetosis.Treatment by surgical intervention can obviously have the most immediate impact, again however, it is not a cure-all.  In patients that have cerebral palsy as the cause of their athetosis, it has been demonstrated that a subthalamotomy tends to help relieve the extent of athetosis in approximately half of patients.  Additionally, late 19th and early 20th century surgical accounts state that athetosis can be relieved by the removal of a part of the cerebral motor cortex or by cutting a part of the posterior spinal roots.  Patients who undergo surgical treatment to relieve the athetosis often see significant improvement in the control of their limbs and digits.  While surgery is often very beneficial in the short term and can produce near immediate results, in the long term it has been seen that its effects are not incredibly long lasting.

Related disorders
Choreoathetosis
Chorea is another condition which results from damage to the basal ganglia. Similar to athetosis, it results from mutations affecting the pallidum inhibition of the thalamus as well as increased dopaminergic activity at the level of the striatum. Considering the etiology of both disorders are fairly similar, it comes as no surprise that chorea and athetosis can and usually do occur together in a condition called choreoathetosis.

Cerebral palsy
Athetosis is a commonly occurring symptom in the disease cerebral palsy.  Of all people with the disease, between 16% and 25% of them actually exhibit the symptom of athetosis.  A component of this is the finding that most often the symptoms that involve athetosis occur as a part of choreoathetosis as opposed to athetosis alone.It is also noteworthy that the presence of athetosis in cerebral palsy (as well as other conditions) causes a significant increase in a persons basal resting metabolic rate.  It has been observed that those who have cerebral palsy with athetosis require approximately 500 more Calories per day than their non-cerebral palsy non-athetoid counterpart.

Pseudoathetosis
Pseudoathetosis is a movement disorder, very similar to athetosis, in which the symptoms are not differentiable from those of actual athetosis, however the underlying cause is different.  While actual athetosis is caused by damage to the brain, specifically in the basal ganglia, pseudoathetosis is caused by the loss of proprioception.  The loss in proprioception is caused by damage to the area between the primary somatosensory cortex and the muscle spindles and joint receptors.  Additionally, when observing an MRI, it can be seen that in the brain of a pseudoathetoid patient, lesions on the brain are not seen in the basal ganglia, the area that is oftentimes the cause of athetosis.

Social implications
Athetosis is characterized as a symptom that is present in many forms of central nervous system disorders that affect the body movement coordination, such as cerebral palsy.  Children may struggle to engage in social communication, since the poor coordination of the tongue and mouth muscles can reduce their speech ability and hinder their social interaction to a greater degree. The caregivers of the affected children are encouraged to closely monitor their nutrition and growth and to provide them with hearing aids in order to relieve their symptoms as well as support their academic plans. A growing number of patients is shown to benefit from communication devices such as shorthand typing programs and computer speech devices, as well as simple picture boards.Patients living with the disorder into their adulthood often have trouble being involved in daily activities such as eating, walking, dressing, as well as performing everyday tasks. They are consistently faced with challenges that limit their ability to live on their own. They are more reluctant to be involved in social activities and romantic relationships and more likely to develop poor self-esteem and self-image related to their physical limitations as well as cognitive disabilities, though such habitual thinking is shown to decline when they feel they are accepted and supported by their peers. Patients are also inclined to associate themselves with people who tend not to be engaged in physical activities, according to the September 2008 issue of “Journal of Physical Activity and Health.”

History
The first noted case of athetosis was discovered by W. A </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 Spinal cord injury and can you explain it in depth? [/INST] A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. Symptoms may include loss of muscle function, sensation, or autonomic function in the parts of the body served by the spinal cord below the level of the injury. Injury can occur at any level of the spinal cord and can be complete, with a total loss of sensation and muscle function at lower sacral segments, or incomplete, meaning some nervous signals are able to travel past the injured area of the cord up to the Sacral S4-5 spinal cord segments. Depending on the location and severity of damage, the symptoms vary, from numbness to paralysis, including bowel or bladder incontinence. Long term outcomes also range widely, from full recovery to permanent tetraplegia (also called quadriplegia) or paraplegia. Complications can include muscle atrophy, loss of voluntary motor control, spasticity, pressure sores, infections, and breathing problems.
In the majority of cases the damage results from physical trauma such as car accidents, gunshot wounds, falls, or sports injuries, but it can also result from nontraumatic causes such as infection, insufficient blood flow, and tumors. Just over half of injuries affect the cervical spine, while 15% occur in each of the thoracic spine, border between the thoracic and lumbar spine, and lumbar spine alone. Diagnosis is typically based on symptoms and medical imaging.Efforts to prevent SCI include individual measures such as using safety equipment, societal measures such as safety regulations in sports and traffic, and improvements to equipment. Treatment starts with restricting further motion of the spine and maintaining adequate blood pressure. Corticosteroids have not been found to be useful. Other interventions vary depending on the location and extent of the injury, from bed rest to surgery. In many cases, spinal cord injuries require long-term physical and occupational therapy, especially if it interferes with activities of daily living.
In the United States, about 12,000 people a year survive a spinal cord injury. The most commonly affected group are young adult males. SCI has seen great improvements in its care since the middle of the 20th century. Research into potential treatments includes stem cell implantation, hypothermia, engineered materials for tissue support, epidural spinal stimulation, and wearable robotic exoskeletons.

Classification
Spinal cord injury can be traumatic or nontraumatic, and can be classified into three types based on cause: mechanical forces, toxic, and ischemic (from lack of blood flow).  The damage can also be divided into primary and secondary injury: the cell death that occurs immediately in the original injury, and biochemical cascades that are initiated by the original insult and cause further tissue damage.  These secondary injury pathways include the ischemic cascade, inflammation, swelling, cell suicide, and neurotransmitter imbalances.  They can take place for minutes or weeks following the injury.At each level of the spinal column, spinal nerves branch off from either side of the spinal cord and exit between a pair of vertebrae, to innervate a specific part of the body. The area of skin innervated by a specific spinal nerve is called a dermatome, and the group of muscles innervated by a single spinal nerve is called a myotome. The part of the spinal cord that was damaged corresponds to the spinal nerves at that level and below. Injuries can be cervical 1–8 (C1–C8), thoracic 1–12 (T1–T12), lumbar 1–5 (L1–L5), or sacral (S1–S5). A persons level of injury is defined as the lowest level of full sensation and function. Paraplegia occurs when the legs are affected by the spinal cord damage (in thoracic, lumbar, or sacral injuries), and tetraplegia occurs when all four limbs are affected (cervical damage).SCI is also classified by the degree of impairment.  The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), published by the American Spinal Injury Association (ASIA), is widely used to document sensory and motor impairments following SCI. It is based on neurological responses, touch and pinprick sensations tested in each dermatome, and strength of the muscles that control key motions on both sides of the body.  Muscle strength is scored on a scale of 0–5 according to the table on the right, and sensation is graded on a scale of 0–2: 0 is no sensation, 1 is altered or decreased sensation, and 2 is full sensation.  Each side of the body is graded independently.

Complete and incomplete injuries
In a "complete" spinal injury, all functions below the injured area are lost, whether or not the spinal cord is severed.  An "incomplete" spinal cord injury involves preservation of motor or sensory function below the level of injury in the spinal cord.  To be classed as incomplete, there must be some preservation of sensation or motion in the areas innervated by S4 to S5, e.g. voluntary external anal sphincter contraction. The nerves in this area are connected to the very lowest region of the spinal cord, and retaining sensation and function in these parts of the body indicates that the spinal cord is only partially damaged.  Incomplete injury by definition includes a phenomenon known as sacral sparing: some degree of sensation is preserved in the sacral dermatomes, even though sensation may be more impaired in other, higher dermatomes below the level of the lesion. Sacral sparing has been attributed to the fact that the sacral spinal pathways are not as likely as the other spinal pathways to become compressed after injury due to the lamination of fibers within the spinal cord.

Spinal cord injury without radiographic abnormality
Spinal cord injury without radiographic abnormality exists when SCI is present but there is no evidence of spinal column injury on radiographs. Spinal column injury is trauma that causes fracture of the bone or instability of the ligaments in the spine; this can coexist with or cause injury to the spinal cord, but each injury can occur without the other. Abnormalities might show up on magnetic resonance imaging (MRI), but the term was coined before MRI was in common use.

Central cord syndrome
Central cord syndrome, almost always resulting from damage to the cervical spinal cord, is characterized by weakness in the arms with relative sparing of the legs, and spared sensation in regions served by the sacral segments. There is loss of sensation of pain, temperature, light touch, and pressure below the level of injury.  The spinal tracts that serve the arms are more affected due to their central location in the spinal cord, while the corticospinal fibers destined for the legs are spared due to their more external location. The most common of the incomplete SCI syndromes, central cord syndrome usually results from neck hyperextension in older people with spinal stenosis.  In younger people, it most commonly results from neck flexion.  The most common causes are falls and vehicle accidents; however other possible causes include spinal stenosis and impingement on the spinal cord by a tumor or vertebral disk.

Anterior cord syndrome
Anterior cord syndrome, due to damage to the front portion of the spinal cord or reduction in the blood supply from the anterior spinal artery, can be caused by fractures or dislocations of vertebrae or herniated disks. Below the level of injury, motor function, pain sensation, and temperature sensation are lost, while sense of touch and proprioception (sense of position in space) remain intact. These differences are due to the relative locations of the spinal tracts responsible for each type of function.

Brown-Séquard syndrome
Brown-Séquard syndrome occurs when the spinal cord is injured on one side much more than the other. It is rare for the spinal cord to be truly hemisected (severed on one side), but partial lesions due to penetrating wounds (such as gunshot or knife wounds) or fractured vertebrae or tumors are  common. On the ipsilateral side of the injury (same side), the body loses motor function, proprioception, and senses of vibration and touch. On the contralateral (opposite side) of the injury, there is a loss of pain and temperature sensations.

Posterior cord syndrome
Posterior cord syndrome, in which just the dorsal columns of the spinal cord are affected, is usually seen in cases of chronic myelopathy but can also occur with infarction of the posterior spinal artery.  This rare syndrome causes the loss of proprioception and sense of vibration below the level of injury while motor function and sensation of pain, temperature, and touch remain intact.  Usually posterior cord injuries result from insults like disease or vitamin deficiency rather than trauma. Tabes dorsalis, due to injury to the posterior part of the spinal cord caused by syphilis, results in loss of touch and proprioceptive sensation.

Conus medullaris and cauda equina syndromes
Conus medullaris syndrome is an injury to the end of the spinal cord, located at about the T12–L2 vertebrae in adults. This region contains the S4–S5 spinal segments, responsible for bowel, bladder, and some sexual functions, so these can be disrupted in this type of injury.  In addition, sensation and the Achilles reflex can be disrupted. Causes include tumors, physical trauma, and ischemia. The Cauda equina syndrome may also be caused by central disc prolapse or slipped disc, infections such as epidural abscess, spinal haemorrhages, secondary to medical procedures and birth abnormalities.Cauda equina syndrome (CES) results from a lesion below the level at which the spinal cord splits into the cauda equina, at levels L2–S5 below the conus medullaris. Thus it is not a true spinal cord syndrome since it is nerve roots that are damaged and not the cord itself; however, it is common for several of these nerves to be damaged at the same time due to their proximity. CES can occur by itself or alongside conus medullaris syndrome. It can cause low back pain, weakness or paralysis in the lower limbs, loss of sensation, bowel and bladder dysfunction, and loss of reflexes. Patient may present with bilateral sciatica with central disc prolapse and altered gait. Unlike in conus medullaris syndrome, symptoms often occur on only one side of the body. The cause is often compression, e.g. by a ruptured intervertebral disk or tumor.  Since the nerves damaged in CES are actually peripheral nerves because they have already branched off from the spinal cord, the injury has better prognosis for recovery of function: the peripheral nervous system has a greater capacity for healing than the central nervous system.

Signs and symptoms
Signs (observed by a clinician) and symptoms (experienced by a patient) vary depending on where the spine is injured and the extent of the injury.
A section of skin innervated through a specific part of the spine is called a dermatome, and injury to that part of the spine can cause pain, numbness, or a loss of sensation in the related areas. Paraesthesia, a tingling or burning sensation in affected areas of the skin, is another symptom. A person with a lowered level of consciousness may show a response to a painful stimulus above a certain point but not below it.
A group of muscles innervated through a specific part of the spine is called a myotome, and injury to that part of the spinal cord can cause problems with movements that involve those muscles.  The muscles may contract uncontrollably (spasticity), become weak, or be completely paralysed. Spinal shock, loss of neural activity including reflexes below the level of injury, occurs shortly after the injury and usually goes away within a day. Priapism, an erection of the penis may be a sign of acute spinal cord injury.The specific parts of the body affected by loss of function are determined by the level of injury. Some signs, such as bowel and bladder dysfunction can occur at any level. Neurogenic bladder involves a compromised ability to empty the bladder and is a common symptom of spinal cord injury. This can lead to high pressures in the bladder that can damage the kidneys.

Lumbosacral
The effects of injuries at or above the lumbar or sacral regions of the spinal cord (lower back and pelvis) include decreased control of the legs and hips, genitourinary system, and anus. People injured below level L2 may still have use of their hip flexor and knee extensor muscles. Bowel and bladder function are regulated by the sacral region. It is common to experience sexual dysfunction after injury, as well as dysfunction of the bowel and bladder, including fecal and urinary incontinence.

Thoracic
In addition to the problems found in lower-level injuries, thoracic (chest height) spinal lesions can affect the muscles in the trunk. Injuries at the level of T1 to T8 result in inability to control the abdominal muscles. Trunk stability may be affected; even more so in higher level injuries. The lower the level of injury, the less extensive its effects.  Injuries from T9 to T12 result in partial loss of trunk and abdominal muscle control.  Thoracic spinal injuries result in paraplegia, but function of the hands, arms, and neck are not affected.One condition that occurs typically in lesions above the T6 level is autonomic dysreflexia (AD), in which the blood pressure increases to dangerous levels, high enough to cause potentially deadly stroke. It results from an overreaction of the system to a stimulus such as pain below the level of injury, because inhibitory signals from the brain cannot pass the lesion to dampen the excitatory sympathetic nervous system response.  Signs and symptoms of AD include anxiety, headache, nausea, ringing in the ears, blurred vision, flushed skin, and nasal congestion.  It can occur shortly after the injury or not until years later.Other autonomic functions may also be disrupted. For example, problems with body temperature regulation mostly occur in injuries at T8 and above.
Another serious complication that can result from lesions above T6 is neurogenic shock, which results from an interruption in output from the sympathetic nervous system responsible for maintaining muscle tone in the blood vessels. Without the sympathetic input, the vessels relax and dilate.  Neurogenic shock presents with dangerously low blood pressure, low heart rate, and blood pooling in the limbs—which results in insufficient blood flow to the spinal cord and potentially further damage to it.

Cervical
Spinal cord injuries at the cervical (neck) level result in full or partial tetraplegia (also called quadriplegia). Depending on the specific location and severity of trauma, limited function may be retained. Additional symptoms of cervical injuries include low heart rate, low blood pressure, problems regulating body temperature, and breathing dysfunction. If the injury is high enough in the neck to impair the muscles involved in breathing, the person may not be able to breathe without the help of an endotracheal tube and mechanical ventilator.

Complications
Complications of spinal cord injuries include pulmonary edema, respiratory failure, neurogenic shock, and paralysis below the injury site.
In the long term, the loss of muscle function can have additional effects from disuse, including atrophy of the muscle.  Immobility can lead to pressure sores,  particularly in bony areas, requiring precautions such as extra cushioning and turning in bed every two hours (in the acute setting) to relieve pressure. In the long term, people in wheelchairs must shift periodically to relieve pressure.  Another complication is pain, including nociceptive pain (indication of potential or actual tissue damage) and neuropathic pain, when  nerves affected by damage convey erroneous pain signals in the absence of noxious stimuli. Spasticity, the uncontrollable tensing of muscles below the level of injury, occurs in 65–78% of chronic SCI. It results from lack of input from the brain that quells muscle responses to stretch reflexes.  It can be treated with drugs and physical therapy. Spasticity increases the risk of contractures (shortening of muscles, tendons, or ligaments that result from lack of use of a limb); this problem can be prevented by moving the limb through its full range of motion multiple times a day.  Another problem lack of mobility can cause is loss of bone density and changes in bone structure. Loss of bone density (bone demineralization), thought to be due to lack of input from weakened or paralysed muscles, can increase the risk of fractures. Conversely, a poorly understood phenomenon is the overgrowth of bone tissue in soft tissue areas,  called heterotopic ossification.  It occurs below the level of injury, possibly as a result of inflammation, and happens to a clinically significant extent in 27% of people.

People with SCI are at especially high risk for respiratory and cardiovascular problems, so hospital staff must be watchful to avoid them. Respiratory problems (especially pneumonia) are the leading cause of death in people with SCI, followed by infections, usually of pressure sores, urinary tract infections and respiratory infections. Pneumonia can be accompanied by shortness of breath, fever, and anxiety.Another potentially deadly threat to respiration is deep venous thrombosis (DVT), in which blood forms a clot in immobile limbs; the clot can break off and form a  pulmonary embolism, lodging in the lung and cutting off blood supply to it. DVT  is an especially high risk in SCI, particularly within 10 days of injury, occurring in over 13% in the acute care setting.  Preventative measures include anticoagulants, pressure hose, and moving the patients limbs. The usual signs and symptoms of DVT and pulmonary embolism may be masked in SCI cases due to effects such as alterations in pain perception and nervous system functioning.Urinary tract infection (UTI) is another risk that may not display the usual symptoms (pain, urgency, and frequency); it may instead be associated with worsened spasticity. The risk of UTI, likely the most common complication in the long term, is heightened by use of indwelling urinary catheters. Catheterization may be necessary because SCI interferes with the bladders ability to empty when it gets too full, which could trigger autonomic dysreflexia or damage the bladder permanently.  The use of intermittent catheterization to empty the bladder at regular intervals throughout the day has decreased the mortality due to kidney failure from UTI in the first world, but it is still a serious problem in developing countries.An estimated 24–45% of people with SCI have disorders of depression, and the suicide rate is as much as six times that of the rest of the population. The risk of suicide is worst in the first five years after injury. In young people with SCI, suicide is the leading cause of death. Depression is associated with an increased risk of other complications such as UTI and pressure ulcers that occur more when self-care is neglected.

Causes
Spinal cord injuries are most often caused by physical trauma. Forces involved can be hyperflexion (forward movement of the head); hyperextension (backward movement); lateral stress (sideways movement); rotation (twisting of the head); compression (force along the axis of the spine downward from the head or upward from the pelvis); or distraction (pulling apart of the vertebrae). Traumatic SCI can result in contusion, compression, or stretch injury. It is a major risk of many types of vertebral fracture. Pre-existing asymptomatic congenital anomalies can cause major neurological deficits, such as hemiparesis, to result from otherwise minor trauma.In the US, Motor vehicle accidents are the most common cause of SCIs; second are falls, then violence such as gunshot wounds, then sports injuries. Another study from Asia, found that the most common cause of the SCI is fall (31.70%) from various sites such as fall from roof-tops (9.75%), electric pole (7.31%), fall from tree (7.31%) etc. Whereas road traffic accidents count for 19.51%, firearm injuries (12.19%), slipped foot (7.31%) and sports injuries (4.87%). As a result of injury, 26.82% In some countries falls are more common, even surpassing vehicle crashes as the leading cause of SCI. The rates of violence-related SCI depend heavily on place and time. Of all sports-related SCIs, shallow water dives are the most common cause; winter sports and water sports have been increasing as causes while association football and trampoline injuries have been declining.  Hanging can cause injury to the cervical spine, as may occur in attempted suicide. Military conflicts are another cause, and when they occur they are associated with increased rates of SCI. Another potential cause of SCI is iatrogenic injury, caused by an improperly done medical procedure such as an injection into the spinal column.SCI can also be of a nontraumatic origin. Nontraumatic lesions cause anywhere from 30 to 80% of all SCI; the percentage varies by locale, influenced by efforts to prevent trauma. Developed countries have higher percentages of SCI due to degenerative conditions and tumors than developing countries.  In developed countries, the most common cause of nontraumatic SCI is degenerative diseases, followed by tumors; in many developing countries the leading cause is infection such as HIV and tuberculosis. SCI may occur in intervertebral disc disease, and spinal cord vascular disease. Spontaneous bleeding can occur within or outside of the protective membranes that line the cord, and intervertebral disks can herniate. Damage can result from dysfunction of the blood vessels, as in arteriovenous malformation, or when a blood clot becomes lodged in a blood vessel and cuts off blood supply to the cord. When systemic blood pressure drops, blood flow to the spinal cord may be reduced, potentially causing a loss of sensation and voluntary movement in the areas supplied by the affected level of the spinal cord. Congenital conditions and tumors that compress the cord can also cause SCI, as can vertebral spondylosis and ischemia. Multiple sclerosis is a disease that can damage the spinal cord, as can infectious or inflammatory conditions such as tuberculosis, herpes zoster or herpes simplex, meningitis, myelitis, and syphilis.

Prevention
Vehicle-related SCI is prevented with measures including societal and individual efforts to reduce driving under the influence of drugs or alcohol, distracted driving, and drowsy driving.  Other efforts include increasing road safety (such as marking hazards and adding lighting) and vehicle safety, both to prevent accidents (such as routine maintenance and antilock brakes) and to mitigate the damage of crashes (such as  head restraints, air bags, seat belts, and child safety seats).  Falls can be prevented by making changes to the environment, such as nonslip materials and grab bars in bathtubs and showers, railings for stairs, child and safety gates for windows. Gun-related injuries can be prevented with conflict resolution training, gun safety education campaigns, and changes to the technology of guns (such as trigger locks) to improve their safety.  Sports injuries can be prevented with changes to sports rules and equipment to increase safety, and education campaigns to reduce risky practices such as diving into water of unknown depth or head-first tackling in association football.

Diagnosis
A persons presentation in context of trauma or non-traumatic background determines suspicion for a spinal cord injury. The features are namely paralysis, sensory loss, or both at any level. Other symptoms may include incontinence.A radiographic evaluation using an X-ray, CT scan, or MRI can determine if there is damage to the spinal column and where it is located. X-rays are commonly available and can detect instability or misalignment of the spinal column, but do not give very detailed images and can miss injuries to the spinal cord or displacement of ligaments or disks that do not have accompanying spinal column damage. Thus when X-ray findings are normal but SCI is still suspected due to pain or SCI symptoms, CT or MRI scans are used. CT gives greater detail than X-rays, but exposes the patient to more radiation, and it still does not give images of the spinal cord or ligaments; MRI shows body structures in the greatest detail. Thus it is the standard for anyone who has neurological deficits found in SCI or is thought to have an unstable spinal column injury.Neurological evaluations to help determine the degree of impairment are performed initially and repeatedly in the early stages of treatment; this determines the rate of improvement or deterioration and informs treatment and prognosis. The ASIA Impairment Scale outlined above is used to determine the level and severity of injury.

Management
Prehospital treatment
The first stage in the management of a suspected spinal cord injury is geared toward basic life support and preventing further injury: maintaining airway, breathing, and circulation and restricting further motion of the spine.
In the emergency setting, most people who has been subjected to forces strong enough to cause SCI are treated as though they have instability in the spinal column and have spinal motion restricted to prevent damage to the spinal cord. Injuries or fractures in the head, neck, or pelvis as well as penetrating trauma near the spine and falls from heights are assumed to be associated with an unstable spinal column until it is ruled out in the hospital. High-speed vehicle crashes, sports injuries involving the head or neck, and diving injuries are other mechanisms that indicate a high SCI risk. Since head and spinal trauma frequently coexist, anyone who is unconscious or has a lowered level of consciousness as a result of a head injury is spinal motion restricted.A rigid cervical collar is applied to the neck, and the head is held with blocks on either side and the person is strapped to a backboard. Extrication devices are used to move people without excessively moving the spine if they are still inside a vehicle or other confined space. The use of a cervical collar has been shown to increase mortality in people with penetrating trauma and is thus not routinely recommended in this group.Modern trauma care includes a step called clearing the cervical spine, ruling out spinal cord injury if the patient is fully conscious and not under the influence of drugs or alcohol, displays no neurological deficits, has no pain in the middle of the neck and no other painful injuries that could distract from neck pain. If these are all absent, no spinal motion restriction is necessary.If an unstable spinal column injury is moved, damage may occur to the spinal cord. Between 3 and 25% of SCIs occur not at the time of the initial trauma but later during treatment or transport. While some of this is due to the nature of the injury itself, particularly in the case of multiple or massive trauma, some of it reflects the failure to adequately restrict motion of the spine. SCI can impair the bodys ability to keep warm, so warming blankets may be needed.

Early hospital treatment
Initial care in the hospital, as in the prehospital setting, aims to ensure adequate airway, breathing, cardiovascular function, and spinal motion restriction. Imaging of the spine to determine the presence of a SCI may need to wait if emergency surgery is needed to stabilize other life-threatening injuries. Acute SCI merits treatment in an intensive care unit, especially injuries to the cervical spinal cord. People with SCI need repeated neurological assessments and treatment by neurosurgeons. People should be removed from the spine board as rapidly as possible to prevent complications from its use.If the systolic blood pressure falls below 90 mmHg within days of the injury, blood supply to the spinal cord may be reduced, resulting in further damage. Thus it is important to maintain the blood pressure which may be done using intravenous fluids and vasopressors. Vasopressors used include phenylephrine, dopamine, or norepinephrine. Mean arterial blood pressure is measured and kept at 85 to 90 mmHg for seven days after injury.The CAMPER Trial led by Dr Kwon and subsequent studies by the UCSF TRACK-SCI group (Dhall) have shown that spinal cord perfusion pressure (SCPP) goals are more closely associated with better neurologic recovery than MAP goals. Some institutions have adopted these SCPP goals and lumbar CSF drain placement as a standard of care. The treatment for shock from blood loss is different from that for neurogenic shock, and could harm people with the latter type, so it is necessary to determine why someone is in shock. However it is also possible for both causes to exist at the same time. Another important aspect of care is prevention of insufficient oxygen in the bloodstream, which could deprive the spinal cord of oxygen. People with cervical or high thoracic injuries may experience a dangerously slowed heart rate; treatment to speed it may include atropine.The corticosteroid medication methylprednisolone has been studied for use in SCI with the hope of limiting swelling and secondary injury. As there does not appear to be long term benefits and the medication is associated with risks such as gastrointestinal bleeding and infection its use is not recommended as of 2018. Its use in traumatic brain injury is also not recommended.Surgery may be necessary, e.g. to relieve excess pressure on the cord, to stabilize the spine, or to put vertebrae back in their proper place.  In cases involving instability or compression, failing to operate can lead to worsening of the condition. Surgery is also necessary when something is pressing on the cord, such as bone fragments, blood, material from ligaments or intervertebral discs, or a lodged object from a penetrating injury. Although the ideal timing of surgery is still debated, studies have found that earlier surgical intervention (within 12 hours of injury) is associated with better outcomes. This type of surgery is often referred to as "Ultra-Early", coined by Burke et al. at UCSF. Sometimes a patient has too many other injuries to be a surgical candidate this early. Surgery is controversial because it has potential complications (such as infection), so in cases where it is not clearly needed (e.g. the cord is being compressed), doctors must decide whether to perform surgery based on aspects of the patients condition and their own beliefs about its risks and benefits. Recent large-scale studies have shown that patients who do undergo earlier surgery (within 12–24 hours) experience significantly lower rates of life-threatening complications and spend less time in hospital and critical care.
However, in cases where a more conservative approach is chosen, bed rest, cervical collars, motion restriction devices, and optionally traction are used.  Surgeons may opt to put traction on the spine to remove pressure from the spinal cord by putting dislocated vertebrae back into alignment, but herniation of intervertebral disks may prevent this technique from relieving pressure.  Gardner-Wells tongs are one tool used to exert spinal traction to reduce a fracture or dislocation and to reduce motion to the affected areas.

Rehabilitation
SCI patients often require extended treatment in specialized spinal unit or an intensive care unit.  The rehabilitation process typically begins in the acute care setting. Usually, the inpatient phase lasts 8–12 weeks and then the outpatient rehabilitation phase lasts 3–12 months after that, followed by yearly medical and functional evaluation. Physical therapists, occupational therapists, recreational therapists, nurses, social workers, psychologists, and other health care professionals work as a team under the coordination of a physiatrist to decide on goals with the patient and develop a plan of discharge that is appropriate for the persons condition.

In the acute phase physical therapists focus on the patients respiratory status, prevention of indirect complications (such as pressure ulcers), maintaining range of motion, and keeping available musculature active.For people whose injuries are high enough to interfere with breathing, there is great emphasis on airway clearance during this stage of recovery. Weakness of respiratory muscles impairs the ability to cough effectively, allowing secretions to accumulate within the lungs.  As SCI patients have reduced total lung capacity and tidal volume, physical therapists teach them accessory breathing techniques (e.g. apical breathing, glossopharyngeal breathing) that typically are not taught to healthy individuals.  Physical therapy treatment for airway clearance may include manual percussions and vibrations, postural drainage, respiratory muscle training, and assisted cough techniques. Patients are taught to increase their intra-abdominal pressure by leaning forward to induce cough and clear mild secretions. The quad cough technique is done lying on the back with the therapist applying pressure on the abdomen in the rhythm of the cough to maximize expiratory flow and mobilize secretions. Manual abdominal compression is another technique used to increase expiratory flow which later improves coughing. Other techniques used to manage respiratory dysfunction  include respiratory muscle pacing, use of a constricting abdominal binder, ventilator-assisted speech, and mechanical ventilation.The amount of functional recovery and independence achieved in terms of activities of daily living, recreational activities, and employment is affected by the level and severity of injury. The Functional Independence Measure (FIM) is an assessment tool that aims to evaluate the function of patients throughout the rehabilitation process following a  spinal cord injury or other serious illness or injury.  It can track a patients progress and degree of independence during rehabilitation.  People with SCI may need to use specialized devices and to make modifications to their environment in order to handle activities of daily living and to function independently.  Weak joints can be stabilized with devices such as ankle-foot orthoses (AFOs) or knee-ankle-foot orthoses (KAFOs), but walking may still require a lot of effort. Increasing activity will increase chances of recovery.

For treatment of paralysis levels in the lower thoracic spine or lower, starting therapy with an orthosis is promising from the intermediate phase (2–26 weeks after the incident). In patients with complete paraplegia (ASIA A), this applies to lesion heights between T12 and S5. In patients with incomplete paraplegia (ASIA B-D), orthoses are even suitable for lesion heights above T12. In both cases, however, a detailed muscle function test must be carried out to precisely plan the construction with an orthosis.

Prognosis
Spinal cord injuries generally result in at least some incurable impairment even with the best possible treatment. The best predictor of prognosis is the level and completeness of injury, as measured by the ASIA impairment scale. The neurological score at the initial evaluation done 72 hours after injury is the best predictor of how much function will return. Most people with ASIA scores of A (complete injuries) do not have functional motor recovery, but improvement can occur. Most patients with incomplete injuries recover at least some function. Chances of recovering the ability to walk improve with each AIS grade found at the initial examination; e.g. an ASIA D score confers a better chance of walking than a score of C. The symptoms of incomplete injuries can vary and it is difficult to make an accurate prediction of the outcome.  A person with a mild, incomplete injury at the T5 vertebra will have a much better chance of using his or her legs than a person with a severe, complete injury at exactly the same place. Of the incomplete SCI syndromes, Brown-Séquard and central cord syndromes have the best prognosis for recovery and anterior cord syndrome has the worst.People with nontraumatic causes of SCI have been found to be less likely to develop complete injuries and some complications such as pressure sores and deep vein thrombosis, and to have shorter hospital stays. Their scores on functional tests were better than those of people with traumatic SCI upon hospital admission, but when they were tested upon discharge, those with traumatic SCI had improved such that both groups results were the same. In addition to the completeness and level of the injury, age and concurrent health problems affect the extent to which a person with SCI will be able to live independently and to walk.  However, in general people with injuries to L3 or below will likely be able to walk functionally, T10 and below to walk around the house with bracing, and C7 and below to live independently. New therapies are beginning to provide hope for better outcomes in patients with SCI, but most are in the experimental/translational stage.One important predictor of motor recovery in an area is presence of sensation there, particularly pain perception. Most motor recovery occurs in the first year post-injury, but modest improvements can continue for years; sensory recovery is more limited.  Recovery is typically quickest during the first six months. Spinal shock, in which reflexes are suppressed, occurs immediately after the injury and resolves largely within three months but continues resolving gradually for another 15.Sexual dysfunction after spinal injury is common.  Problems that can occur include erectile dysfunction, loss of ability to ejaculate, insufficient lubrication of the vagina, and reduced sensation and impaired ability to orgasm.  Despite this, many people learn ways to adapt their sexual practices so they can lead satisfying sex lives.Although life expectancy has improved with better care options, it is still not as good as the uninjured population.  The higher the level of injury, and the more complete the injury, the greater the reduction in life expectancy. Mortality is very elevated within a year of injury.

Epidemiology
Worldwide, the number of new cases since 1995 of SCI ranges from 10.4 to 83 people per million per year. This wide range of numbers is probably partly due to differences among regions in whether and how injuries are reported. In North America, about 39 people per every million incur SCI traumatically each year, and in Western Europe, the incidence is 16 per million.  In the United States, the incidence of spinal cord injury has been estimated to be about 40 cases per 1 million people per year or around 12,000 cases per year. In China, the incidence is approximately 60,000 per year.
The estimated number of people living with SCI in the world ranges from 236 to 4187 per million. Estimates vary widely due to differences in how data are collected and what techniques are used to extrapolate the figures. Little information is available from Asia, and even less from Africa and South America. In  Western Europe the estimated prevalence is 300 per million people and in North America it is 853 per million. It is estimated at 440 per million in Iran, 526 per million in Iceland, and 681 per million in Australia. In the United States there are between 225,000 and 296,000 individuals living with spinal cord injuries, and different studies have estimated prevalences from 525 to 906 per million.SCI is present in about 2% of all cases of blunt force trauma. Anyone who has undergone force sufficient to cause a thoracic spinal injury is at high risk for other injuries also. In 44% of SCI cases, other serious injuries are sustained at the same time; 14% of SCI patients also have head trauma or facial trauma. Other commonly associated injuries include chest trauma, abdominal trauma, pelvic fractures, and long bone fractures.Males account for four out of five traumatic spinal cord injuries. Most of these injuries occur in men under 30 years of age.  The average age at the time of injury has slowly increased from about 29 years in the 1970s to 41. In Pakistan, spinal cord injury is more common in males (92.68%) as compared to females in the 20-30 years of age group with a median age of 40 years, although people from 12-70 years of age suffered from spinal cord injury  Rates of injury are at their lowest in children, at their highest in the late teens to early twenties, then get progressively lower in older age groups; however rates may rise in the elderly. In Sweden between 50 and 70% of all cases of SCI occur in people under 30, and 25% occur in those over 50. While SCI rates are highest among people age 15–20, fewer than 3% of SCIs occur in people under 15.  Neonatal SCI occurs in one in 60,000 births, e.g. from breech births or injuries by forceps. The difference in rates between the sexes diminishes in injuries at age 3 and younger; the same number of girls are injured as boys, or possibly more. Another cause of pediatric injury is  child abuse such as shaken baby syndrome. For children, the most common cause of SCI (56%) is vehicle crashes. High numbers of adolescent injuries are attributable in a large part to traffic accidents and sports injuries. For people over 65, falls are the most common cause of traumatic SCI. The elderly and people with severe arthritis are at high risk for SCI because of defects in the spinal column. In nontraumatic SCI, the gender difference is smaller, the average age of occurrence is greater, and incomplete lesions are more common.

History
SCI has been known to be devastating for millennia; the ancient Egyptian Edwin Smith Papyrus from 2500 BC, the first known description of the injury, says it is "not to be treated".  Hindu texts dating back to 1800 BC also mention SCI and describe traction techniques to straighten the spine.  The  Greek physician Hippocrates, born in the fifth century BC, described SCI in his Hippocratic Corpus and invented traction devices to straighten dislocated vertebrae. But it was not until Aulus Cornelius Celsus, born 30 BC, noted that a cervical injury resulted in rapid death that the spinal cord itself was implicated in the condition. In the second century AD the Greek physician Galen experimented on monkeys and reported that a horizontal cut through the spinal cord caused them to lose all sensation and motion below the level of the cut. The seventh-century Greek physician Paul of Aegina described surgical techniques for treatment of broken vertebrae by removing bone fragments, as well as surgery to relieve pressure on the spine.  Little medical progress was made during the Middle Ages in Europe; it was not until the Renaissance that the spine and nerves were accurately depicted in human anatomy drawings by Leonardo da Vinci and Andreas Vesalius.In 1762 a surgeon named Andre Louis removed a bullet from the lumbar spine of a patient, who regained motion in the legs. In 1829 the surgeon Gilpin Smith performed a successful laminectomy that improved the patients sensation.  However, the idea that SCI was untreatable remained predominant until the early 20th century.  In 1934, the mortality rate in the first two years after injury was over 80%, mostly due to infections of the urinary tract and pressure sores, the latter of which were believed to be intrinsic to SCI rather than a result of continuous bedrest. It was not until the second half of the century that breakthroughs in imaging, surgery, medical care, and rehabilitation medicine contributed to a substantial improvement in SCI care.  The relative incidence of incomplete compared to complete injuries has improved since the mid-20th century, due mainly to the emphasis on faster and better initial care and stabilization of spinal cord injury patients.  The creation of emergency medical services to professionally transport people to the hospital is given partial credit for an improvement in outcomes since the 1970s.  Improvements in care have been accompanied by increased life expectancy of people with SCI; survival times have improved by about 2000% since 1940. In 2015/2016 23% of people in nine spinal injury centres in England had their discharge delayed because of disputes about who should pay for the equipment they needed.

Research directions
Scientists are investigating various avenues for treatment of spinal cord injury. Therapeutic research is focused on two main areas: neuroprotection and neuroregeneration. The former seeks to prevent the harm that occurs from secondary injury in the minutes to weeks following the insult, and the latter aims to reconnect the broken circuits in the spinal cord to allow function to return.  Neuroprotective drugs target secondary injury effects including inflammation, damage by free radicals, excitotoxicity (neuronal damage by excessive glutamate signaling), and apoptosis (cell suicide). Several potentially neuroprotective agents that target pathways like these are under investigation in human clinical trials.

Stem cell transplantation is an important avenue for SCI research: the goal is to replace lost spinal cord cells, allow reconnection in broken neural circuits by regrowing axons, and to create an environment in the tissues that is favorable to growth. A key avenue of SCI research is research on stem cells, which can differentiate into other types of cells—including those lost after SCI. Types of cells being researched for use in SCI include embryonic stem cells, neural stem cells, mesenchymal stem cells,  olfactory ensheathing cells, Schwann cells, activated macrophages, and induced pluripotent stem cells. Hundreds of stem cell studies have been done in humans, with promising but inconclusive results </s>